GenVec, Inc. (Nasdaq:GNVC) announced that it has received a Small Business Innovation and Research (SBIR) grant from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) to support the company's malaria vaccine program. This grant, valued at approximately $600,000 over two years, will be used to develop enhancements to the company's vectors for vaccine applications against malaria.
GenVec is applying its adenovector technology to the development of malaria vaccine candidates in collaboration with the U.S. Naval Medical Research Center (NMRC) and PATH's Malaria Vaccine Initiative. The NMRC is currently conducting a Phase I/II clinical study to assess the safety and immunogenicity of a vaccine candidate developed under this program.
"In addition to advancing our malaria vaccine program, work under this grant may provide improvements to our technology that could be applied to other adenovector-based vaccines and therapeutics," said Dr. Rick King, GenVec's Senior Vice President of Research.
About GenVec
GenVec, Inc. is a biopharmaceutical company developing novel therapeutic drugs and vaccines. GenVec's lead product, TNFerade™, is currently in a pivotal clinical study (PACT) in locally advanced pancreatic cancer. Additional clinical trials are in progress in rectal cancer, head and neck cancer and melanoma. GenVec also uses its proprietary adenovector technology to develop vaccines for infectious diseases including HIV, malaria, foot-and-mouth disease, respiratory syncytial virus (RSV), and influenza. Additional information about GenVec is available at http://www.genvec.com and in the company's various filings with the Securities and Exchange Commission.
Statements herein relating to future financial or business performance, conditions or strategies and other financial and business matters, including expectations regarding future revenues and operating expenses, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. GenVec cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks and uncertainties, including the failure by GenVec to secure and maintain relationships with collaborators; risks relating to the early stage of GenVec's product candidates under development; uncertainties relating to clinical trials; risks relating to the commercialization, if any, of GenVec's proposed product candidates; dependence on the efforts of third parties; dependence on intellectual property; and risks that we may lack the financial resources and access to capital to fund our operations. Further information on the factors and risks that could affect GenVec's business, financial conditions and results of operations, are contained in GenVec's filings with the U.S. Securities and Exchange Commission (SEC), which are available at http://www.sec.gov. These forward-looking statements speak only as of the date of this press release, and GenVec assumes no duty to update forward-looking statements.
GenVec
Monday, April 7, 2008
Taro Receives Tentative FDA Approval For Lamotrigine Tablets ANDA
Taro Pharmaceutical Industries Ltd. ("Taro," the "Company," Pink Sheets: TAROF) reported today that it has received tentative approval from the U.S. Food and Drug Administration ("FDA") for its Abbreviated New Drug Application ("ANDA") for Lamotrigine Tablets 25 mg, 100 mg, 150 mg, and 200 mg ("Lamotrigine Tablets").
Lamotrigine is a prescription product used for the treatment of seizures and is bioequivalent to GlaxoSmithKline's Lamictal® Tablets. According to industry sources, Lamictal® Tablets had annual U.S. sales of approximately $2.6 billion.
The tentative ANDA approval for Taro's Lamotrigine Tablets is an FDA determination that Taro's ANDA submission for this product currently satisfies the substantive requirements for approval, subject to the expiration of all relevant patents or statutorily imposed exclusivities and restrictions (currently expected to occur during January 2009), or any new information that may come to the FDA's attention. Tentative approvals do not grant marketing rights; a company may only market a product upon receiving final approval for an ANDA submission.
Taro Pharmaceutical Industries Ltd. is a multinational, science-based pharmaceutical company, dedicated to meeting the needs of its customers through the discovery, development, manufacturing and marketing of the highest quality healthcare products.
For further information on Taro Pharmaceutical Industries Ltd., please visit the Company's website at http://www.taro.com.
Certain statements in this release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company's lamotrigine product. Although Taro Pharmaceutical Industries Ltd. believes the expectations reflected in such forward-looking statements to be based on reasonable assumptions, it can give no assurance that its expectations will be attained. Factors that could cause actual results to differ include failure to receive final approval for Taro's ANDA submission for Lamotrigine Tablets; the granting of additional exclusivities or restrictions to Lamictal® Tablets; industry and market conditions; slower than anticipated penetration of new markets; physician, pharmacist or patient acceptance of Taro's Lamotrigine Tablets; changes in the Company's financial position; regulatory actions; and, other risks detailed from time to time in the Company's SEC reports, including its Annual Reports on Form 20-F. Forward-looking statements speak only as of the date on which they are made. The Company undertakes no obligation to update, change or revise any forward-looking statements, whether as a result of new information, additional or subsequent developments or otherwise.
Taro Pharmaceutical Industries Ltd.
Lamotrigine is a prescription product used for the treatment of seizures and is bioequivalent to GlaxoSmithKline's Lamictal® Tablets. According to industry sources, Lamictal® Tablets had annual U.S. sales of approximately $2.6 billion.
The tentative ANDA approval for Taro's Lamotrigine Tablets is an FDA determination that Taro's ANDA submission for this product currently satisfies the substantive requirements for approval, subject to the expiration of all relevant patents or statutorily imposed exclusivities and restrictions (currently expected to occur during January 2009), or any new information that may come to the FDA's attention. Tentative approvals do not grant marketing rights; a company may only market a product upon receiving final approval for an ANDA submission.
Taro Pharmaceutical Industries Ltd. is a multinational, science-based pharmaceutical company, dedicated to meeting the needs of its customers through the discovery, development, manufacturing and marketing of the highest quality healthcare products.
For further information on Taro Pharmaceutical Industries Ltd., please visit the Company's website at http://www.taro.com.
Certain statements in this release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company's lamotrigine product. Although Taro Pharmaceutical Industries Ltd. believes the expectations reflected in such forward-looking statements to be based on reasonable assumptions, it can give no assurance that its expectations will be attained. Factors that could cause actual results to differ include failure to receive final approval for Taro's ANDA submission for Lamotrigine Tablets; the granting of additional exclusivities or restrictions to Lamictal® Tablets; industry and market conditions; slower than anticipated penetration of new markets; physician, pharmacist or patient acceptance of Taro's Lamotrigine Tablets; changes in the Company's financial position; regulatory actions; and, other risks detailed from time to time in the Company's SEC reports, including its Annual Reports on Form 20-F. Forward-looking statements speak only as of the date on which they are made. The Company undertakes no obligation to update, change or revise any forward-looking statements, whether as a result of new information, additional or subsequent developments or otherwise.
Taro Pharmaceutical Industries Ltd.
FDA Approves ROTARIX(R) Rotavirus Vaccine
AVANT Immunotherapeutics, Inc. (Nasdaq: AVAN) announced that its partner, GlaxoSmithKline (GSK), has received approval from the U.S. Food and Drug Administration (FDA) for ROTARIX® for the prevention of rotavirus gastroenteritis in infants. With only two doses, ROTARIX will offer protection against the most commonly circulating rotavirus types in the U.S. and allow infants to complete the vaccination series by four months of age. The U.S. Centers for Disease Control and Prevention (CDC) currently recommends that children complete the rotavirus immunization series by six months of age. Rotavirus infects virtually every child in the United States by age five and is the leading cause of severe gastroenteritis in infants and young children worldwide. ROTARIX may help prevent many of the 55,000 - 70,000 hospitalizations by young children that result from rotavirus in the U.S. each year.
Not only does ROTARIX confer protection at an early age, but clinical trials have shown that protection is broad and sustained. ROTARIX is indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9) when administered as a two-dose series in infants and children. Clinical data published on the two-dose series of ROTARIX show that protection was sustained through the first two years of life and was highly efficacious against rotavirus hospitalizations (96%) and severe rotavirus gastroenteritis (90%). In addition, ROTARIX was effective against rotavirus gastroenteritis of any severity (79%). Specifically, significant protection was demonstrated against severe rotavirus gastroenteritis during two rotavirus seasons caused by types G1 (96%), G2 (86%), G3 (94%), G4 (95%), and G9 (85%), the most commonly circulating rotavirus types in the U.S.
"We are delighted that our partner GSK has received approval of ROTARIX in the United States," said Una S. Ryan, Ph.D., President and Chief Executive Officer of AVANT Immunotherapeutics. "With only two doses, ROTARIX will allow infants to complete the vaccination series against rotavirus earlier than ever before. We have great expectations for GSK to launch ROTARIX prior to the upcoming rotavirus season."
AVANT licensed the technology for ROTARIX to GSK in 1997 for worldwide commercialization. The vaccine was originally developed at Cincinnati Children's Hospital Medical Center. The FDA's approval of ROTARIX was based on one of the largest clinical development plans undertaken by a vaccine manufacturer and includes data from nearly 75,000 infants. These clinical trials were conducted in the Americas, Europe, Asia and Africa and reflect an ethnically diverse population.
About ROTARIX
ROTARIX is an oral live-attenuated human rotavirus vaccine licensed in more than 100 countries around the world. More than 25 million doses of ROTARIX have been distributed worldwide. The vaccine was developed for the prevention of rotavirus gastroenteritis by mimicking the protective effects of natural human rotavirus infection. Naturally occurring human rotavirus infection provides significant protection against subsequent moderate to severe rotavirus gastroenteritis regardless of the infecting serotype(s). Five Phase 3 clinical trials were conducted worldwide to assess the safety and efficacy of ROTARIX in support of U.S. licensure. The clinical trials conducted in support of U.S. licensure demonstrated efficacy against rotavirus gastroenteritis of any severity due to the most common currently circulating rotavirus types in the U.S. In clinical studies, common adverse events were fussiness/irritability, cough/runny nose, fever, loss of appetite, and vomiting. ROTARIX is contraindicated in certain individuals with a history of uncorrected congenital malformation of the gastrointestinal tract.
About Rotavirus
Rotavirus infects virtually every child worldwide by age five and is the leading cause of severe gastroenteritis in infants and young children in the U.S. and worldwide. Severe, dehydrating gastroenteritis can occur as young as three months of age. In the U.S. each year, 2.7 million children younger than five years of age suffer from rotavirus disease, resulting in 410,000 clinic visits and up to 272,000 emergency department visits. In addition, between 55,000 and 70,000 children are hospitalized and 20 to 60 die each year. In the U.S., the rotavirus season typically begins in the southwest during November-December and spreads to the northeast by April-May.
About GlaxoSmithKline: A Leader in Vaccines
GlaxoSmithKline, with U.S. operations in Philadelphia, PA, and Research Triangle Park, NC, is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer.
GlaxoSmithKline Biologicals (GSK Biologicals) is a global vaccine company which has shown to be a leader in innovation. The company is active in the fields of vaccine research, development and production with over 30 vaccines approved for marketing and 20 more in development. Headquartered in Belgium, GSK Biologicals has 14 manufacturing sites strategically positioned around the globe. In 2007 GSK Biologicals distributed 1.1 billion doses of vaccines to 169 countries in both developed and the developing world -- an average of 3 million doses a day.
GSK Biologicals employs over 9,000 people worldwide including more than 1,600 passionate scientists engaged in research aimed at discovering innovative vaccines that contribute to the health and well-being of people of all generations around the world.
About AVANT Immunotherapeutics, Inc.
AVANT Immunotherapeutics, Inc. is a NASDAQ-listed company discovering and developing innovative vaccines and targeted immunotherapeutics for the treatment of cancer, infectious and inflammatory diseases. AVANT focuses on the use of tumor-specific targets and human monoclonal antibodies (mAbs) to precisely deliver therapeutic agents through its novel "targeted immunization" approach. AVANT also possesses innovative bacterial vector delivery technologies with unique manufacturing and preservation processes that offer the potential for a new generation of infectious disease vaccines. AVANT's deep product pipeline consists of products in varying stages of development, with its lead candidate, CDX-110, currently undergoing evaluation in a Phase 2/3 clinical trial in newly diagnosed glioblastoma multiforme, one of the most aggressive forms of brain cancer. AVANT also has five product candidates in its development pipeline including:
- CDX-1307, a product based on its proprietary APC Targeting Technology™, which is in two Phase 1 clinical trials for patients with advanced pancreatic, bladder, breast and colon cancer;
- a complement inhibitor, TP10, in development for transplantation and other indications; and
- three candidates based on its oral, rapidly-protecting, single-dose and temperature-stable vaccine technology, including combination vaccines for travelers, the military and global health needs.
AVANT has three commercialized products, including ROTARIX for the prevention of rotavirus infection and two human food safety vaccines for reducing salmonella infection in chickens and eggs.
AVANT Immunotherapeutics, Inc.
Not only does ROTARIX confer protection at an early age, but clinical trials have shown that protection is broad and sustained. ROTARIX is indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9) when administered as a two-dose series in infants and children. Clinical data published on the two-dose series of ROTARIX show that protection was sustained through the first two years of life and was highly efficacious against rotavirus hospitalizations (96%) and severe rotavirus gastroenteritis (90%). In addition, ROTARIX was effective against rotavirus gastroenteritis of any severity (79%). Specifically, significant protection was demonstrated against severe rotavirus gastroenteritis during two rotavirus seasons caused by types G1 (96%), G2 (86%), G3 (94%), G4 (95%), and G9 (85%), the most commonly circulating rotavirus types in the U.S.
"We are delighted that our partner GSK has received approval of ROTARIX in the United States," said Una S. Ryan, Ph.D., President and Chief Executive Officer of AVANT Immunotherapeutics. "With only two doses, ROTARIX will allow infants to complete the vaccination series against rotavirus earlier than ever before. We have great expectations for GSK to launch ROTARIX prior to the upcoming rotavirus season."
AVANT licensed the technology for ROTARIX to GSK in 1997 for worldwide commercialization. The vaccine was originally developed at Cincinnati Children's Hospital Medical Center. The FDA's approval of ROTARIX was based on one of the largest clinical development plans undertaken by a vaccine manufacturer and includes data from nearly 75,000 infants. These clinical trials were conducted in the Americas, Europe, Asia and Africa and reflect an ethnically diverse population.
About ROTARIX
ROTARIX is an oral live-attenuated human rotavirus vaccine licensed in more than 100 countries around the world. More than 25 million doses of ROTARIX have been distributed worldwide. The vaccine was developed for the prevention of rotavirus gastroenteritis by mimicking the protective effects of natural human rotavirus infection. Naturally occurring human rotavirus infection provides significant protection against subsequent moderate to severe rotavirus gastroenteritis regardless of the infecting serotype(s). Five Phase 3 clinical trials were conducted worldwide to assess the safety and efficacy of ROTARIX in support of U.S. licensure. The clinical trials conducted in support of U.S. licensure demonstrated efficacy against rotavirus gastroenteritis of any severity due to the most common currently circulating rotavirus types in the U.S. In clinical studies, common adverse events were fussiness/irritability, cough/runny nose, fever, loss of appetite, and vomiting. ROTARIX is contraindicated in certain individuals with a history of uncorrected congenital malformation of the gastrointestinal tract.
About Rotavirus
Rotavirus infects virtually every child worldwide by age five and is the leading cause of severe gastroenteritis in infants and young children in the U.S. and worldwide. Severe, dehydrating gastroenteritis can occur as young as three months of age. In the U.S. each year, 2.7 million children younger than five years of age suffer from rotavirus disease, resulting in 410,000 clinic visits and up to 272,000 emergency department visits. In addition, between 55,000 and 70,000 children are hospitalized and 20 to 60 die each year. In the U.S., the rotavirus season typically begins in the southwest during November-December and spreads to the northeast by April-May.
About GlaxoSmithKline: A Leader in Vaccines
GlaxoSmithKline, with U.S. operations in Philadelphia, PA, and Research Triangle Park, NC, is one of the world's leading research-based pharmaceutical and healthcare companies and is committed to improving the quality of human life by enabling people to do more, feel better and live longer.
GlaxoSmithKline Biologicals (GSK Biologicals) is a global vaccine company which has shown to be a leader in innovation. The company is active in the fields of vaccine research, development and production with over 30 vaccines approved for marketing and 20 more in development. Headquartered in Belgium, GSK Biologicals has 14 manufacturing sites strategically positioned around the globe. In 2007 GSK Biologicals distributed 1.1 billion doses of vaccines to 169 countries in both developed and the developing world -- an average of 3 million doses a day.
GSK Biologicals employs over 9,000 people worldwide including more than 1,600 passionate scientists engaged in research aimed at discovering innovative vaccines that contribute to the health and well-being of people of all generations around the world.
About AVANT Immunotherapeutics, Inc.
AVANT Immunotherapeutics, Inc. is a NASDAQ-listed company discovering and developing innovative vaccines and targeted immunotherapeutics for the treatment of cancer, infectious and inflammatory diseases. AVANT focuses on the use of tumor-specific targets and human monoclonal antibodies (mAbs) to precisely deliver therapeutic agents through its novel "targeted immunization" approach. AVANT also possesses innovative bacterial vector delivery technologies with unique manufacturing and preservation processes that offer the potential for a new generation of infectious disease vaccines. AVANT's deep product pipeline consists of products in varying stages of development, with its lead candidate, CDX-110, currently undergoing evaluation in a Phase 2/3 clinical trial in newly diagnosed glioblastoma multiforme, one of the most aggressive forms of brain cancer. AVANT also has five product candidates in its development pipeline including:
- CDX-1307, a product based on its proprietary APC Targeting Technology™, which is in two Phase 1 clinical trials for patients with advanced pancreatic, bladder, breast and colon cancer;
- a complement inhibitor, TP10, in development for transplantation and other indications; and
- three candidates based on its oral, rapidly-protecting, single-dose and temperature-stable vaccine technology, including combination vaccines for travelers, the military and global health needs.
AVANT has three commercialized products, including ROTARIX for the prevention of rotavirus infection and two human food safety vaccines for reducing salmonella infection in chickens and eggs.
AVANT Immunotherapeutics, Inc.
Carl Zeiss Meditec Delivers Key Technological Advances In Optical Coherence Tomography
Carl Zeiss Meditec, a leader in ophthalmic devices and surgical systems, announced today that two new optical coherence tomography (OCT) applications will be available for the first time at the American Society of Cataract and Refractive Surgeons (ASCRS) meeting in Chicago, IL at booth 2028. With advanced algorithms available for Cirrus™ HD-OCT and Stratus™ OCT, ophthalmologists now have the most advanced imaging capabilities available for assessing and managing glaucoma and diseases of the retina.
The Cirrus HD-OCT, the latest addition to the Zeiss OCT family of products, provides the most detailed scan patterns and layer maps available for identifying retinal and glaucoma disease characteristics, and monitoring disease progression. Nearly 1000 Cirrus HD-OCT units have been sold worldwide since its introduction last November. It is the first in its category to deliver high-definition 3D maps to spectral domain technology.
"The Cirrus HD-OCT 3-D images bring us a new level of insight into the detailed structure of the retina," said Peter K. Kaiser, MD, Director of the Clinical Research Center, Cole Eye Institute in Cleveland. "Combined with the proprietary image analysis algorithms developed by the veteran Zeiss team, the Cirrus gives us new volumetric data that expands our ability to interpret the three dimensional images in a highly reproducible, quantitative fashion."
For the first time, Stratus OCT features both Advanced Serial Analysis and Guided Progression Analysis™ (GPA) software for objective measurement and subjective clinical evaluation in the detection of glaucoma and retinal diseases. Advanced Serial Analysis plots RNFL thickness over time and reports statistically significant change, enabling practitioners to project future vision loss and make timely treatment decisions.
Stratus OCT is the standard of care system for comprehensive retinal scanning. With nearly 9,000 Stratus OCT units in use worldwide, more than 37,000 scans performed each year and backed by over 100 U.S. clinical studies for retinal disease, the Stratus OCT is the most widely adopted and researched OCT system in the world.
"From pioneering the first OCT platform nearly a decade ago to launching the newest Cirrus HD-OCT system late last year, Zeiss continues its tradition of leadership with spectral domain technology," said Jim Taylor, Carl Zeiss Meditec president and chief executive officer. "The new features for the Cirrus and Status OCT systems provide efficiencies that allow physicians to more easily gather and interpret detailed disease information while streamlining workflow processes that impact the entire practice. Our ultimate goal is to enable our customers to provide the best quality of care possible to their patients."
Optical coherence tomography (OCT) is an imaging method that uses light to scan the retina, and can be performed on undilated pupils as small as 3 mm in diameter. It provides detailed, real-time information about the structure of the living eye available to the clinician. Using light to scan the retina and optic disc, this pioneering technology brought new clinical tools for the diagnosis and management of retinal disease and glaucoma.
About Carl Zeiss Meditec
Carl Zeiss Meditec AG (ISIN: DE 0005313704) is one of the world's leading medical technology companies. This market position is based on over 160 years of experience in optical innovation.
The company has two primary areas of activity: In the field of ophthalmology Carl Zeiss Meditec offers integrated solutions for treating the four main eye ailments: vision defects (refraction), cataract, glaucoma and retinal disorders. The company's system solutions are employed in all phases of the disease management, from diagnosis to treatment and aftercare. Carl Zeiss Meditec has always applied its technological expertise to product innovations. These innovations range from basic systems such as slit lamps and fundus cameras to standard setting diagnostic systems such as the Humphrey® Field Analyzer, the Stratus OCT™ and the IOLMaster®, through to the surgical microscopes and innovative treatment systems in refractive laser surgery. The product portfolio in ophthalmic surgery is rounded off by intraocular lenses and consumables.
In the field of neuro and ENT surgery, Carl Zeiss Meditec is the world's leading provider of surgical microscopes and microsurgical visualization solutions for a very broad range of applications, such as tumor and vascular surgery in the head region and/or spinal surgery. The most recent example of the innovative performance in the area of microsurgery is the OPMI Pentero® visualization system, which allows efficient and ergonomic patient treatment. Carl Zeiss Meditec will systematically expand its product range in this area and become a solution provider in neuro and ENT surgery as well.
Carl Zeiss Meditec's medical technology portfolio is rounded off by visualization systems for doctors in private practice and promising future technologies such as intraoperative radiation therapy, which allows the targeted treatment of breast cancer and brain cancer directly during surgery.
Carl Zeiss Meditec AG is based in Jena, Germany, with subsidiaries in Germany (Carl Zeiss Surgical GmbH, Carl Zeiss Meditec Vertriebsgesellschaft mbH, *Acri.Tec AG and Carl Zeiss Medical Software GmbH), the USA (Carl Zeiss Meditec, Inc., Dublin), in Japan (Carl Zeiss Meditec Co., Ltd., Tokyo), Spain (Carl Zeiss Meditec Iberia S.A., Madrid) and France (Carl Zeiss Meditec S.A.S., La Rochelle, and Carl Zeiss Meditec France SAS, Le Pecq).
Carl Zeiss Meditec
The Cirrus HD-OCT, the latest addition to the Zeiss OCT family of products, provides the most detailed scan patterns and layer maps available for identifying retinal and glaucoma disease characteristics, and monitoring disease progression. Nearly 1000 Cirrus HD-OCT units have been sold worldwide since its introduction last November. It is the first in its category to deliver high-definition 3D maps to spectral domain technology.
"The Cirrus HD-OCT 3-D images bring us a new level of insight into the detailed structure of the retina," said Peter K. Kaiser, MD, Director of the Clinical Research Center, Cole Eye Institute in Cleveland. "Combined with the proprietary image analysis algorithms developed by the veteran Zeiss team, the Cirrus gives us new volumetric data that expands our ability to interpret the three dimensional images in a highly reproducible, quantitative fashion."
For the first time, Stratus OCT features both Advanced Serial Analysis and Guided Progression Analysis™ (GPA) software for objective measurement and subjective clinical evaluation in the detection of glaucoma and retinal diseases. Advanced Serial Analysis plots RNFL thickness over time and reports statistically significant change, enabling practitioners to project future vision loss and make timely treatment decisions.
Stratus OCT is the standard of care system for comprehensive retinal scanning. With nearly 9,000 Stratus OCT units in use worldwide, more than 37,000 scans performed each year and backed by over 100 U.S. clinical studies for retinal disease, the Stratus OCT is the most widely adopted and researched OCT system in the world.
"From pioneering the first OCT platform nearly a decade ago to launching the newest Cirrus HD-OCT system late last year, Zeiss continues its tradition of leadership with spectral domain technology," said Jim Taylor, Carl Zeiss Meditec president and chief executive officer. "The new features for the Cirrus and Status OCT systems provide efficiencies that allow physicians to more easily gather and interpret detailed disease information while streamlining workflow processes that impact the entire practice. Our ultimate goal is to enable our customers to provide the best quality of care possible to their patients."
Optical coherence tomography (OCT) is an imaging method that uses light to scan the retina, and can be performed on undilated pupils as small as 3 mm in diameter. It provides detailed, real-time information about the structure of the living eye available to the clinician. Using light to scan the retina and optic disc, this pioneering technology brought new clinical tools for the diagnosis and management of retinal disease and glaucoma.
About Carl Zeiss Meditec
Carl Zeiss Meditec AG (ISIN: DE 0005313704) is one of the world's leading medical technology companies. This market position is based on over 160 years of experience in optical innovation.
The company has two primary areas of activity: In the field of ophthalmology Carl Zeiss Meditec offers integrated solutions for treating the four main eye ailments: vision defects (refraction), cataract, glaucoma and retinal disorders. The company's system solutions are employed in all phases of the disease management, from diagnosis to treatment and aftercare. Carl Zeiss Meditec has always applied its technological expertise to product innovations. These innovations range from basic systems such as slit lamps and fundus cameras to standard setting diagnostic systems such as the Humphrey® Field Analyzer, the Stratus OCT™ and the IOLMaster®, through to the surgical microscopes and innovative treatment systems in refractive laser surgery. The product portfolio in ophthalmic surgery is rounded off by intraocular lenses and consumables.
In the field of neuro and ENT surgery, Carl Zeiss Meditec is the world's leading provider of surgical microscopes and microsurgical visualization solutions for a very broad range of applications, such as tumor and vascular surgery in the head region and/or spinal surgery. The most recent example of the innovative performance in the area of microsurgery is the OPMI Pentero® visualization system, which allows efficient and ergonomic patient treatment. Carl Zeiss Meditec will systematically expand its product range in this area and become a solution provider in neuro and ENT surgery as well.
Carl Zeiss Meditec's medical technology portfolio is rounded off by visualization systems for doctors in private practice and promising future technologies such as intraoperative radiation therapy, which allows the targeted treatment of breast cancer and brain cancer directly during surgery.
Carl Zeiss Meditec AG is based in Jena, Germany, with subsidiaries in Germany (Carl Zeiss Surgical GmbH, Carl Zeiss Meditec Vertriebsgesellschaft mbH, *Acri.Tec AG and Carl Zeiss Medical Software GmbH), the USA (Carl Zeiss Meditec, Inc., Dublin), in Japan (Carl Zeiss Meditec Co., Ltd., Tokyo), Spain (Carl Zeiss Meditec Iberia S.A., Madrid) and France (Carl Zeiss Meditec S.A.S., La Rochelle, and Carl Zeiss Meditec France SAS, Le Pecq).
Carl Zeiss Meditec
Patients Help Crack Nurses' And Midwives' Code, UK
To mark World Health Day, the Nursing & Midwifery Council (NMC) today launches a new Code for the UK's 674,000 nurses and midwives
With events held in Edinburgh, Belfast, Glamorgan and London, the launch of the new Code aims to clarify expectations; setting out for nurses and midwives what is expected of them as professionals, and showing members of the public what standard of care they can expect to receive.
"Practise is continually changing and nurses and midwives are increasingly faced with situations that challenge their accountability," said Nancy Kirkland, NMC President. "Nurses and midwives should see the Code as a support tool to help them in practise so if they are faced with an ethical, moral or professional dilemma, they can refer to the Code for guidance and advice," she said.
As part of the review in 2007, the NMC met with stakeholders from all corners of the UK, including nurses, midwives, employers, members of the public, patient groups, unions and professional bodies. These views have been the primary influence in developing the new Code.
Dee Stanley-Smith, Provider Services Clinical Lead at Derby City PCT who was involved in the consultation process said, "The Code puts into words what it means to be a nurse, spelling out my responsibility to the patient, the service and the profession. It reminds me that I am proud to be a nurse successfully working in an ever-changing world."
A recent NMC online poll of more than 800 nurses and midwives showed that 34 per cent were not confident they knew what was in their Code.
Ms Kirkland added, "Not only are healthcare services continually changing, so too are the needs of patients. Instead of the Code setting out pages of rules, which would be unsuitable considering the varied roles and individual patient needs, the pocket-sized Code provides a broad set of principles that nurses and midwives can apply to their own area of practise and the diverse environments in which patients receive care."
The NMC Code comes into effect on 1 May 2008.
The Nursing & Midwifery Council (NMC) is the UK regulator for two professions, nursing and midwifery. To be eligible to work as a nurse or midwife in the UK, they must be registered with the NMC. There are currently more than 674,000 nurses and midwives on the register. The primary purpose of the NMC is to safeguard the health and wellbeing of the public. It does this through maintaining a register of all nurses and midwives to practise within the UK and by setting standards for their education, training and conduct.
Nursing & Midwifery Council
With events held in Edinburgh, Belfast, Glamorgan and London, the launch of the new Code aims to clarify expectations; setting out for nurses and midwives what is expected of them as professionals, and showing members of the public what standard of care they can expect to receive.
"Practise is continually changing and nurses and midwives are increasingly faced with situations that challenge their accountability," said Nancy Kirkland, NMC President. "Nurses and midwives should see the Code as a support tool to help them in practise so if they are faced with an ethical, moral or professional dilemma, they can refer to the Code for guidance and advice," she said.
As part of the review in 2007, the NMC met with stakeholders from all corners of the UK, including nurses, midwives, employers, members of the public, patient groups, unions and professional bodies. These views have been the primary influence in developing the new Code.
Dee Stanley-Smith, Provider Services Clinical Lead at Derby City PCT who was involved in the consultation process said, "The Code puts into words what it means to be a nurse, spelling out my responsibility to the patient, the service and the profession. It reminds me that I am proud to be a nurse successfully working in an ever-changing world."
A recent NMC online poll of more than 800 nurses and midwives showed that 34 per cent were not confident they knew what was in their Code.
Ms Kirkland added, "Not only are healthcare services continually changing, so too are the needs of patients. Instead of the Code setting out pages of rules, which would be unsuitable considering the varied roles and individual patient needs, the pocket-sized Code provides a broad set of principles that nurses and midwives can apply to their own area of practise and the diverse environments in which patients receive care."
The NMC Code comes into effect on 1 May 2008.
The Nursing & Midwifery Council (NMC) is the UK regulator for two professions, nursing and midwifery. To be eligible to work as a nurse or midwife in the UK, they must be registered with the NMC. There are currently more than 674,000 nurses and midwives on the register. The primary purpose of the NMC is to safeguard the health and wellbeing of the public. It does this through maintaining a register of all nurses and midwives to practise within the UK and by setting standards for their education, training and conduct.
Nursing & Midwifery Council
Replacement Drug For Treating Cocaine Addiction Has Positive Finding In Animal Model
New research in monkeys suggests the feasibility of treating cocaine addiction with a "replacement" drug that mimics the effects of cocaine but has less potential for abuse - similar to the way nicotine and heroin addictions are treated.
Reporting at the annual meeting of the American Society of Pharmacology and Experimental Therapeutics in San Diego, Calif., scientists from Wake Forest University School of Medicine said treating monkeys with amphetamine significantly reduced their self-administration of cocaine for up to a month.
"This suggests the possibility of developing an amphetamine-like drug for treating cocaine addiction," said Paul Czoty, Ph.D., lead author and assistant professor of physiology and pharmacology. "The research also demonstrates the usefulness for conducting studies in monkeys to test potential treatments."
Czoty said the quest to develop a treatment for cocaine addiction has been ongoing for decades with little success. "While we have medications for heroin and tobacco abuse, there is no FDA-approved treatment for cocaine," he said.
With both heroin and tobacco, there are treatments to replace the addictive drug with a drug that has similar effects on the body, but with less potential for abuse.
"With this strategy in mind, clinical researchers have turned to drugs currently available, including amphetamines," said Czoty. "While it's unlikely that amphetamine itself will turn out to be the best treatment, these drugs allow us to prove the concept of using a replacement drug to combat cocaine addiction."
Amphetamines have been used in clinical studies with some success, said Czoty. His research in monkeys may help identify the best dose and schedule for administering a replacement drug - as well as evaluate potential treatment candidates and estimate potential side effects.
For the study, a monkey was taught to press levers multiple times to obtain food or a cocaine injection. With each injection, the number of required lever presses increased so that the animal had to work harder for the cocaine.
"This procedure measures the strength of the reinforcing effects of drugs," said Czoty. "Each injection requires more and more work and eventually it gets to the point where it's not worth it to the monkey because more than 1,000 presses are required."
Access to cocaine was then removed and the monkey was treated intravenously with an amphetamine 24 hours per day. When re-exposed to cocaine one week later, a dramatic decrease in responding for cocaine was observed. They tested three different doses of amphetamine and found that a moderate dose was most effective. Although the treatment also decreased lever-pressing for food - which could be predictive of side effects in humans - this effect disappeared within one week while the effect on responding for cocaine injections persisted for up to one month.
"This was a very positive finding - exactly what we had hoped to see," said Czoty. "Cocaine use was significantly reduced - by about 60 percent."
The researchers are currently repeating the study in additional animals. They hope it could eventually lead to identifying a slightly different drug that will obtain the same results as amphetamines.
Czoty said the study is significant because it and other similar studies in monkeys duplicate what has been found in small studies in humans, which suggests that the animal model can be used to test other treatments. The researchers, for example, plan to test topiramate (Topamax®), an anti-convulsant drug that is sometimes used to treat epilepsy and may be effective in treating alcoholism.
"We have found a model we can use to test new drugs and have an idea of what positive or negative effects would look like," said Czoty.
Reporting at the annual meeting of the American Society of Pharmacology and Experimental Therapeutics in San Diego, Calif., scientists from Wake Forest University School of Medicine said treating monkeys with amphetamine significantly reduced their self-administration of cocaine for up to a month.
"This suggests the possibility of developing an amphetamine-like drug for treating cocaine addiction," said Paul Czoty, Ph.D., lead author and assistant professor of physiology and pharmacology. "The research also demonstrates the usefulness for conducting studies in monkeys to test potential treatments."
Czoty said the quest to develop a treatment for cocaine addiction has been ongoing for decades with little success. "While we have medications for heroin and tobacco abuse, there is no FDA-approved treatment for cocaine," he said.
With both heroin and tobacco, there are treatments to replace the addictive drug with a drug that has similar effects on the body, but with less potential for abuse.
"With this strategy in mind, clinical researchers have turned to drugs currently available, including amphetamines," said Czoty. "While it's unlikely that amphetamine itself will turn out to be the best treatment, these drugs allow us to prove the concept of using a replacement drug to combat cocaine addiction."
Amphetamines have been used in clinical studies with some success, said Czoty. His research in monkeys may help identify the best dose and schedule for administering a replacement drug - as well as evaluate potential treatment candidates and estimate potential side effects.
For the study, a monkey was taught to press levers multiple times to obtain food or a cocaine injection. With each injection, the number of required lever presses increased so that the animal had to work harder for the cocaine.
"This procedure measures the strength of the reinforcing effects of drugs," said Czoty. "Each injection requires more and more work and eventually it gets to the point where it's not worth it to the monkey because more than 1,000 presses are required."
Access to cocaine was then removed and the monkey was treated intravenously with an amphetamine 24 hours per day. When re-exposed to cocaine one week later, a dramatic decrease in responding for cocaine was observed. They tested three different doses of amphetamine and found that a moderate dose was most effective. Although the treatment also decreased lever-pressing for food - which could be predictive of side effects in humans - this effect disappeared within one week while the effect on responding for cocaine injections persisted for up to one month.
"This was a very positive finding - exactly what we had hoped to see," said Czoty. "Cocaine use was significantly reduced - by about 60 percent."
The researchers are currently repeating the study in additional animals. They hope it could eventually lead to identifying a slightly different drug that will obtain the same results as amphetamines.
Czoty said the study is significant because it and other similar studies in monkeys duplicate what has been found in small studies in humans, which suggests that the animal model can be used to test other treatments. The researchers, for example, plan to test topiramate (Topamax®), an anti-convulsant drug that is sometimes used to treat epilepsy and may be effective in treating alcoholism.
"We have found a model we can use to test new drugs and have an idea of what positive or negative effects would look like," said Czoty.
Rapid Weight Gain Of Freshmen Unsubstantiated By Study
The "freshman 15" - the rapid weight gain believed to afflict many new college students when they begin school - appears to be a bit of an urban legend: a cautionary tale often told but not well substantiated.
Now a study of 36 freshmen at Auburn University - located in one of the states with the highest prevalence of obesity in the nation - reports an average gain of only 1.9 pounds during the first semester, with women gaining slightly more than men, and an average gain of only 4.8 pounds for the entire freshman year (with males gaining an average of 5.4 pounds and women gaining an average of 3.2 pounds). Some students lost weight. But even when only those who gained were considered, the average weight gain was 5.8 pounds, a long way from the often-popularized 15.
Dr. Sareen Gropper presented the study at the Experimental Biology 2008 meeting in San Diego on Sunday, April 6. The presentation is part of the scientific program of the American Society for Nutrition.
The 36 freshman (26 females and 10 males) were weighed and their body composition and shape measured when they began college and then again at the end of the fall semester and the end of the spring semester. The urban legend is correct in the sense that a majority of freshmen in the study (71.4 percent) did gain weight, notes Dr. Gropper, but only 21 percent gained five pounds or more. The largest gainers in the fall semester were a woman who gained nine pounds and a male who gained 10 pounds. For the academic year, the largest weight gains observed were 13 pounds for one male and 12 pounds for one female. No one gained the freshman 15.
Dr. Gropper and colleagues have begun a larger study of 240 students who entered Auburn in the fall semester of 2007. Like the pilot study, participants had to be between 17 and 19 years of age, not married, having no children, and without diagnosed eating disorders. At the end of the first semester, 68.7 percent of students had gained weight: an average of 2.1 pounds. Only 21 percent of students gained 5 pounds or more.
Among those who gained weight, the average was 4.1 pounds. Males gained an average of 4.8 pounds and females an average of 3.7 pounds their first semester at college. Seven students (3.3 percent) gained 10 pounds or more, but only one student gained at least 15 pound, a female who gained 16.2 pounds.
"It does happen," says Dr. Gropper, "even if not very often." She and her colleagues are following the 240 students throughout their freshman and beginning of their sophomore years, with questionnaires that examine factors that might contribute to the gain, however small, that the majority of college freshman appear to experience. The researchers also are collecting data on weight changes throughout the year, including five, 10, even 15+ pound losses within the first year of school.
Unique to this study, says Dr. Gropper, is the partnership with colleagues from Auburn University's Department of Consumer Affairs who use a 3-D whole body scanner to collect information on body size and shape. This technology quickly captures exact body measurements, which can be visually displayed in cross sections of body areas like the bust, waist and hips to show where changes occur in measurements over time. Understanding where weight is deposited on the body helps assess the potential risk of diseases such as heart disease and metabolic syndrome.
Now a study of 36 freshmen at Auburn University - located in one of the states with the highest prevalence of obesity in the nation - reports an average gain of only 1.9 pounds during the first semester, with women gaining slightly more than men, and an average gain of only 4.8 pounds for the entire freshman year (with males gaining an average of 5.4 pounds and women gaining an average of 3.2 pounds). Some students lost weight. But even when only those who gained were considered, the average weight gain was 5.8 pounds, a long way from the often-popularized 15.
Dr. Sareen Gropper presented the study at the Experimental Biology 2008 meeting in San Diego on Sunday, April 6. The presentation is part of the scientific program of the American Society for Nutrition.
The 36 freshman (26 females and 10 males) were weighed and their body composition and shape measured when they began college and then again at the end of the fall semester and the end of the spring semester. The urban legend is correct in the sense that a majority of freshmen in the study (71.4 percent) did gain weight, notes Dr. Gropper, but only 21 percent gained five pounds or more. The largest gainers in the fall semester were a woman who gained nine pounds and a male who gained 10 pounds. For the academic year, the largest weight gains observed were 13 pounds for one male and 12 pounds for one female. No one gained the freshman 15.
Dr. Gropper and colleagues have begun a larger study of 240 students who entered Auburn in the fall semester of 2007. Like the pilot study, participants had to be between 17 and 19 years of age, not married, having no children, and without diagnosed eating disorders. At the end of the first semester, 68.7 percent of students had gained weight: an average of 2.1 pounds. Only 21 percent of students gained 5 pounds or more.
Among those who gained weight, the average was 4.1 pounds. Males gained an average of 4.8 pounds and females an average of 3.7 pounds their first semester at college. Seven students (3.3 percent) gained 10 pounds or more, but only one student gained at least 15 pound, a female who gained 16.2 pounds.
"It does happen," says Dr. Gropper, "even if not very often." She and her colleagues are following the 240 students throughout their freshman and beginning of their sophomore years, with questionnaires that examine factors that might contribute to the gain, however small, that the majority of college freshman appear to experience. The researchers also are collecting data on weight changes throughout the year, including five, 10, even 15+ pound losses within the first year of school.
Unique to this study, says Dr. Gropper, is the partnership with colleagues from Auburn University's Department of Consumer Affairs who use a 3-D whole body scanner to collect information on body size and shape. This technology quickly captures exact body measurements, which can be visually displayed in cross sections of body areas like the bust, waist and hips to show where changes occur in measurements over time. Understanding where weight is deposited on the body helps assess the potential risk of diseases such as heart disease and metabolic syndrome.
Sunday, April 6, 2008
Researchers Report Neublastin Virtually Restores Complete Long Term Sensory Motor Function In Preclinical Studies
Biogen Idec (Nasdaq: BIIB), in collaboration with scientists at the University of Arizona and Tufts University reported in the April issue of the journal Nature Neuroscience that in preclinical studies, injections of the protein neublastin promoted the regeneration of damaged sensory nerve cells and produced virtually complete, long-term restoration of sensory and motor function. These studies suggest neublastin has potential for further development as a treatment for traumatic nerve injury.
Neublastin, also known as artemin, belongs to a family of proteins, called glial-derived neurotrophic factors (GDNF), which promote nerve cell survival. The protein is unique because it acts selectively on sensory neurons. In previous preclinical studies, neublastin reversed a number of features of chronic pain associated with peripheral nerve injury.
Specifically in the studies, six neublastin injections were administered over 11 days following injury to the dorsal root, a bundle of peripheral nerve fibers adjacent to the spinal cord that transmit sensory information to the central nervous system. The injections promoted nerve growth into the spinal cord and restored the ability to respond normally to a variety of sensory stimuli and perform complex motor activities such as grasping an object on contact. The functional recovery occurred even after a two-day delay in administering neublastin and lasted for more than six months.
"Sensory nerves entering the spinal cord have minimal capacity to regenerate and severe injury often results in permanent loss of sensory functions," said Frank Porreca, PhD, Professor of Pharmacology at the University of Arizona, the study's senior author. "The results of our preclinical studies, showing dramatic, long-term recovery of pain sensation and complex motor skills after neublastin injections, represent an important and novel advance in research efforts in the area of traumatic nerve injury."
In a series of biochemical, molecular and electrophysiology studies, the researchers also demonstrated that neublastin promoted the regeneration of multiple classes of nerve cells back into the spinal cord and the re-establishment of functional connections with their spinal targets.
"These exciting results support further research, as the data suggest that neublastin may have the potential to promote sensory neuronal regeneration and functional recovery following injury," said Ken Rhodes, PhD, Vice President, Discovery Neurobiology, Biogen Idec. "The neublastin program is part of Biogen Idec's commitment to innovative neurological science and discovery."
Biogen Idec is developing neublastin for use in treating peripheral nervous system diseases under an exclusive license from NsGene. Scientists at NsGene discovered neublastin in 1998.
About Biogen Idec
Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling, press releases and additional information about the company, please visit http://www.biogenidec.com.
Biogen Idec Safe Harbor
This press release contains forward-looking statements regarding the development of neublastin (also known as artemin) and its potential as a treatment for various indications. These statements are based on Biogen Idec's current beliefs and expectation, based on preclinical studies conducted to date. Drug development involves a high degree of risk. Factors which could cause actual results to differ materially from current expectations include: the risk that unexpected concerns may arise from additional data or analysis, that regulatory authorities may require additional information and/or further studies before further development is conducted, or may fail to approve the drug. The company may also encounter other unexpected hurdles. For more detailed information on the risks and uncertainties associated with Biogen Idec's drug development and other activities, see the periodic reports of Biogen Idec filed with the Securities and Exchange Commission. Biogen Idec assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Neublastin, also known as artemin, belongs to a family of proteins, called glial-derived neurotrophic factors (GDNF), which promote nerve cell survival. The protein is unique because it acts selectively on sensory neurons. In previous preclinical studies, neublastin reversed a number of features of chronic pain associated with peripheral nerve injury.
Specifically in the studies, six neublastin injections were administered over 11 days following injury to the dorsal root, a bundle of peripheral nerve fibers adjacent to the spinal cord that transmit sensory information to the central nervous system. The injections promoted nerve growth into the spinal cord and restored the ability to respond normally to a variety of sensory stimuli and perform complex motor activities such as grasping an object on contact. The functional recovery occurred even after a two-day delay in administering neublastin and lasted for more than six months.
"Sensory nerves entering the spinal cord have minimal capacity to regenerate and severe injury often results in permanent loss of sensory functions," said Frank Porreca, PhD, Professor of Pharmacology at the University of Arizona, the study's senior author. "The results of our preclinical studies, showing dramatic, long-term recovery of pain sensation and complex motor skills after neublastin injections, represent an important and novel advance in research efforts in the area of traumatic nerve injury."
In a series of biochemical, molecular and electrophysiology studies, the researchers also demonstrated that neublastin promoted the regeneration of multiple classes of nerve cells back into the spinal cord and the re-establishment of functional connections with their spinal targets.
"These exciting results support further research, as the data suggest that neublastin may have the potential to promote sensory neuronal regeneration and functional recovery following injury," said Ken Rhodes, PhD, Vice President, Discovery Neurobiology, Biogen Idec. "The neublastin program is part of Biogen Idec's commitment to innovative neurological science and discovery."
Biogen Idec is developing neublastin for use in treating peripheral nervous system diseases under an exclusive license from NsGene. Scientists at NsGene discovered neublastin in 1998.
About Biogen Idec
Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling, press releases and additional information about the company, please visit http://www.biogenidec.com.
Biogen Idec Safe Harbor
This press release contains forward-looking statements regarding the development of neublastin (also known as artemin) and its potential as a treatment for various indications. These statements are based on Biogen Idec's current beliefs and expectation, based on preclinical studies conducted to date. Drug development involves a high degree of risk. Factors which could cause actual results to differ materially from current expectations include: the risk that unexpected concerns may arise from additional data or analysis, that regulatory authorities may require additional information and/or further studies before further development is conducted, or may fail to approve the drug. The company may also encounter other unexpected hurdles. For more detailed information on the risks and uncertainties associated with Biogen Idec's drug development and other activities, see the periodic reports of Biogen Idec filed with the Securities and Exchange Commission. Biogen Idec assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Data From Ortho Biotech Sponsored Studies To Be Presented At National Kidney Foundation 2008 Spring Clinical Meetings
Data from five studies sponsored by Ortho Biotech Products, L.P. will be presented at the National Kidney Foundation (NKF) 2008 Spring Clinical Meetings from April 2 - 6, 2008; three utilization studies involve PROCRIT® (Epoetin alfa).
The data include studies that compare drug utilization patterns and costs of PROCRIT® (EPO) and darbepoetin alfa (DARB), evaluate medical costs related to chronic kidney disease (CKD) patients with hypertension or diabetes, and show the impact on hemoglobin (Hb) control using a software-based management tool. These retrospective analyses used data from actual clinical practice.
Data on Drug Utilization Patterns and Costs of Epoetin Alfa and Darbepoetin Alfa
Abstract: Assessment of Drug Utilization Patterns and Costs for Erythropoietic Stimulating Agents in Patients with Chronic Kidney Disease
Patrick Lefebvre, M.A., Groupe d'analyse, Ltée, Montréal, Québec, Canada
A retrospective analysis of medical claims was conducted using the Ingenix Impact National Managed Care Database to examine recent EPO and DARB treatment patterns and corresponding drug costs in newly-initiated CKD patients treated with EPO (n=1,110) or DARB (n=723) not receiving dialysis.bMean cumulative dose was used to calculate drug costs based on October 2007 wholesale acquisition unit prices.
Abstract: Drug Utilization and Cost Considerations of Predialysis Chronic Kidney Disease Patients Receiving Erythropoietic Stimulating Agents Through Pharmacy Benefits
François Laliberté, M.A., Groupe d'analyse, Ltée, Montréal, Québec, Canada
A retrospective analysis of pharmacy claims using the PharMetrics Patient-Centric Database, which represents approximately 85 managed healthcare plans, was conducted to compare drug utilization patterns and costs of a newly-initiated, managed care predialysis chronic kidney disease population receiving EPO (n=1,066) or DARB (n=375) through a pharmacy benefit. Drug cost was based on cumulative dose and October 2007 wholesale acquisition cost.
Data on Medical Costs Related to Chronic Kidney Disease Patients with Hypertension or Diabetes
Abstract: Medical Costs of Chronic Kidney Disease in Patients with Diabetes: A Managed Care Perspective
François Laliberté, M.A., Groupe d'analyse, Ltée, Montréal, Québec, Canada
A retrospective analysis of medical claims and laboratory data from a large managed care database was conducted to quantify the incremental direct healthcare costs of CKD in patients with diabetes. Analyses compared diabetes patients who developed CKD versus those who did not for yearly direct healthcare costs, which consisted of outpatient services, inpatient services and pharmacy dispensing claims. A total of 30,480 patients with diabetes were identified, of whom 859 developed CKD during the study period.
Abstract: The Effect of Anemia in Hypertensive Patients with Chronic Kidney Disease: Hospital Costs and Length of Stay
Sandra Sulsky, M.P.H, Ph.D., ENVIRON International Corporation, Amherst, MA
A retrospective analysis of hospital discharge records from the 2004 Nationwide Inpatient Sample of the Hospital Cost and Utilization Project, which comprises approximately 90 percent of all hospital discharges in the U.S., was conducted to determine the effect of anemia on hospital costs and length of stay in hypertensive patients with CKD. Analyses were adjusted for age, gender, income level, severity of disease, and hospital characteristics to control for the confounding effects of anemia, CKD and a combination of both on study outcomes.
Data on the Impact on Hemoglobin Control Using a Software-Based Management Tool
Abstract: Use of Epoetin Alfa in Maintaining Hemoglobin Control Through a Software-Based Management Tool in a Community Nephrology Setting
Craig Kleinmann, D.O., Nephrology Associates, Mobile, AL
A retrospective, observational chart review from a large U.S. nephrology clinic was conducted in May 2007 to analyze the impact of EPO on mean Hb over time as well as subsequent dose holds in anemic non-dialysis CKD patients in a community practice setting using TrakAnemia, a software-based tool. Eighty-seven patients who had a documented diagnosis of anemia due to non-dialysis CKD, initiated EPO, and had greater than or equal to six months of follow-up data were included in the final analysis.
About PROCRIT® (Epoetin alfa)
PROCRIT® is used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.
Important U.S. Safety Information for PROCRIT®
Boxed WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION
Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
Cancer:
-- ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of > 12 g/dL.
-- The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of < 12 g/dL.
-- To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
-- Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
-- Discontinue following the completion of a chemotherapy course.
Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.
Contraindications
PROCRIT® is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.
Additional Important Safety Information
The dose of PROCRIT should be titrated for each patient to achieve and maintain the following hemoglobin levels:
Chronic renal failure patients hemoglobin levels between 10 to 12 g/dL. If a patient does not attain hemoglobin levels of 10 to 12 g/dL despite 12 weeks of appropriate PROCRIT® therapy, see DOSAGE and ADMINISTRATION in the PROCRIT® Prescribing Information.
Cancer or HIV patients the lowest hemoglobin level sufficient to avoid transfusion and not to exceed 12 g/dL.
Monitor hemoglobin regularly during therapy, more frequently following a dosage adjustment or until hemoglobin becomes stable.
Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients with chronic renal failure receiving PROCRIT® by subcutaneous administration. If any patient develops a sudden loss of response to PROCRIT® , accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT® and other erythropoietic proteins. Contact ORTHO BIOTECH (1-888-2ASKOBI or 1-888-227-5624) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT® should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
-- The safety and efficacy of PROCRIT® therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes or hypercoagulable disorders).
-- In some female patients, menses have resumed following PROCRIT® therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
-- Prior to and regularly during PROCRIT® therapy monitor iron status; transferrin saturation should be ³ 20% and ferritin should be ³ 100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT®.
-- During PROCRIT® therapy, blood pressure should be monitored carefully and aggressively managed, particularly in patients with an underlying history of hypertension or cardiovascular disease.
-- In studies, the most common side effects included fever (pyrexia), diarrhea, nausea, vomiting, swelling of hands or feet (edema), lack or loss of strength or weakness (asthenia, fatigue), shortness of breath, high blood pressure, headache, joint pain (arthralgias), abnormal skin sensations (as tingling or tickling or itching or burning; paresthesia), rash, constipation and upper respiratory infection.
Please visit http://www.procrit.com for the full Prescribing Information, including the Boxed WARNINGS.
About Ortho Biotech Products, L.P.
Ortho Biotech Products, L.P. is a leading biopharmaceutical company devoted to helping improve the lives of patients with cancer and with anemia due to multiple causes, including chronic kidney disease. Since it was founded in 1990, Ortho Biotech and its worldwide affiliates have earned a global reputation for researching, manufacturing and marketing innovative products that enhance patients' health. Located in Bridgewater, N.J., Ortho Biotech is an established market leader in Epoetin alfa therapy for anemia management. The company also markets treatments for recurrent ovarian cancer, rejection of transplanted organs and other serious illnesses. For more information, visit http://www.orthobiotech.com
The data include studies that compare drug utilization patterns and costs of PROCRIT® (EPO) and darbepoetin alfa (DARB), evaluate medical costs related to chronic kidney disease (CKD) patients with hypertension or diabetes, and show the impact on hemoglobin (Hb) control using a software-based management tool. These retrospective analyses used data from actual clinical practice.
Data on Drug Utilization Patterns and Costs of Epoetin Alfa and Darbepoetin Alfa
Abstract: Assessment of Drug Utilization Patterns and Costs for Erythropoietic Stimulating Agents in Patients with Chronic Kidney Disease
Patrick Lefebvre, M.A., Groupe d'analyse, Ltée, Montréal, Québec, Canada
A retrospective analysis of medical claims was conducted using the Ingenix Impact National Managed Care Database to examine recent EPO and DARB treatment patterns and corresponding drug costs in newly-initiated CKD patients treated with EPO (n=1,110) or DARB (n=723) not receiving dialysis.bMean cumulative dose was used to calculate drug costs based on October 2007 wholesale acquisition unit prices.
Abstract: Drug Utilization and Cost Considerations of Predialysis Chronic Kidney Disease Patients Receiving Erythropoietic Stimulating Agents Through Pharmacy Benefits
François Laliberté, M.A., Groupe d'analyse, Ltée, Montréal, Québec, Canada
A retrospective analysis of pharmacy claims using the PharMetrics Patient-Centric Database, which represents approximately 85 managed healthcare plans, was conducted to compare drug utilization patterns and costs of a newly-initiated, managed care predialysis chronic kidney disease population receiving EPO (n=1,066) or DARB (n=375) through a pharmacy benefit. Drug cost was based on cumulative dose and October 2007 wholesale acquisition cost.
Data on Medical Costs Related to Chronic Kidney Disease Patients with Hypertension or Diabetes
Abstract: Medical Costs of Chronic Kidney Disease in Patients with Diabetes: A Managed Care Perspective
François Laliberté, M.A., Groupe d'analyse, Ltée, Montréal, Québec, Canada
A retrospective analysis of medical claims and laboratory data from a large managed care database was conducted to quantify the incremental direct healthcare costs of CKD in patients with diabetes. Analyses compared diabetes patients who developed CKD versus those who did not for yearly direct healthcare costs, which consisted of outpatient services, inpatient services and pharmacy dispensing claims. A total of 30,480 patients with diabetes were identified, of whom 859 developed CKD during the study period.
Abstract: The Effect of Anemia in Hypertensive Patients with Chronic Kidney Disease: Hospital Costs and Length of Stay
Sandra Sulsky, M.P.H, Ph.D., ENVIRON International Corporation, Amherst, MA
A retrospective analysis of hospital discharge records from the 2004 Nationwide Inpatient Sample of the Hospital Cost and Utilization Project, which comprises approximately 90 percent of all hospital discharges in the U.S., was conducted to determine the effect of anemia on hospital costs and length of stay in hypertensive patients with CKD. Analyses were adjusted for age, gender, income level, severity of disease, and hospital characteristics to control for the confounding effects of anemia, CKD and a combination of both on study outcomes.
Data on the Impact on Hemoglobin Control Using a Software-Based Management Tool
Abstract: Use of Epoetin Alfa in Maintaining Hemoglobin Control Through a Software-Based Management Tool in a Community Nephrology Setting
Craig Kleinmann, D.O., Nephrology Associates, Mobile, AL
A retrospective, observational chart review from a large U.S. nephrology clinic was conducted in May 2007 to analyze the impact of EPO on mean Hb over time as well as subsequent dose holds in anemic non-dialysis CKD patients in a community practice setting using TrakAnemia, a software-based tool. Eighty-seven patients who had a documented diagnosis of anemia due to non-dialysis CKD, initiated EPO, and had greater than or equal to six months of follow-up data were included in the final analysis.
About PROCRIT® (Epoetin alfa)
PROCRIT® is used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.
Important U.S. Safety Information for PROCRIT®
Boxed WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION
Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
Cancer:
-- ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of > 12 g/dL.
-- The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of < 12 g/dL.
-- To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
-- Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
-- Discontinue following the completion of a chemotherapy course.
Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.
Contraindications
PROCRIT® is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.
Additional Important Safety Information
The dose of PROCRIT should be titrated for each patient to achieve and maintain the following hemoglobin levels:
Chronic renal failure patients hemoglobin levels between 10 to 12 g/dL. If a patient does not attain hemoglobin levels of 10 to 12 g/dL despite 12 weeks of appropriate PROCRIT® therapy, see DOSAGE and ADMINISTRATION in the PROCRIT® Prescribing Information.
Cancer or HIV patients the lowest hemoglobin level sufficient to avoid transfusion and not to exceed 12 g/dL.
Monitor hemoglobin regularly during therapy, more frequently following a dosage adjustment or until hemoglobin becomes stable.
Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients with chronic renal failure receiving PROCRIT® by subcutaneous administration. If any patient develops a sudden loss of response to PROCRIT® , accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT® and other erythropoietic proteins. Contact ORTHO BIOTECH (1-888-2ASKOBI or 1-888-227-5624) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT® should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
-- The safety and efficacy of PROCRIT® therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes or hypercoagulable disorders).
-- In some female patients, menses have resumed following PROCRIT® therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
-- Prior to and regularly during PROCRIT® therapy monitor iron status; transferrin saturation should be ³ 20% and ferritin should be ³ 100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT®.
-- During PROCRIT® therapy, blood pressure should be monitored carefully and aggressively managed, particularly in patients with an underlying history of hypertension or cardiovascular disease.
-- In studies, the most common side effects included fever (pyrexia), diarrhea, nausea, vomiting, swelling of hands or feet (edema), lack or loss of strength or weakness (asthenia, fatigue), shortness of breath, high blood pressure, headache, joint pain (arthralgias), abnormal skin sensations (as tingling or tickling or itching or burning; paresthesia), rash, constipation and upper respiratory infection.
Please visit http://www.procrit.com for the full Prescribing Information, including the Boxed WARNINGS.
About Ortho Biotech Products, L.P.
Ortho Biotech Products, L.P. is a leading biopharmaceutical company devoted to helping improve the lives of patients with cancer and with anemia due to multiple causes, including chronic kidney disease. Since it was founded in 1990, Ortho Biotech and its worldwide affiliates have earned a global reputation for researching, manufacturing and marketing innovative products that enhance patients' health. Located in Bridgewater, N.J., Ortho Biotech is an established market leader in Epoetin alfa therapy for anemia management. The company also markets treatments for recurrent ovarian cancer, rejection of transplanted organs and other serious illnesses. For more information, visit http://www.orthobiotech.com
Cancer Research Taking The Main Stage At Baylor University
Two Baylor University faculty members are working to create and test dozens of new cancer fighting compounds that disrupt solid cancer tumors and target any remaining tumor cells that may grow after the tumor is treated. In another project, two Baylor adjunct faculty members and a Baylor graduate student are developing vaccines against melanoma. These are just two examples of some of the latest cancer research projects faculty and students are involved with at Baylor and at Baylor's Institute of Biomedical Studies.
With more than 30 students and more than 40 faculty and adjunct faculty members, Baylor's Institute of Biomedical Studies is an interdisciplinary program in biomedical-related areas of science leading to the doctoral degree. The program combines graduate students with an extremely diverse faculty who are actively involved in basic and translational research, both at Baylor University in Waco and at the Baylor University Medical Center (BUMC) in Dallas.
Cancer research funding comes from numerous public and private outlets, including one project that is looking into two main kinds of tumor-starving compounds, which has resulted in several patents for several Baylor professors like Dr. Kevin Pinney, professor of chemistry at Baylor. In Pinney's research, he and his team are creating new bioreductive compounds that take advantage of the lack of oxygen in the tumor. These compounds damage the tumor's DNA, so the tumor can not divide effectively. In another project, Baylor researchers are working to create a new type of Vascular Disrupting Agent. VDAs target the flow of blood to solid cancer tumors and other abnormal blood vessels while leaving healthy cells intact.
Baylor University
One Bear Pl. #97024
Waco, TX 76798-7024
United States
http://www.baylor.edu
With more than 30 students and more than 40 faculty and adjunct faculty members, Baylor's Institute of Biomedical Studies is an interdisciplinary program in biomedical-related areas of science leading to the doctoral degree. The program combines graduate students with an extremely diverse faculty who are actively involved in basic and translational research, both at Baylor University in Waco and at the Baylor University Medical Center (BUMC) in Dallas.
Cancer research funding comes from numerous public and private outlets, including one project that is looking into two main kinds of tumor-starving compounds, which has resulted in several patents for several Baylor professors like Dr. Kevin Pinney, professor of chemistry at Baylor. In Pinney's research, he and his team are creating new bioreductive compounds that take advantage of the lack of oxygen in the tumor. These compounds damage the tumor's DNA, so the tumor can not divide effectively. In another project, Baylor researchers are working to create a new type of Vascular Disrupting Agent. VDAs target the flow of blood to solid cancer tumors and other abnormal blood vessels while leaving healthy cells intact.
Baylor University
One Bear Pl. #97024
Waco, TX 76798-7024
United States
http://www.baylor.edu
Scarless Nephrectomy By Transgastric And Transvesical Combined Approach
UroToday.com - Dr. Lima from Porto, Portugal presented the novel concept of "natural orifices translumenal endoscopic surgery" (NOTES) as applied to nephrectomy in an experimental model. Their team assessed the feasibility of a combined transgastric and transvesical approach for performing nephrectomy in a porcine model.
In a non-survival study, a transgastric and transvesical combined approach was applied in 6 female pigs. Under ureteroscopic control, they placed a transvesical 5-mm over tube into the peritoneal cavity, and a flexible gastroscope was passed orally into the peritoneal cavity by a gastrotomy. Four right and two left nephrectomies were performed using instruments introduced by both devices. The pigs suffered no complications during creation of transvesical and transgastric access. In all animals, they visualized both kidneys, and the renal vessels and ureter were identified and ligated separately with ultrasonic scissors, which were introduced through the transvesical port. In two early cases, mild bleeding occurred after ultrasonic ligation. Complete renal release and mobilization to the stomach was achieved in all animals. During the discussion, it became apparent that none of the "resected" kidneys were removed from the porcine bodies, and this would require some sort of incision.
Presented by: E. Lima, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy
Reported by UroToday.com Contributing Editor, Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
In a non-survival study, a transgastric and transvesical combined approach was applied in 6 female pigs. Under ureteroscopic control, they placed a transvesical 5-mm over tube into the peritoneal cavity, and a flexible gastroscope was passed orally into the peritoneal cavity by a gastrotomy. Four right and two left nephrectomies were performed using instruments introduced by both devices. The pigs suffered no complications during creation of transvesical and transgastric access. In all animals, they visualized both kidneys, and the renal vessels and ureter were identified and ligated separately with ultrasonic scissors, which were introduced through the transvesical port. In two early cases, mild bleeding occurred after ultrasonic ligation. Complete renal release and mobilization to the stomach was achieved in all animals. During the discussion, it became apparent that none of the "resected" kidneys were removed from the porcine bodies, and this would require some sort of incision.
Presented by: E. Lima, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy
Reported by UroToday.com Contributing Editor, Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
Management Of Superficial Bladder Tumors
UroToday.com - An Italian study group presented data on the optimal schedule regimen and the role of maintenance intravesical chemotherapy or BCG immunotherapy after transurethral resection (TUR for non muscle-invasive transitional cell cancer of the bladder (NMI TCCB) for patients at intermediate risk.
Between 2002 and 2003, 577 patients, undergoing TUR for NMI TCCB, were recruited. All patients underwent TUR and early (within 6 hours) intravesical chemotherapy with epirubicin at the dose of 80 mg diluted in 60 ml of saline solution. When histology was available, 95 patients were excluded from the study since they were harboring T1G3, TIS and single and primary Ta G1-G2 tumors. 482 patients with intermediate risk tumors were randomized according 2 different regimens: arm A: 5 more weekly instillations; arm B: 5 more weekly instillations plus monthly instillations for a total of 16 instillations. All patients were submitted every 3 months for the first 2 years and then 6-monthly to cytology, cystoscopy and biopsy of every suspicious bladder lesion.
From 482 randomized patients, 396 are evaluable for toxicity and 392 for efficacy. The tumors were multiple in 318 patients (66.2%) and recurrent in 192 (39.8%). No difference emerged between the 2 arms in relation to tumors' characteristics. The median follow-up time was 22 months. Eighty-two (20.9%) patients recurred at a median time of 9 months from TUR and 4 patients (1%) progressed. The incidence of recurrences was 24.4% in arm A and 18.5% in arm B. No difference emerged between the two arms for recurrence rate at 3 months. Statistical analysis demonstrated an advantage in favor of maintenance in terms of recurrence rate at 6 (p=0.01), 9 (p=0.04) and 12 months (p=0.03) and in terms of recurrence-free interval (p=0.03). No difference for toxicity emerged according to treatment schedule. The conclusion is that 0ne-year maintenance significantly reduces the risk of tumor recurrence, without enhanced toxicity, in patients with intermediate risk NMI TCCB treated with early epirubicin intravesical chemotherapy followed by 5 weekly instillations.
Presented by: V. Serretta, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy
Reported by UroToday.com Contributing Editor, Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
Between 2002 and 2003, 577 patients, undergoing TUR for NMI TCCB, were recruited. All patients underwent TUR and early (within 6 hours) intravesical chemotherapy with epirubicin at the dose of 80 mg diluted in 60 ml of saline solution. When histology was available, 95 patients were excluded from the study since they were harboring T1G3, TIS and single and primary Ta G1-G2 tumors. 482 patients with intermediate risk tumors were randomized according 2 different regimens: arm A: 5 more weekly instillations; arm B: 5 more weekly instillations plus monthly instillations for a total of 16 instillations. All patients were submitted every 3 months for the first 2 years and then 6-monthly to cytology, cystoscopy and biopsy of every suspicious bladder lesion.
From 482 randomized patients, 396 are evaluable for toxicity and 392 for efficacy. The tumors were multiple in 318 patients (66.2%) and recurrent in 192 (39.8%). No difference emerged between the 2 arms in relation to tumors' characteristics. The median follow-up time was 22 months. Eighty-two (20.9%) patients recurred at a median time of 9 months from TUR and 4 patients (1%) progressed. The incidence of recurrences was 24.4% in arm A and 18.5% in arm B. No difference emerged between the two arms for recurrence rate at 3 months. Statistical analysis demonstrated an advantage in favor of maintenance in terms of recurrence rate at 6 (p=0.01), 9 (p=0.04) and 12 months (p=0.03) and in terms of recurrence-free interval (p=0.03). No difference for toxicity emerged according to treatment schedule. The conclusion is that 0ne-year maintenance significantly reduces the risk of tumor recurrence, without enhanced toxicity, in patients with intermediate risk NMI TCCB treated with early epirubicin intravesical chemotherapy followed by 5 weekly instillations.
Presented by: V. Serretta, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy
Reported by UroToday.com Contributing Editor, Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
Management Of Superficial Bladder Tumors
UroToday.com - This presentation addressed the issue that recurrence at first follow-up cystoscopy (RR-FFC) after TURBT has been attributed to incomplete resection of the tumor. Furthermore, an EORTC analysis of multicenter trials suggested the inter-institutional variability of RR-FFC was a result of variable TURBT 'quality'. Dr. Mariappan and members of the Edinburgh Uro-Oncology Group aimed to determine if (a) detrusor muscle can be a surrogate marker of this 'quality' and (b) the presence of detrusor is dependant on surgeon's experience.
The researchers reviewed their prospectively maintained database of patients with newly diagnosed bladder tumors in 2005-2006, to determine surgeon status, tumor characteristics and RR-FFC. Only patients with complete resections as determined by the surgeon were included. For analysis, surgeons were stratified into (a) seniors (consultant and Year 5 or 6 trainees) and (b) juniors (trainees < year 5). One investigator, blinded to the above characteristics, interrogated our pathology database to confirm histological tumor grade, stage and detrusor muscle status. Logistic regression analysis was carried out.
A total of 356 patients were suitable for analysis. The majority of tumors in this cohort were small (73.3%), single (84.6%) and high grade (48.3%). Seniors performed 66.1% of the resections. Overall, detrusor muscle was present in 241 (67.7%) of resections. Logistic regression multivariate analysis revealed large tumors, high grade tumors and surgery carried out by senior surgeons were associated with presence of detrusor (Table 1). The overall RR-FFC was 26.8%. The risk of early recurrence following TURBT was 35.9% and 21.5% when detrusor muscle was absent and present, respectively (OR=2.1, 95%CI=1.1-4, p=0.02). Dr. Mariappan concluded that the presence of detrusor muscle in the TURBT specimen was more likely when surgery was performed by senior surgeons and this predicted a lower RR-FFC. This parameter appears to be a surrogate marker of the quality of TURBT.
Presented by: P. Mariappan, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy
Reported by UroToday.com Contributing Editor, Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
The researchers reviewed their prospectively maintained database of patients with newly diagnosed bladder tumors in 2005-2006, to determine surgeon status, tumor characteristics and RR-FFC. Only patients with complete resections as determined by the surgeon were included. For analysis, surgeons were stratified into (a) seniors (consultant and Year 5 or 6 trainees) and (b) juniors (trainees < year 5). One investigator, blinded to the above characteristics, interrogated our pathology database to confirm histological tumor grade, stage and detrusor muscle status. Logistic regression analysis was carried out.
A total of 356 patients were suitable for analysis. The majority of tumors in this cohort were small (73.3%), single (84.6%) and high grade (48.3%). Seniors performed 66.1% of the resections. Overall, detrusor muscle was present in 241 (67.7%) of resections. Logistic regression multivariate analysis revealed large tumors, high grade tumors and surgery carried out by senior surgeons were associated with presence of detrusor (Table 1). The overall RR-FFC was 26.8%. The risk of early recurrence following TURBT was 35.9% and 21.5% when detrusor muscle was absent and present, respectively (OR=2.1, 95%CI=1.1-4, p=0.02). Dr. Mariappan concluded that the presence of detrusor muscle in the TURBT specimen was more likely when surgery was performed by senior surgeons and this predicted a lower RR-FFC. This parameter appears to be a surrogate marker of the quality of TURBT.
Presented by: P. Mariappan, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy
Reported by UroToday.com Contributing Editor, Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
Laparoscopic Renal Cryoablation (LRC) Of Small Renal Masses
UroToday.com - A group from Milan, Italy prospectively analyzed the outcome of patients with kidney masses treated with laparoscopic cryoablation over a 7-year period. Beginning in September 2000, 104 patients (mean age 61.6 years; 78 male and 26 female) underwent LRC for renal masses. The mean lesion diameter was 2.2cm. The procedure was performed transperitoneally in 60 cases and in 44 patients it was done retroperitoneoscopically, based upon the tumor position or potential difficulties due to previous abdominal surgery. Fifty-six patients (54%) had concomitant comorbidities.
The intra-operative mean diameter of the ice ball was 4.93cm. All the procedures were successfully completed laparoscopically, except 3 cases that were converted to open surgery, two of them due to bleeding from the site of the cryoprobe insertion (one of them requiring radical nephrectomy). Mean surgical time was 202.6min (range 90-320 min) and mean intra-operative blood loss was 211.6 cc (range 10-3.200 cc). Pathological evaluation of the intra-operative needle biopsies documented renal cell carcinoma in 64 cases, 23 oncocytomas, 6 angiomyolipomas, 1 case of Xantogranulomatous pyelonephritis and 10 cases "undefined" disease. Post-operative stay was 4.7 days (range 2-13). Postoperative complications were always treated conservatively and included 7 cases of transient fever, 2 cases of small peri-renal hematomas, 1 case of pulmonary edema, 9 patients with significant blood loss and 1 case of gross hematuria. Delayed complication included 1 case of UPJ obstruction requiring open pyeloplasty 8 months after surgery and open nephrectomy one year after surgery due to suspected recurrence of the disease. Six patients died during the follow-up, 5 due to previous illness and 1 patient due to worsening cirrhosis one month after surgery. No patients died secondary to renal cancer.
MRI scans on postoperative day one revealed a mean lesion of 4.91cm. Progressive reduction in size of the ablated lesion was visible in all patients with only a renal scar visible after 24 months of follow-up. This remained constant over time with 36 patients being followed up for 5 years and 11 patients for 7. In the question period, Dr. Jewett (Toronto) pointed out that 40% of the patients with benign lesions had unnecessary treatment and perhaps the biopsies should be performed a few weeks prior to the intended procedure.
Presented by: A. Cestari, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy
Reported by UroToday.com Contributing Editor, Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
The intra-operative mean diameter of the ice ball was 4.93cm. All the procedures were successfully completed laparoscopically, except 3 cases that were converted to open surgery, two of them due to bleeding from the site of the cryoprobe insertion (one of them requiring radical nephrectomy). Mean surgical time was 202.6min (range 90-320 min) and mean intra-operative blood loss was 211.6 cc (range 10-3.200 cc). Pathological evaluation of the intra-operative needle biopsies documented renal cell carcinoma in 64 cases, 23 oncocytomas, 6 angiomyolipomas, 1 case of Xantogranulomatous pyelonephritis and 10 cases "undefined" disease. Post-operative stay was 4.7 days (range 2-13). Postoperative complications were always treated conservatively and included 7 cases of transient fever, 2 cases of small peri-renal hematomas, 1 case of pulmonary edema, 9 patients with significant blood loss and 1 case of gross hematuria. Delayed complication included 1 case of UPJ obstruction requiring open pyeloplasty 8 months after surgery and open nephrectomy one year after surgery due to suspected recurrence of the disease. Six patients died during the follow-up, 5 due to previous illness and 1 patient due to worsening cirrhosis one month after surgery. No patients died secondary to renal cancer.
MRI scans on postoperative day one revealed a mean lesion of 4.91cm. Progressive reduction in size of the ablated lesion was visible in all patients with only a renal scar visible after 24 months of follow-up. This remained constant over time with 36 patients being followed up for 5 years and 11 patients for 7. In the question period, Dr. Jewett (Toronto) pointed out that 40% of the patients with benign lesions had unnecessary treatment and perhaps the biopsies should be performed a few weeks prior to the intended procedure.
Presented by: A. Cestari, MD, et al, at the European Association of Urology - 23rd Annual EAU Congress - March 26 - 29, 2008 - Milan, Italy
Reported by UroToday.com Contributing Editor, Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
Non Hodgkin Lymphoma Is Focus Of Cancer In Iowa Report
Non-Hodgkin lymphoma is one of the most rapidly increasing types of cancer diagnosed in the United States with new diagnoses having more than doubled since the 1970s. However, over the past 10 years, mortality rates have begun to decline, indicating that progress is being made in its treatment.
According to the newly issued State Health Registry of Iowa "Cancer in Iowa: 2008" report, non-Hodgkin lymphoma will cause an estimated 270 cancer deaths in Iowa in 2008, accounting for 4.3 percent of cancer deaths in both men and women. This year in Iowa, there will be an estimated 740 new cases (340 women and 400 men), making non-Hodgkin lymphoma the sixth most common cancer in Iowa.
"The exact causes of non-Hodgkin lymphoma are not known, and there are no routine or simple screening methods," said Charles Lynch, M.D., Ph.D., medical director of the registry, which is based in the Department of Epidemiology at the University of Iowa College of Public Health. "Certain risk factors have been shown to be associated with the disease, including a weak immune system, some types of viruses and bacteria, environmental risk factors like pesticides, and occupations such as farming."
"Although Iowa is a farming state, its rates of non-Hodgkin lymphoma are close to the national average," added Lynch, who also is a University of Iowa professor of epidemiology. "This indicates that farming is not a major risk factor for this disease."
Non-Hodgkin lymphoma originates in a subset of white blood cells called lymphocytes, which are part of the body's immune system. The disease can occur in people of all ages and swell lymph nodes, create masses and cause weight loss and fatigue.
"Non-Hodgkin lymphoma is a spectrum of diseases that share similarities but also can be separated into subtypes that are increasingly being found to have unique risk factors and to respond to different therapies," Lynch said.
Some subtypes of non-Hodgkin lymphoma are among the most aggressive of all cancers, while other subtypes are so slow growing, they do not even need immediate treatment, noted George Weiner, M.D., director of the Specialized Program for Research Excellence (SPORE) in lymphoma research at the University of Iowa and head of Holden Comprehensive Cancer Center at the UI.
The University of Iowa's lymphoma SPORE, funded by the National Cancer Institute, is one of only three lymphoma SPORE grant programs in the country. Experts at Mayo Clinic work with the UI as part of the UI SPORE grant. More than 2,000 patients participate in the SPORE.
"A primary goal of the SPORE is to understand how lymphoma treatments work and how to improve them," Weiner said "We are making significant progress in the treatment of non-Hodgkin lymphoma due partly to figuring out how to use the immune system to fight this cancer.
Anti-lymphoma monoclonal antibodies are extremely helpful in treating many lymphoma patients, but not in others, Weiner said. One project supported by the SPORE focuses on understanding these differences by exploring in detail how antibodies direct the patient's own immune system to attack the lymphoma. Another is evaluating how inborn differences in the immune system impact on how well the antibodies work.
"This SPORE research is leading to new approaches to using current antibodies and to the design of stronger antibodies that we hope will be better than those currently available. This research could have an impact on other cancers, as well," Weiner said.
More than 150 hospitals, clinics and medical laboratories across Iowa, as well as referral facilities in neighboring states, contribute data to the State Health Registry of Iowa. The registry is one of 17 registries nationwide that currently are funded to provide data to the National Cancer Institute. Iowa's registry staff includes 50 members, half of whom are located throughout the state and help collect data from many facilities. The registry has been gathering cancer incidence and follow-up data for the state since 1973.
To learn more about non-Hodgkin lymphoma, visit the National Cancer Institute at http://www.cancer.gov/cancertopics/types/non-hodgkin.
To learn more about the University of Iowa and Mayo Clinic Specialized Program of Research Excellence in lymphoma based at the University of Iowa, visit http://www.uihealthcare.com/depts/cancercenter/research/ncispore.html.
University of Iowa Health Sciences
5141 Westlawn
Iowa City, IA 52242
United States
http://www.uiowa.edu
According to the newly issued State Health Registry of Iowa "Cancer in Iowa: 2008" report, non-Hodgkin lymphoma will cause an estimated 270 cancer deaths in Iowa in 2008, accounting for 4.3 percent of cancer deaths in both men and women. This year in Iowa, there will be an estimated 740 new cases (340 women and 400 men), making non-Hodgkin lymphoma the sixth most common cancer in Iowa.
"The exact causes of non-Hodgkin lymphoma are not known, and there are no routine or simple screening methods," said Charles Lynch, M.D., Ph.D., medical director of the registry, which is based in the Department of Epidemiology at the University of Iowa College of Public Health. "Certain risk factors have been shown to be associated with the disease, including a weak immune system, some types of viruses and bacteria, environmental risk factors like pesticides, and occupations such as farming."
"Although Iowa is a farming state, its rates of non-Hodgkin lymphoma are close to the national average," added Lynch, who also is a University of Iowa professor of epidemiology. "This indicates that farming is not a major risk factor for this disease."
Non-Hodgkin lymphoma originates in a subset of white blood cells called lymphocytes, which are part of the body's immune system. The disease can occur in people of all ages and swell lymph nodes, create masses and cause weight loss and fatigue.
"Non-Hodgkin lymphoma is a spectrum of diseases that share similarities but also can be separated into subtypes that are increasingly being found to have unique risk factors and to respond to different therapies," Lynch said.
Some subtypes of non-Hodgkin lymphoma are among the most aggressive of all cancers, while other subtypes are so slow growing, they do not even need immediate treatment, noted George Weiner, M.D., director of the Specialized Program for Research Excellence (SPORE) in lymphoma research at the University of Iowa and head of Holden Comprehensive Cancer Center at the UI.
The University of Iowa's lymphoma SPORE, funded by the National Cancer Institute, is one of only three lymphoma SPORE grant programs in the country. Experts at Mayo Clinic work with the UI as part of the UI SPORE grant. More than 2,000 patients participate in the SPORE.
"A primary goal of the SPORE is to understand how lymphoma treatments work and how to improve them," Weiner said "We are making significant progress in the treatment of non-Hodgkin lymphoma due partly to figuring out how to use the immune system to fight this cancer.
Anti-lymphoma monoclonal antibodies are extremely helpful in treating many lymphoma patients, but not in others, Weiner said. One project supported by the SPORE focuses on understanding these differences by exploring in detail how antibodies direct the patient's own immune system to attack the lymphoma. Another is evaluating how inborn differences in the immune system impact on how well the antibodies work.
"This SPORE research is leading to new approaches to using current antibodies and to the design of stronger antibodies that we hope will be better than those currently available. This research could have an impact on other cancers, as well," Weiner said.
More than 150 hospitals, clinics and medical laboratories across Iowa, as well as referral facilities in neighboring states, contribute data to the State Health Registry of Iowa. The registry is one of 17 registries nationwide that currently are funded to provide data to the National Cancer Institute. Iowa's registry staff includes 50 members, half of whom are located throughout the state and help collect data from many facilities. The registry has been gathering cancer incidence and follow-up data for the state since 1973.
To learn more about non-Hodgkin lymphoma, visit the National Cancer Institute at http://www.cancer.gov/cancertopics/types/non-hodgkin.
To learn more about the University of Iowa and Mayo Clinic Specialized Program of Research Excellence in lymphoma based at the University of Iowa, visit http://www.uihealthcare.com/depts/cancercenter/research/ncispore.html.
University of Iowa Health Sciences
5141 Westlawn
Iowa City, IA 52242
United States
http://www.uiowa.edu
Computational Quantum Chemical Methods Promising For Drug Development
Research, led by a Virginia Tech chemist, may someday help natural-products chemists decrease by years the time it takes to develop certain types of medicinal drugs. The research by T. Daniel Crawford, associate professor of chemistry, involves computations of optical rotation angles on chiral non-superimposable molecules
Many chiral molecules are important for medical treatment for illnesses ranging from acid-reflux to cancer. The term "chiral" means that two mirror images of a molecule cannot be superimposed onto each other. In other words, some are "left-handed" and some are "right-handed."
"Most drugs have this handedness property," Crawford said, "and for many of these drugs, even though both hands can cause a reaction, it is a situation where one hand does a good thing and one does a bad thing." He used thalidomide as an example. A mixture of both hands of the drug was used in the late 1950s and early 1960s to treat morning sickness in pregnant women. Later studies revealed that, while one of the two hands acted as the desired sedative, the other hand was found to cause significant birth defects. Thalidomide was never approved by the FDA in the United States and was eventually taken off the market in Europe.
For chemists, therefore, it is often vital to determine which hand of a molecule they are using. In other words, when you have a sample of a chiral molecule, how do you distinguish between the left and right hand?
This is where a technique called polarimetry comes in to play. By shooting plane-polarized light through a sample of one hand, the chiral molecule in question will rotate to a characteristic angle either clockwise or counterclockwise, and the two hands of a chiral molecule produce opposite rotations.
"So if we figure out the direction and rotation of the light or each hand, we have a frame of reference for determining whether we have the left or right hand of a molecule," Crawford said.
The problem with this method is that synthesizing the two hands of chiral molecules is often extremely time consuming. "It can take anywhere from weeks to years," Crawford said.
Crawford's research applies the theory of quantum mechanics to devise computational methods in order to eliminate having to create a synthetic molecule. "The hope is that this will allow us to calculate things like optical rotation very accurately," he said. "So when an organic chemist has a molecule and doesn't know if it is left- or right-handed, we can calculate that directly on the computer."
Crawford said the ultimate goal in his research is to be able to provide organic chemists with computational tools to determine the handedness of a particular molecule they are working with. He said that such tools could speed up the drug development process by years.
The research titled, The Current State of 'Ab Initio' Calculations of Optical Rotation and Electronic Circular Dichcoism Spectra, by Crawford and Mary C. Tam of Virginia Tech and Mica Abrams of the University of Central Arkansas, appeared as the cover article in the November 2007 Journal of Physical Chemistry A. Get the complete article at: http://pubs.acs.org/cgi-bin/article.cgi/jpcafh/2007/111/i48/html/jp075046u.html
About the College of Science
The College of Science at Virginia Tech gives students a comprehensive foundation in the scientific method. Outstanding faculty members teach courses and conduct research in biology, chemistry, economics, geosciences, mathematics, physics, psychology, and statistics. The college is dedicated to fostering a research intensive environment and offers programs in many cutting edge areas, including those in nanotechnology, biological sciences, information theory and science, and supports the university's research initiatives through the Institute for Critical Technologies and Applied Sciences, and the Institute for Biomedical and Public Health Sciences. The College of Science also houses programs in intellectual property law and pre-medicine.
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Many chiral molecules are important for medical treatment for illnesses ranging from acid-reflux to cancer. The term "chiral" means that two mirror images of a molecule cannot be superimposed onto each other. In other words, some are "left-handed" and some are "right-handed."
"Most drugs have this handedness property," Crawford said, "and for many of these drugs, even though both hands can cause a reaction, it is a situation where one hand does a good thing and one does a bad thing." He used thalidomide as an example. A mixture of both hands of the drug was used in the late 1950s and early 1960s to treat morning sickness in pregnant women. Later studies revealed that, while one of the two hands acted as the desired sedative, the other hand was found to cause significant birth defects. Thalidomide was never approved by the FDA in the United States and was eventually taken off the market in Europe.
For chemists, therefore, it is often vital to determine which hand of a molecule they are using. In other words, when you have a sample of a chiral molecule, how do you distinguish between the left and right hand?
This is where a technique called polarimetry comes in to play. By shooting plane-polarized light through a sample of one hand, the chiral molecule in question will rotate to a characteristic angle either clockwise or counterclockwise, and the two hands of a chiral molecule produce opposite rotations.
"So if we figure out the direction and rotation of the light or each hand, we have a frame of reference for determining whether we have the left or right hand of a molecule," Crawford said.
The problem with this method is that synthesizing the two hands of chiral molecules is often extremely time consuming. "It can take anywhere from weeks to years," Crawford said.
Crawford's research applies the theory of quantum mechanics to devise computational methods in order to eliminate having to create a synthetic molecule. "The hope is that this will allow us to calculate things like optical rotation very accurately," he said. "So when an organic chemist has a molecule and doesn't know if it is left- or right-handed, we can calculate that directly on the computer."
Crawford said the ultimate goal in his research is to be able to provide organic chemists with computational tools to determine the handedness of a particular molecule they are working with. He said that such tools could speed up the drug development process by years.
The research titled, The Current State of 'Ab Initio' Calculations of Optical Rotation and Electronic Circular Dichcoism Spectra, by Crawford and Mary C. Tam of Virginia Tech and Mica Abrams of the University of Central Arkansas, appeared as the cover article in the November 2007 Journal of Physical Chemistry A. Get the complete article at: http://pubs.acs.org/cgi-bin/article.cgi/jpcafh/2007/111/i48/html/jp075046u.html
About the College of Science
The College of Science at Virginia Tech gives students a comprehensive foundation in the scientific method. Outstanding faculty members teach courses and conduct research in biology, chemistry, economics, geosciences, mathematics, physics, psychology, and statistics. The college is dedicated to fostering a research intensive environment and offers programs in many cutting edge areas, including those in nanotechnology, biological sciences, information theory and science, and supports the university's research initiatives through the Institute for Critical Technologies and Applied Sciences, and the Institute for Biomedical and Public Health Sciences. The College of Science also houses programs in intellectual property law and pre-medicine.
Virginia Tech (Virginia Polytechnic Institute and State University)
Room 1, Media Bldg. (0109)
Blacksburg, VA 24061
United States
http://www.vt.edu
Caution Advised When Using Hormone Therapy For Prostate Cancer
In men with localized but aggressive prostate cancer, the combination of testosterone-lowering therapy and radiation improves survival substantially more than radiation therapy alone. But testosterone-lowering therapy isn't so hot for the heart, reports the April issue of the Harvard Heart Letter. Low testosterone can increase harmful LDL cholesterol, blood sugar, blood pressure, and weight. It can also make arteries stiffer, promote formation of artery-clogging plaque, and allow blood clots to form more readily.
Preliminary results show that testosterone-lowering therapy is associated with more diabetes, more heart disease, and earlier heart attacks. However, this hormone therapy does have a significant benefit in curing prostate cancer. For instance, one study of patients with localized but unfavorable prostate cancer found that about 90% of otherwise healthy men who underwent radiation and hormone therapy were still alive after eight years, compared with about 65% of those who had only radiation therapy. The reverse was true among those with moderate or severe health problems in addition to their prostate cancer: only about 25% of those who underwent the combination were still alive, compared with 55% of those who had radiation alone.
These findings don't mean hormone therapy should be off limits. Quite the contrary suppressing testosterone is a life-prolonging addition to radiation therapy for men with locally advanced prostate cancer or cancer that has spread. The Harvard Heart Letter suggests that hormone therapy be used with caution in men who have had a heart attack or who are at high risk for cardiovascular disease.
Harvard Heart Letter
Harvard Health Publications Harvard Medical School 10 Shattuck St., Ste. 612
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http://www.health.harvard.edu
Preliminary results show that testosterone-lowering therapy is associated with more diabetes, more heart disease, and earlier heart attacks. However, this hormone therapy does have a significant benefit in curing prostate cancer. For instance, one study of patients with localized but unfavorable prostate cancer found that about 90% of otherwise healthy men who underwent radiation and hormone therapy were still alive after eight years, compared with about 65% of those who had only radiation therapy. The reverse was true among those with moderate or severe health problems in addition to their prostate cancer: only about 25% of those who underwent the combination were still alive, compared with 55% of those who had radiation alone.
These findings don't mean hormone therapy should be off limits. Quite the contrary suppressing testosterone is a life-prolonging addition to radiation therapy for men with locally advanced prostate cancer or cancer that has spread. The Harvard Heart Letter suggests that hormone therapy be used with caution in men who have had a heart attack or who are at high risk for cardiovascular disease.
Harvard Heart Letter
Harvard Health Publications Harvard Medical School 10 Shattuck St., Ste. 612
Cambridge, MA 02115
United States
http://www.health.harvard.edu
Improved Quality Of Life For Women On Continuous Oral Contraceptives
Continuous oral contraceptives may be more effective than the standard 28-day birth control pills in suppressing the ovary, according to researchers. They say that the continuous pill also causes a significant improvement in pain and behavioral changes.
"We have provided a biological proof of concept that both the ovary and the lining of the uterus are suppressed better and quicker with the continuous pill than with the cyclic pill. And there is no harmful effect on the lining of the uterus either," said Richard Legro, M.D., professor of obstetrics and gynecology, Penn State College of Medicine and lead author of the study.
Standard 28-day birth control pills mimic a woman's natural menstrual cycle, while preventing pregnancy. A standard dose includes 21 hormone pills to suppress growth in the endometrium, the lining of the uterus, and seven placeholder placebo pills.
Continuous oral contraceptives may be more effective in treating several medical conditions, where continuous ovarian suppression is desired, such as acne, hirsutism, premenstrual syndrome, endometriosis and polycystic ovary syndrome. But there have been few detailed studies of ovarian function on the pill to demonstrate this effect.
Legro and his colleagues compared the effectiveness of continuous oral contraceptives with that of the cyclical pills. The researchers monitored 62 healthy women, randomly assigned to receive either cyclical or continuous birth control pills, for six months with both researchers and participants blinded to the study group.
"We monitored vaginal bleeding, quality of life, and ovarian and endometrial suppression," said Legro, whose team's findings appeared in a recent issue of the Journal of Clinical Endocrinology and Metabolism.
The researchers found a significant decrease in moderate to heavy bleeding days among women who received the continuous birth control regimen. Women in the continuous group also had a significant decline in circulating and urinary estrogen levels, total ovarian volume and lead follicle size - all biomarkers that indicate the ovary is less active - and reported less pain and behavioral changes compared to women in the cyclic group.
However, results from the study also indicate greater breakthrough bleeding, or spotting, among women in the continuous group. Legro says that while greater breakthrough bleeding may be a truly objectionable side effect for many women, it does not seem to affect their quality of life.
"That is one of the unique things of this study. The quality of life did not necessarily decrease as it was counterbalanced by improvements in other areas such as pain and mood swings," the Penn State researcher added.
According to Legro, the study suggests that there may be diverse mechanisms of breakthrough bleeding depending on whether a woman is using either a cyclical or continuous regimen of birth control pills.
In the case of cyclic pills, the ovary comes back into the equation during the pill free interval leading to a rebound increased secretion of ovarian hormones, which in turn contributes to some breakthrough bleeding, he explained.
"Breakthrough bleeding in the continuous group, in our opinion, is most likely due to the fact that the pill does too good of a job in suppressing the ovary and the lining of the uterus gets a little bit thin and fragile so that from time to time there is a little bit of bleeding," added Legro, whose work is funded by the National Institutes of Health.
The study provides a physical reason for continuous oral contraceptive pills to treat such chronic medical conditions such as polycystic ovary syndrome, endometriosis and premenstrual syndrome, where additional suppression of the ovary or the endometrium is desired, and Legro noted that other chronic conditions such as hypertension or diabetes are treated continuously, not three weeks out of four. Further studies showing a favorable risk benefit ratio of continuous oral contraceptives on these disorders are the next step.
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
Other researchers on the paper are Jaimey G. Pauli, M.D.; Allen R. Kunselman, senior research assistant; Richard J. Zaino, M.D., professor of anatomic pathology; Laurence M. Demers, M.D., distinguished professor emeritus; Carol L. Gnatuk, M.D.; and William C. Dodson, M.D., all at Penn State College of Medicine; and Juliana W. Meadows, Ph.D., and James Kesner, Ph.D., both at the National Institute for Occupational Safety and Health, Cincinnati, Ohio.
Source: Amitabh Avasthi
Penn State
"We have provided a biological proof of concept that both the ovary and the lining of the uterus are suppressed better and quicker with the continuous pill than with the cyclic pill. And there is no harmful effect on the lining of the uterus either," said Richard Legro, M.D., professor of obstetrics and gynecology, Penn State College of Medicine and lead author of the study.
Standard 28-day birth control pills mimic a woman's natural menstrual cycle, while preventing pregnancy. A standard dose includes 21 hormone pills to suppress growth in the endometrium, the lining of the uterus, and seven placeholder placebo pills.
Continuous oral contraceptives may be more effective in treating several medical conditions, where continuous ovarian suppression is desired, such as acne, hirsutism, premenstrual syndrome, endometriosis and polycystic ovary syndrome. But there have been few detailed studies of ovarian function on the pill to demonstrate this effect.
Legro and his colleagues compared the effectiveness of continuous oral contraceptives with that of the cyclical pills. The researchers monitored 62 healthy women, randomly assigned to receive either cyclical or continuous birth control pills, for six months with both researchers and participants blinded to the study group.
"We monitored vaginal bleeding, quality of life, and ovarian and endometrial suppression," said Legro, whose team's findings appeared in a recent issue of the Journal of Clinical Endocrinology and Metabolism.
The researchers found a significant decrease in moderate to heavy bleeding days among women who received the continuous birth control regimen. Women in the continuous group also had a significant decline in circulating and urinary estrogen levels, total ovarian volume and lead follicle size - all biomarkers that indicate the ovary is less active - and reported less pain and behavioral changes compared to women in the cyclic group.
However, results from the study also indicate greater breakthrough bleeding, or spotting, among women in the continuous group. Legro says that while greater breakthrough bleeding may be a truly objectionable side effect for many women, it does not seem to affect their quality of life.
"That is one of the unique things of this study. The quality of life did not necessarily decrease as it was counterbalanced by improvements in other areas such as pain and mood swings," the Penn State researcher added.
According to Legro, the study suggests that there may be diverse mechanisms of breakthrough bleeding depending on whether a woman is using either a cyclical or continuous regimen of birth control pills.
In the case of cyclic pills, the ovary comes back into the equation during the pill free interval leading to a rebound increased secretion of ovarian hormones, which in turn contributes to some breakthrough bleeding, he explained.
"Breakthrough bleeding in the continuous group, in our opinion, is most likely due to the fact that the pill does too good of a job in suppressing the ovary and the lining of the uterus gets a little bit thin and fragile so that from time to time there is a little bit of bleeding," added Legro, whose work is funded by the National Institutes of Health.
The study provides a physical reason for continuous oral contraceptive pills to treat such chronic medical conditions such as polycystic ovary syndrome, endometriosis and premenstrual syndrome, where additional suppression of the ovary or the endometrium is desired, and Legro noted that other chronic conditions such as hypertension or diabetes are treated continuously, not three weeks out of four. Further studies showing a favorable risk benefit ratio of continuous oral contraceptives on these disorders are the next step.
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
Other researchers on the paper are Jaimey G. Pauli, M.D.; Allen R. Kunselman, senior research assistant; Richard J. Zaino, M.D., professor of anatomic pathology; Laurence M. Demers, M.D., distinguished professor emeritus; Carol L. Gnatuk, M.D.; and William C. Dodson, M.D., all at Penn State College of Medicine; and Juliana W. Meadows, Ph.D., and James Kesner, Ph.D., both at the National Institute for Occupational Safety and Health, Cincinnati, Ohio.
Source: Amitabh Avasthi
Penn State
Saturday, April 5, 2008
Sequencing Of Giant Panda Genome
Cardiff University is contributing to the first genome project to assist conservation efforts for an endangered species.
Researchers in the Cardiff School of Biosciences will work with international colleagues on the 'Giant Panda Genome Project'.
The panda is often referred to as a 'living fossil', given evidence that its ancestors existed in China more than 8 million years ago. Research by Professor Mike Bruford, Cardiff School of Biosciences, previously found that the decline of the species can be linked directly to human activities rather than a genetic inability to adapt and evolve.
However, little research has been done on a genomic scale. The giant panda genome is approximately the same size as the human genome, and is thought to have 20,000-30,000 genes. Taxonomy and genetic studies indicate that the giant panda is most closely related to bears, not to raccoons as was once considered, given their unique physical characteristics.
Professor Bruford said: "This international collaboration will help scientists to understand the genetic basis for the giant panda's unique adaptations, including its dietary specialisation, and will reveal the history of the species in unparalleled detail."
The project is a further example of conservation work of international significance undertaken by the School of Biosciences' Biodiversity and Ecology Research Group.
This week Wales' Minister for the Environment, Sustainability and Housing Jane Davidson learned more about Cardiff's conservation research at the opening of the Group's new research facilities.
Jane Davidson, AM said: "Jane Davidson, said: "I am delighted to see the important biodiversity research that is taking place in the Cardiff School of Bioscience. Protecting biodiversity - so that it can provide essential ecosystem services that will help us to deal with social, economic and environmental changes - will be an essential ingredient of our success in achieving the future we want for Wales."
Researchers in the Cardiff School of Biosciences will work with international colleagues on the 'Giant Panda Genome Project'.
The panda is often referred to as a 'living fossil', given evidence that its ancestors existed in China more than 8 million years ago. Research by Professor Mike Bruford, Cardiff School of Biosciences, previously found that the decline of the species can be linked directly to human activities rather than a genetic inability to adapt and evolve.
However, little research has been done on a genomic scale. The giant panda genome is approximately the same size as the human genome, and is thought to have 20,000-30,000 genes. Taxonomy and genetic studies indicate that the giant panda is most closely related to bears, not to raccoons as was once considered, given their unique physical characteristics.
Professor Bruford said: "This international collaboration will help scientists to understand the genetic basis for the giant panda's unique adaptations, including its dietary specialisation, and will reveal the history of the species in unparalleled detail."
The project is a further example of conservation work of international significance undertaken by the School of Biosciences' Biodiversity and Ecology Research Group.
This week Wales' Minister for the Environment, Sustainability and Housing Jane Davidson learned more about Cardiff's conservation research at the opening of the Group's new research facilities.
Jane Davidson, AM said: "Jane Davidson, said: "I am delighted to see the important biodiversity research that is taking place in the Cardiff School of Bioscience. Protecting biodiversity - so that it can provide essential ecosystem services that will help us to deal with social, economic and environmental changes - will be an essential ingredient of our success in achieving the future we want for Wales."
Genetic Reprogramming
To radiation, chemotherapy, surgery and biological therapies deployed to wage war on cancer, M. D. Anderson researchers have added a new approach diplomacy.
"In this instance, we're not trying to kill cancer cells, rather we talk to cells and remind them of their regular programming. We persuade them to return to their normal behavior," says Jean-Pierre Issa, M.D., professor in M. D. Anderson's Department of Leukemia.
The instruments of persuasion are drugs that awaken cancer-suppressing genes in cancer cells by sweeping away chemical "off" switches connected to those genes. Methyl groups which consist of a carbon atom surrounded by hydrogen atoms silence genes by attaching at a certain spot, hanging off the gene like a tag or bookmark.
Issa and Leukemia Department Chair Hagop Kantarjian, M.D., are pioneers in the emerging field of epigenetics, the study of changes in gene expression and cellular behavior that are not caused by physical damage or mutation of the genes themselves. DNA methylation, for example, is epigenetic.
Issa and Kantarjian revived a failed chemotherapy, for instance, by turning it from attack to diplomatic mode. Using a low-dose, low-toxicity, longer-term approach, they showed that decitabine extends the life of some leukemia patients by demethylating, or turning on, genes.
Based on a clinical trial led by Kantarjian, the U.S. Food and Drug Administration last year approved decitabine (Dacogen™) for treatment of myelodysplastic syndrome, a lethal failure of the bone marrow to produce enough normal blood cells. The latest research by the group shows 70% of patients experienced some relief from MDS, with 35% experiencing complete remission. The median time of remission was 20 months.
Only the Beginning
Before the development of decitabine and another epigenetic agent called azacytidine (Vidaza™), MDS was a disease "with no treatment," Issa says. There was no chance of putting it in remission with a drug. Only supportive care, such as a blood transfusion, was available. Bone marrow transplants worked for a small number of patients.
"I see this as the beginning of the development of epigenetic therapy," Kantarjian says. "FDA approval of decitabine was just the beginning. This is when the real research starts, when the drug becomes accessible to investigators in an easy manner so they can develop new concepts and new strategies to optimize the use of the drug as a single agent, in combinations and across many tumors."
The leukemia group has a leading program, investigating epigenetic agents in 18 clinical trials. Four of those trials involve azacytidine, a drug that acts in a similar manner as decitabine. The two medications are the first epigenetic therapies approved for cancer.
Kantarjian, Issa, MDS Section Chief Guillermo Garcia- Manero, M.D., and colleagues have pressed ahead refining the optimal decitabine dosage for MDS, exploring its use in other leukemias, in combination with other drugs, and addressing how cancer becomes resistant to the drug. Azacytidine trials explore similar issues. Issa also collaborates with a team from Duke University on the use of decitabine for melanoma and renal cell carcinoma.
Nearly one-half of the 32 epigenetic trials at M. D. Anderson study decitabine. Not bad for a drug that was left for dead 25 years ago.
Drug Revival
Kantarjian's and Issa's work to revive decitabine is a classic example of the major role academic medical institutions play in drug discovery and development.
Decitabine was discovered in Czechoslovakia and tested against leukemia as traditional high-dose, cell-killing chemotherapy in Europe. The drug showed activity against the disease but was dogged by dangerous and unpredictable myelosuppression the shutting down of blood production in the bone marrow.
This side effect caused the drug's manufacturer, Pharmachemie BV of Europe, to shelve it in the 1980s.
Decitabine still intrigued Kantarjian, who was following the newborn field of epigenetics and suspected the drug had potential if used properly.
Pharmachemie was not interested in sponsoring any more clinical trials, but agreed to provide Kantarjian with decitabine. He filed his own investigational new drug application with the FDA and went to work. Kantarjian recalls that it was the early 1990s and he was the only physician in the United States working with the drug.
At the time, Issa was on the faculty at Johns Hopkins studying epigenetics. His research in DNA methylation led him to believe that decitabine might work epigenetically as a demethylating agent.
The two met in 1993 at a scientific meeting when Issa sought out Kantarjian and his poster on use of decitabine for chronic myelogenous leukemia. A collaboration was born.
They developed a Phase I clinical trial using decitabine intravenously for MDS at doses ranging from one-twentieth to one-fiftieth of the doses employed in the European trials. The trial showed that the drug was safe and active, with the lower dose preventing dangerous incidents of myelosuppression. Lab research indicated it worked by wiping out methyl tags.
Issa came to M. D. Anderson in 1999, where he and Kantarjian developed and led a pivotal Phase III multi-center trial in 2001. Results were reported early last year in the journal Cancer, citing that 17% of patients had some response, with responders having a median time to disease progression or death of 17.8 months, compared with 9.8 months for patients who didn't respond.
By the time the FDA approved decitabine in May 2006, the drug had been held by four companies: Pharmachemie, TEVA, SuperGen and finally MGI Pharma, which purchased the drug from SuperGen in September 2004 and shepherded it through the FDA fast-track process. The frequent change of companies was another challenge in keeping decitabine alive, Kantarjian says.
Azacytidine, developed on a parallel track by a team at Mount Sinai Medical Center in New York, and owned by Pharmion, was approved by the FDA in 2004.
Decitabine, researchers note, is the more potent demethylating agent of the two.
Thinking Outside the Box
"Dr. Issa and Dr. Kantarjian brought a unique assimilation of scientific and clinical expertise that enabled them to think about developing decitabine in a different way," says Mary Lynne Hedley, Ph.D., chief scientific officer of MGI Pharma. "And that's really why decitabine ended up being so useful for patients."
They upset three dogma of drug development and patient care, Hedley notes. First, they took a general cell-killing drug and by understanding its biological activity, transformed it into an early version of targeted therapy.
Second, they rejected the common practice of administering the maximum tolerated dose of a medication. And third, they focused on longer-term courses of therapy and disease management, rather than short courses of treatment.
The key to improved outcomes seen in the MDS follow-up study was prolonged treatment at low doses, Kantarjian says. "The best results with decitabine will be achieved by giving the drug to patients for one or two years, consisting of 20 to 24 courses of treatment, rather than three or four courses."
Beyond MDS
Kantarjian leads a Phase III clinical trial of decitabine for acute myelogenous leukemia the most common form of the disease in adults. Kantarjian notes that AML also is a leukemia that has shown the least improvement in treatment outcomes over the last 30 years.
A Phase II trial for decitabine as frontline therapy for AML in elderly patients, those with the grimmest prospects, also is under way.
Most patients over 65 go untreated, except for receiving supportive care, because of the toxicities associated with chemotherapy used against the disease. Their median survival is 1.7 months.
A poster presented by the team at the 2007 American Society of Clinical Oncology meeting showed how decitabine, with its low-intensity and minimal side effects, might help older AML patients. Total response rate was 52%, with 24% having complete remissions. Median survival time at the 20-month mark of the study was 12.6 months.
A study published this year comparing the effectiveness of decitabine to that of high-intensity chemotherapy in high-risk MDS patients showed comparable remission rates for each option, but those receiving decitabine had nearly doubled the mean survival time 22 months versus 12 months. "Chemotherapy gets patients to remission, but it's very toxic and remissions tend to be short-lived," Issa says.
Other M. D. Anderson researchers also are testing epigenetic drugs alone or in combinations against solid tumors as well as myeloma and lymphoma.
David Stewart, M.D., professor in the Department of Thoracic/Head and Neck Medical Oncology, for example, is exploring in a Phase I trial the use of the drug for solid tumors and lymphomas that have resisted other treatment.
Some solid tumors, such as colon and head and neck cancers, are known to have a great deal of methylation. Issa notes that earlier clinical trials of decitabine against these cancers also failed, but they repeated the same mistake as the European trials, using maximum tolerated doses for short periods.
"This drug really hasn't been properly tested at low doses over longer periods as a demethylating agent against those cancers," Issa says.
More to Learn
There is still plenty to understand about how demethylating agents such as decitabine work. Their effect is global because they demethylate and switch on many genes. The research team is pinpointing specific cancer-suppressing genes that are silenced by methylation.
MDS eventually becomes resistant to decitabine. Issa says resistance starts as early as six months or as late as 3.5 years. The drug strips away all methyl tags, both normal and abnormal. The normal tags come back quickly, while the abnormal tags return more slowly. "If they come back, the drug stops working," Issa notes.
Initial research in DNA methylation indicated that removing the tags might promote cancer by turning on oncogenes. However, Issa notes, subsequent research showed that methylation silenced hundreds of genes, inactivating those involved in tumor suppression and programmed cell death of cancerous cells.
Since tumors rely more on gene silencing to survive than normal adult cells do, the overall effect of demethylation is favorable for treatment.
Two for One
One potential answer to the problem of resistance is to combine agents, explains Garcia-Manero, M.D., an expert in epigenetics and associate professor of leukemia.
Garcia-Manero was lead author of a major study published in the journal Blood late last year. It combined decitabine with valproic acid, an anti-convulsant drug used for epilepsy.
Valproic acid hits a different epigenetic target, Garcia-Manero explains, inhibiting the removal of chemical "on" switches acetyl tags that activate genes.
Combining the two drugs in a group of 54 AML and MDS patients was shown to be safe and effective, Garcia-Manero notes. Methyl "off" switches were stripped from DNA, and two types of histone acetylation were achieved and an important tumor-suppressing gene was reactivated.
Of 10 elderly MDS and AML patients, five responded to the combination, with four of them experiencing remission. Overall, 22% of patients got some relief from the combination, with 19% having complete remission. While the study was too small to draw conclusions about the drugs' effectiveness, it points to the need for follow-up clinical trials.
"We're testing a number of epigenetic agents that have exciting potential," Garcia-Manero notes. His team has a paper pending in Blood that shows promising results with the combination of valproic acid, azacytidine and all-trans retinoic acid for AML and MDS patients. Overall, 42% of 53 patients showed some response to the three-drug combination, with 22% having complete remissions.
Garcia-Manero also is testing three other epigenetic agents, all of which protect acetyl "on" switches: vorinostat, MGCD0103 and LBH589.
Razelle Kurzrock, M.D., professor in the Department of Experimental Therapeutics and director of M. D. Anderson's Phase I Clinical Trials Program, leads a clinical trial testing azacytidine and valproic acid in advanced metastatic cancers.
Issa remembers presenting a research poster on epigenetics to the 1992 annual meeting of the American Association for Cancer Research, "There was one other poster on the subject out of 4,000," he says.
At this year's AACR meeting, there were 500 posters on epigenetic approaches genetic diplomacy marches on.
Genes Misbehaving
Cancer remains a disease of genes and genetic mutations, changes that drive cancer and make it hard to treat. But it's also a disease of genetic expression genes behaving badly and that, Jean-Pierre Issa, M.D., explains, is where epigenetics comes in.
To understand epigenetics, you have to start at the beginning, at the embryonic stage. An embryo's cells all have an identical set of genes. Its next job is to use those genes to differentiate cells into varied organs and tissues to build the body. This is accomplished with epigenetic signals that turn on the genes needed to create an organ while blocking other genes, explains Issa, professor in M. D. Anderson's Department of Leukemia.
The crucial actors here are methyl groups (off switches) and acetyl groups (on switches). Methyl tags attach to specific areas of genes. Acetyl tags have a more complex story, connecting with histone proteins to turn genes on.
Histones wrap around DNA. This histone-DNA combination forms the chromatin complex, which in turn composes chromosomes. When acetyl groups attach to histones, they turn on the accompanying gene. When acetyl tags are removed, the histone tightens around genes, turning them off.
Epigenetic drugs wipe out the methyl groups temporarily or block the stripping of acetyl groups from histones.
While some cancers are tied to inherited genetic variations, others are launched by damage to DNA. Mutated or damaged genes generally are impervious to repair by treatment. Therapies generally target these cells for death. Genes that are suppressed, Issa notes, can be manipulated through epigenetics a more diplomatic approach.
"Our genome is set. It can't be modified. Our epigenome is more dynamic. It's something we can affect with epigenetic drugs or by our behavior," Issa says.
Think of genes as hardware and epigenetics as the operating system software, explains Cheryl Lyn Walker, Ph.D., professor in M. D. Anderson's Department of Carcinogenesis at the Virginia Harris Cockrell Cancer Research Center in Smithville, Texas.
External carcinogenic factors such as diet, tobacco use or environmental toxins can cause cancer both via direct DNA damage and epigenetic effects, Walker says. She and her colleagues are focusing on all suspects that turn normal cells into cancer cells.
Walker, for example, studies genetic predisposition to cancer and how cancer-causing chemicals, or carcinogens, interact with genetic factors to cause cancer.
She examines the impact of xenoestrogens chemicals present in our environment that act like estrogens which are taken in through environmental exposures or in food, such as a plant phytoestrogen that is present in soy. Walker studies how exposure to xenoestrogens affects the development of uterine fibroids. Fibroids occur in upwards of 50% to 75% of women, and these tumors are the principal reason for hysterectomy in women of reproductive age.
Working in a rodent model, Walker found that those with a genetic predisposition to develop fibroids and who are exposed to environmental estrogens at crucial times during development have dramatically increased risk of developing tumors later.
"This is called developmental reprogramming. When you disrupt a tissue while it's developing, you worsen the risk of disease in adulthood," Walker says. "We're finding that for this type of environmental exposure, it's all about timing."
Reprogramming probably is accomplished through an epigenetic mechanism, Walker says, and so may be susceptible to epigenetic treatment.
Interestingly, Issa has found that methyl tags accumulate over time, shutting down genes. It's a tantalizing possible connection to aging, he says, but that's another story.
Epigenetics By Definition:
Acetylation: a reaction that introduces an acetyl group into a molecule of an organic compound. Acetyl tags work by connecting to specific proteins and act as a genetic on switch.
Demethylation: the chemical process of removing a methyl group from a molecule, which, in turn, can reactivate tumor-suppressor genes that are silenced by methylation.
Epigenetics: the study of changes in gene expression and cellular behavior that are not caused by physical damage or mutation of the genes themselves.
Methylation: an enzyme-mediated chemical modification that adds methyl groups at selected sites on proteins, DNA and RNA. Methyl tags work by attaching to specific areas of genes and act as a genetic off switch.
University of Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd., Box 229
Houston, TX 77030
United States
http://www.mdanderson.org
"In this instance, we're not trying to kill cancer cells, rather we talk to cells and remind them of their regular programming. We persuade them to return to their normal behavior," says Jean-Pierre Issa, M.D., professor in M. D. Anderson's Department of Leukemia.
The instruments of persuasion are drugs that awaken cancer-suppressing genes in cancer cells by sweeping away chemical "off" switches connected to those genes. Methyl groups which consist of a carbon atom surrounded by hydrogen atoms silence genes by attaching at a certain spot, hanging off the gene like a tag or bookmark.
Issa and Leukemia Department Chair Hagop Kantarjian, M.D., are pioneers in the emerging field of epigenetics, the study of changes in gene expression and cellular behavior that are not caused by physical damage or mutation of the genes themselves. DNA methylation, for example, is epigenetic.
Issa and Kantarjian revived a failed chemotherapy, for instance, by turning it from attack to diplomatic mode. Using a low-dose, low-toxicity, longer-term approach, they showed that decitabine extends the life of some leukemia patients by demethylating, or turning on, genes.
Based on a clinical trial led by Kantarjian, the U.S. Food and Drug Administration last year approved decitabine (Dacogen™) for treatment of myelodysplastic syndrome, a lethal failure of the bone marrow to produce enough normal blood cells. The latest research by the group shows 70% of patients experienced some relief from MDS, with 35% experiencing complete remission. The median time of remission was 20 months.
Only the Beginning
Before the development of decitabine and another epigenetic agent called azacytidine (Vidaza™), MDS was a disease "with no treatment," Issa says. There was no chance of putting it in remission with a drug. Only supportive care, such as a blood transfusion, was available. Bone marrow transplants worked for a small number of patients.
"I see this as the beginning of the development of epigenetic therapy," Kantarjian says. "FDA approval of decitabine was just the beginning. This is when the real research starts, when the drug becomes accessible to investigators in an easy manner so they can develop new concepts and new strategies to optimize the use of the drug as a single agent, in combinations and across many tumors."
The leukemia group has a leading program, investigating epigenetic agents in 18 clinical trials. Four of those trials involve azacytidine, a drug that acts in a similar manner as decitabine. The two medications are the first epigenetic therapies approved for cancer.
Kantarjian, Issa, MDS Section Chief Guillermo Garcia- Manero, M.D., and colleagues have pressed ahead refining the optimal decitabine dosage for MDS, exploring its use in other leukemias, in combination with other drugs, and addressing how cancer becomes resistant to the drug. Azacytidine trials explore similar issues. Issa also collaborates with a team from Duke University on the use of decitabine for melanoma and renal cell carcinoma.
Nearly one-half of the 32 epigenetic trials at M. D. Anderson study decitabine. Not bad for a drug that was left for dead 25 years ago.
Drug Revival
Kantarjian's and Issa's work to revive decitabine is a classic example of the major role academic medical institutions play in drug discovery and development.
Decitabine was discovered in Czechoslovakia and tested against leukemia as traditional high-dose, cell-killing chemotherapy in Europe. The drug showed activity against the disease but was dogged by dangerous and unpredictable myelosuppression the shutting down of blood production in the bone marrow.
This side effect caused the drug's manufacturer, Pharmachemie BV of Europe, to shelve it in the 1980s.
Decitabine still intrigued Kantarjian, who was following the newborn field of epigenetics and suspected the drug had potential if used properly.
Pharmachemie was not interested in sponsoring any more clinical trials, but agreed to provide Kantarjian with decitabine. He filed his own investigational new drug application with the FDA and went to work. Kantarjian recalls that it was the early 1990s and he was the only physician in the United States working with the drug.
At the time, Issa was on the faculty at Johns Hopkins studying epigenetics. His research in DNA methylation led him to believe that decitabine might work epigenetically as a demethylating agent.
The two met in 1993 at a scientific meeting when Issa sought out Kantarjian and his poster on use of decitabine for chronic myelogenous leukemia. A collaboration was born.
They developed a Phase I clinical trial using decitabine intravenously for MDS at doses ranging from one-twentieth to one-fiftieth of the doses employed in the European trials. The trial showed that the drug was safe and active, with the lower dose preventing dangerous incidents of myelosuppression. Lab research indicated it worked by wiping out methyl tags.
Issa came to M. D. Anderson in 1999, where he and Kantarjian developed and led a pivotal Phase III multi-center trial in 2001. Results were reported early last year in the journal Cancer, citing that 17% of patients had some response, with responders having a median time to disease progression or death of 17.8 months, compared with 9.8 months for patients who didn't respond.
By the time the FDA approved decitabine in May 2006, the drug had been held by four companies: Pharmachemie, TEVA, SuperGen and finally MGI Pharma, which purchased the drug from SuperGen in September 2004 and shepherded it through the FDA fast-track process. The frequent change of companies was another challenge in keeping decitabine alive, Kantarjian says.
Azacytidine, developed on a parallel track by a team at Mount Sinai Medical Center in New York, and owned by Pharmion, was approved by the FDA in 2004.
Decitabine, researchers note, is the more potent demethylating agent of the two.
Thinking Outside the Box
"Dr. Issa and Dr. Kantarjian brought a unique assimilation of scientific and clinical expertise that enabled them to think about developing decitabine in a different way," says Mary Lynne Hedley, Ph.D., chief scientific officer of MGI Pharma. "And that's really why decitabine ended up being so useful for patients."
They upset three dogma of drug development and patient care, Hedley notes. First, they took a general cell-killing drug and by understanding its biological activity, transformed it into an early version of targeted therapy.
Second, they rejected the common practice of administering the maximum tolerated dose of a medication. And third, they focused on longer-term courses of therapy and disease management, rather than short courses of treatment.
The key to improved outcomes seen in the MDS follow-up study was prolonged treatment at low doses, Kantarjian says. "The best results with decitabine will be achieved by giving the drug to patients for one or two years, consisting of 20 to 24 courses of treatment, rather than three or four courses."
Beyond MDS
Kantarjian leads a Phase III clinical trial of decitabine for acute myelogenous leukemia the most common form of the disease in adults. Kantarjian notes that AML also is a leukemia that has shown the least improvement in treatment outcomes over the last 30 years.
A Phase II trial for decitabine as frontline therapy for AML in elderly patients, those with the grimmest prospects, also is under way.
Most patients over 65 go untreated, except for receiving supportive care, because of the toxicities associated with chemotherapy used against the disease. Their median survival is 1.7 months.
A poster presented by the team at the 2007 American Society of Clinical Oncology meeting showed how decitabine, with its low-intensity and minimal side effects, might help older AML patients. Total response rate was 52%, with 24% having complete remissions. Median survival time at the 20-month mark of the study was 12.6 months.
A study published this year comparing the effectiveness of decitabine to that of high-intensity chemotherapy in high-risk MDS patients showed comparable remission rates for each option, but those receiving decitabine had nearly doubled the mean survival time 22 months versus 12 months. "Chemotherapy gets patients to remission, but it's very toxic and remissions tend to be short-lived," Issa says.
Other M. D. Anderson researchers also are testing epigenetic drugs alone or in combinations against solid tumors as well as myeloma and lymphoma.
David Stewart, M.D., professor in the Department of Thoracic/Head and Neck Medical Oncology, for example, is exploring in a Phase I trial the use of the drug for solid tumors and lymphomas that have resisted other treatment.
Some solid tumors, such as colon and head and neck cancers, are known to have a great deal of methylation. Issa notes that earlier clinical trials of decitabine against these cancers also failed, but they repeated the same mistake as the European trials, using maximum tolerated doses for short periods.
"This drug really hasn't been properly tested at low doses over longer periods as a demethylating agent against those cancers," Issa says.
More to Learn
There is still plenty to understand about how demethylating agents such as decitabine work. Their effect is global because they demethylate and switch on many genes. The research team is pinpointing specific cancer-suppressing genes that are silenced by methylation.
MDS eventually becomes resistant to decitabine. Issa says resistance starts as early as six months or as late as 3.5 years. The drug strips away all methyl tags, both normal and abnormal. The normal tags come back quickly, while the abnormal tags return more slowly. "If they come back, the drug stops working," Issa notes.
Initial research in DNA methylation indicated that removing the tags might promote cancer by turning on oncogenes. However, Issa notes, subsequent research showed that methylation silenced hundreds of genes, inactivating those involved in tumor suppression and programmed cell death of cancerous cells.
Since tumors rely more on gene silencing to survive than normal adult cells do, the overall effect of demethylation is favorable for treatment.
Two for One
One potential answer to the problem of resistance is to combine agents, explains Garcia-Manero, M.D., an expert in epigenetics and associate professor of leukemia.
Garcia-Manero was lead author of a major study published in the journal Blood late last year. It combined decitabine with valproic acid, an anti-convulsant drug used for epilepsy.
Valproic acid hits a different epigenetic target, Garcia-Manero explains, inhibiting the removal of chemical "on" switches acetyl tags that activate genes.
Combining the two drugs in a group of 54 AML and MDS patients was shown to be safe and effective, Garcia-Manero notes. Methyl "off" switches were stripped from DNA, and two types of histone acetylation were achieved and an important tumor-suppressing gene was reactivated.
Of 10 elderly MDS and AML patients, five responded to the combination, with four of them experiencing remission. Overall, 22% of patients got some relief from the combination, with 19% having complete remission. While the study was too small to draw conclusions about the drugs' effectiveness, it points to the need for follow-up clinical trials.
"We're testing a number of epigenetic agents that have exciting potential," Garcia-Manero notes. His team has a paper pending in Blood that shows promising results with the combination of valproic acid, azacytidine and all-trans retinoic acid for AML and MDS patients. Overall, 42% of 53 patients showed some response to the three-drug combination, with 22% having complete remissions.
Garcia-Manero also is testing three other epigenetic agents, all of which protect acetyl "on" switches: vorinostat, MGCD0103 and LBH589.
Razelle Kurzrock, M.D., professor in the Department of Experimental Therapeutics and director of M. D. Anderson's Phase I Clinical Trials Program, leads a clinical trial testing azacytidine and valproic acid in advanced metastatic cancers.
Issa remembers presenting a research poster on epigenetics to the 1992 annual meeting of the American Association for Cancer Research, "There was one other poster on the subject out of 4,000," he says.
At this year's AACR meeting, there were 500 posters on epigenetic approaches genetic diplomacy marches on.
Genes Misbehaving
Cancer remains a disease of genes and genetic mutations, changes that drive cancer and make it hard to treat. But it's also a disease of genetic expression genes behaving badly and that, Jean-Pierre Issa, M.D., explains, is where epigenetics comes in.
To understand epigenetics, you have to start at the beginning, at the embryonic stage. An embryo's cells all have an identical set of genes. Its next job is to use those genes to differentiate cells into varied organs and tissues to build the body. This is accomplished with epigenetic signals that turn on the genes needed to create an organ while blocking other genes, explains Issa, professor in M. D. Anderson's Department of Leukemia.
The crucial actors here are methyl groups (off switches) and acetyl groups (on switches). Methyl tags attach to specific areas of genes. Acetyl tags have a more complex story, connecting with histone proteins to turn genes on.
Histones wrap around DNA. This histone-DNA combination forms the chromatin complex, which in turn composes chromosomes. When acetyl groups attach to histones, they turn on the accompanying gene. When acetyl tags are removed, the histone tightens around genes, turning them off.
Epigenetic drugs wipe out the methyl groups temporarily or block the stripping of acetyl groups from histones.
While some cancers are tied to inherited genetic variations, others are launched by damage to DNA. Mutated or damaged genes generally are impervious to repair by treatment. Therapies generally target these cells for death. Genes that are suppressed, Issa notes, can be manipulated through epigenetics a more diplomatic approach.
"Our genome is set. It can't be modified. Our epigenome is more dynamic. It's something we can affect with epigenetic drugs or by our behavior," Issa says.
Think of genes as hardware and epigenetics as the operating system software, explains Cheryl Lyn Walker, Ph.D., professor in M. D. Anderson's Department of Carcinogenesis at the Virginia Harris Cockrell Cancer Research Center in Smithville, Texas.
External carcinogenic factors such as diet, tobacco use or environmental toxins can cause cancer both via direct DNA damage and epigenetic effects, Walker says. She and her colleagues are focusing on all suspects that turn normal cells into cancer cells.
Walker, for example, studies genetic predisposition to cancer and how cancer-causing chemicals, or carcinogens, interact with genetic factors to cause cancer.
She examines the impact of xenoestrogens chemicals present in our environment that act like estrogens which are taken in through environmental exposures or in food, such as a plant phytoestrogen that is present in soy. Walker studies how exposure to xenoestrogens affects the development of uterine fibroids. Fibroids occur in upwards of 50% to 75% of women, and these tumors are the principal reason for hysterectomy in women of reproductive age.
Working in a rodent model, Walker found that those with a genetic predisposition to develop fibroids and who are exposed to environmental estrogens at crucial times during development have dramatically increased risk of developing tumors later.
"This is called developmental reprogramming. When you disrupt a tissue while it's developing, you worsen the risk of disease in adulthood," Walker says. "We're finding that for this type of environmental exposure, it's all about timing."
Reprogramming probably is accomplished through an epigenetic mechanism, Walker says, and so may be susceptible to epigenetic treatment.
Interestingly, Issa has found that methyl tags accumulate over time, shutting down genes. It's a tantalizing possible connection to aging, he says, but that's another story.
Epigenetics By Definition:
Acetylation: a reaction that introduces an acetyl group into a molecule of an organic compound. Acetyl tags work by connecting to specific proteins and act as a genetic on switch.
Demethylation: the chemical process of removing a methyl group from a molecule, which, in turn, can reactivate tumor-suppressor genes that are silenced by methylation.
Epigenetics: the study of changes in gene expression and cellular behavior that are not caused by physical damage or mutation of the genes themselves.
Methylation: an enzyme-mediated chemical modification that adds methyl groups at selected sites on proteins, DNA and RNA. Methyl tags work by attaching to specific areas of genes and act as a genetic off switch.
University of Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd., Box 229
Houston, TX 77030
United States
http://www.mdanderson.org
UC San Diego Medical Center-Hillcrest Expands Intensive Care For Premature Babies
On April 2, 2008, UC San Diego Medical Center-Hillcrest celebrated the opening of an expanded Neonatal Intensive Care Unit (NICU) designed for the 24-hour specialized care of premature infants and newborns with complications. Nine licensed beds have been added to the existing 40-bed unit to increase the number of infants who can receive Level III neonatal intensive care from 780 newborns per year to more than 900. The $2.6 million dollar project is the first of a series of initiatives to expand and improve women's and infant's services at UC San Diego Medical Center.
"One in eight babies across the U.S. is born prematurely. Here in San Diego we have seen a sustained increase in the number infants needing intensive care for more than five years now," said Neil Finer, M.D., director of the Division of Neonatology at UCSD Medical Center. "By expanding our services, we can treat more of these fragile infants to help ensure healthy outcomes."
Every year, more than 3,000 babies are born at UCSD Medical Center-Hillcrest, the only academic medical center in San Diego, and the only hospital with the combination of a regional Level III NICU and a labor and delivery service on the same floor. The Level III designation is given by California Children's Services to hospitals that have the equipment and staff to handle very complicated births. Level III hospitals care for babies who are delivered before 32 weeks gestation, or who have serious illnesses or abnormalities requiring intensive care before, during, or after delivery.
Of the 780 infants cared for in the NICU each year, more than 90% are born at UCSD Medical Center, a regional center of excellence for high risk pregnancies. Because of its expertise in fetal care, genetics, minimally invasive in-utero fetal surgery, and radiology, families with complicated births are referred to UCSD Medical Center and arrive from throughout the region including Imperial County, Riverside, Los Angeles, San Bernardino, Orange County, and beyond.
The new 1,795 square-foot unit facility was designed by Childs Mascari Warner Architects and built by Turner Construction. The space blends a bright family-centered atmosphere with the most current newborn technology available. Families may personalize their space and rest by their infant's bedside. A 'Parent Resource Room' offers internet access and educational materials. Each of the nine private patient areas can accommodate one critical infant, or be used by up to three less acute babies, allowing for the co-bedding of multiples.
About UCSD's Infants
"Small babies born under 28 weeks may be with us for up to three months. Those with multisystem problems may be here as long as 6 months. The smaller the baby, the longer the time they and their families will be in the unit," said Finer. "The expanded NICU will be used primarily for premature babies who are stabilized beyond their acute needs but still require specialized feeding care and nutrition."
Babies born at less than 25 weeks gestation, sometimes weighing less than 16 ounces, require intensive respiratory, pulmonary and nutritional care. Minute to minute attention is required to prevent neurological damage and possible malnutrition in infants whose internal organs have not yet fully developed.
"In the seventies, a premature baby weighing less than 3 pounds had a 50% chance of surviving," said Jan Hebert, R.N., nurse manager for the NICU. "The application of new research findings and current technology has changed the picture dramatically. Today, the survival rates of these infants are 90% or better."
Premature Birth: A National Trend
The U.S. has one of the highest pre-term birth rates in the world with 12% of babies being born before 37 weeks gestation, according to the Centers for Disease Control. According to the March of Dimes, premature births have been escalating steadily over the past two decades. In 2005, more than 525,000 infants were born prematurely, the highest number ever reported for the U.S. The rate of premature birth increased almost 35 percent between 1981 and 2005 (9.4 to 12.7 percent).
Thomas Moore, M.D., professor and chairman of the Department of Reproductive Medicine at UC San Diego Medical Center cites advanced artificial reproductive technologies and shifts in maternal age as reasons for the increasing numbers of premature and multiples births in the region.
"The reason that the birth rate in the U.S. is generally flat but NICU admissions are rising is the advancing age of mothers at delivery and increasing use of artificial reproductive technologies which produce multiple fetuses," said Moore. "While new technologies have brought fertility to thousands of families who otherwise would not have their own children, the proportion of premature infants has risen to 12% of all births, largely due to multiple gestations of twins, triplets and more."
Moore also points to the nationwide epidemic of obesity as a significant risk factor for newborns who need complex intensive care.
"We are also seeing an epidemic of maternal obesity and gestational diabetes," noted Moore. "Babies of mothers with gestational diabetes are several fold more likely at birth to have respiratory problems, blood glucose regulation problems, and bilirubin issues, all of which requires NICU management, even if only for 1-3 days."
Training for Neonatologists
Key to properly caring for these fragile infants is the advanced medical training of UC San Diego's health care practitioners. Fourteen pediatrics residents from across the U.S. receive training at UCSD Medical Center every year, the only place in the region where doctors can train to become a neonatologist. The UCSD NICU is also one of the most active in the state of California for clinical research with more than 15 active clinical trials to date.
The NICU's largest current research effort is the national SUPPORT Trial funded by the National Institute of Child Health and Human Development. Finer, the principal investigator of the multi-center trial, is comparing two methods of early respiratory support for extremely premature infants and attempting to determine the appropriate oxygen levels needed by such infants. The UCSD Neonatal Program is also evaluating early nutritional interventions, and expanding the role of ultrasound of the heart and bowel to assist in the care of very compromised newborn infants.
"Every day we look for ways to develop better evidence-based treatments for the care of premature infants. We ask ourselves, 'What is the best way to assist the baby's breathing and to maintain appropriate oxygen levels? What is the best way to feed the baby and to optimize the use of maternal breast milk and prevent disease?" said Finer. "This is truly 24-hour care for the tiniest and most delicate of humans."
About Women and Infant Care at UCSD
The UC San Diego Medical Center labor and delivery service, specializing in high-risk pregnancies, and the NICU, are nationally recognized centers of excellence providing the highest level of care available for pregnant women and newborns. UCSD Medical Center became accredited as a Baby Friendly Hospital in 2006; one of a handful of academic hospitals to achieve this prestigious award.
Baby Friendly Hospitals support and promote breastfeeding as the preferred method of infant nutrition. In efforts to extend this support of human milk nutrition to the smallest, most vulnerable infants, UCSD is launching a nutrition program called SPIN, Supporting Premature Infant Nutrition. The new program is focused on the provision, analysis, and research of human milk to improve nutritional and neurodevelopmental outcomes in preterm babies. The program is the first of its kind in the United States.
In July 2008, hundreds of families whose infants have graduated from the NICU will reunite with the staff of UC San Diego Medical Center. The annual "Little Grad Picnic" in Mission Bay Park brings together families throughout California whose children enjoy a celebration of life and friendship.
University of California, San Diego Health Sciences
200 West Arbor Dr.
San Diego, CA 92103
United States
http://som.ucsd.edu
"One in eight babies across the U.S. is born prematurely. Here in San Diego we have seen a sustained increase in the number infants needing intensive care for more than five years now," said Neil Finer, M.D., director of the Division of Neonatology at UCSD Medical Center. "By expanding our services, we can treat more of these fragile infants to help ensure healthy outcomes."
Every year, more than 3,000 babies are born at UCSD Medical Center-Hillcrest, the only academic medical center in San Diego, and the only hospital with the combination of a regional Level III NICU and a labor and delivery service on the same floor. The Level III designation is given by California Children's Services to hospitals that have the equipment and staff to handle very complicated births. Level III hospitals care for babies who are delivered before 32 weeks gestation, or who have serious illnesses or abnormalities requiring intensive care before, during, or after delivery.
Of the 780 infants cared for in the NICU each year, more than 90% are born at UCSD Medical Center, a regional center of excellence for high risk pregnancies. Because of its expertise in fetal care, genetics, minimally invasive in-utero fetal surgery, and radiology, families with complicated births are referred to UCSD Medical Center and arrive from throughout the region including Imperial County, Riverside, Los Angeles, San Bernardino, Orange County, and beyond.
The new 1,795 square-foot unit facility was designed by Childs Mascari Warner Architects and built by Turner Construction. The space blends a bright family-centered atmosphere with the most current newborn technology available. Families may personalize their space and rest by their infant's bedside. A 'Parent Resource Room' offers internet access and educational materials. Each of the nine private patient areas can accommodate one critical infant, or be used by up to three less acute babies, allowing for the co-bedding of multiples.
About UCSD's Infants
"Small babies born under 28 weeks may be with us for up to three months. Those with multisystem problems may be here as long as 6 months. The smaller the baby, the longer the time they and their families will be in the unit," said Finer. "The expanded NICU will be used primarily for premature babies who are stabilized beyond their acute needs but still require specialized feeding care and nutrition."
Babies born at less than 25 weeks gestation, sometimes weighing less than 16 ounces, require intensive respiratory, pulmonary and nutritional care. Minute to minute attention is required to prevent neurological damage and possible malnutrition in infants whose internal organs have not yet fully developed.
"In the seventies, a premature baby weighing less than 3 pounds had a 50% chance of surviving," said Jan Hebert, R.N., nurse manager for the NICU. "The application of new research findings and current technology has changed the picture dramatically. Today, the survival rates of these infants are 90% or better."
Premature Birth: A National Trend
The U.S. has one of the highest pre-term birth rates in the world with 12% of babies being born before 37 weeks gestation, according to the Centers for Disease Control. According to the March of Dimes, premature births have been escalating steadily over the past two decades. In 2005, more than 525,000 infants were born prematurely, the highest number ever reported for the U.S. The rate of premature birth increased almost 35 percent between 1981 and 2005 (9.4 to 12.7 percent).
Thomas Moore, M.D., professor and chairman of the Department of Reproductive Medicine at UC San Diego Medical Center cites advanced artificial reproductive technologies and shifts in maternal age as reasons for the increasing numbers of premature and multiples births in the region.
"The reason that the birth rate in the U.S. is generally flat but NICU admissions are rising is the advancing age of mothers at delivery and increasing use of artificial reproductive technologies which produce multiple fetuses," said Moore. "While new technologies have brought fertility to thousands of families who otherwise would not have their own children, the proportion of premature infants has risen to 12% of all births, largely due to multiple gestations of twins, triplets and more."
Moore also points to the nationwide epidemic of obesity as a significant risk factor for newborns who need complex intensive care.
"We are also seeing an epidemic of maternal obesity and gestational diabetes," noted Moore. "Babies of mothers with gestational diabetes are several fold more likely at birth to have respiratory problems, blood glucose regulation problems, and bilirubin issues, all of which requires NICU management, even if only for 1-3 days."
Training for Neonatologists
Key to properly caring for these fragile infants is the advanced medical training of UC San Diego's health care practitioners. Fourteen pediatrics residents from across the U.S. receive training at UCSD Medical Center every year, the only place in the region where doctors can train to become a neonatologist. The UCSD NICU is also one of the most active in the state of California for clinical research with more than 15 active clinical trials to date.
The NICU's largest current research effort is the national SUPPORT Trial funded by the National Institute of Child Health and Human Development. Finer, the principal investigator of the multi-center trial, is comparing two methods of early respiratory support for extremely premature infants and attempting to determine the appropriate oxygen levels needed by such infants. The UCSD Neonatal Program is also evaluating early nutritional interventions, and expanding the role of ultrasound of the heart and bowel to assist in the care of very compromised newborn infants.
"Every day we look for ways to develop better evidence-based treatments for the care of premature infants. We ask ourselves, 'What is the best way to assist the baby's breathing and to maintain appropriate oxygen levels? What is the best way to feed the baby and to optimize the use of maternal breast milk and prevent disease?" said Finer. "This is truly 24-hour care for the tiniest and most delicate of humans."
About Women and Infant Care at UCSD
The UC San Diego Medical Center labor and delivery service, specializing in high-risk pregnancies, and the NICU, are nationally recognized centers of excellence providing the highest level of care available for pregnant women and newborns. UCSD Medical Center became accredited as a Baby Friendly Hospital in 2006; one of a handful of academic hospitals to achieve this prestigious award.
Baby Friendly Hospitals support and promote breastfeeding as the preferred method of infant nutrition. In efforts to extend this support of human milk nutrition to the smallest, most vulnerable infants, UCSD is launching a nutrition program called SPIN, Supporting Premature Infant Nutrition. The new program is focused on the provision, analysis, and research of human milk to improve nutritional and neurodevelopmental outcomes in preterm babies. The program is the first of its kind in the United States.
In July 2008, hundreds of families whose infants have graduated from the NICU will reunite with the staff of UC San Diego Medical Center. The annual "Little Grad Picnic" in Mission Bay Park brings together families throughout California whose children enjoy a celebration of life and friendship.
University of California, San Diego Health Sciences
200 West Arbor Dr.
San Diego, CA 92103
United States
http://som.ucsd.edu
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