Using MRI To Diagnose BreastCancerIn Its Intraductal Stage May Stem Development Of Invasive Cancer

By using MRI (magnetic resonance imaging) it may be possible to prevent the development of invasive cancer by diagnosing breast caner in its intraductal stage, according to an article in The Lancet. A Comment in The Lancet believes that these findings demonstrate that MRI should now be used as another method, in its own right, to detect early stage breast cancer.
Professor Christiane Kuhl, Department of Radiology, University of Bonn, Germany, and team examined details on 7,319 women over a period of five years. They had all been referred to an academic breast center. As well as conventional mammography for diagnostic assessment and screening they all received MRI as well. The aim here being to find out how sensitive each method was in diagnosing DCIS (ductal carcinoma in situ). Different radiologists then assessed the mammograms and MRI scans. They assessed the relative sensitivity of each detection method by comparing the biological profiles of mammography-detected DCIS with those of MRI-detected DCIS.
The scientists found that:
– Of 167 women who had a DCIS diagnosis, 92% were diagnosed with MRI– Of 167 women who had a DCIS diagnosis, 56% were diagnosed by mammography– MRI sensitivity for diagnosing DCIS increased with nuclear grade– Mammography sensitivity for diagnosing DCIS decreased with nuclear grade– Of 89 women with high grade DCIS diagnosis, 98% were diagnosed by MRI– Of 89 women with high grade DCIS diagnosis, 52% were diagnosed by mammography– 48% were missed by mammography but diagnosed by MRI aloneThe MRI’s higher sensitivity was not linked to a significantly higher number of false positive diagnoses.
“Our study suggests that the sensitivity of film screen or digital mammography for diagnosing DCIS is limited. MRI could help improve the ability to diagnose DCIS, especially DCIS with high nuclear grade,” the authors conclude.
“These findings can only lead to the conclusion that MRI outperforms mammography in tumour detection and diagnosis. MRI should thus no longer be regarded as an adjunct to mammography but as a distinct method to detect breast cancer in its earliest stage. A large-scale multicentre breast-screening trial with MRI in the general population is essential,” Dr Carla Boetes and Dr Ritse Mann, Radboud University Nijmegen Medical Centre, Netherlands, wrote in the accompanying Comment.
http://www.thelancet.com

AHA Affiliate Releases Toolkit For ED-Based HIV Testing Programs

HIV Testing Programs Toolkit, Health Research and Educational Trust: HRET, an affiliate of the American Hospital Association, has launched a no-cost, online toolkit to facilitate planning, implementation or expansion of hospital emergency department-based HIV testing programs for clinicians and administrators. The toolkit examines different approaches, considerations and resources needed in making HIV testing a routine part of ED treatment. The toolkit can be used to guide program-design and resource-allocation decisions, as well as to inform policies for ED HIV testing. The toolkit is based on HRET findings from site visits and interviews with ED personnel and was supported by CDC and the National Center for HIV/AIDS, STD and TB Prevention (HRET, July 2007).
Reprinted with kind permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation.

Blood Clots Outside Hospital Could Be Prevented Inside Hospital

Even though more blood clots, or venous thromboembolisms are diagnosed during the three months after patients’ hospitalizations than while they are in hospital, fewer than half of them receive medications to prevent blood clots while they are inpatients, according to a new report published in Archives of Internal Medicine (a JAMA/Archives journal), July 23 issue.
Researchers examined the results of several previous studies and found that both unfractionated and low-molecular-weight heparin are effective in preventing venous thromboembolisms in the legs and lungs of hospitalized patients.
According to background information in this study, venous thromboembolism and pulmonary embolism are major causes of complications and death among hospitalized patients. It is estimated that up to 10% of hospital deaths may be attributed to pulmonary embolism. Venous thromboembolisms, on the other hand, tend to happen out of the hospital.
Frederick A. Spencer, M.D., McMaster University Medical Center, Hamilton, Ontario, Canada, and team looked at the medical records of people from Worcester, Massachusetts, who were diagnosed with venous thromboembolism during 1999, 2001 and 2003.
The authors wrote that “A total of 1,897 subjects had a confirmed episode of venous thromboembolism. In all, 73.7 percent of patients developed venous thromboembolism in the outpatient setting; a substantial proportion of these had undergone surgery (23.1 percent) or hospitalization (36.8 percent) in the preceding three months.” 67% of all those patients experienced venous thromboembolisms within one month of their hospitalization. Two other risk factors were active cancer (29%) and a previous blood clot (19.9%).
The authors wrote “Because most of the cases of venous thromboembolism occurred within 29 days of hospital discharge (41% occurred within 14 days), it is not unreasonable to assume that some of these cases may have been prevented simply by increased use of appropriate in-hospital deep vein thrombosis prophylaxis (such as, compression stockings, pneumatic compression devices and, in high-risk patients, anticoagulants.”
The study states that about half of the outpatients who experienced venous thromboembolism after hospitalization had been in hospital for four days or less. They indicate that patients who are in hospital for a short time should receive preventative therapy. As hospital stays are getting shorter, patients are spending more recovery time at home without moving about - they would benefit from anti-clotting therapy even after discharge.
Another meta-analysis, carried out by Lironne Wein, Monash University and Alfred Hospital, Melbourne, Australia, and colleagues, looked at 36 previously published randomized controlled trials which compared drugs used to prevent venous thromboembolism - comparisons were made against a control group who did not receive prophylactic therapy. 14 of the studies compared unfractionated heparin with a control, 11 compared low-molecular weight heparin to a control, 10 compared two types of heparin to each other, and 1 compared fondaparinux sodium to a placebo.
The findings were as follows:
* Unfractionated heparin was linked to a 67% lower deep vein thrombosis risk and a 36% lower pulmonary embolism risk, compared to control groups.* Low-molecular-weight heparin was linked to a 44% % lower deep vein thrombosis risk and a 63% lower pulmonary embolism risk, compared to control groups.* Fondaparinux was shown to be effective in preventing venous thromboembolism.* When compared with each other, low-molecular-weight heparin was associated with a 32% lower risk of deep vein thrombosis and a 53% lower rate of hematoma at the injection site.* Prophylactic therapy, however, was not linked to lower mortality rates.
The authors wrote “This meta-analysis has shown that unfractionated heparin and low-molecular-weight heparin are both associated with a reduced risk of venous thromboembolism in medical patients, with low-molecular-weight heparin being more effective in preventing deep vein thrombosis than unfractionated heparin when considering trials that directly compared the two agents. The unfractionated heparin dosage of 5,000 units three times daily was more effective than the unfractionated heparin dosage of 5,000 units twice daily in reducing the risk of deep vein thrombosis. We believe that routine prophylactic anticoagulation has an important place in the medical setting.”
“Although such therapy may not necessarily decrease mortality among hospitalized medical patients, it will reduce the occurrence of deep vein thrombosis and pulmonary embolism and therefore the burden of illness currently caused by these events.”
“Venous Thromboembolism in the Outpatient Setting”Frederick A. Spencer, MD; Darleen Lessard, MS; Cathy Emery, RN; George Reed, PhD; Robert J. Goldberg, PhDArch Intern Med. 2007;167:1471-1475Click here to view abstract online
Related Articles:
Editorial:“Outpatient Venous Thromboembolism - A Common But Often Preventable Public Health Threat”Arch Intern Med. 2007;167:1451-1452.Click here to read the first 150 words of the full text
“Pharmacological Venous Thromboembolism Prophylaxis in Hospitalized Medical Patients: A Meta-analysis of Randomized Controlled Trials”Lironne Wein, Sara Wein, Steven Joseph Haas, James Shaw, and Henry KrumArch Intern Med. 2007;167:1476-1486.Click here to view abstract online

Specific Gene Supressor Described As A 'Dictator With A Conscience'

University of New South Wales (UNSW) researchers have uncovered an important naturally occurring mechanism in the body where “bad” cells that cause blockages in our blood vessels are kept under strict growth control, while “good” cells that keep our blood vessels free of clots and growths are left unaffected.
The discovery is expected to benefit those who will need heart coronary bypass surgery, an angioplasty — the mechanical widening of a narrowed or totally blocked blood vessel — or will undergo haemodialysis.
Professor Levon Khachigian, from UNSW’s Centre for Vascular Research, who previously pioneered “molecular assassin” drug technology, describes this novel mechanism he discovered as “a molecular dictatorship with a conscience”.
“The dictator is a specific gene suppressor called YY1, which has the therapeutically appealing capacity to differentiate between certain cell types when it goes about its activity,” says Professor Khachigian.
This key finding has just been published in the world’s premier cardiovascular research journal, Circulation Research.
Professor Khachigian’s research provides new hope in tackling the global problems of coronary bypass graft failure, and restenosis — the closing or narrowing of an artery that was previously opened by a procedure such as angioplasty.
“While the most effective way to head off restenosis is a drug-coated stent, the drugs that sit on these stents inhibit the growth of good cells as well as the bad.
“If you had to have catheter intervention to re-open an occluded artery, for sustained symptom-free benefit you would be hoping for suppressed smooth muscle cell growth, without affecting endothelial cell growth,” says Professor Khachigian.
“And that’s exactly what happens when we simply top up blood vessels with the body’s natural reserves of YY1.”

Better Clinical Model Required For The Treatment Of Heart Failure And Associated Depression

The National Institute of Mental Health (NIMH) has awarded researchers at the University of Pittsburgh School of Medicine a three-year, $500,000 grant to develop a novel intervention strategy for simultaneously treating congestive heart failure and major depression. The study is designed to obtain the necessary feasibility and clinical data required to plan a large-scale trial, which will compare the impact of a “blended” depression/heart failure care management programs vs. traditional heart failure care management program on cardiovascular morbidity and mortality, health-related quality of life, mood symptoms, health care costs and a variety of other outcomes of interest.
Heart failure affects 5 million Americans, with more than 550,000 newly diagnosed cases, 287,000 deaths and $30 billion in both direct and indirect costs each year. It also is the leading cause for hospitalization, and its five-year mortality rate following first hospital admission for heart failure exceeds that of most cancers.
Depression is present in approximately 20 to 50 percent of heart failure patients and compelling evidence links it to increased morbidity and mortality and reduced quality of life. Yet, although the University of Pittsburgh Medical Center (UPMC) and several other integrated health care delivery systems across the United States have implemented outpatient care management programs for heart failure, none routinely screen for and treat depression.
The study of the connections between mental health and cardiovascular disease is not new to the study’s principal investigator, Bruce L. Rollman, M.D., M.P.H., associate professor of medicine and psychiatry, University of Pittsburgh School of Medicine. Since 2004, he and his co-principal study investigator, Charles F. Reynolds III, M.D., UPMC Professor of Geriatric Psychiatry, University of Pittsburgh School of Medicine, and their research team have been recruiting patients from several Pittsburgh-area hospitals, including UPMC Presbyterian and UPMC Passavant, into the first NIH-funded clinical trial titled, “Bypassing the Blues,” designed to examine the impact of treating depressive symptoms following coronary artery bypass graft (CABG) surgery.
In this latest study, Drs. Rollman and Reynolds, with the help of their co-investigators Dennis McNamara, M.D., professor of medicine and director of UPMC Heart Failure Transplantation, and Rene Alvarez, M.D., associate professor of medicine and director of UPMC Heart Failure/Pulmonary Hypertension Network, will modify their “Bypassing the Blues” protocol for treating post-CABG depression. They will employ the UPMC outpatient guidelines for treating heart failure and then pilot their “blended” treatment strategy for treating depressed heart failure patients. They will recruit approximately 500 patients admitted for an acute episode of heart failure from UPMC Presbyterian, UPMC St. Margaret, UPMC Braddock and UPMC McKeesport hospitals, and then conduct follow-up telephone assessments at one, three and six months to estimate suitably sensitive and specific cut-off scores for treating depression by gender and severity of heart failure.
“The subject of depression and congestive heart failure has received little attention until recently. We need to look at these two conditions differently than in the past, as depression is seldom diagnosed and often untreated in patients with congestive heart failure,” commented Dr. Rollman. “We also hope to learn through the cohort study how to better determine the severity of depressive symptoms that merit further attention from heart failure specialists.”
“Cardiologists can help their patients if they are provided with the knowledge of depression’s devastating effects on heart disease. Early studies have demonstrated that if patients are treated for depression after heart surgery or any invasive heart procedure, they are more likely to stick to their scheduled treatments and have a better, more positive outlook toward recovery,” says Dr. McNamara.
“Depression is a complex disease with many symptoms similar to heart failure. If we can develop a better clinical model in recognizing and detecting depression, we hope to be able to gather enough data to support the need for a large-scale trial to test the effectiveness of a combined depression and heart failure treatment over the current standard of care for heart failure which does not address depression,” added Dr. Reynolds.

Defibrillators Can Control Dangerous Heart Condition

Implantable defibrillators can reduce the risk of sudden death in high-risk patients with hypertrophic cardiomyopathy, a genetically linked thickening of heart muscle.
And a number of people benefiting from the implantable cardioverter-defibrillators (ICDs) had only one risk factor for sudden cardiac death, meaning that more people may benefit, a new study suggests.
“Hypertrophic cardiomyopathy is the most common cause of sudden death in young people, including athletes, and a defibrillator affords the opportunity, as it turns out, to change the natural course of the disease and prevent sudden death,” said Dr. Barry Maron, director of the Hypertrophic Cardiomyopathy Center at the Minneapolis Heart Institute Foundation. “In a way, this highlights the use and effectiveness of the device in this genetic disease in these young patients and expands the number of patients that could be eligible at least for consideration of a defibrillator.”
Maron was lead author of the study, which is published in the July 25 issue of the Journal of the American Medical Association.
Other experts, however, pointed out that much of the information in the study has already been known.
“Some of this data has been published in a smaller number of patients. This study confirms what has already been done,” said Dr. Jose Joglar, director of clinical electrophysiology, and associate professor of medicine at the University of Texas Southwestern Medical Center at Dallas. “This is not going to expand the use of defibrillators.”
Hypertrophic cardiomyopathy is a genetic disease that causes the heart muscles to thicken abnormally. This, in turn, can upset the heart’s electric system and cause life-threatening rhythm disturbances called arrhythmias.
Implantable defibrillators (ICDs), which terminate these dangerous rhythm disturbances, have become routine over the past few years in high-risk patients with hypertrophic cardiomyopathy. But it’s not always easy to identify the people with hypertrophic cardiomyopathy who would benefit from a defibrillator.
“It’s traditionally difficult to determine precisely which patients among all with this disease are at high risk and would deserve consideration for an ICD, because HCM [hypertrophic cardiomyopathy] is a particularly heterogeneous disease,” Maron explained.” Most of the patients at high risk have no symptoms or only mild symptoms and are younger than those who have coronary disease by, on the average, 25 years. And there is no one single risk factor that has emerged such as with coronary disease following a heart attack.”
“Because the patients are younger, the decision for these ICDs are bigger because of the time period they will have them is longer,” he continued.
Although the new study isn’t the first study to look at ICDs in patients with hypertrophic cardiomyopathy, it is the largest.
Maron and his colleagues analyzed data from an international, multi-center registry of defibrillators implanted between 1986 and 2003 in 506 patients with hypertrophic cardiomyopathy. All of the patients, whose average age was 42 years, were considered at high risk for sudden death, although 87 percent had no or only mild symptoms. Average follow-up was 3.7 years. The defibrillators were implanted both in patients who had never had a problem (primary prevention) and in patients who had already had a problem (secondary prevention).
Twenty percent of the patients experienced one or more incidents in which the ICD terminated ventricular fibrillation (severely abnormal heart rhythm that results in cardiac arrest) or ventricular tachycardia (abnormally rapid heartbeat).
The defibrillator terminated abnormal heart rhythms in 10.6 percent of patients annually who had a device for secondary prevention and in 3.6 percent of patients a year for primary prevention.
The probability of a defibrillator intervening five years after implantation was almost 25 percent, the study found.
More than 40 percent of patients in whom the device intervened appropriately were under 40 years of age.
Thirty-five percent of the patients who had a defibrillator for primary prevention had undergone implantation based on just one risk factor. The likelihood that the device would intervene was similar in patients with one, two or three or more risk factors.
The risk factors evaluated in the study included a history of hypertrophic cardiomyopathy-related sudden death in one or more relatives under the age of 50; fainting; and abnormally rapid heart rhythm.
“This is a select patient population. The risk factors are pretty significant; the patients were probably sicker,” Joglar said. “The great majority of patients with HCM will have a better prognosis than that.”
The study authors cautioned that defibrillators should not necessarily be implanted in everyone with hypertrophic cardiomyopathy. Patients will still have to rely on individual doctors’ judgment.

Analyzing Beating Heart Stem Cells Could Lead To Heart Attack Treatments

New research at the University of Nottingham, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), is paving the way for techniques that use stem cells to repair the damage caused by heart attacks.
The research, highlighted in the new issue of BBSRC Business, is looking at the process that turns a stem cell into a cardiomyocyte — the beating cell that makes up the heart. The Nottingham researchers are developing a new system to monitor cardiomyocytes in real time as they differentiate from stem cells into beating heart cells. The system uses electrophysiology to record the electrical properties in a cell and will be the first time it has been used to study cardiomyocyte cells in the UK.
The researchers hope that their research could provide more detailed information on the electrical activity of stem cell derived cardiomyocytes. In the longer term, this could facilitate their use in regenerating the damaged hearts of heart attack victims.
“Human embryonic stem cells promise unrivalled opportunities. However, they are difficult, time-consuming and expensive to grow in the lab”, Dr Denning explains. “Our understanding of how to convert them into cardiomyocytes is poor. At the moment we only know how to produce a few million cardiomyocytes, but to treat just one heart attack patient, we may need one billion that all function in the correct way.”
To help overcome the many challenges that stem cells bring, Dr Denning and his team plan to engineer a novel system for real-time analysis of cardiomyocytes during early development so their properties are better understood.
The team have already demonstrated that sufficient numbers of stem cell-derived cardiomyocytes can be produced for detailed analysis and they plan to use new ‘electrophysiology’ systems to record changes in the cells when cultured. Electrophysiology is the study of cells’ electrical properties and this is the first time that the method has been used in the UK to study stem cell-cardiomyocyte biology.
“This research will enable rapid development of stem cell-derived cardiomyocytes as a tool for understanding the heart and its diseases,” says Dr Denning. However, he cautions: “Before we can consider using stem cells to treat heart-attack patients there are many problems which will take many years to solve. We don’t yet know how to deliver the cells to a patient’s heart and prevent them being washed away so that they actually stay in the heart and both survive and function. It will take many years to overcome these challenges and put stem cell-derived cardiomyocytes into medical usage.”
The researchers will also be monitoring how the cells respond to different pharmacological agents in order to improve drug-screening processes and reduce the need for animal testing.
“A key part of the project is to monitor the effects of different drugs on the cells. At present, only limited information is available on how they respond to pharmacological or gene modulating agents.
“Between 1990 and 2001, 8 different drugs were withdrawn from the market in the USA at an estimated cost of $8billion because they caused unexpected deaths in several hundred patients. Our aim is to reduce such occurrences by having better test methods to test the drugs before they reach the clinic.
“By studying the drugs’ effects on the heart cells in the lab, this could reduce the need for animals in clinical trials.”

Effective-Insecticide Repellent Synergy Against Mosquito Vectors Of Malaria

The mosquitoes responsible for malaria transmission to humans belong to the Anopheles genus. One of the best known and most extensively studied is Anopheles gambiae, Africa’s principal malaria vector. The protection recommended by the World Health Organization for people at risk from this devastating disease is the use of mosquito nets impregnated with pyrethroids, of low toxicity for mammals and highly active against mosquitoes. Unfortunately, excessive and inappropriate use of this family of insecticide, particularly by spraying, has induced a disturbing rise in the number of resistant individuals in the Anopheles populations. The mosquito nets treated with pyrethroids can therefore lose their effectiveness. It is therefore essential to devise new control strategies against these malaria vectors that are resistant to these insecticides.
IRD researchers and their partners (1) obtained encouraging results by combining a non-pyrethroid insecticide, propoxur, and a repellent, N,N-diethyl toluamide (DEET). They based their investigations on previous work which had revealed a strong synergy between the two components. A combination of the two had proved to be much more effective than the straightforward addition of their respective properties. Mosquito nets soaked with this mixture had a lethal power and irritant effect that inhibited the mosquitoes from biting. Moreover, the mosquitoes are hit by a powerful paralysing action, known as the “knockdown” effect (3), on contact with the mixture. The mortality rates determined were satisfactory, in that they equalled those obtained by using deltamethrin, a commonly-used synthetic pyrethroid, highly effective against mosquitoes.
The researchers tested two mixtures composed of a non-pyrethroid insecticide of the organophosphate family, combined with either a standard repellent, DEET, or with a new-generation synthetic repellent. Both of these mixtures show a strong synergy in the resulting lethal and paralysing effects on the mosquitoes. However, only the association between the insecticide and the standard repellent produced a synergistic effect that inhibited the mosquito from taking its blood feed. A synergistic effect was also observed with regard to the treatment’s residual efficacy which is several months longer than that of either agent applied alone. The advantage of the synergistic property of these combinations is enhanced by the fact that it significantly reduced the necessary effective doses against the mosquitoes (about 6 times that of the insecticide applied alone), to attain an efficacy equivalent to that of deltamethrin.
The nets treated with the two mixtures in the laboratory were subsequently tested in field trials, in the rice-growing area 40 km North of Bobo-Dioulasso, in Burkina Faso. This area has the specificity of harbouring two different forms of Anopheles gambiae. The first appears in May and June in the rice-fields. It shows no resistance to pyrethroids. The second emerges in September and October in puddles left by monsoon rains. These do show resistance to these insecticides. As expected, the usual pyrethroid-treated nets turned out to be effective only against non-resistant mosquitoes of the first population. Conversely, the nets pre-soaked with non-pyrethroid-repellent combinations proved excellent protection for the people of the local villages, whatever the population of mosquitoes present. Nevertheless, their residual efficacy (about 15 days) in real conditions did not match the researchers’ expectations. The team consequently envisage working in conjunction with a company able to devise a system for encapsulating the mixture to prolong the residual life of treated mosquito nets.

DNA Damage In A New Light

It has long been known that UV light can damage DNA, reducing its ability to replicate and interact with proteins, and often resulting in the development of skin cancers. However, not much is known about how the elasticity of DNA strands is altered upon exposure to UV light. Now a group of researchers at Duke University have developed a method to measure changes in the mechanical properties of DNA upon irradiation with UV light.
Piotr Marszalek and his colleagues have conducted single-molecule force spectroscopy measurements on viral DNA, which show the unraveling of the DNA double helix upon exposure to UV irradiation. The researchers essentially pick up individual DNA molecules with the tip of a scanning probe microscope and stretch it while measuring the forces generated. These "stretch-release" measurements enable the accurate determination of changes in the elasticity of the DNA strands. Upon exposure to UV light, the force profile of the viral DNA changes dramatically in a dose-dependent manner. The force curve of intact DNA is characterized by a plateau region. This characteristic plateau is drastically reduced in width with increasing exposure to UV light.
UV light induces the crosslinking of the constituent DNA bases within the polynucleotide chains, as well as causes the formation of lesions by linking together the adjacent strands. The small changes in structure induced by this crosslinking can very profoundly affect the ability of DNA to recognize specific molecules, and can thus completely disrupt its ability to replicate and interact with the transcriptional machinery to synthesize proteins. Marszalek and his colleagues have also examined synthetic DNA to figure out the extent to which different bases are affected by UV light. They conclude that the changes in the force profile of viral DNA exposed to UV light are due to the local unwinding of the double helix in some regions arising from the massive formation of crosslinked structures.
"These are the first measurements that establish a relationship between DNA nanomechanics and damage", said Marszalek. He believes that this work paves the way for using stretch-release force spectroscopy measurements in DNA diagnostics.

Innovative Treatment Option Holds Promise For Millions Of People World Wide Suffering From Excessive Sweating

An estimated 3 percent of the world population, or about 197 million people suffer from some form of hyperhidrosis (excessive sweating), many of whom do not receive proper diagnosis or treatment. Hyperhidrosis is a medical condition in which the body sweats three to four times the normal amount. This can lead to undue embarrassment, social and psychological problems, and in the most severe cases, impede normal day-to-day functions. The exact cause of hyperhidrosis is unknown, but researchers have linked it to over activity of the nerves that send signals to the sweat glands in the skin.
This condition typically affects any of the following areas: the palms (palmar hyperhidrosis), the underarms (axillary hyperhidrosis), the face (facial hyperhidrosis), or the feet (plantar hyperhidrosis). Treatment for hyperhidrosis depends on the area of the body affected, but in general consists of the following options: topical and oral medications, iontophoresis, botulinum toxin (Botox) injections, and when these nonsurgical options have proven ineffective - surgery.
Researchers at Barrow Neurological Institute in Phoenix analyzed the outcome of 300 consecutive patients undergoing bilateral sympathectomy for hyperhidrosis between May 1996 and April 2005. One hundred and twenty-nine patients presented with palmar hyperhidrosis, 11 with axillary hyperhidrosis, and 160 with both axillary and palmar hyperhidrosis. The mean age of patients was 27.9. Average follow-up was 10.3 months (range 0.5-36) and obtained either in the clinic, by phone or by written questionnaire.
The results of this study, Biportal Thoracoscopic Sympathectomy for Hyperhidrosis: Experience with 300 Patients, was presented by Gregory Lekovic, MD, PhD, JD, 5:00 to 5:10 p.m. on Tuesday, April 17, 2007, during the 75th Annual Meeting of the American Association of Neurological Surgeons in Washington, D.C. Co-authors are Scott Wait, MD, Kathy J. Kenny, RN, MS, and Curtis A. Dickman, MD.
Advances in technology now enable sympathectomy surgery to be performed thorascopically, using a minimally invasive procedure in which a tiny fiberoptic camera and small surgical instruments are inserted through three small incisions (usually less than half an inch). The nerves that cause the excessive sweating are identified by the camera and then cut. After one side is completed, the identical procedure is performed on the opposite side.
In the 300 patients in this research study, the following outcomes were noted:
– Complete resolution of palmar and axillary hyperhidrosis was seen in 99.3 percent and 61 percent of patients, respectively.
– Serious intraoperative complications included two arrythmias (asystole requiring cardioversion in one patient, bradycardia that resolved without treatment or sequelae in one patient) and postoperative depression in one patient.
– Nine patients had postoperative pneumothorax ( accumulation of air or gas in the pleural cavity) , of which five required chest tube drainage.
– An additional four patients required prophylactic chest tube drainage due to pleural adhesions.
– Severe compensatory hyperhidrosis affected 16 patients. Compensatory hyperhidrosis is typically the most common side effect following surgery. Although patients may no longer sweat excessively in their hands, underarms and/or feet, they often will sweat more in another part of the body, such as the chest, back or legs .
– Seven patients developed Horner’s syndrome. Horner’s syndrome results from inadvertent damage to nerves above those that were cut. This can result in decreased facial sweating, drooping of the eyelid and decreased pupil size on the same side of the body where the nerves were inadvertently injured. Sometimes these symptoms are reversible over a period of weeks to months, but in other cases, may be permanent.
– Six patients were affected by intercostal neuralgia, which is pain caused by damage to the nerves located between the ribs.
"Thoracoscopic sympathectomy is an effective and low-morbidity treatment for patients suffering from severe palmar and axillary hyperhidrosis, in particular when other treatment options have not alleviated the symptoms," said Dr. Lekovic.
Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 6,800 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.

The Effect Of Male Circumcision On Sexuality

UroToday.com- There has been suggestion and debate about whether circumcision affects sexual sensation of the penis but there have been few relevant studies to examine this possible consequence of the procedure. South Korea has one of the highest circumcision rates in the world and most are not performed in the neonatal period. This allows a unique opportunity to examine the effect of adult circumcision on sexuality. A prospective study was performed to compare men who were circumcised or not, and to compare the sex lives of men before and after circumcision. The study, by D. Kim and M.G. Pang from Gyungki-Do Korea, is published in the March 2007 issue of BJU International.
The study included 373 sexually active men aged 30-57 years of whom 255 were circumcised (mean age 37.1 years) and 118 were not (mean age 38.2 years). Of the 255 circumcised men, 138 were sexually active before circumcision, and all were circumcised after the age of 20 years. To address the effects of circumcision on the quality of sex life, including masturbation, a modified Brief Male Sexual Function Inventory (BMSFI) which included additional questions about whether sex life and masturbatory pleasure had improved or worsened after circumcision.
Analysis of the results showed that there were no significant differences in sexual drive, erection, ejaculation and ejaculatory latency time between circumcised and uncircumcised men. Masturbatory pleasure decreased after circumcision in 48% of the respondents, while 8% reported increased pleasure. Masturbatory difficulty increased after circumcision in 63% of the respondents but it was easier in 37%. About 6% answered that their sex lives improved, while 20% reported a worse sex life after circumcision.
This study suggests that adult circumcision adversely affects sexual function in a significant number of men, and the authors suggest that it may be due to loss of nerve endings in the removed skin. In addition, there was an approximately 9% incidence of severe penile scarring or uncomfortable erections from curvature or tethering after circumcision.

New Tortillas Better For Dieters and Diabetics

People with dieting blues should try swapping white corn tortillas for blue. A recent study suggests that the coloured flatbreads are healthier, especially for diabetics and dieters, Sara Jensen reports in Chemistry & Industry, the magazine of the SCI.
Scientists in Mexico, home of the taco, found that tortillas made from blue corn had less starch and a lower glycæmic index than their white counter parts. They also found that the blue tortillas had 20% more protein than white (Journal of the Science of Food and Agriculture, DOI 10.1002/jsfa.3008).
The glycæmic index (GI) ranks carbohydrates according to their effects on blood glucose levels. Foods with a lower GI are considered healthier as they slowly release sugar into the bloodstream. This reduces fluctuations in our blood glucose and insulin levels, helping to maintain a steady supply of energy. Low GI foods are said to have long-term health benefits, reducing your risk of heart disease and diabetes as well as aiding and maintaining weight loss.
Juscelino Tovar, an author of the study, said that one important benefit of the lower GI blue tortillas is their potential role in preventing or controlling metabolic syndrome, a combination of disorders which increase the risk of heart disease, stroke and diabetes.
NB The blue colouring is due to the presence of anthocyanins in the corn. These are the same health promoting compounds found purple berries and red wine.
—————————-Article adapted by Medical News Today from original press release.—————————-
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Diabetes Ethnic Minorities Lose Out In The UK

Patients from ethnic minorities are not only more likely to suffer from diabetes, but also receive lower quality care from the National Health Service (NHS), claims a paper published in the online open access journal, International Journal for Equity in Health.
Michael Soljak, together with colleagues from Imperial College, London, UK, investigated the treatment received in 2002 by 21,343 diabetic patients in three North West London Primary Care Trusts (PCTs): Ealing, Hammersmith & Fulham, and Hounslow. The researchers also compared the patients’ general health, shown by factors such as blood pressure and cholesterol levels, and diabetes control, to the patients’ treatment.
General practitioners (GPs) were encouraged to record new patients’ ethnicity by providing training and support to the practices. Of the diabetic patients in the three PCTs, 70 percent had a valid ethnicity code, obtained through patient questionnaires and entered by practice staff.
The authors found that although diabetes control was worse among the South Asian population, a smaller proportion of South Asians were prescribed insulin. They also found that although the White population studied was older, blood pressure differences between the groups were small, indicating poorer control in non-White ethnic groups.
The poorer quality of care for Asian diabetic patients could be explained by patient factors- such as poor understanding of the disease - or by the standard of care their GPs offered. Institutional racism is unlikely to be a major cause, as many South Asian patients are registered with GPs from their own ethnic group.
“This study highlights the need to capture ethnicity data in clinical trials and in routine care, to specifically investigate the reasons for these ethnic differences. But we don’t just need to know more about both the practice and patient factors involved,” says Soljak, “there should be more intensive management of diabetes and education about the disease in South Asian patients. The best option would be trials comparing different types of such interventions. Our study also shows that in future these trials can be carried out using routinely collected clinical information.”
Ethnic inequalities in the management and outcome of diabetes in three English Primary Care TrustsMichael Soljak, Azeem Majeed, Joseph Eliahoo and Anne DornhorstInternational Journal for Equity in Healthhttp://www.equityhealthj.com/
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New Call For Research Proposals-Diabetes UK

We are calling for research proposals aimed at ‘Improving the day-to-day management of diabetes’.
This call is based on the results of the research priorities survey we conducted earlier this year, which was open to everyone and proved to be the biggest consultation we have ever run.
The new call for proposals has been approved by Diabetes UK’s Board of Trustees. They agreed that they should consider research that would change the ‘here and now’ aspects of diabetes and address quality of life issues.
Research themes included in this call for proposals include:
– prevention and avoidance of complications– prevention and treatment of diabetes using diet and exercise– refinement of existing technologies.
Diabetes UK will particularly welcome proposals in the area of prevention and avoidance of hypoglycaemia.
Diabetes UK will commit £6 million of funds raised over the next few years to support research to improve the day-to-day management of diabetes and is seeking to fund ambitious, innovative, multi-centre collaborative research programmes whose outcomes will make a huge difference to the daily lives of people with diabetes. No funding limit has been set for individual projects.
Applications will be assessed on:
– the potential of the research to make a real difference to the lives of people with diabetes– scientific excellence– calibre of the applicants– value for money.
Outline application forms and further particulars are available to download on the right.
Closing date for receipt of outline applications: 12 noon on Tuesday 4 September 2007.
http://www.diabetes.org.uk

World's Largest Diet-Cancer Study Confirms Current Advice On Alcohol

Experts at the American Institute for Cancer Research (AICR) welcomed the latest results from the world’s largest study on diet and cancer. The new results, published online at the International Journal of Cancer, link alcohol consumption to an increased risk of colon cancer.
According to the study, those participants who reported consuming three or more alcoholic drinks per day had a 26 percent higher lifetime risk of colon cancers than non-drinkers. Smaller increases in risk were observed among those whose alcohol consumption was as low as one drink per day, underscoring the fact that alcohol is a significant risk factor for colon cancer.
These results support AICR’s long-standing advice to limit alcohol consumption. The AICR guideline on alcohol reads: If alcohol is consumed at all, men should consume no more than two drinks per day and women no more than one.
To those members of the public concerned about how these results relate to studies showing that moderate consumption of alcohol benefits heart health, AICR offered some perspective.
“The key word is moderate,” said AICR Nutrition Advisor Karen Collins, MS, RD. “The heart benefits that have been associated with alcohol occur at relatively low levels of consumption - the levels specified in the AICR guidelines.
“When it comes to alcohol and overall health we know one thing for sure - more is not better,” Collins said.
The EPIC Study
The new results come from the largest study of diet and cancer ever undertaken. Called the European Prospective Investigation into Cancer and Nutrition, or EPIC, this ongoing cohort study is currently tracking the diets and disease rates of an unprecedented 521,483 individuals in 10 different European countries. Read more about the EPIC study, how it differs from US cohort studies, and why AICR experts believe it to be so authoritative, here.
Behind the Alcohol - Cancer Link
Alcohol has been linked to cancers of the colon and rectum for years, as well as several other cancers including those of the mouth and throat. Smokers who drink increase their risk of lung cancer significantly. Years of drinking can give rise to liver damage that leads to liver cancer. Alcohol as has also been designated a probable cause for breast cancer.
The reason for these links, experts say, has to do with the behavior of alcohol in the body. Alcohol is a pro-inflammatory, pro-oxidant substance. Sensitive tissues that are repeatedly exposed to it can get damaged in ways that spark the cancer process.
The breast cancer link seems to be a special case, however. Unlike other cancers associated with alcohol consumption, the cells of the breast are only indirectly exposed to alcohol. Yet the association keeps showing up, in study after study.
“The breast cancer link is particularly troubling and consistent, but its precise nature remains unclear,” said Collins. “We do know that a man’s body has more muscle and less fat than a woman’s, so it’s easier for him to dilute and metabolize the alcohol he drinks. Alcohol stays in a woman’s bloodstream longer, and that may be one reason that women who consume even one drink a day have a slightly higher risk of breast cancer compared to non-drinkers.”
Expert Report Will Help Dispel Confusion
On November 1st of this year, AICR and its international affiliate organizations will publish the most comprehensive assessment of the scientific literature on diet, physical activity and cancer risk ever undertaken.
That report, Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective, will synthesize data from thousands of studies like the EPIC study to provide guidelines for the public and for the scientific/medical community. It will provide answers to questions about nutrition and cancer that are based on a thorough review of the available science.
Find out more about the WCRF/AICR Expert Report here.
The American Institute for Cancer Research (AICR) is the cancer charity that fosters research on diet and cancer and educates the public about the results. It has contributed more than $82 million for innovative research conducted at universities, hospitals and research centers across the country. AICR also provides a wide range of educational programs to help millions of Americans learn to make dietary changes for lower cancer risk. Its award-winning New American Plate program is presented in brochures, seminars and on its website, http://www.aicr.org. AICR is a member of the World Cancer Research Fund International.

Eating Soon After A Tummy Tuck Can get Patients Out Of The Hospital Faster

The American Society for Aesthetic Plastic Surgery (ASAPS) announced that withholding oral intake of food in patients after abdominoplasty (”tummy tuck”) may not be necessary, and that feeding patients earlier could allow for quicker discharge after surgery. Findings from a study investigating the impact of early feeding after abdominoplasty on the occurrence of postoperative nausea and vomiting is published in the May/June 2007 issue of the Aesthetic Surgery Journal , the Society’s official peer-reviewed journal.
These findings are important because abdominoplasty is a popular cosmetic surgical procedure. According to the Aesthetic Society’s statistics abdominoplasty was the fourth most popular surgical procedure in 2006, with 172,457 procedures performed, an increase of 407% from 1997.
Postoperative nausea and vomiting (PONV) is among the most disagreeable experiences associated with surgery, causing dehydration and retching, which can lead to poor wound healing, among other adverse effects. While postoperative management of patients undergoing abdominoplasty has traditionally involved withholding food until patients demonstrate evidence of bowel activity, this practice requires patients to remain in the hospital for the administration of intravenous fluids to prevent dehydration. However, no literature exists to support this practice.
“This study demonstrates that early feeding of tummy tuck patients may prevent the need for postoperative hospital admission for intravenous hydration-at least in those patients who can maintain adequate hydration with oral intake alone-and allow for faster hospital discharge,” said Alan Matarasso, MD, a board-certified plastic surgeon in New York, NY, lead author of the study. “While there may be other reasons for admission, routine postoperative admission to prevent dehydration may not be necessary. These findings could change the way we care for our postoperative abdominoplasty patients, improving their comfort and safety, and saving on health care costs.”
The study consisted of a retrospective review of the medical records of 22 patients who underwent abdominoplasty, divided into two groups. Group I followed traditional guidelines for oral intake; members of Group II were allowed to consume a regular diet immediately after surgery. All other aspects of postoperative care remained the same. There was no statistical difference in PONV between the two groups.
Although the findings are promising, physicians remain cautiously optimistic about a full transition to ambulatory abdominoplasty.
“Although a number of abdominoplasties are performed as outpatients, for those patients in whom it is deemed necessary, for safety reasons, to undergo the procedure in a hospital this paper demonstrates that early feeding of patients undergoing abdominoplasty is possible. It does not diminish some of the benefits of postoperative hospital admission,” adds Foad Nahai, MD, Atlanta plastic surgeon, President of ASAPS and Associate Editor of ASJ . “Achievement of adequate pain control, maintenance of a semi-flexed position, and patient and surgeon preference are important variables to consider when choosing between admission and discharge.”

Addition of Folic Acid to bread assists the fight against DEPRESSION

A unique study by researchers at the University of York and Hull York Medical School has confirmed a link between depression and low levels of folate, a vitamin which comes from vegetables.
In research published in the July edition of the Journal of Epidemiology and Community Health, the York team led by Dr Simon Gilbody, concluded that there was a link between depression and low folate levels, following a review of 11 previous studies involving 15,315 participants.
Last month, the Food Standards Agency recommended to UK Health Ministers the introduction of mandatory fortification of either bread or flour with folic acid to prevent neural tube defects, which can result in miscarriage, neonatal death or lifelong disability. The York study suggests that the measure may also help in the fight against depression.
Dr Gilbody said: “Our study is unique in that for the first time all the relevant evidence in this controversial area has been brought together. Although the research does not prove that low folate causes depression, we can now be sure that the two are linked. Interestingly, there is also some trial evidence that suggests folic acid supplements can benefit people with depression. We recommend that large trials should be carried out to further test this suggestion.”
Recent research from the same team published in the American Journal of Epidemiology has also proved that people with depression commonly have a gene that means that they process folate less efficiently. Folate is linked to the production of some of the ‘feel good’ chemicals in the brain, such as serotonin. The identification of this gene provides a plausible explanation as to why folic acid supplements may help people with depression.

Legend and Myth- British

Legends of these half-human, half-fish humanoids have circulated for millennia, even as far back as 5,000 B.C.[1] It has been widely suggested or implied that manatees or dugongs could be behind the myth of the mermaid. An example supporting this theory would be that Christopher Columbus had logged that he had seen mermaids on his journey to the new world, but thought they would be more attractive. These large aquatic mammals are notable for the way in which they carry their young, cradled in their arms much as a human would carry a baby. It is possible that sailors seeing these unfamiliar beasts for the first time, would assume that they had in fact stumbled across some sort of humanoid species, and consequently spread their accounts of the sightings through their homelands on their return from voyages. It has even been posited that the traditional image of a mermaid with long flowing hair could be attributed to manatees breaking the ocean surface underneath patches of seaweed, and giving the unfamiliar observer the impression of having long hair. Sightings from first-hand witnesses generally describe mermaids who do not talk and have green or black hair.[1]

[edit] Ancient Near East
Tales of mermaids are nearly universal. The first known mermaid stories appeared in Assyria, ca. 1000 BC. Atargatis, the mother of Assyrian queen Semiramis, was a goddess who loved a mortal shepherd and in the process killed him. Ashamed, she jumped into a lake to take the form of a fish, but the waters would not conceal her divine nature. Thereafter, she took the form of a mermaid — human above the waist, fish below — though the earliest representations of Atargatis showed her as being a fish with a human head and legs, similar to the Babylonian Ea. The Greeks recognized Atargatis under the name Derketo, where she was often conflated with Aphrodite.
Prior to 546 BCE, the Milesian philosopher Anaximander proposed that mankind had sprung from an aquatic species of animal. He thought that humans, with their extended infancy, could not have survived early on. This idea does not appear to have survived Anaximander's death.
A popular Greek legend has Alexander the Great's sister, Thessalonike, turn into a mermaid after her death.[2] She lived, it was said, in the Aegean and when sailors would encounter her, she would ask them only one question: "Is Alexander the king alive?" (Greek: Ζει ο βασιλιάς Αλέξανδρος;), to which the correct answer would be "He lives and still rules" (Greek: Ζει και βασιλεύει). Any other answer would spur her into a rage, where she transformed into a Gorgon and meant doom for the ship and every sailor onboard.
Lucian of Samosata in Syria (2nd century CE) in De Dea Syria ("Concerning the Syrian Goddess") wrote of the Syrian temples he had visited:
"Among them - Now that is the traditional story among them concerning the temple. But other men swear that Semiramis of Babylonia, whose deeds are many in Asia, also founded this site, and not for Hera Atargatis but for her own Mother, whose name was Derketo"
"I saw the likeness of Derketo in Phoenicia, a strange marvel. It is woman for half its length, but the other half, from thighs to feet, stretched out in a fish's tail. But the image in the Holy City is entirely a woman, and the grounds for their account are not very clear. They consider fishes to be sacred, and they never eat them; and though they eat all other fowls, they do not eat the dove, for she is holy so they believe. And these things are done, they believe, because of Derketo and Semiramis, the first because Derketo has the shape of a fish, and the other because ultimately Semiramis turned into a dove. Well, I may grant that the temple was a work of Semiramis perhaps; but that it belongs to Derketo I do not believe in any way. For among the Egyptians, some people do not eat fish, and that is not done to honor Derketo."[3]

Allergic Reactions To Insulin Have Declined And CSII Could Reduce Them Further

A review of published research from the University of Liege, Belgium, reveals a decline in the number of people experiencing allergic reactions to insulin. This is largely due to better purification of animal insulin and the introduction of human recombinant insulin.
The review also looks forward to the arrival of newly designed molecules that mimic the action of insulin while avoiding triggering an allergic response. In addition new modes of drug delivery, such as continuous subcutaneous insulin infusion (CSII), may help, and early reports suggest that CSII can help people who have previously had an allergic reaction to insulin.
* In the 1950s and 1960s more than half of patients who used insulin experienced some form of allergic reaction. This has reduced considerably, but reports show that 0.1% to 3.0% of people still produce reactions that range from mild irritation to life-threatening incidents.
* Originally insulin was harvested from animals, and advanced purification now makes this safer to use.
* The gene for human insulin has been sequenced, and the sequence placed in bacteria. These modified organisms then produce the human insulin protein which can then be purified and used for therapy. Fewer people react to this ‘recombinant insulin’ because this is the human protein.
* Now that scientists know the gene sequence, the shape of the insulin molecule, and the shape of the active site of the molecule, they can start to redesign it. The idea is to create a molecule that retains the action of insulin, but does not excite the human immune response system. This way it will be active, but will not cause an allergic reaction.
* One potential reason for adverse reaction is that insulin is often injected in sudden doses. This gives unnaturally high peaks and troughs of the hormone. To avoid this variation, pumps have been developed that slowly infuse the hormone throughout the day. Early results on these pumps are promising.
“Our review shows just how much progress has been made in reducing allergic reactions to insulin, but more excitingly it shows that there are definite hopes of improving the situation even further,” says lead author Regis Radermecker, who works at the Division of Diabetes, Nutrition and Metabolic Disorders at the University of Liège, Belgium.

Reducing Insulin Signaling In The Brain Can Prolong Lifespan

One route to a long and healthy life may be establishing the right balance in insulin signaling between the brain and the rest of the body, according to new research from Children’s Hospital Boston. The study, published in the July 20 issue of Science, not only reinforces the value of exercising and eating in moderation, but also helps explain a paradox in longevity research.
Insulin sends a vital signal throughout the body telling cells to use sugar from the blood. But when cells become less sensitive to insulin, which often happens as we age and gain weight, the body must make more insulin to keep sugar under control and avoid type 2 diabetes. For a long time, clinicians and scientists thought that “more insulin was a good thing,” says Morris White, PhD, a Howard Hughes Medical Institute investigator in Children’s Division of Endocrinology, who led the new study. “But the increased insulin also gets into the brain, where it can be detrimental.”
Studies in the worm C. elegans and in fruit flies show that reducing insulin signaling lengthens lifespan. But in humans and rodents, reducing insulin signaling often causes diabetes. The view that insulin could reduce lifespan is difficult to reconcile with decades of clinical practice and scientific investigation to treat diabetes.
White suspected that the key to explaining this paradox and to maximizing both health and longevity is to reduce insulin signaling only in the brain. To test this idea, White’s team measured longevity and other characteristics in several groups of mice. In one group, they used a genetic trick to cut in half the amount of Irs2, a protein that carries the insulin signal inside the cell, in every cell of the body. Two other groups of mice were genetically engineered to have half, or nearly all, Irs2 removed only from the brain cells. Another group of normal mice served as controls.
“To our surprise, all of the engineered mice lived longer,” says Akiko Taguchi, PhD, first author of the study. Even more surprising, the mice lacking Irs2 only in the brain lived almost half a year longer than the normal mice an 18 percent increase in lifespan despite being overweight and having higher blood insulin levels, changes that usually reduce lifespan. These long-lived mice were more active in old age, retained youthful metabolic cycles (burning sugar by day and fat by night) and retained protective levels of anti-oxidant enzymes such as superoxide dismutase, which protect against oxidative stress, or “biological rusting,” in the brain and body.
The mice with normal brain Irs2 levels aged less gracefully they lost the metabolic rhythms of youth, became more sedentary, and had reduced anti-oxidant enzymes after meals, leaving them vulnerable to cellular damage. Such damage correlates with a host of age-related diseases such as atherosclerosis, Alzheimer’s disease and cancer, notes White.
White believes the study findings suggest a new approach to preventing diseases that shorten lifespan. “The engineered mice live longer because the diseases that kill them cancer, cardiovascular disease and others are being postponed by reducing insulin-like signaling in the brain,” he says, “regardless of how much insulin there is in the rest of the body.”
Drugs that regulate Irs2 signaling in the brain (but not elsewhere in the body) are one possible preventive strategy, but no such drug has yet been found. Targeted drugs will be important because Irs2 is needed in other tissues, particularly the pancreatic beta cells that produce insulin.

First Vaccine Against H5N1 Avian flu Approved in US

The Food and Drug Administration (FDA) announced yesterday the first approval in the US of a vaccine against H5N1 avian influenza for use with humans.
Commonly known as bird flu, the current deadly strain of the H5N1 avian virus is not spreading from human to human but only from birds to humans, as well as among birds themselves.
But should H5N1 mutate into a human to human version, this vaccine may give limited early protection until a more effective version can be developed that is more tailored to a pandemic strain.
Dr Andrew C. von Eschenbach, Commissioner of Food and Drugs, said that the threat of a pandemic is one of the most serious worldwide public health issues and that:
“The approval of this vaccine is an important step forward in our protection against a pandemic.”
The vaccine is made by sanofi pasteur, the vaccines division of the sanofi-aventis group, a global pharmaceutical company.
David Williams, president, chairman and chief executive officer of sanofi pasteur spoke of the company’s leadership as a responsible manufacturer of influenza vaccine and that:
“We will play a key role in helping safeguard human health if an influenza pandemic strikes. We look forward to continuing to work with the US government and others, to prepare for this crisis.”
The approval was based on a clinical trial by the National Institute of Allergy and Infectious Diseases that was completed in 2005.
During this trial the vaccine showed an effective immune response against H5N1 with mild side effects when given as two 90 ug/ml intramuscular injections, one month apart, in 103 healthy adults aged from 18 to 64 years.
The most common side effects found in the tral were: pain at the injection site, headache, general ill feeling and muscle pain.
45 per cent of the patients who received the trial dose developed an immune response likely to be sufficient to reduce their risk of contracting the virus. Although the remaining patients’ immune response was lower, it was still thought to be enough to give them some protection against the severity of the virus and reduce likelihood of hospitalization and death.
Meanwhile more information is being collected on the effect of the vaccine on other age groups.
The vaccine will be manufactured but not sold commercially in the US. It will be bought and stockpiled by the federal government for distribution by public health officials when needed.
H5N1 is one version of the influenza A virus commonly found in birds.
Unlike seasonal flu, which produces mild to serious symptoms in most people, H5N1 infection is far more severe and develops quickly, and commonly leads to pneumonia and multi-organ failure.
The US has seen no reported human cases of H5N1 infection, but nearly 300 people have been infected in other countries since 2003, more than half of whom have died.
At the moment H5N1 is primarily a disease of animals, with occasional transmission to humans, albeit with deadly consequences. But should it develop the ability to transmit from human to human, then people would have very little immunity and the ensuing global pandemic would be catastrophic with millions of deaths predicted.
“The timing and severity of an influenza pandemic is uncertain, but the danger remains very real,” said Dr Jesse L. Goodman, Director of FDA’s Center for Biologics Evaluation and Research.
“We are working closely with other government agencies, global partners and the vaccine industry to facilitate the development, licensure and availability of needed supplies of safe and effective vaccines to protect against the pandemic threat,” added Dr Goodman.

Bird flu in Germany

Germany has identified three more cases of the lethal H5N1 strain of bird flu in swan, bringing the total number of wild birds infected to nine, but authorities said they had not changed their risk assessment.The Friedrich Loeffler animal disease institute said the three swans were found near Leipzig in the eastern state of Saxony. Nine wild birds - eight swans and a Canada goose - had now been confirmed as H5N1 cases, it added.
“The new cases from Saxony do not change anything yet in our risk assessment,” Thomas Mettenleiter, president of the institute, said in a statement.
Six birds were confirmed at the weekend as infected with H5N1 after they were found in Nuremberg in south Germany and were examined as part of a national testing programme.
Authorities continued to investigate the Nuremberg outbreak, the first in Germany this year, but the Agriculture Ministry believes the incident could be isolated.
“Given the current finds, our experts are not yet able to judge whether there will be a more widespread epidemic of the disease similar to last year,” Mettenleiter said.
Further tests comparing the latest finds with viruses in Hungary and the Czech Republic should provide clues as to how the H5N1 strain entered Germany, he added.
Poultry farmers in the Nuremberg region have been ordered to confine all poultry to closed stalls. As of Saturday, a 21-day ban was imposed on bringing poultry or poultry products in or out of the area, which is now a quarantine zone.
Last year, some 13 European Union member states had confirmed cases of bird flu - Germany, Austria, Denmark, Italy, Greece, Britain, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, France and Hungary.
Bird flu has been spreading across southeast Asia, killing two people in Vietnam this month, the first deaths there since 2005.
Globally, the H5N1 virus has killed nearly 200 people out of over 300 known cases, according to the World Health Organisation. None of the victims were from Europe.

Alcoholics!!! Avoid Excess Physical and Psychological stress

* The hypothalamic-pituitary-adrenal (HPA) axis defends against stress, starvation and illnesses.
* A new study shows "stunned" adrenocorticotropic hormone (ACTH) and cortisol secretion among alcoholic patients, reflecting changes in the HPA axis.
* Scientists recommend that alcoholics avoid excessive stress - both physical and psychological - during early abstinence.
The hypothalamic-pituitary-adrenal (HPA) axis is a hormonal system that defends against stress, starvation and illnesses. New findings of alterations in adrenocorticotropic hormone (ACTH) and cortisol secretion in alcoholic patients, which reflect changes in the HPA axis, prompt recommendations that alcoholics avoid excessive stress - both physical and psychological - during early abstinence.
Results are published in the May issue of Alcoholism: Clinical & Experimental Research.
"The HPA axis provides the metabolic fuel for the reaction of the brain, muscles and heart against psychological and physical distress," said Vittorio Coiro, aggregate professor in internal medicine at the University of Parma, Italy. "In previous research, tests with psychological and physical challenging stimuli - such as operative traumata, hyperthermia, cold-pressor and public-speaking stress - have shown a deficient HPA reactivity in abstinent alcoholics. However, none of these studies has established a time course of HPA failure during abstinence or has shown the time needed for a possible recovery."
"The HPA axis is an exquisitely sensitive system triggered physiologically by a wide range of psychological and physical stressors," remarked Cristiana Di Gennaro, research doctor at the University of Parma. "A rise in plasma ACTH and cortisol are considered good markers of stress, in terms of both acute reaction and of chronic exposure to stressful situations. An impaired function of HPA axis is well known in alcoholics," she added, "and it has been suggested that a blunted HPA axis responsiveness plays a role in early alcohol relapse following detoxification in alcoholics."
Researchers recruited two groups of males: 10 recently abstinent alcoholics 33 to 45 years of age; and 10 age-matched healthy controls. All participants exercised on a bicycle ergometer for approximately 15 minutes to a workload gradually increased at three-minute intervals until exhaustion (considered a highly reproducible and reliable form of stress). The alcoholics were tested at three time points: four, six and eight weeks after alcohol withdrawal. The controls were tested only once.
Results indicate an only slight ACTH/cortisol response to physical exercise among alcoholics after four weeks of abstinence, returning to near-normal levels at eight weeks.
This means, said Coiro, that not only did his group establish a time course of HPA failure during abstinence, but they also found that physical exercise among abstinent alcoholics may not always be a good thing.
"Guidelines for recovery from alcoholism attribute an important role to physical activity and sport," he said. "Exercise is included in many rehabilitation programs, because it produces physical and emotional effects that benefit the alcohol-dependent subjects during early abstinence. However, in the absence of HPA reactivity, exercise until exhaustion may produce stressful deleterious effects, because alcohol-dependent subjects are more vulnerable to relapse during early abstinence."
"Given that the HPA axis remains ’stunned’ for at least one month from withdrawal, with a full functional recovery only after two months," said Di Gennaro, "caution is to be recommended for patients in rehabilitation programs that include stressful physical exercise. However, since physical activity has been found to be an important therapeutic tool for early alcohol-withdrawing patients, it should be included in treatment even during the first eight weeks of abstinence, albeit mild at the beginning, with a slight progressive increase of physical activity during the first and the second month of abstinence."
"From a research perspective," said Coiro, these results help us to understand entity and time of the effects of alcohol in the central nervous system as ACTH/cortisol measurements represent a ‘window’ through which we can evaluate alcohol damage in central nervous transmission. Practically speaking, guidelines for alcohol-rehabilitation programs should take into account these observations for a better programming of physical exercise and therapeutic follow up. Furthermore, readers should be aware of the increased vulnerability of alcohol-dependent subjects, particularly during the first two months of abstinence, when physical and psychological stress should be absolutely avoided."

Cancer Research Specialist And HSPH Professor Awarded Medal Of Honor From WHO Cancer Agency

Dimitrios Trichopoulos, Vincent L. Gregory Professor of Cancer Prevention at the Harvard School of Public Health (HSPH), was one of three recipients of a medal of honor from the International Agency for Research on Cancer (IARC), part of the World Health Organization. The award was presented at the IARC Headquarters in Lyon, France.
Trichopoulos has conducted seminal work linking passive or “second-hand” smoking to lung cancer. He has also shed light on a host of other health issues, including the role of the Mediterranean diet in decreasing cancer and heart disease risk and increasing longevity. His current main research interest is the evaluation of the hypothesis that hormone-dependent breast cancers have their origin in intrauterine life.
The other two recipients of medals of honor this year were Mariano Barbacid, Director of the Spanish National Cancer Research Center, and Nancy Brinker, founder of The Susan G. Komen Foundation.

10,000 Americans Striding To Raise Funds For Lung Cancer Research

In a grassroots effort that has grown by 5,000% in four years, more than 10,000 individuals over 30 days across 12 states will be striding toward a cure for lung cancer this Fall. Benefiting LUNGevity Foundation, these 20,000 feet are walking and running to raise money for innovative research in the diagnosis, treatment, and cure of the nation’s number one cancer killer.
LUNGevity’s first walk occurred in 2004 in New Jersey, attracted 75 walkers, and raised $30,000. This year, LUNGevity anticipates that 45 events, which include walks, 5K runs, and marathons, will raise $1.2 million.
LUNGevity Foundation is the nation’s leading private supporter of lung cancer research. Since its inception in 2001 by seven lung cancer survivors, LUNGevity has committed more than $3.7 million to lung cancer research.
The LUNGevity events are organized by volunteers, most of whom are either lung cancer survivors or have had family members affected by the disease. The LUNGevity staff provides support for event coordinators and participants, and produces its own events in its hometown of Chicago.
“We get calls every day from people who are interested in walking to support lung cancer research,” said Beth Ida Stern, Executive Director of LUNGevity. “People are literally walking to save their own lives.”
In 2007, an estimated 213,380 people will be newly diagnosed with lung cancer, and an estimated 160,390 people will die of the disease. Lung cancer kills more people each year than breast, prostate, colorectal, and pancreatic cancers combined. And it receives far less than any of those cancers individually.
For more information about LUNGevity’s events calendar, medical research, or support for the lung cancer community, visit http://www.lungevity.org.
About the LUNGevity Foundation:
As the pioneer organization dedicated to funding lung cancer research, LUNGevity Foundation is the leading private provider of research funding for the nation’s number one cancer killer. The Foundation’s goal is to save the lives of the 213,000 Americans newly diagnosed with lung cancer each year, 85 percent of whom will die within five years without the development of new treatment methods. Partnering with the foremost physicians and research scientists in the world, the LUNGevity Foundation funds innovative research designed to treat and cure lung cancer.

Avastin Receives Positive Opinion In Europe For First-line Treatment Of Patients With Advanced Lung Cancer

Roche announced today that the European Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for the first-line use of Avastin in the treatment of the most common form of lung cancer, in combination with platinum based chemotherapy. The CHMP’s decision is based on data from the pivotal US (E4599) study and another phase III Avastin in Lung (AVAiL) study which together demonstrate that Avastin is effective in combination with a broad chemotherapy range.
Lung cancer is responsible for over 3,000 deaths per day worldwide1 and non-small cell lung cancer (NSCLC) is the most common form of the disease accounting for more than 80 percent of all lung cancers.2 Avastin is the only first-line treatment in over a decade that has been shown to extend the life of patients with advanced lung cancer in a disease for which patients typically have an average life expectancy of only 8 to 10 months.
“This is a significant day for healthcare professionals and patients as it brings access to Avastin, with its proven ability to extend life in an extremely difficult to treat disease, one step closer to reality” said Professor Christian Manegold, Professor of Medicine, Heidelberg University, University Medical Center, Mannheim, Germany and Principal Investigator of the AVAiL study. “I believe that Avastin is such an innovative treatment that it will change not only the current standard of care in NSCLC, but it will also re-write our expectations for patient outcomes.”
Avastin is the first and only anti-angiogenic agent which has been shown to consistently deliver improved overall and/or progression-free survival for colorectal, lung, breast, and kidney cancer patients.
“The CHMP opinion is encouraging news for European patients fighting a particularly aggressive and debilitating disease,” said William M. Burns, CEO Pharmaceuticals Division of Roche. “With our Avastin development program - the biggest trial program in oncology ever we will continue to develop the best possible treatment approaches to increase survival and improve quality of life of cancer patients.”
In Europe, Avastin was approved in January 2005 and in the US in February 2004 for first-line treatment of patients with metastatic colorectal cancer. It received another approval in the US in June 2006 as a second-line treatment for patients with metastatic colorectal cancer. In October 2006, following priority review, the world’s first angiogenesis inhibitor was approved by the FDA for the treatment of NSCLC). Most recently in April 2007, Avastin was approved in Europe for the first line treatment of women with metastatic breast cancer and in Japan for use in advanced or recurrent colorectal cancer.
About the Phase III studies that formed part of the data pack submitted to the CHMP
E4599 study
The results of the randomised, controlled, multicentre phase III E4599 study of 878 patients with locally advanced, metastatic or recurrent NSCLC, with histology other than predominant squamous cell, show that median survival of patients treated with Avastin at a dose of 15 mg/kg every three weeks plus chemotherapy was 12.3 months, compared to 10.3 months for patients treated with chemotherapy alone. Patients receiving Avastin at a dose of 15 mg/kg every three weeks plus paclitaxel and carboplatin had an approximate 27 percent improvement in overall survival, compared to patients who received chemotherapy alone. Side effects were generally manageable. Pulmonary haemorrhage (haemoptysis) cases were observed in 1.9% of the patients receiving Avastin plus chemotherapy. The most common adverse events associated with Avastin monotherapy were: hypertension (5.6%), proteinuria (4.2%), fatigue (5.1%) and dyspnoea (5.6%).3
AVAiL study
In the double-blind, randomised, controlled, phase III AVAiL study, patients received treatment with either Avastin at 7.5mg/kg or 15mg/kg + cisplatin/gemcitabine or placebo + cisplatin/gemcitabine. The study involved more than 1,000 patients world-wide with previously untreated advanced NSCLC, with histology other than predominant squamous cell. The results show that by adding Avastin to a cisplatin/gemcitabine regimen progression-free survival was significantly prolonged by 20 30% compared with chemotherapy alone. No new or unexpected adverse events were observed.
About Lung Cancer
According to the World Health Organization (WHO), lung cancer is the leading cause of cancer-related deaths in both men and women,4 responsible for 19.7 percent of all cancer deaths.5 Lung cancer is the single biggest cancer killer in Europe, claiming 334,800 lives in 2006.5 World-wide, there are more than 1.2 million new cases of lung and bronchial cancer diagnosed each year,4 and new treatment options are urgently needed as the disease has a very high mortality rate. The majority of NSCLC cases are still diagnosed at an advanced stage when the cancer is inoperable or has already spread to another part of the body. In spite of the use of chemotherapy as the first-line treatment option, less than five percent of people with advanced NSCLC survive for five years after diagnosis and most die within twelve months.2
About Avastin
Avastin is the first treatment that inhibits angiogenesis the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. Avastin targets a naturally occurring protein called VEGF (Vascular Endothelial Growth Factor), a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth of the tumour and its spread throughout the body (metastasis).
Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Avastin in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma, and others) and different settings (advanced and adjuvant i.e. post-operation). The total development programme is expected to include over 40,000 patients world-wide.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet at http://www.roche.com.
References
1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality,and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006; 24(14): 2137?”50.
2. Wilking N and Jonsson B. A Pan-European comparison regarding patient access to cancer drugs. Karolinska Institute in collaboration with Stockholm School of Economics, Stockholm, Sweden, 2005.
3. Sandler A et al. Paclitaxel-Carboplatin Alone or with Bevacizumab for Non-Small-Cell Lung Cancer. New England Journal of Medicine 2006; 355:2542-50.
4. Stewart BW and Kleihues P. World Cancer Report. IARC Press, Lyon, pp.183-7, 2003
5. Ferlay J, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Annals of Oncology. 2007; 18: 581-92.

Avastin Receives Positive Opinion In Europe For First-line Treatment Of Patients With Advanced Lung Cancer

Roche announced today that the European Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for the first-line use of Avastin in the treatment of the most common form of lung cancer, in combination with platinum based chemotherapy. The CHMP’s decision is based on data from the pivotal US (E4599) study and another phase III Avastin in Lung (AVAiL) study which together demonstrate that Avastin is effective in combination with a broad chemotherapy range.
Lung cancer is responsible for over 3,000 deaths per day worldwide1 and non-small cell lung cancer (NSCLC) is the most common form of the disease accounting for more than 80 percent of all lung cancers.2 Avastin is the only first-line treatment in over a decade that has been shown to extend the life of patients with advanced lung cancer in a disease for which patients typically have an average life expectancy of only 8 to 10 months.
“This is a significant day for healthcare professionals and patients as it brings access to Avastin, with its proven ability to extend life in an extremely difficult to treat disease, one step closer to reality” said Professor Christian Manegold, Professor of Medicine, Heidelberg University, University Medical Center, Mannheim, Germany and Principal Investigator of the AVAiL study. “I believe that Avastin is such an innovative treatment that it will change not only the current standard of care in NSCLC, but it will also re-write our expectations for patient outcomes.”
Avastin is the first and only anti-angiogenic agent which has been shown to consistently deliver improved overall and/or progression-free survival for colorectal, lung, breast, and kidney cancer patients.
“The CHMP opinion is encouraging news for European patients fighting a particularly aggressive and debilitating disease,” said William M. Burns, CEO Pharmaceuticals Division of Roche. “With our Avastin development program - the biggest trial program in oncology ever we will continue to develop the best possible treatment approaches to increase survival and improve quality of life of cancer patients.”
In Europe, Avastin was approved in January 2005 and in the US in February 2004 for first-line treatment of patients with metastatic colorectal cancer. It received another approval in the US in June 2006 as a second-line treatment for patients with metastatic colorectal cancer. In October 2006, following priority review, the world’s first angiogenesis inhibitor was approved by the FDA for the treatment of NSCLC). Most recently in April 2007, Avastin was approved in Europe for the first line treatment of women with metastatic breast cancer and in Japan for use in advanced or recurrent colorectal cancer.
About the Phase III studies that formed part of the data pack submitted to the CHMP
E4599 study
The results of the randomised, controlled, multicentre phase III E4599 study of 878 patients with locally advanced, metastatic or recurrent NSCLC, with histology other than predominant squamous cell, show that median survival of patients treated with Avastin at a dose of 15 mg/kg every three weeks plus chemotherapy was 12.3 months, compared to 10.3 months for patients treated with chemotherapy alone. Patients receiving Avastin at a dose of 15 mg/kg every three weeks plus paclitaxel and carboplatin had an approximate 27 percent improvement in overall survival, compared to patients who received chemotherapy alone. Side effects were generally manageable. Pulmonary haemorrhage (haemoptysis) cases were observed in 1.9% of the patients receiving Avastin plus chemotherapy. The most common adverse events associated with Avastin monotherapy were: hypertension (5.6%), proteinuria (4.2%), fatigue (5.1%) and dyspnoea (5.6%).3
AVAiL study
In the double-blind, randomised, controlled, phase III AVAiL study, patients received treatment with either Avastin at 7.5mg/kg or 15mg/kg + cisplatin/gemcitabine or placebo + cisplatin/gemcitabine. The study involved more than 1,000 patients world-wide with previously untreated advanced NSCLC, with histology other than predominant squamous cell. The results show that by adding Avastin to a cisplatin/gemcitabine regimen progression-free survival was significantly prolonged by 20 30% compared with chemotherapy alone. No new or unexpected adverse events were observed.
About Lung Cancer
According to the World Health Organization (WHO), lung cancer is the leading cause of cancer-related deaths in both men and women,4 responsible for 19.7 percent of all cancer deaths.5 Lung cancer is the single biggest cancer killer in Europe, claiming 334,800 lives in 2006.5 World-wide, there are more than 1.2 million new cases of lung and bronchial cancer diagnosed each year,4 and new treatment options are urgently needed as the disease has a very high mortality rate. The majority of NSCLC cases are still diagnosed at an advanced stage when the cancer is inoperable or has already spread to another part of the body. In spite of the use of chemotherapy as the first-line treatment option, less than five percent of people with advanced NSCLC survive for five years after diagnosis and most die within twelve months.2
About Avastin
Avastin is the first treatment that inhibits angiogenesis the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. Avastin targets a naturally occurring protein called VEGF (Vascular Endothelial Growth Factor), a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth of the tumour and its spread throughout the body (metastasis).
Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Avastin in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma, and others) and different settings (advanced and adjuvant i.e. post-operation). The total development programme is expected to include over 40,000 patients world-wide.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet at http://www.roche.com.
References
1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality,and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006; 24(14): 2137?”50.
2. Wilking N and Jonsson B. A Pan-European comparison regarding patient access to cancer drugs. Karolinska Institute in collaboration with Stockholm School of Economics, Stockholm, Sweden, 2005.
3. Sandler A et al. Paclitaxel-Carboplatin Alone or with Bevacizumab for Non-Small-Cell Lung Cancer. New England Journal of Medicine 2006; 355:2542-50.
4. Stewart BW and Kleihues P. World Cancer Report. IARC Press, Lyon, pp.183-7, 2003
5. Ferlay J, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Annals of Oncology. 2007; 18: 581-92.