Scientists at the Moores Cancer Center at the University of California, San Diego, Stanford University School of Medicine and other centers have identified a mechanism by which a chronic form of leukemia can progress into a deadlier stage of the disease. The findings may provide physicians with an indicator of when this type of cancer – chronic myeloid leukemia (CML) – is progressing, enabling them to make more accurate prognoses for the disease and improved treatment choices.

“If we can predict when a patient is moving from the chronic phase in CML to the blast crisis stage, then we can hopefully intervene before it’s too late,” said Catriona H.M. Jamieson, MD, PhD, assistant professor of medicine at the UC San Diego School of Medicine and Director for Stem Cell Research at the Moores UCSD Cancer Center.

The findings, reported online during the week of February 16, 2009 in the Proceedings of the National Academy of Sciences, also shed light on the development of potentially treatment-resistant leukemia stem cells and provide insights for new strategies against CML and other cancers.

Led by Jamieson and Irving Weissman, MD, director of the Stem Cell Biology and Regenerative Medicine Institute at the Stanford University School of Medicine, the researchers discovered that when a molecular off-switch called glycogen synthase kinase (GSK) 3 beta becomes faulty in chronic stage CML cells, it fails to turn off another protein, beta-catenin. This in turn enables pre-leukemia stem cells to develop into leukemia stem cells and expand their numbers, leading to progression to the more dangerous “blast crisis” stage of CML. This errant off-switch is a potential therapeutic target, Jamieson explained.

“This paper further underscores the importance of the cell type and specific context of molecular events in the evolution of leukemia,” Jamieson said. “It also highlights the malignant consequences of GSK 3 beta deregulation.”

“This knowledge may enable us to design and develop more effective, personalized therapies for these patients,” said staff research associate and co-first author Annelie Abrahamsson.

In CML, an enzyme called ABL goes in overdrive because of a chromosomal mix-up that occurs during blood cell development. The genes ABL and BCR fuse and produce a hybrid BCR-ABL enzyme that drives the excessive proliferation of white blood cells. CML progresses from a chronic stage in hematopoietic stem cells that carry BCR-ABL to the blast crisis stage. This stage is characterized by the over-production of beta-catenin in white blood cells called granulocyte macrophage progenitors (GMP) – in effect, leukemia stem cells.

According to Jamieson, a major roadblock in predicting and stopping the conversion of chronic CML to blast crisis stage was the failure to understand what turned on beta-catenin. The team showed that by injecting blast crisis CML progenitor cells – GMP – into mice lacking working immune systems, they could “transplant” leukemia into the animals. When they did this, they discovered that GSK 3 beta levels dropped. Looking more closely, they found an aberrant “misspliced” form of GSK 3 beta that was unable to turn off beta-catenin, suggesting a potential mechanism behind the change to blast crisis stage.

The scientists also showed that the mice that had received the cells with the bad form of GSK 3 beta developed granulocytic sarcomas, tumors that are seen in patients with the most advanced form of CML.

“Many investigators have questioned the usefulness of finding and purifying leukemia and cancer stem cells,” said Weissman. “This paper shows why. The damage to the enzyme GSK 3 beta that prevents beta-catenin activation of cell proliferation occurs only in the GMP leukemia stem cells, which are only about 1 in 20 bone marrow cells. Trying to analyze the missplicing of GSK in the whole leukemia would not have worked.

“These kinds of changes in gene expression, which are not mutations, need pure cells to find them. The final proof of the cancer stem cell hypothesis will be to show whether a treatment specific for the changed gene expression eliminates the cancer in the patient.”

“Downregulating beta-catenin and GSK deregulation may have other implications in many cancers,” Jamieson said. “By studying CML, we can understand the molecular evolution of disease and the stepwise progression to cancer. It becomes a useful paradigm for understanding how cancers evolve and the pathways that are essential to escape the normal control mechanisms.”

###

Other authors include: Ifat Geron, Kim-Hien Dao, DO, PhD, Charlene Barroga, PhD, Isabel Newton, MD, PhD, UCSD; Jason Gotlib, MD, Remi Creusot, PhD, Mobin Karimi, PhD, Carol Jones, PhD, James Zehnder, MD, PhD, Robert Negrin, MD, Institute of Stem Cell Biology and Regenerative Medicine, Stanford; Francis Giles, MD, University of Texas Health Science Center, San Antonio; Jeffrey Durocher, PhD, Transgenomic Inc., Gaithersberg, MD; and Armand Keating, MD, Princess Margaret Hospital, Toronto. Much of the work received funding from the National Institutes of Health, the California Institute of Regenerative Medicine and the Moores UCSD Cancer Center.

The Moores UCSD Cancer Center is one of the nation’s 41 National Cancer Institute-designated Comprehensive Cancer Centers, combining research, clinical care and community outreach to advance the prevention, treatment and cure of cancer.

Source: Steve Benowitz

University of California – San Diego

With just three weeks to go before the first anniversary of bluetongue being detected in England the JAB campaign group is urging farmers to vaccinate their livestock to stop the disease from taking hold in this country as it has in Europe.

So far this year France has reported 4,543 cases of bluetongue, including cases in Calais, and the Netherlands has just confirmed its first case of the disease in 2008. The affected small holding reported a sick cow found with serotype eight which had not been vaccinated against infection.

With the threat of bluetongue re-emergence in the UK growing by the day, JAB leaders have issued a reminder to farmers to contact their vets as soon as their region is in the protection zone and vaccine is available.

In a statement JAB said: “The amount of cases being reported across Europe shows the disease is on the move. This most recent case in Holland demonstrates that not vaccinating livestock leaves farmers vulnerable to outbreaks now the midge season has started.

“The industry has rallied behind the JAB campaign and has done tremendously well in terms of vaccination. Nearly 19 million doses have already been made available to English farmers, and with another nine million doses planned to be released in the coming weeks we need those areas that are new to the protection zone to vaccinate as soon as they are able. We must remember bluetongue could already be circulating in areas where outbreaks occurred last year so the risks to everyone are very real.

“The explosion in the number of cases on the continent also acts as a timely reminder to those farmers in the current protection zone who have not vaccinated and the dangers this presents to their unprotected livestock

“We are entering the peak period for midge activity so vaccination is the only way to prepare and protect us from any potential outbreaks that may emerge in the coming weeks.”

Notes

1. The bluetongue protection zone was extended on Monday August 11 to cover the counties of Durham and Tyne and Wear (Metropolitan Boroughs of Newcastle Upon Tyne, North Tyneside, Gateshead, South Tyneside and Sunderland) and the Unitary Authorities of Hartlepool, Darlington, Stockton-on-Tees, Middlesbrough, and Redcar and Cleveland.

2. JAB members include: NFU, National Sheep Association, National Beef Association, British Meat Processors Association , Livestock Auctioneers Association, Royal Association of British Dairy Farmers, British Veterinary Association , Country Land and Business Association, Tenant Farmers Association, Association of Independent Meat Suppliers, Dairy UK, British Cattle Veterinary Association, the Sheep Veterinary Society, the Rare Breed Survival Trust, British Alpaca Society, British Llama Society, British Wool Marketing Board, British Simmental Society, English Beef and Lamb Executive and the Sheep Centre.

NFU

UroToday – Stone disease in children seems to be on the rise since I started as a pediatric urologist. The number of children we first saw in one year, I am seeing on a monthly basis.

The latest scare has been in China with melamine-induced kidney stones. Doctors in China have gained a vast experience in childhood stone disease diagnosis and management through screening and treating childhood urinary stones thought to be induced by melamine-tainted formula.

In their review of earlier reports on animals along with recent experiences with children, they concluded that there was no evidence, either from animal experiments or from humans, to support the direct toxicity of melamine on the kidney, although a feasible follow-up and assessment might be needed.

It would be critical in my opinion to evaluate these children from a metabolic standpoint as well. Stones typically are multifactorial and all risk factors must be delineated so that recurrent epsiodes can be prevented as much as possible.

Ding J

Kidney Int. 2009 Feb 25. Epub ahead of print.
doi:10.1038/ki.2009.30

UroToday Medical Editor Pasquale Casale, MD

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
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Copyright © 2009 – UroToday

Ever since an ordinary office inkjet printer had its ink cartridges swapped out for a cargo of cells about 10 years ago and sprayed out cell-packed droplets to create living tissue, scientists and engineers have never looked at office equipment in quite the same way. They dream of using a specialized bio-inkjet printer to grow new body parts for organ transplants or tissues for making regenerative medicine repairs to ailing bodies. Both these new therapies begin with a carefully printed mass of embryonic stem cells. And now there’s progress on getting that initial mass of stem cells printed.

By extending his pioneering acoustical work that applied sound waves to generate droplets from fluids, Dr. Utkan Demirci and his team at Harvard Medical School’s (Brigham and Women’s Hospital) Bio-Acoustic Mems in Medicine Laboratory report encouraging preliminary results at an early and crucial point in a stem cell’s career known as embroid body formation. Their research results appear in the journal Biomicrofluids, published by the American Institute of Physics.

Getting the embroid body formed correctly and without mechanical trauma is key to preserving the stem cells’ astounding ability to develop into any desired tissue. Their new automated bioprinting approach appears to do this better than manual pipetting in the “hang-drop” method traditionally used.

“To have the capability to manipulate cells in a high-throughput environment reliably and repeatedly, whether it is a single cell or tens of thousands of cells in a single droplet, has the potential to enable potential solutions to many problems in medicine and engineering,” Notes Dr. Demirci.

Three research results stand out:
Enhanced uniformity of size and ability to control droplet size. These are key variables because they determine how the embroid bodies will grow.
Achieving a scalable system that can print one cell or tens of thousands per droplet – a level of precise manipulation not previously available.
Faster droplet formation. The new system delivers 160 droplets/seconds, versus 10 minutes for the hang-drop method.

The next step involves assessing the two methods to compare their effects on cell function. Says Dr. Demirci: “We are eager to take it to the next level.”

The article, “Embryonic stem cell bioprinting for uniform and controlled size embryoid body formation,” by Feng Xu, Banupriya Sridharan, SuiQi Wang, Umut Gurkan, Brian Syverud, and Utkan Demirci, appears in the journal Biomicrofluidics.

Source:
Charles E. Blue

American Institute of Physics

Former New Jersey Assemblyman Francis Bodine was surprised and delighted when his radiotherapy treatment sessions for prostate cancer went from about 20 minutes each day to less than five. Midway through his course of treatment, doctors at the Delaware Valley Urology Cancer Center acquired the region’s first RapidArc® radiotherapy technology from Varian Medical Systems (NYSE: VAR), making it possible for them to deliver advanced intensity-modulated radiotherapy (IMRT) treatments two to eight times faster than was previously possible

At the time Bodine’s treatments began, his doctor was using what was then the state-of-the-art for IMRT–an advanced form of treatment that shapes the beam to match the shape of the tumor and minimizes exposure of surrounding healthy tissues.

“I knew exactly how long my treatments were taking, because I was counting the seconds,” Bodine says. “The machine rotated around me and stopped at seven different positions. The time it took to rotate and deliver the radiation from each angle was about 3 minutes and sometimes a few seconds more, so I had to hold still for quite a long time.”

When he was switched to RapidArc radiotherapy, the actual treatment time once he was in position, went down to about 80 seconds, Bodine says. “The machine would rotate around my body without stopping at all. It was so quick, it took more time for me to get undressed and go into the room than it did for the actual treatments.”

“RapidArc® technology enables us to deliver highly-precise IMRT treatment much faster than was previously possible with earlier technology,” says Steven J. DiBiase, MD, chief of radiation oncology services at the Center and clinical associate professor, Robert Wood Johnson School of Medicine. “RapidArc treatments deliver the dose during one continuous arc around the patient. It also uses fewer monitor units–that’s a measure of the amount of radiation being emitted–to complete a treatment. That means there is less low-dose spillage being scattered to other parts of the body.”

Faster treatments confer another potential benefit for the treatment of prostate cancer. “Speed has the potential to increase accuracy,” says Dr. DiBiase. “Prostate tumors can move within the body during longer treatments, due to natural processes like the bladder filling. With RapidArc, the chance of tumor motion during treatment is reduced.”

Bodine chose radiotherapy for prostate cancer because he wanted the least invasive treatment option. “I looked at everything–radical surgery, laparoscopic surgery, seed implants, radiation. I talked with about 15 of my friends who had been through this, and everyone had made a different choice. But I decided on this procedure because I felt it was the least invasive. Normally in the winter, we go away, but I said, ‘Let’s just take care of this.’ I concluded my treatments in March, and 3 months later, my PSA had dropped from 3.9 to 0.5. Three months after that, it dropped again, to 0.3.”

Bodine reports that he suffered few side effects–an outcome that is consistent with many published studies of IMRT in the treatment of prostate cancer (see select examples below). “I did not have problems with urination, no bleeding or leakage. The only side effect was that I was a little tired in the afternoons during my treatments. This summer, my wife and I traveled to Macinaw Island in Michigan. Now we are making plans for traveling this winter. We’ll go to Newport, Rhode Island to see family, and we’re still deciding what to see in January, February, March. We’re very busy, my wife and I, doing the things we missed out on because of the demands of my career and elected office for so many years. I plan to be around for many years to come.”

The American Cancer Society’s most recent estimates show that, in 2008 there were 192,280 new cases of prostate cancer in the United States, with over 6,000 of those occurring in the state of New Jersey.

Source
Varian Medical Systems

Scorching summer temperatures across much of the nation (USA) this month, including record-breaking highs, have prompted a University of North Carolina injury expert to issue a special warning about football players as practice for the 2005 season gets underway.

“Football practice is beginning around the country, and the weather is just brutal in many states,” said Dr. Frederick Mueller, professor and chair of exercise and sport science in UNC’s College of Arts and Sciences. “Coaches, players, parents and others need to take extra precautions to prevent heatstroke and heatstroke deaths.”

In 2002 and 2003, no heatstroke deaths occurred among U.S. football players, but last year, there were three, Mueller said.

“Players die from hidden medical conditions and from freakish accidents just about every year, but no athlete should ever die from getting too hot during practice or games,” he said. “Such tragedies are 100 percent preventable.”

Twenty-four healthy players have died needlessly from heatstroke since 1995, an average of two and half a year, Mueller said.

“Players should get all the water they want in practice and have frequent cooling-off breaks,” he said. “Shorter practices and non-contact drills during which players don’t wear helmets can help prevent heatstroke and also reduce accidents.”

Coaches and trainers need to keep a close watch on temperatures and humidity, especially in August and September. Practices should be held early or late in the day, and if it’s too hot, coaches need to consider canceling them for a day or so until temperatures and humidity drop.

“Players should be encouraged to tell coaches or trainers if they don’t feel good,” Mueller said. “They should never be made to feel weak if they have trouble. Although many coaches used to do that and thought it was the right thing, now we understand that can be disastrous.”

Mueller, chairman of the American Football Coaches’ Committee of Football Injuries, directs the UNC-based National Center for Catastrophic Sports Injuries. Each year, the center produces reports on deaths and severe injuries from amateur and professional sports. The goal is to make football and other sports safer, he said.

Reports are based partly on newspaper stories from around the United States collected and submitted by about 150 volunteers who monitor sports accidents, along with information from the National Collegiate Athletic Association and the National Federation of State High School Associations.

Four high school and one youth league players died from injuries suffered on the playing field during 2004, including four from head injuries, Mueller said. Another 10 deaths resulted from “indirect” causes such as heatstroke, heart conditions, sickle cell disease and lightning. The cause of three could not be undetermined.

“Besides heatstroke, another growing concern was the rise last year in the number of catastrophic injuries involving some kind of permanent paralysis,” he said. “Last year, there were 12, mostly among high school players, and that was the first year since 1990 that there were more than 10.”

Coaches need to remind players often that the head has no place in football, he said. No one should make first contact with his — or her — head when blocking and tackling. That’s against the rules, but more importantly, it’s dangerous.

Between 1960 and 2003, 101 players died from heatstroke, Mueller said. Eight players died from heatstroke in 1970 alone, the highest one-year total. Before 1955, no heatstroke deaths were recorded among football players. Few schools and homes could afford air-conditioning, and it was likely players were better acclimated to hot weather.

That 36 young men died in 1968 as a direct result of football injuries shows how much safer the game has become through rule, equipment, medical and coaching changes that came about in part because of data Mueller and others collected. No such deaths occurred in 1990. A Yale University faculty member began the yearly football death and injury survey in 1931. It moved to Purdue University in 1942 and has been at UNC since 1965. The American Football Coaches Association, the National Collegiate Athletic Association and the National Federation of State High School Associations sponsor the national study.

About 1.5 million junior high school and high school students play football in the United States each year. Colleges and universities field about 75,000 players.

More details about the 2004 season are available at unc.edu//depts/nccsi

Note: Mueller can be reached at (919) 962-5171.

UNC News Services contact: David Williamson, (919) 962-8596

By DAVID WILLIAMSON
UNC News Services
rdtokidsemail.unc.edu
919-962-8596
University of North Carolina at Chapel Hill
unc.edu

Early secondary prevention with Aggrenox® (extended-release dipyridamole [200 mg] plus ASA [25mg]) is at least as effective and safe as initial treatment with ASA 100 mg alone after an ischaemic stroke or transient ischaemic attack (TIA). Results from the EARLY1 study, presented for the first time at the 13th Congress of the European Federation of Neurological Societies in Florence on 15 September 2009, showed that while functional outcome at 3 months was similar between the two treatment groups there were numerically fewer recurrent ischaemic events in patients who received Aggrenox® from the first day after their ischaemic event compared to those patients who received ASA as initial therapy.

“Guidelines recommend administration of ASA as the gold standard for early secondary prevention after ischaemic stroke,” explained Professor Reinhard Dengler, Director of the Neurology Clinic at the Hannover Medical School and Coordinating Investigator of EARLY. “We now have scientifically-based experience with early administration of extended-release dipyridamole plus ASA. EARLY is the first study to have investigated this in a prospective manner.”

EARLY involved more than 250 investigators from 46 stroke units across Germany, who enrolled and treated 543 patients within 24 hours of an ischaemic event. The study is based on the PROBE (prospective, randomized, open-label to treatment blinded to endpoint) design and had two treatment arms:

– 283 patients received Aggrenox® (extended-release dipyridamole [200 mg] plus ASA [25mg]) twice daily from day 1 to day 90 after an ischaemic stroke or TIA

– 260 patients received ASA 100 mg once daily between days one and seven, followed by Aggrenox® (extended-release dipyridamole [200 mg] plus ASA [25mg]) twice daily between days 8 and 90.

The primary efficacy outcome (severity of disability) was measured 90 days after the ischaemic event based on a blinded telephone assessment using the Modified Rankin Scale (mRS). After 90 days, 56.4 per cent of patients who received Aggrenox® treatment from Day 1 had little or no disability (mRS 0-1) compared with 52.4 per cent of patients in the ASA initial therapy group (odds ratio 0.96; 95% CI: 0.65.-1.42; p = 0.83).

For the combined secondary outcome of vascular and non-vascular death, non-fatal stroke, TIA, non-fatal myocardial infarction and bleeding complications, EARLY showed that there were numerically fewer events with early administration of Aggrenox® compared with ASA (hazard ratio [HR]: 0.7; 95% CI: 0.41 1.19; p = 0.19). The relative risk of a relevant outcome was 30 per cent lower in the early Aggrenox® therapy group (28 patients; 9.9 per cent) than in the ASA initial therapy group (38 patients; 14.6 per cent). The difference in the occurrence of non-fatal stroke and TIA was particularly marked, with 32 events (12.3 per cent) in the ASA initial therapy group compared with 20 (7.1 per cent) in the early Aggrenox® therapy group (HR: 0.63; 95% CI: 0.34 1.14; p = 0.12). Although not statistically significant, these data in favour of initial therapy with Aggrenox® are consistent with the results of the ESPS-22 and ESPRIT3 studies, which showed treatment with the extended-release dipyridamole /ASA combination to be safe and superior to treatment with ASA alone.

“Although the trend in favour of early initiation of Aggrenox® is not significant, we see biological pointers which indicate a benefit,” explained Prof. Dengler.

Safety data from EARLY indicate that initial therapy with Aggrenox® was as safe as initial treatment with ASA, with respect to serious adverse events and deaths. In patients who received early initiation with Aggrenox® there was an increased incidence of headache and gastrointestinal complaints.

“EARLY has shown that early initiation of therapy with extended-release dipyridamole plus ASA is at least as safe and effective as early initiation of treatment with ASA alone”, said Prof. Dengler.

Please be advised

This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the U.S.A.

Modified Rankin Scale

The Modified Rankin Scale is a numerical functional assessment scale used to rank levels of disability after stroke. Patients receive a score between 0 and 6, where 0 represents no symptoms at all and higher scores represent increasingly severe disability.4

About ESPS-2

In the ESPS-2 study it was shown that the combination of low dose aspirin plus extended-release dipyridamole (marketed as Aggrenox® and Asasantin Retard®) reduced the risk of recurrent stroke by 37 precent compared to placebo. Stroke risk was reduced by 18.1% in the aspirin-alone group.2

About ESPRIT

The ESPRIT trial compared a combination of ASA and dipyridamole with ASA alone. The majority of patients on the combination received a free combination of ASA and extended-release dipyridamole (200mg twice daily); 8 percent of the patients received the fixed-dose combination (200mg extended-release dipyridamole plus 25 mg ASA twice daily, as marketed as Aggrenox® and Asasantin® Retard). Free ASA dosages varied from 30 to 325mg/day.3

About Aggrenox®

Aggrenox® (marketed as Aggrenox® and as Asasantin® Retard) is an antiplatelet agent that combines extended release dipyridamole and ASA. A product of Boehringer Ingelheim`s research and development, it is indicated for the prevention of recurrent stroke and transient ischaemic attack (TIA).5

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

References:

1 Dengler R et al. Early treatment of Aspirin and Extended-Release Dipyridamole versus Aspirin alone for treatment of Minor Ischaemic Stroke within 24 hour of stroke-onset (EARLY-Trial): a randomised, open-labelled, blinded-endpoint trial. Eur J Neurol 2009 (Suppl).

2 Diener HC et al. European Stroke Prevention Study 2: Efficacy and Safety data. J Neurol Sci 1997: 151 (Suppl); 1 – 77

3 ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT). Lancet 2006: 367; 1665 – 673

4 Modified Rankin Scale. Internet Stroke Center.

5 Summary of product characteristics. Asasantin Retard®.

Source: Boehringer Ingelheim

View drug information on Aggrenox.

The University of California, San Francisco has been designated to lead a new consortium that will study a group of severe immune disorders known as primary immunodeficiencies and aims to improve treatment for these often life-threatening diseases. The Primary Immune Deficiency Treatment Consortium comprises 13 centers throughout the United States and has a $6.25 million funding commitment over five years from the National Institutes of Health.

Serving as the consortium’s principal investigator is Morton Cowan, MD, chief of the Pediatric Blood and Marrow Transplant Program at UCSF Children’s Hospital. According to Cowan, the participating centers all share the common goals of improving the diagnosis, treatment and survival rates for primary immunodeficiencies, which are caused by inherited genetic defects that result in a child being born either without any immune system at all or one that is seriously hampered in its ability to function.

“With this consortium we have an unique opportunity tobring together scientists, physicians and immunologists from centers throughout North America with expertise in and commitment to the diagnosis and management of serious immune disorders,” said Cowan.

While there are more than 140 types of primary immunodeficiencies, each with its own distinct genetic mutations, the consortium will focus on a subset of three disorders that are representative of the entire group in terms of major diagnostic and treatment issues. Consortium researchers will study severe combined immunodeficiency, or SCID; Wiskott-Aldrich syndrome, or WAS; and chronic granulomatous disease, or CGD, both retrospectively, in patients who have already received treatment, and prospectively, by developing new clinical trials.

“It is our hope that this consortium will enable us to better understand these disorders so that we can more effectively treat patients and save lives,” said Jennifer Puck, MD, a professor of pediatrics and human genetics and director of the Pediatric Clinical Research Center at UCSF Children’s Hospital. Puck is a member of the consortium’s steering committee and will oversee a pilot project to assess the effectiveness of a newborn screening test she has developed for SCID.

The consortium will focus on the treatment of the three disorders using hematopoietic stem cell transplantation, or HSCT. HSCT involves taking healthy blood stem cells from the bone marrow or peripheral blood of a healthy donor and intravenously transplanting the cells into a patient. When successful, the implanted cells repopulate the bone marrow and produce new healthy cells, resulting in a normally functioning immune system.

Currently, individual centers have their own approaches to administering HSCT for children with primary immunodeficiencies, which vary in terms of the timing of treatment, the source of donor cells, how the cells are processed and other key factors. Now with the consortium in place, clinical research data will be pooled so that a consensus for best treatment practices can be reached and protocols can be standardized and evaluated prospectively, Cowan explained.

“These are very rare diseases, and no single center sees enough cases to do a large-scale study on its own, so collaboration is particularly important,” Cowan added. “The formation of the Primary Immune Deficiency Treatment Consortium is a quantum step forward in optimizing care for all primary immunodeficiencies.”

The 13 core pediatric centers in the consortium currently treat more than 60 percent of patients with primary immunodeficiencies in North America. A group of 19 smaller centers in the U.S. and Canada that actively treat these disorders and account for another 20 percent of patients also will participate in the research projects.

The consortium will receive $1.25 million each year for the next five years from the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health. In addition to using the funds for research, the consortium will support two fellowships in primary immunodeficiency research at the postdoctoral level each year.

Scientific and administrative aspects of the consortium will be managed by a steering committee whose members include Cowan and Puck of UCSF, as well as Luigi Notarangelo, MD, a professor of pediatrics and pathology at Harvard Medical School; and Donald Kohn, MD, a professor of microbiology, immunology, molecular genetics and pediatrics at the University of California, Los Angeles and director of UCLA’s Human Gene Medicine Program.

The additional core centers are Cardinal Glennon Children’s Medical Center, Cincinnati Children’s Hospital, Children’s Hospital Boston, Children’s Memorial Hospital, The Children’s Hospital of Philadelphia, Children’s Hospital Seattle, Duke University Medical Center, Memorial Sloan-Kettering Cancer Center, St. Jude Children’s Research Hospital, Texas Children’s Hospital, and the University of Minnesota Medical Center.

One of the nation’s top children’s hospitals, UCSF Children’s Hospital creates an environment where children and their families find compassionate care at the healing edge of scientific discovery, with more than 150 experts in 50 medical specialties serving patients throughout Northern California and beyond. The hospital admits about 5,000 children each year, including 2,000 babies born in the hospital.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Source:
Kate Schoen

University of California – San Francisco

UroToday – For men with a relatively low PSA on prostate cancer (CaP) screening, what is their risk on future screening exams of having CaP detected? This question was addressed by Dr. Fritz SchrГ¶der and collaborators in the online edition of the Journal of Urology.

Their work used the Rotterdam Section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) database. Beginning in 1993, men ages 55 to 74 years old underwent screening by PSA, DRE and TRUS. Initially a PSA of >4.0ng/ml prompted a biopsy, but in 1997 this was decreased to >3.0ng/ml. Also, an abnormal DRE or TRUS resulted in the recommendation for a prostate biopsy. Men who did not meet the criteria for a prostate biopsy on the first round of screening, and also had a second screening, comprised the database for this study. To establish the 4-year risk of CaP diagnosis, the number of men in whom CaP was detected at the second screening was divided by the total number of men who completed round 2 of screening. The investigators evaluated 2 populations; population 1 consisted of all men regardless of previous biopsy status (5,176 men) and population 2 excluded the influence of a previous biopsy on the characteristics of PSA as a predictor of CaP, and thus excluded all men who had undergone a biopsy at the first round of screening (3,501 men).

At the first screening, the mean PSA was 2.4ng/ml, and 31.5% met the criteria for prostate biopsy. In population 1, 299 prostate cancer cases were detected among 1,748 biopsies in 5,176 men, reflecting a 5.8% 4-year risk. In population 2, 178 cases of CaP were detected from 760 biopsies in 3,501 men for a 5.1% 4-year risk. This was associated with a mean population PSA of 1.5ng/ml at the first screening. Most cases in the first and second round screening had a Gleason score

Although estimates have been adjusted downward in light of the most recent data, researchers still predict sharp increases in the U.S. incidence and prevalence of end-stage renal disease (ESRD) in the years ahead, according to a paper presented at the American Society of Nephrology’s 40th Annual Meeting and Scientific Exposition in San Francisco.

“The expected number of patients with ESRD in 2020 is almost 785,000, which is an increase of over 60 percent compared to 2005,” comments Dr. David T. Gilbertson of the U.S. Renal Data System (USRDS) and the Minneapolis Medical Research Foundation, Minneapolis, Minn. Using data available through 2005, the study updates previous estimates based on data through 2000.

The researchers used statistical techniques to project available data on the ESRD population to the year 2020. The model took into account a wide range of factors, including expected trends in population growth and the rising rate of diabetes — the main cause of kidney disease. The study also incorporated the latest data on the risk of progression to ESRD once kidney disease is present.

Based on the results, Dr. Gilbertson and colleagues predict that the U.S. incidence (number of new cases) of ESRD will be about 135,000 in 2015. This figure is about 3,000 lower than the previous estimate. For reasons that are not entirely clear, the incidence of ESRD has been decreasing in recent years, and the updated figure accounts for that trend. The predicted prevalence (total number of cases) of ESRD in 2015 is estimated at 680,000 — about 33,000 less than the previous estimate.

Nevertheless, based on a combination of trends — including the aging of the “Baby Boomer” population, rising diabetes rates, and improvements kidney disease treatment allowing better survival — the authors project continued increases in numbers of Americans affected by ESRD. By 2020, the incidence (new cases) of ESRD is expected to rise to 151,000 per year (compared to 107,000 in 2005). Prevalence (all cases) is expected to increase to 785,000 (compared to 485,000 in 2005).

“These projections play an important role in shaping public health policy and health care planning related to the treatment of kidney disease,” says Dr. Gilbertson. “Medicare pays for the care for the vast majority of patients with ESRD, with costs approaching $60,000 per year for every patient.”

The predictions suggest that, despite recent declines in new cases, policymakers should account for continued increases in the health and economic impact of ESRD in the United States. “While relatively flat ESRD incidence rates may show some progress towards Healthy People 2010 goals of reducing ESRD incidence, it is important to know the expected future counts of patients, as opposed to rates, to inform public health policy and health care planning related to the treatment of kidney disease,” Dr. Gilbertson says. “The financial and human resources that will be needed to care for these patients in 2020 will be considerable.”

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The study abstract, “Projecting the ESRD Population to 2020,” (SA-FC046) waspresented as part of a Free Communications session on the topic of “Epidemiology and Consequences of Chronic Kidney Disease.”

The ASN is a not-for-profit organization of 10,500 physicians and scientists dedicated to the study of nephrology and committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on kidney diseases. ASN’s Renal Week 2007, the largest nephrology meeting of its kind, provides a forum for 11,000 nephrologists, to discuss the latest findings in renal research and engage in educational sessions relating advances in the care of patients with kidney and related disorders from October 31 – November 5 at the Moscone Center in San Francisco, CA.

Source: Shari Leventhal

American Society of Nephrology