Now, researchers at NYU School of Medicine have zeroed in on a class of custom-made immune cells that block allergic reactions. These regulatory T cells are manufactured according to instructions from a gene called Foxp3 whenever we eat or inhale a potential allergen for the first time, ensuring that the next time we encounter that substance, we will not mount an allergic response.

"We don't become allergic to lots of things—we eat all kinds of things, we breathe all kinds of things, and what prevents us from developing allergies is that we make regulatory T cells, which specifically recognize this allergen," says Maria A. Curotto de Lafaille, Ph.D., Associate Research Scientist at NYU Langone Medical Center. "Every time we don't react to something or don't become allergic, it's not because nothing is happening," Dr. de Lafaille explains. "It's because something very important is happening: We're making these cells,"

Mucosal tissue, which lines both the respiratory and digestive tracts, has long been known as an effective barrier against allergens, which are always protein molecules. The NYU research shows that Foxp3-directed regulatory T cells (Treg) are produced in the mucosal tissue and remain there to prevent allergic reactions. New ones are tailor-made every time an unknown protein is inhaled or ingested. The inability to make Treg cells results in high susceptibility to becoming allergic.

The NYU researchers induced allergic reactions in mice with a Foxp3 mutation that prevented formation of Treg cells. Exposure to the same allergen—in this case egg protein—did not elicit an allergic response in mice that were able to make Treg cells. The findings are reported in the July 18, 2008, issue of the journal Immunity.

The formation of Foxp3-positive Treg cells occurs in response to any potential allergen, so the findings are applicable to a broad range of allergic reactions and autoimmune diseases, says Dr. de Lafaille. When people suffer from allergies, including life-threatening ones such as asthma, something goes wrong in the process by which Foxp3 signals Treg cell formation. The problem is not necessarily a mutation in the Foxp3 gene, which is known to cause severe autoimmune disease. Rather, something occurs, or fails to occur, in the lungs or the gut that interferes with the production or activity of allergen-specific Treg cells.

The NYU researchers also determined that Treg cells control damage from long-term inflammation. They found high concentrations of Treg cells in inflamed lung tissue of mice without the Foxp3 defect. "The question arose about what these cells are doing in the tissue—are they beneficial or not?" Dr. de Lafaille says. It turns out that even though the Treg cells did not prevent inflammation in an ongoing allergic reaction, they kept it under control, ensuring it did not worsen or spread to other areas of the body. "We think that over time these regulatory T cells become more important than the inflammatory cells and end up completely shutting off the inflammation. But it's not overnight and it's not black and white," Dr. de Lafaille emphasizes.

This finding provides a key to one of the most serious consequences of asthma. In addition to breathing problems during an acute attack, people with asthma have chronic inflammation, which can permanently damage their airways. If a means could be found to increase the number of Treg cells in inflamed tissue, this might be prevented. Allergic asthma, the most common and best-understood type, affects more than 10 million people in the US, many of them children. Acute asthma attacks are responsible for nearly 4000 deaths in the United States each year.

Dr. Yi Ding, Dr. de Lafaille, and other members of Dr. Juan Lafaille’s laboratory have been investigating ways to grow allergen-specific Treg cells in the lab and inject them into people who cannot make their own. The group published a paper in Nature Medicine in February 2008 describing a method of making the cells. "The big challenge is how to isolate the cells that will recognize the right allergens that the person is allergic to," Dr. de Lafaille says. Another approach is to stimulate the body to manufacture the cells itself, an area of ongoing research.

This work represents an important step in understanding the genetic and cellular mechanisms underlying the allergic response, which may lead to more effective therapies. Current treatment is aimed at suppressing symptoms and reducing inflammation after an allergic reaction has already occurred. Having identified the cell type that must be present to prevent allergies, Dr. de Lafaille and her colleagues are now looking for the glitch that blocks formation of those cells.

The study published in the journal Immunity was supported by grants from the National Institutes of Health, the National Multiple Sclerosis Society, and the Sandler Foundation. The co-authors of the study include: Nino Kutchukhidze and Shiqian Shen, former postdoctoral students in pathology, Yi Ding, a graduate student in pathology, and Herman Yee, M.D., Ph.D., associate professor of pathology, and Juan J. Lafaille, Ph.D., associate professor of pathology and Medicine at NYU Langone Medical Center.

About NYU Langone Medical Center
One of the world’s premier academic medical institutions for more than 167 years, NYU Langone Medical Center continues to be a leader in patient care, physician education and scientific research. NYU Langone Medical Center is internationally renowned for excellence in areas such as cardiovascular disease, pediatrics, skin care, neurosurgery, urology, cancer care, rehabilitation, plastic surgery, minimally invasive surgery, transplant surgery, infertility, women’s health and day surgery.

AMGA, located in Alexandria, VA, represents more than 325 medical groups in 42 states that provide healthcare delivery to patients under the multispecialty medical groups model and other organized systems of care.

“We are pleased that Congress passed this bill preventing the 10.6% cut in the Medicare Physician Fee Schedule,” said Don Fisher, Ph.D., AMGA President and CEO.

The legislation also includes two other provisions beneficial to medical groups which AMGA successfully advanced. These include incentive payments for physicians who prescribe electronically for their patients, thus reducing risks of mistakes and drug interactions, and a requirement that the Centers for Medicare and Medicaid (CMS) establish a medical group reporting mechanism for its Physician Quality Reporting Initiative (PQRI).

Fisher added: “As early advocates for the benefits of health information technology, we were doubly delighted that the electronic prescribing provisions we called for made it into law. The same is true for the PQRI reporting language which will lower barriers to our members who wish to participate.”

He also cited Congress for its leadership and foresight in addressing an issue of importance to AMGA members and their Medicare patients.

Fisher identified Finance Committee Chair Max Baucus (D-MT) for particular praise. “Although the legislation approved by Congress is not what Sen. Baucus first introduced two weeks ago, it is clearly reflective of his hard work and persistence on behalf of all Medicare beneficiaries,” Fisher said.

Cinacalcet is one of a family of drugs called calcimimetics. "In hemodialysis patients, the use of calcimimetics decreases the set point of the PTH-calcium curve, which means that PTH secretion by cells is suppressed at low or normal calcium levels," comments Mariano Rodriguez, MD, PhD, of Nephrology Service, Hospital Universitario Reina Sofia in Cordoba, Spain.

Dr. Rodriguez and colleagues studied responses to cinacalcet treatment in nine patients with ESRD receiving long-term hemodialysis to replace lost kidney function. All patients had high levels of PTH, or secondary hyperparathyroidism—a frequent complication of kidney disease that is mainly caused by low calcium levels. Hyperparathyroidism can lead to weakening of the bones and other problems, including cardiovascular disease.

The researchers assessed the "PTH-calcium curve," which reflects the way PTH levels respond to calcium levels, by comparing blood samples obtained during dialysis performed at low and high calcium levels. The study took advantage of a new test that provides more complete information on the dynamics of PTH secretion.

Treatment with cinacalcet led to significant reductions in the patients' blood phosphorus levels. Their levels of PTH before dialysis were also decreased.

Cinacalcet also led to a reduction in the set point of the PTH-calcium curve. This occurred because cinacalcet made parathyroid cells more sensitive to calcium.

The study provides important new information on how cinacalcet and other calcimimetic drugs work to reduce PTH levels. Normally, low calcium levels cause cells to increase secretion of PTH. After cinacalcet treatment, PTH secretion doesn't increase even when calcium levels are low. Cinacalcet doesn't just lower calcium and PTH levels in the short term, the new results suggest—it changes the interaction between calcium and PTH levels in the long term.

Secondary hyperparathyroidism is a common and potentially serious problem in patients with kidney disease. Calcimimetic drugs like cinacalcet provide a valuable new treatment option. "Nowadays the calcimimetics are an essential tool in the treatment of secondary hyperparathyroidism," says Dr. Rodriguez. "With these drugs, the need for surgery to remove the parathyroid gland (parathyroidectomy) is markedly decreased."

The results provide nephrologists with new insights into the way cinacalcet works to control PTH levels in ESRD patients with hyperparathyroidism. "High PTH levels and the excess of calcium in blood are easy to control with calcimimetics," Dr. Rodriguez adds.

The study was limited by the lack of data on the effects of cinacalcet in patients on peritoneal dialysis, although there are no reasons to believe that results would have been different in peritoneal dialyisis patients. In addition, the patients in the study were not taking vitamin D, another effective treatment for hyperparathyroidism. "It would have been interesting to evaluate the combined effect of calcimimetics and vitamin D on the set point of the PTH-calcium curve," says Dr. Rodriguez.

Funding was provided by Government grants from instituto Carlos III, Consejeria de Salud de la Junta de Andalucia and Fundación Nefrologica and Red de Investigación Renal. Funding for the writing was provided by Amgen Europe.

The article, entitled “Cinacalcet Reduces the Set Point of the Parathyroid Hormone -Calcium Curve in Hemodialysis Patients with Secondary Hyperparathyroidism,” will appear online at http://jasn.asnjournals.org/ on July 16, 2008, and in print in the November 2008 issue of JASN.

ASN is a not-for-profit organization of 11,000 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 publishes JASN, the Clinical Journal of the American Society of Nephrology (CJASN), and the Nephrology Self-Assessment Program (NephSAP). In January 2009, the Society will launch ASN Kidney News, a newsmagazine for nephrologists, scientists, allied health professionals, and staff.

The therapy may provide an option for many patients “sensitized” to transplant antigens (human leukocyte antigens, or HLA) who previously would not have been candidates for transplantation because of their intense immune response to these HLA targets.

HLA exposure can come through blood transfusions, previous transplantation or pregnancy. Once exposed, the immune system is sensitized to those antigens and develops antibodies to fight them. If a donor organ with the antigens is later transplanted, the antibodies respond, increasing the risk of rejection and loss of the organ. Antibodies to HLA were previously considered an absolute contraindication to transplantation – the risk was too high for transplantation to be an option.

About 30 percent of the 74,000 patients on the transplant waiting lists for a deceased-donor kidney are sensitized, and those with exceptionally high antibody levels are considered especially poor candidates for transplantation. In fact, each year only 6.5 percent of highly sensitized patients receive a transplant. Most remain on dialysis indefinitely, without hope for a life-saving transplant.

“From a quality-of-life perspective, as well as from the financial standpoint, transplantation is a much better option than years of dialysis,” said Stanley C. Jordan, M.D., director of the Division of Nephrology and medical director of the Renal Transplant Program at Cedars-Sinai. The senior author of the journal article, Jordan developed high-dose intravenous immunoglobulin (IVIG) therapy to “desensitize” highly sensitized patients and increase their chances of successful transplantation. The approach became a Medicare-approved therapy in 2004 at the conclusion of a National Institutes of Health-funded multicenter study.

Cedars-Sinai is a national leader in desensitization for the highly HLA sensitized patient, offering therapy for those awaiting both living-donor and deceased-donor transplantation.

The New England Journal article describes a Phase I/II safety and limited efficacy trial of a combination of IVIG and rituximab, a monoclonal antibody – an antibody engineered to bind to a specific protein. The combination of IVIG and rituximab appears to offer superior benefits to IVIG alone, improving transplant rates to 80 percent of treated patients. The one-year patient and graft survival rates were 100 percent and 94 percent, respectively.

Based on these results, the new protocol is less costly than IVIG alone yet appears to be highly effective in reducing antibody levels and improving transplantation rates. Larger, multicenter trials are necessary to confirm these findings.

Because nearly one-third of kidney failure patients are highly sensitized and few transplant centers specialize in desensitization therapy, many potential candidates are told that a transplant simply is not possible.

“Patients who are on dialysis and those who are progressing toward renal failure should be considered for a kidney transplant. Ideally, they would be referred to a transplant center for evaluation even before they start dialysis because data show that those who get transplanted before starting dialysis do better,” Jordan said. “However, for the highly sensitized patient, transplantation is not an option unless desensitization therapies are used.”

Jordan estimates that about 40 percent of Cedars-Sinai’s kidney transplant patients are highly sensitized and are referred or self-referred to the program because of their highly sensitized state. For many patients, especially those awaiting a deceased-donor transplant, the combination of IVIG and rituximab appears to offer an alternative to ongoing dialysis.

The New England Journal of Medicine article is accompanied by an editorial written by Ron Shapiro, M.D., of the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh. He concludes his comments by saying, “As the authors note, their observations need to be confirmed and validated by other centers and in larger numbers of patients and during longer periods of follow-up. However, their approach may represent a breakthrough in the care of sensitized patients awaiting transplantation and may have the potential to help thousands of patients who are languishing on waiting lists around the world.”

Citation: The New England Journal of Medicine, “Rituximab and Intravenous Immune Globulin for Desensitization during Renal Transplantation,” July 17, 2008.

Disclosure/conflicts: Study supported by Genentech and Biogen Idec, which also provided drugs used in the study. Dr. Reinsmoen received lecture fees from Cylex. Dr. Jordan receives consulting fees and grant support from Talecris and Bristol-Myers Squibb and lecture fees from Genentech. Cedars-Sinai owns a patent: “Use of IVIG in Desensitization.” No other potential conflicts of interest relevant to this article.

American Journal of Public Health Highlights:

Effects on mental health assessed after devastating tsunami in Sumatra

Researchers examined the levels of post traumatic stress reactivity (PTSR) of over 20,000 adult tsunami survivors by analyzing survey data from coastal Aceh and North Sumatra, Indonesia. The findings are from the first wave of a long-term prospective longitudinal follow-up study examining the nature and course of mental health consequences and moderating influences among a population in Indonesia affected by the 2004 Indian Ocean tsunami. Survey respondents were classified into three damage zones using satellite imagery of their pre-tsunami locations of residence from before and after the disaster. Overall, 34 percent of the respondents experienced the trauma of either hearing the tsunami wave or screams about it and 6 percent watched family or friends struggle or disappear. Both exposure to traumatic events at the time of the tsunami and subsequent PTSR scores were highest for respondents from heavily damaged areas. Scores declined over time for respondents from all three damage zones. Gender and age were significant predictors of PTSR, whereas socioeconomic status before the tsunami was not.

“We expect that this 5-year study will provide important knowledge about long-term mental health outcomes after catastrophic disaster and a rationale for attention by international health organizations to sustain interventions beyond the immediate postcrisis period, and will guide the use of stratified public mental health postdisaster programs,” the study’s authors forecast. [From: “Mental Health in Sumatra After the Tsunami,” ].

Menthol in cigarettes promotes smoking among adolescents and young adults

Researchers examined U.S. cigarette brands popular among youth to determine whether or not tobacco manufacturers manipulate menthol in an effort to target young, experimental smokers. Menthol in cigarettes masks harshness and irritation for new smokers. Menthol is used as an additive in approximately 90% of cigarettes manufactured in the United States, although only about one-third of these cigarettes are explicitly marketed as mentholated. This study used data from tobacco industry documents on menthol product development, lab testing results of U.S. menthol brands, market research reports, and the 2006 National Survey on Drug Use and Health, an annual nationally representative survey among U.S. residents aged 12 years and older. The researchers found that tobacco companies control menthol in specific brands to target the sensory preferences of new or younger smokers, primarily by creating milder menthol brands, thereby easing smoking initiation. Menthol brands that have used this strategy have been most successful in attracting youth and young adult smokers and have grown in popularity.

“For decades, tobacco manufacturers have controlled levels of menthol in commercial cigarettes to promote smoking among adolescents and young adults,” the authors said. “To protect public health, tobacco products should be federally regulated and additives such as menthol should be included in that regulation.” [From: “Tobacco Industry Control of Menthol in Cigarettes and Targeting of Adolescents and Young Adults,” ].

Neighborhood psychosocial hazards connected to cardiovascular disease: Case study in Baltimore

Researchers analyzed the associations between cardiovascular disease and neighborhood psychosocial hazards, such as violent crimes, abandoned buildings, and signs of incivility, that lead to an increased sense of threat and vigilance in residents within 65 contiguous neighborhoods in Baltimore, Maryland. A total of 1,140 residents participated in this study who were aged 50 to 70 years and residents of Baltimore for at least 5 years. After adjusting for individual heart disease risk factors, researchers found that residents in neighborhoods with scores in the highest quartile of the psychosocial hazards scale had more than 4 times higher odds of a history of myocardial infarction and more than 3 times higher odds of myocardial infarction, stroke, transient ischemic attack, or intermittent claudication compared with residents living in neighborhoods scoring in the lowest quartile.

“A new wave of research is examining the health consequences of various aspects of residential neighborhoods,” the study’s author said. “Daily exposure to psychosocial hazards in the neighborhood is known to activate a physiological stress response. These findings suggest new targets for intervention and policy change.” [From: “Neighborhood Psychosocial Hazards and Cardiovascular Disease: The Baltimore Memory Study,” ].

U.S. child labor violations found in the retail and service industry

Results from this study found that a substantial proportion of U.S. adolescents working in the retail and service industry were employed in violation of the child labor laws. The Fair Labor Standards Act (FLSA) of 1938 limits the types of jobs youths ages 14 to 17 are allowed to perform, the number of hours they may devote to work, and the timing of these hours. The child labor provisions of this act were created to limit work’s interference with youths’ schooling and to minimize their health and safety risks. Contemporary studies have found that adolescents working more than 20 hours per week during the school year can experience several negative health behaviors and decrements to mental health. In addition, surveillance data show that hundreds of thousands of adolescents are injured at work as a result of performing hazardous tasks. Data for this study were obtained through a survey of a nationally representative sample of working adolescents, and the study investigated reports of select child labor violations. Approximately 37 percent of respondents reported a violation of the Hazardous Occupations Orders, and 40 percent reported a work permit violation. Less than 2 percent reported working more than the maximum weekly hours allowed during the school year, yet 11 percent reported working past the latest hour allowed on a school night, and 15 percent reported working off the clock.

“Further research on child labor violations should examine more carefully how shifts in enforcement activities over the past decade are affecting the detection of violations and the safety of young workers.” The study’s authors urge, “More-detailed research on the reasons for employer noncompliance will help inform and direct future enforcement efforts.” [From: “US Child Labor Violations in the Retail and Service Industries: Findings of a National Survey of Working Adolescents,” ].

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a) incorporate the basic diagnostic symptoms of the significant concurrent co-morbid disorders into the urologic diagnostic protocols;
b) explore, in more detail, the relationship between these co-existing disorders; and
c) develop diagnostic protocols that will allow disease identification by the generalist physician and not limit it to an organ-specific specialist.

The follow-up workshop was held in Bethesda, MD on June 16th and 17th with guest participants from Europe, Asia, and North America and was open to the public and patient organizations. Its purpose was to assemble a group of international experts in urology, gastroenterology, internal medicine, rheumatology, epidemiology, behavioral science and other disciplines with a goal to re-characterize the two most common urologic chronic pelvic pain syndromes, interstitial cystitis (IC) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The meeting was seen as a prelude to the “Multidisciplinary Approach to Pelvic Pain (MAPP) multicenter program, set to begin later this summer. Centers for the MAPP have not been officially announced.

While no conclusions were reached, several interesting papers led to wide ranging discussions on the following topics:

* Is the perception of chronic pelvic pain organ and gender specific?
* Would a questionnaire need to be gender specific?
* Are the current definitions too restrictive?
* What is the relationship between urologic pelvic pain syndromes and the other chronic pelvic pain syndromes?
* Is the relationship an epiphenomenon or do these relationships provide a clue to common pathophysiology?

Andrew Baranowski from Queen Square in London examined the issue of classification. He discussed the classification of bladder pain syndrome put forth by the European Society for the Study of Interstitial Cystitis which classifies patients based on whether or not they had bladder endoscopy or bladder biopsy - and the findings of each procedure. He noted that classification should allow appropriate (best) assessment and management of the condition in its own right and for the patient as a whole. It should provide a platform for future research and be usable for all stakeholders: the practicing physician, researcher, patient, support groups, and reimbursement agencies. A good classification system employing phenotype, terminology, and taxonomy allows logical patient flexibility in the system, enables development within the system, and enables logical empirical and generic treatments to be employed.

Quentin Clemens from the University of Michigan discussed perceptions of urologic pelvic pain. He noted that patients may manifest symptoms from more than one, what he termed “afferent neurourology disorders”: BPS, CP/CPPS, overactive bladder, “bladder hypersensitivity disorder”, orchalgia, and chronic epididymitis. These disorders are common and may have similar patterns in men and women. They may be a part of a systemic disease complex. In one study he noted, only 19% of patients with new onset symptoms of prostatitis had symptoms three months later (Clemens, et.al., J. Urol, Dec. 2005). Interestingly, he cited research indicating that while “prostatitis” may account for 2 million office visits per year, 38% of primary care providers, when presented with a vignette of a man with CPPS, indicated that they had never seen such a patient. Dr. Clemens is currently working on a condition-specific instrument. He concluded that anatomic differences and possible gender differences in how pain is experienced make it necessary to have gender specific terms in any such instrument.

Philip Hanno, your correspondent, discussed the results of the Society for Urodynamics and Female Urology special meeting on bladder pain syndrome in February in Miami (Read Complete Highlights). He stressed the importance of a new terminology. This idea was furthered by Mr. Paul Abrams from Bristol, UK. In an elegant presentation, he concluded that “interstitial cystitis”, as a term, has spurious diagnostic authority which raises patients’ expectations of cure. Specific terms such as “interstitial cystitis” should only be used when histological features reflect the name. The terms “painful bladder syndrome” and “bladder pain syndrome” do not reflect or assume an etiological knowledge. Subsets of patients may be described in the future, perhaps with the aid of the MAPP program, by disease specific terms as pathology and phenotype become well understood. Mr. Abrams concluded by noting that the International Continence Society would be happy with either the term “painful bladder syndrome” or “bladder pain syndrome”. The terminology “BPS including IC” is somewhat misleading as there is no accepted definition of IC per se.

Dr. Anthony Schaeffer from Northwestern University discussed current concepts and etiology in the treatment of chronic prostatitis/chronic pelvic pain syndrome. The syndrome includes most men with prostatitis: and is marked by pain localized to the pelvis for at least 3 months, with or without irritative and obstructive voiding, in the absence of urinary tract infection. The NIH chronic prostatitis symptom index in conjunction with lower urinary tract localization of symptoms, and a residual urine determination, are sufficient in the majority of cases to make the diagnosis. Ejaculatory symptoms and voiding dysfunction may require optional urodynamics and/or pelvic imaging studies. There are no issued guidelines for management of the condition. Dr. Schaeffer concluded with data on monocyte chemoattractant protein-1 and macrophage inflammatory protein-1a and their elevated levels in the expressed prostatic secretion of men with CPPS, suggesting that we may have come full circle, and the prostate itself may be involved with the pathology responsible for this enigmatic syndrome in at least some patients.

Dr. Tony Buffington from Ohio State University focused on stress and the stress response system (SRS). Stress is often defined as “challenging emotional and physiological experiences”, but perhaps is most accurately defined as any “thing” that activates the SRS. BPS may be a sensitized SRS with increase in startle response, increase in autonomic nervous system nervous system activity, and decrease in adrenocortical restraint. He discussed research by Wallach and Jonas (J. Alternative and Complimentary Medicine, volume 10, supplement 1, 2004) indicating that patient rapport, touch, a confident approach, normalizing expectations, and individualizing treatment all play a role in good results. Incorporating reassurance and support and delivering a conditioning stimulus along with effective therapy can improve outcomes. Dr. Buffington concluded that the SRS can affect the bladder. BPS may be an “allostatic” illness. Developmental issues may play a role through epigenetic mechanisms. This view may open additional avenues for basic and clinical research, and become a part of the MAPP effort. For those readers who, like this author, do not have a good comprehension of these terms in this context, Wikipedia is useful. The term epigenetics refers to changes in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. The idea is that environmental factors can cause an organism's genes to behave (or "express themselves") differently, even though the genes themselves don't change. Allostasis is the process of achieving stability, or homeostasis, through physiological or behavioral change.

Dr. Ragi Doggweiler from the University of Tennessee Medical Center in Knoxville gave a beautiful presentation on the mind-body connection. She discussed physical, emotional, cognitive, and behavioral manifestations of stress.

Dr.Jack Warren from the University of Maryland discussed antecedent non-bladder syndromes in a case control study of the disease that has been on-going, concluding that some patients have a systemic syndrome not confined to the bladder. Eleven antecedent syndromes were more often diagnosed in BPS/IC cases, and most syndromes appeared in clusters. Fibromyalgia-chronic widespread pain, chronic fatigue syndrome, sicca, and irritable bowel syndrome comprised the most prominent cluster, and patients with one or more of these syndromes were more likely than controls to have migraine, chronic pelvic pain, depression, and allergy. He then discussed clinical research techniques that may be useful in determining whether the various pains of IC/PBS are from lower spinal cord central sensitization, modification by descending central nervous system signals, or another cause. The goal is to determine whether some, many, or most IC/PBS is a local manifestation of a systemic disorder, and in which cases it is truly an isolated bladder disease.

Dr. Robert Moldwin from the Long Island Jewish Medical Center in New York and Dr. Michel Pontari from Temple University in Philadelphia gave updates on vulvodynia and CP/CPPS respectively. Dr. Moldwin noted that vulvodynia may affect up to 6 million women, the etiology is unclear, pathology is found at the end organ, and may be found at the systemic and genetic level. Multiple comorbidities exist including fibromyalgia, interstitial cystitis, and irritable bowel syndrome. Dr. Pontari presented data suggesting that CP is similar in many aspects of demographics and associated medical conditions with other pain syndromes. There is similar overactivity of the sympathetic nervous system. There may be a different pattern of cortisol response and other differences related to the fact that it is gender specific.

Dr. Afari from the University of California San Diego discussed data she compiled with Dr. Bullones from Spain and Dr. Dedra Buchwald from the University of Washington looking at overlap between chronic pelvic pain syndromes and other unexplained medical conditions (fibromyalgia, chronic fatigue, irritable bowel, and temporomandibular joint syndrome). The most robust evidence was for irritable bowel and urologic pain.

Dr. Curtis Nickel from Kingston, Ontario, Canada concluded the meeting with an upbeat presentation on his pilot study in conjunction with 11 medical centers around the world looking at phenotypic associations between interstitial cystitis/painful bladder syndrome and irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. He not only showed the feasibility of such a study on a shoestring budget, but presented a plan whereby centers could phenotype and treat these patients and correlate data through a multicenter database to see whether phenotypic information provides clues as to symptoms, prognosis, and response to treatment. Such a project could be done in real time without waiting for results from the MAPP project, and would provide synergistic data with the MAPP to accelerate research and hopefully find a way to help patients in both the near and long term.

This was another successful NIDDK meeting planned by Drs. Leroy Nyberg and John Kusek, and it stimulated many thoughtful interactions, the results of which are currently unknown but will undoubtedly bear fruit over time.

“We reviewed patient records to determine the frequency and magnitude of serum creatinine changes in patients who had not received iodinated contrast material. We then compared that to previously published articles which found a relationship between contrast media, serum creatinine levels and nephropathy (kidney damage). “We found that the creatinine level increases just as often in those who do not receive contrast material as in those who do,” said Jeffrey Newhouse, MD, lead author of the study.

According to the study, among the 32,161 patients who had not received contrast material, more than half showed a change of at least 25%, and more than 2/5 showed a change of at least 0.4 milligrams per deciliter. “These changes occurred in patients with both normal and abnormal initial creatinine values and were undoubtedly caused by the entire range of conditions, treatments, and laboratory variations that may alter creatinine levels,” said Dr. Newhouse. “These changes were not different from those seen in previously published studies in which the patients received contrast media.”

“Because serum creatinine levels change frequently in the absence of iodinated contrast media material, prior studies of the relationship between iodinated contrast material and renal function must be interpreted with caution, and future experiments should have appropriate controls,” Dr. Newhouse said. “We don’t claim that IV contrast material never induces nephropathy, but it may do so less frequently and severely than previously thought. If subsequent experimentation proves its safety, it could be used more frequently in patients with renal failure,” he said.

This study will appear in the August issue of the American Journal of Roentgenology.

"This may seem like a small component of the overall procedure, but when you are maneuvering within the heart everything is significant," said Bradley Knight, MD, director of cardiac electrophysiology at the University of Chicago Medical Center, who performed the procedure. "This is a complicated and delicate cardiac intervention, so having the tools to control each step is something that enhances our confidence and extends the number of patients we can help."

Ganschow, 80, suffered from atrial fibrillation, an irregular, overly rapid heart rate. During atrial fibrillation, the heart's two upper chambers (the atria) beat chaotically, out of synch with the two lower chambers (the ventricles) of the heart. This causes poor blood flow to the body, resulting in symptoms such as shortness of breath, weakness and confusion.

For Ganschow--an avid traveler who was remarkably healthy for the first 75 years of her life--the irregular heart rhythm first appeared five years ago, during a 23-hour flight back to Chicago from South Africa. "I just felt awful," she recalled. "It was a miserable flight."

She called her physician as soon as she landed. He promptly sent her to the hospital, where she was diagnosed with atrial fibrillation. Her cardiologist tried to treat the problem with medications for a year, with mixed results, then sent her to a heart rhythm specialist at Good Shepherd Hospital, near her home.

He inserted a catheter through a vein in the groin and guided it into her left atrium, where he used it to deliver radio-frequency energy to ablate the "trouble spot" in her heart, eliminating the problematic electrical pathway that was causing the problem.

That worked--for three years. Then the abnormal rhythm returned. This time it was even worse. Ganschow began to feel tired, and often disoriented. "My legs would just give out," she said. Worse yet, it meant no more traveling. "I did not leave the house with atrial fibrillation," she said.

Because of scar tissue that formed after the first procedure, however, her doctors could not repeat the initial treatment, which required mechanically poking a hole in the septum with a long needle, then passing the catheter through that hole, across the atrial septum, from the right side of the heart to the left, where the problem was centered.

So her cardiologist at Good Shepherd referred her to the University of Chicago Medical Center's Knight, MD, a specialist in difficult cases.

The NRGTM Transseptal needle was designed for the increasing number of patients like Ganshow, whose previous procedures make it dangerous or impossible to cross her septum safely with the traditional needle. Instead of using uncontrolled mechanical force, this new insulated transseptal needle has a closed end that safely delivers radiofrequency energy to create a small hole in the atrial septum, allowing the needle to pass to the left atrium with increased efficacy and control.

Using this device, Knight was able to pass the catheter smoothly from the right to the left atrium so that the ablation procedure could be performed to eradicate the problem. Ganschow went home the next day and recovered quickly.

"I feel good," she said two days after the procedure. "It gets better day by day."

A week later, she upgraded that to "I feel fantastic. I have my life back and I'm so glad."

Less than two weeks after her treatment, she'll do something she hasn't considered since that long fateful flight from South Africa. She'll step onto an airplane, for a quick trip to New York. "I'm not 80," she explained, "when I'm not in A-fib."

About Baylis Medical
Baylis Medical is a world leader in the development, manufacturing, and marketing of innovative medical systems with applications in Interventional Cardiology, Electrophysiology and Interventional Radiology. The Baylis Medical Radiofrequency (RF) Puncture system is designed specifically to safely and effectively create a puncture in tissues with minimal damage to surrounding tissues. The pediatric and adult applications include transseptal punctures, treating conditions associated with pulmonary atresia and re-canalizing peripheral vascular occlusions. For further information please visit our website at: http://www.baylismedical.com

About the University of Chicago Medical Center
The University of Chicago Medical Center, established in 1927, is one of the nation's leading academic medical institutions. University of Chicago physician-scientists performed the first organ transplant and the first bone marrow transplant in animal models, the first successful living-donor liver transplant, the first hormone therapy for cancer and the first successful application of cancer chemotherapy. They discovered REM sleep and were the first to describe many of the stages of sleep. Care is provided by more than 700 attending physicians--most of whom are full-time University faculty members--620 residents and fellows, more than 1,000 nurses and 9,500 employees. The Medical Center, consistently recognized as a leading provider of complex medical care, is the only Illinois hospital ever to make the U.S. News and World Report Honor Roll, with eight clinical specialties--digestive disorders; cancer; endocrinology; neurology and neurosurgery; heart and heart surgery; kidney disease; geriatrics; and ear, nose and throat--ranked among the top 25 programs nationwide. The Medical Center was awarded Magnet status in 2007, the highest level of recognition for nursing care. http://www.uchospitals.edu/

The Pritzker School of Medicine is one of the most selective medical schools in the United States, with a long tradition of close interaction between students and their mentors, the full-time medical school faculty. Although students and residents participate in several small programs for clinical training off-campus, the majority of medical student training has always been centered at the University of Chicago Medical Center (UCMC). That will not change.

This new affiliation, however, will make the ENH hospital locations the primary off-site learning environment for Pritzker students and residents.

Leaders at both organizations believe the fit is a natural, bringing together Pritzker, one of the premiere medical schools in the country, with ENH, one of the nation's leading teaching hospitals. Both share a commitment to the highest levels of patient care and medical research, yet they expose students and residents to different patient populations, operational systems, and an urban-academic-medical-center vs. suburban-community-teaching-hospital patient care setting.

"With an abundance of combined yet very different experiences and a shared commitment to medical education, clinical investigation, and the effort to connect patients to the very best treatments, ENH and the University of Chicago Medical Center will usher in a new generation of healthcare on the North Shore and beyond," said Mark R. Neaman, ENH President and Chief Executive Officer.

"The partnership takes our medical school, one with a top national reputation and highly ranked programs, and makes the educational experience that much stronger," said James L. Madara, MD, Dean of the Biological Sciences and the Pritzker School of Medicine and CEO of the University of Chicago Medical Center. "Both organizations have many similarities across their missions of teaching and research. But we also have a variety of differences in our enterprise strategies that actually complement rather than compete with one another."

The ENH system is one of the most fully integrated, multi-hospital, research and primary care organizations serving northern Illinois. ENH has an established reputation for its emphasis on advanced information technology and the highest quality of health care. UCMC, meanwhile, has a sharp focus on complex care and biomedical science, with many distinguished programs that draw patients from around the country.

The affiliation became effective July 1, 2008, and includes a one-year transition period. In July 2009, medical students and residents from Pritzker-sponsored training programs will begin to gain clinical experience at ENH, working closely with physicians who are part of the ENH-based faculty.

"Health care takes place in a variety of different settings," said Holly J. Humphrey, MD, Dean for Medical Education at the University of Chicago. "Medical schools achieve a diversity of settings by linking up with affiliates, in addition to their own teaching hospitals, to give students a richer variety of patient care experiences. That kind of broad educational exposure is incredibly robust."

"One of the most important elements is the quality and excellence of the physician faculty," she added, "and ENH's physician faculty are among the very best in the country."

The ENH-UCMC affiliation will create opportunities for collaborative research projects that take advantage of each institution’s respective strengths, particularly in the areas of clinical outcomes, clinical trials, oncology and imaging.

ENH and UCMC also intend to mirror efforts in community service. UCMC has a longstanding, deeply-rooted commitment to its community on the South Side. Already among the leading providers of Medicaid in Illinois, the Medical Center recently stepped up its efforts to increase physician access for area residents. It recently embarked on a model for delivering community health, the Urban Health Initiative. That effort represents a collaboration with multiple South Side hospitals and clinics, forming a coordinated network of care so that patients are appropriately seen in the least invasive and least costly setting for their maximum benefit.

"Similarly, as part of this new affiliation agreement," said Neaman, "ENH will oversee an expanding program to establish a health initiative in Lake County, IL, that parallels UCMC's efforts on the South Side of Chicago, in order to improve access to quality health care in underserved areas."

ENH serves a patient base from dozens of communities. It is recognized as a leader in implementing information technology to improve the safety and quality of patient care. Hospitals and Health Networks magazine has named ENH one of the "Most Wired" healthcare organizations in the nation. ENH is also the top 5 percent of all institutions that receive funding from the National Institutes of Health and among multi-specialty independent research hospitals, it ranks 9th in the nation.

The University of Chicago Medical Center, a national destination for patients with the most serious diseases, is in the top one percent of all institutions that receive funding from the National Institutes of Health and is fifth in the nation in NIH grants per faculty member. UCMC serves a diverse patient population. It has made a substantial and increasing commitment to providing care for underserved populations on the South Side of Chicago, establishing a series of partnerships with other South Side institutions to improve health and access to health care.

About Evanston Northwestern Healthcare
Located in Chicago’s northern suburbs, Evanston Northwestern Healthcare (ENH) is an integrated healthcare system that includes Evanston, Glenbrook and Highland Park Hospitals, ENH Medical Group (comprising 65 medical offices and facilities), ENH Home Services, ENH Research Institute and ENH Foundation. ENH is the only Illinois hospital named a 15 Top Major Teaching Hospital by Thomson Healthcare®, and one of the nation's 100 Top Hospitals® 12 times.

At Evanston Hospital, two major construction projects are underway. One is a complete makeover of the 12 operating rooms to create state-of-the-art facilities for patients and surgeons. The other is an expansion of the Kellogg Cancer Care Center, including a new 5-story building on the Evanston campus to serve the increasing health care needs of cancer patients and their families.

About the University of Chicago Medical Center
Located in Hyde Park, on the South Side of Chicago, the University of Chicago Medical Center (UCMC), is ranked 17th out of more than 5,000 U.S. Hospitals, according to U.S. News & World Report, and is the only area hospital ever included on the Best Hospitals "Honor Roll." A nationally recognized leader in numerous areas of specialty care, UCMC is fifth in National Academy of Science membership per faculty. Eleven winners of the Nobel Prize for medicine or physiology have been associated with the University. The Pritzker School of Medicine is the area's highest rated medical school and has risen faster through the rankings than any other medical school in the nation according to U.S.News & World Report. Two of its programs, evolutionary biology and paleontology, are ranked number one in the country.

As part of its history of commitment to the medical and scientific community, the Medical Center funds research and education each year in an amount exceeding $50 million. The Medical Center and the University are the largest employers on the South Side of Chicago. UCMC is one of the state's largest providers of care for those covered by Medicaid.

UCMC will break ground in 2009 on a $700 million, 10-story, 1.2 million-square-foot New Hospital Pavilion (NHP), designed by renowned architect Rafael Viñoly to provide the optimal setting for patient care and collaborative clinical research with the flexibility to adapt to and drive forward the rapid changes sweeping through medicine. The NHP will connect to both the University of Chicago Comer Children's Hospital, which opened in 2005, and the Duchossois Center for Advanced Medicine, the Medical Center's outpatient care facility. It will be adjacent to two new, cutting-edge research facilities: the 430,000 square-foot Gordon Center for Integrative Science, which opened in 2005, and the 330,000 square-foot, 12-story Knapp Center for Biomedical Discovery, to open in 2009.

The variation, described in the journal Cell Host & Microbe, is one of the first genetic risk factors for HIV to be identified only in those of African descent, and puts a spotlight on the differences in our genetic makeup that play a critical role in susceptibility to HIV-AIDS.

In a population of 1,266 HIV-positive U.S. military personnel and 2,000 non-infected healthy personnel, researchers studied the gene that expresses Duffy antigen receptor. This molecule on the surface of red blood cells serves as the docking site for the malaria species Plasmodium vivax.

“Subjects who have a genetic variation do not express Duffy antigen receptor and are known to be less likely to contract malaria vivax,” said Sunil K. Ahuja, M.D., professor at The University of Texas Health Science Center at San Antonio and a senior lead author of the study. “But now it turns out having this variation is a double-edged sword.”

“Duffy antigen influences levels of inflammatory and anti-HIV blood factors called chemokines,” noted Weijing He, M.D., senior post-doctoral fellow in Dr. Ahuja’s laboratory and first author of the paper. “Other as yet undefined host factors likely exert population-specific effects on HIV-AIDS, such that individuals of European or African descent are likely to have distinct host factors that affect their respective susceptibilities to HIV and AIDS.”

HIV affects 25 million people in sub-Saharan Africa today, an HIV burden greater than any other region of the world. Sexual behavior and other social factors do not fully explain the large discrepancy in HIV prevalence compared to populations worldwide, the authors note.

“In sub-Saharan Africa, the vast majority of people do not express Duffy on their red blood cells,” said senior lead author Robin A. Weiss, Ph.D., of University College London. “This is one of the first genetic factors particularly common in Africans that has been shown to confer more susceptibility to HIV.”

Paradoxically, the research team noted that once people become infected, the Duffy-deficient variation actually prolongs survival. Again, this was noted in the U.S. military personnel population.

“This is a clinical cohort of people who have been followed for nearly 25 years,” said a senior lead author, Matthew J. Dolan, M.D., of the Infectious Disease Clinical Research Program, Uniformed Services University, in Bethesda, Md.

“The advantage is we have long-term follow-up, the population is ethnically balanced between European and African Americans, and everyone has had the same employer, health care and HIV medication access.”

Drs. Ahuja, He and Dolan; Hemant Kulkarni, M.D.; and other co-authors have published a series of papers on other genetic variations that play a role in HIV-AIDS susceptibility.

“The Duffy finding is another valuable piece in the puzzle of HIV-AIDS genetics,” Dr. Ahuja said.

Dr. Ahuja is a professor of medicine, microbiology, immunology and biochemistry at The University of Texas Health Science Center and director of the Veterans Administration Research Center for AIDS and HIV-1 Infection in the South Texas Veterans Health Care System. Drs. He and Kulkarni are members of the HIV/AIDS Center.

About the UT Health Science Center San Antonio:

The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $576 million, the Health Science Center is the chief catalyst for the $15.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 23,000 graduates (physicians, dentists, nurses, scientists and allied health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, allied health, dentistry and many other fields. For more information, visit http://www.uthscsa.edu.

FSU will have $4.8 million in total funding after it matches the $2 million NIH award with $2.8 million from monies the university has set aside specifically to support research.

“Installing this groundbreaking technology will place us among the very top imaging centers in the world,” said FSU College of Arts and Sciences Dean Joseph Travis. He declared the competition “unbelievably tough” for HEI grants, which come from the National Center for Research Resources (NCRR), a part of NIH that provides laboratory scientists and clinical researchers with the tools and training they need to understand, detect, treat and prevent a wide range of diseases.

For its $4.8 million investment, FSU will get a fully automated cryo-electron microscope that provides rapid, 3-D imaging of frozen specimens around-the-clock via remote operation, then transmits them over the Internet. In addition to significantly speeding the collection of crucial data, researchers in biology and chemistry at FSU and colleagues at other institutions will get unprecedented views of -- and 24/7 access to -- the intricate interactions of individual proteins and molecular machines within the living cells of complex biological structures.

“Currently, the world’s only working installation of this microscope is in Germany,” Travis said. “In the U.S., FSU will have one of only four. The others will be installed at NIH itself; the University of California-Berkeley; and the National Center for Microscopy and Imaging Research at the University of California-San Diego -- all acknowledged as the best in the nation for structural biology and structural biological imaging. FSU soon will have capabilities unmatched by all but a few institutions in the nation.”

Travis noted that it’s extremely rare to see an HEI grant, especially such a large one, awarded to a single group of investigators; typically awards of that type go to national centers or nationwide facilities serving multiple groups. “It’s quite a testament to the scientific ingenuity of the group that will comprise the instrument’s primary users, the importance of the work they do, and the commitment FSU has made to their research areas,” he said.

“Innovative biomedical research requires frequent access to the newest and most advanced technology,” said Barbara Alving, M.D., director of NCRR. “Such tools play key roles in the study of disease and the fundamental mechanisms of biological function, ultimately leading to new advances and treatments for diseases.”

Expected to stand 16 feet high and weigh 1.7 tons, the new microscope will serve as a crucial tool to the cadre of FSU scientists who will share it once required renovations to the building in which it will be housed are completed in 2009.

“This instrument will be cutting-edge in several ways,” said biological science Professor Kenneth Taylor, the principal investigator on FSU’s award-winning grant application.

“Not only is it robotic, collecting data continually without operation attention, in fact it can only be operated remotely,” Taylor said. “There’s no conventional ‘binocular’ for the user to view the image. What’s more, the microscope can be operated and the images viewed by anyone in the U.S. with high-speed Internet capability and the required, specially designed workstation.”

Five major FSU research projects helped secure the NIH-NCRR grant for 2008.

Among them is a cell adhesion study led by Taylor, a member of the unique interdisciplinary FSU Institute of Molecular Biophysics (http://www.sb.fsu.edu/), where the current research focus is structural biology. Taylor’s work is focused on integrin, a key adhesion/signaling protein, and is critical to a better understanding of why cancer cells don’t respond to the positional signals that encourage good behavior, and instead, wander away to colonize other tissues (metastasis).

The other four collaborating scientists and their winning research include:

*Professor Kenneth Roux (Department of Biological Science), who uses electron microscopy to analyze AIDS virus envelope (Env) proteins, several of which are being considered as vaccine candidates. The work supports the design of neutralizing antibodies and other disease treatments.

*Professor Thomas Roberts (Department of Biological Science), who studies the biophysics and cell biology of crawling motion by amoeboid cells and the structure of certain proteins crucial to that process.

*Assistant Professor Scott Stagg (Department of Chemistry and Biochemistry; member, FSU Institute of Molecular Biophysics) who studies the three-dimensional structures of large biological molecules that play a key role in transporting proteins and fats from the inside of the cell to the outside. Disrupting these functions can cause cell death or one of several diseases.

*Former FSU Professor Dr. Michael Chapman (Department of Chemistry and Biochemistry). Now at Oregon Health Sciences University, he’ll use the new microscope remotely for research begun at FSU on the structure of the Adeno Associated Virus -- which has potential for use in gene therapy.

In addition, the grant application highlighted relevant research by FSU Francis Eppes Professor of Chemistry and Biochemistry, Sir Harold W. Kroto, winner of the 1996 Nobel Prize in Chemistry; and Professor Geoffrey F. Strouse, a member of the Department of Chemistry and the Institute of Molecular Biophysics.

*In the emerging fields of Nanoscience and Nanotechnology, Kroto and colleagues in Germany and Mexico have shown that nanotubes can grow by carbon migration through a metal catalyst and segregate in much the same way that a skin forms on a surface. They will use FSU’s new microscope to help develop novel ways to control the morphology of nanoscale structures.

*Strouse designs biomedical drug therapies combining nanoscience technology and biology’s natural machinery to personalize drug therapies to the individual patient. Using nanomaterial produced at FSU and 1,000 times smaller than a human hair, the technology may one day be used to treat genetic disorders such as heart disease, sickle cell anemia and cystic fibrosis.

“When it is installed next year, our new-generation cryo-electron microscope will complement the sophisticated imaging components FSU already has in place at the National High Magnetic Field Laboratory and in labs on its main campus, and should attract an enormous amount of attention from the rest of the country,” said FSU Vice President for Research Kirby Kemper. “As a result, we expect to draw even more of the nation’s best students to Florida State for some of the world’s best science research opportunities.”

For 2008, FSU (http://www.fsu.edu/) was one of 100 institutions that submitted applications to NCRR (http://www.ncrr.nih.gov) for an HEI grant and among the 20 that garnered one of the coveted awards, which ranged from nearly $851,000 to $2 million. For additional details on this year’s HEI awardees, visit http://www.ncrr.nih.gov/hei_2008. For more information about NIH, part of the U.S. Department of Health and Human Services, go to http://www.nih.gov.

Beverly W. Aisenbrey is a managing director in the New York office of Frederic W. Cook & Co., Inc. She has been with the firm since 1982, held the office of treasurer and continues to serve on its board of directors. An independent advisor to dozens of leading companies, Aisenbrey designs performance-based compensation programs and consults on change-in-control, severance and employment agreements. In this role, she most often works directly with the board of directors' compensation committee.

Aisenbrey is a trustee of Rutgers University, and a member of several advisory boards, including Rutgers Business School and the New Jersey Chapter of the National Association of Corporate Directors and Compensation and Benefits Review. She belongs to the Founding Circle of the Rutgers Women’s Business Leadership Initiative. Aisenbrey received her B.A. from Douglass College and her M.B.A. in finance from Rutgers University.

Tyler E. Jacks, Ph.D., is the director of the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, the David H. Koch professor of biology at MIT, and an investigator with the Howard Hughes Medical Institute.

Jacks’ research interests are in the genetic events that contribute to the development of cancer. His laboratory has engineered a series of novel, mutant mouse strains that accurately mimic human cancer and thus serve as animal models for exploring the cellular pathways regulated by cancer-associated genes.

Jacks is a long-standing member of the AACR, and has served in several leadership positions for the AACR, including as a board member from 2001-2004, as a member of the nominating committee from 2004-2006 and as a member of the Annual Meeting 2003 program committee. Jacks was previously senior editor of Molecular Cancer Research. Jacks received his B.S. in biology from Harvard University and his Ph.D. in biochemistry from the University of California, San Francisco. He completed his post-doctoral training at the Whitehead Institute for Biomedical Research, MIT.

AACR Foundation trustees work collectively to fulfill the Foundation’s mission to accelerate progress in the conquest of cancer by providing financial support for scientific research, education and communication. The Foundation funds programs deemed by the American Association for Cancer Research to be of the highest priority and impact.

For more information about the AACR Foundation for the Prevention and Cure of Cancer and to learn how you can help, please visit our website.

Editor’s note: High resolution photos of Aisenbrey and Jacks are available upon request.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

The new study—only the second to use the test of subconscious bias in doctors—suggests that pediatricians have less "implicit race bias" than physicians in other specialties and the general public and that there was no relationship between subconscious bias and quality of care. "Further research is needed to explore whether physician implicit attitudes and stereotypes about race predict quality of care," according to the new study by Janice A. Sabin, PhD, MSW, and colleagues of University of Washington, Seattle.

Ninety-five pediatricians took an Internet survey called the Race Attitude Implicit Association Test (IAT). The test measures subconscious attitudes and stereotypes, based on how quickly the user makes connections between race and certain "good" versus "bad" concepts. Previous research in more than 1 million Internet users suggest that most people have some degree of "implicit preference" for whites relative to blacks—generally despite a lack of conscious (explicit) bias or prejudice.

Subconscious Bias Is Present, but Lower in Pediatricians
The pediatricians in the study also showed an implicit preference for whites. However, in this group of doctors—who worked at a large urban medical center—the subconscious bias was weaker than in the general population of Internet respondents. The pediatricians' implicit bias was also weaker than that found in a previous study of emergency room doctors. (That report, published last year in the Journal of General Internal Medicine, was the first study to use the Race Attitude IAT to test implicit bias in physicians.)

The pediatricians actually expressed an explicit attitude in favor of African-Americans. However, in addition to their implicit preference for whites, they held a subconscious bias that white patients would be more compliant (co-operative) with medical treatment. Surprisingly, there was also an implicit link between black patients and receiving "preferred" (as opposed to "adequate") medical care.

The pediatricians were also presented with hypothetical case vignettes of white or black children with common medical problems and asked what treatment they would recommend. Only one of the four vignettes showed a significant racial difference between the treatment recommendations (a higher hospitalization rate for white children with urinary tract infections). This lack of evidence that implicit bias affects medical treatment was in contrast to the study of emergency room doctors, in which the recommended treatments for suspected heart attack were less aggressive when the patient was black.

Many studies have shown racial and ethnic disparities in medical care that are not explained by other factors, such as income or access to health care. Researchers are interested in knowing whether bias on the part of health care providers could help to explain these racial/ethnic discrepancies. Some commentators have suggested that unconscious bias might be a more important factor than overt prejudice.

Much More Research Needed
The new study has some key limitations; the number of pediatricians taking the IAT was relatively small, and they were not a representative sample. However, the study provides intriguing clues for further research, including the possibility that implicit bias may vary among different groups of health care providers.

Like the previous study, it suggests that doctors may have an implicit association with black patients as less compliant with medical care, which might affect their treatment recommendations in various ways. "Future research is needed to gain a better understanding of the complex psychological interactions that exist between physician implicit and explicit attitudes and stereotypes about race, physician perceptions of patient characteristics, physician characteristics, organizational characteristics and quality of medical care," Dr. Sabin and coauthors conclude.

"The IAT is an emerging technique for investigating potential subconscious bias in the medical care setting," comments Dr Jeroan J. Allison of University of Alabama-Birmingham, Co-Editor-in-Chief of Medical Care. "The number of studies is limited and the current study has its own limitations. However, the initial findings are provocative though tentative: unconscious racial bias may impact decisions physicians make about patient care."

About Medical Care
Rated as one of the top ten journals in health services research and healthcare administration, Medical Care is devoted to all aspects of the administration and delivery of healthcare. This scholarly journal publishes original, peer-reviewed papers documenting the most current developments in the rapidly changing field of healthcare. Medical Care provides timely reports on the findings of original investigations into issues related to the research, planning, organization, financing, provision, and evaluation of health services. In addition, numerous special supplementary issues that focus on specialized topics are produced with each volume. Medical Care is the official journal of the Medical Care Section of the American Public Health Association. Visit the journal website at http://www.lww-medicalcare.com.

About Lippincott Williams & Wilkins
Lippincott Williams & Wilkins (www.LWW.com) is a leading international publisher for healthcare professionals and students with nearly 300 periodicals and 1,500 books in more than 100 disciplines publishing under the LWW brand, as well as content-based sites and online corporate and customer services. LWW is part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry.

Wolters Kluwer Health is a division of Wolters Kluwer, a leading global information services and publishing company with annual revenues (2007) of €3.4 billion ($4.8 billion), maintains operations in over 33 countries across Europe, North America, and Asia Pacific and employs approximately 19,500 people worldwide. Visit www.wolterskluwer.com for information about our market positions, customers, brands, and organization.

"We've been able to use magnetic nanoparticles to capture free-floating cancer cells and then take them out of the body," said John McDonald, chair of the School of Biology at Georgia Tech and chief research scientist at the Ovarian Cancer Institute. "This technology may be of special importance in the treatment of ovarian cancer where the malignancy is typically spread by free-floating cancer cells released from the primary tumor into the abdominal cavity.”

The idea came to the research team from the work of Ken Scarberry, a Ph.D. student in Tech's School of Chemistry and Biochemistry. Scarberry originally conceived of the idea as a means of extracting viruses and virally infected cells when his advisor, Chemistry professor John Zhang, had another idea. He asked if the technology could be applied to cancer. Scarberry suggested it might be an effective means of preventing cancer cells from spreading.

They began by testing the therapy on mice. After giving the cancer cells in the mice a fluorescent green tag and staining the magnetic nanoparticles red, they were able to apply a magnet and move the green cancer cells to the abdominal region.
“If the therapy is able to pass further tests that show it can prevent the cancer from spreading from the original tumor,” Scarberry said, “it could be an important tool in cancer treatment.”
This technology holds more promise than solely using antibodies to fight cancer because there seems to be less potential for the body to develop an immune response due to the unique peptide-targeting strategy, and the composition of the magnetic nanoparticles.

"If you modify the nanoparticle and target it directly to the tumor cells using a small peptide, you are less likely to generate an undesirable immune response and more accurately target the cells of interest,” said Research Scientist Erin Dickerson.

In addition to testing magnetic nanoparticles, the research team is collaborating with other groups at Georgia Tech to determine how peptide-directed gold nanoparticles and nanohydrogels might also be used in fighting cancer.

“Conventional gastroscopy can diagnose patients with gastric ulcers; however the procedure is invasive and occasionally may miss early stage disease. Our study was designed to determine if MDCT’s multiplanar reformation images plus virtual gastroscopy can help radiologists differentiate cancerous lesions from benign ulcer lesions,” said Chiao-Yun Chen, MD, lead author of the study.

“For virtual gastroscopy, we need to inflate the stomach to perform a CT scan then send all of the raw data to the workstation for post-processing. We can visualize the mucosal surface of the stomach, which traditionally needs to be done by optical gastroscopy,” said Dr. Chen. “However, with virtual gastroscopy alone, no information about the depth of the lesion can be obtained. Therefore, multiplanar reformatted images following intravenous contrast administration plays an important role. We are able to detect each lesion’s depth with CT this way. We can detect enlarged lymph nodes located in the space between the parietal peritoneum and the muscles and bones of the posterior abdominal wall, liver metastasis, etc., that can’t be easily detected using conventional endoscopy,” she said.

The study included 26 patients with gastric cancer (11 with T1 lesions and 15 with T2 lesions) and 26 patients with a benign gastric ulcer. “MDCT had a higher specificity in the diagnosis of malignant gastric ulcers with 77.8% in virtual gastroscopy and 100% in multiplanar reformation images” said Dr. Chen. “High specificity may help avoid delay in the treatment of patients with gastric cancer and thus may improve their survival rate,” she said.

The study appeared in a recent issue of the American Journal of Roentgenology.

That’s the finding of a new study led by University of Michigan Health System researchers, and published early online in the Annals of Emergency Medicine. The results suggest that emergency room teams need to do a better job of making sure patients go home with clear information and instructions – and that patients and their loved ones shouldn’t leave until they fully comprehend their situation.

The researchers carried out detailed interviews with 140 English-speaking patients who visited one of two emergency departments, and were released to go home. They compared those interviews with the patients’ medical records, and found a serious mismatch between what doctors and nurses found or advised, and what patients comprehended.

What’s worse, patients were pretty sure of what they “knew” 80 percent of the time – even if what they knew wasn’t quite right.

“It is critical that emergency patients understand their diagnosis, their care, and perhaps most important, their discharge instructions," says lead author Kirsten Engel, M.D., a former U-M emergency medicine fellow and Robert Wood Johnson Clinical Scholar who is now at Northwestern University. "It is disturbing that so many patients do not understand their post-emergency department care, and that they do not even recognize where the gaps in understanding are. Patients who fail to follow discharge instructions may have a greater likelihood of complications after leaving the emergency department.”

The study’s senior author agrees. “As a physician, I would like to think I could look someone in the eye and ask: ‘Do you have any questions?,’ and those who were confused or overwhelmed would ask for more help,” says Peter Ubel, M.D., a professor of internal medicine at the U-M Medical School. “This study shows that many patients walk away from important clinical encounters confident that they know what happened and why, but with little reason to be so confident.”

The researchers measured the extent to which patients’ reports agreed with their doctors’ records in four areas: diagnosis, emergency care that was given, post-ER care needs and what kinds of symptoms or signs would require the patient to return to the ER or seek immediate care.

Only 22 percent of patients’ reports were in complete harmony with what their care teams reported on all four counts.

Fifty-eight percent of patients understood at least two of the four areas, but 20 percent were off on three or four areas of their care and follow-up needs.

After asking patients about their diagnosis, care and post-ER instructions, the team also asked them if they were not sure about any of the four areas. Interestingly, patients whose understanding perfectly matched their doctors’ records were just as likely to report being unsure as patients whose understanding was lacking.

“Doctors need to not only ask patients if they have questions, but ask them to explain, in their own words, what they think is wrong with their health and what they can do about it,” says Ubel. “And patients need to ask their doctors more questions, and even need to explain, to their doctors, what they think is going on.”

The biggest area of misunderstanding or lack of comprehension was post-emergency care – that is, what steps the patient needs to take to be seen by their regular doctor or a specialist, how soon to see a doctor, or what medicines or self-care steps they need to take, how to take them, and when.

Ubel, Engel and their colleagues found that 34 percent of the deficiencies in patient comprehension reflected a less-than-complete understanding of what their ER team recommended they do after they left the ER. Meanwhile, 22 percent of the deficiencies in the study had to do with patients’ understanding of what symptoms or changes in their condition should spur them to return to the ER.

Recently, the U-M Health System introduced a program that aims directly at this problem: the Emergency Medicine Consult/Referral Service, run by the Department of Emergency Medicine and the Physician and Consumer Communications division of Public Relations & Marketing Communications.

It is staffed by referral coordinators who follow up with ER patients by phone within 24 hours of their ER visit, to help schedule appointments with U-M physicians for specialty care if the patients’ insurance allows it or make sure they know that they need to schedule an appointment elsewhere.

More than 12,000 follow-up appointments have been scheduled for recent U-M ER patients since the program began in February 2007, and 81 percent of those patients have arrived for their scheduled appointments, up from 59 percent before the program began. Appointment cancellations are also down.

Before the program began, 24 percent of U-M ER patients who needed a follow-up appointment never scheduled one. And many patients and clinicians who did try to arrange follow-up care went through a frustrating and confusing process that is repeated every day in hospitals around the country. The new call center offers a standardized, centralized way to make sure patients get scheduled to see the provider they need soon after their ER visit.

The new study involved patients from ages 18 to 83 years, 59 percent of whom were women. Nineteen percent of patients were African-American, and 68 percent were white, with the remaining percentage being other races or without a race recorded on their record. Thirty-five percent had a high school education or less. Patients were given a brief cognition test before being interviewed, to make sure their thinking and understanding abilities were normal. In some cases, caretakers were also interviewed.

In addition to Engel and Ubel, who directs the Program for Behavioral and Decision Sciences in Medicine, the new study’s authors include Michele Heisler, M.D., MPA, Dylan Smith, Ph.D., Claire Robinson, MPH, and Jane Forman, M.D. The study was funded by the Robert Wood Johnson Foundation and the U-M Clinical Scholars Program.

Reference: Annals of Emergency Medicine, doi:10.1016/j.annemergmed.2008.05.016

In the July 15, 2008, issue of Cancer Research, researchers at Harvard Medical School found in animal and laboratory experiments that the anti-rejection, immunosuppressive drug cyclosporine ramps up expression of vascular endothelial growth factor (VEGF), which signals the growth of new blood vessels that can feed tumors.

They also found that simultaneously administering an anti-VEGF therapy with cyclosporine in mice repressed this tumor growth. Several inhibitors of VEGF are already in use in human cancer therapy.

The findings could offer some good news for the 15 to 20 percent of transplant patients who develop cancer within a decade of receiving new organs, according to the study’s senior investigator, Soumitro Pal, Ph.D., an assistant professor at Harvard Medical School’s Transplantation Research Center at Children’s Hospital in Boston.

“It may be that anti-VEGF agents given judiciously after transplantation can reduce future cancer occurrence,” he said.

VEGF expression is markedly increased in patients post-transplantation, and this can aid in the development of a blood supply to a transplanted organ, helping it survive and thrive. “But once the organ has stabilized, it may be possible to lower the level of VEGF expression to prevent tumor growth,” he said. “We would need to figure out how to balance benefit and risk to keep cancer at bay.”

Tumors that develop after transplantation may have three potential sources: they may have pre-existed or could have been a recurrence of previous cancer – and in both of these cases, a patient’s pre-transplant immune system might have kept these cancers in check – or cancer-causing viruses could have come from the donor organ. Physicians have long observed that immunosuppressive agents, such as the class of calcineurin inhibitors that includes cyclosporine, appear to promote cancer development, often in organs that are not transplanted, but the cause of this was unclear. The Harvard team tested the ability of cyclosporine to promote growth of pre-existing tumors in mice implanted with human renal (kidney) cancer cells. Mice treated with the agent formed tumors faster than untreated mice, but anti-VEGF therapy substantially reduced that excessive growth.

Digging deeper into the biological pathway of VEGF activation, the scientists found that cyclosporine activates two of the three forms of the common protein catalyst, protein kinase C, which leads to increased expression of VEGF.

“We think PKC-mediated VEGF transcriptional activation is a key component in the progression of cyclosporine-induced post-transplantation cancer,” Pal said. “It is likely not the whole story, but this gives us a clue that we might be able to use existing or novel therapies to reduce cancer risk in transplanted patients.”

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

The article by senior editor Christopher Kent notes that cutting-edge work is being done in North Dakota, Oklahoma and Florida. The promise of such research includes finding treatments for eye diseases such as glaucoma and macular degeneration. Sanku Mallik, associate professor of pharmaceutical sciences at NDSU, conducts research that uses a nanoparticle called nanoceria as a drug delivery device. It is made of cerium oxide molecules. The brain-blood barrier can prevent medicines from reaching their therapeutic targets, but nanoparticles are so small they are capable of crossing the brain-blood barrier. Quoted in the article, Mallik notes, “So far, nanoceria appears to be nontoxic, but the drugs we attach to the particle might be toxic, so targeting molecules are necessary. These particles can also be used for imaging; we can attach molecules that can be made to glow after they reach targets such as cancer cells.”

So far, the research of Mallik and his associates has been conducted in a controlled environment outside of a living organism and is in its initial stages. Researchers must ensure that the particles are water-soluble for effective delivery and less irritation to the cornea. Glaucoma is the leading cause of blindness if left untreated, according to the Glaucoma Research Foundation. An estimated four million Americans have glaucoma but only half of them know it, according to Prevent Blindness America. Minnesota Twins center fielder Kirby Puckett (1960-2006) was forced to retire due to loss of vision in one eye from glaucoma. Age-related macular degeneration is the leading cause of visual impairment and blindness in Americans older than 50, affecting more than two million people, according to the American Academy of Opththalmology.

The pharmaceutical research of Mallik’s team includes attaching anti-cancer drugs to the nanoparticles and targeting molecules so particles only enter cells that are in need of treatment. Nanotechnology is often defined as the science of the extremely small. A nanometer, for example, is a hundred-thousandth of the thickness of a human hair, or one-billionth of a meter.

Mallik recently received a five-year, $1.46 million grant from the National Institutes of Health National Cancer Institute. D. K. Srivastava, professor of biochemistry and molecular biology at NDSU, is the co-investigator on this award. It relies on the complementary scientific expertise of Mallik and Srivastava. The grant will allow the investigators to prepare selective, “multi-prong” inhibitors for matrix metalloproteinases using lipid-based nanoparticles. They also will use the nanoparticles for isozyme-selective detection of these enzymes.

Mallik received his bachelor’s degree in chemistry from the Indian Institute of Technology, Kharagpur, India, and his doctorate degree in organic chemistry at Case Western Reserve University, Cleveland, Ohio. He completed post-doctoral work at the California Institute of Technology, Pasadena, Calif. He is a past recipient of a National Science Foundation CAREER award, which recognizes and supports the early career-development activities of scholars who are likely to become the academic leaders of the 21st century. Information about Dr. Mallik’s research is available at http://pharmsci.ndsu.nodak.edu/facstaff/mallik/research.htm

“This is the first efficient and consistent model system for HCV to be developed,” said Buck, adding that it will now enable researchers not only to conduct mechanistic experiments in culture, such as blocking the virus pathways, but also to more effectively screen possible therapies for HCV. “There is a need for new treatments, and for development of a possible vaccine for HCV. Now we have a model system to support work by investigators in this area.”

Currently, there is only a single treatment for HCV, PEG- interferon-?. The drug combination has an average response rate of about 50 percent in HCV cases, but it is much lower than that, closer to 20 percent, in individuals with liver cirrhosis. It can also cause severe flu-like side effects. Approximately 10,000 deaths due to cirrhosis of the liver and several thousand more from liver cancer are attributed to HCV infection in the United States each year.

The HCV life cycle is only partially understood because, until now, it has not been possible to efficiently infect normal human hepatocytes, or liver cells, in culture. According to Buck, the valuable Huh-7 system currently in use to test HCV uses cloned, synthetic HCV RNA expressed from liver tumor cells. These cells cannot be infected with naturally occurring HCV obtained from infected patients.

In contrast, the culture developed by the UCSD scientists allows direct infection with HCV genotypes 1, 2, 3 and 4 from the blood of HCV-infected patients. This system will enable researchers to study the complete viral lifecycle in its normal host cell, providing novel scientific opportunities. The study reports that the system has been tested using over 30 virus donors as well as multiple donors of hepatocytes, with the production of infectious HCV for all genotypes tested.

This work was supported by grants from the National Institutes of Health, the Department of Veterans Affairs (Merit Review) and the Medical Research Foundation at UC San Diego. Buck is a recipient of the Howard Temin Award from the National Cancer Institute.