Radiology: Catching Cancer Before It Takes Hold Social Medicine: AIDS Study in Africa Shows Decline Amid Growing Epidemic Cell Biology: Gene Related to Tumor Suppressor Linked to Stem Cell Pool Education: Soma Weiss Day Study Finds Two Thirds Of Breast Cancer Symptoms Require Follow-up Care Crystal Structure Solved for Tumor-Associated Complex ECMO Shows Promise in Some Adults Eating an Egg a Day OK for the Heart HMS Community Meets on Gay and Lesbian Issues Deans Make Case for Meeting on Gay and Lesbian Issues Wilson Outlines $20 Million Study of Welfare Reform A Preview of Alumni Week The Robert H. Ebert Lecture on April 15 In Memoriam: David Smith, Thomas Morris Jr., Eugene Sullivan Memorial Service for John Penney Honors and Advances News Brief The Fay Golden Kass Lecture on May 4 Mining Information from Mountain of Scientific Data Front Page

RESEARCH BRIEFS Study Finds Two Thirds Of Breast Symptoms Require Follow-up Care Women's awareness of breast problems has increased substantially in recent years as breast cancer has become a major focus of media attention and political advocacy. But little has been known about the breast symptoms women bring to their primary physicians in the U.S., the evaluations used to investigate these symptoms, or the outcomes. Mary Barton, instructor; and Suzanne Fletcher, professor, both of ambulatory care and prevention at HMS and Harvard Pilgrim Health Care; with Joann Elmore of the University of Washington, studied records of breast-related visits between 1983 and 1993 among 2,400 women enrolled in Harvard Pilgrim who were between 40 and 69 years of age in 1983. Breast-Symptom Episodes by Patient Age Age Group Rate per 1,000 person-years 40-59 32.0 50-59 23.6 60-69 13.9 70-79 16.9 Source: 20 April 1999 Annals of Internal Medicine Vol. 130 No. 8 A study from HPHC found that younger women sought medical care for breast symptoms nearly twice as often as older women. Unexpectedly, breast cancer was found about as frequently in all age groups. This suggests breast symptoms should be taken seriously in younger women even though their breast cancer rates are lower overall.     Women under age 50 presented with breast symptoms, such as pain, lumps, and skin or nipple changes, nearly twice as often as older women. Clinicians found a breast mass in 34 percent of episodes, fibrocystic changes in 21 percent, and skin changes or nipple discharge in 8 percent. They judged physical findings normal in 33 percent of episodes, abnormal but benign in 27 percent, and suspicious for cancer in six percent, with the remainder indeterminate. Follow-up evaluations, including mammograms, repeat exams, and surgical consultation, were performed for 66 percent of episodes, and invasive procedures such as fine needle aspiration or biopsy were performed for 27 percent. "Cancer was diagnosed in more than four percent of episodes, indicating that follow-up of breast symptoms is important in primary care practice," the authors conclude. The study was published in the April 20 Annals of Internal Medicine. Crystal Structure Solved for Tumor-Associated Complex Families with Von-Hippel Lindau syndrome carry a hereditary mutation in the VHL tumor suppressor gene, putting them at high risk for cancers of the brain, kidney, retina, pancreas, and adrenal gland. Born with one defective copy of VHL in every cell, members of these families develop tumors when a somatic cell suffers a mutation in the remaining copy. About 80 percent of people with non-inherited clear cell renal carcinoma—the most common kidney cancer—also have VHL mutations. The normal functions of the VHL protein are not fully understood, but it is believed to suppress production of vascular endothelial growth factor (VEGF), an angiogenic factor, and related proteins.     In the April 16 Science, William Kaelin, associate professor of medicine at the Dana–Farber Cancer Institute, and researchers at Cornell University and Memorial Sloan-Kettering Cancer Center report the crystal structure of the three-part VCB complex made up of VHL and two other proteins, Elongin C and Elongin B. Many tumorigenic VHL mutations disrupt VHL's binding to Elongin C (which in turn binds Elongin B), suggesting a central role for the complex in VHL's tumor suppressor function.     Based on VCB's similarities to a protein degradation complex known as SCF (Skp1–Cul1–F-box protein), the findings of Kaelin and coauthors strengthen existing evidence that VCB is part of an analogous degradation pathway. Earlier studies showed that Elongin C shares homology with Skp1, and that binding of the VCB complex to Cul2, a homolog of Cul1, is required for VHL to regulate VEGF. The new findings bolster the analogy by revealing that the Elongin C binding portion of VHL has a pattern of hydrophobic amino acids matching that of the F-box protein that binds Skp1. This points to a loose structural similarity between the VHL segment and the F-box, despite DNA sequences with little in common. It also suggests, by analogy to the F-box, that "VHL may have a second macromolecular binding site that is important for its tumor suppressing function and suggests that VHL may function as a modular adapter like the F-box proteins," the authors write.     Kaelin is a coauthor of a related article in the April 23 Science. In this study, scientists show that the VHL and SCF complexes both include an evolutionarily conserved protein called Rbx1, which appears to regulate ubiquitination (tagging proteins for destruction by attaching ubiquitin molecules). The finding provides yet another link between the two complexes and further evidence of a role for VHL in protein degradation. ECMO Shows Promise In Some Adults For newborns with severe acute respiratory failure, survival has improved dramatically thanks to extracorporeal membrane oxygenation (ECMO), a technique using a modified heart–lung machine to maintain adequate blood oxygen until the lungs recover. ECMO has proved less successful in older patients, and its non-neonatal use has been controversial, with critics arguing that it is expensive and largely futile. But a new study by researchers at Massachusetts General Hospital adds to the evidence that ECMO can save the lives of older children and adults if these patients are carefully selected.     Acute respiratory failure occurs rarely in a wide variety of conditions that include sepsis, pneumonia, trauma, and immune deficiency from chemotherapy or transplantation. Many patients can be successfully treated with mechanical ventilation, but for those who cannot, the prognosis is grim, with mortality exceeding 80 percent. One reason is that prolonged use of a ventilator can irreparably damage the lungs.     Peter Masiakos, a research fellow in surgery; Daniel Ryan, assistant professor of surgery; and colleagues at MGH examined records of 34 patients aged 8 days to 56 years who were treated with ECMO between 1990 and 1998, to identify which patients were likely to survive. The study was published in the April Archives of Surgery. They found that all 13 patients with sepsis or viral pneumonia, four of five with respiratory failure of unknown cause, and the sole patient with non-burn inhalation injury survived to discharge. By contrast, only one of eight immunocompromised patients and neither of two trauma or burn patients survived, while four of 10 patients with bacterial or fungal pneumonia lived. Patients under age 10 and those between 30 and 39 were most likely to survive, probably because they are more likely to have conditions effectively treated with ECMO. "Improvements in ECMO technology and the reevaluation of criteria for patient selection ... have greatly improved survival," the authors conclude. One reason for the improved success is the realization that older patients may require substantially longer time on ECMO than do newborns. Eating an Egg a Day OK for the Heart An egg a day may not keep the doctor away, but it probably will not land you in the hospital either, according to an article by Harvard School of Public Health researchers. In the April 21 JAMA, research associate Frank Hu and colleagues at HSPH report findings on more than 100,000 men and women in the Nurses' Health Study and the Health Professionals Follow-Up Study. They found no overall association between consumption of up to one egg per day, either recently or over the past decade, and risk of coronary heart disease or stroke. The finding held up after controlling for variables that influence cardiovascular health, such as smoking, exercise, and other dietary habits.     To keep blood cholesterol low, the public has been advised to consume no more than 300 mg per day of cholesterol and to limit consumption of eggs, which each contain about 213 mg. The authors speculate on why moderate egg consumption does not increase risk. "It is conceivable that the small adverse effect of cholesterol in an egg on plasma low-density lipoprotein levels is counterbalanced by potential beneficial effects on high density lipoprotein (HDL) and triglycerides, and of other nutrients including antioxidants, folate, other B vitamins, and unsaturated fat," they suggest. Also, eating eggs instead of carbohydrate-rich foods might raise HDL levels and decrease blood glucose and insulin. One exception to the overall findings was that people with diabetes showed a possible relationship between egg consumption and coronary heart disease. This warrants further research, the authors write, and may be related to abnormal cholesterol transport due to decreased levels of apolipoprotein E and increased levels of apolipoprotein C-III in diabetic patients. Back to Top