Faculty Bibliography

Dr. Waldo E. Nelson, the author of the leading textbook of pediatrics for 40 years, died on March 2 at his home in Gladwyne, Pa. He was 98. A distinguished medical educator, Dr. Nelson was the chairman of the department of pediatrics at Temple University and the medical director of St. Christopher's Hospital, both in Philadelphia. Many doctors trained by Dr. Nelson are now leaders in pediatrics. Dr. Nelson was also the editor of The Journal of Pediatrics from 1959 through 1978. However, Dr. Nelson was even better known to generations of doctors whom he did not train directly through the classic textbook he wrote, now known as the ''Nelson Textbook of Pediatrics.''

A gene (pncA) with mutations associated with pyrazinamide resistance in Mycobacterium tuberculosis complex members was characterized in 67 pyrazinamide-resistant and 51 pyrazinamide-susceptible isolates recovered from diverse geographic localities and anatomic sites and typed by IS6110 profiling. All pyrazinamide-susceptible organisms had identical pncA alleles. In striking contrast, 72% of the 67 resistant organisms had pncA mutations that altered the primary amino acid sequence of pyrazinamidase. A total of 17 previously undescribed mutations were found, including upstream mutations, missense changes, nucleotide insertions and deletions, and termination mutations. The mutations were arrayed along virtually the entire length of the gene. These data are further evidence that most drug resistance in M. tuberculosis is due to simple mutations occurring in chromosomally encoded genes rather than to acquisition of resistance genes by horizontal transfer events

Large-cell change of hepatocytes (LCC), also called liver cell dysplasia of large-cell type, is a set of cytologic changes comprising nuclear and cytoplasmic enlargement, nuclear pleomorphism, and multinucleation. This entity is encountered frequently on histologic or cytologic examination of specimens obtained from livers with a variety of chronic diseases and originally was thought to have a premalignant nature. Accumulating evidence, however, now suggests that LCC is merely a reactive change. Having often observed LCC in liver specimens with chronic biliary tract disease, that is, in livers where cholestasis preceded hepatocyte injury, we surmised that LCC may be a result of prolonged cholestasis. To determine whether there was any association between LCC and cholestasis, we examined microscopically a series of 400 nodules from 40 consecutive adult cirrhotic livers, resected on transplantation, and graded LCC and cholestasis semiquantitatively. LCC was present diffusely in cirrhotic nodules of 25 specimens (62.5%). Nine additional specimens (22.5%) had focal mild LCC. Usually, LCC and cholestasis occurred together, in the same cirrhotic nodules and in the same areas of nodules. There was a statistically significant association between the presence and grade of LCC and those of cholestasis (p < 0.0001; chi-square test). Within etiological categories of cirrhosis (chronic hepatitis; n = 28; alcoholic liver disease; n = 6; biliary disease: n = 6), the significance was maintained. We conclude that, in cirrhosis of different etiologies, LCC may represent a reactive change that results from prolonged cytoplasmic cholestasis

The national decline in AIDS deaths confirms the trend that New York City health officials reported last month in announcing that their figures for all of 1996 showed the first documented drop in AIDS deaths anywhere in the country -- while the number of AIDS cases nationwide is rising. Today's report refuted some experts who suggested that the improvement in New York City was an isolated phenomenon or was due to incomplete reporting or a statistical quirk. One notable difference between the New York City and national figures is that, for unknown reasons, deaths from AIDS for women rose 3 percent in the national data while AIDS deaths of women in New York City dropped 24.5 percent. Officials at the Federal health agency, in Atlanta, like those at the New York City Health Department, said the drop in deaths was probably due in large part to the success of drug therapies introduced over recent years to fight H.I.V., the virus that causes AIDS, and the many potentially fatal complications of AIDS through opportunistic infections

About 70 percent of the drop in the number of deaths from coronary artery disease can be attributed to use of clot-dissolving drugs, like streptokinase and tissue plasminogen activator, and procedures like angioplasty and bypass surgery for people with coronary artery disease, according to the study, published today in The Journal of the American Medical Association. Dietary changes in the general population aimed at preventing coronary artery disease accounted for only about 25 percent of the drop between 1980 and 1990, said the study's lead author, Dr. Maria G. M. Hunink, of the Harvard School of Public Health and University of Groningen in the Netherlands. Dr. Hunink said in a telephone interview from Groningen that her team had been ''amazed'' to learn that medical treatment had a larger impact than prevention on the incidence of coronary artery disease, the most common type of heart disease. It remains the leading cause of death of Americans, despite a decline of from 2 to 4 percent each year in recent years in this country

Medical treatment has been much more important in the decline of heart-disease deaths than widespread changes in diet and other means of prevention, a statistical study has found. About 70 percent of the drop in the number of deaths from coronary artery disease can be attributed to use of clot-dissolving drugs and procedures such as angioplasty and bypass surgery, according to the study, published today in The Journal of the American Medical Association. Dietary changes in the general population aimed at preventing coronary artery disease accounted for about 25 percent of the drop between 1980 and 1990, said the study's lead author, Dr. Maria G.M. Hunink of the Harvard School of Public Health and the University of Groningen in the Netherlands

Hodgkin's disease (HD) has long been suspected to have an infectious precursor, and indirect evidence has implicated Epstein-Barr virus (EBV), a ubiquitous herpesvirus, as a causal agent. Recent molecular studies using EBER in situ hybridization or latency membrane protein-I (LMP-I) immunohistochemistry have identified EBV latent infection in up to 50% of HD tumors. However, the epidemiologic features of these cases have not been examined in detail. To explore the epidemiology of EBV-positive HD so as to understand the role of EBV in HD etiology more clearly, this project accumulated patient data from 14 studies that had applied these EBV assays to HD tumors. With information on age at diagnosis, sex, ethnicity, histologic subtype, country of residence, clinical stage and EBV tumor status from 1,546 HD patients, we examined risk for EBV-positive disease using logistic regression. Forty percent of subjects had EBV-positive tumors, and EBV prevalence varied significantly across groups defined by the study variables. Odds ratios (OR) for EBV-associated HD were significantly elevated for Hispanics vs. whites (OR = 4.1), mixed cellularity vs. nodular sclerosis histologic subtypes (OR = 7.3, 13.4, 4.9 for ages 0-14, 15-49, 50+ years), children from economically less-developed vs. more-developed regions and young adult males vs. females (OR = 2.5). These findings suggest that age, sex, ethnicity and the physiologic effects of poverty may represent biologic modifiers of the EBV association and confirm that this association is strongly but variably linked to histologic subtype. The data augment biologic evidence that EBV is actively involved in HD pathogenesis in some cases but describe epidemiologic complexity in this process.