Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.      

Cardiac tamponade as a manifestation of tuberculosis

Tuberculosis has been increasing in incidence in recent years. Pericardial involvement and pericardial effusions are well-documented and may result in pericardial tamponade. Despite this, large pericardial effusions are uncommon, and manifestation as cardiac tamponade is rare. We report two cases of tuberculous pericarditis in which the initial feature was tamponade. Since the diagnosis of tuberculosis may be delayed due to the slow-growing nature of the bacterium, physicians need to be aware of this possibility and consider the use of modern diagnostic techniques that may permit an earlier diagnosis.     

Treatment of chronic hepatitis C virus infection

OBJECTIVE: To review the literature on the treatment of chronic hepatitis C virus (HCV) infection. DATA SOURCES: MEDLINE search (1986-December 1999) using key words such as HCV, hepatitis, non-A and non-B hepatitis, as well as terms regarding treatment during that time period. DATA SYNTHESIS: HCV infection was initially treated with interferon monotherapy, but only a minority of patients responded to long-term therapy. A higher rate of response in both interferon-na?ve patients and interferon-relapsers has been achieved by using the combination of interferon and ribavarin. Other treatment regimens including high-dose interferon protocols, ursodeoxycholic acid, amantadine, and nonsteroidal antiinflammatory drugs have been less promising. Many alternative therapies are being investigated. CONCLUSIONS: HCV infection is a major public health problem. It is now possible to achieve a cure in nearly 50% of the patients with this infection. Many additional therapies are being evaluated in order to achieve a higher cure rate.     

Normal pulmonary vascular resistance and left ventricular hypertrophy in young infants with bronchopulmonary dysplasia: an echocardiographic and pathologic study

To evaluate the cardiac anatomy and functional hemodynamics in young infants with chronic lung disease, nine patients, aged 2 to 7 months, with a clinical diagnosis of bronchopulmonary dysplasia (BPD) underwent echocardiographic examination. All infants required supplemental O2 (mean FIO2 35%) to maintain adequate systemic oxygenation (Pao2 greater than 50 mm Hg). None of the infants had evidence of a patent ductus arteriosus at the time of examination. Echocardiographic measurements of left and right ventricular systolic time intervals revealed normal systolic time interval ratios suggesting pulmonary vascular resistances. However, echocardiographic evidence of left ventricular hypertrophy was found in eight of the nine infants, while right ventricular anterior wall thickness and right ventricular diastolic dimensions were not increased. Two infants died; marked left ventricular hypertrophy was noted at the time of postmortem examination while the right ventricular wall thickness was normal. The findings of left ventricular hypertrophy led to a retrospective review of autopsy material of seven patients who died with BPD over the past year. In six of seven cases examined, left ventricular posterior wall thickening was noted (range 7 to 11 mm); while the right ventricular wall thickness was normal (range 2 to 5 mm). These data suggest that (1) as assessed by echocardiography, the pulmonary vascular resistance is not significantly elevated in young infants with BPD, and (2) a hypertrophic left ventricle evolves which may assume importance in the pathogenesis of pulmonary edema in BPD, though the precise etiology remains undetermined.