Effect of low-dose phenobarbital on hepatic microsomal UDP-glucuronyl transferase activity

To determine whether hepatic microsomal enzyme induction occurs in rats following administration of phenobarbital at doses similar to those used in humans (0.5 to 7.5 mg/kg), UDP-glucuronyl transferase (UDPGT) and cytochrome P-450 activities were measured in liver homogenate and microsomal preparations from control rats and rats treated for 6 days with phenobarbital at 1 and 3 mg per kg per day. While no significant increases in liver weight and protein content of homogenate and microsomal preparations were observed with either dose of the drug, both UDPGT and P-450 activities were enhanced significantly following administration of phenobarbital at 3 mg per kg per day. The activity of P-450 was increased by approximately 30% and that of UDPGT by 15-24 and 45-66%, respectively, employing bilirubin and p-nitrophenol as the acceptor substrate. The extent of induction of bilirubin or p-nitrophenol UDPGT was similar when measured with "native" enzyme or with enzyme activated by UDP-N-acetyl glucosamine, digitonin or deoxycholate. These data suggest that the discordant effects of phenobarbital on UDPGT and cytochrome P-450 previously reported in humans and rats may not be attributable solely to differences in the drug doses employed.     

Exercise and heart disease. Epidemiology of the "exercise hypothesis"

The "exercise hypothesis" states that exercise protects against coronary heart disease. Reviewed herein is the epidemiologic evidence for and against the "exercise hypothesis." The weight of evidence supports the view that exercisers have a lower risk of coronary disease, but that vigorous exercise cannot always prevent progression of coronary atherosclerosis and does increase the risk of sudden death in persons with advanced coronary atherosclerosis. It is concluded that the "exercise hypothesis" is plausible, even likely, but still unproved.     

Primary chemotherapy in the treatment of children with bladder--prostate tumors in the Intergroup Rhabdomyosarcoma Study (IRS-II)

Twenty-nine children (24, male; 5, female) with non-disseminated rhabdomyosarcomas of the bladder or prostate were treated (1978-1980) by a primary chemotherapy regimen consisting of vincristine, actinomycin D, and cyclophosphamide ("Pulse" VAC), with or without local radiotherapy. During the initial 20 wk of chemotherapy, nine children achieved a Clinical Complete Response (CCR). Three of these are without evidence of disease (NED) and have functional bladders, two following partial cystectomy. Four who achieved a CCR subsequently relapsed or remained biopsy positive, but are at present NED following radiotherapy and anterior exenteration. Two patients who achieved CCR status relapsed and have died of disease. Twelve patients had a Clinical Partial Response (CPR) in less than 20 wk and two others in less than 40 wk. Seven of these are NED with intact bladders following chemotherapy-radiotherapy; and an additional patient is NED following partial cystectomy. Four patients in the CPR group have been treated by exenteration following failure to achieve complete response, and are NED. One patient has died, and one has progressive disease. Six patients had an inadequate response to chemotherapy (NR). Anterior exenteration was carried out in three, and two of these have survived. The overall results in these 29 patients are: (A) alive and disease-free with functional bladders, 11; (B) alive and disease-free following anterior exenteration, 10; and (C) dead or death from tumor anticipated, 8. The function of retained bladders (11) has been satisfactory.     

Successful Treatment of Erdheim-Chester Disease With Coronary Artery Involvement

Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis and inflammatory myeloid neoplasm with poor prognosis. Symmetric long bone osteosclerosis occurs in nearly all patients, but other organs are often involved. Coronary artery involvement is rare, but was encountered in a patient who experienced angina. Radiologic presentation and histologic findings were consistent with diagnosis of ECD. A soft-tissue mass was found surrounding the right atrium, ascending aorta, and all branches of coronary artery. Interferon-alfa treatment was successful. In conclusion, we recommend coronary artery computed tomography angiography for cardiovascular evaluation of ECD and interferon-alfa to treat ECD.     

Peripherally inserted central catheter-related bloodstream infections in patients with hematological malignancies: A retrospective 7-years single-center study

ObjectivesWe sought to investigate the nature and incidence of bloodstream infection complications and to identify the risk factors of central catheter-related bloodstream infections (CRBSI).MethodsDuring the study period, 291 consecutive patients with hematological malignancies who underwent PICC placement were retrospectively enrolled. We analyzed the covariates that were specified a priori for their association with CRBSI through multivariate Cox proportional hazards regression models. The association between each predictor and the related outcome was expressed using hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).ResultsOf 391 peripherally inserted central catheter (PICCs) were inserted in 291 patients for a total of 63,714 catheter days during 7 years, with an infection rate of 0.71/1,000 catheter days. Among the patients with hematological malignancies, those with acute leukemia were prone to CRBSI. Having previous bloodstream infection (BSI) (HR 18.139; 95% CI, 8.19-40.174; P < .0001), the number of PICCs insertions (HR 4.695; 95% CI, 1.842-11.967; P = .001) (twice), (HR 6.794; 95% CI, 1.909-24.181; P = .003) (≥3 times) were significantly associated with CRBSI. Not accompanied by chronic comorbidities (HR 0.34; 95% CI, 0.131-0.887; P = .028) and longer duration of PICC use (days) (HR 0.997; 95% CI, 0.994-0.999; P = .008) might be protective factors preventing CRBSI.ConclusionsOur finding suggests that previous BSI and a higher number of PICC insertions are associated with an increased risk of CRBSI. A lack of chronic comorbidities may help prevent CRBSI.