Whole body protein turnover in children with human immunodeficiency virus (HIV) infection

The purpose of this study was to determine the rate of whole body protein turnover (WBPT) in human immunodeficiency virus (HIV)-infected children, and to determine the relationship between WBPT and growth. The rate of WBPT was calculated from the cumulative excretion of labeled urinary ammonia after a single intravenous dose of 15N-glycine in three groups of children: 1) HIV+ with growth retardation (HIV+ Gr); 2) HIV+ with normal growth (HIV+); and 3) HIV-uninfected with normal growth (HIV-). Twenty-six children between 2 and 11 y of age were studied (10 HIV+ Gr, 12 HIV+, 4 HIV-). All children were afebrile and free of acute infection during the study. Rates of WBPT (mean +/- SD) for the study groups were: HIV+ Gr, 12.2 +/- 4.8; HIV+, 10.7 +/- 5.1; and HIV-, 8.6 +/- 2.1 g.protein.kg-1.d-1 (NS, P > 0.05). Although not statistically significant, mean WBPT was 42% greater in HIV+ Gr, and 24% greater in HIV+ compared to HIV-. Statistically significant correlations were found between WBPT and Z scores for height (r = -0.39, P = 0.05) and weight-for-age (r = -0.51, P = 0.01) and dietary intake of protein (r = 0.39, P = 0.05), and between protein balance (synthesis-catabolism) and intakes of energy (r = 0.47, P = 0.02) and protein (r = 0.40, P = 0.04). There was no statistically significant correlation between WBPT and resting energy expenditure (r = 0.27, P = 0.19), or CD4 cell number (r = 0.05, P = 0.82). These data suggest an association between increased rates of protein turnover and low weight and height-for-age Z scores, and that it may be possible to achieve positive protein balance given an adequate intake of nutrients.     

Placental transport of Zidovudine in the rhesus monkey

Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey.Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120-130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood , samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance liquid chromatography (HPLC) with ultraviolet (UV) detection.Results: In monkeys who received ZDV, the terminal half-life (T1/2) for ZDV was 37+/-15 and 33 +/- 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal ZDVG was 124 +/- 44 and 142 +/- 50 min in the maternal and fetal compartments, respectively. Peak levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 +/- 0.20 at 20 min to a maximum of 0.74 +/- 1.0 at 120 min and from 0.28 +/- 0.08 at 20 min to 1.4 +/- 1.3 at 180 min, respectively. In monkeys who received ZDVG, the T1/2 for ZDWG in the maternal and fetal compartments was 47 +/- 26 and 119 +/- 164 min, respectively. ZDVG reached its peak in the fetal compartment at 60 min post-injection. The fetal/maternal rafio ranged from 0.08 +/- 0.11 at 20 min to 4.2 +/- 4.2 at 180 min post-injection.Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some metabolism of ZDV to ZDVG occurs in the fetal compartment.     

Where is group practice headed?

A CRAHCA educational program was held recently to determine the changes in the health service environment that are most likely to occur in the near future, and how these changes will affect medical group practice.     

The epidemiology of endometrial cancer in young women

A case-control study was conducted in Los Angeles County, California, of 127 endometrial cancer cases aged 45 years or less at diagnosis, to investigate the role of fertility, obesity and exogenous oestrogens in the development of the disease in young women. Use of sequential oral contraceptive (SOCs) or oestrogen replacement therapy (ERT) for greater than or equal to 2 years was strongly associated with increased risk of endometrial cancer. After excluding these cases, since the SOC or ERT use was probably the cause of their disease, we were left with 110 case-control pairs for further study. Among these remaining case-control pairs increasing parity was strongly associated with decreased risk (relative risk of 0.12 for women of parity 3 compared to nulliparous women, P less than 0.001). Current weight was associated with increased risk (relative risk of 17.7 for women weighing greater than or equal to 190 lbs compared to women weighing less than 130 lbs, P less than 0.001). Combination oral contraceptive (COC) use was associated with a decreased risk, which decreased with duration of COC use (relative risk of approximately 0.28 at 5 years of use, P less than 0.001), but the estimate of the protective effect was reduced and became statistically non-significant when allowance was made for weight and parity. The protective effect of COC use was only clearly evident in women who had less than 3 live-births and weighed less than 170 lbs. These results provide further support for the "unopposed" oestrogen hypothesis of the aetiology of endometrial cancer.     

Bleomycin and brain tumors

A logical inference from the recent reports indicating that malignant brain tumors are composed of a heterogeneous cell population is that combination chemotherapy will be required for effective brain tumor control. For several years we have been investigating the use of Bleomycin as an agent to be used in conjunction with radiation therapy and a nitrosourea compound. Since systemically administered Bleomycin does not cross the blood-brain-barrier and has significant toxicity when used parenterally in high doses, we have studied the use of smaller doses of Bleomycin injected directly into the brain tumor cavity. Such an intracerebral dose was more effective in prolonging survival of rats burdened with experimental 9L gliosarcomas than an intravenous dose that is 25 times as great. The combination of intracerebrally administered Bleomycin and radiation therapy was more effective than either modality alone. Furthermore, the combination of Bleomycin delivered intracerebrally and BCNU given systemically was more effective than eitheragent used alone. Finally, in a Phase I clinical trial of Bleomycin given via an Ommaya reservoir to eight patients with recurrent malignant brain tumors, we have demonstrated that individual doses of up to 7.5 units and cumulative doses of up to 255 units can be administered without significant toxicity.     

A Canadian model for developing mental health services in rural communities through linkages with urban centers

The development of mental health care services in rural areas has been a constant challenge in most countries of significant geographical size. By use of a case study from Canada, the development of a relationship between rural and urban mental health services was described. Issues including referral patterns, service accessibility, professional recruitment and the development of service in rural regions were studied. It is advanced that mental health administrators, policy-makers, clinical service coordinators and educators will find that this approach to the development of mental health services in rural areas has some utility in Canada and in other countries.     

The use of an antibiotic-impregnated spacer block for revision of the septic total knee arthroplasty

Through the use of an antibiotic-impregnated polymethylmethacrylate spacer block in two-stage exchange arthroplasty, the chronically infected total knee arthroplasty can, in most cases, be effectively salvaged. In a review of 28 such consecutive cases by a single surgeon, all revised implants were retained except one which required arthrodesis. In the remaining cases, mean Hospital for Special Surgery knee scores were 86, with mean total range of motion of 90 degrees . All wounds healed eventually, and seven patients were thereafter able to undergo other total joint arthroplasties. Advantages of this technique included maintenance of ligamentous balance as well as bone stock with weight bearing, local antibiotic delivery, and facilitation of reimplantation.     

Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease

Disaggregated ventral mesencephalic tissue from single aborted human fetuses of 11 to 18 weeks' gestation was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease. All were receiving optimum levodopa therapy and were examined preoperatively and at 3,6,9, and 12 months postoperatively. Immunosuppression was not used. There were significant sustained improvements at 12 months in three patients; motor fluctuations were absent in two. There were modest group improvements up to 6 months, with increased quality of "on" and "off" phases, quantity of on times, and specific improvements in contralateral upper limb bradykinesia. Preoperative levodopa requirements were reduced to a mean of 64% at 6 months and 61% at 12 months. Deterioration below baseline ratings occurred in three of nine patients who had consistent follow-up to 12 months. Grafting of midgestational human fetal tissue can lead to improvement in Parkinson's disease. Individual disease severity may be critical, and further trials are needed to identify host factors influencing outcome.     

Surgery centers continue pattern of growth

The number of outpatient surgery centers grew at an 11% clip in 1990, fueled by the continued shift of patients and procedures to the outpatient setting, according to a recent survey by SMG Marketing Group, a Chicago-based healthcare consulting and market research firm. But while figures project continued growth, competition and government regulation could limit future expansion.