Serum and Cerebrospinal Fluid Pharmacokinetics of Intravenous and Oral Lamivudine in Human Immunodeficiency Virus-Infected Children

We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (± standard deviation) in the children was 0.53 ± 0.19 liter/kg/h (229 ± 77 ml/min/m² of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 ± 0.18 and 2.2 ± 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% ± 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 μM for ≥8 h of 24 h on the twice daily oral dosing schedule with doses of ≥2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h.     

Morphologic characterization of osteoblast-like cell cultures isolated from newborn rat calvaria

Summary Two methods for harvesting osteoblast-like cell populations from newborn (10 days) rat calvaria were compared. The first one consisted in culturing the periosteum-free bones and then trypsinizing the cells on the bone surface. The second one involved the migration of the osteoblasts on glass fragments before trypsinization. Since the plating efficiency, the proportion of alkaline phosphatase-positive cells, the population doubling time, and the calcium deposition were more adequate, the second method was used to further characterize the behavior of the cultures. During the first week of culture, the cells featured shapes similar to those observedin vivo on the surface of periosteum-free calvaria. They formed multilayers and, in the presence of ascorbic acid, synthetized an organic matrix containing exclusively type I collagen. Later, small amounts of type III collagen appeared. The cells were embedded in the matrix and progressively acquired the morphologic phenotype of osteocyte-like cells. The matrix mineralized in the presence of β-glycerophosphate. The technique of dropinoculation (high concentration of cells in a small volume of medium) promoted the multilayer formation and the achievement of large mineralized plates (about 1 cm²) in 3 weeks of culture.     

Risk factors of system clotting in heparin-free haemodialysis

Heparin-free haemodialysis must be considered for all dialysis patients with a risk of haemorrhage. This technique is associated with increased danger of system coagulation with a blood loss of up to 250 ml. In 84 patients with a risk of haemorrhage, 296 heparin-free haemodialyses were recorded prospectively. First signs of coagulation were found very much more frequently in the venous airtrap than in the dialyser (146 vs 42). System coagulation occurred in 13 of the 296 dialyses (4%) and was prevented by prophylactic switching of the system and dialyser in 140 dialyses (47%). The time of system coagulation was on average 1.8 hours (+/- 0.2) after the beginning of dialysis. The 13 patients with system coagulation had a reduced blood flow on dialysis (217 +/- 52 vs 240 +/- 36 ml/min). Their initially normal clotting time (12 +/- 5 vs 14 +/- 4 min) was more significantly shortened after 2 h (4 +/- 3 vs 8 +/- 3 min). The activities of antithrombin III (87 +/- 34% vs 88 +/- 39%) and protein C (66 +/- 45% vs 59 +/- 37%) do not differ from those of 47 other patients, even at the time of system coagulation, as measured in five patients (92 +/- 34% for antithrombin III, 51 +/- 29% for protein C). System coagulation and shortening of clotting time thus cannot be regarded as a consequence of absorption of these inhibitory factors of plasmatic coagulation. The danger of system coagulation in heparin-free haemodialysis could probably be further reduced by an improvement of the biocompatibility of systems (airtrap) and dialysers (less activation of thrombocytes).     

Comparison of stress transmission in the IMZ implant system with polyoxymethylene or titanium intramobile element: a finite element stress analysis.

Using the finite element method, this study modeled a 4.0 x 13.0-mm IMZ implant, restored with a cast gold crown, to examine the influence of the polyoxymethylene (POM) intramobile element (IME) on the transmission of vertical and oblique forces. Stress concentrations in the bone and in components of the implant system were much greater under a 30-degree load than under an equal vertical load. Stress transmission to bone occurred chiefly in the crestal region, and these stresses were not reduced when the IME was modeled in POM rather than in titanium. Maximum stress concentrations occurred in the fastening screw.     

Cholesterol, coronary heart disease, and total mortality in middle-aged and elderly men and women in Tecumseh.

Relationships between serum cholesterol and coronary heart disease (CHD) were investigated in Tecumseh men and women who were 45 to 92 years old and initially free of CHD. Recruitment continued through three cycles of examinations over a period of 10 years, beginning in 1959. Follow-up for mortality ended in 1986 to 1987. Age-adjusted relative risks for CHD death for cholesterol levels of 5.2 to 6.2 mmol/L and greater than 6.2 mmol/L, compared with levels less than 5.2 mmol/L for men aged 45 to 64 years, were 1.2 and 1.7; for older men they were 1.0 and 1.8. Comparable relative risks for CHD death by cholesterol level were .7 and 1.4 for 45- to 64-year-old women and .8 and .7 for older women. Coefficients for cholesterol were significant for fatal CHD in men under and those 65 years and older when age, systolic blood pressure, body mass index, cigarette smoking status, and glucose intolerance were controlled in proportional hazards models. Cholesterol was a significant predictor of fatal CHD plus nonfatal myocardial infarction in middle-aged, but not elderly women. Relative risks for total mortality were lowest for middle-aged men and women with cholesterol levels of 5.2 to 6.2 mmol/L and the difference was significant in men.     

Survival rates for four forms of cancer in the United States and Ontario.

OBJECTIVES: In this study, cancer survival rates for patients diagnosed in Ontario and selected areas within the United States were compared. METHODS: Relative survival rates were computed for patients aged 15 through 84 years diagnosed with any of four forms of cancer (breast, colon, lung, and Hodgkin's disease). The cohorts represented those diagnosed over the years 1978 through 1986 in the Canadian province of Ontario and in nine regions covered by the US National Cancer Institute's Surveillance Epidemiology and End Results program. Patients were followed through the end of 1990. RESULTS: The cumulative relative survival rates were similar for American and Canadian patients. The largest difference was observed for breast cancer, where patients in the United States enjoyed a survival advantage throughout the follow-up period. CONCLUSIONS: Patients in the United States and Ontario with the diseases studied, except for breast cancer, experience very similar survival. The greater use of mammographic screening in the United States could account for that country's higher breast cancer survival rate by promoting earlier and therefore more efficacious treatment, by introducing bias, or by a combination of both treatment and bias factors.     

Thoracoscopic pleurodesis in persistent and recurrent pneumothorax]

103 patients with recurrent or persistent pneumothorax have been treated with local application of fibrin and talcum by a thoracoscopic procedure. The method was successful in 97 patients (94.2%) and lead to a stable and complete reexpansion of the lung within 6.3 days. As a direct consequence of the procedure itself only a few and minor complications occurred during a mean hospitalization-time of 10.4 days. The longterm followup over a mean period of 6.4 years revealed a recurrence rate of 15%, although half of the episodes occurred early during the first three months. After 6 years, 80% of the patients were completely asymptomatic and spirometric lung function was restored to normal values. We therefore consider thoracoscopic pleurodesis to be a successful and safe method for treating complicated pneumothorax.