The pharmacokinetic values of d,l-leucovorin and l-leucovorin were compared in eight healthy volunteers following oral administration of 25 mg d,l-leucovorin and 12.5 mg l-leucovorin. Serum levels of l-5-formyltetrahydrofolate, l-5-methyltetrahydrofolate, and total reduced folates were measured by an established microbiological method. Pharmacokinetic data for both preparations were consistent with those previously reported for d,l-leucovorin, with essentially complete first pass metabolism to l-5-methyltetrahydrofolate, the active metabolite. No differences were found between the two preparations in serum concentrations of active folate fractions, AUC, or Cmax, or in clearance and volume of distribution estimates. These data suggest that after administration of 25 mg of d,l-leucovorin, the d-diastereoisomer has no significant effect on the standard pharmacokinetic measurements of the active l-folates.

Adolescent↗

PubMed1993

Is luteal function maintained by factors other than chorionic gonadotrophin in early pregnancy?

Women with ectopic pregnancy (n = 14) and early embryonic arrest ('blighted ovum') (n = 9) were studied 16 days after conception, at a time when they were asymptomatic and serum concentrations of beta-human chorionic gonadotrophin (HCG) were in the normal range and increasing at an apparently normal rate. Serum progesterone and oestradiol concentrations were compared with those from normal women matched for gestational age and serum beta-HCG concentration whose singleton intra-uterine pregnancies proceeded normally beyond 20 weeks. Mean serum progesterone concentrations were significantly lower in the women with ectopic pregnancies than in matched controls (P < 0.002); however, there was no difference in the serum progesterone concentrations between women with blighted ova and matched controls. Statistically significant differences were not seen in serum oestradiol concentrations between either group and matched controls. Similarly there was no difference in serum progesterone or oestradiol concentrations in 20 women who conceived ectopic pregnancies and 20 women conceiving blighted ovum pregnancies and their matched intra-uterine controls when conception followed ovarian stimulation. The low serum progesterone concentrations seen in ectopic pregnancy suggest that there is a specific and selective deficiency in progesterone synthesis, which implies that factors other than HCG may influence luteal function.

Chorionic Gonadotropin↗

PubMed1993

Plasma cell hyperplasia and monoclonal paraproteinemia in human immunodeficiency virus-infected patients.

Twenty-seven bone marrow aspirates and biopsy specimens from human immunodeficiency virus-positive patients with plasmacytosis were analyzed to identify the pathologic correlates of polyclonal and monoclonal hypergammaglobulinemia in these patients, to compare the results with another random group of similar human immunodeficiency virus patients with plasmacytosis who did not have serum protein electrophoresis, and to evaluate the significance of the presence of monoclonal proteins in a few patients. Serum protein electrophoresis and immunoelectrophoresis and/or immunofixation electrophoresis revealed monoclonal spikes in five of 18 patients tested. The remaining patients with an abnormal serum protein electrophoresis showed a polyclonal hypergammaglobulinemia. Immunohistochemical stains for kappa and lambda light chains were performed in the bone marrow specimens to determine the presence and/or absence of light-chain preponderance or monoclonality. The percentage of plasma cells varied from 5% to 30% and atypical plasma cells from 1% to 20%. Plasma cell aggregates were present in every case, but variable in number and generally small. In all these cases, including those with monoclonal spikes, plasma cells expressed lambda and kappa light chains with approximately equal intensity. There were no identifiable morphologic differences between the two groups of patients. The paraproteins observed in these patients are likely a reflection of B-cell overactivation. It is important to be aware of this peculiar subset of human immunodeficiency virus-infected patients to avoid an erroneous diagnosis of plasma cell dyscrasia.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Managing risk. A priority in the health service.

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Anesthesiology↗

PubMed1992

Specificity of antibody HMB-45.

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Adenocarcinoma↗

PubMed1991

Quality assurance. Clinical directorates.

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Decision Making, Organizational↗