Methotrexate in the treatment of pemphigus vulgaris: experience in 23 patients.

BACKGROUND: The standard treatment for patients with pemphigus vulgaris has long consisted of high-dose glucocorticoids. Studies regarding the use of methotrexate in pemphigus vulgaris date back to 1968, but few have quantitatively described a steroid-sparing effect conferred by methotrexate. OBJECTIVES: We sought to evaluate the efficacy of methotrexate in 23 patients with pemphigus vulgaris, using the drug's steroid-sparing effect as the primary indicator of clinical improvement. We investigated whether methotrexate could be used as monotherapy in some patients. METHODS: Retrospective chart review was used to analyse the records of patients with pemphigus vulgaris treated with methotrexate at the New York University Langone Medical Center for at least three consecutive months between 2000 and 2012. Diagnosis was made by tissue biopsy and either direct or indirect immunofluorescence tests and enzyme-linked immunosorbent assay. RESULTS: Improvement in clinical symptoms was observed in 91% of patients. Sixteen patients (70%) were eventually weaned completely off prednisone, with a mean time to discontinuation of 18 months. In total 23% of patients enjoyed a partial steroid-sparing effect, requiring a mean maintenance dose of prednisone of 6·75 mg daily. Two patients (9%) developed possible adverse events requiring cessation of the drug, and one patient received no therapeutic benefit from the drug. CONCLUSIONS: Methotrexate is a useful and well-tolerated therapy with considerable steroid-sparing effect in patients with pemphigus vulgaris. It may be considered a first-line adjuvant therapy in the treatment of this difficult disease.

Reduced Purkinje cell size in the cerebellar vermis of elderly patients with schizophrenia.

OBJECTIVE: The authors' goal was to compare the size and linear density of Purkinje cells in the cerebellar vermis of subjects with and without schizophrenia. METHOD: Blocks of alcohol-fixed cerebellar vermis were dissected at autopsy from the brains of 14 elderly patients with schizophrenia and 13 elderly subjects with no history of neuropsychiatric illness. The blocks of vermis were sectioned and stained with 1% cresyl violet. The linear density and cross-sectional area of Purkinje cells were measured by using computer-assisted image analysis. The subjects with schizophrenia had been assessed with clinical rating scales within 1 year prior to death. RESULTS: The average cross-sectional areas of Purkinje cells of the patients with schizophrenia were significantly smaller (by 8.3%) than those of the subjects without neuropsychiatric illness. No difference in Purkinje cell linear density was observed between the two groups. Significant correlations were seen between Purkinje cell size and scores on the Mini-Mental State, the Brief Psychiatric Rating Scale, and the antipsychotic drug dose. CONCLUSIONS: These data indicate cerebellar involvement in schizophrenia; they are also consistent with reports of reduced neuronal size in other brain regions of patients with schizophrenia. These findings support a model of wide-spread central nervous system abnormality in schizophrenia.

The pharmacokinetics of a single dose of artemisinin in subjects with liver cirrhosis. Bach Mai-Amsterdam Research Group on Artemisinin.

Artemisinin is mainly eliminated by hepatic transformation. To investigate whether the clearance of artemisinin in patients with liver cirrhosis is different from healthy volunteers, a pharmacokinetic study was performed in male Vietnamese patients with Child B cirrhosis of the liver who received 500 mg of artemisinin orally. The results were compared to those found in a previous study in healthy subjects. The mean (+/- SD) area under the concentration time curve was 2365 (+/- 1761) h ng/ml; the mean (+/- SD) clearance, 382 (+/- 303)L/h. The elimination half life was 4 (+/- 1.3) h extimated by log-linear regression and 2.4 +/- 0.9 h estimated by non-linear regression using a one-compartment first order elimination model. The mean (+/- SD) absorption time was 1.55 (+/- 0.8) h. These results were not different from the results of healthy subjects and show that liver disease has no effect on the availability and clearance of oral artemisinin, indicating that artemisinin has an intermediate hepatic extraction ratio and that there is no significant first pass effect.

The pharmacokinetics of a single dose of artemisinin in patients with uncomplicated falciparum malaria.

The pharmacokinetics of artemisinin was studied in 11 Vietnamese patients with uncomplicated falciparum malaria after a single 500 mg oral dose. Curative treatment with mefloquine (15 mg/kg) was provided 24 hr after the artemisinin dose. Artemisinin concentrations were measured by high-performance liquid chromatography with electrochemical detection. The following pharmacokinetic results were found (all mean +/- SD); calculated volume of distribution/bioavailability = 22.8 +/- 16.6 L.kg-1, mean absorption time = 1.16 +/- 0.92 hr, calculated maximum concentration = 364 +/- 250 micrograms.L-1 occurring at 2.88 +/- 1.71 hr after drug intake, and an elimination half-life of 2.72 +/- 1.76 hr. Bioavailability was low. These results do not differ from results in healthy subjects. Parasites disappeared rapidly, with a mean parasite clearance time of 36 hr. No relationship was found between pharmacokinetics and the parasite elimination rate. Tolerance to the single dose of artemisinin was good. No adverse effects were detected. In conclusion, pharmacokinetics of a single dose of artemisinin for uncomplicated falciparum malaria is not different from findings in healthy subjects. A single dose of 500 mg of artemisinin is effective in reducing parasitemia in nonsevere lalciparum malaria and is well-tolerated.

Interaction between dextromethorphan and norpethidine in rats.

With increasing interest in the application of dextromethorphan in pain control, it is probable that patients will receive this drug in combination with analgesics such as opioids, giving rise to the potential for previously unobserved drug interactions. The interaction between dextromethorphan, and its pharmacologically active metabolite dextrorphan, and norpethidine, a toxic metabolite of pethidine, was examined in rats. Rats were assigned to receive dextromethorphan (0, 20 or 40 mg/kg) or dextrorphan (0, 15 or 30 mg/kg) combined with norpethidine (0, 28 or 42 mg/kg). The occurrence of seizures, myoclonic jerks and shivering was recorded for 60 min after drug administration. Norpethidine produced dose-related increases in the incidence of seizures, myoclonic jerks and shivering. Dextromethorphan, but not dextrorphan, increased the incidence of these behaviours. It is recommended that extreme caution be exercised if dextromethorphan and pethidine are to be used together.