Testosterone secretion and pharmacological spermatozoal recovery in the cane toad (Bufo marinus).

The cane toad (Bufo marinus) was used as a model to study male anuran reproductive endocrinology and to develop a protocol for non-invasive sperm recovery. Circulating testosterone concentrations in 6-hourly samples did not vary significantly (P < 0.05) over a 24 h period although there was a tendency (P = 0.06) for testosterone to be elevated at 19:00 h relative to other times of the day, which may be related to the nocturnal activity pattern of this species. Testosterone secretion after intraperitoneal (IP) injection of either a GnRH agonist (5 microg IP) or hCG (1000 IU) was also examined. While the GnRH agonist did not produce a significant increase above basal plasma testosterone (0.29, 95% C.I. of 0.05-1.10 ng/ml), injection of hCG resulted in an increase (P < 0.01) of plasma testosterone with peak concentrations at approximately 120 min (4.17, 95% C.I. of 2.69-7.44 ng/ml) after injection. Non-invasive pharmaceutical sperm recovery was attempted following IP injection of graded doses of GnRH agonist, hCG or FSH. Urine was collected at 3, 6 and 12 h after treatment to assess sperm quality and quantity. The optimal protocol for sperm recovery in cane toads was injection of either 1000 or 2000 IU hCG; there was no significant difference in the quality of the spermic urine samples obtained using either dose of hCG or with respect to collection time. The findings indicated that hCG can be used to assess testicular steroidogenic status and also to induce sperm recovery in the cane toad. The hCG protocols developed in this study will have application in studies on the reproductive biology of rare and endangered male anurans.

Severe fenitrothion poisoning complicated by rhabdomyolysis in psychiatric patient.

Non-traumatic rhabdomyolysis associated with organophosphate intoxication has not been generally reported. We report here in a severe case of fenitrothion poisoning complicated by rhabdomyolysis. A 43-year-old woman ingested approximately 100 ml of fenitrothion emulsion (50%) in an attempt to commit suicide. On day 3 after admission, her creatine phosphokinase (CPK) peaked at 47,762 IU/L. She received supportive treatment included sodium bicarbonate and fluid resuscitation. However, muscarinic symptoms including excessive miosis and salivation developed on day 5 when her CPK levels decreased. The delay in cholinergic symptoms might have been due to the trihexyphenidyl she took with the antipsychotic drugs. Fortunately, the present patient recovered from the acute cholinergic crisis, and acute renal failure was prevented by early diagnosis. This is a case of organophosphate poisoning complicated by rhabdomyolysis in a psychiatric patient. The masking of acute cholinergic symptoms should be taken into consideration in such patients.

Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: possible effect of age, liver disease and length of therapy.

AIMS: To evaluate the reliability of the omeprazole hydroxylation index as a marker for polymorphic CYP2C19 activity in a Japanese population of healthy young subjects (n = 78) and patients with peptic ulcer (n = 72). METHODS: Healthy subjects were administered a single dose of omeprazole (20 mg), whereas patients received 20 mg daily for at least 1 week. The ratio of the serum concentration of omeprazole to hydroxyomeprazole at 3 h postdose was determined and used as a measure of CYP2C19 activity. The CYP2C19 wild type (wt) gene and four mutant alleles associated with the poor metaboliser phenotype of (S)-mephenytoin, CYP2C19*2 in exon 5, CYP2C19*3 in exon 4, CYP2C19m4 in exon 9, and CYP2C19m3 in the initial codon were analysed. RESULTS: In the healthy volunteer study there was complete concordance between genotype and phenotype. However, eight of the patients who had the EM genotype had a high value for their hydroxylation index, and were classified as phenotypic PMs. No CYP2C19m4 and CYP2C19m3 mutations were detected in the eight mismatched patients. They were all genotypic heterozygous EMs, elderly (> or = 65 years) and/or had hepatic disease. Therefore, impaired CYP2C19 activity combined with partial saturation of omeprazole metabolism during multiple dosing may have contributed to the discrepancy between CYP2C19 genotyping and phenotyping. CONCLUSION: Although omeprazole has been used instead of mephenytoin as a probe for polymorphic CYP2C19, it does not appear to be reliable enough for clinical application in Japanese patients.

Recurrent ventricular tachyarrhythmias associated with QT prolongation following hydrofluoric acid burns.

BACKGROUND: Some hydrofluoric acid burns appear initially as only a slight wound, but patients may show dramatic changes within several hours. The extent of such burns are directly related to the concentration, amount, and duration of exposure. CASE REPORT: A 64-year-old man sustained 44% total body surface burns after exposure to 30% hydrofluoric acid. Approximately 5 h after injury, he developed recurrent ventricular tachycardia and ventricular fibrillation which occurred in conjunction with long QT syndrome. In this case, the occurrence of hypocalcemia and especially hypomagnesemia played an important role in the development of long QT syndrome.

Acute organophosphate poisoning after disulfoton ingestion.

A 75-year-old woman attempted suicide by ingesting a large quantity of granular Di-Syston which is an organophosphate insecticide containing 5% disulfoton (ethylthiometon). On admission, the total plasma phosphorodithioate sulfone concentration (disulfoton and its metabolites, phosphorodithioate sulfoxide and its sulfone) determined by gas chromatography was 1095 ng/mL. After gastric lavage, the concentration gradually decreased to 505 ng/mL. However, it began to increase again 20 h after admission and reached the peak concentration (1322 ng/mL) at 56 h. It was concluded that the secondary elevation of the plasma concentration was due to the prolonged absorption of the organophosphate from the residual granules in the stomach, despite the early gastric lavage. Pralidoxime iodide administration temporarily restored erythrocyte cholinesterase activity to almost normal and inhibited the excessive, delayed reduction of cholinesterase activity. It is recommended that poisoning with the granular form of disulfoton should be treated with repetitive or prolonged gastric and intestinal lavage, charcoal, and a continuous intravenous infusion of pralidoxime iodide in addition to atropine sulfate.