Human parathyroid adenoma adenylate cyclase: Stimulation by histamine that is blocked by cimetidine

Recent evidence suggests that the histamine receptor blocking agent cimetidine can decrease parathyroid hormone release from human parathyroids. To determine the mechanism for inhibition we examined the ability of histamine 1 × 10^?5 moles/liter to stimulate adenylate cyclase in a particulate membrane preparation from 13 human parathyroid glands. Histamine significantly increased adenylate cyclase activity as compared to control; however, the degree of stimulation was variable among the individual tissue samples. Enzyme stimulation was dose dependent over the concentration range of 1 × 10^?7 to 1 × 10^?4 moles/liter. Cimetidine at 1 × 10^?4 moles/liter completely abolished the histamine mediated increase in activity, but did not block the epinephrine-induced stimulation. The identification of an adenylate cyclase system in certain human parathyroid adenomas that is stimulated by histamine and blocked by cimetidine may offer a basis for the pharmacologic alteration of parathyroid hormone secretion.     

Hyperchloremic metabolic acidosis after chlorine inhalation

Chlorine gas Inhalation is usually accompanied by pulmonary toxicity and hypoxemia; the associated acidemia, when present, has been attributed to lactic acidosis. This case report describes the development of hyperchloremic metabolic acidosis following accidental chlorine gas exposure. The mechanism postulated for the production of this acidosis is the absorption of hydrochloric acid following the reaction of chlorine gas with tissue water. This may be the first case of chlorine toxicity in which the mechanism of the acidosis has been determined.     

Acute effect of an extract of Ambrosia paniculata (Willd.) O. E. Schultz (mugwort) in several models of experimental epilepsy

The acute effect of Ambrosia paniculata was studied in several animal models of epilepsy. Intraperitoneal injections (0.01 mL/g body wt) of a decoction of the dry leaves significantly enhanced the latency to the first convulsion and survival time in mice injected with picrotoxin (7 mg/kg) or isoniazid (210 mg/kg). Epileptic spikes were induced by topical application of penicillin through a glass electrode filled with a penicillin-agar-saline mixture and recorded in sensorimotor and occipital cortices, in rats immobilized with d-tubocurarine. The plant decoction reduced significantly the spike amplitude in both sites. The mentioned effects were elicited at doses that also reduced general motor activity (Irwin test) and exploratory behavior. The decoctions were not effective against electroshock-induced convulsions in mice. The convulsions induced by isoniazid, picrotoxin, and penicillin differed from those induced by electroshock implicating selective disruption of GABAergic neurotransmission. The results suggest that A. paniculata, like several conventional antiepileptic drugs, might act by enhancing GABAergic neurotransmission, a hypothesis that requires further demonstration. These results explain and justify the traditional use of the plant in epilepsy.     

Eliminating fear in a mentally retarded adult by behavioral hierarchies and operant techniques

A mildly retarded, institutionalized female adult was treated for her fear of riding in cars to an outside workshop via a modification of systematic desensitization. Whereas classical desensitization theraphy utilizes behavioral hierarchies and a respondent technique (pairing relaxation), the modified version presented here utilizes behavioral hierarchies and an operant techniques (token reward). The target behavior was attained within 11 weeks. Follow-up of 58 weeks shows the patient to be free of all aspects of her fear reactions and adjusting well to her workshop setting.     

Rotor's syndrome: A distinct inheritable pathophysiologic entity

Urinary total, isomer I and isomer III coproporphyrin excretion was determined in 11 patients with Rotor's syndrome, 23 phenotypically normal family members, 16 patients with the DubinJohnson syndrome and 20 normal control subjects. Control subjects excreted 24.8 ± 1.3 per cent (mean SEM) of urinary coproporphyrin as isomer I. Patients with the Dubin-Johnson syndrome excreted 88.9 ± 1.3 per cent as urinary coproporphyrin I, and patients with Rotor's syndrome excreted 64.8 ± 2.5 per cent as urinary coproporphyrin I, significantly different from the control subjects and the patients with the Dubin-Johnson syndrome (p < 0.001). Eight phenotypically normal parents and children of patients with Rotor's syndrome excreted 42.9 ± 5.4 per cent as urinary coproporphyrin I, intermediate between results in patients with Rotor's syndrome and control subjects (p < 0.001). Total urinary coproporphyrin excretion was markedly increased in patients with Rotor's syndrome (332 ± 86 μg/g creatinine) as compared to that in control subjects (p < 0.001) or obligate heterozygotes (p < 0.025).With respect to urinary coproporphyrin excretion, Rotor's syndrome and Dubin-Johnson syndrome are both inherited as autosomal recessive traits and are separate pathophysiologic entities. Study of rare but distinct inheritable disorders, such as these, provide insight into the functional dissociation of hepatic transport mechanisms.     

Multicenter evaluation of PCR methods for detecting CMV DNA in blood donors

BACKGROUND: CMV DNA screening may be a useful adjunct to serologic tests in distinguishing potentially infectious blood donations from those that are "CMV-safe." However, there is currently no consensus on the optimal assay method for accurate detection of CMV DNA in donors. STUDY DESIGN AND METHODS: A blinded multicenter evaluation of seven CMV PCR assays was performed by five laboratories by using coded sets of analytical controls and donor blood samples. RESULTS: Five assays displayed sufficient sensitivity for donor screening, as judged by consistent detection of a minimum of 25 CMV genome equivalents (geq) in analytical controls constructed to contain from 1 to 100 CMV geq in background DNA from 250,000 cells, while the other two assays displayed inadequate sensitivity. Three sensitive assays, two based on nested PCR directed at the UL93 and UL32 regions of the CMV genome and another test (Monitor Assay, Roche), did not detect CMV DNA in samples from any of 20 pedigreed CMV-seronegative, Western blot-negative (S-/WB-) donors. Two other assays based on nested PCR occasionally detected CMV DNA in S-WB- samples, and one sensitive nested PCR assay directed at UL123 detected CMV DNA in a large proportion (85%) of S-WB- samples. CONCLUSION: Seven CMV PCR assays currently used for research and/or diagnostic applications displayed marked variations in sensitivity, specificity, and reproducibility when applied to coded analytical and clinical control samples containing cellular DNA from the equivalent of 250,000 WBCs. These results will be useful in the selection of assays with performance characteristics appropriate to donor screening objectives. They may also help explain discrepant findings from previous studies that used PCR to determine CMV DNA prevalence in seronegative and seropositive blood donors.     

Toxic effect of single treatment with bromantane on neurological status of experimental animals

Neurotoxicological profile of actoprotector bromantane was studied on rats using S. Irwin's protocol of multi-test observation. The drug in doses of 30-300 mg/kg stimulated and in doses of 600-9600 mg/kg suppressed behavioral activity. Spontaneous motor activity increased after single treatment with bromantane in doses of 30-300 mg/kg, did not change after treatment in doses of 600 mg/kg, and was inhibited after treatment in doses above 600 mg/kg. In doses of 300-600 mg/kg the drug reduced pain sensitivity threshold and in doses above 600 mg/kg elevated the pain threshold and tactile sensitivity and reaction to knock. Bromantane induced mydriasis in all studied doses; in doses above 10 g/kg the preparation induced blepharoptosis. In doses above 5 g/kg bromantane slightly increased respiration rate and depth (Kussmaul-like respiration). In some animals bromantane in high doses induced regurgitation, diarrhea, and polyuria. Rectal temperature decreased by 0.5-1°C after virtually all doses. Behavioral effects of bromantane in doses of 30 and 600 mg/kg were associated with stimulation of the central dopamine and suppression of muscarinic and nicotinic cholinergic structures, n-cholinolytic effects of bromantane was more pronounced at a dose of 30 mg/kg than at a dose of 600 mg/kg.     

Anterior conduction delay: a possible cause for prominent anterior QRS forces.

Prominently anterior QRS forces often present a diagnostic dilemma. Frequently, right ventricular forces may be eliminated on clinical grounds and dorsal infarction is therefore suspected, especially in a clinical setting of coronary artery disease. In five such patients studied angiographically, the coronary disease was concentrated in the left anterior descending artery and the ventricular dysfunction confined to the anterior wall of the left ventricle. In a sixth case, the prominent anterior forces were observed intermittently together with left anterior hemiblock. These observations, in addition to serial studies following surgery, strongly suggest that the mechanism for prominent anterior QRS forces in these cases is conduction delay in an anterior division of the left bundle branch system.