Central, renal and adrenal effects of lithium in man.

The effect of lithium on thirst and plasma vasopressin concentration was tested in seven subjects with affective psychiatric disorders. Mean ad libitum fluid intake was liberal but no different before (3,293 ml/day) and three to four weeks after treatment with lithium (3,443 ml/day). After fluid deprivation, plasma vasopressin was 1.5 ± 0.39 pg/ml before and 3.72 ± 0.55 pg/ml after treatment with lithium (p < 0.02) as plasma osmolalities and body weights were comparable. Urinary osmolalities were no different (735 versus 759 mOsm/kg) and did riot increase with exogenous vasopressin. With a water load, plasma vasopressin decreased 1.58 to 0.79 pg/ml (p < 0.05) before and from 2.68 to 0.91 pg/ml (p < 0.025) after treatment with lithium. The water load excreted in 4 hours was less during lithium therapy (66 versus 85 per cent, p < 0.05). Lithium therapy had no effect on plasma renin activity (PRA) or aldosterone. On standing, PRA increased from 2.27 to 5.28 ng/ml/hour (p < 0.05) before and from 2.19 to 7.59 ng/ ml/hour (p < 0.05) after lithium therapy. At the same time plasma aldosterone increased from 121 to 365 pg/ml (p < 0.05) before and from 76 to 436 pg/ml (p < 0.05) after treatment with lithium. Lithium had no effect on indices of proximal tubular function (HCO₃^?, HPO₄⁼, glucose, amino acid and uric acid excretion). A lower titratable acid excretion (21 ± 5 versus 32 ± 4 μeq/min, p < 0.05) and higher urine pH (5.40 versus 5.02, p < 0.05) was observed after NH₄Cl ingestion during lithium therapy as compared to control. In conclusion, three to four weeks of lithium therapy neither stimulates thirst nor suppresses vasopressin release; some of the polyuria in patients with affective disorders may be due to their liberal fluid intakes. Lithium does not alter base line or standing PRA, aldosterone or proximal tubular function. Lithium does, however, induce an incomplete renal tubular acidosis.     

Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome.

Most patients with extreme obesity do not exhibit alveolar hypoventilation, but an intriguing minority do. The mechanism(s) of this phenomenon remain unknown. A disorder in ventilatory control has been suggested as a major factor in the pathogenesis of the obesity-hypoventilation syndrome. Accordingly, hypoxic and hypercapnic ventilatory drives were measured in 10 patients with the typical symptoms of the syndrome: obesity, hypersomnolence, hypercapnia, hypoxemia, polycythemia and cor pulmonale. Hypoxic ventilatory drive, measured as the shape parameter A, averaged 21.9 +/- 5.35, approximately one-sixth that in normal controls, A = 126 +/- 8.6 (P less than 0.01). The ventilatory response to hypercapnia also was markedly reduced, the slope of the response averaging 0.51 +/- 0.005, or about one-third the normal value of 1.83 +/- 0.13 (P less than 0.01). This decreased responsiveness in hypoxic and hypercapnic ventilatory drive was consistent throughout the group. The depression in ventilatory drive found in the obesity-hypoventilation syndrome may be causally related to the alveolar hypoventilation manifested by these patients.     

Pure primary hyperaldosteronism due to adrenal cortical carcinoma

A 47-year-old woman is described who had pure primary hyperaldosteronism due to an adrenal cortical carcinoma. This may represent the first such case in which modern laboratory tests allowed specific diagnosis and exclusion of hypersecretion of other adrenal steroids, and also the first reported case in which modern localizing procedures have been utilized. Other interesting facets of the case include calcification of the tumor, visualization with 131l iodomethylnorcholesterol , metaplastic histologic changes, and coexistent bilateral renal artery fibromuscular disease.     

Outbreaks of Infections Associated With Drug Diversion by US Health Care Personnel

ObjectiveTo summarize available information about outbreaks of infections stemming from drug diversion in US health care settings and describe recommended protocols and public health actions.Patients and MethodsWe reviewed records at the Centers for Disease Control and Prevention related to outbreaks of infections from drug diversion by health care personnel in US health care settings from January 1, 2000, through December 31, 2013. Searches of the medical literature published during the same period were also conducted using PubMed. Information compiled included health care setting(s), infection type(s), specialty of the implicated health care professional, implicated medication(s), mechanism(s) of diversion, number of infected patients, number of patients with potential exposure to blood-borne pathogens, and resolution of the investigation.ResultsWe identified 6 outbreaks over a 10-year period beginning in 2004; all occurred in hospital settings. Implicated health care professionals included 3 technicians and 3 nurses, one of whom was a nurse anesthetist. The mechanism by which infections were spread was tampering with injectable controlled substances. Two outbreaks involved tampering with opioids administered via patient-controlled analgesia pumps and resulted in gram-negative bacteremia in 34 patients. The remaining 4 outbreaks involved tampering with syringes or vials containing fentanyl; hepatitis C virus infection was transmitted to 84 patients. In each of these outbreaks, the implicated health care professional was infected with hepatitis C virus and served as the source; nearly 30,000 patients were potentially exposed to blood-borne pathogens and targeted for notification advising testing.ConclusionThese outbreaks revealed gaps in prevention, detection, and response to drug diversion in US health care facilities. Drug diversion is best prevented by health care facilities having strong narcotics security measures and active monitoring systems. Appropriate response includes assessment of harm to patients, consultation with public health officials when tampering with injectable medication is suspected, and prompt reporting to enforcement agencies.     

Cimetidine-drug interactions

The use of cimetidine, the histamine H2 receptor antagonist, is associated with a relatively low incidence of adverse reactions. However, its liberal use has led to the identification of several clinically significant cimetidine-drug interactions that can lead to drug accumulation, toxicity, and life-threatening sequelae. A review of the literature and the clinical significance and physiologic basis of these interactions are presented. Recommended management of cimetidine-drug interactions is discussed.     

Effect of a glucosidase inhibitor on the metabolic response of diabetic rats to a high carbohydrate diet,consisting of starch and sucrose,or glucose

The metabolic consequences of the addition of BAY-g-5421 to a diet whose caloric value included 67% carbohydrate, comprising wheat starch (diet A), equal quantities of wheat starch and sucrose (diet B) or glucose (diet C) were studied in lean diabetic and non-diabetic rats. BAY-g-5421 led to a significant (30%) reduction in daily food intake of diabetic and non-diabetic rats fed diets A and B, respectively. In diabetic rats fed diets A and B with BAY-g-5421, daily urinary glucose was diminished ten-fold, while the post-prandial plasma glucose excursions were almost halved. Serum cholesterol, but not triglyceride concentrations, were reduced after five days, by the addition of BAY-g-5421 to diets A or B in non-diabetic rats, and in diabetic rats when the animals fed diets A and B were combined. BAY-g-5421 did not significantly alter the food intake, urinary glucose excretion, post-prandial plasma glucose excursions nor serum lipids in diabetic and non-diabetic rats fed diet C. These findings illustrate the therapeutic potential of BAY-g-5421 as an adjunct to the dietary management of diabetes mellitus.     

Ethanol-induced inhibition of norepinephrine release from brain slices obtained from LS and SS mice

The effects of ethanol or prostaglandin E₂ (PGE₂) on K⁺-ion-stimulated or spontaneous (³H)-norepinephrine release were assessed in slices prepared from cortex and cerebellum of long-sleep (LS) and short-sleep (SS) mice. These lines were selectively bred for differences in ethanol-induced sleep time. Ethanol inhibited K⁺-stimulated release from LS cortical slices at lower concentrations than that required to inhibit release from SS cortical slices. Spontaneous release, on the other hand, was enhanced at lower ethanol concentrations in SS cortical slices. Ethanol inhibited K⁺-stimulated release equally in LS and SS cerebellar slices. Similarly, ethanol increased spontaneous release equally in LS and SS cerebellar slices. Thus, genotype and brain region influence the effect of ethanol on norepinephrine release. Since PGE₂ has been reported to inhibit norepinephrine release, the effect of PGE₂ on K⁺-stimulated norepinephrine release was examined in LS and SS cortical slices. PGE₂ inhibited norepinephrine release equally in the two mouse lines. These data indicate that ethanol may elicit some of its depressant effects by altering norepinephrine release. The difference between the lines in inhibition of release probably does not involve differences in sensitivity to PGE₂. Differences in ethanol-induced PGE₂ production could, however, explain the differences in sensitivity of LS and SS cortical slices to ethanol-induced inhibition of K⁺-stimulated norepinephrine release.