Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.     

Impaired Lymphocyte Proliferative Response to Mitogen in Alcoholic Patients. Absence of a Relation to Liver Disease Activity

Concanavalin A-induced lymphocyte proliferation was studied in 25 patients with alcoholic hepatitis or compensated alcoholic cirrhosis. Nine alcoholics without evidence of liver disease were also evaluated. A nonlinear correlation equation, which was natural logarithmic, was applied to individual dose-response proliferation curves and permitted comparisons between patient groups and controls. The proliferative response in all patient groups was significantly lower when compared to healthy controls and was independent of the presence or absence of liver disease. This suggests that some changes in immune function observed in alcoholics may be linked to the direct effects of alcohol on the immune system rather than to the associated liver disease.     

Influence of Inhaled Corticosteroids and Dietary Intake on Bone Density and Metabolism in Patients With Moderate to Severe Asthma

Objectives Compare the effect of high doses of inhaled corticosteroids on bone loss in subjects with moderate to severe asthma or mild asthma, and examine the influence of dietary intake on bone metabolism. Design A survey on the effects of corticotherapy and nutrition on bone density was conducted in 74 subjects currently being treated for asthma in the asthma clinic of Hospital Laval (Sainte-Foy, Quebec, Canada). Fifty-eight subjects completed the study (attrition RATE=15%).

Main outcome measures In all subjects expiratory volumes were determined and urinary analysis was conducted for hydroxyproline, calcium, phosphorus, and cortisol levels. Osteocalcin, calcium, phosphorus, cortisol, alkaline phosphatase, and γ-glutamyltransferase levels were measured in blood samples. Bone density of the lumbar spine was determined by means of dual-energy x-ray absorptiometry. Nutrition evaluation was based on a 3-day food diary analyzed using progiciel Nutri 91. The nutritional parameters examined were calcium; phosphorus; magnesium; zinc; vitamins A, C, and D; protein; total fiber; oxalates; energy; caffeine; and alcohol in relation to bone density.

Subjects Thirty-one patients with moderate to severe asthma who had been taking more than 1,000 μg beclomethasone per day or the equivalent for more than 2 years and 27 patients with mild asthma who were taking less than 500 μg beclomethasone per day or the equivalent.

Statistical analyses performed Four factor analysis of variance with hierarchized interactions of four levels, Duncan's test, Pearson correlation coefficients.

Results Blood levels of osteocalcin and protein intake were lower in patients with moderate to severe asthma than in those with mild asthma (P<.05). Significant correlations (P<.02) were observed between bone density and calcium intake (r=.40), phosphorus intake (r=.35), protein intake (r=.30), and serum alkaline phosphatase level (r=−.30). Bone density was not significantly different between the two groups of patients with asthma.

Applications A follow-up of patients with asthma who are taking inhaled corticosteroids is needed to assess bone density, osteocalcin levels, and dietary intakes of calcium. Verify if osteocalcin level decreases over time in patients with moderate to severe asthma, monitor possible modifications in bone density, and verify if the correlation between dietary calcium and bone density is maintained. J Am Diet Assoc. 1997;97:1401–1406.     

Spontaneous Uterine Venous Rupture During Labour: A Case Report With Postoperative Ultrasonographic Findings

EDITORIAL COMMENT: We accepted this case for publication to remind readers that although uterine rupture during labour in a primigravida is extremely uncommon it does occur, or at any rate nulliparas can develop abdominal pain and shock in labour with a haemoperitoneum resulting from a tear in a vein in the lower posterior uterine wall. When one sees the hugely dilated uterine and ovarian venous plexuses at Caesarean section it is easy to believe that bleeding from such a vessel during labour could be prodigious. This case suggests that a dilated vein with blood flow derangements may be the cause. Nonetheless, as the authors warn us, the necessary response is not a precise diagnosis, but rapid laparotomy. See also Editorial Comment to Chin MMS, Harvey JA, Duffy BL. Uterine rupture during labour in a primigravida. Aust NZ J Obstet Gynaecol 1996; 36: 210.     

Wound Botulism Associated with Black Tar Heroin

The incidence of wound botulism is increasing and the epidemiology of the disease is changing. The majority of new cases are associated with injection drug use, in particular, the use of Mexican black tar heroin. This case report and discussion of wound botulism illustrate the following important points: Dysphagia, dysphonia, diplopia, and descending paralysis, in association with injection drug use, should alert the treating physician to the possibility of wound botulism. In such patients, the onset of respiratory failure may be sudden and without clinically obvious signs of respiratory weakness. For the reported patient, maximum inspiratory force measurements were the only reliable indicator of respiratory muscle weakness. This is a measurement not routinely performed in the ED, but may prove essential for patients with suspected wound botulism. To minimize the effect of the botulinum toxin and to decrease length of hospital stay, antitoxin administration and surgical wound debridement should be performed early.     

Tungiasis in New York

A 33-year-old African woman was evaluated for tender nodules on her feet. Accompanied by her four children, she had recently immigrated from Somalia. Before her immigration, she resided in a Kenyan refugee camp for approximately 1 year, where she walked barefoot in sand and dirt. The patient stated that she and her four children, as well as many people living in the same compound, had similar, tender lesions on their feet. Her children were "treated" by their grandmother, who removed the contents of their lesions with a safety pin.
On physical examination the patient had numerous tender, isolated, and clustered hyperkeratotic, crusted papules, measuring 4–6 mm, on the plantar and periungual surfaces. Several lesions were ulcerated (Figs 1 and 2). The hyperkeratotic masses were debrided with a surgical blade. An intact, white, coiled structure was curetted from each papule, leaving numerous empty crater-like lesions (Fig. 3), which were identified on histologic sections as Tunga penetrans. Microscopic examination of unstained specimens showed branching, thin, translucent tubular structures with numerous eggs. Ring-shaped cross-sections of the organism's respiratory and digestive tracts were seen on hematoxylin and eosin stain (Fig. 4).
The patient received a 10-day course of dicloxacillin and topical bacitracin ointment. All lesions were healed within 1 week of therapy.     

The Membrane Lipid Cholesterol Modulates Anesthetic Actions on a Human Brain Ion Channel

Background: Molecular theories of general anesthesia often are divided into two categories: (l) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined.

Methods: Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions.

Results: Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half.