Hyponatremia as a side effect of serotonin uptake inhibitors

Hyponatraemia is a possible, potentially serious adverse reaction to treatment with selected serotonin re-uptake inhibitors (SSRIs). The article consists in a review of the 27 cases of such reactions that have been reported to the Swedish Medical Products Agency. The data from these reports suggest the risk of hyponatraemia to be particularly manifest during the first few weeks of treatment, and to be greater in women, the elderly, and patients concomitantly treated with diuretics. In the event of vague, non-specific symptoms occurring in conjunction with SSRI treatment, measurement of the serum sodium concentration is recommended.     

Galactorrhea and gynecomastia as side effect of drugs

Galactorrhoea or gynaecomastia are common and innocent phenomena, especially in certain age groups. Sometimes, however, they are secondary to serious diseases such as hormone producing tumours. Furthermore, a wide variety of drugs may in different ways induce galactorrhoea or gynaecomastia. A good knowledge of these drugs may prevent unnecessary anxiety and investigations. In spite of an abundance of often anecdotal reports scattered in the literature, little information is available on the identity of the most important drugs causing galactorrhoea or gynaecomastia in medical practice. The country-wide network of regional centres for intensified adverse drug reactions reporting of the Netherlands Pharmacovigilance Foundation LAREB can provide useful information on these and other side effects.     

Vascular leak syndrome: a side effect of immunotherapy

The major dose-limiting toxicity of interleukin-2 (IL-2) and of immunotoxin (IT) therapies is vascular leak syndrome (VLS). VLS is characterized by an increase in vascular permeability accompanied by extravasation of fluids and proteins resulting in interstitial edema and organ failure. Manifestations of VLS include fluid retention, increase in body weight, peripheral edema, pleural and pericardial effusions, ascites, anasarca and, in severe form, signs of pulmonary and cardiovascular failure. Symptoms are highly variable among patients and the causes are poorly understood. The pathogenesis of endothelial cell (EC) damage is complex and can involve activation or damage to ECs and leukocytes, release of cytokines and of inflammatory mediators, alteration in cell-cell and cell-matrix adhesion and in cytoskeleton function. VLS restricts the doses of IL-2 and of ITs which can be administered to humans and, in some cases, necessitates the cessation of therapy. This review discusses the diversity of clinical manifestation, possible mechanisms and therapeutic modalities for VLS induced by IL-2 and ITs.     

Sebaceous gland hyperplasia as a side effect of cyclosporin A. Treatment with the CO2 laser

HISTORY AND CLINICAL FINDINGS: After renal transplantation 11 years previously followed by immunosuppression with cyclosporin A, a 59-year-old man developed, shortly after starting the medication, skin-coloured nodules in the region of both ears and the forehead. In the subsequent years the skin changes spread throughout the entire face. The nodes (up to 2 cm in diameter) and nodules were soft and yellowish-white in colour. In addition there were numerous distinct telangiectasias over the whole face. INVESTIGATIONS: Several skin biopsies were taken. They showed largely unremarkable epidermis but marked enlargement and multiplication of the sebaceous glands. DIAGNOSIS, TREATMENT AND COURSE: In view of the histological findings the diagnosis of sebaceous hyperplasia was established. After a trial with carbon dioxide laser, treatment over the entire surface of the two auricles was undertaken under full anaesthesia. The normal auricular contour was reconstituted by removal of the papules and nodes, without any scar formation. CONCLUSION: In the absence of an alternative medication and if the very marked skin changes show no sign of regression, "shaving off" by scalpel of the nodes and nodules or conventional surgery has been the available treatment. However, removal by carbon dioxide laser has the advantage of fewer side effect, is less stressful to the patient and provides a dry operative field.     

Psychic hygiene as a possible special discipline

One hundred and twenty healthy Nigerian female patients undergoing minor gynaecological operations were divided randomly into two groups. One group of 58 patients received intramuscular atropine as the only premedication on the ward while the other group of 62 patients received their atropine intravenously at the time of induction of anaesthesia. Anaesthesia was induced with thipentone and maintained with nitrous oxide, oxygen, and halothane using a facemask. There was equally satisfactory control of secretions in both groups. However, due to the occasional difficulties in achieving optimal timing of intramuscular atropine as well as the uncomfortably dry mouth complained of by 87.7 per cent of the patients who had intramuscular atropine, the intravenous administration at induction is to be preferred. Moreover, one saves the patient an extra injection.     

Sexually transmitted disease prevention: adolescents' perceptions of possible side effects

Forty-eight sexually active adolescents participated in an open-ended interview about the possible secondary consequences (side effects) of implementing measures to reduce the risk of contracting a sexually transmitted disease (STD). These adolescents noted 134 different consequences, which were grouped into 15 substantive categories. When four prevention measures (using condoms, being selective about sex partner(s), being monogamous, and abstaining from sexual activity) were analyzed, different patterns of consequences that were salient to these adolescents emerged. The results are discussed in terms of their implications for understanding and improving adolescent decision making about STD prevention.     

Hyperforin as a possible antidepressant component of hypericum extracts

We demonstrate that the phloroglucinol derivative hyperforin is not only the major lipophilic chemical constituent of the medicinal plant Hypericum perforatum (St. John's wort) but also a potent uptake inhibitor of serotonin (5-HT), dopamine (DA), noradrenaline (NA), GABA and L-Glutamate with IC50 values of about 0.05-0.10 microg/ml (5-HT, NA, DA, GABA) and about 0.5 microg/ml (L-glutamate) in synaptosomal preparations. Furthermore, potencies of two different hypericum extracts in two conventional pharmacological paradigms useful for the detection of antidepressants (behavioral despair, learned helplessness), closely correlate with their hyperforin contents. In addition, most till now known neuropharmacological properties of the clinically used hypericum extracts can also be demonstrated with pure hyperforin. It appears, therefore, that this non-nitrogenous constituent is a possible major active principle responsible for the observed clinical efficacies of the extract as an antidepressant and that it could also be a starting point for drug discovery projects engaged in the search of psychoactive drugs with novel mode of action.     

Human herpesvirus 6 as a possible cause of pneumonia

BACKGROUND: In biological studies of periodontitis, there has been long-standing confusion between the ubiquitous phenomena of inflammation and the essential criterion of attachment loss. This is partly attributable to inadequate methods of clinical measurement, but seems also to be a consequence of an unproven and usually unstated assumption that the same biological processes underlie both inflammation and attachment loss. Developments in unidimensional clinical probing methods have helped in studies of periodontal treatment. However, such methods are intrinsically unsuitable in studies of periodontal diseases, and may have given them a false sense of security. the confusion has been compounded by inappropriate use of statistical techniques in an attempt to solve problems which do not arise from mathematical models but are intrinsic to measurement methods. OBJECTIVE: This paper is a clinician's attempt to state the current difficulties and suggest some ways forward, including the development of three-dimensional measurement, non-invasive probing, and several objectives for biochemical, microbiological and immunological research.     

Acetonitrile as a possible marker of current cigarette smoking

Volatile nitriles are present in cigarette smoke. We tested the hypothesis that the presence of any of four nitriles in the blood can serve as a marker of recent cigarette smoking. We determined the sensitivity and specificity of these nitriles as indicators of daily cigarette smoking in 24 smokers (Group A) and 18 non-smokers (Group B), as well as the correlation between intensity of daily smoking and the blood concentration of acetonitrile. A new head space GLC assay method was used. Of the four nitriles, only acetonitrile was present in the blood of any study subject. Acetonitrile was moderately sensitive (67%) and entirely specific (100%) for self-reported daily smoking. There was fair correlation between blood acetonitrile concentration and the average daily number of cigarettes smoked (r2 = 0.39; P = 0.001), and the mean blood acetonitrile concentration was significantly higher (P = 0.03) among subjects with higher (> 10 cigarettes per day) current cigarette exposure (148.3 +/- 18.0 micrograms/l) than among smokers with low or minimal (1-10 cigarettes per day) exposure (43.3 +/- 6.0 micrograms/l). Thus, acetonitrile in blood appears to be highly specific and a moderately sensitive marker of cigarette smoking with a dose-effect relationship. As such, acetonitrile shows promise as a marker of current cigarette exposure.     

Cytosolic and mitochondrial proteins as possible targets of cycloheximide effect on adrenal steroidogenesis

We investigated the in vitro and in vivo interaction between amiodarone and lidocaine. The interaction on a molecular level was first studied in microsomes from 11 human livers. Close correlations between amiodarone N-monodesethylase activities and (a) the amounts of cytochrome P-4503A4 (CYP3A4), and (b) the rates of lidocaine N-monodesethylation were observed. Lidocaine inhibited amiodarone N-monodesethylation (Ki = 120 microM) competitively; inversely, amiodarone suppressed lidocaine N-monodesethylase activity in the same manner (Ki = 47 microM). Moreover, the metabolite N-monodesethylamiodarone (DEA) was stable and inhibited lidocaine metabolism in a concentration-dependent manner. The in vivo interaction was investigated in 6 cardiac patients. Each of them received a dose of 1 mg/kg lidocaine hydrochloride intravenously (i.v.) on three different occasions: before amiodarone treatment (control), and after cumulative doses of 3 g (phase I) and 13 g (phase II), respectively, amiodarone hydrochloride. The analysis of lidocaine pharmacokinetics showed an increase in lidocaine area under the curve (AUC) when amiodarone was administered, whereas that of N-monodesethylated lidocaine decreased. Moreover, the systemic clearance of lidocaine decreased, while the elimination half-life (t1/2) and the distribution volume at steady state of lidocaine remained unchanged. The pharmacokinetic parameters during phase II were the same as those during phase 1, indicating that the interaction had already occurred early in the loading phase of amiodarone administration. The interaction between amiodarone and lidocaine may be explained by the inhibition of CYP3A4 by amiodarone and/or by its main metabolite DEA.     

Topical cyclosporine as a possible new antimetabolite in trabeculectomy

BACKGROUND AND OBJECTIVE: The authors conducted a randomized, prospective, and controlled clinical and transmission electron microscopic study to investigate the possible role of cyclosporine in trabeculectomy as an antimetabolite agent. PATIENTS AND METHODS: Twelve patients underwent trabeculectomy with topical cyclosporine and another 12 patients had trabeculectomy without cyclosporine. RESULTS: There was a statistically significant decrease in the postoperative intraocular pressure (P < .05) and in the number of medications needed postoperatively (P < .01) in the cyclosporine group. There were no significant complications in either group. Transmission electron microscopic examinations of the excised trabecular scleral tissue showed that cyclosporine caused inhibition of fibroblasts and led to a disruption in collagen organization at the level of the surgical dissection. Middle scleral layers were generally not affected except in some cyclosporine-treated eyes, which showed only a mild cytopathic effect. CONCLUSION: This study showed that topical cyclosporine was safe and effective for use as an antimetabolite in trabeculectomy. Further studies are needed to substantiate the adjuvant role of cyclosporine in glaucoma filtering operations.     

An impediment to glutathione diffusion in older normal human lenses: a possible precondition for nuclear cataract

Human age-related nuclear cataract is associated with progressive and widespread oxidation of proteins, particularly in the centre of the lens. The reasons for the onset of cataract and why this disease should take place only in the lenses of older individuals remain unclear. However, a common feature of nuclear cataract is the low concentration of reduced glutathione (GSH) in the centre of the lens. GSH is the principal lenticular antioxidant of the lens and it is synthesized and regenerated in the lens cortex. In this study we investigated the diffusion of glutathione within the human lens as a function of age. Normal human lenses were incubated in artificial aqueous humor containing [35S]cysteine and the label was metabolically incorporated into GSH. After 48-h incubation, lenses were sectioned and phosphorimaging was used to determine the distribution of 35S label. In young lenses, label appeared to diffuse uniformly throughout the whole lens. By contrast, in lenses over the age of 30, very little 35S had penetrated to the centre of the lens. A distinct zonal pattern of label distribution was noted in the older lenses after 48 h incubation, which had dimensions of approximately 7.2 mm (diameter) by 2.8 mm (axial). In some older lenses this pattern was noticeable even after 96-h incubation. Thus a barrier to the diffusion of GSH was observed in older normal lenses which was not present in younger lenses. Furthermore, the internal zone thus delineated has dimensions that coincide with those of the coloured and sclerotic zone present in nuclear cataract lenses. Since nuclear cataract is a disease of the elderly, and maintenance of GSH is known to be vital for lens clarity, we propose that the development of a barrier to the movement of GSH from its site of synthesis and regeneration in the cortex, into the nucleus in older normal lenses, may over time allow oxidative modification of protein to take place in the nucleus, resulting ultimately in nuclear cataract.     

Serum hepatocyte growth factor as a possible indicator of arteriosclerosis

OBJECTIVE: To investigate the possible involvement of hepatocyte growth factor in arteriosclerotic lesions, by studying the relationship between serum concentrations of hepatocyte growth factor and grades of retinal arteriosclerosis. METHODS: We measured the blood pressure, body mass index, serum concentrations of total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, uric acid, total protein, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gamma-glutamyltranspeptidase, alkaline phosphatase, and hepatocyte growth factor, erythrocyte counts, hemoglobin concentration, and hematocrit levels of 112 adults. Serum concentrations of hepatocyte growth factor were measured by a specific enzyme-linked immunosorbent assay. For each subject, photographs of both optic fundi were taken, and the grade of arteriosclerotic changes in the retinal arteries was evaluated according to Scheie's classification. RESULTS: Individuals with more advanced grades of arteriosclerotic changes had higher serum hepatocyte growth factor values (grade 0, 0.056 +/- 0.004 ng/ml, n = 86; grade 1, 0.132 +/- 0.026 ng/ml, n = 17, P < 0.01, versus grade 0; grade 2-3, 0.271 +/- 0.023 ng/ml, n = 9, P < 0.01, versus grades 0 and 1). The serum hepatocyte growth factor concentrations were also correlated significantly to the serum uric acid concentrations (r = 0.230, P = 0.015) and erythrocyte counts (r = 0.299, P = 0.001), but not to the systolic and diastolic blood pressures, and other physical and humoral parameters. CONCLUSIONS: Serum hepatocyte growth factor levels are thought to indicate the presence or development of arteriosclerotic lesions and may be a useful biochemical parameter for estimating the development of systemic arteriosclerosis irrespective of blood pressure levels.