Anabolic-androgenic steroids: medical assessment of present, past and potential users.

OBJECTIVE: To document adverse effects of anabolic-androgenic steroid (AAS) use in community-based users attending a medical clinic. DESIGN AND SETTING: Prospective recruitment, questionnaire-based interview, physical examination and investigations, with follow-up, of people who attended, anonymously, an inner-city hospital clinic established specifically to examine AAS use. PARTICIPANTS: 58 men, comprising 27 past AAS users, 14 present users and 17 potential users (who formed the control group). MAIN OUTCOME MEASURE: Clinical adverse effects and abnormal laboratory findings. RESULTS: Cyclical use of oral and intramuscular, human and veterinary AASs were reported. The most commonly reported source of AASs was friends (59%), gymnasiums (25%) and doctors (14%). The most common reported adverse effects were alterations in libido (61%), changes in mood (48%), reduced testis volume (46%) and acne (43%). Although mean systolic and diastolic blood pressure was not significantly different between groups, five present (29%), 10 past (37%) and one potential user (8%) were hypertensive. Gynaecomastia was found in 10 past users (37%; P<0.01 v. potential users), two present users (12%) and no potential users. Mean testis volume was significantly smaller in present users (18 mL; P<0.02) than in the other groups. Twenty past users (83%), eight present users (62%) and five potential users (71%) had abnormal liver function test results (P=0.5). After discussion of test results, only 11 participants (19%) reported they would not use AASs in the future. CONCLUSIONS: Adverse effects were reported by or detected in most of the AAS users who attended the clinic. Despite awareness of adverse consequences, most participants planned future use of AASs.

Cyclic presentation of central macular oedema.

We present the case of a young lady with unilateral pars planitis and associated cystoid macular oedema in whom visual symptoms fluctuated regularly during successive menstrual cycles. To date no such presentation of central macular oedema has been reported in the literature.

Spontaneous pneumomediastinum and diabetic ketoacidosis.

Spontaneous pneumomediastinum is a rare complication of diabetic ketoacidosis. We report two patients with this complication who presented to a Sydney hospital within one week. Although both patients were young backpackers, staying at the same hostel, we believe this was coincidental.

RP 64477: a potent inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase with low systemic bioavailability.

RP 64477 (N-butyl-3-(p-decyloxybenzamido)-4-(methylthio)benzamide) has been shown to be a potent inhibitor of the cholesterol esterifying enzyme Acyl-coenzyme A:cholesterol O-acyltransferase (EC 2.3.1.26; ACAT) in intestinal, hepatic, adrenal, and arterial tissue preparations obtained from a range of animal species. Drug concentrations producing 50% inhibition of enzyme activity (IC50 values) ranged from 14-283 nM. Inhibition by RP 64477 in a rabbit intestinal enzyme preparation was shown to be non-competitive with respect to the substrate oleoyl-CoA. In whole cell assays using human intestinal (CaCo-2), hepatic HepG2) and monocytic (THP-1) cell lines, RP 64477 inhibited ACAT activity with IC50s of 113, 503, and 180 nM, respectively. RP 64477 (0.03% w/w by diet) reduced significantly cholesterol absorption in cholesterol/cholic acid-fed rats from 94+/- 8% to 65 +/- 4%. In cholesterol-fed rabbits, cholesterol absorption was reduced from 72 +/- 5% to 50 +/-5% and 44 +/- 5% at dose levels of 10 and 30 mg kg-1 b.i.d., respectively. Plasma cholesterol levels were reduced dose-dependently in both cholesterol/cholic-acid-fed rats and cholesterol-fed rabbits. Neither cholesterol absorption nor plasma cholesterol levels were reduced significantly in animals maintained on standard laboratory diets. Pharmacokinetic studies indicated that RP 64477 were very poorly absorbed following oral administration to rats. Plasma levels of drug were < 2 ng mL-1 following a dose of 2000 mg kg-1 p.o.. When radiolabelled RP 64477 was administered orally, limited absorption was indicated by the overwhelming elimination of radioactivity in the faces (96.4% of administered material) coupled with low renal clearance (0.6% of dose) and biliary excretion (0.05% of dose). In conclusion, this work shows that RP 64477 is a potent inhibitor of ACAT obtained from a range of animal species and man. Inhibition of cholesterol absorption and hypocholesterolaemic activity has been demonstrated in rats and rabbits maintained on diets supplemented with cholesterol. Pharmacokinetic studies indicate low systemic exposure to RP 64477 as a result of limited absorption of this drug.

Histological evaluation of interleukin-1 beta and collagen in gingival tissue from untreated adult periodontitis.

Interleukin-1 beta (IL-1 beta) may be related to the pathological processes associated with periodontitis, primarily due to its ability to induce collagenase, increase neutrophil chemotaxis, and stimulate bone resorption. This study was designed to histologically quantitate IL-1 beta positive cells from various histologic fields in untreated gingivitis/early periodontitis (G/EP) versus moderate/severe periodontitis (M/SP) gingival tissues, and associate these with collagen loss. Two gingival biopsies from 8 patients were collected, one from a G/EP site and one from a M/SP site. Mouse monoclonal antibodies in combination with an avidin-biotin-peroxidase system were used to stain for IL-1 beta, while the van Gieson method was used to stain for collagen in serial sections. Collagen loss in G/EP (35%) and M/SP (52%) fields was consistent with gingivitis and periodontitis, respectively. IL-1 beta positive cells in combined coronal/sulcular (Co/Su) and apical/sulcular (Ap/Su) fields (nearest the bacterial insult) were significantly more numerous compared to combined coronal/middle (Co/Mi) and apical/middle (Ap/Mi) fields (p < 0.05). While numbers and percentages of IL-1 beta positive cells were generally higher in M/SP biopsies, differences were not significant. Further, there was no correlation between the number of IL-1 beta positive cells and percent collagen loss. However, a significant correlation between IL-1 beta positive cells and corresponding gingival crevicular fluid IL-1 beta concentrations was noted (r = 0.65, p = 0.01). Through the use of immunohistochemistry, this study demonstrated that the presence of IL-1 beta + cells does not appear to have a direct association with collagen loss.

Lateral pontine and extrapontine myelinolysis associated with hypernatremia and hyperglycemia.

Efforts to understand and prevent pontine and extrapontine myelinolysis have focused on the correction of hyponatremia, but controversy persists. We report a woman who presented in hyperosmolar diabetic coma with hypernatremia (169 mEq/l) and hyperglycemia (954 mg/dl). Plasma sodium rapidly increased to 188 mEq/l before gradually returning to normal. She remained obtunded and died 21 days later. Autopsy showed widespread, symmetrical demyelination involving the subcortical white matter, corpus callosum, anterior commissure, extreme, external, and internal capsules, fornix, thalamus, cerebellum, and lateral pons. The central pons and lateral geniculate nuclei were uninvolved. This case illustrates that lateral pontine and extrapontine myelinolysis can be associated with hypernatremia and hyperosmolality. In both hypo- and hypernatremic states, the significant event may be an increase in serum sodium or serum osmolality of sufficient rapidity and magnitude.

Castleman's disease of the leptomeninges. Report of three cases.

Castleman's disease is a rare, benign lymphoproliferative disorder that usually arises in lymph nodes, most commonly in the mediastinum. The authors report the clinical and pathological features of three patients with localized Castleman's disease of the leptomeninges. There were two women, aged 63 and 82 years, and one 25-year-old man. Two patients had progressive focal motor seizures of 3 and 24 months' duration, and the third patient presented acutely with generalized seizures. The clinical diagnosis was meningioma in each case, based on computerized tomography scans, cerebral arteriography, and the operative findings. All three lesions arose in the leptomeninges, compressed the underlying cerebral cortex, and infiltrated the overlying dura to a variable extent. Surgical excision of the tumor resulted in marked clinical improvement in all three patients. Histologically, two cases were classified as the hyaline-vascular type and one as the plasma cell type. Immunohistochemical stains of the latter case revealed a monoclonal population of mature plasma cells. Only a few scattered polyclonal plasma cells were seen in the other two cases. The authors conclude that Castleman's disease involving the leptomeninges is a rare disorder that may mimic meningioma clinically and radiographically.

Fine-needle aspiration cytology of prostate: experience in a nonacademic practice.

Fine-needle aspiration cytology of the prostate is becoming increasingly accepted and used in the United States. This is a report of the experience of a nonacademic practice in which the aspirations were performed by a number of urologists, usually in the office, and were interpreted by a number of pathologists with varying degrees of experience in cytopathology. Of 187 patients, 159 had smears adequate for evaluation, and 99 had histologic/substantiating clinical follow-up for comparison. The resulting specificity was 97%, sensitivity was 91%, and the false-negative rate was 9%. These figures compare favorably with those reported in studies from academic university-based practices.

Primary adrenal tumours--a ten-year experience.

The experience of 31 patients with primary adrenal tumours seen in one teaching hospital over a 10-year period is reviewed. There were 10 patients who had benign cortical adenomas; 11 had adrenal cortical carcinomas, and 10 had phaeochromocytomas, one of which was malignant. During the review period, a primary adrenal mass was discovered in 5% of 2951 autopsies performed in the study institution. The diagnosis and management of these uncommon tumours is reviewed.