Hormone replacement therapy and the risk of myocardial infarction in women with coronary risk factors

To assess the risk of myocardial infarction in users of post-menopausal hormone replacement therapy who are at high risk of coronary disease because of hypertension, diabetes mellitus, or smoking, we used data from a previously published case-control study of women 45-74 years. After adjustment for age, ethnicity, and education, the odds ratio for myocardial infarction in current users of hormone replacement therapy was 0.9 (95% confidence interval (CI) = 0.5-1.6) in women with no major coronary risk factors, 0.8 (95% CI = 0.5-1.8) in women with one risk factor, and 1.1 (95% CI = 0.5-2.2) in women with two risk factors.     

The Effect of Renal Function on Serum Levels of CA 125

Objective: Serum assays for CA 125 are used to monitor disease status in patients undergoing treatment for epithelial ovarian cancer. While a number of benign gynecologic as well as benign and malignant nongynecologic conditions are associated with CA 125 elevations, the established "normal" range describes a healthy population of women. The metabolism and clearance of CA 125 is not well understood. Because mild degrees of renal impairment frequently occur in ovarian cancer patients, we investigated the effect of impaired renal function on basal CA 125 in a population of female dialysis patients. Methods: Twenty-five women on hemodialysis were selected at random. Patients ranged in age from 29 to 87 years. Renal disease was secondary in most cases to diabetes mellitus or hypertension. The creatinine clearance was less than 10 cc/min for all patients. The duration of dialysis ranged from 3 months to 14 years. Serum levels of CA 125 were measured using monoclonal antibodies in an immunoradiometric assay. Results: The mean of duplicate determinations for 23 of 25 (92%) patients fell within the normal range for otherwise healthy women (<35 U/ml). There was no apparent correlation between CA 125 level and age, menopausal status, BUN, serum creatinine, adequacy of dialysis, or primary underlying diagnosis. Of the 2 patients (8%) with CA 125 levels above the normal range, 1 was premenopausal and the other was postmenopausal; their CA 125 elevations were marginal (49.81 and 50.51). Conclusions: The results of this study demonstrate that even marked renal insufficiency is not itself associated with significant elevations of CA 125 above the normal range selected for otherwise healthy women. The development of renal insufficiency during treatment for ovarian cancer should not alter the interpretation of serum levels of CA 125.     

Altered electrodermal response to facial expression after closed head injury

Summary : The objective was to determine whether diffuse damage to orbital and ventromedial regions of the prefrontal cortex usually associated with moderate-to-severe closed head injury (CHI) would affect the ability to perceive and respond to socially relevant information.

Methods : Participants with CHI and age-matched non-injured controls were presented with faces that varied with respect to emotional expression while electrodermal activity (EDA) was monitored. Cognitive and general adaptive functioning was also assessed.

Results : CHI was associated with a failure to increase EDA in response to negative facial expressions and with reduced ability to identify negative expressions, especially fear. The groups differed on other signs of orbital/medial prefrontal damage such as anosmia and in general social adaptability and awareness-of-deficit as measured by the Brock Adaptive Functioning Questionnaire.

Conclusions : CHI affected the ability to identify and respond to negative facial expression. Addressing these deficits may enhance rehabilitative efforts within the social domain.     

Effects on serotonin in rat hypothalamus of D-fenfluramine,aminorex, phentermine and fluoxetine

Hypothalamic 5-HT (serotonin) regulates food intake, energy expenditure and bodyweight. Using in vivo microdialysis, we determined the effects of various anorectic drugs on hypothalamic extracellular 5-HT levels during the dark phase when rats predominantly feed. Phentermine and aminorex, which were originally considered to be catecholaminergic drugs, markedly increased 5-HT efflux in rat hypothalamus. Their actions were less profound than D-fenfluramine, but considerably greater than that of the selective 5-HT reuptake inhibitor, fluoxetine. This suggests that enhanced hypothalamic 5-HT function could be involved in their anorectic actions. Pharmacological characterization revealed that D-fenfluramine, aminorex and probably also phentermine potentiate synaptic 5-HT function predominantly by release, whereas fluoxetine acts exclusively by reuptake inhibition. The results also revealed that the combined actions of phentermine and D-fenfluramine on hypothalamic extracellular 5-HT levels were additive, but not synergistic. In contrast, there was a significant negative cooperative effect on extraneuronal 5-HT of combining phentermine with fluoxetine.     

A role for histamine in cytokine modulation by the adenosine A(3) receptor agonist, 2-Cl-IB-MECA

The effects of adenosine receptor agonists on cytokine production in vivo were investigated in mouse models of endotoxemia. Selective adenosine A(3) (2-chloro-N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide) (2-Cl-IB-MECA) and A(2A) (2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride) (CGS 21860) receptor agonists were found to modulate endotoxin-induced cytokine responses in mice sensitized to D-galactosamine or primed with Corynebacterium parvum. The adenosine receptor agonists had similar effects in these models of endotoxemia, suppressing the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-12 while enhancing that of interleukin-10. However, 2-Cl-IB-MECA also caused a dramatic increase in circulating histamine levels shortly after its injection into mice. The cytokine modulatory activities of 2-Cl-IB-MECA were mimicked by the mast cell depleting compound 48/80 and both drugs only produced such effects at doses that caused an elevation in circulating histamine levels. Furthermore, the capacity of 2-Cl-IB-MECA to modulate cytokine responses was greatly diminished when the drug was administered to mast cell deficient (WBB6F-W/W(V)) mice. Together, these results strongly suggest a role for histamine in cytokine modulation by 2-Cl-IB-MECA. Cimetidine, a histamine H(2) receptor antagonist, did not reverse cytokine modulation by 2-Cl-IB-MECA and pyrilamine, a histamine H(1) receptor antagonist, prevented the increase in serum histamine that was induced by 2-Cl-IB-MECA. This effect of pyrilamine and other histamine H(1) receptor antagonists confounded attempts to determine a role for the histamine H(1) receptor in cytokine modulation by 2-Cl-IB-MECA. However, under some experimental conditions, pyrilamine appeared to antagonize the modulatory effects of the adenosine A(3) receptor agonist on cytokine responses. The apparent antagonism of pyrilamine was unrelated to its suppressive effects on histamine release and appeared to reflect activity at the level of the histamine H(1) receptor.     

Postoperative Follow-Up of Anal Condylomata Acuminata in HIV-Positive Patients

PURPOSE: The purpose of this study was to analyze the postoperative follow-up of HIV-positive patients with anal condylomata acuminata, associating recurrence to the AIDS status. METHODS: Ninety-seven male, homosexual patients with anal condylomata were submitted to surgical treatment from August 1992 to December 1997. Specimens were obtained for histologic investigation of Ki-67 cell proliferation marker and for polymerase chain reaction to define the human papillomavirus type. The patients were advised to return weekly during the first month, and monthly up to the sixth month, to evaluate recurrence. Patients with high-grade anal intraepithelial neoplasia remain in follow-up. RESULTS: Histology revealed low-grade anal intraepithelial neoplasia in 81.44 percent of patients and high-grade lesions in 18.56 percent. The results showed that high-grade lesions were not more frequent in late-stage AIDS patients. Ki-67 expression, a cell proliferation marker, was greater in high-grade than in low-grade anal intraepithelial neoplasia, but had no association with AIDS status. Nononcogenic human papillomavirus 6 and 11 were the commonest types. Comparing papillomavirus types and anal intraepithelial grade, we noticed that both oncogenic and nononcogenic types were responsible for high-grade lesions. All patients healed and 51 (52.6 percent) had recurrence up to the sixth month. AIDS status and papillomavirus type were not associated with recurrence. However, high-grade anal intraepithelial neoplasia patients had more recurrence than those with low-grade lesions. Topical treatment failed in 20 patients (41.6 percent), and these were submitted to new surgical treatment. All of them were in the late stage of AIDS. Three who had high-grade lesions in the first operation had low-grade lesions in specimens from the second surgery. The same histologic pattern was observed in 17 patients who had low-grade lesions in warts removed in the first operation. Other patients with high-grade lesions had no recurrence or evolution to invasive carcinoma from five to ten years of follow-up. CONCLUSION: High-grade anal intraepithelial neoplasia and late-stage AIDS are risk factors for recurrence of anal condylomata.     

Pyridoxine-dependent seizures and cognition in adulthood

A case report of neonatal onset pyridoxine-dependent seizures in a male patient with early diagnosis and treatment is presented. The patient's epilepsy was recognized and treated with pyridoxine (vitamin B6) within 8 hours of birth. Treatment has been nearly continuous since that time. This paper reports the results of a full neuropsychological evaluation at age 37 years and MRI completed at age 31 years. Consistent with other case reports in the literature, there was a significant Performance IQ (PIQ) advantage with decreased Verbal IQ (VIQ) and expressive language skills (Full-Scale IQ 71, VIQ 64, PIQ 85). MRI demonstrated characteristic thinning of the posterior corpus callosum. This report provides an example of early treatment that nonetheless results in a mild mental retardation. The similarity of the structural changes on MRI and the cognitive profile of this patient to those of others reported in the literature suggest that the underlying mechanism for both may be the same.