Aromatase cytochrome P450 enzyme expression in prolactinomas and its relationship to tumor behavior

The aim of the study was to evaluate the presence of aromatase cytochrome P450 enzyme (P450AROM) expression in normal pituitary tissues and tumor tissues of patients with prolactinoma and to examine the impact of the P450AROM expression on clinical outcome. Twenty-six consecutive human pituitary tissue samples were obtained from autopsies performed at the Institute of Forensic Medicine. Sixty-four patients who had an adenomectomy between 2000 and 2009 after prolactinoma diagnosis with histologically confirmed pituitary tumor tissues were retrospectively included in this study. The slices from the pituitary tissues were subjected to immunohistochemical staining for evaluation of P450AROM and estrogen receptor beta (ER beta) subunit. Immunohistochemistry results were compared according to age, gender, remission rate, resistance and invasion status of the patients. Higher than normal P450AROM expression was found in the pituitary tissues of the patients with prolactinoma (p < 0.001). P450AROM intensity had no relation to resistance or remission in patients with prolactinoma (p = 0.44, p = 0.45, respectively). The subgroup analysis showed that compared to males without invasive adenoma, males with invasive adenoma had higher P450AROM expression (p = 0.048). ER beta was found to have an impact on resistance (p = 0.049). This study shows that P450AROM expression is present in the pituitary tissues of patients with prolactinoma and that this presence could be important in development and tumor behavior of prolactinomas.     

The effect of the nitric oxide synthesis inhibitor L-NAME on amitriptyline-induced hypotension in rats

OBJECTIVE: Hypotension induced by tricyclic antidepressants is multifactorial. Previous animal experiments suggest a contribution from nitric oxide production. Our study aimed to evaluate the role of nitric oxide in amitriptyline-induced hypotension using N-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, and 3-morpholino sydnonimine, a nitric oxide donor, in anesthetized rats. METHODS: Amitriptyline intoxication was induced by the continuous infusion of amitriptyline 0.625 mg/kg/min throughout the experiment in anesthetized rats. Fifteen and 25 minutes after amitriptyline infusion began, two bolus doses of 10 mg/kg of N-nitro-L-arginine methyl ester (n = 8) or an equivalent volume of 5% dextrose solution (n = 8) was administered to each rat (Protocol 1). To investigate whether the effect of N-nitro-L-arginine methyl ester on blood pressure is counteracted by 3-morpholino sydnonimine, after the same protocol of amitriptyline infusion and 5 minutes after an N-nitro-L-arginine methyl ester bolus, a bolus of 3000 nmol/kg of 3-morpholino sydnonimine was administered (n = 8) to each rat (Protocol 2). To investigate the effect of N-nitro-L-arginine methyl ester on 3-morpholino sydnonimine induced hypotension, a group of rats received a continuous infusion of 0.54 mg/kg/h of 3-morpholino sydnonimine until 50% reduction was observed in mean arterial blood pressure followed by a bolus dose of 10 mg/kg of N-nitro-L-arginine methyl ester (n = 6) or 5% dextrose solution (n = 6) (Protocol 3). Outcome measures included mean arterial blood pressure, heart rate, and QRS duration in electrocardiogram. Student's t test and survival analysis were used for selected comparisons. RESULTS: For all parameters, the treatment groups were similar at baseline and at postamitriptyline periods before therapy was rendered. Amitriptyline infusion significantly reduced mean arterial blood pressure by 50.8 +/- 2.2% and prolonged QRS by 23.9 +/- 7.2% after 15 minutes. In Protocol 1, N-nitro-L-arginine methyl ester significantly increased mean arterial blood pressure compared to dextrose-treated control animals within 30 minutes (77.9 +/- 8.5% vs. 49.7 +/- 5.0% mmHg, p < 0.01, 95% CI 57.1-98.7%). QRS duration progressively increased during the amitriptyline infusion; however, there was no significant difference in QRS width between N-nitro-L-arginine methyl ester and control groups at any time point. N-nitro-L-arginine methyl ester increased survival time compared to controls (33.4 +/- 4.1 vs. 19.9 +/- 2.7 minutes, p < 0.01, 95% CI 25.4-41.3) but did not affect mortality. In Protocol 2 of continuous infusion of amitriptyline, 3-morpholino sydnonimine counteracted the N-nitro-L-arginine methyl ester-induced increase in mean arterial blood pressure. In both protocols, heart rate decreased significantly during amitriptyline infusion but there was no difference between treatment and control groups. In Protocol 3, N-nitro-L-arginine methyl ester bolus reversed 3-morpholino sydnonimine-induced hypotension compared to dextrose bolus. (83.8 +/- 5.7% vs. 54.6 +/- 4.8%, p < 0.01, 95% CI 69.2-98.4). CONCLUSION: N-nitro-L-arginine methyl ester is found to be effective in temporarily improving hypotension and prolonging survival time but does not affect overall mortality. Because this effect was antagonized by 3-morpholino sydnonimine, nitric oxide production appears to contribute to the pathophysiology of amitriptyline-induced hypotension.     

Treatment modalities and outcome of the renal victims of the Marmara earthquake

BACKGROUND/AIMS: Circulating CD14+CD16+ monocytes, a potent phagocytosing and antigen-presenting monocyte population, have been reported to be expanded in patients on hemodialysis (HD). In this study, changes in the population of CD14+CD16+ monocytes were analyzed during a single session of HD therapy, and the influence of dialyzer membrane materials on these monocytes was investigated. METHODS: Nine patients were hemodialyzed using regenerated cellulose (RC) membranes and thereafter polysulfone (PS) membranes. Peripheral blood cells were taken from these subjects, and these cells were stained with anti-CD14 and anti-CD16 antibodies. The percentages of CD14- and CD16-expressing monocytes were analyzed by two-color flow cytometric analysis. Moreover, the serum soluble CD14 (sCD14) levels were measured with an ELISA kit. RESULTS: It was found that CD14+CD16+ monocytes before HD were significantly increased in patients on HD as compared to healthy controls. In the RC group, CD14+CD16+ monocytes were decreased at both 30 and 240 min after the initiation of HD. The reduction rate of CD14+CD16+ monocytes in the RC group was higher than that in the PS group. There was no significant difference in sCD14 levels between the two groups. CONCLUSION: Monocytes are activated in patients on HD. Furthermore, the population of CD14+CD16+ monocytes was stimulated to a greater extent during HD in the RC group than in the PS group. The significant reduction in CD14+CD16+ monocytes by RC membranes indicated that the level of CD14+CD16+ monocytes is a sensitive marker for the biocompatibility of HD membranes.     

Renal replacement therapies in the aftermath of the catastrophic Marmara earthquake

BACKGROUND: Renal replacement therapy is of vital importance in the treatment of crush syndrome victims, who are frequently encountered after catastrophic earthquakes. The Marmara earthquake, which struck Northwestern Turkey in August 1999, was characterized by 477 victims who needed dialysis. METHOD: Within the first week of the disaster, questionnaires containing 63 clinical and laboratory variables were sent to 35 reference hospitals that treated the victims. Information considering the features of dialyses obtained through these questionnaires was submitted to analysis. RESULTS: Overall, 639 casualties with renal complications were registered, 477 of whom (mean age 32.3 +/- 13.7 years, 269 male) needed dialysis. Among these, 452 were treated by a single dialysis modality (437 intermittent hemodialysis, 11 continuous renal replacement therapy and 4 peritoneal dialysis), while 25 victims needed more than one type of dialysis. In total, 5137 hemodialysis sessions were performed (mean 11.1 +/- 8.0 sessions per patient) and mean duration of hemodialysis support was 13.4 +/- 9.0 days; this duration was shorter in the non-survivors (7.0 +/- 8.7 vs. 10.0 +/- 9.8 days, P = 0.005). Thirty-four victims who underwent continuous renal replacement therapy had higher mortality rates (41.2 vs. 13.7%, P < 0.0001). Only eight victims were treated by peritoneal dialysis, four of whom also required hemodialysis or continuous renal replacement therapy. The mortality rate in the dialyzed victims was 17.2%, a significantly higher figure compared to the mortality rate of the non-dialyzed patients with renal problems (9.3%; P = 0.015). CONCLUSION: Substantial amounts of dialysis support may be necessary for treating the victims of mass disasters complicated with crush syndrome. Dialyzed patients are characterized by higher rates of morbidity and mortality.     

Sex difference in perceptual-verbal ability in relation to body size

Sex difference in verbal ability was reconsidered in relation to body size. The perceptual-verbal ability (PVA) was assessed using the A's Test. For the raw data, women excelled men, as expected. PVA positively correlated with height and weight of the subjects, but only for women. As a covariate of height, sex difference increased by increasing the women's score; men's score did not change. Tall women had much higher scores than short men. It was concluded that sex difference in PVA is stable despite the smaller body size of females than males, and body height may be predictive for this ability, but only in women.     

Can negative appendectomy rate be decreased by using spiral computed tomography without contrast material?

Approximately 15-20% of error in the diagnosis of acute appendicitis argues for new diagnostic methods. In recent years it has been proposed that Computed Tomography be used in the diagnosis of acute appendicitis with high sensitivity and specificity. In our study, the effect of Computed Tomography on the diagnosis of acute appendicitis and on negative appendectomy was investigated on patients with suspected acute appendicitis. In the last 18 months, spiral Computed Tomography without contrast material has been used for 65 patients. The history, physical findings, laboratory results and Computed Tomography images of patients were compared and the final decision to operate was always made by an attending surgeon. The results of Computed Tomography have been correlated with the reports of pathology and operation findings. Other patients who have not been operated on have been followed up clinically. Correlating Computed Tomography results with operation findings revealed; 42 true positive, 3 false positive, 17 true negative and 3 false negative results. The sensitivity and specificity of CT have been found to be 93.3% and 85% respectively. Forty-eight out of 65 patients have been operated on for acute appendicitis and the negative appendectomy rate has been calculated as 6.25%. As a consequence, it was thought that in the diagnosis of acute appendicitis the use of Computed Tomography could decrease the negative appendectomy rate when used together with clinical follow-up.