N-METHYL-d-ASPARTATE ANTAGONISTS, GLUTAMATE RELEASE INHIBITORS, 4-AMINOPYRIDINE AT NEUROMUSCULAR TRANSMISSION

It is thought that glutamate (GLU) and acetylcholine (ACh) are co-released in the neuromuscular junction (NMJ). Consequently, GLU is also a mediator or modulator of neuromuscular transmission (n-m) together with ACh. Therefore we decided to investigate the role of GLU in n-m by using isolated rat phrenic nerve–hemidiaphragm preparations. Since the GLU receptors present at NMJ have been reported to be predominantlyN-methyl-d-aspartate (NMDA) subtype, some non-competitive and competitive NMDA receptor blockers, MK801, ketamine, dextromethorphan and CGP 37849, and GLU release inhibitors, clonidine, guanfacine, tizanidine were used at their optimum concentrations in medium after having found them from dose–response curves. The preparations were first stimulated indirectly in the presence of the optimum concentrations of the drugs used and tensions developed were recorded isometrically through a force displacement transducer on a polygraph linked to a computer + Math coprocessor by an analog converter. All drugs at their optimum concentrations suppressed contractions significantly. Prolyl-glycinamide (PLG) or phenyl-succinate, both of which are the inhibitors of GLU production also suppressed the contraction significantly, following depletion of GLU stores by tetanic contraction in nerve endings. 4-Aminopyridine, which has been shown to release GLU augmented the contractions which were also completely abolished by the NMDA receptor antagonists or GLU release inhibitors at their higher concentrations than their optimum ones. The direct stimulation of the muscles elicited statistically insignificant but higher contractions than controls at the optimum concentrations of the antagonists or inhibitors in medium. The results were discussed and it was concluded that blockade of NMDA receptors, the inhibition of GLU release or the suppression of GLU production inhibit the contractions of the rat-isolated hemidiaphragms elicited by indirect electrical stimulation, without altering acetylcholinergic part of the contraction cascade.     

Right Ventricular Dysfunction and the Incidence of Implantable Cardioverter‐Defibrillator Therapies

Introduction: Implantable cardioverter‐defibrillator (ICD) therapy is well established in preventing sudden cardiac death in patients with left ventricular dysfunction. The influence of right ventricular (RV) function on ICD therapy for sudden cardiac death (SCD) is not known. Methods: We retrospectively studied 222 patients receiving an ICD for primary prevention of SCD. Baseline clinical and echocardiographic data were gathered. RV systolic function was qualitatively assessed as normal or abnormal (described as mildly, moderately, or severely reduced). Primary endpoint was combined ICD therapy or death and secondary endpoint was ICD therapy alone. Results: The mean follow‐up was 940 ± 522 days. The mean left ventricular ejection fraction was 0.23 ± 0.07. By Kaplan‐Meier analysis, RV dysfunction was predictive of combined ICD therapy or death when comparing between normal and abnormal RV function (P = 0.008) and among qualitative ranges of RV function (P = 0.012). RV dysfunction was not predictive of ICD therapy alone with either type of classification. After adjusting for clinical covariates, severe RV dysfunction was predictive of the combined endpoint of ICD therapy or death (HR 2.02, 95% CI 1.04–3.92, P = 0.037). Conclusion: Severe RV dysfunction appears to be an independent predictor of the combined endpoint of ICD therapy or death. RV dysfunction does not reliably predict the incidence of ICD therapy alone.     

Psychological trauma of circumcision in the phallic period could be avoided by using topical steroids

OBJECTIVE: The objective of our study was to assess the efficacy of topical steroids in the treatment of phimosis and evaluate patients using the Diagnostic and Statistical Manual-III-Revised (DSM-III-R) test with the aim of eliminating castration anxiety of circumcision in the phallic period. METHODS: One hundred and forty-nine children with phimosis who required circumcision were included the study. The average age of the children was 4.47 years. All children underwent the DSM-III-R test and their parents were questioned. Patients were separated randomly into three groups. Group I comprised 51 children who would undergo circumcision; group II comprised 50 children who would be treated with a topical corticosteroid (0.05% bethamethasone cream) twice daily for 1 month; and group III comprised 48 children who would be treated with a topical placebo cream. On the 5th day of treatment, parents were told to retract the prepuce and were given hygiene routine instructions. Patients were seen immediately after treatment and again 2 months later. RESULTS: In group II, 16 of the 50 children had non-retractable prepuce. Forty-two cases of phimosis were corrected after treatment. Eight patients received further monthly treatment and five benefited from the second course of treatment. In group III, 17 of the 48 patients had non-retractable prepuce and four had satisfactory results. Forty-four patients received placebo treatment for another month and eventually, 40 children underwent circumcision in this group. DSM-III-R test results showed a significant shift to anxiety in the circumcision group. The were no significant differences in the other groups. CONCLUSION: Topical steroids for the treatment of phimosis is a highly effective treatment alternative to surgery. It avoids or delays circumcision and can be practised during the phallic period to decrease castration anxiety. The treatment is suitable for patients from any religious or cultural background.     

Histopathological changes and tumour necrosis factor-α, transforming growth factor-β and tenascin expression in patients with primary type I membranoproliferative glomerulonephritis in remission

Aim:   Primary type I membranoproliferative glomerulonephritis (MPGN) is a rare cause of glomerular disease with a high relapse rate and poor prognosis. The aim of this study was: (i) to evaluate the histopathological findings associated with remission; and (ii) to document the possible clinical and histopathological factors predicting relapses.
Methods:   Eleven type I MPGN patients (five men, six women; mean age, 38.8 ± 13.5 years) who were in remission for at least 1 year after the cessation of immunosuppressive drugs were re-biopsied. The intensity of immunostaining for tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and tenascin was graded from 0 (no staining) to 3+ (maximum staining).
Results:   Mean baseline mesangial cellularity score and tubulointerstitial infiltration score were reduced and mesangial matrix expansion score was increased at protocol re-biopsies compared to baseline. The glomerular and tubulointerstitial staining scores for TGF-β1 and tenascin were higher than that of baseline. Reduced tubulointerstitial TNF-α expression was found in re-biopsy specimens compared to baseline. Patients have been followed for a mean time of 51.5 ± 22.2 months after the protocol biopsy. Eight patients had a relapse. Mesangial cellularity score and glomerular tenascin expression at re-biopsy specimens were higher in relapsed patients compared to those without a relapse.
Conclusion:   Our study shows that mesangial cellularity and tubulointerstitial cell infiltration are reducing whereas mesangial matrix expansion, glomerular and tubulointerstitial TGF-β1 and tenascin expression are increasing with remission. The higher mesangial cell proliferation and glomerular tenascin scores in remission are associated with the development of relapse.     

Long‐term prognosis of nonalcoholic fatty liver disease: Is pharmacological therapy actually necessary?

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) comprises a wide spectrum of liver injury, ranging from steatosis and steatohepatitis to cirrhosis. Reasons for the different natural course in individuals with NAFLD are still unclear. The aim of this study was to describe the natural course of disease in individuals with NAFLD who did not receive pharmacological therapy. Methods: A total of 27 individuals with NAFLD (male/female ratio: 10/17, mean age 49.7 years) were prospectively enrolled. Management after diagnosis consisted of establishment of an appropriate diet and exercise (walking and jogging) program, treatment of associated metabolic conditions such as diabetes and dyslipidemia, and discontinuation of potentially hepatotoxic drugs if the patient was taking these. Liver tests were performed at diagnosis and at 3‐month intervals during the follow‐up period. Mean follow‐up period was 43.3 months (range 36–49 months). Results: From baseline to the end of the follow‐up period, although there was no significant difference observed in terms of the mean body mass index, serum aminotransferase levels significantly improved (48.8 ± 29.9 U/L to 31.6 ± 16.0 U/L for aspartate aminotransferase [AST] and 66.3 ± 38.3 U/L to 39.6 ± 22.9 U/L for alanine aminotransferase [ALT]; P < 0.05). No significant differences in platelet counts, serum albumin level or prothrombin time were observed (P > 0.05). No patient developed signs of advanced liver disease during the follow‐up period. Conclusion: A treatment strategy comprising diet, exercise and management of associated metabolic conditions is associated with improvement in aminotransferases among patients with NAFLD. Further investigation is needed to examine the long‐term efficacy of this approach on liver histology and clinical outcomes.     

Possible effect of leptin on renal magnesium excretion in adolescent patients with type 1 diabetes

BACKGROUND: Hypomagnesaemia and hyperleptinemia are common in patients with diabetes. Moreover, it has been demonstrated that leptin stimulates diuresis and natriuresis. The aim of this study was to evaluate the relationship between serum leptin, serum magnesium (Mg) and urinary Mg/urinary creatinine levels in patients with type 1 diabetes. METHODS: Serum leptin and Mg and urinary Mg/urinary creatinine levels were measured in 67 patients with diabetes (33 girls and 34 boys). The age, diabetes duration, anthropometric and metabolic parameters of the subjects were matched between girls and boys. The relation of serum leptin levels to serum and urinary Mg/urinary creatinine levels was assessed. RESULTS: Serum leptin levels of girls with diabetes were higher than those of the boys (14 +/- 5.3 microg/L vs 5.8 +/- 1.5 microg/L, P < 0.001, respectively). The differences for serum Mg and for urinary Mg/urinary creatinine levels were not significant between girls and boys with diabetes. Leptin levels were correlated with urinary Mg/urinary creatinine levels in both girls and boys (r = 0.39, P = 0.02 and r = 0.37, P = 0.03, respectively). In a multivariate regression model, leptin emerged as independent correlates for mean urinary Mg/urinary creatinine in both girls and boys with the total variance explained being 14%, and 15%, respectively. CONCLUSION: The data suggest that serum leptin might be related to increased urinary Mg loss in patients with type I diabetes.     

Retrospective analysis of 135 renal trauma cases

BACKGROUND: We review our trauma cases over the last 11 years and discuss our diagnosis and treatment modalities. METHODS: One hundred and thirty-five patients with renal injuries who had been hospitalized in the Urology and General Surgery clinics of Dicle University hospital between 1990 and 2001 were reviewed retrospectively. Patients were evaluated with regard to age, sex, cause of trauma, transport time, diagnostic methods, grade of injuries, associated organ injuries, treatments and complications. RESULTS: One hundred and forty-one renal injuries were established in 135 patients. The patients were between 5 and 65 years old; 114 (84.4%) were male and 21 (15.6%) were female. The most common cause of injuries (99 patients) was penetrating injuries. The transport time to hospital after injury was approximately 116 min. Immediate laparotomy was performed in 95 hemodynamically unstable patients. Radiological investigations were carried out in the remaining 40 patients. Most of the injuries were grade 4 (28, 19.86%) or 5 (60, 42.55%). Isolated renal injury was established in only 22 of 135 patients. Nephrorrhaphy was performed in 45 of 141 kidneys. Twelve injured kidneys were managed conservatively. Nephrectomy was performed in 66 of 141 kidneys. The remaining injured kidneys were managed with different treatment methods. Twenty-nine (21.48%) patients were lost intraoperatively or during the early postoperative period. CONCLUSION: We believe that our rates of nephrectomy and mortality were high because of the long transport time, unsuitable transport type, frequent high grade and high rate of associated organ injuries.     

Therapeutic effect of spiramycin in brucellosis

OBJECTIVE: This study was undertaken to investigate the usefulness of spiramycin in treatment for brucellosis in an animal model. METHODS: Eighty-four Sprague-Dawley rats were infected by intraperitoneal injection of Brucella melitensis suspension. Seven days after inoculation, four rats were selected randomly, killed and spleen cultures and Brucella standard tube agglutination test were carried out. All four rats were found to be infected. Eighty adult rats were randomly divided into four groups of 20 rats each. Tap water was given to the first group. Rifampicin 50 mg/kg per day and doxycycline 40 mg/kg per day were given to the second group, spiramycin 50 mg/kg per day orally was given to the third group, and a combination of spiramycin and rifampicin at the same dose and period was given to the fourth group. Duration of therapy regimens in all groups was 21 days. The spleens of all 80 rats were removed aseptically, homogenized, and placed onto Brucella agar plates to determine if viable bacteria were present. RESULTS: Bacterial growth occurred in all of the rats' spleens in the first group and in two rats' spleens in the spiramycin group. Mean colony forming unit (c.f.u.) values were at the highest in the first group. The effectivities of spiramycin and rifampicin-spiramycin were similar to rifampicin-doxycycline. There were no differences in the treatment results between the three groups that received combined rifampicin-doxycycline, rifampicin-spiramycin and only spiramycin (P>0.05). CONCLUSIONS: The results show that spiramycin cures experimental rat brucellosis and may be an effective alternative in the therapy of human brucellosis.