Distribution of gene mutations associated with familial normosmic idiopathic hypogonadotropic hypogonadism

Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.     

Correlation between histological grade and MIB-1 and p53 immunoreactivity in meningiomas

OBJECTIVE: Meningiomas for the most part are slow-growing benign tumors, but complete removal can be difficult and recurrence is an issue. The aim of this study was to re-evaluate tumors diagnosed as meningioma previously in our hospital, according to the latest World Health Organization classification. We also examined the relationships among parameters such as brain invasion, histological grade and Ki-67 and p53 expression in these tumors. MATERIALS AND METHODS: Meningioma biopsy specimens numbering 60 (48 grade I, 11 grade II, and 1 grade III tumors) were examined immunohistochemically using monoclonal antibodies for Ki-67 (MIB-1) and p53 protein. The MIB-1 labeling index (LI) for each tumor was calculated as a percentage based on the number of stained cells per total cells counted. The level of p53 expression in each sample was semiquantatively evaluated as < 1%, 1 - 10%, 10 - 70%, or > 70%. Any value > 1% was accepted as presence of p53 expression. RESULTS: Of the 60 meningiomas, 7 (11.7%) exhibited brain invasion. The mean MIB-1 LI values for the grade I and grade II tumors were 1.1% and 2.3%, respectively. The corresponding levels of p53 protein expression in these groups were 54.1% and 72.7%. The MIB-1 LI and the level of p53 expression in the one grade III meningioma were 6.7% and 10 - 70%, respectively. Histological grade was significantly correlated with MIB-1 LI and with p53 expression (p < 0.01 for both). Brain invasion was not correlated with histological grade, MIB-1 LI, or p53 expression. CONCLUSION: The results indicate that MIB-1 LI and p53 protein expression are good indicators of histological grade in meningioma and may be particularly valuable for distinguishing borderline atypical meningiomas. The number of cases was limited, but the findings also suggest that brain invasion is a prognostic parameter independent of grade, MIB-1 LI and p53 expression.     

Langzeitergebnisse nach lumbalen Bandscheibenerkrankungen

The therapeutic results of operatively and conservatively treated patients with lumbar disc syndromes were reviewed in a retrospective study. The patients were treated during a 10-years period (1976-1985). A total of 330 patients with lumbar disc prolapses were treated in the hospital during this period 44% were treated surgically. The data on 100 operated and 100 conservatively treated cases, registered in this random test sample, have been compared with respect to: pain; neurological deficits; subjective problems and sociomedical questions. The average patient age of both groups was about 41 years, and the patients predominant were male (about 70%). The therapeutic results of both operatively and conservatively treated patients were good, which is also by the high percentage of employment (80%-90%) in the two treatment groups. The critical evaluation showed more neurological disturbances and limited vocational activity in the group of cases operated upon. More than 70% of the operated cases showed radicular syndromes of the follow-up examination although it was not of essential functional importance. The period inability to work and the percentage of disablement were also much higher in this group. The pain symptoms were particularly relevant in our examination. Only 12%-16% of the patients in the two groups that took part in the follow-up examinations reported freedom from pain. It was apparent that atypical pain syndromes were correlated with personality psychological disturbances. Nearly one-third of our patients mentioned psychological problems. The prognosis of the conservative treatment of lumbar disc prolapse was equivalent to operative therapy (disregarding the absolute indications for operations). There were no definite advantages found for either of the two methods of treatment. The necessity for a specialized follow-up treatment of patients with sciatica due to herniated lumbar discs is discussed, and differentiated selection for operative therapy is given. Here the treatment of pain should be considered most important.     

Cytokine gene polymorphisms in Turkish patients with inflammatory bowel disease

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the bowel, the causes of which are not fully known. Ethnic differences in disease prevalence, familial aggregation of the disease and studies of twins provide the most important evidence to suggest that genetic factors play a role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to examine the allelic polymorphisms that can determine the immune response levels in tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1B), interleukin-1 receptor antagonist ( IL-1RN) and interleukin-10 (IL-10) genes and to investigate their roles in the inflammatory pathway in IBD. MATERIAL AND METHODS: The study included 120 patients with UC and 70 patients with CD who were diagnosed either endoscopically or histopathologically. The control group comprised 105 healthy individuals who stated that they had never had any bowel disease during their life span. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method for polymorphisms in the TNFalpha gene at positions -308 and -238, the IL-10 gene at positions -1082 and -627, the IL-1B gene at -511 regions and the variable number of tandem repeat (VNTR) method for polymorphism in the intron 2 of the IL-1RN gene were performed. The results were analyzed on agarose gel electrophoresis. RESULTS: No significant differences were found in the allele and genotype frequencies of the polymorphisms in the IL-1B, IL10, TNFalpha and IL-1RN genes between the patients with UC and CD and controls. CONCLUSIONS: The results suggest that these polymorphisms were not important risk factors in the susceptibility to IBD in Turkish patients.     

Nitrosative tissue damage and apoptotic cell death in kidneys and livers of naturally ethylene glycol (antifreeze)-poisoned geese.

Three naturally ethylene glycol (EG)-intoxicated geese were investigated for pathological changes, nitrosative tissue damage and apoptotic cell death. Severe degeneration of kidney tubular epithelium and congestion of kidney and liver tissues were observed. Immunohistochemical staining for inducible nitric oxide synthase and nitrotyrosine revealed strong immunoreactivity with both antibodies in kidney and liver tissues compared with the weak immunostaining in the control animals. In both tissues of the EG-intoxicated geese, erythrocytes were also highly immunoreactive with nitrotyrosine antibody. A high degree of apoptotic cell death was present in the kidney tubule epithelium of EG-intoxicated geese. Some apoptotic cells were also observed in the liver. These results show that nitrosative tissue damage and apoptotic cell death takes place in kidney and liver during EG intoxication in geese.     

Role conflict, role ambiguity, and burnout in nurses and physicians at a university hospital in Turkey

In many countries currently, health-care professionals experience burnout in their professional life. This study explored the relationship between burnout, and role conflict and role ambiguity in nurses and physicians at a university hospital in Turkey. The data were collected by questionnaires that included sociodemographic variables, Maslach's Burnout Inventory (MBI), and Rizzo's Role Conflict and Role Ambiguity Scales. Two hundred and fifty one health-care professionals (170 physicians and 81 nurses) responded to the survey. There was a strong positive correlation between the MBI and Rizzo's Role Conflict and Role Ambiguity Scales. The nurses showed significantly higher levels of role conflict, role ambiguity, and burnout compared to the physicians. A multiple regression analysis showed that role conflict and role ambiguity might help to explain the higher level of burnout experienced by the nurses compared to the physicians. Future research is needed to develop preventive measures for the burnout of health-care professionals.