The importance of genomic copy number changes in the prognosis of glioblastoma multiforme

Glial tumors are the most common tumors of the nervous system, affecting individuals at any age. Since understanding of the molecular pathologies underlying human gliomas is still very poor, the treatment and therefore prognosis of this malignancy could not yet be improved. In order to determine whether different glioblastoma-associated genomic aberrations may serve as prognostic markers in combination with histopathological findings, 20 primary glioblastoma multiforme tumors were screened by comparative genomic hybridization, and the results were compared with histopathological and clinical features. All tumors showed genomic copy aberrations detected by comparative genomic hybridization. Regional and numerical increases in chromosome 7 copy number were the most frequently seen abnormality (10/20 tumors), followed by loss of chromosome 10 (8/20). Both of these aberrations were associated with shorter surveillance time. Chromosome 12q amplification was detected in seven tumors. Loss of 17p, 1p, and 19q in combination was seen in three cases. One of them was a giant cell GBM, whereas the remaining two cases were still alive. Combination of chromosome 1p and 19q deletions was also seen in a case with long surveillance. According to the preliminary findings of this study, in addition to the EGFR gene, amplification of other genes on chromosome 7 and the deletion of PTEN gene and other cancer-related genes on chromosome 10 appeared important to the development of glioblastoma multiforme and were associated with poor prognosis, whereas the combination of chromosome 1p and 19q deletions seems to be an informative molecular marker for better prognosis. The clinical features and genetic alterations of primary and secondary glioblastoma multiforme should be compared in large series to clarify the effective prognostic markers; and further molecular analyses focused on chromosomes 7 and 10 will be very helpful for understanding the molecular mechanisms underlying the progression of glioblastoma.     

Protective effects of melatonin and vitamin E in brain damage due to gamma radiation

Gamma radiation is known to cause serious damage in the brain, and many agents have been used for neuroprotection. In this study, lipid peroxidation levels and histopathological changes in brain tissues of whole-body irradiated rats with likely radiation injury were compared to those with melatonin and vitamin E protection. Forty rats in four equal groups were used. The control group received neither radiation nor medication. The remaining groups received doses of 720 cGy in two equal fractions 12 h apart. The second group received radiation but no medication, the third received radiation plus 100 mg/kg per day of vitamin E i.p., and the fourth received radiation plus 100 mg/kg per day of melatonin i.p. over 5 days. On the 10th postoperative day, all the rats were decapitated and specimens from parietal cortices were analyzed for tissue malondialdehyde (MDA) levels and histopathological changes. Increases in MDA were relatively well prevented by melatonin treatment but less so with vitamin E therapy. On histopathological examination, melatonin significantly reduced the rates of edema, necrosis, and neuronal degeneration, whereas vitamin E reduced only necrosis. Neither substance was capable of preventing vasodilatation. In conclusion, melatonin may be useful in preventing the pathological changes of secondary brain damage as a result of free oxygen radicals generated by irradiation.     

Osteochondroma leading to proximal tibiofibular synostosis as a cause of persistent ankle pain and lateral knee pain: a case report

This paper presents a case report of persistent ankle pain and lateral knee pain due to existing proximal tibiofibular synostosis.     

Head injury-associated bone fractures induce bacterial translocation: an experimental study

OBJECTIVES: To determine whether long bone fractures cause bacterial translocation and to investigate the effect of concomitant head trauma on this process. DESIGN: An in vivo animal model. SETTING: Animal Laboratory, University of Mersin School of Medicine, Mersin, Turkey. SUBJECTS: Male Sprague-Dawley rats (n = 60). INTERVENTION: Sixty male Sprague-Dawley rats were divided into five groups: (1). anesthesia only (control group, n = 12); (2). anesthesia and tibia fracture (n = 12); (3). anesthesia, tibia fracture, and femur fracture (n = 12); (4). anesthesia, tibia fracture, femur fracture, and moderate head trauma (n = 12); and (5). moderate head trauma only (n = 12). After 24 hours, mesenteric lymph nodes, liver, spleen, ileum, and systemic blood samples were quantitatively cultured for aerobic organisms. MAIN OUTCOME MEASUREMENTS: Colony-forming unit per gram for bacteria count. RESULTS: The incidence of bacterial translocation was higher in groups that had fractures (4/12 in group 2; 5/12 in group 3) than in the control group (2/12); however, this did not reach statistical significance. There was a significant increase in the number of subjects with bacterial translocation in group 4 (9/12) compared with the control group and group 5 (3/12) (P = 0.0123, P = 0.0391). CONCLUSIONS: Multiple fractures of long bones associated with head injury promote bacterial translocation.     

A simple positioning device for radiographic imaging of the patellofemoral joint: a technical note

The informative value of axial radiographs of the patellofemoral joint is highly dependent on application techniques and knee positioning. We developed a simple device that enables an appropriate and easy positioning. With the use of this device, patellofemoral axial radiographs can be obtained at 30 degrees of knee flexion.     

Inhibin alpha and beta expression in ovarian stromal tumors and their histological equivalences

Inhibin is a heterodimeric protein hormone that appears to be a sensitive immunohistochemical marker of sex cord-stromal tumors. Although sex cord-stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. The purposes of this study were to examine inhibin alpha and beta immunoreactivity in a wide range of gonadal stromal neoplasms and to assess its value in the differential diagnosis of problematic tumors. A total of 108 paraffin-embedded ovarian and extraovarian tumors were examined immunohistochemically by using anti-alpha inhibin and anti-beta inhibin. Inhibin alpha immunostaining was identified in 46 (81%) of 57 gonadal stromal tumors, one (14%) of seven endometrial stromal tumors, and one (50%) of two primary ovarian carcinoid tumors. Inhibin beta immunostaining was detected in 55 (96%) of 57 gonadal stromal tumors, two (29%) of seven endometrial stromal tumors, one (50%) of two dysgerminomas, and in all of two (100%) primary ovarian carcinoid tumors. Inhibin alpha expression was not detected in any ovarian surface epithelial tumor cells. Some surface epithelial tumors showed stromal inhibin alpha (15% of cases) and inhibin beta (48% of cases) positivity. Weak immunoreactivity for inhibin beta was found in most (83% of cases) ovarian surface epithelial tumors. Two ovarian Burkitt lymphomas were negative for inhibin alpha and beta. Inhibin alpha is a sensitive immunohistochemical marker of gonadal stromal tumors and is of value in the differential diagnosis of ovarian neoplasia. Inhibin beta is a nonspecific marker for ovarian neoplasms, showing expression on tumor and stromal cells of different epithelial or stromal tumors.     

Psychosocial correlates of substance use among adolescents in Mersin, Turkey

The objective of this study was to determine the effects of psychosocial factors such as peer group, family and academic self-perception on smoking, alcohol and substance use by adolescents living in Mersin, Turkey. The study included a total of 3282 students from the sixth and tenth grades and college. The number of participating students required from each school was obtained through stratification, and by weighing the enrolled student population in each subgroup. The final sample was derived using a simple random sampling technique. A 45-item self-administered questionnaire was used. The questionnaire included questions about socio-demographic characteristics and lifetime and current (i.e. within the past month) use of cigarettes, alcohol, cannabis, inhalants and other illicit drugs (heroin, cocaine, sedative-hypnotic drugs, etc.). This study found that: (1) higher socio-economic status of the family increased the likelihood of smoking and alcohol use in adolescents; (2) the prevalence of alcohol use was higher in adolescents whose mothers had a higher educational level and whose mothers and fathers drank alcohol; (3) there was a significant association between substance use and having a peer who used a substance; and (4) the prevalence of smoking was significantly higher in students who perceived their academic performance to be poor. Understanding the role and importance of psychosocial factors associated with smoking, alcohol and substance use will be crucial to develop preventive measures for adolescents.     

Specificity of action of bisindolylmaleimide protein kinase C inhibitors: do they inhibit the 70kDa ribosomal S6 kinase in cardiac myocytes?

Bisindolylmaleimide protein kinase C (PKC) inhibitors, such as GF109203X and Ro31-8220, are used as pharmacological tools in many cellular systems. However, in vitro, GF109203X and Ro31-8220 also inhibit the 70 kDa ribosomal S6 kinase (p70^S6K) with similar potency. We determined whether GF109203X and Ro31-8220 inhibit p70^S6K activity in intact adult rat ventricular myocytes (ARVM). First, we confirmed that increased phosphorylation of the 40S ribosomal S6 protein (a cellular substrate for both p70^S6K and the 90 kDa ribosomal S6 kinase) in response to stimulation of ARVM by insulin-like growth factor-1 (300 ng/mL; 10 min) occurs specifically through rapamycin-sensitive activation of p70^S6K. Then, using this response as the index of cellular p70^S6K activity, we determined the effects of GF109203X and Ro31-8220 (1, 3 or 10 μM) on such activity. At these concentrations, neither GF109203X nor Ro31-8220 inhibited cellular p70^S6K activity. In contrast, even at 1 μM, cellular PKC activity (stimulated by a 3 min exposure to 30 nM phorbol 12-myristate 13-acetate) was significantly inhibited by each agent. We conclude that; (1) data obtained in vitro may not necessarily be extrapolated to intact cells and (2) inhibition of p70^S6K is unlikely to contribute to the actions of GF109203X and Ro31-8220 in ARVM.