The Effects of O6-methyl Guanine DNA-methyl Transferase Promotor Methylation and CpG1, CpG2, CpG3 and CpG4 Methylation on Treatment Response and their Prognostic Significance in Patients with Glioblastoma.

This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O6- methyl guanine methyl transferase (MGMT) and meth-ylation of CpG 1, CpG2, CpG3 and CpG4 in glioblastoma (GB) patients received postoperative radiotherapy (PORT), with or without adjuvant temozolomide (TMZ). One hundred patients with GB who received PORT with concomitant TMZ plus adjuvant TMZ or PORT alone, were included. The MGMT promoter methylation of CpG1, CpG2, CpG3 and CpG4 islands were examined. Overall, MGMT-methylation emerged as a significant prognostic factor for better overall survival (OS) and progression-free survival (PFS) [odds ratio (OR): 0.609, 95% confidence interval (95% CI): 0.395-0.939, p = 0.02; OR: 0.662,95% CI: 0.430-1019, p = 0.5, respectively]. The methylation of each CpG1, CpG2, CpG3 and CpG4 islands was found to have no significant effects on OS and the methylation of each CpGl, CpG2 and CpG4 islands had no significant effect on PFS (p <0.05 for all). On the other hand, the methylation of CpG3 had a positive prognostic effect on PFS (OR: 2.1, 95% CI: 0.99-4.67, p = 0.04). In the group that only received radiotherapy (RT), CpG1 and CpC3 methylations were found to have a positive prognostic significance in terms of PFS (OR: 266, 95% CI: 1.05-6.75, p -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, p = 0.04 for CpG3). The MGMT promoter methylation represents an important biomarker for predicting response to therapy. Individual islands, particularly CpG3, deserves further investigation as a prognostic marker. Further studies need to be done with larger sample sizes to clarify the results.

Severe skin reactions associated with cladribine in people with multiple sclerosis.

OBJECTIVE: To report three cases of severe skin reactions in patients treated with cladribine for multiple sclerosis. METHODS: Case study. RESULTS: Patients developed severe rash 3-192 days after receiving cladribine. All were effectively treated with steroids and antihistamines. Additional doses of cladribine were administered after pretreatment with steroids and anti-histamines. One patient developed mild recurrence following re-exposure, which resolved within three days, whilst another patient tolerated re-exposure without further adverse reaction. CONCLUSION: Severe skin reactions, well described in patients receiving cladribine for treatment of haematological conditions, may occur in patients treated with this compound for multiple sclerosis. Neurologists need to be aware of this rare, but significant adverse reaction. Re-exposure may be safe with standard pre-treatment against allergic reactions.

In vitro cytotoxic activity of microalgal extracts loaded nano-micro particles produced via electrospraying and microemulsion methods.

Reactive oxygen species can bind protein, DNA, lipids, and carbohydrates and thus cause an oxidation reaction that induces various syndromes such as cardiovascular diseases, degenerative disease, and cancer types in the human body. Bioactive compounds, such as PUFA, EPA, DHA, and carotenoids in algae, have a chain ring and protect the tissue from chemical damage and reverse the symptoms of some diseases. Algal bioactives also have various biological properties such as anticoagulants, antiviral, antiangiogenic, antitumor, anti-inflammatory, antioxidant, antiproliferative, and immune modulation properties. This study aimed to show in vitro cytotoxic activity effect of Chlorella protothecoides and Nannochloropsis oculata microalgal extracts loaded nano-microparticles on A-172 (Homo sapiens brain glioblastoma) and HCT-116 (H. sapiens colon colorectal carcinoma) cell lines because of the increasing importance of algal biotechnology. MTT viability tests were performed on HUVEC, A172, and HCT 116 cells with particles obtained at optimum process parameters. The cell viability rates of encapsulated particles were also compared with pure algae extracts. Microalgal extracts loaded nano-micro particles showed very promising results for cytotoxic effect on cancer cells.

Assessment of concomitant versus sequential trastuzumab on radiation-induced cardiovascular toxicity.

There are limited data regarding effect of trastuzumab on radiation-induced cardiovascular toxicity when used sequentially or concomitantly. This experimental study aims to investigate effect of trastuzumab on radiation-induced cardiovascular toxicity with respect to the treatment sequence. One hundred and eight female Wistar albino rats were divided into six groups (G): G1 was control, G2 was trastuzumab, and G3 was radiotherapy (RT); G4 and G6 were sequential RT and trastuzumab; and G5 was concomitant RT and trastuzumab groups, respectively. Rats were killed at 6th h, 21st and 70th days after RT; thoracic aorta and heart samples were obtained. Transthoracic echocardiography and functional studies evaluating relaxation of thoracic aorta were performed. Subendothelial edema scores of thoracic aorta samples at 21st and 70th days were higher in RT groups (G3, G4, G5, and G6) ( p < 0.001). There was a deterioration of relaxation responses of thoracic aorta samples in RT groups ( p < 0.001). Cardiac fibrosis (CF) scores revealed detrimental effect of RT beginning from 6th h and trastuzumab from 21st day. RT groups showed further deterioration of CF at 70th day. Ejection fraction, left ventricular mass, and fractional shortening were significantly decreased in G4, G5, and G6. Trastuzumab may increase pathological damage in cardiovascular structures when used with RT regardless of timing.

Activating c-KIT mutations confer oncogenic cooperativity and rescue RUNX1/ETO-induced DNA damage and apoptosis in human primary CD34+ hematopoietic progenitors.

The RUNX1/ETO (RE) fusion protein, which originates from the t(8;21) chromosomal rearrangement, is one of the most frequent translocation products found in de novo acute myeloid leukemia (AML). In RE leukemias, activated forms of the c-KIT tyrosine kinase receptor are frequently found, thereby suggesting oncogenic cooperativity between these oncoproteins in the development and maintenance of t(8;21) malignancies. In this report, we show that activated c-KIT cooperates with a C-terminal truncated variant of RE, REtr, to expand human CD34+ hematopoietic progenitors ex vivo. CD34+ cells expressing both oncogenes resemble the AML-M2 myeloblastic cell phenotype, in contrast to REtr-expressing cells which largely undergo granulocytic differentiation. Oncogenic c-KIT amplifies REtr-depended clonogenic growth and protects cells from exhaustion. Activated c-KIT reverts REtr-induced DNA damage and apoptosis. In the presence of activated c-KIT, REtr-downregulated DNA-repair genes are re-expressed leading to an enhancement of DNA-repair efficiency via homologous recombination. Together, our results provide new mechanistic insight into REtr and c-KIT oncogenic cooperativity and suggest that augmented DNA repair accounts for the increased chemoresistance observed in t(8;21)-positive AML patients with activated c-KIT mutations. This cell-protective mechanism might represent a new therapeutic target, as REtr cells with activated c-KIT are highly sensitive to pharmacological inhibitors of DNA repair.

Preoperative chemoradiotherapy improves local recurrence free survival in locally advanced rectal cancer.

PURPOSE: Preoperative chemoradiotherapy (pre-CRT) followed by total mesorectal excision (TME) is the recommended therapy for patients with locally advanced rectal cancer (LARC). The primary aim of this study was to compare the rates of local and distant recurrence and overall survival (OS) in LARC patients who received pre-CRT vs postoperative (post) CRT. METHODS: The medical records of 158 rectal cancer patients with clinical stage T3, T4 or N positive disease who received either pre-CRT or post-CRT between 2000-2009 were retrospectively analysed. Pre-CRT employed protracted 5-fluorouracil (5FU) infusion, whereas post-CRT included bolus 5FU and leucovorin concurrently with radiation therapy (RT). Radiation dose was 50.4 Gy in 82% and 45 Gy in 18% of the patients. RESULTS: 158 patients (65 females, 93 males) were analysed. Median age was 56.5 years (range 19-78). Fifty-three (34%) patients received pre-CRT and 105 (66%) post-CRT. Median follow-up was 43.3 months (range 8-182) and 47.6 months (range 9-194) in pre-CRT and post-CRT patients, respectively. After pre-CRT, significant downstaging was achieved. However, the type of surgical resection was not influenced by the administration of pre-CRT in tumors ≥5 cm distant from the anal verge (p=0.3). Pathologic complete response was achieved in 20% of the patients in the pre-CRT group. Local recurrence free survival (LRFS) at 5-years was 89.2% in the pre-CRT and 74.8% in the post-CRT group (p=0.04). Distant recurrence free survival (DRFS) at 5-years was 81.7% and 68.5 % in pre-CRT and post-CRT groups, respectively (p=0.1). OS was similar in the two groups (71.4 vs 64.4%, p=0.9). CONCLUSION: Treatment of LARC with pre-CRT followed by surgery improved LRFS as compared to surgery followed by post-CRT, but failed to improve DRFS or OS in our patient population.

A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with Type 2 diabetes (MODEST Study).

OBJECTIVE: It has been suggested that lipid-lowering treatment with the use of statins adversely affects the steroid hormones. However, the safety of lipid lowering treatment targeting very low levels of LDL with respect to the steroid hormones has not been established. RESEARCH DESIGN AND METHODS: A prospective, randomized, multicenter trial was conducted involving 98 patients. The patients were randomized into 2 groups: group-I received 10 mg of atorvastatin plus 10 mg of ezetimibe and group-II 80 mg of atorvastatin for the first 3 months. After crossover, the first group received 80 mg of atorvastatin and the second group 10 mg of atorvastatin plus 10 mg of ezetimibe for the following 3 months. Cortisol, DHEAS, testosterone, and estradiol levels were measured at the enrollment and at the end of the 1st, 2nd, 3rd, and 6th months. RESULTS: Along with a decrease in LDL level, the levels of DHEAS, testosterone, and estradiol decreased in both groups (p<0.001). While cortisol levels were maintained in the group given 10 mg of atorvastatin plus 10 mg of ezetimibe, it decreased significantly after the crossover to 80 mg of atorvastatin (p<0.001). The group initially given 80 mg of atorvastatin measured a lower level of cortisol for the first 3 months and it returned to normal levels after switching to 10 mg of atorvastatin plus 10 mg of ezetimibe. CONCLUSION: Eighty milligrams of atorvastatin decreased all adrenal and gonadal steroids, whereas 10 mg of ezetimibe combined with 10 mg of atorvastatin had at least no impact on cortisol levels.

Effects of depression and anxiety on quality of life of patients with rheumatoid arthritis, knee osteoarthritis and fibromyalgia syndrome.

OBJECTIVE: To measure the effects of depression and anxiety on quality of life (QoL) in patients with rheumatoid arthritis (RA), knee osteoarthritis (OA) and fibromyalgia syndrome (FMS). METHODS: One hundred and fifty-four patients with RA, knee OA, and FMS who presented to the physical medicine and rehabilitation department were studied. For evaluation of the patients, Beck depression scale, Beck anxiety scale, and Short Form-36 were used. RESULTS: Twenty-two per cent of patients (n = 34) were diagnosed with of RA, 52.6% (n = 81) knee OA and 25.3% (n = 39) FMS. Except for the subscales, of physical and emotional role, there were statistically significant differences among diagnostic groups in the rest of the SF-36 subscales. In the physical functioning subscale, the highest score was obtained in the fibromyalgia group and the lowest in the RA group (p < 0.001). However, in the bodily pain subscale, the lowest score was recorded in the fibromyalgia group (p = 0.019). In all diagnostic groups, the scores of SF-36 subscales were significantly low in patients who scored above the threshold value of Beck depression scale (p < 0. 001). A strong negative correlation was detected between scores of Beck anxiety scale and the scores of all SF36 subscales in patients with RA and knee OA. On the other hand, in patients with FMS, anxiety scores correlated negatively with only physical and somatic function scores of SF-36. CONCLUSION: Quality of life is significantly low in patients with RA, knee OA and FMS, whose depression and/or anxiety scores are high. Therefore, these patients should be managed using a multidisciplinary approach including psychiatric support.

Effects of depression and anxiety on quality of life of patients with rheumatoid arthritis, knee osteoarthritis and fibromyalgia syndrome / Efectos de la depresión y la ansiedad sobre la calidad de los pacientes con artritis reumatoide, osteoartritis de la rodilla y síndrome de fibromialgia

OBJECTIVE: To measure the effects of depression and anxiety on quality of life (QoL) in patients with rheumatoid arthritis (RA), knee osteoarthritis (OA) and fibromyalgia syndrome (FMS). METHODS: One hundred and fifty-four patients with RA, knee OA, and FMS who presented to the physical medicine and rehabilitation department were studied. For evaluation of the patients, Beck depression scale, Beck anxiety scale, and Short Form-36 were used. RESULTS: Twenty-two per cent of patients (n = 34) were diagnosed with of RA, 52.6% (n = 81) knee OA and 25.3% (n = 39) FMS. Except for the subscales, of physical and emotional role, there were statistically significant differences among diagnostic groups in the rest of the SF-36 subscales. In the physical functioning subscale, the highest score was obtained in the fibromyalgia group and the lowest in the RA group (p < 0.001). However, in the bodily pain subscale, the lowest score was recorded in the fibromyalgia group (p = 0.019). In all diagnostic groups, the scores of SF-36 subscales were significantly low in patients who scored above the threshold value of Beck depression scale (p < 0. 001). A strong negative correlation was detected between scores of Beck anxiety scale and the scores of all SF36 subscales in patients with RA and knee OA. On the other hand, in patients with FMS, anxiety scores correlated negatively with only physical and somatic function scores of SF-36. CONCLUSION: Quality of life is significantly low in patients with RA, knee OA and FMS, whose depression and/or anxiety scores are high. Therefore, these patients should be managed using a multidisciplinary approach including psychiatric support.

OBJETIVO: Medir los efectos de la depresión y la ansiedad sobre la calidad de vida (CdV) en pacientes con artritis reumatoide (AR), osteoartritis de la rodilla (OA) y síndrome de fibromialgia (SFM). MÉTODOS: Se estudiaron ciento cincuenta y cuatro pacientes con RA, OA de la rodilla, y, que acudieron al departamento de medicina física y rehabilitación. Para la evaluación de los pacientes se utilizaron la escala de depresión de Beck, la escala de ansiedad de Beck, y el cuestionario de salud SF-3. RESULTADOS: Al veintidós por ciento de los pacientes (n = 34) se les diagnosticó RA, al 52.6% (n = 81) OA de la rodilla, y al 25.3% (n = 39) SFM. Excepto para las subescalas del rol físico y emocional, hubo diferencias estadísticamente significativas entre los grupos diagnósticos en el resto de las subescalas del cuestionario SF-36. En la subescala del funcionamiento físico, la puntuación más alta se obtuvo en el grupo de fibromialgia y la más baja en el de RA (p < 0.001). Sin embargo, en la subescala de dolor corporal, la puntuación más baja se registró en el grupo de fibromialgia (p = 0.019). En todos los grupos diagnósticos, las puntuaciones de las subescalas del cuestionario fueron significativamente más bajas en los pacientes que obtuvieron puntos por encima del valor umbral de la escala de depresión de Beck (p < 0.001). Una fuerte correlación negativa fue detectada entre las puntuaciones de la escala de ansiedad de Beck y las puntuaciones de todas las subescalas del cuestionario SF-36 en pacientes con RA y OA de la rodilla. Por otro lado, en pacientes con SF, las puntuaciones de ansiedad tuvieron una correlación negativa con solo puntuaciones de función física y somática de SF-36. CONCLUSIÓN: La calidad de vida es significativamente mas baja en pacientes con RAD, OA de la rodilla y SFM, cuyas puntuaciones de depresión y/o ansiedad son elevadas. Por lo tanto, estos pacientes deben de ser tratados haciendo uso de enfoques multidisciplinarios, incluyendo apoyo...

Metastatic primitive neuroectodermal tumor of the ovary in pregnancy.

Primitive neuroectodermal tumor (PNET) is a small round tumor belonging to the PNET/Ewing's sarcoma family. We hereby report a case of PNET of the ovary, which was detected at the second trimester of pregnancy. Chemotherapy was administered and a healthy baby was delivered by cesarean section. After the pregnancy, the mother was found to have metastatic disease. Chemotherapy was continued, but she died due to progressive disease 13 months after the initial diagnosis. In this case report, we discuss chemotherapy options during pregnancy and the importance of multidisciplinary approach to unusual presentations of rare tumors.

Leptin, soluble interleukin-6 receptor, C-reactive protein and soluble vascular cell adhesion molecule-1 levels in human coronary atherosclerotic plaque.

The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes.

Importance of timing of antiaggregant treatment in the prevention of radiation induced enteropathy.

Chronic radiation enteropathy (CRE) is an undesirable radiation-induced toxicity and a common health problem in patients with pelvic or abdominal malignancies. Damage to microvascular endothelial cells and connective tissue is blamed to cause this adverse effect. It is shown that platelets are the first cellular elements that initiate the homeostatic and inflammatory responses and release of several proinflammatory and fibrinogenic mediators. Antiplatelet agents such as ticlopidine and clopidogrel were shown to prevent CRE and this effect is believed to be directed by their activities against thrombocytes. However, recent studies have shown that these drugs also induce apoptosis in endothelial cells and may lead to decreased expression of endothelial prostacyclin and thrombomodulin (TM) and increased release of von Willebrand factor which are shown to be major contributors of coagulation process. Assuming that radiation induced apoptosis occur 6-10h after irradiation, we think that timing of these antiaggregant drugs with irradiation is important and a 6-10h interval between these may be beneficial to avoid this adverse interaction.

1,25-Dihydroxy vitamin D3: can it be an effective therapeutic option for aggressive fibromatosis.

Aggressive fibromatosis (AF), also known as desmoid tumor is a monoclonal fibroblastic proliferation in a collagen matrix that arises in musculoaponeurotic structures. Though considered as benign, they are locally invasive and their propensity for recurrence after conservative surgery is well documented. Addition of postoperative adjuvant radiotherapy produces higher local control rates, although recurrence rates are still high in patients with positive margins. The antineoplastic activity of vitamin D has been demonstrated both in vitro and in vivo models of several cancers. The proposed mechanisms for antineoplastic activity include inhibition of proliferation associated with cell cycle arrest, induction of apoptosis and reduction in invasiveness and angiogenesis. It has also been shown that vitamin D has a negative impact on collagen homeostasis by inhibiting the formation and increasing its degradation. Since vitamin D has an antineoplastic activity and negative effect on collagen synthesis and deposition, it is proposed that 1,25-dihydroxy vitamin D3 can be a right therapeutic option for the management of desmoid tumors.

Effects of azithromycin on cyclosporine-induced gingival hyperplasia in renal transplant patients.

BACKGROUND: Gingival hyperplasia is a well-known complication of cyclosporine therapy, affecting 21% to 35% of renal transplant patients. Metronidazole, clarithromycin, and azithromycin, all azalid antimicrobial agents derived from the macrolide antibiotic erythromycin, have been used for treatment. Marked improvements in gingival hyperplasia have been recorded in particular with azithromycin. The aim of the present study was to investigate histopathological features of cyclosporine-induced gingival hyperplasia and to evaluate the quantitative efficacy of short-term azithromycin therapy. METHODS: Eighteen renal transplant patients with cyclosporine-induced gingival hyperplasia were included in the study. All patients received azithromycin with a dose of 500 mg/d for 3 consecutive days. Changes in gingival hyperplasia were evaluated by measuring the gingival sulcus depth to the cementum-enamel junction of every tooth in each of the four quadrants on days 0, 7, 30, 90, 180. Gum biopsies were obtained on days 0 and 30; the degree of inflammation was classified as "mild," "intermediate," and "severe". RESULTS: Gingival hyperplasia was reduced in all treated patients throughout the study. The degree of improvement was more significant between 0 to 7 and 7 to 30 days than at other times (respectively, P < .0001 and P < .002). Histopathologically, eight patients had severe and one patient moderate chronic inflammation at the beginning of therapy. Three other biopsies were reported as papilloma, mucosal hyperplasia, and normal gingival tissue biopsy. CONCLUSIONS: Azithromycin appears to be useful to treat cyclosporine-induced gingival hyperplasia in renal transplant patients. Treatment is inexpensive and free from known adverse effects.

Nocardia brain abscess mimicking brain tumour in immunocompetent patients: report of two cases and review of the literature.

Nocardia brain abscess is a rare intracranial lesion and has been reported in immunocompromised patients. An optimal treatment approach has not been established. However, early diagnosis and appropriate antimicrobial therapy are very important factors for a good outcome. We report two unusual cases of Nocardia brain abscess simulating brain tumour in immunocompetent patients. One of the cases was presumed to be a primary brain tumour and the other a metastatic brain tumour. They underwent surgical gross total resection. After Nocardia asteroides was seen on Gram's stain and subsequently identified by culture, appropriate antibiotic therapy was initiated.

The importance of serial measurements of cytokine levels for the evaluation of their role in pathogenesis in familial Mediterraean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent fever of unknown origin, renal amyloidosis, peritonitis, pleuritis and/or synovitis. There have been many studies to elucidate the etiopathogenesis of FMF. IL-6 is a cytokine that can induce the formation of serum amyloid A and C-reactive protein, both of which are important in development of amyloidosis. IL-6 was determined to be strongly associated in the etiopathogenesis of periodic fever in Chinese-pei dogs. The dogs with this syndrome experience periodic fever, arthritis, renal amyloidosis, a clinical picture very alike of human FMF. Here, we aimed to study mainly whether IL-6 had a similar etiopathogenetic role in human FMF as in Chinese-pei dogs syndrome. The median IL-6 blood levels were found to be higher in patients with acute (n=8) FMF attack (1.85 U/ml) compared to those (n=33) with asymptomatic ones (1.0 U/ml) (p=0.16). There are mainly two results: first; the study should be designed with a larger sample size of patients with acute attack in order to alleviate underestimation of significance, second; sampling time may give various results because of dynamic changes of cytokine levels during acute attack period.

Polymicrobial ventriculitis and evaluation of an outbreak in a surgical intensive care unit due to inadequate sterilization.

At the end of 1999, a case of polymicrobial ventriculitis in the Department of Neurosurgery followed by an outbreak of Serratia marcescens mediastinitis in the intensive care unit of cardiovascular surgery occurred. These nosocomial surgical infections were considered to be the result of contamination of surgical sites with inadequately sterilized instruments or theatre linen. An epidemiological survey was focused on the central sterilization unit of the hospital. The microbiological results of this survey proved that the cause of the outbreak was the use of inadequately decontaminated theatre linen. This study indicates that strict infection control measures including the control of sterilization procedures and a well-organized infection control team are necessary to prevent nosocomial surgical infections.

Radiation nephropathy in rats and its modification by the angiotensin converting enzyme inhibitor enalapril.

PURPOSE: The ability of prophylactic enalapril treatment to prevent or retard the development of radiation-induced nephropathy was studied in male Wistar rats. METHODS: Prior to irradiation, the rats were randomized to groups receiving enalapril or no treatment, and both kidneys of rats were irradiated with either a 10 Gy single dose or 26 Gy at a rate of 2 Gy per fraction per day. Renal function was assessed prior to radiotherapy and at intervals of 8 weeks thereafter. A subgroup of animals was sacrificed for histopathology at 4, 8, 16, and 24 weeks after irradiation. RESULTS: At 16 weeks after irradiation, renal function showed deterioration without any significant differences between groups. At 24 weeks after irradiation, all irradiation dose groups with or without enalapril treatment showed some improvement in functional terms. Morphological evaluation revealed that enalapril had a marked beneficial effect on renal radiation injury in the 10 Gy single-dose group and at 8 weeks after irradiation. At 16 weeks after irradiation the histological appearance of the dose groups with or without enalapril treatment was similar. CONCLUSION: We conclude that enalapril, when used preventively from the time of irradiation, has a beneficial effect only after high doses per fraction and at the early phases of renal radiation injury.

The clinical value of the ratio of free prostate specific antigen to total prostate specific antigen.

OBJECTIVE: To examine the usefulness of the ratio of free prostate specific antigen (FPSA) to total prostate specific antigen (TPSA) in men with serum TPSA concentration of 4 to 10 ng/mL by using the cut off value of 0.15 for avoiding unnecessary biopsies. PATIENTS AND METHODS: Two hundred thirty-six men aged between 52 and 91 with symptoms of prostatism were evaluated with digital rectal examination (DRE), FPSA and TPSA measurements. Patients with TPSA values under 4 ng/mL were biopsied if they had positive DRE and/or a FPSA/TPSA ratio lower than 0.15. All patients with TPSA values higher than 4 ng/mL were also biopsied. The predictive value and sensitivity of FPSA/TPSA ratio and TPSA alone were calculated. RESULTS: Eleven patients out of 170 with a TPSA value lower than 4 ng/mL were biopsied. Fifty-five patients had a value between 4.1 and 10 ng/mL. We performed transrectal ultrasound (TRUS) and prostate biopsy in these men except one patient. Biopsy proven prostate cancer was detected only in 12 patients. In this group of patients the predictive value of TPSA was 21%, but the predictive value of FPSA/TPSA ratio of 0.15 was 78% maintaining at least 90% sensitivity. Eleven of the patients had a prostate specific antigen (PSA) value higher than 10 ng/mL. In 6 of these patients the biopsy result was prostate cancer and 10 of these patients had a FPSA/TPSA ratio lower than 0.15. CONCLUSION: In patients with TPSA values between 4-10 ng/mL the cut off value of FPSA/TPSA ratio of 0.15 can be used to eliminate unnecessary biopsies with minimal loss of cancer patients.

Establishment and characterization of a human glioblastoma multiforme cell line.

Cell lines provide a useful system for further understanding the biology of glioblastoma multiforme. In this study, a new glioblastoma multiforme cell line, GATAGM-96 (Gulhane Askeri Tip Akademisi-Gliblastoma Multiforme-96), was established from a tumor specimen removed from an 80-year-old male patient who underwent surgery for intracranial tumor. Morphologic examination, immunocytochemical staining, growth kinetics, and karyotypic characteristics of this cell line were studied. The cytoskeleton was positive for neuron-specific enolase, vimentin, and neurofilament, and it was negative for glial fibrillary acidic protein, S-100 protein, p53 protein, epidermal growth factor, and transforming growth factor alpha. Growth kinetic studies demonstrated an approximate population doubling time of 38 to 42 h and a colony forming efficiency of 83.3%. The karyotype of the cells demonstrated it as hyperdiploid, with a large subpopulation of polyploid cells. There were numerous structural and numerical chromosome aberrations; most of them were present as clonal events. The phenotypic and chromosomal features detailed on the GATAGM-96 cell line should make it a useful addition to the cell lines currently available for in vitro and in vivo studies of glioblastoma multiforme.