Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy

PurposeExcision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.Materials and methodsThirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival.ResultsPathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012–0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2–11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤60 years) (HR 3.4, 95% CI 1.2–9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014–0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9–19.9, P = 0.002) were significantly associated with OS.ConclusionsOur results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.     

Beneficial Effect of Etanercept on Hyperoxic Lung Injury Model in Neonatal Rats

Purpose: To determine whether prophylaxis with etanercept, an anti-inflammatory drug, would decrease the severity of lung injury in a neonatal rat model of bronchopulmonary dysplasia (BPD); Materials and Methods: Rat pups were divided into three groups: pups exposed to room air (group 1; n = 10), to hyperoxia + placebo (group 2; n = 9), and to hyperoxia + etanercept (group 3; n = 8). Lung morphology was assessed by alveolar surface area percentage, which is a measure of alveolar size. The severities of lung inflammation and antioxidant capacity were assessed by quantifying tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), malondialdehyde (MDA), and superoxide dismutase (SOD) from lung homogenate; Results: The percentage of alveolar surface areas were significantly higher in group 3 compared to group 2 (p = .004) and similar in both group 1 and group 3 (p = .21). The mean level of lung MDA was significantly higher in group 2 compared to group 1 and group 3 (p < .05 for both). Lung homogenate SOD activities in group 3 was significantly higher than group 2 (p < .001). Furthermore, group 3 pups had lower levels of TNF-α and TGF-β in lung homogenate than that in group 2 (p < .05 for both) but similar in both group 1 and group 3; Conclusion: Etanercept has favorable effects on alveolarization as well as inflammation and oxidative stress markers in a neonatal rat model of BPD.     

Polymorphisms in the tumor necrosis factor-alpha gene in Turkish women with pre-eclampsia and eclampsia

The genetic background predisposing pregnant women to pre-eclampsia/eclampsia (PE/E) is still unknown. The aim of the current study was to investigate whether there is an association between the TNF-alpha-308 and 850 polymorphisms and PE or eclampsia. In this study, 40 cases of eclampsia, 113 cases of PE and 80 normotensive control cases were genotyped for the TNF-alpha-G-308A and C-850 polymorphisms. At position 308, the replacement of Guanine with Adenosine was denoted as TNF2. We found a significant difference between the TNF2 allele frequencies of the eclamptic, pre-eclamptic and normotensive controls. TNF2 (AA) polymorphism frequency was significantly higher among the eclamptics and pre-eclamptics (control : 5%, PE : 13.3%, E : 12.9%). A significantly different genotype distribution of C-850T polymorphism was observed between the PE/E and control groups, with the frequency of the variant TT genotype being significantly reduced in the preeclamptics (PE : 17% ; E : 17.5%) when compared with the control group (24.3%). We have demonstrated an association between TNF-alpha polymorphisms and pre-eclampsia susceptibility. However, it is not known whether C-850T polymorphism has a functional effect on the TNF-alpha gene. In addition, it was not possible to determine whether this polymorphism promotes the progression from PE to eclampsia because of no statistically significant difference between eclampsia and the controls.     

Neonatal Infection with Neisseria meningitidis: Analysis of a 97-Year Period Plus Case Study

Neisseria meningitidis is one of the major causes of meningitis in children and adolescents, but it is rarely found during the neonatal period. Here, we describe a neonate with meningococcal sepsis who was admitted to the hospital on postnatal day 10, and we discuss the clinical features of neonatal infection with N. meningitidis in relation to the literature (analysis of a 97-year period).     

Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson’s disease

Journal of Neurology - Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson’s disease (PD), but a limitation is the formation of troublesome s.c. nodules....     

Isola spinal instrumentation system for idiopathic scoliosis

Since the definition of three-dimensional components of the scoliotic deformity, there have been important improvements in the surgical treatment of the problem. A derotation maneuver was proposed as a treatment option with CD instrumentation, but the reports of imbalance and decompensation with this system repopularized sublaminar wiring and translation as a corrective maneuver. Isola spinal instrumentation is one of the modern systems that utilizes vertebral translation instead of rod rotation. This study analyzes the results of 24 patients with idiopathic scoliosis who had been followed up for at least 2 years, and were surgically treated with titanium Isola Spinal Instrumentation in the Department of Orthopaedics and Traumatology, Ankara Social Security Hospital. Patients were grouped according to the King-Moe classification. Patients with type III, IV or V curves received only posterior instrumentation while this procedure followed anterior release and discectomy in the same session in patients with type I or II curves. A translation maneuver was utilized in the correction of scoliotic curves using the cantilever technique, either alone or supplemented by sublaminar wiring with Songer multifilament titanium cables. This study aimed to elucidate the effects of this technique in the frontal and sagittal plane curves and the trunk balance. The balance was analyzed clinically and radiologically by measurement of the lateral trunk shift (LT), shift of stable vertebra (SS), and shift of head (SH) in vertebral units (VU). The postoperative correction was significant in the frontal plane for all types of curves (p < 0.05). The postoperative correction was 80.9% +/- 9.5% in type III curves. Overall, the mean Cobb angle of the major curve value in the frontal plane was 66.9 degrees +/- 18.8 degrees, and it was corrected by 62.8% +/- 20.1%. The correction loss of Cobb angles in the frontal plane was 5.4 degrees +/- 5.5 degrees at the last follow-up visit. A normal physiologic thoracic contour (30 degrees - 50 degrees) was achieved in 83.3% of the patients and normal lumbar contour (40 degrees - 60 degrees) in 66.7% of the patients in the sagittal plane. The correction was found to be significant in all balance values (p < 0.05). The postoperative correction in LT values correlated with the correction of the Cobb angle values in the frontal plane. All patients had complete balance (SH: 0 VU and SS: 0 VU) or balanced curves (0 VU < SH, SS < 0.5 VU).Finally, the study concluded that the translation maneuver, especially when used with the cantilever technique, resulted in high correction rates in the frontal plane. Additionally, the technique was also successful in obtaining normal sagittal contours and correcting balance values.     

Effects of neonatal monosodium glutamate and aging on morphine dependence development.

Administration of monosodium glutamate (MSG) to neonatal rats has been reported to destroy aspartatergic (ASPergic) and glutamatergic (GLUergic) neurons. Ageing has been shown to induce cell loss, a rather general CNS atrophy, and slowness in the CNS functions. On the other hand, it has been hypothesized that two of the main reasons for opiate dependence development are the blockade by opiates of the NMDA receptors and their associated upregulation and supersensitivity. Accordingly, the abstinence syndrome precipitating effect of naloxone (NL) has been assumed to be the consequences of the removal by NL of opiate from NMDA receptors without being able to prevent upregulated and supersensitive NMDA receptors from being stimulated stronger than normal. To investigate the role of the decrease in the number of NMDA receptors in the development of morphine (M) physical dependence, 4 g/kg MSG was SC injected into neonatal rats on days 2, 4, 6, 8 and 10 after birth. Their littermate controls SC received equimolar NaCl solution. Three or 14 months later, three pellets containing 75 mg base M were SC implanted into male rats treated neonatally with MSG or equimolar NaCl solution. Seventy-two hours after pellet implantation, all rats were injected with 2 mg/kg NL intraperitoneally. Some abstinence syndrome signs were counted or rated for 15 min immediately after NL injection and then statistically evaluated. The NL-precipitated abstinence syndrome was less intense in 3-month-old MSG-treated rats than in controls, most probably due to the decrease in the number of NMDA receptors in MSG-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)