Gamma-radiation sensitivity and risk of glioma

BACKGROUND: About 9% of human cancers are brain tumors, of which 90% are gliomas. gamma-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to gamma-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the gamma-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma. METHODS: We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We gamma-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided. RESULTS: We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P<.001). Using 0.40 (the median number of chromatid breaks per cell in control subjects) as the cut point for defining mutagen sensitivity and adjusting for age, sex, and smoking status, we found that mutagen sensitivity was statistically significantly associated with an increased risk for glioma (odds ratio = 2.09; 95% CI = 1.43 to 3.06). When the data were divided into tertiles, the relative risk for glioma increased from the lowest tertile to the highest tertile (trend test, P<.001). CONCLUSION: gamma-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.     

Mitral valve surgery in patients with ischemic and nonischemic dilated cardiomyopathy

Congestive heart failure (CHF) is a chronic, progressive disease and its central element is the remodeling of the cardiac chamber associated with ventricular dilatation. Secondary mitral regurgitation is a complication of end-stage cardiomyopathy and is associated with a poor prognosis. It is due to progressive mitral annular dilatation and alteration in the geometry of the left ventricle. A vicious cycle of continuing volume overload, ventricular dilatation, progression of annular dilatation, increased left ventricular wall tension and worsening mitral regurgitation and CHF occurs. The mainstays of medical therapy are diuretics and afterload reduction, which are associated with poor long-term survival in these patients. Historically, the surgical approach to patients with mitral regurgitation was mitral valve replacement, but these patients were not considered operative candidates because of their high morbidity and mortality. Heart transplantation is now considered standard treatment for select patients with end-stage heart disease; however, it is applicable only to a small number of patients. Mitral valve replacement in these patients is associated with adverse consequences on left ventricular systolic function resulting from interruption of the annulus-papillary muscle continuity. Preserving the mitral valve apparatus and left ventricle in mitral valve repair enhances and maintains left ventricular function and geometry with an associated decrease in wall stress. Using these operative techniques to alter the shape of the left ventricle, in combination with optimal medical management for heart failure, improves survival and may avoid or postpone transplantation.     

Fate of Ventricular and Valve Performance Following Early Bidirectional Glenn Procedure After Norwood Operation Controlled for Hypoplastic Left Heart Syndome Anatomic Subtype

The Norwood operation (NO) with a right ventricle (RV)-to-pulmonary artery (PA) shunt (NRVPA) is reportedly associated with early hemodynamic advantage. Shunt strategy has been implicated in ventricular function. Outcomes after NRVPA compared with classic procedure as part of a strategy involving early bidirectional Glenn (BDG) procedure were analyzed with reference to RV, tricuspid, and neoaortic valve performance. Between January 2005 and December 2010, 128 neonates with hypoplastic left heart syndrome (HLHS) underwent NO. Controlled for aortic/mitral stenosis (AS–MS) subtype, 28 patients underwent NRVPA (group A), and 26 patients had classic procedure (group B). The patients with a non-HLHS single-ventricle anatomy and those who had undergone a hybrid approach for HLHS were excluded from the study. The mean age at NO was 6.8 ± 3.5 days in group A and 6.9 ± 3.6 days in group B. Transthoracic echocardiographic evaluation (TTE) after NO (TTE-1) at the midinterval between NO and BDG (TTE-2), before BDG (TTE-3), before Fontan (TTE-4), and at the last follow-up evaluation (TTE-5) was undertaken. Cardiac catheterization was used to assess hemodynamic parameters before the Glenn and Fontan procedures. The operative, interstage, and pre-Fontan survival rates for AS–MS after NO were respectively 88.1 % (90.3 % in group A vs. 84.7 % in group B; p = 0.08), 82.5 % (82.7 % in group A vs. 81.8 % in group B; p = 0.9), and 80.7 % (79.5 % in group A vs. 81.8 % in group B; p = 0.9). The median follow-up period was 39.6 months (interquartile range 2.7–4.9 months). The RV global function, mid- and longitudinal indexed dimensions, fractionated area change before BDG (TTE-1, TTE-2, TTE-3) and after BDG (TTE-4, TTE-5), and right ventricular end-diastolic pressure did not differ statistically between the groups (p > 0.05). No statistically significant difference in tricuspid or neoaortic intervention was found between the groups (p > 0.05). Controlled for the AS–MS HLHS subtype, shunt strategy showed no midterm survival or hemodynamic (ventricular or valve) impact. At midterm, the follow-up need for neoaortic or tricuspid valve surgical intervention was not affected by shunt selection. The structural ventricular adaptation after reversal of shunt physiology was irrespective of shunt strategy.     

Hepatoprotective effect of a curcumin/absinthium compound in experimental severe liver injury

OBJECTIVE: A preliminary in vitro study with hepatocyte culture showed that concentrations as low as 10 µg/mL of PN‐M001 are able to significantly mitigate CCl4 hepatocyte damage (P < 0.05) comparable to 100 µg/mL silymarin, and 100 µg/mL proved to be more protective than either silymarin 100 µg/mL or glycyrrhizin 10 µg/mL (P < 0.05). METHODS: Wistar rats were allocated into three groups: (A) 0.1 mL/100 g body weight (BW) mixture of CCl₄ in olive oil (1 : 1 v/v) subcutaneous injection twice daily for 4 weeks; (B) as A, plus oral administration of 50 mg/kg of K‐17.22 dissolved in 5% glucose; (C) as B but with PN‐M001 given 1 week after the first injection of CCl₄. Rats were killed at the end of the study and blood and liver samples were obtained. RESULTS: When compared with a control, group A showed a significant decrease of glutathione (GSH;>45%, P < 0.001) and oxidized GSH (GSSG; P < 0.01) liver content, a lower liver wet weight (P < 0.01) together with an increase of both transaminases (>15‐fold, P < 0.001) whereas groups B and C both showed only a mild increase in transaminases (<4‐fold, P < 0.05). Group A showed a significant decrease of Y‐protein fraction and of GST activity, as tested by both substrates (P < 0.01 vs control). However, both these parameters were reverted to normal by PN‐M001 (P < 0.05 vs A). CONCLUSIONS: These preliminary data suggest that PN‐M001 exerts a highly protective and prolonged effect (either preventive or therapeutic) on GSH depletion in CCl₄‐induced liver injury, which suggests its potential use in the clinical setting.     

Tetralogy of Fallot With Atrioventricular Septal Defect: Surgical Strategies for Repair and Midterm Outcome of Pulmonary Valve-Sparing Approach

Repair for tetralogy of Fallot (TOF) with complete atrioventricular septal defect (CAVSD) has been reported with good early and intermediate outcomes. Morbidity, however, remains significantly high. To date, repair of CAVSD/TOF using a pulmonary valve-sparing technique (PVS) and freedom from valve reoperation are not well defined. A study was undertaken to investigate outcomes. This study was conducted in as a retrospective investigation. Between January 1988 and December 2008, 13 consecutive patients with CAVSD/TOF were identified, and their records were reviewed retrospectively. Of these 13 patients, 9 had Rastelli type C CAVSD. Trisomy 21 was present in 9 cases (69 %; 7 with type C). Five patients had received a systemic-to-pulmonary shunt (SPS) before complete repair at a mean age 1.7 ± 0.6 months. All the patients survived until complete repair. At complete CAVSD/TOF repair, AVSD was corrected with a two-patch technique in all patients. For eight patients (61.5 %), PVS was used. The remaining five patients had transannular patch (TAP) repair. The mean age at complete repair was 6.3 ± 2.4 months. At complete repair, the mean cardiopulmonary bypass time was 173.5 ± 30.6 min, and the cross-clamp time was 134.7 ± 28.8 min. There was one hospitalization and no late deaths. The median follow-up period was 9.2 years [interquartile range (IQR), 4.7–13.3 years]. The actuarial survival was 90.0 ± 9.5 % at 1 year, 90 ± 9.5 % at 5 years, and 90 ± 9.5 % at 8 years. Of the 12 survivors, 6 had some reintervention during the follow-up period. Within the first 11 years after complete repair, two patients underwent left atrioventricular (AV) valve repair, and one patient had right AV valve repair. Two patients had residual VSD closure. Four patients underwent the first right ventricular outflow tract (RVOT) reintervention for critical insufficiency or stenosis at a mean interval of 6 ± 21) months. One patient had a second RVOT reoperation. Findings showed that CAVSD/TOF with PVS was related to significantly higher freedom from RVOT reintervention (100 % at 1, 5, and 8 years compared with 80 ± 17.9 % at 1 year, 60 ± 21.9 % at 5 years, and 40 ± 21.9 % at 8 years for CAVSD/TOF using TAP; P < 0.05). No patient who underwent PVS had left ventricular outflow tract obstruction requiring reoperation. Overall freedom from any reintervention was 90.9 ± 8.6 % at 1 year, 71.6 ± 14.0 % at 5 years, and 53.7 ± 8.7 % at 8 years in this group of patients. Correction of TOF with CAVSD can be performed at low risk with favorable intermediate-term survival and satisfactory freedom from reoperation. Use of TAP can be avoided in almost two thirds of patients and may influence freedom from early RVOT reintervention.     

Hodgkin disease risk: role of genetic polymorphisms and gene-gene interactions in inflammation pathway genes

Inflammation is a critical component of cancer development. The clinical and pathological features of Hodgkin disease (HD) reflect an abnormal immunity that results from cytokines secreted by Reed-Sternberg cells and the surrounding tumor. Numerous studies have reported the association between genetic polymorphisms in cytokine genes and the susceptibility to different hematologic cancers. However, the effects of such SNPs on modulating HD risk have not yet been investigated. We hypothesized that gene-gene interactions between candidate genes in the anti- and pro-inflammatory pathways carrying suspicious polymorphisms may contribute to susceptibility to HD. To test this hypothesis, we conducted a study on 200 HD cases and 220 controls to assess associations between HD risk and 38 functional SNPs in inflammatory genes. We evaluated potential gene-gene interactions using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction, and classification and regression tree (CART) approaches. We observed that, in combination, allelic variants in the COX2, IL18, ILR4, and IL10 genes modify the risk for developing HD. Moreover, the cumulative genetic risk score (CGRS) revealed a significant trend where the risk for developing HD increases as the number of adverse alleles in the cytokine genes increase. These findings support the notion that epigenetic-interactions between these cytokines may influence pathogenesis of HD modulating the proliferation of regulatory T cells. In this way, the innate and adaptative immune responses may be altered and defy their usual functions in the host anti-tumor response. Our study is the first to report the association between polymorphisms in inflammation genes and HD susceptibility risk.     

Controlled comparison of percutaneous and microsurgical sperm retrieval in men with obstructive azoospermia

A controlled comparison of the efficacy and reliability of sperm retrieval by testicular fine needle aspiration (TFNA), percutaneous testicular needle biopsy (PercBiopsy) and microsurgical epididymal sperm aspiration (MESA) was performed in nine patients with obstructive azoospermia. During a planned MESA procedure, sperm retrieval was attempted on the same testis with TFNA and PercBiopsy. Spermatozoa were obtained from all patients using MESA and PercBiopsy. Spermatozoa were retrieved using TFNA from 6/9 (67%) men. The mean number of epididymal spermatozoa retrieved with MESA (15 x 106) was significantly higher (P = 0.003) than that retrieved percutaneously from the testis. The mean number of spermatozoa obtained by PercBiopsy was 0.116 x 10(6) while TFNA recovered 0.014 x 106 spermatozoa (P = 0.025). MESA is the optimal choice to retrieve the greatest number of spermatozoa with highest motility for assisted reproduction and subsequent cryopreservation. However, percutaneous testicular retrieval does not require microsurgical expertise and is less invasive. Our results suggest that the optimal percutaneous procedure for sperm retrieval from the testis involves percutaneous testicular needle biopsy with an automatic biopsy gun.