Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma

ABSTRACT: We report two cases of gastrointestinal perforation (GIP) after radiotherapy in patients receiving tyrosine kinase inhibitor (TKI) for advanced renal cell carcinoma (RCC). Case 1 was a 61-year-old woman with lung metastases after a radical nephrectomy for a right RCC (cT3aN0M0) treated with interferon-alpha (OIF, 5 MIU, three times per week). She developed lytic metastases of the left femur and the left acetabulum. She was treated with palliative radiotherapy to the metastatic portion (3 Gy [MULTIPLICATION SIGN] 10 fractions), and 400 mg sorafenib twice per day plus continuing interferon alpha. She experienced sudden left lower abdominal pain after four weeks of treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. Case 2 was a 48-year-old man with lung, lymph node, and bone metastases after a radical nephrectomy for a right RCC (cT2N0M0), and was treated with 400 mg sorafenib twice per day. He developed lytic bone metastases of the lumbar vertebrae, which was treated with palliative radiotherapy to L2-4 (3 Gy [MULTIPLICATION SIGN] 10 fractions). He experienced sudden abdominal pain after two months of radiation treatment, and was diagnosed with a perforation of the sigmoid colon with fecal peritonitis. These cases underwent radiotherapy, and therefore this may be related to the radiosensitivity of TKI.     

Performance of ¿VIKIA Malaria Ag Pf/Pan¿ (IMACCESS®), a new malaria rapid diagnostic test for detection of symptomatic malaria infections

ABSTRACT: BACKGROUND: Recently, IMACCESS[REGISTERED SIGN] developed a new malaria test (VIKIA Malaria Ag Pf/Pan[TRADE MARK SIGN]), based on the detection of falciparum malaria (HRP-2) and non-falciparum malaria (aldolase). METHODS: The performance of this new malaria rapid diagnostic test (RDT) was assessed using 1,000 febrile patients seeking malaria treatment in four health centres in Cambodia from August to December 2011. The results of the VIKIA Malaria Ag Pf/Pan were compared with those obtained by microscopy, the CareStart Malaria[TRADE MARK SIGN] RDT (AccessBio[REGISTERED SIGN]) which is currently used in Cambodia, and real-time PCR (as "gold standard"). RESULTS: The best performances of the VIKIA Malaria Ag Pf/Pan[TRADE MARK SIGN] test for detection of both Plasmodium falciparum and non-P. falciparum were with 20--30 min reading times (sensitivity of 93.4% for P. falciparum and 82.8% for non-P. falciparum and specificity of 98.6% for P. falciparum and 98.9% for non-P. falciparum) and were similar to those for the CareStart Malaria[TRADE MARK SIGN] test. CONCLUSIONS: This new RDT performs similarly well as other commercially available tests (especially the CareStart Malaria[TRADE MARK SIGN] test, used as comparator), and conforms to the World Health Organization's recommendations for RDT performance. It is a good alternative tool for the diagnosis of malaria in endemic areas.     

Adipocytokine levels mark endothelial function in normotensive individuals

ABSTRACT: BACKGROUND: Endothelial dysfunction is an independent risk factor for cardiovascular events. Inflammatory mediators released by the adipose tissue can lead to local insulin resistance and endothelial dysfunction. This study addressed the relationship of adipocytokines with endothelial function and blood pressure. METHODS: In 92 newly diagnosed, drug-naive essential hypertensive patients (HT, mean age 49 yrs) without organ damage and 66 normotensive subjects (NT, mean age 47 yrs), by an automated system, we measured endothelium-dependent and -independent vasodilation as brachial artery flow-mediated dilation before and after administration of glyceryl-trinitrate. Retinol binding protein-4 (RBP4) and resistin levels were determined by ELISA and RIA, respectively. Oxidative stress was evaluated by measuring serum malondyaldehyde (MDA). RESULTS: Flow-mediated dilation was significantly (p = 0.03) lower in HT (5.3 [PLUS-MINUS SIGN] 2.6%) than NT (6.1 [PLUS-MINUS SIGN] 3.1%), while response to glyceryl-trinitrate (7.5 [PLUS-MINUS SIGN] 3.7% vs 7.9 [PLUS-MINUS SIGN] 3.4%) was similar. RBP4 (60.6 [PLUS-MINUS SIGN] 25.1 vs 61.3 [PLUS-MINUS SIGN] 25.9 mug/ml), resistin (18.8 [PLUS-MINUS SIGN] 5.3 vs 19.9 [PLUS-MINUS SIGN] 6.1 ng/ml) and MDA levels (2.39 [PLUS-MINUS SIGN] 1.26 vs 2.08 [PLUS-MINUS SIGN] 1.17 nmol/ml) were not different in HT and NT.RBP4 (r = [MINUS SIGN]0.25; p = 0.04) and resistin levels (r = [MINUS SIGN]0.29; p = 0.03) were related to flow-mediated dilation in NT, but not in HT (r = [MINUS SIGN]0.03 and r = [MINUS SIGN]0.10, respectively). In NT multivariate analysis, including RBP4 and confounders showed that only BMI or waist circumference remained related to flow- mediated dilation. In the multivariate model including resistin and confounders, BMI, age and resistin were significantly related to flow-mediated dilation, while only age significant correlated with this parameter when BMI was replaced by waist circumference. CONCLUSIONS: Adipocytokine levels may be independent predictors of endothelial dysfunction in the peripheral circulation of healthy subjects, providing a pathophysiological link between inflammation from adipose tissue and early vascular alterations.     

Very high gravity ethanol fermentation by flocculating yeast under redox potential-controlled conditions

ABSTRACT: BACKGROUND: Very high gravity (VHG) fermentation using medium in excess of 250 g/L sugars for more than 15 % (v) ethanol can save energy consumption, not only for ethanol distillation, but also for distillage treatment; however, stuck fermentation with prolonged fermentation time and more sugars unfermented is the biggest challenge. Controlling redox potential (ORP) during VHG fermentation benefits biomass accumulation and improvement of yeast cell viability that is affected by osmotic pressure and ethanol inhibition, enhancing ethanol productivity and yield, the most important techno-economic aspect of fuel ethanol production. RESULTS: Batch fermentation was performed under different ORP conditions using the flocculating yeast and media containing glucose of 201 [PLUS-MINUS SIGN] 3.1, 252 [PLUS-MINUS SIGN] 2.9 and 298 [PLUS-MINUS SIGN] 3.8 g/L. Compared with ethanol fermentation by non-flocculating yeast, different ORP profiles were observed with the flocculating yeast due to the morphological change associated with the flocculation of yeast cells. When ORP was controlled at [MINUS SIGN]100 mV, ethanol fermentation with the high gravity (HG) media containing glucose of 201 [PLUS-MINUS SIGN] 3.1 and 252 [PLUS-MINUS SIGN] 2.9 g/L was completed at 32 and 56 h, respectively, producing 93.0 [PLUS-MINUS SIGN] 1.3 and 120.0 [PLUS-MINUS SIGN] 1.8 g/L ethanol, correspondingly. In contrast, there were 24.0 [PLUS-MINUS SIGN] 0.4 and 17.0 [PLUS-MINUS SIGN] 0.3 g/L glucose remained unfermented without ORP control. As high as 131.0 [PLUS-MINUS SIGN] 1.8 g/L ethanol was produced at 72 h when ORP was controlled at [MINUS SIGN]150 mV for the VHG fermentation with medium containing 298 [PLUS-MINUS SIGN] 3.8 g/L glucose, since yeast cell viability was improved more significantly. CONCLUSIONS: No lag phase was observed during ethanol fermentation with the flocculating yeast, and the implementation of ORP control improved ethanol productivity and yield. When ORP was controlled at [MINUS SIGN]150 mV, more reducing power was available for yeast cells to survive, which in turn improved their viability and VHG ethanol fermentation performance. On the other hand, controlling ORP at [MINUS SIGN]100 mV stimulated yeast growth and enhanced ethanol production under the HG conditions. Moreover, the ORP profile detected during ethanol fermentation with the flocculating yeast was less fluctuated, indicating that yeast flocculation could attenuate the ORP fluctuation observed during ethanol fermentation with non-flocculating yeast.     

Vocal fold composition and early glottic carcinoma infiltration

ABSTRACT: BACKGROUND: Current imaging techniques provide only limited information pertaining to the extent of infiltration of laryngeal carcinomas into vocal fold tissue layers. Therefore, it is needed to seek the contribute to the body of knowledge surrounding examination and characterization in laryngeal carcinoma infiltration. METHODS: Excised larynges were collected from 30 male laryngectomy patients with an average age of 43.5 years (ranging 36 to 55 years) and history of smoking ([GREATER-THAN OR EQUAL TO]10 years) exhibiting T1, T2, or subglottal (normal vocal fold) carcinomas. Vocal folds were preserved via freezing or immersion in paraffin. The depth of the mucosa, submucosa, and muscular layers in both normal vocal folds and tumor tissues of afflicted vocal folds was measured. RESULTS: The average depths of the mucosa, submucosa, and muscular layers in normal vocal folds were 0.15 [PLUS-MINUS SIGN] 0.06 mm, 2.30 [PLUS-MINUS SIGN] 0.59 mm, and 2.87 [PLUS-MINUS SIGN] 0.88 mm, respectively. Infiltration measurements of T1 tumors showed a depth of 1.62 [PLUS-MINUS SIGN] 0.51 mm and 1.32 [PLUS-MINUS SIGN] 0.49 mm in frozen sections and paraffin-embedded samples, respectively. Similarly, T2 tumors showed a depth of 2.87 [PLUS-MINUS SIGN] 0.68 mm and 2.58 [PLUS-MINUS SIGN] 0.67 mm in frozen sections and paraffin-embedded samples, respectively. T1 and T2 tumors occupied 24.8 [PLUS-MINUS SIGN] 10 and 48.5 [PLUS-MINUS SIGN] 15 percent of the normal vocal fold depth, respectively. CONCLUSION: This data provides a baseline for estimating infiltration of laryngeal carcinomas in vocal fold tissue layers, of particular interest to surgeons. This information may be used to assess typical depths of infiltration, thus allowing for more appropriate selection of surgical procedures based on individual patient assessment.     

Brachial Artery Flow-mediated Dilation Following Exercise with Augmented Oscillatory and Retrograde Shear Rate

ABSTRACT: BACKGROUND: Acute doses of elevated retrograde shear rate (SR) appear to be detrimental to endothelial function in resting humans. However, retrograde shear increases during moderate intensity exercise which also enhances post-exercise endothelial function. Since SR patterns differ with the modality of exercise, it is important to determine if augmented retrograde SR during exercise influences post-exercise endothelial function. This study tested the hypothesis that (1) increased doses of retrograde SR in the brachial artery during lower body supine cycle ergometer exercise would attenuate post-exercise flow-mediated dilation (FMD) in a dose-dependent manner, and (2) antioxidant vitamin C supplementation would prevent the attenuated post-exercise FMD response. METHODS: Twelve men participated in four randomized exercise sessions (90 W for 20 minutes) on separate days. During three of the sessions, one arm was subjected to increased oscillatory and retrograde SR using three different forearm cuff pressures (20, 40, 60 mmHg) (contralateral arm served as the control) and subjects ingested placebo capsules prior to exercise. A fourth session with 60 mmHg cuff pressure was performed with 1 g of vitamin C ingested prior to the session. RESULTS: Post-exercise FMD following the placebo conditions were lower in the cuffed arm versus the control arm (arm main effect: P < 0.05) and without differences between cuff pressures (20 mmHg: 5.7 [PLUS-MINUS SIGN] 2.2 %; 40 mmHg: 4.7 [PLUS-MINUS SIGN] 1.3 %; 60 mmHg: 5.4 [PLUS-MINUS SIGN] 2.4 %) (P > 0.05). Following vitamin C treatment, post-exercise FMD in the cuffed and control arm increased from baseline (P < 0.05) but were not different (control: 7.1 [PLUS-MINUS SIGN] 3.5 % vs. cuffed: 6.6 [PLUS-MINUS SIGN] 3.3 %) (P > 0.05). CONCLUSIONS: These results indicate that augmented oscillatory and retrograde SR in non-working limbs during lower body exercise attenuates post-exercise FMD without an evident dose--response in the range of cuff pressures evaluated. Vitamin C supplementation prevented the attenuation of FMD following exercise with augmented oscillatory and retrograde SR suggesting that oxidative stress contributes to the adverse effects of oscillatory and retrograde shear during exercise on FMD.     

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma

ABSTRACT: We investigated the relationship of End-to-end distance between VH and VL with different peptide linkers and the activity of single-chain antibodies by computer-aided simulation. First, we developed (G4S)n (where n = 1-9) as the linker to connect VH and VL, and estimated the 3D structure of single-chain Fv antibody (scFv) by homologous modeling. After molecular models were evaluated and optimized, the coordinate system of every protein was built and unified into one coordinate system, and End-to-end distances calculated using 3D space coordinates. After expression and purification of scFv-n with (G4S)n as n = 1, 3, 5, 7 or 9, the immunoreactivity of purified ND-1 scFv-n was determined by ELISA. A multi-factorial relationship model was employed to analyze the structural factors affecting scFv: rn=ABn[MINUS SIGN]ABO2+CDn[MINUS SIGN]CDO2+BCn[MINUS SIGN]BCst2. The relationship between immunoreactivity and r-values revealed that fusion protein structure approached the desired state when the r-value = 3. The immunoreactivity declined as the r-value increased, but when the r-value exceeded a certain threshold, it stabilized. We used a linear relationship to analyze structural factors affecting scFv immunoreactivity.     

Balancing selected medication costs with total number of daily injections: a preference analysis of GnRH-agonist and antagonist protocols by IVF patients

ABSTRACT: BACKGROUND: During in vitro fertilization (IVF), fertility patients are expected to self-administer many injections as part of this treatment. While newer medications have been developed to substantially reduce the number of these injections, such agents are typically much more expensive. Considering these differences in both cost and number of injections, this study compared patient preferences between GnRH-agonist and GnRH-antagonist based protocols in IVF. METHODS: Data were collected by voluntary, anonymous questionnaire at first consultation appointment. Patient opinion concerning total number of s.c. injections as a function of non-reimbursed patient cost associated with GnRH-agonist [A] and GnRH-antagonist [B] protocols in IVF was studied. RESULTS: Completed questionnaires (n = 71) revealed a mean +/[MINUS SIGN] SD patient age of 34 +/[MINUS SIGN] 4.1 yrs. Most (83.1 %) had no prior IVF experience; 2.8 % reported another medical condition requiring self-administration of subcutaneous medication(s). When out-of-pocket cost for [A] and [B] were identical, preference for [B] was registered by 50.7 % patients. The tendency to favor protocol [B] was weaker among patients with a health occupation. Estimated patient costs for [A] and [B] were $259.82 +/[MINUS SIGN] 11.75 and $654.55 +/[MINUS SIGN] 106.34, respectively (p < 0.005). Measured patient preference for [B] diminished as the cost difference increased. CONCLUSIONS: This investigation found consistently higher non-reimbursed direct medication costs for GnRH-antagonist IVF vs. GnRH-agonist IVF protocols. A conditional preference to minimize downregulation (using GnRH-antagonist) was noted among some, but not all, IVF patient sub-groups. Compared to IVF patients with a health occupation, the preference for GnRH-antagonist was weaker than for other patients. While reducing total number of injections by using GnRH-antagonist is a desirable goal, it appears this advantage is not perceived equally by all IVF patients and its utility is likely discounted heavily by patients when nonreimbursed medication costs reach a critical level.     

橘小实蝇成虫肠道可培养细菌群落结构分析

【目的】研究橘小实蝇(Bactrocera dorsalis) 3个种群(实验室正常喂养种群、实验室无菌糖水喂养种群和野生种群)成虫肠道可培养细菌的群落结构组成。【方法】利用16S rRNA基因的聚合酶链式反应-变性梯度凝胶电泳(PCR-DGGE)分析技术,结合菌落形态观察和生理生化特征鉴定细菌种类。【结果】从橘小实蝇3个种群成虫肠道600株可培养细菌得到53种不同细菌遗传型,分属于肠杆菌科(Enterobacteriaceae)、肠球菌科(Enterococcaceae)和芽孢杆菌科(Bacillaceae)等3个科。其中肠杆菌科是肠道可培养细菌最优势的细菌种类。同样以序列相似性大于97%的菌株归为相同的细菌种类为标准,找到了橘小实蝇3个种群可培养细菌的共有菌种,结合菌落形态观察和生理生化特征鉴定,确定共有菌种为肠杆菌属5株,克雷伯氏菌属2株,柠檬酸杆菌属1株,泛菌属1株,肠球菌属2株,以及芽孢杆菌属4株。【结论】通过研究橘小实蝇成虫肠道可培养细菌群落结构组成,可为探讨肠道菌群对寄主的生理功能和生态学意义奠定基础,最终为利用微生物防治此类害虫提供新思路。     

Pharmacokinetic analysis of topical tobramycin in equine tears by automated immunoassay

ABSTRACT: BACKGROUND: Ophthalmic antibiotic therapy in large animals is often used empirically because of the lack of pharmacokinetics studies. The purpose of the study was to determine the pharmacokinetics of topical tobramycin 0.3% ophthalmic solution in the tears of normal horses using an automated immunoassay analysis. RESULTS: The mean tobramycin concentrations in the tears at 5, 10, 15, 30 minutes and 1, 2, 4, 6 hours after administration were 759 ([PLUS-MINUS SIGN]414), 489 ([PLUS-MINUS SIGN]237), 346 ([PLUS-MINUS SIGN]227), 147 ([PLUS-MINUS SIGN]264), 27.6 ([PLUS-MINUS SIGN]28.4), 14.8 ([PLUS-MINUS SIGN]66.6), 6.7 ([PLUS-MINUS SIGN]18.6), and 23.4 ([PLUS-MINUS SIGN]73.4) mg/L. Mean tobramycin concentration was maintained above the MIC90 for commonly isolated bacteria for 68.5 min. CONCLUSION: A single dose of topical tobramycin resulted in therapeutic concentrations of tobramycin in the tears for 1 h after administration. Therapeutic levels of tobramycin remained in equine tears 6 times longer than was reported in rabbit tears.     

Using shared goal setting to improve access and equity: a mixed methods study of the Good Goals intervention in children's occupational therapy

ABSTRACT: BACKGROUND: Access and equity in children's therapy services may be improved by directing clinicians' use of resources toward specific goals that are important to patients. A practice-change intervention (titled 'Good Goals') was designed to achieve this. This study investigated uptake, adoption, and possible effects of at intervention in children's occupational therapy services. METHODS: Mixed methods case studies (n = 3 services, including 46 therapists and 558 children) were conducted. The intervention was delivered over 25 weeks through face-to-face training, team workbooks, and 'tools for change'. Data were collected before, during, and after the intervention on a range of factors using interviews, a focus group, case note analysis, routine data, document analysis, and researchers' observations. RESULTS: Factors related to uptake and adoptions were: mode of intervention delivery, competing demands on therapists' time, and leadership by service manager. Service managers and therapists reported that the intervention: helped therapists establish a shared rationale for clinical decisions; increased clarity in service provision; and improved interactions with families and schools. During the study period, therapists' behaviours changed: identifying goals, odds ratio 2.4 (95% CI 1.5 to 3.8); agreeing goals, 3.5 (2.4 to 5.1); evaluating progress, 2.0 (1.1 to 3.5). Children's LoT decreased by two months [95% CI [MINUS SIGN]8 to +4 months] across the services. Cost per therapist trained ranged from [POUND SIGN]1,003 to [POUND SIGN]1,277, depending upon service size and therapists' salary bands. CONCLUSIONS: Good Goals is a promising quality improvement intervention that can be delivered and adopted in practice and may have benefits. Further research is required to evaluate its: (i) impact on patient outcomes, effectiveness, cost-effectiveness, and (ii) transferability to other clinical contexts.     

Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy

ABSTRACT: BACKGROUND: Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to produce large batches for preclinical and clinical trials. This process is not only critical but also difficult as it involves various formulation parameters to be modulated all in the same process. METHODS: In our present study, we formulated curcumin loaded poly (lactic acid-co-glycolic acid) nanoparticles (PLGA-CURC). This improved the bioavailability of curcumin, a potent natural anticancer drug, making it suitable for cancer therapy. Post formulation, we optimized our process by Reponse Surface Methodology (RSM) using Central Composite Design (CCD) and scaled up the formulation process in four stages with final scale-up process yielding 5 g of curcumin loaded nanoparticles within the laboratory setup. The nanoparticles formed after scale-up process were characterized for particle size, drug loading and encapsulation efficiency, surface morphology, in vitro release kinetics and pharmacokinetics. Stability analysis and gamma sterilization were also carried out. RESULTS: Results revealed that that process scale-up is being mastered for elaboration to 5 g level. The mean nanoparticle size of the scaled up batch was found to be 158.5 [PLUS-MINUS SIGN] 9.8 nm and the drug loading was determined to be 10.32 [PLUS-MINUS SIGN] 1.4 %. The in vitro release study illustrated a slow sustained release corresponding to 75 % drug over a period of 10 days. The pharmacokinetic profile of PLGA-CURC in rats following i.v. administration showed two compartmental model with the area under the curve (AUC0-[INFINITY]) being 6.139 mg/L h. Gamma sterilization showed no significant change in the particle size or drug loading of the nanoparticles. Stability analysis revealed long term physiochemical stability of the PLGA-CURC formulation. CONCLUSIONS: A successful effort towards formulating, optimizing and scaling up PLGA-CURC by using Solid-Oil/Water emulsion technique was demonstrated. The process used CCD-RSM for optimization and further scaled up to produce 5 g of PLGA-CURC with almost similar physicochemical characteristics as that of the primary formulated batch.     

The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

ABSTRACT: BACKGROUND: Previous studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals. METHODS: Thirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.ResultPercentage decreases from FMD0 to FMD60 were significantly greater in the TM group ([MINUS SIGN]21.19 % [PLUS-MINUS SIGN] 17.90 %; P < 0.001) and the OG group ([MINUS SIGN]17.59 % [PLUS-MINUS SIGN] 26.64 %) than in the control group (6.46 % [PLUS-MINUS SIGN] 9.17 %; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group ([MINUS SIGN]18.91 % [PLUS-MINUS SIGN] 16.58 %) than in the control group (6.78 % [PLUS-MINUS SIGN] 11.43 %; P < 0.001) or the TM group (5.22 % [PLUS-MINUS SIGN] 37.22 %; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = [MINUS SIGN]0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = [MINUS SIGN]0.462; P < 0.05) and the AUC of IRI (r = [MINUS SIGN]0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables. CONCLUSION: Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.     

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

ABSTRACT: BackroundNeuroprotective strategies after cardiopulmonary resuscitation are currently the focus of experimental and clinical research. Levosimendan has been proposed as a promising drug candidate because of its cardioprotective properties, improved haemodynamic effects in vivo and reduced traumatic brain injury in vitro. The effects of levosimendan on brain metabolism during and after ischaemia/hypoxia are unknown. METHODS: Transient cerebral ischaemia/hypoxia was induced in 30 male Wistar rats by bilateral common carotid artery clamping for 15 min and concomitant ventilation with 6 % O2 during general anaesthesia with urethane. After 10 min of global ischaemia/hypoxia, the rats were treated with an i.v. bolus of 24 mug kg-1 levosimendan followed by a continuous infusion of 0.2 mug kg-1 min-1. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glutamate were monitored by microdialysis. In addition, the effects on global haemodynamics, cerebral perfusion and autoregulation, oedema and expression of proinflammatory genes in the neocortex were assessed. RESULTS: Levosimendan reduced blood pressure during initial reperfusion (72 [PLUS-MINUS SIGN] 14 vs. 109 [PLUS-MINUS SIGN] 2 mmHg, p = 0.03) and delayed flow maximum by 5 minutes (p = 0.002). Whereas no effects on time course of lactate, glucose, pyruvate and glutamate concentrations in the dialysate could be observed, the lactate/pyruvate ratio during initial reperfusion (144 [PLUS-MINUS SIGN] 31 vs. 77 [PLUS-MINUS SIGN] 8, p = 0.017) and the glutamate release during 90 minutes of reperfusion (75 [PLUS-MINUS SIGN] 19 vs. 24 [PLUS-MINUS SIGN] 28 mumol[MIDDLE DOT]L-1) were higher in the levosimendan group. The increased expression of IL-6, IL-1ss TNFalpha and ICAM-1, extend of cerebral edema and cerebral autoregulation was not influenced by levosimendan. CONCLUSION: Although levosimendan has neuroprotective actions in vitro and on the spinal cord in vivo and has been shown to cross the blood--brain barrier, the present results showed that levosimendan did not reduce the initial neuronal injury after transient ischaemia/hypoxia.     

蜜蜂成虫工蜂肠道可培养细菌群落结构分析

【目的】研究2种蜜蜂(健康意大利蜜蜂和健康中华蜜蜂)成虫工蜂肠道可培养细菌的群落结构组成。【方法】利用16S r RNA基因的聚合酶链式反应-变性梯度凝胶电泳(PCR-DGGE)分析技术,结合菌落形态观察和生理生化特征鉴定细菌种类。【结果】从2种蜜蜂成虫工蜂肠道200株可培养细菌得到18种不同细菌遗传型,分属于肠杆菌科(Enterobacteriaceae)、弧菌科(Vibrionaceae)和肠球菌科(Enterococcaceae)3个科。其中肠杆菌科是肠道可培养细菌最优势的细菌种类。同样以序列相似性大于97%的菌株归为相同细菌种类为标准,找到了2种蜜蜂可培养细菌的共有菌种,结合菌落形态观察和生理生化特征鉴定,确定肠道可培养细菌为肠杆菌属8株,克雷伯氏菌属1株,肠球菌属2株,以及气单胞菌属1株。【结论】通过研究健康意大利蜜蜂和中华蜜蜂成虫工蜂肠道可培养细菌群落结构组成,可为开展蜜蜂的微生态研究提供基础性资料。     

Frequency of poor quality of life and predictors of health related quality of life in cirrhosis at a tertiary care hospital Pakistan

ABSTRACT: BACKGROUND: Cirrhosis produces variety of symptoms which eventually lead to a negative impact on Health Related Quality of Life (HRQOL). The general aim of this study was to evaluate the magnitude of poor HRQOL and to assess factors related with HRQOL in patients with CLD in Pakistan. FINDINGS: This was a cross sectional study conducted in gastroenterology outpatient clinics of Aga Khan University Hospital, Karachi on adult patients with cirrhosis. In this study chronic liver disease questionnaire (CLDQ) was used to assess HRQOL of these patients and CLDQ score was used as an outcome measure to determine factors related with HRQOL. 273 participants were recruited in the study; 155 (57%) were males. Mean age of participants was 49 [PLUS-MINUS SIGN] 11 years. The most common cause for cirrhosis was viral infection 247(91.5%). Mean Model for End Stage Liver Disease (MELD) score was 12.6 [PLUS-MINUS SIGN] 6.8 and 2/3 of patients 209 (76.6%) had advanced cirrhosis in Child Turcot Pugh (CTP) B or C stage. Poor HRQOL was seen in 187(69%; 95% C.I.: 63%, 74%) of the participants. Mean CLDQ score was 4.36 [PLUS-MINUS SIGN]1.1. Amongst all of the domains, fatigue domain had lower CLDQ score. Hemoglobin (beta = 0.09 [SE = 0.04]), Albumin (beta = 0.32[SE = 0.09]), Diastolic Blood Pressure (DBP) (beta = 0.01[0.005) prior history of decompensation (beta = 0.98[SE = 0.39] were significant factors associated with HRQOL in patients with liver cirrhosis. CONCLUSION: Frequency of poor health related quality of life determined by CLDQ score is high in patients with liver cirrhosis. Hemoglobin, serum albumen, prior history of decompensation (like encephalopathy and upper gastro intestinal bleed), are associated with health related quality of life.     

Ambulatory ECG-based T-wave alternans and heart rate turbulence can predict cardiac mortality in patients with myocardial infarction with or without diabetes mellitus

ABSTRACT: BACKGROUND: Many patients who survive a myocardial infarction (MI) remain at risk of sudden cardiac death despite revascularization and optimal medical treatment. We used the modified moving average (MMA) method to assess the utility of T-wave alternans (TWA) and heart rate turbulence (HRT) as risk markers in MI patients with or without diabetes mellitus (DM). METHODS: We prospectively enrolled 248 consecutive patients: 96 with MI (post-MI patients); 77 MI with DM (post-MI + DM patients); 75 controls without cardiovascular disease (group control). Both TWA and HRT were measured on ambulatory electrocardiograms (AECGs). HRT was assessed by two parameters [BOX DRAWINGS LIGHT HORIZONTAL] turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO [GREATER-THAN OR EQUAL TO]0% and TS [LESS-THAN OR EQUAL TO]2.5 ms/R-R interval were met. The endpoint was cardiac mortality. RESULTS: TWA values differed significantly between MI and controls. Post-MI + DM patients had higher TWA values than post-MI patients (58 [PLUS-MINUS SIGN] 21 muV VS 52 [PLUS-MINUS SIGN] 18 muV, P = 0.029). Impaired HRT--increased TO and decreased TS were observed in MI patients with or without DM. During follow-up of 578 [PLUS-MINUS SIGN] 146 days, cardiac death occurred in ten patients and three of them suffered sudden cardiac death (SCD). Multivariate analysis determined that a HRT-positive outcome [HR (95% CI): 5.01, 1.33--18.85; P = 0.017], as well as the combination of abnormal TWA ([GREATER-THAN OR EQUAL TO]47 muV) and positive HRT had significant association with the endpoint [HR (95% CI): 9.08, 2.21--37.2; P = 0.002)]. CONCLUSION: This study indicates that AECGs-based TWA and HRT can predict cardiac mortality in MI patients with or without DM. Combined analysis TWA and HRT may be a convenient and useful method of identifying patients at high risk for cardiovascular death.     

Rate of cardiac arrhythmias and silent brain lesions in experienced marathon runners: rationale, design and baseline data of the Berlin Beat of Running study

ABSTRACT: BACKGROUND: Regular exercise is beneficial for cardiovascular health but a recent meta-analysis indicated a relationship between extensive endurance sport and a higher risk of atrial fibrillation, an independent risk factor for stroke. However, data on the frequency of cardiac arrhythmias or (clinically silent) brain lesions during and after marathon running are missing.Methods/ DesignIn the prospective observational "Berlin Beat of Running" study experienced endurance athletes underwent clinical examination (CE), 3 Tesla brain magnetic resonance imaging (MRI), carotid ultrasound imaging (CUI) and serial blood sampling (BS) within 2-3 days prior (CE, MRI, CUI, BS), directly after (CE, BS) and within 2 days after (CE, MRI, BS) the 38th BMW BERLIN-MARATHON 2011. All participants wore a portable electrocardiogram (ECG)-recorder throughout the 4 to 5 days baseline study period. Participants with pathological MRI findings after the marathon, troponin elevations or detected cardiac arrhythmias will be asked to undergo cardiac MRI to rule out structural abnormalities. A follow-up is scheduled after one year. RESULTS: Here we report the baseline data of the enrolled 110 athletes aged 36-61 years. Their mean age was 48.8 [PLUS-MINUS SIGN] 6.0 years, 24.5 % were female, 8.2 % had hypertension and 2.7 % had hyperlipidaemia. Participants have attended a mean of 7.5 [PLUS-MINUS SIGN] 6.6 marathon races within the last 5 years and a mean of 16 [PLUS-MINUS SIGN] 36 marathon races in total. Their weekly running distance prior to the 38th BMW BERLIN-MARATHON was 65 [PLUS-MINUS SIGN] 17 km. Finally, 108 (98.2 %) Berlin Beat-Study participants successfully completed the 38th BMW BERLIN-MARATHON 2011. DISCUSSION: Findings from the "Berlin Beats of Running" study will help to balance the benefits and risks of extensive endurance sport. ECG-recording during the marathon might contribute to identify athletes at risk for cardiovascular events. MRI results will give new insights into the link between physical stress and brain damage.Trial registrationclinicaltrials.gov NCT01428778.     

The detection of hTERC amplification using fluorescence in situ hybridization in the diagnosis and prognosis of cervical intraepithelial neoplasia: a case control study

ABSTRACT: BACKGROUND: Currently the routine non-invasive screening methods for cervical intraepithelial neoplasia (CIN) and cervical cancer are Thinprep cytology test (TCT) and human papillomavirus testing. However, both methods are limited by the high false positive and false negative rates and lack of association with patients' prognosis, especially for the early detection of pro-malignant CIN. The aim of the study was to investigate the role of genomic amplification of human telomerase gene (hTERC) in the diagnosis and prognosis of CIN. METHODS: The study group consisted of specimens of exfoliated cervical cells from 151 patients, including 27 with CIN I, 54 with CIN II/III, 17 with carcinoma in situ, and 28 with invasive squamous carcinoma, as well as 25 patients who were at 2-year follow-up after either Loop Electrosurgical Excision treatment (n = 11) or radical surgery (n = 14). hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH), and the results were compared with TCT and histologic examination. The final diagnosis was determined by the pathological examination. The control group consisted of specimens of exfoliated cervical cells from 40 normal women. RESULTS: The percentage of cervical exfoliated cells with positive hTERC amplification and incidence rates of hTERC amplification were 9.2% [PLUS-MINUS SIGN] 4.6% and 44.4% (12/27) respectively in patients with CIN I; 16.0% [PLUS-MINUS SIGN] 14.4% and 85.1% (46/54) in patients with CIN II/III; 19.7% [PLUS-MINUS SIGN] 13.3% and 88.3% (15 /17) in patients with carcinoma in situ; 47.0% [PLUS-MINUS SIGN] 25.2% and 100% (28/28)in patients with invasive squamous carcinoma. There was statistically significant difference between the control and study group (P <0.01), and between the patients with various diseases within the study group (P <0.05). CONCLUSION: The detection of genomic amplification of hTERC using FISH is a non-invasive and effective approach for CIN.