Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

A multi-center study on recurrent inguinal hernias: assessment of surgeons’ compliance to guideline-based repair and evaluation of short-term outcomes

Hernia - As patients with recurrent inguinal hernia (RIH) are at a higher risk of perioperative complications, international guidelines have been developed to mitigate these risks by recommending...     

Emergency surgery comparison of right versus left acute colonic diverticulitis: A 10-year outcome analysis

IntroductionThe difference in outcome between right (RCD) and left colonic diverticulitis (LCD) is not well established. The aim of this study was to analyse the presentation and surgical outcome of RCD versus left-sided disease following emergency surgery.MethodWe conducted a retrospective review of patients presenting with acute diverticulitis over a 10-year period from 2004 to 2014 to a tertiary unit. Patient demographics, Hinchey classification, need for emergency surgery, perioperative outcome and recurrence were evaluated.ResultsIn total 360 patients presented with acute diverticulitis, 218 (61%) were right-sided and 142 (39%) were left-sided. The mean age (57 yrs vs 68 yrs) and median length of stay (4 days vs 5 days) were significantly less in RCD (p < 0.001). The need for emergency surgery was similar between RCD and LCD (30.7% vs 23.2%, p = 0.12). Sixty-seven (31%) patients with RCD required emergency surgery, 42 (62.7%) of these were based on a presumptive diagnosis of appendicitis and underwent laparoscopic appendicectomy only. Operative morbidity (10.4% vs 51.5%, p < 0.001) and mortality were significantly higher in LCD (1.5% v 15.2%, p = 0.007). Subgroup analysis of non-appendicectomy, RCD patients, showed LCD were more likely to require surgery (11.5% vs 23.2%, p = 0.003). There was no difference in recurrence (p = 0.6).ConclusionRight colonic diverticulitis patients are younger and disease course is more benign compared to LCD. Presentation can be confused with appendicitis without proper imaging. In the rare cases where emergency surgery is required, RCD is associated with a lower operative morbidity and mortality compared to left-sided disease.     

Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66–0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66–0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = −0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.     

带有蛋白转导结构域的bcr/abl癌蛋白片段表达及其跨膜转运

0　引言　人类免疫缺陷病毒 (human immunodeficiencyvirus,HIV) - 1编码的反式激活蛋白 TAT具有独特的跨膜运转方式 ,而且有转导速度快 ,效率高的特点 ,被称为蛋白转导结构域 (protein transduction domain,PTD) [1 ,2 ] .本研究用PCR扩增了慢性粒细胞白血病慢粒 bcr/ abl融合蛋白的基因片段 ,在其 5′端融合 PTD结构域的编码区后在大肠杆菌中进行了表达 .表达产物经纯化后 ,加入培养的 HL 6 0细胞 ,表达的蛋白可直接进入细胞内 .这一结果为用外源蛋白负载(L oading)免疫细胞提供了新的途径 .1　材料和方法1.1　 DNA重组　人工合…     

Evaluation of oxidative DNA damage in human sperm and its association with male infertility

Recently, there is increasing evidence suggesting that oxidative sperm DNA damage is closely associated with impaired sperm function and male infertility. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a precise and sensitive biomarker of oxidative DNA damage. The present study was thus designed to evaluate the extent of oxidative DNA damage in sperm and its association with male infertility by assaying the 8-OHdG levels in human sperm samples. A total of 114 subjects (60 infertile patients and 54 age-matched healthy workers) participated in this study. The level of 8-OHdG in sperm DNA was determined by high-performance liquid chromatography with electrochemical detection, and the conventional seminal parameters were also measured according to World Health Organization guidelines. It was found that the level of sperm 8-OHdG in infertile patients was significantly higher than that in healthy subjects (10.03 vs. 4.79 8-OHdG/10(5) dG; geometric mean, P < 0.001). The correlation between sperm 8-OHdG levels and conventional seminal parameters were also analyzed. There is a significant positive correlation between 8-OHdG and sperm head defects (r = 0.38, P < 0.001), whereas significant inverse correlations were noted for 8-OHdG with sperm density (r = -0.42, P < 0.001), total sperm number (r = -0.42, P < 0.001), sperm motility (r = -0.24, P < 0.01), and normal sperm morphology (r = -0.39, P < 0.001). Data from this study thus indicate that oxidative damage to sperm DNA may be important in the etiology of male infertility and that the assay of sperm 8-OHdG may have potential diagnostic value in the evaluation of sperm function and male fertility.     

Evaluation of oculokinetic perimetry

BACKGROUND AND METHOD: Oculokinetic perimetry (OKP) was performed on 98 patients (187 eyes) using the Damato 26-point glaucoma screening chart. Results were compared with those obtained from a 24-2 full threshold test on a Humphrey Field Analyser (HFA). RESULTS: In its ability to detect pathology in individual eyes, OKP had a sensitivity of 75.0% and a specificity of 71.4%. To detect glaucoma, OKP demonstrated a sensitivity of 86.0% and a specificity of 56.1%. The number of OKP defects detected increased with increasing HFA mean defect and corrected pattern standard deviation. Whereas moderate and severe field defects were almost always detected, smaller and shallower glaucoma defects were often missed. CONCLUSION: The fall in sensitivity and specificity of the OKP chart in identifying milder glaucomatous field defects diminishes its value as a screening test. However, its introduction into wider use in the community may increase awareness of glaucoma amongst general practitioners and members of the public, and help to detect previously undiagnosed glaucoma with moderate to severe damage. A normal OKP finding does not exclude the presence of early glaucoma. Combined with ophthalmoscopy, OKP may improve glaucoma detection rates amongst non-ophthalmologists.     

PREVALENCE OF MICROALBUMINURIA IN NON-INSULIN-DEPENDENT DIABETES MELLITUS

The prevalence of microalbuminuria was assessed in 50 patients of non-insulin dependent diabetes mellitus. The mean age of patients was 52.1 ± 11.6 years and the duration of diabetes was 8.3 ± 6.8 years. Twenty (40%) patients had microalbuminuria. Microalbuminuria was more common in patients with a longer duration of diabetes (more than 5 years), a poor glycaemic control, and higher systolic blood pressure.KEY WORDS: Microalbuminuria, Diabetes mellitus, Diabetic nephropathy, Chronic renal failure