Protein kinase C inhibition and diabetic retinopathy: a shot in the dark at translational research

TRANSLATIONAL RESEARCH IN PRACTICE: a PKC-beta inhibitor for diabetic retinopathy     

Schistosoma mansoni myeloradiculopathy in an 8-year-old Omani boy

An 8-year-old Omani boy presented with progressive ascending weakness of the lower limbs with bowel and bladder incontinence. A diagnosis of myeloradiculopathy was made on neurologic examination. Eosinophilia in the peripheral blood count and suspected endemicity in his region of residence raised the diagnostic possibility of neuroschistosomiasis. Cerebrospinal fluid findings, high schistosoma antibody titre, magnetic resonance imaging of the spine, and detection of Schistosoma mansoni eggs in the stool confirmed the diagnosis. The boy recovered significantly after receiving praziquantel and methylprednisolone. Neurological symptoms at presentation could be due to parasitic infection and should be considered in an endemic region. Eosinophilia in the peripheral blood count may be the first indicator.     

Left ventricular mass measured by myocardial perfusion gated SPECT. Relation to three-dimensional echocardiography

PURPOSE: The purpose of this investigation was to determine whether left ventricular mass (LVM) assessed from myocardial perfusion gated SPECT (GSPECT) data corresponds with echocardiographic estimates, and whether mass accuracy decreases as relative myocardial wall thickness increases. MATERIALS AND METHODS: Myocardial perfusion tomograms were selected retrospectively for 37 patients, of whom 18 had Tl-201 and 19 had Tc-99m sestamibi GSPECT poststress data collections, which were subsequently processed using quantitative gated SPECT software (Cedars Sinai Medical Center, Los Angeles, CA). These patients also had clinically indicated echocardiograms for assessment of wall thickness and possible valvular involvement. In addition, LV internal diameter and posterior wall thickness were measured at end-diastole by two-dimensional guided M-mode echocardiography to assess relative myocardial wall thickness, and LVM was measured by three-dimensional echocardiography using an acoustic spatial locator device. RESULTS: LVM values were not significantly different between GSPECT and three-dimensional echocardiography (153 +/- 39 g versus 146 +/- 35 g, respectively; P = NS). GSPECT correlated significantly (r = 0.63, P < 0.0001) with three-dimensional echocardiography, with a mean difference of 7 +/- 32 g but a substantial root mean squared error of 31 g. Results were similar for similar mass ranges when subgrouped by isotope and by the presence of significant myocardial perfusion defects. Results were independent of relative myocardial wall thickness determined by two-dimensional echocardiography. The two methods yielded similar results in the highest mass range of 400 to 500 g. CONCLUSIONS: GSPECT and three-dimensional echo LVM correlated significantly, but given the large spread of statistical errors, these two techniques should not be considered interchangeable. Because gamma camera resolution is limited, GSPECT LVM should be viewed as an approximation.     

皮质类固醇治疗外伤性视神经病变的四天关键时期(英文)

目的:评估静脉注射甲基强的松龙(IVMP)对外伤性视神经病变患者的疗效。方法:回顾性分析2000-01至2007-06我院收治的16例外伤性视神经病变(TON)患者的临床资料。1g甲基强的松龙分3d静脉应用,然后口服泼尼松龙11d,并逐渐减量。记录从损伤开始到治疗开始的时间。视力变化是本研究结果的主要功能评价指标。在入院时,治疗后1,2,3d;1wk和1mo时,分别记录最佳矫正视力(BCVA)。结果:共有16例患者纳入本研究,平均年龄为30岁,其中男性14例、女性2例。引起TON的主要原因有摩托车事故(占69%),打架斗殴(占19%)和体育运动(占12%)。所有患者都表现有相对传入性瞳孔障碍。在损伤后4d内开始静脉注射甲基强的松龙,采用Snellen视力表检查视力,绝大部分(56%)患者视力提高超过3行或大于等于0.5(6/12)。在损伤后5d以上才开始用类固醇治疗,视力则没有任何进步。结论:治疗TON,静脉注射中等到大剂量甲基强的松龙仍将起到重要作用。静脉注射甲基强的松龙治疗TON可能存在伤后4d的关键时期,超过了这个时期,该治疗可能就毫无效果。但还需要有更多的研究来为我们提供有明显统计学意义的数据。     

Peanut butter intake, GSTM1 genotype and hepatocellular carcinoma: a case–control study in Sudan

Objective: Hepatocellular carcinoma (HCC) is one of the major cancers in the world. In Sudan the incidence is thought to be high and increasing. This study aims to assess the association between peanut butter intake, as a source of aflatoxins, and the GSTM1 genotype in the etiology of HCC. Method: A case–control study was conducted among 150 patients and 205 controls from two regions in Sudan. Food habits with special reference to peanut butter consumption, as well as peanut storage systems, have been investigated, as well as confounders such as hepatitis, drinking and smoking habits, and demographic characteristics. GSTM1 genotype was assessed in DNA extracted from blood samples (110 cases, 189 controls). Results: A positive association was observed for highest vs. lowest quartile of peanut butter intake, humid storage system and HCC, with ORs (95% CI) being 3.0 (1.6–5.5) and 1.6 (1.1–2.5) respectively. The positive association with peanut butter intake was essentially limited to subjects with GSTM1 null genotype with OR for highest vs. lowest quartile 16.7 (2.7–105). Conclusion: Peanut butter consumption has been identified as a strong risk factor of HCC in a region with endemic aflatoxin contamination in Sudan and was essentially limited to subjects with the GSTM1 null genotype.     

Genotypic and phenotypic relationship in Burkholderia pseudomallei indicates colonization with closely related isolates

Seven isolates of Burkholderia pseudomallei from cases of melioidosis in human (2 isolates) and animal (2 isolates), cat (one isolate) and from soil samples (2 isolates) were examined for in vitro sensitivity to 14 antimicrobial agents and for presence of plasmid DNA. Randomly amplified polymorphic DNA (RAPD) analysis was used to type the isolates, using two arbitrary primers. All isolates were sensitive to chloramphenicol, kanamycin, carbenicillin, rifampicin, enrofloxacin, tetracycline and sulfamethoxazole-trimethoprim. No plasmid was detected in all the isolates tested. RADP fingerprinting demonstrated genomic relationship between isolates, which provides an effective method to study the epidemiology of the isolates examined.     

Mutations of the p53 gene in oral squamous-cell carcinomas from Sudanese dippers of nitrosamine-rich toombak and non-snuff-dippers from the Sudan and Scandinavia

Using PCR-SSCP/DNA sequencing methods, we analyzed 14 oral squamous-cell carcinomas (OSCCs) and 8 pre-malignant oral lesions from different Sudanese patients for prevalence of mutations in exons 5 to 9 of the p53 gene in relation to toombak-dipping status. OSCCs (14 from Sudan, 28 from Scandinavia), and 3 pre-malignant oral lesions from Sudanese non-dippers were used as controls. A statistically significant increased incidence in mutations of the p53 gene was found in OSCCs from toombak dippers (93%; 13/14), as compared with those from non-dippers in Sudan (57%; 8/14) and in Scandinavia (61%; 17/28) respectively. In OSCCs from dippers, mutations were found in exons 5 to 9, while in those from non-dippers they were found in exons 5, 7, 8, 9, and no mutations were found in exon 8 in any of the OSCCs from Sudan. Certain types of mutations, however, were similar with respect to exposure to toombak. OSCCs from dippers showed 15 transversions, 9 transitions, 3 insertions and one deletion, compared with 7 transversions, 2 transitions and one deletion found in OSCCs from Sudanese non-dippers, and 9 transversions, 17 transitions and 2 insertions found in those from non-dippers in Scandinavia. No mutations were found in any of the non-malignant oral lesions in relation to dipping or non-dipping status. These findings suggest that (i) the use of toombak plays a significant role in induction of increased p53 gene mutations, (ii) mutations observed were similar to those induced by tobacco-specific N-nitrosamines (TSNAs) in experimental animal models and those already reported in toombak dippers, (iii) types of mutations associated with TSNAs were similar in the exposed and the control groups, (iv) a novel mutation in exon 6 was found in the OSCCs from toombak dippers, (v) the p53 exons 5 (codon 130), 6 (codons 190, 216) and 7 (codons 229, 249, 252) mutations are probable hot spots for toombak-related OSCCs. Further studies are necessary to validate the increased incidence and exon locations of the p53-gene mutations as a biomarker of malignant transformation in populations in which the oral use of tobacco is habitual.     

Simultaneous total arch replacement and abdominal aortic surgery

It is common to encounter patients with coexisting aortic arch aneurysm and abdominal aortic lesions. We conducted simultaneous total arch replacement and abdominal aortic surgery in 3 patients having such lesions. Mean operative time was 511 minutes and no in-hospital mortality occurred. Postoperative respiratory failure was observed in an 80-year-old patient who recovered and all three patients were discharged in good condition. No other postoperative complication was seen. Simultaneous total arch replacement and abdominal aortic surgery may thus offer advantages to patients with such double aortic lesions if it can be conducted safely.     

Behavioural Effects of the Methanolic Root Bark Extract of Securinega Virosa in Rodents

Securinega virosa is used traditionally as sedative in children and in mental illnesses. In this study, the behavioral effects of methanolic root bark extract of S. virosa were investigated in mice. The results revealed that the extract significantly (P<0.05) and dose-dependently reduced the onset and prolonged the duration of sleep. The extract significantly (P<0.05) decreased exploratory activity and reduced the rate of apomorphine-induced stereotyped climbing at the doses tested (6.25–25mg/kg). It also produced a significant and dose-dependent motor coordination deficit in mice at the doses tested (P<0.01). The intraperitoneal median lethal dose in mice was 774.6mg/kg while the preliminary phytochemical screening revealed the presence of alkaloids, tannins, saponins and flavonoids. These results suggest that methanolic root bark extract of S. virosa contains biologically active principles that are sedative in nature and lend pharmacological credence to the ethnomedical use of the plant.