Impact of Dnmt1 deficiency,with and without low folate diets,on tumor numbers and DNA methylation in Min mice

Although a number of studies have suggested that diets with low intake of folate, an important methyl donor, are associated with increased risks of colon cancer and its precursor the adenomatous polyp, the underlying mechanisms are poorly understood. Dysregulation and instability of DNA methylation and alterations in the levels of the predominant DNA methylating enzyme, DNA (cytosine-5)-methyltransferase 1 (Dnmt1), have also been linked to tumorigenesis. We have used a combination of genetic and dietary manipulation to assess the effects of reduced Dnmt1 expression with and without folate deficiency on tumor induction in the Apc(Min) mouse. Apc(Min) mice with a reduction in Dnmt1 expression (Apc(Min/+)/Dnmt1(C/+)) had significantly lower tumor numbers than Apc(Min) mice with normal Dnmt1 (Apc(Min/+)/Dnmt1(+/+)). Dietary folate deficiency from weaning to 13 weeks of age did not affect tumor number or size in Apc(Min/+)/Dnmt(+/+) mice. However, in Apc(Min/+)/Dnmt1(C/+) mice with high baseline tumor numbers (41 +/- 4), folate deficiency was associated with a decreased absolute number of tumors (27 +/- 3), but a higher proportion of larger tumors as compared with mice on the control diet. In the repeat experiment, Apc(Min/+)/Dnmt1(C/+) mice had low baseline tumor numbers (20 +/- 2) and folate deficiency did not affect tumor number (23 +/- 4) or size as compared with the same mice on the control diet. These results suggest that, in the presence of Dnmt1 deficiency, the effects of folate deficiency on tumor number and size may depend on the stage of adenoma development when folate deficiency is initiated. We also show that folate deficiency with or without reductions in Dnmt1 did not affect overall genomic DNA methylation or the methylation levels of two candidate genes, E-cadherin or p53, in normal or neoplastic intestinal tissue. In conclusion, genetic deficiency in Dnmt1 with or without folate deficiency decreases tumor number in the Apc(Min) mouse model, but this effect may not be mediated by changes in SAM or SAH levels, nor by alterations in global methylation in the pre-neoplastic intestinal tissue.     

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。     

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.     

Benefits of early admission to a comprehensive trauma center for patients with spinal cord injury

Patients with spinal cord injury may be admitted directly to a trauma center with a dedicated rehabilitation unit or transferred there days or weeks later. This study analyzed the relationship between time of transfer to a Level I Trauma Center with a spinal cord injury service and efficacy of subsequent rehabilitation. We examined the records of all patients admitted to the service between September 1981 and August 1983 and followed at least one year. There were 197 patients, 102 quadriplegics and 95 paraplegics, aged 15 to 77 years (average = 29.4 years). Median time from injury to admission was 11 days for quadriplegics and 21 days for paraplegics; this was used to define early and late groups. The early quadriplegic group began rehabilitation 2.94 days postinjury; the late quadriplegic group, 74.87 days (p less than .01). Time in rehabilitation did not differ (128.22 days, early; 122.61, late), but total hospitalization--from injury to discharge--was 131.16 days for the early quadriplegic group and 197.27 for the late quadriplegic group (p less than .01). Average duration of prerehabilitation care for the paraplegic groups was 6.19 days (early) and 58.58 days (late) (p less than .01). Time in rehabilitation was the same for both paraplegic groups, but total hospitalization was shorter for early admissions (82.91 days vs 125.90 days, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Amplification of the c-myc gene in human medulloblastoma cell lines and xenografts

Cultured cell lines and xenografts derived from 7 human medulloblastomas were evaluated for amplification of the c-myc, N-myc, epidermal growth factor receptor, and gli genes by Southern blot analysis. Karyotypes of the original biopsies and early passaged cells demonstrated double minute chromosomes in 4 of the 7 cases. All 7 samples (3 cell lines and 4 xenografts) from the 4 tumors with double minute chromosomes contained amplification of the c-myc gene. Cell lines and xenografts derived from the 3 biopsies without double minute chromosomes failed to demonstrate amplification of the 4 genes which were tested, but a rearrangement of the c-myc gene occurred in 1 of the 3 tumors. These observations demonstrate that the c-myc gene is often amplified and/or rearranged in human medulloblastomas and suggest that amplification of this gene provides a growth advantage for medulloblastoma cells in vitro and in vivo.     

Speech-controlled generation of radiology reports

Voice entry has been successfully employed to generate radiology reports with a word recognizer with a 1,000-word lexicon capacity. About 50% of reports were able to be dictated with a single 900-word lexicon. This was split into five sections by anatomic or subspecialty application. Each was augmented to 900 words. By switching from one lexicon to another, it was possible to dictate more than 70% of reports. With exclusive use of three lexicons in subspecialty areas (gastrointestinal radiology, neuroradiology, and mammography), and with further modification of the respective vocabulary, it has been possible to employ the system 88% of the time. Twelve percent of cases included wording that was beyond the scope of the lexicon. Computer subsets that allow different translations of some words when used in different contexts have been used. Some of these are used as triggers that will print whole lines, sentences, or even complete reports. Dictation times with voice entry take about 20% longer. Recognition reliability has been greater than 95%.     

The efficacy of '0.05% Clobetasol + 2.5% zinc sulphate' cream vs. '0.05% Clobetasol alone' cream in the treatment of the chronic hand eczema: a double-blind study

Background Many therapeutic modalities have been suggested for treatment of the chronic hand eczema. Despite good immediate efficacy of some of these treatments, there is high recurrence of the dermatitis following cessation of the treatment. Aim Regarding the beneficial effects of the zinc sulfate on the skin, we designed a double blind study to evaluate the efficacy of the ‘0.05% Clobetasol + 2.5% zinc sulphate’ cream versus ‘0.05% Clobetasol alone’ cream in the treatment of the chronic hand eczema. Subjects and Methods This study was a double‐blind, right to left, prospective, clinical trial. In total, 47 patients with chronic hand eczema admitted to dermatology center of Isfahan University of Medical Sciences were selected and their right hand or left hand were selected at random to be treated with either the ‘0.05% Clobetasol + 2.5% zinc sulphate’ cream or ‘0.05% Clobetasol alone’ cream twice daily for 2 weeks. All of the patients were treated for 2 weeks and were followed up at weeks 2, 4, 6 and 8 after starting the treatment. For determining the severity of chronic hand eczema, we assessed and scored 4 different characteristics of the lesions including redness; scaling; lichenification and pruritus. The data were analyzed using SPSS program (release 13) and statistical tests including Mann‐Whitney test. Results Overall, 47 patients (94 samples) were evaluated. All of these patients had similar and symmetrical lesions on their right and left hands. Out of them, 35 patients were females and 12 patients were male. In all of the evaluated characterisitics, the ‘0.05% Clobetasol + 2.5% zinc sulphate’ cream was more effective than ‘0.05% Clobetasol alone’ cream (P < 0.05). The recurrence rate of eczema was significantly lower in the group treated with this combination treatment (P < 0.05). Conclusion With regard to the encouraging results of the combination treatment with Clobetasol + zinc sulphate, we suggest that in a more extensive clinical trial, the efficacy of this treatment against chronic hand dermatitis be evaluated. In addition, evaluation of this combination therapy against other inflammatory dermatosis seems to be logical.     

Prothrombin and PIVKA-II Levels in Cord Blood from Newborn Exposed to Anticonvulsants During Pregnancy

PURPOSE: To determine whether anticonvulsant exposure during human pregnancy caused an increase of the abnormal form of prothrombin, known as PIVKA-II (prothrombin induced by vitamin K absence for factor II), and a decrease in total prothrombin, in the blood of the newborn. METHODS: Cord blood was collected from the placenta at the time of parturition from 12 women who had received anticonvulsant therapy during pregnancy and from 11 control women. RESULTS: PIVKA-II was present in cord blood from control mothers at low or nondetectable levels. In the same samples, total prothrombin concentrations were approximately 50% of adult levels, but there was wide variation between individuals. Exposure to carbamazepine (CBZ) alone during pregnancy was associated with markedly increased PIVKA-II levels in four of six samples and decreased total prothrombin levels for the whole group. High PIVKA-II levels also were recorded in one cord blood sample from a mother who received phenytoin (PHT) and vigabatrin (VGB). Two cases of PHT alone and one of valproic acid (VPA) alone were not associated with increased PIVKA-II levels. CONCLUSIONS: These results are consistent with the hypothesis that some anticonvulsants (particularly CBZ) interfere with vitamin K metabolism during pregnancy and may result in hematologic signs of vitamin K deficiency in the newborn.