In the shadow of HIV-HTLV infection in England and Wales, 1987-2001

Like human immunodeficiency virus (HIV), human T-cell leukaemia/ lymphoma viruses (HTLV) I and II are persistent retroviral infections. Once infected, the lifetime risk of developing the HTLV-associated diseases, malignant or inflammatory, is low (approximately 5%). For those affected, however, these diseases are debilitating, with few treatment options and a poor prognosis. Surveillance of HTLV infections by the Communicable Disease Surveillance Centre (CDSC) has been ongoing since serological testing became available in 1986. Testing of blood donations in England and Wales commenced during August 2002 and awareness of HTLV infection is likely to increase. Therefore, a baseline retrospective review of cases prior to 2002 was conducted. The age and sex distribution of identified HTLV cases has differed little over time. Eighty-five per cent of individuals were linked to the Caribbean by birthplace or ethnicity. Though HTLV infection is chronic and incurable, preventive measures are possible. Improved surveillance is needed to support effective prevention activities.     

Promoter Hypermethylation Frequency and BRAF Mutations Distinguish Hereditary Non-Polyposis Colon Cancer from Sporadic MSI-H Colon Cancer

BACKGROUND: Colorectal cancers resulting from defective DNA mismatch repair can occur in both hereditary non-polyposis colon cancer (HNPCC) and in the sporadic setting. They are characterised by a high level of microsatellite instability (MSI-H) and superficially resemble each other in that they are frequently located in the proximal colon and share features such as circumscribed tumour margins and tumour-infiltrating lymphocytes. However, significant differences can be demonstrated at the molecular level including widespread promoter hypermethylation and BRAF -activating mutations which occur significantly less often in HNPCC. AIMS: In this study, we sought to determine whether the presence of widespread promoter hypermethylation and BRAF mutations would exclude HNPCC. MATERIALS AND METHODS: We investigated the methylation status of four methylated in tumour markers (MINTs 1,2,12 and 31), and the promoter regions of 5 genes hMLH1, HPP1, MGMT, p16INK4A and p14ARF, in 21 sporadic MSI-H colorectal cancers and compared these with 18 cancers from HNPCC patients. The methylation status of CpG islands were determined by either methylation specific PCR (MSP) or combined bisulfite restricton analysis (COBRA). In addition we considered the BRAF mutation status of 18 HNPCC tumours and 19 sporadic MSI-H cancers which had been previously determined by RFLP analysis and confirmatory sequencing. RESULTS: Methylation of the promoter regions in target genes occurred less frequently within the HNPCC tumours (27% of analyses), compared with the sporadic MSI-H tumours (59% of analyses) (P < 0.001). Methylation of MINTs 1, 2, 12 and 31 occurred in 4% of analyses for HNPCC tumours contrasted with 73% for sporadic MSI-H tumours (P < 0.001). BRAF mutations were detected in 74% of sporadic tumours but none of the HNPCC cancers tested. CONCLUSIONS: The total number of genes and MINTs methylated in HNPCC was lower than in MSI-H colorectal tumours. No HNPCC tumour showed evidence of widespread promoter hypermethylation or BRAF mutation suggesting this feature could be used as a discriminator between familial and sporadic cases.     

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales,Australia. III. Release,persistence and rate of spread of an identifiable strain of myxoma virus

An identifiable strain of myxoma virus was introduced into four local populations of wild rabbits Oryctolagus cuniculus on the southern tablelands of New South Wales (NSW) and its spread in the presence of other field strains was monitored for 6 months. The main vector in this region was considered to be the European rabbit flea Spilopsyllis cuniculi. Each population of rabbits was of a high density and living in groups of warrens covering areas from 59 to 87 hectares. Rabbits occupying centrally located warrens were inoculated with the virus in late September or early October (spring) and the subsequent appearance of myxomatosis across the sites monitored by trapping, shooting and visual observations. Samples, taken from rabbits with myxomatosis, were examined by polymerase chain reaction (PCR) that allowed identification of the introduced strain. On all four sites the introduced virus spread from the inoculated rabbits in the centrally located warrens to rabbits in surrounding warrens. On Sites 1 and 3, this spread continued across the entire site persisting for at least 118 and 174 days respectively. On Sites 2 and 4, the virus was detected for 78 and 62 days respectively and the subsequent inability to detect the introduced virus correlated with the appearance of an unrelated field strain. Using three different methods of calculation, rates of spread ranged from 3.7 to 17.8 m d(-1).     

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales,Australia. I. Natural occurrence of myxomatosis

A survey of rabbit populations in the southern tablelands of New South Wales, Australia, was carried out to establish the pattern of occurrence of myxomatosis in preparation for a deliberate release of myxoma virus. Myxomatosis was first detected in December and cases were found on most sites through to May. The serological profiles of rabbit populations suggested that their susceptibility to myxoma virus was generally low in winter and highest in spring and summer reflecting the presence of increasing numbers of susceptible young rabbits. This was consistent with the pattern of rabbit breeding, as determined from the distribution of births and reproductive activity in females and males, which occurred maximally in spring and early summer. The serology and age structure of rabbit populations on sites suggested that some rabbit populations can escape an annual myxomatosis epizootic. Although fleas were present on rabbits throughout the year and therefore not considered to be a limiting factor in the spread of myxomatosis, their numbers peaked at times coincident with peak rabbit breeding. It was concluded that mid to late spring was an optimal time for a deliberate release.     

Nurse endoscopy in a district general hospital

INTRODUCTION: This study describes the first full year of independent practice by a newly appointed nurse endoscopist in a district general hospital. PATIENTS AND METHODS: Patients underwent either 'one stop' flexible sigmoidoscopy and barium enema or flexible sigmoidoscopy alone. Barium enema results, video photography, clinical follow-up, and histology were used to validate the results of the flexible sigmoidoscopy. One stop clinic: 161 endoscopies were performed, with 104 female patients (65%), and a mean age of 64 years. There was one failed endoscopy due to poor bowel preparation. Abnormalities were identified in 84% of endoscopies. Flexible sigmoidoscopy detected abnormalities not seen on the barium enema in 28 cases, all of which were polyps (18%). Barium enema identified one abnormality within reach of the flexible sigmoidoscope not identified at endoscopy (small polyp in sigmoid; 1%). Elective flexible sigmoidoscopy list: 121 endoscopies were performed, with 65 female patients (54%), and a mean age of 59 years. There were two failed endoscopy procedures, both attributed to poor bowel preparation. Two-thirds of patients had an abnormality on investigation. There were no complications in either group of patients. CONCLUSIONS: The nurse-led endoscopy service has been successfully initiated with a high completion rate for flexible sigmoidoscopies. All significant conditions were identified with 99% sensitivity. Nurse endoscopy is a safe, useful and practical procedure in the setting of this district general hospital.     

Major histocompatibility complex phenotypes influence serum testosterone concentration

OBJECTIVES: (a) To confirm our earlier observation that the phenotype HLA-DR4,7 occurs with higher frequency in male patients with rheumatoid arthritis (RA) than in female patients. (b) To test the hypothesis that DR7 is associated with low normal serum testosterone (Te) levels in healthy males; this might explain the increased frequency of DR4,7 in male patients since there appears to be a relationship between low serum Te and RA. (c) To characterize the association between HLA alleles and serum Te concentration in healthy males. METHODS: An additional 82 Newfoundland (NF) RA patients were HLA-DR typed and, combined with our earlier data and data from the 11th International Histocompatibility Workshop, gave HLA-DR and sex information on 373 RA patients. Ninety-four healthy NF males were typed for HLA, the microsatellite marker TNFa (located close to the tumour necrosis factor alpha gene) and complement factor B (BF). An additional 38 males were included, selected partly based on their HLA-B type. RESULTS: We confirmed our earlier finding of a higher frequency of HLA-DR4,7 in male RA patients compared with female RA patients (P<0.01). Contrary to our expectations we found that DR7 was associated with higher than mean values of Te as were B5, B27, DR1, TNFa7 and BF F positivity. Conversely, low Te concentrations were found in men with B15, DR2, DR5, TNFa5 and who were BF F negative. In 28 male 'early-onset' RA patients we did not find an increased frequency of HLA alleles associated with low Te levels as compared with the frequency in 41 'late-onset' patients, suggesting that if low Te level is a risk factor and is present before onset of RA then the level cannot be explained by an association between Te level and major histocompatibility complex (MHC) phenotype. CONCLUSION: This study indicates that a man's MHC phenotype may influence his serum Te concentration, but the relationship of this, if any, to the pathogenesis of RA remains an area of speculation.     

Experimental intrahepatic portacaval anastomosis: use of expandable Gianturco stents

Original Gianturco expandable stents and their modifications were used to create an experimental intrahepatic portacaval anastomosis (EIPCA) in 30 young domestic swine without portal hypertension. The study focused on the design of a suitable stent, the technique of its application, and the evaluation of short-term patency of the EIPCA. A stent with a 2.5-cm-long body and wire skirts on both ends was most suitable for EIPCA creation. Well-positioned stents shunted most of the portal blood in the inferior vena cava circulation and remained patent for 4-6 weeks. Ingrowth of liver parenchyma and abundant proliferation of the intima and connective tissue inside the stent lumen in these rapidly growing animals gradually decreased EIPCA patency, and thrombus formation with diminished blood flow closed them completely.     

小鼠脑缺血后的能量代谢改变和药物的作用

应用部分结扎小鼠颈总动脉(包括迷走神经)及小鼠断头法引起脑缺血后,脑组织的ATP和磷酸肌酸明显降低,乳酸明显升高。部分结扎颈动脉出现四肢无力、转圈及昏睡等症状,其严重程度与脑能量代谢改变相平行。皮下注射尼莫地平、硝苯吡啶、尼卡地平和三七皂甙对脑缺血有一定保护作用。苯巴比妥钠能改善正常和脑缺血小鼠的脑能量代谢,人参皂甙Rb₁可降低正常小鼠脑乳酸含量。