Experimental infection of chimpanzees with hepatitis C virus of genotype 5a: genetic analysis of the virus and generation of a standardized challenge pool

Six major genotypes (genotypes 1-6) of hepatitis C virus (HCV) have been identified. These genetic variants are being transmitted to chimpanzees, the only recognized animal model for the study of HCV. Genotype 5a (strain SA13), a variant found primarily in South Africa, has been transmitted to chimpanzees for the first time. Experimental infection of 2 chimpanzees was characterized by early appearance of viremia and peak virus titers of 10(5)-10(6) genome equivalents/mL. The HCV infection was resolved by week 15 after inoculation in 1 chimpanzee and persisted in the other. Both chimpanzees became anti-HCV-positive by week 14 after inoculation. Both chimpanzees developed viral hepatitis. The infectivity titer of a genotype 5a challenge pool prepared from the first passage of HCV in a chimpanzee was approximately 10(4) infectious doses/mL. Finally, sequence analysis of strain SA13 confirmed that genotype 5a is genetically distinct from other genotypes of HCV.     

Stage T1-2 prostate cancer: a multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy

PURPOSE: Prostate-specific antigen (PSA) is extensively used in case selection and outcome evaluation after treatment of clinically localized prostate cancer. Careful case selection can have a profound impact on pathologic findings and ultimate outcome. In addition, salvage treatment is frequently initiated at the time of biochemical relapse rather than clinical recurrence. Consequently, patterns of failure can be significantly altered compared to previous times when PSA was not available. To better understand the impact of PSA on pathologic findings, outcome, and salvage treatment, we reviewed our experience in the PSA era with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. METHODS AND MATERIALS: Between 1987 and 1993, 423 cases could be identified with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. The distribution of cases by pretreatment PSA levels was as follows: < or = 4 ng/ml (18%), 4-10 ng/ml (42%), 10-20 ng/ml (21%), > 20 ng/ml (14%), and unknown (5%). The median pretreatment PSA level for the entire group was 8.0 ng/ml. Sixteen patients received adjuvant or neoadjuvant androgen suppression and 13 received postoperative radiotherapy. Only 31 patients (7%) had pathologically positive pelvic lymph nodes. The overall margin involvement rate was 46%. Fifty-three percent of patients had surgical Gleason scores > or = 7, and 65% had extracapsular extension. The median follow-up time was 41 months. RESULTS: The projected overall survival at 7 years after surgery was 90%. The 5-year clinical relapse-free survival rate was 84%. At 5 years, the local control and distant failure rates were 92% and 91%, respectively. Biochemical relapse was defined as a detectable or rising PSA level after prostatectomy. The 5-year biochemical relapse-free survival (bRFS) rate was 59%. The 5-year RFS was 88% in patients with preoperative PSA levels < or = 4, 62% for 4-10, 48% for 10-20, and 31% for > 20. Combining the two independent preoperative variables, iPSA and biopsy GS (bGS), two risks groups were defined: low risk [initial PSA (iPSA) levels < or = 10.0 and bGS < or = 6] and high risk (iPSA levels > 10.0 ng/ml or bGS > or = 7). The 5-year bRFS rate for the low-risk cases was 81% vs. 40% for high-risk cases (p < 0.001). On multivariate analysis, three factors independently predicted biochemical relapse: iPSA levels (p = 0.005), Gleason score from the surgical specimen (sGS) (p = 0.002), and positive surgical margins (p < or = 0.001). The 5-year bRFS rates for margin positive vs. margin negative patients were 37% vs. 78%, respectively. The 5-year bRFS rates for GS > or = 7 vs. GS > or = 6 were 42% vs. 80%, respectively. All clinical relapses were accompanied by a rise in PSA. In patients who manifested biochemical failure followed by a clinical failure, the median interval between the PSA rise and clinical failure was 19 months (range 7-71). Margin involvement was the only independent predictor of local failure (p = 0.019). The 5-year local failure-free survival for negative margin cases was 96% vs. 87% for positive margin cases (p = 0.012). Lymph node (LN) involvement and high-risk group were the two independent predictors of distant failure. The 5-year distant failure-free survival for negative LN cases was 94% vs. 67% for positive LN cases (p < 0.001). The 5-year distant failure-free survival for low-risk cases was 97% vs. 85% for high-risk cases (p = 0.005). For the 124 patients failing biochemically, 85 were observed and 39 were treated either with radiation or androgen deprivation. With a median follow-up of 32 months, the clinical disease relapse-free survival was 79% for the treated patients vs. only 32% for the patients observed (p < 0.001). CONCLUSION: Pretreatment PSA is the most potent clinical factor independently predicting biochemical relapse, thereby allowing markedly better case selection. Achieving negative margins, even in relatively advanced disease, provides excellent lon     

Men, medicine and machines

PURPOSE: To examine the management and possible causes of primary valve malfunction of the Krupin eye valve with disk. METHODS: The authors reviewed the results of 113 patients undergoing implantation of the Krupin eye valve with disk and identified eight patients with primary valve malfunction requiring surgical revision. RESULTS: Valve revision involved manipulation (n = 1 case), explantation of the malfunctioning valve and implantation of a new valve (n = 2), and amputation of the valve (n = 5). Six of eight patients had final intraocular pressures of < 21 mmHg on one or no medications at a mean interval of 15.9 months (range 5-36) after surgical revision. Transient postoperative hypotony was noted in three patients and chronic hypotony with loss of light perception in one patient. One explanted valve was examined and found to have partially fused leaflets. CONCLUSIONS: Surgical revision in cases of primary valve malfunction of the Krupin eye valve with disk may be accomplished relatively safely with an acceptable level of postoperative complications. The etiology of primary valve malfunction may be related to the sterilization process and prolonged storage before implantation.     

Selective removal technology using chemical etching and excimer assistance in precision recycle of color filter

Color filters are produced using semiconductor production techniques although problems with low yield remain to be addressed. This study presents a new means of selective removal using excimer irradiation, chemical etching, or electrochemical machining on the fifth generation TFT LCDs. The selective removal of microstructure layers from the color filter surface of an optoelectronic flat panel display, as well as complete removal of the ITO thin-films, RGB layer, or resin black matrix (BM) layer from the sub...     

Isolation of aerobic microbes from Ixodes scapularis (Acari: Ixodidae), the vector of Lyme disease in the eastern United States

The spirochete Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Benner is transmitted by Ixodes scapularis Say, a vector of Lyme disease. As a 1st step into investigating the possibility of biocontrol of the tick, we identified the microbiota associated with the ticks. We collected, identified, and determined the sex of ticks from foliage and deer. Seventy-three initial bacterial isolates were recovered from 43 ticks (27 adults and 16 nymphs). The bacteria isolated from nymphs were qualitatively different (mainly gram-negative cocci) from the bacteria isolated from adult ticks (gram-negative and gram-positive rods). To determine long-term viability, these isolates were stored for 6 mo under laboratory conditions. After storage, 63 surviving bacterial isolates were characterized using the Biology System of identification by substrate utilization. Forty-four isolates were identified to the species level. Our characterization efforts focused on the 40 spore-forming bacteria, which could prove useful in the biocontrol of ticks. Eleven species of Bacillus were identified. Bacillus thuringiensis-B. cereus was the predominant species group isolated. Six isolates from this group formed crystals.     

Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient

OBJECTIVE: To investigate the production of proinflammatory cytokines and expression of cell adhesion molecules in the rheumatoid nodule. METHODS: Cytokine content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein levels, and cell adhesion molecule expression were studied in 16 rheumatoid nodules and 6 synovial membranes. RESULTS: Macrophages in the rheumatoid nodules contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in perivascular cells of the stroma and in the palisading layer. All cell adhesion molecules studied were expressed in both the rheumatoid nodules and synovial membranes, with increased expression of E-selectin in the rheumatoid nodule compared with the synovial membrane, and with the absence of vascular cell adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid nodule. CONCLUSION: The presence of similar proinflammatory cytokines and cell adhesion molecules in the rheumatoid nodule and synovial membrane suggests that similar pathogenic processes result in the chronic inflammation and tissue destruction in these lesions.     

Arthrodesis of the shoulder for synovial osteochondromatosis

OBJECTIVES: To identify the reasons for non-compliance with fecal occultblood test in the screening programme for colorectal cancer. DESIGN AND SETTING: The people who had never participated in the screening programme for colorectal cancer served as the subjects of this study. A structured questionnaire which included the reasons for rejection was sent to each of non-compliers. They were requested to choose two major reasons which were described in a best way that why they did not participate in the programme. The frequency of the stated reasons were analysed from the viewpoint of both sex and age effects. MAIN RESULTS:A total of 439 people was identified as non-compliers, and 356 (81.1%) people completed the questionnaire. No significant difference was noted in response to the questionnaire between male and female as well as aged 40-59 and those 60-79. The most commonest reason was felt well (47.8%) in male, fear or shyness of further examination (40.2%) in female, and also felt well (48.5%) in aged 40-59, fear or shyness of further examination (40.1%) in aged 60-79. Significant differences were observed in the frequencies of felt well (p<0.01), fear or shyness of further examination (p<0. 01), busy for work (p<0.01) and fear of cancer (p<0.01) between male and female, and also felt well (p<0.01), fear or shyness of further examination (p<0.01), busy for work (p<0.01) and coexistent disease (p<0.01) between aged 40-59 and those 60-79. CONCLUSIONS: These results suggest that public education about the concept of asymptomatic illness, the benefits of early detection, the safety and painless colonoscopy, and the effective treatment should be emphasised to increase compliance with screening for fecal occult blood.     

Diode laser cyclophotocoagulation: histopathology in two cases of clinical failure

We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.     

Successful innominate thromboembolectomy of a paradoxic embolus

A 54 year-old man had symptoms of acute right hemispheric cerebral ischemia. He was initially considered for participation in a trial of early thrombolysis in stroke, but an innominate artery embolus was found with no apparent arterial source. The embolus was removed by means of a combined brachial and carotid bifurcation approach to protect the cerebral vasculature from embolic fragmentation during extraction. Further investigation revealed deep venous thrombosis, evidence of pulmonary emboli, and a patent foramen ovale, supporting a diagnosis of paradoxic embolus. Additional treatment included anticoagulation and placement of an inferior vena caval filter. The unusual condition of paradoxic embolus is reviewed, and the management of this patient is discussed.