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At least 307 records · Page 17Linked to original sources
PubMed1997

Genotype, viral load and age as independent predictors of treatment outcome of interferon-alpha 2a treatment in patients with chronic hepatitis C. Construct group.

Patients with chronic hepatitis C respond differently when treated with interferon. We randomized 116 patients with chronic hepatitis C in order to compare two dosage regimens of recombinant interferon alpha 2a:3 MIU x 3 per week for 6 months (arm A) or 6 MIU x 3 per week for 3 months and then 3 MIU x 3 per week for 3 months (arm B). There were no significant differences concerning outcome between the two dose regimens: sustained clearance of HCV viremia 6 months after the end of treatment was obtained in 12/59 (20%) in group A compared with 18/57 (32%) in group B (p = 0.24). In patients with genotype 1a, 4/31 (13%), in genotype 1b, none of 9 (0%), 9/15 (60%) in genotype 2, and 17/58 (29%) in genotype 3, showed sustained clearance of HCV viremia 6 months after the end of treatment (p = 0.002). In a stepwise logistic regression analysis, only pretreatment viral load (p = 0.0001), genotype (p = 0.001) and age (p = 0.04) were identified as independent predictors of sustained clearance of HCV viremia. Liver histology as assessed by Knodell index was significantly improved in patients with sustained HCV RNA response 6 months after the end of treatment (5.2 +/- 2.2 vs 2.6 +/- 2.2, p < 0.001), but not in responders with relapse or in non-responders. In conclusion, stepwise logistic regression analysis showed that viral load, HCV genotype and age were the only independent predictors for sustained HCV RNA response.

Age Factors↗
PubMed2006

Clinical perspectives of emerging pathogens in bleeding disorders.

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma.

Animals↗
PubMed1993

Thymic hyperplasia in adults following chemotherapy for malignancy.

BACKGROUND: The accuracy of the assessment of patients with malignant disease and of their response to chemotherapy has been significantly improved with the routine availability of computerized tomography (CT) scanning. CT abnormalities, however, may be non-specific, especially after chemotherapy. Rebound enlargement of the thymus gland after chemotherapy induced atrophy is one cause of an abnormal thoracic CT scan on re-staging. AIMS: This phenomenon has previously been reported mainly in relation to the treatment of lymphoma and germ cell cancers. This paper highlights the occurrence of thymic hyperplasia after chemotherapy in these and other tumour types. METHODS: We discuss five cases including three patients with malignancies other than lymphoma in whom thymus enlargement occurred during or after intensive chemotherapy. RESULTS: Clear identification of the nature of CT abnormalities after chemotherapy, particularly in the mediastinum, is required prior to embarking on further anti-cancer treatments.

Adult↗
PubMed2006

Addressing the "New" NEC: Part I: rediscovering the basics.

Epithelial cell functions ultimately define the ability of the extremely low birth weight human fetus to survive outside of the uterus. These specialized epithelial cell capacities manage all human interactions with the ex utero world including: (i) lung mechanics, surface chemistry and gas exchange, (ii) renal tubular balance of fluid and electrolytes, (iii) barrier functions of the intestine and skin for keeping bacteria out and water in, plus enabling intestinal digestion, as well as (iv) maintaining an intact neuroepithelium lining of the ventricles of the brain and retina. In Part I of this two part review, the authors describe why the gut barrier is a clinically relevant model system for studying the complex interplay between innate and adaptive immunity, dendritic &epithelial cell interactions, intraepithelial lymphocytes, M-cells, as well as the gut associated lymphoid tissues where colonization after birth, clinician feeding practices, use of antibiotics as well as exposure to prebiotics, probiotics and maternal vaginal flora all program the neonate for a life-time of immune competence distinguishing "self" from foreign antigens. These barrier defense capacities become destructive during disease processes like necrotizing enterocolitis (NEC) when an otherwise maturationally normal, yet dysregulated and immature, immune defense system is associated with high levels of certain inflammatory mediators like TNFa. In Part II, the authors will discuss the theoretical advantages of using rhG-CSF in managing NEC or sepsis by augmenting neonatal neutrophil number and killing capacity including an unexpected, paradoxical and potent anti-TNFa function that may serve to limit extension of tissue destruction without impairing bacterial killing capacity. The authors conclude by arguing that NEC may be the ideal disease process for testing whether a clearly defined clinical benefit of cytokine therapy can prove beneficial.

Antibody Formation↗
PubMed2002

Early treatment with allopurinol in familial juvenile hyerpuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease.

BACKGROUND: The efficacy of allopurinol in autosomal dominant familial juvenile hyperuricaemic nephropathy (FJHN) has been disputed. AIM: To address this question, in the absence of controlled trials. DESIGN: Retrospective long-term follow-up study. METHODS: All kindreds were biochemically screened. Measurements included uric acid clearance, creatinine clearance, serum creatinine, and glomerular filtration rate (GFR). We used five siblings who had died or progressed to transplantation, ten other deceased relatives, and two index cases (one untreated, one non-compliant) as controls to assess the effects of allopurinol. RESULTS: Of eight families with FJHN, six had a strong history of renal disease and early parental death (mean age 41 years, n=10). Of 27 patients started immediately on allopurinol and treated uninterruptedly, 21 responded well, including three children born subsequently. Eight siblings (mean age 19 years) with a normal plasma creatinine at start (<120 micromol/l, mean GFR 80 ml/min/1.73 m(2)) retained stable renal function (mean 14.5 years, mean age 34 years, GFR 85 ml/min/1.73 m(2)). Of the 13 other responders, treated for up to 34 years, 10 with a creatinine <200 micromol/l at diagnosis (mean age 28 years, mean creatinine 137 micromol/l at start) now have a mean creatinine of 210 micromol/l. In contrast, five patients (mean age 26 years) with a creatinine >200 micromol/l (GFR <35 ml/min/1.73 m(2)) when allopurinol commenced, plus one untreated index case, all progressed rapidly (mean 6 years) to end-stage renal failure. In two others (one non-compliant, one initially untreated), GFR fell by >50% in 7 years. Introduction of allopurinol in the latter has stabilized GFR. DISCUSSION: Allopurinol reduced the morbidity and mortality from renal failure seen in untreated siblings and previous generations of these families. Early diagnosis of FJHN is important, so that treatment can begin before irreversible renal damage has developed.

Adolescent↗
PubMed1989

Regional monoamine and metabolite levels in a feline brain tumor model.

The presence of a brain tumor alters regional cerebral blood flow, oxygen consumption, and glucose utilization in adjacent and remote brain tissue, but its effect on brain neurotransmitter levels is unclear. In the present report, the levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in tumor tissue and gray and white matter obtained from cats with induced brain tumors were measured. Glioma cells (9L) were xenotransplanted into the central white matter of the right hemisphere, and 15 d later the brains were frozen in vivo. Samples of tumor, parietal (peritumor), temporal, and frontal gray and white matter were divided for analysis of water content and quantification of amines and their metabolites. The water content of white matter, but not gray matter, adjacent to the tumor was increased. Neurotransmitter amine and metabolite levels were much lower in the tumor than in brain tissue. In gray matter adjacent to the tumor, concentrations of DA and its metabolites HVA and DOPAC were significantly decreased from control, whereas 5-HIAA was increased. The NA, DA, HVA, and DOPAC levels were decreased in temporal gray matter, whereas all amine and metabolite levels were unchanged in frontal gray matter. These results indicate that altered neurotransmitter metabolism is one of the effects of the presence of a brain tumor.

Animals↗
PubMed1987

Gastrointestinal features of culture-positive Yersinia enterocolitica infection.

Yersinia enterocolitica was cultured from feces of 122 symptomatic adults in a single facility using selective culture media; all isolates were confirmed in an independent reference laboratory. Of 128 isolates, multiple serotypes were defined and all were biochemically typical for Yersinia enterocolitica. Other agents were seen in 20 patients; of these, seven were Yersinia fredriksenii and six were Clostridium difficile. Diarrhea (80%) and abdominal pain (64%) were common, whereas other features such as fever (9%) and bloody stools (8%) were unusual. Use of antibiotics (24%) or opiates (28%) in the month before culture was common. The terminal ileum was seen radiographically in 20 patients, but only two barium studies showed abnormalities. Fiberoptic endoscopy and biopsy studies, done in greater than 50% of the cases, showed minimal or no changes in most patients. However, 3 patients had pseudomembranous colitis with concomitant Clostridium difficile cytotoxin and 7 had diffuse severe colitis. New culture techniques, and possibly geographic differences, have contributed to the high isolation rates of this organism. Yersinia enterocolitica occurs sporadically, involves a variety of serotypes, and is associated with a broader clinical spectrum than was formerly appreciated.

Adolescent↗
PubMed1995

Quantitative evaluation of heme biosynthetic pathway parameters as biomarkers of low-level lead exposure in rats.

Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, erythrocyte zinc protoporphyrin (ZPP)/heme ratio, and urinary coproporphyrin (UC) concentration have been employed as biological indicators of moderate-to high-level lead exposure, corresponding to blood levels in excess of 50 micrograms/dl, in human subjects. The comparative efficacy of these measures as indicators of lead exposure consistent with sustained lower blood lead levels has not been systematically evaluated. In the present studies, we examined the relative sensitivity and magnitude of response of these three bioindicators in rats during chronic exposure to 0, 100, or 1000 ppm lead as lead acetate in drinking water for up to 10 wk, followed by a 10-wk postexposure period, with weekly assessments, or during subchronic exposure to 0 or 1000 ppm lead as lead acetate in drinking water for 6 d, with daily assessments. Analysis of variance (ANOVA) was used to determine if the lead-treated rats differed from controls and to distinguish between dose groups with respect to the three biochemical indices of lead exposure. The data were normalized by conversion to Z scores in order to compare indicators with regard to magnitude of change in response to lead treatment. The order of sensitivity of each indicator was determined by considering the magnitude of the correlation coefficient (r) between the indicator and the blood lead concentration in each study. The indicators in order of decreasing sensitivity to lead in the chronic study were UC > ZPP/heme > ALAD. The indicators in order of decreasing magnitude of change in response to change in blood lead level were also UC > ZPP/heme > ALAD. None of the heme pathway parameters was judged a satisfactory substitute for direct blood lead measurement as an indicator of low-level lead exposure. However, urinary coproporphyrin appears most useful in this respect owing to highest sensitivity and magnitude of change relative to blood lead content and relatively low variation of mean coproporphyrin levels.

Analysis of Variance↗
PubMed2006

Interventions for the prevention and management of neck/upper extremity musculoskeletal conditions: a systematic review.

Considered from medical, social or economic perspectives, the cost of musculoskeletal injuries experienced in the workplace is substantial, and there is a need to identify the most efficacious interventions for their effective prevention, management and rehabilitation. Previous reviews have highlighted the limited number of studies that focus on upper extremity intervention programmes. The aim of this study was to evaluate the findings of primary, secondary and/or tertiary intervention studies for neck/upper extremity conditions undertaken between 1999 and 2004 and to compare these results with those of previous reviews. Relevant studies were retrieved through the use of a systematic approach to literature searching and evaluated using a standardised tool. Evidence was then classified according to a "pattern of evidence" approach. Studies were categorised into subgroups depending on the type of intervention: mechanical exposure interventions; production systems/organisational culture interventions and modifier interventions. 31 intervention studies met the inclusion criteria. The findings provided evidence to support the use of some mechanical and modifier interventions as approaches for preventing and managing neck/upper extremity musculoskeletal conditions and fibromyalgia. Evidence to support the benefits of production systems/organisational culture interventions was found to be lacking. This review identified no single-dimensional or multi-dimensional strategy for intervention that was considered effective across occupational settings. There is limited information to support the establishment of evidence-based guidelines applicable to a number of industrial sectors.

Cost-Benefit Analysis↗
PubMed1987

Mortality of workers exposed to styrene in the manufacture of glass-reinforced plastics.

Epidemiologic studies have suggested an increased risk of leukemia and lymphoma among workers exposed to styrene. In a further exploration of this possible hazard, an analysis was conducted of the mortality among 7,949 men and women employed during 1947-1984 in eight British companies manufacturing glass-reinforced plastics. The subjects were identified from company files and traced to the end of 1984 through National Health Service and National Insurance records. The overall mortality in the cohort was less than in the national population (693 deaths observed, 830.1 expected) as was mortality from cancer (181 deaths observed, 223.7 expected). In particular, there was a deficit of deaths from lymphoid and hemopoietic cancer (6 observed, 14.9 expected). The small excess of lung cancer (89 deaths observed, 80.1 expected) was not statistically significant and can probably be attributed to chance. Among 3,494 hand laminators (the job with the highest exposure to styrene) there was one death from lymphoma and none from leukemia. The findings do not exclude the possibility that styrene is a human carcinogen, but give no support to the hypothesis that it causes leukemia and lymphoma.

Female↗
PubMed1979

Hypertension, renal function and gout.

Hypertension was found in 18% of 65 patients with untreated gout, a lower prevalence than that previously reported. The clinical characteristics and renal function of these patients were compared with those of age matched groups of both normotensive gouty subjects and normouricaemic patients. The hypertensive patients had significantly greater body weights than their controls and also had a lower glomerular filtration rate. Other aspects of renal function were not significantly different between the three groups. The association of hypertension with gout and impaired renal function is complicated by many possible contributory factors and a simple cause and effect relationship is unlikely.

Adult↗
PubMed1997

Association between chronic hepatitis C infection and hepatocellular carcinoma in a Scottish population.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The geographical prevalence varies considerably in different countries and Scotland is regarded as an area of low risk for the disease. AIMS: To assess the association between chronic hepatitis C infection (HCV) and HCC in a population of patients presenting to a single hospital. PATIENTS: One hundred and fourteen cases of histologically confirmed liver cancer presenting to the Royal Infirmary of Edinburgh between 1985 and 1994 were examined. METHODS: Of 114 cases of HCC, 80 samples of stored sera were available. Samples positive for HCV Ab were genotyped by restriction fragment length polymorphism analysis of HCV c-DNA. A population of 29 cirrhotic patients (diagnosed between 1985 and 1994) with chronic HCV infection was also genotyped. RESULTS: Chronic HCV infection was a major risk factor (30% of tested HCC patients) identified. HCV genotype 1b was predominant (16 of 20 patients). The time from HCV transmission to development of cancer ranged from 10 to 50 years (median 30). In the cirrhotic patient population, a broader distribution of genotypes was present (genotype 1a: 7; genotype 1b: 8; genotype 2b: 3; genotype 3a: 8 and genotype 4: 2). However, this population was significantly younger. (Mean (SD) 52 (14.5) years) (p = 0.0002) and demonstrated a significantly shorter duration of infection: range 10-40 years (median: 19). CONCLUSION: There is a strong association between chronic HCV infection, cirrhosis, and hepatocarcinogenesis in this Scottish population. The study was unable to distinguish whether the high prevalence of genotype 1b in the HCC population reflected increased oncogenicity in itself, or whether 1b was simply the most prevalent genotype in Scotland when these patients were infected.

Aged↗
PubMed2001

Reconstructing the origins of human hepatitis viruses.

Infections with hepatitis B and C viruses (HBV, HCV) are widespread in human populations throughout the world, and are major causes of chronic liver disease and liver cancer. HBV, HCV and the related hepatitis G virus or GB virus C (referred to here as HGV/GBV-C) are capable of establishing persistent, frequently lifelong infections characterized by high levels of continuous replication. All three viruses show substantial genetic heterogeneity, which has allowed each to be classified into a number of distinct genotypes that have different geographical distributions and associations with different risk groups for infection. Information on their past transmission and epidemiology might be obtained by estimation of the time of divergence of the different genotypes of HCV, HBV and HGV/GBV-C using knowledge of their rates of sequence change. While information on the latter is limited to short observation periods and is therefore subject to considerable error and uncertainty, the relatively recent times of origin for genotype of each virus predicted by this method (HCV, 500-2000 years; HBV, 3000 years; HGV/GBV-C, 200 years) are quite incompatible with their epidemiological distributions in human populations. They also cannot easily be reconciled with the recent evidence for species-associated variants of HBV and HGV/GBV-C in a range of non-human primates. The apparent conservatism of viruses over long periods implied by their epidemiological distributions instead suggests that nucleotide sequence change may be subject to constraints peculiar to viruses with single-stranded genomes, or with overlapping reading frames that defy attempts to reconstruct evolution according to the principles of the 'molecular clock'. Large population sizes and intense selection pressures that optimize fitness may be additional factors that set virus evolution apart from that of their hosts.

Animals↗
PubMed1999

A new variant of GB virus C/hepatitis G virus (GBV-C/HGV) from South Africa.

Phylogenetic analysis of the 5' non-coding region (5'NCR) sequences has demonstrated that GB virus C/hepatitis G virus (GBV-C/HGV) can be separated into three major groups that correlate with the geographic origin of the isolate. Sequence analysis of the 5'NCR of 54 GBV-C/HGV isolates from 31 blood donors, 11 haemodialysis patients and 12 patients with chronic liver disease suggests the presence of a new variant of GBV-C/HGV in the province of KwaZulu Natal, South Africa. Eleven isolates grouped as group 1 variants (bootstrap support, 90%) found predominantly in West and Central Africa, a further six isolates grouped as group 2 variants (bootstrap support, 58%) found in Europe and North America; five of which grouped as 2a (bootstrap support, 91%) and one as 2b (bootstrap support, 87%), the latter also includes isolates from Japan, East Africa and Pakistan. Although the remaining 37 GBV-C/HGV isolates were more closely related to group 1 variants (bootstrap support, 90%), they formed a cluster, which was distinct from all other known GBV-C/HGV sequences. None of the South African isolates grouped with group 3 variants described from Southeast Asia. Three variants of GBV-C/HGV exist in KwaZulu Natal: groups 1, 2 and a new variant, which is distinct from other African isolates.

Base Sequence↗