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Biomedical subjects

A Fletcher

Publications and source records attributed to A Fletcher.

At least 55 records · Page 3Linked to original sources
PubMed2000

Basement membrane peptides as markers of liver disease in chronic hepatitis C.

BACKGROUND/AIM: Chronic hepatitis C is characterised by slow progression to liver fibrosis. In liver fibrosis, basement membrane components are increasingly deposited around the vessels and in the portal tracts. Serum assays can measure the two major components of the basement membrane, type IV collagen and laminin. The aim of this study was to determine whether serum levels of type IV collagen and laminin are related to severity of liver injury in chronic hepatitis C. METHODS: Thirty-seven patients with chronic hepatitis C (CHC) and five healthy controls were studied. Serum type IV collagen was measured by a one-step sandwich EIA kit (Fuji, Japan) and serum laminin was measured by RIA (CIS, UK). Liver biopsies in patients with CHC were scored using a previously described grading and staging system. Liver biopsy scores were compared to serum levels of laminin, type IV collagen and alanine aminotransferase (ALT). Receiver operating characteristic (ROC) analysis was used to compare the ability of the assays to detect advanced liver injury. RESULTS: The median serum concentration of type IV collagen was 127.1 ng/ml (range 17.7 to 317.4) in CHC patients compared to a median of 61.3 ng/ml (range 11.5 to 102.3) in controls, p=0.006. The median serum concentration of laminin was 1.12 U/ml (range 0.74 to 2.46) in CHC compared to a median of 0.87 U/ml (range 0.83 to 1.06) in controls, p=0.07. Both serum type IV collagen and laminin were significantly correlated with the fibrotic stage and also with the necroinflammatory injury scores- histological activity index, portal inflammation and periportal hepatitis. Serum ALT was significantly correlated with portal inflammation. Using ROC analysis, the area under the curve for type IV collagen and laminin was 0.83 (p=0.001) and 0.82 (p=0.0017), respectively, while the area under the curve for ALT was 0.54 (p=0.1). CONCLUSIONS: Serum assays of basement membrane peptides are accurate non-invasive markers of liver fibrosis and liver inflammation in chronic hepatitis C. These markers are superior to serum ALT in reflecting liver injury and they have high specificity and sensitivity in detecting advanced liver disease in chronic hepatitis C.

Basement Membrane↗
PubMed2000

Influence of neuroticism, catastrophizing, pain duration, and receipt of compensation on short-term response to nerve block treatment for chronic back pain.

This study investigated the influence of pain catastrophizing, neuroticism, pain duration, and receipt of compensation for 60 patients undergoing nerve block treatment for chronic back pain. Follow-up assessment 1 week following nerve block treatment found that neither neuroticism nor catastrophizing predicted level of reported pain or extent of disability. However, receipt of compensation and duration of pain were both associated with reduced benefit from treatment. The above four variables combined were able to account for 24% of the outcome variance in both level of pain and extent of disability. Possible causal patterns related to compensation and treatment outcome, limitations of the study, and directions for future research are discussed.

Adult↗
PubMed2000

Recent advances in the pre-mortem diagnosis of Creutzfeldt-Jakob disease.

Included in the spectrum of human transmissible spongiform encephalopathies are Creutzfeldt-Jakob disease (CJD) and the new variant form (vCJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, kuru and various less distinct neuropsychiatric disorders. Progress in our understanding of this group of disorders continues at a prodigious rate, although important vexing practical issues persist. The definitive confirmation of symptomatic prion disease still requires pathological examination, most reliably performed post-mortem. However, paralleling the recent advances in the molecular biological understanding of normal prion protein (PrP(c)) function and the pathophysiology of prion diseases, there have been worthwhile developments in the pre-mortem diagnosis of CJD. Efforts to develop less invasive but very reliable ante-mortem diagnostic tests have received an additional impetus because of the potential epidemic of vCJD. Historically, the ancillary investigation of most merit has been the EEG, whereas the recent advances have encompassed a broader range of technologies, including both magnetic resonance and radioisotopic neuroimaging, and immunoassays for a range of non-specific marker proteins in both CSF, and less commonly, blood. However, given the recent refinement of sophisticated immunoassays, it is envisaged that the pathognomonic, protease-resistant, disease-associated isoforms of the prion protein (PrPres) may soon be directly detectable in the blood and tissues of patients manifesting or incubating a spongiform encephalopathy.

Biomarkers↗
PubMed2000

Creutzfeldt-Jakob disease: diagnostic utility of 14-3-3 protein immunodetection in cerebrospinal fluid.

With the aim of improving the pre-mortem diagnostic accuracy of sporadic Creutzfeldt-Jakob disease (CJD), there has been considerable recent interest in the merit of immunodetecting 14-3-3 proteins in the cerebrospinal fluid (CSF) using Western blotting, with cumulative support for the utility of this technique. As a corollary, during a 20 month period, CSF samples from an unselected prospective series of 124 patients in whom sporadic CJD was a differential diagnostic possibility were examined by the Australian Creutzfeldt-Jakob disease Registry (ACJDR) for the presence of 14-3-3 proteins. Follow up to achieve a final diagnosis or clinical outcome was successful in 119. For definite and probable sporadic CJD combined, a positive result was 91.4% sensitive, while the sensitivity for the pathologically verified group alone was 96.0%. A negative outcome was 92.5% specific with false positive results seen in five patients with diagnoses which included inflammatory CNS disorders, cerebral ischaemia and dementia with Lewy bodies (DLB). Immunodetectable 14-3-3 proteins were present in three of four symptomatic patients with prion protein gene (PRNP) mutations. CSF samples containing significant amounts of blood were confirmed as suboptimal, with weak or qualitatively unusual positive results found in greater than 50% of such specimens, with only one of 14 such cases ultimately classified as definite or probable CJD.

14-3-3 Proteins↗
PubMed2000

Re-survey of the Whitehall study of London civil servants: changes in risk factors for cardiovascular disease during 29 years of follow-up.

BACKGROUND: Substantial uncertainty persists about the relevance of blood pressure and cholesterol to the risk of cardiovascular disease in the elderly. OBJECTIVE: To investigate the determinants of cardiovascular risk in old age, and the relevance of such risk factors when recorded in middle and old age. METHODS: A re-survey in 1997 of 8537 survivors of a cohort of men who were originally examined in 1967-1970 when aged 40-69 years. RESULTS: Completed questionnaires were received from 7050 (82%) of the survivors, and blood pressure and blood samples from 5427 (64%). The response rate declined with increasing age, was inversely related to markers of socioeconomic status in 1967-70 and in 1997, and was lower in those who had been current smokers or had a higher blood pressure level in 1967-70. After excluding those with reported cardiovascular disease (25% of respondents), the mean levels of total cholesterol and apolipoprotein B were lower in older age groups, whereas apolipoprotein A1 levels did not vary much with age. Among those with risk factors recorded both in 1967-70 and 1997, the prevalence of smoking had declined by two-thirds (32% in 1970 and 12% in 1997), the prevalence of diabetes had increased (0.3% versus 4.5%), and the mean systolic blood pressure had increased by 16 mmHg (130 versus 146 mmHg), but the diastolic blood pressure had not changed materially (80 versus 81 mmHg), and the measured levels of total cholesterol had increased by 0.5 mmol/l (although that change may be artefactual). CONCLUSION: Follow-up of vital status in this cohort should permit an assessment of the relevance of risk factors recorded in middle and old age to cardiovascular disease in old age.

Adult↗
PubMed2000

Gyrodactylus anguillae (Monogenea: Gyrodactylidae) from anguillid eels (Anguilla australis and Anguilla reinhardtii) in Australia: a native or an exotic?

A species of Gyrodactylus collected from 2 species of anguillid eels (Anguilla australis Richardson, 1841 and Anguilla reinhardtii Steindachner, 1867) from Australia is identified as Gyrodactylus anguillae Ergens, 1960. The morphology of sclerites of G. anguillae specimens from Australia is in accordance with previous descriptions of specimens collected from A. anguilla (Linnaeus, 1758) from Europe and A. anguilla imported into Japan. Gyrodactylus anguillae was previously thought to be a parasite specific to A. anguilla, an eel that is native to freshwater catchments throughout Europe. Information on eel translocations and host and parasite biology is reviewed and it is hypothesized that G. anguillae is a naturally occurring parasite in Australia and not an introduction.

Anguilla↗
PubMed1999

Sleeping with an electric blanket: effects on core temperature, sleep, and melatonin in young adults.

Previous studies have inferred a relationship between core temperature and sleep disruption from manipulations of core temperature such as heating prior to sleep or administration of hyperthermic substances. To examine the relationship more directly, this study aimed to produce a direct increase in core temperature during the sleep period. Following an adaptation night, 16 subjects underwent counter-balanced baseline and experimental conditions, on non-consecutive nights between 1900 and 0800h. In the experimental condition, subjects were heated between 0230h and wake up, which significantly increased mean core temperature from baseline levels between 0400 and 0700h by 0.18 +/- 0.03 degree C (mean +/- SEM, p < 0.05). This increase in core temperature was associated with a significant decrease in sleep efficiency between 0330 and 0730h of 5.5 +/- 0.9% (mean +/- SD, p < 0.05). Polysomnographic measures indicated a significant increase in the number of stage changes and the amounts of stage 0 and stage 1 sleep (p < 0.05). Other stages of sleep and the number and duration of arousals were not significantly effected by heating. There was a strong trend toward and increase in the number of arousals (p = 0.054), however, core body temperature did not increase across arousals. Also, melatonin output was not effected by heating. Taken together, these results suggest that increased nocturnal core temperature alone may disrupt sleep. Additionally, the results support evidence suggesting that the circadian regulation of the sleep/wake cycle may be mediated via core temperature.

Adult↗
PubMed1999

Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study.

BACKGROUND: Apart from the small number of iatrogenic and familial cases, the cause of most cases of Creutzfeldt-Jakob disease (CJD) is not known. We aimed to identify risk factors for sporadic CJD. METHODS: In a case-control study, we compared the medical history and selected demographic characteristics of 241 definite (neuropathologically confirmed) and probable (clinically likely) patients with CJD, ascertained from the Australian National Creutzfeldt-Jakob Disease Registry between Jan 1, 1970, and October 31, 1997, and of 784 controls, recruited from the community by random telephone interview in August, 1997. Standard logistic regression was used for the comparisons. FINDINGS: Surgical procedures were significantly associated with the development of sporadic CJD. This risk progressively increased with the number of surgical treatments to a maximum for three procedures (odds ratio 2.13 [95% Cl 1.34-3.41], p=0.002). There was also a significant association between risk of CJD and residence or employment on a farm (p<0.001) or market garden (p=0.002) for longer than 10 years. We found no significant risk associated with a history of blood transfusion, organ transplantation, major dental work, or occupation. INTERPRETATION: Our findings accord with the hypothesis that a range of surgical treatments may serve as unrecognised contamination events and account for a proportion of cases of sporadic CJD. Possible biases in different methods and times for the acquisition of data on cases and controls suggest our findings need to be replicated in independent studies with community controls.

Adolescent↗
PubMed1999

Comparison of assays for N-amino terminal propeptide of type III procollagen in chronic hepatitis C by using receiver operating characteristic analysis.

OBJECTIVE: During the process of liver fibrosis, type III procollagen is converted to type III collagen by cleavage of its amino terminal and carboxy terminal propeptides. Serum levels of amino terminal propeptide of type III procollagen (PIIINP) are a marker of collagen turnover in liver fibrosis. Two assays for PIIINP are available, one which measures both Col 1-3 (collagen synthesis) and Col 1 (collagen degradation) peptides, and one which measures Col 1-3 only. Using receiver operating characteristic analysis, the two PIIINP assays were compared with serum ALT as markers of liver disease in chronic hepatitis C. METHODS: Serum PIIINP was measured using both assays in 33 patients with chronic hepatitis C and five healthy controls. Liver biopsies in chronic hepatitis C patients were scored using a previously described grading and staging system. RESULTS: Serum PIIINP was significantly elevated in chronic hepatitis C compared to controls using both the combined Col 1-3 and Col 1 (median 0.61 vs 0.33 U/ml, P=0.001) and Col 1 assays (median 6.5 vs 3.5 microg/l, P=0.006). Serum PIIINP measured by the combined assay was significantly related to liver fibrosis, periportal necrosis and histological activity index (P<0.05). The area under the curve for specificity and sensitivity in detecting advanced liver disease was only significant for the combined assay (P=0.017). Serum PIIINP measured by the Col 1 assay was not related to these indices of disease severity while serum ALT was only related to portal inflammation. CONCLUSION: A serum PIIINP assay which measures both Col 1-3 and Col 1 peptides instead of Col 1-3 peptide alone is more predictive of severity of liver disease and should be used in preference as a non-invasive marker of liver injury in chronic hepatitis C.

Adult↗
PubMed1999

Socioeconomic and demographic predictors of mortality and institutional residence among middle aged and older people: results from the Longitudinal Study.

STUDY OBJECTIVES: To identify socioeconomic and demographic predictors of long term mortality and institutional residence in old age, taking into account changes in socioeconomic and demographic circumstances between the 1971 and 1981 censuses. DESIGN: Multivariate logistic regression modelling of outcomes for 10 year age cohorts of each gender. The outcomes were death by 31 December 1992; being in an institution in 1991. SETTING: Members of the Longitudinal Study (a 1% sample of the British Census): 43,092 men and 50,839 women aged 55-74 in 1971. MAIN RESULTS: Being in rented accommodation and in a household without access to a car carried 35-45% higher mortality rate over 21 years and similar excess risk of being in an institution in 1991. Marital status and living arrangements were weaker predictors of death but being single was a major predictor of moving to an institution for men. Losing household access to a car was a strong factor for mortality for men and for institutionalisation for men aged 55-64 in 1971. The effects were weaker for women. Moving into rented accommodation was a predictor of both outcomes for women and of death for the younger cohort of men. People who started to live alone in the inter-census period were at reduced risk of dying. CONCLUSIONS: These results demonstrate persistence of inequalities in health related outcomes throughout old age, both in those with unfavourable circumstances in mid-life and in those who, in later life, have lost earlier advantages.

Aged↗
PubMed1998

Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings.

The Munc-18-syntaxin 1A complex has been postulated to act as a negative control on the regulated exocytotic process because its formation blocks the interaction of syntaxin with vesicle SNARE proteins. However, the formation of this complex is simultaneously essential for the final stages of secretion as evidenced by the necessity of Munc-18's homologues in Saccharomyces cerevisiae (Sec1p), Drosophila (ROP), and Caenorhabditis elegans (Unc-18) for proper secretion in these organisms. As such, any event that regulates the interaction of these two proteins is important for the control of secretion. One candidate for such regulation is cyclin-dependent kinase 5 (Cdk5), a member of the Cdc2 family of cell division cycle kinases that has recently been copurified with Munc-18 from rat brain. The present study shows that Cdk5 bound to its neural specific activator p35 not only binds to Munc-18 but utilizes it as a substrate for phosphorylation. Furthermore, it is demonstrated that Munc-18 that has been phosphorylated by Cdk5 has a significantly reduced affinity for syntaxin 1A. Finally, it is shown that Cdk5 can also bind to syntaxin 1A and that a complex of Cdk5, p35, Munc-18, and syntaxin 1A can be fashioned in the absence of ATP and promptly disassembled upon the addition of ATP. These results suggest a model in which p35-activated Cdk5 becomes localized to the Munc-18-syntaxin 1A complex by its affinity for both proteins so that it may phosphorylate Munc-18 and thus permit the positive interaction of syntaxin 1A with upstream protein effectors of the secretory mechanism.

Animals↗
PubMed1998

High-resolution sonography of the abnormal cranial suture.

OBJECTIVE: The purpose of this investigation is to elucidate the sonographic features of abnormal major cranial sutures. MATERIALS AND METHODS: Eight excised synostosed suture specimens were evaluated. The high-resolution sonographic appearance was correlated with the histological section, plain radiographs, CT and MRI. Diastatic and molded sutures were also evaluated with sonography and compared with the normal cranial suture appearance. RESULTS: Synostosed sutures demonstrated one or more of the following features: (a) loss of echo-poor fibrous gap between bony plates (five sagittal and coronal synostoses); (b) irregular thickened inner sutural margin (three lambdoid synostoses); (c) loss of bevelled edge (one lambdoid synostosis); (d) asymmetric anterior fontanelle (one coronal synostosis). Cranial molding results in an overlap of echogenic bony plates. Sutural width (the distance between bony plates) is increased in cases of elevated intracranial pressure. CONCLUSION: Sonography is an inexpensive, radiation-free modality which can confirm synostosis versus molding versus an underlying intracranial lesion as a cause of plagiocephaly. The high-resolution sonographic images also provide a relatively easy means to assess sutural width and may provide information in regard to increased intracranial pressure.

Cranial Sutures↗
PubMed1998

The Madurai Intraocular Lens Study. III: Visual functioning and quality of life outcomes.

PURPOSE: To compare the effects of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) vs intracapsular cataract extraction with aphakic glasses (ICCE-AG) on everyday visual functioning and quality of life. METHODS: In a nonmasked randomized controlled clinical trial, 3,400 bilateral vision-impaired patients, aged 40 to 75 years, with operable cataract were randomly assigned to receive one of the two treatment options. One half in each group were randomly selected for interviewer administration of visual functioning and quality of life questionnaires before surgery and at 6 and 12 months after surgery. RESULTS: Both ICCE-AG and ECCE/PC-IOL produced dramatic improvements in visual functioning and quality of life scores. Patients receiving ECCE/PC-IOL reported larger beneficial changes than did those receiving ICCE-AG, compatible with additional beneficial effects of a moderate magnitude for visual functioning and of a smaller beneficial magnitude for quality of life. All between-group differences were highly statistically significant (P < .00001). The additional benefits of ECCE/PC-IOL are not explained by visual acuity differences. A higher proportion of patients in the ICCE-AG group reported problems on a vision problem checklist at 6 months (more than 50%) than did patients in the ECCE/PC-IOL group (approximately 30%). CONCLUSIONS: In this developing-country setting, ICCE-AG and ECCE/PC-IOL were associated with substantial benefits in improved everyday vision function and vision-related quality of life. Patients who received ECCE/PC-IOL reported greater benefits and fewer problems with vision than did patients who received ICCE-AG.

Adult↗
PubMed1998

Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety.

The elevated plus-maze is a commonly used model to identify putative anxiolytic and anxiogenic drugs. However, the validity of elevated plus-maze and other recently developed variants such as the elevated zero-maze has recently been questioned on the grounds that both the reference anxiolytic drug chlordiazepoxide and the psychostimulant d-amphetamine increase open arm exploration and stimulate locomotor activity. These findings suggest that measures of "anxiety" in the elevated maze cannot be adequately dissociated from simple changes in locomotor activity, which may confound the interpretation of results obtained using these models. A variety of approaches to assess drug effects on locomotor activity in the elevated maze have been suggested, including the use of total and closed arm entries, as well as supplementary tests such as exploration of the holeboard apparatus. However, all these approaches utilise the measurement of exploration in a novel environment, and as such, could potentially be influenced by either changes in anxiety or locomotor activity. Recently, it has been shown that ethological measures of "risk assessment", such as stretched-attend postures and head-dipping, are sensitive indicators of drug-effects in the elevated maze. The present study assessed the utility of ethological analysis in dissociating locomotor activity from "anxiety" by comparing the effects of d-amphetamine to those of chlordiazepoxide in the rat elevated zero-maze. The results showed that both chlordiazepoxide and d-amphetamine increase the amount of time spent in the open arms and reduce "risk assessment" without increasing line crossing or rearing. These results confirm that under certain test conditions, psychostimulants are capable of producing "false-positives" in elevated maze models, and that both traditional methods and the ethological measures used in this study fail to unequivocally dissociate drug effects on anxiety from effects on locomotor activity. Further studies using other species and different classes of psychostimulants are warranted to determine the generality of these findings.

Animals↗