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Biomedical subjects

W Smith

Publications and source records attributed to W Smith.

At least 109 records · Page 6Linked to original sources
PubMed1998

Diabetes in an older Australian population.

PURPOSE: To describe the prevalence of self-reported diabetes and undiagnosed diabetes using new fasting plasma glucose (FPG) criteria, and vascular associations with diabetes history in a representative sample of older Australians attending the population-based Blue Mountains Eye Study. METHODS: 3654 people aged 49 years or older, representing 88% of permanent residents in two postcode areas west of Sydney, underwent a detailed medical and eye examination. This included history of diabetes, vascular events and vascular risk factors. Fasting pathology tests, including glucose, were obtained for 88% of these subjects. RESULTS: A diabetes history was given by 217 people (5.9%), including 7.0% of men and 5.2% of women. Elevated FPG (> or = 7.0 mmol/l) was found in a further 66 people (2.2% of persons who had FPG performed) and Impaired Fasting Glucose (FPG > or = 6.1 mmol/l and < 7.0 mmol/l) was found in a further 127 people (4.2%). History of diabetes was associated with an increased prevalence of obesity, elevated mean blood pressure and serum triglycerides, and lower mean serum cholesterol and HDL-cholesterol. Statistically significant associations were found between diabetes history and history of angina, acute myocardial infarction, stroke, gout and thyroid disease, after adjusting for age and sex using logistic regression. The vascular relationships with diabetes were stronger among people who currently smoked. CONCLUSIONS: This study has found similar diabetes prevalence to recently published Australian National Health Survey findings. Strong cross-sectional associations between diabetes history and vascular events and increased prevalence of vascular risk factors among older subjects with diabetes emphasise the need to address vascular risk factors in this group.

Aged↗
PubMed1998

Sulfur mustard induces markers of terminal differentiation and apoptosis in keratinocytes via a Ca2+-calmodulin and caspase-dependent pathway.

Sulfur mustard (SM) induces vesication via poorly understood pathways. The blisters that are formed result primarily from the detachment of the epidermis from the dermis at the level of the basement membrane. In addition, there is toxicity to the basal cells, although no careful study has been performed to determine the precise mode of cell death biochemically. We describe here two potential mechanisms by which SM causes basal cell death and detachment: namely, induction of terminal differentiation and apoptosis. In the presence of 100 microM SM, terminal differentiation was rapidly induced in primary human keratinocytes that included the expression of the differentiation-specific markers K1 and K10 and the cross-linking of the cornified envelope precursor protein involucrin. The expression of the attachment protein, fibronectin, was also reduced in a time- and dose-dependent fashion. Features common to both differentiation and apoptosis were also induced in 100 microM SM, including the rapid induction of p53 and the reduction of Bcl-2. At higher concentrations of SM (i.e., 300 microM), formation of the characteristic nucleosome-sized DNA ladders, TUNEL-positive staining of cells, activation of the cysteine protease caspase-3/apopain, and cleavage of the death substrate poly(ADP-ribose) polymerase, were observed both in vivo and in vitro. Both the differentiation and the apoptotic processes appeared to be calmodulin dependent, because the calmodulin inhibitor W-7 blocked the expression of the differentiation-specific markers, as well as the apoptotic response, in a concentration-dependent fashion. In addition, the intracellular Ca2+ chelator, BAPTA-AM, blocked the differentiation response and attenuated the apoptotic response. These results suggest a strategy for designing inhibitors of SM vesication via the Ca2+-calmodulin or caspase-3/PARP pathway.

Apoptosis↗
PubMed1998

Cleveland Clinic continuous flow blood pump: progress in development.

The Cleveland Clinic continuous flow blood pump is the central element of our innovative ventricular assist system (IVAS). Recent progress has been made in the design/fabrication of a pulsatile mock loop, journal bearing materials testing, and evaluation of a system control algorithm. These results have allowed an acceleration of our program.

Algorithms↗
PubMed1998

Reversible renal failure in a patient with the hypereosinophilia syndrome during therapy with alpha interferon.

Human recombinant interferon (IFN)-alpha (alpha)-2b was given to a 57-year-old man with hypereosinophilia syndrome refractory to prednisone and hydroxyurea. One year later, he developed progressive renal failure and nephrotic-range proteinuria. Percutaneous kidney biopsy showed focal and segmental glomerular and mesangial sclerosis, chronic interstitial nephritis, and focal tubular necrosis. Discontinuation of cytokine therapy led to marked improvement in renal function and significant reduction in proteinuria. The potential role of IFN-alpha as the cause of renal failure and nephrotic-range proteinuria is discussed. The spectrum of renal disease attributed to IFN-alpha and the proposed pathogenic mechanisms are reviewed.

Acute Kidney Injury↗
PubMed1998

Family history and age-related maculopathy: the Blue Mountains Eye Study.

PURPOSE: To assess the associations between stages of age-related maculopathy (ARM) and reported family history of this eye disease. METHODS: A cross-sectional study of 3654 subjects from a defined geographical area west of Sydney (NSW, Australia) identified subjects with late age-related macular degeneration (AMD) and early ARM from masked detailed grading of retinal photographs. Interviewer-administered questionnaires provided data on family history of ARM. Logistic regression was used to assess associations, adjusting for other known risk factors. RESULTS: A family history of ARM was significantly associated with both late AMD (odds ratio (OR) 3.92; 95% confidence interval (CI) 1.34-11.46) and early ARM (OR 2.17; 95% CI 1.04-4.55). The association was highest for neovascular AMD. CONCLUSIONS: These findings provide persuasive evidence that a stated family history of ARM is an important risk factor for ARM.

Aged↗
PubMed1998

Prevalence and vascular associations with migraine in older Australians.

BACKGROUND: Migraine is a common disorder with recently described vascular associations, yet there are few Australian population-based data describing migraine prevalence. AIMS: To assess the prevalence and vascular associations with lifetime past history of typical migraine headache in a representative sample of older Australians. METHODS: The Blue Mountains Eye Study examined 3654 permanent residents aged 49 or older living in two postcode areas, west of Sydney (82.4% participation) during 1992-4. A structured interview was administered, including questions about past or present history of typical migraine. The diagnosis was consistent with International Headache Society criteria. RESULTS: A lifetime past history of typical migraine was given by 17% of participants, including 22% of women and 10% of men, a female:male ratio of 2.3:1. A marked trend for declining lifetime migraine frequency with increasing age was found for both sexes. Modest statistically significant associations were found with vascular disease history, after multivariate adjustment, which included vascular risk factors. These associations were stronger in men than in women. Among men, typical migraine was significantly associated with history of angina, odds ratio (OR) 2.0, acute myocardial infarction (OR 1.9) and stroke (OR 2.2). Among women, statistically significant associations were present only with history of myocardial infarct (OR 1.8). CONCLUSIONS: These data indicate similar prevalence rates for lifetime typical migraine history in a representative sample of older Australians, compared to recent US and Canadian populations. Modest, statistically significant associations between typical migraine and past history of vascular disease were found, with the strongest associations found in men.

Aged↗
PubMed1998

Validity and reproducibility of a self-administered food frequency questionnaire in older people.

This study assesses the validity and reproducibility of a 145-item self-administered food frequency questionnaire (FFQ) in a representative older population aged 63 to 80. Semi-quantitative FFQs were completed by 89% of 3,654 residents attending a community-based eye study in Sydney, Australia. The FFQ's validity was assessed against three, four-day weighed food records (WFRs) completed four months apart by 79 people. A further 152 subjects completed a repeat FFQ about a year after the baseline FFQ, of whom 131 completed a second repeat FFQ about six weeks later. Both short and long-term reproducibility of the FFQ were assessed using data from these subjects. Comparison of the FFQ with the average of the three, four-day weighed food records resulted in energy-adjusted Spearman correlations above 0.5 for most of the nutrients. The proportion of subjects correctly classified to within one quintile category for each nutrient intake ranged from 57% for zinc to 82% for vitamin C. with most nutrients correctly classified within one quintile for about 70% of subjects. Quadratic weighted kappas were reasonable, between 0.3 and 0.5 for most nutrients. The FFQ was highly reproducible in the short term, with correlations for most nutrients about 0.70 to 0.80 and acceptably reproducible in the longer term, with correlations mostly 0.60 to 0.70. The results verify that it is possible to use relatively simple, but comprehensive, self-administered FFQs to study nutrient exposures in large-scale epidemiological studies of the elderly and to expect reasonably high FFQ response rates.

Aged↗
PubMed1998

Bilateral involvement by age related maculopathy lesions in a population.

AIMS: To describe the influences of age and sex on the frequency of bilateral age related macular degeneration (AMD) and age related maculopathy (ARM) lesions. METHODS: The Blue Mountains Eye Study examined 3654 older Australians, 82% of permanent residents living in an area west of Sydney. Stereo macular photographs were graded for AMD (neovascular maculopathy and geographic atrophy) and early ARM lesions (soft drusen, reticular drusen, hyperpigmentation, and hypopigmentation). RESULTS: Among 230 gradable cases of AMD or early ARM, 183 (80%) were bilateral. For AMD, 39/69 cases (57%) were bilateral, while for early ARM, 123/161 cases (77%) had signs in both eyes. Of the individual lesions, reticular drusen (91%) and indistinct soft drusen (79%) were most frequently present in both eyes. Geographic atrophy was bilateral in 56%, neovascular AMD in 40%, and distinct soft drusen in 47%, while hyperpigmentation was bilateral in 38% and hypopigmentation in only 28% of cases. A consistent age related increase in bilateral distribution was observed for most lesions. After adjusting for effects of age, current smoking, and AMD family history AMD and ARM component lesions, except for soft drusen, were more frequently bilateral in women. This sex difference was significant only for neovascular AMD, odds ratio 7.7 (95% confidence intervals 1.3-46.7). An AMD family history was more frequently reported in cases with bilateral involvement. CONCLUSIONS: This study has documented differences in the age related bilaterality of individual ARM components with higher bilateral rates for reticular or indistinct soft drusen compared with other lesions. The increased bilaterality of most ARM lesions among women is likely to contribute to the increased age adjusted risk of AMD blindness found in women.

Age Factors↗
PubMed1998

House dust mite allergen characterisation: implications for T-cell responses and immunotherapy.

T cells are central regulators and mediators of allergic sensitisation and disease. The house dust mite allergens are a biochemically diverse group of proteins which are present in extracts and the environment in a wide range of concentrations. Here the importance of ascertaining the contribution of the different allergens to Th2 lymphokine production and the development of allergy is discussed as well as the effect of allelic polymorphisms and inter-species sequence diversity on T-cell activation. The imbalances in allergen concentrations in commercial extracts, the sequence variations from allergens in the environment and the poor discrimination of allergy due to different mite species points to areas of improvement and the development of novel immunotherapeutic strategies and reagents.

Alleles↗
PubMed1998

Antimicrobial properties of human lysozyme transgenic mouse milk.

The antimicrobial properties of standard human lysozyme and the milk of transgenic mice expressing human lysozyme were investigated using bacterial strains important to the dairy industry. Standard human lysozyme was found to be effective at significantly slowing the growth of the milk cold-spoilage organism Pseudomonas fragi (P < 0.001), of a clinical isolate of the mastitis-causing organism Staphylococcus aureus (P < 0.005), and a nonpathogenic strain of E. coli (P < 0.05). Milk from transgenic mice secreting human lysozyme in their milk at an average concentration of 0.3 mg/ml was found to be bacteriostatic against the cold-spoilage organisms Pseudomonas fragi and Lactobacillus viscous and a mastitis-causing strain of Staphylococcus aureus, but not against a pathogenic strain of E. coli. These results demonstrate that transgenic animals producing human lysozyme in their milk can affect the microbial nature of milk.

Animals↗
PubMed1998

Hematological indices in an older population sample: derivation of healthy reference values.

Factors affecting hematological values were explored, and healthy reference values were estimated from a cross-sectional survey of a population (n = 4433), ages 49 years or more, residing permanently in a defined geographic region. Nursing home residents were excluded. Details of medication use and medical history were obtained by interview, and participants were asked to return after an overnight fast for blood sampling. The participation rate was 82.4%, of whom 88.4% provided a fasting blood sample. Hemoglobin, hematocrit, and erythrocyte counts were higher in men, whereas platelet counts were higher in women. Statistical associations between each hematological index and smoking, alcohol intake, use of certain drugs, chronic disease, and high creatinine values were tested by unpaired t-tests. Separate reference groups were defined for each hematological index by excluding subjects with any of the factors found to be of importance. The resulting reference values are particularly appropriate for evaluating hematological test results in older individuals.

Aged↗
PubMed1998

Refractive error and age-related maculopathy: the Blue Mountains Eye Study.

PURPOSE: To assess associations between refractive error (hyperopia, myopia, and spherical equivalent [SEq]) and age-related maculopathy (ARM) in an older population. METHODS: A population-based survey examined 3654 people aged 49 years or older, 82% of whom were permanent residents in an area west of Sydney, Australia. Participants had a detailed eye examination, including standardized refraction and stereo macular photographs. ARM was diagnosed from blinded photographic grading. Autorefractor measurements and subjective refraction were used to assess SEq refractive error for each eye in diopters. Mean SEq of the two eyes was used to define emmetropia, myopia, and hyperopia in each person. RESULTS: After known ARM risk factors (age, sex, ARM family history, current smoking) had been adjusted for, no association was found between mean SEq (two eyes) and late ARM (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.9-1.1). However, a statistically significant increased risk of early ARM was found for each diopter of increase in mean SEq (OR, 1.1; CI, 1.0-1.2). In logistic regression models, moderate to high hyperopia was significantly associated with increased early ARM risk (OR, 2.0; CI, 1.2-3.4). When a generalized estimating equation model (GEE), which assessed the relationship at eye level while accounting for the correlation between the two eyes, was used, this association was marginally insignificant (OR, 1.3; CI, 0.9-1.9). No significant associations were found between myopia and any ARM stage with either model. CONCLUSIONS: These population-based data suggest a weak association between hyperopia and early ARM.

Age Distribution↗
PubMed1997

Differential localization of voltage-dependent calcium channel alpha1 subunits at the human and rat neuromuscular junction.

Neurotransmitter release is regulated by voltage-dependent calcium channels (VDCCs) at synapses throughout the nervous system. At the neuromuscular junction (NMJ) electrophysiological and pharmacological studies have identified a major role for P- and/or Q-type VDCCs in controlling acetylcholine release from the nerve terminal. Additional studies have suggested that N-type channels may be involved in neuromuscular transmission. VDCCs consist of pore-forming alpha1 and regulatory beta subunits. In this report, using fluorescence immunocytochemistry, we provide evidence that immunoreactivity to alpha1A, alpha1B, and alpha1E subunits is present at both rat and human adult NMJs. Using control and denervated rat preparations, we have been able to establish that the subunit thought to correspond to P/Q-type channels, alpha1A, is localized presynaptically in discrete puncta that may represent motor nerve terminals. We also demonstrate for the first time that alpha1A and alpha1B (which corresponds to N-type channels) may be localized in axon-associated Schwann cells and, further, that the alpha1B subunit may be present in perisynaptic Schwann cells. In addition, the alpha1E subunit (which may correspond to R/T-type channels) seems to be localized postsynaptically in the muscle fiber membrane and concentrated at the NMJ. The possibility that all three VDCCs at the NMJ are potential targets for circulating autoantibodies in amyotrophic lateral sclerosis is discussed.

Amyotrophic Lateral Sclerosis↗