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Biomedical subjects

D H Wilson

Publications and source records attributed to D H Wilson.

At least 19 recordsLinked to original sources

Changes in the use of hormone replacement therapy in South Australia.

OBJECTIVE: To determine changes in the use of hormone replacement therapy (HRT) in South Australia between 1991 and 1993. DESIGN AND SETTING: Survey of women aged 40 years and over, as part of the 1991 and 1993 South Australian Health Omnibus Surveys (household interviews); 868 were interviewed in 1991 and 790 in 1993. OUTCOME MEASURES: Rates of HRT use. RESULTS: In 1993, 19.0% of women aged 40 years and over were taking HRT and 28.5% had ever taken it (currently or in the past). The highest rates were in the 50-54 years age group (46.2% current use and 57.8% ever use). Between 1991 and 1993 there was a 40% increase in the number of women taking HRT and a significant increase (P < 0.01) in the median duration of therapy, from 38 to 54 months. There were also significant increases in rates of use by country women and Australian-born women (P < 0.01). Premarin and Provera remained the most commonly used products in 1993. CONCLUSION: Australian perimenopausal women are increasingly using HRT. This may reflect recent educational programs on the menopause for both health professionals and the public, and also an increasing number of choices of therapy.

Adult

Fully automated assay of glycohemoglobin with the Abbott IMx analyzer: novel approaches for separation and detection.

We describe a novel assay for measuring glycohemoglobin directly from anticoagulated whole blood with the Abbott IMx analyzer. The glycohemoglobin is labeled with a soluble polyanionic affinity reagent and the anionic complex is then captured with a cationic solid-phase matrix. Glycohemoglobin is quantified by measuring the quenching by heme of the static fluorescence from an added fluorophore. The assay is standardized to report both percent total glycohemoglobin (%GHb) and percent hemoglobin A1c (%HbA1c). Glucose, bilirubin, triglycerides, labile fraction, and hemoglobin variants do not interfere in the assay. Within- and between-run CVs are approximately 4-5%, with total CVs of approximately 6.5%. Highly significant linear correlations (r > 0.97) were obtained in comparison studies with two major assay methodologies. The time to obtain one result is approximately 10 min (including assay of a control), 56 min for 22 results. We describe the development, standardization, and validation of this new method.

Autoanalysis

South Australian hypertension survey. General practitioner experiences with drug treatment.

OBJECTIVE: To investigate prescribing habits, educational approaches and perceived needs of general practitioners in the drug treatment of hypertension. DESIGN, SETTING AND PARTICIPANTS: Of 156 randomly selected South Australian general practitioners 132 responded to a questionnaire survey. MAIN FINDINGS: Diuretics are the most commonly chosen drug for the initial management of uncomplicated moderate hypertension. Equivalent patients aged 45, 60 and 75 years would be prescribed a diuretic as drug of first choice in 41%, 55% and 68% of cases respectively. Despite this, there are wide differences in the choice of initial therapy between individual practitioners. These differences can have a substantial cost impact, given that in Australia the cost of diuretic therapy for one month can be as low as $1.97 compared with $34.08 for standard angiotensin converting enzyme inhibitor therapy for one month. There was also a perceived need, and demand, for patient education materials to assist practitioners in the drug treatment of hypertension.

Adult

South Australian hypertension survey. General practitioner knowledge and reported management practices--a cause for concern?

OBJECTIVE: To survey South Australian general practitioners to investigate their knowledge and reported management of patients with hypertension. DESIGN, SETTING AND PARTICIPANTS: Of 156 randomly selected SA general practitioners 132 responded to a questionnaire survey. RESULTS: This survey showed substantial differences between general practitioners in their knowledge about hypertension and in their reported practices for diagnostic levels, investigations to be undertaken once diagnosis had been made, levels at which pharmaceutical treatment should be initiated, at which level treatment was regarded as having attained satisfactory control, and length of time for routine review. There was also a demand for materials to be provided to assist in the management of this important condition. CONCLUSIONS: There is a perceived need for better and more appropriate educational materials and a need for a different approach to try and reduce the reported variability in management of patients with hypertension by general practitioners.

Aged

Generation of T cells with lytic specificity for atypical antigens. I. A mitochondrial antigen in the rat.

F1 rats primed with normal parental strain lymphocyte populations and restimulated in culture with parental lymphoblasts generate potent cytotoxic T cell responses to unusual antigen systems. Here we describe in the Lewis (L)/DA anti-DA combination an antigen system most likely of mitochondrial origin with the following properties: it is transmitted maternally from DA strain females, inherited in an extra-chromosomal manner, restricted by class I RT1Aa major histocompatibility complex gene products, extinguished on target cells treated with chloramphenicol, and its pattern of expression in different rat strains correlates with restriction fragment-length polymorphisms of mitochondrial DNA. Sequence analysis of the rat ND1 gene indicates that the maternally transferred factor in the rat is not a homologue of the maternally transmitted factor responsible for the mitochondrial antigen in mice. In keeping with its inheritance from DA females, this antigen is present on target cells from (DA female x L male)F1 donors and all other F1 combinations derived from DA female parents, but absent from target cells from some F1 combinations (L/DA and Wistar-Furth [WF]/DA) derived from DA strain males. The presence of this antigen in other F1 combinations (Brown Norway [BN]/DA, August 2880 [AUG]/DA, and PVG/DA) indicates that this mitochondrial antigen system is shared by the DA, BN, and PVG strains, but not by the L and WF strains.

Amino Acid Sequence

Generation of T cells with lytic specificity for atypical antigens. II. A novel antigen system in the rat dependent on homozygous expression of major histocompatibility complex genes of the class I-like RT1C region.

Lymphocytes from parental strain DA rats can induce potent killer cell responses to atypical antigen systems in F1 Lewis (L)/DA and DA/L recipients. Here, we describe an antigen system, H, present on homozygous parental target cells, but not on F1 cells. This antigen system is unusual in several respects: it does not involve class I RT1A gene products usually used by killer cell responses in the rat, it maps to the major histocompatibility complex (MHC) class I-like RT1C region, and it requires homozygous expression of RT1Cav1 alleles. This may be another example, this time involving the RT1C region, of an MHC gene product antigenically altered by an MHC-linked trans-activating modifier gene.

Animals

Generation of T cells with lytic specificity for atypical antigens. III. Priming F1 animals with antigen-bearing cells also having reactivity for host alloantigens allows for potent lytic T cell responses.

Here, we explore the conditions required for generating two different highly potent F1 antiparental killer cell populations to unusual antigens in rats. The first, L/DA anti-DA, has lytic specificity for two antigen systems: MTA, a mitochondrial antigen expressed on DA and DA Lewis (L) target cells restricted by RT1A class I molecules; and H, an antigen that maps to the class I-like RT1C region and is present only on parental target cells from donors homozygous at the major histocompatibility complex. The second killer population is generated in the reciprocal DA/L anti-DA combination and has lytic specificity only for the H antigen system. We show that the killer cells are T cells, and that generation of these F1 cytotoxic T lymphocytes (CTL) requires an in vivo priming step in which it is essential that the inoculated parental cells bear the relevant target antigens and possess alloreactivity for F1 host antigens. The requirement for alloreactivity and antigen on the same priming cell population suggests that these potent lytic responses depend on a situation akin to a hapten-carrier effect that bypasses otherwise ineffective helper responses by the host to these unusual antigens. Restimulation of F1 lymphocytes in culture is also necessary, requiring the presence of antigen on irradiated lymphoblast stimulator cells, but alloreactivity to responder cell antigens is not necessary; normal, nonactivated lymph node cells are completely ineffective as stimulators. For effective lysis, the target cells need not possess the potential for alloreactivity to responder F1 CTL. We also demonstrate in a preliminary way additional antigen systems defined by killer populations raised with other F1 antiparental strain combinations.

Animals

Predictors of functional outcome and resource utilization in inpatient rehabilitation.

Consecutive patients (n = 1,289) discharged from two inpatient rehabilitation facilities were prospectively examined to determine the extent to which rehabilitative outcomes, functionally based progress, and associated resource utilization (in terms of rehabilitation length of stay) can be concomitantly predicted using the Tufts/New England Medical Center functional assessment tool and bivariate and multivariate statistical comparisons. A high percentage (greater than 50%) of statistically significant associations between the predictor variables and seven outcome measures were seen. The R2s corresponding to these associations were generally small and resistant to enhancement by commonly accepted statistical manipulations. Consequently, they are, in general, of limited predictive value for determining functional prognosis or resource utilization among rehabilitation inpatients. Although functionally based predictors appear to be the best predictors of functional progress, their effectiveness as predictors of other domains (eg, discharge outcome and rehabilitation length of stay) is variable. The implication is that a prospective payment system using such an array of predictors and directed primarily at cost containment is likely to overlook potentially important gains in functional progress and patient outcome. Furthermore, the functionally based predictors, taken individually, varied in effectiveness as predictors among facilities, and, taken collectively, they varied in effectiveness as predictors for different diagnostic groupings within a facility. The inconsistency of predictions according to the various domains appears to further limit their application to a prospective payment model.

Activities of Daily Living

"Sick of Smoking": evaluation of a targeted minimal smoking cessation intervention in general practice.

Several smoking intervention studies have been conducted overseas which use a minimal amount of general practitioners' time and are conducted within the constraints of a normal consultation. However, there are no published reports of minimal interventions in Australian general practice. This study reports on 1238 South Australian smokers who were assigned to a non-intervention control group or a group which received firm general practitioner advice to quit smoking plus literature. At one-year follow-up, 7.5% of smokers in the minimal advice group who had quit for six or more months remained non-smokers compared with 3.2% in the control group. If similar analytical procedures had been used in this study as were used in the benchmark study in England in 1979, the quit rate for this study would have been 11.3% in the intervention group, and 4.8% in the control group--a net gain of 6.5%. These results are discussed with regard to widespread implementation in Australian general practice.

Adolescent

Kinetic analysis of the pre-equilibrium steps in the self-assembly of RecA protein from Escherichia coli.

Total intensity light scattering is employed to investigate the self-assembly kinetics of RecA protein. Reaction conditions are employed where the kinetics of self-assembly are slow enough to yield reliable scattered intensity measurements over the range of scattering angles from 40 to 130 degrees as a function of time. From these measurements the time-dependent behavior of the weight average molecular weight, Mr, and radius of gyration, RG, of the associating protein species as a function of [MgCl2], [NaCl], [RecA], and pH was determined. The temperature dependence of RecA self-assembly was also investigated and allowed an evaluation of the activation thermodynamic parameters of association. Results reveal RecA self-assembly is bi-phasic under all conditions examined. The first phase, referred to as "filamentation" is second-order in [RecA] and occurs via a quasi linear condensation scheme with an Arrhenius activation energy of 88.6 kcal/mol. Filamentation assembly involves the uptake of one proton, one MgCl2, the release of five to six NaCls, and is driven by the release of approximately 70 water molecules. The evaluated activation parameters of the first kinetic phase are consistent with the proposition that linear self-assembly of RecA protein into ordered filaments is entropically driven. The second kinetic phase, referred to as "bundling" is greater than second-order in both [RecA] and [MgCl2], is considerably slower that filamentation assembly, and is apparently initiated by 2nd order collisions of linear filaments.

Escherichia coli

Structure and dynamics of M13mp19 circular single-strand DNA: effects of ionic strength.

Dynamic and static light scattering, CD, and optical melting experiments have been conducted on M13mp19 viral circular single-strand DNA as a function of NaCl concentration. Over the 10,000-fold range in concentration from 100 microM to 1.0 M NaCl, the melting curves and CD spectra indicate an increase in base stacking and stability of stacked regions with increased salt concentration. Analysis of dynamic light scattering measurements of the single-strand DNA solutions as a function of K2 from 1.56 to 20 X 10(10) cm-2 indicates the collected autocorrelation functions are biexponential, thus revealing the presence of two decaying dynamic components. These components are taken to correspond to (1) global translational motions of the molecular center of mass and (2) motions of the internal molecular subunits. From the evaluated relaxation rates of these components, diffusion coefficients D0 and Dplat are determined. The center of mass translational diffusion coefficient D0, varies in a nonmonotonic manner, by 10%, from 3.75 X 10(-8) to 3.39 X 10(-8) cm2/s over the NaCl concentration range from 100 microM to 1.0 M. Likewise, the radius of gyration RG, obtained from static light scattering experiments, varies by 15% from 699 to 830 A over the same NaCl range Dplat, the diffusion coefficient of the internal subunits, displays a different dependence on the NaCl concentration and decreases, by nearly 22% in a titratable fashion, from 12.46 X 10(-8) to 10.26 X 10(-8) cm2/s, when the salt is increased from 100 microM to 1.0 M. A semiquantitative interpretation of these results is provided by analysis of the light scattering data in terms of the circular Rouse-Zimm chain. Rouse-Zimm model parameters are estimated from the experimental results, assuming the circular chains are composed of a fixed number of Gaussian segments, N + 1 = 15. The rms displacement of the internal segments, b, is estimated to be the smallest (442 A) in 100 mM NaCl. Increases of b to 467 A in 100 microM and 524 A in 1.0 M NaCl are observed. Meanwhile, the hypothetical friction factor of the internal subunits, f, progressively increases as the NaCl concentration is raised. It is inferred from the evaluated Rouse-Zimm model parameters that both the static flexibility of the circular chain and diffusive displacements of the internal subunits decrease with increases in NaCl concentration from 100 mM to 1.0 M.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Phenomena

The acid instability of myelin. A model for myelin degeneration in multiple sclerosis.

Electron micrographs of samples of bovine spinal cord which have been briefly acidified (10 mM lactate buffer, pH 5.5, 25 degrees C, 15 minutes) prior to being fixed for EM examination, reveal extensive vesicular disruption of the myelin lamellae; micrographs of control samples incubated under identical conditions at pH 7.0, show normal compact lamellae. Culture of thioglycollate-elicited rat peritoneal macrophages in the presence of derivatized, non-ingestible, bovine CNS material results in the secretion of lactic acid and the acidification of the culture medium to levels which are comparable to those which cause lamellae disruption in the tissue slices. Because of the sensitivity of the myelin lamellae to an acidic microenvironment, it is suggested that a local hyperlactemia, with the resulting decrease in interstitial pH, may be a major pathological process in cell-mediated inflammatory demyelination. Antihyperlactemics may therefore provide a new therapeutic approach to minimizing myelin degeneration in multiple sclerosis and in other CNS disorders characterized by inflammatory demyelination.

Animals

Prevention of nitroimidazole resistance in Campylobacter pylori by coadministration of colloidal bismuth subcitrate: clinical and in vitro studies.

One hundred patients with duodenal ulceration and Campylobacter pylori in their stomach were entered into a double blind placebo controlled prospective study. Treatment schedules were cimetidine and placebo, or cimetidine and tinidazole, or colloidal bismuth subcitrate (CBS) and placebo, or CBS and tinidazole. Seventeen per cent of isolates of C pylori obtained at the first endoscopy were resistant to tinidazole and 70% of the second isolates from patients given cimetidine and tinidazole became tinidazole resistant. Suspensions of nitroimidazole sensitive cultures of C pylori showed that three of 22 isolates had a nitroimidazole resistant subpopulation. In patients who healed and remained free of C pylori after treatment ulcers recurred less often than in patients who healed but retained C pylori (23% v 73% over 12 months, p less than 0.001).

Anti-Ulcer Agents

Concentrations of serotonin in plasma--a test for appendicitis?

We assessed the value of measuring serotonin (5-hydroxytryptamine) in plasma (by HPLC) in the diagnosis of acute appendicitis. Values for patients with subsequently confirmed appendicitis (11-145 nmol/L, median 70 nmol/L) significantly (P congruent to 0.005) exceeded those for patients with abdominal pain in whom appendicitis was only a possible diagnosis (2-45 nmol/L, median 20 nmol/L). The results for appendicitis patients were bimodally distributed, with low results found in patients where surgery revealed gangrenous appendicitis with little viable appendicular tissue. We conclude that measuring serotonin may be of value in confirming or excluding the diagnosis of early acute appendicitis where the physical signs are equivocal, and thus helps reduce unnecessary appendectomies. However, serotonin is of little help in diagnosing gangrenous appendicitis, where physical signs are more likely to be clearcut.

Appendectomy