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Biomedical subjects

A Muir

Publications and source records attributed to A Muir.

At least 55 records · Page 3Linked to original sources
PubMed1994

Syphilis in pregnant patients and their offspring.

OBJECTIVES: To determine the prevalence of syphilis in antenatal women and their babies at birth. METHODS: A cross-sectional study was made of 1508 women who delivered consecutively at Pelonomi Hospital, Bloemfontein. The initial test on each mother was a rapid plasma reagin test (RPR). If reactive, it was followed by a venereal disease research laboratory test (VDRL) and a confirmative Treponema pallidum hemagglutination test (TPHA). Cord blood was tested by a RPR test. Babies with reactive tests were examined clinically, and in addition the cord blood was tested with the VDRL test as well as the enzyme linked immunosorbent assays (ELISA) for IgG and IgM. RESULTS: At delivery the data on 1476 mothers and 1399 babies were available for analysis. Sixty-five percent of the mothers had attended antenatal clinics at least once and 17% of them had tested positive for syphilis. Only 22% of these patients had been completely treated. At delivery 15% of the mothers (including women without antenatal care) tested positive for syphilis and 8% of the babies had a reactive RPR test. Clinical stigmata of congenital syphilis were evident in 15% of these babies. CONCLUSIONS: An extremely high prevalence of syphilis (15%) was documented, as well as a major deficiency in the treatment program of these patients.

Adult↗
PubMed1994

Resistant hypertension and preoperative silent myocardial ischaemia in surgical patients.

We studied 325 patients undergoing elective noncardiac surgery who had preoperative ambulatory ECG monitoring performed for a duration of 5130 h (range 8-24 h; mean 15.8 h). Sixty-four subjects (20%) had one or more episodes of ST segment depression consistent with myocardial ischaemia. Of all preoperative cardiovascular variables measured, the presence of elevated arterial pressure, despite patients being maintained on long term antihypertensive therapy, was the only factor associated significantly with the presence of preoperative silent myocardial ischaemia (P < 0.002). This correlation was confirmed when arterial hypertension was defined in four separate ways. The incidence of silent ischaemia in these patients was 33-55%. We suggest that admission arterial pressure may therefore be a useful screening test to identify patients at risk of preoperative myocardial ischaemia.

Adult↗
PubMed1994

Effect of condensed tannins from birdsfoot trefoil on endoglucanase activity and the digestion of cellulose filter paper by ruminal fungi.

The ruminal fungi Neocallimastix frontalis RE1, Neocallimastix patriciarum 27, Piromyces communis 22, and Orpinomyces joyonii 19-2 were examined for their ability to digest filter paper in the presence of condensed tannins from birdsfoot trefoil (Lotus corniculatus L.). For all four fungi, inhibition of endoglucanases was evident at 100 micrograms condensed tannins.mL-1 with nearly complete inhibition at 300 micrograms condensed tannins.mL-1. At 100 and 200 micrograms condensed tannins.mL-1, the endoglucanase activity of N. frontalis RE1 was greater (P < 0.01) than that of the other three fungal species. Exposure to 100 micrograms condensed tannins.mL-1 did not affect the ability of N. frontalis RE1 or N. patriciarum 27 to digest filter paper, and although digestion was reduced, N. frontalis RE1 and P. communis 22 solubilized more than 20% of the filter paper at 500 micrograms condensed tannins.mL-1. In contrast, O. joyonii 19-2 was virtually unable to digest filter paper at 300 micrograms condensed tannins.L-1. Mycelia of fungi grown with condensed tannins were covered by filamentous material, which may have arisen from the formation of condensed tannin-protein complexes. Less than 86% of the condensed tannins (as measured by the H2SO4 method) were recovered after 120 h of incubation with N. frontalis RE1, P. communis 22, and N. patriciarum 27. The need for detailed studies to examine the ability of ruminal fungi to metabolize condensed tannins is evident.

Animals↗
PubMed1994

Islet cell antibodies predict insulin-dependent diabetes in United States school age children as powerfully as in unaffected relatives.

Islet cell antibodies (ICA) in the sera of nondiabetic relatives of patients with insulin-dependent diabetes (IDD) are predictive of the disease, a finding that permits the design of intervention strategies to prevent it. However, 85% or more of patients with new onset IDD have no affected relative. We therefore screened 9,696 schoolchildren between the ages of 5 and 18 yr (mean age 10.7 yr) in Pasco County, Florida for ICA in three surveys during 1984/5, 1987/8, and 1990/1 and have followed them prospectively. Approximately 4,000 of these children have been followed for nearly 8 yr. ICA titers > or = 10 Juvenile Diabetes Foundation units on replicate tests were detected in 57 of the children (0.59%). 10 children have developed diabetes so far, and all had ICA detected beforehand. The likelihood of developing IDD among the ICA-positive children was compared with 2,959 age-matched nondiabetic first degree relatives of IDD probands who were screened for ICA by our laboratory during the same time period and also followed prospectively. Of 103 (3.5%) ICA-positive relatives, 31 have developed IDD. Life table analysis reveals no statistically significant differences in the probability of developing IDD between the ICA-positive schoolchildren and ICA-positive first degree relatives (P = 0.3). The estimated risk of developing IDD by 7 yr in the ICA-positive schoolchildren was 45% (95% confidence interval 15-74%) compared with 43% (confidence interval 22-63%) in the relatives. We conclude that ICA appear to be as predictive of IDD in low-risk schoolchildren as they are in high-risk relatives. These data suggest that it is feasible to predict IDD by screening a general population of schoolchildren for ICA and that those found to be positive could be considered, in addition to relatives, for intervention protocols to prevent the disease.

Adolescent↗
PubMed1994

Autoantibody epitope mapping of the 21-hydroxylase antigen in autoimmune Addison's disease.

Patients with idiopathic Addison's disease are characterized by cytoplasmic adrenal autoantibodies, detectable by indirect immunofluorescence of cryocut sections of human adrenal cortex. Recently, autoantibodies that bind a 55-kilodalton protein in the microsomal fraction of adrenal gland extracts identified to be the cytochrome P450 enzyme 21-hydroxylase have been found in Addisonian patient sera. We confirm the finding and report here the autoantigenic epitopes involved in the autoantibody reactivity using recombinant DNA technology. Six cDNA fragments spanning different regions of the 21-hydroxylase gene were expressed as fusion proteins with glutathione S-transferase in Escherichia coli. Immunoblot analyses were used to evaluate the reactivity of the recombinant proteins with patients' sera to determine the autoepitopes involved. We found that a conserved region (amino acids 164-356) reacted with 25 of 30 adrenal autoantibody-positive sera tested. One serum sample reacted only with the amino portion of the 21-hydroxylase (amino acids 1-162). In addition, 4 other enzymes important to steroid hormone biosynthesis, 11 beta-hydroxylase, 17 alpha-hydroxylase, side-chain cleavage enzyme P450, and 3 beta-hydroxysteroid dehydrogenase, were expressed in E. coli, but none of them gave positive autoantibody reactions by Western blot assays, even using sera from 5 patients with type I autoimmune polyglandular syndrome. The availability of recombinant antigens has permitted structural analysis of the autoepitopes involved in the autoimmune response to 21-hydroxylase in Addison's disease. Our findings should lead to the development of a simple and specific tool for immunodiagnosis of the disease.

Addison Disease↗
PubMed1994

Additive susceptibility to insulin-dependent diabetes conferred by HLA-DQB1 and insulin genes.

Several genomic polymorphisms at the insulin (INS) gene and its flanking regions were analyzed in 197 unrelated Caucasian patients affected by insulin-dependent diabetes (IDDM) and 159 ethnically matched, normal controls ascertained from the South-Eastern United States. We found that the frequency of homozygotes for the common variant at the insulin gene was significantly increased in the diabetic population (RR = 2.0, p < 0.005). However, the polymorphisms in the 5' and 3' regions flanking the INS were not significantly associated with IDDM. These results suggest that the IDDM susceptibility locus on chromosome 11p is located within the region extending from the 5' VNTR to the 3' end of the INS gene. We determined the HLA-DQB1 genotypes by denaturing gradient gel electrophoresis (DGGE) and/or sequence-specific primers (SSP) techniques to assess the possible interactions between INS and HLA. DQB1*0302 had the strongest predisposing effect on IDDM susceptibility (RR = 9.3) and DQB1*0602 the strongest protective effect (RR = 0.02). However, a significant predisposing effect of DQB1*0201 could be demonstrated only after removal of the effects of DQB1*0302 and DQB1*0602. Analyses of the genotypes revealed that all genotypes containing 0602 were protective and that the heterozygous genotype 0201/0302 and homozygous genotype 0302/0302 confer the highest risk (RR = 20.9 and 12.9 respectively). However, heterozygous genotypes 0302/X (X excludes 0201, 0302 and 0602) have a significantly lower predisposing risk. Similarly, there is heterogeneity in risk between predisposing 0201/0201 homozygous individuals and protective 0201/X individuals. When subjects were stratified by HLA genotypes, the relative risks conferred by INS did not vary, thus suggesting that the susceptibility effects conferred by HLA and INS are additive rather than interactive.

Base Sequence↗
PubMed1994

Prevalence of vaginitis, syphilis and HIV infection in women in the Orange Free State.

OBJECTIVE: To determine the prevalence of vaginitis, syphilis and HIV infection in women in the Orange Free State. METHOD: By cluster sampling, 120 rural (farm) and 120 urban (local authority) clusters, each containing 4 women, were selected. Women aged 18-49 years who were included in the study had a cervical smear taken for cytological evaluation and blood specimens drawn for syphilis and HIV testing; they were questioned on their knowledge of AIDS. RESULTS: Trichomonas vaginalis vaginitis was present in 27.4% of the rural women and 29.6% of the urban women, Gardnerella vaginalis in 7.2% and 8.4% and Candida spp. in 2.6% and 6.7% respectively. Syphilis serology was positive in 12% of rural and 16% of urban women. HIV was present in 0.4% of rural and 1.5% of urban women. Ninety per cent of urban women and 74% of rural women knew AIDS was a sexually transmitted disease. CONCLUSIONS: The prevalences of trichomonas vaginitis and syphilis were unusually high, while HIV positivity was similar to that in other reports in South Africa.

Adolescent↗
PubMed1993

Validity of symphysis fundus growth measurements.

OBJECTIVES: Evaluation of symphysis fundus measurements in a large antenatal clinic. METHODS: The obstetrical records were reviewed for all patients that had delivered over a 3-month period. From this group of 1455, a sample of 386 was taken that had a singleton pregnancy, had booked before 24 weeks' gestation and had attended the antenatal clinic at least twice. The study group comprised 65 patients with less than expected symphysis fundus growth and a control group of 249 in whom growth seemed adequate. The remaining 72 subjects' files were either incomplete or the interobserver variation of the symphysis fundus measurements at the end of pregnancy seemed too high. RESULTS: Deficient intra-uterine growth, as shown by the symphysis fundus measurements, was significantly associated with both low birthweight (< 2500 g) (odds ratio 3.02) and intra-uterine growth retardation (IUGR) (odds ratio 3.43), but no association was found with perinatal mortality. The sensitivity for detecting IUGR was 42%. CONCLUSIONS: Symphysis fundus measurements, as made in our antenatal clinic, seem of limited value. We propose that the number of observers be restricted in order to decrease the interobserver variation.

Embryonic and Fetal Development↗
PubMed1993

Intervention therapies for insulin-dependent diabetes.

Treatment of insulin-dependent diabetes remains problematic since there continues to be high rates of morbidity and mortality among affected patients. Good outcomes are most likely to be more common among patients who maintain endogenous insulin reserves for the longest time following diagnosis. The disease process can now be identified in its early, pre-symptomatic stages and thus, the time has come for the investigation of preventive therapies through multicenter clinical trials. A wide variety of strategies are available and their choice should be dependent on the pathogenic stage of disease at which treatment is initiated. This stage-specific approach to prevention is discussed with a particular focus on those therapies that will soon be tested in clinical trials.

Animals↗
PubMed1992

Further evidence of increased polymorphonuclear cell activity in patients with Raynaud's phenomenon.

The role of polymorphonuclear cells (PMNs) in the pathophysiology of ischaemic vascular disease has been increasingly recognized in recent years. Activated PMNs may physically obstruct blood flow. Subsequent release of reactive oxygen radicals and lytic enzymes lead to continued damage. Previous studies have shown increased white cell activity in patients with secondary Raynaud's syndrome (RS). However, whether this is related to the underlying condition or to digital vasospasm is not clear. Using a more physiological whole blood PMN aggregation assay, we assessed PMN activity in 38 patients with severe Raynaud's phenomenon (RP) [16 had systemic sclerosis (SSc) and secondary RS; 22 had RP alone and no other features of a connective tissue disease]. Additionally, plasma levels of malondialdehyde (MDA), an indicator of free radical activity, were measured. Results were compared with those obtained from 56 matched volunteers. In order to assess if changes in PMN activity was directly related to digital vasospasm, patients were asked to record the duration and frequency of their Raynaud's attacks during a 2-week period using a pocket sized diary. Correlation between these clinical variables of Raynaud's severity and white cell activity was assessed. Patients with RP, both with and without SSc, showed a significantly greater fall in single PMN count when compared with control subjects [SSc associated RS 48.2 (41.4-56)% versus control, P = 0.04; RP alone 49.3 (46.8-52.1)% versus control, P = 0.01 (Mann-Whitney U-test)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Investigation of structure function relationships in cathepsin B.

Previous suggestions from sequence alignment studies and examination of the recently determined X-ray crystal structures of cathepsin B point to roles for several specific residues in substrate binding and catalysis. The role of these groups is being examined by studying cathepsin B mutants produced using a yeast expression system. The substitutions Gly198Asp, Arg202Ala, His111Gln and Glu245Gln provide a mechanistic basis for the exopeptidase activity of cathepsin B and the ability of this cysteine proteinase to accept an arginine residue in the S2 subsite.

Amino Acid Sequence↗
PubMed1992

The pathogenesis, prediction, and prevention of insulin-dependent diabetes mellitus.

The past decade has seen great advances in our understanding of the pathogenesis of IDDM. This knowledge has led to investigate use of a battery of immunologic, genetic, and metabolic tests for identifying people with prediabetes. Therapies designed to arrest autoimmunity have been associated with incomplete responses and the complications of immunosuppression. Ultimately, we hope that IDDM can be eradicated by inducing tolerance to the diabetogenic autoantigen(s).

Animals↗
PubMed1991

Macrophage-specific chemotactic lipid release by in vivo streptozocin-administered mouse islets.

The development of insulitis in animal models of immune-mediated diabetes mellitus is preceded by an influx of macrophages into the islets. In this study, ICR mice were given four 30-mg/kg doses of streptozocin over 36 h to induce insulitis. The islets were subsequently isolated and cultured in suspension. A macrophage-specific islet infiltration was observed within 48 h of the first drug injection. Concurrent with this leukocyte influx, enhanced in vitro release of a macrophage-specific chemotactic lipid by islets from streptozotocin-administered animals was observed. By chromatographic analysis, the islet-derived chemotactic factor appears to resemble a moderately polar complex lipid that is distinct from previously characterized lipid chemoattractants. Secretion of the factor is not dependent on cyclooxygenase activity. Identification of this lipid may provide important insights into the etiology of insulin-dependent diabetes mellitus and other autoimmune diseases.

Animals↗
PubMed1991

Autoimmune diseases of the adrenal glands, parathyroid glands, gonads, and hypothalamic-pituitary axis.

Autoimmunity directed against the adrenal glands, parathyroid glands, gonads, and hypothalamic-pituitary axis can arise in isolation or as part of a polyglandular autoimmune syndrome. Affected patients can be asymptomatic, but they may also suffer significant morbidity or even mortality. Currently, treatment is restricted largely to hormone replacement when end-organ destruction is almost complete. As our understanding of the pathogenesis of autoimmune endocrinopathies improves, it is probable that early patient detection will become practical and trials of protective immunotherapies entertained.

Addison Disease↗
PubMed1990

Alpha-1-antitrypsin (protease inhibitor) phenotypes and longevity.

We have tested the hypothesis that the protease inhibitor phenotypes MZ and MS are disadvantageous and reduce survival by comparing the prevalence of these phenotypes in a group of 707 very old people (hospital patients) with the prevalences reported in younger populations of blood donors. The MS and MZ phenotypes appear to be no less common among those who have survived to old age, but a highly significant difference was found in the occurrence of the M subtypes. The M1 type was more common in the elderly, and the M heterozygotes were less common than would be predicted from the reported incidence in younger groups and from the Hardy-Weinberg equilibrium. This discrepancy appeared to be smaller in subjects of Mediterranean origin than in those of British or Irish genetic background.

Aged↗