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Biomedical subjects

D Morris

Publications and source records attributed to D Morris.

At least 37 records · Page 2Linked to original sources
PubMed1996

Evaluation of the BCL-2 gene locus as a susceptibility locus linked to the clinical expression of systemic lupus erythematosus (SLE).

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of a large number of autoantibodies. It has been postulated that this may be the result of prolonged longevity of auto-reactive B cells due to defective regulation of programmed cell death (apoptosis). The proto-oncogene bcl-2 is involved in the control of apoptosis in immunocompetent cells, and its over-expression is noted in T and B cells from SLE patients. This study examined the genetic linkage between the bcl-2 gene locus and SLE susceptibility using the affected sib-pair method in SLE families. Seventeen caucasian multiplex families were evaluated. A polymorphic microsatellite marker closely linked to the bcl-2 gene on 18q21.3 was used to determine the bcl-2 genotype. We demonstrated that haplotype sharing among the affected sibling pairs was not statistically different from random (P > 0.5). This suggests that the bcl-2 gene locus does not confer a genetic susceptibility to SLE expression.

Alleles↗
PubMed1996

A comparison of nebulized budesonide with oral prednisolone in the treatment of exacerbations of obstructive pulmonary disease.

Nebulized corticosteroids in acute bronchospasm may offer topical anti-inflammatory activity while minimizing undesirable systemic effects. We compared the side-effect profile of nebulized budesonide (2 mg twice daily) with that of oral prednisolone (30 mg once daily) in a randomized parallel-group study of 19 adults with severe acute airway obstruction. Over the 5 days of the study, baseline forced expiratory volume in 1 second (FEV1) increased from 1.8 (95% confidence interval [CI], 0.7) to 2.1 (95% CI, 0.7) L in the group that received oral corticosteroids compared with 1.9 (95% CI, 0.7) to 2.0 (95% CI, 0.7) L in the group that received nebulized corticosteroid. All biochemical variables were similar at day 1. Comparison of budesonide treatment with prednisolone on day 5 showed that urinary corticosteroid metabolites were significantly higher (2012 [95% CI, 812] compared with 1079 [95% CI, 346] mg/24 hr [p < 0.05]), urinary androgen metabolites were not different, serum osteocalcin was elevated (2.3 [95% CI, 1.4] compared with 0.6 [95% CI, 0.6] ng/ml [p < 0.05]), and 24-hour urinary calcium to creatinine ratios were lower (0.28 [95% CI, 0.1] compared with 0.53 [95% CI, 0.2]), whereas urinary hydroxyproline to creatinine ratios were similar. The biochemical markers associated with corticosteroid side effects improve in patients treated with nebulized corticosteroids compared with patients who receive conventional treatment.

Acute Disease↗
PubMed1996

Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar-coding strategy.

A quantitative and highly parallel method for analysing deletion mutants has been developed to aid in determining the biological function of thousands of newly identified open reading frames (ORFs) in Saccharomyces cerevisiae. This approach uses a PCR targeting strategy to generate large numbers of deletion strains. Each deletion strain is labelled with a unique 20-base tag sequence that can be detected by hybridization to a high-density oligonucleotide array. The tags serve as unique identifiers (molecular bar codes) that allow analysis of large numbers of deletion strains simultaneously through selective growth conditions. Hybridization experiments show that the arrays are specific, sensitive and quantitative. A pilot study with 11 known yeast genes suggests that the method can be extended to include all of the ORFs in the yeast genome, allowing whole genome analysis with a single selective growth condition and a single hybridization.

DNA↗
PubMed1996

Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays.

Naturally occurring mutations in HIV-1-infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV-1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first clinical application of high-density oligonucleotide array sequencing, the sequences of 167 viral isolates from 102 patients have been determined. The DNA sequence of USA HIV-1 clade B proteases was found to be extremely variable and 47.5% of the 99 amino acid positions varied. This level of amino acid diversity is greater than that previously known for all worldwide HIV-1 clades combined (40%). Many of the amino acid changes that are known to contribute to drug resistance occurred as natural polymorphisms in isolates from patients who had never received protease inhibitors.

Amino Acid Sequence↗
PubMed1996

Successful treatment of HTLV-1-associated acute adult T-cell leukaemia lymphoma by allogeneic bone marrow transplantation.

HTLV-1-associated acute adult T-cell leukaemia-lymphoma (ATL) is a highly aggressive malignant disorder with a median survival of 6 months or less. We describe an Afro-Caribbean female with very poor prognosis ATL who underwent chemotherapy with a 4 d infusion schedule of cyclophosphamide, doxorubicin and etoposide, followed by successful allogeneic bone marrow transplantation (BMT) from her HTLV-1-negative histocompatible sister. The patient remains in complete remission 23 months after BMT and has 100% donor haemopoiesis with no evidence of HTLV-1 infection on PCR testing. We suggest that allo-BMT can prolong disease free survival or may even be curative in HTLV patients.

Adult↗
PubMed1996

Evaluation of the Technicon Immuno 1 free thyroxine assay.

The Technicon Immuno 1 free thyroxine (fT4) assay, a modified two-step procedure that is fully automated on a random access analyzer, was evaluated-at two clinical sites. The method had excellent precision and correlated well overall with three other estimates of free thyroxine: free thyroxine index (FTI) measured on the Immuno 1; the Abbott IMx fT4 assay (Abbott Park, IL); and the Clinical Assays two-step manual fT4 assay. Using a combination of thyrotropin and FTI assay results as a "gold standard" for defining thyroid status, the Immuno 1 fT4 method had a sensitivity of 100% and specificity of 98.3% for hyperthyroidism, versus 93.8% and 99.3%, respectively, for hypothyroidism. In conclusion, the Immuno 1 fT4 assay is useful in screening for thyroid disease.

Autoanalysis↗
PubMed1996

Scleroderma and silicone gel breast prostheses--the Sydney study revisited.

BACKGROUND: Silicone augmentation mammoplasty has been postulated as a cause of environmentally-induced scleroderma. While representing a small proportion of all alleged causes of scleroderma, the issue has huge social, ethical and medicolegal ramifications. The hypothesis, however, has been recently questioned in results of comparative studies. We have previously reported no association between augmentation mammoplasty and scleroderma. However, all information was self-reported including augmentation mammoplasty status, and the prosthesis type was not identified. In addition, data were not available from untraceable cases. The current study addresses these issues. AIMS: To validate self-reported augmentation mammoplasty status, re-analyse rates of exposure to silicone gel breast prostheses in 556 scleroderma patients and 289 general practice controls and evaluate whether silicone gel breast prostheses are causally linked to scleroderma. METHODS: Study design-population-based case-control study; Cases-scleroderma patients resident in Sydney for at least six consecutive months between 1974-1988; Controls-patients from 29 randomly selected Sydney general practices, age- and gender-group-matched with cases. Validation of augmentation mammoplasty exposure was ascertained from the general medical practitioner of each interviewed case and control, or from the medical records of each deceased or untraceable case. Validation of the date of surgery and prosthesis type was from the relevant plastic surgeon. For each augmentation mammoplasty-positive case, validation of both the date and nature of the scleroderma onset was from the patient's medical records. Controls were given a "control date' for disease onset to adjust for duration of potential exposure. RESULTS: Validation of augmentation mammoplasty status was possible in 252 (87.2%) living controls, and 532 (95.7%) cases, of whom 287 were living. Self-reported augmentation mammoplasty status was highly reliable in living non-senile cases (kappa = 1), and living validated controls (kappa = 0.86). No association was identified between silicone gel augmentation mammoplasty and scleroderma with unadjusted odds ratios of 1.33 (95% CI: 0.26-6.71), and 1.00 (95% CI: 0.16-6.16) following adjustment for potential confounders of age, socioeconomic status and ethnicity. CONCLUSIONS: This validates the self-reported augmentation mammoplasty status previously reported and does not support the hypothesis that silicone gel augmentation mammoplasty is an environmental inducer of scleroderma in females.

Adult↗
PubMed1996

Hormone replacement therapy and coronary artery disease.

The association of estrogen therapy with reduced levels of coronary artery disease in postmenopausal women has resulted in a burst of investigations into the mechanism(s) by which protection is offered. Findings published in the past year suggest that estrogen replacement alters every stage of the disease, from atherogenesis and plaque formation, to vascular responsiveness in already diseased arteries. The lipid metabolic alterations caused by estrogen replacement therapy have been confirmed and appear unaffected by the concurrent use of progestins. Consensus reports have recommended that high cardiovascular disease risk be added to the indications for the use of postmenopausal hormone replacement.

Coronary Disease↗
PubMed1995

Evaluation of paradoxic beneficial effects of smoking in patients receiving thrombolytic therapy for acute myocardial infarction: mechanism of the "smoker's paradox" from the GUSTO-I trial, with angiographic insights. Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: Our purpose was to evaluate the relation between smoking and the outcomes of patients receiving thrombolysis for acute myocardial infarction. BACKGROUND: A paradoxic beneficial effect has been observed in smokers with a myocardial infarction. We analyzed outcomes and baseline characteristics of 11,975 nonsmokers, 11,117 ex-smokers and 17,507 current smokers in a multinational trial of thrombolysis for acute myocardial infarction. METHODS: Patients were randomized to one of four thrombolytic protocols. An angiographic substudy in 2,431 patients evaluated reperfusion, reocclusion and ventricular function. Effects of smoking were evaluated by logistic regression analysis after adjustment for age and gender. A mortality model evaluated the simultaneous effect of baseline characteristics on the prognostic importance of smoking. These processes were performed with data from both the main trial and the angiographic substudy; then angiographic factors (coronary anatomy, patency and ejection fraction) were added to the model. RESULTS: Smokers were significantly younger by a mean of 11 years) and had less comorbidity or severe coronary artery disease than nonsmokers. Nonsmokers had significantly higher hospital and 30-day mortality rates (9.9% and 10.3%, respectively) than smokers (3.7% vs. 4%, respectively, both p < 0.001) and more in-hospital complications. The unadjusted odds ratio for 30-day mortality in nonsmokers was 3.36 (95% confidence interval [CI] 2.08 to 5.41), 1.21 (95% CI 0.71 to 2.08) after adjustment for age and gender and 1.08 (95% CI 0.59 to 1.96) after adjustment for all clinical baseline characteristics. CONCLUSIONS: Smokers receiving thrombolysis for acute myocardial infarction presented 11 years earlier than nonsmokers, which generally accounted for their better outcome. When other differences in clinical and angiographic baseline factors and therapeutic responses were evaluated, no significant difference in mortality was seen between smokers and nonsmokers.

Adult↗
PubMed1995

Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators.

BACKGROUND: The Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial was designed to test whether thrombolytic strategies achieving more complete, early, sustained coronary artery patency would lead to further reductions in mortality in patients with acute myocardial infarction. An angiographic substudy within GUSTO-I provided a unique opportunity to examine the relation between mortality and degrees of patency among the regimens. METHODS AND RESULTS: Four thrombolytic strategies were compared in 41,021 patients in GUSTO-I: streptokinase with subcutaneous or intravenous heparin, accelerated tissue plasminogen activator (TPA) with intravenous heparin, and combination streptokinase plus TPA with intravenous heparin. Accelerated TPA was associated with lower 30-day mortality (6.3%) than the other strategies (7.2%, 7.4%, and 7.0%, respectively). Among the 1210 patients in the angiographic substudy randomized to angiography 90 minutes after starting treatment, there was improved patency, particularly Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, with accelerated TPA over the other regimens (P < .0001). Coronary artery perfusion (TIMI grade 3) at 90 minutes was also a significant predictor of 30-day survival (P < .01). To determine whether differences in mortality among the four strategies matched differences in 90-minute patency, a model was developed for predicting mortality differences in the main trial from the angiographic substudy. The model assumed that any differences in treatment effects on 30-day mortality were mediated through differences in 90-minute patency for the four treatments. The predicted rates were then compared with observed mortality rates of the remaining patients in the main trial for each treatment group. The predicted and observed 30-day mortality rates of the four treatments were streptokinase with subcutaneous heparin, 7.46% versus 7.28%; streptokinase with intravenous heparin, 7.26% versus 7.39%; accelerated TPA, 6.31% versus 6.37%; and streptokinase plus TPA, 6.98% versus 6.96%. The correlation between predicted and observed results was .97, and the proportion of squared error explained (R2) was .92. CONCLUSIONS: The close relation between the predicted and observed 30-day mortality rates supports the concept that an important mechanism for improved survival with thrombolytic therapy is achievement of early, complete perfusion. The close match provides a strong biological explanation for the mortality differences seen in GUSTO-I and a sound rationale for the additional survival advantage of the accelerated TPA regimen. Irrespective of which treatment is used, early and complete restoration of infarct artery perfusion represents an essential goal of myocardial reperfusion therapy.

Coronary Angiography↗
PubMed1995

Presence of Y chromosome sequences and their effect on the phenotype of six patients with Y chromosome anomalies.

The extent of Y chromosome material was determined in 6 southern African subjects with sex chromosome anomalies. Four of the subjects were phenotypically female, and 2 were phenotypically male. Molecular and cytogenetic findings were correlated with phenotypic expression. An X;Y translocation was found in both male subjects, and in one female subject. The remaining female subjects were characterized by an isodicentric Y, an isochromosome Yq, and a micromarker of undetermined origin, respectively. The individuals were tested for the presence of a number of Y-specific DNA sequences. Molecular findings were generally compatible with the cytogenetic findings, and also with the phenotypic sex of the patients. All the female subjects had Y material and all but one were negative for the sex determining region of the Y (SRY). The somatic Ullrich-Turner-like findings present in 3 of the females were attributed to either the presence of a 45,X cell line and/or a single copy of Xp. The males both showed X;Y translocations without any detectable loss of Y DNA. Although molecularly very similar, the disparate clinical findings in these 2 subjects could have been accounted for by different X inactivation patterns.

Adolescent↗
PubMed1995

A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice.

To test the behaviour of a mutant form of p53 in the presence and absence of wild-type p53 in vivo, we mated p53-deficient mice containing a p53 null allele to transgenic mice containing multiple copies of a mutant p53 gene (Val 135). Animals hemizygous for the endogenous wild-type p53 gene with the mutant transgene exhibited accelerated tumour development and an altered tumour spectrum compared to their non-transgenic counterparts. In contrast, transgenic and non-transgenic animals nullizygous for endogenous p53 developed tumours at the same rate. Thus, the mutant Val-135 p53 allele may act in vivo in a dominant negative manner in the presence of wild-type p53 but does not display gain of function activity in the absence of wild-type p53.

Animals↗
PubMed1995

The etiology of hyperandrogenism in women.

This review considers recent evidence which has implicated steroidogenic alterations as elements on the etiology of the androgen excess associated with polycystic ovary syndrome. The importance of circulating dehydroepiandrosterone sulphate as a precursor for ovarian follicular testosterone is discussed and evaluated in the face of indications that the activity of P450-c17-alpha-hydroxylase is altered at both adrenal and ovarian level in polycystic ovary syndrome. The impact of weight and insulin resistance on circulating dehydroepiandrosterone concentrations is discussed, and related to the endocrine changes in polycystic ovary syndrome. Androgen excess in women arises from multiple endocrine disturbances, which evidently commonly include the steroidogenic pathways.

Androgens↗
PubMed1995

Customer complaints in the National Health Service.

This paper addresses the role of consumer complaints in the flourishing quality assurance industry within the National Health Service (NHS), and considers the traditional ethos of complaints within the service. The advent of the internal market is considered as one of a range of factors which may change attitudes of NHS staff to complaints. In evaluating how complaints services might develop relevant literature is reviewed and recent national data on complaints procedures are cited.

Attitude of Health Personnel↗