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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 325 records · Page 18Linked to original sources
PubMed1994

Cost-effectiveness analysis of hormone replacement therapy and lifestyle intervention for hip fracture.

We compared the cost-effectiveness of interventions to prevent osteoporosis using a decision analytic model for a hypothetical cohort of 100,000 healthy perimenopausal women. The interventions were: oestrogen from age 50 for life, oestrogen from age 50 for 15 years, oestrogen from age 65 years for life, and a lifestyle regime of calcium supplements and exercise. The four interventions were compared with the case of no intervention by examining the effects on medical and nursing home costs, life years gained, quality-adjusted life years (QALYs) gained and costs per QALY gained. Lifetime oestrogen therapy from age 65 years achieved the lowest cost per life year gained and the lowest cost per QALY gained. The lifestyle intervention was the most expensive intervention by all measures but was sensitive to the cost of exercise and to the effects of exercise on cardiovascular mortality. Conventionally, oestrogen therapy begins at the menopause to avoid the rapid decline in bone mass that occurs with normally decreasing oestrogen levels. These results indicate that there is evidence, both in terms of fracture prevention and cost, to justify introduction of treatment at a later age. If a lifestyle intervention regimen can reduce cardiovascular mortality as well as hip fracture, this may provide an alternative means of reducing osteoporotic hip fracture at a reasonable cost.

Aged↗
PubMed1994

Retinal blood velocities during carbogen breathing using scanning laser ophthalmoscopy.

Hyperoxic-hypercapnic gas mixture ('carbogen': 6% CO2-94% O2) is widely used clinically. Its influence on retinal perfusion remains unclear, since past work suggests that high O2 may reduce and high CO2 may increase retinal blood flow. To examine the changes in retinal blood velocity during 'hyperoxic-hypercapnic' gax mixture breathing, we quantified retinal blood velocity indices. Twenty-eight healthy subjects were studied using scanning laser video fluorescein angiograms at baseline and after gas inhalation. Retinal arteriovenous passage time and mean arterial dye velocity were measured by means of a digital image processing system. Arterial diameter measurements showed no change (4%) during carbogen breathing. Increased arterial Pco2 and Po2 resulted in small but statistically significant increases in systolic and diastolic blood pressure and heart rate (each c. 8%, p < 0.05), and a dramatic increase in mean dye velocity (27%, p < 0.01), with parallel reduction in arteriovenous passage time (40%, p < 0.01). The substantial acceleration of retinal dye velocity and transit under combined hyperoxia and hypercapnia strongly suggests that this clinically standard gas mixture may indeed improve oxygenation without reducing retinal perfusion.

Adult↗
PubMed1994

Frequency of arylsulphatase A pseudodeficiency associated mutations in a healthy population.

Arylsulphatase A (ASA, EC 3.1.6.1) is a lysosomal enzyme that catalyses cerebroside sulphate degradation. ASA deficiency is associated with metachromatic leucodystrophy (MLD), a rare autosomal recessive disorder, which is characterised by the storage of cerebroside sulphate. Low ASA activities can be also observed in clinically healthy persons, a condition termed ASA pseudodeficiency. Two mutations responsible for the majority of pseudodeficiency alleles have been defined in the ASA gene. These are both A-->G transitions. One causes an asparagine to serine substitution (N350S). The second changes the first polyadenylation signal downstream of the stop codon (1524 + 95A-->G), which causes a severe deficiency of one ASA mRNA species. The incidence of the pseudodeficiency allele is estimated to be high in the general population and can be found in families carrying MLD associated mutations. We report a reliable stratagem for detecting the two PD associated mutations separately, which we have applied to a healthy population. Two homozygotes for the N350S and 1524 + 95A-->G mutations were detected, which gives a population frequency of 2.6%. The overall frequencies of the ASA-PD mutations were shown to be 17.5% for the N350S change and 13.0% for the 1524 + 95A-->G change, estimating each mutation separately. In addition, the frequency of both PD associated mutations occurring together on the same chromosome was found to be 12.3% in our population. The study has also allowed us to establish a new control ASA activity range, which was based on assay of blood from persons who had been shown at the DNA level not to carry ASA PD associated mutations.

Base Sequence↗
PubMed1994

A single origin for the most frequent mutation causing late infantile metachromatic leucodystrophy.

Metachromatic leucodystrophy is an autosomal recessive degenerative disease of the nervous system caused by the deficiency of the lysosomal enzyme arylsulphatase A (ARSA). We report here on the high incidence of late infantile MLD among Muslim Arabs originating from Jerusalem, most probably because of a founder effect. All the patients were found to be homozygous for 459 + 1 G-->A, a mutation which destroys the splice donor site of exon 2 of the ARSA gene. This mutation has been reported to be the most common mutation causing MLD. We studied the ARSA haplotype defined by three intragenic polymorphic sites in DNA samples from Muslim Arab patients from Jerusalem, a Christian Arab patient originating from the region, and eight other white patients, all homozygous for the 459 + 1 G-->A mutation. All the alleles carried the same haplotype which is in complete linkage disequilibrium with the mutation. This finding indicates a common origin for the 459 + 1 G-->A mutation which may have been introduced into Jerusalem at the time of the Crusades.

Alleles↗
PubMed1994

Commissioning diabetic eye screening by optometrists: a local initiative at the primary-secondary care interface.

The rationale behind the decision of a London family health services authority (Lambeth, Southwark, and Lewisham) to embark on a programme for diabetic eye screening by optometrists is outlined, discussing the way in which the scheme was set up and its possible future development. This family health services authority brought together a range of professionals across primary and secondary care to reach agreement on development of the service, and a consensus on clinical guidelines for operation of the scheme. This was particularly difficult in an area served by four hospitals which provide care to diabetics. Development of the scheme identified key questions about quality which have promoted a separate research agenda.

Accreditation↗
PubMed1994

Developmental expression of mucin genes MUC1 and MUC2.

The mucin gene MUC1, is expressed in a number of human ductal epithelia in vivo including those within the pancreas, mammary gland, kidney and genital ducts. Further it is expressed at a high level in certain tumours and tumour-derived cell lines. MUC2 was initially isolated from a human jejunum cDNA library and is thought to be one of the major intestinal mucin genes, though it is also expressed in the trachea. We have examined the developmental expression of these two mucin genes in human tissues. High level expression of MUC1 has been seen by 12.5 weeks of gestation in the epithelial of the distal respiratory tract and the collecting ducts in the kidney. By 18 weeks MUC1 mRNA is detectable in the colon but pancreatic expression of MUC1 is not seen until late in gestation. MUC2 mRNA is seen by 12 weeks of gestation in the jejunum, ileum and colon, and in large bronchioles of the lung by 18 weeks. The pattern of expression of MUC1 suggests that this mucin may not be involved in early ductal obstruction in the CF pancreas, but both MUC1 and MUC2 may play a role in the development of intestinal disease and MUC1 in early respiratory disease associated with CF.

Cystic Fibrosis↗
PubMed1994

Plasma and urinary levels of vasopressin in enuretic and non-enuretic children.

Plasma and urinary levels of vasopressin were measured by radioimmunoassay in 18 children with primary nocturnal enuresis and 20 age and sex matched controls. All subjects followed a protocol whereby all urine were collected and divided up into daytime (8 a.m.-8 pm) and night-time (8 p.m. - 8 a.m.) samples. Urine osmolality and urinary vasopressin levels were measured and, following an overnight observation period, the following morning (8 a.m.) plasma vasopressin was measured. Plasma vasopressin was significantly lower in the enuretic group (2.86 +/- 0.44 pg/ml) compared to the control group (3.64 +/- 1.35 pg/ml) (p = 0.011). Total urinary vasopressin excretion over 24 hours was lower in the enuretic group but the difference was not significant. These results support the hypothesis that one of the factors responsible for nocturnal enuresis in children may be due to a reduced nocturnal secretion of vasopressin. This may explain why the vasopressin substitution therapy is able to successfully abolish nocturnal enuresis symptoms.

Adolescent↗
PubMed1994

Hypergranulation tissue: a nontraumatic method of management.

Granulation tissue above the periwound area is usually considered an impediment to wound healing. Although there is very little in the literature regarding hypergranulation tissue, the fact that there are numerous treatments by various wound clinicians demonstrates the recognition of its presence as a clinical problem. The paucity of published information prompted the authors to design a study to collect objective data on a treatment method they had found useful in their practices. This article explores the issue of hypergranulation and offers a nontraumatic method of management. A prospective non-controlled correlational study was undertaken with ten patients and twelve wounds using a polyurethane foam dressing to reduce hypergranulation tissue. The results demonstrated a significant decrease in height of 2 mm of granulation tissue from initial measurements to measurements taken two weeks later (p < 0.01).

Aged↗
PubMed1994

Correlates of acute exercise-induced ocular hypotension.

PURPOSE: To understand those factors that determine the decrease in intraocular pressure (IOP) that occurs during acute dynamic exercise. METHODS: Three aspects of the exercise-IOP relationship were studied. These included graded exercise, with and without CO2 addition for isocapnia; comparison of the IOP response of trained and sedentary subjects to a fixed external work load; and exercise after ocular beta-adrenoceptor blockade. Graded exercise consisted of 7 minutes each at 30 and 90 watts on a cycle ergometer, then progressive work to exhaustion. Trained and sedentary subjects were defined on the basis of the blood lactate response to fixed external work (10 minutes at 90 watts). Selective beta 1-adrenoceptor blockade (betaxolol) and nonselective beta-adrenoceptor blockade (levobunolol) were superimposed on graded exercise. Intraocular pressure was measured using applanation tonometry. RESULTS: Graded exercise: Intraocular pressure decreased in proportion to exercise intensity. Hypocapnia developed in the last minutes of exhausting work, but preventing hypocapnia with CO2 addition failed to lessen the decrease in IOP. Response to fixed external work load: Intraocular pressure decreased significantly more in sedentary than in trained subjects; this decline was correlated with elevations in blood lactate but not with changes in metabolic rate or plasma osmolarity. Selective and nonselective beta-adrenoceptor blockade: Both drugs lowered IOP at baseline and throughout graded exercise; the drugs and exercise had apparently additive ocular hypotensive effects. CONCLUSIONS: Acute dynamic exercise lowers IOP in a graded fashion proportional to relative, not absolute, work load. The IOP decline is correlated with blood lactate but not with PCO2 or plasma osmolarity changes, and exercise potentiates the ocular hypotensive effects of beta-adrenoceptor blockade.

Betaxolol↗
PubMed1994

Expression of human immunodeficiency virus antigens in an attenuated Salmonella typhi vector vaccine.

Human immunodeficiency virus is known to enter the host at parenteral and mucosal sites and consequently an effective vaccine should stimulate immunity at both routes of entry. One approach toward stimulating HIV-specific mucosal and systemic immunity is the use of candidate live oral Salmonella typhi vector vaccine, strain CVD 908, which has been shown to stimulate mucosal and systemic immunity in volunteers. Using recombinant DNA techniques we constructed an expression cassette which comprises the lpp promoter (Plpp) and sequences encoding recombinant gp120 (rgp120). When the Plpp-rgp120 expression cassette is integrated into the chromosome of CVD 908 in the delta aroC allele, high levels of recombinant gp120 expression are observed. It is likely that effective immunity against HIV in humans will require immunization with multiple HIV antigens. Hence, a second expression cassette encoding two additional HIV antigens with vaccine potential, p24 (a HIV-1 gag gene product) and Nef (a putative regulator of HIV-1 gene expression) has been constructed. We plan to integrate the p24-Nef-encoding expression cassette into the aroD locus in the chromosome of CVD 908 delta aroC::rgp120 in a stable manner to produce a CVD 908-HIV vector vaccine that expresses multiple HIV antigens.

AIDS Vaccines↗
PubMed1994

Reductions of 56Fe heavy-particle irradiation-induced deficits in striatal muscarinic receptor sensitivity by selective cross-activation/inhibition of second-messenger systems.

Recent experiments have revealed radiation-induced (600 MeV/u 56Fe energetic particles) losses of sensitivity of rodent neostriatal muscarinic receptors to stimulation by cholinergic agonists that appears as reductions in oxotremorine enhancement of K(+)-evoked dopamine release. These losses were postulated to be the result of radiation-induced alterations early in phosphoinositide-mediated signal transduction. Additional findings indicated that if the ligand-receptor-G protein interface was by passed no radiation deficits were seen. In the present study, radiation-induced deficits in K(+)-evoked dopamine release were examined in perifused striatal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of 56Fe particles (600 MeV/u). Results showed that these deficits could be reduced by co-applying combinations of various pharmacological agents that were known to have differential effects on various second messengers such as 1,4,5-inositol-trisphosphate (IP3). Combinations included oxotremorine-carbachol, and either oxotremorine or carbachol with arginine vasopressin or arachidonic acid. These results are discussed in terms of putative radiation-induced changes in receptor-containing membranes which alter receptor-G protein coupling/uncoupling.

Analysis of Variance↗
PubMed1993

Bowringia mildbraedii agglutinin: polypeptide composition, primary structure and homologies with other legume lectins.

The amino-acid sequences of the subunits of the lectin BMA from seeds of Bowringia mildbraedii have been determined. The data indicate that the lectin consists of a precursor polypeptide of approx. 29 kDa that is cleaved almost completely into two fragments of approx. 13.3 kDa (alpha subunit) and approx. 11.9 kDa (beta subunit), respectively. The beta subunit represents the N-terminal half of precursor polypeptides and is disulphide-linked in a beta beta dimer in the native (alpha beta)2 protein. BMA shows extensive amino-acid sequence homologies with known legume lectins. The site of post-translational proteolysis of the putative precursor occurs at a position similar to that identified in lectins obtained from other Sophoreae plants such as Sophora japonica and in Diocleae lectins such as Concanavalin A, but different from that of two chain lectins obtained from other tribes of the Papilionaceae.

Agglutinins↗
PubMed1993

bcl-2 protein in non-small-cell lung carcinoma.

BACKGROUND: The proto-oncogene bcl-2 encodes a protein that inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but no data are available on the frequency or clinical importance of its expression in carcinoma. We studied bcl-2 expression in patients with non-small-cell lung carcinoma and correlated this phenomenon with survival. METHODS: Immunochemical analysis with a monoclonal antibody specific for bcl-2 was used to detect the protein in tumor samples from 122 patients undergoing surgery for squamous-cell carcinoma (80 patients) or adenocarcinoma (42 patients). The possibility that bcl-2 expression correlated with survival was investigated with use of the log-rank test, hazard ratios, and their confidence intervals. RESULTS: We detected bcl-2 protein in 25 percent of squamous-cell carcinomas (20 of 80) and 12 percent of adenocarcinomas (5 of 42). In adjacent normal respiratory epithelium, bcl-2 was expressed only in basal cells. Survival at five years was higher among patients with bcl-2-positive tumors, both in the group as a whole (P < 0.1) and in the group with squamous-cell carcinoma (P < 0.02). Patients 60 years of age or older who had bcl-2-positive tumors had the best prognoses, both in the group as a whole (P < 0.02) and in the group with squamous-cell carcinoma (P < 0.01). CONCLUSIONS: The proto-oncogene bcl-2 is abnormally expressed in some lung carcinomas, and its expression may have prognostic importance.

Adenocarcinoma↗
PubMed1993

Developing a research and development strategy for primary care.

General practice research has been a minority activity and underfunded in the past. The creation of the purchaser and provider split, the introduction of medical audit, and the new research and development strategy for the NHS provide an opportunity to focus research on the health needs of the population. FHSAs, with the regional health authority, should develop a local strategy for research and development and appoint a lead officer, who may be the medical adviser. When negotiating contracts FHSAs need to back up their arguments with research evidence. NHS development research should cover quality, distribution, accessibility, outcome, and effectiveness. FHSAs should play a part in disseminating knowledge in the interests of achieving an effective and high quality service. GPs should be encouraged to participate in research by relaxing the regulations of compulsory hours of patient service and by creating a practice development allowance.

Family Health↗
PubMed1993

Construction of a 5.2-megabase physical map of the human X chromosome at Xq22 using pulsed-field gel electrophoresis and yeast artificial chromosomes.

Several genes involved in human genetic diseases map to the Xq22 band on the long arm of the human X chromosome. We have constructed a long-range restriction map of the most proximal part of Xq22. Initially, pulsed-field gel electrophoresis, in combination with rare-cutting restriction enzymes, was used to try and establish physical linkage of 11 polymorphic and nonpolymorphic DNA markers. This approach resulted in the construction of three long-range restriction maps around groups of physically linked Xq22 markers that spanned over 5.0 Mb of DNA. Yeast artificial chromosome clones were used to organize the three long-range maps onto a contiguous 5.2-Mb stretch of Xq22. The order of markers in this region was shown to be cen-GLA-DXS178-DXS101-DXS83-DXS24-DXS101-+ ++DXS54-PLP-DXS94-DXS147-DXS17-DXS87-tel . The results of this study suggest that the proximal part of Xq22 may be rich in genes. Construction of a physical map for this region will, therefore, facilitate the localization and subsequent isolation of novel genes.

Chromosome Mapping↗