Search PubMed⌕ Search

Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 307 records · Page 17Linked to original sources
PubMed1994

HIV-specific T-helper activity in seronegative health care workers exposed to contaminated blood.

OBJECTIVE: To evaluate human immunodeficiency virus (HIV) type 1-specific cellular immune responses in HIV-seronegative health care workers with occupational high-risk exposures to HIV-infected (HIV-positive) patients. DESIGN: Peripheral blood mononuclear cells (PBMCs) were obtained after occupational exposures to HIV, and PBMCs from health care workers exposed to HIV-negative patients served as controls. The PBMCs were stimulated in vitro with HIV envelope synthetic peptides. Interleukin 2 (IL-2) production was measured in a bioassay. The HIV antibody status was determined by standard enzyme-linked immunosorbent assays. Exposed individuals were also evaluated for HIV proviral DNA by polymerase chain reaction techniques. PARTICIPANTS: The PBMCs from eight health care workers with high-risk exposures and nine control health care workers were studied. RESULTS: The PBMCs from all individuals showed strong IL-2 production to control antigens, indicating intact T-helper function. Interleukin 2 production to HIV peptides was detected in PBMCs from six of eight HIV-exposed individuals, but in only one of the nine health care workers exposed to HIV-negative body fluids (P < .008). None of the HIV-exposed health care workers became infected as determined by negative HIV antibody and polymerase chain reaction analysis after follow-up evaluation that ranged from 8 to 64 weeks. CONCLUSION: Human immunodeficiency virus-specific T-helper activity was detected in six (75%) of eight HIV-negative health care workers with exposure to HIV-positive body fluids. Potent HIV-specific T-helper activity was detectable 4 to 8 weeks after the exposure and was lost in individuals followed up for 8 to 64 weeks. Three health care workers remained responsive at 8, 19, and 24 weeks. Exposure to HIV without evidence of subsequent infection appears to result in activation of cellular immunity without activation of antibody production.

Adult↗
PubMed1994

A 6.5-Mb yeast artificial chromosome contig incorporating 33 DNA markers on the human X chromosome at Xq22.

The Xq22 region of the human X chromosome contains genes for a number of inherited disorders. Sixty-nine yeast artificial chromosome clones have been isolated and assembled into a 6.5-Mb contig that contains 33 DNA markers localized to this region. This contig extends distally from DXS366 to beyond DXS87 and includes the genes involved in X-linked agammaglobulinemia (btk), Fabry disease (GLA), and Pelizaeus-Merzbacher disease (PLP). The order of markers in this contig is consistent with the known genetic and physical mapping information of Xq22. This cloned material provides a source from which to isolate other genes located in this part of the X chromosome.

Adult↗
PubMed1994

Identification of rare and novel mutations in the CFTR genes of CF patients in southern England.

Cystic fibrosis patients referred to two genetics centres in southern England and not found to carry common CF-associated mutations in one or both of their CFTR genes have been subjected to an extensive mutation search. The whole of the coding region of the CFTR gene, all intron-exon boundaries and 5' and 3' untranslated regions have been examined by a combination of single stranded conformational polymorphism analysis and chemical mismatch detection; 48 chromosomes with rare mutations have been identified, including 7 novel mutations, 182delT in exon 1, G27X in exon 2, Q151X in exon 4, Q220X in exon 6a, Q525X in exon 10, 3041delG in exon 16, and 4271delC in exon 23.

Base Sequence↗
PubMed1994

Molecular genetics of metachromatic leukodystrophy.

Metachromatic leukodystrophy is an autosomal recessive inherited lysosomal storage disease. It can be caused by mutations in two different genes, the arylsulfatase A and the prosaposin gene. These genes encode two proteins that are needed for the proper degradation of cerebroside sulfate, a glycolipid mainly found in the myelin membranes. Deficiency of arylsulfatase A or of a proteolytic product of prosaposin leads to the accumulation of cerebroside sulfate, which causes a lethal progressive demyelination. Mutations in the arylsulfatase A gene are far more frequent than those of the prosaposin gene. So far 31 amino acid substitutions, one nonsense mutation, three small deletions, three splice donor site mutations, and one combined missense/splice donor site mutation have been identified in the arylsulfatase A gene. Two of these mutant alleles are frequent, accounting for about one-half of all mutant alleles, whereas the remainder are heterogeneous. Amino acid substitutions cluster in exons 2 and 3, a region that shows a high degree of conservation among sulfatases of different function and origin. Different mutations are associated with phenotypes of different severity, but there is a remarkable variability of severity when patients with identical genotypes are compared. Demonstration of an arylsulfatase A deficiency is not a proof of metachromatic leukodystrophy, since a substantial deficiency without any clinical consequences is frequent in the general population. This deficiency is caused by an arylsulfatase A allele, which due to certain mutations encodes greatly reduced amounts of functional enzyme. However, these amounts are sufficient to sustain a normal phenotype. In the diagnosis and genetic counseling, these deficiencies must be differentiated from those causing metachromatic leukodystrophy. So far only six patients with mutations in the prosaposin gene have been described, in which three defective alleles two with amino acid substitutions and one with a 33-bp insertion have been identified.

Cerebroside-Sulfatase↗
PubMed1994

Perifoveal microcirculation with non-insulin-dependent diabetes mellitus.

Fluorescein angiograms were performed to evaluate perifoveal capillary blood velocities (v), capillary density (perifoveal intercapillary areas: PIA) and the foveal avascular zone (FAZ) by means of the scanning laser technique (SLO-101 Rodenstock). The angiograms were digitally stored and the data quantified off-line with an image analyzing system (IBAS). In the present study 46 patients with non-insulin-dependent diabetes mellitus (NIDDM) were examined and their data compared with that of 31 healthy volunteers. The perifoveal capillary flow velocity of the NIDDM subjects (v = 2.33 +/- 0.36 mm/s) was significantly (P < 0.01) decreased as compared to healthy subjects (v = 2.86 +/- 0.41 mm/s). The perifoveal intercapillary areas in the foveal avascular zone were significantly increased in patients with NIDDM (PIA = 10029 +/- 3402 microns2; FAZ = 0.415 +/- 0.272 mm2) as compared with healthy subjects (PIA = 3965 +/- 467 microns2; FAZ = 0.221 +/- 0.071 mm2). These data suggest the possibility that a decrease in perifoveal capillary blood velocities in combination with decreased capillary density (enlarged PIA) and an enlargement of the foveal avascular zone may occur in patients with NIDDM. The determination of these parameters could help in monitoring the progress of diabetic retinopathy and diabetic maculopathy.

Adult↗
PubMed1994

Maxi K+ channels on human vas deferens epithelial cells.

The vas deferens forms part of the male reproductive tract and extends from the cauda epididymis to the prostate. Using the patch clamp technique, we have identified a Ca(2+)-activated, voltage-dependent, maxi K+ channel on the apical membrane of epithelial cells cultured from human fetal vas deferens. The channel had a conductance of approximately 250 pS in symmetrical 140 mM K+ solutions, and was highly selective for K+ over Na+. Channel activity was increased by depolarization and by an elevation of bath (cytoplasmic) Ca2+ concentration, and reduced by cytoplasmic Ba2+ (5 mM) but not by cytoplasmic TEA (10 mM). Channel activity was also dependent on the cation bathing the cytoplasmic face of the membrane, being higher in a Na(+)-rich compared to a K(+)-rich solution. We estimated that up to 600 maxi K+ channels were present on the apical membrane of a vas cell, and that their density was 1-2 per mu 2 of membrane. Activity of the channel was low on intact cells, suggesting that it does not contribute to a resting K+ conductance. However, fluid in the lumen of the human vas deferens has a high K+ concentration and we speculate that the maxi K+ channel could play a role in transepithelial K+ secretion.

Calcium↗
PubMed1994

Increased abdominal pain during final examinations.

Anecdotes and animal experiments alike suggest that physiological and psychological stress can profoundly alter gastrointestinal function. However, few studies have examined, in humans, real-world stress to see if free-living persons exhibit gut alterations similar to those produced in the laboratory. To investigate this possibility, we studied 16 medical and premedical students during final written examinations. As compared to a control day, the examination created a classic stress response: elevated serum cortisol (16 +/- 1 to 21 +/- 3 micrograms/dl; P < 0.05), ACTH (31 +/- 1 to 33 +/- 1 pg/ml; P < 0.05), heart rate (72 +/- 3 to 79 +/- 3 beats/min; P < 0.05), arterial blood pressure (systolic pressure 106 +/- 2 to 120 +/- 2 torr; P < 0.05; diastolic pressure 72 +/- 2 to 77 +/- 1 torr; P < 0.05), and subjective anxiety (raw score 28 +/- 2 to 47 +/- 3; P < 0.0001). In contrast, subjects displayed identical orocecal liquid transit time (of 0.36 g/kg lactulose in a 240-ml, 250-kcal liquid meal) under control (103 +/- 8 min) and examination conditions (106 +/- 8 min; P = NS). Mean subjective reports of gas, diarrhea, and borborygmi were unchanged on the day of the experiment, although the examination did increase reported abdominal pain (from 0.5 +/- 0.4 to 2.1 +/- 0.5 on a 0-5 analog scale; P < 0.05). We conclude that examination stress in humans can increase gastrointestinal symptoms without altering orocecal transit.

Abdominal Pain↗
PubMed1994

Physiological perturbation of ocular and cerebral blood flow as measured by scanning laser ophthalmoscopy and color Doppler imaging.

Retinal blood flow regulation in health remains poorly described. We hypothesized that retinal perfusion is controlled to provide constant O2 delivery to that tissue, and that changes in retinal blood flow in response to chemical stimuli parallel changes in carotid and retrobulbar perfusion. Accordingly, in 11 young adults with normal eye examinations, we measured retinal blood flow indices (via scanning laser ophthalmoscopy [SLO] during fluorescein angiography) and carotid, ophthalmic, and central retinal arterial blood flow indices (via Doppler imaging [CDI]) under control, hypoxic (alveolar PO2 = 55 +/- 3 mmHg) and hyperoxic (alveolar PO2 = 655 +/- 18 mmHg) conditions. The three conditions were counterbalanced in order and isocapnia was maintained in each. Retinal arterial mean dye velocity and arteriovenous passage time, as measured by SLO, were slowed by hyperoxia and accelerated by hypoxia, in rough proportion to the changes in arterial O2 content (+/- 10%; p < 0.05). In the seven subjects in which relative measurements of retinal arterial diameters were obtained, neither hypoxia nor hyperoxia significantly altered vessel diameter. At the same time, mean retinal capillary transit velocity was independent of PO2, suggesting that, in health, retinal capillaries may be recruited as PO2 falls. O2-induced changes in carotid, ophthalmic, or central retinal arterial blood flow velocities (via CDI) were not found, though a wide coefficient of variation (30% for CDI vs. 14% for SLO) may have contributed to this failure. We conclude that, under isocapnic conditions, retinal perfusion may be regulated to provide constant O2 delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The visual response to increased ocular blood flow in normal pressure glaucoma.

The vascular reactivity to breathing carbon dioxide represents a widely used method in neurology to diagnose microvascular cerebral disorders. Fifteen eyes of 15 patients suffering from confirmed normal pressure glaucoma were included in the study. The ocular carbon dioxide reactivity was determined by recording ocular pulse amplitudes (OPA) by means of oculo-oscillo-dynamography (OODG). The initial pulse amplitudes were found to be comparable to healthy subjects. According to the results obtained during breathing increased carbon dioxide concentrations (95% O2; 5% CO2; endtidal CO2 approx. 6.5%), the collective of 15 patients could be subdivided into two subgroups. One group (n = 9) showed a carbon dioxide reactivity that was comparable to healthy subjects, i.e., an increase of ocular pulse amplitudes of 57%. The remaining six eyes, however, showed a statistically significantly higher OPA increase compared to the first subgroup. According to the results obtained and to evaluate the hypothesis that these hemodynamic changes are accompanied by functional improvements, central visual fields were performed during breathing room air or increased inspiratory carbon dioxide concentrations. After exposure to carbon dioxide the visual fields improved significantly in patients who showed a significant increase in OPA. An increased carbon dioxide reactivity in some normal pressure glaucoma patients, i.e., a significant increase of OPA and a significant improvement of the central visual field during exposure to increased inspiratory carbon dioxide concentrations, may be due to an initial ocular vasospasm in these patients, which can be released by induced vasodilation due to carbon dioxide exposure.

Aged↗
PubMed1994

Effect of local inhibition of nitric oxide synthesis on forearm blood flow and dorsal hand vein size in patients with alcoholic cirrhosis.

1. Nitric oxide (NO) is a potent endogenous vasodilator and plays a role in the control of resting vascular tone. Patients with cirrhosis have a hyperdynamic circulation with reduced blood pressure and decreased peripheral resistance, and it is possible that increased production of NO due to induction of NO synthase may be involved in maintaining this vasodilatation. We have examined this possibility by studying the effects of local infusions of NG-monomethyl-L-arginine (an inhibitor of NO synthase) in the forearm arteriolar bed and the superficial dorsal hand veins of patients with alcoholic cirrhosis. 2. Drugs were either infused locally into the brachial artery and forearm blood flow was measured by venous occlusion plethysmography, or into a vein on the back of the hand and vein diameter was measured using a linear displacement technique. 3. Basal forearm blood flow was increased and vascular resistance was decreased in the patients with alcoholic cirrhosis compared with healthy control subjects. Noradrenaline and NG-monomethyl-L-arginine caused dose-dependent falls in forearm blood flow in both healthy control subjects and patients with cirrhosis. There was no significant difference in the responses to either noradrenaline or NG-monomethyl-L-arginine between the two groups. 4. In the superficial hand veins there was no change in vein size in response to NG-monomethyl-L-arginine infused alone, and venoconstriction to local infusion of noradrenaline was unaffected by co-infusion with NG-monomethyl-L-arginine. 5. Our results confirm that patients with alcoholic cirrhosis are vasodilated compared with healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The changing role of the nurse in neonatal care: a study of current practice in England.

The boundaries of nursing in neonatal care, and the interface between the work of nursing and medical staff in delivering care, are changing. The enhanced or expanding role of the neonatal nurse is not a universally accepted one. If this professional development is to be widely accepted and implemented, some key issues will need to be addressed so that the changing role of the nurse and associated skill base are well founded. As part of a large-scale national study of neonatal nursing in England, data were collected from nurses working in 24 different units. Regional centres, subregional centres and district units from six widely separated health regions participated, and individual data were collected from 718 nurses (599 D-I grades and 119 A-C grades). While indicating that there is inter-unit variation in nursing practice, the results also show that many nurses are already in the process of changing their role in this acute specialty. Nurses doing so are more likely to have a qualification in this specialty, though not all of them have. A small number of nursery nurses and nursing auxiliaries were undertaking tasks that could be considered part of an expanded role. The implications of the findings are discussed.

Attitude of Health Personnel↗
PubMed1994

Training and education for nurses working in neonatal care.

The issue of nurse education and training in the context of providing a high-quality service for sick and small babies and their families is a paramount concern. As part of a large-scale study of neonatal nursing in the United Kingdom, data were collected on nurses' educational background, professional qualifications, experience, orientation, appraisal and update. The results reveal a qualification in specialty (QIS) rate for trained nurses of 53% and large variation not directly related to size or type of unit. The proportion of nurses having appraisal interviews (47% in the last year) and professional development plans (19%) was low and a clear gap existed between policy and practice. The implications of the findings are discussed and the need for management training, targeting of neonatal units with low QIS rates, and more flexible education programmes are emphasized.

Adult↗
PubMed1994

Analysis of mutations and alternative splicing patterns in the CFTR gene using mRNA derived from nasal epithelial cells.

Ten to fifteen percent of CF chromosomes carry mutations which are not detected by routine screening of the CFTR gene for known mutations. Many techniques have been used to screen the CFTR gene for these remaining mutations. Most of the methods use genomic DNA, and since the CFTR gene contains 27 exons, are necessarily labour intensive. We have screened the entire coding region of CFTR, by chemical cleavage of 7 overlapping segments of amplified cDNA. Using this method we have identified 4 sequence changes which had not been detected by screening genomic DNA, and successfully detected 10 out of 13 known mutations. In addition, we have identified 8 alternatively spliced forms of CFTR mRNA, 4 of which have not been described previously. These include transcripts lacking a) exon 3, b) exons 2 + 3, c) exons 9 + 12, and d) the final 357 bp of exon 15 as a result of use of the cryptic splice donor site CA2863/GTTCGT).

Base Sequence↗
PubMed1994

Nursing skill mix in neonatal care.

A large scale study of neonatal nursing was carried out with data collected from 56 sites (4 hospitals from each of the health regions of England). In the area of skill mix the key findings were: the largest segment of the neonatal nursing workforce is made up of staff nurses and staff midwives, and of these there are greater numbers of staff nurses; the E grade at 31% is the most frequently found, followed by the G (19%) and F grades (16%); vacancies were disproportionately high at staff nurse/staff midwife level; nursery nurses were employed for direct nursing care in 80% of units; nursing auxilliaries were employed in 70% of units, though in only half were they involved in the direct care of babies. Staffing policies were diverse and not clearly related to the type of unit or the numbers of designated intensive and special care costs. There was a tendency to employ more junior staff at night, the use of support staff varied widely, and in many units was at very low levels or absent. In addition to differing service demands that may affect the skill mix required, there is a clear need for the profession to address the questions that arise from changing roles and areas of responsibility in the spheres of management, teaching and clinical practice.

Career Mobility↗
PubMed1994

Sequelae of Haemophilus influenzae type b meningitis in aboriginal and non-aboriginal children under 5 years of age.

Between 1984 and 1990, 257 cases of Haemophilus influenzae type b (Hib) meningitis occurred in children under five years of age in Western Australia. We obtained information on possible sequelae in 131 cases (all non-Aboriginal) by medical record review and parental interview, and in a further 116 cases (60 non-Aboriginal, 56 Aboriginal) by medical record review only; no follow-up information was available for ten children (nine non-Aboriginal, 1 Aboriginal). The incidence of Hib meningitis in children under five years of age was 26.3 per 100,000 for non-Aboriginal and 152.2 per 100,000 for Aboriginal children. The case fatality rate was 3.5% for non-Aboriginal children and 14.0% for Aboriginal children. Sequelae were recorded for 17.1% of non-Aboriginal and 22.4% of Aboriginal children who survived Hib meningitis. Surviving Aboriginal children experienced severe sequelae following Hib meningitis almost three times more frequently than surviving non-Aboriginal children (10.5% vs 3.6%), although mild and moderate sequelae were not more common in Aboriginal children. The information on incidence and severity of sequelae in this study was obtained by chart review and parental interview, and hence may be subject to error or bias, particularly for mild and moderate disabilities. Outcomes like death and severe sequelae, such as cerebral palsy and profound intellectual and physical disability, are less subject to bias. Of Aboriginal children who contracted Hib meningitis in Western Australia over the study period, 22.8% either died or had severe sequelae, while only 7.0% of non-Aboriginal children experienced these severe outcomes.

Cerebral Palsy↗