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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 289 records · Page 16Linked to original sources
PubMed1995

Three unrelated Gaucher's disease patients with three novel point mutations in the glucocerebrosidase gene (P266R, D315H and A318D).

Three novel point mutations were detected in the glucocerebrosidase gene of three unrelated Gaucher's disease patients by direct sequencing of PCR products. The first is a C to G change at position 4263 in the genomic sequence (exon 7) which results in a proline to arginine change at position 266 in the mature enzyme (P266R). The second is a G to C change at position 5276 in the genomic sequence (exon 8) which results in an aspartic acid to histidine change at position 315 (D315H). The third is a C to A change at position 5286 in the genomic sequence (exon 8) which results in an alanine to aspartic acid change at position 318 (A318D). The first mutation destroys an AvaII restriction endonuclease site, the second creates a BspMI site and the third creates a BamH I site.

Adult↗
PubMed1995

CO2 dependence of retinal arterial and capillary blood velocity.

OBJECTIVE: Blood flow to the brain is extremely sensitive to changes in PCO2. While animal studies show a similar potent PCO2 dependence in retinal and choroidal vessels, the PCO2-retinal blood flow relationship has never been adequately studied in humans. METHODS: Video scanning laser ophthalmoscopy after fluorescein angiography was used to analyze retinal arterial and capillary blood velocity under conditions of mild hypercapnia and hypocapnia. Control conditions (end-tidal PCO2 = 38.3 +/- 0.4 mmHg) were contrasted with hyperventilation-induced hypocapnia (PCO2 = 34.0 +/- 0.4 mmHg) and hypercapnia (PCO2 = 42.3 +/- 0.5 mmHg) created by PCO2 addition to inspired gas. RESULTS: Both larger vessel and macular capillary blood velocity was dependent upon PCO2: arteriovenous passage time fell as PCO2 rose, and both mean arterial dye velocity and capillary blood velocity rose as PCO2 rose (all p < 0.05). These changes in flow velocity occurred despite unchanged heart rate, arterial systolic and diastolic blood pressure, intraocular pressure, and calculated ocular perfusion pressure. Contrast sensitivity was also unchanged by PCO2 variation. CONCLUSIONS: The human retinal circulation, like the whole cerebral circulation, may be strongly dependent upon PCO2 in a manner that is unrelated to perfusion pressure and apparently outside strict autoregulatory controls.

Adult↗
PubMed1995

Maternal perceptions of neonatal care.

In a large-scale study of neonatal care in England, hospital and questionnaire data were collected on the experiences of an unselected group of 420 mothers whose babies had recently been admitted for neonatal care to one of 23 widely distributed hospitals. Perceptions of their infant while in the neonatal unit differed in relation to gestational age, whether or not the baby required assisted ventilated, the mother's own health and if she had previously had a baby cared for in this way. This investigation of how mothers see and adjust to their small, sick baby in the neonatal unit confirmed the crisis nature of the birth and admission, and provides insights for staff and other health professionals about the salient issues for parents at this time.

Adult↗
PubMed1995

Macular microcirculation in cystoid maculopathy of diabetic patients.

BACKGROUND: In patients with diabetic macular oedema and central cysts ischaemia of the retina appears to be an important contributing factor in the pathogenesis of cysts. This study was performed to further elucidate the role of the inner retinal microcirculation in diabetic cystoid macular oedema (CMO). METHODS: Video fluorescein angiography allows visualisation of the macular microvasculature and measurements of the capillary blood velocity (CBV), foveal avascular zone (FAZ), and perifoveal intercapillary area (PIA, characterising capillary density). RESULTS: Twenty three diabetic subjects with CMO, matched diabetic patients without macular oedema (n = 23), and healthy subjects (n = 23) were included. CBV, PIA, and FAZ did not differ significantly among diabetic groups regardless of presence of cystoid changes. CBV was significantly reduced (p < 0.0001) and PIA was more than doubled in both diabetic groups (p < 0.0001) when compared with healthy subjects. Furthermore, FAZ showed a nearly doubled size in diabetic patients without macular oedema (p < 0.01) and a less pronounced enlargement (by 29%) in diabetics with CMO (p < 0.05). CONCLUSION: The results indicate that the retinal microcirculation in diabetic patients is markedly altered when compared with healthy subjects, regardless of CMO presence. In CMO patients the microcirculatory changes are similar to those of diabetic patients without macular oedema. Thus inner retinal perfusion does not contribute to tissue ischaemia leading to cystoid formations in diabetic maculopathy.

Adult↗
PubMed1995

Detection of cytomegalovirus using PCR in serum from renal transplant recipients.

AIMS: To develop a polymerase chain reaction (PCR) assay for the detection of cytomegalovirus (CMV) DNA in serum and leucocytes of renal transplant recipients and compare this assay with CMV culture and serodiagnosis. METHODS: Monthly specimens were obtained from 12 patients starting immediately before transplant. CMV infection was monitored by IgM enzyme linked immunosorbent assay, virus culture and PCR on serum and leucocytes. RESULTS: Two of four IgG positive patients had reactivation of CMV disease confirmed by culture, three of eight seronegative patients had a primary infection, one confirmed by serology and two by culture. PCR was positive earlier than conventional methods in three cases and concurrently in two. No positive PCR reactions occurred in the seven patients who remained negative by culture and serology. CONCLUSIONS: CMV DNA is detectable in serum; serum may be positive before virus is detectable by buffy coat culture; and PCR may be useful as an early indication of potential CMV disease in renal transplant recipients.

Adult↗
PubMed1995

Cystic fibrosis.

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Animals↗
PubMed1995

Visceral varicella zoster infection after bone marrow transplantation without skin involvement and the use of PCR for diagnosis.

A 41-year-old patient with acute myeloid leukemia was transplanted from an HLA-identical but ABO-incompatible sibling. The post-transplant course was complicated by pure erythrocyte aplasia and mild chronic graft-versus-host disease. Eleven months after transplant while on steroid therapy she developed abdominal pain rapidly followed by fatal fulminant hepatic failure. Varicella zoster virus (VZV) was detected using the polymerase chain reaction from blood and liver obtained at necropsy even though no skin manifestations of VZV were present. This case confirms previous reports of visceral VZV infection in the absence of skin lesions thus emphasising the importance of suspecting the presence of VZV in this clinical setting and outlines the possible value of PCR in the rapid diagnosis of infection.

Adult↗
PubMed1995

High dose interferon alpha-2b therapy for chronic hepatitis C: an open label study of the response and predictors of response.

OBJECTIVES: The current recommended dose of interferon (IFN) for chronic hepatitis C is 3 million units (m.u.) 3 times a wk for 6 months, although the optimal dose is uncertain. In an open label cohort format, we evaluated the response rate at 6 months, the relapse rate at 12 months, the predictors of response, and adverse effects in 34 patients (mean age 42.4 +/- 2.4 yr) with chronic hepatitis C who were treated with 5 m.u. IFN 3 times a wk for 6 months. RESULTS: Twenty-nine patients (85%) responded either totally (TR) or partially (PR), and five (15%) showed no response (NR). Of 18 TR, eight (45%) showed a sustained response (SR), and nine (50%) patients relapsed at 12 months of follow-up with an overall SR rate of 24%. Despite the high frequency of side effects (17-70%), all patients completed the treatment. Of interest, two of three PR treated for an additional 3-6 months with 7.5 m.u. of IFN became TR at 12 months. Univariate and multivariate analysis demonstrated that the known duration of hepatitis and/or abnormal ALT elevation was longer in responders (43.5 +/- 9.1 months) compared with NR (8.2 +/- 1.4 months) (p = 0.018). Age, alcohol abuse, mode of acquisition, transaminase levels, and liver histology did not differ significantly between responders and NR. HCV-RNA in serum by RT-PCR assay was performed in six TR and four PR pretreatment, immediately posttreatment, and 3-6 months later. Five TR showed disappearance of viral RNA posttreatment with reappearance at low concentrations in two patients who relapsed. In four PR, viral RNA was detectable at low concentrations posttreatment. CONCLUSIONS: 1) Higher dose IFN therapy yields higher response rates at 6 months than the dose currently recommended with acceptable toxicity, but does not improve the sustained response rate; 2) the only predictor of a favorable response in this study was a longer known duration of hepatitis/abnormal ALT elevations; 3) serum HCV-RNA levels often disappear with a total response and may be used to monitor the response to treatment and relapse.

Adult↗
PubMed1994

Color Doppler analysis of ocular vessel blood velocity in normal-tension glaucoma.

The pathogenesis of normal-tension glaucoma remains unknown. Because ocular vasospasm has been proposed as a possible mechanism, we investigated ocular vessel flow velocity in normal-tension glaucoma patients at rest and under treatment with a cerebral vasodilator. Ten normal-tension glaucoma patients and nine age- and gender-matched controls had flow velocity measured in three vessels (ophthalmic artery, central retinal artery, and temporal short posterior ciliary artery) by using color Doppler imaging, under baseline conditions and during carbon dioxide supplementation sufficient to increase end-tidal PCO2 by 15%. Peak systolic and end-diastolic velocities were measured, and the resistance index (peak systolic velocity minus end-diastolic velocity, divided by peak systolic velocity) was calculated. Compared with controls, these normal-tension glaucoma patients had significantly lower end-diastolic velocities (P = .002) and higher resistance indices (P = .007) in the ophthalmic artery at baseline. When PCO2 was increased, control subjects remained unchanged, whereas it increased end-diastolic velocity in patients (P = .003) and abolished the difference in resistance index between the two groups. Patients and control subjects differed little in their baseline or carbon dioxide response velocities or in resistance in the other two vessels. These results indicate that at baseline these normal-tension glaucoma patients may have increased vascular resistance distal to the ophthalmic artery, although this increased resistance cannot be specifically ascribed to the central retinal arterial or to temporal short posterior ciliary arterial vascular beds. The responsiveness of these patients to a cerebral vasodilator (increased PCO2) indicates further that the increased resistance distal to the ophthalmic artery may be the reversible result of vasospasm.

Adult↗
PubMed1994

Expression of xenobiotic-metabolizing enzymes by primary and secondary hepatic tumors in man.

PURPOSE: To determine the immunohistochemical expression of xenobiotic-metabolising enzymes (XME) in normal livers, primary hepatocellular carcinomas (hepatomas) and secondary hepatic tumors from colonic primary tumors. METHODS AND MATERIALS: The expression of XME in primary (n = 16) and secondary (n = 21) hepatic tumors and patients with no malignancies (n = 20) were investigated using polyclonal antibodies raised against the following rat enzymes CYP1A1, CYP2B1, CYP2C6, CYP3A1, CYP4A1, cytochrome P-450 reductase, epoxide hydrolase and testosterone UDP-glucuronyl transferase. The rat cytochrome P-450 antibodies recognize various human isoenzymes within the same gene family. Immunohistochemistry was undertaken using the immunoperoxidase and alkaline phosphatase anti-alkaline phosphatase techniques. RESULTS: There was a reduction in the overall expression of all XME by tumor tissue compared to adjacent nonneoplastic liver cells (p = 0.008), more in livers with secondary tumors (p < 0.0001) and reduced expression of XME by hepatomas and secondary liver tumors compared to livers with no malignancy. A tendency for higher expression of all XME by nonneoplastic liver cells from patients with hepatomas relative to nonmalignant livers was observed, with significantly higher expression of CYP3A4/5 and testosterone UDP-GT enzymes (odds ratio 3.12; CI 1.59-6.10). CONCLUSION: The expression of XME by tumor tissue is reduced in primary and secondary hepatic malignancies. The expression of XME by nonneoplastic liver cells is higher in patients with hepatomas than patients with no hepatic malignancies. These alterations in XME activities may have important therapeutic implications in the response and toxicity to systemic anti-cancer therapy, due to altered pharmacokinetics. In addition, differential expression of these enzymes by normal and malignant cells may be important for the rational design of selective anti-tumor drugs.

Adult↗
PubMed1994

The burden of Haemophilus influenzae type b disease in Australia and an economic appraisal of the vaccine PRP-OMP.

OBJECTIVES: To estimate the incidence and sequelae of Haemophilus influenzae type b disease (Hib) in the Australian population, and to evaluate the costs and outcomes of a vaccination program using the vaccine PRP-OMP at two, four and 12 months. DESIGN: The evaluation was based on a decision analytic model developed by Merck Sharp and Dohme (Australia) Pty Ltd, to predict the number of children who would contract Hib, and suffer mild or severe sequelae or die as a result. The state of health of a cohort of children was modelled each month over a five-year period. A survey of medical records and interviews with parents of children who contracted meningitis in Western Australia from 1984-1990 was undertaken to provide data on the extent and costs of sequelae. RESULTS: The incidence of Hib among non-Aboriginal Australians under five years of age was estimated as 53 per 100,000, and 460 per 100,000 among Aborigines. In a single year at least 630 children may contract Hib, up to 19 may die, and a further 46 may have neurological damage, this being severe in up to 18 children. The number of deaths could be reduced by 17 per year and a further 25 cases of severe and 16 cases of mild disability could be averted. At a price of $20 per dose, and a 5% discount rate, the expected cost per year of life extended by a vaccination program is $3148. When adjusted for the increased number of years without neurological impairment, the incremental cost per quality adjusted life year (QALY) is $1965. Compared with a single vaccine at 18 months, the incremental cost per additional QALY gained is $5047. A separate analysis of the Aboriginal population showed that the proposed vaccination program would be of significant benefit, leading to a saving of resources.

Age Factors↗
PubMed1994

A nuclear factor that binds purine-rich, single-stranded oligonucleotides derived from S1-sensitive elements upstream of the CFTR gene and the MUC1 gene.

We have identified two regions of non-random purine/pyrimidine strand asymmetry that were nearly identical in sequence in the 5' flanking (promoter) regions of the human cystic fibrosis transmembrane conductance regulator (CFTR) gene and the human MUC1 gene. These regions contain perfect mirror repeat elements, a sequence motif previously found to be associated with the formation of H-DNA conformations. In this report we demonstrate that a single-stranded non-B DNA conformation exists at low pH in supercoiled plasmids containing the similar mirror repeat elements, and that S1 nuclease digestion maps the single-stranded region to the position of the mirror repeats. In addition, we identify a nuclear protein of approximately 27 kD that binds to single-stranded oligonucleotides corresponding to the purine-rich strand of this region, but not to the pyrimidine-rich strands or to double-stranded oligonucleotides with corresponding purine/pyrimidine strand asymmetry.

Base Sequence↗
PubMed1994

The stop mutation R553X in the CFTR gene results in exon skipping.

Stop or nonsense mutations are known to disrupt gene function in a number of different ways. We have studied the effects of the stop mutation R553X in exon 11 of the CFTR gene by analyzing mRNA extracted from nasal epithelial cells harvested from patients with cystic fibrosis. Four patients who were compound heterozygotes for the R553X mutation were studied. Ten non-CF control subjects were also studied. In all four patients, full-length CFTR mRNA was identified, but only a very small proportion of this was derived from the R553X allele. A smaller transcript, lacking exon 11, was also seen in the R553X patients but not in the controls. Most of this transcript was derived from the R553X allele. These results suggest that the R553X mutation results in skipping of the exon in which it is located.

Alleles↗