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Biomedical subjects

R H Moore

Publications and source records attributed to R H Moore.

At least 19 recordsLinked to original sources
PubMed1992

An audit of appropriate tests in renal biopsy coagulation screens.

Hematological, biochemical, and clinical data was collected over a 15-month period on all adult (greater than 16 years) patients assessed for percutaneous biopsy of native kidneys in a major renal unit. The frequency, causes, interrelationships, and treatment of the abnormalities, along with factors resulting in delay or cancellation of renal biopsies were subsequently subjected to audit. Overall, 30 of 147 coagulation screens were abnormal. The most common coagulopathy was a prolonged bleeding time (BT), which accounted for 58.6% of these. A prolonged BT was not clearly related to other hematological or biochemical indices, and proved to be treatable with arginine vasopressin (DDAVP). The majority of abnormalities occurred in isolation (23/30), and eight of 30 were related directly to current anticoagulant or antiplatelet medication. All but two patients with abnormalities proceeded to renal biopsy after successful corrective measures, but 21 of 30 were delayed by between 1 hour and 14 days. None of the remaining 117 biopsies were delayed, although seven were cancelled for a variety of reasons. The prothrombin consumption index provided no additional useful management information. Our clotting screen, modified by this audit, should safely and efficiently detect clotting abnormalities before renal biopsy.

Adolescent↗
PubMed1992

HLA-DP region gene polymorphism in primary IgA nephropathy: no association.

Many features suggest that a genetically mediated abnormality of the IgA immune response is central in the pathogenesis of IgA nephropathy (IgAN). Candidate disease susceptibility genes include those encoding the MHC class II antigens, HLA-DR, -DQ, and -DP, and we have recently described an HLA-DQB1 association in IgAN. Polymorphisms of the HLA-DP region loci have been shown to associate with autoimmune diseases which share immunological features with IgAN; coeliac disease (CD) and dermatitis herpetiformis (DH). We have therefore examined restriction fragment length polymorphisms (RFLPs) of the DP alpha and DP beta chain genes (DPA1 and DPB1 respectively) in IgAN, and have studied three caucasoid populations (North, Mid, Southern Europe) to determine whether ethnic variation in genetic susceptibility exists. DNA was extracted from blood (IgAN, UK n = 89, Italy n = 75, Finland n = 49; Controls, UK n = 99, Italy n = 54, Finland n = 45), and studied by Southern blot hybridization techniques using the restriction enzymes BgI II and Msp I and cDNA 32P-labelled DPA1 and DPB1 probes respectively. The frequency distribution of the DPA1 and DPB1 fragments was similar between the three caucasoid IgAN patient groups compared to their respective controls. There was no association of DPA1 or DPB1 RFLPs with clinical features. These results suggest that HLA-DP region genes are not important in conferring disease susceptibility to IgAN and do not influence clinical disease expression. Moreover, different immunogenetic mechanisms operate in IgAN, CD, and DH.

Glomerulonephritis, IGA↗
PubMed1992

Selective IgA deficiency associated with glomerulonephritis and oligoarthritis.

A 59 year old woman with selective IgA deficiency associated with oligoarthritis and glomerulonephritis is described. She was seropositive for rheumatoid factor and renal histological examination showed a focal glomerulonephritis. High titre rheumatoid factor and a focal glomerulonephritis were also present in the only other well documented report of selective IgA deficiency and renal disease. Histological examination of the kidney suggested that the glomerulonephritis was mediated by immune complexes.

Antigen-Antibody Complex↗
PubMed1992

Stroke volume and cardiac output decrease at termination of obstructive apneas.

Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations of systemic arterial pressure that occur in association with changes in respiration and changes in sleep state. To investigate cardiac function during the cycle of obstruction (apnea) and resumption of ventilation (recovery), we continuously measured left ventricular stroke volume (LVSV) and mean arterial blood pressure (MAP) during non-rapid-eye-movement sleep in six males with severe OSA (apnea/hypopnea index > or = 30 events/h associated with oxygen saturation < 82%). LVSV was assessed continuously using an ambulatory ventricular function monitor (VEST; Capintec). The apnea-recovery cycle was divided into three phases: 1) early apnea (EA), 2) late apnea (LA), and 3) recovery (Rec). In all subjects recovery was associated with an abrupt decrease in LVSV [54.0 +/- 14.5 (SD) ml] compared with either EA (91.4 +/- 14.7 ml; P < 0.001) or LA (77.1 +/- 15.2 ml; P < 0.005). Although heart rate increased with recovery, the increase was not sufficient to compensate for the decrease in LVSV so that cardiac output (CO) fell (EA: 6,247 +/- 739 ml/min; LA: 5,741 +/- 1,094 ml/min; Rec: 4,601 +/- 1,249 ml/min; EA vs. Rec, P < 0.01; LA vs. Rec, P < 0.025). Recovery was also associated with a significant increase in MAP. We speculate that such abrupt decreases in LVSV and CO at apnea termination, occurring coincident with the nadir of oxygen saturation, may further compromise tissue oxygen delivery.

Adult↗
PubMed1991

Crescentic transformation in primary membranous glomerulonephritis.

A 31 year old man first developed steroid-resistant idiopathic membranous glomerulonephritis in 1981. Stable normal renal function was maintained until August 1988 when he suffered a clinical relapse with heavy proteinuria and declining renal function. Immunosuppressive therapy with prednisolone and cyclophosphamide was instituted in an attempt to arrest this relapse. Despite this, he later developed acute renal failure with histological evidence of crescentic transformation of his nephritis. This unusual transformation was not associated with features of systemic vasculitis or positive anti-glomerular basement membrane and anti-neutrophil cytoplasmic antibodies.

Adult↗
PubMed1991

Cardiac blood-pool scintigraphy in rats and hamsters: comparison of five radiopharmaceuticals and three pinhole collimator apertures.

Preclinical evaluation of cardiac drugs may require evaluation of cardiac function in intact animals. To optimize the quality of radionuclide measurements of ventricular function in small animals, a comparison was made of gated blood-pool scans recorded with five blood-pool radiopharmaceuticals (99mTc-labeled human polyclonal IgG, 99mTc-human serum albumin labeled by two methods, and red blood cells radiolabeled with 99mTc via in vivo and in vitro methods) in rats and three pinhole apertures in hamsters. The quality of the radiopharmaceuticals was evaluated by comparing count density ratios (LV/BACKGROUND and LV/LIVER) and ejection fractions recorded with each agent. The edge definition of the left ventricle and count rate performance of the 1-, 2-, and 3-mm apertures was evaluated in hamsters. In general, the images obtained with the radiolabeled cells were superior to those obtained with the labeled proteins and no significant differences between the protein preparations were detected. Left ventricular ejection fractions calculated with all five radiopharmaceuticals were not significantly different. The best quality images were obtained with the 1-mm pinhole collimator. Ejection fraction and acquisition time were inversely related to aperture size. A good compromise between resolution and sensitivity was obtained with the 2-mm pinhole collimator.

Animals↗
PubMed1990

Evaluation of left ventricular diastolic function using an ambulatory radionuclide monitor: relationship to left ventricular systolic performance.

Abnormalities of left ventricular (LV) filling may occur prior to systolic dysfunction in patients with both coronary and noncoronary heart disease. To determine the incidence of diastolic dysfunction and to assess the relationship of such dysfunction to systolic performance, we measured systolic and diastolic function at rest in a series of healthy volunteers (n = 10) and in patients with cardiovascular disease (n = 42). Twenty patients had coronary artery disease (CAD) with prior myocardial infarction, six patients had CAD without myocardial infarction, and the remaining 16 patients had a variety of noncoronary heart diseases, including valvular heart disease, dilated cardiomyopathy, and hypertensive disease. The 42 patients manifested a wide variation in LV systolic function (ejection fractions ranged from 6% to 65%). Patients with reduced LV ejection fraction (EF) manifested a reduction in cardiac output and peak ejection rate proportionate to the reduction in EF. Diastolic function showed a fall in LV peak (PFR) and average (AFR) filling rates; these were reduced in proportion to the fall in EF. Heart rate was an insensitive index of the magnitude of impairment of LV systolic function. These data suggest that measurements of diastolic function do not provide additional information in patients with impaired systolic function.

Adult↗
PubMed1990

T-cell receptor beta-subunit gene polymorphism and autoimmune disease.

We have investigated the distribution of genotypes of a restriction fragment length polymorphism of the T-cell receptor beta-subunit gene in Caucasoid controls and patients with insulin-dependent diabetes mellitus, celiac disease, dermatitis herpetiformis, and idiopathic membranous nephropathy and also in South Indian controls and diabetics. We found no significant differences between the controls and patients with any disease in either ethnic group, a result which contrasts with previous reports of associations with both insulin-dependent diabetes mellitus and idiopathic membranous nephropathy. However, the most striking finding was a marked disparity between the genotype distribution in our Caucasoid control population and that previously reported by other investigators.

Autoimmune Diseases↗
PubMed1990

Immunoglobulin heavy chain switch region gene polymorphisms in glomerulonephritis.

Much evidence suggests that primary IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN) are immune complex mediated diseases. Moreover, genetic factors may play an important role in their pathogenesis. Recently, restriction fragment length polymorphisms (RFLPs) of the immunoglobulin heavy chain genes have been described which appear to associate with glomerulonephritis. We have studied RFLPs of the switch region of the IgM (S mu) and IgA1 (S alpha 1) heavy chain in MN and IgAN. DNA obtained from British Caucasoids with IgAN (N = 75), MN (N = 43), and normal controls (N = 73), was digested with the restriction enzyme Sac1, and studied using Southern blot techniques and hybridization with a 32P labelled DNA probe homologous to S mu. This probe detects RFLPs at the S mu and S alpha 1 loci. The genotypic and allelic frequencies of the S mu and S alpha 1 alleles in IgAN and MN was similar to normal controls. Caucasoid subjects with IgAN from Northern and Southern Europe (Finland and Italy, respectively) were also studied to determine whether an ethnic variation in genetic susceptibility to IgAN exists. The frequency of the S mu and S alpha 1 alleles was similar between the patient groups and their respective local healthy controls. These results do not support the recent findings of an association with RFLPs of the S mu and S alpha 1 loci in IgAN and MN, and suggest that the immunoglobulin heavy chain switch region genes are not important in conferring disease susceptibility to IgAN or MN.

Blotting, Southern↗
PubMed1990

HLA DQ region gene polymorphism associated with primary IgA nephropathy.

IgA nephropathy (IgAN) has been associated with HLA-DR4. We have recently described two non-allelic Taq I DQ beta gene-associated fragments sized 2.0 kb (T2) and 6.0 kb (T6), which strongly associate with DR4. T2 represents a polymorphism of the DQ beta gene and has been redesignated DQw8 (10th International HLA Workshop). The origin of the T6 fragment has not been determined, but probably represents a polymorphism of either the DQ beta or DX beta gene. When present together T2 and T6 define a subgroup of DR4 subjects at high risk of developing autoimmune disease. We have, therefore, studied DQ beta gene polymorphisms in IgAN. The DR antigen distribution was similar in IgAN and normal controls. The T2+/T6+ phenotype was present in 49% patients with IgAN compared to 15% of controls [P less than 0.0001, chi 2 = 32.8, Cramer's V = 0.41; relative risk = 5.5 (range, 2.8-11.0)]. Seventy-two percent of DR4+ IgAN patients and 29% of DR4+ controls were T2+/T6+ (P = 0.007, chi 2 = 17.0). These findings confirm the hypothesis that disease susceptibility genes are important in IgAN, and suggest that the putative gene(s) are located within or near to the DQ subregion. Moreover, similar DQ beta gene associations have been found in IDDM and pemphigus vulgaris, pointing to a common immunogenetic mechanism predisposing to several autoimmune diseases.

Blotting, Southern↗
PubMed1989

Left ventricular performance during psychological stress.

Left ventricular ejection fraction, systolic blood pressure and plasma norepinephrine were measured in six normotensive and six mildly hypertensive subjects during rest and psychological stress. Compared with rest, 8 of the 12 subjects developed significant (P less than 0.05) changes in ejection fraction (increase in 6, decrease in 2); 10 of 12 subjects developed significant elevations of plasma norepinephrine; and all developed significant increases in systolic blood pressure. When the stress effects were examined for the total group, as opposed to within subjects, there were significant increases in plasma norepinephrine (P less than 0.001) and systolic blood pressure (P less than 0.001) but, interestingly, mean ejection fraction and stroke volume remained unchanged, implying stress led to increased left ventricular contractility.

Adult↗
PubMed1989

Gated blood pool tomography: a technology whose time has come.

Tomographic gated blood pool imaging is a natural extension of the technologies of planar gated blood pool scanning and rotating Anger camera single photon emission computed tomography (SPECT). The high photon flux, optimum 140 keV energy, and volume sampling of tomography permit reconstruction of the data in any perspective. The true three-dimensional nature of this process allows the evaluation of regional wall motion of all the cardiac chambers, unencumbered by overlapping structures. The heart can be viewed from any angle, including a long axis, short axis, apical four chamber, and a true inferior view. In addition to evaluation of regional wall motion, precise determination of chamber volumes and ejection fractions is possible. Early clinical experience has demonstrated the superiority of tomographic gated blood pool imaging over planar blood pool imaging for precisely defining subtle functional abnormalities. The enormous amount of data generated by this procedure taxes the capacity of most nuclear medicine computer systems. However, the availability of 32-bit processors and large amounts of image memory in new machines should ultimately reduce this processing time to less than ten minutes. The combination of complete visualization and quantitation suggests that a renaissance for blood pool imaging is on the horizon.

Heart↗
PubMed1989

Uranium in the tissues of an occupationally exposed individual.

Uranium concentrations were radiochemically determined in samples of lung, kidney, liver and bone collected at autopsy from an occupationally exposed individual. Levels of U in these tissues were clearly in excess of those expected from environmental exposure. Deposition followed the pattern: skeleton greater than liver greater than kidney, with ratios of 63:2.8:1. The data suggest there is an important long-term storage depot in the skeleton, but the fraction transferred to this compartment, as proposed by ICRP 30, may be too small. In vivo chest counts obtained over about a 10-y period prior to death indicated about a factor of 2 greater in total U content and 235U enrichment than deposition estimates made at autopsy for the lungs and associated lymph nodes.

Bone and Bones↗
PubMed1987

Antibody titres to a rough-mutant strain of Escherichia coli in patients undergoing allogeneic bone-marrow transplantation. Evidence of a protective effect against graft-versus-host disease.

Much clinical and experimental evidence suggests that infection and graft-versus-host disease (GvHD) are commonly associated as complications of bone-marrow transplantation (BMT). A likely basis for this association is the gram-negative faecal flora,the origin of many septicaemias and a source of bacterial endotoxin, which has potent immunostimulatory effects. A rough-mutant strain, Escherichia coli J5, has only core determinants in its endotoxin,and antibodies to E coli J5 protect animals and human beings from the consequences of septic shock. Naturally occurring antibodies to E coli J5 ("anti-endotoxin") were assayed in serum from patients undergoing BMT, healthy controls, and patients with obstructive jaundice. BMT recipients had significantly lower titres than the other two groups. Furthermore, the titre of IgM class anti-J5 antibody was significantly associated with protection from GvHD.

Acute Disease↗
PubMed1979

The quantitative determination of acrylonitrile, acrolein, acetonitrile and acetone in workplace air.

A simple and sensitive procedure for the routine determination of personnel exposures to organic vapors in the workplace has been developed using porous polymer adsorption/thermal desorption with a subsequent analysis by gas chromatography. Detailed instructions for the packing of the adsorption tube and the operation of the thermal concentrator (flasher) are given. Calibration data obtained with both a static on tube injection procedure and a dynamic method using a permeation device are discussed. More than two years of experience with 6000 samples involving a wide variety of compounds has shown the sensitivity and versatility of the techniques. The additional equipment involved is commercially available costing about $2000.

Acetone↗
PubMed1979

Adenosine deaminase activity in a transplantable murine renal adenocarcinoma.

Adenosine deaminase (ADA) activity was studied in tumor tissue, spleen, and bone marrow of animals bearing a transplantable murine renal carcinoma. Tumor tissue and splenic ADA specific activities were elevated in these animals when compared to controls although splenic specific activity subsequently declined with increasing tumor burden. Marrow ADA specific activity was the same in tumor bearing animals as in controls regardless of variations in tumor size. Studies of this enzyme may offer insight into salvage pathways of purine biosynthesis thereby suggesting exploitable targets for chemotherapy.

Adenocarcinoma↗