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Biomedical subjects

G M Bell

Publications and source records attributed to G M Bell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Physiological abnormalities of skeletal muscle in dialysis patients.

BACKGROUND: Muscle weakness is a common but unexplained feature of dialysis patients. This study investigated the prevalence and causes of muscle weakness in dialysis patients by examining the quadriceps muscle force and contractile properties. METHODS: The quadriceps femoris was studied in terms of force, force-frequency curve, and speed of muscle relaxation in 49 dialysis patients and 27 healthy subjects. In addition nutritional, haematological, biochemical, and histological assessments were performed, and steps of force generation were analysed to reach the possible mechanisms leading to the observed weakness. RESULTS: Muscle weakness, though invariable as a symptom, was subtle or absent on clinical examination. Quadriceps force measurements, however, revealed unequivocal weakness in most of the patients (71%). The quadriceps muscle was weaker (317 +/- 115 versus 460 +/- 159 N, P < 0.01) compared to healthy individuals, but there was no evidence of impaired excitation-contraction coupling (0.79 +/- 0.05 versus 0.76 +/- 0.07, P = 0.1). Among dialysis patients the older and the malnourished (n = 23) were the weaker but there was no relationship to the type or duration of dialysis. The serum albumin was the only biochemical parameter related to the muscle force (r = 0.6, P = 0.01). The other most prominent abnormality of quadriceps muscle function observed in this study was slowing of relaxation (patients versus controls; 8.7 +/- 1.8% versus 10.8 +/- 1.1% force loss/10 ms, P < 0.0001) particularly in the malnourished group (malnourished versus well nourished; 8.3 +/- 2.1 versus 9.4 +/- 0.95, P = 0.03). Muscle histology was investigated (n = 12) and revealed that type II fibres were mildly atrophic in 40% of the biopsies in most areas, but predominantly type IIB. Although type IIB fibre areas are slightly smaller in the dialysis patients compared to the controls, this was not statistically significant (3025 +/- 578 versus 4406 +/- 1582, P = 0.1) except in the malnourished group compared to the well-nourished dialysis patients (2092 +/- 304 versus 4346 +/- 1496, P = 0.04), and in the malnourished dialysis patients type IIB fibre area was significantly correlated to the strength (r = 0.6, P = 0.02). CONCLUSIONS: The only significant predictor of loss of muscle strength and abnormality of relaxation in this study was the nutritional state. A regular assessment of the nutritional state is required to ensure adequate nutrition to prevent the observed abnormalities of the skeletal muscles.

Adult↗
PubMed1997

Genetic variants of microsomal metabolism and susceptibility to hydrocarbon-associated glomerulonephritis.

Hydrocarbon (HC) exposure can play a role in the development of chronic glomerulonephritis (GN). Interindividual variations in various metabolizing enzymes may influence HC biotransformation, and hence susceptibility to HC-associated GN. We evaluated the role of human genotypic polymorphism in HC-associated GN, in 41 patients (30 male, 11 female) with primary GN (17 diffuse mesangial proliferative GN, 12 focal segmental GN, 11 membranous GN, one membranoproliferative GN) and 60 (46 male, 14 female) healthy controls. Genotypic polymorphisms of (CYP) P450 2D6 (CYP2D6), glutathione S-transferases mu (GSTM1) and theta (GSTT1) and N-acetyltransferase (NAT-2) were determined using polymerase chain reaction analysis of white-blood-cell DNA. HC exposure scores were determined using a validated questionnaire, and were significantly elevated in GN patients compared to controls. While no significant differences in the various genotypic frequencies were observed in the GN group overall, compared to controls, there was a significant increase in GSTM1 null (n = 10) to GSTM1 wild type (n = 1), and NAT fast (n = 10) to slow (n = 1) acetylators, in the membranous GN group compared to controls (p < 0.05). These results suggest a possible role for GSTM1 null and NAT fast acetylator in the development of HC-associated membranous GN.

Acetyltransferases↗
PubMed1997

Retrospective estimation of exposure to benzene in a leukaemia case-control study of petroleum marketing and distribution workers in the United Kingdom.

OBJECTIVE: To provide quantitative estimates of exposure to benzene for cases and controls in an epidemiology study to investigate the risk of leukaemia in petroleum distribution workers. METHODS: Work histories were obtained for cases and controls together with detailed information on the distribution sites. For each job in the work history, an estimate of exposure (parts per million (ppm)) was obtained by multiplying a measure derived from exposure data by modifying factors to reflect the differences between the conditions that existed at the time of measurement and those at the time of interest. The modifying factors used related to job activity, the number of road tankers loaded, the benzene content of the gasoline, the mixture of products handled, temperature, and loading technology. Cumulative exposures for each case and control were obtained by multiplying the exposure estimates for each job by the duration of time in the respective jobs, and summing these over all jobs in the work history. Peak exposure and exposure through dermal contact were quantitatively classified for each job. RESULTS: Measured exposures were obtained for 30 job categories, and ranged from 0.003 to 8.20 ppm. 40% of work histories were assigned background exposures, with a further 34% assigned the exposure estimate for a driver carrying out top submerged loading of motor fuel into road tankers. Cumulative exposures ranged from < 1 to > 200 ppm-years, although 81% were < 5 ppm-years. Comparison of the exposure estimates for selected jobs with data from sources not used in the study showed similar results. CONCLUSION: The estimates of exposure to benzene in this study provide a sound basis for the epidemiological analyses.

Benzene↗
PubMed1996

The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2.

CD2, a cell surface glycoprotein expressed on T cells and natural killer cells, can couple to signaling pathways that result in T cell proliferation. An Src-like protein tyrosine kinase, p56lck, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity of p56lck, suggesting that an interaction with p56lck contributes to CD2-mediated signaling. Herein, we investigate the mechanism by which CD2 associates with p56lck. We demonstrate that CD2 and p56lck associate when coexpressed in nonlymphoid cells, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p56lck mediates its interactions with CD2. Using truncation mutants of CD2, we identify two regions in the cytoplasmic domain of CD2 involved in binding p56lck. Each region contains a proline-rich sequence that, in the form of a synthetic peptide, directly binds p56lck. Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p56lck.

Amino Acid Sequence↗
PubMed1996

Monitoring of endothelial leucocyte adhesion molecule-1 in anti-neutrophil-cytoplasmic-antibody-positive vasculitis.

Soluble endothelial leucocyte adhesion molecule-1 (ELAM-1) has been shown to act as a neutrophil chemoattractant and may also represent a specific marker of endothelial cell damage or activation. Nine patients with anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis (p-ANCA: n = 4, c-ANCA: n = 5) were prospectively monitored for disease activity by serial serum ELAM-1, C-reactive proteins (CRPs), von Willebrand factor (vWF) and ANCA levels. Six patients presented acutely with biopsy-proven renal vasculitis. One patient on dialysis, one in remission with stable renal function and one renal transplant patient developed clinical and serological relapse. Seven patients had abnormally high ELAM-1 (>60 ng/ml) levels at presentation. These fell within normal limits a week following pulse methyl prednisolone therapy. This preceded a fall in CRP, vWF and subsequent clinical remission. p-ANCA serology remained positive in 3 cases. One patient relapsed with rising ELAM-1 levels. Two patients developed erroneously positive ANCA serology but serum ELAM-1 remained normal. Six patients with chronic renal impairment of non-vasculitic origin who presented acutely with septicaemia had normal serum ELAM-1 levels (mean +/- SD: 31 +/- 10 ng/ml) at presentation and during the subsequent clinical course. These preliminary findings are encouraging, especially when ELAM-1 is combined with ANCA monitoring in vasculitis. However, further data from larger controlled studies are needed to validate the utility of ELAM-1 in the monitoring of patients with vasculitis.

Adult↗
PubMed1996

A case of resistant Goodpasture's syndrome and staghorn calculus--treatment with bilateral nephrectomy.

We report the case of a 49-year-old female with severe Goodpasture's syndrome, staghorn calculus, and subacute thyroiditis. Despite the use of a combined therapy with corticosteroid, cyclophosphamide, azathioprine and plasma exchange, we were unable to suppress the disease activity or normalize the anti-glomerular basement membrane (GBM) antibody levels. Disease remission with a parallel reduction in anti-GBM antibody titer was only achieved after sequential bilateral nephrectomy.

Adrenal Cortex Hormones↗
PubMed1995

Tubular damage in microalbuminuric patients with primary glomerulonephritis and diabetic nephropathy.

Tubular damage as suggested by enzymuria and tubular proteinuria is a recognized feature of glomerulonephritis (GN) with clinical proteinuria and both incipient and overt diabetic nephropathy (DN). However, little is known about the presence of tubulopathy in patients with primary GN, microalbuminuria [albumin excretion (AER) 30-300 mg/d] and microhematuria. Three groups were studied. The GN group comprised 17 (2 F) patients with biopsy-proven GN with microalbuminuria. The DN group comprised 35 (14 F) patients with incipient diabetic nephropathy with AER 30-300 mg/d, and controls comprised 38 (15 F) normal subjects with normal AER < 30 mg/d. Serum creatinine, albuminurinuria, transferrinuria, and markers of tubular damage such as urinary excretion of N-acetyl-glucosaminidase (NAG), leucine aminopeptidase (LAP), gamma-glutamyl transferase (gGT), and retinol binding protein (RBP) were measured. GN and DN had comparable degrees of albuminuria, transferrinuria, and LAP excretion, and these were significantly higher than controls. Serum creatinine was significantly higher in GN than DN and controls. DN had significantly higher NAG and RBP, and lower gGT than GN and controls. In both GN and DN groups, both glomerular proteins correlated with each other and NAG correlated significantly to LAP and gGT. Albuminuria correlated to tubular enzymuria in GN group but not in patients with DN. The results suggest that tubular damage is less marked in microalbuminuric patients with GN than those with DN despite similar degree of glomerular proteinuria. The pattern of tubulopathy is also different in the two groups, indicating differences in the pathogenesis of tubular damage in these two clinical settings.

Acetylglucosaminidase↗
PubMed1995

Biochemical markers of basement membrane disturbances and occupational exposure to hydrocarbons and mixed solvents.

To investigate possible mechanisms of hydrocarbon or solvent-induced renal damage, we studied three groups of healthy men employed in a UK manufacturing plant. Group 1 (n = 111) were occupationally exposed to hydrocarbon-based paints, Group 2 (n = 100) were occupationally exposed to petroleum-based mineral oils, and Group 3 (n = 92) had low background occupational exposure to hydrocarbons. Occupational atmospheric exposure levels for toluene, xylene, butanol and oil mist around the time of this study were within UK permissible limits. Group 4 (controls) were males with no known occupational hydrocarbon or solvent exposure (n = 108). Circulating laminin antibodies and the auto-antibody implicated in Goodpasture's syndrome (anti-GBM) were measured, as were serum laminin, a basement membrane turnover marker, and soluble E-selectin, an endothelial activation marker. Group 1 had a significantly greater proportion of subjects with high levels of both anti-laminin antibodies and soluble E-selectin; Group 2 had significantly more subjects with raised anti-GBM antibodies, laminin and soluble E-selectin. Mean levels of soluble E-selectin were increased in Groups 1 and 2. In a small but significant proportion of these workers exposed to hydrocarbons/mixed solvents there are alterations both to basement membranes, resulting in auto-antibody production, and to overlying vascular endothelial cells.

Adult↗
PubMed1994

Occupational hydrocarbon exposure and diabetic nephropathy.

Exposure to hydrocarbons has been implicated in the pathogenesis of glomerulonephritis but its role in the development of diabetic nephropathy remains unknown. Three groups of patients with Type 1 diabetes of over 10 years duration were studied. Group 1 comprised 45 patients (23 F) with no diabetic nephropathy (urinary albumin excretion (AER) < 30 mg 24 h-1), group 2 comprised 37 patients (17 F) with incipient diabetic nephropathy (AER between 30-300 mg 24 h-1), and group 3 comprised 31 patients (15 F) with overt diabetic nephropathy (AER > 300 mg 24 h-1). The groups were comparable for age, sex, duration of diabetes, recent glycaemic control, social class, and residential area. Patients were assessed blindly by a validated questionnaire and interview for hydrocarbon exposure, consumption of tobacco, analgesic agents, and alcohol. Exposure scores to hydrocarbons derived from the questionnaire were significantly higher in patients with incipient and overt diabetic nephropathy with smoking adjusted odds ratios of 3.6 and 5.2, respectively. The consumption of alcohol, analgesic agents, tobacco, and smoking habits were similar in the three groups. In conclusion, hydrocarbon exposure may be a key environmental factor in the development of diabetic nephropathy in patients with Type 1 diabetes.

Adult↗
PubMed1994

Arterial thrombosis in the nephrotic syndrome.

Thrombosis is a frequent cause of morbidity and mortality in patients with the nephrotic syndrome. Venous thrombotic complications are well recognized but arterial complications are rare. Thrombosis is multifactorial, and has been attributed to a hypercoaguable state due to alterations in blood levels of the various factors involved in the coagulation and fibrinolytic systems, alterations in platelet function, venous stasis, haemoconcentration, increased blood viscosity and possibly the administration of steroids. Thrombosis in general and arterial thrombosis in particular is a significant and potentially serious problem in nephrotic patients. Awareness of the condition and its pathogenesis is needed. Assessment for the risk factors is required to allow appropriate prophylactic measures to be taken.

Adult↗
PubMed1994

Occupational factors and renal disease.

The male-to-female ratio of patients requiring dialysis treatment commonly approaches 2:1. It is proposed that environmental factors, particularly occupational exposure to hydrocarbons, may account for the excess number of male patients. The term "hydrocarbon" refers to the aliphatic, alicyclic, aromatic, and halogenated hydrocarbons (carbon tetrachloride, chloroform); glycols (ethylene glycol, diethylene glycol, dioxane, glycerol); and organic solvents. Hydrocarbons commonly find use as solvents in industrial manufacturing practices because of their lipid solubility. Hydrocarbons have long been known to be neurotoxicants, affecting both peripheral and central nervous systems. Although benzene and its derivative have a known association with uroepithelial tumors, there is now a considerable body of evidence suggesting a possible role for hydrocarbon exposure in the development of non-neoplastic renal diseases. This article presents an epidemiological case for such an association and critically reviews the literature.

Case-Control Studies↗
PubMed1994

Tubulopathy with macroalbuminuria due to diabetic nephropathy and primary glomerulonephritis.

Tubular damage is a recognized feature of both overt diabetic nephropathy and glomerulonephritis. However, the pattern and mechanism of tubular damage in the two clinical settings remain unclear. Two groups of patients with macroalbuminuria (albuminuria > 300 mg/day) were studied. Group 1 comprised 41 patients with biopsy proven primary glomerulonephritis and group 2 comprised 28 patients with clinical diabetic nephropathy due to insulin dependent diabetes mellitus. Serum creatinine, creatinine clearance, glomerular proteinuria (albuminuria and transferrinuria), markers of tubular damage such as urinary excretion of lysosomal enzyme (N-acetyl glucosaminidase), brush border enzymes (leucine aminopeptidase and gamma-glutamyl transferase) and retinol binding protein (tubular protein) were measured. Both groups were comparable in serum creatinine, creatinine clearance, glomerular proteinuria and excretion of N-acetyl-glucosaminidase. However, a significantly higher degree of tubular brush border enzymuria and a lower level of tubular proteinuria were seen in group 1 than in group 2. In group 1, albuminuria correlated to tubular enzymuria and tubular proteinuria. However, there was no correlation in diabetic patients between parameters of glomerular and tubular damage or dysfunction. The data presented suggested that the pattern of tubulopathy is different in patients with comparable degree of macroalbuminuria due to diabetic nephropathy and glomerulonephritis. Moreover, in diabetic nephropathy contrary to glomerulonephritis, markers of tubular damage are unrelated to glomerular proteinuria. This may suggest different mechanisms of tubular damage in the two clinical settings. We recommended that in all patients with proteinuria, particularly those with diabetic nephropathy, markers of renal tubular damage may be useful in monitoring the course of their disease.

Acetylglucosaminidase↗
PubMed1994

Relationship between hydrocarbon exposure and nephropathology in primary glomerulonephritis.

It has been proposed that renal tubular damage and chronic hydrocarbon exposure are causally related to progression of renal failure in primary glomerulonephritis. We examined the relationship between hydrocarbon exposure and morphological parameters of tubulointerstitial damage in 59 patients with biopsy-proven primary glomerulonephritis (proliferative, n = 52; membranous, n = 7). From a mean follow-up period of 6 years patients were divided into two groups (GP) according to the presence or absence of progressive renal failure (GP 1, n = 24 with progressive renal failure) and (GP 2, n = 35 without progressive renal failure). The two groups were comparable in age, sex, duration of diagnosis (since the time of biopsy) and blood-pressure control. Patients were blindly assessed for chronic hydrocarbon exposure by a validated questionnaire. Biopsy cylinders were blindly assessed retrospectively for relative interstitial volume of the renal cortex by the point-counting method. In addition an assessment was made of the degree of fibrosis and chronic inflammatory cellular infiltrate. Hydrocarbon exposure score derived from the questionnaire until the time of renal biopsy correlated both with interstitial volume (r = 0.55; P < 0.001) and serum creatinine (r = 0.46; P < 0.001). Moreover, interstitial volume also correlated with serum creatinine (r = 0.63; P < 0.001). Chronic hydrocarbon exposure scores and relative interstitial volume in the renal cortex at the time of renal biopsy was significantly higher in GP 1 than GP 2 (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Evidence of oxidant injury and tubular damage in early diabetic nephropathy.

Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30-300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy.

Adult↗