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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 199 records · Page 11Linked to original sources
PubMed1991

Experience with a new method for percutaneous renal biopsy.

Between January 1989 and August 1990 a new technique for percutaneous renal biopsy was evaluated in all patients undergoing native kidney biopsy in our hospital. The method combines the use of an automated biopsy device, disposable biopsy needles, and a needle guide attached to an ultrasound probe. This allows real-time ultrasound scanning throughout the procedure. All biopsies were performed by trainee nephrologists. The success of the technique was evaluated by analysis of histopathological data, and the complications of the procedure from case-notes and nursing records. During the study 192 biopsies were attempted, of which 188 (97.8%) were successful. For each biopsy a mean of 2.8 needle passes were required and 75% of these obtained cores of tissue. An average of 25 glomeruli (range 1-90) were seen per biopsy. Although microscopic haematuria was almost invariable, there were no episodes of frank haematuria and no blood transfusion or surgical intervention was required. The new method is simple, providing accurate localisation of the kidney coupled with direct visualisation of the biopsy, and results in a very high success rate. Intrarenal needle dwell time is kept to a minimum and there were only minor complications. This technique deserves more widespread use.

Adult↗
PubMed1991

Coagulation studies and fistula blood flow during erythropoietin therapy in haemodialysis patients.

An increased incidence of fistula thrombosis has been reported in haemodialysis patients treated with recombinant human erythropoietin (rHuEpo). The present study sought to investigate this problem by measuring fistula blood flow, blood viscosity, and a variety of tests of coagulation and haemostasis in a group of ten haemodialysis patients treated with rHuEpo. Fistula blood flow did not alter during the first 12 months of rHuEpo despite a significant increase in whole-blood viscosity. Bleeding time improved in all ten patients after 4 months of therapy, and this improvement was maintained at 12 months. There were no significant changes in one-stage prothrombin time, kaolin cephalin clotting time, whole-blood clotting time, prothrombin consumption index, plasma fibrinogen factor VII, factor VIII, antithrombin III, or platelet aggregability to ADP over the first 4 months of rHuEpo. In contrast, protein C decreased from 84.3 to 66.4% (P less than 0.01) and protein S from 124.1 to 68.3% (P less than 0.001) over the first 4 months. By 8 and 12 months, the concentrations of these substances had returned to pretreatment values. The levels of protein C and S attained at 4 months are known to predispose to thrombosis, and it is possible that this effect may contribute to the increased incidence of fistula thrombosis observed in haemodialysis patients treated with rHuEpo.

Adult↗
PubMed1991

Rheological studies during treatment of renal anaemia with recombinant human erythropoietin.

Whole blood, plasma, and serum viscosity together with red cell deformability were measured before and during treatment of renal anaemia with recombinant human erythropoietin (EPO). Whole blood viscosity (WBV) progressively increased during the first 4 months of treatment in association with the rise in haemoglobin concentration. When the WBV was corrected to a standard haemoglobin concentration no change in blood viscosity was observed, neither was there any alteration in a derived index of red cell deformability, or in the plasma and serum viscosities. In addition, a direct measurement of red cell deformability using a filtration technique before EPO therapy was similar to that obtained in 30 healthy volunteers. There was no significant change in this parameter over the first 9 months of treatment. The rheological changes which occur with correction of anaemia with EPO can be explained solely by the increase in circulating haemoglobin mass rather than to any change in the properties of the plasma or red cells themselves.

Adult↗
PubMed1991

The complement-inhibiting protein, protectin (CD59 antigen), is present and functionally active on glomerular epithelial cells.

Protectin (CD59 antigen) is a 20-kD phosphatidyl-inositol-linked membrane protein that inhibits formation of the membrane attack complex (MAC) of complement on homologous cells. Although the antigen has been identified in a number of human tissues, until recently a functional role had been demonstrated only in circulating cells. Using immunofluorescence techniques we have shown the presence of protectin on human glomerular epithelial cells (GEC) in culture and on GEC, tubular epithelial cells and endothelial cells in frozen sections of normal human renal cortex. In addition, we present evidence that this protein functions in protection of GEC from homologous complement: cultured cells incubated with the Fab2 fragment of a monoclonal anti-protein antibody were markedly more susceptible to killing by homologous serum than were cells in the absence of Fab2 anti-protectin. These findings suggest that this protein may be important in the maintenance of glomerular integrity in vivo, and may be of relevance in certain renal diseases.

Animals↗
PubMed1991

Characterisation and distribution of epidermal growth factor receptors in equine hoof wall laminar tissue: comparison of normal horses and horses affected with chronic laminitis.

Epidermal growth factor (EGF) receptors were detected in plasma membrane preparations of equine hoof wall laminar tissue at concentrations comparable to that of equine liver. Scatchard analysis of the equilibrium binding data suggested the presence of two classes of EGF binding sites in most of the controls (plasma membranes from clinically normal horses); a high-affinity class and a more numerous low-affinity class. The dissociation constant of the low-affinity class of EGF-specific receptors (KD = 1 x 10(-9)M) is in reasonable agreement with other values established for the EGF receptor. The variability between individual estimates for the KD of the high-affinity receptor class precluded an accurate estimate for those sites. A possible explanation is discussed. The high-affinity binding sites were uniformly absent in plasma membranes prepared from horses affected by chronic laminitis. Autoradiographic analysis localised the EGF receptors primarily to the secondary epidermal laminae, with an apparent greater density over the proliferative basal keratinocytes. Little label was associated with the dermal or the keratinised primary epidermal laminae. Tissue from horses with chronic laminitis had EGF receptors located uniformly over the hyperplastic epidermal keratinocytes. These data suggest that an EGF-mediated response may be involved in the hyperproliferative response that is characteristic of chronic laminitis.

Animals↗
PubMed1991

Analysis of serotypes and electropherotypes of equine rotaviruses isolated in the United States.

Equine group A rotaviruses isolated over a 10-year period in New York State, New Jersey, Kentucky, and Texas were compared serotypically and electropherotypically. All isolates were determined to be serotype 3 by reaction with hyperimmune antiserum to the serotype 3 H-2 strain of equine rotavirus. All displayed RNA electrophoretic migration patterns related to that of the H-2 strain but distinct from that of serotype 5 strain H-1. A serologic survey of 184 mares in Kentucky, which was done to determine the incidence of H-1 and H-2 infections, showed geometric mean serum neutralizing titers to the H-2 strain of equine rotavirus to be significantly higher than those to the H-1 strain. These data suggest that the serotype 3 H-2 strain is the dominant equine rotavirus in Kentucky and perhaps elsewhere in the United States. We were unable to produce confirmational evidence that the H-1 strain occurs as a natural infection in the United States.

Animals↗
PubMed1991

Airway response to exercise and methacholine in children with respiratory symptoms.

Thirty atopic and 30 non-atopic subjects were identified from a population of 7-8 year old children with current respiratory symptoms. The response of the airways to exercise and provocation by methacholine were compared. In these children, who had symptoms but were not necessarily asthmatic, there was no significant correlation between the two stimuli. The atopic children were, however, significantly more responsive than the non-atopic children to both. For the whole group, odds ratios derived for atopy and for an increased response to methacholine (expressed as a PD20--the dose that caused the forced expiratory volume in one second (FEV1) to fall by 20%--of less than 6.4 mumol/l), a positive exercise test (greater than 15% fall in FEV1), and the presence of asthma were 13.5, 3.3, and 21.0, respectively; that for positive response to methacholine and positive exercise challenge was 1.5. Thus though increased bronchial responsiveness to methacholine and exercise challenge are both associated with a diagnosis of asthma, the association between the two stimuli is complex, and supports the view that they reflect entirely different components of airways dysfunction.

Asthma↗
PubMed1991

The use of erythropoietin in renal failure.

The treatment of renal anaemia by recombinant human erythropoietin (EPO) is now well established. Several studies have examined the pharmacokinetics and efficacy of the drug given intravenously, intraperitoneally and subcutaneously and there is increasing evidence that the subcutaneous route has several advantages including the requirement for a lower dose. It is also important to stress the need for careful determination of baseline iron status of all patients before commencing EPO therapy. In the long term the extremely high iron stores of transfusion dependent patients will disappear. In the short term, however, the majority of the patients whose serum ferritin is less than 100 micrograms/l will require iron supplementation to allow an appropriate haemoglobin response. Alternatively, a fall in transferrin saturation to less than 20% is certainly an indication for iron supplementation and if oral iron therapy is not adequate then intravenous preparations may have to be considered. Although the anaemia of renal failure can be fully corrected by EPO, partial correction may be sufficient to reverse the problems of reduced exercise capacity, myocardial ischaemia and cardiomegaly which are frequently associated with end-stage renal disease. Partial correction will also result in a lesser rise in whole blood viscosity and, in turn, possibly reduce hypertension, thrombosis and increased peripheral resistance and thus lessen the side effects of EPO therapy.

Anemia, Hypochromic↗
PubMed1991

Effect of atopy on the natural history of symptoms, peak expiratory flow, and bronchial responsiveness in 7- and 8-year-old children with cough and wheeze. A 12-month longitudinal study [published errarum appears in Am Rev Respir Dis 1992 Aug;146(2):540].

Recurrent lower respiratory tract symptoms are common and disabling in childhood, but little is known of their natural history and relationship to asthma. We report a 12-month longitudinal study designed to determine the influence of atopy on respiratory symptoms and bronchial responsiveness in 7- and 8-yr-old children. A postal questionnaire inquiring into the presence of respiratory symptoms was sent to 3,698 children aged 7 and 8 yr. Those reporting either current wheeze (14.8%) or current cough in the absence of wheeze (12.8%) were randomized, and a sample was invited to attend for skin testing. The following groups of symptomatic children entered the longitudinal study: 48 atopic children with cough, 48 atopic children with wheeze, 48 nonatopic children with cough, and 48 nonatopic children with wheeze. All children recorded twice daily the best of three peak expiratory flow (PEF) measurements and completed a 10-point symptom score card, each day for 1 yr. They also recorded all treatment taken and made a note of relevant life events. Each child was seen monthly for general assessment and for measurement of methacholine bronchial responsiveness. Despite the arduous nature of the study 183 of the 192 children (95.3%) successfully completed the 12 months of observation. Symptom groups were compared with regard to FEV1, bronchial responsiveness, symptom chronicity and severity, and diurnal and day-to-day variation in PEF. Atopy was associated with a lower FEV1, increased prevalence of bronchial hyperresponsiveness, greater within-day and between-day variation in PEF, and greater severity of respiratory symptoms compared with the absence of atopy. Wheeze was associated with lower FEV1, increased prevalence of bronchial hyperresponsiveness, greater within-day and between-day variation in PEF1 and greater severity of respiratory symptoms compared with cough [corrected].

Bronchial Provocation Tests↗
PubMed1991

Transdermal glyceryl trinitrate to allow peripheral total parenteral nutrition: a double-blind placebo controlled feasibility study.

Seventy-two consecutive patients requiring total parenteral nutrition (TPN) were randomized to two groups. Group A received daily a peripheral intravenous regimen which provided 10 g nitrogen and 1400 non-nitrogen kcal (5.9 MJ). Group B received daily a peripheral intravenous regimen which delivered 9.4 g nitrogen and 1900 non-nitrogen kcal (8.0 MJ). Each group was further randomized to receive a self-adhesive patch of transdermal glyceryl trinitrate (GTN) or an identical placebo. Infusion survival was the main end-point. For group A, the median time of infusion survival was 74 h (range: 58-100) in the control group compared with 108 h (range: 68-156) in the group that received transdermal GTN (P less than 0.001). For group B, the median infusion survival was 67 h (range: 46-92) in the control group compared with 103 h (range: 66-151) in the treatment group (P less than 0.001). TPN is feasible via peripheral veins and the incidence of infusion failure can be effectively reduced by transdermal GTN.

Administration, Cutaneous↗
PubMed1991

Clinical pharmacokinetics of epoetin (recombinant human erythropoietin).

Epoetin (recombinant human erythropoietin, EPO) is of proven benefit in the treatment of renal anaemia, and preliminary reports suggest that it may have a role in the management of other anaemic conditions. Pharmacokinetic and therapeutic studies have examined the use of epoetin administered intravenously, intraperitoneally and subcutaneously, and there is accumulating evidence that the last route has several advantages. After intravenous administration, epoetin is distributed in a volume comparable to the plasma volume, and plasma concentrations decay monoexponentially with a half-life of between 4 and 12 hours. Administration of epoetin in peritoneal dialysis fluid results in detectable concentrations in the bloodstream after 1 to 2 hours, and peak concentrations of the order of 2 to 4% of those obtained with the same intravenous dose are found after approximately 12 hours. The bioavailability of epoetin administered intraperitoneally in dialysis fluid is about 3 to 8%, but this may be increased by injecting the drug into a dry peritoneal cavity. Subcutaneous administration results in peak concentrations at about 18 hours which are 5 to 10% of those found after the same intravenous dose. The bioavailability of subcutaneous epoetin is about 20 to 30% and detectable serum concentrations are still present 4 days after administration, in contrast to intravenous administration after which concentrations have returned to baseline within 2 to 3 days. Remarkably little is known about the metabolic fate of either erythropoietin or epoetin. In addition, there is much controversy surrounding the relative roles of the kidney and liver in the catabolism of epoetin. About 3 to 10% of epoetin is excreted unchanged in the urine. In common with other glycoproteins, the carbohydrate residues which constitute 40% of its molecular size are essential for maintaining the stability of epoetin in circulation. Desialated epoetin, although biologically active in vitro, is cleared very rapidly from plasma with resultant loss of activity. Further work is required, however, in identifying the pathways of metabolism and elimination of this glycoprotein hormone.

Animals↗
PubMed1991

Effect of stage of gestation on efficacy of Brucella abortus strain-19 vaccination in cattle.

Seventy-nine cattle in all stages of gestation were inoculated with a low dose (2.5 x 10(8) colony-forming units) of Brucella abortus strain 19, then challenge exposed with pathogenic B abortus strain 2308 during the subsequent gestation. A brucellosis case was defined by isolation of strain 2308 from dam or calf samples. Cumulative incidence of brucellosis cases was 48, 33, 25, or 47% for cattle that were, respectively, not pregnant, or 19 to 87, 100 to 167, or 190 to 253 days in gestation at vaccination. The cumulative incidence was 56% in 27 nonvaccinated controls. The 95% confidence intervals for risk ratios included 1 in all cattle, except those that were 100 to 167 days in gestation at vaccination (ie, second trimester); the confidence interval for this group was 0.21 to 0.97. The prevented fraction (1-risk ratio) attributed to strain 19, in ascending order, was 0.14, 0.16, 0.4, or 0.55, respectively, for cattle that were not pregnant, or were 190 to 253, 19 to 87, or 100 to 167 days in gestation at vaccination. Potential confounders of breed, pen effect, and gestation days at challenge exposure did not significantly affect results. Results supported the hypothesis that stage of gestation at vaccination will affect the prevented fraction of brucellosis, or efficacy of strain 19, in cattle vaccinated with a low dose and, therefore, is one factor that may explain variation in strain 19-induced protection.

Animals↗
PubMed1990

Differential augmentation by recombinant human tumor necrosis factor-alpha of neutrophil responses to particulate zymosan and glucan.

Zymosan (Z) and its major insoluble carbohydrate component beta-linked glucan activate human neutrophils (PMN) through a trypsin-sensitive recognition mechanism. This mechanism is believed to involve the PMN CR3R. Both Z and glucan generated dose and time-dependent release of the secondary lysosomal granule marker vitamin B12 binding protein, leukotriene B4 (LTB4) and superoxide from PMN and were phagocytosed with similar dose-dependent kinetics. The PMN superoxide and LTB4 responses to glucan; however, were consistently greater than those to the same doses of Z. The phagocytosis of both particles was significantly reduced after partial digestion with beta-laminarinase but not beta-glucosidase or alpha-mannosidase suggesting a recognition mechanism dependent on intact beta-1,3-glucosidic bonds in both particles. TNF-alpha (rhTNF-alpha) promoted a time- and dose-dependent increase in the expression of PMN CR3 up to 60 min. The increased expression of CR3 was paralleled by the release of the secondary lysosomal granule marker vitamin B12-binding protein. This granule contains a population of CR3R in its boundary membrane and it is the fusion of this membrane with the plasma membrane that may represent the mechanism by which CR3 expression is increased. Preincubation of PMN with 10(-9)M rhTNF-alpha augmented phagocytosis, LTB4, and superoxide generation by PMN in response to activation by Z. In contrast, none of the responses to glucan was significantly increased after incubation with rhTNF-alpha. These differences suggest a lack of absolute homology between the recognition mechanisms for zymosan and glucan and that there is a component of the recognition mechanism for zymosan that is independent of that for glucan and is up-regulated after rhTNF-alpha pretreatment.

Glucans↗
PubMed1990

Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm.

Treatment with erythropoietin is highly effective and beneficial if given with care. In view of its cost, however, it is essential to exclude and treat other causes of anaemia before considering using this hormone. After treatment is started the important points for success are regular review of iron availability state combined with a slow correction of the anaemia. Failure of response requires a thorough search for a possible cause, which should be corrected before considering an increased dose of the hormone. Regular monitoring for potential complications, particularly a rise in blood pressure, is required.

Algorithms↗
PubMed1990

Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin.

The long-term cardiorespiratory effects of recombinant human erythropoietin treatment were investigated in ten haemodialysis patients by means of maximum exercise testing, lung function tests, echocardiography, chest X-ray, and rheological assessment over 12 months. There were significant rises in exercise time (mean [SD] 13.2 [5.5] to 20.0 [6.2] min), maximum oxygen consumption (19.1 [7.0] to 25.0 [6.7] ml.min-1.kg-1), and anaerobic threshold (11.7 [3.6] to 15.4 [4.8] ml.min-1.kg-1) after 2 months of erythropoietin treatment. The improvements were maintained but not augmented on repeat testing after 4, 8, and 12 months of therapy. Carbon monoxide transfer [corrected] rose from 15.5 (2.9) to 18.6 (3.7) ml.min-1.mm Hg-1. There was a substantial reduction in exercise-induced cardiac ischaemia (eight patients had significant ST segment depression before erythropoietin, only one after 2 months' treatment, and none after 12 months' treatment), despite a significant rise in whole blood viscosity. Left ventricular mass, as estimated by echocardiography, progressively decreased from 354 (169) g to 251 (95) g after 12 months' treatment, and four patients showed a reduction in cardiothoracic ratio on chest X-ray.

Adult↗