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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 19 recordsLinked to original sources
PubMed1992

Isolation and characterization of a membrane protein from rat erythrocytes which inhibits lysis by the membrane attack complex of rat complement.

The membrane attack complex (MAC) of complement in humans is regulated by several membrane-bound proteins; however, no such proteins have so far been described in other species. Here we report the isolation and characterization of a rat erythrocyte membrane glycoprotein of molecular mass 21 kDa which inserts into cell membranes and is a potent inhibitor of the rat MAC. This protein, here called rat inhibitory protein (RIP), was first partially purified by column chromatography from a butanol extract of rat erythrocyte membranes. Monoclonal antibodies (Mabs) were raised against RIP and used for its affinity purification. Affinity-purified RIP was shown to inhibit in a dose-dependent manner the cobra venom factor (CVF)-mediated 'reactive' lysis of guinea pig erythrocytes by rat complement. Conversely, the anti-RIP MAbs 6D1 and TH9 were shown to markedly enhance the CVF-mediated lysis of rat erythrocytes by rat complement. RIP acted late in the assembly of the MAC (at or after the C5b-8 stage) and was releasable from the membranes of rat erythrocytes by phosphatidylinositol-specific phospholipase C. These features, together with its size, deglycosylation pattern and N-terminal amino acid sequence, lead us to conclude that RIP is the rat homologue of the human MAC-inhibitory protein CD59 antigen.

Amino Acid Sequence↗
PubMed1992

Flush aortic tie versus selective preservation of the ascending left colic artery in low anterior resection for rectal carcinoma.

The effects of two methods of colonic vascular ligation were studied in 143 consecutive patients who underwent low anterior resection with total mesorectal excision and full mobilization of the splenic flexure. Either the ascending left colic artery (ALCA) was selectively preserved (n = 52) or a flush aortic ligation was performed (n = 91). In those with a protective colostomy, the radiological leak rate was 12 per cent when the ALCA was preserved (n = 41) and 10 per cent when a flush aortic tie was performed (n = 60) (P greater than 0.95; 95 per cent confidence interval (c.i.) for difference -10 to +15 per cent). In those without a colostomy, the clinical leak rates of 9 per cent when the ALCA was preserved (n = 11) and 19 per cent when a flush aortic tie was performed (n = 31) were not significantly different (P greater than 0.10; 95 per cent c.i. for difference -12 to +32 per cent). Proportional hazards analysis showed no association between the method of vascular ligation and the risk of tumour recurrence and death. Anastomotic leak rates, tumour recurrence and survival were not related to the method of vascular ligation.

Anastomosis, Surgical↗
PubMed1992

Criteria for diagnosis of urinary tract infection and evaluation of therapy.

Patients with urinary tract infections are commonly used to study the efficacy of new antibiotics. Some criteria, for example the presence of more than 100,000 organisms of a single species per ml as an indicator of infections, have been accepted for many years but all rules have exceptions. Other criteria such as relapse, re-infection are less clearly agreed. Furthermore, timing of collection of specimens during and after treatment shows great variation in protocols and in definition. These criteria and the methodology of collecting, transportation and examination of urine are discussed.

Humans↗
PubMed1992

In vitro susceptibility of Haemophilus influenzae to cefaclor, cefixime, cefetamet and loracarbef.

The susceptibility of 2,212 Haemophilus influenzae isolates cultured in UK clinical laboratories in 1991 was determined for four orally-administered beta-lactam drugs. These isolates included 1,893 ampicillin-susceptible, 191 beta-lactamase-positive and 128 ampicillin-resistant, beta-lactamase-negative Haemophilus influenzae. While 150 (6.8%) isolates were resistant to cefaclor (MIC > or = 16 mg/l) and 85 (3.8%) to loracarbef, all were inhibited by < or = 2 mg/l cefetamet and < or = 1 mg/l cefixime and were therefore susceptible to these agents. Ranges and modes of inhibition zone diameters and MICs indicated that the susceptibility of a variable proportion of the 191 beta-lactamase-positive isolates to cefaclor, loracarbef and cefetamet was reduced compared with the fully susceptible population. In contrast, a major reduction in susceptibility to all four antimicrobial agents was seen among the 128 ampicillin-resistant (MIC 1-64 mg/l) beta-lactamase-negative isolates such that these accounted for 53% and 67% of the total number of organisms resistant to cefaclor and loracarbef respectively. In addition, 23 of 25 isolates inhibited only by > or = 1 mg/l cefetamet and all eight inhibited only by > or = 0.5 mg/l cefixime showed this type of resistance to ampicillin. Results indicate the importance of detecting non-beta-lactamase-mediated resistance to ampicillin and any concomitant diminished susceptibility to other beta-lactam drugs.

Ampicillin Resistance↗
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

Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus.

Little information is available regarding renal hemodynamics in non-insulin dependent diabetics (NIDDMs), despite their numerical significance to renal support programs. Therefore, simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (expressed to 1.73 m2 surface area) was performed in 110 newly presenting normotensive NIDDMs [mean (SD) age: 52.5 (10.1) years] and compared with 32 normal subjects of similar age range [age: 52.2 (11.3) years]. Mean (SD) GFR, ERPF and filtration fraction (FF) for the NIDDMs were: 117 (22) ml/min (range: 74 to 178), 534 (123) ml/min and 22.4 (3.0)%, and for the normals: 95 (12) ml/min (range: 75 to 119), 472 (70) ml/min and 20.2 (2.2%), respectively. As a group, NIDDMs demonstrated significantly greater GFR (P less than 0.001), ERPF (P less than 0.005) and FF (P less than 0.001). GFR values above 140 ml/min were observed in 16% of the NIDDMs, while 45% had GFRs in excess of mean +/- 2 SD of the normals. NIDDMs demonstrated a positive relationship for GFR with ERPF (P less than 0.001) and an inverse association for both GFR and ERPF with age (P less than 0.001). Multivariable regression analysis revealed ERPF as the strongest explanatory variable for GFR in the NIDDMs (P less than 0.001), followed by age (P less than 0.01). Significant contributions to the regression analysis were not observed for body mass index, systolic or diastolic blood pressures, glycosylated hemoglobin nor fasting levels of plasma glucose, cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides. Urinary albumin excretion rates were not correlated with GFR, ERPF or FF. Microalbuminuria was detected in 7% of the NIDDMs in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1992

Antimicrobial resistance in Haemophilus influenzae from England and Scotland in 1991.

Twenty-two laboratories in England and Scotland sent 2212 clinical isolates of Haemophilus influenzae to The London Hospital Medical College (LHMC) between 1 January and 31 March 1991. After confirmation of identity, the prevalence of resistance was determined and compared with results from previous similar surveys. beta-Lactamase was produced by 8.3% of non-capsulate isolates and 21% of 52 type b isolates; both figures were higher than the 6% and 18% figures recorded, respectively, in 1986. There was an increase in the prevalence of non-beta-lactamase-mediated diminished susceptibility to ampicillin (5.8%) and co-amoxiclav (6.1%) compared with 1986 (4%). Whereas fewer H. influenzae isolates were resistant to tetracycline (1.4%) or chloramphenicol (0.8%), there was an increase in resistance to trimethoprim (6.8%) and to sulphamethoxazole (16.9%) compared with 1986 (4.2% and 3.5% respectively). In addition, 95 isolates (4.3%) were resistant to both of these anti-folate antimicrobials. Six isolates (one type b from CSF) were resistant to all drugs tested, except for co-amoxiclav. Overall, the results demonstrated that changes have occurred in the last decade in England and Scotland, such that H. influenzae isolates are increasingly likely to be resistant to ampicillin, co-amoxiclav and co-trimoxazole.

Chloramphenicol Resistance↗
PubMed1992

Comparative in-vitro activity of azithromycin, macrolides (erythromycin, clarithromycin and spiramycin) and streptogramin RP 59500 against oral organisms.

The in-vitro activities of azithromycin, clarithromycin, spiramycin and RP 59500 were compared with erythromycin against a wide range of oral organisms which have been implicated in oral infections and/or endocarditis (clindamycin was included for oral streptococci). All compounds tested showed good activity against many of these organisms, although some variation was observed with different species. Clarithromycin was the most active of the antibiotics tested against Gram-positive anaerobes, including Actinomyces spp., Propionibacterium spp., Lactobacillus spp. and Bifidobacterium dentium. Azithromycin was slightly less active than erythromycin against these species. In general, RP 59500 had higher MICs than the macrolides, other than spiramycin, against these organisms, but was superior in activity against Peptostreptococcus spp., inhibiting all isolates at 2 mg/L. Azithromycin was, in general, the most active antibiotic tested against the Gram-negative anaerobes: Fusobacterium spp., Bacteroides spp., Wolinella spp., Actinobacillus actinomycetemcomitans, Selenomonas spp. and Mitsuokella multiacida, including those isolates which were insusceptible to erythromycin. Clarithromycin showed similar activity to erythromycin against most Gram-negative species, but was superior against Capnocytophaga ochraceus and Eikenella corrodens. RP 59500 was less active than the macrolides against most Gram-negative anaerobes, but was superior to erythromycin and clarithromycin against Fusobacterium spp. and Leptotrichia buccalis, some strains of which were moderately resistant to erythromycin. The macrolides and clindamycin were about equally active against the oral streptococci, whereas RP 59500 showed lower inhibitory activity. The in-vitro results suggest that azithromycin and clarithromycin may be of value in the treatment of dental sepsis and the prophylaxis of endocarditis. RP 59500 showed useful activity against Gram-positive anaerobes and, because of its bactericidal activity against oral streptococci, may also prove to have a role in these areas.

Anti-Bacterial Agents↗
PubMed1992

The antimicrobial susceptibility of Moraxella catarrhalis isolated in England and Scotland in 1991.

Between 1 January and 31 March 1991, 20 laboratories in England and Scotland sent a total of 413 consecutive clinical isolates of Moraxella catarrhalis to The London Hospital Medical College (LHMC). After confirmation of identity, the susceptibility of all isolates to 11 antimicrobial agents was determined. Of the 375 (90.8%) isolates which were found at LHMC to be beta-lactamase-positive, 174 produced zones of inhibition around 2 micrograms ampicillin disc which were greater than or equal to 20 mm in diameter and 252 were inhibited by less than or equal to 0.5 mg/L of ampicillin. However, 71 of these 375 had been reported to be ampicillin-susceptible by peripheral centres. While beta-lactamase had not been detected in 35 of these 71 isolates, the other 36 had been reported to be ampicillin-susceptible and beta-lactamase-positive. All 38 beta-lactamase-negative isolates produced zones greater than or equal to 30 mm in diameter and were inhibited by less than or equal to 0.06 mg/L of ampicillin. No M. catarrhalis isolate was found to be resistant to co-amoxiclav, tetracycline, chloramphenicol or cefaclor. Two strains showed intermediate susceptibility to erythromycin (MIC 1 mg/L) and 27 required greater than or equal to 32 mg/L of sulphamethoxazole for inhibition. Resistance to trimethoprim was uniform (MICs 2-128 mg/L). Two isolates showed intermediate susceptibility to cefixime (MIC 2 mg/L) but none was resistant to the new oral cephalosporin cefetamet or to the oral carbacephem loracarbef.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1992

Missing generations of spermatocytes and spermatids in seminiferous epithelium contribute to low efficiency of spermatogenesis in humans.

Daily sperm production per gram parenchyma (DSP/g) in humans is only 25 or 35% of that for most species including rats and nonhuman primates. To explain the low efficiency of spermatogenesis in humans, the number of generations of germ cells (spermatocytes and spermatids) and the number of these germ cells in each generation were determined for each spermatogenic stage in men with varied efficiencies. Testes were obtained at autopsy, fixed by vascular perfusion with glutaraldehyde, further fixed in osmium, and embedded in Epon 812 before 0.5-micron sections were stained with toluidine blue. Tubular cross sections were photographed, and spermatogenic stages were determined by two observers. Testes were divided into three groups on the basis of DSP/g. The number of generations of spermatocytes and spermatids was greater (p < 0.05) in the high (2.01 +/- 0.05) and intermediate (1.77 +/- 0.04) than in the low (1.45 +/- 0.15) DSP/g group. All groups had a lower number of generations of spermatocytes and spermatids compared to the optimum value of three. The number of these generations per cross section was related (r = 0.85; p < 0.01) to DSP/g in these men. The number per cross section of spermatocytes, spermatids, and the combined number of germ cells was higher (p < 0.01) in the high than in the low DSP/g group. The combined number of germ cells per cross section was related (r = 0.85; p < 0.01) to DSP/g. The combined number of germ cells was higher in the high versus the low DSP/g group in stages I through V, but this difference was significant only in stages IV and V.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Profile of bronchial responsiveness in children with respiratory symptoms.

A postal questionnaire inquiring into the presence of respiratory symptoms was sent to 3698 children aged 7 and 8 years. Those reporting either cough or wheeze were randomised, and a sample invited to attend for skin testing. A total of 192 symptomatic children, half of whom were atopic and half non-atopic, were randomly selected to enter the study. All children performed and recorded best of three peak expiratory flow measurements twice a day and completed a 10 point respiratory symptom score card each day for one year. 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 nonspecific bronchial responsiveness to methacholine. Of the 192 children, 183 successfully completed the study. For six subjects 11 measurements of the provocation dose required to cause a 20% fall in forced expiratory volume in one second (PD20) were available for analysis and on the remaining 177, greater than or equal to 12 measurements. The prevalence and degree of bronchial hyper-responsiveness (PD20 less than 6.4 mumol) and its relationship to atopy was examined by comparing the percentage of members of each symptom group demonstrating bronchial hyper-responsiveness and the number of occasions on which they did so, and by comparison of minimum and median PD20 values. The range of bronchial responsiveness shown during the study period by each child was expressed as doubling doses of methacholine and compared between symptom groups. Atopy and wheeze were both independently associated with an increased prevalence and greater degree of bronchial hyper-responsiveness when compared with non-atopy and cough respectively, all differences being significant a the 0.001 level.. Thirty three per cent of subjects demonstrated a rnge of methacholine responsiveness of >4 and 13.4% of >6 doubling doses during one year.

Bronchi↗
PubMed1992

Estimation of erythropoietin secretion rate in normal and uremic subjects.

We have developed a method for directly estimating the secretion rate of endogenous erythropoietin (EPO) in human subjects. Carrier-free recombinant human EPO was labeled with 125I by the chloramine T method. Human serum albumin was then added prior to removal of free iodide. Seven normal subjects and nine patients with chronic uremia and anemia were studied. Each subject received a bolus of 125I-EPO according to body size and then a constant infusion for 5 h. Secretion rate was calculated as the rate of infusion divided by serum EPO specific activity given by the protein-bound counts divided by the EPO concentration. Serum EPO concentration was significantly higher in the patients than the controls (mean 30.9 pg/ml vs. 11.1 pg/ml, P < 0.05), although all values were within the normal range. Mean EPO secretion rate was 255 in the patients (range 68-1,101) and 190 pg.kg-1 x h-1 in the normal group (range 52-382). This difference was not significant. As the subjects were in a steady state, EPO disappearance/degradation was the same in patients compared with controls despite a relatively hypoplastic marrow.

Adult↗
PubMed1992

Protein kinase C activation modulates tumour necrosis factor-alpha priming of human neutrophils for zymosan-induced leukotriene B4 release.

Neutrophil (PMN) activation by the yeast component zymosan involves the complement receptor type 3 (CD11b/CD18). Recombinant human tumour necrosis factor-alpha (rhTNF-alpha) augmented the zymosan-stimulated leukotriene B4 (LTB4) release from PMN, reaching a fourfold increase at 10(-9) M. Co-incubation of PMN with 10(-9) M rhTNF-alpha and staurosporine resulted in a further dose-dependent increase, which became significantly greater than a purely additive effect at a staurosporine concentration of 10 nM. This synergy was maintained at all doses of staurosporine tested. In addition, doses of phorbol 12-myristate 13-acetate (PMA) that do not activate protein kinase C (PKC) (below 10(-9) M) also augmented the zymosan-stimulated release of LTB4. However, doses of PMA above 10(-9) M progressively inhibited the response to levels below that of zymosan alone. Staurosporine at 50 nM completely prevented, and 10(-9) M rhTNF-alpha partially but significantly (P less than 0.02 at 10(-8) M PMA, P less than 0.01 at 10(-7) M PMA) reversed, this high-dose PMA inhibition. PKC activation thus opposes the priming effect of rhTNF-alpha on neutrophils, while PKC inhibition may enhance the ability of rhTNF-alpha to prime PMN for zymosan activation. The combined effect of rhTNF-alpha and staurosporine suggests an intracellular synergy rather than simply a direct action due to increased zymosan receptor expression. Thus there appear to be mechanisms whereby the responses of neutrophils may be augmented without activating PKC. Indeed, kinase activation may even exert a degree of feedback control that is antagonized by rhTNF-alpha treatment.

Alkaloids↗
PubMed1992

Down-regulation of cyclooxygenase product generation by human peritoneal macrophages.

Isolated human peritoneal macrophages under resting conditions synthesize and release significant quantities of the cyclooxygenase products prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). These increased linearly with time and were dependent on de novo protein synthesis. Following the addition of calcium ionophore A23187 there was a marked decrease in total generation of immunoreactive cyclooxygenase products. In contrast, there was a concomitant increase in the release of 5-lipoxygenase products. The down-regulation of both PGE2 and TXB2 was not due to diversion of substrate from the cyclooxygenase pathway to the 5-lipoxygenase pathway nor was it due to inhibitory effects of products of the 5-lipoxygenase pathway on the generation of cyclooxygenase products. Instead, the inhibitory effects of A23187 were thought to be due to a down-regulation of cyclooxygenase itself, a hypothesis supported by the finding that TXA2 synthase proved to be unaltered and Western analysis of crude peritoneal macrophage (PM phi) membranes demonstrated lesser quantities of cyclooxygenase in membranes from A23187-treated PM phi than in those prepared from control cells.

Adult↗
PubMed1992

Effect of dialyser composition and reuse on neutrophil count and elastase alpha-1 proteinase inhibitor complex formation.

To assess the inter-relationship of leucopenia and PMN elastase release we undertook a prospective crossover study of 6 patients dialysed with new and reused cuprophane, cellulose acetate and polysulfone membranes. Serial blood samples were analysed for PMN count, and elastase-alpha 1-proteinase inhibitor complex (E alpha 1PI) concentrations. After 15 min dialysis with new membranes median PMN counts fell by 72.2%, 25.3% and 22.1% with cuprophane, cellulose and polysulfone, respectively. With reuse the decreases were reduced to 6.4%, 8% and 13.6%. All membranes produced a gradual increase of E alpha 1PI. Median E alpha 1PI accumulation rates (ng ml-1 min-1) with new membranes were 175, 169 and 187 for cuprophane, cellulose acetate and polysulfone, respectively. With reuse of cuphrophane and cellulose acetate these rates fell to 99 and 109 (p less than 0.05 and p less than 0.05, respectively), however, with polysulfone it remained unchanged at 180 ng ml-1 min-1. This study highlights differences between two aspects of the neutrophil response to haemodialysis, and demonstrates that extrapolation from individual parameters to conclusions concerning biocompatibility may be inappropriate.

Adult↗
PubMed1992

A comparison of end-tidal halothane concentrations measured at proximal and distal ends of the endotracheal tube in the horse.

Measurements (n = 126) of end-tidal halothane concentrations were taken from 21 horses anesthetized for routine and emergency surgery. One hundred five paired values allowed comparison of gas samples taken near the oral end of the endotracheal tube (Y1) to samples obtained at the cuffed end of the endotracheal tube (Y2). Twenty-one paired readings were assessed to compare samples taken 25 cm beyond the cuffed end of the tube (Y3) to samples from Y1. Measurements were made at all locations at 15-minute intervals starting 30 minutes after beginning halothane. All measurements were made in triplicate at end-expiration, and both sites were sampled within 1 minute of each other. Halothane concentration was measured by rapid infrared analysis with a gas sampling rate of 150 ml/min and displayed as a digital reading. Calibration of the machine was checked regularly. The difference between readings (Y1-Y2 or Y1-Y3 = Sdif) was tested using general linear models and a significance level of p less than 0.05 was used. The variable Sdif was analyzed with respect to time, mode of ventilation, and type of recumbency; no effects of these variables were detected. The mean values (+/- SD) of 105 readings for Y1 and Y2 were 2.41 vol% (+/- 0.49) and 2.39 vol% (+/- 0.49) respectively, and the Pearson's correlation coefficient (Y1 vs Y2) was 0.96. The mean values (+/- SD) of 21 measurements for Y1 and Y3 were 2.31 vol% (+/- 0.27) and 2.32 vol% (+/- 0.28) respectively and the Pearson's correlation coefficient (Y1 vs Y3) was 0.98.

Anesthesia, Inhalation↗
PubMed1991

Effects of stage of gestation and breed on bovine responses to vaccination with Brucella abortus strain 19.

Eighty-eight cattle were injected SC with 2.5 x 10(8) viable cells of Brucella abortus strain 19. All but 1 heifer became seropositive on the basis of the results of 7 brucellosis tests, and the proportion positive decreased with time. The proportion of cattle that were seropositive during a 20- to 67-week period after vaccination was as follows, in decreasing order: hemolysis-in-gel, 59%; buffered-acid plate antigen, 39%; ELISA, 16%; card, 10%; rivanol, 8%; cold complement-fixation, 7%; and automated complement-fixation, 5%. Using the serologic classification in Uniform Methods and Rules for brucellosis eradication, 7 cattle tested brucellosis-positive (2 suspects and 5 reactors). None of the 27 nonpregnant heifers tested positive. Of 18 heifers that were 84 to 135 days in gestation when vaccinated, 6 (33%) tested positive for brucellosis, compared with 0 of 13 and 1 (3%) of 30 heifers that were 11 to 78 and 145 to 253 days in gestation at vaccination, respectively (X2 = 12.07; 2 df; P less than 0.01). Neither breed (Angus, Hereford, Jersey, and Brahman) nor calf survival was related to brucellosis-positive results. Postpartum milk samples from 61 heifers and 24 tissues from 2 reactor cattle were culture-negative for B abortus.

Animals↗