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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 181 records · Page 10Linked to original sources

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↗

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↗

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↗

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↗

Failure of two macrolide antibiotics to prevent post-extraction bacteraemia.

Two macrolide antibiotics, erythromycin and josamycin, were compared in a double-blind trial to examine their efficacy in the prevention of post-dental extraction bacteraemia in a group of healthy patients. An in vitro blood culture system was used. Isolates of streptococci were identified to species level. Minimum inhibitory concentrations (MICs) of erythromycin and of josamycin for each isolate were estimated by an agar dilution technique, with controls. Levels of drug in the serum of volunteers and of patients were assayed after oral doses of the macrolide antibiotics. Levels found achieved early peaks and satisfactory concentrations for activity against streptococci. Within the specified parameters, the results demonstrated that the antibiotics failed to prevent survival in blood culture of various strains of streptococci for up to 24 hours following collection of the blood. It is recommended that an alternative antibiotic to either erythromycin or to josamycin be used to achieve prophylaxis against streptococci in infective endocarditis risk patients who are allergic to penicillin.

Adolescent↗

Thermospray liquid chromatography-mass spectrometry with a quadrupole ion trap mass spectrometer.

A theromospray ion source using corona discharge ionization was interfaced to a quadrupole ion trap mass spectrometer via a multi-element lens system. Ions were injected into the trap periodically where they were stabilized by collisions with helium bath gas. Mass spectra were recorded on the trapped ions using the mass-selective instability scan mode. Data are shown for a peptide and a nucleoside and the effects of some experimental variables on the spectra are explored.

Adenosine↗

Spectrum of activity of azithromycin.

In recent years, a number of newer macrolides have been developed. One such antibiotic is azithromycin, which has a 15-membered ring structure and is classed as an azalide. The limitations of erythromycin and the discovery of pathogenic bacteria such as Campylobacter, Legionella and Chlamydia species provide incentives to study the usefulness of newer antibiotics of this class. Azithromycin has good activity against staphylococci, streptococci, Moraxella catarrhalis and other rapidly growing pyogenic bacteria. The good activity of azithromycin against Haemophilus influenzae (MIC90 0.5 mg/l) is particularly important as erythromycin has only marginal activity against this organism. Azithromycin has also been shown to be more potent than the macrolides against Enterobacteriaceae. In common with erythromycin and tetracycline, the agent has good activity against Legionella, Chlamydia and Campylobacter. Opportunistic infections involving Toxoplasma gondii and Pneumocystis carinii are an increasing problem and azithromycin is particularly interesting in view of its activity against these difficult-to-treat organisms.

Animals↗

Bladder capacity in infants.

Bladder capacity was measured at micturating cystourethrography and normal ranges were established for children up to 1 year of age. Bladder capacity was compared with patient weight and distance from first lumbar to third lumbar vertebrae (L1 to L3). The simplified formula--Capacity (mL) = 7 x weight (kg)--was shown to give a reliable estimate of the expected bladder capacity in infants independent of age; this is useful in those infants whose weight lies outside the normal range for their age. Similarly, a formula was deduced relating expected bladder capacity to the measured L1 to L3 distance on an anteroposterior radiograph, which is of potential use to radiologists.

Body Weight↗

Comparison of results from five serologic methods used for detecting Brucella abortus antibody activity in coyote sera.

A total of 423 serum samples representing 94 coyotes which were wild trapped in east Texas were used to compare the serologic results from five different methods for detecting antibodies to Brucella abortus. The sera were tested for Brucella spp. antibody activity by the Card (CARD), rivanol precipitation (RIV), standard agglutination tube (SAT), cold complement fixation test (CF), and enzyme linked immunosorbent assay (ELISA) methods. Each serum sample selected for this comparison demonstrated antibody activity by one or more of the five serologic methods. When the serologic results of the five different methods were compared, 143 sera were positive according to the CF test and agreement was 67.1-70.6% with CARD, RIV and SAT. The maximum agreement for CF positive was with CARD (70.6%) and the lowest agreement fro CF negative was also with CARD (56.4%). Agreement among the serologic methods for the SAT positive ranged from 69.1% (CARD) to 72.7% (RIV). Agreement between SAT and ELISA was poor with only 38.1% agreement for SAT positive and 11.3% agreement for SAT negative. Agreement between methods for CARD positive sera was poor, with a low of 43% for both SAT and ELISA, and a high of 55.6% for RIV. Agreement between methods for 149 RIV positive sera was 83.2% for CARD, 67.8% for SAT, 64.4% for CF and only 50.3% for ELISA. Agreement between methods for ELISA positive results ranged from 49.0% for RIV to 62.7% for CARD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Diseases↗

Enalapril can treat the proteinuria of membranous glomerulonephritis without detriment to systemic or renal hemodynamics.

The effect of enalapril on renal hemodynamics and glomerular permselectivity was studied in eight patients with nephrotic syndrome secondary to biopsy-proven membranous glomerulonephritis. The patients received the drug in incremental doses (median, 5 mg) until 24-hour urinary protein excretion had decreased persistently by 30%. Median treatment duration was 6 weeks. Patients were studied three times: (I) after a 4-week run-in period, (II) on the final day of treatment, and (III) after a 4-week wash-out. Median 24-hour urinary protein excretion decreased on treatment from 10.45 g/d to 5.25 g/d and increased to pretreatment levels after the drug was stopped (P less than 0.05 for both changes). Fractional clearance of dextrans greater than 4.1 nm decreased on treatment, indicating both a reduction of macromolecules passing through the shunt pathway of the glomerular basement membrane (GBM) and a possible decrease in ultrafiltration coefficient. There were no significant changes in glomerular filtration rate (GFR), effective renal plasma flow (ERPF), or mean arterial blood pressure (MAP) throughout the study. The effect of enalapril in treating proteinuria appears therefore to be due to a specific intraglomerular action.

Adult↗

A population survey of cardiovascular disease in elderly people: design, methods and prevalence results.

A cross-sectional survey of an age- and sex-stratified random sample of the elderly population living in Southampton was undertaken with the object of measuring the frequency of cardiovascular disease by questionnaire and examination, and assessing cardiac anatomy and physiological function by noninvasive methods. The response rate was 64% and 259 men and women aged between 65 and 95 years were interviewed and examined and had a twelve-lead ECG and chest radiograph. Forty per cent of men and 47% of women reported a diagnosis of one or more cardiovascular diseases, of which high blood pressure 33%, coronary heart disease 14% (angina pectoris 11% and myocardial infarction 8%), peripheral arterial disease of the lower limbs 7%, and cerebrovascular disease 6% occurred most frequently. With the exception of high blood pressure, which women reported more frequently than men (40% vs 27%), the prevalence of these diagnoses by sex was similar. The self-administered WHO questionnaires gave point prevalence estimates for angina pectoris of 13%, possible myocardial infarction 7% and intermittent claudication 5%, which were similar to reported prevalences of these diseases, although disagreement in the classification of individuals for each disease was common. When comparing the WHO chest pain questionnaire with the doctors' independent diagnosis of angina pectoris in this population, the sensitivity of the WHO questionnaire was 79%, with a specificity of 98% and a predictive value of 88%. For each sex the sensitivity of the WHO chest pain questionnaire was similar but specificity and predictive value were both lower for women.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Effect of pretreatment with oral pyridostigmine on subsequent activity of alcuronium in non-anaesthetized subjects.

We have studied the effects of alcuronium in 10 healthy, non-anaesthetized volunteers after they had been taking oral pyridostigmine 30 mg 8 hourly. The responses of adductor pollicis were recorded using an isolated forearm procedure (IFP) during onset and recovery of neuromuscular block produced by 1.5 mg of relaxant. Previously noted disparities between mechanomyogram and electromyogram measurement of the first response of the train-of-four (T1) and the ratio of the fourth (T4) to the first response (TOF ratio) were found in most cases, but were unaffected by pyridostigmine. Pyridostigmine did not affect significantly the overall characteristics of neuromuscular block, but repeated IFP after a placebo unexpectedly produced marginally less depression of T1 and more rapid recovery. The hysteresis relationship between T1 and T4 during onset and recovery of block was confirmed, but was not affected by pyridostigmine. Clinically, the results may indicate that pyridostigmine pretreatment is unlikely to have significant effects on the subsequent use of alcuronium.

Administration, Oral↗

The response of human peritoneal macrophages to stimulation with bacteria isolated from episodes of continuous ambulatory peritoneal dialysis-related peritonitis.

The metabolism of arachidonic acid, by isolated peritoneal macrophages in response to stimulation with microorganisms isolated from continuous ambulatory peritoneal dialysis (CAPD) patients, is not specific to the individual strain but is determined by species. Isolates of Staphylococcus aureus (n = 7) and Staphylococcus epidermidis (n = 13) produced a significant increase in leukotriene B4 generation by peritoneal macrophages compared with unstimulated cells (P less than .001). The coincubation of peritoneal macrophages with gram-negative organisms (n = 3), however, did not result in an increase in leukotriene B4 synthesis. In contrast, all the organisms tested significantly inhibited the formation of prostaglandin E2 and thromboxane B2 but the degree of inhibition was species dependent. The above results were reproduced using bacteria-free supernatants, indicating that the interaction was dependent on a secreted bacterial product. Thus in response to certain bacterial species, the recruitment of neutrophils may be facilitated by the generation of leukotriene B4 from peritoneal macrophages. In addition, the reduction in synthesis of prostaglandin E2 may remove a regulatory effect that this metabolite has on the immune response.

Adult↗

Human neutrophil responses to pathogenic Escherichia coli are receptor-specific and selectively augmented by recombinant human tumor necrosis factor-alpha.

The effect of recombinant human tumor necrosis factor-alpha (rhTNF alpha) on neutrophil (PMNL) response to uropathogenic Escherichia coli was assessed. A strain expressing mannose-sensitive adhesins (type 1 fimbriae) stimulated significant primary granule, secondary granule, and leukotriene B4 (LTB4) release. The same strain grown to suppress fimbrial expression and three non-type 1-fimbriated strains stimulated only background low-level PMNL activation. The binding of the type 1-fimbriated strain to PMNL was inhibitable by D-mannose and concanavalin A, while that of non-type 1-fimbriated strains was not but was inhibited by antibodies to the PMNL complement receptors 1 and 3. TNF alpha (10(-9) M) synergistically augmented the non-type 1-fimbriated E. coli-stimulated LTB4 release and additively increased secondary granule release without affecting primary granule release. In contrast, none of the responses to the type 1-fimbriated strain were augmented by TNF alpha. In the absence of mannose-sensitive adhesins, the activation of PMNL by E. coli may involve both complement receptors 1 and 3 and be augmented by TNF alpha.

Bacterial Adhesion↗

Gram-positive infections related to CAPD.

The majority of infections associated with continuous ambulatory peritoneal dialysis (CAPD) are caused by Gram-positive bacteria. The coagulase-negative staphylococci are the most common cause of peritonitis and Staphylococcus aureus is the organism most frequently associated with tunnel and exit site infections. The advent of newer techniques for bag change in CAPD has significantly reduced the incidence of peritonitis but relapse is still common among a few isolated individuals. Carriage of staphylococci in the nose is important in predisposing individuals for exit site infections. The possibility that eradication of nasal carriage may prevent CAPD infection has yet to be evaluated.

Bacterial Adhesion↗

Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis isolated in the UK from sputa.

Four hundred and thirty-one Streptococcus pneumoniae, 1272 Haemophilus influenzae and 305 Moraxella (Branhamella) catarrhalis were isolated from sputa and identified in 28 UK laboratories during a ten week period in 1990. Disc diffusion susceptibility testing was performed in each centre using identical methods. Species-specific susceptibility breakpoints applied to data for six antimicrobial agents were determined from the distribution of isolates according to zone diameters of inhibition measured in participating laboratories and were correlated with minimum inhibitory concentration data obtained with 302 isolates sent to the coordinating centre. Inter-laboratory reproducibility was estimated by comparing peripheral and coordinating centre results for these 302 isolates and by distributing five reference strains to all laboratories for testing. Reduced susceptibility to ampicillin and amoxycillin-clavulanate was detected in less than 3% of S. pneumoniae, but 8.1% were resistant to tetracycline and 6.5% to erythromycin. Resistance to ampicillin due to production of beta-lactamase occurred in 9.4% of H. influenzae; another 5.2% were resistant to ampicillin and amoxycillin-clavulanate but were beta-lactamase-negative. 4.5% were resistant to tetracycline and most (86.6%) had MICs greater than or equal to 1 mg/L of erythromycin. Zone diameters around ampicillin discs were greater than or equal to 10 mm smaller than those around amoxycillin-clavulanate discs for 241 (79%) of M. catarrhalis. Although only 193/241 had been reported to be beta-lactamase positive by participating laboratories, data obtained at the coordinating centre confirmed that greater than or equal to 10 mm and less than or equal to 3 mm zone size differences correlated with beta-lactamase-positive and -negative isolates respectively. No M. catarrhalis were resistant to amoxycillin-clavulanate and less than 4% were resistant to either tetracycline or erythromycin. The prevalence of resistance to cefaclor was highest among H. influenzae (5.2%) and lowest among S. pneumoniae (0.9%). Only seven of 2008 isolates (two to three per species) were resistant to cefixime. The data suggest that the prevalence of resistance to ampicillin, tetracycline and erythromycin must be taken into consideration when treating respiratory infections.

Ampicillin Resistance↗