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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 235 records · Page 13Linked to original sources
PubMed1990

The selective augmentation by recombinant human tumour necrosis factor-alpha of neutrophil responses to pathogenic Escherichia coli.

Endotoxin release may amplify the neutrophil (PMN) responses to bacterial infection through the release of monocyte-derived tumour necrosis factor (TNF). The present study was designed to assess the effect of recombinant human TNF-alpha (rhTNF-alpha) on the in vitro response of human PMN to two defined strains of pathogenic Escherichia coli. In the absence of rhTNF-alpha, a P-fimbriate strain caused significant release of the PMN secondary granule marker vitamin B12-binding protein (B12 BP), and a low level of release of leukotriene B4 (LTB4). Type 1-fimbriate strain 504, however, stimulated the release of the primary granule marker myeloperoxidase (MPO) and PMN chemiluminescence (CL), in addition to B12 BP and LTB4 release. Following rhTNF-alpha (10(-9) M) pretreatment, the release of LTB4 by PMN stimulated with the P-fimbriate strain was synergistically augmented, while B12 BP and MPO release were additively increased. In contrast, rhTNF-alpha did not significantly affect any of the responses by the type 1-fimbriate strain. These results suggest selectivity in the priming of PMN by rhTNF-alpha and confirm the independence of PMN responses to phagocytic stimuli.

Cells, Cultured↗
PubMed1990

Zymosan-induced leukotriene B4 generation by human neutrophils is augmented by rhTNF-alpha but not chemotactic peptide.

Tumour necrosis factor (TNF) is a mediator of inflammation that has been shown to enhance neutrophil responses to soluble and particulate stimuli. The release of leukotriene B4 (LTB4) by human neutrophils stimulated by unopsonized zymosan was measured in the presence or absence of recombinant human TNF-alpha (rhTNF-alpha) preincubation. There was a threefold increase in the LTB4 response at an optimal TNF concentration of 10(-9) M and an optimal preincubation time of 10-20 min. A similar time and dose dependency was observed for CR3 receptor expression and for the release of the secondary lysosomal granule marker, vitamin B12-binding protein. In contrast, the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP), although stimulating an increase in both CR3 receptor number and in particle phagocytosis, failed to induce an increase in LTB4 release in response to zymosan. In addition, the present study demonstrated that, unlike FMLP, the exocytotic mechanism for secondary granule release by rhTNF-alpha functioned in the absence of a rise in cytosolic free calcium. Furthermore, it was independent of changes in cyclic nucleotide concentrations and did not require an intact cytoskeleton. Thus the capacity of rhTNF-alpha to amplify the neutrophil response to zymosan through the CR3 receptor appears to be related to the amplification of post-membrane events as well as to an increase in the number of functionally active receptors.

Antigens, CD↗
PubMed1990

Surgical treatment for infarct-related ventricular septal defects. Improved early results combined with analysis of late functional status.

A total of 101 patients (mean age 64.9 years) underwent surgical correction of postinfarction ventricular septal defect at this institution over a 15-year period (1973 to 1988). The overall early mortality rate was 20.8%, although the most recent experience with 36 patients (January 1987 to October 1988) has seen this decline to 11.1%. Factors found to influence early death significantly, when analyzed univariately, were as follows: (1) site of infarction (anterior 12.1%, inferior 32.6%, p = 0.02); (2) time interval between infarction and operation (less than 1 week 34.1%, greater than 1 week 10.5%, p = 0.008); (3) cardiogenic shock (present 38.1%, absent 8.5%, p = 0.001). Nonsignificant variables included preoperative renal function, age, and concomitant coronary artery bypass, although older age (greater than 65 years) became significant when examined in a multivariate fashion. Of the 80 hospital survivors, eight were subsequently found to have a recurrent or residual defect necessitating reoperation, with survival in seven. Late follow-up is 99% complete and reveals an actuarial survival rate for 100 patients of 71.1% at 5 years (95% confidence interval 60.6 to 80.0), and 40.0% at 10 years (95% confidence interval 21.7 to 58.4). A significant recent change in policy of not using coronary angiography in patients with a ventricular septal defect caused by anterior wall infarction has not resulted in any increase in either the early mortality or in the late prevalence of angina. The functional status of 38 surviving patients has been analyzed by a graded treadmill exercise protocol, whereas left ventricular functional assessment was by nuclear scan with additional information on mitral valve function by echocardiogram. Color Doppler flow mapping has been used to determine the presence of a residual defect. Most late survivors have limited exercise tolerance related to both cardiac and noncardiac factors. Left ventricular function is moderately impaired (mean ejection fraction = 0.39). However, many patients are elderly and have adapted to their residual symptoms without significant changes in life-style.

Age Factors↗
PubMed1990

Optimal operative treatment in acute septic complications of diverticular disease.

There is still no unanimity regarding optimal operative treatment in acute septic complications of diverticular disease. Logistic regression analysis was used to investigate factors influencing inpatient mortality in 100 patients who underwent urgent laparotomy for such complications. Thirteen preoperative and operative factors including operation type were investigated and odds ratios (OR) were calculated to indicate the approximate risk associated with each factor. A significant advantage for excision/exteriorisation operations compared with defunctioning operations was found (OR 0.17, 95% confidence interval (CI) 0.04-0.79). Although more conservative procedures (mainly laparotomy with drainage) were associated with an increased mortality relative to defunctioning procedures, this difference just failed to reach statistical significance (OR 3.83, 95% CI 0.89-16.5). Age (OR 1.14, 95% CI 1.05-1.24), co-existing illness (OR 2.38, 95% CI 1.08-5.25) and preoperative shock (OR 4.63, 95% CI 1.00-21.5) were significant as adverse prognostic factors. A higher proportion of survivors treated by defunction than by excision/exteriorisation underwent colostomy closure, but this was in part due to the higher proportion of excision/exteriorisation operations in the latter part of the series. We conclude that in patients requiring urgent laparotomy for septic complications of diverticular disease, the septic focus should be removed from the abdominal cavity. This is most often achieved using a Hartmann's procedure and we recommend this form of treatment.

Abscess↗
PubMed1989

The assessment of relative surface hydrophobicity as a factor involved in the activation of human polymorphonuclear leukocytes by uropathogenic strains of Escherichia coli.

The initiation of the respiratory burst and the degranulation of human polymorphonuclear leukocytes (PMN) in response to stimulation by uropathogenic strains of Escherichia coli is dependent on the expression of Type 1 fimbriae by those strains. These PMN responses correlate with an increasing tendency of the interacting E. coli strain to be retained on hydrophobic columns. The present work assessed the measurement of relative surface hydrophobicity in relation to PMN activation. Type 1 fimbriate organisms bound most readily to Octyl-Sepharose columns and were strongly agglutinated in the salt aggregation test. In contrast, the same organisms partitioned to the dextran-rich (hydrophilic) phase of aqueous two-polymer phase systems. Electron microscopic observation of the organisms eluted from the Octyl-Sepharose columns and of the organisms recovered from both phases of the aqueous two-phase systems demonstrated, however, that both Type 1 and P-fimbriate organisms were retained on the columns and partitioned into the dextran-rich phase as a consequence of their being fimbriate and failed to identify this as a major factor in the activation of PMN. In addition electron microscopy demonstrated that each P-fimbriate population had fewer organisms expressing fimbriae than did Type 1 fimbriate populations, confirming the importance of phase variation as a factor affecting the physicochemical characteristics of a bacterial population.

Agglutination↗
PubMed1989

Variable expression of P fimbriae in Escherichia coli urinary tract infection.

Fresh urinary isolates were examined by immunofluorescence with polyclonal rabbit antibodies against type 1 and P fimbriae. This procedure showed P-fimbriate Escherichia coli in 22 of 24 samples from patients with asymptomatic bacteriuria, 24 of 26 samples from patients with cystitis, and 6 of 6 samples from patients with pyelonephritis. Type 1 fimbriae were expressed by less than 40% of isolates in all three groups. There was no relation between the presence of symptoms or the site of infection and fimbrial expression, of P or type 1, by bacteria adherent to freshly isolated uroepithelial cells.

Adolescent↗
PubMed1989

Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis.

To determine the optimum regimen for giving recombinant human erythropoietin (EPO) to patients on continuous ambulatory peritoneal dialysis (CAPD), the pharmacokinetics of single-dose EPO administered intravenously (120 U/kg), intraperitoneally (50,000 U), and subcutaneously (120 U/kg) was investigated. After intravenous administration serum EPO levels decayed exponentially from a peak of 3959 mU/ml, with a half-life of 8.2 h. 2.3% of the total intravenous dose was lost in the dialysate during the first 24 h. Peak serum EPO levels of 375 mU/ml at 12 h and 176 mU/ml at 18 h were attained following intraperitoneal and subcutaneous administration, respectively. The bioavailability of subcutaneous EPO (21.5%) was seven times greater than that of intraperitoneal EPO (2.9%). These results suggest that subcutaneous EPO represents the most satisfactory route of administration for CAPD patients.

Absorption↗
PubMed1989

Surveillance of antibiotic resistance in South East Asia.

Antibiotic resistance in Gram-negative bacteria, particularly Salmonella and Shigella, requires surveillance worldwide. This study describes results of surveys in Hong Kong, Bangkok and Kuala Lumpur. All strains were isolated in hospitals which have large community catchment areas in addition to specialised hospital units. The prevalence of resistant strains was high in all areas. Gram-negative bacteria such as Enterobacter associated with hospital infections were resistant to penicillins and cephalosporins, with gentamicin resistance ranging from about 20% in Kuala Lumpur and Hong Kong, to 35% in Bangkok. Ninety-seven percent of Shigella isolated in Thailand were resistant to ampicillin. About 10% of Salmonella were resistant to chloramphenicol in all three centres.

Acinetobacter↗
PubMed1989

Marginal seal of injection-molded ceramic crowns cemented with three adhesive systems.

This in vitro investigation evaluated the marginal seal of an injection-molded ceramic crown system used in combination with three adhesive luting systems. One of these systems was a glass-ionomer cement and the other two were based on composite resin materials. One of the latter materials is claimed by the manufacturer to bond to tooth structure and also to porcelain. The final luting material was used in conjunction with a commercially available porcelain bonding system and specific dentin bonding pretreatments. Following thermocycling, the marginal seal of the crowns was tested by use of a chemical marker intrusion technique. The extent of leakage along the sectioned crown/luting agent/tooth structure interfaces was recorded by using digital imaging microscopy. Minimal microleakage was demonstrated with the composite luting cement used in association with specific porcelain and dentin bonding pretreatments.

Adhesives↗
PubMed1989

Correlation of bone marrow colony growth in the myelodysplastic syndromes with the FAB classification and the Bournemouth score.

Erythroid and myeloid colonies were grown from the bone marrow of 81 patients with myelodysplasia and the median number of colonies correlated with the FAB classification and Bournemouth score. CFU-GM were increased in CMML compared to RAEB and RAEBt. BFU-E were higher in RA than in the other FAB subgroups. Patients with a high Bournemouth score had poorer CFU-GM and BFU-E growth than those with a low score.

Anemia, Refractory↗
PubMed1989

Complications of anterior chamber lens implants and their effects on the endothelium.

A five-year follow-up study of 186 eyes which were subject to intracapsular cataract extraction and rigid anterior chamber lens implantation is reported. Ninety-two per cent of cases achieved a visual acuity of 6/12 or better. Serial corneal endothelial cell counts were performed. In 37 pairs of eyes the median difference in operative endothelial cell loss between the operated and un-operated eyes was -7.3% (95% Confidence Interval from -8.7 to -6.1%). Iris tuck occurred in 22.0% and late 'iris ovalling' developed in a further 15.6% of eyes. The median operative endothelial cell loss for those eyes with iris tuck was -9.7% and this was significantly higher than that of eyes with no long-term complications (median loss = -7.3%). The median operative endothelial cell loss for those eyes which developed late ovalling was -8.0% and this was not significantly greater than that of the eyes with no long-term complications (p = 0.745). There was a progressive median endothelial cell loss for all operated eyes and this progressive cell loss was significantly greater for those eyes with iris tuck when compared with those with no complications (p = 0.045).

Aged↗
PubMed1989

Type 1 fimbriate strains of Escherichia coli initiate renal parenchymal scarring.

The renal scarring which characterizes chronic pyelonephritis is initiated by bacterial infection and is independent on the activation of an inflammatory response. Although the presence of polymorphonuclear leukocytes (PMN) is essential for initiating the scarring process, the bacterial structures responsible for their activation have not been investigated. In an animal model of chronic pyelonephritis the surface area of the renal scars produced by Type 1 fimbriate escherichia coli (E. coli) was significantly greater than that of those produced by P fimbriate and non-fimbriate strains (P less than 0.01). The activation of human PMN by the same Type 1 fimbriate organisms resulted in a significant release of lysosomal neutral protease activity (P less than 0.001) and activation of the respiratory burst (P less than 0.01). The neutral protease release in response to P fimbriate and non-fimbriate organisms was not significantly increased. The extent of renal scarring also correlated with the release of neutral protease activity (P less than 0.02) and with the degree of activation of the respiratory burst (P less than 0.05). These results demonstrate that the ability of E. coli strains to cause renal scars may be related to their capacity to express Type 1 fimbria, which may be a causative factor in the in vivo activation of the inflammatory response.

Animals↗
PubMed1989

Train-of-four fade during onset and recovery of neuromuscular block: a study in non-anaesthetized subjects.

The actions of alcuronium, vecuronium and tubocurarine have been studied in the isolated forearms of six healthy, non-anaesthetized volunteers. The responses of adductor pollicis were measured during onset and recovery of neuromuscular block for each agent. There was a drug-related disparity between mechanomyogram (MMG) and electromyogram (EMG) measurement of the first response of the train-of-four (T1) and of the ratio of the fourth (T4) to the first response (TOF ratio). There were significantly higher T1 values for the EMG than for MMG during alcuronium blockade (P = 0.03). For tubocurarine, however, the relationship was reversed. The relationship between T1 and TOF ratio during onset and recovery of neuromuscular block was a hysteresis. The TOF ratio at 50% T1 was significantly higher during onset than during recovery for all three drugs, measured by MMG or EMG (P less than 0.005). Analysis of variance of the differential fade loops failed to show a drug-related effect. We conclude that care should be taken in assuming interchangeability between MMG and EMG measurement of T1. Relationships between T1 and TOF ratio derived during recovery do not necessarily apply during onset and may lead to error in estimating the degree of muscle relaxation.

Alcuronium↗
PubMed1989

Pharmacokinetics of intraperitoneal ciprofloxacin in patients on CAPD.

The concentration of ciprofloxacin was assayed in plasma and peritoneal dialysate following intraperitoneal administration of the drug in the absence of bacterial peritonitis. After administration of a single dose of 5 mg/kg, ciprofloxacin was rapidly absorbed, producing a peak plasma concentration of 1.9 +/- 0.6 mg/l after 3-4 h with an apparent bioavailability of 0.84. In a separate study, following the administration of 25 mg/l for eight consecutive CAPD cycles the intraperitoneal concentration of ciprofloxacin fell to a mean of 8.4 +/- 4.6 mg/l after 4 h cycles and to a mean of 3.0 +/- 3.2 mg/l after 12 h cycles. During the period of administration the mean plasma concentration was 0.5 +/- 0.2 mg/l. Analysis of dialysate for 48 h after cessation of drug administration demonstrated ciprofloxacin to be present in effluent from only two of the six patients, confirming its poor peritoneal elimination.

Ciprofloxacin↗