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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 217 records · Page 12Linked to original sources
PubMed1990

Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases.

Survival benefit from hepatic artery embolization (HAE) or hepatic arterial infusion chemotherapy (HAI) in patients with unresectable colorectal liver metastases has not previously been assessed in a randomized controlled trial. Sixty-one patients were randomized, 20 to receive no treatment, 22 to receive HAE, and 19 to receive HAI with 5-fluorouracil and degradable starch microspheres. Both treatments were acceptable to the patients in terms of low treatment morbidity rate. Median survival from diagnosis of metastases was 9.6 months for controls, 8.7 months for the HAE group and 13.0 months in the HAI group. There was no apparent survival benefit for the HAE group. The increased survival in the HAI group was observed in all the subgroups analysed but failed to reach statistical significance. The greatest observed benefit was achieved in the subgroup with less than 50 per cent hepatic replacement with tumour at presentation (median survival from diagnosis 10.0 months for controls, 10.2 months for HAE and 23.6 months for HAI); 36 per cent of patients developed extrahepatic disease recurrence. No significant benefit has been shown from either HAE or HAI, but a more carefully selected group of patients with only low volume hepatic disease may benefit from HAI therapy.

Adolescent↗
PubMed1990

Prospects for standardisation of methods and guidelines for disc susceptibility testing.

The disc diffusion method of susceptibility testing is widely used in diagnostic laboratories throughout the world. It is simple to perform and very suited to the clinical laboratory where a single isolate can be tested with a series of antibiotics in one experiment. For these two reasons the test is by far the commonest type of susceptibility method used. Other methods such as determination of the minimum inhibitory concentration or "breakpoint" methods are used in only a small number of laboratories. If standardisation of methods is to be achieved in order to agree on uniform reporting and guidelines, methods using disc tests are of the highest priority.

Anti-Bacterial Agents↗
PubMed1990

EGF receptor-binding activity in the urine of normal horses and horses affected by chronic laminitis.

A heterologous radioreceptor binding assay (RRA) has been developed capable of detecting nanogram amounts of epidermal growth factor (EGF) receptor-binding activity in equine urine. The binding parameters of [125I]mEGF (murine EGF) to EGF receptors on equine plasma membranes are in good agreement with values from other EGF-RRA systems. The dissociation constant estimated from equilibrium methods (KD = 4 X 10(-10) M) is in reasonable agreement with that determined from the rate constants (KD = 6 X 10(-10) M) and is in good agreement with values determined in other species. The assay is specific for equine EGF (eEGF) receptor-binding activity and capable of detecting less than 0.34 nM eEGF receptor-binding activity in urine. Equine EGF receptor-binding activity in equine urine form adult horses varied widely between samples (8.5 +/- 6.5 nM). This variability was somewhat reduced when values were adjusted for dilutional effects using urine creatinine as an indicator (3.6 +/- 2.0 nanomoles/g creatinine). No significant differences were demonstrated between the means of EGF binding activity concentrations in clinically normal horses and horses affected by chronic laminitis.

Animals↗
PubMed1990

Antibacterial and mutagenic activity of inhaled bronchodilators on the respiratory pathogen Haemophilus influenzae.

The U.K. prevalence of non-beta-lactamase-mediated resistance to ampicillin among Haemophilus influenzae reached 4% in 1986. The majority (70%) of isolates of this type come from sputa of patients with chronic obstructive airways disease. This study investigated whether bronchodilator drugs delivered directly to the respiratory tract have any antibacterial activity and/or play a role in promoting selection of organisms with this type of resistance. Antibacterial activity was detected in two out of six pharmaceutical preparations for nebulization examination but was entirely attributable to the preservative (benzalkonium chloride) in them. Exposure of ampicillin-susceptible H. influenzae (minimum inhibitory concentration 0.25 mg l-1) to concentrations of salbutamol, fenoterol and beclomethasone theoretically attainable in vivo resulted, after 48 h, in isolation of colonies with reduced susceptibility to ampicillin (minimum inhibitory concentration 1-4 mg l-1) but reversion to beta-lactam susceptibility occurred following serial subculture on chocolate agar. Organisms with stable reduced susceptibility to ampicillin were obtained when exposure to one of these three bronchodilators in broth was followed by serial subculture on agar containing the same preparations at equivalent concentrations and when the period of exposure to salbutamol at 100 mg l-1 in broth was extended to 5 days. The occurrence of these phenomena in vivo might be contributing to failures in treatment of exacerbations with ampicillin and to an increasing prevalence of beta-lactamase-negative, ampicillin-resistant H. influenzae.

Ampicillin↗
PubMed1990

Eicosanoid synthesis in human peritoneal macrophages stimulated with S. epidermidis.

Peritoneal macrophages isolated from CAPD patients phagocytosed S. epidermidis in a time dependent manner. Coincident with a maximum phagocytic uptake of 56% by 12 hours, there was secretion of a significant amount of neutral protease (1.37 +/- 0.2 mg [3H]-casein degraded/10(6) cells, P = 0.05). In contrast to these delayed effects, coincubation of PMO with S. epidermidis resulted in a significant increase in both LTB4 and LTC4 synthesis above that of controls, with 6.33 +/- 1.20 ng LTB4/10(6) cells (P less than 0.01) and 2.06 +/- 0.68 ng LTC4/10(6) cells (P = 0.014) being generated by three hours. The generation of these lipoxygenase products was both time and dose dependent, and the rapid production and release of the potently chemotactic LTB4 is consistent with the observed clinical response, where a rapid influx of PMN into the peritoneal cavity occurs during episodes of peritonitis, while the generation of LTC4 may contribute to the hyperemia and interstitial edema. In contrast, although there was a time dependent rise in cyclooxygenase product generation by unstimulated cells, a dose dependent inhibition of synthesis was clearly demonstrated when cells were incubated with bacteria, with a mean 40% reduction in generation of PGE2 and a mean 34% reduction in TXB2 generation (P = 0.01 and P less than 0.025, respectively). It was demonstrated that the inhibition was not due to lack of available substrate and that the generation of eicosanoids was unrelated to phagocytosis, bacterial/PMO contact or bacterial surface characteristics. Instead, the observed effect of S. epidermidis on the PMO was attributable to a secreted bacterial product.

Arachidonic Acid↗
PubMed1990

Isolation, culture and characterization of human peritoneal mesothelial cells.

This study establishes a reproducible technique for the culture of human peritoneal mesothelial cells. Direct explants, as well as enzymatically degraded specimens, of human omentum have been used as the source of cells. Cells were grown on collagen and gelatin coated matrices and were maintained in supplemented Ham's F-12 medium containing 10% (vol/vol) Fetal calf serum. Morphologically and ultrastructurally, the cells formed a homogeneous population. They were polygonal when confluent and devoid of contaminating fibroblasts, endothelial cells and macrophages. Cultured mesothelial cells co-expressed cytokeratin and vimentin and synthesized laminin, fibronectin, mesosecrin, non-specific esterase and collagen Types I and III but not Type IV. Ultrastructural features included numerous surface microvilli, cytoplasmic vesicles and an abundant endoplasmic reticulum. The stimulation of mesothelial cells by the calcium ionophore A23187 demonstrated that the two major products of arachidonic acid metabolism were prostacyclin and prostaglandin E2. The peritoneal mesothelial cell may be pivotal in the initiation of the inflammatory response during peritonitis and its establishment in culture will provide the basis for an in vitro model of peritoneal inflammation.

Cells, Cultured↗
PubMed1990

Activation of the inflammatory response of neutrophils by Tamm-Horsfall glycoprotein.

The activation of human polymorphonuclear leukocytes (PMN) by particulate Tamm-Horsfall glycoprotein (THG) represents an interaction hitherto unrecognized. The potential pathophysiological effect of this phenomenon within the interstitium of the kidney is highlighted by the activation of the respiratory burst, as well as by comprehensive PMN degranulation. Products of the interaction are expressed in terms of phagocytosis, luminol-dependent chemiluminescence, granule marker enzyme release and arachidonic acid metabolism. Significant quantities of the primary, secondary and tertiary granule markers, myeloperoxidase, vitamin B12 binding protein and N-acetyl-beta-D-glucosaminidase, respectively, were secreted in a dose and time-dependent manner. Phagocytosis of the glycoprotein was accompanied by the generation of significant quantities of leukotriene B4. Furthermore, the ability of such a particulate ligand to activate the alternative pathway of complement clearly represents a capacity to augment the inflammatory response. Should the interaction of THG with PMN take place within the interstitium of the kidney, augmented by the deposition of complement proteins on the surface of insoluble aggregates, the resulting inflammatory response may lead to marked tissue damage and eventually result in interstitial fibrosis.

Complement Pathway, Alternative↗
PubMed1990

Comparative efficacy and tolerance of erythromycin and josamycin in the prevention of bacteraemia following dental extraction.

The tolerance and pharmacokinetics of erythromycin stearate and josamycin base were compared in healthy dental students. The efficacy and tolerance of the two antibiotics were compared in the prevention of bacteraemia following dental extraction. Erythromycin achieved higher serum levels at the time of extraction in dental patients than did josamycin. Erythromycin was rapidly and better absorbed than josamycin in the student volunteers, but josamycin caused less gastrointestinal side effects than erythromycin. Both antibiotics were only marginally more effective than placebo in preventing bacteraemia following dental extraction.

Adult↗
PubMed1990

Comparative in-vitro activity of azithromycin and erythromycin against Gram-positive cocci, Haemophilus influenzae and anaerobes.

The in-vitro activities of azithromycin and erythromycin were compared against 689 clinical isolates, including Gram-positive cocci, Haemophilus influenzae, and anaerobes. Of the 100 methicillin-susceptible isolates of Staphylococcus aureus tested, 77% were susceptible to 1 mg/l azithromycin and 0.5 mg/l erythromycin, whereas 22% were resistant to 32 mg/l of both compounds. All methicillin-resistant S. aureus isolates were highly resistant to both macrolides (MIC greater than 64 mg/l). Coagulase-negative staphylococci showed a wide range of susceptibilities to both compounds; MIC50 values for azithromycin and erythromycin for all isolates were 0.5 and 0.25 mg/l, respectively. With the exception of enterococci, both macrolides showed similar activity against streptococci; MIC90 values for both group A and group B streptococci were 0.03 and 0.06 mg/l for erythromycin and azithromycin, respectively. Azithromycin was less active than erythromycin against enterococci, with mode MICs of 4.0 and 1.0 mg/l, respectively; about 20% of isolates were highly resistant to both compounds. Azithromycin was substantially more active than erythromycin against H. influenzae; 41% of isolates were inhibited by 0.5 mg/l azithromycin and all isolates were inhibited by 2 mg/l. The MIC90 for erythromycin was 8 mg/l; 36% of isolates required concentrations of greater than or equal to 4 mg/l for inhibition. The anaerobic bacteria tested showed similar susceptibility to both azithromycin and erythromycin.

Azithromycin↗
PubMed1990

Predominance of resistant oral streptococci in saliva and the effect of a single course of josamycin or erythromycin.

We have investigated the influence of the macrolides erythromycin and josamycin on the selection of resistant oral streptococci by sampling saliva of volunteers before and after oral administration of 1.5 g of either agent followed by a further 0.5 g of the same drug after 6 h, as in routine prophylaxis for oral or dental procedures. The small proportion of resistant organisms present before antibiotic administration increased substantially 48 h after the macrolides were given. After antibiotic administration mean counts of oral streptococci resistant to 1, 4 and 64 mg/l erythromycin were 23%, 17% and 6%, respectively, of the total numbers of streptococci isolated; after josamycin, the values were 13%, 6% and 4% respectively. The proportion of resistant streptococci then declined gradually but remained above pre-antibiotic levels three months later. Streptococci isolated on media containing 64 mg/l of macrolides were mainly Streptococcus sanguis and S. mitis with one isolate of S. salivarius; the majority were resistant to 256 mg/l erythromycin, josamycin, all other macrolides tested and clindamycin. Amoxycillin and pristinamycin were the only compounds tested that were inhibitory to these organisms at therapeutically attainable concentrations.

Adolescent↗
PubMed1990

The treatment of renal anaemia in CAPD patients with recombinant human erythropoietin.

Fifteen severely anaemic patients receiving CAPD were treated with subcutaneous recombinant human erythropoietin (Epo). Ten subjects had a good response with the haemoglobin concentration increasing from less than 8 g/dl to greater than 10 g/dl within 16 weeks. Four patients had a poor response, which was due to infection in two, myelofibrosis in one and unknown cause in another. Epo was ineffective in the remaining individual, probably due to the presence of occult metastatic carcinoma. Iron supplementation in the form of intravenous iron dextran was given to 12 patients when transferrin saturation decreased below 20%. There was a significant increase in red cell volume (P less than 0.005), with a decrease in plasma volume (P less than 0.005). Red cell iron turnover increased (P less than 0.05) but there was no change in red cell lifespan or deformability. Biochemical parameters remained unaltered, as did peritoneal function. Exercise duration improved (P less than 0.001), as did maximal oxygen consumption (P less than 0.01). Four patients required an increased dose of hypotensive drugs. Epo is a safe effective therapy for the anaemia of CAPD subjects.

Adult↗
PubMed1990

Calcium-channel blockers and other factors influencing delayed function in renal allografts.

A retrospective analysis was undertaken to examine the influence of calcium-channel blocking drugs on early renal allograft function. Delayed function was defined as the need for dialysis or a reduction in serum creatinine of less than 15% within 4 days of transplantation. The drug histories of 172 patients were examined. After exclusions, the data from 138 patients were analysed. No patient was taking any calcium-channel blocking drug other than nifedipine. Thirty-one patients were taking nifedipine at the time of transplantation and these had a delayed function rate of 16% compared with 40% for 107 patients not taking nifedipine (chi 2, P less than 0.05). Delayed function occurred in 61% of cases when the donor age was over 50 years compared with 29% with younger donors (chi 2, P less than 0.05). A total ischaemic time of longer than 24 h and administration of inotropic support to the donor were associated with delayed function (chi 2, P less than 0.05). Administration to the donor of mannitol, steroids, phenoxybenzamine and heparin had no effect on the rate of delayed function. Recipients treated with low-dose dopamine in the perioperative period had no advantage. Elevated trough whole blood concentrations of cyclosporin in the first week after transplant were associated with delayed function (Mann-Whitney U, P less than 0.05).

Adult↗
PubMed1990

Brucella abortus in captive bison. I. Serology, bacteriology, pathogenesis, and transmission to cattle.

Two groups of six, non-brucellosis vaccinated, brucellosis seronegative pregnant American bison (Bison bison) were individually challenged with 1 x 10(7) colony forming units (CFU) of Brucella abortus strain 2308. Three days after challenge, each bison group was placed in a common paddock with six non-vaccinated, brucellosis susceptible, pregnant domestic heifers. In a parallel study, two groups of six susceptible, pregnant cattle were simultaneously challenged with the identical dose as the bison and each group was placed with six susceptible cattle in order to compare bison to cattle transmission to that observed in cattle to cattle transmission. Blood samples were collected from bison and cattle weekly for at least 1 mo prior to exposure to B. abortus and for 180 days post-exposure (PE). Sera from the bison and cattle were evaluated by the Card, rivanol precipitation, standard plate agglutination, standard tube agglutination, cold complement fixation tube, warm complement fixation tube, buffered acidified plate antigen, rapid screening, bovine conjugated enzyme linked immunosorbent assay, bison or bovine conjugated enzyme linked immunosorbent assay, and the hemolysis-in-gel techniques for the presence of antibodies to Brucella spp. At the termination of pregnancy by abortion or birth of a live-calf, quarter milk samples, vaginal swabs, and placenta were collected from the dam. Rectal swabs were collected from live calves, and mediastinal lymph nodes, abomasal contents and lung were taken at necropsy from aborted fetuses for culture of Brucella spp. These tissues and swabs were cultured on restrictive media for the isolation and identification of Brucella spp. Pathogenesis of brucellosis in bison was studied in an additional group of six pregnant bison which were challenged with 1 x 10(7) CFU of B. abortus strain 2308. One animal was euthanatized each week PE. Tissues were collected at necropsy and later examined bacteriologically and histologically. Lesions of brucellosis in bison did not significantly differ grossly or histologically from those in cattle. There were six abortions and two nonviable calves in the bison group, as compared to nine abortions in the 12 similarly inoculated cattle. As determined by bacterial isolations, transmission of B. abortus from bison to cattle (five of 12 susceptible cattle became infected) did not differ statistically from cattle to cattle transmission (six of 12 susceptible cattle became infected) under identical conditions. No single serologic test was constantly reliable to diagnosing B. abortus infected bison for 8 wk PE.(ABSTRACT TRUNCATED AT 400 WORDS)

Agglutination Tests↗
PubMed1990

Stimulation of human rheumatoid synovial cells by non-lethal complement membrane attack.

The effects of non-lethal complement attack on cultured human rheumatoid synovial cells have been investigated by measuring a variety of parameters. Within 3-4 min of initiating non-lethal complement membrane attack there was a rise in reactive oxygen metabolite release from cultured synovial cells, which slowly returned to basal levels over a period of 45 min. The response was dependent on the formation of the complete C5b-9 complex. Prostaglandin E2 was also released during non-lethal attack in a biphasic manner, an early phase of release occurring within the first hour and a second, larger phase commencing at 4 hr and rising to levels of over 1000 ng/10(6) cells at 24 hr, compared to control levels at this time of less than 100 ng/10(6) cells. This response was dependent on the formation of the C5b-8 complex but did not require C9. Removal of extracellular calcium reduced release of prostaglandin E2 to background levels, and inclusion of an inhibitor of protein synthesis abolished the second phase of release but not the first phase. Non-lethal attack caused release of small amounts of leukotriene B4 but no detectable release of tumour necrosis factor.

Cells, Cultured↗