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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 271 records · Page 15Linked to original sources

The effect of dialysate on peritoneal phagocyte oxidative metabolism.

The respiratory and oxidative responses of human peritoneal polymorphonuclear leukocytes (PMN) and peritoneal macrophages (PM phi) following exposure to unused continuous ambulatory peritoneal dialysis fluid (CAPD) and early dwell effluent were studied using an open oxygen (O2) electrode system and by measurement of oxygen radical-derived luminol-dependent chemiluminescence. Both cell types responded to stimulation by increasing O2 consumption and by generating chemiluminescence even at external O2 concentrations below 50 microM O2. Oxygen concentrations in the dialysate, as measured by blood gas analysis, were never lower than 118 +/- 8.3 microM O2 even during active peritonitis. Thus oxygen availability does not appear to be rate limiting for phagocyte oxidative metabolism in the peritoneal cavity. Preexposure of both inflammatory cell types to unused fluid or early dwell CAPD effluent significantly reduced both stimulated oxygen uptake and the subsequent ability of these cells to generate chemiluminescence without significantly affecting their viability. Further investigation of this down regulatory phenomenon using unused fluid and laboratory prepared dialysis fluid revealed that low pH (5.3) and high sodium lactate concentration in combination are directly responsible for the suppressive effect of unused fluid and early dwell effluent on cell function. These observations demonstrate that cellular host defense may be impaired early in the dialysis cycle as a result of lactate mediated "stunning" of resident phagocytes. The precise nature of the molecular species responsible for this suppressive effect remains to be identified.

Dialysis Solutions↗

In-vitro activity of cefaclor, cephalexin and ampicillin against 2458 clinical isolates of Haemophilus influenzae.

The zone sizes and MICs of ampicillin, cefaclor and cephalexin were determined for 2458 clinical isolates of Haemophilus influenzae collected in 1986 during a national survey of the prevalence of resistance in this species. Cefaclor showed greater in-vitro activity than cephalexin against all isolates, with a modal MIC of 4 mg/l compared with 8 mg/l. MIC50 values for the 2201 ampicillin-sensitive and 157 beta-lactamase-positive resistant strains were similar for both cephalosporins (4 mg/l for cefaclor, and 8 mg/l for cephalexin). A further 100 strains with a reduced zone (less than 20 mm) to a 2 micrograms ampicillin disc showed a definite (MIC greater than or equal to 4 mg/l) or intermediate (MIC 1 or 2 mg/l) degree of intrinsic resistance to ampicillin. Both cephalosporins showed a marked and significant rise in MIC values for this group. Cefaclor is the more active agent against ampicillin-sensitive and beta-lactamase-positive H. influenzae but strains with an intrinsic mechanism of resistance to ampicillin are markedly less sensitive to both cefaclor and cephalexin.

Ampicillin↗

Standardization of inoculum size for disc susceptibility testing: a preliminary report of a spectrophotometric method.

Many methods of disc susceptibility testing aim at an inoculum to yield a semi-confluent growth. We have improved the means of standardizing inoculum by measuring the turbidity with a spectrophotometer. Absorbance measurements were made for various bacterial suspensions and dilutions thereof, from 1 in 2 to 1 in 1000. Volumes of 0.1 ml of each dilution were spread on to Diagnostic Sensitivity Test agar. Viable counts of bacteria were made for each absorbance reading and for what constituted semi-confluent growth. Suspensions of bacteria having similar absorbance readings contained variable numbers of viable bacteria depending on the species. The number of bacterial cells that yielded semi-confluent growth also varied with different bacterial species. A chart was prepared to indicate the appropriate dilutions of bacterial suspensions with different absorbance readings to produce semi-confluent growth in sensitivity testing of each species.

Bacteria↗

Antibacterial characteristics of YTR 830, a sulfone beta-lactamase inhibitor, compared with those of clavulanic acid and sulbactam.

The antibacterial activity, binding to penicillin-binding proteins, and morphological changes effected by YTR 830, a sulfone beta-lactamase inhibitor, were studied in comparison with those of other beta-lactamase inhibitors. YTR 830 had very poor antibacterial activity, bound to PBP 2 of gram-negative organisms, and at the MIC caused rapid lysis of spheroplasts formed.

Bacteria↗

Type 1 fimbriate Escherichia coli stimulates a unique pattern of degranulation by human polymorphonuclear leukocytes.

Uropathogenic strains of Escherichia coli bearing mannose-sensitive (type 1) fimbriae promote a unique pattern of degranulation from human polymorphonuclear leukocytes (PMN). Significant quantities of the primary (1 degree) and tertiary (3 degree) granule markers, neutral protease-myeloperoxidase and N-acetyl-beta-D-glucosaminidase, respectively, were released by PMN in a dose- and time-dependent manner when stimulated by these defined bacterial strains. Organisms bearing mannose-resistant (P) fimbriae promoted release of only the secondary (2 degree) granule marker, vitamin B12-binding protein. When this pattern of degranulation was compared to that produced by PMN in response to a variety of soluble and particulate stimuli, only the calcium ionophore A23187 similarly triggered 1 degree and 3 degree granule marker release. All the other stimuli tested--zymosan, serum-treated and unopsonized; n-formylmethionyl-leucyl-phenylalanine; and phorbol myristate acetate--promoted release of only the 2 degree granule marker. These results demonstrate selectivity of PMN degranulation in response to a number of transmembrane signals. In addition, the capacity of E. coli to promote PMN degranulation is dependent on its phenotypic fimbrial expression, a surface characteristic which correlates significantly with its relative surface hydrophobicity as measured by binding to octyl Sepharose. Those bacteria demonstrating the greatest hydrophobicity were capable of triggering discharge of all three granule marker proteins. Thus, the mannose-sensitive fimbriae of uropathogenic E. coli may contribute significantly to their potential pathophysiologic role in renal scarring.

Cytoplasmic Granules↗

Detection of ampicillin resistant Haemophilus influenzae in United Kingdom laboratories.

Susceptibility of Haemophilus influenzae clinical isolates to ampicillin reported by 23 laboratories, using a variety of methods, was compared with results obtained following retesting at The London Hospital Medical College. Beta lactamase production was not detected on initial isolation in 25 of 157 isolates (16%) found to be positive on retest. One hundred beta lactamase negative isolates, which gave reduced zone diameters (less than 20 mm) around 2 micrograms discs and required 1-64 mg/l ampicillin for inhibition, were detected at The London Hospital. Eighty five of these had been reported as sensitive to ampicillin by the laboratories of origin. Many of these 100 isolates showed reduced susceptibility to other beta lactam antibiotics. Accurate detection of non-enzymic reduced susceptibility to ampicillin may emerge as an important guide to the likely sensitivity of H influenzae isolates to the enzyme stable beta lactams.

Ampicillin Resistance↗

Epidermal growth factor-mediated effects on equine vascular smooth muscle cells.

Epidermal growth factor (EGF) receptor binding kinetics and EGF-mediated stimulation of DNA synthesis and cellular proliferation were studied in cultured vascular smooth muscle cells (VSMC) from the equine thoracic aorta. Binding studies, using murine 125I-labeled EGF, indicate the presence of a single class of high-affinity binding sites (apparent KD = 2.8 X 10(-11) M), with an estimated maximal binding capacity of 5,800 sites/cell. EGF stimulated [3H]thymidine uptake in confluent quiescent monolayers in a dose-dependent fashion, half-maximal stimulation occurring at 7.5 X 10(-11) M. Likewise, EGF-mediated cellular proliferation was dose dependent (50% effective dose = 5 X 10(-11) M) under reduced serum concentrations. Equine VSMC contain specific receptors for EGF, and EGF can stimulate DNA synthesis and proliferation in these cultured cells, which suggests that EGF may participate in the proliferative changes observed in equine distal digital peripheral vascular disease.

Animals↗

Importance of beta-lactamases and clinical implications of their inhibitors.

The production of beta-lactamases has constituted the main line of defence of bacteria exposed to beta-lactam antibiotics. beta-Lactamases may be part of the natural constitution of the cell, acquired by DNA transferred from other bacteria or induced by exposure to a beta-lactam antibiotic. Many different types of beta-lactamases have been described in a variety of bacteria.

Drug Resistance, Microbial↗

Interspecific transmission of Brucella abortus from experimentally infected coyotes (Canis latrans) to parturient cattle.

In four separate trials, 10 coyotes (Canis latrans) which had been individually fed mascerated bovine placental tissue experimentally inoculated with Brucella abortus strain 2308 were placed in a 1 ha isolation area with six parturient, non-B. abortus vaccinated, Brucella spp. seronegative Hereford heifers. During the second trial, three of the heifers became Brucella spp. seroreactive (as determined by the card, standard agglutination tube, rivanol, complement fixation, and enzyme labeled immunosorbent assay tests) 14 days after exposure to the B. abortus infected coyotes. Five of 10 coyotes in the second trial seroconverted to Brucella spp. positive by day 14 postexposure (PE) and by day 27 PE seven of the 10 coyotes were Brucella spp. reactive. The three Brucella spp. seroreactive heifers subsequently aborted on days 35, 64 and 66 PE and B. abortus strain 2308 was isolated from vaginal swabs, milk, and placental and fetal tissues. There was no serologic or bacteriologic evidence of transmission from B. abortus infected coyotes to the susceptible cattle recorded in the other three trials.

Animal Feed↗

Relationship of days in gestation at exposure and development of brucellosis in strain 19-vaccinated heifers.

Heifers injected with 10(8) (n = 40), 10(9) (n = 39), or 10(10) (n = 39) colony-forming units of Brucella abortus strain 19 were conjunctivally exposed to 10(7) colony-forming units of strain 2308 during gestation. At parturition, milk from each quarter of the udder, a piece of placenta, and 2 swab specimens of the uterus from the dam plus a swab specimen of the rectum from each calf were cultured for Brucella. If the calf was dead or died, additional specimens of lung, stomach contents, and a mediastinal lymph node also were cultured. Days in gestation was determined for each heifer, using data from rectal palpation after breeding and crown-rump length and weight of calf at parturition, with the median value used for data analysis. In each vaccine dosage group, the proportion (%) of heifers developing brucellosis increased as days in gestation at exposure increased. Strain 2308 was isolated from 3 (11%) of 26, 16 (25%) of 64, and 18 (64%) of 28 heifers that were grouped as less than 121, 121 to 150, and greater than 150 days in gestation at time of exposure, respectively. Thirty-two (86%) of the 37 infected heifers were less than 260 days in gestation at parturition, and calves were premature. Heifers with premature calves were more likely to be infected, and tissues were more likely to yield multiple isolations of strain 2308, regardless of days in gestation at exposure or of days after exposure to parturition. Days after exposure to premature parturition of infected heifers ranged from 35 to 110.

Animals↗

Bells against palsy.

A technique is described in which "jingle bells" are sutured in three positions on the face at the points of maximum excursion of the facial musculature when stimulated by a Hilger nerve stimulator set at 2 mA. The procedure is used to monitor movement of the facial nerve while the surgeon dissects the nerve in the cerebellopontine angle and internal auditory canal.

Facial Nerve↗

Resistance of clinical isolates of Haemophilus influenzae in United Kingdom 1986.

Between 1 January and 31 March 1986, 2434 strains of Haemophilus influenzae collected from 23 laboratories in the United Kingdom were examined. With the same criteria as previous studies in 1977 and 1981 the prevalence of resistance was: ampicillin 7.8% (6.2% beta-lactamase producers and 1.6% non-producers), tetracycline 2.7%, chloramphenicol 1.7%, trimethoprim 4.2%, and sulphamethoxazole 3.5%. of the 87 capsulated strains, 15 produced beta-lactamase, nine were resistant to ampicillin but did not produce beta-lactamase, and two strains, one of which produced beta-lactamase, were resistant to chloramphenicol and tetracycline. Since 1977 the prevalence of resistance to ampicillin, chloramphenicol, and trimethoprim has increased significantly. During 1981-6 strains resistant to ampicillin but not producing beta-lactamase and strains resistant to trimethoprim have significantly increased.

Ampicillin↗

In-vitro susceptibility of oral streptococci to pristinamycin.

The inhibitory activity of pristinamycin against oral streptococci was compared with that of amoxycillin, erythromycin and vancomycin. Minimum inhibitory concentrations (MICs) of pristinamycin ranged from 0.03-1 mg/l (mode 0.25 mg/l), similar to those for amoxycillin. Erythromycin had a mode MIC of 0.06 mg/l and vancomycin, the least active, 1 mg/l. However, in killing curve experiments to compare the bactericidal activities of pristinamycin and erythromycin against several strains of oral streptococci, pristinamycin was substantially more active, consistently producing a rapid decrease in viable count during the first few hours of incubation. Pristinamycin may prove to be of value for the prophylaxis of post-dental extraction bacteraemia.

Amoxicillin↗

Penicillin-binding proteins in Streptococcus faecalis and S. faecium.

Penicillin-binding proteins (PBPs) of Streptococcus faecalis NCTC 775, S. faecium NCTC 7171 and an isolate of S. faecium (strain 37) highly resistant to beta-lactam antibiotics were visualised by autoradiography. Five PBPs were detected in S. faecalis NCTC 775 and six in S. faecium NCTC 7171. Additional PBPs could not be found in the resistant isolate of S. faecium. The PBP affinities of beta lactams were compared with MIC values. The affinities of PBPs 3 and 4 of S. faecalis NCTC 775 for penicillin G, ampicillin, cefathiamidine, cephaloridine and cephazolin were related to the sensitivity of the strain to these antibiotics as were the affinities of PBPs 4 and 5 in each S. faecium strain for the beta lactams. It is postulated that PBPs 3 and 4 of S. faecalis NCTC 775 and PBPs 4 and 5 of S. faecium are the relevant target enzymes of the test antibiotics. PBPs 4 and 5 of the highly beta-lactam-resistant S. faecium strain 37 showed proportionally low affinities for the five beta lactams compared to that of the less resistant strain S. faecium NCTC 7171. Decreased affinities of PBPs 4 and 5 may account for the resistance in S. faecium strain 37 to beta lactams. The affinities for PBP 1, 2 and 5 in S. faecalis NCTC 775 and PBPs 1, 2, 3 and 6 in S. faecium were not related to the antibiotic sensitivities.

Bacterial Proteins↗