Biomedical subjects
D G White
Publications and source records attributed to D G White.
The detection of changes in psychological state using a novel pharmacological conditioning procedure.
Using a novel pharmacological conditioning procedure, pigs were conditioned to discriminate the effects of a subconvulsant dose of the anxiogenic drug pentylenetetrazole (PTZ; 2.8-10 mg/kg, i.v.) from saline. The operant chamber provided two levers at which pigs were trained to press at a fixed ratio of 20 presses per food reward (FR 20). The animals were conditioned to select both levers alternately following saline treatment and to select one lever only following PTZ treatment. This procedure enabled the onset and offset of the PTZ stimulus to be detected within single test sessions; infusion of PTZ to animals already selecting both levers alternately after a saline pretreatment induced a period of response exclusive to the PTZ lever followed by a return to an alternation of lever selection response. The ability of the novel procedure to detect the time course of the drug cue should improve future evaluations of the psychological states induced by centrally acting drugs. With PTZ as the training drug, the novel procedure presents a valuable means to study the neurobiology of anxiety.
A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies.
Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.
Endothelin ETA and ETB receptors mediate vascular smooth muscle contraction.
1. We have investigated the receptors mediating endothelin-induced contraction of rabbit isolated jugular vein (RJV) and rat isolated thoracic aorta (RTA). 2. Endothelin-1 (ET-1) and endothelin-3 (ET-3) contracted RJV preparations with similar potency (EC50 values approximately 1 nM), whereas, ET-1 (EC50:4.5 nM) was approximately 80 fold more potent than ET-3 in contracting RTA. In addition, the ETB receptor-selective agonist [Ala1,3,11,15]ET-1 contracted RJV (EC50:2.1 nM) but not RTA. 3. The ETA receptor antagonist, BQ123, competitively antagonized (pA2 6.93) the contraction of RTA produced by ET-1, but had no effect (at 10 microM) on the contractile effects of either ET-1, ET-3 or [Ala1,3,11,15]ET-1 in RJV. 4. These data suggest that both ETA and ETB receptors can mediate vascular smooth muscle contraction.
Outer membrane protein patterns mark clones of Escherichia coli O2 and O78 strains that cause avian septicemia.
Major outer membrane proteins were isolated from 36 Escherichia coli strains representing six common clones of the O2 and O78 serogroups implicated in avian colisepticemia. Clonal relationships among isolates were inferred from an analysis of polymorphism at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. For isolates of these clones, there was a high concordance (greater than 90%) between identity in multilocus genotype and major outer membrane protein patterns. The results indicate that major outer membrane protein patterns discriminate among the genetically different clonal groups that constitute the heterogeneous O2 and O78 serogroups associated with avian disease.
Combined effect of infection and heavy wrapping on the risk of sudden unexpected infant death.
Three methods were used to investigate the role of infection in sudden unexpected infant death (SUD): (i) microbiological comparison of SUD victims and matched, live, community controls; (ii) postmortem classification of the contribution of infection to death; and (iii) case-control analysis of the relative risk associated with both infection and heavy wrapping. Limited sampling from the upper respiratory tract and gut in SUD victims and controls showed no significant excess of viral infection in the SUD victims (odds ratio = 1.98, 95% confidence interval (CI) 0.9 to 4.5). At postmortem examination, infection explained death in 3/95 babies and may have contributed to death in 37/95. Over 70 days of age, the combined presence of viral infection and wrapping in excess of 10 togs produced an odds ratio of SUD of 51.5 (95% CI 5.64 to 471.48) compared with wrapping of less than 6 togs. Viral infection was not a major risk factor as long as babies were lightly wrapped. In heavily wrapped babies the presence of a viral infection greatly increased the risk of SUD.
An analysis of concordant xenografting.
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Wearing a wife-assault-prevention button: impact on a family practice.
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Differentiation of Acanthamoeba strains from infected corneas and the environment by using restriction endonuclease digestion of whole-cell DNA.
Restriction endonuclease digestion of Acanthamoeba whole-cell DNA was used to study the relationship between 33 morphologically identical strains from keratitis cases (30 strains), contact lens storage containers (2 strains), and soil (1 strain). Samples digested with BglII, EcoRI, or HindIII and separated by agarose gel electrophoresis contained detectable mitochondrial DNA restriction fragment length polymorphisms (RFLPs). By comparing RFLPs, the strains could be assigned to seven multiple-strain and three single-strain groups. The largest of these contained nine strains, eight of which were isolated in keratitis cases in various locations worldwide and may indicate a group particularly associated with keratitis. Restriction endonuclease analysis of whole-cell DNA is proposed as a valuable technique for detecting mitochondrial DNA RFLPs in the differentiation of morphologically identical Acanthamoeba strains and may therefore be useful in resolving the complex taxonomy of the genus, which has hitherto been founded on subjective morphological criteria.
Incidence of penicillin tolerance among blood culture isolates of Streptococcus sanguis, 1987-88.
Laboratories that reported isolations of Streptococcus sanguis from blood cultures to the Communicable Disease Surveillance Centre (CDSC) Colindale were requested to submit strains to Bath Public Health Laboratory to allow the prevalence of penicillin tolerance within different biotypes of this species to be studied. One hundred and fifty one Streptococcus spp were received from 78 United Kingdom laboratories in one year. Strains were identified using the API 20 Strep, and minimum inhibitory concentrations (MICs) of penicillin were determined using the spiral gradient plate method. Penicillin tolerance was detected by spraying beta-lactamase over inoculated gradient plates, reincubating for 48 hours and counting the number of surviving organisms represented by colonies. There were 57 different API identification profiles encountered in the survey. Most S sanguis I/1 strains were penicillin tolerant, most S sanguis II strains were non-tolerant. The overall geometric mean MIC of penicillin was considerably lower for S sanguis I/1 than for all other biotypes. The distribution of biotypes and the geometric mean MIC of penicillin for each biotype were not significantly different for infective endocarditis strains than for all strains tested, suggesting little or no association between penicillin tolerance and the seeding of endocardium. When the reactions obtained using API 20 Strep were compared with a recent taxonomic study of viridans streptococci, 22 of 38 S sanguis I/1 strains could be reclassified as S gordonii; all these strains were penicillin tolerant. Such reclassification would allow likely penicillin tolerant strains to be predicted.
Isolation of Staphylococcus aureus from sites other than the lactating mammary gland.
The body sites of 163 heifers, bedding and feedstuff samples, flies, and hands and nares of the research personnel were sampled in order to determine the sources of Staphylococcus aureus in a dairy herd other than the lactating mammary gland. Lesions on the udder of lactating animals and the air in the milking parlor were also sampled. Staphylococci isolated from bedding samples were identified as to species. Staphylococcus aureus was isolated from all sources examined except flies. An enrichment procedure was necessary for isolating S. aureus from two bedding samples although other Staphylococcus species were present in high numbers. The designation "environmental staphylococci" is proposed for Staphylococcus species that were apparently free-living in the environment.
Colostral supplements and substitutes.
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Genetic relationships among strains of avian Escherichia coli associated with swollen-head syndrome.
Genetic diversity among 22 Escherichia coli strains isolated from chickens with swollen-head syndrome (SHS), an acute respiratory disease of domestic poultry, and 93 strains isolated from birds with colibacillosis was assessed on the basis of allelic variation at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. SHS isolates from Spain and Canada were polymorphic at 14 loci and were classified into 19 multilocus genotypes, defining clones that differed on average at 34% of the loci. In most cases, SHS isolates of different clonal genotypes were distinct in O:H serotype and expressed different fimbrial antigens. Comparisons with 93 isolates obtained from birds with colibacillosis revealed enzyme polymorphisms at 17 of 20 loci, with an average of 3.5 alleles per locus. In the total sample, 56 clonal genotypes were distinguished, with 27 (23%) of the isolates belonging to one of three common clones. Both SHS and colibacillosis isolates were genetically diverse, with an average single-locus diversity of 0.36, indicating that a wide variety of naturally occurring bacterial clones is associated with these acute avian infections. Six previously defined groups of clones identified in diseased birds from the United States were represented in isolates from Spain, indicating that similar clones occur in widely separated geographic areas. In addition, one group of SHS isolates was closely related to a recognized widespread clone complex incriminated in human septicemia and meningitis. The results suggest that certain strains implicated in SHS infections belong to a clone complex whose members have special attributes that promote involvement in invasive diseases in humans and animals.
Laboratory investigation of Acanthamoeba keratitis.
Following the diagnosis of Acanthamoeba keratitis in a contact lens wearer, the antimicrobial susceptibility of the clinical isolate and the environmental source of the infection were investigated. Contrary to previous reports, in vitro antimicrobial testing showed that the infecting strain was inherently resistant to propamidine isethionate. Restriction endonuclease digestion analysis of Acanthamoeba whole-cell DNA of strains isolated from the patient's cornea, contact lens storage container, saline rinsing solution, and kitchen cold-water tap showed that the isolates were identical. This implicates, for the first time, domestic tap water as the source of Acanthamoeba sp. in this infection. It is therefore recommended that the use of homemade saline solutions and the rinsing of contact lenses in tap water be strongly discouraged.
Fluorogenic assay for differentiating Staphylococcus warneri and Staphylococcus hominis strains of bovine origin.
A fluorogenic assay for the detection of beta-glucosidase was developed as part of a simplified conventional method to distinguish Staphylococcus warneri and Staphylococcus hominis isolated from bovine body sites. The assay is based on the fact that strains of S. warneri produce beta-glucosidase, while strains of S. hominis do not.
Topical antibiotics in the treatment of superficial skin infections in general practice--a comparison of mupirocin with sodium fusidate.
A total of 413 eligible patients took part in an observer-blind randomised multicentre clinical trial in order to compare the clinical and bacteriological efficacy of mupirocin (Bactroban) ointment with sodium fusidate (Fucidin) ointment for treating superficial skin infections seen in general practice. Mupirocin was applied twice daily and sodium fusidate thrice daily for a period of 7 days. Both treatments were similarly effective with 97% patients treated with mupirocin and 93% patients treated with sodium fusidate responding. Mupirocin was significantly more effective in the treatment of acute primary skin infections and in the treatment of a subgroup of patients with impetigo (P less than 0.01). Of the organisms detected before treatment began, 93% were not found after treatment with mupirocin compared with 89% after treatment with sodium fusidate. Staphylococcus aureus and/or beta-haemolytic streptococci appeared to be eliminated in significantly more patients treated with mupirocin (96%) compared with those treated with sodium fusidate (88%), (P = 0.03). Both treatments were well tolerated.
The effects of salbutamol on blood pressure and heart rate in Large White and Pietrain-cross breeds of pig.
The effects of the beta 2-agonist salbutamol, on pig heart rate and blood pressure were evaluated at the expected commercially used concentration of 3 ppm in final feed, and at three times this level. Salbutamol was administered to pigs previously fed on control diet ('naive'), and in a second study to pigs fed 3 ppm salbutamol for 19 days ('acclimatized'). Heart rate and blood pressure were measured in conscious 30 kg pigs before (pre-ingestive), during (ingestive) and after ingestion (absorptive) of feed containing 3 or 9 ppm salbutamol. To assess any interaction with 'stress genotype' pigs, measurements were performed in Large White and Pietrain-cross breeds. The mean preingestive heart rates for the Large White and Pietrain-cross pigs were 127 and 109 beats/min, respectively. The corresponding figures for mean arterial blood pressure were 121 and 122 mmHg. The act of ingesting control feed caused heart rate to rise by 36-39% and blood pressure to increase by 17-27%. During the absorptive phase for 'naive' pigs fed 3 ppm salbutamol in the diet, blood pressure fell 5-11% and heart rate increased 20-24%, reflecting a classical baroreceptor mediated response. At 9 ppm the fall in blood pressure of 5-11% was similar to that at 3 ppm, while the rise in heart rate was larger at 31-38%. The magnitude of the changes at both 3 and 9 ppm was less than that evoked by the act of ingestion, with the exception of the heart rate response in Large Whites at 9 ppm, which was similar. The responses of the two breeds were comparable, indicating that salbutamol is unlikely to exacerbate the cardiovascular responses seen in potentially stress-susceptible pigs. The acute changes elicited by 3 ppm salbutamol during the absorptive phase in 'naive' pigs were abolished or substantially less in acclimatized pigs, implying a tachyphylaxis to the agonist's actions. This was confirmed by 9 ppm of salbutamol increasing heart rate of 'acclimatized' Large Whites to the same degree as 3 ppm in 'naive' counterparts. The desensitization in Pietrain-cross pigs was even more marked with no increase in heart rate produced by 9 ppm salbutamol following acclimatization. These data, combined with the rapid tachyphylaxis of response, indicate that salbutamol at the intended commercial inclusion of 3 ppm will not compromise the cardiovascular stability of the growing pig at rest.
Differential control and calcium-dependence of production of endothelium-derived relaxing factor and prostacyclin by pig aortic endothelial cells.
1. Production of endothelium-derived relaxing factor (EDRF) by primary cultures of pig aortic endothelial cells was assessed indirectly by measuring endothelial cyclic GMP content, and prostacyclin production was measured by radioimmunoassay of 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha). 2. The resting level of cyclic GMP fell significantly following removal of extracellular calcium (1 mM EGTA present), but elevations of cyclic GMP content induced by sodium azide (10 microM) or atriopeptin II (10 nM) were similar in the absence and presence of extracellular calcium. 3. Haemoglobin (10 microM) reduced the resting level of cyclic GMP in the presence, but not the absence of extracellular calcium. M&B 22,948 (100 microM), superoxide dismutase (30 u ml-1), bradykinin (0.1 microM), ATP (10 microM) and ionophore A23187 (0.1 microM) each induced an increase in endothelial cyclic GMP content that was reduced in the absence of extracellular calcium. 4. In cascade bioassay experiments using endothelial cells on microcarrier beads and perfused in columns, continuous infusion of bradykinin (0.1 microM) induced release of EDRF, assayed on rabbit aortic rings, that was maximal after 2 min and still detectable up to about 16 min. 5. In the presence of extracellular calcium, the time course of bradykinin (0.1 microM)-stimulated production of EDRF, assessed as endothelial cyclic GMP content was maximal within 1 min, declined thereafter, but was still significant after 30 min. Production of 6-keto PGF1 alpha, measured simultaneously rose rapidly but was complete within 3 min. 6. In the absence of extracellular calcium the resting endothelial content of cyclic GMP fell, but resting production of 6-keto PGF1 alpha was unaffected. 7. In the presence of TMB-8 (100 microM) resting endothelial content of cyclic GMP rose slightly, but production of 6-keto PGFg fell. The bradykinin (0.1 microM)-stimulated increase in cyclic GMP content was augmented, but the stimulation of 6-keto PGF1I production was blocked. Results from cascade bioassay experiments confirmed that TMB-8 (100 microM) did not inhibit bradykinin-induced production of EDRF. 8. The data suggest that resting production of EDRF but not prostacyclin is dependent upon the presence of extracellular calcium. Bradykinin-stimulated production of EDRF is sustained and requires the presence of extracellular calcium, but stimulated production of prostacyclin is transient and may result from discharge of an intracellular pool of calcium. 9. The vascular endothelial cell appears therefore to control differentially production of EDRF and prostacyclin.