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Biomedical subjects

P Williams

Publications and source records attributed to P Williams.

At least 19 recordsLinked to original sources
PubMed1999

Effect of rate of distraction on loss of range of joint movement, muscle stiffness, and intramuscular connective tissue content during surgical limb-lengthening: a study in the rabbit.

Surgical lengthening of limbs often results in loss of range of joint movement and this has been shown to be associated with an increase in passive tension and an increase in collagen content of the muscles. In this study, we have investigated the length/tension properties and the connective tissue component of muscle distracted at three different rates in order to determine whether low rates of distraction would enable the connective tissue component, as well as the contractile component (number of serial sarcomeres), to adapt more completely to the increased functional length of the muscle and thus lead to improved range of joint movement. It was found that loss of range of movement varied with rate of distraction. At the low rate, there was no change in the passive tension or collagen content compared to muscles from sham-operated animals, and range of movement was significantly greater than at the other rates. At the medium rate, although the muscles showed good adaptation in terms of serial sarcomere number, passive tension and collagen content was increased and range of movement reduced, indicating that changes in the connective tissue component are important factors in loss of joint movement. In the case of muscle distracted at a high rate, failure of the muscle fibres to add on sufficient sarcomeres, combined with changes in the connective tissue, resulted in almost total loss of joint movement.

Animals↗
PubMed1999

Parachuting for charity: is it worth the money? A 5-year audit of parachute injuries in Tayside and the cost to the NHS.

All parachute injuries from two local parachute centres over a 5-year period were analysed. Of 174 patients with injuries of varying severity, 94% were first-time charity-parachutists. The injury rate in charity-parachutists was 11% at an average cost of 3751 Pounds per casualty. Sixty-three percent of casualties who were charity-parachutists required hospital admission, representing a serious injury rate of 7%, at an average cost of 5781 Pounds per patient. The amount raised per person for charity was 30 Pounds. Each pound raised for charity cost the NHS 13.75 Pounds in return. Parachuting for charity costs more money than it raises, carries a high risk of serious personal injury and places a significant burden on health resources.

Accidents, Aviation↗
PubMed1999

External oblique aponeurosis nerve entrapment as a cause of groin pain in the athlete.

BACKGROUND: Groin pain in sportsmen is a common management problem. The results of surgical exploration in 25 male athletes presenting with groin pain are described. METHODS: All patients had had failed non-operative management. All groins were explored via an inguinal incision and the patients were reviewed for the presence of pain, function and their own subjective opinion. RESULTS: Nineteen injuries were unilateral and six bilateral. One patient had an occult inguinal hernia and another had a patent processus vaginalis. In the others, defects were found in the external oblique aponeurosis through which neurovascular bundles containing terminal branches of the iliohypogastric nerve passed. These tears were repaired after division of the bundles. The mean time to referral was 29.3 weeks (range 4-79 weeks). After operation no pain or only mild pain was experienced in 28 groins. All had improved function. Twenty of 23 patients described the operation as good or excellent. The mean time to resumption of sporting activities after operation was 11.6 (range 4-20) weeks. CONCLUSION: Athletes' groin pain may be due to nerve entrapment in the external oblique aponeurosis. An awareness of this injury may reduce delays in operating leading to an earlier return to sport.

Adult↗
PubMed1999

Changing attitudes about schizophrenia.

Research on the effectiveness of short-term education programs in changing societal attitudes about mental illness has been mixed. Education efforts seem to be mediated by characteristics of the program participants. This study determines whether the effects of a specially prepared, semester-long course on severe mental illness are mediated by pre-education knowledge about and contact with severe mental illness. Eighty-three participants who were enrolled in either a course on severe mental illness or general psychology completed the Opinions about Mental Illness Questionnaire before beginning the course and at completion. Research participants also completed a pre-and posttest of knowledge about mental illness and a pretest on their contact with people who have severe mental illness. The education program had positive effects on some attitudes about mental illness. Interestingly, the effects of education group interacted with pre-education knowledge and contact and varied depending on attitude. Participants with more pre-education knowledge and contact were less likely to endorse benevolence attitudes after completing the education program. Participants with more intimate contact showed less improvement in attitudes about social restrictiveness. Implications of these augmentation and ceiling effects are discussed.

Adult↗
PubMed1999

Dose-rate effects of ethylene oxide exposure on developmental toxicity.

In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.

Administration, Inhalation↗
PubMed1999

The staphylococcal transferrin-binding protein is a cell wall glyceraldehyde-3-phosphate dehydrogenase.

Staphylococcus aureus and Staphylococcus epidermidis possess a 42-kDa cell wall transferrin-binding protein (Tpn) which is involved in the acquisition of transferrin-bound iron. To characterize this protein further, cell wall fractions were subjected to two-dimensional sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis blotted, and the N-terminus of Tpn was sequenced. Comparison of the first 20 amino acid residues of Tpn with the protein databases revealed a high degree of homology to the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Analysis of staphylococcal cell wall fractions for GAPDH activity confirmed the presence of a functional enzyme which, like Tpn, is regulated by the availability of iron in the growth medium. To determine whether Tpn is responsible for this GAPDH activity, it was affinity purified with NAD+ agarose. Both S. epidermidis and S. aureus Tpn catalyzed the conversion of glyceraldehyde-3-phosphate to 1,3-diphosphoglycerate. In contrast, Staphylococcus saprophyticus, which lacks a Tpn, has no cell wall-associated GAPDH activity. Native polyacrylamide gel electrophoresis of the affinity-purified Tpn revealed that it was present in the cell wall as a tetramer, consistent with the structures of all known cytoplasmic GAPDHs. Furthermore, the affinity-purified Tpn retained its ability to bind human transferrin both in its native tetrameric and SDS-denatured monomeric forms. Apart from interacting with human transferrin, Tpn, in common with the group A streptococcal cell wall GAPDH, binds human plasmin. Tpn-bound plasmin is enzymatically active and therefore may contribute to the ability of staphylococci to penetrate tissues during infections. These studies demonstrate that the staphylococcal transferrin receptor protein, Tpn, is a multifunctional cell wall GAPDH.

Amino Acid Sequence↗
PubMed1999

Analysis of quorum-sensing-dependent control of rhizosphere-expressed (rhi) genes in Rhizobium leguminosarum bv. viciae.

The rhi genes of Rhizobium leguminosarum biovar viciae are expressed in the rhizosphere and play a role in the interaction with legumes, such as the pea. Previously (K. M. Gray, J. P. Pearson, J. A. Downie, B. E. A. Boboye, and E. P. Greenberg, J. Bacteriol. 178:372-376, 1996) the rhiABC operon had been shown to be regulated by RhiR and to be induced by added N-(3-hydroxy-7-cis-tetradecenoyl)-L-homoserine lactone (3OH, C14:1-HSL). Mutagenesis of a cosmid carrying the rhiABC and rhiR gene region identified a gene (rhiI) that affects the level of rhiA expression. Mutation of rhiI slightly increased the number of nodules formed on the pea. The rhiI gene is (like rhiA) regulated by rhiR in a cell density-dependent manner. RhiI is similar to LuxI and other proteins involved in the synthesis of N-acyl-homoserine lactones (AHLs). Chemical analyses of spent culture supernatants demonstrated that RhiI produces N-(hexanoyl)-L-homoserine lactone (C6-HSL) and N-(octanoyl)-L-homoserine lactone (C8-HSL). Both of these AHLs induced rhiA-lacZ and rhiI-lacZ expression on plasmids introduced into an Agrobacterium strain that produces no AHLs, showing that rhiI is positively regulated by autoinduction. However, in this system no induction of rhiA or rhiI with 3OH,C14:1-HSL was observed. Analysis of the spent culture supernatant of the wild-type R. leguminosarum bv. viciae revealed that at least seven different AHLs are made. Mutation of rhiI decreased the amounts of C6-HSL and C8-HSL but did not block their formation, and in this background the rhiI mutation did not significantly affect the expression levels of the rhiI gene or rhiABC genes or the accumulation of RhiA protein. These observations suggest that there are additional loci involved in AHL production in R. leguminosarum bv. viciae and that they affect rhiI and rhiABC expression. We postulate that the previously observed induction of rhiA by 3OH,C14:1-HSL may be due to an indirect effect caused by induction of other AHL production loci.

4-Butyrolactone↗
PubMed1999

Evaluation of the buccal component of systemic absorption with inhaled fluticasone propionate.

BACKGROUND: Inhaled corticosteroids have dose related systemic effects determined by oral (swallowed or oropharyngeal absorption) and lung bioavailability. A study was undertaken to evaluate the significance of oropharyngeal absorption for fluticasone propionate. METHODS: Sixteen healthy volunteers of mean age 29.3 years were studied using an open randomised, placebo controlled, four way crossover design. Treatments were: (a) fluticasone metered dose inhaler (pMDI) 250 microg, 8 puffs; (b) fluticasone pMDI 250 microg, 8 puffs + mouth rinsing/gargling (water); (c) fluticasone pMDI 250 microg, 8 puffs + mouth rinsing/gargling (charcoal); and (d) placebo pMDI, 8 puffs + mouth rinsing/gargling (water). Overnight (ONUC) and early morning (EMUC) urinary cortisol/creatinine ratios and 8 am serum cortisol (SC) levels were measured. RESULTS: Significant (p<0. 05) suppression of ONUC, EMUC, and SC occurred with each active treatment compared with placebo. The mean values (95% CI for difference from placebo) were: (a) ONUC (nmol/mmol): fluticasone (2. 8, 95% CI 3.6 to 7.9), fluticasone + water (3.1, 95% CI 3.3 to 7.7), fluticasone + charcoal (2.3, 95% CI 4.1 to 8.5); placebo (8.6); (b) EMUC (nmol/mmol): fluticasone (5.6, 95% CI 8.4 to 24.5), fluticasone + water (7.6, 95% CI 6.6 to 22.4); fluticasone + charcoal (5.6, 95% CI 8.7 to 24.5); placebo (22.1). There were no significant differences between active treatments. The numbers of subjects with an overnight urinary cortisol of <20 nmol/10 hours were 0 (placebo), 11 (fluticasone), 12 (fluticasone + water), and 13 (fluticasone + charcoal). CONCLUSIONS: Oropharyngeal absorption of fluticasone does not significantly contribute to its overall systemic bioactivity as assessed by sensitive measures of adrenal suppression. In view of almost complete hepatic first pass inactivation with fluticasone, there is no rationale to employ mouth rinsing to reduce its systemic effects although it may be of value for reducing oral candidiasis.

Absorption↗
PubMed1999

Acute lung injury after hepatic cryoablation: correlation with NF-kappa B activation and cytokine production.

BACKGROUND: Previous clinical reports have documented multisystem organ injury after hepatic cryoablation. We hypothesized that hepatic cryosurgery, but not partial hepatectomy, induces a systemic inflammatory response characterized by distant organ injury and overproduction of nuclear factor kappa B (NF-kappa B)-dependent, proinflammatory cytokines. METHODS: In this study, rats underwent either cryoablation of 35% of liver parenchyma or a similar resection of left hepatic tissue. Serum tumor necrosis factor-alpha and macrophage inflammatory protein-2 levels and NF-kappa B activation were assessed by electrophoretic mobility shift assay at 30 minutes 1, 2, 6, and 24 hours after either procedure. RESULTS: Cryoablation of 35% of liver (n = 22 rats) resulted in lung injury and a 45% mortality rate within 24 hours of surgery, whereas 7% treated with 35% hepatectomy (n = 15 rats) died during the 24 hours after surgery (P < .05, cryoablation vs hepatectomy). Serum tumor necrosis factor-alpha and macrophage inflammatory protein-2 levels were markedly increased in rats (n = 10 rats) 1 hour after hepatic cryoablation compared with rats that underwent partial hepatectomy (P < .005). We evaluated NF-kappa B activation by electrophoretic mobility shift assay in nuclear extracts of liver and lung after cryosurgery and found that NF-kappa B activation was strikingly increased in the liver but not the lung at 30 minutes and in both organs 1 hour after cryosurgery, and returned to baseline in both organs by 2 hours. In rats undergoing 35% hepatectomy, no increase in NF-kappa B activation was detected in nuclear extracts of either liver or lung at any time point. CONCLUSIONS: These data show that hepatic cryosurgery results in systemic inflammation with activation of NF-kappa B and increased production of NF-kappa B-dependent cytokines. Our data suggest that lung injury and death in this animal model is mediated by an exaggerated inflammatory response to cryosurgery.

Acute Disease↗
PubMed1998

Construction and analysis of luxCDABE-based plasmid sensors for investigating N-acyl homoserine lactone-mediated quorum sensing.

Plasmid reporter vectors have been constructed which respond to activation of LuxR and its homologues LasR and RhlR (VsmR) by N-acyl homoserine lactones (AHLs). The expression of luxCDABE from transcriptional fusions to PluxI, PlasI and PrhlI respectively, occurs in the presence of activating AHLs. A profile of structure/activity relationships is seen where the natural ligand is most potent. The characterisation of individual LuxR homologue/AHL combinations allows a comprehensive evaluation of quorum sensing signals from a test organism.

4-Butyrolactone↗
PubMed1998

Engineering the luxCDABE genes from Photorhabdus luminescens to provide a bioluminescent reporter for constitutive and promoter probe plasmids and mini-Tn5 constructs.

The luxCDABE operon of Photorhabdus luminescens has been cloned and engineered as an easily mobilisable cassette flanked by sites for commonly used restriction enzymes. Constitutive and promoter probe plasmids utilising the P. luminescens luxCDABE have been constructed using a number of compatible replicons and antibiotic markers. Complementary to these plasmids, a range of promoterless and constitutive luxCDABE mini-Tn5 derivatives has been constructed. The potential of coupling mini-Tn5 luxCDABE promoter probe transposons with automated luminometry and photometry to screen for mutants that exhibit growth phase variation in gene expression is demonstrated.

Cloning, Molecular↗
PubMed1998

An unusual case of hyperdontia [corrected].

The presence of supernumerary teeth is not uncommon but there have been very few documented cases of bilateral maxillary and mandibular supernumeraries distal to third molars. This case study looks at the frequency of and complications arising from supernumeraries as well as specifically covering the presentation and subsequent removal in practice of five supernumeraries distal to third molars. Good and thorough radiographs are essential for correct diagnosis.

Adult↗
PubMed1998

Lutzomyia longipalpis: pH in the gut, digestive glycosidases, and some speculations upon Leishmania development.

Screening for digestive glycosidases in different parts of the gut and associated organs of Lutzomyia longipalpis is reported. Searches for the enzymes were made in blood-fed and non-blood-fed females and the enzymes were characterized as soluble or membrane-bound molecules. A total of four different activities were detected, corresponding to the following specificities: an alpha-glucosidase, an N-acetyl-beta-d-glucosaminidase, an N-acetyl-beta-d-galactosaminidase, and an alpha-l-fucosidase. Their possible role and importance for Leishmania development are discussed and the alpha-glucosidase enzyme was partially characterized. The pH inside the gut of non-blood-fed phlebotomines was measured with pH indicator dyes. The pH ranges obtained for crop, midgut, and hindgut were, respectively, higher than pH 6, pH 6, and lower than pH 6. A hypothesis concerning these data and Leishmania development is proposed.

Animals↗
PubMed1998

Training 'greeble' experts: a framework for studying expert object recognition processes.

Twelve participants were trained to be experts at identifying a set of 'Greebles', novel objects that, like faces, all share a common spatial configuration. Tests comparing expert with novice performance revealed: (1) a surprising mix of generalizability and specificity in expert object recognition processes; and (2) that expertise is a multi-faceted phenomenon, neither adequately described by a single term nor adequately assessed by a single task. Greeble recognition by a simple neural-network model is also evaluated, and the model is found to account surprisingly well for both generalization and individuation using a single set of processes and representations.

Computer Simulation↗