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Biomedical subjects

P Williams

Publications and source records attributed to P Williams.

At least 253 records · Page 14Linked to original sources
PubMed1995

Adenovirus pneumonia in lung transplant recipients.

Although Adenovirus (ADV) pneumonia has been documented in bone marrow, kidney, and liver transplantation recipients, it has only been sporadically reported in lung transplantation recipients. Among our 308 lung transplantation recipients, we identified four who developed ADV pneumonia. Formalin-fixed paraffin-embedded biopsy and autopsy specimens on all cases were studied by routine histology, immunohistochemistry (IHC), and by in situ hybridization (ISH) for evidence of ADV, and the results were correlated with the patients' clinical progression. Three of the four patients were children, and all four had a progressive and rapidly fatal course within 45 days posttransplantation. The lungs showed necrotizing bronchocentric pneumonia with tendency to spread diffusely to produce alveolar damage and organizing pneumonia. The occurrence of this rapidly fatal ADV pneumonia mainly affecting the pediatric population, early in the posttransplantation course, suggests that the infection is primary to the recipient with ADV either originating and reactivating in the donor lung or acquired from the upper respiratory tract of the recipient. The characteristic smudgy intranuclear inclusions of ADV, as well as IHC and ISH positivity, were observed in the lungs of all autopsies. Antemortem biopsy demonstration of ADV by inclusion formation, IHC, and ISH was observed in two patients. In another patient, antemortem ADV was shown only by ISH, and the recognition of inclusions was made difficult by coexistent CMV infection. Although IHC and ISH may have the potential for detecting early infection, recognition of the characteristic clinical setting with necrotizing bronchocentric pneumonia and smudgy intranuclear inclusions should alert one to the diagnosis of ADV pneumonia.

Adenoviridae Infections↗
PubMed1995

A long-term study of the interaction between iron and alcohol in an animal model of iron overload.

BACKGROUND/AIMS: The hypothesis that chronic alcohol ingestion potentiates iron-associated liver injury was investigated in the 'carbonyl iron-overload rat model'. METHODS: Newborn male and female Wistar-Furth rats (seven per group) were used to investigate iron-alcohol interaction over a 26-week period. Groups 1 and 2 were iron loaded from birth, while the others received normal diet. At 10 weeks all rats commenced Lieber-DeCarli liquid diet; additional treatments were: group 1 6 g carbonyl iron/1000 ml diet plus alcohol; group 2 carbonyl iron in the liquid diet; group 3 alcohol in the liquid diet; group 4, the controls, received liquid diet only. RESULTS: This study confirmed our previous observation that iron-loading from birth resulted in grade III-IV siderosis, in both male and female rats, and caused fibrosis associated with periportal macrophages. Alcohol-feeding, in addition to iron-feeding for 26 weeks significantly lowered the hepatic iron concentration in both male and female rats compared to those fed iron only (p < 0.05). Alcohol feeding did increase hepatic fibrosis in the iron-loaded animals. However, serum alanine aminotransferase activity was significantly higher in the iron-alcohol group than in the other groups (p < 0.05). CONCLUSIONS: Thus, contrary to expectation, chronic alcohol feeding failed to potentiate hepatic fibrosis in iron-overloaded rats, although there was rather more hepatocyte necrosis, and the serum alanine aminotransferase activity was significantly higher in the iron-alcohol group than in the other groups.

Alcoholism↗
PubMed1995

Continuous ambulatory peritoneal dialysis-associated peritonitis as a model device-related infection: phenotypic adaptation, the staphylococcal cell envelope and infection.

During the development of infection, pathogens are translocated from one body site to another and so must readily adapt to changing environmental conditions. The influence of host environment on bacterial behaviour and virulence gene expression is, however, often overlooked. Environmental signals such as temperature, pH and nutrient (especially iron) availability which inform pathogens of their living conditions thus contribute to both bacterial survival and virulence. In the context of medical device-associated infections such as peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients, the pathogenesis of infection is related to the ability of the infecting organism to multiply, to adhere to catheter polymers and host tissues and to evade host defences. Coagulase-negative staphylococci (CNS) such as Staphylococcus epidermidis are commonly responsible for CAPD-associated peritonitis. Although staphylococci cannot grow in commercial peritoneal dialysate solutions, these fluids are modified during dialysis and become enriched by a plasma ultrafiltrate which can support bacteria growth. Given that growth environment exerts considerable influence on bacterial behaviour, the physiology of CNS cultured in vitro in a model system employing pooled human peritoneal dialysate and in vivo in implanted peritoneal chambers in the rat has been investigated. Using such models marked variation in surface physicochemistry, antibiotic susceptibility and adherence to catheter polymers has been observed. This plasticity is clearly reflected in the cell envelope phenotype of CNS, the study of which has recently lead to the discovery of a staphylococcal receptor for the iron-binding serum glycoprotein, transferrin.

Animals↗
PubMed1995

Physiologic, health and lifestyle factors associated with femoral neck bone density in older women.

Three hundred eleven women aged between 60 and 91 years (mean age 72.2) who were randomly recruited from the community underwent bone density assessments of the femoral neck. Two complementary multivariate techniques were used to assess the relationships between femoral neck bone density and a range of anthropometric, health, and lifestyle measures. Stepwise multiple linear regression analysis revealed age, weight, height, quadriceps strength, and lifelong smoking to be variables that independently and significantly explained part of the variance in femoral neck bone density within the group. Multiple logistic regression revealed that after adjusting for established predictors of bone mineral density, age, height, and weight, reduced quadriceps strength, lifelong smoking, and little childhood activity were significantly associated with low bone density (< 0.70 g/cm2), whereas superior quadriceps strength, nonsmoking, and high levels of current physical activity were significantly associated with high bone density (> 0.84 g/cm2). In contrast, current calcium intake was not significantly associated with bone density. The study findings highlight possible public health initiatives for minimizing age-related femoral neck bone loss in older women.

Aged↗
PubMed1995

Comparison of the ClearView uterine manipulator with the Cohen cannula in laparoscopy.

The ClearView Uterine Manipulator was compared with the Cohen acorn-tipped cannula for efficacy and safety in patients undergoing laparoscopy at the University of Utah Medical Center. Fifty consecutive patients were randomized by computer to have either the ClearView instrument or the Cohen cannula used as a uterine manipulator (25 patients each). The ClearView manipulator was statistically superior to the Cohen cannula for range of motion in the anterior and posterior sagittal plane (p <0.0001). The Cohen cannula was consistently inserted in less time (p <0.02). There was no statistically significant difference between the instruments in ease of uterine manipulation, ease of dye instillation, percentage of dye leakage from the cervix, overall ease of use, ease of device insertion, and ease of device removal. Two cervical perforations occurred during cervical dilatation in the ClearView manipulator group in patients with cervical stenosis requiring dilatation with metal dilators (os <2 mm). No patients in the Cohen cannula group had cervical stenosis. In that group two cervical lacerations occurred requiring suture ligation. The ClearView instrument provides a greater range of motion, does not require an assistant to maintain uterine position, and allows manipulation without a cervical tenaculum. Its insertion occasionally (36%) required tenaculum placement, uterine sounding, and cervical dilatation, increasing the time of insertion compared with placement of the Cohen cannula. In patients with cervical stenosis, use of a uterine sound and cervical dilatation increase the risk of perforation.

Adult↗
PubMed1995

Predictors of adherence to a structured exercise program for older women.

This study examined whether psychological, physiological, and health and lifestyle measures were associated with adherence to a structured exercise program for older women. Women aged "60 to 85 years (N = 102)," randomly recruited from the community, were assessed on these measures before and after a 12-month exercise trial. Sixty-nine women completed the trial, and 54 continued participation after the trial for at least 6 months. Adherence was examined at various stages during the trial. Multiple regression analysis revealed that reduced muscle strength, slow reaction time, and psychoactive drug use explained most of the variance in adherence during the trial. In contrast, muscle strength, reasoning ability, depression, and self-reported improvement in strength best predicted continued participation after the trial. The findings have implications for community-based exercise programs and research trials.

Aged↗
PubMed1995

A plasmid-based self-amplifying Sindbis virus vector.

Sindbis virus was used as a self-amplifying eukaryotic expression vector. A recombinant cDNA genome of this (+)-strand RNA virus was placed under the transcriptional control of a Rous sarcoma virus LTR (RSV) promoter. Transfection of this plasmid construct into mammalian cell lines (3T3, HepG2, and 293 cells) resulted in expression of the luciferase reporter gene. High-expression levels were also measured after transfection into primary rat myoblasts. In differentiated myotubes, expression levels generated by the Sindbis virus vector were up to 200 times higher than those obtained with a conventional RSV expression vector. In vivo expression was detected after injection of plasmid DNA into mouse quadriceps. In vivo expression was transient and undetectable by day 16. This self-amplifying expression vector can be used for generating high-level expression of transgenes in vitro and in vivo. Its transient nature in vivo could allow for safe, short-term delivery of gene products in gene therapy protocols. It should facilitate the study of Sindbis and other RNA viruses.

3T3 Cells↗
PubMed1995

Diagnosis and treatment of pneumonia in the nursing home.

Risk factors, diagnosis, ethical considerations, and treatment of pneumonia in a nursing home setting are summarized. Risk factors for pneumonia include age-associated changes, co-morbid conditions, declining general health, and iatrogenic factors. Diagnosis can be challenging in geriatric residents because of atypical presentations and complex underlying diseases. Key features of presentation include rhonchi and confusion. An increased respiratory rate can be a sensitive indicator for pneumonia. Ethical dilemmas include identifying a resident's wishes for treatment in the event of an acute illness and the decision on whether to relocate the resident to an acute care facility. Decisions are based on available resources, medical stability of the resident, unimpeded access to a hospital, and the resident's well-informed decision. The common etiologic pathogen(s) of nursing-home-acquired pneumonia reflect a mixture between community-acquired and hospital-acquired pathogens. Multiple pharmacologic interventions are available, as well as supportive measures including oxygen therapy and hydration. Preventive measures are utilized to decrease the incidence of further infection.

Aged↗
PubMed1995

Carbapenem antibiotic production in Erwinia carotovora is regulated by CarR, a homologue of the LuxR transcriptional activator.

Strain GS101 of Erwinia carotovora makes the carbapenem antibiotic, 1-carbapen-2-em-3-carboxylic acid. Mutants defective in antibiotic production can be assigned to two groups, group 1 and group 2. Group 2 mutants are defective in the carl gene encoding a protein responsible for synthesis of the Lux autoinducer N-(3-oxohexanoyl)-L-homoserine lactone (OHHL), which is required to induce carbapenem synthesis in strain GS101. In this paper we describe the molecular genetic analysis of the group 1 mutants which we presumed were defective in the carbapenem biosynthesis (car) genes. We isolated a cosmid (cWU142) that complemented the group 1 mutants of strain GS101. A small (1.03 kb) subclone of cWU142 complemented most of the group 1 mutants, and the sequence revealed that the relevant gene (carR) encodes a homologue of the Vibrio fischeri LuxR protein. A disproportionately high frequency of carR mutants arose in strain GS101 and this was due to carR acting as a 'hot spot' target for secondary transposition of a Tn5 element in this strain. The CarR protein joins a rapidly growing list of homologues, found in taxonomically unrelated bacteria, which act as positive transcriptional activators of genes encoding diverse metabolic functions, including bioluminescence, exoenzyme virulence factor synthesis, cell division, plasmid conjugation, rhizosphere-specific gene induction, surfactant synthesis and antibiotic production. Most of these LuxR-type regulators have been shown to depend, for their function, on N-acyl homoserine lactones, which act as chemical signals enabling co-ordination of gene expression with cell density.

Amino Acid Sequence↗
PubMed1995

Psychoactive medication use, sensori-motor function and falls in older women.

1. A 1 year prospective study was undertaken to identify possible mediating physiological mechanisms for the association between psychoactive medication use and falls in 414 women aged 65 to 99 years (mean age 73.7 years, s.d. = 6.3) who were randomly selected from the community. 2. Women taking certain psychoactive medications showed impaired performance in a number of sensori-motor measures, including tactile sensitivity, lower limb muscle strength, reaction time and balance control compared with women not taking these medications. Those using psychoactive medications were also comparatively inactive--taking part in only 1.1 h of planned exercise per week compared with 2.6 h for non-users (F = 12.44, df = 1,412, P < 0.01). 3. Multiple logistic regression analysis revealed that use of long-acting benzodiazepines (OR = 7.03, 95% CI = 2.12-23.28) and antidepressants (OR = 2.84, 95% CI = 1.00-8.02) was significantly associated with multiple falls, whilst adjusting for age, other drug category use, frequency of alcohol use, and number of medical conditions. Use of any two psychoactive medications was also significantly associated with falling frequency (Chi-square = 13.91, df = 1, P < 0.01). 4. Path analysis revealed a significant direct association (P < 0.001) between psychoactive medication use and falls, and a significant indirect association mediated via reduced physiological functioning (P < 0.001). Postural hypotension was not significantly associated with falls (RR = 1.37, 95% CI = 0.84-2.22). 5. The findings suggest that psychoactive medication use may predispose older people to falling by impairing important sensori-motor systems that contribute to postural stability.

Accidental Falls↗
PubMed1995

Multiple homologues of LuxR and LuxI control expression of virulence determinants and secondary metabolites through quorum sensing in Pseudomonas aeruginosa PAO1.

In Pseudomonas aeruginosa PAO1, expression of elastase is dependent upon an interaction between the positive transcriptional activator LasR and the auto-inducer molecule N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), the synthesis of which is directed by LasI. Previously we have shown that in PAN067, an elastase-negative mutant of PAO1, elastase production can be restored to some extent by addition of exogenous N-(3-oxohexanoyl)-L-homoserine lactone (OHHL). Here we report that PAN067 is also defective in the production of alkaline protease, haemolysin, cyanide, pyocyanin and autoinducer(s). As neither addition of exogenous OdDHL nor introduction of lasR restored PAN067 to the parental phenotype, we sought to complement PAN067 with PAO1 DNA. From a cosmid library, a 2 kb DNA fragment was identified which re-established production of autoinducer(s) and exoproducts in PAN067. From the nucleotide sequence of this fragment, two genes termed rhIR and rhII were identified. RhII is responsible for autoinducer synthesis and shares 31% homology with LasI; RhIR has been previously identified in P. aeruginosa strain DSM2659 as a regulator of rhamnolipid biosynthesis and shares 28% identity with LasR. These data provide clear evidence that multiple families of quorum-sensing modulons interactively regulate gene expression in P. aeruginosa.

Amino Acid Sequence↗
PubMed1995

Characterisation of the yenI/yenR locus from Yersinia enterocolitica mediating the synthesis of two N-acylhomoserine lactone signal molecules.

Yersinia enterocolitica produces compounds capable of transcriptionally activating the Photobacterium fischeri bioluminescence (lux) operon. Using high-performance liquid chromatography, high resolution tandem mass spectrometry in conjunction with chemical synthesis, two signal molecules were identified and shown to be N-hexanoyl-L-homoserine lactone (HHL) and N-(3-oxohexanoyl)-L-homoserine lactone (OHHL). A gene (yenI) was isolated from Y. enterocolitica and demonstrated to direct the synthesis of both HHL and OHHL. DNA sequence analysis revealed an open reading frame (ORF) of 642 bp encoding a protein (YenI) of 24.6 kDa with approximately 20% identity to the LuxI family of proteins. Northern blot analysis of yenI expression indicated yenI is transcribed as a single gene and 5' transcript mapping of yenI identified a transcriptional start site 89 bp upstream of the ORF. DNA sequence analysis of the region downstream of yenI located a second ORF, termed yenR, with significant homology to the LuxR family of transcriptional activators. An insertion mutation of yenI abolishes HHL and OHHL production, indicating its central role in N-acylhomoserine lactone synthesis in Y. enterocolitica. Transcriptional analysis using a chromosomal yenI::luxAB fusion has demonstrated that yenI is not subject to autoinduction but is expressed constitutively. Whilst production of the Yop proteins in the wild type and in yenI mutants is indistinguishable, two-dimensional SDS-PAGE analysis of total cell proteins indicated that a number of proteins lack the yenI mutant.

4-Butyrolactone↗
PubMed1995

The bacterial 'enigma': cracking the code of cell-cell communication.

In recent years it has become clear that the production of N-acyl homoserine lactones (N-AHLs) is widespread in Gram-negative bacteria. These molecules act as diffusible chemical communication signals (bacterial pheromones) which regulate diverse physiological processes including bioluminescence, antibiotic production, plasmid conjugal transfer and synthesis of exoenzyme virulence factors in plant and animal pathogens. The paradigm for N-AHL production is in the bioluminescence (lux) phenotype of Photobacterium fischeri (formerly classified as Vibrio fischeri) where the signalling molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) is synthesized by the action of the LuxI protein. OHHL is thought to bind to the LuxR protein, allowing it to act as a positive transcriptional activator in an autoinduction process that physiologically couples cell density (and growth phase) to the expression of the bioluminescence genes. Based on the growing information on LuxI and LuxR homologues in other N-AHL-producing bacterial species such as Erwinia carotovora, Pseudomonas aeruginosa, Yersinia enterocolitica, Agrobacterium tumefaciens and Rhizobium leguminosarum, it seems that analogues of the P. fischeri lux autoinducer sensing system are widely distributed in bacteria. The general physiological function of these simple chemical signalling systems appears to be the modulation of discrete and diverse metabolic processes in concert with cell density. In an evolutionary sense, the elaboration and action of these bacterial pheromones can be viewed as an example of multicellularity in prokaryotic populations.

4-Butyrolactone↗
PubMed1995

Comparison of relaxation responses of detrusor strips from neuropathic and control patients.

OBJECTIVES: To confirm the existence of relaxation responses to electrical-field stimulation in strips of human detrusor, and to compare these responses in strips from control subjects with those in strips from a group of neuropathic patients exhibiting hyperreflexia. PATIENTS AND METHODS: Detrusor specimens were obtained at operation from a group of control patients, and from a group of patients with neuropathy (mainly spina bifida) and a history of hyper-reflexia. Muscle strips were prepared from these, mounted in organ baths, and contracted by exposure to a modified Krebs' solution containing 26 mM KCl and atropine. Relaxation responses were induced by an electrical-field stimulation (50 V, 90 microsecond pulses at 2-16 Hz for 10 s). RESULTS: Of 29 strips, 20 (69%) from control patients showed relaxations, compared with 17 of 28 strips (61%) from neuropathic patients (P > 0.1). The maximum relaxation response in the control strips was 49 +/- 5.6% (mean +/- SEM) of the maximum relaxation induced by isobutyl methylxanthine, compared with 43 +/- 4.8% in the strips from neuropathic patients (P > 0.1). The maximum response occurred at similar frequencies (4 or 8 Hz) in the two groups. The relaxations were reduced by the inhibitor of nitric oxide synthase, N-nitro L-arginine methyl ester (0.1 mM, P < 0.05), but were not affected by guanethidine (50 microM) or tetrodotoxin (0.5 microM). CONCLUSION: These results confirm the existence of field stimulation-induced relaxation in human detrusor, but suggest that hyper-reflexia in the neuropathic bladder cannot be accounted for by any deficiency in this response.

1-Methyl-3-isobutylxanthine↗
PubMed1995

The effect of a 12-month exercise trial on balance, strength, and falls in older women: a randomized controlled trial.

OBJECTIVE: To determine whether a 12-month program of regular exercise can improve balance, reaction time, neuromuscular control, and muscle strength and reduce the rate of falling in older women. DESIGN: A randomized, controlled trial of 12 months duration. SETTING: Conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia. PARTICIPANTS: One hundred ninety-seven women aged 60 to 85 years (mean age 71.6, SD = 5.4) who were randomly recruited from the community. OUTCOME MEASURES: Accidental falls, postural sway, reaction time, neuromuscular control, and lower limb muscle strength. MAIN RESULTS: Exercise and control subjects were tested before, midway through, and at the end of the trial. At initial testing, exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors. The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 (range 26-82). At the end of the trial, the exercise subjects showed improved performance in all five strength measures, in reaction time, neuromuscular control, body sway on a firm surface with the eyes open, and body sway on a compliant surface with the eyes open and closed. In contrast, there were no significant improvements in any of the test measures in the controls. In one test measure, hip flexion strength, the exercisers showed continued improvement throughout the study year. There was no significant difference in the proportion of fallers between the exercise and control subjects. Interesting trends were evident, however, between falls frequency and adherence to the exercise program. CONCLUSIONS: These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons. The findings also suggest that high compliance to an exercise program may reduce falls frequency, although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls.

Accidental Falls↗
PubMed1995

Do we have optimal screening limits in Sweden for vision testing at the age of 4 years?

The purpose of this study was to evaluate the Swedish screening criteria for referral of children to ophthalmic care after visual acuity testing at the age of 4 years. The screening limit has generally been 0.8. To what extent do children with 0.65 in each eye (0.65/0.65) or 0.65 in one and 0.8 in the other (0.65/0.8) at the age of 4 years have visual defects needing early treatment? Sixty-three children who had failed screening underwent orthoptic and ophthalmologic evaluation. Twenty-four patients (38%) saw 0.65/0.65 or 0.65/0.8 and were studied further. None of them had manifest strabismus. Refractive errors were minor except in 2 patients who had significant hyperopia. Twenty-two of these 24 patients returned for reevaluation at the age of five years and that time 18 of them saw 0.8 or more without treatment. Our findings suggest that children with visual acuity of no less than 0.65 and no more than one line's difference between the eyes at 4 years of age seldom have visual defects needing treatment.

Child, Preschool↗