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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 199 records · Page 11Linked to original sources
PubMed1998

Anticarcinogenic responses in rodent cancer bioassays are not explained by random effects.

Anticarcinogenicity in a long-term rodent bioassay is defined as a statistically significant decrease of a specific tumor type in a dosed group following chemical exposure. About 92% of chemicals tested by the National Toxicology Program prior to 1983 reveal at least one site with a significant (p < or = 0.05) tumor rate decrease in one or more tested groups, a result consistent with those of J. K. Haseman and F. M. Johnson (1996, Mutat. Res. 350, 131-141) for a database of recently tested chemicals. Detection of tumor decreases in a specific site can be explained not only by biological effects, but also as a result of random variability in the background tumor rates, decreases in body weight, or decreases in survival of treated animals. This paper evaluates the rate of false-positive anticarcinogenic findings due to random effects (variations in tumor rates and the multiple comparisons undertaken in evaluating a bioassay), while a companion paper addresses the influence of weight and survival depression. Monte-Carlo simulation was conducted to assess the contribution of random effects. This contribution was found to be important even when a statistical significance cutoff of p0 < or = 0.05 was chosen. If a more stringent statistical criterion was used (p0 < or = 0.01 or p < or = 0.005), the proportion of false positive determinations diminishes. The number of anticarcinogens in the database remains substantially higher than predicted by the stimulations. An examination of the distribution of all p values (T. Schweder and E. Spjøtvoll, 1982, Biometrika 69, 493-502) also indicates that statistically significant anticarcinogenic responses are found in the database at a higher rate than would result from purely random responses. Finally, the cross-species prediction of anticarcinogenic responses was examined in a manner similar to a study of cross-species prediction of carcinogenic responses (G. M. Gray et al., 1995, Reg. Toxicol. Pharmacol. 20, 281-301). The analyses show that anticarcinogenic effects in one rodent species predict well anticarcinogenic effect in another rodent species. It seems likely that biological factors are involved in anticarcinogenic responses observed in rodent cancer bioassays.

Animals↗
PubMed1998

Erythrocyte glutathione balance and membrane stability during preeclampsia.

This study aimed to determine whether oxidative damage to the erythrocyte occurs in preeclampsia, and relates to disease severity. The oxidative status of intact erythrocytes from preeclamptic patients and normal pregnant women was determined using spin echo 1H-NMR, which measures both the concentration and redox state of intracellular glutathione. Previous studies of preeclampsia have only measured total glutathione levels. Membrane fragility was determined from the degree of lysis caused by incubation in hypotonic saline. Erythrocytes from moderate-severe preeclamptic patients underwent more lysis than erythrocytes from control pregnant women (p < .05) or mild preeclamptic patients. It is suggested that increased lysis results from oxidative damage to the erythrocyte membrane, causing a decrease in membrane fluidity and reducing its ability to withstand osmotic changes. Intracellular glutathione was more oxidized in erythrocytes from pregnant women compared to nonpregnant controls (p < .05), and there was a less significant trend toward more oxidized glutathione with increasing severity of preeclampsia. The moderate-severe group showed a clear division in glutathione redox status: some patients had very oxidized glutathione while others had a normal redox balance. This novel finding suggests that some patients may be unusually susceptible to erythrocyte glutathione oxidation, possibly leading to general cellular damage, in particular HELLP Syndrome.

Erythrocyte Membrane↗
PubMed1998

The Drosophila protein Dof is specifically required for FGF signaling.

Receptor tyrosine kinases (RTKs) transmit signals to the cell nucleus via the MAP kinase (MAPK) cascade, using specific molecules to link the activated receptors to the MAPK cascade activator, Ras. We have identified a component of the FGF receptor (FGFR) signal transduction pathway, Downstream of FGFR (Dof). Dof is an intracellular protein that is essential for signal transmission by the FGFR and acts downstream of the receptor and upstream of Ras. Unlike other signaling molecules that act downstream of RTKs, Dof is not expressed ubiquitously but is present exclusively in cells that express FGFRs. Dof is needed in these cells for activation of the MAPK cascade via FGF signaling, but not for activation via other RTK ligands. Dof therefore appears to be committed exclusively to FGFR-mediated signal transduction.

Amino Acid Sequence↗
PubMed1998

Paediatric resuscitation--by phone.

OBJECTIVE: To ascertain the training and knowledge of paediatric resuscitation amongst all paediatric residents in New Zealand. METHOD: A validated national telephone survey. RESULTS: Interviews were conducted with 96 out of a possible 109 paediatric residents. Most had been qualified less than 5 years and a third had received some training in paediatric resuscitation in the last year. The initial dose of intravenous adrenaline was known by 61% but only 10% knew the recommended ten-fold increase in subsequent doses. Recognition of the importance of cervical spine management in trauma was poor. Correct resuscitation fluids and volumes were selected by 90%, though infusion rates were frequently too slow. Residents with paediatric qualifications and greater experience scored significantly higher. CONCLUSION: Many junior paediatric staff are inadequately prepared for resuscitating children. We believe improved regular training is required and that the introduction of a nation-wide Advanced Paediatric Life Support course, subsequent to the completion of this survey, will lead to improved standards. Its effectiveness needs to be audited.

Child↗
PubMed1998

A new ambulatory classification and funding model for radiation oncology: non-admitted patients in Victorian hospitals.

The Victorian Department of Human Services has developed a classification and funding model for non-admitted radiation oncology patients. Agencies were previously funded on an historical cost input basis. For 1996-97, payments were made according to the new Non-admitted Radiation Oncology Classification System and include four key components. Fixed grants are based on Weighted Radiation Therapy Services targets for megavoltage courses, planning procedures (dosimetry and simulation) and consultations. The additional throughput pool covers additional Weighted Radiation Therapy Services once targets are reached, with access conditional on the utilisation of a minimum number of megavoltage fields by each hospital. Block grants cover specialised treatments, such as brachytherapy, allied health payments and other support services. Compensation grants were available to bring payments up to the level of the previous year. There is potential to provide incentives to promote best practice in Australia through linking appropriate practice to funding models. Key Australian and international developments should be monitored, including economic evaluation studies, classification and funding models, and the deliberations of the American College of Radiology, the American Society for Therapeutic Radiology and Oncology, the Trans-Tasman Radiation Oncology Group and the Council of Oncology Societies of Australia. National impact on clinical practice guidelines in Australia can be achieved through the Quality of Care and Health Outcomes Committee of the National Health and Medical Research Council.

Abstracting and Indexing↗
PubMed1998

Home health nurses' initial experiences with wireless, pen-based computing.

Eight home health nurses from the Visiting Nurse Service of New York participated in a focus group discussion after their initial experiences using wireless, pen-based computing in the inner-city, home care environment. Transcripts of the nurses' responses to open-ended questions were analyzed and central themes were found, following the method of concept analysis described by Strauss and Corbin (1990). The central concepts were "Readiness," "A thousand pounds on my back," "Call for support," "Problems with transmission," "Using the computer as an assistant," "Nurses discovered glitches," and "Everybody has to have a computer." These themes reflected the nurses' initial experiences with the wireless computers and also revealed their concerns. This article will describe these themes and will discuss the implications of current improvements in wireless computing for health care. The focus group themes aided in understanding how this group of experienced home health nurses began to transition from handwriting on several different forms to checking-off items on a small, hand-held computer screen, from innovating methods to communicate when telephones were not available, to using a wireless computer to send and receive data involved in the patient admission process

Attitude of Health Personnel↗
PubMed1998

Effect of dirithromycin on Haemophilus influenzae infection of the respiratory mucosa.

Macrolides have properties other than their antibiotic action which may benefit patients with airway infections. We have investigated the effect of dirithromycin (0.125 to 8.0 microg/ml) on the interaction of Haemophilus influenzae with respiratory mucosa in vitro using human nasal epithelium, adenoid tissue, and bovine trachea. Dirithromycin did not affect the ciliary beat frequency of the nasal epithelium or the transport of mucus on bovine trachea, but dirithromycin (1 microg/ml) did reduce the slowing of the ciliary beat frequency and the damage to the nasal epithelium caused by H. influenzae broth culture filtrate. Amoxicillin (2 microg/ml) did not reduce the effects of the H. influenzae broth culture filtrate. H. influenzae infection of the organ cultures for 24 h caused mucosal damage and the loss of ciliated cells. Bacteria adhered to damaged epithelium and to a lesser extent to mucus and unciliated cells. Incubation of H. influenzae with dirithromycin at sub-MICs (0.125 and 0.5 microg/ml) prior to infection of the organ cultures did not reduce the mucosal damage caused by bacterial infection. By contrast, incubation of adenoid tissue with dirithromycin (0.125 to 1.0 microg/ml) for 4 h prior to assembling the organ culture reduced the mucosal damage caused by subsequent H. influenzae infection by as much as 50%. The number of bacteria adherent to the mucosa was reduced, although the tissue that had been incubated with dirithromycin (0.125 and 0.5 microg/ml) did not inhibit bacterial growth. This was achieved by a reduction in the amount of damaged epithelium to which H. influenzae adhered and a reduction in the density of bacteria adhering to mucus. We conclude that dirithromycin at concentrations achievable in vivo markedly reduces the mucosal damage caused by H. influenzae infection due to a cytoprotective effect.

Amoxicillin↗
PubMed1998

Cells for the study of acidic dissolution in packed apatite powders as model systems for dental caries.

A number of different designs of cells have been developed for the study of dissolution processes in packed apatite powders. Basic design requirements were that no deleterious processes, such as high temperature sintering or binding agents, were involved, and that there was maximum opportunity for experimental study. One design used alternating filter paper discs and apatite layers (typically 42 mg). At the end of an experiment, the cell could be disassembled and infrared spectra and X-ray powder diffraction patterns made of individual layers. Cells without filter paper discs were also made, but terminal sampling at well-defined depths was more difficult or impossible. The cells were constructed from poly(methylmethacrylate) so the course of dissolution could be monitored by radiography. Subsurface loss of apatite was almost always seen after from 2 weeks to 8 months exposure to buffer solutions at pH 3.0-5.5. The greatest loss of apatite was typically 0.4-2 mm below the surface, which is at a larger distance than usually seen for dental enamel. This may be attributable to the low packing density (typically 35-60 vol%) found in the present systems compared with enamel.

Acids↗
PubMed1998

Polyclonal Mycobacterium avium complex infections in patients with nodular bronchiectasis.

Mycobacterium avium complex (MAC) isolates among patients with chronic lung disease were studied for their heterogeneity using genetic identification methods, pulsed field gel electrophoresis (PFGE) and seroagglutination. A mean of 7.3 cultures per patient were collected from 17 patients with nodular bronchiectasis who were elderly (mean age 66 yr), predominantly female (76%), had smoked a mean of only 5 pack-years, and had multifocal bronchiectasis. A mean of 7.7 cultures per patient were collected from nine patients with upper lobe cavitary disease who were younger (mean age 52 yr), predominantly male (78%), and heavy smokers (mean 56 pack-yr). A mean of 2.9 PFGE types (genotypes) per patient (range, 1 to 9) were identified in the nodular bronchiectasis group, with 15 of 17 patients (88%) having two or more genotypes and 9 of 17 (53%) having three or more genotypes. In contrast a mean of 1.2 genotypes were identified in the patients with cavitary disease, with only 1 of 9 (11%) having two or more genotypes. Mycobacterium intracellulare was the most frequently recovered genotype in both groups and most isolates were rough or nontypable by seroagglutination. Some genotypes from the same patient considered different by current PFGE criteria had the same serotype and shared 11 to 20 common PFGE bands, suggesting they were related. These data demonstrate that patients with nodular bronchiectasis have multiple and/or repeated infections due to MAC whereas patients with upper lobe cavitary disease are usually infected with only a single strain.

Adult↗
PubMed1998

Effect of inhibition of nitric oxide synthase on Pseudomonas aeruginosa infection of respiratory mucosa in vitro.

We studied the effect of the nitric oxide synthase (NOS) inhibitor asymmetric dimethyl arginine (ADMA) and the inactive enantiomer N G-methyl-D-arginine (D-NMMA) on Pseudomonas aeruginosa infection of the respiratory mucosa in nasal turbinate organ cultures. We also investigated the effect of P. aeruginosa culture filtrate on the expression of inducible NOS (iNOS) messenger RNA (mRNA) by an epithelial cell line (A549). Organ cultures were preincubated with ADMA (0.1 to 4 x 10(-4) M) or D-NMMA (2 x 10(-4) M) for 30 min prior to bacterial infection. Infected organ cultures (8 h) had significantly (P <= 0.05) greater epithelial damage and fewer ciliated and unciliated cells than did control cultures. There was an increased level of nitrite in the medium feeding infected organ cultures as compared with control cultures. ADMA significantly (P <= 0.05) reduced both bacterially induced epithelial damage and loss of ciliated cells in a concentration-dependent manner. D-NMMA did not influence the effect of P. aeruginosa infection of the mucosa. ADMA, but not D-NMMA, significantly (P <= 0.04) reduced total bacterial numbers adherent to the respiratory mucosa. P. aeruginosa culture filtrates (24 h and 36 h) significantly (P = 0.02) increased iNOS with respect to glyceraldehyde-3-phosphate dehydrogenase mRNA expression. These results show that P. aeruginosa stimulates iNOS expression by a cell line and NO production by an organ culture. ADMA reduces mucosal damage and loss of ciliated cells, which suggests that NO may be a mediator of epithelial damage caused by P. aeruginosa.

Arginine↗
PubMed1998

Effect of salmeterol on Haemophilus influenzae infection of respiratory mucosa in vitro.

Haemophilus influenzae is a common bacterial pathogen causing human respiratory tract infections. We have previously shown that the beta2-agonist salmeterol reduces damage to the respiratory mucosa caused by Pseudomonas aeruginosa in vitro. We have now investigated the effect of salmeterol on H. influenzae infection of adenoid tissue in an organ culture by scanning electron microscopy. Tissue was preincubated with or without salmeterol (4x10(-7)M), prior to infection with H. influenzae and incubated for 12 or 24 h. Infected organ cultures had increased epithelial damage and decreased numbers of both ciliated and unciliated cells at 12h, which were significantly different (p < or = 0.01) from the controls at 24 h. Salmeterol (4x10(-7)M) significantly (p < or = 0.03) reduced damage and loss of ciliated cells in infected organ cultures at both 12 and 24, and significantly (p < or = 0.03) reduced loss of unciliated cells at 24 h. Salmeterol had no effect on the density of bacteria adhering to each individual mucosal feature or the total number of bacteria adhering to the organ culture. These results suggest that salmeterol protects the respiratory epithelium against Haemophilus influenzae-induced damage. The mechanism of salmeterol cytoprotection and its potential clinical relevance remain to be investigated.

Adenoids↗
PubMed1998

Systemic markers of inflammation in stable bronchiectasis.

Patients with bronchiectasis have an active local and systemic inflammatory response during infective exacerbations. Systemic markers of inflammation were investigated during a stable phase of their illness, because continued inflammation could affect their general health and be involved in disease progression. The relationship between levels of various systemic markers of inflammation and extent of disease on computed tomographic scan, lung function, sputum bacteriology and health related quality of life (HRQoL) was investigated in 87 noncystic fibrosis bronchiectasis patients. Several markers were elevated and correlated with the extent of disease and poor lung function. The total white cell count, neutrophil count and erythrocyte sedimentation rate correlated with both disease measures. Sputum bacteriology did not correlate with inflammation markers and patients with positive and negative cultures were similar. C-reactive protein and total white cell count correlated with some components of a disease-specific HRQoL questionnaire. In conclusion, patients with bronchiectasis in a stable phase have raised systemic markers of inflammation. Some markers, particularly the neutrophil count, correlate with disease severity. This result is in keeping with the hypothesis that the level of inflammation determines disease progression and health status.

Adult↗
PubMed1998

Primary ciliary dyskinesia: diagnosis and standards of care.

Primary ciliary dyskinesia (PCD) is characterized by disease of the upper and lower respiratory tract, in association with visceral mirror image arrangement in 50% of cases, due to abnormal structure and/or function of cilia. The purpose of this paper is to review the clinical features, diagnosis and management of PCD. Presentations include neonatal respiratory distress, recurrent lower respiratory tract infection, chronic rhinosinusitis and male infertility. PCD enters the differential diagnosis of bronchiectasis, atypical asthma, and unusually severe upper airway disease. Diagnosis is by a cascade of investigations, starting with the saccharin test in patients older than 10 yrs; ciliary beat frequency and pattern on light microscopy; and electron microscopy to assess ciliary morphology and orientation. It is important not to confuse primary and secondary ciliary abnormalities. Nasal nitric oxide is low in PCD, and this measurement shows promise as a screening test for PCD. Diagnosis is important, in order to prevent the development of bronchiectasis and to avoid any unnecessary otorhinolaryngological procedures. Regular follow-up is essential, and management should be multidisciplinary, with input from centres with a special interest in PCD, having access to paediatric and adult chest physicians, otolaryngologists and audiological physicians, physiotherapists, counselling services and fertility clinics. The prognosis is good, but morbidity can be considerable if PCD is incorrectly managed.

Adult↗
PubMed1998

The role of infection in COPD.

Clinical studies of acute exacerbations of COPD are difficult because of the heterogeneous nature of COPD, diffuse symptoms that can vary spontaneously, and difficulties in defining clinical response both in the short and long term. The role of bacterial infection, and thus use of antibiotics, in COPD is controversial. The available evidence shows that bacterial infection has a significant role in acute exacerbations, but its role in disease progression is less certain. Upper respiratory tract commensals, such as nontypable Haemophilus influenzae, cause most bronchial infections by exploiting deficiencies in the host defenses. Some COPD patients are chronically colonized by bacteria between exacerbations, which represents an equilibrium in which the numbers of bacteria are contained by the host defenses but not eliminated. When an exacerbation occurs, this equilibrium is upset and bacterial numbers increase, which incites an inflammatory response. Neutrophil products can further impair the mucosal defenses, favoring the bacteria, but if the infection is overcome, symptoms resolve. However, if the infection persists, chronic inflammation may cause lung damage. About half of exacerbations involve bacterial infection, but these patients are not easy to differentiate from those who are uninfected, which means that antibiotics have to be given more often than is strictly necessary. Further research is needed to characterize those patients in whom bacterial infection has a more important role.

Anti-Bacterial Agents↗
PubMed1998

Evidence for carbimazole as an antioxidant?

There is evidence in the literature to support the view that antioxidants are involved in the pathogenesis of Graves disease and that antioxidants may act as free radical scavengers. This study has compared the effects of a 12 month course of conventional Carbimazole therapy on peripheral blood antioxidant levels with those of a 12 month course of a higher dose treatment regime. Fifty seven patients were enrolled into the study. Those in Group 1 (n = 23) received a 12 month course of 60 mg/day Carbimazole. Those in Group 2 (n = 34) received 45 mg/day for the first month, 30 mg/day for the second and 20 mg/day for the remaining 10 months of treatment. T3 was added in both groups after 2-4 months to maintain patients euthyroid. Baseline samples were also obtained from 30 control subjects. Blood samples were taken for the measurement of plasma thiol (PSH), lysate thiol (LSH), superoxide dismutase (SOD) and caeruloplasmin (CP) and for routine thyroid function tests (TT4, TT3 and TSH). In untreated Graves' patients, serum levels of PSH and SOD were reduced and levels of LSH increased compared to controls. Following 2 months high dose Carbimazole therapy there was a significant increase in PSH levels and a significant reduction in CP levels compared to presentation levels. In the more conventional dose Group 2 patients PSH levels also rose significantly during the first 2 months of treatment. Levels for both groups were still significantly lower than the control group. After 12 months high dose Carbimazole therapy PSH levels had decreased so that they no longer differed from untreated levels. LSH and SOD levels still remained abnormal. CP levels continued to fall. Similar findings were obtained in those patients receiving the more conventional course of treatment. At no point was their any significant difference in antioxidant levels between the two treatment groups. The abnormal levels of antioxidants in the serum of untreated Graves' patients confirm their involvement in the pathogenesis of Graves' disease. Carbimazole therapy appeared to have only short term effects on the peripheral blood levels of the antioxidants measured. Carbimazole appeared to act only on the extra cellular markers of antioxidant activity (PSH, CP) although the disease itself had marked intracellular effects (LSH, SOD). These findings suggest that Carbimazole does not act as a free radical scavenger.

Adult↗