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Biomedical subjects

P D Davies

Publications and source records attributed to P D Davies.

At least 19 recordsLinked to original sources
PubMed2001

Drug-resistant tuberculosis: concluding remarks.

This paper summarizes the presentations of the meeting on drug-resistant tuberculosis held in London in March of 2001. Multidrug-resistant tuberculosis (MDR TB) is defined and the causes, risk factors, and recent treatment advances are briefly described. The larger social and economic environment in which MDR TB occurs is discussed.

Humans↗
PubMed2001

A case-control study of lifestyle risk factors associated with tuberculosis in Liverpool, North-West England.

The aim of this study was to identify the subtle influences of exposure and individual lifestyles on the risk of developing tuberculosis. A retrospective case-control study (with matching by sex, age, postcode and ethnicity) of all tuberculosis cases notified over a 7-yr period in Liverpool, UK, was carried out. Multiple logistic regression showed that, before diagnosis, cases were 7.4 times more likely to have had visitors from abroad; 4.0 times more likely to have been born abroad; and 3.8 times more likely to have lived with someone with tuberculosis. Subtle socioeconomic factors were also evident with cases 4.0 times less likely to have additional bathrooms. Lifestyle factors emerged with cases 2.3 times more likely to have smoked for at least 30 yrs, 3.8 times less likely to eat dairy products every week and 2.6 times less likely to have had high blood pressure. At interview, these factors were still evident, but cases, unlike controls, had reduced their smoking and alcohol consumption and were less likely to go out of the home or exercise than before their illness. Within individuals, lifestyle consequences of tuberculosis lead to a "healthier" lifestyle on the one hand (less smoking and alcohol consumption), but a reduced quality of life (social activity) on the other.

Case-Control Studies↗
PubMed2001

FGF: an autocrine regulator of human lens cell growth independent of added stimuli.

PURPOSE: Posterior capsule opacification (PCO) arises because of a persistent growth of lens epithelial cells. Cultured human lens cells residing on their native collagen capsule and maintained in serum-free medium actively grow and thus show an intrinsic capacity for regulation. In the present study, the authors investigated the role of the putative FGF autocrine system in human capsular bags. METHODS: Capsular bags were prepared from human donor eyes and maintained in a 5% CO(2) atmosphere at 35 degrees C. On-going observations were by phase-contrast microscopy. Cellular architecture was examined by fluorescence cytochemistry. De novo protein synthesis was determined by the incorporation of 35S-methionine. Basic fibroblast growth factor (FGF) and FGF receptor (R)-1 were detected using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) techniques. FGFR-1 inhibition was achieved using the specific antagonist SU5402. RESULTS: Human lens epithelial cells can maintain metabolic activity for more than 1 year in a protein-free medium. Basic FGF was shown to be present in capsular bags throughout culture and also in capsular bags removed from donor eyes that had previously undergone cataract surgery. Furthermore, FGFR-1 was identified. Inhibition of FGFR-1 caused a significant retardation of growth on the posterior capsule. On no occasion did any treated bag reach confluence, whereas all match-paired control samples did. CONCLUSIONS: The results provide evidence that FGF plays an integral role in the long-term survival and growth of human lens epithelial cells, independent of external stimuli. Inhibition of FGFR-1 by specific synthetic molecules, such as SU5402, could provide a potential therapeutic approach to resolving PCO.

Autocrine Communication↗
PubMed2001

Comparison of international guidelines on the control and prevention of tuberculosis.

Within the last two yrs a number of countries and organisations have published guidelines on the control of tuberculosis. Though all guidelines have the same principals of disease control, namely the identification and treatment of patients with disease, the screening of individuals at high risk and the giving of preventive therapy to selected individuals with latent tuberculosis infection and the protection of the remainder of the population, they differ in the detail of how this may best be achieved. This article attempts to compare the differences and find the way through to the best practice.

Global Health↗
PubMed2001

Capture recapture as a method of determining the completeness of tuberculosis notifications.

Notification of tuberculosis cases is often incomplete but combining data from several sources can provide a more accurate estimate of the number of cases. Data for the city of Liverpool were collected over an eight-year period from three sources: notifications, microbiological records and in-patient discharge coding data. Capture-recapture (CR) techniques were used to estimate the total number (including unreported cases) of tuberculosis cases in the city. By creating a log-linear model from the pattern of case replication between data sets, a model of best fit was created from which the number of cases present in the population, but not identified in any of the data sets, was estimated. False positive diagnoses were found in 67/516 (13%) of notifications and in 65/241 (27%) of in-patient codings. After excluding these, the total combined number of cases from all data sources was 473. CR methods identified only twelve extra cases (2.5%) making the estimated number of true cases total 485. Of these, in-patient codings identified 36.3%, microbiological records 56.3% and notifications 92.6%. It was concluded that notification of tuberculosis is very complete in Liverpool. Capture-recapture methods can be used to assess completeness of notification data in other settings.

Adolescent↗
PubMed2000

Mycobacterial culture results of smear-positive patients with suspected pulmonary tuberculosis in Liverpool.

The aim of this study was to assess the final mycobacterial culture results of patients with smear-positive sputum or bronchial washings and to investigate the efficiency of local tuberculosis (TB) contact-tracing. Retrospective analysis of mycobacterial cultures and contact-tracing was performed in every patient with smear-positive sputum or bronchoalveolar lavage (BAL) in two Liverpool teaching hospitals (1996-1998). Of these patients 116 with smear-positive sputum or BAL were identified. Mycobacterium tuberculosis (M. tuberculosis) was cultured in 57 (49%), environmental mycobacteria in 37 (32%) and cultures were negative in 22 (19%) of the patients. Contact-tracing information was available in 107 of the 116 (92%) patients. A total number of 1,357 contacts were screened for possible tuberculosis. Of these, 420 (31%) were contacts of patients who cultured environmental organisms or had negative cultures. In this study, 51% of smear-positive patients in Liverpool did not have tuberculosis. Inefficiencies in current contact-tracing procedures have been identified which result from screening contacts of index cases that are subsequently found not to have cultured Mycobacterium tuberculosis. The authors believe that there are clear grounds for using rapid tests to identify and type mycobacteria more quickly than current solid or liquid media methods. It is also suggested that regional variations in the frequency of infection with environmental mycobacteria should be considered when formulating tuberculosis contact-tracing procedures.

Adolescent↗
PubMed2000

Tuberculosis: the global epidemic.

The modern era of tuberculosis(TB) began in the mid 1980s. In 1993, WHO took the unique step of declaring TB to be a world emergency. Despite this intervention it is estimated that deaths from TB will increase from 3 million a year currently to 5 million by the year 2050. There are 4 principal reasons: World population's increase, co-infection with HIV/AIDS, poverty and programme decline. Other causes contributing to the global epidemic are multidrug resistant TB, immigration, and indifference. The practical solution must concentrate on the completed correct treatment of the disease particularly in those who are sputum smear positive. For this reason WHO is vigorously promoting the Directly Observed Therapy Short course (DOTS) campaign. Doctors treating TB should ideally be part of the public health system. They should have access to first class bacteriological services, good quality of drugs and should make sure that the patient receives the drugs under supervision. Though the reasons for increasing TB are multifactorial it is within the capability of the world to re-exert control providing that the political will is present.

AIDS-Related Opportunistic Infections↗
PubMed1999

Oropharyngeal gram-negative bacillary carriage in chronic obstructive pulmonary disease: relation to severity of disease.

The prolonged presence of aerobic Gram-negative bacilli (AGNB) in the oropharynx is termed 'carriage'. AGNB carriage rates are low in populations of healthy individuals. Previously, severity of underlying disease has been positively correlated with oropharyngeal AGNB carriage rate. Overgrowth of AGNB at the oropharynx poses a significant risk of endogenous infection in end-stage chronic obstructive pulmonary disease (COPD) patients. The aims of this study were to undertake an epidemiological survey of the oropharyngeal flora of COPD patients and to correlate oropharyngeal carriage of AGNB with severity of disease. Two oral rinses were obtained, within a 2-day interval, from 40 COPD patients comprising three disease severity groups: 1. mild, 2. moderate and 3. severe. Eighty oral rinses were quantitatively (1:10 dilution series) cultured for AGNB and yeasts using broth enrichment. The mean AGNB carriage rate was 15%. AGNB carriage rates of 0, 7.7 and 29.4% were observed within the mild, moderate and severe disease groups, respectively. The mean yeast carriage rate was 33.3%. Yeast carriage rates of 33.3, 15.4 and 64.7% were observed within the mild, moderate and severe disease groups, respectively. Carriage of Staphylococcus aureus was 5%. Rates of oropharyngeal carriage of AGNB (1/23 vs. 5/17) and yeasts (5/23 vs. 11/17) were significantly higher within the severe disease group than in non-severe disease groups. Oropharyngeal carriage of AGNB in end-stage COPD patients (forced expiratory volume in 1 sec, FEV1 < 50% predicted) presents a potential source of Gram-negative endogenous pneumonia. This outcome may be promoted by intubation and some flora-suppressing antibiotic therapies.

Adult↗
PubMed1999

Comparative bioavailability of three different preparations of rifampicin.

OBJECTIVE: To study the relative bioavailabilities of two generic rifampicin preparations with Rimactane. METHOD: Each of nineteen healthy volunteers received a single oral dose of 600 mg of rifampicin in an open cross-over randomised three-way single-dose design with a washout period of 7 days between each doses. Plasma concentrations of rifampicin were determined by HPLC. In vitro dissolution profiles of the same drugs were determined and compared with human bioavailability study results. RESULTS: No statistically significant difference was found in main bioavailability parameters between Rimactane and generic preparations studied. Both generic preparations also fulfilled the bioequivalence criteria based on the 90% confidence intervals. There was a good correlation between in vivo and in vitro results: faster dissolution time corresponded to the lower Tmax value; lower percentage of released compound to the lower AUC value. Significant intersubject variations were found in main bioavailability parameters; significant negative correlation was found between average AUC values and body weight of the volunteer. CONCLUSION: All three products were bioequivalent. Our results also suggest the suitability of one-compartmental model with lag time, first order input and first order output to describe the kinetics of rifampicin.

Administration, Oral↗
PubMed1999

Social factors associated with increases in tuberculosis notifications.

This study assessed the contribution of immigration and deprivation to the changes in tuberculosis notifications in Liverpool over the last 20 yrs. Ethnic origin was retrospectively assigned to all named cases from 1974 to 1995. Average tuberculosis rates were calculated for the 33 council wards in Liverpool for 1981-1985 and 1991-1995. Multiple regression was used to determine the independent effects of socioeconomic and population measures from the 1981 and 1991 censuses in explaining these ward-based rates. Since 1974, there has been a steady increase in the percentage of non-Caucasian cases of tuberculosis, from 8.7% in 1975-1977, 15.1% in 1981-1983, 17.5% in 1987-1989 to 28.0% in 1993-1995. Multiple regression analysis showed that in 1981 only unemployment had a significant independent relationship with tuberculosis rates, but in 1991 two indices of deprivation and ethnicity had a significant influence. The increasing proportion of non-Caucasian tuberculosis cases, both while the number of notifications was declining before 1987 and increasing afterwards, is not necessarily consistent with the concept that immigration has influenced the recent increase. However, the fact that ethnicity now independently explains some of the council ward variations but did not in the early 1980s suggests that immigration does influence the distribution of disease within the city.

Adolescent↗
PubMed1999

Oropharyngeal Gram-negative bacillary carriage: a survey of 120 healthy individuals.

BACKGROUND: The presence of aerobic Gram-negative bacilli (AGNB) in the oropharynx can be either temporary or persistent. Prolonged colonization (ie, carriage) is distinguished from transient presence (ie, acquisition), which often occurs in healthy individuals but less frequently in those with underlying disease. Prevalence rates of up to 61.1% quoted previously for healthy individuals were obtained by using single sample surveys, which fail to differentiate acquisition from carriage. STUDY OBJECTIVES: To illustrate the need to distinguish carriage from acquisition in a healthy population at risk of acquisition of AGNB, and to show that although differing groups of healthy individuals may acquire oropharyngeal AGNB at differing frequencies, carriage is rare in healthy individuals. PARTICIPANTS: Two oral rinses were obtained within a 2-day interval from 120 healthy individuals comprising 40 nurses, 40 students, and 40 laboratory-associated persons. DESIGN: Two hundred forty oral rinses were quantitatively (1:10 dilution series) cultured for AGNB by using broth enrichment. MEASUREMENTS AND RESULTS: The rate of AGNB carriage based on two consecutive samples positive for the same AGNB was 6.6%; the rate of AGNB acquisition based on one positive sample was 35.8%. The concentrations of all carried and acquired AGNB were < or = 103 cfu/mL. AGNB acquisition was significantly higher in students (52.5%) compared to nurses (32.5%) and laboratory-associated persons (22.5%; p < 0.05). CONCLUSION: Healthy individuals rarely carry oropharyngeal AGNB, suggesting effective oropharyngeal clearance in a healthy population predisposed to acquisition. Apparently, the oropharyngeal mucosa in healthy individuals is not receptive to adhesins of AGNB, resulting in rapid elimination of these bacteria.

Adolescent↗