Pleural tuberculosis.

Pleural effusions in tuberculosis are commonly seen in young adults as an immunological phenomenon occurring soon after primary infection. However, the epidemiology and demographics of tuberculous pleurisy are changing due to the impact of HIV co-infection and the increasing number of pleural effusions seen as part of re-activation disease. Pleural biopsy for histology and culture is the mainstay of diagnosis with closed needle biopsy adequate in the majority of cases. Techniques such as PCR of biopsy specimens and the role of pleural fluid ADA are still being evaluated as a diagnostic aid. Tuberculous empyema is less commonly seen in the western world and the diagnostic yield from pleural fluid here is greater than in "primary" effusions. Treatment with appropriate antituberculous chemotherapy is generally successful though there is currently insufficient evidence to recommend the routine use of corticosteroids in this condition.

Smoking and tuberculosis: the epidemiological association and immunopathogenesis.

There is increasing evidence of a link between tuberculosis and smoking. This paper reviews the epidemiological evidence from the UK, China, India and the USA, summarizing some of the main papers which indicate an association. Where an association has been found there seems to be an increase in tuberculosis case rates of between two- and four-fold for those smoking in excess of 20 cigarettes a day, but it may be difficult to control for other factors, particularly alcohol consumption. The final part of the paper reviews possible mechanisms. A likely possibility is that nicotine turns off the production of TNF-alpha by the macrophages in the lungs, rendering the patient more susceptible to the development of progressive disease from latent Mycobacterium tuberculosis infection.

Elevated mortality following diagnosis with a treatable disease: tuberculosis.

OBJECTIVE: To determine whether previous diagnosis with tuberculosis (TB) increases the risk of mortality. DESIGN: A retrospective survey of 439 TB patients in the city of Liverpool, population 439500, over an 8-year period. OUTCOMES: Mortality compared with the general population; cause of death as identified from death certificates. RESULTS: A total of 104 (23.7%) TB cases had died within the follow-up period. For 45-54 year olds, the standardised mortality ratio (SMR) was 1101, an 11-fold higher mortality than expected from the Liverpool population. The SMR then declined with age, but remained higher in males than in females. Death certificates showed that 34 (30.8%) died from TB and 26 (21%) from bronchopneumonia. Malignancy was the cause of death in 24 cases (28%), including 16 with lung tumours, all in patients aged under 75 years. This gave a 30-fold greater mortality from lung cancer compared with the general population aged under 75. CONCLUSIONS: TB increases the risk of mortality compared with the general population, with unexpectedly high mortality from lung cancer in cases aged under 75. Older patients die from TB itself or other chest diseases. Common risk factors for the Liverpool population probably contribute to elevated mortality from all chest-related diseases, including TB.

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.

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.

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.

Thapsigargin-coated intraocular lenses inhibit human lens cell growth.

Cataract is responsible for rendering several million people blind throughout the world and is also by far the most common cause of low visual acuity. Although cataract surgery is common, routine and effective, posterior capsule opacification (PCO) occurs in 30-50% of patients following modern cataract surgery. This condition arises from stimulated cell growth within the capsular bag after surgery. The resulting decline in visual acuity requires expensive laser treatment, and PCO therefore prevents modern cataract surgery from being carried out routinely in underdeveloped countries. The present study, using a human lens capsular bag culture system, has confirmed that cells from a wide age range of donors proliferate in the absence of added serum protein and explains why PCO is such a common problem even in aged patients. This study also provides one possible solution for PCO by using polymethylmethacrylate (PMMA) implanted intraocular lenses as a drug delivery system. PMMA lenses coated with thapsigargin, a hydrophobic inhibitor of endoplasmic reticulum (ER) (Ca2+)-ATPase, greatly reduced cell growth in the capsular bag at relatively low coating concentrations (200 nM) but, more significantly, induced total cell death of the residual anterior epithelial cells at higher concentrations (>2 microM).

Phacoemulsification versus extracapsular cataract extraction: a comparative study of cell survival and growth on the human capsular bag in vitro.

AIMS/BACKGROUND: Phacoemulsification is rapidly replacing conventional extracapsular cataract extraction (ECCE) as the method of choice for cataract surgery in the Western world. However, posterior capsule opacification (PCO) still remains the major postoperative complication, affecting 20-50% of patients, and results from persistent cell growth of epithelial cells remaining after surgery. This study aimed to compare cell survival and growth on capsular bags following ECCE and phacoemulsification surgery using an established human capsular bag culture system. METHODS: Sham ECCE and phacoemulsification cataract operations were performed on pairs of human donor eyes. Capsular bags were dissected free, pinned flat on a petri dish, and incubated with Eagle's minimum essential medium (EMEM) alone or EMEM supplemented with 10% fetal calf serum (FCS). Ongoing observations were made using phase contrast microscopy. RESULTS: Cell growth was observed across the posterior capsule of all preparations studied. It was found that there was no significant difference in the rate of cell growth on the posterior capsule with the two extraction methods, such that 50% confluency was achieved in 7.0 (SD 1.8) (n = 7) days for ECCE and 7.43 (2.1) (n = 7) days for phacoemulsification surgery. The physical changes to the capsule as a result of cell growth, such as wrinkling and capsular tensioning, were also seen in both groups. CONCLUSIONS: Cell survival and growth is dependent on the donor, rather than the surgical technique performed. There is no significant difference between phacoemulsification and ECCE surgery on the rate and nature of cell growth on the posterior capsule in vitro.

A study of human lens cell growth in vitro. A model for posterior capsule opacification.

PURPOSE: After intraocular lens (IOL) implant surgery for cataract, cell growth on the posterior capsule is responsible for renewed visual impairment in approximately 30% of patients. The authors have, therefore, developed a human lens capsule system to study this growth in vitro. METHODS: Sham cataract surgery, including anterior capsulorhexis, nucleus hydroexpression, and aspiration of lens fibers, was performed on donor eyes. In some cases, a polymethylmethacrylate IOL implant was placed in the capsular bag. The capsular bag was dissected free, pinned flat on a plastic culture dish, covered with Eagle's minimum essential medium supplemented with 10% fetal calf serum and observed by phase-contrast and dark-field microscopy for as long as 100 days. At the end-point, capsules were examined by fluorescence microscopy for actin, vimentin, and chromatin. RESULTS: Within 24 hours, there was evidence of cell growth in the equatorial region. After 2 to 3 days, cells were normally observed growing from the rhexis onto the posterior capsule and across the anterior surface of the IOL, if present. Growth proceeded rapidly so that the posterior capsule, for example, was totally covered by a confluent monolayer of cells at 5.8 +/- 0.6 days and 7.2 +/- 0.7 days for capsules aged < 40 years and > 60 years, respectively. Total cover of the anterior IOL surface generally followed 4 to 5 days behind that of the capsule. Capsular wrinkles became increasingly apparent as time progressed, causing a marked rise in light scatter. An increase in capsular tension also occurred, and the actin filaments became more polarized near the wrinkles. CONCLUSIONS: The model presented here for posterior capsule opacification shows many of the changes seen in vivo, including rapid lens cell growth, wrinkling, tensioning, and light scatter in the posterior capsule. It will be possible to develop strategies for inhibiting cell growth with this system.

Tuberculosis among elderly Chinese in residential homes: tuberculin reactivity and estimated prevalence.

Objectives of this study were to determine the prevalence of positive tuberculin reactivity and associated factors among elderly nursing home residents in a population with a relatively high tuberculosis notification rate, to estimate the prevalence of active tuberculosis, and to assess tuberculin reactivity as a screening tool. A stratified, disproportional, randomized cluster sample of residents was selected and the Mantoux test (using 0.1 ml of 5 tuberculin units of purified protein derivative of tuberculin) carried out. All subjects with a positive test had a chest X-ray followed by sputum smear and culture if the X-ray was abnormal. Sputum examination was also carried out in a random sample of controls, matched for age and gender, drawn from subjects with a negative Mantoux test. Information regarding medical history, tobacco smoking habits, symptoms related to tuberculosis, and communal eating habits were gathered. Also anthropometric data were collected. Sixteen nursing homes in the catchment area of a major district hospital in Hong Kong comprising 587 residents (136 men, 451 women, mean age 80 +/- 8 years) participated in this study. The weighted prevalence of tuberculin reactivity was 43.8%. It was higher in men, among those who took their meals in a common area, in the younger age group, and in those with no previous history of hospitalization. No association was found between prevalence and duration of residence, smoking, skinfold thickness, past medical history, or any relevant symptoms. Following radiological and sputum examination, the estimated prevalence of active tuberculosis ranged from 1.2 to 2.6%. The sensitivity of the tuberculin test was 86, the specificity 30%. The prevalence of active tuberculosis in nursing homes in Hong Kong is high, but it is unclear whether cross-infection or poor health of the residents is the major contributing factor. Tuberculin skin testing does not appear to be a useful screening method in this population.

Tuberculin testing in residential homes for the elderly.

BACKGROUND: Evidence from the United States has shown that tuberculin sensitivity increases with length of stay among residents in homes for the elderly, implying an increasing risk of infection. There is no evidence as to whether or not residents in homes in the United Kingdom have a similar risk. METHODS: A study was undertaken to determine whether residence in a home for the elderly increases the risk of tuberculosis infection. Over a six month period all residents in homes for the elderly in Liverpool received a tuberculin test. A health questionnaire was completed by the field team for each resident. A total of 2665 residents in homes for the elderly were surveyed. RESULTS: Heaf test grade positivity declined with age, the odds ratio being 0.71 for each 10 year period. Adjusting for age, there was no change in Heaf test grade with length of stay in the home. Heaf test positivity was stronger in smokers (odds ratio 1.59) than ex-smokers (odds ratio 1.20) and non-smokers. Heaf test grade positivity was directly related to pack years. Allowing for age and smoking, the odds ratio for men compared with women for a positive test was 1.62 (95% confidence interval 1.32 to 1.99). CONCLUSIONS: Heaf test positivity declines with age. Residence in a home for the elderly is not associated with increased rate of tuberculosis sensitivity. Smoking and male gender is associated with increased Heaf test positivity.

Attitudes to smoking and smoking habits among hospital staff.

BACKGROUND: Health professionals should take an active role against smoking, so it is relevant to have information on their smoking habits and their attitudes towards smoking, especially with a view to identifying and offering help to those smokers who wish to stop. Staff in Llandough Hospital were surveyed to determine their smoking habits and attitudes, and the findings were compared with those of a similar survey at Llandough in 1987. METHODS: In October 1991 a questionnaire was sent to each member of staff employed half time or more requesting data on age, sex, department, smoking habit, attitudes to smoking in various areas of the hospital, and attitudes to access to smoking rest rooms for patients, staff, and visitors. Smokers were asked whether they would like to join a "quit smoking" group. Non-responders were sent a reminder four weeks later and all replies returned by 31 December 1991 were analysed. RESULTS: The response rate was 82%; of the respondents, 65% were non-smokers, 15% ex-smokers, and 20% current smokers. The prevalence of current smokers was 5% among doctors, 20% among nurses, 18% among administrative and clerical staff, and 40-42% among domestics, catering, and portering staff. Thirty eight per cent of responders wished smoking to be completely forbidden in all areas of the hospital and 90% in certain areas such as wards, offices, cafeteria, and laboratories. Nearly half wanted smoking to be allowed in rest rooms and over 60% wanted a 24 hour facility for smoking for staff, 56% for patients, and 44% for visitors. Only 39% of smokers wished to join a "quit smoking" support group. In comparison with the 1987 survey, the response rate in this study was higher (82% v 70%), the proportion of non-smokers had increased (65% v 59%), and more smokers wanted help (39% v 26%). Fewer wanted 24 hour access to smoking areas for staff and for visitors. CONCLUSION: This hospital should capitalise on these changes of attitude among staff and proceed more rapidly with the implementation of policies to further reduce smoking among staff, visitors, and patients. As a first step a smoking cessation counsellor has been appointed.

Screening for tuberculosis: current practices and attitudes of hospital workers.

To examine the current practices and attitudes of health workers to the prevention of tuberculosis in our 55-bed chest unit, we investigated the tuberculin reactor status, reviewed pre-employment screening and reviewed the action taken after contact with tuberculosis by staff members. We assessed all 61 staff members, including 44 nurses, 1 physiotherapist, 11 doctors and 5 domestic workers. 47/61 staff members had had BCG vaccination. Heaf testing revealed 3 Heaf-negative subjects and, of the remainder, 52 had grade 3 or stronger reactions. Only 3/11 doctors, 36/44 nurses and 4/5 domestic workers had had any pre-employment screening. No action was taken by any doctor after their last contact with tuberculosis, whereas 10/44 nurses and 3/5 domestic workers had had chest X-rays. This study shows the low importance with which the risk of tuberculosis is perceived, particularly by doctors and demonstrates the need for stricter supervision and improved quality of pre-employment screening.

Attitudes to smoking and smoking habit among the staff of a hospital.

A survey of the smoking habits and attitudes towards smoking of all staff working in a teaching hospital with a specialist thoracic department has been carried out. Six hundred and sixty three (70%) of the 949 members of staff returned a voluntary self completed questionnaire. Completion rates were highest among medical, administrative, and clerical staff, and lowest among domestic and catering staff. Of the 663 responders, 136 (23%) admitted to being current smokers and 135 (19%) to being ex-smokers. The great majority of responders (81-94%, depending on area of work) believed that more areas of the hospital should be entirely smoking free. Most responders, however, believed that some accommodation should be made available to staff (70%), patients (52%), or visitors (59%) who wished to smoke. About a quarter of smokers expressed interest in joining a group to help them give up smoking.

The effect of anti-tuberculosis chemotherapy on vitamin D and calcium metabolism.

Serum 25-hydroxycholecalciferol (25-(OH)D3), calcium and albumin have been measured in 27 patients undergoing treatment for pulmonary tuberculosis. Patient 25-(OH)D3 was significantly lower than controls pre-treatment. Throughout the period of treatment patient median 25-(OH)D3 remained below 10 ng/ml, significantly lower than levels in matched healthy controls. Patients' median serum levels varied between 35% and 66% of controls' values during treatment, but rapidly rose to equal control values once treatment had been stopped. Patients' serum calcium, corrected for albumin, remained virtually identical with control values throughout treatment. Clinicians should be aware that standard anti-tuberculosis chemotherapy may depress Vitamin D stores and that this may be important for patients who are already at risk from osteomalacia.