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Biomedical subjects

U G Lalloo

Publications and source records attributed to U G Lalloo.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of plain chest radiography and high-resolution CT in human immunodeficiency virus infected patients with community-acquired pneumonia: a sub-Saharan Africa study.

The objective of the study was to determine the proportion of patients with missed lesions on plain chest radiographs compared with high-resolution computed tomography (HRCT) in 49 human immunodeficiency virus (HIV) infected patients with community-acquired pneumonia (CAP). Patients underwent plain chest radiography and HRCT scans of the chest at admission. Microbiological investigations for CAP were performed. An experienced radiologist, without knowledge of clinical or pathological data, reported the chest radiographs and HRCT scans. The study group included 26 females and 23 males, aged 18-53 years (mean age 36 years). Organisms were isolated from 26 patients (53%). In 40 patients (82%), the HRCT scans demonstrated lesions not visualized on the plain chest radiographs. There was 100% correlation between plain radiographic and HRCT scan findings in nine cases (18%). Lesions that were not visualized on the plain radiographs but elucidated on HRCT included: pleural effusion (n = 14), ground-glass opacification (n = 20), pericardial effusion (n = 8), cavitation (n = 4), cysts (n = 4), bullae (n = 4), abscess (n = 1) and pneumothorax (n = 1). In 20 of 23 cases, hilar lymphadenopathy, identified on HRCT, was not recognized on plain chest radiographs. In patients in whom an organism was isolated, a correct HRCT diagnosis of pulmonary tuberculosis, bacterial pneumonia and Pneumocystis carinii pneumonia (PCP) was made in 80%, 84% and 100% of cases, respectively. The proportion of patients with missed lesions on plain chest radiographs in HIV infected patients with CAP was high. This has important implications for management and prognosis. HRCT scans correlate well with the microbiological diagnosis when reported by an experienced radiologist.

Adolescent↗
PubMed2006

Management of chronic asthma in adults in diverse regions of the world.

Asthma is a chronic inflammatory disease of the lungs associated with significant morbidity and mortality worldwide. Adoption of current treatment guidelines that propose inhaled corticosteroids (ICS) as the foundation for asthma treatment should control most patients with chronic asthma. Rapid-acting inhaled beta (beta) 2-agonists are best reserved for acute symptom relief. Long-acting beta-2-agonists in combination with ICS are the most effective asthma treatment currently available when asthma is not controlled on low-dose ICS alone; however, they are not universally available due to cost. Slow-release theophylline may be an alternative cost-effective add-on therapy to ICS in resource-poor areas, although its potential for toxicity has limited its use over the last decade. New targeted anti-inflammatory therapies lack the broad anti-inflammatory activity of ICS and are unaffordable in most settings. Implementation of guidelines for asthma care is an unresolved challenge, and major gaps in asthma care are consistent across the globe. Review of asthma management worldwide shows that control of the disease in relation to the Global Initiative for Asthma (GINA) goals of asthma treatment is not achieved in a large proportion of patients, despite the widespread availability of guidelines and even with access to effective treatment in resource-rich settings. Many resource-poor countries have the additional challenge of lack of access to basic asthma treatment such as ICS. The challenge is to provide global access to core asthma medications, particularly ICS, at affordable prices, to improve implementation of treatment guidelines and to encourage better health care provider and patient education.

Adult↗
PubMed2006

Serum procalcitonin distinguishes CAP due to bacteria, Mycobacterium tuberculosis and PJP.

SETTING: Procalcitonin (PCT), a propeptide of the hormone calcitonin, is a novel marker of the inflammatory response to infection. It has been used to discriminate between infectious and non-infectious causes of inflammation, and as a marker of severe sepsis in the intensive care unit. OBJECTIVE: To evaluate the utility of PCT in distinguishing community-acquired pneumonia (CAP) due to common bacteria, Mycobacterium tuberculosis and Pneumocystis jirovecii in a high human immunodeficiency virus (HIV) prevalence setting. METHODS: Two hundred and sixty-six patients admitted with a diagnosis of CAP were investigated. Serum samples for PCT were collected on admission. PCT levels were measured using a commercial immunoluminometric assay. RESULTS: A microbiological diagnosis was obtained in 169/266 patients: 44 pulmonary tuberculosis (PTB), 31 P. jirovecii pneumonia (PJP), and 35 bacterial pneumonia. The PCT levels were PTB 4.16 ng/ml (SEM 1.197; 95% CI 1.749-6.579); PJP 1.138 ng/ml (SEM 0.2911; 95% CI 0.543-1.734); and bacterial pneumonia 19.48 ng/ml (SEM 5.64; 95% CI 8.021-30.938, P < 0.0004). Thirty-six had co-infections. CONCLUSION: PCT levels differ significantly in patients with CAP due to TB, PJP and bacteria. PCT may be important in distinguishing M. tuberculosis and PJP in a high HIV prevalence setting where atypical presentations often confound the empirical clinical diagnosis.

Analysis of Variance↗
PubMed2004

Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.

BACKGROUND: The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz. METHODS: In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat. FINDINGS: Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine. INTERPRETATION: Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.

Adult↗
PubMed2004

Experience with azathioprine in systemic sclerosis associated with interstitial lung disease.

The aim of this study was to evaluate the safety and efficacy of azathioprine in the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SSc). The records of patients with SSc with ILD who were treated with azathioprine were reviewed. Patients were treated with azathioprine and low-dose prednisone if they had progressive pulmonary symptoms (deterioration in the dyspnea score) or poor or deteriorating lung function. Response was classified as improved if the FVC increased more than 10% from baseline, and stable if it remained within 10% of baseline. Serial dyspnea scores were recorded. Eleven patients were treated with azathioprine, three of whom received treatment for 6 months or less owing to adverse effects (nausea, leukopenia and pulmonary tuberculosis in one patient each). The remaining eight patients received at least 12 months' treatment and the results suggested an improvement in the mean percent predicted FVC from a baseline value of 54.25+/-3.53 to 63.38+/-6.15 after 12 months ( p=0.101). Overall, five patients improved and three remained stable. The mean dyspnea score ( n=8) improved from a baseline of 1.55+/-0.19 to 0.50+/-0.19 at 12 months ( p=0.011). This is the first case series of patients with SSc-associated ILD treated with azathioprine. Our results suggest that azathioprine may have a role in stabilizing lung function and improving symptoms in SSc, although this needs confirmation by a randomized controlled trial.

Azathioprine↗
PubMed2001

Occupational asthma as identified by the Surveillance of Work-related and Occupational Respiratory Diseases programme in South Africa.

BACKGROUND: The nationwide Surveillance of Work-related and Occupational Respiratory Diseases in South Africa, SORDSA, was established in 1996 to provide systematic information on occupational respiratory diseases. OBJECTIVE: SORDSA's objectives are to monitor the nature, extent and distribution of occupational respiratory diseases, and to increase awareness of their diagnosis and prevention. This paper describes the programme and results obtained for occupational asthma in the first 2 years, ending in October 1998. METHODS: SORDSA identifies newly diagnosed cases of occupational respiratory disease through voluntary reporting by pulmonologists, occupational medicine doctors and occupational health nurses. Initially, recruitment of the above health care providers was done through the membership infrastructure of their respective professional societies. Booklets with prescribed monthly reporting forms were distributed annually to all reporting members and a core of reporting providers was established through a proactive method of data collection. Information dissemination and reporting feedback takes place through quarterly newsletters and issue-specific brochures on certain hazardous agents. RESULTS: Over the initial 2-year period, 3285 cases of occupational respiratory disease were reported to SORDSA by 203 doctors and 97 occupational health nurses. After pneumoconiosis and associated respiratory conditions, occupational asthma was the second most commonly reported disease with 225 cases (6.9%). The average annual incidence for occupational asthma in South Africa was 13.1 per million employed people, with the highest incidence reported from the Western Cape province (37.6 per million). Latex was the most frequently reported agent for occupational asthma, followed by isocyanates and platinum salts. Low molecular weight agents accounted for 59.6% of the cases of occupational asthma. CONCLUSION: The results from this initial phase show that despite some limitations, SORDSA has the potential to obtain useful data on the industries, agents and occupations causing occupational asthma in South Africa.

Asthma↗
PubMed2001

Exhaled nitric oxide is elevated in patients with progressive systemic sclerosis without interstitial lung disease.

BACKGROUND: Progressive systemic sclerosis (PSS) is a multisystem disorder of unknown etiology. Interstitial lung disease (ILD) is a major cause of mortality in this condition, and a major challenge in this regard is to identify parameters that would predict the onset or progression of ILD in patients with PSS. Abnormal cellularity of BAL fluid (BALF) has been demonstrated in patients with PSS without ILD. STUDY OBJECTIVES: We investigated exhaled nitric oxide (NO) as a noninvasive marker of pulmonary inflammation in patients with PSS with and without clinical and radiologic evidence of ILD. This was compared with the cellularity of BALF. Our hypothesis was that exhaled NO was elevated in patients with PSS without ILD who had abnormal BALF cellularity. SETTING: Pulmonology and rheumatology units of a university-based, tertiary referral hospital in Durban, South AFRICA: STUDY METHODS: Exhaled NO was measured using a chemiluminescence analyzer in 12 patients with PSS and ILD and in 12 patients without clinical or radiologic evidence of ILD and in 30 healthy control subjects. BAL was performed in patients with PSS with and without the presence of ILD and in six healthy control subjects. RESULTS: Subclinical inflammation was confirmed by increased inflammatory cell counts in BALF from patients with PSS without ILD. Exhaled NO (mean [SEM]) was elevated in patients with PSS without ILD at 9.6 (0.7) parts per billion (ppb) compared to patients with PSS and ILD at 6.2 (0.6) ppb (p < 0.001) and healthy control subjects at 6.3 (0.2) ppb (p < 0.001). CONCLUSION: Exhaled NO may therefore be an important noninvasive surrogate marker of inflammation in patients with PSS without ILD.

Adult↗
PubMed2001

Occupational respiratory diseases in South Africa--results from SORDSA, 1997-1999.

OBJECTIVES: To describe the nature and extent of work-related respiratory diseases reported to the national Surveillance of Work-related and Occupational Respiratory Diseases in South Africa (SORDSA) reporting scheme. The causative agents and industrial categories in which they occurred are also characterised. DESIGN: Voluntary monthly reporting of newly diagnosed cases by pulmonologists, occupational medicine practitioners and occupational health nurses. SETTING: Medical and occupational health referral centres in the nine provinces of South Africa. SUBJECTS: Cases were workers from non-mining industries or ex-miners, suffering from a newly diagnosed occupational respiratory disease, reported to SORDSA between October 1996 and December 1999. OUTCOME MEASURES: Frequencies of reported occupational respiratory disease by year, reporting source, province and sex. Frequencies of short- and long-latency diseases by industry and causative agent. RESULTS: There was incomplete reporting coverage of the nine provinces in the first 3 years. Reporting was most comprehensive from Gauteng, KwaZulu-Natal and the Western Cape. Diseases with long latency periods made up 76.2% of the cases. Pneumoconiosis, even in non-mining industries, was the most frequently reported disease, followed by inhalation accidents. Occupational asthma was the fourth most reported disease. Apart from the prominence of pneumoconiosis, the results obtained by SORDSA are similar to those from a British occupational lung disease surveillance scheme. This study showed that newly diagnosed cases of occupational lung disease occurred in many industries and were caused by a variety of agents. CONCLUSION: SORDSA has contributed insight into the nature, extent and distribution of occupational respiratory diseases in South Africa. It has also highlighted important causes of occupational respiratory diseases in South Africa, as well as hazardous industries. The data indicate that South Africa has a widespread occupational lung disease problem, and provide a platform for targeted prevention strategies.

Accidents, Occupational↗
PubMed2000

Correlation of CD4:CD8 ratio and tumour necrosis factor (TNF)alpha levels in induced sputum with bronchoalveolar lavage fluid in pulmonary sarcoidosis.

BACKGROUND: An increased CD4:CD8 lymphocyte ratio and raised cytokine levels in bronchoalveolar lavage (BAL) fluid are characteristic of pulmonary sarcoidosis. Sputum induction has been used as a non-invasive tool for investigating the airways and may be useful in investigating inflammation in patients with sarcoidosis in whom endobronchial, peribronchial, and parenchymal inflammation is present. This study aimed to correlate the total and differential cell counts, CD4:CD8 ratio, and tumour necrosis factor (TNF)alpha levels between induced sputum and BAL fluid in patients with pulmonary sarcoidosis. METHODS: Fourteen patients with newly diagnosed biopsy proven sarcoidosis and six healthy controls were investigated. Sputum induction and BAL was carried out at the initial visit and repeated following six months of treatment with oral prednisone. RESULTS: There was no correlation of differential cell counts between induced sputum and BAL fluid. The CD4:CD8 ratio in induced sputum correlated strongly with that in BAL fluid (5.5 (0. 4:1) versus 4.4 (0.2:1); r = 0.8, p<0.001) and the fall in the ratio following six months of treatment in sputum paralleled that in BAL fluid (3.4 (0.2:1) versus 2.4 (0.2:1)). The TNF alpha levels in sputum also correlated with levels in the BAL fluid (11.9 (1.5) pg/ml versus 17.6 (2.7) pg/ml; r = 0.8, p<0.001). The fall in sputum TNF alpha levels following six months of treatment paralleled the fall in BAL fluid levels (6.7 (0.9) pg/ml versus 11.6 (1.3) pg/ml). CONCLUSIONS: The CD4:CD8 ratio and TNF alpha levels in induced sputum correlated with those in BAL fluid and paralleled changes with treatment. Induced sputum may therefore be a non-invasive surrogate for certain parameters in BAL fluid in patients with sarcoidosis.

Adult↗
PubMed2000

Neutrophils in induced sputum arise from central airways.

A high neutrophil count is often found in induced sputum compared to bronchoalveolar lavage fluid (BALF). This study investigated whether such a high neutrophil count may be a response to inhaled hypertonic saline or that the airway compartment sampled by induced sputum has a higher concentration of neutrophils than BALF. Saliva and induced sputum samples were taken at 10 and 20 min following inhalation of 3% hypertonic saline from an ultrasonic nebulizer in 12 healthy nonsmoking subjects. Four days later the 12 subjects underwent bronchoscopy (six following inhalation with 3% saline). Tracheal, proximal bronchial secretions, bronchial washings and BALF samples were obtained. The neutrophil count (% total leukocytes) increased significantly in saliva at 10 and 20 min post nebulization with 3% saline, although there was no change in neutrophils in induced sputum at 10 and 20 min. There was no significant difference in neutrophil count in the subjects who inhaled 3% saline as compared to those who did not, in secretions from the trachea, proximal bronchi, bronchial washings and BALF. Neutrophil counts were significantly higher in the trachea, proximal bronchi and bronchial washings as compared to BALF (p<0.001). It is concluded that neutrophil counts in healthy subjects increase from the peripheral towards the proximal airways, in the absence of hypertonic saline-induced changes. This suggests that the relatively high neutrophil count in induced sputum arises from the proximal airways and is not a response to inhaled hypertonic saline during the procedure.

Adult↗
PubMed2000

Guideline for the management of chronic asthma in adults--2000 update. South African Pulmonology Society Adult Asthma Working Group.

OBJECTIVE: To make recommendations for the cost-effective management of asthma incorporating recent advances in the understanding and treatment of asthma since the last guideline statement in 1992. The guideline is applicable to adults and children over 12 years of age. OPTIONS: Asthma should be graded according to standard severity criteria. The principle of 'hit early, hit hard' with corticosteroids to achieve rapid control is encouraged; thereafter treatment should be tailed down to the lowest dose of corticosteroids that maintains the aims of asthma treatment. OUTCOMES: The aims of asthma management should be achieved; these include: (i) avoidance of causative and trigger factors; (ii) abolition of symptoms and ability to lead a normal lifestyle; (iii) restoration of normal (or best possible) lung function; (iv) reduction of the risk of severe attacks; and (v) optimisation of treatment with minimal side-effects. EVIDENCE: Based on a selective review of randomised, controlled studies to support an evidence-based approach to treatment. BENEFITS, HARMS AND COSTS: Appropriate management of asthma should lead to a reduction in morbidity and mortality of asthma and a consequent reduction in cost of asthma care. Side-effects of corticosteroids are placed in perspective together with a strategy to minimise these effects. RECOMMENDATIONS: Asthma should be managed with inhaled corticosteroids as the most important anti-inflammatory treatment, except in the case of mild intermittent asthma which may be treated with beta 2 agonists on a pro re nata (prn) basis. It is preferable to add long-acting beta 2 agonists to low-dose inhaled corticosteroids before increasing corticosteroids. Leukotriene receptor antagonists are currently recommended for use in combination with inhaled corticosteroids pending further data on their long-term benefits. Differentiation of asthma from chronic obstructive pulmonary disease (COPD) is important. Early referral to a pulmonologist in difficult cases is encouraged. VALIDATION: Endorsed by the South African Pulmonology Society, the Allergy Society of South Africa and the South African Medical Association. The guideline is compatible with those of other international societies.

Adrenal Cortex Hormones↗
PubMed1999

Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis.

Cytokines such as tumour necrosis factor-alpha and interferon gamma are associated with active pulmonary inflammation in sarcoidosis and they upregulate inducible nitric oxide synthase (iNOS). The objectives of this study were to examine iNOS upregulation in sarcoidosis by showing raised exhaled nitric oxide and increased iNOS activity in lung biopsy specimens of these patients utilizing immunohistochemistry. Exhaled NO was measured by a chemiluminescence analyser in 12 patients with newly diagnosed biopsy-proven sarcoidosis before and after 6 weeks of corticosteroid therapy. Lung biopsy specimens from these patients were subjected to immunohistochemical staining with a specific iNOS antibody. Exhaled NO was raised in newly diagnosed sarcoidosis (mean+/-SEM): 9.8+/-0.4 versus 4.1+/-0.2 parts per billion (ppb) in 21 healthy controls, p<0.001; and fell significantly after 6 weeks treatment with corticosteroids to 5.9+/-1.4 ppb; p<0.01. There was no correlation between exhaled NO and other markers of disease activity. Immunohistochemical staining demonstrated iNOS activity in respiratory epithelium and granulomas in patients with sarcoidosis. Exhaled nitric oxide is raised in patients with active pulmonary sarcoidosis and may be a result of inducible nitric oxide synthase upregulation. The fall in exhaled nitric oxide following corticosteroid therapy may reflect inhibition of inducible nitric oxide synthase in the respiratory epithelium and granulomas.

Adult↗
PubMed1999

Increased neutrophils and cytokines, TNF-alpha and IL-8, in induced sputum of non-asthmatic patients with chronic dry cough.

BACKGROUND: The pathogenesis of non-asthmatic chronic dry cough remains unclear. METHODS: A study was undertaken to determine whether airway inflammation could be a contributing factor by analysing inflammatory cells and cytokines in induced sputum from 19 patients with chronic dry cough of varying aetiology, excluding asthma and bronchiectasis, and from 10 normal controls. The associated causes for the chronic cough were postnasal drip (n = 5), gastro-oesophageal reflux (n = 4), and idiopathic (n = 10). All patients had an enhanced cough reflex to capsaicin. RESULTS: Sputum neutrophilia (median (interquartile range)) was found in the patients with chronic cough (59.4 (27.1)%) compared with the normal controls (28.4 (22.0)%; p < 0.01, 95% CI 11.3 to 42.2). Sputum levels of interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were also significantly increased compared with normal controls (0.57 (1.08) and 0.25 (0.72) ng/ml; p < 0.05 (95% CI 0.05 to 1.75) for IL-8; 48.3 (34.4) and 12.6 (33.6) pg/ml, p < 0.01 (95% CI 8.8 to 69.8) for TNF-alpha). CONCLUSION: Neutrophils and cytokines associated with neutrophil chemotaxis and activation may contribute to the pathogenesis of non-asthmatic chronic dry cough.

Chemotaxis, Leukocyte↗
PubMed1998

Increased sensitivity of the cough reflex in progressive systemic sclerosis patients with interstitial lung disease.

Cough is a common presenting symptom of interstitial lung disease (ILD). The aim of this study was to examine the cough reflex in patients with progressive systemic sclerosis (PSS), with and without associated ILD. The cough reflex to inhalation of chloride deficient solutions and capsaicin was determined in patients with PSS with associated ILD (n=12), compared to patients with PSS without ILD (n=12). In addition, patients with a chronic dry cough (n=12) and healthy subjects (n=10) without cough were studied. Cough responses to inhalation of isotonic solutions containing 150, 75, 37.5 and 0 mM Cl- ions and of capsaicin (0.9-500 mM) were measured. PSS patients with ILD reported a significantly higher cough score than PSS patients without ILD (p<0.03). ILD patients coughed more than those without ILD to Cl- of 37.5 and 0 mM (19.1+/-5.0 vs 6.2+/-1.9 coughs x min(-1) (p<0.03), and 29.2+/-5.0 vs 14.1/-4.1 coughs x min(-1) (p<0.04), respectively). The log concentration of capsaicin causing two or five coughs was lower in PSS with ILD compared to PSS without ILD (0.74+/-0.15 mM vs 2.12+/-0.26 mM; p<0.002). Patients with chronic dry cough had a similar degree of response to low-chloride and capsaicin solutions as patients with PSS and ILD, whilst healthy controls had a similar degrees of response to PSS patients. There is an increased cough reflex in patients with interstitial lung disease, which may represent sensitization of airway sensory nerves. This may be the basis for the chronic dry cough in patients with interstitial lung disease.

Bronchial Provocation Tests↗