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Biomedical subjects

U G Lalloo

Publications and source records attributed to U G Lalloo.

32 records · Page 2Linked to original sources

An evaluation of the respiratory health status of automotive spray-painters exposed to paints containing hexamethylene di-isocyanates in the greater Durban area.

OBJECTIVE: A survey of automotive spray-painting establishments was undertaken to evaluate the respiratory health status of spray-painters exposed to paints containing hexamethylene di-isocyanates (HDIs). DESIGN: This was a cross-sectional study. SETTING: Spray-painting establishments in the Durban municipal area. PARTICIPANTS: Spray-painters from a random sample of 40 (25%) of the registered spray-painting establishments were studied. MAIN OUTCOME MEASURES: Responses to an Interviewer-administered standardised respiratory health questionnaire and a cross-shift spirometric lung function test were obtained for each spray-painter, questionnaires assessing the firm's compliance with the spray-painting safety requirements were also obtained. RESULTS: The mean cross-shift decrease in forced expiratory volume in 1 second (FEV1) was 130.5 ml (SD 203.19) (P = 0.0002). The lung function data indicated that of the 40 spray-painters examined, 10 (25%) showed clinically significant cross-shift decreases in FEV1, viz, decreases > 250 ml. Only 2 subjects had a diagnosis of asthma. Chronic respiratory symptoms of cough, wheeze and wheeze with breathlessness were similar to those noted in community-based studies. A high proportion had eye irritation (55%) and dermatitis of the hand (32%). The potential determinants of FEV1 were examined in a multiple linear regression analysis and only the isocyanate concentration levels approached statistical significance (P = 0.082), suggesting that other factors such as duration of exposure, spray-paint 'bounce-back' phenomenon, and 'healthy worker' effect may be more important. ('Bounce back' refers to the phenomenon whereby some of the mist from the spray-gun, after striking the surface being painted, is deflected back into the operator's breathing zone in the form of fine droplets or aerosols.) Forty per cent of the 40 spray booths had ventilation standards substantially below that specified in current South African legislation. Only 21 (55%) spray-painters were provided with the regulation respiratory protective equipment, and in the cases where it was provided, 7 (33%) of these spray-painters used the positive pressure air-line respiratory recommended by the leading manufacturers of isocyanate-based paints. CONCLUSIONS: The findings in this study confirm the risk of exposure to HDIs in the spray-painting industry and highlight the need for more stringent industrial hygiene controls.

Adult↗

Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough.

Cough accompanied by an increased sensitivity of the cough reflex is the most common symptom of inflammatory airway disease. This symptom is also frequently reported in patients receiving angiotensin-converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension, although the underlying mechanism is unknown. We have investigated the possibility that the inflammatory peptide bradykinin, normally degraded by ACE, causes sensitization of airway sensory nerves and an enhancement of the cough reflex in conscious guinea pigs. Treatment of guinea pigs for two weeks with captopril led to an increased cough response to inhaled citric acid, which was prevented by concomitant treatment with the bradykinin receptor antagonist icatibant. A similar icatibant-sensitive enhancement of citric acid-evoked cough was seen in untreated animals after prior inhalation of bradykinin, although cough evoked by hypertonic saline was unaffected. In electrophysiological studies performed in vitro, responses of single vagal C fibers to capsaicin, applied to receptive fields of single-fiber units in the trachea, were also markedly increased after perfusion with bradykinin, whereas A delta fiber responses to hypertonic saline were unaffected. These results indicate that bradykinin-evoked sensitization of airway sensory nerves may underlie the pathogenesis of ACE-inhibitor cough. Bradykinin receptor antagonists may be of benefit in treating chronic cough seen with this and other inflammatory conditions.

Angiotensin-Converting Enzyme Inhibitors↗

Airway and cough responsiveness and exhaled nitric oxide in non-smoking patients with stable chronic heart failure.

OBJECTIVE: To investigate the airway and cough responsiveness in non-smoking patients with stable chronic heart failure. Cough and wheeze, features associated with hyper-responsive airways, are not uncommon especially in decompensated chronic heart failure. Bronchial hyperresponsiveness has previously been demonstrated in chronic heart failure but this may have been confounded by smoking and acute decompensation. DESIGN: Case-control study. SETTING: Tertiary specialist hospital. PATIENTS AND INTERVENTIONS: Airway responsiveness to methacholine (a direct stimulant of smooth muscle in the airways), sodium metabisulphite (a putative stimulant of airway sensory nerves), and exercise was examined in 10 non-smoking patients with stable chronic heart failure (age 56.5 (3.2) (SEM) years; 7 men; radionuclide left ventricular ejection fraction 20.8 (2.9)%; radiographic cardiothoracic ratio 0.56 (0.02)). Exhaled nitric oxide, a product of the action of proinflammatory cytokines, was also measured to assess the contribution of local inflammation to airway responsiveness. The cough responses to low-concentration chloride solutions and to capsaicin were studied. Because all patients were receiving angiotensin-converting enzyme inhibitors, which may influence airway responsiveness and cough, 8 asymptomatic non-smoking controls taking angiotensin-converting enzyme inhibitors for essential hypertension were also studied (age 54.3 (2.8) years; 6 men; radiographic cardiothoracic ratio 0.46 (0.01)). RESULTS: The mean provocative concentration that induced a 20% decrease in forced expiratory volume in 1 second (FEV1) was 67.6 v 79.8 mg/ml (P = 0.71) for methacholine and 276.7 v 290.4 mg/ml (P = 0.79) for sodium metabisulphite in chronic heart failure patients and controls respectively. The change in FEV1 after maximal cardiopulmonary exercise testing was +1.44% in patients and +2.53% in controls (P = 0.47), indicating that there was no exercise-induced bronchospasm in either group (peak oxygen consumption was 16.9 (1.3) v 26.5 (2.3) ml/kg/min respectively, P < 0.01). Exhaled nitric oxide concentration was not increased in chronic heart failure (12.3 (1.7) v 16.2 (3.3) ppb, P = 0.32). The median cough counts after nebulised 0 mM and 37.5 mM chloride solutions were 2.5 v 1.0 (P = 0.6) and 5.5 v 5.5 (P = 0.5) respectively and the capsaicin concentration causing two or more coughs was 13.5 v 6.5 microM (P = 0.5). CONCLUSION: Airway hyper-responsiveness is not a predominant feature in non-smoking patients with stable chronic heart failure treated with, and tolerant to, angiotensin-converting enzyme inhibitors. It is unlikely to contribute to the exertional dyspnoea seen in these patients.

Adult↗

Diagnosis and management of chronic persistent dry cough.

Cough is one of the commonest symptoms of lung disease and is a frequent problem encountered in general practice as well as in hospital practice. A wide range of disease processes may present with cough and definitive treatment depends on making an accurate diagnosis of the cause. A diagnostic work-up for patients with persistent dry cough is presented. The most common associated conditions are post-viral cough, asthma, rhinosinusitis (post-nasal drip or 'nasal catarrh') and gastro-oesophageal reflux. Treatment with angiotensin-converting enzyme inhibitors can also lead to a persistent dry cough. Specific treatment of the cause should control the cough, but this may not occur in all cases and in a sizeable proportion of patients, no associated cause can be found. An increased sensitivity of the cough reflex can be observed in patients with persistent dry cough. Symptomatic relief must be considered when the cough interferes with the patient's health and sleep but the most effective antitussive opiates cause sedation and may be addictive. Treatment of persistent dry cough remains a challenge in some patients and there is still scope for improvement in its diagnosis and effective therapy.

Angiotensin-Converting Enzyme Inhibitors↗

Pathophysiology and clinical presentations of cough.

The human cough reflex is still poorly understood, although it is known to occur independently of bronchoconstriction. Sensitization of the cough reflex is a unifying hypothesis for chronic dry cough in several conditions, including gastroesophageal acid reflux, angiotensin-converting enzyme inhibitor cough, and cough-variant asthma. The most common cause of chronic dry cough is a group of related conditions of chronic rhinitis, sinusitis, and postnasal drip. In these cases the cough reflex may be sensitized through an action of inflammatory mediators from the nasal mucosa on the airways or a reflex sensitization of airway sensory nerves. The association of cough with gastroesophageal reflux may occur through a local esophageal-tracheobronchial reflex. Angiotensin-converting enzyme inhibitor cough is a side effect of treatment in about 10% of patients; it probably results from inhibition of the degradation of kinins, particularly bradykinin, in the airway. Why some patients with asthma have cough as the principal feature of their disease is unclear. Tachykinins are probably involved in the mechanism of sensitization of the cough reflex, and the development of neuropeptide antagonists may open new research opportunities. A study that used ambulatory recording of cough in a group of subjects with asthma confirmed the presence of significant cough, the frequency of which did not correlate with lung function or diurnal variation in peak flow. This finding highlights the problem of cough in patients with asthma, a problem that probably has been underestimated in the past.

Angiotensin-Converting Enzyme Inhibitors↗

Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs.

Acidic solutions mimick many of the effects of capsaicin (Cap), including pain, bronchoconstriction, cough, and sensory neuropeptide release. Evidence from the use of the Cap antagonist capsazepine suggests that in some cases protons act at the Cap receptor. In the present study, we have investigated whether cough evoked by Cap and citric acid (CA) is mediated specifically via the Cap receptor on airway sensory nerves. We have examined the effects of capsazepine on Cap-, CA-, and hypertonic saline-induced cough and also on CA-induced nasal irritation in awake guinea pigs. Capsazepine was nebulized for 5 min before cough challenges with Cap for 5 min and CA for 10 min. Control animals were pretreated with vehicle alone. Capsazepine (100 microM) inhibited the cough response to 30 microM Cap from 0.77 +/- 0.14 coughs/min in control animals to 0.23 +/- 0.08 coughs/min (P < 0.05) and to 80 microM Cap from 1.4 +/- 0.23 to 0.3 +/- 0.11 coughs/min (P < 0.01). There was no effect, however, of lower concentrations of capsazepine (5 and 10 microM) against Cap-evoked cough. At a concentration of 100 microM, capsazepine also inhibited the coughing induced by 0.25 M CA from 1.8 +/- 0.26 to 0.93 +/- 0.31 coughs/min (P < 0.05) but not that induced by 0.5 M CA. Nasal irritation induced by 0.25 M CA, but not by 0.5 M CA, was also inhibited by capsazepine from 2.47 +/- 0.37 to 0.75 +/- 0.31 nose wipes/min (P < 0.05). This inhibitory effect of capsazepine did not appear to reflect a nonspecific suppression of the cough reflex, since cough evoked by exposure to hypertonic (7%) saline for 10 min was unaffected by pretreatment with capsazepine (100 microM). These data show that capsazepine is a specific inhibitor of Cap- and CA-induced cough in guinea pigs. Moreover, they suggest that low pH stimuli evoke cough and nasal irritation by an action at the Cap receptor, either directly or through the release of an intermediate agent.

Animals↗

Review and analysis of variation between spirometric values reported in 29 studies of healthy African adults.

Within- and between-population variation in spirometric measurements has been addressed in a systematic review of spirometric measurements from 29 studies published between 1965 and 1990 involving 9,690 men and 2,638 women of sub-Saharan African ancestry; FVC and FEV1 were age- and height-standardized at BTPS. Between- population differences were related to geographic region and sample source (workforce versus community). The effects of altitude, variation in sample mean height, and year of study publication were also significant variables in multivariate models explaining between-population differences. Altitude was the most important variable with an effect of 263 ml/1,000 m (95% confidence interval [CI] 120-410) on FVC in men. In women, variation in sample mean height was also important, with taller populations having larger values for FVC (64 ml/cm). In men, secular trends were evident, with date of study associated with negative trends among men in the U.S.A. (-35.3 ml/year), and positive trends (14.7 ml/year) in other regions. These differences in trend could not be explained. Population selection factors, altitude, date of study, and other biological sources of variation need to be taken into account in evaluating between- and within-population comparisons of spirometric measurements.

Adult↗

Listeria monocytogenes meningitis at King Edward VIII Hospital, Durban. A 10-year experience, 1981-1990.

Nine cases, 3 adults and 6 children, with Listeria monocytogenes meningitis were seen over a 10-year period at King Edward VIII Hospital, Durban. These cases accounted for 0.8% (3/374) and 0.6% (6/1,210) of all culture-positive cases of acute bacterial meningitis in adults and children, respectively, and represented 2.9% (4/136) of all culture-positive cases in the neonatal age group and 5.7% (3/53) of culture-positive cases in adults 50 years and older. The patients had positive blood and cerebrospinal fluid (CSF) cultures. All isolates were sensitive to ampicillin, chloramphenicol, sulphamethoxazole-trimethoprim combination and gentamicin. One isolate in an 11-month-old child was resistant to penicillin and 2 isolates in the adult patients displayed intermediate sensitivity to this antibiotic. The adults were over 50 years of age and presented with an abrupt onset of a pyrexial illness, meningitis and focal neurological signs; only 1 survived. Only 1 8-week-old infant of the paediatric cases survived. A polymorphonuclear leucocytosis, low serum glucose and elevated protein values were common findings in the CSF and the features in some patients mimicked tuberculous or viral meningitis. The fulminant course of the disease and the fact that penicillin and not ampicillin is the first-line antibiotic makes it essential to consider listeriosis as a possible diagnosis, particularly in the very ill patient.

Anti-Bacterial Agents↗

Lymphomatoid granulomatosis. A report of 4 cases.

Only 1 case of lymphomatoid granulomatosis has previously been reported from South Africa. Experience with 4 such adult patients (2 blacks and 2 whites) is described. These patients were followed up for 15-48 months and none developed evidence of a lymphoma during this period. Fever, weight loss, cough and breathlessness were prominent symptoms in all patients. One patient, a black woman, with a diffuse interstitial pattern of lung involvement, had digital clubbing--a rare accompaniment that resolved after therapy. Dilated congestive cardiomyopathy was found in association with pulmonary nodules in a black male patient. All 4 patients were treated with cytotoxic regimens. The 2 patients treated with oral cyclophosphamide and prednisolone responded favourably. The possible explanation for paucity of reports of lymphomatoid granulomatosis from South Africa could be under-reporting, underdiagnosis or a true geographic/ethnic variation in the incidence of this condition.

Adult↗

Effect of standing versus sitting position on spirometric indices in healthy subjects.

This study examined the effect of the standing versus the sitting position on spirometric indices in 94 healthy non-obese adult subjects (41 men and 53 women) with the order of testing randomised. On average all the spirometric indices examined, except the peak expiratory flow rate, were higher in the standing compared to the sitting position although the change was only significant at the 5% level for FEV1 in women. The fall in FEV1 with the change in position was statistically related to the ponderal index but not to age, height or the initial lung function level. A uniform posture for spirometry is recommended in epidemiological studies examining longitudinal trends in lung function, as well as in cross-sectional aetiological studies examining, for instance, the effects of environmental and/or occupational exposures. A uniform posture is also recommended for clinical studies which involve repeated measurements over time, for instance to measure the effect of treatment or the natural history of airways disease.

Adult↗

Autonomic nervous system dysfunction in severe tetanus: current perspectives.

The enigma of autonomic nervous system dysfunction in severe tetanus is discussed in the light of recent and older evidence concerning the nature and action of tetanus toxin, its clinical effects, and therapy. Some suggestions for the pathogenesis and management of the cardiovascular disturbances are made.

Autonomic Nervous System Diseases↗

Cerebral blastomycosis. A report of 2 cases.

Following recent documentation of blastomycosis in the RSA, a report of a further 2 cases in Natal is presented. The unusual feature of both cases was the presence of central nervous system involvement. In the first patient intracerebral involvement occurred after apparent good response to ketoconazole when he defaulted from therapy after 3 months. The second patient presented with cerebral involvement and died soon after admission to hospital.

Adult↗

Accelerated silicosis in a foundry shotblaster. A case report.

A case of accelerated silicosis in a shotblaster in an iron foundry is described. The clinical course was notable for the rapid progression of cor pulmonale and the appearance of clubbing over a period of 2-3 months. Radiographic and pathological features atypical of the more chronic forms of the disease are described. The importance of the occupational history and the need for the strictest respiratory protection in such work are illustrated. Stringent control of this type of operation is urgently needed.

Humans↗