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Biomedical subjects

N C Barnes

Publications and source records attributed to N C Barnes.

At least 73 records · Page 4Linked to original sources

Thoracoscopy.

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Humans↗

Incidence of abdominal tuberculosis in Bangladeshi migrants in east London.

A retrospective epidemiological study of abdominal tuberculosis in a defined population in the London Borough of Tower Hamlets was conducted between January 1985 and 31 December 1989. The total population of 163,900 included a mean of 20,732 Bangladeshis. Of the 13 cases diagnosed 8 were Bangladeshi, with equal involvement of the peritoneum and intestine. The crude incidence in the Bangladeshi community was 7.7 cases/10(5)/year, which was significantly higher than that in Europeans (0.3 cases/10(5)/year, chi 2 with Yate's correction = 14.0 P < 0.001). The highest age-specific incidence was amongst those aged 16-20 years and 41-45 years. Most patients had a laparotomy or peritoneal biopsy to confirm the diagnosis. The response to therapy was good. Only 62% of cases were notified. This study confirms the importance of tuberculosis in the differential diagnosis of abdominal symptoms in Bangladeshi patients.

Adolescent↗

Safety of high-dose inhaled corticosteroids.

Inhaled corticosteroids are being given to more patients, at increasing doses and for longer periods of time. This has led to renewed concern about side-effects, particularly when higher doses (> 1 mg day-1) are used. The side-effects of particular concern are adrenocortical suppression, bone resorption, decreased growth in children, skin thinning and cataract formation. Changes in adrenocortical function are seen in a small proportion of patients given doses of 1-2 mg day-1. Long-term studies of the effect of inhaled corticosteroids on bone density are not available. Cross-sectional studies of bone density have been performed, but confounding variables, such as previous courses of oral corticosteroids and poor matching of control groups, make the studies difficult to interpret. Short-term effects on markers of bone turnover have been demonstrated, but their relevance to the long-term risk of osteoporosis is unclear. Studies reporting an increased incidence of skin changes and cataract formation are difficult to interpret because of confounding variables and inadequate control groups. Further studies of the long-term side-effects of inhaled corticosteroids are now required to enable prescribers to judge better the relative benefits and risks of this important asthma therapy.

Administration, Inhalation↗

Effect of the platelet-activating factor antagonist UK-74,505 on the early and late response to allergen.

The effect of UK-74,505, a specific platelet-activating factor (PAF) antagonist, on the early (EAR) and late asthmatic response (LAR) to inhaled allergen was studied in a randomized, double-blind, placebo-controlled crossover study. A total of eight adult male atopic asthmatic subjects completed the protocol (one withdrew after screening), all having demonstrated a dual response to inhaled allergen (EAR, > 20% fall in FEV1 between 0 and 1 h; LAR, > 15% fall in FEV1 between 4 and 8 h after challenge). Subjects were studied on 2 days at least 10 days apart. After measurement of baseline FEV1, subjects ingested a single oral dose of 100 mg UK-74,505 or matched placebo (P). Allergen challenge was performed 3 h later and the FEV1 was then measured for 8 h. There was no difference between UK-74,505 and placebo in the maximum percentage change from baseline (+/- SEM) for either EAR or LAR (EAR, UK-74,505 -25.6 +/- 4.8%, P -24.0 +/- 3.3%; LAR, UK-74,505 -20.8 +/- 4.4%, P -25.7 +/- 3.8%). There was no significant difference in the area under the percentage change from baseline FEV1-time curve. Ex vivo platelet aggregation to PAF was measured at 0, 2, 6, 8, and 10 h after the dose. There was marked inhibition of platelet aggregation to PAF for 10 h following UK-74,505 but not placebo (% maximum aggregation to PAF, UK-74,505, -69.9%; P, 0.13%; p = 0.0001). Histamine challenge was performed in five patients the day before and after each study day. There was no significant difference between UK-74,505 and placebo in PD20 to histamine (mean PD20 before and after UK-74,505, 1.31 and 0.96 mumol; P, 1.32 and 1.17 mumol). UK-74,505 did not affect either the EAR or the LAR to inhaled allergen or bronchial responsiveness, despite its potency and long duration of action. This suggests that PAF does not have a major role in the acute response to inhaled allergen.

Adolescent↗

A comparison of fluticasone propionate, 1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. International Study Group.

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n = 82), or 2 mg.day-1 beclomethasone dipropionate (n = 72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 l.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta 2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant. However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p = 0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78% with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg.day-1 fluticasone propionate was as effective as 2 mg.day-1 beclomethasone dipropionate in the control of severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Betel-nut chewing and asthma.

Two Asian patients admitted to hospital with acute severe asthma had been chewing betel nut immediately before the attacks. Arecoline, a cholinergic alkaloid, is a major constituent of Areca catechu (betel) nut and causes the euphoric effects. We sought an association between betel-nut chewing and bronchoconstriction in asthmatic patients. In vitro, arecoline caused dose-related contraction of human bronchial smooth-muscle strips, with one-tenth the potency of methacholine. In a double-blind challenge study, inhalation of arecoline caused bronchoconstriction in six of seven asthmatic patients and one of six healthy subjects; methacholine caused bronchoconstriction in all the asthmatic patients and in five controls. The geometric mean concentrations of arecoline and methacholine that caused 20% falls in the forced expiratory volume in 1 s (PC20 FEV1) in the asthmatic subjects were 5.2 mg/ml and 1.6 mg/ml, respectively. We then studied four Bengali asthmatic patients, regular users of betel nut, during a betel-nut challenge. Three showed no adverse effects, but one showed a 30% fall in FEV1 by 150 min after chewing; the effect was reproducible. In the UK, the rate of hospital admission for acute asthma is higher among Asians than among other groups in the population; betel-nut chewing may be one of several factors that affect asthma control and severity of attacks.

Adult↗

Trial of cyclosporin in corticosteroid-dependent chronic severe asthma.

The treatment of chronic severe asthma is unsatisfactory for many patients. In a randomised, double-blind, placebo-controlled, crossover trial we have tested whether cyclosporin, which is thought to act primarily by inhibition of T lymphocyte activation, improves lung function in corticosteroid-dependent asthmatics. After a 4-week run-in period, 33 patients with longstanding asthma (mean duration 27 years), and who had required continuous oral corticosteroids for a mean of 9.3 years, were randomised to receive either cyclosporin (initial dose 5 mg/kg per day) or placebo for 12 weeks, crossing over after a 2-week washout period. Mean baseline forced expiratory volume in 1 s (FEV1) was 60.1% of the predicted value. 2 patients failed to complete the protocol and 1 withdrew because of hypertrichosis. Cyclosporin therapy resulted in a mean increase above placebo of 12.0% in morning peak expiratory flow rate (PEFR; p less than 0.004) and 17.6% in FEV1 (p less than 0.001). The frequency of disease exacerbations requiring an increased prednisolone dose was reduced by 48% in patients on cyclosporin compared with placebo (p less than 0.02). Diurnal variation in PEFR decreased by a mean of 27.6% (p = 0.04). Cyclosporin for 12 weeks was well tolerated by this group of chronic asthmatics, in whom the mean whole-blood trough concentration was 152 micrograms/l. These findings provide further evidence of a role for activated T lymphocytes in the pathogenesis of asthma. Specific pharmacological targeting of this cell could form the basis of a novel approach to the treatment of asthma.

Adult↗

Notification of tuberculosis: how many cases are never reported?

BACKGROUND: Notification of tuberculosis is essential for local contact tracing and for assessing the national incidence of tuberculosis. The accuracy of notification figures is uncertain. This study examined the notification rates of all patients diagnosed as having tuberculosis at two hospitals in the East End of London over five years. METHODS: In a retrospective survey of all patients aged 16 years or more presenting with tuberculosis to the London Chest Hospital or the Royal London Hospital from 1 January 1985 to 31 December 1989, cases of tuberculosis were identified from microbiology and histology records, statutory notifications, necropsy reports, coroners' records, hospital activity data, and death certificates. Clinical data were obtained from case notes and notification was determined from the local authority notification lists. RESULTS: Six hundred and nine adult patients with tuberculosis were identified. Notes were available for 580 cases (95%), of which 426 (73%) had been notified. The proportion of cases notified varied according to the specialty of the clinician in charge of the patient at diagnosis. Patients with a past history of tuberculosis and those who died within one year were less likely to have had their tuberculosis notified. Age, race, and lack of microbial or histological confirmation of diagnosis did not influence the proportion of cases notified. One hundred and eighty five patients had smear positive sputum, but 25 of these cases (14%) were not notified. Eighty five patients who had presented with pulmonary tuberculosis did not have their disease notified; 20 (24%) had smear positive sputum. CONCLUSIONS: Many cases of tuberculosis are not notified (27%). Fourteen per cent of all sputum smear positive cases of tuberculosis were not notified, and these patients are a considerable public health risk. The true incidence of tuberculosis in the area studied is at least one third higher than current notification figures suggest.

Adolescent↗

Preoperative laser therapy in a patient with resectable bronchogenic carcinoma and severe coronary artery disease.

A 67 year old man with severe coronary artery disease was found to have a resectable bronchogenic carcinoma. Myocardial revascularisation and lung resection were considered to be unduly hazardous as either separate or combined operations. Preoperative laser therapy, however, enabled the two procedures to be performed in greater safety in the most appropriate sequence.

Aged↗

Lung function improvement in asthma with a cysteinyl-leukotriene receptor antagonist.

In a double-blind study ten asthmatic patients with impaired lung function received the cysteinyl-leukotriene receptor antagonist ICI 204,219 (40 mg by mouth) and placebo in random order on 2 days at least 1 week apart. The increase in forced expiratory volume in 1 s (FEV1) above baseline was significantly greater after ICI 204,219 than after placebo. This effect persisted after nebulised salbutamol. These findings suggest that cysteinyl-leukotrienes are one of the causes of persistent bronchoconstriction in chronic asthma.

Administration, Inhalation↗

Effect of a 5-lipoxygenase inhibitor on leukotriene generation and airway responses after allergen challenge in asthmatic patients.

The effect of a single oral dose (800 mg) of zileuton (A-64077), a specific 5-lipoxygenase inhibitor, on the early and late airway responses to inhaled allergen was studied in a randomised, double blind, placebo controlled, and crossover trial in nine subjects with atopic asthma. Leukotriene generation was also assessed in vivo by measuring urinary leukotriene (LT) E4 excretion, and ex vivo by measuring calcium ionophore stimulated whole blood LTB4 production. Zileuton almost completely inhibited ex vivo LTB4 production but reduced urinary excretion of LTE4 by only about half. There was a trend for the early asthmatic response to be less on the day of zileuton treatment, but this did not reach statistical significance (p = 0.08). The zileuton induced reduction in maximum fall in FEV1 in the early asthmatic response was, however, significantly related to the reduction in urinary LTE4 excretion (r = 0.8), but not to the reduction in LTB4 generation ex vivo. There was no significant change in the allergen induced late asthmatic response, or in the increase in airway responsiveness to methacholine following antigen. The results provide some support for the hypothesis that the cysteinyl leukotrienes have a role in the allergen induced early asthmatic response. More complete in vivo inhibition of 5-lipoxygenase may be needed to produce a significant reduction in airway response to allergen challenge.

Adult↗