The treatment of spinal tuberculosis: a retrospective study.

BACKGROUND: There are conflicting guidelines and variations in clinical practice in the management of bone tuberculosis (TB), including spinal TB. A case who received 6 months of treatment in line with current British Thoracic Society (BTS) guidelines, and subsequently relapsed, prompted a survey of treatment and outcomes of spinal and other bone TB. METHODS: A retrospective study examining the clinical features, treatment duration and outcome of patients presenting with spinal and other bone TB to the Leeds Teaching Hospitals National Health Service Trust, between 1998 and 2002. RESULTS: Forty-two patients were identified. Notes from 34 patients with spinal TB and four patients with TB of other bones were reviewed. Of eight patients who received 6 months of therapy, five relapsed. Of 30 patients who received treatment for 9 months or longer, none relapsed (P < 0.05). CONCLUSION: Six months of treatment, as currently recommended by the BTS, may be inadequate for bone TB, including spinal TB.

The parasympathetic nervous system and the diurnal variation of lung mechanics in asthma.

In a placebo-controlled double-blind experiment the effects of cholinergic blockade with 30 micrograms kg-1 atropine administered by intravenous injection have been studied in nocturnal asthma. Cholinergic blockade at night reversed the changes in indices of airflow in small airways and of gas trapping to the values seen after administration of atropine during the daytime. However, the improvement in indices of airflow in large airways was not complete, reaching only the daytime placebo levels. No changes were seen in any aspect of breathing pattern. The results are discussed in relation to the literature.

Time of development of tuberculosis in contacts.

The British Thoracic Association has recommended that close contacts of smear-positive cases of tuberculosis be followed up for at least 2 yrs (Tubercle 1978; 59: 245-259) but Selby et al. have recently suggested that a reduction in duration of follow up may be appropriate (Respir Med 1989; 83: 353-355). We have reviewed the results of contact procedures in Leeds to determine whether our experience supports reduction in the duration of follow up of contacts of patients with tuberculosis. In the 5-yr period 1983-87 there were 555 cases of tuberculosis (135 in Asians) of whom 42 (7.6%) were identified by contact procedures. In addition, contact procedures identified 35 children who were given chemoprophylaxis for positive Heaf tests (grade 2 or more). Of the 42 contacts with tuberculosis, 30 (71%) were diagnosed at the first visit, eight (19%) were diagnosed 6 months later and four (10%) were diagnosed 16-24 months after their initial clinic attendance. Five of the 42 contacts with TB were Asian, two of whom were diagnosed late. Seven out of ten non-Asian contacts who were diagnosed late had initial Heaf reactions of grade 1 or 2. All cases diagnosed late were contacts of a sputum-positive source. Poverty, as defined by residence in the Leeds Urban Priority Area, was associated with an increased risk of 3.3-fold for tuberculosis and a sixfold risk for chemoprophylaxis diagnosed by contact procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Response to nebulized ipratropium bromide and terbutaline in acute severe asthma.

Outpatient studies on asthmatics have shown that inhaled anti-cholinergic agents decrease in efficacy as FEV1 falls. To determine whether there are changes in response to inhaled anti-cholinergics during acute bronchoconstriction we have examined the effects of nebulized ipratropium and terbutaline in nine hospitalized patients recovering from acute severe asthma. At 6 a.m. each day throughout the admission, baseline PEFR was recorded. Ipratropium bromide, 1 mg, was nebulized and PEFR measured again 1 h later. Following this, terbutaline, 5 mg, was nebulized with further measurement of PEFR 15 min after nebulization. Results were analysed by paired t-tests. Mean baseline PEFR rose from 157 l m-1 on patients worst day to 300 l m-1 on their best day (P less than 0.01). Ipratropium improved mean PEFR by 55 l m-1 and 42 l m-1 on patients worst and best days respectively (P less than 0.01). Subsequent terbutaline improved mean PEFR on patients worst day by 23 l m-1 (P less than 0.01) but only by a non-significant 4 l m-1 on their best day (P = 0.09). Hence, ipratropium produced 96% of total bronchodilatation when baseline was highest, but achieved only 71% of total response when baseline was lowest, a highly significant change in response (P less than 0.01). We conclude that in acute severe asthma as baseline PEFR rises response to inhaled ipratropium improves, compared with total response to combined ipratropium followed by terbutaline.

Local anaesthesia for fibreoptic bronchoscopy: comparison between intratracheal cocaine and lignocaine.

In a double-blind study of 60 patients undergoing fibreoptic bronchoscopy we have compared the local anaesthetic effects of intratracheal injections of cocaine (4 ml, 2.5%) and lignocaine (4 ml, 4%). The two local anaesthetics were equally effective in terms of cough suppression, requirement for extra local anaesthetic, patient discomfort and operator acceptability.

Bambuterol: effective in nocturnal asthma.

Bambuterol was compared with placebo in 28 patients with nocturnal asthma in a randomized, double-blind cross-over study. All patients were symptomatic despite taking inhaled beta 2-agonists, inhaled corticosteroids (in 26 patients the median daily dose was 1500 micrograms) and oral corticosteroids (in eight patients the median daily dose was 10 mg). Patients demonstrated > or = 20% overnight fall in peak expiratory flow (PEF) for at least half of the 14-day run-in period. They then entered two treatment periods lasting 14 days when bambuterol 20 mg nocte and placebo were given in random order. Compared to placebo, bambuterol produced a 16% improvement in mean PEF on waking (271 l min-1 vs. 239 l min-1 P = 0.0002) and a 10% improvement in evening PEF measured 24 h after drug intake (318 l min-1 vs. 296 l min-1 P = 0.01). Bambuterol significantly reduced frequency of nocturnal awakening from 1.1 to 0.7 per night (P = 0.01) and nocturnal beta 2-agonist use from 2.7 to 2.1 puffs (P = 0.0004). Other nocturnal symptoms: cough, wheeze and dyspnoea were also significantly reduced during bambuterol treatment and patients quality of sleep was improved. The results indicate bambuterol (20 mg nocte) provides effective nocturnal bronchodilation with sustained effect for 24 h and may have a useful therapeutic role in the control of symptomatic nocturnal asthma.

Outbreak of tuberculosis in a poor urban community.

A woman from a poor urban community presented recently with pulmonary tuberculosis. Screening of contacts revealed 10 cases of tuberculosis, eight of whom were children. A further 10 children had grade 2-3 positive Heaf tests and were given chemoprophylaxis. Tuberculosis remains a potential problem, particularly in young unimmunized children in deprived areas.

The effects of various time patterns of alveolar CO 2 and O 2 on breathing in man.

We have studied the responses of human arterial chemoreceptors to various patterns of quick change of stimulation. (i) Transient abolition of hypercapnia lowers VE after 2 breaths (chemoreceptor latency) only if PAO2 is low, therefore hypoxia is necessary for an arterial chemoreceptor response to CO2. (ii) Alternate breaths of euoxia and hypoxia, and of eucapnia and hypercapnia, separately and combined, have no special effect on mean V. However, oscillating CO2 commonly causes breath-by-breath alternation of V, but only if hypoxia is present; oscillating only the low O2 seldom causes oscillation of V. Concluded (a) that chemoreceptor responses to delta-CO2 are quicker than to delta-O2; (b) that, above CO2 threshold, response to rising CO2 is equal and opposite to response to falling CO2. (iii) Three time patterns of PACO2 within single respiratory cycles have been compared in hypoxia. At a single mean arterial PCO2, a small sharp fall of PACO2 early in inspiration depresses mean V, while a smaller sharp fall of PACO2 late in inspiration increases mean V. Concluded that human respiratory system distinguishes between these rather similar patterns presumably through arterial chemoreceptor pathway since the phenomenon depends on the presence of hypoxia. The importance of exact timing is emphasised.

BCG immunisation of infants by percutaneous multiple puncture.

PIP: The safety, efficacy, and ease of administration of percutaneous multiple-puncture gun immunization of infants with BCG was compared with intradermal injection with a syringe. 214 consecutive infants scheduled for BCG were alternately given percutaneous or intradermal injections over the left deltoid muscle by 1 of 3 doctors. The Modified Heaf gun with 20 needles set to penetrate 1 mm, or a syringe with a 24 gauge short beveled needle was used. Doctors recorded bleeding and ease of administering the vaccine. The intradermal method was recorded as difficult in 36 cases, very difficult in 4, and the percutaneous method was deemed difficult in 1 case. Of the 200 infants remaining in contact 3-7 days later, 141 were read as positive. There were no significant differences in amount of bleeding or seroconversion. A difference in seroconversion was observed, however, between the different doctors using the intradermal technique. The percutaneous method resulted in less ulceration and scarring, gave consistent seroconversion, and was easier to administer.^ieng

Adrenaline and nocturnal asthma.

OBJECTIVE: To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN: Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given. PATIENTS: Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study. MAIN OUTCOME MEASURES: Peak expiratory flow rate and plasma adrenaline. RESULTS: Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine. CONCLUSION: A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma.

Asthma and airways collapse in two heritable disorders of connective tissue.

OBJECTIVES: This study investigated the clinical impression that there was an increased prevalence of respiratory disorders in both the Hypermobility Syndrome (HMS)/Benign Joint Hypermobility Syndrome (BJHS) and Ehlers-Danlos Syndrome (EDS), compared with the normal population. METHODS: A questionnaire was distributed to 509 subjects (221 healthy controls, 126 HMS, 162 EDS) who documented respiratory symptoms and previously diagnosed respiratory and atopic disorders. A subgroup of 157 responders underwent full clinical and serological assessments, and 57 subjects were assessed physiologically. RESULTS: A significant increase in the frequency of a wide range of respiratory symptoms and reduced exercise tolerance was observed in subjects with both HMS and EDS compared with controls. In particular, there was an increased prevalence of asthmatic symptoms (HMS: OR 2.4, 95% CI 1.4-4.1, p = 0.002; EDS: OR 3.1, 95% CI 1.8-5.2, p<0.001) and atopy (HMS: OR 2.7, 95% CI 1.6-4.5, p<0.001; EDS: OR 2.6, 95% CI 1.6-4.4, p<0.001), which was subsequently confirmed by clinical assessment. Pulmonary physiological studies revealed increased lung volumes, impaired gas exchange and an increased tendency of both the lower and upper airways to collapse. CONCLUSIONS: We have demonstrated, for the first time, that individuals with HMS/BJHS and EDS have respiratory symptoms in association with various pulmonary physiological abnormalities. The increased prevalence of asthma may be due to linkage disequilibrium between the genes causing these conditions or a function of the connective tissue defect itself. In the non-asthmatic population, changes in the mechanical properties of the bronchial airways and lung parenchyma may underlie the observed increased tendency of the airways to collapse.

Daytime variability of baroreflex function in patients with obstructive sleep apnoea: implications for hypertension.

Obstructive events during sleep in patients with obstructive sleep apnoea (OSA) cause large alterations in blood pressure, and this may lead to changes in baroreflex function with implications for long-term blood pressure control. This study examined the daytime variations in the responses to carotid baroreceptor stimulation in OSA patients. We determined the cardiac and vascular responses every 3 h between 09.00 and 21.00 h in 20 patients with OSA, using graded suctions and pressures applied to a neck collar. These responses were plotted against estimated carotid sinus pressures and, from these plots, baroreflex sensitivities and operating points were taken as the maximal slopes and the corresponding carotid sinus pressures, respectively. We found that at 09.00 h, sensitivity for the control of vascular resistance was at its lowest (--1.2 +/- 0.2% mmHg(-1), compared with --1.9 +/- 0.3% mmHg(-1) at 12.00 h, P < 0.02) and operating point for control of mean arterial pressure was at its highest (101.1 +/- 5.8 mmHg, compared with 94.1 +/- 5.8 mmHg at 12.00 h, P < 0.05). This is in contrast to previous data from normal subjects, in whom sensitivity was highest and operating point lowest at 09.00 h. We suggest that the higher baroreflex sensitivity and lower operating point seen in the mornings in normal subjects may provide a protective mechanism against hypertension and that this protection is absent in patients with OSA. It is possible that the reduced reflex sensitivity and increased operating point in the mornings may actually promote hypertension.

Interaction of chemoreceptor and baroreceptor reflexes by hypoxia and hypercapnia - a mechanism for promoting hypertension in obstructive sleep apnoea.

Asphyxia, which occurs during obstructive sleep apnoeic events, alters the baroreceptor reflex and this may lead to hypertension. We have recently reported that breathing an asphyxic gas resets the baroreceptor-vascular resistance reflex towards higher pressures. The present study was designed to determine whether this effect was caused by the reduced oxygen tension, which affects mainly peripheral chemoreceptors, or by the increased carbon dioxide, which acts mainly on central chemoreceptors. We studied 11 healthy volunteer subjects aged between 20 and 55 years old (6 male). The stimulus to the carotid baroreceptors was changed using graded pressures of -40 to +60 mmHg applied to a neck chamber. Responses of vascular resistance were assessed in the forearm from changes in blood pressure (Finapres) divided by brachial blood flow velocity (Doppler) and cardiac responses from the changes in RR interval and heart rate. Stimulus-response curves were defined during (i) air breathing, (ii) hypoxia (12% O(2) in N(2)), and (iii) hypercapnia (5% CO(2) in 95% O(2)). Responses during air breathing were assessed both prior to and after either hypoxia or hypercapnia. We applied a sigmoid function or third order polynomial to the curves and determined the maximal differential (equivalent to peak sensitivity) and the corresponding carotid sinus pressure (equivalent to 'set point'). Hypoxia resulted in an increase in heart rate but no significant change in mean blood pressure or vascular resistance. However, there was an increase in vascular resistance in the post-stimulus period. Hypoxia had no significant effect on baroreflex sensitivity or 'set point' for the control of RR interval, heart rate or mean arterial pressure. Peak sensitivity of the vascular resistance response to baroreceptor stimulation was significantly reduced from -2.5 +/- 0.4 units to -1.4 +/- 0.1 units (P < 0.05) and this was restored in the post-stimulus period to -2.6 +/- 0.5 units. There was no effect on 'set point'. Hypercapnia, on the other hand, resulted in a decrease in heart rate, which remained reduced in the post-stimulus period and significantly increased mean blood pressure. Baseline vascular resistance was significantly increased and then further increased in the post-control period. Like hypoxia, hypercapnia had no effect on baroreflex control of RR interval, heart rate or mean arterial pressure. There was, also no significant change in the sensitivity of the vascular resistance responses, however, 'set point' was significantly increased from 74.7 +/- 4 to 87.0 +/- 2 mmHg (P < 0.02). This was not completely restored to pre-stimulus control levels in the post-stimulus control period (82.2 +/- 3 mmHg). These results suggest that the hypoxic component of asphyxia reduces baroreceptor-vascular resistance reflex sensitivity, whilst the hypercapnic component is responsible for increasing blood pressure and reflex 'set point'. Hypercapnia appears to have a lasting effect after the removal of the stimulus. Thus the effect of both peripheral and central chemoreceptors on baroreflex function may contribute to promoting hypertension in patients with obstructive sleep apnoea.

Regular nebulised terbutaline in chronic obstructive airways disease: dose-response studies fail to detect tolerance.

1. To determine the effects of high dose terbutaline on the possible development of tolerance we have examined the influence on dose-response of regular nebulised terbutaline. 2. We studied 10 subjects with severe chronic obstructive airways disease (COAD), mean age 63 years mean (s.e. mean) PEFR 142 l min-1 (19), FEV1 0.77 1 (0.12) and FVC 1.93 (0.19). Cumulative dose-response curves were measured (PEFR, FEV1 and FVC) to six incremental doses of terbutaline (0.5-8 mg) before and 1, 4, 8 and 12 weeks after starting nebulised terbutaline 5 mg four times a day. 3. Maximal bronchodilatation (Emax) was calculated by polynomial regression. Responses were examined by analysis of variance. 4. Mean baseline PEFR increased by 32 l min-1 (P less than 0.05), FEV1 by 0.16 1 (NS) and FVC by 0.54 l (P less than 0.05) after 12 weeks. Initial mean Emax PEFR was maintained throughout the study. The percentage of mean Emax PEFR achieved by each cumulative dose of terbutaline either increased (0.5 mg, 1 mg and 2 mg, P less than 0.01) or was maintained (4 mg, 6 mg and 8 mg) throughout the study. 5. We conclude that in severe COAD regular nebulised terbutaline 5 mg four times a day produces a sustained improvement in baseline lung function without changes in dose-response which would suggest tolerance.

The effect of the circadian rhythm of vagal activity on bronchomotor tone in asthma.

1. The effect of the diurnal activity of the parasympathetic nervous system on bronchomotor tone and heart rate was studied in seven asthmatics with nocturnal asthma using both intravenous atropine and nebulised ipratropium at 04.00 h and 16.00 h. 2. A diurnal variation in vagal activity was demonstrated with higher vagal activity occurring at night. 3. There was a strong correlation between the initial response of both airway calibre and heart rate to vagal block both at 04.00 h and 16.00 h. However the duration of bronchodilation after vagal block was greater than with the heart rate suggesting differing sensitivities of pulmonary and cardiac muscarinic receptors to anticholinergic antagonists. 4. The bronchodilation seen after ipratropium was less than that after atropine suggesting that the intravenous route is preferable to study the physiological effect of vagal block in vivo.