Administration of the BCG vaccination using the multipuncture method in schoolchildren: a comparison with the intradermal method.

BACKGROUND: BCG vaccination using the multipuncture device (the Heaf gun) is recommended in the UK for infants and very small children only. The aim of this study was to investigate the rate of conversion of the tuberculin test, the safety and acceptability of BCG vaccination using the multipuncture device and to compare it with the conventional intradermal method in schoolchildren. METHODS: Schoolchildren attending schools in Tower Hamlets who were eligible for BCG vaccination were tuberculin tested using the Heaf gun. Those with grade 0-1 reaction were randomised to receive BCG vaccination using either the multipuncture or the intradermal method. The site of BCG vaccination was inspected after eight weeks for inflammatory changes and scarring. A questionnaire about pain and inflammation at the site of vaccination was completed. The Heaf test was repeated at eight weeks and its results were assessed by an examiner unaware of the results of the previous Heaf test and the method of BCG administration. The Heaf test conversion was deemed to have occurred if there was a change of at least one grade in the response. RESULTS: One hundred and sixty nine children (83 girls) of mean age 11.8 years completed the study, of which 81 received BCG by the multipuncture method. The Heaf test did not convert in 22 of 81 (27. 2%) receiving BCG by the multipuncture device compared with six of 88 (6.8%) who received the vaccine by the intradermal method (odds ratio 0.2, 95% confidence interval 0.07 to 0.55). The BCG scar was visible in all children who had intradermal BCG compared with 67 of 81 (81.8%) of the multipuncture group. The multipuncture method was less painful and caused fewer inflammatory changes than the intradermal method. CONCLUSIONS: In schoolchildren the multi-puncture device for administering BCG caused a lower rate of tuberculin conversion as measured by the Heaf test and less of an inflammatory response than the intradermal method. The method needs to be modified before it is applied on a wider scale to schoolchildren.

Comparison of characteristics of patients and treatment outcome for pulmonary non-tuberculous mycobacterial infection and pulmonary tuberculosis.

BACKGROUND: Patients with non-tuberculous mycobacteria are usually started on conventional antituberculous triple therapy once acid fast bacilli are detected, before the exact type of mycobacteria has been identified. The ability to identify the characteristics of patients with tuberculous and non-tuberculous mycobacteria may be helpful in identifying before treatment those patients more likely to have non-tuberculous infection. METHODS: A retrospective study was conducted of all patients in one unit in whom non-tuberculous mycobacteria were identified in sputum or bronchoalveolar washings in the period 1987-93. The pattern of drug resistance was determined from laboratory records, and all case notes and chest radiographs were reviewed to identify the underlying disease and treatment outcome. All cases were compared with a matched control group of patients with culture positive Mycobacterium tuberculosis diagnosed during the same period. RESULTS: In the period studied there were 70 non-tuberculous and 221 tuberculous isolates. The non-tuberculous bacteria were typed as follows: M xenopi 23 (33%), M kansasii 19 (27%), M fortuitum 14 (20%), others 14 (20%). Of those with non-tuberculous mycobacteria, 83% were white subjects compared with 47% for tuberculosis. Patients with non-tuberculous mycobacteria were older than those with tuberculosis. Pre-existing lung disease or AIDS was present in 81% of patients with non-tuberculous mycobacteria and in 17% of patients with tuberculosis. Sensitivity to rifampicin and ethambutol was seen in 95% of M xenopi and 96% of M kansasii isolates. Relapse occurred in 60% of cases infected with M xenopi, 20% infected with M kansasii, and in 7% of cases with tuberculosis. CONCLUSIONS: In the population studied non-tuberculous mycobacteria occurred most frequently in elderly white subjects with pre-existing lung disease. If mycobacteria are detected in this group, consideration should be given to the possibility of non-tuberculous infection before embarking on treatment. A combination containing rifampicin and ethambutol is effective. The relapse rate for infection with M xenopi is high and prospective studies of the effect of the above combination of antituberculosis drugs are needed.

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.

BACKGROUND: The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS: The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS: Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS: Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis.

Bronchial hyperresponsiveness in normal subjects during attenuated influenza virus infection.

Fourteen healthy male subjects with hemagglutination-inhibition antibody titers of 1:8 or less to homologous influenza A virus were studied. Six subjects received live, attenuated influenza virus by nasal drops and by aerosol. Although infection occurred in these six subjects, with the development of 4-fold or greater increases in hemagglutination-inhibition antibody titers, they remained asymptomatic. Eight subjects received placebo via the same route, and did not develop symptoms and showed no increase in antibody titer. Prior to administration of virus or placebo, histamine diphosphate aerosol increased airway resistance only slightly, and there was no difference between the virus and placebo groups. Two days after inoculation, bronchomotor responses in the placebo group were unchanged (p greater than 0.05), but in the virus-infected group, bronchomotor responses were significantly greater than in the preinfected state (p less than 0.01). Isoproterenol hydrochloride reversed and prevented the increase in airway resistance after histamine, suggesting that the bronchoconstriction was caused by smooth muscle contraction. Our findings indicate that transient, asymptomatic respiratory virus infection augments airway smooth muscle responses.

Effect of diazepam on sleep in patients with chronic airflow obstruction.

The effect of a single dose of diazepam on sleep and respiration was studied in nine patients with chronic airflow obstruction with moderate arterial hypoxaemia but no hypercapnia. Diazepam improved sleep duration without exacerbating nocturnal hypoxaemia and there was no change in the number of apnoeic events after a single 5 mg dose at night.

Platelet size in patients with chronic airflow obstruction with and without hypoxaemia.

Platelet size, expressed as mean platelet volume, was estimated in 35 patients with chronic airflow obstruction and a wide range of arterial oxygen tension (PaO2) values. In these patients there was a negative correlation between MPV and PaO2 (r = -0.70). Mean platelet volume was greater (9.41 (0.86) fl) in 20 patients with an arterial PaO2 of 8 kPa (60 mm Hg) or less than in 18 normal subjects (8.21 (0.63) fl; p less than 0.001). After 24 hours of supplemental oxygen treatment there was a small fall in mean platelet volume, from 9.47 (1.06) to 8.96 (0.8) fl (p less than 0.05) in 12 hypoxaemic patients (PaO2 breathing air less than or equal to 8 kPa) but no change in nine non-hypoxaemic patients. Larger platelets are considered to be haemostatically more active, leading to abnormal platelet function, which may contribute to the development of pulmonary vascular damage in chronic hypoxaemia. Supplemental oxygen may partially reverse these changes by modifying platelet size and activity.

Calf blood flow and oxygen carriage after reversal of polycythaemia secondary to hypoxic lung disease.

Reduction of packed cell volume has been recommended as a therapeutic procedure in patients with polycythaemia secondary to hypoxic lung disease. We have investigated the effects of this policy on blood flow and oxygen carriage to the calf in 12 such patients. Packed cell volume was decreased from 0.61 to 0.51 (mean) by isovolaemic haemodilution on a cell separator, with significant reductions in blood viscosity at high and low shear rates. Resting calf blood flow was unchanged but peak flow during reactive hyperaemia increased by 17% and 21% one and seven days after the procedure. Oxygen carriage to the calf at rest was initially unchanged but had fallen by 20% at seven days. During reactive hyperaemia oxygen carriage was not impaired by the reduction in packed cell volume since the rise in blood flow offset any reduction in arterial oxygen content. This study has shown that when blood flow is stressed during reactive hyperaemia oxygen carriage is not compromised by a therapeutic reduction in packed cell volume.

Effects of packed cell volume reduction on renal haemodynamics and the renin-angiotensin-aldosterone system in patients with secondary polycythaemia and hypoxic cor pulmonale.

Polycythaemia was corrected by erythrapheresis in ten patients with hypoxic cor pulmonale who were stable on regular diuretic therapy. Renal haemodynamics, renal function and the renin-angiotensin-aldosterone system were assessed before and afterwards. Before erythrapheresis effective renal plasma flow (ERPF) was reduced (63% predicted) but glomerular filtration rate (GFR) was preserved (88% predicted) by a rise in filtration fraction (FF) (138% predicted). A negative correlation existed between ERPF and packed cell volume (r = -0.723; P less than 0.02) and also between ERPF and PaCO2 (r = -0.710; P less than 0.05). Polycythaemia was sufficient to maintain renal oxygen delivery (97% predicted). After erythrapheresis systemic blood pressure, blood volume and blood viscosity all decreased. ERPF increased by 18% (P less than 0.02). FF fell by 11% (P less than 0.05) and GFR was unchanged. Renal oxygen delivery diminished by 25% (P less than 0.001). Plasma renin activity was increased in five patients and plasma aldosterone increased in two patients before erythrapheresis. No sustained fall occurred in plasma renin activity or plasma aldosterone, possibly because the haemodynamic consequences of the procedure had opposing actions on renin secretion. Although the reduction in FF would per se tend to enhance renal sodium and water excretion, a diuresis or natriuresis did not occur consistently.

Effects of haematocrit reduction on the haemoglobin-oxygen saturation curve in polycythaemia secondary to hypoxic lung disease.

20 patients were studied with chronic airflow obstruction and arterial hypoxaemia, 10 with and the other 10 without secondary polycythaemia. There were no differences in the value of the P50 for the two patient groups (Polycythaemics 3.31 +/- 0.17 kPa; non-polycythaemics 3.47 +/- 0.25 kPa). Isovolaemic haemodilution was performed by erythrapheresis on a cell separator in the 10 polycythaemic patients. Following removal of a mean 558 ml of packed red cells, there was a fall in the mean PCV from 0.57 +/- 0.02 to 0.46 +/- 0.04. There was no change in the value of the P50 when estimated 24 hrs after treatment. Reduction of an elevated haematocrit in hypoxic polycythaemic patients had no effect on the haemoglobin-oxygen saturation curve.

Effects of erythrapheresis on pulmonary haemodynamics and oxygen transport in patients with secondary polycythaemia and cor pulmonale.

Reducing packed cell volume has been advocated as a therapeutic procedure in patients with polycythaemia secondary to hypoxic cor pulmonale. The aim of this investigation was to evaluate the effects of this manoeuvre on resting pulmonary haemodynamics and tissue oxygenation in 12 such patients. The subjects were studied whilst they were breathing air (n = 12), after breathing 35% oxygen for 30 min (n = 11) and breathing air 30 min after isovolaemic reduction in packed cell volume, from 0.61 +/- 0.02 to 0.50 +/- 0.02 (mean +/- SEM), by erythrapheresis (n = 12). Initial values for the group were: PaO2 6.5 +/- 0.3 kPa; red cell mass 152 +/- 12% predicted; mean pulmonary artery pressure (PAP) 41 +/- 3 mmHg; cardiac index 3.1 +/- 0.31 min-1 m-2. Breathing 35% oxygen reduced PAP by 3.1 +/- 1.0 mmHg (P less than 0.02), cardiac index by 0.28 +/- 0.121 min-1 m-2 (P less than 0.05) and right ventricular stroke work by 0.05 +/- 0.01 J (P less than 0.01). Systemic vascular resistance was unchanged. Systemic oxygen transport increased and peripheral oxygen consumption was unaltered. Erythrapheresis reduced blood viscosity at shear rates 23 S-1 and 230 S-1. PAP fell by 2.4 +/- 1.1 mmHg (P less than 0.05) and cardiac index increased by 0.32 +/- 0.091 min-1 m-2 (P less than 0.01), but right ventricular stroke work was unchanged. Systemic vascular resistance was reduced by 25 +/- 7 kPa S l-1 (P less than 0.01). Systemic oxygen transport decreased but peripheral oxygen consumption was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Nocturnal hypoxia and sleep apnoea in asymptomatic obese men.

A disorder of breathing during sleep with a fall in arterial oxygen saturation (%SaO2) and apnoea is reported in association with obesity. In obese women an increased severity of oxygen desaturation and the appearance of sleep apnoea is often seen after the menopause whereas the factors influencing sleep-breathing patterns in obese men are uncertain. We investigated this by studying respiration during sleep in 20 asymptomatic obese men (mean wt 125 kg, age range 18-59 y) and 20 control men of normal weight (mean wt 67 kg, age range 19-67 y). In the obese men the mean awake %SaO2 measured in the supine position was significantly less than controls (obese 95 +/- 0.4, controls 97 +/- 0.2, P less than 0.01) and a greater fall in %SaO2 occurred in this group during sleep (mean asleep %SaO2 obese 90.5 +/- 0.9, controls 96 +/- 0.2, P less than 0.01). In addition, the minimum asleep %SaO2 was significantly less in the obese (mean minimum %SaO2 obese 75 +/- 3, controls 93 +/- 0.9, P less than 0.001). Sleep apnoea was uncommon and infrequent in the controls but was seen in nine obese men and was frequent throughout the night in seven of them. In the obese group increasing age and increasing obesity were not significantly correlated with an increased severity of nocturnal oxygen desaturation. We conclude that disordered sleep-breathing with marked oxygen desaturation and apnoea is a common finding in extremely obese men of all ages and suggest that this results from the mechanical impedence of breathing due to abdominal adipose tissue combined with abnormal central respiratory control.

Respiration and sleep in Parkinson's disease.

Sleep and respiration during sleep were studied in patients with idiopathic Parkinson's disease, patients with Parkinsonism with autonomic disturbance, and normal age and sex matched controls. Patients with idiopathic Parkinson's disease showed significantly reduced REM sleep, and more frequent and prolonged waking throughout the night. Hypoventilation and sleep apnoea did not occur in the idiopathic Parkinson's disease or normal groups, but respiration was disorganised with frequent central and obstructive apnoeas in the autonomic disturbance group. Respiratory rate during non rapid eye movement sleep was similar in the idiopathic Parkinson's disease and normal groups, but patients with idiopathic Parkinson's disease showed tachypnoea awake and during REM sleep.

Serum immunoreactive erythropoietin in hypoxic lung disease with and without polycythaemia.

We studied 20 patients with chronic airflow obstruction, 10 patients without polycythaemia and 10 patients with compensatory polycythaemia having respectively mean red cell mass 24.7 (SD 4.2) and 47.8 (SD 7.5) ml/kg, mean daytime PaO2 7.6 and 6.9 kPa, mean FEV1 0.85 and 0.821. Groups were matched for severity of daytime arterial hypoxaemia but nocturnal arterial oxygen desaturation was more severe in the patients with polycythaemia than in those without. We also studied six additional patients with chronic airflow obstruction and polycythaemia and 19 normal controls. Estimates of serum immunoreactive erythropoietin (siEp) in those without polycythaemia were 19 m-i.u./ml (geometric mean) with 95% confidence range 11-35 m-i.u./ml and stable during 3 months. In those with polycythaemia they were similar and consistent in five and, in the other five, higher on at least one occasion. There was no significant difference between siEp in daytime (12.00 hours to 16.00 hours) and morning (07.00 hours) samples but geometric mean estimates of erythropoietin in paired daytime and morning samples were higher and more variable in patients with polycythaemia than in those without. The geometric mean estimate of siEp in all patients with chronic airflow obstruction and polycythaemia was greater than in normal subjects but, despite secondary polycythaemia, siEp could be in the range for normal subjects. In the patients with polycythaemia we were unable to predict the finding of normal or elevated siEp. Changes in siEp after erythrapheresis (10-26% reduction in packed cell volume) were observed in the 10 patients with polycythaemia and in one without. One month after erythrapheresis, packed cell volume remained below and siEp was above initial pretreatment levels, implying an erythropoietin secretory response and that the development of secondary polycythaemia had induced a fall in siEp.