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.

Efficacy and safety of short-term administration of aerosolised recombinant human DNase I in adults with stable stage cystic fibrosis.

Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis. High levels of DNA in the sputum make the sputum viscous and difficult to expectorate. Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to reduce the viscoelasticity of the sputum from CF patients. We have done a phase II double-blind randomised placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for 10 days. All patients had forced vital capacity (FVC) above 40% predicted and were clinically stable. Patients were followed up for 42 days from the start of drug/placebo administration. All 71 randomised patients, aged 16-55, completed every aspect of the study and baseline characteristics were similar in the two groups. Baseline forced expiratory volume in one second (FEV1) was 46% of predicted for patients randomised to rhDNase, and 48% for those randomised to placebo; and baseline FVC was 76% of predicted for both groups. The mean percentage change in FEV1 from baseline was a 13.3% rise on rhDNase and a 0.2% fall on placebo (p < 0.001). FVC rose 7.2% in the rhDNase group and 2.3% in the placebo group (not significant). There were no life-threatening adverse events and no anaphylactic reactions. There was no significant difference in side-effects between the groups. This study confirms that short-term administration of rhDNase in stable patients with cystic fibrosis is safe and improves lung function.

Sequential treatment with low dose almitrine bismesylate in hypoxaemic chronic obstructive airways disease.

Daily dose schedules of 100-200 mg of almitrine bismesylate improve arterial blood gases in patients with hypoxaemic chronic obstructive airways disease (COPD) but dose related side effects are evident. In the present study, daily doses approximately half of those previously used were employed in a randomised double blind manner in 85 patients (age 35-79 years) with hypoxaemic COPD. After a one month period to check stability of arterial blood gases, patients were allocated to almitrine (A) or placebo (P) using an unequal code (60% A, 40% P). Tablets, 50-100 mg daily were stopped for one month after 3, 6 and 9 months to counteract drug accumulation. 50 patients in group A and 35 in group P were comparable on entry; mean age 65 (SD = 8) yrs., Pao2 7.8 (0.7) kPa (58.3 (5.0) mmHg), PaCO2 5.8 (0.8) kPa (43.2 (6.0) mmHg), forced expiratory volume in one second--FEV1 0.89 (0.25) l and 6 minute walking distance 296 (97) metres. The improvement in baseline PaO2 values was the same 0.8-1.3 kPa (6-9.8 mmHg) as with previous higher dose therapy. Approximately one third of patients did not respond, defined as PaO2 elevation > 0.67 kPa (5 mmHg). The sequential dosing scheme stabilised blood levels of almitrine within the therapeutic range of 280-300 ng.ml-1. After withdrawal of therapy arterial blood gases and spirometry reverted to pre-treatment levels, suggesting no permanent reversal of pathophysiology. Dose related side effects of breathlessness, indigestion and peripheral neuropathy were not observed. Nerve conduction studies revealed no difference in peripheral nerve dysfunction in hypoxaemic COPD between active and placebo therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Fine structural changes in idiopathic pulmonary haemosiderosis.

Lung biopsies from four children and two adults with idiopathic pulmonary haemosiderosis have been examined by transmission electron microscopy. No qualitative differences were identified between the children and the adults but the changes were more severe in the children. In each case the major damage involved the capillary endothelium and its basement membrane. Capillary endothelial swelling was very noticeable and in one case the endothelium was attenuated but gaps between endothelial cells were very difficult to find. Capillary narrowing and platelet aggregation were common. The capillary endothelial basement membrane showed focal thickening, particularly on the thick side of the air/blood barrier, but no electron dense deposits were identified. Degenerative changes in the alveolar epithelium were not so marked as those in the capillary endothelium and the epithelial basement membrane was normal except for haemosiderin deposition. Haemosiderin was also noted on elastin and within intra-alveolar macrophages. Other secondary changes included mild interstitial oedema and fibrosis. These findings indicate that the major site of damage is the alveolar capillary, but provide no evidence of the cause of the disease.

The initial surgical intensive care unit nursing experience with the permanent total artificial heart.

The Utah experience with implantation of the Jarvik-7 demonstrated that this TAH can be implanted successfully within the confines of the adult human mediastinum. The device has proven its capacity to sustain the patient's life without causing the patient pain. There is no immunologic rejection of the heart, and in fact most other organ systems appear to accommodate well to the artificial pump. As is the nature of any experiment, problems were encountered and questions raised. Laboratory investigation is underway to test the durability of various prosthetic valves in the Jarvik-7. Subsequent recipients of the Jarvik-7 implant have experienced embolic episodes. The quick connects are being scrutinized closely for a predilection for thrombi accumulation. The significance of reperfusing persons who have adapted to chronic states of low cardiac output is still not completely understood. The ramifications of rapidly reperfusing cellular and organ systems is currently being studied. Ethical considerations as described by Woolley are being discussed at length. Protocols are being established with flexible guidelines for management of the TAH patient. Some of these protocols include infection control, anticoagulation, and hematological guidelines; nutritional support, physical therapy, and rehabilitation programs. More extensive preoperative evaluation and testing protocols are being developed. Further clarifications of the nurses' responsibility in maintaining the TAH equipment are being made. Certification methods are being developed to ensure the nurse's competency. Data collection methods are being refined by adapting information flow charts and computer hard copies specifically to the TAH patient. The Utah experience with TAH implantation in humans is still in its infancy. Twenty years of animal research provided a strong base from which to approach the first human subject. However, "there are limitations in extrapolating information from the best animal models and relating it to the critically ill human being." Animals used in the research were young and healthy; human candidates who meet the criteria for implant are generally extremely debilitated. This, coupled with the absence of human historical perspective or precedent, left many unknowns for the first TAH recipient. Our patient expired on March 23, 1982 of pseudomembranous colitis. Despite his death after 112 days of life sustained on the mechanical heart, he participated in a successful pioneering scientific experiment.

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.