Didanosine for zidovudine-intolerant patients with HIV disease.
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Didanosine↗
Biomedical subjects
J H Darbyshire
Publications and source records attributed to J H Darbyshire.
Patterns of tuberculosis in Indian and Pakistani/Bangladeshi patients: effects of age, date of first entry and ethnic group.
The pattern of tuberculosis in Indian, Pakistani and Bangladeshi patients in Blackburn (1978-1987) was compared with that for England and Wales (MRC Survey), with particular reference to the proportion with parenchymal lung disease, by a generalized linear model allowing for age, ethnic group and time since first entry. In Blackburn, the proportion with lung disease was higher in Pakistani/Bangladeshi (46%) compared with 28% in Indians, although in both groups this increased with age. In the MRC Survey, the proportions with lung disease were similar (Pakistani/Bangladeshi 36.5%, Indians 34%) but there was an increase in lung disease with age and year since first entry in the Indian ethnic group only. The reasons for the differences, and their implications are discussed.
Age Factors↗
HIV infection and tuberculosis.
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Africa↗
Early HIV infection: to treat or not to treat?
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AIDS-Related Complex↗
Six year follow up of lung function in men occupationally exposed to formaldehyde.
The long term effects of formaldehyde on the respiratory tract have been investigated in a group of 164 workers exposed daily to the chemical during the production of urea formaldehyde resin, together with 129 workers not exposed to free formaldehyde. Exposure was classified as high (corresponding to an eight hour time weighted exposure of more than 2.0 ppm), medium (0.6 to 2.0 ppm), or low (0.1 to 0.5 ppm). Twenty five per cent of workers had had high exposure at some time and 17% moderate exposure. Both the exposed and unexposed groups had an annual assessment that included lung function. The proportion with self reported respiratory symptoms was similar in the two groups, 12% and 16% reporting breathlessness on hurrying and 26% and 20% wheezing. The initial forced expiratory volume in one second (FEV1) was within 0.5 l (approximately one standard deviation (SD)) of the predicted value (by age and height) in 65% of the exposed and 59% of unexposed workers and more than 0.5 l below the predicted value in 9% of exposed and 11% of unexposed workers. The mean decline in FEV1 was 42 ml a year (SD 45) in the exposed group and 41 ml a year in the unexposed group (SD 40 ml a year). The rate of decline showed the expected association with smoking in the unexposed group, but in the exposed group the mean rate of decline in the never smokers was similar to that in current smokers. There were, however, relatively few never smokers and considerable variation in the rates of decline. In the exposed group no association was found between the rate of decline and indices of exposure to formaldehyde. Thus there is no evidence from this study of an excess of respiratory symptoms or decline in lung function in the workers exposed to formaldehyde. The similar rate of decline of FEV1 however in never smokers and smokers of the exposed group is consistent with findings of other studies for workers exposed to formaldehyde and to toluene di-isocyanate.
Adolescent↗
Controlled trial of natamycin in the treatment of allergic bronchopulmonary aspergillosis.
Allergic bronchopulmonary aspergillosis often requires treatment with oral corticosteroids to control the host response to Aspergillus fumigatus. In a double blind study 25 patients with allergic bronchopulmonary aspergillosis taking maintenance oral corticosteroids were randomly allocated to receive 5 mg natamycin or placebo by nebuliser twice daily for one year. The primary aim of the study was to assess the steroid sparing potential of natamycin. Standardised reductions in corticosteroid dosage were therefore undertaken every five weeks, unless clinically contraindicated. Five patients were withdrawn in the first four months: two (1 natamycin, 1 placebo) died, two (1 natamycin, 1 placebo) had suspected drug reactions, and one (natamycin) was non-compliant. The pretreatment characteristics of the 20 patients (10 in each group) who completed the study were similar, 17 (9 natamycin, 8 placebo) having evidence of recent disease activity. At the end of the study prednisolone dose had been reduced by a similar amount in each group (median natamycin 2.25 mg, placebo 2.5 mg). Evidence of disease activity during the study year (transient shadowing on the chest radiograph, blood eosinophilia, or increases in antibodies to A fumigatus, or any combination of these) was observed in similar numbers of patients in each group (5 natamycin, 7 placebo). There was no evidence that natamycin conferred benefit on these patients with allergic bronchopulmonary aspergillosis.
Adult↗
Short course chemotherapy for pulmonary tuberculosis in routine service in Kenya.
The results are reported of the application of a short-course regimen for pulmonary tuberculosis in routine service in three districts in Kenya. All patients were treated in hospital for one month receiving Streptomycin, Isoniazid, Rifampicin and Pyrazinamide daily and followed by Rifampicin and Isoniazid daily on outpatient basis for five months. There was no failure of chemotherapy among 194 patients with pre-treatment sensitive strains at the end of chemotherapy. Six (3.9%) had a doubtful status but none relapsed during follow-up. Among 123 patients assessed after completion of follow-up only one (0.8%) relapsed and 16 of 22 patients with pretreatment resistant strains had a favourable response at the end of chemotherapy and follow-up. The therapeutic results achieved are excellent under programme conditions though of necessity with some amount of supervision that is not routinely available. Considering the advantages of short course regimens, a case for the choice of an appropriate short regimen to be used nationwide in the near future is made.
Adolescent↗
Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis.
Thirty-eight patients with bronchiectasis and daily expectoration of purulent sputum despite conventional antibiotic courses were randomly allocated to receive a sachet of amoxycillin (3 g) or matched placebo twice daily for 32 weeks in a double-blind study. Nine patients (four amoxycillin, five placebo) were withdrawn from the study treatment; the response of the two patients (both on amoxycillin) withdrawn within the first six weeks was not assessed. The pretreatment characteristics of the two groups were similar. Independent assessment of overall response based on patients' diary cards showed that a higher proportion improved in the amoxycillin group (11 of 17) than in the placebo group (four of 19; p = 0.02). Patients in the amoxycillin group spent significantly less time confined to bed and away from work during treatment. The frequency of exacerbations during the study treatment phase was similar in the two groups but they were less severe than before study treatment in the amoxycillin group. There was a greater reduction in purulent sputum volume between exacerbations during the study treatment in the amoxycillin group to 20 per cent of pretreatment volume than in the placebo group (88 per cent of pretreatment volume, p = 0.008), although the concentrations of Haemophilus spp. in sputum between exacerbations was similar in the two groups. Adverse effects experienced were minor except in one patient (amoxycillin) withdrawn after developing a rash and in six patients (three amoxycillin, three placebo) who had diarrhoea lasting more than one week necessitating withdrawal of two patients (one amoxycillin, one placebo) from study treatment. Sputum and stool cultures collected regularly during the study showed no important changes in the bacterial flora in either group. Prolonged higher-dose antibiotic therapy in these patients with severe purulent bronchiectasis significantly reduced the host (patient) inflammatory response to colonizing microorganisms and reduced morbidity.
Adult↗
Tuberculosis in prisons.
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Acquired Immunodeficiency Syndrome↗
Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis.
In a randomised, controlled study alternate day prednisolone with an initial high dose phase ("prednisolone only series") has been compared with cyclophosphamide plus alternate day low dose prednisolone ("cyclophosphamide-prednisolone series") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed. Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two of the 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamide-prednisolone series (three of the seven had stopped treatment because of toxicity). Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive of outcome. Analyses of subgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment.
Adult↗
Controlled clinical trial of a regimen of two durations for the treatment of isoniazid resistant pulmonary tuberculosis.
Patients with pulmonary tuberculosis who were failures of primary chemotherapy with strains resistant to isoniazid or to isoniazid and streptomycin were allocated at random to receive a regimen of rifampicin and ethambutol for 6 (4RE) or 9 months (7RE), supplemented in both treatment series by streptomycin plus pyrazinamide for the first 2 months. The patients were treated in hospital for the first 2 months and thereafter treatment was supervised on a daily basis in the nearest health institution by an appointed member of staff or at home by responsible members of the community. A total of 306 patients was admitted and 226 patients remained for analysis at the end of chemotherapy, 179 with a strain resistant to isoniazid alone and 47 with a strain resistant to isoniazid and streptomycin. There were only two failures at the end of chemotherapy, one in the 6-month series who had resistance to both isoniazid and streptomycin pretreatment, and one in the 9-month series who had resistance to isoniazid alone. For the 144 patients with initial resistance to isoniazid alone assessed up to 30 months, the relapse rates were low in both series: 4% for the 72 patients in the 6-month series and 3% for the 72 patients in the 9-month series. However, for the 34 patients with resistance to both drugs, three of the 14 in the 6-month but none of 20 in the 9-month series relapsed.
Adolescent↗
Changes in tuberculosis notification rates in the white ethnic group in England and Wales between 1953 and 1983.
Since the early 1960s notification rates for tuberculosis in England and Wales for the whole population have been influenced by high rates in certain ethnic groups. Using data based on country of birth from the British (Thoracic and) Tuberculosis Association surveys of 1965 and 1971, and based on ethnic origin from the Medical Research Council surveys in 1978/79 and 1983, rates for the white ethnic group have been estimated at those four times, and compared with the published rates for the whole population in 1953, when only a very small proportion was of non-white ethnic origin. Between 1953 and 1983 the notification rate for the white ethnic group fell from 122.2 to 11.3 per 100,000 for males, an annual decline of 7.7%, the corresponding rates for females being 90.1 and 5.8, an annual decline of 8.8%. The greatest annual declines occurred between 1953 and 1965, 9.4% for males and 11.2% for females. The annual declines in the most recent period, 1978/79 to 1983, were 6.9% for males and 7.3% for females. In both sexes the decline was greatest in the 15-24 year age group and least in the oldest age group, and this has led to a change in the age pattern of annual notification rates. The highest rates in both sexes occurred in young adults in 1953 but in the oldest age groups in 1983. There is however no evidence of any cohort experiencing an increase in notification rate with increasing age.
Adolescent↗
A study of the use of maternity and child welfare clinics in case-finding for pulmonary tuberculosis in Kenya.
This investigation is the seventh in a series of case-finding studies in Kenya. It explores the potential value of questioning mothers attending maternity and child welfare (M & CW) clinics to identify tuberculosis suspects (individuals aged 6 years or more with a cough for 1 month or more or hemoptysis) living in their households. The study was carried out in all the eight M & CW clinics in two divisions (populations 86,000 and 112,000) of two different districts. The mothers were asked to give a standard letter, which explained the possible importance of a chronic cough, to each suspect they identified and invited the suspect to attend the district hospital chest clinic. Each suspect attending the clinic was entered in a special register and two sputum specimens were collected. For those who failed to attend, the specimens were collected at a home visit. Of the total of 342 suspects living in the two study areas who were registered at the M & CW clinics during 1 year, 261 were identified by the mothers but 19 denied having received the standard letter. The remaining 81 had not been identified by mothers but had attended the M & CW clinics on their own initiative. Of the 242 suspects who received the letter, 89 (39%) attended the hospital chest clinic, 74% within a week of the letter being issued from the M & CW clinic. The main reasons given for not attending the hospital chest clinic by the remaining suspects were financial or because their cough had improved or disappeared. Sputum was collected from 238 suspects and examined bacteriologically: in six (2.5%) it was positive for tubercle bacilli on smear and culture and in a further two (0.8%) the sputum was positive on culture only. Of those attending the hospital chest clinic 2.9% were smear- and culture-positive and 4.7% were culture positive. This method of case-finding has yielded disappointing results, for only 4% of the estimated annual incidence of smear-positive cases was detected.
Adult↗
Coronavirus IBV: virus retaining spike glycopolypeptide S2 but not S1 is unable to induce virus-neutralizing or haemagglutination-inhibiting antibody, or induce chicken tracheal protection.
Avian infectious bronchitis coronavirus (IBV) inactivated by beta-propiolactone induced partial protection of the trachea in up to 40% of chickens following one intramuscular inoculation 4 to 6 weeks prior to challenge. Retention of an intact tracheal ciliated epithelium 4 days after challenge was the criterion of protection. There was no correlation between protection and serum titres of virus-neutralizing (VN) and haemagglutination-inhibiting (HI) antibody, which were maximal at about 4 weeks after inoculation. Virus from which the S1 but not the S2 (spike-anchoring) spike glycopolypeptide had been removed by urea did not induce protection or VN or HI antibody. Four intramuscular inoculations of monomeric S1 induced VN and HI antibody in two and four chickens respectively. These results indicate that VN and HI antibodies are induced primarily by S1, that intact spikes are a major requirement for the induction of protective immunity and that this property is probably associated with S1.
Animals↗
Changes in annual tuberculosis notification rates between 1978/79 and 1983 for the population of Indian subcontinent ethnic origin resident in England.
In two national surveys of tuberculosis notifications in England conducted in 1978/79 and 1983 the estimated annual notification rates for the Indian subcontinent (Indian, Pakistani, and Bangladeshi) ethnic groups were considerably higher than the rate for the white ethnic group. The mean annual decline in rates between the surveys appeared to be greater for the Indian and the Pakistani and Bangladeshi ethnic groups, 15% and 16% respectively, than for the white ethnic group (7%). Data from two small sample population surveys, the National Dwelling and Housing Survey in 1978 and the Labour Force Survey in 1983, were used to calculate the rates. However, comparison of the estimates for the population of Indian subcontinent ethnic origin in England from these surveys revealed discrepancies between them. Additional information from the Labour Force Survey on the year of first entry to the United Kingdom (UK) permitted the calculation of new estimates for the 1978 population, and based on these estimates the annual notification rates for 1978/79 were 287 per 100,000 for the Indian and 286 per 100,000 for the Pakistani and Bangladeshi ethnic groups. The rates for 1983 were 178 and 169 respectively, and the mean annual decline between the surveys was 11% for the Indian and 12% for the Pakistani and Bangladeshi ethnic groups. There were important changes in the characteristics of the population of Indian subcontinent ethnic origin in England between 1978 and 1983, and therefore the rates for both surveys have been standardised by the method of direct standardisation to a common reference population. Standardizing for year of entry to the UK, place of birth (UK or abroad), age, and sex reduced the mean annual decline in the notification rate to 4% for the Indian and 9% for the Pakistani and Bangladeshi ethnic groups. The much greater reduction in the rate of decline in the Indian ethnic group is due to the substantial decline between the surveys in the proportion of recent immigrants, the group with the highest annual notification rate, in that population. Future trends will continue to be influenced by immigration patterns, but it will also be important to monitor the rates among the increasing proportion of the population born in the UK or resident in England for more than five years.
Bangladesh↗
[Results of a therapeutic trial comparing a 6-month regimen to a 12-month regimen in the treatment of pulmonary tuberculosis in the Algerian Sahara. Final report: results 3 years after the onset of treatment].
This study has compared a daily 6-month short-course chemotherapy regimen and a daily 12-month standard duration regimen in the treatment of smear positive pulmonary tuberculosis in a rural area of Algeria where the population contains a relatively high proportion of nomads. The 6-month regimen (6M) was isoniazid and rifampicin throughout with ethambutol and pyrazinamide in addition for the first 2 months, and the 12-month regimen (12M) was isoniazid and ethambutol supplemented by streptomycin during the first month. All the 601 patients admitted had one or more sputum smears positive on examination in the local laboratory and 70% had a positive culture in the reference laboratory in Algiers. Most patients were admitted to hospital initially for one or two months where chemotherapy was fully supervised and subsequently it was self-administered. In both nomads and settled residents known to have fully sensitive strains of tubercle bacilli pretreatment the 6-month regimen was highly effective with no failures during chemotherapy and only 3% relapses after stopping chemotherapy in 126 patients compared with a combined failure rate during chemotherapy and relapse rate of 21% in the 152 patients receiving the 12-month regimen (P less than 0.001). The results in patients with isoniazid-resistant strains pretreatment were also significantly better for the 6-month than for the 12-month regimen, one of 15 and 8 of 17 patients respectively being classified as failures or relapses (P = 0.03). To assess the results which might be achieved by these regimens under programme conditions the outcome at 3 years was also assessed in all patients admitted to the study irrespective of whether the disease was confirmed in the reference laboratory or at independent assessment and whether or not the allocated chemotherapy was modified or further courses of chemotherapy were given. At 3 years, 82% of the 6M and 80% of the 299 12M patients had achieved a favourable status and only one 6M patient and 4 12M patients were still known to have active disease with a positive culture. A further 23 6M and 22 12M patients were known to have died, 11 in each series probably or definitely from tuberculosis. The remaining 28 6M and 34 12M patients were lost from follow-up, but 24 and 22 respectively had completed their allocated chemotherapy before defaulting. It was estimated that, overall, 272 (94%) of the 6M and 263 (91%) of the 12M patients had a favourable status at 3 years.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Studies of case-finding for pulmonary tuberculosis in outpatients at 4 district hospitals in Kenya.
This investigation is the sixth in a series of case-finding studies in Kenya. It explores the potential for case-finding by the identification of tuberculosis suspects (individuals with a cough for 1 month or more) through careful screening of general outpatients attending 4 district hospitals for the first time. Of 2299 suspects identified among 87 845 new outpatients attending the hospitals, 4.7% had culture-positive pulmonary tuberculosis, 3.6% having sputum positive on smear as well. In the 3 hospitals with radiographic facilities, 1.3% of suspects (whose sputum was negative on culture) were considered on review of their clinical history and chest radiograph by an independent assessor to have radiographically active tuberculous lesions and a further 2.5% to have inactive lesions. The proportion of bacteriologically positive cases per 1000 of the general population aged 6 years or more decreased as the distance of their homes from the hospital increased (P less than 0.001 for the trend). However, the proportion of cases per 1000 of the suspects identified increased as the distance of their homes from the hospital increased (P less than 0.001 for the trend). History of cough for between 1 and 12 months was the most useful factor for the identification of cases of tuberculosis among the suspects, and would have identified 92% of the smear-positive cases from the examination of 70% of the suspects; a history of weight loss identified 84% of the smear-positive cases from the examination of 64% of the suspects. A history of weight loss and/or a history of cough for between 1 and 12 months would have detected all the smear-positive cases from the examination of 89% of the suspects. The proportion of bacteriologically positive cases in the younger suspects aged 9-32 years (who had been eligible for a mass BCG campaign) was greater among the non-vaccinated than among the vaccinated suspects, 4.9% and 2.3% respectively (P=0.04), implying protection from vaccination of the order of 50%.
Adolescent↗