Analyses of the NRAMP1 and IFN-gammaR1 genes in women with Mycobacterium avium-intracellulare pulmonary disease.

Mycobacterium avium-intracellulare (MAI) pulmonary disease causes substantial morbidity in a population of older, HIV-negative women without preexisting lung disease. The cause for disease susceptibility in these patients is unknown, although their relative phenotypic homogeneity suggests the existence of a common, subtle immune deficiency. An investigation was undertaken to determine if these patients have a defect in their natural resistance-associated macrophage protein (NRAMP1) or interferon gamma receptor 1 (IFN-gammaR1) genes. A point mutation in murine nramp, an autosomal recessive gene controlling resistance to intracellular organisms, correlates with overwhelming Mycobacterium bovis infection in mice. The corresponding region in human NRAMP1, two coding polymorphisms and one promoter NRAMP1 polymorphism, as well as two IFN-gammaR1 polymorphisms, were analyzed to determine if an allele was present to correlate with disease. Genomic DNA was purified from eight women with MAI pulmonary disease and four controls. Regions of interest were amplified by PCR; three sites were analyzed by restriction fragment length polymorphisms, and three were analyzed using denaturing high-performance liquid chromatography. The NRAMP1 promoter polymorphism of 18 additional random controls was analyzed by microsatellite sizing. No allelism was found in NRAMP1 corresponding to the murine mutation, or in the two coding regions. In the NRAMP1 promoter microsatellite, 3 of 8 patients were heterozygous for a dinucleotide sequence insertion, as were 10 of 22 controls. None of the patients had either of the two known IFN-gammaR1 mutations. In conclusion, in women with MAI pulmonary disease, there is no evidence for a genetic defect in NRAMP1 or IFN-gammaR1 to correlate with disease.

A national census of those attending UK accident and emergency departments with asthma. The UK National Asthma Task Force.

OBJECTIVE: To obtain a representative national picture of the type of people with asthma attending accident and emergency (A&E) departments in the UK, the reasons why they attend, and to determine the proportion admitted to hospital. DESIGN: A national census involving questionnaires. SETTING: 100 A&E departments throughout the UK. SUBJECTS: All those with asthma attending because of asthma during a one week period in September 1994. RESULTS: Details were obtained about 1292 attendances. About half of all attendances were by adults and half by children, and 87.8% were previously diagnosed asthmatics; 18.8% of adult attenders were unemployed. Perceived severity of asthma was the reason for attendance in 65.5%, but 11.5% reported non-availability, or perceived non-availability, of the general practitioner (GP) as the reason for attending. One fifth of adults had been kept awake by their asthma for over three nights before attendance. 425 of the 1292 attenders (32.9%) had been admitted to hospital in the previous 12 months and 316 (24.5%) had attended the A&E department in the previous three months. Only 24.6% of attenders had had contact with their general practitioner in the previous 24 h. 61.6% of under-5 attenders (n = 341) were admitted to hospital; the figures for those aged 5-15 and 15+ years and above were 265 (41.4%) and 665 (38.7%). CONCLUSIONS: Many people with asthma attend A&E departments without first having seen their GP. In many adult cases the asthma, while severe, is not acute, but a high proportion of both adults and children are admitted to hospital. Many of these attendances and admissions are repeat attendances. To enhance the quality of care provided to those with asthma may require easier access to primary care, enhanced patient education, or enhanced health professional education. Further study is needed of a variety of potential interventions.