To demonstrate human leukocyte antigen (HLA)-linked control of susceptibility to pulmonary tuberculosis, 25 multiple-case families were tissue typed for class I and class II HLA specificities. Eight non-HLA genetic markers were also examined for any indication of other genetic factors that might influence the Mycobacterium tuberculosis infection. Observations on estimated HLA haplotype segregation in the sibs suggest that 84% of the affected sibs shared significantly more often than expected a common haplotype with each other than the normal unaffected sibs (P less than 0.001). Also, there was a skewed transmission of DR2 to diseased offspring from diseased parents (21 of 27) and to diseased offspring from healthy parents (15 of 17) in contrast to the transmission of DR2 from either group of parents to healthy offspring (six of 15 and 10 of 16, respectively). The segregation of non-HLA polymorphisms did not deviate significantly from the expected figures. These data provide strong evidence in favor of DR2-associated susceptibility to pulmonary tuberculosis.

HLA antigens were studied by serology and polymerase chain reaction-based sequence-specific oligonucleotide hybridization techniques in 153 patients with pulmonary tuberculosis (PTB) and 289 healthy controls. HLA-DR2 was present more frequently in PTB patients than in controls (51% vs. 36.3%; corrected P[Pc]=.029, relative risk [RR] = 1.8). The DR2 association was stronger in patients in the drug-failure group (n=56; Pc=.000012, RR=3.7) than in healthy controls and in patients in the drug-responder group. No significant deviation was observed in HLA allelic frequencies in various patient groups, as determined by radiographs of lung lesions. Molecular subtyping of DR2 revealed that the bulk of the allele was DRB1*1501 and DRB1*1502 in patients and controls. There was no skewing of the frequency of these molecular subtypes of DR2 in patients, suggesting that the whole DR2 molecule or its closely linked gene(s) may be involved in governing patient susceptibility to PTB and, particularly, development of the severe drug-resistant form of the disease.

The subdivisions of the lung volume, pulmonary mechanics, and resting steady state pulmonary transfer factor were measured in 31 patients with bronchographically proven bronchiectasis. In seven patients the process of gas exchange was further investigated by fractionating the total alveolar-arterial oxygen tension gradient into diffusion, distribution, and true shunt components.A restrictive type of ventilatory defect with varying degrees of airway obstruction was observed in a majority of the patients; the airway obstruction was partially reversed by a bronchodilator. Dynamic compliance was usually decreased and the pulmonary resistance increased.Pulmonary transfer factor was decreased in proportion to the number of segments involved. Vital capacity, maximum breathing capacity, and dynamic compliance bore a less significant correlation with the extent of disease. The degree of airway obstruction, as judged by pulmonary resistance, was independent of the extent of disease.All the patients were hypoxaemic and some had hypercapnia as well. The alveolar-arterial oxygen tension gradient was widened primarily because of distributional abnormalities and, to some extent, by the presence of true right-to-left shunts. The latter amounted to 13-6% of the total cardiac output.Surgical resection of the affected lobe or segments resulted in a further deterioration of all the parameters of pulmonary function tested.

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The clinical and pathological features of acute pulmonary oedema of high altitudes have been the subject of several recent reports (Houston, 1960;Hultgren et al., 1961; Penialoza, 1962;Arias-Stella and Kruger, 1963;Nayak, Roy, and Narayanan, 1964;Menon, 1965;Singh et al., 1965), but the haemodynamic effects of the illness are not well delineated (Fred et al., 1962;Hultgren et al., 1964). The purpose of this communication is to present data on the circulatory and respiratory parameters observed in (1) 6 subjects with high altitude pulmonary oedema studied at 3658 metres within 24 hours of the onset of the illness, and (2) 3 subjects restudied 5 times after recovery. SUBJECTS AND METHODSClinical History. Cases 1, 2, and 3 (Table I)