SUMMARY Virus-induced IL-1β and IL-18 production in macrophages is mediated via a caspase-1 pathway. Multiple microbial components, including viral RNA, are thought to trigger assembly of the cryopyrin inflammasome and consequent caspase-1 activation. Here we demonstrate that cryopyrin−/− and caspase-1−/− mice are more susceptible than wildtype controls following infection with a pathogenic influenza A virus. This profile of enhanced morbidity correlates with decreased neutrophil and monocyte recruitment and reduced cytokine and chemokine production. Despite the effect on innate immunity, cryopyrin-deficiency was not associated with any obvious defect in virus control or on the later emergence of the adaptive response. Early epithelial necrosis was, however, more severe in the infected mutants, with extensive collagen deposition leading to later respiratory compromise. These findings reveal a novel function of the cryopyrin inflammasome in healing responses. Cryopyrin and caspase-1 are clearly central to both innate immunity and to moderating lung pathology in influenza pneumonia.

A third of the world’s population uses solid fuel derived from plant material (biomass) or coal for cooking, heating, or lighting. These fuels are smoky, often used in an open fire or simple stove with incomplete combustion, and result in a large amount of household air pollution when smoke is poorly vented. Air pollution is the biggest environmental cause of death worldwide, with household air pollution accounting for about 3·5–4 million deaths every year. Women and children living in severe poverty have the greatest exposures to household air pollution. In this Commission, we review evidence for the association between household air pollution and respiratory infections, respiratory tract cancers, and chronic lung diseases. Respiratory infections (comprising both upper and lower respiratory tract infections with viruses, bacteria, and mycobacteria) have all been associated with exposure to household air pollution. Respiratory tract cancers, including both nasopharyngeal cancer and lung cancer, are strongly associated with pollution from coal burning and further data are needed about other solid fuels. Chronic lung diseases, including chronic obstructive pulmonary disease and bronchiectasis in women, are associated with solid fuel use for cooking, and the damaging effects of exposure to household air pollution in early life on lung development are yet to be fully described. We also review appropriate ways to measure exposure to household air pollution, as well as study design issues and potential effective interventions to prevent these disease burdens. Measurement of household air pollution needs individual, rather than fixed in place, monitoring because exposure varies by age, gender, location, and household role. Women and children are particularly susceptible to the toxic effects of pollution and are exposed to the highest concentrations. Interventions should target these high-risk groups and be of sufficient quality to make the air clean. To make clean energy available to all people is the long-term goal, with an intermediate solution being to make available energy that is clean enough to have a health impact.

Pneumocystis carinii pneumonia has emerged as a significant cause of morbidity and mortality in immunocompromised patients with and without AIDS. To determine differences in P. carinii pneumonia in patients with and without AIDS, the P. carinii parasite numbers, lung inflammatory cell populations, gas exchange, and survival were assessed in a series of 75 consecutive patients with P. carinii pneumonia. Bronchoalveolar lavage was used to quantify the parasite and inflammatory cell numbers in these patients. The data from this study indicate: (1) patients with P. carinii pneumonia and AIDS have significantly greater numbers of P. carinii per ml of lavage compared to other immunocompromised patients with P. carinii pneumonia (p less than 0.0001); (2) patients with P. carinii pneumonia and AIDS also have significantly fewer neutrophils recovered in the lavage compared to other immunocompromised patients with P. carinii pneumonia (p = 0.0001); (3) patients with AIDS and P. carinii pneumonia have higher arterial oxygen tensions than those patients with P. carinii pneumonia in conditions other than AIDS (p = 0.008); and (4) increased lavage neutrophils (rather than parasite number) correlate with poorer oxygenation and poorer patient survival (p = 0.01). This investigation demonstrates substantial differences in lung inflammation and parasite number during P. carinii pneumonia in patients with and without AIDS. The data further suggest that lung inflammation contributes substantially to respiratory impairment in patients with P. carinii pneumonia.

The effect of the competitive inhibitor of L-arginine, N0-monomethyl L-arginine (L-NMMA) on the response of the rat anococcygeus muscle to nonadrenergic, non-cholinergic (NANC) inhibitory nerve stimulation has been examined. L-NMMA causes a rise in muscle tone and inhibition of the response to nerve stimulation. The stereoisomer D-NMMA is without effect. The rise in tone and inhibition of the nerve response is reversed by L-arginine. Another analogue, L-canavanine, which is effective against L-arginine utilization in the macrophage, was without effect on the rat anococcygeus. These results provide indirect evidence for nitric oxide (NO) or a substance releasing NO as the transmitter of the NANC nerves in this tissue.

The combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF.

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The minimal inhibitory concentrations of 601 clinical isolates of anaerobic bacteria to 10 different antimicrobial agents were determined by an agar-dilution technique. Nearly all strains were resistant to kanamycin and gentamicin, although moderate activity to both drugs was noted with Fusobacterium sp., anaerobic cocci, some strains of Bacteroides melaninogenicus, and nonsporeforming gram-positive bacilli. Chloramphenicol at 12.5 ,ug/ml inhibited all but three of the strains tested. Tetracycline at 6.25 ,ug/ml had high activity against all groups tested, with the exception that only 39% of strains of Bacteroidesfragilis were inhibited at this concentration. Excluding certain species of Bacteroides, the majority of anaerobes were inhibited by penicillin at 3.1 ,ug/ml or less and by cephalothin at 12.5 ,ug/ml or less. Lincomycin at 6.2 ,ug/ml or less was active against nearly all strains. Erythromycin at a concentration of 3.1 ,ug/ml was active against B. fragilis; however, erythromycin was less active against the other groups. Most of the minimal inhibitory concentrations of lincomycin exceeded those of clindamycin by fourfold; Rifampin inhibited virtually all strains at 3.1 /Ag/ml.

This study applied the structured observation technique developed by Mintzberg to the high school principalship. Observation of the activities performed by five principals resulted in a characterization of school administration that paralleled private sector management in many respects. Principals exercised building-level authority over such matters as organizational maintainance, the administration of the instructional program, pupil control, and extra-curricular activities. They spent comparatively little time on affairs external to the school organization. Although their work pace was hectic, there were certain cyclic features which could be identified.William J. Martin is Principal of Williamsport High School, Williamsport, Pennsylvania, and Donald J. Willower is Professor of Education, The Pennsylvania State University.The principal of the modern high school is among the most familiar of community figures. However, the more popular descriptions of the principalship are based upon quite indirect methods of investigation. These include surveys that measure the characteristics of persons in the position, and questionnaires that assay their self perceptions.' METHODOLOGY An obvious strategy for examining role behavior is to observe the task-performance patterns of persons in the position in question. Surprisingly, this strategy seems to have been ignored by most educational researchers with a few noteworthy exceptions.2 Mintzberg maintains that such direct research is a technique that makes up in depth what it lacks in at UNIV NEBRASKA LIBRARIES on April 12, 2015 eaq.sagepub.com Downloaded from