Alpha 1 antitrypsin deficiency in association with both cirrhosis and chronic obstructive lung disease in two sibs

Alpha₁ antitrypsin deficiency was present in three sibs; in two of these both liver and lung disease developed whereas the third remained healthy. Two of the sibs of the proband (one affected and the unaffected) were of protease inhibitor (Pi) phenotype ZZ, the parents were of phenotype MZ. The proband died at 11 years of age of massive intra-abdominal hemorrhage, secondary to hepatic cirrhosis. She had panlobular emphysema of all lung lobes, and destruction of bronchiolar elastica was demonstrated. In the other affected sib, the disease seems to run a more benign course. Presently, at 12 years of age, he has clinical but no laboratory evidence of cirrhosis, no clinical but laboratory evidence of lung involvement. Liver biopsy specimens from the two affected sibs at three and four and a half months of age, respectively, revealed a similar picture of incipient perilobular cirrhosis. Liver cells were swollen and, especially toward the peripheries of the lobules, were shown to contain many diastasefast, periodic acid-Schiff-positive granules and hyaline masses. These were increased in number and size in the second liver biopsy specimen obtained from the girl at six years of age, but their distribution and occurrence were less uniform at this age and even less so at necropsy.     

Using school staff to establish a preventive network of care to improve elementary school students' control of asthma

School-based asthma interventions delivered by nonschool staff have been successful but are limited in their reach because of the cost and effort of bringing in outside educators and their inability to establish improved communication about asthma between schools, families, and primary care providers (PCPs). To address these problems, Columbia University and the New York City Department of Education and the New York City Department of Health and Mental Hygiene undertook a randomized controlled trial to test the efficacy of a comprehensive school-based asthma program. In this intervention, school nurses were trained to facilitate the establishment of a preventive network of care for children with asthma by coordinating communications and fostering relationships between families, PCPs, and school personnel. PCPs also received training regarding asthma management. There was limited support for this model. While case detection helped nurses identify additional students with asthma and nurses increased the amount of time spent on asthma-related tasks, PCPs did not change their medical management of asthma. Few improvements in health outcomes were achieved. Relative to controls, 12-months posttest intervention students had a reduction in activity limitations due to asthma (-35% vs -9%, p < .05) and days with symptoms (26% vs 39%, p = .06). The intervention had no impact on the use of urgent health care services, school attendance, or caregiver's quality of life. There were also no improvements at 24-months postintervention. We faced many challenges related to case detection, training, and implementing preventive care activities, which may have hindered our success. We present these challenges, describe how we coped with them, and discuss the lessons we learned.     

A population-based study of congenital diaphragmatic hernia outcome in New South Wales and the Australian Capital Territory, Australia, 1992-2001

Purpose

The aim of the study was to describe the incidence and survival of infants born with congenital diaphragmatic hernia (CDH) in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), Australia.

Methods

A population-based cohort study of all infants inclusive up to 1 month of age diagnosed with CDH in NSW and the ACT between 1992 and 2001 was conducted. Data sources were the NSW and ACT Neonatal Intensive Care Data Collection (Neonatal Intensive Care Units Study), NSW Birth Defects Register, Population Health Research Centre of ACT Health, and NSW Midwives Data Collection.Individual risk factors for mortality were assessed using the χ² test with P < .05 being considered statistically significant. Multivariate analysis was performed using logistic regression to adjust for potential confounding variables.

Results

From the databases used, the incidence of CDH in NSW and the ACT was 1 per 3800 births. Of 242 infants identified with CDH, 8% underwent termination of pregnancy, 10% were stillborn after 20 weeks' gestation, and 82% were liveborn.Most liveborn infants (70%) were delivered at term with a 64% survival, whereas 30% were preterm with a 35% survival. For liveborn infants, the overall preoperative mortality was 35% with 56% surviving to discharge.Logistic regression identified a low 5-minute Apgar score, prematurity, and air leak as independent risk factors for mortality.

Conclusions

This population-based study of CDH provides us with baseline data for our states. Mortality is high in preterm infants and in the preoperative period. Avoiding preterm delivery and improving preoperative stabilization are the measures most likely to improve survival.     

Elevated endothelial nitric oxide bioactivity and resistance to angiotensin-dependent hypertension in 12/15-lipoxygenase knockout mice

12/15-Lipoxygenase (12/15-LOX) plays a pathogenic role in atherosclerosis. To characterize whether 12/15-LOX also contributes to endothelial dysfunction and hypertension, regulation of vessel tone and angiotensin II (ang II) responses were characterized in mice deficient in 12/15-LOX. There was a twofold increase in the magnitude of l-nitroarginine-methyl ester-inhibitable, acetylcholine-dependent relaxation or phenylephrine-dependent constriction in aortic rings isolated from 12/15-LOX(-/-) mice. Plasma NO metabolites and aortic endothelial NO synthase (eNOS) expression were also elevated twofold. Angiotensin II failed to vasoconstrict 12/15-LOX(-/-) aortic rings in the absence of L-nitroarginine-methyl ester, and ang II impaired acetylcholine-induced relaxation in wild-type, but not 12/15-LOX(-/-) rings. In vivo, 12/15-LOX(-/-) mice had similar basal systolic blood pressure measurements to wild type, however, blood pressure elevations in response to ang II infusion (1.1 mg/kg/day) were significantly attenuated (maximal pressure, 143.4 +/- 4 mmHg versus 122.1 +/- 5.3 mmHg for wild type and 12/15-LOX(-/-), respectively). In contrast, vascular hypertrophic responses to ang II, and ang II type 1 receptor (AT1-R) expression were similar in both strains. This study shows that 12/15-LOX(-/-) mice have increased NO biosynthesis and impaired ang II-dependent vascular responses in vitro and in vivo, suggesting that 12/15-LOX signaling contributes to impaired NO bioactivity in vascular disease in vivo.     

In vitro comparison of four aminoglycoside antibiotics: sisomicin, gentamicin, tobramycin, and BB-K8

The activity of sisomicin, gentamicin, and tobramycin against 273 clinical bacterial isolates was about equal (except for greater activity of tobramycin against Pseudomonas) and was greater than that of BB-K 8 as determined by antibiotic dilution methods in agar and broth.