Outpatient inhaled nitric oxide in a patient with idiopathic pulmonary fibrosis: a bridge to lung transplantation.

Inhaled nitric oxide (INO) has been shown to improve oxygenation and decrease intrapulmonary shunt and pulmonary hypertension in various lung diseases. In this study we report a patient with end-stage idiopathic pulmonary fibrosis and pulmonary hypertension who received INO after coronary artery bypass surgery, with significant improvement in arterial oxygenation and pulmonary arterial pressure. Using a pulsing delivery system, the patient continued to receive outpatient INO for 30 months while waiting for lung transplantation. Exercise study and two-dimensional echocardiogram, after 3 months of inhaled NO, demonstrated continued benefits of INO for improvement of arterial oxygenation, pulmonary arterial pressure and exercise tolerance.

Alcohol availability and injury: the role of local outlet densities.

BACKGROUND: We analyzed the relationship between alcohol availability and injury that occurred during the 6 months before survey administration. METHOD: The data examined were from a general population survey administered to 13,440 California respondents as part of a community-based project to reduce alcohol-involved injury and death. Two separate analyses were performed. The first considered individual local outlet densities (which included both on-premise establishments such as bars and restaurants and off-premise establishments such as liquor and grocery stores) as they affect individual phone survey respondents' self-reported injuries. To address potential spatially autocorrelated errors and geographically lagged effects, a second analysis considered aggregate outlet densities within geographic areas as they affect the proportion of survey respondents who reported injury. No spatial autocorrelation or significant lagged effects were found, which supported our individual-level analyses. RESULTS: Our analyses indicated an association between both on-premise and off-premise individual-level outlet densities and self-reported injuries. CONCLUSION: Alcohol availability seems to be related to self-reported injury. The mechanisms behind this relationship, however, are not clear, and further study is indicated.

Utility of measurements of oxygen cost of breathing in predicting success or failure in trials of reduced mechanical ventilatory support.

OBJECTIVE: Test whether a change in oxygen consumption produced by a reduction in level of mechanical ventilatory support predicts failure to tolerate the reduction in level of support. DESIGN: Prospective study of the sensitivity and specificity of increased oxygen cost of breathing as a predictor of failure to tolerate a reduction in ventilatory support in patients undergoing weaning, using a protocol that incrementally reduces the level of mechanical ventilatory support. SETTING: University medical center. METHODS: We studied 228 trials in 30 patients who had required mechanical ventilatory support for at least 72 hours and who were being weaned using a standardized protocol that provided for three 30-minute trials of reduced mechanical ventilatory support per day, followed by ventilatory muscle rest. Using a metabolic monitor, we monitored oxygen consumption (V(O(2))) prior to and during 228 incremental reductions in level of mechanical ventilatory support conducted as part of a standardized weaning protocol. Oxygen cost of breathing was defined as the difference in V(O(2)) (Delta V(O(2))) during the trial of reduced mechanical ventilatory support, compared to a 30-minute resting period immediately before the trial. A successful trial was defined as one that could be continued for 30 minutes without development of clinical signs of ventilatory failure. Changes in V(O(2)) and the ratio of respiratory frequency to tidal volume (f/V(T)) during a weaning trial were evaluated as predictors for failure of a 30-minute trial of reduced ventilatory support. RESULTS: A 15% increase in oxygen cost of breathing predicted failure in the trial, with a sensitivity of 96.6%, specificity of 85.7%, positive predictive value of 98.5%, and negative predictive value of 72.0%. Neither change in V(O(2)) measured early in the trial nor f/V(T) proved to be as successful in predicting failure to tolerate an incremental reduction in ventilatory support. CONCLUSION: Change in V(O(2)) following an incremental reduction in level of mechanical ventilatory support may be a useful predictor for determining which patients will rapidly fail to tolerate that level of reduction.

Neighborhood characteristics of alcohol-related pedestrian injury collisions: a geostatistical analysis.

This study conducted a geostatistical analysis of ecological data to examine the relationships of neighborhood characteristics, including alcohol availability and alcohol consumption patterns to pedestrian injury collisions. The central research question asked whether it was possible to identify unique neighborhood characteristics related to alcohol- and non-alcohol-involved pedestrian injuries. It was hypothesized that greater numbers of alcohol-involved pedestrian injuries would be observed in areas with greater concentrations of alcohol outlets, even after adjusting for socioeconomic characteristics, environmental factors, and drinking patterns of neighborhood residents. It was also hypothesized that independent of drinking patterns and alcohol availability, greater numbers of pedestrian injuries would be observed in areas with higher unemployment, lesser income, greater population, and a predominance of younger or older age populations. Archival and individual-level data from a general population telephone survey were obtained from four California communities. The survey data included sociodemographic and drinking pattern measures. Archival data included environmental measures relevant to pedestrian travel and measures of alcohol availability. Units of analysis were geographic areas within each community defined by the spatial clustering of telephone survey respondents. The results showed that alcohol-involved pedestrian collisions occurred more often in areas with greater bar densities and greater population, and where the local population reported drinking more alcohol per drinking occasion. Pedestrian collisions not involving alcohol occurred more often in lower income areas with greater population and cross-street densities, and in areas having either younger or older age populations. The identification of neighborhood variables associated with pedestrian collisions has important implications for policy formation and targeted prevention efforts.

Drinking and driving: explaining beverage-specific risks.

OBJECTIVE: This study tested whether the association of beer drinking with drinking and driving is due to cultural norms or is an artifact arising from the demographic profile of beer drinkers (young and male), the drinking patterns of this subpopulation (frequent and heavy), and the venues in which they prefer to drink (bars and restaurants). METHOD: Telephone survey data from six U.S. communities were used to establish the demographic characteristics of drinkers, their consumption patterns, beverage preferences, preferred drinking venues and self-reported drinking and driving rates. The survey completion rate was 64.6%. A total sample of 5,231 drinkers was divided into test and validity samples. After deletion of cases with missing data, the test sample included 2,275 drinkers, of whom 985 had driven after drinking. RESULTS: Controlling for a broad set of covariates, the analyses showed that frequent consumers were more likely to drink outside the home, preferred beer and spirits to wine, and were more likely than others to drink and drive. Beverage preferences were not directly associated with drinking and driving. Beer drinkers, however, were from the subpopulation most likely to drink and drive: heavier drinking younger men, who prefer to drink at bars and restaurants. CONCLUSIONS: These results suggest that the association of beer consumption with drinking-driving arises from the circumstances in which the subpopulation of beer drinkers more commonly find themselves (as a result of their efforts to maximize, within economic constraints, the social and amenity value of drinking), as opposed to any culturally induced disposition beer drinkers may have to drink and drive.

Drinking over the life course within gender and ethnic groups: a hyperparametric analysis.

OBJECTIVE: This study examines drinking patterns over the life course among males and females and among three ethnic groups (whites, blacks and Hispanics) in order to compare gender group and ethnic group differences in alcohol use as a continuous function of age. METHOD: Data are from a general population sample of 13,553 respondents aged 12 to 80 interviewed by telephone in 20 urban areas of the United States. Drinking measures include total consumption, drinking participation, drinking frequency and average drinks per occasion. RESULTS: In the total sample over age cohorts, total consumption, participation and average drinks per occasion rose rapidly before age 21, peaked in young adulthood and declined gradually thereafter. Drinking frequency rose rapidly before age 21, but generally showed no decline thereafter. As expected, compared to women, men consumed more total alcohol, were more likely to participate in drinking, drank more often and drank more per occasion. Men did not differ from women in the age at which peak drinking occurred. Relationships of drinking to ethnicity were more complex. Although white total consumption exceeded that of blacks and Hispanics over the entire life course, the other drinking measures involved interactions in which white participation and frequency exceeded that of blacks and Hispanics in later adulthood, but black and Hispanic average drinks per occasion exceeded that of whites in later adulthood. CONCLUSIONS: Differences in drinking patterns over the life course among gender groups and ethnic groups are largely a result of differences in rates of change over age cohorts in alcohol use, both in rates of increase in youth and of decrease thereafter.

Sample selection bias in the emergency room: an examination of the role of alcohol in injury.

AIMS: Injury location, injury cause and patient drinking patterns were used to predict blood alcohol content (BAC) and self-reported drinking before injury using emergency room (ER) data. DESIGN: Models estimating both BAC and self-reported drinking among emergency room injury patients were used; the ER sample was also compared to an injured sample from the general population. SETTING: Data were from three of six communities participating in the project "Preventing Alcohol Trauma: a community trial". PARTICIPANTS: ER data were collected from nine hospitals on Friday and Saturday nights between 6 p.m. and 2 a.m. on alternate weekends from June 1992 to December 1995. Telephone survey data were collected between April 1992 and March 1996. MEASUREMENTS: Drinking measures included drinking frequency, drinks per occasion, and variance. Other measures involved injury time, location, and type; drinking before and after injury; and age, race, gender, education, marital status and household income. Model estimation corrected both for selection bias and censoring of the dependent measure. FINDINGS: The results indicate: (1) ER populations tended to be female, less well educated, non-white, poor and younger; (2) there were significant selection bias effects in the ER sample; (3) assaults were more likely to involve drinking than other injury types; (4) drinking patterns were significant non-linear predictors of alcohol involvement; and (5) self-reported drinking before injury was both a sensitive and specific indicator of measured BAC. CONCLUSIONS: Assaults uniquely involve the use of alcohol and selection bias may threaten ER study validity.

Age-related differences in risks of drinking and driving in gender and ethnic groups.

We examine the extent to which empirically observed age-related differences in rates of drinking and driving can be explained by concurrent differences in drinking patterns. Building on previous research showing significant age differences in drinking patterns between men and women and among three ethnic groups, Whites, Blacks, and Hispanics, our study considers whether there are unique gender and ethnic group differences in patterns of drinking and driving. Data were from 4395 respondents 12 to 80 years old in a general population survey of 20 urban areas in the United States. During the month preceding the interview, 1130 (25.7%) of all respondents had driven after having one or more drinks. Drinking pattern measures included drinking frequency, average drinking quantity, and the variance in the number of drinks consumed per occasion. To assess the relationships of drinking patterns to drinking and driving across age groups, two sets of analyses were conducted, one set in which age differences in drinking patterns were statistically controlled and one set in which they were not. Although the statistical control for drinking patterns reduced age differences between gender and ethnic groups, it did not eliminate them. The reduction demonstrated that part of observed group differences in driving after drinking over age among gender and ethnic groups is due to age-related differences in drinking patterns. However, despite controlling drinking patterns young respondents remained more likely to drink and drive. A supplementary analysis of self-reported incidents of driving while intoxicated (i.e., driving after having five or more drinks) further indicated that, controlling for drinking patterns, young respondents are most at risk.

Inhaled nitric oxide (40 ppm) during one-lung ventilation, in the lateral decubitus position, does not decrease pulmonary vascular resistance or improve oxygenation in normal patients.

OBJECTIVES: To determine the effects of inhaled nitric oxide (NO) on venous admixture (Qs/Qt), mean pulmonary artery pressure (MPAP), and pulmonary vascular resistance (PVR) in patients undergoing one-lung ventilation (1LV) in the lateral decubitus position. DESIGN: Prospective, blinded, crossover. SETTING: University hospital. PARTICIPANTS: Six adult patients scheduled for thoracotomy. INTERVENTIONS: Patients were anesthetized with thoracic epidural lidocaine, intravenous fentanyl, and inhaled isoflurane and were monitored with a systemic and pulmonary artery catheter (PAC). In the lateral decubitus position, the dependent lung was ventilated with 70% oxygen (O2) and 30% nitrogen (N2) for the control 1LV condition. For the experimental 1LV condition, the dependent lung was ventilated with the same gas concentration + NO at 40 ppm. Patients were alternated between the control and the experimental NO (40 ppm) conditions every 15 minutes for as long as the case would allow. MEASUREMENTS AND MAIN RESULTS: During all conditions, oxygenation, Qs/Qt, and pulmonary and systemic hemodynamics were measured in a double-blinded fashion. The mean PVR during 1LV was 128 +/- 39 (SD) dyne.s.cm(-5). Inhaled NO at 40 ppm did not affect MPAP, PVR, or Qs/Qt. CONCLUSIONS: Inhaled NO at 40 ppm, during 1LV in the lateral decubitus position, did not significantly decrease MPAP in patients with normal baseline PVR. Oxygenation and Qs/Qt did not change in this setting because MPAP was not altered. At present, interventions other than administration of inhaled NO should be applied to patients with normal PVR who experience hypoxia during one-lung ventilation.

Pulsed delivery of inhaled nitric oxide to patients with primary pulmonary hypertension: an ambulatory delivery system and initial clinical tests.

BACKGROUND: Inhaled nitric oxide (NO) has been shown to be a selective pulmonary vasodilator in certain patients with primary pulmonary hypertension (PPH). OBJECTIVES: The purpose of this study was to design and test a system for delivery of NO to awaken, ambulatory patients with PPH and to evaluate this system in the home setting. METHODS: The ambulatory delivery system consisted of a tank of 80 ppm of NO (balance N2), a modified gas-pulsing device, and nasal cannulas. The pulsing device was set to deliver NO for 0.1 s at the beginning of each inspiration. RESULTS: Using this system, eight patients with PPH were studied with pulmonary artery catheters in place. Inhalation of NO led to significant reductions in both mean pulmonary arterial pressure (PAPm) (51 +/-12 to 43 +/- 10 mm Hg; p=0.001) and pulmonary vascular resistance (PVR) (790 +/- 285 to 620 +/- 208 dyne x s x cm-5; p=0.01). Three of the eight patients had both greater than 20% and greater than 30% decreases in PAPm and PVR, respectively. No exhaled NO or N02 was detectable in any of the eight patients. One patient was discharged home from the hospital on a regimen of inhaled NO. At 9 months, no adverse effects were noted and the system was working well. CONCLUSIONS: Pulsed delivery of inhaled NO to ambulatory patients with PPH, via nasal prongs, is feasible and, in some patients, leads to significant improvement in pulmonary hypertension. Inhaled 09NO, therefore, may have a role in the long-term treatment of patients with PPH.

Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction in dogs. A practical nitric oxide delivery and monitoring system.

Nitric oxide (NO) is a potent dilator of vascular smooth muscle that likely represents an important endothelium-dependent relaxing factor. Recent interest has focused on inhaled NO as a pulmonary vasodilator. The purpose of this study was to design a reliable NO delivery system with on-line monitoring of NO and nitrogen dioxide (NO2) concentrations, and to test the effects of inhaled NO in a dog model of acute hypoxic pulmonary vasoconstriction (HPV). Six canines were studied. Marked HPV was induced using a hypoxic gas mixture. Using a standard blender. NO was delivered through a volume-cycled ventilator. We were able to rapidly adjust the delivered NO concentration using this system. An on-line chemoluminescence analyzer was used to continuously measure NO and NO2 concentrations. Inhaled NO at 40 and 80 ppm for 30 min rapidly reversed HPV in all animals (PVR 502 +/- 154 dynes.s.cm-5 with hypoxia, 244 +/- 52 with 40 ppm NO, 227 +/- 47 with 80 ppm NO). No significant NO2 or methemoglobin production was noted during the study. We conclude that inhaled NO can be easily delivered through a ventilator and the dose rapidly adjusted, NO and NO2 concentrations can be monitored continuously on-line, inhaled NO rapidly reverses HPV in dogs, and with short-term NO inhalation, there is no significant NO2 or methemoglobin formation. Inhaled NO may, therefore, have a future clinical role as a new agent in the diagnosis and treatment of other forms of pulmonary hypertension.

Improvement in pulmonary hypertension and hypoxemia during nitric oxide inhalation in a patient with end-stage pulmonary fibrosis.

A patient with severe interstitial pulmonary fibrosis, hypoxemia, pulmonary hypertension, and cor pulmonale was given inhaled nitric oxide (NO) followed by intravenous PGE1 to assess the reversibility of pulmonary hypertension. During NO inhalation, there was marked reduction in pulmonary vascular resistance, increased cardiac output, and dramatic improvement in arterial oxygenation. There was no effect on systemic vascular resistance. In contrast, intravenous PGE1 led to rapid arterial oxygen desaturation and worsened dyspnea. The beneficial responses to inhaled NO in this patient suggest that, even in severe chronic lung disease, reversible pulmonary vasoconstriction is present. Inhaled NO thus has a potential therapeutic role as a selective pulmonary vasodilator in patients with interstitial pulmonary fibrosis and cor pulmonale.

Biological factors and psychometric intelligence: a review.

Results from a synthesis of correlations between psychometric intelligence and two physical traits, head size and body size, are reported. Within-family studies are reviewed for evidence of pleiotropy, the effect of a single genetic factor on two traits. Studies are also reviewed to determine whether prenatal effects bias twin studies, leading to underestimates of genetic influence. An N-weighted mean partial correlation (controlling height) of .10 between intelligence and head size was found. Using a method developed by Van Valen (1974), the correlation of intelligence and brain size was estimated as .29 based on all the intelligence/head-size studies of adults and adolescents, and .44 based on studies measuring intelligence with IQ tests. The N-weighted mean partial correlations (controlling age) of intelligence and height were .18 for children and .22 for adults. The within-family studies indicated that pleiotropy may contribute to the correlation of intelligence with head size and to the correlation of intelligence with body size. Prenatal effects are not an important source of bias in twin studies or for heritability estimates based on them.

Intracerebral infection of mice with ovine strains of Chlamydia psittaci: an animal screening test for the assay of vaccines.

Intracerebral inoculation of mice with the A22 strain of ovine C. psittaci gave a reproducible non-lethal infection; multiplication of the inoculum could be quantitated by titration of mouse brain extracts in tissue culture. Mice which had recovered from infection, or which had been inoculated subcutaneously with living organisms of A22 strain, showed solid resistance to intracerebral challenge infection. However, subcutaneous inoculation of formalin-inactivated chlamydia showed little protective effect unless given in very high dosage. Inactivated vaccines of the heterologous ZC113 strain gave better, but still incomplete, protection against A22 challenge infection than did the homologous inactivated vaccine. The implication of these findings is discussed. The mouse intracerebral protection test appears to be a suitable laboratory procedure for assessing the potency of vaccines against enzootic ewe abortion and for comparing the immunological cross-protection between the various strains of C. psittaci currently found in the natural disease in sheep.

Severe Chlamydia psittaci sepsis in pregnancy.

Two patients with severe chlamydial sepsis in pregnancy are described and compared with previously published case reports. The infections appear to have been zoonotic, the patients acquiring their infections as a result of exposure to enzootic abortion of ewes. This is an important but poorly recognised human infection which because of its severity in pregnancy deserves consideration in patients with an appropriate occupational history.

Acute placentitis and spontaneous abortion caused by chlamydia psittaci of sheep origin: a histological and ultrastructural study.

A sheep farmer's wife who had been assisting with lambing developed an influenza like illness in the 28th week of pregnancy. After five days of malaise she spontaneously delivered a stillborn infant; she became acutely ill during the immediate postpartum period with septicaemic shock, acute renal failure, and disseminated intravascular coagulation. The diagnosis was made by isolation and identification of Chlamydia psittaci from the placenta, fetal heart blood, and fetal lung, together with maternal serological evidence. The prominent histological and ultrastructural appearances of the chlamydial placentitis are described.

Abortion due to infection with Chlamydia psittaci in a sheep farmer's wife.

A farmer's wife who had helped with lambing aborted spontaneously in March after a short febrile illness in the 28th week of her pregnancy. She developed disseminated intravascular coagulation post partum with acute renal failure and pulmonary oedema. Recovery was complete after two weeks of hospital care. A strain of Chlamydia psittaci, probably of ovine origin, was isolated from the placenta and fetus. The patient's serum showed rising titres of antibody against chlamydia group antigen; the placental and fetal isolates; and a known ovine abortion, but not a known avian, strain of C psittaci. IgG against both ovine abortion and enteric strains of C psittaci was detected, but IgM against only an abortion strain was detected. Histological examination showed pronounced intervillus placentitis with chlamydial inclusions in the trophoblast but no evidence of fetal infection or amnionitis. Laboratory evidence of chlamydial infection was found in an aborting ewe on the farm in January and in remaining sheep and lambs in July. Doctors should recognise the possible risk to pregnant women in rural areas where chlamydial infections in farm animals are widespread.

Isolation of Chlamydia psittaci from nasal and conjunctival exudate of a domestic cat.

A feline strain of Chlamydia psittaci was isolated in tissue culture from nasal and conjunctival swabs from a free range domestic cat with bilateral conjunctivitis and rhinitis, living in the Liverpool area of the UK. The isolate was identified as C psittaci on the basis of its characteristic inclusion morphology in cell culture and by means of specific indirect immunofluorescence with known C psittaci specific antiserum. The isolate could be differentiated from other chlamydiae of non-feline origin by its amino acid nutritional requirements.

Simple transport medium for the isolation of Chlamydia psittaci from clinical material.

Infectious elementary bodies of Chlamydia psittaci in tissue samples from field cases of enzootic abortion were placed in five different transport media (A to E). In one medium, in the absence of refrigerative storage, the organism remained viable for 30 days and at 4 degrees C for 34 days. This was medium D; it consisted of sucrose (74.6 g/litre), K2HPO4 (1.237 g/litre), L-glutamic acid (0.721 g/litre), fetal calf serum (10 per cent v/v), vancomycin and streptomycin (100 micrograms/ml) and nystatin and gentamicin (50 micrograms/ml). Samples of this transport medium were supplied to veterinary investigation centres throughout the UK. Of 1862 samples submitted for diagnosis of enzootic abortion only 1.55 per cent were so contaminated that chlamydiae could not be detected. This transport medium permits the isolation of C psittaci from clinical material for up to about one month, even in the absence of conventional storage facilities.