Effects of autoprothrombin II-A on epinephrine-induced platelet aggregation of normal- and coumadin-treated dogs.

Platelet-rich plasma from dogs and from coumadin-treated dogs aggregated at the same optimum concentration of epinephrine. Neither protein C nor its active form called autoprothrombin II-A was necessary for aggregation of dog platelets with epinephrine. For platelet aggregation, suboptimal concentrations of epinephrine were potentiated by addition of purified autoprothrombin II-A. The latter, by itself, induced platelet aggregation in high concentration.

Somatostatin-induced changes in the hemostasis of rats.

Somatostatin (SRIF) given intravenously, either as a single bolus or as a 2 hr infusion caused a significant prolongation of partial thromboplastin time (PTT) and depressed platelet counts and platelet aggregation in the rat. Following daily injections of protamin-zinc SRIF for 2 weeks the platelet count returned to normal, PTT remained prolonged and platelet aggregation was enhanced. The doses of SRIF used in this work were adequate to suppress the secretion of insulin and glucagon by the isolated pancreatic islets of treated animals.

Prognostic value of exercise-induced ventricular ectopic activity for mortality after acute myocardial infarction.

To evaluate the importance of ventricular ectopic activity on the predischarge treadmill exercise test for predicting mortality in patients after acute myocardial infarction (AMI), 163 patients with uncomplicated AMI were studied using symptom limited low-level treadmill exercise testing and 24-hour ambulatory electrocardiographic monitoring before hospital discharge. All patients were followed for at least 2 years or until recurrent AMI, coronary artery bypass grafting or death. Seventeen patients (10%) died during the follow-up period, 15 patients (9%) had recurrent AMI and 45 patients (28%) underwent bypass surgery. Ventricular ectopic activity was the only single treadmill abnormality that predicted subsequent cardiac death; angina pectoris, electrocardiographic ST-segment depression and a hypotensive blood pressure response did not. The mortality rate in the 20 patients with exercise-induced ventricular ectopic activity was 25%, compared with 8% in those without (p less than 0.004). Furthermore, in this patient population, exercise-induced ventricular ectopic activity was a much better predictor of cardiac death than that detected by ambulatory monitoring. Thus, ventricular ectopic activity on the predischarge treadmill exercise test is an important risk factor for death after AMI.

Prognostic value of electrocardiographic exercise testing and noninvasive assessment of left ventricular ejection fraction soon after acute myocardial infarction.

To determine the relative value of clinical findings, results of low-level treadmill electrocardiographic (ECG) exercise testing and left ventricular (LV) ejection fraction (EF) for predicting cardiac events in the year after an acute myocardial infarction (AMI), 72 patients who had had an uncomplicated AMI were studied with either radionuclide angiography or 2-dimensional echocardiography to assess LVEF and a low-level treadmill exercise test before hospital discharge. All patients were followed for 1 year. Nineteen patients (26%) had at least 1 cardiac event: coronary artery bypass grafting (11 patients), recurrent AMI (6 patients) or cardiac death (6 patients). Multiple logistic regression analysis revealed that total cardiac events were predicted by exercise ECG ST-segment depression or angina, prior AMI, ventricular ectopic activity during exercise and digoxin therapy (cumulative r = 0.58, p less than 0.001). Coronary artery bypass grafting was predicted by exercise ECG ST-segment depression or angina (r = 0.29, p = 0.01). Recurrent AMI was predicted by exercise ECG ST-segment depression or angina, prior AMI and ventricular ectopic activity during exercise (cumulative r = 0.49, p less than 0.001). Cardiac death was predicted by an LVEF of 40% or less (r = 0.38, p = 0.01). The presence of both an LVEF of 40% or less and ECG ST-segment depression on treadmill exercise testing defined a subgroup of patients with a high incidence of early cardiac death (33%).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional blood flow distribution during extracorporeal membrane oxygenation in rabbits.

To study regional blood distribution during extracorporeal membrane oxygenation, we stabilized three groups of five rabbits each (3 to 5 kg) on venoarterial bypass at a flow rate of 30 ml/kg/min. Albumin aggregates (15 to 30 microns) labeled with technetium 99m were injected into the left ventricle during bypass (ventricle), the perfusion cannula during bypass (cannula), and the left ventricle with no bypass (control). Animals were put to death, organs were removed, and the percent distribution was determined with a gamma camera. The Student Newman-Keuls test was used for statistical comparisons. Distribution to both the heart and brain in the cannula group were decreased from control by 55% and 35%, respectively. Distribution to the brain in the ventricle group was also decreased from control by 39%. Intestinal distribution was elevated above control in the ventricle group by 37%, whereas musculoskeletal distribution was elevated 33% above control in the cannula group. No significant changes were noted for the kidneys, stomach, or liver. These data suggest that overall perfusion of some vital organs may be significantly reduced during low-flow extracorporeal membrane oxygenation, specifically in the case of the heart and brain, which may be deprived of oxygenated blood.

The effects of indoor environmental factors on respiratory illness in primary school children in Kuala Lumpur.

The effects of indoor environmental factors on respiratory illness were studied in 15017-12 year old school children in Kuala Lumpur. Exposure to mosquito coil smoke for at least three nights a week was independently associated with asthma and persistent wheeze. Passive smoking, defined as sharing a bedroom with an adult smoker, was independently associated with a chest illness in the past year. No relationships were found between exposure to kerosene stoves, wood stoves, fumigation mat mosquito repellents or aerosol insecticides and respiratory illness. Host factors predictive of at least one respiratory outcome included family history of chest illness, history of allergy, male sex, hospitalization in the neonatal period and low paternal education. With 95% confidence, avoidance of regular exposure to mosquito coil smoke and passive smoking could reduce the prevalences of persistent wheeze, asthma and chest illness by up to 29%. Measurements of lung function confirmed the validity of questions pertaining to wheezing and asthma in the study questionnaire.

Increased wheeze but not bronchial hyperreactivity near power stations.

STUDY OBJECTIVE: In a previous study a higher than expected prevalence of asthma was found in Lake Munmorah, a coastal town near two power stations, compared with another coastal control town. This study aimed to compare atopy, bronchial hyperreactivity, and reported symptoms of asthma in the power station town and a second control area with greater socioeconomic similarity. DESIGN: A cross sectional survey was undertaken. SETTINGS: Lake Munmorah, a coastal town near two power stations, and Dungog, a country town in the Hunter Valley, NSW, Australia. PARTICIPANTS: All children attending kindergarten to year 6 at all schools in the two towns were invited to participate in 1990. The response rates for the questionnaire for reported symptoms and associated demographic data were 92% in Lake Munmorah and 93% in Dungog, with 84% and 90% of children respectively being measured for lung function, atopy, and bronchial reactivity. There were 419 boys and 432 girls aged 5 to 12 years. MEASUREMENTS AND MAIN RESULTS: Main outcome measures were current wheeze and bronchial hyper-reactivity, defined as a fall in forced expiratory volume in 1 second (FEV1) or peak expiratory flow (PEF) of 20% or more. Current wheeze was reported in 24.8% of the Lake Munmorah children compared with 14.6% of the Dungog children. Bronchial hyper-reactivity was similar for both groups--25.2% in Lake Munmorah and 22.3% in Dungog. The mean baseline FEV1 was lower in Lake Munmorah than in Dungog (p < 0.001). Dungog children were more likely to have positive skin test to house dust mite (Dungog 27.0%, Lake Munmorah 20.2%, p = 0.028) but there were no other differences in skin test atopy in the two towns. After adjusting for age, gender, any smoker in the house, and positive dust mite skin test, the odds of current wheeze in Lake Munmorah compared with Dungog was 2.16 (95% confidence interval 1.45, 3.15). CONCLUSIONS: Baseline lung function was lower and reported symptoms of asthma were higher in the power station town, but bronchial hyper-reactivity and skin test defined atopy were similar in the two communities. These results are consistent with the previous study and confirm the increased presence of reported symptomatic illness in the town near power stations.

Platelet aggregation and disaggregation in the streptozotocin induced diabetic rat: the effect of sympathetic inhibition.

Alterations in platelet function have been observed in a number of diabetic states. Increased responsiveness to platelet-aggregating agents in diabetes associated with increased catecholamine production and/or turnover suggested that heightened sympathetic activity may contribute to this increased platelet aggregation response. To investigate this possibility, we made male Wistar-Furth rats diabetic with streptozotocin and treated them either with adrenergic inhibitors (clonidine, yohimbine, reserpine) or saline. After 2 weeks, arterial blood samples were collected in 3.8% sodium citrate or acid citrate dextrose (ACD). Platelet-rich plasma (PRP) was prepared, and platelet aggregation studies were conducted directly or conducted on washed platelets prepared from PRP collected with ACD. Platelet aggregation in response to ADP by PRP was reduced while the rate of disaggregation was increased in platelets from diabetic animals when compared to controls. However, platelet aggregation in response to ADP in washed platelets was increased in diabetic animals when compared to controls. Clonidine, reserpine and yohimbine significantly decreased the diabetes-induced increase in maximum aggregation. Thrombin-induced aggregation was not altered by diabetes or any of the treatments. The platelet size was increased in the diabetic animals and was decreased toward controls by clonidine, reserpine and yohimbine treatment. These studies suggest that diabetes increases platelet aggregation response in diabetic rats, and that blockage or suppression of adrenergic activity reverses or attenuates the diabetes-induced hypersensitivity to ADP.

Effects of indoor air pollution on lung function of primary school children in Kuala Lumpur.

In a cross-sectional study of 7-12 year-old primary school children in Kuala Lumpur city, lung function was assessed by spirometric and peak expiratory flow measurements. Spirometric and peak expiratory flow measurements were successfully performed in 1,214 and 1,414 children, respectively. As expected, the main predictors of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were standing height, weight, age, and sex. In addition, lung function values of Chinese and Malays were generally higher than those of Indians. In multiple regression models which included host and environmental factors, asthma was associated with significant decreases in FEV1, FEF25-75, and PEFR. However, family history of chest illness, history of allergies, low paternal education, and hospitalization during the neonatal period were not independent predictors of lung function. Children sharing rooms with adult smokers had significantly lower levels of FEF25-75. Exposures to wood or kerosene stoves were, but to mosquito repellents were not, associated with decreased lung function.

Hemoptysis following blunt trauma: case report.

A 9-year-old boy developed significant hemoptysis and pulmonary parenchymal injury following blunt trauma. There was delayed development of hemoptysis following chest injury, and the trauma did not produce any evidence of external body injury.

Mucoid Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis.

The aim of this study was to assess the prognostic significance of mucoid and non-mucoid isolates of Pseudomonas aeruginosa (muPs and non-muPs) from the sputa of patients with cystic fibrosis (CF). Eighty-one children with CF who coughed up sputum daily were recruited and followed over 12 months with frequent sputum cultures. At the end of this observation period they were classified to one of three age-matched groups. In 50 mPs was isolated on one or more occasions; 19 grew non-muPs but not muPs, and 12 grew no isolates of Ps aeruginosa. These 81 children and adolescents were followed for a further 8 years or until they died. Twenty-one (42%) of the muPs patients died compared with two (11%) of the non-muPs and one (8%) of the no Ps patients (P less than 0.01). Stepwise regression indicated that forced expiratory volume in 1 second (FEV1) had the main predictive effect but that age, Shwachman score and muPs also had a predictive effect. Identification of mucoid forms of Ps aeruginosa is an unfavorable prognostic factor but the isolation of non-mucoid strains does not appear to be any more important than the isolation of other common respiratory pathogens.

Cerebral abscess as a complication of cystic fibrosis.

Two male patients with cystic fibrosis (CF), both 18 years old, developed frontal lobe brain abscesses. Both patients presented with histories of intermittent headache over several days and occasional vomiting. Headache was not more evident in the mornings and not associated with visual disturbance in either patient. Neither was hypertensive nor had visual disturbance. Both patients had documented pansinusitis and nasal polyposis. Both men had had few admissions for pulmonary exacerbations, and neither was significantly malnourished. The abscess in neither patient grew Pseudomonas species.

Defining an exacerbation of pulmonary disease in cystic fibrosis.

Despite the importance of pulmonary exacerbations in CF in both clinical and research settings, both published evidence and consensus are lacking concerning the criteria used to define an exacerbation. The use of hospitalization as a surrogate measure presupposes uniformity among clinicians in diagnosis and treatment of exacerbations. Our aims were to evaluate consensus among clinicians about the variables considered helpful in diagnosing an exacerbation requiring treatment. A comprehensive list of symptoms, signs, and investigations used to define exacerbations was compiled from published trials. A written self-administered questionnaire included the list in age-appropriate groups to survey opinion about the helpfulness of each item, and the estimated proportion of patients admitted within a month of diagnosis of an exacerbation. This was sent to all clinicians managing CF patients in Australia. There were replies from 59/91 clinicians (65%), 41/60 (68%) from those managing children and 18/31 (58%) from those managing adults. Responses of those managing children and adults differed for 7/32 variables (Mann-Whitney test, P < 0.05). Clinic grouping did not show greater consensus among responses of pediatricians (Kruskal-Wallis test, P = 0.362). Consensus, >74% or <26% of respondents rating a variable helpful/very helpful, was found in only 50% of variables listed. Estimated admission rate within a month of diagnosis was 61% (30-100%) for those managing adults and 48% %5-100%) for pediatricians. A lack of consensus was found among clinicians managing CF about the variables considered in diagnosing an exacerbation. The estimated proportion admitted within a month of diagnosis was very variable. This demonstrated inhomogeneity in approach to diagnosis and management of an exacerbation suggests a significant heterogeneity of clinical care.

Pattern of airway inflammation and its determinants in children with acute severe asthma.

The aim of this study was to examine the relationship between sputum cell counts and clinical variables in children with an acute exacerbation of asthma. Sputum was successfully obtained from 37 of 42 children presenting to the Emergency Department with acute asthma, using ultrasonically nebulized normal saline (n = 19) or spontaneous expectoration (n = 18). Sputum portions were selected and dispersed, and total and differential cell counts were performed. Sputum supernatant was assessed for eosinophil cationic protein (ECP), interleukin (IL)-5, and IL-8. The exacerbations were of 3 inflammatory cell patterns: eosinophilic (n = 16 or 43% of total), combined eosinophilic/neutrophilic (E/N; n = 13.3 or 35% of total), or noneosinophilic (n = 8 or 22% of total). IL-5 was highest in eosinophilic exacerbations. Combined E/N exacerbations had increased mast cells (77%) and higher sputum ECP levels than eosinophilic exacerbations: 2,146 ng/mL vs. 666 ng/mL (P = 0.04). The speed of onset of the exacerbation was not related to the inflammatory cell profile. Logistic regression identified maintenance asthma treatment (odds ratio (OR), 5.9; 95% confidence interval (CI), 1.3-26.8) and lung function during the acute episode (OR, 4.0; 95% CI, 1.7-93) as significantly associated with the intensity of sputum eosinophilia. Eosinophils were lowest in children who received maintenance treatment with oral corticosteroids compared to those with no background asthma preventer therapy (P = 0.001). In conclusion, we identified three distinct patterns of airway inflammation in children with acute asthma; they included increased eosinophils, combined eosinophilic-neutrophilic infiltration, and a noneosinophilic pattern. Eosinophil degranulation was greatest with the combined eosinophilic/neutrophilic pattern of airway inflammation. Sputum eosinophils were associated with clinical severity, and background asthma therapy, but not with outcome, nor with speed of onset of exacerbations. These different inflammatory cell profiles imply different etiological agents and may require differing treatment strategies.

Chemotherapy for malignancy induces a remission in asthma symptoms and airway inflammation but not airway hyperresponsiveness.

Inflammation with infiltrations of eosinophils and mast cells into the walls of airways is considered to increase airway hyperresponsiveness (AHR), which in turn characterizes asthma. We present a child with AHR in whom the clinical course of asthma was related to eosinophilic bronchitis. Our patient was admitted at age 6 months with bronchiolitis and at age 4 years with asthma. Inhaled corticosteroids were begun at age 7 years. At age 8 he developed a meningeal sarcoma. While on chemotherapy, his asthma symptoms resolved and he no longer required prophylactic asthma treatment. After 14 months off all chemotherapy, he again had mild episodic asthma. While receiving chemotherapy for malignancy, he had an admission with a coagulase negative staphylococcal bacteremia. During sputum induction with 4.5% saline, he developed cough, wheeze, and a 20% reduction in peak expiratory flow (220 to 180 L/min) that reversed after treatment with salbutamol. The sputum cell count was 1.7 x 10(6)/ml with 1.1 x 10(6) being neutrophils. Two weeks later and prior to the induction of the second sputum, a 21% increase in FEV1 was recorded after bronchodilator inhalation (82% to 99% of predicted). The second sputum contained 2.7 x 10(6)/ml cells with 1.6 x 10(6)/ml neutrophils. Neither eosinophils nor mast cells were identified in the sputum. A third sputum obtained 14 months after the cessation of chemotherapy showed a sputum cell count of 16 x 10(6)/ml, with 11.6 x 10(6) neutrophils and 0.4 x 10(6) eosinophils; no mast cells were detected. A reversible 15% reduction in FEV1 was detected on hypertonic saline challenge testing. This boy had persistent airway hyperreactivity and reversible airways obstruction on three occasions during and following chemotherapy. When he developed asthma symptoms, his sputum contained neutrophils and eosinophils; while on chemotherapy his sputum did not contain eosinophils and he was symptom-free and off all asthma therapy. One can speculate that chemotherapy for malignancy can induce a remission in asthma symptoms but not AHR, and remission in symptoms is associated with a lack of eosinophilic or mast cell infiltrates in the sputum.

Asthma in the vicinity of power stations: I. A prevalence study.

Respiratory symptoms, atopy, and bronchial reactivity were measured in primary school children living in Lake Munmorah (LM), a coastal town near two power stations, and in Nelson Bay (NB), a coastal town free from any possible major sources of outdoor air pollution. A prevalence survey and longitudinal follow-up study were performed 1 year apart. In both studies, the prevalence of ever wheezed, current wheezing, breathlessness, wheezing with exercise, diagnosed asthma, and use of drugs for asthma at LM were all approximately double the prevalence at NB (all P values less than 0.01). The prevalence of bronchial reactivity was significantly greater at LM than NB (P less than 0.01) at the first but not the second survey. By contrast, no significant differences were found between the two areas for skin test atopy or for parental history of allergic disease. Multivariate analysis supported the conclusion from the univariate analysis that there was more wheezing at LM compared to NB at both studies, when adjusted for atopy, smoking in the home, age, and sex. As expected, a positive skin test reaction to house dust mite was the predominant explanatory variable. Asthma was more common in the community near power stations (LM) than in the NB area. The absence of significant differences in skin test atopy and parental history of allergic disease argued against major genetic differences between the two groups. By contrast, the more common reporting of siblings' chest disease and asthma in Lake Munmorah supported an environmental cause.

Asthma in the vicinity of power stations: II. Outdoor air quality and symptoms.

To assess longitudinally the effect of living in the vicinity of coal-fired power stations on children with asthma, 99 schoolchildren with a history of wheezing in the previous 12 months were studied for 1 year, using daily diaries and measurements of air quality. The children had been identified in a cross-sectional survey of two coastal areas: Lake Munmorah (LM), within 5 km of two power stations, and Nelson Bay (NB), free from major industry. Daily air quality [sulphur dioxide (SO2) and nitrogen oxides (NOx)], respiratory symptoms, and treatment for asthma were recorded throughout the year. Measurements of SO2 and NOx at LM were well within recommended guidelines although they were several times higher than at NB: maximum daily levels in SO2 (micrograms/m3) were 26 at LM, 11 at NB (standard, 365); yearly average SO2 was 2 at LM, 0.3 at NB (standard, 60); yearly average NOx (micrograms/m3) was 2 at LM, 0.4 at NB (standard, 94). Marked weekly fluctuations occurred in the prevalence of cough, wheezing, and breathlessness, without any substantial differences between LM and NB. Overall, the prevalence of symptoms was low (10% for wheezing, 20% for any symptom). Whether the daily SO2 and NOx levels affected the occurrence of respiratory symptoms was investigated in children at LM using a logistic regression (Korn and Whittemore technique). For these children as a group, air quality measurements were not associated with the occurrence of symptoms.

Airway inflammation after treatment with aerosolized deoxyribonuclease in cystic fibrosis.

Recombinant human deoxyribonuclease (rhDNase) has been shown to reduce sputum viscoelasticity and to improve lung function in patients with cystic fibrosis (CF). The aim of this study was to determine whether airway inflammation would decrease after administration of rhDNase. Twenty patients with CF and chronic suppurative lung disease inhaled 2.5 mg of rhDNase daily for 1 month. Before and after the 1-month trial, lung function was measured and sputum was obtained, either after spontaneous expectoration or after sputum induction with hypertonic saline. Sputum total cell and differential counts were measured using techniques previously described. The mean age of the patients was 16.8 years (range, 6.7-27.5). After 1 month of rhDNase, mean FEV1 increased from a baseline of 62.3% predicted to 70.8% (P= 0.02, paired t test); and FVC increased from 74.4% to 83.9% predicted (P=0.007). No significant differences were found in sputum cytology before or after rhDNase (median total cell counts 16.0 x 10(6)/ml vs. 19.3 x 10(6)/ml, P=0.68). Thirteen patients had a 10% or greater increase in FEV1 after rhDNase (responders). Initial lung function was less in responders than in nonresponders (53.5% vs. 78.6%, P=0.007). There was no significant change in total cell count and neutrophil count after rhDNase in either responders or nonresponders. We conclude that airway inflammation, as measured by total cell counts in sputum, was a prominent feature in cystic fibrosis, and neutrophils were the dominant inflammatory cells. Although the administration of rhDNase resulted in significant improvements in FEV1, there was no evidence of accompanying changes in airway inflammation.

Characterization of photosystem 1 chlorophyll a/b-binding apoprotein accumulation in developing soybean using type-specific antibodies.

The structure and supramolecular assembly of the soybean photosystem 1 (PS 1) chlorophyll a/b-binding antenna (LHC 1) was examined. We identified the subunit composition of LHC 1 in soybean and followed the accumulation of individual subunits during light-induced assembly. We observed four LHC 1 subunits, at 23, 22, 21 and 20.5 kDa, obtained partial sequence information by amino-terminal sequence analysis, and classified the 20.5, 22, and 21 kDa subunits as being encoded by type I, II, and IV chlorophyll a/b binding protein genes, respectively. Antisera against LHC 1 subunits were used to follow the accumulation of individual subunits during the light-initiated transition from etioplast to chloroplast. Several points are noteworthy. First, monospecific antibody against the 22 kDa subunit decorated a 25 kDa peptide in etiolated tissue, which declined during maturation. This decline correlated with the light-induced appearance of mature 22 kDa peptide, suggesting a precursor/product relationship. Second, the same antibody identified a 22 kDa protein in mature corn, but not a larger band in etiolated corn, suggesting that LHC 1 accumulation is regulated differently between species before the onset of chlorophyll biosynthesis. Third, the mature 22 kDa subunit appeared somewhat later than the other LHC 1 peptides during greening, implying that this subunit is less intimately associated with the PS1 core than are the subunits appearing earlier in development.

Development and use of domain-specific antibodies in a characterization of the large subunits of soybean photosystem 1.

The molecular architecture of the soybean photosystem 1 reaction center complex was examined using a combination of surface labeling and immunological methodology on isolated thylakoid membranes. Synthetic peptides (12 to 14 amino acids in length) were prepared which correspond to the N-terminal regions of the 83 and 82.4 kDa subunits of photosystem 1 (the PsaA and PsaB proteins, respectively). Similarly, a synthetic peptide was prepared corresponding to the C-terminal region of the PsaB subunit. These peptides were conjugated to a carrier protein, and were used for the production of polyclonal antibodies in rabbits. The resulting sera could distinguish between the PsaA and PsaB photosystem 1 subunits by Western blot analysis, and could identify appropriate size classes of cyanogen bromide cleavage fragments as predicted from the primary sequences of these two subunits. When soybean thylakoid membranes were surface-labeled with N-hydroxysuccinimidobiotin, several subunits of the complete photosystem 1 lipid/protein complex incorporated label. These included the light harvesting chlorophyll proteins of photosystem 1, and peptides thought to aid in the docking of ferredoxin to the complex during photosynthetic electron transport. However, the PsaA and PsaB subunits showed very little biotinylation. When these subunits were examined for the domains to which biotin did attach, most of the observed label was associated with the N-terminal domain of the PsaA subunit, as identified using a domain-specific polyclonal antisera.