Hyperoxic exposure in humans. Effects of 50 percent oxygen on alveolar macrophage leukotriene B4 synthesis.

The pathogenesis of oxygen toxicity remains unknown but may involve leukocyte mediated injury. The effects of hyperoxia on several lower respiratory tract parameters were examined in bronchoalveolar lavage fluid of normal nonsmoking subjects who inhaled a fractional inspired oxygen concentration of 50 percent (mean exposure: 44 h). Evidence that 50 percent O2 produced oxidative stress in the lung included recovery of fluorescent products of lipid peroxidation and partial oxidation of alpha 1-antitrypsin in BAL fluid obtained after O2 exposure. To examine whether alveolar macrophage-derived leukotriene B4 may be generated in response to 50 percent O2, AM were isolated from O2-exposed subjects and compared with AM recovered from subjects breathing room air. Leukotriene B4 levels were elevated in supernatants from both unstimulated and arachidonic acid-stimulated AM obtained from hyperoxia-exposed subjects. In hyperoxia-exposed individuals, LTB4 levels were also elevated in extracted BAL fluid. The percentage of BAL neutrophils was also significantly increased after O2 exposure (2.8 +/- 0.6 vs 1.2 +/- 0.4 percent, p = 0.05). We conclude that an FIO2 of 50 percent inhaled for 44 h is associated with enhanced oxidative stress, stimulation of AM to release LTB4, and a small but significantly increased percentage of neutrophils recovered in BAL fluid.     

Sinoaortic denervation does not increase cardiovascular/endocrine responses to stress.

Sinoaortic baroreceptor denervation is reported to produce exaggerated centrally derived cardiovascular and endocrine responses. We examined the effect of sinoaortic denervation (SAD) on the cardiovascular and endocrine responses to two acute stressors, footshock and immobilization, in male Sprague-Dawley rats. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and plasma levels of oxytocin (OT) and vasopressin (VP). Baseline MAP was elevated in the SAD group (approximately 25 mm Hg) and footshock stress increased arterial pressure equivalently in both groups. This stress caused tachycardia and increased plasma OT, with a tendency for the SAD group to show blunted responses. Immobilization increased HR but caused no change in MAP and no significant difference between the groups. This form of stress also increased plasma OT, and again the SAD group showed a diminished response. Plasma VP was not significantly altered by either stressor. The results of these studies indicate that SAD does not uniformly increase the cardiovascular and endocrine responses to all stressors or centrally derived stimuli. These results also suggest that the lack of an increase in plasma VP is not related to baroreceptor-mediated inhibition of secretion under stressful conditions.     

Echocardiographic features of carcinoid heart disease

We reviewed the records of the Mayo Clinic patients with known carcinoid syndrome in whom echocardiographic studies had been done. Nineteen patients had M-mode and 2-dimensional echocardiographic examinations, and 1 patient had an M-mode examination only. Of the 20 patients, 8 had no evidence by echocardiogram of carcinoid heart disease; 2 had changes in the tricuspid valve echogram suggestive of early carcinoid heart disease, and the other 10 patients had the following distinctive echocardiographic findings: (1) the pattern of right ventricular volume overload (enlarged right ventricle with abnormal septal motion); (2) abnormal right-sided valves, including (a) a striking appearance of the tricuspid valve, the leaflets appearing thickened, retracted, and fixed in a semiopen position throughout the cardiac cycle, and (b) thickened, retracted pulmonic valve cusps, when visualized; and (3) the left-sided valves and chambers rarely involved. These echocardiographic features are distinctive of advanced carcinoid heart disease and correlate closely with pathologic findings.     

Oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease. A meta-analysis.

PURPOSE: To evaluate the effectiveness of oral corticosteroid therapy in patients with stable chronic obstructive pulmonary disease. DATA IDENTIFICATION: An English-language literature search using MEDLINE (1966 to 1989) and a bibliographic review of all retrieved articles identified 33 original studies of oral corticosteroid use in chronic obstructive pulmonary disease published since 1951. STUDY SELECTION: We submitted a photocopy of each study's "methods" section to three nonstudy physician-investigators who used nine explicit criteria to independently assess study quality. Ten studies met all criteria and five studies met some of the criteria. DATA EXTRACTION: To compare outcomes across all qualifying studies, we defined response to therapy as a 20% or greater increase in the baseline forced expiratory volume in 1 second (FEV1); we defined the treatment effect size for each study as the proportion of patients who responded to corticosteroid therapy minus the proportion of patients who responded to placebo. Potential confounding variables as related to eligibility criteria and treatment protocols were also assessed for each study. RESULTS OF DATA SYNTHESIS: Among ten studies that met all nine criteria, we found no significant differences in eligibility criteria, treatment protocol, or study design. No association was found between treatment effect size and publication date, study size, mean patient age, or FEV1. These studies had reported effect sizes ranging from 0% to 56%; we calculated a weighted mean effect size of 10% (95% CI, 2% to 18%). When studies meeting only some of the criteria were included in the calculation, the weighted mean effect size was 11% (95% CI, 4% to 18%). CONCLUSIONS: Patients with stable chronic obstructive pulmonary disease receiving oral corticosteroid therapy have a 20% or greater improvement in baseline FEV1 approximately 10% more often than similar patients receiving placebo.     

The Effects of Inattention/Impulsivity and Aggression on the Development of Toddlers with Autism Spectrum Disorder

Autism spectrum disorder (ASD) frequently co-occurs with additional symptoms of psychopathology and challenging behaviors. While aggressive behaviors are often associated with attention deficits and hyperactivity in children with ASD, there is limited research on the impact that inattention/impulsivity and aggressive behaviors have on the developmental functioning of toddlers with ASD. However, identifying comorbidities is necessary for proper intervention. The aim of the current study was to examine the effects of inattention/impulsivity and aggressive behaviors on several domains of developmental functioning in infants and toddlers with ASD as measured by the Battelle Developmental Inventory, Second Edition (BDI-2). This study compared four groups consisting of 29 toddlers each: without inattention/impulsivity or aggressive behaviors (i.e., -I/-A), with inattention/impulsivity but without aggressive behaviors (i.e.,?+?I/-A), without inattention/impulsivity but with aggressive behaviors (i.e., –I/?+?A), and with both inattention/impulsivity and aggressive behaviors (i.e.,?+?I/?+?A). The results of the current study revealed significant group differences in Personal-Social, Communication, Motor, and Cognitive domains of the BDI-2. The significance and implications of the present study are discussed.