Experimentally induced pulmonary arterial occlusion with detachable balloon in pigs: thin-section CT findings

RATIONALE AND OBJECTIVES: The authors evaluated changes of lung attenuation in pigs, with special attention to the mosaic pattern of low attenuation, at thin-section computed tomography (CT) after obstruction of the proximal pulmonary artery with a detachable balloon. MATERIALS AND METHODS: In seven pigs, nine sites of the descending pulmonary artery were obstructed with detachable balloons. This-section CT scans of the lungs were obtained immediately (n = 9) and at 1 week (n = 5), 2 weeks (n = 1), 3 weeks (n = 2), 4 weeks (n = 1), 6 weeks (n = 1), 8 weeks (n = 1), and 12 weeks (n = 1) after pulmonary artery obstruction. RESULTS: No statistically significant difference was found between the measured lung attenuation of the normal lung and that of the lung distal to the obstruction. Of the nine sites of pulmonary artery obstruction, five (56%) showed an irregular area of increased lung attenuation without lobular architecture. The diameter of the pulmonary artery after obstruction, compared with the diameter before obstruction, decreased by a range of 13%-57% (mean, 35%) and by 0-67% (mean, 44%) at levels 1 cm and 2 cm distal to the obstruction, respectively. CONCLUSION: This experimental study reveals that regional low-attenuation areas do not develop for up to 12 weeks after the obstruction of proximal pulmonary artery, despite a marked decrease in the diameter of the pulmonary artery distal to the obstruction.     

Clinical efficiency tools improve stroke management in a rural southern health system

BACKGROUND AND PURPOSE: Ischemic stroke is a high-volume and financially draining diagnosis at this rural health system. The purpose of this clinical practice analysis was to identify resource utilization and clinical process inefficiencies and to promote clinically efficient, evidence-based improvements. METHODS: A retrospective analysis of medical record and financial databases of 356 patients with ischemic stroke was performed. The medical record data were adjusted for severity, and outliers were eliminated. The resources utilized by each physician were determined. Comparative graphs were prepared, presented, and discussed. The physicians implemented two types of changes: (1) alteration of resource utilization and consultation patterns and (2) support of clinical process improvement. In 1997, a follow-up analysis of 399 patients was performed. RESULTS: The initial comparison of internists' to neurologists' patient populations found the following: patient age (75 versus 65 years), patient severity ratings (2.8 versus 2.5), length of stay (10.7 versus 8.8 days), costs ($7360 versus $6862), mortality rates (12.5% versus 8.9%), and aspiration pneumonia rate (8.5% versus 3.8%). A comparison of the 1995 analysis to the 1997 analysis revealed the following per patient resource utilization decreases (all P < 0.05): chemistry laboratory, 2.65 to 1.95 studies; intravenous fluids, 2.85 to 1.85 L; oxygen use, 6.06 to 2.75 U; and nifedipine use, 1.62 to 0.33 capsules. The clinical process improvements resulted in the following overall outcomes (all P < 0.05 except mortality): length of stay (7.2 days), nonadjusted costs ($6246), mortality (6.5%), and rates of pneumonia (2.7%). CONCLUSIONS: Objective analysis of resource utilization resulted in physicians changing their individual management of stroke and collectively supporting clinical process changes that improved clinical and financial outcomes.     

Comparison of the precision of two vertebral morphometry programs for the lunar EXPERT-XL imaging densitometer

Comparative precision tests of the vertebral height measurement function of the Aberdeen Vertebral Morphometry System (AVMS) software and Lunar EXPERT-XL software were undertaken using four vertebrae from the same lateral spine dual energy X-ray absorptiometry (DXA) image of the same subject (male, 67 years). Two of the vertebrae were abnormal and two were normal. Three observers inexperienced in morphometry and one experienced observer took part in the study. Repeatability was obtained from 10 sequential measurements of the posterior, middle and anterior heights at the same sitting by the same observer. Intraobserver reproducibility compared the means of one set of measurements for all vertebrae with another taken 1 week later. Interobserver reproducibility compared the means of one set of measurements for all vertebrae from an experienced and an inexperienced observer, and from two inexperienced observers. The AVMS software had significantly higher (p < 0.05) repeatability (mean coefficient of variability, CV = 3.5%) than the Lunar software (mean CV = 5%), significantly higher (p < 0.01) intraobserver reproducibility (mean CV = 4.6%) than the Lunar software (mean CV = 8.5%), and significantly higher (p < 0.05) interobserver reproducibility (mean CV = 4.7%) than the Lunar software (mean CV = 7.5%). In conclusion, the new AVMS method possessed higher precision when measuring both abnormal and normal vertebrae and when used by both experienced and inexperienced observers.     

CD4+ and CD8+ lymphocyte and cortisol response patterns in elderly and young males after methylprednisolone exposure

The elderly have impaired cellular immunity and are more predisposed to opportunistic infections after long term glucocorticoid treatment. No data, examining the response of lymphocyte subsets (CD4+, CD8+) under baseline conditions and after exposure to methylprednisolone in young and elderly males, are available. This crossover study examined lymphocyte subsets and cortisol response patterns in seven elderly males (66-82 years) and five young males (24-37 years) randomized into Phase I (24 hr baseline) and Phase II (10 mg intravenous dose of methylprednisolone). Whole blood samples were obtained at 0, 4, 8, 12 and 24 hr to determine total lymphocytes and CD4+ and CD8+ cells utilizing monoclonal antibodies and flow cytometry. The absolute number of lymphocyte subsets and the lymphocyte area under the time curve (AUC) were measured and a 12 and 24 hr lymphocyte response ratio (AUC Phase II divided by AUC Phase I) was determined. Serial plasma samples over 24 hours were collected to quantitate cortisol (Phase I) and methylprednisolone concurrent with cortisol (Phase II). Pharmacokinetic parameters were generated and the cortisol AUC was determined. The AUC values for lymphocytes and cortisol from Phase II quantitated the pharmacologic response to methylprednisolone exposure while Phase I data described the interpatient variability in these parameters. Diurnal patterns for lymphocytes and cortisol were noted in all subjects during Phase I. The mean CD4+ and CD8+ lymphocyte AUC from 0 to 24 hr during Phase I was significantly smaller for the elderly when compared to young men. However, after exposure to methylprednisolone, lymphopenia occurred in all subjects with a mean decline of 54% in the elderly and 60% (p = 0.44) in young subjects for the total lymphocyte count and returned to baseline by 8-12 hr. During Phase II, the CD4+ lymphocytes (72% decline in elderly; 70% in young; p = 0.71) demonstrated a more notable decline than CD8+ cells (44% decline in elderly; 52% in young; p = 0.31) with a nadir occurring between 4 to 6 hr for both subsets. The lymphocyte response ratio was not significantly different between groups for total, CD4+, and CD8+ cells at 12 hr or 24 hr determinations. A slower clearance of methylprednisolone was noted in the elderly (mean: 256 mL/hr/Kg) than in the young men (mean: 359 mL/hr/Kg; p < 0.05) during Phase II with no significant difference found between groups for volume of distribution, elimination rate constant or half-life. A significantly smaller cortisol suppression ratio [0.36+/-0.11 (elderly) versus 0.58+/-0.11 (young), p = 0.01] which indicates a more profound cortisol suppression was noted. A significant correlation of -0.61 (p < 0.05) between drug exposure (methylprednisolone AUC) and pharmacologic effect (cortisol suppression ratio) was noted for the combined data in the young and elderly males. During Phase I, the CD4+ and CD8+ lymphocyte AUC was significantly smaller in the elderly. A definite suppression pattern for total, CD4+ and CD8+ lymphocytes and cortisol was noted after methylprednisolone exposure in young and elderly males. An age-dependent suppression of cortisol during Phase II was noted but the degree of lymphopenia after drug exposure did not differ between the young and elderly group for any of the cell subsets. These data from healthy elderly provide a basis for further studies to assess immunologic and endocrinologic responses among elderly patients requiring chronic glucocorticoid therapy.     

Phosphorylation sites in the integrin beta3 cytoplasmic domain in intact platelets

Protein seryl/threonyl phosphatase inhibitors such as calyculin A block inside-out and outside-in platelet signaling. Our studies demonstrate that the addition of calyculin A blocks platelet adhesion and spreading on fibrinogen, responses that depend on integrin alphaIIb beta3 signaling. We hypothesized that this reflects a change in alphaIIb beta3 structure caused by a specific state of phosphorylation. We show that addition of calyculin A leads to increased phosphorylation of the beta3 subunit, and phosphoamino acid analysis reveals that only threonine residues become phosphorylated; sequence analysis by Edman degradation established that threonine 753 became stoichiometrically phosphorylated during inhibition of platelet phosphatases by calyculin A. This region of beta3 is linked to outside-in signaling such as platelet spreading responses. The effect of calyculin A on platelet adhesion and spreading and on the phosphorylation of T-753 in beta3 is reversed by the calcium ionophore A23187, demonstrating that these effects of calyculin A are not generally toxic ones. We propose that phosphorylation of beta3 on threonine 753, a region of beta3 linked to outside-in signaling, may be a mechanism by which integrin alphaIIb beta3 function is regulated.     

3T3-L1 adipocytes express two isoforms of phospholipase D in distinct subcellular compartments

Phospholipase D has been implicated as an important enzyme in a range of cellular responses, including regulated secretion and the formation of secretory vesicles, cell proliferation and control of cell morphology. As insulin treatment of adipocytes has been shown to stimulate a phosphatidylcholine-specific phospholipase D and also modulates membrane trafficking, we wished to determine which isoform(s) of phospholipase D were present within adipocytes, to identify their subcellular distribution, and examine how this distribution may change in response to insulin. Using RT-PCR, 3T3-L1 adipocytes were found to express two isoforms of phospholipase D, specifically PLD1b and PLD2a. Using isoform-specific antibodies, PLD1 and PLD2 were found to be present predominantly in intracellular membranes, unlike the situation reported in other cells. Detailed analysis of the intracellular localisation of PLD1 and PLD2 revealed that these isoforms are differentially localised within adipocytes, implying functionally distinct roles for PLD activity in distinct subcellular compartments.     

Depletion of iron and ascorbate in rodents diminishes lung injury after silica

Exposures of the lung to iron chelates can be associated with an injury. The catalysis of oxygen-based free radicals is postulated to participate in this injury. Such oxidant generation by mineral oxide particles can be dependent on availability of both iron and a reductant. We tested the study hypothesis that lung injury after silica is associated with the availability of both iron and ascorbate in the host by depleting this metal and reductant in the lungs of rats and guinea pigs, respectively. Rats were fed either a normal diet or a diet deficient of iron. After 30 days, animals were instilled with either saline or 1.0 mg Minusil-5 silica. Relative to saline, silica significantly increased neutrophils and lavage protein. Iron depletion significantly diminished both the cellular influx and injury but only at 1 week after silica exposure. Guinea pigs were provided either a normal diet supplemented with 1,000 ppm vitamin C or a diet deficient in ascorbate. After 14 days, the guinea pigs were instilled with either saline or 1.0 mg silica. Silica exposure significantly increased neutrophils and lavage protein. Ascorbate depletion significantly diminished the influx of inflammatory cells and injury at both 1 day and 1 week after silica exposure. We conclude that host concentrations of both iron and ascorbate can affect lung injury after silica exposure.     

The platelet in cardiopulmonary bypass

Platelets are the smallest of the blood cells and are known to be activated during cardiopulmonary bypass. They play a role in many associated complications. Both quantitative and qualitative platelet defects have been demonstrated, resulting in microvascular hemorrhage and thromboembolism. As their interactions with endothelium and other blood cells are unraveled, the important contribution they make toward the systemic inflammatory response to operation seen in cardiopulmonary bypass is increasingly evident. In this review, we consider platelet activation during cardiopulmonary bypass, the resultant clinical effects, and potential approaches to therapy and prevention.     

Modulation of the discriminative stimulus and rate-altering effects of cocaine by competitive and noncompetitive N-methyl-D-aspartate antagonists

Preschool antecedents of the use of defense mechanisms were longitudinally studied using data from 90 nursery school children who were again evaluated at age 23. Defense use was determined by coding Thematic Apperception Test (H.A. Murray, 1943) stories with a method previously shown to be reliable and valid. The findings indicated continuity between preschool personality and subsequent defense use for male participants but little continuity for female participants. Young men's use of the age-inappropriate defense of denial was predicted by indications at ages 3-4 of low ego resiliency and psychological difficulties in the areas of emotion, intellect, impulse control, and social interactions.     

Acute septicaemic pasteurellosis in Vietnamese pigs

Sixteen isolates of Pasteurella multocida were cultured from cases diagnosed as acute septicaemic pasteurellosis in Vietnamese pigs. The HSB-PCR assay provided rapid presumptive determination of 10 isolates of P. multocida identified as haemorrhagic septicaemia (HS) causing type B cultures (B:2, B:5, B:2,5). Serological designation using the Carter and Heddleston typing systems confirmed these findings, and identified the six HSB-PCR negative cultures as either A:1, A:3 or D:3,4. Biochemical fermentation and REP-PCR revealed phenotypic and genotypic identity between P. multocida type A:1 isolated from Vietnamese pigs and poultry. Marked homogeneity was also demonstrated among HSB-PCR positive swine isolates, which were shown to possess genotypic identity with P. multocida type B:2 from buffaloes diagnosed with HS.