Characterization of the antigen reactive with anti-Scl-70 antibodies and its application in an enzyme-linked immunosorbent assay

The characteristics of the Scl-70 antigen (topoisomerase I) have been analyzed by means of autoantibodies. This antigen is a DNA-binding protein, dissociable from DNA at 0.3M NaCl and bound to a fraction of DNA that is very sensitive to nucleases. The molecular weight of the antigen is 105,000 daltons, whether dissociation conditions are used or not. Using chicken erythrocytes, and taking advantage of the strong interaction of the antigen with hydroxyapatite, we have designed a simple and fast purification protocol that allows the determination of anti-topoisomerase I antibodies by enzyme-linked immunosorbent assay.     

Cardiovascular tissue banking in the non-cadaveric setting: ten-year experience of a university hospital-based bank with active organ donation program

BACKGROUND AND AIM OF THE STUDY: Today, transplantation of cardiovascular tissues is common practice, and tissue banking has become routine. Consequently, many institutions exist which carry out high-quality tissue banking. METHODS: The Hospital Clinico of the University of Barcelona established its cardiovascular tissue bank in 1989. The bank follows international and national regulations, and functions as a non-profit-making organization. Organ and tissue donors are recruited by the Transplant Coordination unit, which works closely with the Catalonian Organ Transplant Network (OCAT) and the Spanish National Organ Transplantation Network (ONT). The hearts are removed during multi-organ donation and processed using aseptic techniques in a laminar flow hood. Hearts are only accepted from brain-dead multiorgan and non-beating-heart donors. The heart valves are dissected, decontaminated, cryopreserved in specific media and stored in liquid nitrogen at -196 degrees C under strict bacteriological and serological control. RESULTS: Between 1989 and 1999, a series of 1,005 cardiovascular donors from within Spain was identified, from which 840 hearts were processed. After evaluation, 1,099 (65.4%) valves were cryopreserved, and 1,023 (61.5%) given clearance for implantation. In total, 534 aortic, 530 pulmonary, 33 mitral and two tricuspid valves were processed; ultimately 92.8% of aortic and 93.9% of pulmonary valves were accepted for clinical implantation. The rejection rate was 39.1%. Homografts were transported to their destination in dry ice in a cryogenic container. Overall, 608 valves were implanted at our own institution and at hospitals in Barcelona and Europe. Only two cases of complaint were received from implanting surgeons. CONCLUSION: After ten years' experience, the degree of satisfaction of implanting surgeons appears to be adequate. Strict control of the entire tissue banking process has permitted the availability of high-quality homografts for clinical implantation.     

Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort. Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr? (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n = 111) or medical management (n = 60). At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean ± SD change in forced expiratory volume in 1 s (7 ± 20% versus 0.5 ± 19%; p = 0.067), cycle ergometry (2 ± 14 W versus -3 ± 10 W; p = 0.04) and St George's Respiratory Questionnaire (-5 ± 14 points versus 0.3 ± 13 points; p = 0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean ± SD lobar volume reduction of -80 ± 30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes. Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.     

Impaired circadian variation of platelet activity in patients with sleep apnea

Background  

Cardiovascular diseases are frequent in patients with obstructive sleep apnea (OSAS). There is evidence that the day–night pattern of myocardial infarction and sudden cardiac death observed in the general population is altered in patients with OSAS. This study investigates potential abnormalities in the circadian profiles of platelet activity in OSAS.     

Effects of propranolol on arterial oxygenation and oxygen transport to tissues in patients with cirrhosis

Patients with cirrhosis may show ventilation-perfusion (VA/Q) inequality in the absence of any intrinsic heart or lung disease. However, the high cardiac output of cirrhosis generally prevents or minimizes the appearance of a severe degree of arterial hypoxemia. Propranolol has been used to reduce cardiac output and portal pressure in these patients. We wondered whether it might alter arterial oxygenation and reduce O2 transport to tissues. We studied eight patients (three women) 54 +/- 3 (SEM) yr of age before and after intravenous propranolol (0.1 mg/kg followed by 2 mg/h). Cardiac output (QT) fell from 7.8 +/- 0.7 to 6.0 +/- 0.7 L/min (p less than 0.05), and portal pressure was reduced (22 +/- 2 to 19 +/- 2 mm Hg, p less than 0.01). Arterial PO2 did not change (88 +/- 4 to 89 +/- 5 mm Hg) because the fall in mixed venous PO2 (43 +/- 1 to 40 +/- 1 mm Hg, p less than 0.01) that followed the lower QT was counterbalanced by a lower intrapulmonary shunt (multiple inert gas technique) (4 +/- 2 to 2 +/- 1%, p less than 0.05) and a shift of the VA/Q distributions toward a higher VA/Q ratio. Paralleling the fall in QT, oxygen transport to tissues (QO2) was reduced (19 +/- 2 to 14 +/- 1 ml/min/kg, p less than 0.01). However, O2 uptake (VO2) remained constant (3.4 +/- 0.2 to 3.6 +/- 0.2 ml/min/kg) because O2 extraction by the tissues increased appropriately (22 +/- 2 to 28 +/- 1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Rats with minimal hepatic encephalopathy due to portacaval shunt show differential increase of translocator protein (18 kDa) binding in different brain areas,which is not affected by chronic MAP-kinase p38 inhibition

Neuroinflammation plays a main role in neurological deficits in rats with minimal hepatic encephalopathy (MHE) due to portacaval shunt (PCS). Treating PCS rats with SB239063, an inhibitor of MAP-kinase-p38, reduces microglial activation and brain inflammatory markers and restores cognitive and motor function. The translocator protein-(18-kDa) (TSPO) is considered a biomarker of neuroinflammation. TSPO is increased in brain of PCS rats and of cirrhotic patients that died in hepatic coma. Rats with MHE show strong microglial activation in cerebellum and milder in other areas when assessed by MHC-II immunohistochemistry. This work aims were assessing: 1) whether binding of TSPO ligands is selectively increased in cerebellum in PCS rats; 2) whether treatment with SB239063 reduces binding of TSPO ligands in PCS rats; 3) which cell type (microglia, astrocytes) increases TSPO expression. Quantitative autoradiography was used to assess TSPO-selective ³H-(R)-PK11195 binding to different brain areas. TSPO expression increased differentially in PCS rats, reaching mild expression in striatum or thalamus and very high levels in cerebellum. TSPO was expressed in astrocytes and microglia. Treatment with SB239063 did not reduces ³[H]-PK11195 binding in PCS rats. SB239063 reduces microglial activation and levels of inflammatory markers, but not binding of TSPO ligands. This indicates that SB239063-induced neuroinflammation reduction in PCS rats is not mediated by effects on TSPO. Also, enhanced TSPO expression is not always associated with cognitive or motor deficits. If enhanced TSPO expression plays a role in mechanisms leading to neurological alterations in MHE, SB239063 would interfere these mechanisms at a later step.     

Paraneoplastic neurological syndromes associated with renal or bladder cancer: case series and PRISMA-IPD systematic review

Journal of Neurology - The link between paraneoplastic neurological syndromes (PNS) and renal cell and bladder cancer (RCC/BC) is rare and uncertain. Our aim was to clinically evaluate, in light of...     

Oxyhemoglobin affinity in patients with chronic obstructive pulmonary disease and acute respiratory failure: role of mechanical ventilation

Oxyhemoglobin affinity was assessed in 20 subjects with chronic obstructive pulmonary disease, all of whom experienced acute respiratory failure. PaCO2, pH, and 2,3-diphosphoglycerate (2,3-DPG) were measured 24 and 48 h after admission, and then during weaning (for the ten patients on mechanical ventilation) or on discharge (for the ten nonventilated patients). At 24 h, nonventilated patients had a lower pH (p less than .001) and 2,3-DPG concentration (p less than .05) and a higher PaCO2 (p less than .01) than ventilated patients; 48 h later only PaCO2 was higher (p less than .01) in the former, and there were no differences between the two groups in the final set of measurements. There was a persistent left shift in the oxyhemoglobin dissociation curve (P50 at pH 7.4) in both groups throughout the study period. In contrast, the in vivo P50 was significantly lower in ventilated patients only at 24 h (22.7 +/- 2.2 vs. 25.8 +/- 1.5 torr, respectively, p less than .005). Our results suggest that changes of in vivo P50 in ventilated patients are probably related to the Bohr effect induced by mechanical ventilation. The latter swiftly corrects severe respiratory acidosis, causing an intra-erythrocytic alkalotic pH and raising the levels of 2,3-DPG.     

Demonstration of surface antigens on bronchoalveolar lavage cells using the immunoalkaline phosphatase method

The immunoalkaline phosphatase procedure is described as a method for labelling bronchoalveolar lavage cellular specimens with monoclonal antibodies. This method has several advantages over conventional immunofluorescent techniques: it can be performed on cytocentrifuge preparations stored for long periods before staining; cell morphology can be observed in detail in positive and negative cells; the staining is permanent and stable, and, the reaction can be evaluated with a light microscope. Normal values for lymphocyte subpopulations in smokers and nonsmokers are also reported.