Additional myocardial salvage by coadministration of the epoprostenol analog taprostene to recombinant single-chain urokinase-type plasminogen activator in a canine coronary thrombosis model

In open chest dogs myocardial ischemia was induced by formation of an occlusive thrombus in the left anterior circumflex artery (LCX). Reperfusion of the LCX was achieved by infusion of the fibrin specific recombinant single-chain urokinase-type plasminogen activator (r-scu-PA). The myocardial salvage by r-scu-PA alone and in combination with the epoprostenol (prostacyclin) analog taprostene (CG 4203) was compared. There were four experimental groups: group 1 (n = 4) did not receive any treatment after LCX thrombosis; in group 2 (n = 9) at 100 min after LCX thrombosis r-scu-PA (20 micrograms.kg-1.min-1 i.v. for 30 min) was infused; in groups 3 and 4 treatment with taprostene started concomitantly with r-scu-PA infusion. The taprostene infusions lasted for 120 min and the doses were 0.1 microgram.kg-1.min-1 in group 3 (n = 6) and 0.215 microgram.kg-1.min-1 in group 4 (n = 6). Time to r-scu-PA-induced recanalisation ranged from 18-22 min with no significant difference between groups 2-4. Percent of left ventricle at risk did not differ between the groups. Infarct size as percent of the risk zone was 48.3 +/- 7.7 in group 1, 25.3 +/- 3.7 in group 2, 21.3 +/- 6.5 in group 3 and 17.1 +/- 3.5 in group 4 (p less than 0.05 groups 2-4 vs group 1). Incidence of ectopic beats increased after r-scu-PA-induced reperfusion in groups 2-4, but was significantly reduced by taprostene.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative immunocytology as a marker for indications and follow-up of recurrence prevention of superficial urinary bladder cancers

In 1985, we initiated a prospective clinical trial to evaluate the risk of recurrence for superficial bladder cancer. Up to now, 41 patients subjected to TUR have subsequently been monitored by immunocytology with a monoclonal antibody (mab 486 p) recently developed in our laboratory. Of these patients, 15 (36.6%) remained marker-negative and received no prophylactic therapy. There was only one recurrence (6.7%) in this subset of patients, whereas 10 out of 26 (38.5%) marker-positive patients have so far developed recurrent malignancies. In all cases, the conversion of immunocytological characteristics preceded visible recurrence by 2-5 months. These preliminary results indicate that immunocytology might make it possible to identify patients at low risk of recurrence more accurately than has so far been feasible with standard cytology or flow-cytometry.     

Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients

Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity.

Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity.

Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0).     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

Table 1     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.     

Job characteristics and satisfaction of pharmacy technicians

Perceptions of job characteristics and job satisfaction of central-area technicians and drug-administration technicians at The Ohio State University Hospitals were analyzed. A questionnaire was administered to 79 pharmacy drug-administration technicians; 44 central-area technicians; 10 pharmacy residents, who served as objective raters (5 in the central area and 5 in the decentral area); 13 central-area pharmacists; and 17 decentral-area pharmacists. Perceived job characteristics were measured with the Job Characteristics Inventory; job satisfaction was measured by the Minnesota Job Satisfaction Questionnaire. The two groups of technicians differed significantly in their perceptions of task identity, task significance, and dealing with others. Significantly greater autonomy in technicians' jobs was perceived to exist by pharmacists and raters in both areas than by technicians. Significantly greater task identity was perceived by the central-area technicians than by their raters, and significantly greater task importance was perceived by both groups of technicians than by their pharmacists and raters. Friendship opportunities were perceived to exist to a significantly greater degree by decentral pharmacists and raters than by the drug-administration technicians. In the institution studied, both central-area and drug-administration technicians tended to be dissatisfied with their jobs. Central-area technicians' satisfaction was influenced most by the technicians' relationships with their supervisors and the feelings of accomplishment they gained. Drug-administration technicians were most satisfied if they believed they had opportunities to use their abilities. Efforts to increase job satisfaction among pharmacy technicians should focus on increasing feedback and task identity.     

Alternaria alternata NADP-dependent mannitol dehydrogenase is an important fungal allergen.

BACKGROUND: Alternaria alternata is one of the most important allergenic fungi worldwide. Mannitol dehydrogenase (MtDH) has previously been shown to be a major allergen of Cladosporium herbarum and cross-reactivity has been demonstrated for several fungal allergens. OBJECTIVE: The present study's objective was to clone the MtDH from an A. alternata cDNA library, express and purify the recombinant non-fusion protein and test its IgE-binding properties. Methods A cDNA library prepared from A. alternata hyphae and spores was screened for mannitol dehydrogenase by DNA hybridization with the radioactively labelled C. herbarum homologue as a probe. The resulting clone was sequenced and heterologously expressed in Escherichia coli as a recombinant non-fusion protein, which was purified to homogeneity and analysed for its IgE-binding capacity. RESULTS: The coding sequence of the full-length cDNA clone comprises 798 bp encoding a protein with a molecular mass of 28.6 kDa and a predicted pI of 5.88. Protein sequence analysis revealed an identity of 75% and a homology of 86% between the MtDHs of A. alternata and C. herbarum. The functional mannitol dehydrogenase was expressed in the E. coli strain BL21(DE3) transformed with the vector pMW172 and purified to homogeneity. The enzyme catalyses the NADPH-dependent conversion of d-fructose to d-mannitol. In IgE-ELISA and immunoblots, MtDH is recognized by 41% of A. alternata-allergic patients. In vivo immunoreactivity of the recombinant MtDH was verified by skin prick testing. Finally, inhibition-ELISA experiments confirmed cross-reactivity between the MtDHs of A. alternata and C. herbarum. CONCLUSION: Mannitol dehydrogenase (Alt a 8) represents an important new allergen of the ascomycete A. alternata that might be suitable for improving diagnostic and therapeutic procedures.     

Sticky Platelet Syndrome: An Underrecognized Cause of Graft Dysfunction and Thromboembolic Complications in Renal Transplant Recipients

Sticky platelet syndrome (SPS) leads to hyperaggregabilty of platelets in response to physiologic stimuli. In this report we describe three patients with clinical symptoms of SPS after renal transplantation. The first patient developed an infarction of her transplant kidney with additional, subsequent renal microinfarctions. The second patient suffered multiple strokes and deep vein thrombosis with episodes of pulmonary embolism and ischemic bowel disease due to colonic microinfarctions. The third patient experienced a long episode of unexplained respiratory and graft dysfunction immediately after transplantation until therapy for SPS was initiated, at which point symptoms resolved quickly. Kidney transplant recipients with SPS may be at increased risk of developing thrombosis, given that most immunosuppressive drugs are known to induce either endothelial cell damage or augment platelet aggregation. All patients awaiting renal transplantation should be screened for a history of thrombosis and, if appropriate, tested for SPS. Affected patients should receive dose-adjusted acetylsalicylic acid.