Enhancement of spontaneous fibrinolytic activity in diabetic retinopathy.

The fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.     

Treatment of 2d and 3d degree complicated tibial shaft fractures with the PMMA bead pouch technic

In a consecutive series of 222 compound fractures treated at the University of Louisville Level I Trauma Center from November 1984 to January 1987, 21 severe compound tibia shaft fractures in 20 patients were managed with the antibiotic bead pouch technique. There were 5 tibia shaft fractures and 16 tib-fib fractures. There were 9 type II and 12 type III (4 III A and 8 III B) open tibias. The patients' ages ranged from 16 to 50 years; the mean age was 29 years. There were 19 men and 1 woman. The Injury Severity Score (I.S.S.) ranged from 9 to 34; the mean I.S.S. was 14.4. Porous plastic film (Opsite) is placed over the soft tissue defect to establish a "closed" bead - hematoma - fracture environment containing high local levels of antibiotic at the fracture site. All patients had external skeletal fixation, serial wound débridement, and parenteral systemic antibiotics (cefazolin, penicillin, tobramycin). An aggregate of 46 bead pouch changes were performed in the 21 tibia fractures. During these changes, 86 cultures were taken, 5 of which were positive. One patient developed a wound infection, which was caused by tobramycin-resistant Pseudomonas and Enterococcus. No cases of osteomyelitis were observed at the fracture site. Wound closure was obtained in 9 fractures with delayed primary closure, and in 12 fractures with flap coverage and/or split thickness skin grafting. All patients underwent autogenous cancellous bone grafting after wound closure was established. The mean follow-up was 26 months (range 13-43 months). At final follow-up, 4 results were rated excellent, 11 good, 3 fair and 3 poor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Homologous recombination in the fission yeast Schizosaccharomyces pombe: different requirements for the rhp51+, rhp54+ and rad22+ genes

The Schizosaccharomyces pombe rhp51 ⁺ , rad22 ⁺ and rhp54 ⁺ genes are homologous to RAD51, RAD52 and RAD54 respectively, which are indispensable in the recombinational repair of double-strand breaks (DSBs) in Saccharomyces cerevisiae. The rhp51Δ and rhp54Δ strains are extremely sensitive to ionizing radiation; the rad22Δ mutant turned out to be much less sensitive. Homologous recombination in these mutants was studied by targeted integration at the leu1-32 locus. These experiments revealed that rhp51Δ and rhp54Δ are equally impaired in the integration of plasmid molecules (15-fold reduction), while integration in the rad22Δ mutant is only reduced by a factor of two. Blot-analysis demonstrated that the majority of the leu⁺ transformants of the wild-type and rad22Δ strains have integrated one or more copies of the vector. Gene conversion events were observed in less than 10% of the transformants. Interestingly, the relative contribution of gene conversion events is much higher in a rhp51Δ and a rhp54Δ background. Meiotic recombination is hardly affected in the rad22Δ mutant. The rhp51Δ and rhp54Δ strains also show minor deficiencies in this type of recombination. The viability of spores is 46% in the rad22Δ strain and 27% in the rhp54Δ strain, as compared with wild-type cells. However, in the rhp51Δ mutant the spore viability is only 1.7%, suggesting an essential role for Rhp51 in meiosis. The function of Rhp51 and Rhp54 in damage repair and recombination resembles the role of Rad51 and Rad54 in S. cerevisiae. Compared with Rad52 from S. cerevisiae, Rad22 has a much less prominent role in the recombinational repair pathway in S. pombe. Received: 20 July 1996     

Clinical review: Biomarkers of acute kidney injury: where are we now?

The recognition that acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality has resulted in a substantial number of publications over the past 5 years or more. In no small part these have, to a degree, highlighted the inadequacy of conventional markers of renal insufficiency in the acute setting. Much effort has been invested in the identification of early, specific AKI markers in order to aid early diagnosis of AKI and hopefully improve outcome. The search for a 'biomarker' of AKI has seen early promise replaced by a degree of pessimism due to the lack of a clear candidate molecule and variability of results. We outline the major studies described to date as well as discuss potential reasons for the discrepancies observed and suggest that evolution of the field may result in success with ultimately an improvement in patient outcomes.     

Efficacy and acceptability of rilmenidine for mild to moderate systemic hypertension

A double-blind multicenter trial compared rilmenidine with placebo in the treatment of 126 patients with mild to moderate hypertension after a 4-week placebo run-in period. Patients with mild hypertension (study 1) with mean supine diastolic blood pressure (BP) between 95 and 104 mm Hg received either rilmenidine 1 mg/day (n = 31) or placebo (n = 35) for 4 weeks. In study 2, patients with moderate hypertension (mean supine diastolic BP between 105 and 115 mm Hg) received either rilmenidine 1 mg twice a day (n = 30) or placebo twice a day (n = 30) for 4 weeks. All 61 patients taking rilmenidine completed the study; 8 of the 65 patients taking placebo were withdrawn because of an increase in BP. Rilmenidine significantly reduced mean systolic and diastolic BP compared with placebo in both studies. BP was normalized (systolic less than 160 mm Hg and diastolic less than or equal to 90 mm Hg in 61% of the patients taking rilmenidine as opposed to 23% of those taking placebo (p less than 0.001). There was no significant difference in the incidence of either dry mouth or daytime drowsiness between rilmenidine, 1 mg/day, and placebo. Dry mouth was significantly more frequent with rilmenidine, 2 mg/day, than with placebo, but this difference was transient and no longer significant at the end of the study. No unexpected adverse effects occurred. Rilmenidine as single therapy appears to be effective and well accepted in the management of mild to moderate hypertension, in particular at the 1-mg/day dose, which normalized 84% of mild hypertensive patients and did not induce any significant adverse effects compared with placebo.     

Hospital readmission after transvenous cardioverter/defibrillator implantation; a single centre study.

AIMS: Hospital readmission after implantation of cardioverter/defibrillators has a major impact on quality of life and cost-effectiveness in defibrillator patients. Rehospitalization has not been studied in large patient populations with modern transvenous defibrillation systems. METHODS AND RESULTS: We report on incidence, reasons, time in follow-up, duration and predictors of hospital readmission in 180 patients after transvenous implantation of a cardioverter/defibrillator during a follow-up period of 25+/-18 months. There were 156 readmissions in 79 patients with a 0.87 readmission rate per patient during the time followed, a 0.46 readmission rate per patient-year of follow-up and a 0.38 readmission rate per patient-year of follow-up for cardiac reasons. The majority of readmissions was caused by multiple appropriate shock interventions (26%), battery depletion (19%) and lead- and device-related complications (14%). The time to first hospital readmission was 12+/-9 months for arrhythmia-related and 20+/-16 months for other cardiac-related reasons (P<0.05), and could not be predicted by clinical variables, respectively. The duration of rehospitalization was 14+/-15 days for cardiac-related reasons and 12+/-17 days for arrhythmia-related reasons. Age >60 years was an independent predictor of rehospitalization time per patient-year of follow-up for both cardiac-related (P<0.005) and arrhythmia-related reasons (P<0.05). CONCLUSION: The rate of hospital readmission per patient-year of follow-up is as high as 0.46 after implantation of a modern cardioverter/defibrillator. Rehospitalization time in such patients is significantly longer in the patient cohort >60 years. The majority of readmissions is caused by multiple appropriate shock treatments. Further studies are needed to systematically investigate strategies for the prevention of rehospitalization in modern ICD therapy.