Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

Early and late visual prognosis in solar retinopathy

Background: Solar retinopathy was observed in a total of 86 eyes of 58 patients following the solar eclipse over Turkey in April 1976. The visual prognosis and the presence of late complications were evaluated at the early and late periods. Methods: Of the 58 patients, 34 (51 eyes) presented during the first week and came for follow-up examination in the succeeding week, also after 1, 3, 12 and 18 months. After that they were examined at yearly intervals (mean 4.2 years). Twenty-four patients (35 eyes) presented during the period between 1 and 11 years post-eclipse and were followed up for a mean period of 3.4 years. After a period of 15 years, all of the patients were invited for re-examination and nine patients (14 eyes) attended. Results: The improvement in visual acuity was observed to have taken place mostly during the first 2 weeks to 1 month after the eclipse. Further improvement in visual acuity was not observed in any of the eyes after the 18-month examination. The improvement in visual acuity was more prominent and earlier in the eyes that had visual acuity of 0.2 or better initially. Only the eyes with initial visual acuity equal to or better than 0.4 had a chance to improve their acuity to 10/10. Having observed the 51 eyes for mean period of 4.2 years and the 35 eyes for 3.4 years, no change in visual acuity was observed. Among the total of 86 eyes, 9 were found to have pseudolamellar macular holes. Conclusion: Correlation was found between initial visual acuity and the funduscopic appearance after the 2nd week. Fluorescein angiography was not found to be a conclusive test in solar retinopathy. No late complications were observed.     

Comparative genomic analysis of the interferon/interleukin-10 receptor gene cluster

Interferons and interleukin-10 are involved in key aspects of the host defence mechanisms. Human chromosome 21 harbors the interferon/interleukin-10 receptor gene cluster linked to the GART gene. This cluster includes both components of the interferon alpha/beta-receptor (IFNAR1 and IFNAR2) and the second components of the interferon gamma-receptor (IFNGR2) and of the IL-10 receptor (IL10R2). We report here the complete gene content of this GART-cytokine receptor gene cluster and the use of comparative genomic analysis to identify chicken IFNAR1, IFNAR2, and IL10R2. We show that the large-scale structure of this locus is conserved in human and chicken but not in the pufferfish Fugu rubripes. This establishes that the receptor components of these host defense mechanisms were fixed in an ancestor of the amniotes. The extraordinary diversification of the interferon ligand family during the evolution of birds and mammals has therefore occurred in the context of a fixed receptor structure.     

Apoptosis in brain biopsies of subacute sclerosing panencephalitis patients

Subacute sclerosing panencephalitis (SSPE) is associated with inflammatory infiltration, neuronal loss, and demyelination. The pathogenesis of these changes is unclear. We examined DNA fragmentation and Bcl-2 expression in brain biopsies of nineteen SSPE patients to investigate the role of apoptosis in tissue damage. DNA fragmentation was present in oligodendroglia, and, in tissues with neuronal loss, in neurons. Reactive astrocytes had no DNA fragmentation, but strong Bcl-2 expression. These results suggest apoptosis as one of the mechanisms for oligodendroglial and neuronal death in SSPE.     

Effect of pediatric advanced life support course on pediatric residents' intubation success

Background: The Pediatric Advanced Life Support Program (PALS) course very important for teaching about intubation, resuscitation, shock, trauma, respiratory failure and rhythm disturbances. The aim of the present study was to evaluate the effect of the PALS course on pediatric residents' intubation success during their rotation, daytime and night‐time practice in the pediatric intensive care unit (PICU). Methods: The study was carried out from 1 March 2005 to 28 February 2007. The study period had two parts, in that the number of attempts and successful intubations performed by pediatric residents, and the pediatric intensivist successful intubation ratio were evaluated in two different periods: before the PALS course, 1 March 2005–28 February 2006, and after the PALS course, 5 March 2006–28 February 2007. The participating residents' pediatric levels (PL) were classed as PL‐1, PL‐2, PL‐3, PL‐4, and all had first experience in the PICU at the PL‐1 level. The PALS instructor was a pediatric emergency or intensive care doctor. We evaluated whether the PALS course influenced intubation success or not. Results: Sixteen residents participated in the study. The proportion of successful intubations was 110 (53.3%) and 104 (65.4%) attempts before and after the PALS course, respectively. The proportion of intubations done by intensivists decreased from 49.1% to 31.7% before and after PALS. The most frequently used endotracheal tube (ETT) internal diameter (ID) was 4.0 mm, and cuffed ETT was used 16% and 21% before and after the course, respectively. Appropriate placing of ETT tip occurred 70.4% and 82.2% of the time before and after the PALS course, respectively. Proportion of successful intubations by residents increased in all levels, except for PL‐1. The most important reason for unsuccessful attempts was inappropriate patient position. Only one patient could not be intubated, and laryngeal mask airway was used in that case. During intubation, complications were broken teeth in two patients before the course, and subglottic stenosis developed in only one patient due to cuffed ETT. Conclusion: Successful intubation is a life‐saving intervention during resuscitation, ETT revision for extubation or obstruction for extubation or obstruction during mechanical ventilation. This skill can be developed in the PALS course and by clinical study in PICU and pediatric emergency services. The PALS course must be given to pediatric residents especially within the first year. Also, cuffed ETT can be used for infants and children.     

A late complication of transobturator tape procedure: vaginocutaneous fistula formation with vaginal mesh erosion

Transobturator tape procedures are a common treatment modality in patients with stress urinary incontinence (SUI). Various complications have been reported related to this procedure. We present a rare case of vaginocutaneous fistula formation 5 years after transobturator tape surgery. A 56-year-old woman presented with complaints of increased vaginal discharge, difficulty in coitus, and serosanguineous discharge from the left groin 5 years after transobturator tape surgery for SUI. Pelvic examination revealed 2–3 cm of extruded mesh at the anterior vaginal wall. The vaginocutaneous fistula was detected at surgery. The suburethral tape was removed, and the fistula tract was excised and repaired primarily. Postoperative period was uneventful, and the patient was still continent 6 weeks postoperatively. With widespread use of mesh for treating SUI, we will likely see a variety of complications in the long term.     

Congenital Horner’s Syndrome Associated with Unilateral Agenesis of the Internal Carotid Artery and Unusual Aortic Arch Anomaly

Unilateral congenital agenesis of the internal carotid artery (ICA) is a very rare vascular anomaly. Rarely, congenital Horners syndrome has been associated with agenesis of the ICA. This article describes a rare case of congenital Horners syndrome in a patient with ICA agenesis and very unusual aortic arch anomaly. This study was done at Zonguldak Karaelmas University, Faculty of Medicine, No financial support was required for this study.     

Interferon-alpha and -beta differentially regulate osteoclastogenesis: role of differential induction of chemokine CXCL11 expression

In humans, type I interferon (IFN) is a family of 17 cytokines, among which the alpha subtypes and the beta subtype are differentially expressed. It has been suggested that IFN-beta activates a specific signaling cascade in addition to those activated by all type I IFNs. Nevertheless, no true biological relevance for a differential activity of alpha and beta IFN subtypes has been identified so far. Because type I IFNs are critical for the regulation of osteoclastogenesis in mice, we have compared the effect of IFN-alpha2 and IFN-beta on the differentiation of human monocytes into osteoclasts. Primary monocytes undergoing osteoclastic differentiation are highly and equally sensitive to both alpha2 and beta IFNs as determined by measuring the induction levels of several IFN-stimulated genes. However, IFN-beta was 100-fold more potent than the alpha2 subtype at inhibiting osteoclastogenesis. Expression profiling of the genes differentially regulated by IFN-alpha2 and IFN-beta in this cellular system revealed the chemokine CXCL11 as the only IFN-induced gene differentially up-regulated by IFN-beta. We show that recombinant CXCL11 by itself inhibits osteoclastic differentiation. These results indicate that autocrine-acting CXCL11 mediates, at least in part, the regulations of osteoclastogenesis by type I IFNs.