Autoimmune responses against renal tissue proteins in long-term surviving allograft recipients

Major histocompatibility complex antigens (MHC) are classical targets of recipient responses to allotransplants. However, the role of an immune response directed against autologous graft tissue determinants is poorly defined. In this study, we investigated (i) whether autologous kidney tissue extract can induce an immune response to autologous kidney proteins in normal rats, and (ii) if a similar autologous response develops in the long-term surviving LEW.1A recipients of an MHC-mismatched LEW.1W kidney (RT1^u to RT1^a). LEW.1A rats immunized with allo- or syngeneic soluble kidney extracts developed a T-cell response to self antigens as shown by the frequency of specific IFN-γ-producing T cells from LEW.1A rats in the presence of extracts (ELISPOT). In contrast, they responded only marginally to dominant RT1^u determinants. The ELISPOT against fractions of soluble autologous kidney extracts separated by an FPLC gel-filtration system indicated a preferential response to megalin, a high molecular weight protein that has been shown to be involved in experimental Heymann nephritis. In a model of long-term kidney allograft survival by anti-CD28 administration, recipients also developed humoral but not cellular responses to megalin. Our data suggest that autoimmune processes develop in long-term surviving kidney allograft recipients.     

Uso de terapia con presión negativa en heridas con fístulas entéricas

Objective

Negative pressure therapy (VAC, vacuum assisted closure) is a method used still in our country. It consists of a system of aspirating a wound by means of a piece of foam and a few adhesive films. It allows the treatment of complex wounds, included (although this is still controversial) those with intestinal fistulas. We present 3 cases of treatment with VAC in this situation and a review of the published literature.

Patients and method

We have treated 10 patients, since VAC therapy was introduced into our centre of which 3 of whom had a fistula in the bed of the surgical wound. We describe the clinical information of the patients and the therapy that followed in each of the cases.

Results

Significant local clinical improvement of the disease, with control of the symptoms, was achieved in all 3 cases. We were able to re-operate to close the fistula in one of the patients, with subsequent good progression of the wound. In the other two cases it gave them a better quality of life although both died due to the overall complexity of their situation.

Conclusions

VAC therapy, although controversial in the treatment of intestinal fistulas, can help to improve the local situation of the wounds, the comfort of the patients and their general situation.     

Tools for Acquisition, Processing and Knowledge-Based Diagnostic of the Electroencephalogram and Visual Evoked Potentials

The objective of our research is to develop computer-based tools to automate the clinical evaluation of the electroencephalogram (EEG) and visual evoked potentials (VEP). This paper describes a set of solutions to support all the aspects regarding the standard procedures of the diagnosis in neurophysiology, including: (1) acquisition and real-time processing and compression of EEG and VEP signals, (2) real-time brain mapping of spectral powers, (3) classifier design, (4) automatic detection of morphologies through supervised neural networks. (5) signal analysis through fuzzy modelling, and (6) a knowledge based approach to classifier design.     

Keratan sulfate glycosaminoglycan and the association with collagen fibrils in rudimentary lamellae in the developing avian cornea

PURPOSE: Keratan sulfate (KS), through its association with fibrillar collagen as KS-substituted proteoglycan (KS PG), is thought to be instrumental in the structural development of the corneal stroma. The authors used two different sulfate motif-specific antibodies to identify the sequence of appearance, and the association with collagen, of sulfated KS during avian corneal morphogenesis. METHODS: Corneas from chicken embryos throughout the developmental period, from day 8 through day 18 of incubation, were examined by immunofluorescence and immunoelectron microscopy using monoclonal antibodies 5D4 and 1B4, which react with high- and low-sulfated epitopes on KS, respectively. RESULTS: KS was identified as punctate labeling at incubation day 8, the earliest stage examined, suggesting a cell-associated distribution. By day 10, labeling was more homogeneous, indicating that KS sulfation motifs were present in the stromal extracellular matrix. At day 12 through day 14, immunopositive sites were concentrated primarily in the anterior stroma but became more uniform throughout the full stromal thickness by day 18. From day 10 on, electron microscopy revealed a high-sulfated KS epitope closely associated with bundles of regularly arranged collagen fibrils, initially near cell surfaces in rudimentary lamellae. Individual cells, associated with collagen bundles with different fibril orientations, imply the potential for simultaneous deposition of multiple lamellae. CONCLUSIONS: During chick corneal morphogenesis, significant matrix deposition of high-sulfated KS epitope occurs by day 10, with accumulation subsequently proceeding in an anterior-to-posterior manner. High-sulfated KS likely serves to help define the regular spatial organization of collagen fibrils in bundles newly extruded into the extracellular milieu.     

The Roles of PAX6 and SOX2 in Myopia: lessons from the 1958 British Birth Cohort

PURPOSE: Myopia is a common complex trait that affects up to 60% of some populations. Its development is influenced by multiple genes and environmental factors. PAX6 and SOX2 are genes with fundamental roles in ocular growth and development, and they have been linked with myopia in a recent linkage study. The authors investigated the roles of PAX6 and SOX2 in common myopia as part of a broader association study of refractive error. METHODS: Five hundred ninety-six persons from the 1958 British Birth Cohort, a nationally representative population, were randomly selected from the outer tertiles of the refractive error (RE) distribution and were genotyped using 25 tagSNPs across PAX6 and 3 tagSNPs across SOX2 and their putative control regions. This experiment had 80% power to exclude either gene contributing more than 10% of the variance of refractive error. RESULTS: All SNPs were in Hardy-Weinberg equilibrium, and the genotyping failure rate was less than 5%. Accounting for multiple testing, no significant association (P < 0.05) was found between any of the SNPs or haplotypes and refractive error. CONCLUSIONS: PAX6 and SOX2 are obvious candidates in RE genetic studies because of their biological roles and prior linkage studies. The present findings strongly suggest refractive error is not directly affected in this population by variants in either gene or by their known promoters/enhancers. The authors suggest that neither PAX6 nor SOX2 should be prioritized in the international search for genetic modifiers of refractive error. Their findings contribute to broader understanding of the pathophysiology of refractive error and highlight the critical role of replication in genetic research on complex disorders.     

Monocanalicular silastic intubation for the initial correction of congenital nasolacrimal duct obstruction.

BACKGROUND: Treatment of persistent nasolacrimal duct (nasolacrimal duct obstruction) obstruction traditionally has consisted of simple probing. The most common complication with this approach has been recurrent obstruction, requiring another probing, often with the use of bicanalicular silastic intubation. Monocanalicular silastic tubing offers the possibility of increased success rates over simple probing while theoretically minimizing the insertion and removal difficulaties posed by bicanalicular techniques. We report, to our knowledge, the largest series to date of patients undergoing monocanalicular silastic intubation, as well as the first report evaluating this technique as the primary treatment for congenital nasolacrimal duct obstruction obstruction. METHODS: This was a retrospective chart review of 635 children treated by 3 pediatric ophthalmologists via probing with monocanalicular silastic intubation as the initial procedure for congenital nasolacrimal duct obstruction obstruction. Success was defined as good clearance of fluorescein dye and/or the absence of symptomatic tearing. Failure was defined as recurrent symptomatic tearing or inadequate clearance of fluorescein dye, leading to the performance of a second tear duct operation. RESULTS: We identified 635 children who underwent probing with monocanalicular intubation as the primary treatment for congenital nasolacrimal duct obstruction obstruction (mean age at time of probing 18 months). The overall success rate for the 803 eyes undergoing surgery was 96%. The success rate for treatment performed in infants younger than 24 months of age (684 eyes) was 97%, declining to 90% when surgery was performed in infants older than 24 months of age (119 eyes; p < 0.001). These success rates compare favorably to previous reports of primary probing without silastic intubation, especially in children older than 12 months at the time of the probing. The only complication in the current study was conjunctival-corneal abrasion, occurring in 2% of cases. CONCLUSIONS: Probing with monocanalicular silastic intubation as the initial surgical procedure for patients with congenital nasolacrimal duct obstruction obstruction is associated with a very high success rate and low complication rate, especially when performed by the age of 24 months.     

Periungual porocarcinoma

We describe a patient who developed a porocarcinoma in the nail bed. His profession had exposed him to X-rays for many years, resulting in chronic radiodermatitis of several digits on both hands. He displayed an ulcer in the lateral nail fold of the right third digit which extended into the nail bed. The histology of the lesion was consistent with malignant eccrine poroma. Porocarcinoma has not been previously published in this location and this tumor must be considered in differential diagnosis of subungual malignant tumors.     

Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome

Introduction  

Management of the early stage of sepsis is a critical issue. As part of it, infection control including appropriate antibiotic therapy administration should be prompt. However, microbiological findings, if any, are generally obtained late during the course of the disease. The potential interest of procalcitonin (PCT) as a way to assess the clinical efficacy of the empirical antibiotic therapy was addressed in the present study.