Experimental Lead Neuropathy: Ultrastructural And Molecular Changes In The Rat Sciatic Nerve

Experimental lead intoxication is an important model for the study of cellular and molecular mechanisms of segmental demyelination in peripheral nerve. In this report we have compared pathological changes with the molecular and immunohistochemical expression of the proteins of compact and non-compact myelin in the demyelinating neuropathy induced in Sprague-Dawley rats after chronic administration (3 and 6 months) of lead acetate in drinking water. All the rats underwent the neurophysiological determination of the conduction velocity in the tail nerve at baseline and 3, 4.5 and 6 months after the beginning of the lead acetate administration. At the end of the treatment period the rats were sacrificed and sciatic nerve specimens were obtained. The neurophysiological study demonstrated a significant decrease in the nerve conduction velocity, which was already evident at the first determination (3 months) and persisted along the entire experiment. The neurophysiological results were in agreement with the pathological observations performed in the sciatic nerve, where several large demyelinated fibers were observed in the lead-intoxicated rats. Northern and Western blot analysis demonstrated that steady state mRNA and protein levels for P0, MBP, PMP22 and PLP were not changed comparing treated and control rats. Immunohistochemistry on teased fibers revealed that those proteins were distributed in areas of compact myelin along the internodes. In control fibers, as expected, MAG was found in the periaxonal cytoplasm, at nodes of Ranvier, and in the Schmidt-Lanterman incisures. In lead neuropathy, MAG was still limited to discrete regions, but the intensity of staining was reduced, in accordance with changes of paranodal structures. Immunohistochemical localization of other proteins of non-compacted myelin, including connexin-32, E-cadherin and β-catenin was also examined. Our data further suggest that chronic lead intoxication in the rat produces segmental demyelination due primarily to Schwann cell dysfunction.     

Are psychotic symptoms related to vagus nerve stimulation in epilepsy patients?

Four patients with refractory epilepsy presented with psychotic symptoms following treatment with vagus nerve stimulation (VNS) to control seizures. Besides its anti-epileptic effect VNS has been shown to have an effect on various cognitive and behavioural functions. VNS is known to increase alertness and reduce sedation, which is independent from seizure control. VNS has also been shown to positively affect cognition and to exert strong antidepressant effects. Co-morbidity in epilepsy often comprises psychiatric illnesses. Increased psychiatric symptoms have mainly been described in association with successful outcome following epilepsy surgery as a result of 'forced normalisation'. Different hypotheses on the underlying aetiology of VNS-induced psychotic symptoms other than the previously described 'forced normalisation' are discussed.     

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.     

Patient-reported outcomes for patients undergoing radical cystectomy: a prospective case–control study

Purpose

The purpose of this study was to measure patient-reported outcomes (PROs) for patients with muscle-invasive bladder cancer (BC) before the diagnosis of BC was known, thus before cystectomy, and until 1 year postcystectomy. The differences in outcomes between a health status (HS) and quality of life (QoL) questionnaires were examined.

Methods

From July 2007 to July 2010, 598 patients with primary hematuria were enrolled in this prospective, multi-centre case–control (CC) study. Patients undergoing radical cystectomy (RC; N?=?18) were compared with patients with other causes of hematuria (CC, N?=?20). Measurement points were before diagnosis as well as 3, 6 and 12 months postcystectomy. Questionnaires used were the WHOQOL-BREF, SF-12, International Index of Erectile Function, and 10-item STAI-Trait scale.

Results

Prediagnosis patients who later appeared to have BC had the same QoL compared to CC patients. The prediagnosis physical component scale of HS and sexual function were significantly lower for RC vs. CC patients. RC patients had a better prediagnostic QoL and HS than postcystectomy at all time points.

Conclusions

This is the first case–control study with a baseline measurement of PROs before the diagnosis of BC was known. It shows lower physical health and sexual function for RC vs. CC before diagnosis is known. Until 1 year postcystectomy, QoL does not return to baseline level. Future studies including comorbidity and smoking history are needed to examine the generalizability of our results.     

Identification of four new members of the internalin multigene family of Listeria monocytogenes EGD.

Listeria monocytogenes is a bacterial pathogen that is able to invade nonphagocytic cells. Two surface proteins, internalin, the inlA gene product, and InlB, play important roles in the entry into cultured mammalian cells. These proteins also have extensive sequence similarities. Previously, Southern hybridization predicted the existence of an internalin multigene family. Recently, InlC, a secreted protein of 30 kDa homologous to InlA and InlB, was identified. In this work, we identified and characterized four new members of the internalin multigene family, inlC2, inlD, inlE, and inlF which encode proteins of 548, 567, 499, and 821 amino acids respectively. inlC2, inlD, and inlE are contiguous on the chromosome of L. monocytogenes EGD, whereas inlF is located in a different chromosomal region. These four inl gene products display the principal features of internalin, namely, a signal sequence, two regions of repeats (or LRR and B repeats), and a putative cell wall anchor sequence containing the sorting motif LPXTG. The four inl genes were maximally expressed albeit at a low level during early exponential growth in bacterial medium at 37 degrees C. The role of these inl genes in L. monocytogenes invasion was assessed by constructing isogenic chromosomal deletion mutants and testing them for entry into various nonphagocytic cells. Unexpectedly, the inlC2, inlD, inlE, and inlF null mutants were not affected for entry into any of the cell lines tested, raising the possibility that these genes are needed for an aspect of pathogenicity other than invasion. The identity of such an aspect remains to be determined.     

Persistent synovitis in children with Lyme arthritis: two unusual cases. An immunogenetic approach

We report on two patients with a persistent Lyme arthritis. In addition both had a peculiar disease history. The first patient had oligoarticular juvenile idiopathic arthritis in remission. Five months after an infected tick bite, she developed a relapse of arthritis in the same knee. We considered Lyme borreliosis as the possible trigger for this reactivation. The disease history of the second patient was that of a classical non-responder. After extensive antibiotic treatment osteolytic lesions became visible. MRI images suggested an erosive arthropathy and arthroscopy was used to investigate possible erosive arthritis. Studies on collected material made us consider the following hypothesis. Despite demonstration of a spirochete fragment in a synovial biopsy, the patient recovered without additional antibiotic treatment. Conclusion: delay of antibiotic treatment after appearance of erythema migrans may cause systemic spread of the antigen and predispose to Lyme arthritis. If intra-articular steroids are considered when spontaneous resolution of Lyme arthritis does not occur, magnetic resonance imaging of the affected joint, prior to administration, may provide additional information. The success of synovectomy may be related to removal of undegraded antigenic material which may prolong the inflammation.Abbreviations ELISA enzyme-linked immunosorbent assay - EM erythema migrans - JIA juvenile idiopathic arthritis - LA Lyme arthritis - LD Lyme disease - LIV Lyme index value     

Trisomy 7 mosaicism, maternal uniparental heterodisomy 7 and Hirschsprung's disease in a child with Silver-Russell syndrome

Prenatal trisomy 7 is usually a cell culture artifact in amniocytes with normal diploid karyotype at birth and normal fetal outcome. In the same way, true prenatal trisomy 7 mosaicism usually results in a normal child except when trisomic cells persist after birth or when trisomy rescue leads to maternal uniparental disomy, which is responsible for 5.5-7% of patients with Silver-Russell syndrome (SRS). We report here on the unusual association of SRS and Hirschsprung's disease (HSCR) in a patient with maternal uniparental heterodisomy 7 and trisomy 7 mosaicism in intestine and skin fibroblasts. HSCR may be fortuitous given its frequency, multifactorial inheritance and genetic heterogeneity. However, the presence of the trisomy 7 mosaicism in intestine as well as in skin fibroblasts suggests that SRS and HSCR might possibly be related. Such an association might result from either an increased dosage of a nonimprinted gene due to trisomy 7 mosaicism in skin fibroblasts (leading to SRS) and in intestine (leading to HSCR), or from an overexpression, through genomic imprinting, of maternally expressed imprinted allele(s) in skin fibroblasts and intestine or from a combination of trisomy 7 mosaicism and genomic imprinting. This report suggests that the SRS phenotype observed in maternal uniparental disomy 7 (mUPD(7)) patients might also result from an undetected low level of trisomy 7 mosaicism. In order to validate this hypothesis, we propose to perform a conventional and molecular cytogenetic analysis in different tissues every time mUPD7 is displayed.     

Antimicrobial resistance of Acinetobacter spp. in Europe

Bacteria of the genus Acinetobacter are ubiquitous in nature. These organisms were invariably susceptible to many antibiotics in the 1970s. Since that time, acinetobacters have emerged as multiresistant opportunistic nosocomial pathogens. The taxonomy of the genus Acinetobacter underwent extensive revision in the mid-1980s, and at least 32 named and unnamed species have now been described. Of these, Acinetobacter baumannii and the closely related unnamed genomic species 3 and 13 sensu Tjernberg and Ursing (13TU) are the most relevant clinically. Multiresistant strains of these species causing bacteraemia, pneumonia, meningitis, urinary tract infections and surgical wound infections have been isolated from hospitalised patients worldwide. This review provides an overview of the antimicrobial susceptibilities of Acinetobacter spp. in Europe, as well as the main mechanisms of antimicrobial resistance, and summarises the remaining treatment options for multiresistant Acinetobacter infections.