Upper limb motor evoked potentials as outcome measure in progressive multiple sclerosis.

OBJECTIVE: To assess the usefulness of upper limb (UE) motor evoked potential (MEPs) as a marker of motor impairment in a cohort of people with progressive multiple sclerosis (PwPMS). METHODS: we evaluated UE and lower extremities (LE) MEPs, 6-minutes walk-test (6MWT), 10-meter walk-test (10MWT), EDSS, 9-hole peg-test (9HPT), and measures of strength (MRC) and tone (MAS) to the UE and LE in 50 PwPMS (EDSS 4.0-6.5; P ≥ 3, C ≤ 2). RESULTS: Bilateral absence of LE-MEPs, found in 74% of cases, was associated with worse 10MWT and 6MWT. UE-MEPs were rarely absent (8%) but often delayed (74%). Abnormal UE-MEPs were associated with worse performance at 9HPT (25.8 vs 33.2 s). UE-MEPs latency correlated with 10MWT (rho = 0.597), 6MWT (rho = -0.425) and EDSS (rho = 0.296). CONCLUSION: UE-MEPs may represent a clinically relevant outcome measure to quantify corticospinal tract integrity in PwPMS, at least when LE-MEPs cannot provide a measurable response. SIGNIFICANCE: The strive for novel remyelination strategies in MS points to the need for quantitative conduction measurements in addition to clinical outcomes. The frequent absence of MEPs to the lower limbs in PwPMS may greatly limits their usefulness in monitoring progression or response to therapies. With this respect, the upper extremities may represent a better target.

Acquired haemophilia A as a secondary autoimmune disease after alemtuzumab treatment in multiple sclerosis: A case report.

Alemtuzumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS). During the immune reconstitution following the use of this treatment severe secondary autoimmune diseases (SADs) can develop. We present the case of a patient affected by active MS who failed to achieve disease control with several disease-modifying drugs and was thereafter successfully treated with alemtuzumab, obtaining no evidence of disease activity and a high quality of life. Twenty months after the first infusion of alemtuzumab the patient developed acquired haemophilia A (AHA), a treatable but potentially lifethreatening condition that should be considered a possible SADs associated to this drug. In order to allow an early diagnosis and to prevent possible complications of AHA, routine coagulation tests (prothrombin time and activated partial thromboplastin time) should be included in the laboratory serological monitoring of patients treated with alemtuzumab.

Unsaturated acyl chains dramatically enhanced cellular uptake by direct translocation of a minimalist oligo-arginine lipopeptide.

The recurring issue with cell penetrating peptides is how to increase direct translocation vs. endocytosis, to avoid premature degradation. Acylation by a cis unsaturated chain (C22:6) of a short cationic peptide provides a new rational design to favour diffuse cytosolic and dense Golgi localisations.

Four glycoproteins are expressed in the cat zona pellucida.

The mammalian oocyte is surrounded by a matrix called the zona pellucida (ZP). This envelope participates in processes such as acrosome reaction induction, sperm binding and may be involved in speciation. In cat (Felis catus), this matrix is composed of at least three glycoproteins called ZP2, ZP3, and ZP4. However, recent studies have pointed to the presence of a fourth protein in several mammals (rat, human, hamster or rabbit), meaning that a reevaluation of cat ZP is needed. For this reason, the objective of this research was to analyze the protein composition of cat ZP by means of proteomic analysis. Using ZP from ovaries and oocytes, several peptides corresponding to four proteins were detected, yielding a coverage of 33.17%, 71.50%, 50.23%, and 49.64% for ZP1, ZP2, ZP3, and ZP4, respectively. Moreover, the expression of four genes was confirmed by molecular analysis. Using total RNA isolated from cat ovaries, the complementary deoxyribonucleic acids encoding cat ZP were partially amplified by reverse-transcribed polymerase chain reaction. Furthermore, ZP1 was totally amplified for the first time in this species. As far as we are aware, this is the first study that confirms the presence of four proteins in cat ZP.

Complement component C6 deficiency in a Spanish family: implications for clinical and molecular diagnosis.

Complement component C6 deficiency is a genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. This disorder has rarely been diagnosed in the Spanish population. In this work we report the immunochemical and molecular characterization of complement C6 deficiency in a Spanish patient showing no detectable functional activity of either the classical or alternative complement pathways and reporting a history of several episodes of meningococcal meningitis. The levels of individual complement components C3, C4, C5, C7, C8 and C9 were within the normal range. However, C6 level was low in the patient's serum as measured by radial immunodiffusion. Exon-specific polymerase chain reaction and sequencing of the C6 gene revealed a previously described homozygous single base deletion in exon 6 (c.821delA), leading to a shift in the reading frame that caused the generation of a downstream stop codon, which, in turn, provoked the truncation of the C6 protein (p.Gln274fs). To our knowledge, this is the first report on the c.821delA mutation in the Spanish population, which has previously only been identified in individuals of African ancestry. Characterization of this mutation was thought interesting in order to elucidate its source and help understand the molecular basis of this uncommon deficiency in our population. Moreover, this report highlights the importance of complement screening in cases of repeated meningococcal infections in order to establish its involvement and to consider adequate clinical recommendations such as prophylactic antibiotics or meningococcal vaccines and, subsequently, for genetic counselling.

Post-transplant increase in soluble human leukocyte antigen-G associated with non-severe cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the single most important long-term limitation to heart transplantation. This study aimed to assess the value of monitoring soluble human leukocyte antigen-G (sHLA-G) during the first year post-transplantation to predict the severity of CAV, in 21 out of 77 heart recipients assessed by intravascular ultrasound (IVUS). Serum sHLA-G concentration increased after transplant in recipients free of severe CAV, but decreased in recipients suffering from severe CAV, significant differences between these two groups were found 6 to 12 months post-transplantation. The optimal value of the change in post-transplant sHLA-G for identifying severe CAV was ≥0.062%, which maximized sensitivity (80%) and specificity (100%). Importantly, increases in post-transplant sHLA-G were inversely associated with severe CAV, but directly associated with human cytomegalovirus reactivation. In addition, recipients presenting non-severe CAV or an increased sHLA-G post-transplantation, showed higher numbers of CD8(+)CD28(-) T cells and a down-modulation of CD28 on CD4(+) lymphocytes, which typically identifies CD8(+) regulatory T cells and anergic/tolerogenic T helper cells, respectively. In conclusion, quantification of sHLA-G might offer a complementary non-invasive method for identifying recipients at risk of more severe CAV and who might benefit from earlier preventive therapies, although these results need to be confirmed in larger series.

Fully covered self-expandable metallic stents in benign biliary strictures: a multicenter study on efficacy and safety.

BACKGROUND AND STUDY AIM: Benign biliary diseases include benign biliary stricture (BBS), lithiasis, and leaks. BBSs are usually treated with plastic stent placement; use of uncovered or partially covered metallic stents has been associated with failure related to mucosal hyperplasia. Some recently published series suggest the efficacy of fully covered self-expandable metal stents (FCSEMSs) in BBS treatment. We aimed to assess the efficacy and safety of FCSEMS in a large series of patients with BBS and a long follow-up.  PATIENTS AND METHODS: Prospective multicenter clinical study at three tertiary referral centers: ISMETT/UPMC Italy, Palermo, San Paolo Hospital, Milan, and the ARNAS Civico Hospital, Palermo, Italy. All consecutive patients with BBS were treated with placement of FCSEMS rather than plastic stents, as first approach (11 patients, 17.7 %), or as a second approach after failure of other treatments (51 patients, 82.2 %). RESULTS: From January 2008 to March 2011, 62 patients (40 male) were included. Mean period of FCSEMS indwelling was 96.7 days (standard deviation [SD] 6.5 days). In 15 patients (24.2 %) the SEMS migrated. Resolution of BBS occurred in 56 patients (90.3 %), while in 6 (9.6 %) the treatment failed. Mean (SD) follow-up after SEMS removal was 15.9 (10) months. FCSEMS placement as first- or second-line approach showed no difference in failure. Recurrence was observed in 4 /56 patients (7.1 %); all were transplant recipients: P = 0.01; odds ratio (OR) 1.2, confidence interval (CI) 1.1 - 1.3. CONCLUSIONS: Despite the noteworthy migration rate, FCSEMSs should be considered effective for refractory benign biliary strictures. Further studies are needed to assess their role as a first approach in the management of BBS.

Covered self expandable metallic stent with flared plastic one inside for pancreatic pseudocyst avoiding stent dislodgement.

Endoscopic ultrasound-guided drainage has recently been recommended for increasing the drainage rate of endoscopically managed pancreatic fluid collections and decreasing the morbidity associated with conventional endoscopic trans-mural drainage. The type of stent used for endoscopic drainage is currently a major area of interest. A covered self expandable metallic stent (CSEMS) is an alternative to conventional drainage with plastic stents because it offers the option of providing a larger-diameter access fistula for drainage, and may increase the final success rate. One problem with CSEMS is dislodgement, so a metallic stent with flared or looped ends at both extremities may be the best option. An 85-year-old woman with severe co-morbidity was treated with percutaneous approach for a large (20 cm) pancreatic pseudocyst with corpuscolated material inside. This approach failed. The patient was transferred to our institute for EUS-guided transmural drainage. EUS confirmed a large, anechoic cyst with hyperechoic material inside. Because the cyst was large and contained mixed and corpusculated fluid, we used a metallic stent for drainage. To avoid migration of the stent and potential mucosal growth above the stent, a plastic prosthesis (7 cm, 10 Fr) with flaps at the tips was inserted inside the CSEMS. Two months later an esophagogastroduodenoscopy was done, and showed patency of the SEMS and plastic stents, which were then removed with a polypectomy snare. The patient experienced no further problems.

Fully covered metallic stents in biliary stenosis after orthotopic liver transplantation.

BACKGROUND AND STUDY AIMS: Data from a preliminary study suggested that the placement of a fully covered metal stent may be a valid alternative to surgery in patients who do not respond to standard endoscopic treatment. The aims of the current study were to evaluate the clinical success of self-expandable metallic stents (SEMS) in a large cohort of patients and with a long followup,and the effectiveness of SEMS placement as a first-line procedure. MATERIALS AND METHODS: Between January 2008 and August 2010, 54 consecutive patients with biliary complications following orthotopic liver transplantation were treated with SEMS placement:39 after failure of conventional endoscopic therapy (Group I), and 15 with no previous endoscopic treatment who were undergoing SEMS placement as first-line treatment for complications(Group II). RESULTS: In Group I, resolution after SEMS removal was observed in 71.8% of patients. Mean followup after resolution was 22.1 ±10 months. Recurrence of the complication was observed in 14.3%of patients after a mean of 8.5 months and SEMS migration was observed in 33.3% of patients. In Group II, resolution was observed in 53.3% of patients.Mean follow-up after resolution was 14.4±2.2 months. Recurrence was observed in 25% of patients and SEMS migration was observed in 46.7 %. CONCLUSIONS: For endotherapy of biliary complications after orthotopic liver transplantation, metallic stents should not be used as the primary modality. In patients in whom the standard approach fails, treatment with temporary SEMS placement can solve biliary complications in almost three-quarters of cases; however stent migration(33 %) remains a problem.

Air embolism during endoscopic retrograde cholangiopancreatography in a pediatric patient.

This is a case of a venous air embolism in a pediatric patient with splenomesenteric portal shunt for portal cavernoma, who underwent endoscopic retrograde cholangiopancreatography under inhalator general anesthesia, without using N2O. There is ample data in the literature about the occurrence of venous air embolism during an endoscopic procedure. We believe it is important to call attention to this rare, but possible, and sometimes fatal, complication.

Usefulness of the "rendezvous" technique in living related right liver donors with postoperative biliary leakage from bile duct anastomosis.

This is a report on two cases of large bile leak following right hepatectomy performed for living related liver transplantation, originating from the stump of the ligated right bile duct, and treated with the placement of large percutaneous biliary catheters through a combined percutaneous transhepatic and endoscopic approach (rendezvous technique).

Behavioral consequences of bone marrow transplantation in the treatment of murine mucopolysaccharidosis type VII.

The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII caused by deficient beta-glucuronidase activity. Bone marrow transplantation has been shown to correct some of their biochemical and pathological abnormalities but its efficacy in correcting their neurological functional deficits is unknown. We transplanted the neonatal gusmps/gusmps mice and their normal controls and evaluated their central nervous system function with two behavioral tests: the grooming test, a developmentally regulated and genetically based activity, and a Morris water maze test which assessed spatial learning abilities. The two transplanted groups groomed less than the normals, were unable to remember the location of an invisible platform from day to day, and were severely impaired at developing strategies to locate the platform in unfamiliar locations. The performance of both normal and mutant transplanted groups was clearly inferior to the untreated normals and, in some instances, close to or worse than the untreated mutants, even though the enzyme abnormalities of the mutants have been partially corrected. Hence, the behavioral deficits in the mutant mice were not restored to normal while similarly treated normal mice showed significant functional deterioration, indicating the detrimental consequence of this therapy in the neonatal period.

Behavioural abnormalities in a murine model of a human lysosomal storage disease.

The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII due to deficient beta-glucuronidase activity. We now report behavioural abnormalities associated with this single gene defect. In grooming, a developmentally regulated and genetically based activity, the mutant mice spent 1-5% of the normal time for body grooming and about 60% of the normal time in face grooming when stimulated with a light water mist. In the Morris water maze which tests spatial learning, the mutants could learn to locate an invisible platform but were deficient in remembering its location the next day or developing strategies to locate it in new positions. Thus, the gusmps/gusmps mouse demonstrates behavioural, memory and cognitive deficiencies suitable for monitoring functional restorations in therapy.

Regionally selective roles of the rat's striatum in modality-specific discrimination learning and forelimb reaching.

Rats with ibotenate lesions of either the medial striatum or the lateral striatum were trained in a forelimb reaching task and in acquisition, retention and reversal of either turn (left-right) discrimination or brightness (black-white) discrimination in a cross-shape maze. Compared with the controls, the rats with lesions of the medial striatum showed a reliable, modality-selective impairment in reversal of turn discrimination, but no significant impairment of reaching. In contrast, the rats with lateral striatal lesions showed a significant impairment of forelimb reaching, but not of reversal of either discriminations. Neither medial nor lateral lesions significantly affected acquisition and retention of both discriminations. The findings indicate a predominant role of the medial striatum in monitoring of directional responses, confirm the regionally specific role of the lateral striatum in reaching, and are interpreted to support the hypothesis of parallel motor and cognitive forebrain circuits comprising distinctive regions of the striatum.

Clinical assessment of the Hitachi 736-30 chemistry analyzer.

We assessed the Hitachi 736-30 as a possible replacement for the SMAC I and as a laboratory cost-saving measure. For 24 analytes, both intra- and interassay precisions were acceptable; they also had good measuring ranges. Essentially no interference from lipemia was observed, while minimal interference from bilirubin was demonstrated. Hemoglobin interfered in the measurement of 12 of the analytes. Correlation with the SMAC I, Demand, Astra-8, ACA, and Varian Atomic Absorption Spectrophotometer was found to be acceptable, except for chloride which showed poor correlation with SMAC I and Astra-8 (Hitachi = 0.888 [SMAC] + 11.102, r = 0.9652; Hitachi = 0.885 [Astra] + 10.264, r = 0.9136). The Hitachi 736-30 offers reagent and method flexibility, high volume capability, and "walk-away" operation.