Effectiveness of Delayed-release Dimethyl Fumarate on Clinical and Patient-reported Outcomes in Patients With Relapsing Multiple Sclerosis Switching From Glatiramer Acetate: RESPOND,a Prospective Observational Study

Purpose

The goal of this study was to evaluate clinical outcomes and patient-reported outcomes (PROs) over 12 months in patients with relapsing multiple sclerosis (RMS) who switched from glatiramer acetate (GA) to delayed-release dimethyl fumarate (DMF) 240 mg BID after suboptimal response to GA in real-world clinical practice.

Characteristics of Tuberculosis Cases that Started Outbreaks in the United States, 2002–2011

A review of 26 tuberculosis outbreaks in the United States (2002–2011) showed that initial source case-patients had long infectious periods (median 10 months) and were characterized by substance abuse, incarceration, and homelessness. Improved timeliness of diagnosis and thorough contact investigations for such cases may reduce the risk for outbreaks.     

Chronic cerebrolysin administration attenuates neuronal abnormalities in the basolateral amygdala induced by neonatal ventral hippocampus lesion in the rat

The neonatal ventral hippocampal lesion (nVHL) has emerged as a model of schizophrenia‐related behavior in the rat. Our previous report demonstrated that cerebrolysin (Cbl), a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair, promoted recovery of dendritic and neuronal damage of the prefrontal cortex and nucleus accumbens and behavioral improvements in postpubertal nVHL rats. We recently demonstrated that nVHL animals exhibit dendritic atrophy and spine loss in the basolateral amygdala (BLA). This study aimed to determine whether Cbl treatment was capable of reducing BLA neuronal alterations observed in nVHL rats. The morphological evaluation included examination of dendrites using the Golgi‐Cox procedure and stereology to quantify the total cell number in BLA. Golgi‐Cox staining revealed that nVHL induced dendritic retraction and spine loss in BLA pyramidal neurons. Stereological analysis demonstrated nVHL also produced a reduction in cells in BLA. Interestingly, repeated Cbl treatment ameliorated dendritic pathology and neuronal loss in the BLA of the nVHL rats. Our data show that Cbl may foster recovery of BLA damage in postpubertal nVHL rats and suggests that the use of neurotrophic agents for the management of some schizophrenia‐related symptoms may present an alternative therapeutic pathway in these disorders. Synapse, 68:31–38, 2014 . © 2013 Wiley Periodicals, Inc.     

Laparoscopic cholecystectomy can be safely performed in a resource-limited setting: the first 49 laparoscopic cholecystectomies in Yemen.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the gold standard for gallstone disease. Many studies have confirmed the safety and feasibility of LC and have shown that it is comparable regarding complications to open cholecystectomy (OC). The aim of this study was to evaluate the outcomes of LC including safety, feasibility in a resource-poor setting like Yemen, and also to compare the outcomes of LC with those of OC. METHODS: This was a prospective, nonrandomized, comparative study of 112 patients who were admitted to Alburaihy Hospital with a diagnosis of gallstone disease and underwent cholecystectomy from July 1998 to March 2004. Hospital stay, duration of operation, postoperative analgesia, and morbidity due to wound infection, bile leak, common bile duct (CBD) injury, missed CBD stone, bleeding, subphrenic abscess, and hernia were evaluated. Patients were followed up on an outpatient basis. RESULTS: Forty-nine patients underwent LC and 63 patients underwent OC. The mean age of LC patients was 43.96 years and of OC patients was 44.63 years. The 2 groups were similar in terms of age (p=0.740) and sex (p=0.535). No significant difference was found in the incidence of acute cholecystitis between the 2 groups (p=0.000). The mean operative duration for LC was 39.88 minutes versus 56.76 minutes for OC (p=0.000), and the mean hospital stay was 1.63 and 5.38 days for LC and OC, respectively (p=0.000). A drain was used frequently in OC (p=0.000). LC patients needed less analgesia (p=0.000). The morbidity rate in LC was 12.2% versus 6.3% for OC, which was not statistically significant (p=0.394), (p>0.05). Wound infection and bile leak were more common with LC. No mortalities were reported in either group. CONCLUSION: An experienced surgeon can perform LC safely and successfully in a resource-limited setting. As in other studies, LC outcomes were better than OC outcomes.     

Bilateral renal cell carcinoma: report of a case

A case of asynchronous bilateral renal cell carcinoma is reported. The patient was a 71-year-old man who visited our clinic with complaints of asymptomatic macrohematuria and fever on November 20, 1960. Clinical diagnosis was left renal tumor and left nephrectomy was performed on December 4, 1960. Histological diagnosis was renal cell carcinoma (common type, clear cell subtype, alveolar type and G1). The postoperative course was uneventful until complaints of diarrhea and weight loss in November, 1983. He visited our clinic again with a right abdominal mass on January, 1984. Right renal selective angiography revealed an enlargement and abnormal vascularity with tumor stain, hypervascularity and pooling in the whole kidney except for the upper pole lesion. CT scan revealed a space occupying lesion. Right radical nephrectomy was performed on March 6, 1984. Histological diagnosis was renal cell carcinoma (common type, mixed subtype, alveolar and tubular type, G2). He was treated by hemodialysis and steroid therapy after right nephrectomy but he died of massive gastro-intestinal bleeding on April 22, 1984. The paper is the 15th report of a bilateral renal cell carcinoma in Japan.     

Mitochondrial inhibitor 3‐nitroproprionic acid enhances oxidative modification of alpha‐synuclein in a transgenic mouse model of multiple system atrophy

Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by autonomic failure, parkinsonism, cerebellar ataxia, and oligodendrocytic accumulation of alpha‐synuclein (αsyn). Oxidative stress has been linked to neuronal death in MSA and the mitochondrial toxin 3‐nitropropionic acid (3NP) is known to enhance the motor deficits and neurodegeneration in transgenic mice models of MSA. However, the effect of 3NP administration on αsyn itself has not been studied. In this context, we examined the neuropathological effects of 3NP administration in αsyn transgenic mice expressing human αsyn (hαsyn) under the control of the myelin basic protein (MBP) promoter and the effect of this administration on posttranslational modifications of αsyn, on levels of total αsyn, and on its solubility. We demonstrate that 3NP administration altered levels of nitrated and oxidized αsyn in the MBP‐hαsyn tg while not affecting global levels of phosphorylated or total αsyn. 3NP administration also exaggerated neurological deficits in the MBP‐hαsyn tg mice, resulting in widespread neuronal degeneration and behavioral impairment. © 2009 Wiley‐Liss, Inc.     

Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin

Alzheimer’s disease (AD) continues to be the most common cause of cognitive and motor alterations in the aging population. Accumulation of amyloid β (Aβ)-protein oligomers and the microtubule associated protein-TAU might be responsible for the neurological damage. We have previously shown that Cerebrolysin (CBL) reduces the synaptic and behavioral deficits in amyloid precursor protein (APP) transgenic (tg) mice by decreasing APP phosphorylation via modulation of glycogen synthase kinase-3β (GSK3β) and cyclin-dependent kinase-5 (CDK5) activity. These kinases also regulate TAU phosphorylation and are involved in promoting neurofibrillary pathology. In order to investigate the neuroprotective effects of CBL on TAU pathology, a new model for neurofibrillary alterations was developed using somatic gene transfer with adeno-associated virus (AAV2)-mutant (mut) TAU (P301L). The Thy1-APP tg mice (3 m/o) received bilateral injections of AAV2-mutTAU or AAV2-GFP, into the hippocampus. After 3 months, compared to non-tg controls, in APP tg mice intra-hippocampal injections with AAV2-mutTAU resulted in localized increased accumulation of phosphorylated TAU and neurodegeneration. Compared with vehicle controls, treatment with CBL in APP tg injected with AAV2-mutTAU resulted in a significant decrease in the levels of TAU phosphorylation at critical sites dependent on GSK3β and CDK5 activity. This was accompanied by amelioration of the neurodegenerative alterations in the hippocampus. This study supports the concept that the neuroprotective effects of CBL may involve the reduction of TAU phosphorylation by regulating kinase activity. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Uselessness of anti-actin antibody in celiac disease screening

BACKGROUND: Serum anti-actin IgA antibodies (AAA) were identified in patients with celiac disease (CD), and a close correlation emerged between the presence of AAA and mucosa damage, but test for AAA found in celiacs have a wide range of sensitivity and specificity values. AIM: To compare 1) the sensitivity and specificity of untreated, calcium-chelated and heated sera from 102 celiacs, 52 sick patients and 103 healthy controls in the determination of AAA, and 2) the reliability of AAA with anti-transglutaminase antibodies (anti-tTG) in diagnosing celiac disease and in predicting intestinal damage. The intestinal derived AAA was isolated by using the phage-display library technique. RESULTS: Treated sera was significantly more sensitive than untreated (p=0.0001), and showed a significant correlation between AAA and the three degrees (3a, 3b, 3c) of intestinal damage (p=0.01). Sensitivity and specificity values of anti-tTG assay were higher than the AAA assay, and anti-tTG serum-concentration was only significantly correlated with more severe (3b and 3c) intestinal damage degrees. AAA isolated by phage display showed similar results of serum AAA in immunofluorescence assay. CONCLUSIONS: Notwithstanding correlation between AAA and celiac disease, AAA assay, also after treatments, has little to offer in screening for CD compared to the well-established anti-transglutaminase assay.     

Sensitivity and specificity of rapid influenza testing of children in a community setting

Please cite this paper as: Stebbins et al. (2011) Sensitivity and specificity of rapid influenza testing of children in a community setting. Influenza and Other Respiratory Viruses 5(2), 104–109. Introduction Rapid influenza testing (RFT) allows for a rapid point‐of‐care diagnosis of influenza. The Quidel QuickVue^® Influenza A+B test (QuickVue) has a reported manufacturer’s sensitivity and specificity of 73% and 96%, respectively, with nasal swabs. However, investigators have shown sensitivities ranging from 22% to 77% in community settings. Methods The QuickVue rapid influenza test was evaluated in a population of elementary (K‐5) school children, using testing in the home, as part of the Pittsburgh Influenza Prevention Project during the 2007–2008 influenza season. The QuickVue test was performed with nasal swab in full accordance with package instructions and compared with the results of nasal swab semi‐quantitative RT‐PCR. Results Sensitivity of the QuickVue was found to be 27% in this sample. There was no statistically valid correlation between the semi‐quantitative PCR result and the QuickVue result. Conclusions This study is consistent with the low sensitivity of the QuickVue test also reported by others. Viral load, technique, and the use of nasal swabs were examined as contributing factors but were not found to be explanations for this result. Community testing includes patients who are on the lower spectrum of illness which would not be the case in hospital or clinic samples. This suggests that RFT is less sensitive for patients at the lower spectrum of illness, with less severe disease.