Effects of acute and chronic denervation on human myotonia

A 32-year-old man with myotonia congenita (Becker type) sustained multiple gunshot wounds. These produced a partial thoracic spinal cord injury and a severe sciatic nerve injury. Six days following the incident, clinical (percussion) and electrophysiologic (EMG) myotonia could be elicited in paretic leg muscles resulting both from the myelopathy and peripheral nerve disruption. Eight months later, the myotonia was no longer present in denervated muscles from the sciatic nerve injury, but was still noted in muscles with upper-motor neuron weakness from the myelopathy. Although myotonia is related principally to abnormalities in the muscle fiber itself, it appears that it is also dependent upon the structural integrity of the peripheral nerve supply to the muscle for myotonia to continue to occur. The findings in this patient suggest that myotonia may well have diminished and disappeared in muscles shortly after the nerves had undergone Wallerian degeneration. Myotonia does not recur if there is no significant reinnervation.     

Change of antimicrobial susceptibility among Escherichia coli strains isolated from female patients with community-onset acute pyelonephritis

Purpose

There is a concern on which antimicrobials are appropriate as empirical agents for community-onset acute pyelonephritis (APN) in regions where the fluoroquinolone resistance rate is high, such as in Korea.

Materials and Methods

Three hundred and two strains of E. coli in 2001-2002 and 349 strains in 2008-2009 were isolated from the urine cultures of female adult APN patients, and the antimicrobial susceptibility was compared according to each study period. All the patients were classified as uncomplicated or complicated APN, and a subgroup analysis was done thereafter.

Results

The E. coli strains isolated in 2008-2009 showed improved susceptibility to trimethoprim-sulfamethoxazole compared to those isolated in 2001-2002. However, the third generation cephalosporin and gentamicin susceptibility was worsened. Of the 232 isolates from the uncomplicated APN patients, there was no difference between the two different time periods. On the other hand, of the 419 isolates from the complicated APN patients, the susceptibility to third generation cephalosporin, gentamicin and ciprofloxacin was significantly worsened.

Conclusion

The antimicrobial susceptibility of E. coli changed over the study period, however, this change occurred mainly in the complicated APN patients. In Korea, ciprofloxacin is still useful as an empirical agent for uncomplicated APN patients, but this is not the case for patients with complicated APN because of high resistance rate to ciprofloxacin in these patients. For the complicated APN patients, the rate of resistance to ciprofloxacin is already more than 30%.     

SOST expression is restricted to the great arteries during embryonic and neonatal cardiovascular development.

Spatial-temporal regulation of bone morphogenetic protein (BMP) and Wnt activity is essential for normal cardiovascular development, and altered activity of these growth factors causes maldevelopment of the cardiac outflow tract and great arteries. In the present study, we show that SOST, a Dan family member reported to antagonize BMP and Wnt activity, is expressed within the medial vessel wall of the great arteries containing smooth muscle cells. The ascending aorta, aortic arch, brachiocephalic artery, common carotids, and pulmonary trunk were all associated with SOST expressing smooth muscle cells, while the heart itself, including the valves, and more distal arteries, that is, pulmonary arteries, subclavian arteries, and descending aorta, were negative. SOST was expressed from embryonic day 15.5 up to the neonatal period. SOST expression, however, did not correspond with inhibition of Smad-dependent BMP activity or beta-catenin-dependent Wnt activity in the great arteries. Activity of both signaling pathways was already down-regulated before induction of SOST expression.     

TRARESA: a tissue microarray-based hospital system for biomarker validation and discovery

Formalin fixed and paraffin embedded tissue (FFPE) collections in pathology departments are the largest resource for retrospective biomedical research studies. Based on the literature analysis of FFPE related research, as well as our own technical validation, we present the Translational Research Arrays (TRARESA), a tissue microarray centred, hospital based, translational research conceptual framework for both validation and/or discovery of novel biomarkers. TRARESA incorporates the analysis of protein, DNA and RNA in the same samples, correlating with clinical and pathological parameters from each case, and allowing (a) the confirmation of new biomarkers, disease hypotheses and drug targets, and (b) the postulation of novel hypotheses on disease mechanisms and drug targets based on known biomarkers. While presenting TRARESA, we illustrate the use of such a comprehensive approach. The conceptualisation of the role of FFPE-based studies in translational research allows the utilisation of this commodity, and adds to the hypothesis-generating armamentarium of existing high-throughput technologies.     

Long-Term Antibody and Immune Memory Response Induced by Pulmonary Delivery of the Influenza Iscomatrix Vaccine

Pulmonary delivery of an influenza Iscomatrix adjuvant vaccine induces a strong systemic and mucosal antibody response. Since an influenza vaccine needs to induce immunological memory that lasts at least 1 year for utility in humans, we examined the longevity of the immune response induced by such a pulmonary vaccination, with and without antigen challenge. Sheep were vaccinated in the deep lung with an influenza Iscomatrix vaccine, and serum and lung antibody levels were quantified for up to 1 year. The immune memory response to these vaccinations was determined following antigen challenge via lung delivery of influenza antigen at 6 months and 1 year postvaccination. Pulmonary vaccination of sheep with the influenza Iscomatrix vaccine induced antigen-specific antibodies in both sera and lungs that were detectable until 6 months postimmunization. Importantly, a memory recall response following antigenic challenge was detected at 12 months post-lung vaccination, including the induction of functional antibodies with hemagglutination inhibition activity. Pulmonary delivery of an influenza Iscomatrix vaccine induces a long-lived influenza virus-specific antibody and memory response of suitable length for annual vaccination against influenza.     

Routine outcome monitoring in the Netherlands: practical experiences with a web‐based strategy for the assessment of treatment outcome in clinical practice

Routine outcome monitoring (ROM) is a method devised to systematically collect data on the effectiveness of treatments in everyday clinical practice. ROM involves documenting the outcome of treatments through repeated assessments. Assistants are employed who perform a baseline assessment comprising a standardized diagnostic interview, administration of rating scales and completion of several self‐report measures by the patient. At fixed time intervals, assessments are repeated. Dedicated Web‐based software has been developed to assist in this task. ROM informs therapists and patients on the severity of the complaints at intake, and the waxing and waning of symptoms over the course of treatment. Researchers can use ROM for effectiveness research, and managers can use it for benchmarking. The use of ROM for research is illustrated by presenting data on the diagnostic status of patients participating in ROM and data on treatment outcome of a subgroup of patients (with panic disorder) in our database. The results show that implementation of ROM is feasible, and after some initial reservations, most therapists now consider ROM to be a necessary and important adjunct to the clinical treatment. In addition, ROM furthers research as the data can be used to study the phenomenology of psychiatric disorders and the outcome of treatments delivered in everyday practice. Copyright © 2010 John Wiley & Sons, Ltd. Key Practitioner Message: ? A form of tracking the progress of treatment through routine outcome monitoring (ROM) is described. ? Implementation of ROM appears feasible and can be carried out in large institutions as well as smaller practices. ? Providing feedback about outcome in an appealing format is highly valued by both therapists and patients. ? ROM data enable investigation of the effectiveness of treatments in everyday clinical practice.     

Using distraction forces to drive an autodistractor during limb lengthening

Distraction osteogenesis can result in high forces developing in the limb. To determine and control the distraction forces (DF), a motorized distractor driven by feedback from DF was developed and used to lengthen the tibiae of 6 sheep undergoing distraction osteogenesis. The forces were measured continually, and, in 4 of the sheep, a force threshold was set, above which an increase in rate was initiated. The rate kept increasing to a set limit if forces remained above the threshold; otherwise, the rate was decreased. Radiographs were acquired biweekly, and muscle samples were analyzed from both the operated and contralateral limbs upon termination of the experiment. Results demonstrated a drop in DF associated with increased lengthening rate, attributed to separation of the callus as indicated by radiography. Histological evidence of muscle damage generally correlated with higher DF levels. There was a significant decrease in muscle fiber diameter in lengthened relative to contralateral limbs. Collectively, the results demonstrated the use of a force-driven distraction system and support the need for considering force data in regulating distraction rates to achieve optimal clinical outcomes.     

Effect of Hydroxychloroquine Treatment on Dry Eyes in Subjects with Primary Sj?gren’s Syndrome: a Double-Blind Randomized Control Study

The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren''s syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. {"type":"clinical-trial","attrs":{"text":"NCT01601028","term_id":"NCT01601028"}}NCT01601028).     

Evaluation of Antiviral Activities of Four Local Malaysian Phyllanthus Species against Herpes Simplex Viruses and Possible Antiviral Target

Nucleoside analogues such as acyclovir are effective antiviral drugs against herpes simplex virus infections since its introduction. However, with the emergence of acyclovir-resistant HSV strains particularly in immunocompromised patients, there is a need to develop an alternative antiherpetic drug and plants could be the potential lead. In this study, the antiviral activity of the aqueous extract of four Phyllanthus species were evaluated against herpes simplex virus type-1 (HSV-1) and HSV-2 in Vero cells by quantitative PCR. The protein expressions of untreated and treated infected Vero cells were studied by 2D-gel electrophoresis and Western blot. This is the first study that reported the antiviral activity of P. watsonii. P. urinaria was shown to demonstrate the strongest antiviral activity against HSV-1 and HSV-2, with SI >33.6. Time-of-addition studies suggested that the extract may act against the early infection stage and the replication stage. Protein expression studies indicated that cellular proteins that are involved in maintaining cytoskeletal structure could be potential target for development of antiviral drugs. Preliminary findings indicated that P. urinaria demonstrated potent inhibitory activity against HSV. Hence, further studies such as in vivo evaluation are required for the development of effective antiherpetic drug.