Synchronous cytomegalovirus and Clostridium difficile infection of the pouch: a trigger for chronic pouchitis?

Pouchitis occurs in up to one half of patients after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Cytomegalovirus (CMV) and Clostridium difficile are among the commonest secondary identifiable etiologies. A 17-year-old male with ulcerative colitis underwent IPAA due to refractory disease. Nine months later he experienced bloody diarrhea and fever. Laboratory testing and endoscopy confirmed pouch inflammation. Testing for C. difficile toxins A and B was positive. Histology revealed affluent inclusion bodies and immunohistochemistry detected reactivity against CMV protein. Treatment with metronidazole and vancomycin offered partial improvement, whereas the addition of gancyclovir led to a successful recovery. One month after completion of treatment symptoms recurred. Repeat testing precluded an identifiable infectious cause and the diagnosis of idiopathic chronic pouchitis was established. The patient is currently on maintenance treatment with the probiotic compound VSL#3.     

Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease

Background

TNF-like cytokine 1A provides co-stimulatory signals to activated lymphocytes through binding to death-domain receptor-3. Decoy receptor-3 inhibits death-domain receptor-3 signalling, rendering immunocytes resistant to apoptosis. These functions may be important for the pathogenesis of Crohn's disease.

Aims

To study the mucosal and systemic expression of Decoy receptor-3 and TNF-like cytokine 1A in Crohn's disease, in relation to disease activity, localization, and response to treatment.

Methods

Soluble Decoy receptor-3 and TNF-like cytokine 1A were measured by ELISA in active or quiescent Crohn's disease. Relative mRNA expression in non-affected and inflamed intestinal mucosa was determined by real-time RT-PCR.

Results

We found significant upregulation of Decoy receptor-3 and its ligands TNF-like cytokine 1A and FasL in inflamed intestinal mucosa of Crohn's disease patients. During active disease, Decoy receptor-3 and TNF-like cytokine 1A were detected in the serum in the majority of patients. Intestinal inflammation was strongly associated with these elevations as they were absent during remission and significantly reduced with anti-inflammatory treatment. Regional diversity was observed as Decoy receptor-3 was upregulated in colonic and ileal sites, whereas TNF-like cytokine 1A was preferentially induced in the large bowel mucosa and systemic circulation of patients with colonic involvement.

Conclusions

TNF-like cytokine 1A and Decoy receptor-3 are upregulated during active Crohn's disease and may participate in disease pathogenesis and offer novel therapeutic opportunities.     

Local Immune Response Predicts Survival in Patients with Thick (T4) Melanomas

Background

Tumor infiltrating lymphocytes (TIL) and histological regression in primary melanoma are generally considered indicators of the local immune response but their roles as prognostic factors have been variably reported. We examined the prognostic role of these variables in patients with high risk (T4) primary melanomas in a large series of patients with long-term follow-up.

Methods

From a prospectively maintained cohort of patients diagnosed between 1971 and 2004, 161 patients were retrospectively identified with primary thick melanomas (>4 mm), no clinical evidence of regional nodal disease (RND) at diagnosis and complete histopathologic data. Univariate and multivariate Cox regression models were performed to identify clinical and histopathologic predictors of disease-specific survival (DSS) and to identify subgroups with differential survival.

Results

Factors significantly associated with decreased DSS by univariate analysis included male gender, age ≥ 60 years, axial anatomic location, presence of ulceration, RND, absence of TIL, and presence of regression. In the final multivariate model, TIL and regression, as interacting variables, and RND status remained significantly associated with DSS. In the presence of TIL, concomitant regression was associated with significantly worse survival (p ≤ 0.0001). In the absence of TIL, there was no effect of regression on survival (p = 0.324).

Conclusions

Primary TIL and regression status and RND status are independently associated with melanoma-specific survival in patients with T4 melanomas; presence of TIL in the primary melanoma with concomitant radial growth phase regression is associated with a poor prognosis and may reflect an ineffective local regional immune response.     

Effects of Strength vs. Ballistic-Power Training on Throwing Performance

The purpose of the present study was to investigate the effects of 6 weeks strength vs. ballistic-power (Power) training on shot put throwing performance in novice throwers. Seventeen novice male shot-put throwers were divided into Strength (N = 9) and Power (n = 8) groups. The following measurements were performed before and after the training period: shot put throws, jumping performance (CMJ), Wingate anaerobic performance, 1RM strength, ballistic throws and evaluation of architectural and morphological characteristics of vastus lateralis. Throwing performance increased significantly but similarly after Strength and Power training (7.0-13.5% vs. 6.0-11.5%, respectively). Muscular strength in leg press increased more after Strength than after Power training (43% vs. 21%, respectively), while Power training induced an 8.5% increase in CMJ performance and 9.0 - 25.8% in ballistic throws. Peak power during the Wingate test increased similarly after Strength and Power training. Muscle thickness increased only after Strength training (10%, p < 0.05). Muscle fibre Cross Sectional Area (fCSA) increased in all fibre types after Strength training by 19-26% (p < 0.05), while only type IIx fibres hypertrophied significantly after Power training. Type IIx fibres (%) decreased after Strength but not after Power training. These results suggest that shot put throwing performance can be increased similarly after six weeks of either strength or ballistic power training in novice throwers, but with dissimilar muscular adaptations.

Key points

• Ballistic-power training with 30% of 1RM is equally effective in increasing shot put performance as strength training, in novice throwers, during a short training cycle of six weeks.
• In novice shot putters with relatively low initial muscle strength/mass, short-term strength training might be more important since it can increase both muscle strength and shot put performance.
• The ballistic type of power training resulted in a significant increase of the mass of type IIx muscle fibres and no change in their proportion. Thus, this type of training might be used effectively during the last weeks before competition, when the strength training load is usually reduced, in order to increase muscle power and shot put performance in novice shot putters.

Key words: Shot put, muscle fibres, ultrasound, ballistic training, muscle mass.     

Pilot Randomized Trial of a Family Management Efficacy Intervention for Caregivers of African American Adolescents with Disruptive Behaviors

Background

Caregivers of adolescents diagnosed with Oppositional Defiant Disorder and/or Conduct Disorder (ODD/CD) experience unique challenges when interacting with child service systems involved in their adolescents’ care. Absent from the literature are interventions to improve these interactions, which in the long term may improve adolescent behavioral health outcomes.

Objective

To examine feasibility/acceptability of Family Management Efficacy (FAME) intervention content, structure, delivery, and appropriateness of selected measures for caregivers of African American adolescents with ODD/CD. Secondary aim was to explore changes in FAME caregivers’ interaction self-efficacy, stress, quality of life, and family functioning scores relative to caregivers receiving treatment as usual (TAU).

Method

A pilot two-group randomized trial was conducted with caregivers of African American adolescents (ages 12–18 years) diagnosed with ODD/CD receiving FAME (n?=?11) or TAU (n?=?9). Feasibility outcomes of enrollment/attrition, measurement completion, session attendance, and homework completion were assessed using tracking logs and field notes, and acceptability through caregiver satisfaction scores and interviews. Preliminary outcomes were assessed at baseline, post- and 2-months post intervention.

Results

FAME was highly acceptable and met a priori thresholds for feasibility in enrollment (56%), attrition (35%), caregiver attendance (55%), and homework completion (50%), with lower than anticipated kin attendance (42%) and measurement completion (55%). Preliminary outcomes suggest FAME may benefit caregivers in areas of family communication, cohesion, and quality of life, but lacked observed benefit for self-efficacy and problem solving indicating need for refinement.

Conclusion

Results inform changes to FAME content, measurement, and delivery schedule in preparation for a fully powered randomized controlled trial.

     

Contemporary Analysis of Sentinel Lymph Node Biopsy Performance Among Patients with Clinically Localized Merkel Cell Carcinoma

Annals of Surgical Oncology -     

Acute effects of second-hand smoke on complete blood count

We assessed the acute effects of a 1-h exposure to second-hand smoke (SHS) on complete blood count (CBC) markers in a controlled simulated bar/restaurant environment. Nineteen adult never-smokers completed a 1-h .exposure to SHS at bar/restaurant levels, and a 1-h exposure to normal room air. Blood samples were collected at the baseline at 30?min during each exposure, and at 0, 0.5, 1, 2, 3, and 4?h after each exposure. The values of white blood cells (WBC) at 1?h (p?=?0.010), 3?h (p?=?0.040), and 4?h (p?=?0.008) following SHS were significantly increased compared with the baseline values. Also, there was a positive association between the WBC and cotinine levels (r?=?0.28, p?=?0.007). A 1-h exposure to SHS at bar/restaurant levels significantly increased the WBC for at least 4?h following the exposure time. This effect of SHS on WBC has dose–response characteristics and should be considered to prescribing CBC.     

Exposure to secondhand smoke promotes sympathetic activity and cardiac muscle cachexia

Recent trials demonstrated that a single brief exposure to secondhand smoke (SHS) generates acute adverse health effects. We evaluated the acute (immediately after exposure) and short-term (0.5, 1, 2, 3 and 4?h after exposure) effects of SHS on cardiac autonomic control and myocardial integrity. Nineteen adult healthy never-smokers underwent a 1?h exposure to SHS at bar/restaurant levels and a 1?h control exposure. Heart rate variability (HRV), serum cotinine, and six cardiac protein markers were assessed before, during, and up to four hours following each exposure. SHS reduced the standard deviation of normal-to-normal intervals and increased cotinine levels, creatine kinase (CK)-MB, and myoglobin (p?相似文献   

Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain

Epigenetic processes play a key role in the central nervous system and altered levels of 5-methylcytosine have been associated with a number of neurologic phenotypes, including Alzheimer's disease (AD). Recently, 3 additional cytosine modifications have been identified (5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine), which are thought to be intermediate steps in the demethylation of 5-methylcytosine to unmodified cytosine. Little is known about the frequency of these modifications in the human brain during health or disease. In this study, we used immunofluorescence to confirm the presence of each modification in human brain and investigate their cross-tissue abundance in AD patients and elderly control samples. We identify a significant AD-associated decrease in global 5-hydroxymethylcytosine in entorhinal cortex and cerebellum, and differences in 5-formylcytosine levels between brain regions. Our study further implicates a role for epigenetic alterations in AD.     

Comparative strength measurements of five different fixation systems applied on an in vitro model of femoral midshaft osteotomy

. Oblique midshaft fractures of long bones can be stabilized using either plates and screws, lag screws, wires, cerclages, or a combination of these methods. Fractures at the distal tip of a well-fixed femoral prosthesis are difficult to stabilize with plates and screws because of the underlying intramedullary stem, polymethylmetacrylate (PMMA) cement, and thin periprosthetic femoral cortex. In this study we compared in vitro the mechanical performance of five different osteosynthesis techniques applied on an oak femoral model obliquely oscillated to mimic a short oblique fracture: (a) Double stainless steel wiring; (b) two 4.5 mm lag screws; (c) combination of one 4.5 mm cortical screw and one stainless steel wire; (d) one titanium compression cerclage Gundolf (CCG) combined with one 4.5 mm screw; and (e) double CCG. The five fixation constructs were subjected to a noncyclic destructive axial compression and torsional loading. The highest torque stiffness proved to be the double CCG and the double screw constructs, followed by and combination of CCG-screw and double screw constructs. The mode of failure in torque was a longitudinal crack close to the screw tip and loosening of the CCG and wire. The double screw, double CCG, and screw-CCG constructs provided the highest stiffness in axial compressive forces. The mode of failure in compression was loosening of the CCG and wire and bending of the screw. This comparative study showed that double CCG can theoretically replace the conventional methods of "minimal" osteosynthesis in the midshaft of long bones, and thus shows promise in the treatment of difficult short-oblique type femoral fracture at the distal tip of a well-fixed femoral prosthesis. The advantages of using the CCG is simplicity of technique, biocompatibility of titanium, no interference in modern imaging techniques, and avoidance of stripping of muscles and degloving of bone surfaces, as often happens in platting. Résumé. Etude comparative de la robustesse de cinq systèmes d'ostéosynthèse diaphysaire appliqués à un modèle in vitro d'ostéotomie fémorale. Les fractures diaphysaires obliques peuvent être stabilisées grace à des systèmes vis plaques, vis décalées, fils métalliques ou cerclages, ou encore grace à une combinaison de ces différents systèmes. Les fractures diaphysaires survenant au niveau de l'extrémité distale d'une tige fémorale bien fixée sont difficile à stabiliser par le biais de plaques vissées, en raison de la présence de la tige fémorale, du ciment, et du fin cortex fémoral périprothétique. Nous avons comparé dans cette étude le comportement mécanique "in vitro" de cinq techniques d'ostéosynthèse diaphysaires appliquées à un modèle fémoral en bois de chêne, coupé en son milieu par un plan oblique simulant une fracture courte oblique. Les cinq systèmes testés sont: (a) double ligature inox; (b) 2 vis décalées 4,5 mm; (c) combinaison d'une vis corticale de 4,5 mm et d'une ligature inox (d) un cerclage titane CCG (cerclage de compression de Gundolf) combiné à une vis de 4,5 mm; (e) un double cerclage CCG. Les cinq montages d'ostéosynthèse sont soumis à des chargements non-cycliques jusqu'à rupture, en compression, et en Torsion. La rigidité en Torsion la plus élevée est mesurée pour le double CCG et les deux vis décalées. Les modes de ruptures observés en torsion sont une brèche longitudinale près de l'extrémité des vis, et un desserrage des cerclages et ligatures. Les deux vis, le double CCG et la combinaison Vis-CCG sont les plus rigides en compression. Les modes de rupture observés en compression sont un desserrage des CCG et des ligatures, et un pliage des vis. Cette étude comparative montre que le CCG peut remplacer en théorie les méthodes conventionnelles d'ostéosynthèse diaphysaires "A minima", et est à ce titre très prometteur dans le cadre de fractures diaphysaires courtes obliques en extrémité de tiges fémorales bien fixées.