Role of nerve growth factor in the trinitrobenzene sulfonic acid-induced colonic hypersensitivity

The majority of patients with digestive disorders display visceral pain. In these troubles, visceral pain threshold is decreased, demonstrating visceral hypersensitivity. There is growing evidence that nerve growth factor (NGF) may function as a mediator of persistent pain states. This hypothesis was tested in a model of colonic hypersensitivity measured by isobaric distension in conscious rats. This study was designed to evaluate (1) the effect of exogenous NGF on colonic pain threshold, (2) the involvement of NGF in trinitrobenzene sulfonic acid (TNBS)-induced colonic hypersensitivity, by testing an anti-NGF antibody, and (3) finally the involvement of sensory nerves on NGF and TNBS effects using rats treated neonatally with capsaicin. Intra-peritoneal injection of NGF (0.1-100 ng/rat) decreased in a dose-related manner colonic pain threshold in naive rats. This effect was reversed by anti-NGF antibody (1/2000; 2 ml/kg). TNBS-induced colonic hypersensitivity was also reversed by anti-NGF antibody (1/2000; 2 ml/kg): 37.7 +/- 1.7 and 17.6 +/- 0.7 mmHg (p<0.01) for anti-NGF antibody- and vehicle-treated group, respectively. Neonatal capsaicin pre-treatment inhibited NGF- and TNBS-induced decrease in colonic pain threshold: 49.4 +/- 5.3 versus 22.3 +/- 1.6 mmHg (p<0.01) for capsaicin versus vehicle in NGF-treated rats and 39.6 +/- 3.3 versus 18.0 +/- 1.0 mm Hg (p<0.001) for capsaicin versus vehicle in TNBS-treated rats. These data suggest that the action of NGF on sensory neurons contributes to the development of visceral hypersensitivity and that anti-NGF strategy may be of some therapeutic benefits in digestive sensory disorders.     

Early Autism Spectrum Disorders in Children Born to Fertile,Subfertile, and ART-Treated Women

Introduction

We examined the prevalence of autism spectrum disorders (ASDs) in Massachusetts (MA) comparing children born via assisted reproductive technology (ART) and children born to women with indicators of subfertility but no ART (Subfertile), to children born to women with neither ART nor indicators of subfertility (Fertile). We assessed the direct, indirect, and total effects of ART and subfertility on ASD among singletons.

Methods

This study included 10,147 ART, 8072 Subfertile and 441,898 Fertile MA resident births from the MA Outcome Study of ART (MOSART) database linked with Early Intervention program participation data. ART included fresh in vitro fertilization (IVF), fresh intracytoplasmic sperm injection (ICSI), and frozen embryo transfer. We estimated the prevalence of ASD by fertility group. We used logistic regression to assess the natural direct effect (NDE), natural indirect effect (NIE) through preterm birth, and total effects of each fertility group on ASD.

Results

The NDE indicated that, compared to the Fertile group, the odds of ASD were not statistically higher in the ART (OR_NDE 1.07; 95% CI 0.88–1.30), Subfertile (OR_NDE 1.11; 95% CI 0.89–1.38), IVF (OR_NDE 0.91; 95% CI 0.68–1.22), or ICSI (OR_NDE 1.13; 95% CI 0.84–1.51) groups, even if the rate of preterm birth was the same across all groups. The total effect (product of NDE and NIE) was not significant for ART (OR_{Total Effect} 1.08; 95% CI 0.89–1.30), Subfertile (OR_{Total Effect} 1.11; 95% CI 0.89–1.38), IVF (OR_{Total Effect} 0.92; 95% CI 0.69–1.23), or ICSI (OR_{Total Effect} 1.13; 95% CI 0.84–1.52).

Conclusion

Compared to children born to Fertile women, children born to ART, ICSI, or IVF, or Subfertile women are not at increased risk of receiving an ASD diagnosis.

     

Perinatal outcomes of singleton siblings: the effects of changing maternal fertility status

Purpose

The objective of this study was to evaluate the effect of changing fertility status on perinatal outcomes of singleton siblings, conceived with and without assisted reproductive technology (ART).

Method

A longitudinal cohort study of Massachusetts resident women having two consecutive singleton births during 2004–2010 was performed. Women were classified as ART (A), subfertile (S), or fertile (F) and categorized by their fertility status in each birth as A-A, A-S, S-A, S-S, F-A, F-S, and F-F. Within categories, adjusted mean birthweights, gestations, and birthweight Z scores were estimated with linear generalized estimating equations. Risks of low birthweight (LBW, <2500 g), preterm birth (PTB, <37 weeks), and placental complications were modeled using logistic regression by fertility status as adjusted odds ratios (AORs) and 95 % confidence intervals (CIs).

Results

Birthweights in second pregnancies averaged 74–155 g higher, except for births to F-A women, who averaged ?16 g lower. Most women had a reduction in length of gestation in their second pregnancies, with F-A women having the largest decline (?0.5 weeks). In first birth models, the risks for LBW and placental complications were increased for subfertile (AOR 1.39 [1.07–1.81] and 1.97 [1.33–2.93], respectively) and ART women (AOR 1.58 [1.29–1.93] and 3.40 [2.64–4.37], respectively). Second birth models showed increased risks for ART births of LBW (AOR 3.13 [2.19–4.48]) and placental complications (AOR 2.45 [1.56–3.86]) and greater risks of PTB for both ART (AOR 2.37 [1.74–3.23]) and subfertile women (AOR 1.47 [1.02–2.13]).

Conclusions

Declining fertility status, with and without assisted reproductive technology treatment, is associated with increasing risks for adverse outcomes, greatest for women whose fertility status declined the most.

     

Bankart repair versus Bankart repair plus remplissage: an in vitro biomechanical comparative study

Purpose

To biomechanically compare Bankart lesion repair alone and Bankart lesion repair associated with infraspinatus capsulotenodesis described as «remplissage», in the treatment of combined Bankart and Hill-Sachs lesions.

Methods

Seven pairs (right and left) of cadaveric shoulders have been tested, first without any lesion and then after performing a combined Bankart and Hill-Sachs lesions. For each pair, the specimens were then randomly assigned for Bankart lesion repair alone on one side or for Bankart lesion repair associated with remplissage on the other side. During tests, the shoulder was placed at 90° of abduction and at maximal external rotation, which value was recorded. A 50 N postero-anterior load was then applied to the proximal humerus, and the stiffness was calculated from the obtained load–displacement curve.

Results

Bankart and Hill-Sachs lesions significantly (p < 0.05) decreased joint stiffness compared with intact joint. Bankart lesion repair alone did not restore stiffness to the level of intact, while adding the remplissage to the Bankart lesion repair did. External rotation was significantly increased after creation of the Bankart and Hill-Sachs lesion; Bankart repair restored the external rotation to the level of intact, while Bankart lesion repair associated with remplissage significantly decreased external rotation compared with intact and to Bankart lesion repair alone.

Conclusion

In cadaveric shoulders with combined Bankart and Hill-Sachs lesions, Bankart lesion repair associated with remplissage restored intact joint stiffness contrary to Bankart lesion repair alone. This increase in stiffness was associated with a decrease in external rotation.

     

Study rationale,design, and pretransplantation alloantibody status: A first report of Clinical Trials in Organ Transplantation in Children‐04 (CTOTC‐04) in pediatric heart transplantation

Anti‐HLA donor‐specific antibodies are associated with worse outcomes after organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor‐specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase posttransplantation morbidity and mortality. We address this clinical challenge in a prospective, multicenter, observational cohort study of children listed for heart transplantation (Clinical Trials in Organ Transplantation in Children‐04 [CTOTC‐04]). Outcomes were compared among sensitized recipients who underwent transplantation with positive crossmatch, nonsensitized recipients, and sensitized recipients without positive crossmatch. Positive crossmatch recipients received antibody removal and augmented immunosuppression, while other recipients received standard immunosuppression with corticosteroid avoidance. This first CTOTC‐04 report summarizes study rationale and design and relates pretransplantation sensitization status using solid‐phase technology. Risk factors for sensitization were explored. Of 317 screened patients, 290 were enrolled and 240 underwent transplantation. Core laboratory evaluation demonstrated that more than half of patients were anti‐HLA sensitized. Greater than 80% of sensitized patients had class I (with or without class II) HLA antibodies, and one‐third of sensitized patients had at least 1 HLA antibody with median fluorescence intensity of ≥8000. Logistic regression models demonstrated male sex, weight, congenital heart disease history, prior allograft, and ventricular assist device are independent risk factors for sensitization.     

Incidence,characterization, and impact of newly detected donor‐specific anti‐HLA antibody in the first year after pediatric heart transplantation: A report from the CTOTC‐04 study

Data on the clinical importance of newly detected donor‐specific anti‐HLA antibodies (ndDSAs) after pediatric heart transplantation are lacking despite mounting evidence of the detrimental effect of de novo DSAs in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSAs in the first year posttransplantation to determine their incidence, pattern, and clinical impact. One‐third of patients developed ndDSAs; when present, these were mostly detected within the first 6 weeks after transplantation, suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of preexisting DSAs, patients with ndDSAs had significantly more acute cellular rejection but not antibody‐mediated rejection, and there was no impact on graft and patient survival in the first year posttransplantation. Risk factors for ndDSAs included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year after pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pretransplantation antibody screen. The impact on late graft and patient outcomes of first‐year ndDSAs is being assessed in an extended cohort of patients.     

Peripheral benzodiazepine receptor-induced myocardial protection is mediated by inhibition of mitochondrial membrane permeabilization

Opening of the permeability transition pore (PTP) is a key event in ischemia-reperfusion injury and several ligands of the peripheral benzodiazepine receptor (PBR), a mitochondrial outer membrane protein possibly associated with PTP, have been demonstrated as potent cardioprotective agents. Here, we investigated the mechanisms by which the specific PBR ligand 4'-chlorodiazepam (CDZ) protected the myocardium against ischemia-reperfusion. In either global or regional models of myocardial ischemia-reperfusion in rats, CDZ reduced infarct size in a dose-dependent manner (e.g., 11 +/- 1% of the area at risk at 10 mg/kg versus 31 +/- 3% in control; p < 0.05) and to a similar extent as ischemic or diazoxide-induced preconditioning. CDZ (10 mg/kg) reduced apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining), restored mitochondrial recovery, improved oxidative phosphorylation parameters, and reduced mitochondrial membrane permeabilization with inhibition of cytochrome c and apoptosis-inducing factor releases. CDZ increased the resistance of mitochondria to Ca2+-induced PTP opening. All these cardioprotective effects of CDZ were associated with an improved stabilization of the association of Bcl-2 with the mitochondrial membrane and inhibition of the association of a cytosolic fragment of Bax, occurring during ischemia-reperfusion, with the outer mitochondrial membrane. In addition, the PTP opener atractyloside (20 microM) and the Bcl-2 inhibitor ethyl-2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1) (20 microM) abrogated CDZ-induced reduction of infarct size. These results demonstrate that PBR occupancy by CDZ renders the heart more resistant to ischemia-reperfusion injury by limiting mitochondrial membrane permeabilization. This is due to a reorganization of the balance between pro- and antiapoptotic proteins of the Bcl-2 family proteins at the level of mitochondrial membranes.     

Comparison of the enzyme-linked immunosorbent assay (ELISA) with standard tests used to detect yellow fever virus antibodies

The enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to yellow fever virus in 110 sera from patients living in an epidemic yellow fever area. The results were then compared with those obtained with the hemagglutination-inhibition (HI), complement-fixation (CF), neutralization (NT), and indirect immunofluorescence (IFA) tests. This ELISA, which used a type-specific antigen, showed the same results as the NT test and was found to be more sensitive and more specific than the HI and CF tests.     

Pleural effusion as a first sign of Ig D lambda multiple myeloma

Immunoglobulin D (IgD) multiple myeloma is rare, accounting for less than 2% of all patients with multiple myeloma. The main presenting features are bone pain in 70% of patients. Extramedullary involvement is less common. We report a case of Ig D lambda multiple myeloma in a 74-year-old man that was revealed by pleural effusion and dyspnea. This effusion was found to be caused by multiple myeloma after electrophoretic and cytologic assays. The patient received a course of chemotherapy with melphalan and prednisone. The patient died one month later with signs of septic shock. Pleural effusion as a first sign of Ig D multiple myeloma is rarely described and the prognosis associated with such a localisation is very poor.     

Synchronous pyogenic liver abscess and acute cholecystitis: how to recognize it and what to do (emergency cholecystostomy followed by delayed laparoscopic cholecystectomy)

Background  

The treatment of synchronous pyogenic liver abscess (PLA) and acute cholecystitis (AC) may be challenging. Moreover, because of the similarity of symptoms and the suboptimal accuracy of ultrasound (US), PLA(s) may be undetected, unless a computer tomography (CT) scan is performed. The aims of this study were (1) to evaluate the results of emergency cholecystostomy (CS) and late laparoscopic cholecystectomy (LC) in such a population and (2) to identify the criteria for selecting patients with AC and a high risk of having synchronous PLA(s) for referral for a CT scan.