Richter’s hernia occurring through a 5-mm laparoscopy sheath incision

We report a case of postoperative Richter’s hernia presenting through a 5-mm sheath incision. A 58-year-old woman having undergone laparoscopic hysterectomy 8 days before presented with severe left abdominal pain, nausea and light-headedness. The hypothesis of a sigmoid volvulus was suggested based on peroperative rectum and sigmoid release, the X-ray finding, and pain evolution. A secondary laparoscopic procedure allowed both diagnosis of a Richter’s hernia through a 5-mm sheath incision and surgical repair of the hernia. The use of this sheath during the laparoscopic vagina suture caused extension of the wound. Large 5-mm sheath defect sufficient for a Richter’s hernia can be created by multiple passes with small instruments and require surgical closure at the end of laparoscopy. Laparoscopy is useful in cases of postoperative complications, particularly when other complementary examinations are less informative.     

Emergency ligation of anomalous left coronary artery arising from the pulmonary artery

We report two cases of successful emergency ligation of anomalous left coronary artery arising from the pulmonary artery (ALCAPA) in patients with previous cardiac arrest. Both patients had regained marginal cardiac output after cardiopulmonary resuscitation and had maximal doses of inotropic support. The ALCAPA ligation was then performed as a life-saving procedure in the absence of any kind of mechanical circulatory support.     

Induction of apoptosis and cell cycle arrest by imexon in human pancreatic cancer cell lines

Imexon is an aziridine-containing small molecule currently in Phase I clinical trials. This agent has been shown to bind to thiols and increase intracellular oxidants, inducing apoptosis in hematologic cancer cells. Pancreatic cancers are known to be sensitive to oxidation, suggesting this disease may be an appropriate target for this agent. The current report examines the activity of imexon in pancreatic cells. Imexon induced concentration-dependent and time-dependent apoptosis in a panel of six human pancreatic carcinoma cell (PCC) lines. The mean IC₅₀ (SD) for growth inhibition by the SRB assay was 200 (101) µM for a 48 h exposure with a range of 64–358 µM. Cell killing was schedule-dependent, favoring exposure times ≥48 h. Imexon-treated MiaPaCa-2 cells underwent non-lethal growth arrest following exposure to concentrations ≤200 µM for 48 h. When concentrations were increased to 300 µM for ≥48 h, the MiaPaCa-2 cells arrested in G₂ phase and activated caspases 3, 8, and 9 were detected. After a 72 h exposure to the IC₈₀ concentration of imexon, cells exhibited a loss of mitochondrial membrane potential detected by CMXRos staining. However, there was no loss of reduced cellular thiols unless very high concentrations of ≥400 µM were used. In contrast, reactive oxygen species (ROS) were elevated in a dose-dependent fashion, starting at very low imexon concentrations. Imexon also significantly inhibited MiaPaCa-2 tumor growth in SCID mice at 100 mg/kg/d for 9 d. The tumor growth inhibition (% T/C) was 27% of control, and the tumor growth delay was 21 d, indicating an active agent by NCI standards. The levels of imexon that are cytotoxic in human PCC’s are achievable based on the preliminary results of the ongoing Phase I trial. Imexon appears to be active against PCCs in vitro and has an entirely novel mechanism of action involving G₂ arrest, accumulation of ROS, and the induction of apoptosis.     

The effect of divalent cations on neuronal nitric oxide synthase activity.

Neuronal nitric oxide synthase (NOS I) is a Ca(2+)/calmodulin-binding enzyme that generates nitric oxide (NO*) and L-citrulline from the oxidation of L-arginine, and superoxide (O(2)*(-)) from the one-electron reduction of oxygen (O(2)). Nitric oxide in particular has been implicated in many physiological processes, including vasodilator tone, hypertension, and the development and properties of neuronal function. Unlike Ca(2+), which is tightly regulated in the cell, many other divalent cations are unfettered and can compete for the four Ca(2+) binding sites on calmodulin. The results presented in this article survey the effects of various divalent metal ions on NOS I-mediated catalysis. As in the case of Ca(2+), we demonstrate that Ni(2+), Ba(2+), and Mn(2+) can activate NOS I to metabolize L-arginine to L-citrulline and NO*, and afford O(2)*(-) in the absence of L-arginine. In contrast, Cd(2+) did not activate NOS I to produce either NO* or O(2)*(-), and the combination of Ca(2+) and either Cd(2+), Ni(2+), or Mn(2+) inhibited enzyme activity. These interactions may initiate cellular toxicity by negatively affecting NOS I activity through production of NO*, O(2)*(-) and products derived from these free radicals.     

Molecular mechanisms of platinum resistance: still searching for the Achilles' heel.

The platinum compounds cisplatin and carboplatin are commonly used in cancer chemotherapy. However, tumors frequently develop resistance to these compounds, significantly decreasing their usefulness in the clinic. In the past few years, basic research has unraveled novel and unexpected mechanisms for the development of platinum resistance. For example, it has been reported that MUC1 expression and particularly the localization of its C-terminal subunit to the mitochondria may affect cisplatin resistance. Another recent finding suggests that cisplatin damage may activate DNA-dependent protein kinase (DNA-PK) to initiate a death signal that can be transmitted to neighboring cells through gap junctions, adding to a growing belief that the interactions of cancer cells with their surroundings may be important to the outcome of chemotherapy. While most clinical efforts have focused on identifying alternative regimens for drug-resistant cancer, it might be possible to exploit our knowledge of the mechanism of platinum resistance to specifically reverse resistance and increase platinum efficacy. The strategy of drug resistance reversal therapy (DRRT) may have significant impact on our approaches to the treatment and management of drug-resistant tumors.     

Motivation in pediatric motor rehabilitation: A systematic search of the literature using the self-determination theory as a conceptual framework

Objective: Motivation is suggested as an important factor in pediatric motor rehabilitation. Therefore, we reviewed the existing evidence of (motivational) motor rehabilitation paradigms, and how motivation influences rehabilitation outcome using self-determination theory as conceptual framework. Methods: PubMed and Web-of-Science databases were systematically searched until June 2015. Data were independently extracted and critiqued for quality by three authors. Studies reporting motivational aspects were included. Most studies examined new technology (e.g., virtual reality [VR]). Results: Out of 479 records, three RCT, six case-control, and six non-comparative studies were included with mixed quality. Motivation was rarely reported. Training individualization to the child’s capabilities with more variety seemed promising to increase motivation. Motivation increased when the exercises seemed helpful for daily activities. Conclusions: Motivation in pediatric rehabilitation should be comprehensively assessed within a theoretical framework as there are indications that motivated children have better rehabilitation outcomes, depending on the aspect of motivation.     

Facteurs pronostiques en insémination avec sperme de donneur : suivi rétrospectif d’une cohorte de 188 patientes

ObjectivesImproving our practice by a constant evaluation is essential in the field of donor semen insemination (DI). Our center examined the prognosis factors for DI success in order to standardize patient treatment options.Patients and methodsWe retrospectively analysed all couples referred for DI from January 2000 till December 2010.ResultsWe analysed 551 cycles among 188 patients. Pregnancy rate by stimulation cycle was 19,8% with birth rate of 16.7%. The rate of pregnancy was improved till the fourth trial then plateau. On a patient-based analysis, success factors were age (P = 0.04), previous successful DSI (P = 0.02), and no previous failure of an ICSI-C (P = 0.035). On a cycle-based analysis, success factors were the number of follicles greater than 15 mm (P = 0.04) and than 18 mm (P = 0.001). The percentage of 68.1 patients obtained a child by IVF-D after a failed DI.ConclusionThere are two predictive factors for DI success: the age of the patient and the number of mature follicles. It seems accurate to referred patients to IVF-D after four unsuccessful cycles of DSI. This recommendation may be adapted according to patient's age and hormonal evaluation.     

Targeting the “Cytokine Storm” for Therapeutic Benefit

Inflammation is the body''s first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.