Successful treatment of a bowel perforation after chemotherapy for Burkitt lymphoma

Chemotherapy-induced intestinal perforation after treatment for Burkitt lymphoma is a known potential complication. However, there are very few reports in the pediatric literature that discuss this complication in any detail, and most incidents are secondary to surgical complications such as anastomotic leaks. Furthermore, there are no reports of children that have survived chemotherapy-induced perforation, and thus, guidelines for the diagnosis and treatment of this complication or for the continuation of chemotherapy are lacking. We present a case of a 5-year-old boy who survived jejunal perforation after treatment for his Burkitt lymphoma, and the critical aspects of his care are discussed.     

Respiratory compensation and blood pH regulation during variable intensity exercise in trained versus untrained subjects

To determine whether endurance-trained cyclists (T; n = 10) have a superior blood-respiratory buffering for metabolic acidosis relative to untrained subjects (UT; n = 10) during variable intensity exercise (VAR). On three occasions, T and UT pedaled for 24 min alternating high- and low-intensities as percentage of their second ventilatory threshold (VT₂): VAR_LOW 87.5–37.5% VT₂, VAR_MODERATE 125–25% VT₂, and VAR_HIGH 162.5–12.5% VT₂ to complete the same amount of work. Before and just after each VAR trial, maximal cycling power (P_MAX) was assessed. For each trial, the respiratory compensation for exercise acidosis (ventilatory equivalent for CO₂) and the final blood pH, lactate and bicarbonate concentrations were similar for T and UT subjects. However, after VAR_HIGH, UT reduced P_MAX (−14 ± 1%; P < 0.05) while T did not. Our data suggest that endurance training confers adaptations to withstand the low pH provoked by VAR without losing cycling power, although this response is not due to differences in blood-respiratory buffering.     

Neurometabolic disorders and dysfunction in autism spectrum disorders

The cause of autism remains largely unknown because it is likely multifactorial, arising from the interaction of biologic, genetic, and environmental factors. The specific role of metabolic abnormalities also is largely unknown, but current research may provide insight into the pathophysiologic underpinnings of autism, at least in some patients. We review a number of known neurometabolic disorders identified as having an autistic phenotype. We also discuss the possible involvement of mitochondrial disorders and dysfunction as well as a theory regarding an increased vulnerability to oxidative stress, by which various environmental toxins produce metabolic alterations that impair normal cellular function. Finally, we review various strategies for metabolic work-up and treatment. Accurate diagnosis of neurometabolic disorders and a broader understanding of underlying metabolic disturbance even in the absence of known disease have important implications both for individual patients and for research into the etiology of autism.     

The effect of Nigella sativa alone, and in combination with dexamethasone, on tracheal muscle responsiveness and lung inflammation in sulfur mustard exposed guinea pigs

Ethnomedical relevance

The anti-inflammatory activity of both systemic and local administrations of essential oil from Nigella sativa L. has been shown.

Aim of the study

Therefore, the effect of Nigella sativa on tracheal responsiveness (TR) and lung inflammation of sulfur mustard (SM) exposed guinea pigs was examined.

Materials and methods

Guinea pigs were exposed to diluent solution (control group), inhaled SM (SME group), SME treated with Nigella sativa (SME + N), SME treated with dexamethasone (SME + D) and SME treated with both drugs (SME + N + D), (n = 7 for each group). TR to methacholine, total white blood cell (WBC) and differential WBC count of lung lavage, and serum cytokines were measured 14 days post-exposure.

Results

The values of TR, eosinophil, monocyte, lymphocyte, interleukine-4 (IL-4) and interferon gamma (IFN-γ) of SME group were significantly higher than those of controls (p < 0.05 to p < 0.001). The TR in SME + N, SME + D and SME + N + D was significantly lower compared to that of SME group (p < 0.01 for all cases). The percentage of eosinophil in SME + D, and the percentage of monocyte in SME + N + D (p < 0.05 to p < 0.01) were significantly lower than those in SME group. The neutrophil number was decreased in SME + N and SME + N + D groups compared to SME animals (p < 0.05 to p < 0.01). IL-4 levels in serum of SME + N (p < 0.01), SME + D (p < 0.05), SME + N + D (p < 0.01) and IFN-γ in SME + N (p < 0.05) were greater than those in SME animals.

Conclusions

These results showed a preventive effect of Nigella sativa on TR and lung inflammation of SM exposed guinea pigs.     

Inhibition of T-cell activation and proliferation by mycophenolic acid in patients awaiting liver transplantation: PK/PD relationships

Mycophenolic acid (MPA) plasma concentrations were reported to be associated with a decrease in T-cell proliferation, and in both IL-2 α-chain (CD25) and transferin receptor (CD71) expression. The aim of this study was to confirm, quantify and model these PK/PD relationships.Full profiles of MPA plasma concentrations, T-cell proliferation, intracytoplasmic IL-2 and TNF-α expression, and both CD71 and CD25 expression were collected over the 12 h after dosing in 10 patients on the waiting list for liver transplantation. Data were analyzed using NONMEM^®.Both CD25 and CD71 expression and T cell proliferation clearly decreased (median of decrease from baseline 62%, 68% and 94%, respectively) with increasing MPA concentrations, in contrast to IL-2 and TNF-α expression. The CD25 and CD71 baseline expression (E₀) and maximum effect (E_max) were correlated with the E₀ and E_max values of T-cell proliferation (r² = 0.509 and r² = 0.622, respectively). The CD25, CD71 expression and T-cell proliferation profiles were adequately fitted using a sigmoid inhibitory E_max model. Low estimated values (≤2 mg/L) for 50% inhibitory MPA concentrations were obtained. This study confirmed a transient MPA concentration-dependent decrease in T-cells expressing CD25 and CD71 and a strong reduction of T-cell proliferation and showed that CD25 and CD71 expression was correlated with T-cell proliferation.     

In vitro mitogen-stimulated T-cell from hepatitis C virus-positive liver transplantation candidates, increases T-cell activation markers and T-cell proliferation

The incidence of acute rejection is significantly higher in hepatitis C virus (HCV) liver-transplant patients than in patients who have received a graft for other liver diseases, i.e., mainly alcoholic cirrhosis. The aim of this study was to assess T-cell function, i.e., intralymphocyte cytokine expression (IL-2 and TNF-alpha), T-cell activation [i.e., transferrin receptor (CD71) and interleukin (IL)-2 alpha-chain (CD25) expression], and T-cell proliferation using a flow-cytometry whole-blood assay in patients waiting for a liver transplantation (n=49). Our data suggest that, in mitogen-stimulated T-cells, (i) intra-lymphocyte cytokine expression is significantly higher in patients with liver disease than in healthy volunteers (n=25); (ii) the expression of T-cell activation markers is decreased in patients with liver cirrhosis compared to healthy volunteers, and (iii) the expression of T-cell activation markers and T-cell proliferation are increased in patients with HCV infection (n=15) compared to those without HCV infection (n=34), particularly compared to patients with alcoholic liver disease (n=19). Circulating CD19-positive cells count was also significantly higher in HCV-positive patients. In conclusion, in vitro, mitogen-stimulated T-cell seem to induce a higher immune response in the blood from patients waiting for a liver transplant for HCV-related liver disease than those without HCV infection, and particularly those with alcoholic liver disease.     

Monitoring of calcineurin inhibitors induced-nephrotoxicity

Chronic allograft nephropathy is characterized by an increase over time of interstitial fibrosis, tubular atrophy, fibrointimal thickening, arteriolar hyalinosis and glomerulosclerosis, resulting in progressive renal dysfunction. It is mainly caused by calcineurin inhibitors-induced nephrotoxicity, which is related to an imbalance between vasoconstrictor and vasodilator factors. Cyclosporine A-induced nephrotoxicity is particularly due to the activation of pro-apoptotic genes leading to tubular atrophy with tubular cell apoptosis and to hemodynamic changes inducing interstitial fibrosis by the activation of factors stimulating the fibroblast proliferation (TGFbeta, Endothelin-A and Plasminogen activator inhibitor-1). Calcineurin inhibitors (CNI) treatment monitoring is essentially based on histology, but a better follow-up of drug exposure post-transplantation leading to a regular and rapid adjustment of the doses to avoid extended periods of overexposure, could enable to decrease their nephrotoxicity and improve graft survival in treated patients. CNIs dose reduction or conversion to proliferating signal inhibitors may be a therapeutic alternative.     

Hepatitis C virus viral load after conversion from tacrolimus to cyclosporine in liver transplant patients: a pilot study

We assessed whether conversion from tacrolimus (TAC) to cyclosporine (CsA) was associated with a reduction in hepatitis C virus (HCV) viral load among HCV-positive liver transplant (OLT) patients. PATIENTS AND METHODS: Nine OLT patients with recurrent HCV have TAC and prednisone immunosuppression. None received any HCV antiviral therapy. After the last intake of TAC, the patients underwent a 12-hour area under the curve (AUC(12)) measurement of both TAC and HCV viral loads. The next morning (D(0)) patients were given CsA (4 mg/kg bid). At the first intake of CsA and at 1 month (M(1)) later, the patients underwent AUC(12) for CsA and HCV viral loads. Biological data, including aspartate (AST) and alanine (ALT) aminotransferase, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), and bilirubin levels, were collected during AUC(12), and at M(1) and M(3). RESULTS: With respect to liver enzymes (AST, ALT, GGT), there was no significant difference between D(0), M(1), and M(3). Conversely, there was a significant decrease in AP between D(0) and M(3) (P = .02), and a significant increase in total bilirubin between D(0) and M(1) (P = .04), and between D(0) and M(3) (P = .01). HCV viral load significantly increased by M(3) (P = .01). At no time (D(0), M(1)) was there any correlation between the AUC(12) of TAC or CsA, and between AUC(12) HCV viral load. CONCLUSION: This pilot study found no acute or chronic anti-HCV effects from CsA that were evident within 12 hours after CsA administrations or beyond 1 month of CsA therapy, respectively.