EBV+ B Lymphoma Cell Lines from Patients with Post-Transplant Lymphoproliferative Disease Are Resistant to TRAIL-Induced Apoptosis

Lymphomas associated with post-transplant lymphoproliferative disease (PTLD) represent a significant complication of immunosuppression in transplant recipients. In immunocompetent individuals, EBV-specific cytotoxic T lymphocytes (CTL) prevent the outgrowth of activated B lymphoblasts through apoptosis induction. Soluble versions of TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL) can induce apoptosis in numerous tumor cell types. Given the therapeutic potential of TRAIL, we examined the sensitivity of EBV⁺ spontaneous lymphoblastoid cell lines (SLCL) derived from patients with PTLD to treatment with soluble TRAIL. Despite abundant expression of TRAIL receptors (TRAIL-R), resistance to TRAIL-induced apoptosis was observed in all SLCL examined. This resistance could not be overcome by concomitant treatment with several pharmacological agents. Unlike BJAB positive control cells, for each SLCL tested, cleavage and activation of caspase 8 was inhibited due to failed recruitment of FADD and caspase 8 to TRAIL receptors upon stimulation. Further indicative of a proximal defect, TRAIL receptor aggregation could not be detected on the cell surface of SLCL following ligand engagement. These results suggest that the use of TRAIL for eliminating PTLD-associated tumors may be of limited clinical utility, and illustrate another mechanism by which EBV⁺ B lymphoma cells can evade tumor surveillance at the level of death receptor signaling.     

Effect of dietary fat content on the bioavailability of a sustained release quinidine gluconate tablet

Quinidine gluconate 324 mg sustained release tablets (Quinaglute) was administered as a single dose to 15 healthy male subjects following an overnight fast, immediately following a high fat (HF) breakfast or immediately following a low fat (LF) breakfast. Serum samples were obtained over a 48 h period and analyzed for quinidine content using a high performance liquid chromatographic assay. Under the conditions of the study, both the rate and extent of quinidine bioavailability was significantly affected by food. The extent of bioavailability was statistically significantly greater (p less than 0.05) following both the HF and LF meals as compared to that in the fasted state. Rate of bioavailability was significantly enhanced following the LF meal as compared to that of the other two treatment groups. Although peak concentrations were greater and time to peak concentrations somewhat later following the HF meal versus those under fasting conditions, these differences were not statistically significant. In addition, the characteristics of the serum concentration-time profile (as defined by the number, magnitude, and time of occurrence of the multiple absorption maxima) was unique for each of the three treatment groups. Possible mechanisms underlying these results are explored.     

Arylsulfatase A in urine of patients with urothelial tumors

A significant increase in urine arylsulfatase A activity (p less than 0.01) was found in patients with urothelial tumors. Arylsulfatase A activity was 1.36 +/- 1.10 U/24-h urine in control specimens, 1.90 +/- 1.66 U/24-h urine in various genitourinary tract disorders, and 3.90 +/- 1.98 U/24-h urine in transitional cell carcinoma specimens. Surgical treatment of the neoplastic patients lowered the arylsulfatase A activity found in urine to within reference values. The arylsulfatase A excreted by patients with these tumors was highly sensitive to thermal inactivation while the enzyme activity in the control urines was less affected by the heat treatment. The time course of the arylsulfatase A reaction with 4-nitrocatechol sulfate was not linear in normal individuals, while it was linear in 90% of patients with urothelial tumors. This difference in the kinetic pattern of the enzyme could be used to increase the diagnostic specificity of the determination.     

Barley diets with different fat sources have hypocholesterolemic effects in chicks.

Saturated fat is known to elevate serum cholesterol, whereas soluble dietary fiber has a hypocholesterolemic effect. The objective of this study was to compare the effects of barley and wheat diets supplemented with five fat sources on lipid metabolism in chicks. In two separate experiments, broiler chicks were fed isonitrogenous diets containing 23% protein, 11.4% dietary fiber and 10% dietary fat for 17 d. Diets contained 60% either hull-less barley or red spring wheat, with either palm oil, dehydrated egg yolk, butter, tallow or corn oil. Growth, feed efficiency, plasma lipids, liver cholesterol, and fecal fat and dry matter were measured. All chicks fed wheat grew faster and had greater food efficiency than those fed barley. All barley-fed chicks had lower (P less than 0.0001) total plasma cholesterol concentration (3.1 to 4.0 mmol/L) than those fed wheat (6.0 to 11.3 mmol/L). Chicks fed palm oil with wheat had the highest total cholesterol, 11.3 mmol/L. Liver cholesterol concentration was higher (P less than 0.0001) for all wheat-fed chicks (22.8-86.4 mmol/g) compared with those fed barley (6.7 to 12.2 mmol/g). Fecal crude fat was higher (P less than 0.05) for chicks fed barley, and excreta dry matter was lower for barley-fed chicks. Results indicate that the high soluble fiber content of this barley exerts a hypocholesterolemic effect in chicks regardless of dietary fat source, possibly mediated through lowered fat absorption.     

3D imaging and pathology of the base of the skull in children]

Three dimensional computed tomography was performed in 150 children suffering from a bone lesion of the base of the skull and face. These lesions were either malformative, neoplastic, infectious or traumatic. 3D CT provided an essential anatomical approach to the lesions facilitating the choice of the most appropriate treatment. 3D CT is also indicated in the follow-up of these operated children, particularly of the growth of the operated bone segment and its relations with adjacent structures.     

Simple algorithms for the management of genital ulcers: evaluation in a primary health care centre in Kigali, Rwanda.

A cross-sectional study was conducted among 395 patients presenting with genital ulcers at a primary health care centre in Kigali, Rwanda. Using clinical data and the results of a rapid plasma reagin (RPR) test, we simulated the diagnostic outcome of two simple WHO flowcharts for the management of genital ulcers. These outcomes and a clinical diagnosis were then compared with the laboratory diagnosis based on culture for genital herpes and Haemophilus ducreyi and serology for syphilis. The prevalence of HIV infection was high (73%) but there was no difference between HIV-positive and HIV-negative patients in the clinical presentation and etiology of genital ulcer disease. The proportion of correctly managed chancroid and/or syphilis cases was 99% using a syndromic approach, 82.1% using a hierarchical algorithm including an RPR test, and 38.3% with a clinical diagnosis. In situations where no laboratory support is available, a simple syndromic approach is preferable to the clinical approach for the management of genital ulcer. If an RPR test can be included in the diagnostic strategy, patients with a reactive RPR test should be treated for both syphilis and chancroid infection.     

Myomucosal shunt following total laryngectomy: a report of 31 cases

An original technique of voice rehabilitation following total laryngectomy based on the concept of a myomuscosal unit was originally described by Strome. Thirty-one cases of myomucosal shunts (MMS) are analyzed in the present report. The 14 initial cases failed because of a lack clinical and surgical experience and insufficient selection of the patients. Among the last 17 cases, 1 was lost to follow-up, 1 had an insufficient follow-up, and 2 patients refused to speak with the MMS instead of a patent shunt; 5 of the remaining patients had voices evaluated as excellent, 7 had voices interpreted as good and only 1 patient had a voice evaluated as poor. Aspiration was not a problem. Eleven patients were found to stenose their shunt, but fistula were recalibrated successfully. The MMs can be used safely in oncological surgery and only 1 of 31 deaths in our total experience was due to a local recurrence. These findings show that the MMS is a reliable procedure for voice restoration following total laryngectomy; a prosthesis is not required and there are currently no oncological limits to the procedure. However, a very close follow-up of the patients is required after surgery.     

Opioid receptors are involved in an NMDA receptor-independent mechanism of LTP induction at hippocampal mossy fiber-CA3 synapses.

Long-term potentiation (LTP) of mossy fiber responses in area CA3 of the rat hippocampus in vivo is blocked by naloxone, an opioid receptor antagonist, in a stereospecific and dose-dependent manner. LTP of commissural afferents to the same population of CA3 pyramidal cells is not attenuated by naloxone. This suggests that opioid receptors are involved in a mechanism of LTP induction that is specific to mossy fiber synapses, and that endogenous opioid receptors are involved in a mechanism of LTP induction that is specific to mossy fiber synapses, and that endogenous opioid peptides, presumably released as a result of mossy fiber stimulation, may be necessary for the induction of mossy fiber LTP. The naloxone sensitivity is limited to the induction phase of LTP, since naloxone does not reverse previously established LTP. These data suggest that LTP at the mossy fiber-CA3 synapse constitutes an NMDA receptor-independent, opioid receptor-dependent, form of hippocampal synaptic plasticity.