Epstein Barr virus latent membrane protein-1 in Hodgkin's lymphoma in Nigerians

Background

The burden of lymphomas on the health care system in Nigeria is enormous. Correct diagnosis and identification of aetiological factor are important steps in reducing this burden.

Methods

Eight cases diagnosed as HL within a period of six years at the Obafemi Awolowo University teaching Hospital, Ile-Ife, Nigeria by haematoxylin and eosin (Hand E) only were immunophenotyped using the indirect immunoperoxidase method. Epstein-Barr virus latent membrane protein-1 (LMP-1), CD15 and CD30 immunohistochemistry was also performed. The clinical characteristics of each patient were documented.

Objectives

To document the frequency of involvement of Epstein-Barr virus in cases of HL seen in a university hospital in Nigeria.

Results

Out of the eight cases diagnosed by H&E as HL immunophenotyping showed only five were HL. The rest were non-Hodgkin''s lymphoma (2 diffuse large B-cell and 1 null cell ALCL). All were cases of classical HL with 60% being of the mixed cellularity (MC) subtype. There were 2 males and 3 females with ages ranging from 7 years to 40 years. All presented with cervical lymphadenopathy and three had splenomegaly in addition. 60% of the tumour was EBV positive, all of the MC subtype. Three patients had chemotherapy. Eventually all were lost to follow-up. There was no case of the nodular lymphocyte predominance variant.

Conclusion

Mixed cellularity is the most common subtype and is the only subtype associated with EBV positivity in this study. Epstein-Barr virus probably plays an important role in the aetiology of HL in Nigerians.Running title: Epstein-Barr virus, Hodgkin''s lymphoma in Nigerians     

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

Desensitization of endothelial P2Y1 receptors by PKC-dependent mechanisms in pressurized rat small mesenteric arteries

Background and purpose:

Extracellular nucleotides play a crucial role in the regulation of vascular tone and blood flow. Stimulation of endothelial cell P2Y1 receptors evokes concentration-dependent full dilatation of resistance arteries. However, this GPCR can desensitize upon prolonged exposure to the agonist. Our aim was to determine the extent and nature of P2Y1 desensitization in isolated and pressurized rat small mesenteric arteries.

Experimental approach:

The non-hydrolyzable selective P2Y1 agonist ADPβS (3 µM) was perfused through the lumen of arteries pressurized to 70 mmHg. Changes in arterial diameter and endothelial cell [Ca²⁺]_i were obtained in the presence and absence of inhibitors of protein kinase C (PKC).

Key results:

ADPβS evoked rapid dilatation to the maximum arterial diameter but faded over time to a much-reduced plateau closer to 35% dilatation. This appeared to be due to desensitization of the P2Y1 receptor, as subsequent endothelium-dependent dilatation to acetylcholine (1 µM) remained unaffected. Luminal treatment with the PKC inhibitors BIS-I (1 µM) or BIS-VIII (1 µM) tended to augment concentration-dependent dilatation to ADPβS (0.1–3 µM) and prevented desensitization. Another PKC inhibitor, Gö 6976 (1 µM), was less effective in preventing desensitization. Measurements of endothelial cell [Ca²⁺]_i in pressurized arteries confirmed the P2Y1 receptor but not M₃ muscarinic receptor desensitization.

Conclusions and implications:

These data demonstrate for the first time the involvement of PKC in the desensitization of endothelial P2Y1 receptors in pressurized rat mesenteric arteries, which may have important implications in the control of blood flow by circulating nucleotides.     

Long-term functional outcome and satisfaction of patients with hypospadias repaired in childhood

Introduction

Potential long-term sequelae of hypospadias and its surgical correction include difficulties in voiding, sexual function, psychosexual adjustment and self-appraisal. These difficulties often evolve long after surgical repair as children grow to adulthood. Despite this, patient-driven data on long-term functional outcomes and satisfaction are limited, leaving the true success of hypospadias surgery essentially unknown. The aim of this study was to address these deficiencies.

Methods

We conducted a chart review for all patients operated on by a single urologist from 1981 to 1988. Extensive efforts were made to obtain accurate current address information for patients. A database of patient demographics and pathology, operative details and complications was created. A 22-item questionnaire was mailed to study subjects. Telephone follow-up by an independent research nurse bolstered response rates. Responses from returned questionnaires were pooled and analyzed.

Results

The chart review included 115 patients. Of 100 patients (with address information) who were sent questionnaires, 28 ultimately responded. The chart review group was comparable to groups in other published studies. Despite a slightly higher initial major complication rate (57.2%), respondents reported few long-term complications (11% fistula, 29% persistent chordee and 10% stricture) and excellent urinary and sexual functional results. The most common functional complaints were spraying and hesitancy during micturition. Overall, 86% of patients were satisfied with their surgical result, and 52% wished they had been provided longer follow-up.

Conclusion

Long-term outcomes data are critical to an honest account of success rates for hypospadias surgery. Obtaining these data remains challenging. In this series, despite high initial complication rates, most patients reported excellent long-term functional results and were quite satisfied with their overall outcome.     

损伤性癫痫模型大鼠海马和额叶突触蛋白的动态表达

Objective To observe the time course of changes in synaptophysin (P38) expression in the cortex and hippocampus of rats with posttraumatic epilepsy (PTE), and explore the role of synaptic plasticity in the epileptogenesis of PTE. Methods Thirty-seven male Sprague-Dawley rats were randomized into normal control group (n=5), sham-operated group (n=12) with intracortical saline injection, and PTE model group (n=20) with stereotactic FeCl<,2> injection (0.1 mol/L, 10 μ1) into the motor cortex. The expression of P38 in the brain cortex and hippocampus of the rats was detected immunohistochemically at 1 h and 7, 14 and 30 days after the injections. Results Most of the rats with FeCl<,2> injection developed isolated epileptiform discharges soon alter the injection. Compared with the sham-operated groups, the rats in PTE group showed significantly decreased P38 expression in the right frontal cortex at all the time points of measurement (P<0.05). At 1 h after FeCl<,2> injection, P38 expression in the polymorphic layer, stratum lacunosum and stratum radiatum of the right hippocampai CA3 area and DG molecular layer underwent no significant changes (P>05), but at 7 days, the expression increased significantly in all the stratum regions of the right hippocampal CA3 area, and this high expression level was maintained till 30 days after the injection. Conclusion Synaptic plasticity alterations in relation to P38 expression changes in the cortex and hippocampus may play an important role in the epileptogenesis of PTE in this rat model.     

Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer

AIM: To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant therapy of superficial bladder transitional cell carcinoma, with respect to recurrence, progression and survival. Prognostic factors are also evaluated. METHODS: Between October 1991 and September 1999, all patients harboring superficial bladder cancers (Ta or T1) with any of the relevant criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors), after complete transurethral resection were randomized to receive either 81 mg Connaught strain BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover, even repeatedly, until progression. Recurrence, progression and survival were analyzed in relation to initial treatment, patient characteristics and tumor characteristics. RESULTS: There were 209 patients included in the study, 149 men and 60 women. The mean age was 69.9 years (range, 24-92). The BCG group consisted of 102 patients and the epirubicin group contained 107 patients. Final analysis was made at a median follow up of 23, 47 and 61 months for recurrence, progression and survival, respectively. The 10-year Kaplan-Meier estimates for recurrence-free, progression-free and disease-specific survival were 61%, 78% and 80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and 92%, respectively, for the epirubicin group. Time to recurrence differed significantly between two treatment groups (P=0.0004). Multiplicity increased the risk of recurrence, while grading influenced recurrence, progression and disease specific survival. CONCLUSIONS: Bacillus Calmette-Guerin prolonged time to recurrence when compared with epirubicin. Grading was shown to be a universal prognostic factor for recurrence, progression and disease specific survival.     

Renal cell carcinoma and vasculitis: report of two cases

A 63-year-old caucasian male with systemic leukocytoclastic vasculitis involving the skin, lungs, and gastrointestinal tract was found to have a renal cell carcinoma at autopsy. A 77-year-old-woman with a history of hypertension was felt to have temporal arteritis that was confirmed by biopsy. The autopsy revealed a renal cell carcinoma in association with widespread giant cell arteritis. The possible association of renal cell carcinoma with vasculitis and an assessment of the possible clinical usefulness are presented and cases of vasculitis with renal neoplasms are briefly reviewed.