Flowcytometric immunophenotyping of peripheral-blood leukocytes in relation to immunopathology and cellular proliferation of pleural mesothelioma

Immunomodulation of malignant mesothelioma (MM) is variable considering host immune mechanisms. This study has investigated the immunophenotyping of peripheral-blood leukocytes of patients with mesothelioma in relation to different histopathologic types and proliferative potentiality. The study was achieved on 18 patients presented by massive effusion accompanying MM. Circulating CD4+ and CD8+ T cells were counted using two-colour flowcytometry. Pleural effusion cell block preparation and pleural biopsies were processed for immunohistochemical analysis of intratumoral CD8+ lymphocytes, cytokeratin and vimentin antigens expression, and modified one step silver stain to identify the Argyrophilic nucleolar organizer regions (AgNors) for evaluation of the proliferative potentiality of the tumor. Blood samples of five normal individuals were considered as controls. Histopathologic examination demonstrated epithelial variant in 12 cases, mixed (biphasic) variant in 4 cases and 2 cases were sarcomatoid. Flowcytometric analysis exhibited a significant increase in the mean percentage of circulating CD4+ T cell count in mesothelioma (56.7% +/- 6.99) versus control (43% +/- 1.58), p < 0.001. In contrast, cytotoxic CD8+ cells were significantly reduced (p < 0.001) in comparison to the control (25.2% +/- 2.96 versus 32% +/- 4.6 respectively). CD4/CD8 ratio was significantly increased versus control (2.06 +/- 0.57 versus 1.3 +/- 0.02 p < 0.05). Intratumoral CD8+ lymphocytes were depleted in mesothelioma cases. There was significant reduction of circulating cytotoxic T lymphocytes (CTL) in relation to mixed and sarcomatoid variants versus epithelial differentiation (mean = 25.25 +/- 4.86, 22 +/- 1.41 and 29.5 +/- 9.9 respectively with a p value < 0.05). Reduction of cytotoxic T cells was also associated with increased expression of vimentin and increased proliferative activity which has been identified by increased AgNors in mixed and sarcomatoid differentiation. In conclusion, mesothelioma might be associated with modulation of the tumoricidal effect of cytotoxic T lymphocytes in relation to tumor differentiation and its proliferative potentiality. Immunophenotyping analysis of leukocytes may reflect the competence of immune system against malignancy and act as an additive prognostic parameter for mesothelioma progression and probably expecting response to oncotherapy protocols.     

Differential pulse cathodic voltammetric determination of floctafenine and metopimazine

A simple, rapid and sensitive voltammetric method for the determination of floctafenine (FFN) and metopimazine (MPZ) was developed. Well-defined cathodic waves were obtained for both drugs in Britton-Robinson buffer pH 9.0 using the differential-pulse mode at the hanging mercury drop electrode (HMDE). The current-concentration relationship was found to be linear over the ranges 0.4-3.6 and 0.4-2.4 microg ml(-1) for FFN and MPZ, respectively. The quantification of the two drugs in their pharmaceutical formulations was carried out using the proposed voltammetric method and compared with spectrophotometric analysis data. The mechanisms of the electrode reactions for the two drugs were proposed.     

Prevalence of juvenile idiopathic arthritis in Sharkia Governorate, Egypt: epidemiological study

Our objective was to determine the prevalence juvenile idiopathic arthritis (JIA) in Sharkia Governorate, Egypt. Population-based study was performed to identify the prevalence of JIA in Sharkia Governorate, Egypt, between November 2009 and November 2010. Prevalence of JIA was 3.43 per 100,000 (95 % CI 3.1–4.3). Prevalence in boys was 2.58 per 100,000 (95 % CI 2.4–3.6) and in girls 4.33 per 100,000 (95 % CI 3.3–5.1). Uveitis presented in 19.7 % of cases, antinuclear antibody in 48.5 %, and rheumatoid factor in 27.2 %. Oligoarthritis representing 52.2 % of the total population, and enthesitis-related arthritis presented only in 6 patients. No cases of undifferentiated arthritis or psoriatic arthritis were found. This is the first epidemiological study of JIA in Sharkia, Egypt. Oligoarthritis was the most common subtype.     

Diclofenac sodium loaded-cellulose acetate butyrate: Effect of processing variables on microparticles properties,drug release kinetics and ulcerogenic activity

The aim of this study was to develop and characterize diclofenac sodium loaded-cellulose acetate butyrate microparticles in order to obtain a controlled-release system. The influence of the type of polymer, the volume and composition of the internal phase, drug loading, surfactant concentration and additive added on microparticles characteristics (particle size, encapsulation efficiency, surface morphology and in vitro release profiles) was studied to optimize the microparticles system. The resultant microparticles were evaluated for the recovery, average particle size, drug loading and incorporation efficiency. The microparticles exhibited good flowing nature and compressibility index when compared to pure drug. Dissolution rate of diclofenac sodium in phosphate buffer (pH 6.8) increased with increases in initial drug loading, surfactant concentration and addition of alcohol as co-solvent but decreased with increases in the concentration of additives such as Gantrez® AN or Eudragit S100 in the internal phase. The dissolution data showed a Higuchi diffusion pattern for most of the formulations. About 56–81% reduction in ulcerogenic activity was observed with microparticles containing Eudragit S100 17–25%, based on total polymer concentration, when compared with pure diclofenac sodium.     

Evaluation of the effect of neoadjuvant chemotherapy on tumor and axillary lymph nodes in locally advanced breast cancer:a study of 50 patients

The purpose of the study was to correlate between ef ect of pre neoadjuvant chemotherapy (NACT) and post NACT clinical, sonographic and pathologic features of the tumor and axil ary lymph nodes (ALNs) and to raise the possibility of applying the concept of sentinel lymph node biopsy (SLNB) in patients with initial y positive ALNs before NACT. Methods:A prospective study of 50 female patients with local y advanced breast cancer (LABC) with clinical y palpable and cytological y (under ultrasonographic guidance) positive ALNs. Al patients received NACT and then referred for ultrasono graphic assessment of the axil a regarding any detectable sonographic criteria of metastatic deposits in ALNs as wel as the tumor size in relation to its pre chemotherapy size. Al patients were then subjected either to modified radical mastectomy or breast conserving surgery. The clinical, sonographic and pathological response of the tumor and the ALNs were documented, classified and correlated with each other. Results:Patients’ mean age was 47.7 ± 9.1 years. The mean clinical tumor size was 6.7 ± 1.4 cm;stage IIIA that was presented in 32 patients (64%) and IIIB was presented in 18 patients (36%). Chemotherapy was given for a median of 4 cycles. there was reduction of the mean clinical tumor size from 6.7 ± 1.4 cm to 4.3 ± 2.7 cm (P<0.001). Clinical response was complete in 5 (10%) tumors, complete pathological tumor response (post neoadjuvant) was detected in 8 (16%) of patients. Complete clinical nodal response (post neoadjuvant) in 23 (46%) axil ae, on sonographic assessment of the axil a, response was complete in 17 (34%) axil ae. Complete pathological nodal response occurred in 16 (32%) axil ae. Out of 17 axil ae that showed complete sonographic response 11 axil ae showed complete pathological nodal response (P<0.001). Conclusion:Formal axil ary lymph node dissection can be avoided and replaced by SLNB post NACT in patients with LABC with metastatic ALNs if there were complete clinical and sonographic criteria of nodal response as wel as complete pathological tumor response.     

Short wavelength automated perimetry can detect visual field changes in diabetic patients without retinopathy

Purpose:

The purpose of the following study is to compare short wave automated perimetry (SWAP) versus standard automated perimetry (SAP) for early detection of diabetic retinopathy (DR).

Materials and Methods:

A total of 40 diabetic patients, divided into group I without DR (20 patients = 40 eyes) and group II with mild non-proliferative DR (20 patients = 40 eyes) were included. They were tested with central 24-2 threshold test with both shortwave and SAP to compare sensitivity values and local visual field indices in both of them. A total of 20 healthy age and gender matched subjects were assessed as a control group.

Results:

Control group showed no differences between SWAP and SAP regarding mean deviation (MD), corrected pattern standard deviation (CPSD) or short fluctuations (SF). In group I, MD showed significant more deflection in SWAP (−4.44 ± 2.02 dB) compared to SAP (−0.96 ± 1.81 dB) (P =0.000002). However, CPSD and SF were not different between SWAP and SAP. In group II, MD and SF showed significantly different values in SWAP (−5.75 ± 3.11 dB and 2.0 ± 0.95) compared to SAP (−3.91 ± 2.87 dB and 2.86 ± 1.23) (P =0.01 and 0.006 respectively). There are no differences regarding CPSD between SWAP and SAP. The SWAP technique was significantly more sensitive than SAP in patients without retinopathy (p), but no difference exists between the two techniques in patients with non-proliferative DR.

Conclusion:

The SWAP technique has a higher yield and efficacy to pick up abnormal findings in diabetic patients without overt retinopathy rather than patients with clinical retinopathy.     

Transforming growth factor beta cooperates with persephin for dopaminergic phenotype induction

The aim of the present study was to investigate the putative cooperative effects of transforming growth factor beta (TGF-beta) and glial cell line-derived neurotrophic factor (GDNF) family ligands in the differentiation of midbrain progenitors toward a dopaminergic phenotype. Therefore, a mouse midbrain embryonic day (E) 12 neurospheres culture was used as an experimental model. We show that neurturin and persephin (PSPN), but not GDNF, are capable of transient induction of dopaminergic neurons in vitro. This process, however, requires the presence of endogenous TGF-beta. In contrast, after 8 days in vitro GDNF rescued the TGF-beta neutralization-dependent loss of the TH-positive cells. In vivo, at E14.5, no apparent phenotype concerning dopaminergic neurons was observed in Tgf-beta2(-/-)/gdnf(-/-) double mutant mice. In vitro, combined TGF-beta/PSPN treatment achieved a yield of approximately 20% TH-positive cells that were less vulnerable against 1-methyl-4-phenyl pyridinium ion toxicity. The underlying TGF-beta/PSPN differentiation signaling is receptor-mediated, involving p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. These results indicate that phenotype induction and survival of fully differentiated neurons are accomplished through distinct pathways and individual factor requirement. TGF-beta is required for the induction of dopaminergic neurons, whereas GDNF is required for regulating and/or maintaining a differentiated neuronal phenotype. Moreover, this study suggests that the combination of TGF-beta with PSPN is a potent inductive cocktail for the generation of dopaminergic neurons that should be considered in tissue engineering and cell replacement therapies for Parkinson's disease.     

Sirolimus-eluting stents versus bare-metal stents in routine clinical use: a nonrandomized comparison

Conflicting patient outcomes have been reported after the use of sirolimus-eluting stents or bare-metal stents. In this nonrandomized study, we examine the outcomes after placement of sirolimus-eluting versus bare-metal stents in an unselected population of patients who underwent percutaneous coronary revascularization.We used THIRD-base, a longitudinal data registry of patients who underwent revascularization at our institution, to compare demographics and outcomes in patients treated with a sirolimus-eluting or bare-metal stent from January 2001 through June 2006. Outcome measures included major acute coronary and cerebral events at 30 days, target-vessel failure at 9 months and at 3 years, and stent thrombosis. Target-vessel failure was defined as the composite of all-cause death, recurrent myocardial infarction in the treated vessel distribution, and target-vessel revascularization. Logistic regression and Cox proportional regression models were used to determine the predictors of outcome.Of the 6,425 patients analyzed, 2,581 patients (40.2%) received only sirolimus-eluting stents, and 3,844 patients (59.8%) received only bare-metal stents. Early major acute coronary and cerebral events and stent thrombosis at 30 days and 9 months were similar in both groups. Target-vessel failure was less frequent in sirolimus-eluting stent patients than in bare-metal stent patients at 9 months (4.84% vs 11.81%, P < 0.0001) and at 3 years (29% vs 32%, P < 0.0001).Use of sirolimus-eluting stents improved target-vessel failure survival at 9 months and at 3 years. Late adverse events were determined by known risk factors for atherosclerosis, not by stent type.     

Can gymnastic teacher predict leisure activity preference among children with developmental coordination disorders (DCD)?

The aims of the study were to analyze: (1) whether significant differences exist between children with typical development and children with developmental coordination disorders (DCD) in their preference to participate in leisure activities (2) whether the teacher estimation of activity form (TEAF) evaluation predicts participation preference. Participants were 68 children, aged 6-9.83 years, 35 diagnosed as DCD by pediatrician and based on the Movement ABC (M-ABC) and 33 children with typical development. The controls were matched by age and gender to the DCD group. The children filled the preference for activities of children (PAC) and their sport teacher completed the TEAF. Significant differences were found between the groups in their participation preference based on the PAC items and subscales as well as in the TEAF scores. Significant correlations were found between the TEAF and PAC subscales. TEAF score significantly predicted children's preference to participate in leisure activities. Study results recommend using the TEAF for screening DCD and to further consider participation issues among children with DCD as a preventive aid for consequently socio-emotional implications of DCD.