Aboul Ella Hassanien (Abo)

BACKGROUND: Loss of heterozygosity (LOH) in tumor samples is believed to be a marker for the absence of a functional tumor suppressor gene. Non-random chromosome deletion and LOH at specific chromosomal regions are identified in a number of common human cancers including carcinoma of the bladder, which is considered the most predominant cancer in Egypt due to the prevalence of schistosomiasis.

PURPOSE: The main objective of the present study is to clarify the role of chromosomes 8 and 9 in the establishment and/or progression of schistosomiasis-related bladder cancer through detection of LOH of 8 microsatellite markers on both chromosomes. It also aims to compare the LOH pattern of the tested markers between schistosomiasis- associated and non schistosomiasis-associated bladder cancer.

MATERIAL AND METHODS: To achieve this purpose, DNA was extracted from the tumor specimens and the corresponding peripheral blood samples of 42 primary bladder cancer patients (schistosomal and non schistosomal). Twenty nine of these were diagnosed as squamous cell type (SCC), 11 were transitional (TCC), and 2 were adenocarcinoma (with different stages and grades). LOH at chromosomes 8 and 9 was evaluated for 8 highly polymorphic microsatellite markers distributed at different regions of both chromosomes using the dinucleotide repeat-PCR technique.

RESULTS: The overall percentage of LOH in chromosome 8 was 74% in at least one marker. The highest incidence of LOH was recorded for D8S84 (41%) followed by 37% for D8S87, 29% for D8S85, and 25% for D8S88. Deletions at chromosome 8 were shown to be associated with high grade of the tumor and LOH at D8S85 was associated with metastatic lymph nodes. The overall percentage of LOH in chromosome 9 was 54% and its highest incidence was for D9S126 (36%), followed by 26%, 21%, 19% for D9S166, D9S128 and D9S180, respectively. Fifty nine percent (59%) of the cases with LOH at 9q were diagnosed as squamous cell type (SCC), whereas 9% only were transitional cell type (TCC). No significant association was recorded between the presence of schistosomiasis and LOH detected in all markers used in this study.

CONCLUSION: Our data indicate that more than one tumor suppressor gene on chromosomes 8 and 9 are involved in high grades of bladder carcinogenesis, one at 8p12 and another at 8q21.1 regions. Also, a region at 8q23-quarter may harbor tumor suppressor gene that involved in metastasis of bladder cancer. Our study also revealed that 9p21 (p16INK4) region is involved in both types of the tumor (SCC & TCC). PTCH located at 9q22.3, as well as the TSC gene at 9q34 are involved in squamous cell carcinoma rather than transitional carcinoma. Region 9q12-13 is considered to be a critical region of urothelial tumor suppressor genes. Finally, the present study shows no line of demarcation between schistosomiasis-associate and non schistosomiasis-associated bladder cancer in terms of LOH of the tested microsatellite markers on chromosome 8 and 9. This suggests that data obtained from schistosoma-associated bladder cancer can be extrapolated to bladder cancer induced by a schistosomiasis independent mechanism.

Dicationic guanidine, N-alkylguanidine, and reversed amidine derivatives of fused ring systems have been synthesized from their corresponding bis-amines. DNA binding studies suggest that the diguanidines and the N-alkyl diguanidines fluorenes bind in the minor groove in a manner similar to that of the previously reported dicationic carbazole derivatives. The diguanidines and the N-alkyl diguanidines showed promising in vitro activity against both Trypanosoma brucei rhodesiense and Plasmodium falciparum. Promising in vivo biological results were obtained for the dicationic N-isopropylguanidino-9H-fluorene, giving 4/4 cures of the treated animals in the STIB900 animal model for African trypanosomiasis. The N-methyl analogue showed high activity as well. In addition, with the goal of enhancing the oral bioavailability, two novel classes of potential guanidine prodrugs were prepared. The N-alkoxyguanidine derivatives were not effective as prodrugs. In contrast, a number of the carbamates showed promising activity. The value of the carbamate prodrugs was clearly demonstrated by the results, which gave 4/4 cures on oral administration in the STIB900 mouse model.

PURPOSE: To investigate changes in cancer of the uterine cervix during radiotherapy (RT) with respect to G2/M transition in relation to tumor cell apoptosis and changes in the tumor vasculature in cervical carcinoma.

METHODS AND MATERIALS: A total of 40 consecutive patients with Stage IIA-IIIB cervical cancer underwent RT without any chemotherapy. Tumor biopsy was obtained before RT and after five fractions of 1.8 Gy. The tumor samples were stained for cyclin B1, cdc2, and Ki-67, the apoptotic index, using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining. The tumor vasculature density was assessed. In 38 cases, the tissue samples were informative.

RESULTS: Cyclin B1 was positive in all biopsies before and after initiation of RT, and staining for cdc2 was positive in 35 (92%) of 38 biopsies before and 33 (87%) of 38 after 1 week of RT. Nuclear staining for cyclin B1 was observed in 92% of patients, staining an average of 15% of cells before RT. After initiating RT, 73% of patients showed positive staining on about 5% of tumor cells (p < 0.01). Nuclear staining for cdc2 was detected in 89% of patients, staining an average of 21% of cells before RT. After initiating RT, 79% of patients showed positive staining on 9% of cells (p < 0.01). The apoptotic index of the tumor cells increased after initiating RT, and a slight decrease in the vascular density after 1 week of RT was noted (p = 0.08). Changes in G2/M were associated with the clinical response, but changes in apoptosis or tumor vasculature were not.

CONCLUSION: RT leads to significant changes in the cell cycle in cervical cancer indicating intact G2/M checkpoint function. Targeting G2/M with compounds interfering with G2/M transition may further enhance the effect of RT in cervical cancer patients.

OBJECTIVE: To compare the effects of surgical and device closure of atrial septal defects on atrial and ventricular performance assessed by the novel tissue Doppler derived strain rate.

BACKGROUND: Despite the increasing number of transcatheter closures, there is no information comparing the effect of the transcatheter closure technique on atrial performance with that of conventional surgery. Tissue Doppler derived strain rate can effectively quantify local myocardial function independent of the overall heart motion.

DESIGN AND PATIENTS: Twenty-four patients [aged 21.5 (6-70) years] with isolated atrial septal defect of the secondum type before and 1 week after surgical (n = 12) or Amplatzer Septal Occluder closure (n = 12) and 30 healthy controls [aged 26.0 (2-58) years] were studied. Atrial and ventricular strain rate curves were assessed in the middle of their corresponding lateral walls in an apical four-chamber view. The systolic, early diastolic, and late diastolic strain rates peaks were measured.

RESULTS: Compared to preclosure condition, the right atrial late diastolic (P < 0.01), right ventricular systolic (P < 0.01), right ventricular early diastolic (P < 0.01), and left atrial late diastolic peak (P < 0.01) strain rates were reduced after surgery but not after Amplatzer Septal Occluder closure. The LV parameters did not significantly differ before and after atrial septal defect closure by either technique.

CONCLUSIONS: In contrast to surgery, transcatheter closure of atrial septal defect preserves atrial and right ventricular function. Tissue Doppler derived strain rate can be applied to provide quantitative analysis of regional atrial and ventricular performance.

INTRODUCTION: The long-term follow-up of patients with D-transposition of the great arteries after atrial switch operation shows specific problems such as tricuspid valve insufficiency, rhythm disturbances and failure of the morphologic right ventricle in systemic position. Assessment of the myocardial contractility of the subaortic right ventricle by conventional echocardiography is limited. The usage of tissue Doppler echocardiography with strain combined with strain rate imaging provides a new approach for quantitative analysis of longitudinal myocardial function. The aim of this study was to assess patterns of wall motion and regional contractile function of the systemic right ventricle in patients after atrial switch operation for D-transposition of the great arteries and to compare them to those of normal subjects.

PATIENTS AND METHODS: Twenty-four patients with Dtransposition of the great arteries after atrial switch operation with a mean age of 21.3 (range, 13 to 31) years and a postoperative period of 16.9 years were examined and compared to 22 control individuals with a mean age of 21.5 (range, 3 to 43) years. Tissue Doppler studies were obtained from apical 4- chamber view to determine regional systolic (Syst(T)) and diastolic (E(T), A(T)) velocities as well as E(T)/A(T) ratio at the basal free wall. The presystolic isovolumic contraction peak was assessed and the ratio of the presystolic peak velocity to the isovolumic acceleration time as the IVA index was calculated. Strain and peak systolic and diastolic strain rates were assessed on basal, middle and apical segments of the right ventricular free wall. Data obtained from the morphologic right systemic ventricle in patients were compared to those derived from the left and the right ventricle in controls.

RESULTS: The right ventricular free wall systolic velocities were significantly reduced in patients compared to velocities obtained from the normal right and left ventricle. On the other hand, the IVA index was only reduced in patients compared to the IVA index in the normal subpulmonary right ventricle. Compared to data obtained from the normal systemic left ventricle, the IVA index in patients was not significantly different. In contrast, strain and strain rate parameters in all analyzed segments mostly showed a highly significant reduction compared to normal right and left ventricular data.

CONCLUSION: Tissue Doppler echocardiography is a promising tool for the evaluation of regional myocardial contractile function of the morphologic right systemic ventricle in patients following atrial switch operation for D-transposition of the great arteries. Presystolic, systolic and diastolic regional ventricular function was reduced in the systemic right ventricle. However, further comparative studies using other quantitative parameters of global and regional myocardial function derived from cardiac catheterization or MRI should be performed in order to evaluate the reliability of tissue Doppler echocardiography for the assessment of global right ventricular function in these patients.

A case of branchio-oculo-facial syndrome with bilateral linear scars affecting both sides of the neck is described. The disease occured in a male patient aged 20 years and presented with facial asymmetry, pre and postauricular pits, lip pits, microphthalmia, broad malformed nose, colobomas and dystrophic right kidney. In addition, there were bilateral linear hypertrophic scars on both sides of the neck. We believe that the latter lesions may represent the end stage of dermal thymus; a rare condition which has been reported so far in only four cases, two of which had branchio-oculo-facial syndrome.

BACKGROUND: Most of the world's children live in regions where laboratory facilities are not available. In these regions, clinical prediction rules can be useful to guide clinicians' decisions on antibiotic therapy for streptococcal pharyngitis, and to reduce routine presumptive antibiotic therapy for all pharyngitis.

METHODS: Prospective cohort study to assess diagnostic signs and develop a prediction rule. Bivariate and multivariate analyses were used to develop clinical rules. Participants were 410 children in Cairo, Egypt, aged from 2 to 12 y, presenting with complaint of sore throat and whose parents provided consent. Main outcome measures included presence of signs and symptoms, and positive group A beta hemolytic streptococcal (GABHS) culture.

RESULTS: 101 (24.6%) children had positive GABHS culture. Pharyngeal exudate, tender or enlarged anterior cervical lymph nodes, season, absence of rash, or cough or rhinitis were associated with positive culture in bivariate and multivariate analyses. Three variables (enlarged nodes, no rash, no rhinitis), when used in a cumulative score, showed 92% sensitivity and 38% specificity in these children.

CONCLUSIONS: The proposed three-variable clinical prediction rule for GABHS may be useful when diagnostic laboratories are not available. In this setting, the rule identified more than 90% of true cases. Compared to universal treatment of all pharyngitis, the rule will reduce antibiotic use in GABHS-negative cases by about 40%.

To investigate the immunomodulatory effect of the Th1 mediated cytokine IFN-alpha on schistosomiasis, this cytokine was weekly injected into mice experimentally infected with S. mansoni, beginning from day 0 (group II), week 3 (group III), week 6 (group IV) and week 10 (group V) post-infection. TGF-beta1 serum levels were estimated on a weekly basis and beginning one week after initiation of IFN-alpha therapy, while all animals were sacrified on week 14 to be used for egg counts in liver and small intestine, oogram study for determination of the maturity of deposited eggs, and histopathological examination of stained liver sections. IFN-alpha treated groups were characterized by a more intense oviposition in the intestine (liver/intestine ratio less than 1), with higher egg numbers the earlier IFN-alpha was administered. Oograms of the intestine indicated the level of immature eggs to be statistically significantly higher in group II, III and IV than in the control group I (p < 0.05). In IFN-alpha medicated mice, the mean numbers and diameters of hepatic granulomas were less than in GI, in addition to a lower representation of fibrocellular and fibrous granulomas among them (all parameters p < 0.05), especially in Gs IV & V. The inflammatory cell population in the form of eosinophils, histiocytes and giant cells was more pronounced in Gs III, IV & V. TGF-beta1 serum levels showed a progressive rise, however more pronounced in the untreated control. A statistically positive significant was established between TGF-beta1 levels and number, size and percentage of fibrotic hepatic granulomas in all groups.

BACKGROUND: Hepatic fibrosis and cirrhosis develop progressively in extrahepatic biliary atresia (EHBA) despite timely surgical intervention.

PURPOSE: The aim of the study was to define CD4+ helper T lymphocytes, cytotoxic CD8+ T lymphocytes, and CD68+ (macrophages) infiltration of portal tracts and lobules and hepatic fibrosis as possible predictive measures of outcome of infants having EHBA.

METHODS: The outcome of 32 infants with EHBA was correlated to their percutaneous biopsy and postportoenterostomy core liver tissue infiltration by CD4+, CD68+, and CD8+ cells and to the degree of detected fibrosis.

RESULTS: Portoenterostomy cores were heavily infiltrated by CD4+, CD8+, and CD68+, compared with the preoperative liver biopsy (P = .008, .004, and .017, respectively). Infants having favorable outcome had more macrophage infiltration in portoenterostomy core compared with those having an unfavorable outcome (25.66 +/- 29.77 per HPF compared with 11.62 +/- 4.58, P = .000). Mean CD4+/CD8+ ratio was 1.54 +/- 1.37 in those who died within 18 months postoperatively and 0.733 +/- 0.48 in others (P = .021).

CONCLUSION: Immune-mediated destruction of portal tracts is an integral part of pathogenesis of EHBA.

BACKGROUND AND PURPOSE: Spinal cord involvement is a rare manifestation of schistosomiasis. We describe the MR imaging findings of spinal cord schistosomiasis in correlation with surgery and pathology.

METHODS: We report eight cases of spinal cord schistosomiasis. All patients were men (mean age, 16.7 years) with neurologic manifestations who had been referred for spinal MR imaging. In all cases, spinal masses were surgically removed. MR imaging findings were correlated with surgery and pathology.

RESULTS: MR imaging showed moderate expansion of the distal spinal cord in all cases. Abnormalities were isointense to cord in T1 and patchy hyperintense in T2-weighted spin-echo images (n = 8). Three forms of contrast enhancement were recognized: (1) intramedullary nodular (n = 8); (2) peripheral (n = 8); and (3) linear radicular (n = 4). Total gross surgical removal of masses by using the Cavitron ultrasonic surgical aspirator was possible in six cases. Diagnosis was established by identification of ova in histopathologic studies: Schistosoma mansoni (n = 3), S. hematobium (n = 1), and uncertain species (n = 4). Intramedullary nodular enhancement was correlated to multiple schistosomiasis microtubercles. Peripheral enhancing lesions correlated to thickened leptomeninges infested by chronic granulomatous inflammatory cells and schistosoma eggs. Linear radicular enhancement correlated with thickened resected nervous roots infested by granulomatous cells and schistosoma eggs.

CONCLUSION: Multinodular intramedullary contrast enhancement of the distal cord enabled correct presumptive preoperative MR imaging diagnosis of spinal schistosomiasis in three cases. Accurate diagnosis, through recognition of its MR imaging appearance, allows early treatment and better prognosis of spinal cord schistosomiasis.

In a trial at determining the most relevant immunoglobulin isotype that could reflect success of praziquantel treatment, an ELISA using soluble egg antigen (SEA) was applied on sera of Egyptian patients suffering from active intestinal schistosemiasis without hepatic complications, determining the levels of IgE, IgA, IgM, IgG1, IgG2, IgG3 and IgG4 raised against the SEA, both, pre- and early post-treatment. The positive results obtained to all anti-SEA immunoglobulin isotypes before treatment support the usefulness of this technique in the diagnosis of schistosomiasis. Except for IgG3 subclass, a statistically significant correlation was found between egg output-reflecting intensity of infection- and the different immunoglobulin levels, especially anti-SEA IgG4. When repeating the assay 5-6 months after treatment, the immunoglobulin levels showed either a rise (in case of IgE) or a drop (in case of IgA, IgM & IgG1-4), all of statistical significance, yet, IgG1-4 were still positive. So, ELISA could not give a definite indication of cure after anti-bilharzial treatment. IgE, IgG2 and IgG4 were revealed to be the most significant immunoglobulin isotypes at the post-treatment level, both statistically and due to their implications on resistance/ susceptibility to re-infection and also due to the correlation of IgG4 with the tendency to develop periportal fibrosis. Conclusively, although not having defined a particular Ig isotype as marker for cure, yet it exposed the urge for early post-treatment determination of IgE and IgG4 isotypes, which could serve as markers for picking up high risk patients susceptible to reinfection or liable to develop bilharzial periportal fibrosis, and who might benefit from a second course of specific treatment.

OBJECTIVES: Bloodstream infections (BSI) remain a major cause of morbidity and death in patients undergoing treatment for cancer. However, all recent epidemiological and therapeutic studies underline the absolute need for knowledge of the factors governing the infections in each center. The aim of this study is to identify the factors affecting BSI in the pediatric service of the National Cancer Institute (NCI) at Cairo University. More tailored policies for the treatment of patients with febrile neutropenia following chemotherapy can then be created.PATIENTS AND METHODS: Over a 12-month period, all children with cancer and fever, with or without neutropenia, who were admitted to the NCI for empirical therapy of febrile episodes and who had a microbiologically confirmed bloodstream infection were studied retrospectively.
RESULTS: A total of 328 BSI occurred in 1135 febrile episodes in pediatric cancer patients at the NCI in one year. Gram-positive bacteria were isolated in 168 episodes (51.2%) and 61.9% of the total isolates (either single or mixed), Gram-negative in 97 (29.6%), and mixed infections in 45 (13.7%). The common causative agents of bloodstream infections in this study were coagulase-negative staphylococci (16.2%), Staphylococcus aureus (13.4%), Streptococcus spp. (12.1%) followed by Acinetobacter spp. (6.7%) and Pseudomonas spp. (5.5%). Fungemia was encountered in 18 episodes, being mixed in nine of them. A more serious BSI in terms of a prolonged episode was encountered in 30.2% of the episodes and was significantly associated with patients being hospitalized, having intensified chemotherapy, polymicrobial and fungal infection, lower respiratory tract infections and persistent neutropenia at day seven.
CONCLUSIONS: In a large population of children, common clinical and laboratory risk factors were identified that can help predict more serious BSI. These results encourage the possibility of a more selective management strategy for these children.

PURPOSE: The purpose of this study is to evaluate pediatric GIT lymphomas as regards clinico-pathological features, controversies in surgical treatment, role of chemotherapy and the prognostic features.PATIENTS AND METHODS: This study included forty three patients with pediatric GIT Non-Hodgkin's lymphoma collected over 7 years at the NCI Cairo University between January 1997 and December 2003. The data of every patient included: Age, sex, presenting symptoms and signs, preoperative investigations, extent of the disease at diagnosis and the type of resection performed, histopathological examination, details of chemotherapy and state at follow up. Overall and disease free survival were calculated and correlated with all parameters.
RESULTS: The study included 30 boys and 13 girls with median age 5.00 years (range: 0.4:17). The lesions were located in the small intestine (n=15), the large intestine (n=14), the ileocecal region (n=10), stomach (n=2), and multifocally (n=2). Burkitt's lymphoma was the commonest histological type (n=24). The majority were stage IIE and IIIE (22 and 17 respectively). Exploration was done in thirty nine patients (complete resections were done in 23 cases, incomplete resections (debulking) were done in 14 cases and in 2 cases only lymph node biopsies were done). All patients received a sort of systemic chemotherapy. The median follow up duration was 44 months (range 4- 116 months). The only parameters that had significantly affected the overall survival were localized disease, complete resection, earlier stage and response to chemotherapy with p values, (0.005, 0.001, 0.005 and <0.001 respectively). As regards the disease free survival the only significant factor was localized disease (p=0.035).
CONCLUSION: The extent of disease at presentation is the most important prognostic factor in pediatric GIT lymphoma. Surgery still plays an important role such as complete resection in localized disease, management of complicated disease and diagnostic biopsy. There is no value of debulking and surgery is not advised for gastric lesions. Chemotherapy represents a cornerstone in the treatment and offers an excellent chance for long term, disease free survival.

The electrical resistivity, magnetic susceptibility, and the thermoelectric power of Zn-substituted Li-La mixed ferrite with formula Li 0.5-0.5xZnxLayFe2.5-0.5x-yO 4 at 0.1 ≤ x ≤0.9; y = 0.04 were studied as a function of temperature and frequency. X-ray analysis and Seebeck coefficient measurement were carried out in order to assure the formation of the sample in single spinel phase and to know the type of charge carriers participating in the conduction mechanism. The dependence of the electrical resistivity of Li-Zn ferrite on Zn content and temperature is explained on the basis of the cation distribution. The transition from the ferromagnetic to paramagnetic state is accompanied by an increase in the thermo EMF. Li-Zn ferrite shows n- and p-types conductivity due to the presence of Fe2+ ions. The creation of lattice vacancies is due to the presence of Li ions which give rise of p-type conductivity. © 2004 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

The study of the thermal behavior (DSC) of hydration products in ordinary Portland cement (OPC), as a function of water cement ratios (W/C) (0.2, 0.25, ... 0.4), and the partial substitution of (35 % fly ash), (35 % slag) and (35 % fly ash + 35 % slag) to the OPC system by weight separately was carried out. It was found that the additive materials (pozzlans) increase its durability when added to the OPC. The most important effects in the cement paste microstructure are the changes in pore structure produced by the reduction in the grain size caused by the pozzlanic reactions. The study revealed that the changes in all the thermal parameters depend on the variation of W/C ratios. The systematic changes in the activation energy through all systems occur at (0.3) W/C in the phase (C-H) and (0.35) W/C in the phase (C-S-H). This means that at these ratios of W/C the two phases (C-H) and (C-S-H) further accelerated the process of cement hydration reactions, and at the same time the addition to OPC system may provide enough space for hydration products to be distributed uniformly. © 2005 American Institute of Physics.