Aboul Ella Hassanien (Abo)

Brine shrimp toxicity and TLC analysis guided the isolation of five new and biologically active meroditerpenoids [2beta,3alpha-epitaondiol (1), flabellinol (2), flabellinone (3), stypotriolaldehyde (4), and stypohydroperoxide (5)] along with five known compounds from the marine brown alga Stypopodium flabelliforme collected in Papua New Guinea. The planar structures of compounds 1-5 were determined by extensive spectroscopic analysis (1D and 2D NMR, LRMS, HRMS, IR, and UV), while relative configuration was determined by 1D and 2D NOE experiments. X-ray crystallography confirmed the relative configuration of 2beta,3alpha-epitaondiol (1), and the modified Mosher's ester method was used to establish its absolute configuration. All of the new metabolites were moderately toxic to murine neuro-2a cells (LC50 2-25 microM), and three [2beta,3alpha-epitaondiol (1), flabellinol (2), and flabellinone (3)] possessed potent sodium channel blocking activity. Stypotriolaldehyde (4) had a biphasic effect on the concentration of intracellular Ca2+ in rat cerebellar granule neurons (CGN). The previously known compound, stypoldione (6), also modulated intracellular calcium concentration and was cytotoxic in CGN. Metabolites 2beta,3alpha-epitaondiol (1), flabellinol (2), and flabellinone (3) displayed moderate cytotoxicity to the NCI-H460 human lung cancer cell line.

PURPOSE: To describe and evaluate a new technique that helps identification and unroofing of Schlemm's canal during deep sclerectomy.

DESIGN: A prospective, interventional case series.

METHODS: This pilot study was conducted on 15 eyes with various types of glaucoma. After dissecting the superficial scleral flap, the trabeculotome was inserted inside the Schlemm's canal. During deep flap dissection, a direct incision was made over the trabeculotomy to open and unroof Schlemm's canal. Five of the excised deep flaps were submitted for histologic examination.

RESULTS: In 13 of the 15 eyes, the Schlemm's canal was properly identified and unroofed. Schlemm's canal endothelium was identified in all the examined specimens. The mean intraocular pressure was reduced from 26.66 +/- 4.54 mm Hg to 12.2 +/- 3.5 mm Hg at the end of a mean follow-up of 9.4 +/- 2.9 months.

CONCLUSION: The insertion of the trabeculotome inside Schlemm's canal before dissection of the deep flap helped Schlemm's canal unroofing.

The isolation, purification and structural characterization of human liver heparan sulfate are described. 1H-NMR spectroscopy demonstrates the purity of this glycosaminoglycan (GAG) and two-dimensional 1H-NMR confirmed that it was heparan sulfate. Enzymatic depolymerization of the isolated heparan sulfate, followed by gradient polyacrylamide gel, confirmed its heparin lyase sensitivity. The concentration of resulting unsaturated disaccharides was determined using reverse phase ion-pairing (RPIP) HPLC with post column derivatization and fluorescence detection. The results of this analysis clearly demonstrate that the isolated GAG was heparan sulfate, not heparin. Human liver heparan sulfate was similar to heparin in that it has a reduced content of unsulfated disaccharide and an elevated average sulfation level. The antithrombin-mediated anti-factor Xa activity of human liver heparan sulfate, however, was much lower than porcine intestinal (pharmaceutical) heparin but was comparable to standard porcine intestinal heparan sulfate. Moreover, human liver heparan sulfate shows higher degree of sulfation than heparan sulfate isolated from porcine liver or from the human hepatoma Hep 2G cell line.

BACKGROUND AND AIM: The present study was conducted to address whether homozygous deletion (HZD) or transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCC).

METHODS: Homozygous deletion of the FHIT gene at exons 3-9 was assessed as well as mRNA FHIT expression using reverse transcription polymerase chain reaction. The study included 23 samples of HCC, 11 on top of cirrhosis and 12 non-cirrhotic, in addition to five cases with chronic active hepatitis (CAH), as well as seven morphologically normal tissues distant to the tumor (NDT) and 10 normal liver samples from liver transplantation donors.

RESULTS: Homozygous deletion was found in 18 of 23 HCC cases. The highest incidence of deletion was detected in exon 9 (52.0%) and the lowest in exon 7 (4.3%). Ten of the 18 cases (55.5%) showed deletion in more than one exon, eight in two exons, one in three exons and one in five exons. There was a significant association between HZD of exons 5 and 9 and HCC arising on top of cirrhosis (P = 0.041 and 0.006, respectively) as well as between exons 8 and 9 and the presence of CAH (P = 0.029 and 0.034, respectively). Aberrant FHIT transcripts were detected in 15 HCC cases (65.2%), 13 of them showed complete reduction of the mRNA transcripts and two showed abnormal bands. Sequence analysis of abnormal-sized transcripts revealed that they were generated by the fusion of exons 5 and 7 as well as exons 7 and 9. In contrast, six of the seven NDT samples tested (85.6%) showed HZD in one or more exons. None of the normal liver samples from liver transplantation donors showed any changes. The highest incidence of HZD was detected in exon 9 (five of six cases representing 83.3%) and the lowest was in exon 4 (one of six cases representing 16.7%). Four cases showed the same aberrant FHIT HZD in both NDT and matched HCC.

CONCLUSIONS: The results of the present study indicate that the FHIT gene is a frequent target in hepatitis C virus-associated HCC and that alterations affecting this gene could be an early event in this type of neoplasm as they were detected in cirrhotic and CAH patients. However, this should be confirmed by a larger, extended study including more cases of cirrhotic and CAH patients as well as matched tumor and normal samples.

Retrovirus-mediated interferon alpha (IFN-alpha) gene transfer was evaluated with regard to its possible protective effects against aflatoxin B1 (AFB1)-initiated and carbon tetrachloride (CCl4)-promoted hepatic carcinogenesis in rats. To our knowledge, this is the first time an experimental in vivo gene therapy trial was conducted in Egypt. Two genes were examined in liver tissue by RT-PCR: the first was glutathione-S-transferase placental (GST-P) isoenzyme, as an early marker to detect hepatic malignancy; the second was IFN-alpha gene expression to detect the efficiency of gene uptake and its persistence after transduction. Forty male rats, divided equally into 4 groups, were included in the study: the first group was the control; the second group received CCl4 0.2 ml subcutaneously twice weekly for 12 weeks and AFB1 0.25 mg/kg body wt intraperitoneally twice weekly for 6 weeks; the third group received IFN-alpha (10(8) pfu) intravenously in the tail vein prior to the start of CCl4 and AFB1 injections; and the fourth group received IFN-alpha (10(8) pfu) by intrahepatic injection under ultrasonography guide after termination of the CCl4 and AFB1 injection schedule. The results showed that IFN-alpha has a marked and significant protective effect against hepatic fibrogenesis as well as hepatic carcinogenesis. Pathological examination of liver tissue proved that IFN-alpha minimized both fibrotic and cirrhotic processes. The amount of fibrosis was less in both groups receiving IFN-alpha, with more protection in the group that received IFN-alpha intravenously prior to CCl4 and AFB1. The results of RT-PCR showed that the IFN-alpha gene was significantly expressed in both groups receiving IFN-alpha, with a more intense expression in the group that received IFN-alpha by intrahepatic injection after termination of CCl4 and AFB1 injections. The IFN-alpha gene was detected after three months of gene transduction in rats receiving IFN-alpha intravenously prior to CCl4 and AFB1 and after one month of gene transduction in the post CCl4 and AFB1 rats. IFN-alpha gene was not expressed in the two groups that did not undergo gene transfer. Histopathological signs of premalignant macronodules were evident in the group receiving CCl4 and AFB1, but not IFN-alpha as well as in the group that received IFN-alpha at the end of the experiment. GST-P gene expression was also detected in these two groups, confirming early malignant transformation. In conclusion, IFN-alpha exerts significant protective effects, but more so when the gene is administered before fibrogenic and carcinogenic induction in hepatic tissues. IFN-alpha gene therapy may be justified in clinical trials for high-risk candidates with hepatic carcinogenesis.

The phenanthridinium dye ethidium bromide is a prototypical DNA intercalating agent. For decades, this anti-trypanosomal agent has been known to intercalate into nucleic acids, with little preference for particular sequences. Only polydA-polydT tracts are relatively refractory to ethidium intercalation. In an effort to tune the sequence selectivity of known DNA binding agents, we report here the synthesis and detailed characterization of the mode of binding to DNA of a novel ethidium derivative possessing two guanidinium groups at positions 3 and 8. This compound, DB950, binds to DNA much more tightly than ethidium and exhibits distinct DNA-dependent absorption and fluorescence properties. The study of the mode of binding to DNA by means of circular and electric linear dichroism revealed that, unlike ethidium, DB950 forms minor groove complexes with AT sequences. Accurate quantification of binding affinities by surface plasmon resonance using A(n)T(n) hairpin oligomer indicated that the interaction of DB950 is over 10-50 times stronger than that of ethidium and comparable to that of the known minor groove binder furamidine. DB950 interacts weakly with GC sites by intercalation. DNase I footprinting experiments performed with different DNA fragments established that DB950 presents a pronounced selectivity for AT-rich sites, identical with that of furamidine. The replacement of the amino groups of ethidium with guanidinium groups has resulted in a marked gain of both affinity and sequence selectivity. DB950 provides protection against DNase I cleavage at AT-containing sites which frequently correspond to regions of enhanced cleavage in the presence of ethidium. Although DB950 maintains a planar phenanthridinium chromophore, the compound no longer intercalates at AT sites. The guanidinium groups of DB950, just like the amidinium group of furamidine (DB75), are the critical determinants for recognition of AT binding sites in DNA. The chemical modulation of the ethidium exocyclic amines is a profitable option to tune the nucleic acid recognition properties of phenylphenanthridinium dyes.

Squamous cell carcinoma of the urinary bladder, though uncommon in Europe and the United States, is the most common variety of bladder tumor in countries where urinary bilharziasis prevails. A great controversy still exists regarding its natural history and management. Here, we review the literature of bilharzial and nonbilharzial squamous cell carcinoma of the urinary bladder, focusing on large series. Our aim was to gather most of the published data about this disease entity, report it in a systematic comparative review, and attempt to identify the adverse features and variables behind its dismal outcome. The conclusions are that squamous cell carcinoma, whether bilharzial or nonbilharzial, has distinctive clinicopathological features, different from those of the transitional cell variety. These tumors usually present in advanced (muscle-invasive) stages. Pelvic nodal metastases are not common, and the incidence of distant metastases is less than that reported with transitional cell carcinoma. Local treatment, including cystectomy and adjunctive radiotherapy, is the most acceptable way of treating such tumors.

BACKGROUND: In clinical settings an easy and reliable method for following up right ventricular (RV) function in patients after repair of tetralogy of Fallot (TOF) is needed. It is, however, unclear whether the novel modified short axis view from echocardiography is superior to the apical four chamber view in this aspect.

MATERIALS AND METHODS: Thirty postoperative TOF patients with median age 17 years (range 6-45 years) and follow up period of 10 years (range 0.5-40 years) were examined echocardiographically using the apical four chamber view and the novel modified short axis view. RV areas in end-systole (Amin) and end-diastole (Amax) were measured and an area fraction [(Amax - Amin)/Amax * 100%] was calculated from the respective view. RV ejection fraction was assessed through magnetic resonance imaging (MRI). The RV area fractions from echocardiography were compared to the RV ejection fraction.

RESULTS: The right ventricular area fraction derived from the modified short axis view was significantly lower than that from the apical four chamber view (34.3+/-9.1% vs. 42.5+/-10.2%, p=0.007). Both the RV area fractions obtained from the modified short axis view (r=0.674, p<0.001) and from the apical four chamber view (r=0.512, p=0.025) correlated significantly with the MRI derived RV ejection fraction.

CONCLUSION: The novel modified short axis view from echocardiography may be superior to the apical four chamber view for routine follow up of patients after TOF repair, in whom the right ventricular outflow tract plays an important role in the right ventricular systolic function.

BACKGROUND: Little is known of common normal labor hospital practices in Egypt or of their relationship to evidence-based obstetrics. This study documented facility-based practices for normal labor and delivery in Egypt for the first time by categorizing 44 practices observed in a busy obstetric teaching hospital according to the World Health Organization (WHO) Technical Working Group on Normal Birth classification of normal birth practices.

METHODS: A multidisciplinary approach combined directly observing practices that were applied to individual laboring women and their newborns, observing ward activities, interviews, and focus groups. One hundred seventy-five normal births were observed in their entirety, over 28 days and nights, by medically trained observers using an observation checklist that documented 537 variables for each woman. Mothers were interviewed postpartum, and findings were shared with practitioners for their feedback. Observed practices were categorized according the 1999 WHO classification of 59 practices for normal birth, depending on their usefulness, effectiveness, or harmfulness.

RESULTS: There was infrequent use of beneficial practices that should be encouraged and an unexpectedly high level of harmful practices that should be eliminated. Some beneficial practices were applied inappropriately, and practices of unproved benefit were also documented, some of which are potentially harmful to childbearing mothers and their babies.

CONCLUSIONS: Hospital practices for normal labor were largely not in accordance with the WHO evidence-based classification of practices for normal birth. The findings are worrying, given the increasing proportion of hospital-based births in Egypt and the country's improved but relatively high maternal and neonatal mortality rates. Obstacles to following evidence-based protocols for normal labor require examination.

PURPOSE: To evaluate the safety and efficacy of perfluorocarbon-perfused vitrectomy (PCPV) as a novel technique in obtaining a large undiluted vitreous biopsy.

DESIGN: Cross-sectional interventional study.

METHODS: Patients with undiagnosed posterior uveitis scheduled for vitreous biopsy underwent PCPV. A syringe containing 5 ml of perfluorocarbon liquid (PCL) was connected to the infusion line. Aspiration of the central and superior vitreous was initiated with simultaneous infusion of the PCL.

RESULTS: Twenty eyes of 20 patients were included in this study. The mean +/- SD amount of PCL used in each eye was 4.50 +/- 0.69 ml. The volume of vitreous sample obtained in each eye was 2.25 +/- 0.413 ml. No complications occurred.

CONCLUSIONS: PCPV is a safe and effective method for obtaining large undiluted vitreous biopsy.

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.