Mahmoud Abd El Hafez M. Adam

The effects of the protein kinase A (PKA) inhibitor H-89 on ATP-sensitive K+ (KATP) and inward rectifier K+ (Kir) currents were examined in rabbit coronary arterial smooth muscle cells using the patch clamp technique. The H-89, in a dose-dependent manner, inhibited KATP and Kir currents with apparent Kd values of 1.19+/-0.18 and 3.78+/-0.37 microM, respectively. H-85, which is considered as an inactive form of H-89, inhibited KATP and Kir currents, similar to the result of H-89. KATP and Kir currents were not affected by either Rp-8-CPT-cAMPs, which is a membrane-permeable selective PKA inhibitor, or KT 5720, which is also known as a PKA inhibitor. Also, these two drugs did not significantly alter the effects of H-89 on the KATP and Kir currents. These results suggest that H-89 directly inhibits the KATP and Kir currents of rabbit coronary arterial smooth muscle cells independently of PKA inhibition.

Cardiovascular disease and the development of coronary artery atherosclerosis play a pivotal role in increasing mortality in patients with diabetes. The aim of the present study was to determine the presence of subclinical atherosclerosis (measured as carotid intima-media thickness [cIMT] and to study possible associated risk factors in adolescents with type 1 diabetes. Forty type 1 diabetic subjects, aged 11-30 years, with duration of diabetes 3-25 years and 40 normal healthy controls, were included. Blood pressure (BP) measurement, as well as screening for diabetic complications, was performed. Lipid profile, albumin/creatinine ratio, renal functions and glycosylated hemoglobin (HB A(1)c) were assayed. Carotid intima-media thickness (cIMT) was measured using ultrasound. The mean aggregate cIMT was higher in diabetics than controls (0.6 mm 00 +/- 0.1 vs. 0.4 mm +/- 0.1, p = 0.000). Moreover, it was higher in patients with positive family history of type 2 diabetes than in those with negative family history (mean 0.7 mm +/- 0.1 vs. 0.6 mm +/- 0.1, p = 0.018). cIMT was found to positively correlate with: age in both diabetics and controls (r = 0.76, p = 0.000, r = 0.74, p = 0.000 respectively), body mass index (BMI) in diabetics but not controls (r = 0.82, p = 0.000, r = 0.30, p = 0.06 respectively). In diabetics, mean aggregate cIMT positively correlated with duration of diabetes (r = 0.66, p = 0.000), systolic blood pressure (r = 0.82, p = 0.000), diastolic BP (r = 0.83, p = 0.000), as well as HB A1c (r = 0.40, p = 0.004) and correlated negatively with high density lipoprotein -cholesterol (HDL-C) (r = -0.88, p = 0.000). As cardiovascular morbidity is high in diabetes, non-invasive methods for monitoring vascular changes as cIMT might be useful in clinical practice for early diagnosis of subclinical atherosclerosis, which can allow for strategies designed to reduce the cardiovascular event rate in those patients.

BACKGROUND: In Gaucher disease, the infiltration of the bone marrow by glucocerebroside-laden macrophages (Gaucher cells) triggers a diverse pattern of skeletal disease that results in crippling complications. Reliable ascertainment of the severity and pattern of skeletal disease is essential to determine disease status and the response to enzyme replacement therapy (ERT). Although there is ample documentation of reversal of haematological and visceral disease by ERT, there is a paucity of data on skeletal response to ERT in children.

AIM: To delineate the pattern of bone disease in children with Gaucher disease in Egypt and to evaluate its response to ERT.

METHOD: Twenty-two children with Gaucher disease were treated with ERT. Phenotyping by clinical, laboratory and radiological criteria was performed at baseline and following 11.2 +/- 4 months of ERT. Genotyping for glucocerebrosidase (GBA) mutations was performed by gene sequencing, and genotype-phenotype correlations were performed.Results. Two-thirds of the patients were from consanguineous pedigrees and 14/22 patients were homozygous or compound heterozygous for L444P and D409H mutations. Bone involvement was detected by plain radiology in 11 children (50%) and in 16 (73%) by magnetic resonance imaging (MRI). There was no correlation of severity of bone involvement and GBA genotype. ERT ameliorated bone disease: 10 of the 11 children with abnormal radiographic findings at baseline showed improvement in skeletal lesions; while 9/16 showed improvement of marrow disease by MRI. Radiographic sensitivity and specificity were 62% and 82% compared to MRI for detection of bone involvement in this patient population. At baseline, bone pain was present in 5 patients and ERT resulted in complete symptomatic remission in all of them. ERT was associated with significant improvement in growth parameters and amelioration of haematological and visceral involvement.

CONCLUSION: Symptomatic and radiological skeletal disease is common in children with Gaucher disease in Egypt. MRI is the most accurate technique for detecting early skeletal involvement. There was no correlation between severity of skeletal involvement and GBA genotype. ERT was effective in ameliorating radiological manifestations of skeletal disease and achieving complete remission of bone pain.

We used proteomics to detect regional differences in protein expression levels from mitochondrial fractions of control, ischemia-reperfusion (IR), and ischemic preconditioned (IPC) rabbit hearts. Using 2-DE, we identified 25 mitochondrial proteins that were differentially expressed in the IR heart compared with the control and IPC hearts. For three of the spots, the expression patterns were confirmed by Western blotting analysis. These proteins included 3-hydroxybutyrate dehydrogenase, prohibitin, 2-oxoglutarate dehydrogenase, adenosine triphosphate synthases, the reduced form of nicotinamide adenine dinucleotide (NADH) oxidoreductase, translation elongation factor, actin alpha, malate dehydrogenase, NADH dehydrogenase, pyruvate dehydrogenase and the voltage-dependent anion channel. Interestingly, most of these proteins are associated with the mitochondrial respiratory chain and energy metabolism. The successful use of multiple techniques, including 2-DE, MALDI-TOF-MS and Western blotting analysis demonstrates that proteomic analysis provides appropriate means for identifying cardiac markers for detection of ischemia-induced cardiac injury.

AIM: To study the safety and efficacy of hepatitis A vaccine (HAV) in children with chronic liver disease of various etiologies.

METHODS: Eleven children with chronic liver disease and thirteen age- and sex-matched controls negative for HAV antibodies were vaccinated against hepatitis A after they gave their informed consent. Children with uncontrolled coagulopathy or signs of hepatic decompensation were excluded. The vaccine (Havrix: 720 ELISA units in 0.5 mL, from GlaxoSmithKline Biologicals) was given intramuscularly in the deltoid in 2 doses 6 mo apart. Children were tested for HAV antibodies one and six months after the 1st dose and one month after the 2nd dose. Total serum bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined immediately before and after one month of the 1st dose of the vaccine.

RESULTS: Only 7 out of the 11 patients were positive for HAV antibodies after the 1st dose of the vaccine, as compared to 100% of the controls. One month after the 2nd dose, all patients tested were positive for HAV antibodies. No deterioration in liver functions of patients was noted after vaccination. No adverse events, immediate or late, were reported by the mothers after each dose of the vaccine.

CONCLUSION: Hepatitis A vaccine is both safe and effective in this small studied group of children with chronic liver disease. Given the high seroconversion rate, post-vaccination testing for HAV antibodies is not needed.

AIM: To study the safety and efficacy of hepatitis A vaccine (HAV) in children with chronic liver disease of various etiologies.

METHODS: Eleven children with chronic liver disease and thirteen age- and sex-matched controls negative for HAV antibodies were vaccinated against hepatitis A after they gave their informed consent. Children with uncontrolled coagulopathy or signs of hepatic decompensation were excluded. The vaccine (Havrix: 720 ELISA units in 0.5 mL, from GlaxoSmithKline Biologicals) was given intramuscularly in the deltoid in 2 doses 6 mo apart. Children were tested for HAV antibodies one and six months after the 1st dose and one month after the 2nd dose. Total serum bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined immediately before and after one month of the 1st dose of the vaccine.

RESULTS: Only 7 out of the 11 patients were positive for HAV antibodies after the 1st dose of the vaccine, as compared to 100% of the controls. One month after the 2nd dose, all patients tested were positive for HAV antibodies. No deterioration in liver functions of patients was noted after vaccination. No adverse events, immediate or late, were reported by the mothers after each dose of the vaccine.

CONCLUSION: Hepatitis A vaccine is both safe and effective in this small studied group of children with chronic liver disease. Given the high seroconversion rate, post-vaccination testing for HAV antibodies is not needed.

AIM: To study the safety and efficacy of hepatitis A vaccine (HAV) in children with chronic liver disease of various etiologies.

METHODS: Eleven children with chronic liver disease and thirteen age- and sex-matched controls negative for HAV antibodies were vaccinated against hepatitis A after they gave their informed consent. Children with uncontrolled coagulopathy or signs of hepatic decompensation were excluded. The vaccine (Havrix: 720 ELISA units in 0.5 mL, from GlaxoSmithKline Biologicals) was given intramuscularly in the deltoid in 2 doses 6 mo apart. Children were tested for HAV antibodies one and six months after the 1st dose and one month after the 2nd dose. Total serum bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined immediately before and after one month of the 1st dose of the vaccine.

RESULTS: Only 7 out of the 11 patients were positive for HAV antibodies after the 1st dose of the vaccine, as compared to 100% of the controls. One month after the 2nd dose, all patients tested were positive for HAV antibodies. No deterioration in liver functions of patients was noted after vaccination. No adverse events, immediate or late, were reported by the mothers after each dose of the vaccine.

CONCLUSION: Hepatitis A vaccine is both safe and effective in this small studied group of children with chronic liver disease. Given the high seroconversion rate, post-vaccination testing for HAV antibodies is not needed.

AIM: To study the safety and efficacy of hepatitis A vaccine (HAV) in children with chronic liver disease of various etiologies.

METHODS: Eleven children with chronic liver disease and thirteen age- and sex-matched controls negative for HAV antibodies were vaccinated against hepatitis A after they gave their informed consent. Children with uncontrolled coagulopathy or signs of hepatic decompensation were excluded. The vaccine (Havrix: 720 ELISA units in 0.5 mL, from GlaxoSmithKline Biologicals) was given intramuscularly in the deltoid in 2 doses 6 mo apart. Children were tested for HAV antibodies one and six months after the 1st dose and one month after the 2nd dose. Total serum bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined immediately before and after one month of the 1st dose of the vaccine.

RESULTS: Only 7 out of the 11 patients were positive for HAV antibodies after the 1st dose of the vaccine, as compared to 100% of the controls. One month after the 2nd dose, all patients tested were positive for HAV antibodies. No deterioration in liver functions of patients was noted after vaccination. No adverse events, immediate or late, were reported by the mothers after each dose of the vaccine.

CONCLUSION: Hepatitis A vaccine is both safe and effective in this small studied group of children with chronic liver disease. Given the high seroconversion rate, post-vaccination testing for HAV antibodies is not needed.

AIM: To study the safety and efficacy of hepatitis A vaccine (HAV) in children with chronic liver disease of various etiologies.

METHODS: Eleven children with chronic liver disease and thirteen age- and sex-matched controls negative for HAV antibodies were vaccinated against hepatitis A after they gave their informed consent. Children with uncontrolled coagulopathy or signs of hepatic decompensation were excluded. The vaccine (Havrix: 720 ELISA units in 0.5 mL, from GlaxoSmithKline Biologicals) was given intramuscularly in the deltoid in 2 doses 6 mo apart. Children were tested for HAV antibodies one and six months after the 1st dose and one month after the 2nd dose. Total serum bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined immediately before and after one month of the 1st dose of the vaccine.

RESULTS: Only 7 out of the 11 patients were positive for HAV antibodies after the 1st dose of the vaccine, as compared to 100% of the controls. One month after the 2nd dose, all patients tested were positive for HAV antibodies. No deterioration in liver functions of patients was noted after vaccination. No adverse events, immediate or late, were reported by the mothers after each dose of the vaccine.

CONCLUSION: Hepatitis A vaccine is both safe and effective in this small studied group of children with chronic liver disease. Given the high seroconversion rate, post-vaccination testing for HAV antibodies is not needed.

BACKGROUND: Leukemia is a type of cancer that starts in the bone marrow. The anticancer drugs used in the treatment of patients suffering from the disease have many side effects due to their toxicity. This fact has prompted researchers to search for other agents instead of, or in combination with, these anticancer drugs. Differentiating agents (DAs) including Na-Butyrate (NaBu), trans-retinoic acid (TRA), dibutyryl- cAMP (Bu-cAMP) and many others have been used for this purpose.

MATERIALS AND METHODS: In this investigation, we studied 120 patients with acute myeloid leukemia (AML),presenting to the Oncology Institute of Tanta, Egypt. We studied the effect of some differentiating agents (DAs)mainly Na-Butyrate (Na-Bu., 1mM), trans-retinoic acid (TRA, l micro M) and dibutyryl-cAMP (Bu-cAMP, lmM) on the morphology of leukemia cells propagated ex-vivo for 3 and 6 days. We also studied the level of interferon- gamma and its release in the conditioned media of the leukemic cells compared to normal leukocytes.

RESULTS: The results revealed that DAs enhanced the conversion of the immature granulocytes into mature ones clearly at 6 days of treatment when we used the agents in combination. The results also showed that statistically significant elevation (p<0.001) of interferon- gamma level was found to be in the conditioned media of the treated leukemic cells (3 and 6 days) using the previously mentioned agents alone or in combination; that could reach almost the level in the cultured media of normal leukocytes.

CONCLUSION: In conclusion, this work could highlight the possibility of using DAs as a novel complementary therapy in the management of acute myeloid leukemia (AML) via the activation of the immune surveillance of patients suffering from AML through raising the interferon- gamma level. Further work is recommended to use DAs in clinical trials with and without conventional anticancer drugs for the management of patient with AML.

PURPOSE: To characterize, and evaluate the surgical management of, patients with unilateral deficiency of depression in adduction, suggesting superior oblique muscle underaction, without significant ipsilateral inferior oblique muscle overaction.

METHODS: Such patients were identified who also had received either ipsilateral inferior oblique (IO) muscle weakening or contralateral inferior rectus muscle recession. Their histories, motility patterns, intraoperative findings, types of strabismus surgery, and postoperative results were analyzed.

RESULTS: Twelve patients were identified with unilateral deficiency of depression in adduction, with no or minimal ipsilateral IO muscle overaction. Three of these patients (25%) had previously had surgery for Brown syndrome. Four (33%) had prior orbital floor trauma. On exaggerated forced duction testing recorded for nine patients, a tight IO muscle was recorded in 78%, with no laxity of the superior oblique tendon. Four patients (33%) underwent contralateral inferior rectus muscle recession, but in all four the deficiency of depression in adduction recurred. The other eight (67%) had an IO muscle weakening procedure and achieved overall improvement of ocular alignment. Nine subsequent patients with a similar pattern of misalignment were each managed with an IO weakening procedure, with good results.

CONCLUSIONS: This motility pattern, which we are calling an "inverted Brown pattern," is caused by a tight or inelastic IO muscle. In such cases, IO muscle weakening yields better results than contralateral inferior rectus muscle recession, even though there is no significant IO muscle overaction preoperatively.

AIMS: QRS prolongation is a negative prognostic factor for the development of ventricular arrhythmia after repair of tetralogy of Fallot (TOF). In this MRI study, we performed a multivariate analysis to determine the influence of volumetric and functional parameters as well as time factors on QRS duration.

METHODS AND RESULTS: Sixty-seven patients after surgical repair of TOF were studied using a 1.5T MRI. Measurement of the ventricles was performed with a multislice-multiphase sequence. Left and right ventricular volumes, ejection fractions (EF) and myocardial masses were determined. Pulmonary regurgitant fraction (PRF) was quantified by velocity encoded flow measurement in the main pulmonary artery. Maximum QRS duration was taken from a 12-channel ECG. Mean maximum QRS duration was 132 ms (+/- 29 ms). Mean PRF was 29.2% (+/- 13.4%). QRS duration correlated significantly with PRF (r = 0.49; p < 0.01; n = 54) and with right ventricular enddiastolic volume index (RVEDVI) (r = 0.29; p < 0.05; n = 67). Multivariate analysis revealed that the combination of PRF, postoperative period, age at surgical repair, and left ventricular (LV) enddiastolic volume are correlated with QRS prolongation.

CONCLUSION: In patients after repair of TOF, pulmonary regurgitation is related to QRS prolongation. Furthermore, even LV size plays a role in the enlargement of the QRS complex.

Diamidines 10a-g and 18a,b were obtained from dinitriles 9a-g and 15a,b by treatment with lithium trimethylsilylamide or upon hydrogenation of bis-O-acetoxyamidoximes. Dinitriles 9a-g were prepared via Suzuki reactions between arylboronic acids and arylnitriles. Potential prodrugs 12a-f and 17 were prepared via methylation of the diamidoximes 11a-f and 16a. Significant DNA affinities for rigid-rod molecules were observed. Compounds 10a, 10b, 10d, 18a, and 18b show IC50 values of 5 nM or less against Trypanosoma brucei rhodesiense (T. b. r.) and 10a, 10b, 10e, 18a, and 18b gave similar ones against Plasmodium falciparum (P.f.). The dications, 10a, 10d, 10f, and 10g are more active than furamidine in vivo. The prodrugs are only moderately effective on oral administration. Mouse liver microsome bioconversion of the methamidoxime prodrugs is significantly reduced from that of pafuramidine and suggests that the in vivo efficacy of these prodrugs is, in part, due to poor bioconversion.

Forty nine stool specimens collected from severe diarrheic patients. Eight were suffering from Hodgkin's lymphoma, and the rest were suffering from acute lymph plastic leukaemia. All were examined microscopically for protozoan parasites mainly, Cryptosporidium parvum and Cyclospora cayetanensis. Of the patients, 34 (69.4%) were positive and 15 (30.6%) were negative by both microscopy and nested PCR. An additional 12 (24.5%) who were negative by microscopy were positive by nested PCR. Stool examination revealed 16 cases with C. parvum, and 6 with C. cayetanensis, and 3 cases showed mixed infection. The results were compared with the established nested PCR assay to detect DNA directly from stool specimens. The patients <3 years old more affected by Cryptosporidium infection, unlike Cyclospora sp. Infection was in older age groups, which reflected the modes of parasite' transmission.. Diarrheal illness was stronger for Cyclospora than for Cryptosporidium. After the extraction of DNA from stool, a 402-bp fragment of C. parvum, and 602 bp fragment of C. cayetanensis was amplified. The amplified products, 194-bp DNA fragment for C. parvum, and 306 bp DNA fragment of C. cayetanensis were used for the second run. This study indicated that primers were specific for DNA of C. parvum and C. cayetanensis. PCR detected a total of 22 (44.9%) positives for C. parvum infection (6 negative by AF stool examination), and 12 (24.5%) positives for C. cavetanensis. Infection (6 negative by AF stool examination), 7 (14.3%) showed mixed infection (4 negative by AF stool examination), all microscopic negative specimens were positive by successive stool examination. Microscopy exhibited sensitivity of 72.7% for C. parvum, 50% for C. cayetanensis and 100% specificity for both parasites compared to 100% sensitivity and specificity with PCR. So, PCR is more sensitive and easier to interpret but required more hands-on time to perform and is more expensive. However, PCR batch analysis reduces the cost considerably.

PURPOSE: We sought to evaluate the sensory status of patients with acquired esotropia who were able to re-establish stable alignment by optical correction and surgery and to determine the possible predictors of the different sensory outcomes.

METHODS: Thirty-four successfully aligned esotropic patients were included in the study. Preoperative evaluation comprised history taking, measurement of visual acuity, evaluation of the sensory status (using the Worth 4-Dot test, and the Titmus Stereo test), measurement of ocular deviation, cycloplegic refraction, and fundus examination. All patients underwent successful surgical alignment to within 10 prism diopters (Delta) of orthotropia. At each postoperative follow-up visit, the sensory functions and ocular alignment were assessed. Statistical analysis of the results was performed.

RESULTS: Among the 34 patients included in the study, 62% achieved fusion, 17% had diplopia, 15% had suppression, and 6% had a variable response to the Worth 4-Dot test at 6 months after surgery. Stereopsis was achieved in 32% as determined by the Titmus Stereo test. Statistical analysis revealed a significant relationship between the sensory status and the duration of strabismus (P=.00002), the age at surgery (P=.00289), and postoperative ocular alignment (P=.02211).

CONCLUSION: Early surgical and optical ocular alignment of strabismic patients is advisable to achieve fusion and stereopsis.

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The electrical properties measurements were carried out for the complex (CH2)2(NH3)2Mn1-xCdxCl4, 0.0 ≤ x ≤ 1.0 at different temperatures as a function of frequency (100-1000 kHz). Four transition points were obtained for x = 0.5, which are assigned as thermochromism, interlayer exchange interaction, order-disorder and chain melting. The presence of more than one straight line in the conductivity data clarifies the presence of more than one conduction mechanism, and the calculated values of the activation energy indicate the semiconducting characteristics of the investigated complexes. The values of the calculated relaxation time indicate its dependence on Cd content as well as the heating temperature. The expected critical concentration at x = 0.5 agree well with the percolation theory of Mont-Carlo group. The IR spectra indicate that the force constant of the bonds and the atomic mass vibration are affected by Cd content. © 2005 Elsevier B.V. All rights reserved.

The electrical conductivity of a range of ordinary Portland cement based mortars was studied over a period of 6h hydration. The influence of water/cement (w/c) ratio (0.20, 0.25 , up to 0.40), thermal cycling curing temperature (20, 30 and 40°C ), and the pozzolanic additions [35% fly ash, 35% slag and (35% fly ash+ 35% slag) to the OPC separately] on conductivity was investigated, and the activation energy E g established for conduction processes. E g was found to be system specific and was in the range -0.12 up to -0.212 eV at w/c = 0.20. Results indicate that the changes in the electrical conductivity and the activation energy of each system mainly depend on the microstructural changes, occurring during the hydration mechanism. These changes are not constant with the curing time and the w/c ratios. The proper consideration in the change of the pore microstructure leads to the optimization of the finer pores microstructure which occurs at the w/c ratios 0.30 and 0.35 in all various cementitious systems. Those ratios are considered to be the optimum ratios for reducing the porosity.