Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome.

BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response.     

Denervation of taste buds in the rabbit

Twenty-five rabbits were used to study the effect of glossopharyngeal nerve transection upon the number, size and cellular constitution of the taste buds. The glossopharyngeal nerve was cut on one side, the other being left undisturbed as a control. The animals were sacrificed in groups of three after 7, 10, 14, 21, and 30 days, and 2 and 4 months after the operation. Seven days after the operation the size and number of intragemmal cells were decreased in the taste buds. The taste pores with hairlets passing through them disappeared. The number of taste buds on circumvallate papillae decreased. After ten days taste buds in both types of papillae showed signs of degeneration. Fourteen days after the operation there was a marked decrease in size and number of taste buds. The circumvallate papillae now possessed no taste buds. After 21 days few taste buds were present in foliate gutters. These consisted of one or two sustentacular cells each. After 30 days there were no taste buds on foliate papillae, and thickness of the epithelium lining the gutters was decreased. Two or four months after denervation, the foliate gutters were shallow and some had become flattened. The importance of the gustatory nerve for development and maintenance of the normal status of the taste buds is discussed.     

Synthesis and reactions of some pyridazine derivatives

3,4-Diphenyl-5-cyanopyridazin-6-one 3 was prepared from the reaction of cyano-acetamide2 with benzilhydrazone in dry pyridine. A series of its derivatives was prepared. Tolyl and benzene sulphonyl derivatives6a and6b are also prepared. 3,4-Diphenyl-5-cyano-pyridazin-6-thione5 was obtained from3 by the action of P₂S₅ while 3,4-diphenyl-5-cyano-6-chloropyridazine4 was obtained from3 by the action of POCl₃. The reaction of4 with hydrazine hydrate directly afforded the pyrazolopyridazine derivative7. Compound4 also reacted with phenylhydrazine, aniline, thiophenol and anthranilic acid to yield pyridazine derivatives8, 9, 10 and11, respectively. On treatment of compound11 with acetic anhydride it cyclised to afford pyridazino pyrimidine derivatives12.     

Assessment of mitral annular velocities by Doppler tissue imaging in predicting left ventricular thrombus formation after first anterior acute myocardial infarction

IntroductionThis study was carried out in cardiology department, Zagazig University from August 2005 to December 2006. This study included 60 patients with first acute anterior myocardial infarction. These patients were 36 male (72%) and 14 female (28%).Aim of the workThe aim of this study is to determine whether early assessment of mitral annular velocities by pulsed wave tissue Doppler imaging predicts left ventricular thrombus formation after first acute anterior myocardial infarction or not.Patients and methodsPatients included in our study represented by first time anterior wall acute myocardial infarction who met the following criteria; chest pain lasting more than 30 min, ST segment elevation greater than 2 mm in two consecutive anterior electrographic leads and transient elevation of biochemical cardiac markers. Patients were excluded if they had evidence of previous anterior myocardial infarction, valvular heart disease, patients with poor Echo window and conduction abnormalities. All patients were subjected to the following: complete history taking, thorough physical examination, laboratory tests, 12-lead surface ECG, determination if the patient was received thrombolytic therapy or not and echocardiographic evaluation (M-mode, two-dimensional and DTI assessment) was performed for all patients within 24 h of arrival to CCU to evaluate LV function and to measure mitral annular velocities then two-dimensional echocardiography to determine thrombus was formed on days 7 and 30. Patients were divided into two groups: group (1); patients with LV thrombus (19 patients “31.6%”) and group (2); patients without LV thrombus (41 patients “68.4%”).ResultsThere was no significant difference between the two groups as regards age, gender, diabetes mellitus, hypertension, heart rate, peak CPK and whether patients received thrombolytic therapy or not. LVESV and LVEDV were higher in group (1) than in group (2) while EF was lower in group (1) than in group (2). As regards WMSI is higher in group (1) than in group (2). E wave velocity was higher in group (1) than in group (2), while A wave velocity was lower in group (1) than in group (2) and E/A ratio is higher in group (1) than in group (2). Deceleration time of E wave was shorter in group (1) than in group (2) and IVRT were lower in group (1) than in group (2). Em wave velocity was lower in group (1) than in group (2), Am wave velocity had no significant difference between the two groups while Em/Am ratio was lower in group (1) than in group (2) and E/Em ratio was higher in group (1) than in group (2). Sm wave velocity was lower in group (1) than in group (2). From previous data and correlation of TDE finding with other echocardiographic data, we found that systolic and diastolic functions were impaired in patients of group (1) than in group (2) but Sm velocity and WMSI had higher sensitivity and higher specificity (94.7% sensitivity, 95.1% specificity for Sm wave velocity and 94.2% sensitivity, 90.2% specificity for WMSI).ConclusionFrom our study, we can conclude that TDE can be used for estimation of systolic and diastolic functions of LV and hence identification of patients at high risk for LV thrombus formation after first time acute anterior myocardial infarction and we recommend more studies to support our results about the importance of the role of oral anticoagulant after AMI.     

Meta-analysis indicates lack of local adaptation of Schistosoma mansoni to Biomphalaria alexandrina in Egypt

In Egypt, reclaiming portions of the desert using water from the Nile has resulted in large-scale invasion of Biomphalaria alexandrina in these regions. Studies exploring the local adaptation of Schistosoma mansoni to its snail host have been carried out to predict the extension of schistosomiasis to newly reclaimed areas. A meta-analysis of the relevant reports was conducted to compare the different biological characteristics of sympatric and allopatric Schistosoma mansoni and Biomphalaria alexandrina using different experimental designs. The results showed that there were no significant differences in the biological characteristics of sympatric and allopatric populations. The experimental design of some of the studies analyzed was found to affect the total cercarial production. The distance between the origin of the parasite and that of the snail did not affect any of the biological characteristics. The results showed that there is no evidence of local adaptation between Schistosoma mansoni and Biomphalaria alexandrina; however, the parasite is adapted to its intermediate host throughout the water bodies located in Egypt. The absence of local adaptation between Schistosoma mansoni and Biomphalaria alexandrina is likely of critical importance in predicting public health risks engendered by future reclaimed agriculture projects. Indeed, these results could assist in determining the appropriate balance between the development of water resource projects and schistosomiasis control in Egypt.     

IL-10 and IL-12p40 in Egyptian patients with HCV-related chronic liver disease

Hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide with a prevalence of approximately 14% in Egypt. IL-10 is a cytokine produced by Th2 cells. It down-regulates the proinflammatory response and modulates hepatic fibrogenesis. IL-12 is produced by antigen presenting cells. It promotes Th1 cell response and has many antiviral properties. Data concerning the Th-1/Th-2 balance in chronic hepatitis C (CH-C) are rather conflicting. Using ELISA, we assessed serum IL-10 and IL-12p40 levels in 66 Egyptian patients with HCV-related liver illness (CH-C, cirrhosis, and HCC), and their relationship to disease activity. Our results showed that spontaneous IL-10 was undetectable in patients with CH-C, HCC or controls. Only 5/22 (23%) of patients with cirrhosis showed detectable levels of IL-10. IL-12p40 was elevated in the patient groups compared to controls (p= 0.01, p= 0.01, p= 0.05 in CH-C, cirrhosis and HCC, respectively). The presence of IL-12p40 was associated with HCV level of viremia and serum AST. Serum ALT level was significantly associated with the level of IL-12p40. IL-12p40 was unrelated to liver histology or fibrosis. We concluded that in the Egyptian patients an augmentation of IL-12p40 and a suppression of IL-10 are both found. Whether this pattern is related to HCV genotype 4, or to the presence of schistosomiasis would need to be further investigated.     

Vascular cell adhesion molecule-1 (VCAM-1), flow mediated dilatation (FMD) and carotid intima media thickness (IMT) in children with juvenile idiopathic arthritis: Relation to disease activity,functional status and fatigue

Background

There is risk of premature atherosclerosis in juvenile idiopathic arthritis (JIA) patients which predisposes to cardiovascular disease (CVD) in adulthood. This can be assessed by flow mediated dilatation (FMD) and carotid intima media thickness (IMT) of the arterial wall and by soluble vascular cell adhesion molecule (sVCAM-1).