Mohamed Ghoneim

Coadministration of ketoconazole to cyclosporin-treated kidney transplant recipients : a prospective randomized study

In this work, 100 living related donor kidney transplant recipients under cyclosporin (CsA) therapy were randomly distributed to two groups. Group 1 were administered ketoconazole, with group 2 serving as the control. Ketoconazole was given orally, 100 mg/day, while the dose of CsA was adjusted for a CsA whole blood trough level of 100-150 ng/ml. Patients and controls were assessed regularly in an outpatient clinic for 12 months and compared statistically for CsA dose, graft and liver functions, cholesterol, blood sugar, CsA nephrotoxicity, acute rejection episodes, chronic rejection and fungal skin infections. Statistical analysis showed a significant reduction in the CsA dose in the ketoconazole-treated group (73-76%), along with significantly lower alanine aminotransferase, aspartate aminotransferase, bilirubin, and serum creatinine values. CsA chronic nephrotoxicity and chronic rejections were also significantly lower in the ketoconazole-treated group, as was fungal skin infection (6.6 vs 63.2%). From this study, we conclude that addition of a low dose of ketoconazole to CsA-treated kidney transplant recipients not only saves costs, but may also have a favorable effect on graft function, chronic CsA nephrotoxicity, chronic rejection and fungal skin infection.

Expression of cell cycle–related molecular markers in patients treated with radical cystectomy for squamous cell carcinoma of the bladder

We evaluated the association of p53, p21, p27, cyclin E, and Ki-67 expression with pathologic features and clinical outcomes of patients with squamous cell carcinoma (SCC) of the urinary bladder. Immunohistochemical staining was performed on radical cystectomy specimens with pure SCC from 1997 to 2003. Bright field microscopy imaging coupled with advanced color detection software was used. The relationship between these markers and pathologic parameters as well as clinical outcome was assessed. The study included 152 patients (80.9% with bilharziasis), 99 males and 53 females, with a median age of 51 years (range, 36-74 years). The presenting stage was T2 or higher, and the presenting grade was grade II or lower in 93.4% of patients. Altered cyclin E expression was associated with stages (P = .02), altered p21 with grades (P = .02), and altered p27 with lymphovascular invasion (P = .01). In multivariable analyses, altered p53 expression was the only marker associated with an increased risk of disease recurrence (hazards ratio, 1.77; 95% confidence interval, 1.03-3.38, P = .04; and hazards ratio, 2.28; 95% confidence interval, 1.01-5.70, P = .05) and bladder cancer-specific mortality (hazards ratio, 1.76; 95% confidence interval, 1.06-2.99, P = .05, and hazards ratio, 2.64; 95% confidence interval, 1.05-5.54, P = .05) in all patients and in patients with T1-3N0 tumors, respectively. In conclusion, cell cycle-related molecular markers are commonly altered in SCC of the urinary bladder. Only p53 had a prognostic role in patients treated with radical cystectomy for SCC. Our findings support the need for further evaluation of molecular markers and their signaling pathways in SCC.

Effect of Colchicine on Chronic Ciclosporin Nephrotoxicity in Sprague-Dawley Rats

Thirty male Sprague-Dawley rats were given ciclosporin (Cs) orally, 15 mg/kg daily for 80 days. Fifteen served as positive controls, while the other 15 were given daily colchicine at a dose of 30 µg/kg in addition to Cs. Additional 15 rats were given olive oil only and served as negative controls. The animals were subjected every other week to laboratory assessment of serum creatinine, sodium, potassium, and Cs whole-blood trough levels; also urine samples were examined for creatinine, sodium, potassium, and protein concentrations. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. Comparing negative control versus Cs-treated and Cs-plus-colchicine-treated rats, there were no significant differences in serum creatinine, creatinine clearance, and serum and urine values of sodium and potassium as well as urinary protein/creatinine ratios. Yet histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner stripe of the outer medulla in all Cs-treated animals and in only 1 of the colchicine-treated group, but in none of the negative controls. Histological changes in other kidney zones in different animal groups were minor and not different. From this study, we may conclude that colchicine is of protective value against chronic Cs nephrotoxicity in Sprague-Dawley rats.

Effect of Treatment of Anaemia with Erythropoietin on Neuromuscular Function in Patients on Long Term Haemodialysis

To study the effect of treatment of anaemia with recombinant human erythropoietin (r-HUEPO) on neuromuscular function in patients undergoing haemodialysis for chronic renal failure, six patients were given r-HUEPO in an initial dose of 50 u/kg three times a week and their haemoglobin concentration was measured. The dose was increased by 25 u/kg every four weeks if the response was not satisfactory. In five patients anaemia had been corrected within 12 weeks of initiation of treatment. Neuromuscular function was evaluated before treatment, half way through, and after correction of anaemia by clinical examination and neurophysiological studies including motor nerve conduction velocity, distal latency, electromyography and test for neuromuscular fatigue. After correction of anaemia there was a significant increase in motor nerve conduction velocity, a decrease in the duration of motor unit action potential, and a lessening of neuromuscular fatigue. We conclude that treatment of anaemia with r-HUEPO in patients with chronic renal failure undergoing haemodialysis may improve neuromuscular function.

Primary adenocarcinoma of the urinary bladder: value of cell cycle biomarkers.

Primary adenocarcinomas of the urinary bladder are uncommon, and the molecular pathways are currently not well defined. In this study, we assessed the association between biologic markers and clinicopathologic characteristics in a cohort of 21 patients with primary urinary bladder adenocarcinoma. Immunohistochemical staining for cell cycle-specific markers, including p53, p21, p27, Ki-67, and cyclin E, were performed on sections of a tissue microarray construct. The tumors were high grade in 12 (57%) and pT2 or higher in 18 (86%); lymph nodes were involved in 6 cases (29%); and there was pathologic evidence of schistosomiasis in 14 (67%). The best prognostic combination of markers was combined alterations in p27 and Ki-67 and was associated with stage (P = .012), grade (P = .005), DNA ploidy (P = .005), and lymph node involvement (P = .04). Stage, lymph node involvement, combined alterations of p27 and Ki-67, and combined alterations of all 5 biomarkers were associated with increased probability of disease recurrence and cancer-specific mortality (P < .05).

Schistosoma mansoni nephropathy in Syrian golden hamsters : effect of dose and duration of infection

In this work, 180 golden hamsters were infected with Schistosoma mansoni and 30 hamsters matched for age and sex served as controls. According to the number of injected cercariae, infected hamsters were divided into six main groups (20, 50, 100, 150, 200 and 250 cercariae). Each group was divided into five subgroups, according to the duration of infection after which animals were sacrificed (4, 6, 8, 12 and 24 weeks). Control and infected hamsters were subjected to laboratory evaluations (serum creatinine, blood urea nitrogen, cholesterol, albumin, total protein and urine protein concentration) and histopathologic examinations of kidney and liver tissues. A significant proteinuria, hypoalbuminemia and hypercholesterolemia was observed in schistosome infected (50 cercariae or more) but not in the controls and the group infected with 20 cercariae. There was significant correlation between these changes and duration of infection and the number of adult worm recovered from the mesenteric circulation at the end of the experiments. Histopathologic evaluation showed appearance of the circulating schistosome antigens, circulating anodic antigen (CAA) and circulating cathodic antigen (CCA), and of IgG glomerular deposits by the 6th week following infection; mesangial hypercellularity appeared early after infection (6-8 weeks), renal amyloid deposition appeared later (8-12 weeks). Egg antigens were not detected in the renal glomeruli. There was a significant correlation between the pathologic changes and duration of infection and the number of recovered adult worms from the mesenteric circulation. No histopathologic lesions were detected in controls and the group injected with 20 cercariae. A significant correlation was found between hepatic periportal fibrosis, amyloidosis and immune complex, deposition in the renal glomeruli. Hamsters did not tolerate infection with 150 cercariae or more for more than 12 weeks, and 20 cercariae caused no detectable glomerular disease. From this study, we concluded that S. mansoni infection causes nephropathy in the Syrian golden hamster. The disease became biochemically and histopathologically manifest by the 6th week following infection. Both immune complex deposition and renal amyloidosis stand as major pathogenic mechanisms. CAA and CCA are the major responsible antigens. Hepatic disease has an impact on the kidney lesion. 50 cercariae are the best dose to produce disease without early death of the animal. There is a significant correlation between the kidney disease and the duration and the load of S. mansoni infection.

Progressive Encryption and Controlled Access Scheme for JPEG 2000 Encoded Images

In this paper we propose a progressive encryption and controlled access scheme for JPEG 2000 encoded images. Our scheme applies SNOW 2 stream cipher to JPEG 2000 codestreams in a way that preserves most of the inherent flexibility of JPEG 2000 encoded images and enables untrusted intermediate network transcoders to downstream an encrypted JPEG 2000 image without access to decryption keys. Our scheme can also control access to various image resolutions or quality layers, by granting users different levels of access, using different decryption keys. Our scheme preservers most of the inherent flexibility, scalability, and transcodability of encrypted JPEG 2000 images and also preserves end-to-end security.

Sirolimus for visceral and cutaneous Kaposi's sarcoma in a renal-transplant recipient

The incidence of Kaposis sarcoma among recipients of solid organs is about 500 times the rate in the general population, suggesting a role for immunosuppression in its development. On the basis of these findings, we investigated the impact of sirolimus on cutaneous and disseminated visceral Kaposis sarcoma in a renal-transplant recipient. The introduction of sirolimus in this patient allowed complete regression of Kaposis sarcoma (cutaneous and visceral) with preservation of excellent renal function. Meanwhile, in view of the available observational reports, we think that sirolimus should be included in the standard treatment for Kaposis sarcoma after transplantation, to permit remission of the sarcoma (both cutaneous and visceral) while preserving the renal function.

Prospective randomized study of azathioprine vs cyclosporine based therapy in primary haplo-identical living-donor kidney transplantation: 20-year experience.

BackgroundThe achievements in short-term graft survival since the introduction of cyclosporine (CsA) have not been matched by improvements in long-term graft function. Chronic allograft nephropathy (CAN) remains the second most common cause of graft attrition over time, after patient mortality. We aimed to evaluate the long-term results of azathioprine vs CsA in live-donor kidney transplantation in a prospective randomized study.MethodsWe studied 475 renal transplant recipients who had had transplantations performed at the Urology and Nephrology Center, Mansoura University, before 1988 and who had received a primary immunosuppressive protocol consisting of either steroid and azathioprine (steroid/Aza; group 1, 300 patients) or steroid and CsA (steroid/CsA; group 2, 175 patients). Only adult primary renal transplant recipients aged between 18 and 60 years and with one haplotype HLA mismatch were included. All patients received kidneys from living-related donors, with previous donor nonspecific blood transfusions. The study was based on the long-term follow-up data of these renal transplant recipients. Comparative analyses included patient and graft survival rates, condition at last follow up, rejection (acute and chronic), and graft function (serum creatinine and creatinine clearance).ResultsThe overall frequency of acute rejection episodes was not significantly different between the two groups. Graft survival rates were: group 1 vs group 2, 69% vs 58% at 5 years, and 52% vs 36% at 10 years, but at 20 years, graft survival rates had declined to 26% and 24%. No significant differences were encountered between the two groups regarding post-transplant malignancies, diabetes mellitus, hepatic impairment, or serious bacterial infections.ConclusionsFrom this study we can conclude that the long-term result of historical conventional therapy (steroid/Aza) without induction therapy is effective for living-donor kidney transplants. In spite of the comparable graft function for the two groups, the steroid/CsA group experienced more hypertension, as well as many adverse reactions to CsA. Nowadays, since the introduction of induction therapy and the utilization of newer maintenance immunosuppressive agents – such as mycophenolate mofetil (MMF) and rapamycin – it is possible to achieve an excellent calcineurin inhibitors (CNI)-free regimen.

Effect of Colchicine on Schistosoma-lnduced Renal Amyloidosis in Syrian Golden Hamsters

Seventy Syrian golden hamsters were infected with Schistosoma haematobium, and 10 uninfected hamsters served as negative controls. Of the schistosome-infected hamsters, 10 served as positive controls (infected but untreated) and the rest (60 hamsters) received treatment. In 30 hamsters treatment was given 9 weeks after infection (before the appearance of renal amyloidosis) and in the other 30 it was given after the appearance of amyloid deposits, 15 weeks after infection. Each treatment group was subdivided into 3 groups (10 hamsters each) in which treatment was either anti-schistosomal alone, combined anti-schistosomal and colchicine, or colchicine alone. Eighteen weeks after infection half of the animals in each group were sacrificed, while the rest were sacrificed 24 weeks after infection. Kidney specimens were evaluated semiquantitatively for renal amyloid deposits. Significant reductions in renal amyloid deposits and proteinuria were observed when combined treatment was given. This was nearly complete with early treatment and only partial when treatment was given late. When colchicine was given alone, a partial but significant reduction in proteinuria with no recognizable effect on renal amyloid deposits was observed. We conclude that colchicine is effective for the prevention and cure of schistosome-related renal amyloidosis in golden hamsters.