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Biomedical subjects

M Ghoneim

Publications and source records attributed to M Ghoneim.

At least 19 recordsLinked to original sources

Assay of terfenadine in pharmaceutical formulation and human plasma by adsorptive stripping voltammetry.

The controlled adsorptive accumulation of Zn(II)-terfenadine complex (1:1) onto a hanging mercury drop electrode (HMDE) provides the basis for determination of the antihistamine drug terfenadine by differential pulse cathodic adsorptive stripping voltammetry. The adsorbed Zn(II)-terfenadine complex (1:1) at the HMDE developed a stripping voltammetry peak at more negative potential than that of the free Zn(II) ions. The peak current was used for the determination of terfenadine in pharmaceutical formulation and human plasma in 0.1 mol l(-1) sodium perchlorate solution under the optimized conditions (E(acc), -0.5 V; t(acc) 360 s; scan rate, 5 mV s(-1) and pulse height 100 mV). The developed peak current (i(p)) showed a linear dependence with terfenadine concentration within the range of 6 x 10(-8) - 9 x 10(-7) mol l(-1). The recoveries were found 98.97-99.35%, 99.72-99.02% and 100.58-101.08% with the R.S.D. 0.16-0.27%, 0.25-0.82% and 0.44-1.14% in authentic form, pharmaceutical formulations and human plasma, respectively. The detection limits were 0.4505 and 0.6115 ng ml(-1) terfenadine in pharmaceutical formulations and human plasma, respectively.

Chemistry, Pharmaceutical↗

Cathodic adsorptive stripping square-wave voltammetry of the anti-inflammatory drug meloxicam.

The adsorptive behavior of the anti-inflammatory drug meloxicam was studied by cyclic, differentia-pulse and square-wave voltammetry on a hanging mercury drop electrode (HMDE). The drug was accumulated at HMDE and a well-defined stripping peak current was obtained at -1.42 V vs. Ag/AgCl (saturated KCl) electrode in acetate buffer solution (pH 5.0). A voltammetric procedure was developed for the determination of meloxicam using square-wave cathodic adsorptive stripping voltammetry (SW-CASV). The optimum working conditions for the determination of the drug were established. The analysis of meloxicam in human plasma was carried out satisfactorily.

Anti-Inflammatory Agents, Non-Steroidal↗

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 microg/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.

Animals↗

Schistosomal-specific nephropathy in Syrian golden hamsters: treatment by induction of antigen excess.

One hundred and twenty Syrian golden hamsters were infected with Schistosoma mansoni cercariae and 20 served as negative controls (group I). Of the S. mansoni-infected hamsters, 20 served as positive controls (group II) and 100 hamsters were treated for 12 weeks post-infection by loading with S. mansoni adult worm antigen. Animals were divided into groups according to the dose of adult worm antigen injected: group III (5-fold increase in circulating antigen concentration), group IV (10-fold increase), group V (20-fold increase), group VI (40-fold increase), and group VII (80-fold increase). Each of the groups was subdivided into four groups (sacrificed at 1, 2, 4 or 7 days after initiation of antigen loading or the corresponding time points in the case of the control groups). At sacrifice, blood and urine were obtained for laboratory assessment (serum creatinine, protein, albumin, cholesterol and urinary proteins). Kidney, liver and spleen tissue specimens were obtained for light, immunofluorescent and electron microscopic examinations. At sacrifice, significant proteinuria, hypoalbuminaemia and hypercholesterolaemia were observed in S. mansoni-infected hamsters when compared with negative control animals. Histopathologic assessment showed changes compatible with those previously reported, mainly immune complex glomerular deposits, mesangial proliferation and renal amyloid deposits. Significant laboratory improvement was observed in animals treated with antigen loading, especially those treated with 80-fold antigen excess and sacrificed at 7 days postinitiation of treatment. Histopathologic evaluation showed significantly less immune complex glomerular deposits, less mesangial hyperplasia, and less amyloid deposits in hamsters treated with antigen loading. It is concluded that induction of antigen excess by antigen loading induces biochemical and histopathologic regression of schistosomal-specific nephropathy in S. mansoni-infected Syrian golden hamsters.

Animals↗

Study of morphologic risk factors in graft biopsies from patients with living related donor kidney transplants.

In this work, 205 graft biopsies obtained from 161 living related donor kidney transplant recipients were blindly reevaluated by our nephropathologist, and individual lesions were evaluated semiquantitatively. Glomerular lesions included capillary thrombosis, cellular infiltrate, mesangial matrix thickening, glomerulonephritis and the presence of glomerular crescents. Tubulointerstitial lesions included tubular necrosis, tubulitis, tubular atrophy, interstitial hemorrhage, interstitial inflammatory cellular infiltrate and infarction. Vascular lesions included endovasculitis, arteriolar wall fibrinoid necrosis and intimal fibrosis. Graft outcome was assessed by looking for the changes in serum creatinine at 3 months postbiopsy and regularly every 3 months until 36 months thereafter. Other variables were considered including patient age, timing of biopsy posttransplantation, and type of immune suppression. Statistical analyses were performed to study the impact of each individual lesion on graft outcome as judged by changes in serum creatinine. Furthermore, models were constructed for short- and long-term graft outcome. Arteriolar wall fibrinoid necrosis, tubular necrosis, glomerular capillary thrombosis and increased mesangial matrix thickness were the most serious lesions affecting graft outcome.

Adolescent↗

Study of neuromyopathy in amyloid kidney transplant patients.

Neuromuscular status of amyloid and control groups of kidney transplant recipients was assessed through complete neurological examination, assay for serum levels of muscle enzymes (CPK and LDH), electromyography and nerve conduction velocity studies. Neuromyopathic findings were detected in both groups but without severe disabling clinical manifestations. These findings were more prominent in the amyloid group, evidenced by a more significant increase in polyphasicity detected by electromyography and longer prolongation of terminal latency measured in the median nerve. From this study, we concluded that amyloid kidney transplant recipients are more prone to neuromyopathy than the general kidney transplant population, which is mostly due to the amyloidosis itself and/or the colchicine therapy.

Amyloidosis↗

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.

Adult↗

Effect of colchicine on schistosoma-induced 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.

Amyloidosis↗

Ileocecal valve reconstruction during continent urinary diversion.

During construction of an ileocecal reservoir, such as the Mainz or Indiana pouch, the ileocecal valve is lost. Subsequently, the intestinal transit time is shortened and malabsorption as well as diarrhea may result. Patients having undergone previous bowel resection as well as children with myelomeningocele who often already have frequent defecations will be heavily affected by the loss of the ileocecal valve. We have functionally reconstructed the ileocecal valve by embedding ileum into the ascending colon via a submucosal tunnel in analogy to the technique used when creating the continence mechanism during the Mainz pouch procedure using the appendix. Experimental results in 15 dogs demonstrated that the surgically reconstructed valve genuinely mimics the physiological function of the authentic valve and confirmed a marked transit time prolongation without evidence of obstruction. Our first clinical experience in 12 patients using this operative technique is promising. Equally, the morphological appearance of the newly created valve closely resembles the genuine ileocecal valve during barium enema as well as endoscopic investigations.

Adolescent↗

Study of live donor kidney transplantation outcome in recipients with renal amyloidosis.

We studied the results of renal transplantation in 16 patients with renal amyloidosis and in 46 controls with primary glomerulonephritis. Amyloidosis was primary in five and secondary to familial Mediterranean fever (FMF) in 11. All patients received live related donor kidneys and the majority had one-haplotype HLA match. One- and 5-year graft and patient survival rates were comparable in both groups. Moreover, the frequency of acute rejection episodes and the mean serum creatinine values were not significantly different between members of the two groups. Significant gastrointestinal symptoms in the form of nausea, vomiting, abdominal pains, and diarrhoea occurred in seven of the patients with amyloidosis (43.7%) and in only one of the controls (2%) (P = 0.001). All seven recipients with amyloidosis who developed the gastrointestinal manifestations were receiving cyclosporin and six had FMF. Maintenance colchicine treatment prevented recurrence of FMF symptoms. In one patient discontinuation of colchicine was followed by recurrence of FMF symptoms. Recurrence of renal amyloidosis was not observed in five patients subjected to Trucut graft biopsies 1, 2, 3, 18 and 72 months post-transplantation. It is concluded that live-related donor kidney transplantation is a safe procedure in patients with amyloidosis and follows a course similar to glomerulonephritis patients.

Adult↗

Serum and endometrial copper, zinc, iron and cobalt with inert and copper-containing IUCDs.

Serum and endometrial copper (Cu), zinc (Zn), iron (Fe) and serum cobalt (Co) were measured in the mid-follicular and mid-luteal phases of the menstrual cycles in 30 Lippes loops users, 30 CuT-200 IUCD users and 24 matched controls by atomic absorption spectrophotometry. In the control group, there was no statistically significant difference in mean mid-luteal, compared to mid-follicular, levels of serum Cu, Zn, Fe and Co and endometrial Zn. Mid-luteal endometrium contained significantly higher mean Cu, and lower mean Fe levels. In Lippes loop users, compared to controls, the only statistically significant differences were lower mean mid-follicular serum Zn, lower mean endometrial Zn and Fe, and higher mean mid-luteal endometrial Fe. In CuT-200 users, compared to controls, there was significantly higher mean mid-follicular serum Zn and lower mean mid-luteal serum Co, higher mean mid-follicular endometrial Cu and lower mean mid-follicular endometrial Fe levels. Compared to Lippes loop, CuT-200 users had significantly higher mean mid-follicular serum Co and endometrial Cu and Zn, and lower mean mid-follicular endometrial Fe.

Adult↗

Serum and endometrial sodium and potassium levels with inert and copper-containing IUCDs and relation to serum steroid levels.

Serum and endometrial sodium (Na) and potassium (K) levels and serum estradiol, progesterone, testosterone and cortisol were measured in the mid-follicular and mid-luteal phases of the menstrual cycle in 20 Lippes loop and 20 CuT-200 IUCD users and 20 matched controls. Na and K were measured by atomic absorption spectrophotometry, while serum steroids were measured by RIA. Regarding steroids, the only significant difference between the three groups was a significantly lower mean mid-luteal serum estradiol in CuT-200 IUCD users compared to Lippes loop users (p less than 0.05). Regarding sodium in the control group, there was significantly lower mean mid-luteal serum and endometrial Na (p less than 0.01) that was not found in both groups of IUCD users. In the mid-follicular phase, there was significantly higher mean serum Na in both Lippes loop and CuT-200 groups compared to controls (p less than 0.05). Mean endometrial Na showed no significant difference between the three groups in both phases of the menstrual cycle. Regarding potassium in the control group, there was significantly lower mean levels in the mid-luteal-phase of the cycle (p less than 0.01) that was not seen with both groups of IUCD users. Serum K showed no significant difference in the three groups in both phases of the menstrual cycle. Endometrial K showed a significantly higher mean level in both Lippes loop and CuT-200 IUCD users compared to controls in the mid-luteal (p less than 0.01), but not in the mid-follicular phases of the cycle.

Analysis of Variance↗

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.

Adult↗

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.

Animals↗

Bile duct carcinoma in Egypt: possible etiological factors.

Contrary to an old belief, bile duct carcinoma is not a rare disorder in Egypt. Among 730 patients referred for an ERCP examination, twenty-nine consecutive patients were diagnosed as having bile duct carcinoma. The cause of this type of carcinoma remains unknown. In the present study, only seven of the 29 (24.1%) with bile duct carcinoma patients had associated gallstones. In order to investigate the possible association between typhoid carrier state and bile duct carcinoma, stool cultures were performed for Salmonella typhi and Salmonella paratyphi A and B. Nine out of 23 patients (39.1%) with bile duct carcinoma, 17 out of 50 (34%) with calcular obstructive jaundice, and 1 out of 50 (2%) healthy individuals proved to be salmonella carriers. Statistical analysis of the results confirmed the presence of a significant association between chronic fecal thyphoid carrier state and bile duct carcinoma, while that between calcular obstructive jaundice and bile duct carcinoma was not significant. In conclusion, there might be an association between chronic fecal typhoid carrier state and bile duct carcinoma.

Adenoma, Bile Duct↗

Long-term follow-up of the remaining kidney in living related kidney donors.

In this work 45 living related kidney donors (LRD) and 20 healthy sex and age matched controls were examined. Donors were evaluated up to 122 months after donation. Hyperfiltration was observed in the remaining kidney with a mean one-kidney GFR value of 82.9 +/- 36.8 ml/min while the control value was 71.04 +/- 31.5 ml/min. The kidney was significantly larger in the donor group than in the controls. In the LRD group, 3 were hypertensive, 7 showed microscopic haematuria and 5 had mild proteinuria. In the control group 3 were mildly hypertensive, and 2 showed microscopic haematuria. Serum creatinine of the donor group was found to be significantly higher than in the controls, yet it was stable and within the normal range (0.89 +/- 0.28 mg/dl). Examination for microalbuminuria showed that 11% of the donor group excreted higher amounts of albumin, being above the upper limit of the control group. We have concluded that kidney donation will result in minor abnormalities in kidney functions which will not affect the donor morbidity or mortality.

Adult↗

Selective in vivo tumor localization of heptacarboxylic porphyrin isomer I in a bladder tumor model: a novel technique to modulate porphyrin localization.

We were the first to report that uroporphyrin isomer I is a superior tumor localizer when compared with hematoporphyrin derivative. In the present study, we have examined the tumor localization of heptacarboxylic porphyrin isomer I (hepta-P) using a bladder tumor model. We have also compared it to that found with uroporphyrin isomer I (Uro-P). We now show, for the first time, that (hepta-P) isomer I can be selectively retained in bladder malignant cells, a novel observation which has not yet been described by other investigators. Furthermore, we have provided a novel technique to modulate and manipulate blood protein binding to porphyrin in a controlled manner, such that the tumor localization properties can be effectively utilized without prolonged retention in the skin and to produce high uptake in the tumor, i.e., a higher therapeutic ratio. The biodistribution of hepta-P in different organs is presented.

Animals↗