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Biomedical subjects

S Ahmed

Publications and source records attributed to S Ahmed.

At least 361 records · Page 20Linked to original sources

Delayed management of posterior urethral disruption in children.

OBJECTIVE: To review the results of delayed operative treatment of total disruption of the posterior urethra in children. PATIENTS AND METHODS: Twelve boys (3-12 years, mean 7.5) with a suprapubic catheter were referred after primary management in other hospitals. All but one had been involved in road traffic accidents. In addition to their urethral injury, they all had pelvic fractures and the majority also had other major associated injuries. Six to 14 months after injury, abdominoperineal transpubic urethroplasty was performed in 11 patients according to Turner-Warwick. In one case a perineal anastomotic urethroplasty was performed. RESULTS: After the operation, voiding cysto-urethrography showed a wide anastomosis in all cases. After 3 to 45 months follow-up, there were no strictures. Eight boys were continent, two were totally incontinent, two had stress incontinence and one nocturnal enuresis. All patients with confirmed erections after injury also had erections after their operation. CONCLUSION: Primary suprapubic cystostomy and delayed repair can be used successfully for the treatment of posterior urethral disruption in children.

Accidents, Traffic↗

Cytokines in the stools of children with complicated shigellosis.

The pathogenesis of the systemic complications, leukemoid reaction and hemolytic uremic syndrome, associated with Shigella dysenteriae type 1 infection is not well understood. The excessive production of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), has been suggested as a possible factor. We measured IL-6 and TNF-alpha in stools of 56 children with S. dysenteriae 1 infection and 29 children without any apparent infection, all age 12 to 60 months. Sixteen children with S. dysenteriae 1 infection had leukemoid reaction or hemolytic uremic syndrome (complicated shigellosis), while the others did not (uncomplicated shigellosis). Stool IL-6 and TNF-alpha concentrations were higher in children with uncomplicated shigellosis than in children with complicated shigellosis (P = 0.009 and < 0.001, respectively) or in uninfected children (P < 0.001). It is concluded that complicated infection is not associated with higher concentrations of the proinflammatory cytokines IL-6 and TNF-alpha in stool.

Child, Preschool↗

The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts.

The Ras-related protein Cdc42 plays a role in yeast cell budding and polarity. Two related proteins, Rac1 and RhoA, promote formation in mammalian cells of membrane ruffles and stress fibers, respectively, which contain actin microfilaments. We now show that microinjection of the related human Cdc42Hs into Swiss 3T3 fibroblasts induced the formation of peripheral actin microspikes, determined by staining with phalloidin. A proportion of these microspikes was found to be components of filopodia, as analyzed by time-lapse phase-contrast microscopy. The formation of filopodia was also found to be promoted by Cdc42Hs microinjection. This was followed by activation of Rac1-mediated membrane ruffling. Treatment with bradykinin also promoted formation of microspikes and filopodia as well as subsequent effects similar to that seen upon Cdc42Hs microinjection. These effects of bradykinin were specifically inhibited by prior microinjection of dominant negative Cdc42HsT17N, suggesting that bradykinin acts by activating cellular Cdc42Hs. Since filopodia have been ascribed an important sensory function in fibroblasts and are required for guidance of neuronal growth cones, these results indicate that Cdc42Hs plays an important role in determining mammalian cell morphology.

Actin Cytoskeleton↗

Serum ferritin levels in carriers of beta-thalassaemia trait.

Hypochromic and microcytic red cell morphology is the most commonly encountered abnormality in a clinical laboratory. Most of such cases have iron deficiency anaemia. However, in Pakistan about 5% of the individuals with a hypochromic and microcytic blood picture have the beta-thalassaemia trait. These individuals are more than often in a positive iron balance. However iron deficiency (being common) may be associated with the beta-thalassaemia trait. This study of serum ferritin levels was carried out on 135 confirmed cases of the beta-thalassaemia trait. A ferritin assay was done by a radioimmunoassay technique. The results show that the level of serum ferritin in 100 (74%) cases was within normal limits, in 17 (12.6%) cases it was above the normal range, whereas in 18 (13.4%) cases the level was lower than normal. The importance of serum ferritin estimation in carriers of the beta-thalassaemia trait is highlighted.

Adolescent↗

A case of non-Hodgkin's lymphoma presenting with polyuria and acute renal insufficiency.

A case of non-Hodgkin's lymphoma presenting with polyuria, enlarged kidneys, and renal insufficiency is reported. The diagnosis was made by percutaneous needle biopsy of the kidney. Renal failure reversed and the kidneys regressed in size on exhibition of the first cycle of chemotherapy. The rarity of polyuria at presentation, the role of renal biopsy in the diagnosis, and the response of renal failure to specific chemotherapy are discussed.

Acute Kidney Injury↗

Evaluation of M/H ratio for screening of beta thalassaemia trait.

This study was done to evaluate the efficiency of M/H ratio between the percentages of microcytic and hypochromic cells as a screening procedure for thalassaemia trait in Pakistani population. A total of 150 subjects, were included in this study. The analysis of results revealed that M/H ratio is a very sensitive index for beta thalassaemia trait. The sensitivity, predictive value and diagnostic accuracy of the M/H ratio for beta thalassaemia trait was 100%, 90.4% and 90.4% respectively. It also picked up all cases of beta thalassaemia trait with co-existent iron deficiency. It is therefore concluded that M/H ratio is an easy, reliable and sensitive index which can be used for mass screening of beta thalassaemia trait, particularly in a population where iron deficiency is also prevalent.

Adolescent↗

BDNF enhances the differentiation but not the survival of CNS stem cell-derived neuronal precursors.

We have previously reported the isolation of an EGF-responsive precursor from the embryonic and adult mouse striatum. This precursor exhibits self renewal and the ability to produce a sphere of undifferentiated cells which can be induced to differentiate into neurons and glia. RT-PCR analysis of these spheres of undifferentiated cells revealed the expression of mRNA for the trkB neurotrophin receptor, both with and without the catalytic domain, and little or no expression of trkA or trkC. We examined the actions of BDNF on the fate of EGF-generated neural precursors. Ten days after a one-time exposure to BDNF, single EGF-generated spheres showed a twofold increase in neuron number and a marked enhancement in neurite outgrowth. Examination of neuronal nuclei with immunochemical probes for c-fos and bromodeoxyuridine revealed that the actions of BDNF were directly upon neuronal cells and did not involve division of neuronal precursors. The twofold increase in neuronal number due to BDNF, observed after 10 d in vitro, was significantly reduced after 21 d in vitro and was not apparent at 27 d in vitro. Quantitative analyses revealed that while repeated application of BDNF did not prevent the loss of neuron number over time, it did result in a significant increase in neurite numbers. Moreover, delayed addition of BDNF mimicked the increase in neuronal numbers seen when BDNF was present throughout. These BDNF actions did not appear to involve the enhancement of a novel neuronal phenotype, with all effects being due to increase in the numbers and neurite outgrowth of neurons that colocalize GABA and substance P. These findings suggest that BDNF markedly enhances the antigenic and morphologic differentiation of EGF-generated neuronal precursors. BDNF alone does not appear to act as a survival factor for neuronal precursors nor is it sufficient for preventing their death over time.

Animals↗

Granulocytic sarcoma in patients with chronic myeloid leukaemia.

Granulocytic sarcoma is an unusual variant of myeloid malignancy most commonly encountered in the course of chronic or acute myeloid leukaemia. Of 60 patients of chronic myeloid leukaemia studied over 21 months, we encountered 6 (10%) cases of granulocytic sarcoma. Four of these had granulocytic sarcoma on their first presentation. All those who were receiving hydroxyurea did not fare well but one who was put on DAT (daunorubicin, cyftosine arabinocide, 6 thioguanine)regimen went into remission with complete disappearance of lesions.

Adolescent↗

Management of urinary calculi associated with renal failure.

Three hundred and sixty patients of urinary calculi associated with renal failure were included in this prospective study. The male to female ratio was 4.1:1 while adult to paediatric ratio was 6.5:1. One hundred and eighteen (32.8%) patients presented with calculus anuria while 242 (67.2%) were admitted with symptoms of chronic renal failure. Serum creatinine at the time of first admission ranged from 3-35 mg/100 ml. In the initial management, percutaneous needle nephrostomy was done in 217 cases, dialysis in 106, dialysis and PCN in 22 and retrograde catheterisation followed by JJ stent in 15. Definitive surgical procedures were undertaken in 277 cases; 29 passed stones spontaneously after PCN. At two year follow-up 72% patients of calculus anuria and 49.5% of calculus renal failure improved their renal function and remained with serum creatinine below 2 mg/100 ml. There was 13.6% mortality in calculus anuria group and 17.4% in calculus renal failure. Overall loss to follow-up was 7.6% and 12% in the two groups respectively.

Adolescent↗

Synthesis and biological evaluation of imidazole based compounds as cytochrome P-450 inhibitors.

Several phenyl ethyl and phenyl propyl imidazole based compounds have been synthesised and their biological activity evaluated against human placental Aromatase (AR), rat testicular 17 alpha-hydroxylase/ 17,20-lyase (P450(17) alpha) and bovine cholesterol side chain cleavage (CSCC). The compounds showed good selectivity towards AR with N-[2-(4'-Nitrophenyl) ethyl] imidazole (2) (IC50 = 0.16 +/- 0.01 microM, Ki = 0.09 +/- 0.01 microM), the most potent AR inhibitor, showing some 130 times greater potency over Aminoglutethimide (AG) (IC50 = 20.0 +/- 2.6 microM, Ki = 11.0 +/- 2.0 microM). N-[3-(4'-Fluorophenyl) propyl] imidazole (10) (IC50 = 0.31 +/- 0.01 microM, Ki = 0.34 +/- 0.05 microM), N-(2-(4'-Fluorophenyl ethyl) imidazole (5) (IC50 = 0.74 +/- 0.01 microM, Ki = 0.40 +/- 0.02 microM), N-(3-(4'-Chlorophenyl propyl) imidazole (9) (IC50 = 0.82 +/- 0.02 microM) and N-[3-(4'-Nitrophenyl) propyl] imidazole (7) (IC50 = 0.84 +/- 0.02 microM, Ki = 0.10 microM) were also more potent than AG. Of the compounds tested for P450(17) alpha activity, 7 (IC50 = 25.0 +/- 2.0 microM), N-[2-(4'-Aminophenyl) ethyl] imidazole (3) (IC50 = 27.6 +/- 0.10 microM), 9 (IC50 = 29.0 +/- 4.0 microM) and 2 (IC50 = 30.2 +/- 2.0 microM) showed the highest activity, possessing approximately half the activity of Ketoconazole (IC50 = 12.1 +/- 2.9 microM). Compounds 1, 2, 3, and 7 showed 0% inhibitory activity towards CSCC at 200 microM whilst AG showed 83% inhibition under the same conditions. The compounds proved themselves to be excellent lead compounds and supported the novel models developed by Ahmed for AR and P450(17) alpha.

Animals↗

Association of herpes simplex virus type-I and human papilloma virus with carcinoma of the oral cavity and oropharynx.

This study consists of 56 carcinoma cases of the oral cavity and oropharynx, 56 controls matched for age, sex, and habits, and 100 other controls proportionate to the population of Karachi. Biopsy material of the carcinoma cases and oral smears of the two control groups were negative for HSVI and HPV with peroxidase-antiperoxidase staining. The Enzyme Immunosorbent assay (EIA) of sera revealed significantly high levels of anti HSV-I IgG and IgM antibodies in carcinoma cases (96.43% and 25.00%, respectively) when compared with matched controls (73.21% and 3.5%, respectively).

Antibodies, Viral↗

Synthesis and biological evaluation of novel pyrrolidine-2,5-dione inhibitors as potential anti-tumour agents.

Several novel pyrrolidine-2,5-dione based compounds have been synthesised and evaluated for their biological activity against human placental aromatase (AR), rat testicular 17 alpha-hydroxylase/17,20-lyase (P450(17) alpha) and bovine cholesterol side chain cleavage (CSCC). The compounds showed good inhibition towards AR with 1-cyclohexyl-3-[2'(4"-aminophenyl) ethyl] pyrrolidine-2,5-dione (3) (IC50 = 23.8 +/- 4.6 microM) and 1-octyl-3-[2'(4"-aminophenyl) ethyl] pyrrolidine-2,5-dione (4) (IC50 = 24.6 +/- 1.8 microM) showing equipotent activity with Aminoglutethimide (AG) (IC50 = 20.0 +/- 2.6 microM, Ki = 11.0 +/- 2.0 microM). Of the compounds tested for P450(17) alpha activity, 3 (IC50 = 18.5 +/- 1.9 microM) again showed the highest activity, being equipotent to Ketoconazole (IC50 = 12.1 +/- 2.9 microM). 3 was a poor inhibitor of CSCC with some 22% inhibitory activity at an inhibitor concentration of 200 microM, as compared to AG with 72% inhibitory activity under the same conditions. The compounds proved themselves to be excellent lead compounds and supported the novel models developed by Ahmed for AR and P450(17) alpha.

Adrenal Glands↗

Serum complement C4 levels during acute malarial infection and post-treatment period.

The researches are conducted in adults and children infected with the species P. falciparum and P. vivax. The results indicated that complement C4 level showed a marked fall during the course of acute malaria in both the children and adults infected with both species. A highly significant hypocomplementaemia was recorded (p < 0.01). Children infected with P. falciparum developed acute cerebral malaria, which was associated with marked hypocomplementaemia. A marked rise in C4 level was noticed on 10th day and it was found normal with reference to control, on 20th and 30th day. A considerable reduction in C4 complement was recorded in P. falciparum when compared to P. vivax.

Acute Disease↗

Breakpoint cluster region gene product-related domain of n-chimaerin. Discrimination between Rac-binding and GTPase-activating residues by mutational analysis.

The breakpoint cluster region gene product (Bcr) is a GTPase-activating protein (GAP) for members of the Rho family, Cdc42Hs, and Rac1, as is the brain protein n-chimaerin. At least 15 proteins have sequence identity to the GAP domain (150 amino acid residues) of Bcr. The widespread occurrence of proteins that possess sequence identity to the Bcr-related GAP domain makes it especially important to understand its structure/function relationships. Amino acid sequence alignment of these proteins reveals three blocks of conservation in the GAP domain. Here, we present a mutational analysis of this domain using n-chimaerin sequences. Ten mutations were constructed (at least two in each of the blocks of conservation), expressed as glutathione S-transferase fusion proteins in Escherichia coli, and purified. Seven of the mutants, including deletions, still possessed GAP activity for Rac1. Three of the mutants had no Rac1-GAP activity but were still able to bind Rac1. IC50 values obtained from competition experiments suggest that n-chimaerin and the mutants with no GAP activity bound Rac1 with similar apparent binding constants. Thus, this mutant analysis allows discrimination between Rac1-binding and Rac1 GTPase- activating residues.

Amino Acid Sequence↗

Focal xanthogranulomatous pyelonephritis in a young child.

An 18-month-old female child presented with fever and an abdominal mass, which, after ultrasonography, computed tomography, and magnetic resonance imaging was considered to be an atypical cystic renal neoplasm. Nephrectomy was performed. Histopathological examination demonstrated the mass to be focal xanthogranulomatous pyelonephritis. This lesion should be considered in the differential diagnosis of renal neoplasms in childhood, particularly cystic Wilms' tumor or Wilms' tumor with significant intratumoral hemorrhage.

Diagnosis, Differential↗