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Biomedical subjects

S Ibrahim

Publications and source records attributed to S Ibrahim.

At least 19 recordsLinked to original sources

Regulation of PDGF-stimulated SHIP2 tyrosine phosphorylation and association with Shc in 3T3-L1 preadipocytes.

In 3T3-L1 and human preadipocytes, insulin results in the isolated rise in phosphatidylinositol (PI)-3,4,5-P3, whereas PDGF produces PI(3,4)P2 in addition to PI(3,4,5)P3. SH2 domain-containing inositol 5-phosphatase 2 (SHIP2) converts PI(3,4,5)P3 into PI(3,4)P2. PDGF, but not insulin, stimulates SHIP2 tyrosine phosphorylation and its association with Shc in human and 3T3-L1 preadipocytes. We now demonstrate that SHIP2 tyrosine phosphorylation and association with Shc in PDGF-treated 3T3-L1 preadipocytes was reduced by bisindolylmaleimide I (BisI), an inhibitor of conventional/novel protein kinase C (PKC). However, the production of PI(3,4)P2 and PI(3,4,5)P3 by PDGF was unaffected by BisI. Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) was not sufficient to induce SHIP2 tyrosine phosphorylation. Furthermore, we identified threonine 958 (T958) as a novel PDGF-responsive SHIP2 phosphorylation site. Mutation of T958 to alanine reduced PDGF-stimulated SHIP2 tyrosine phosphorylation and association with Shc, but did not alter its anti-proliferative effect on preadipocytes. This study demonstrates that SHIP2 tyrosine phosphorylation and Shc association can be regulated by serine/threonine signaling pathways, either indirectly (via PKC), or directly (via T958). Interestingly, the anti-proliferative effect of SHIP2 T958A, as well as another SHIP2 mutant (Y986F, Y987F) that also displays defective tyrosine phosphorylation and Shc association, does not depend on these molecular events.

3T3-L1 Cells↗

Slipped capital femoral epiphysis (SCFE): a 12-year review.

Slipped capital femoral epiphysis (SCFE) is a relatively uncommon hip disorder in adolescents and its prevalence in Malaysia has not been studied. This retrospective study is undertaken to provide an overview of a 12-year review of SCFE treated in our institution. Fourteen patients (19 hips) with slipped capital femoral epiphysis (SCFE) admitted to Hospital UKM from 1990 to 2002 were reviewed with respect to demographic profile, functional outcome according to the Iowa Hip Score, and complications. There were ten boys (average age, 12.5 years) and four girls (average age, 12 years). Eight were Malays and six were Indians. The average body mass index was 26.1 verweight). The left hips (11 hips) were affected more than the right hips (eight hips). Five patients had bilateral slips. Thirteen hips were considered stable while the other six hips were unstable. The majority of cases were moderate slips (12 hips), four hips had severe slips while three hips had mild slips. Several methods of treatment were instituted. These include in situ cannulated screw fixation (11 hips), Knowles pin fixation (three hips) and gentle closed manipulative reduction with cannulated screw fixation (three hips). One patient with bilateral slips refused surgical treatment. Based on the Iowa Hip Score, most patients (nine) had satisfactory results (excellent or good), three had fair results while one patient had a poor result. Avascular necrosis developed in five hips while chondrolysis occurred in one hip. In situ cannulated screw fixation is the treatment of choice. SCFE is an uncommon condition in Malaysia.

Adolescent↗

Gene expression profiling of arthritis using a QTL chip reveals a complex gene regulation of the Cia5 region in mice.

One of the major quantitative trait loci (QTLs) associated with arthritis in crosses between B10.RIII and RIIIS/J mice is the Cia5 on chromosome 3. Early in the congenic mapping process it was clear that the locus was complex, consisting of several subloci with small effects. Therefore, we developed two novel strategies to dissect a QTL: the partial advanced inter-cross (PAI) strategy, with which we recently found the Cia5 region to consist of three loci, Cia5, Cia21 and Cia22, and now we introduce the QTL-chip strategy, where we have combined congenic mapping with a QTL-restricted expression profiling using a novel microarray design. The expression of QTL genes was compared between parental and congenic mice in lymph node, spleen and paw samples in five biological replicates and in dye-swapped experiments at three time points during the induction phase of arthritis. The QTL chip approach revealed 4 genes located in Cia21, differently expressed in lymph nodes, and 14 genes in Cia22, located within two clusters. One cluster contains six genes, differently expressed in spleen, and the second cluster contains eight genes, differently expressed in paws. We conclude the QTL-chip strategy to be valuable in the selection of candidate genes to be prioritized for further investigation.

Animals↗

Successful management of a bleeding duodenal varix by endoscopic banding.

Endoscopic treatment of bleeding duodenal varices is less invasive than the usual surgical options. However, there is limited experience with endoscopic treatment of bleeding duodenal varices, especially with that of endoscopic ligation. We report a 55-year-old man with a bleeding duodenal varix that was successfully ligated endoscopically. He has been followed up for nine months with no recurrence of bleeding. Endoscopic ligation may offer a new and effective treatment modality for bleeding duodenal varix.

Duodenoscopy↗

Revision surgery for developmental dysplasia of the hip.

Revision surgery following failed open reduction for developmental dysplasia of the hip (DDH) is technically demanding. We reviewed 12 patients in our institution that required a revision surgery between January 1994 and December 2003. The aims of this study are to identify the causes of redislocation after the primary open reduction and to determine the clinical and radiological outcome after the revision surgery. The mean age at presentation for DDH was 31 months (range 1-84) and the mean age at primary open reduction surgery was 38 months (range 15-84) and the mean age at revision surgery was 69 months (range 21-180). The mean follow-up period after revision surgery was 20 months (range 3-84). All the revision surgery was performed via an anterior Smith Peterson approach. The most common cause for redislocation was inadequate exposure and failure to release the obstructing soft tissues around the hip. The bony factors for redislocation included failure to perform a femoral shortening and excessive derotation of an anteverted femoral head combined with a Salter osteotomy. Three cases with posterior acetabular wall deficiency needed immobilization of the hip in extension as the hip tended to dislocate in flexion. Six patients had limb length discrepancy ranging from 1 cm to 4 cm and 50% developed avascular necrosis. Only 2 patients were asymptomatic and the majority had a limp and limitation of motion. All were pain free except one. In view of the technically demanding surgery and poor results after revision, the surgeon should recognize the pathology and ensure that the primary procedure achieves a stable and concentric reduction.

Adolescent↗

Sengers disease: a rare association of hypertrophic cardiomyopathy and congenital cataracts.

Hypertrophic cardiomyopathy is an uncommon childhood cardiac disease and can be primary or secondary. Several systemic diseases are known to be associated with this entity. Senger's disease is a mitochondrial disorder causing congenital cataracts lactic acidosis and skeletal and cardiac myopathy. Diagnosis should be kept in mind when routine neonatal eye screening reveals absent red reflex. The authors report a case of Sengers disease and discuss the underlying pathogenetic mechanisms.

Blood Chemical Analysis↗

Transient atypical monocytosis mimic acute myelomonocytic leukemia in post-chemotherapy patients receiving G-CSF: report of two cases.

Granulocyte colony-stimulating factor (G-CSF) is now widely used in patients with malignant disorders receiving intensive chemotherapy to increase leukocyte count and to upregulate phagocyte function during neutropenia. Monocytosis associated with G-CSF has been reported in anecdotal literature. We report two cases of pseudoleukemia secondary to G-CSF administration. Both patients initially presented with myelodysplastic syndrome with chromosome 7 abnormalities that evolved into acute myeloid leukemia. Case one had deletion 7q while case two initially had monosomy 7 and subsequently developed a balanced translocation between the short (p) arm of chromosome 1 and long (q) arm of chromosome 15. Following the induction chemotherapy and G-CSF administration, both of these patients developed pseudoleukemia. Patient 1 had white blood cell (WBC) count of 26 x 10(9)/l with 72% monocytes, while patient two had WBC of 14.1 x 10(9)/l with 30% monocytes. In both patients the monocytosis resolved after the discontinuation of G-CSF therapy. In summary, patients treated with G-CSF should be followed closely. In those cases with pseudoleukemia discontinuation of the drug with no supplemental chemotherapy is probably enough to control the atypical monocytosis.

Aged↗

In vitro differences of hydroxyapatite from different resources in simulated body fluid.

Hydroxyapatite (HA; Ca10(PO4)6(OH)2), is one of the significant implant materials used in Orthopaedics and Dental applications. However, synthetically produced HA may not be stable under ionic environment, which it will unavoidably encounter during its applications. In this paper, the in vitro effects of three HA materials derived from different resources, i.e. commercial HA (HAC), synthesised HA from pure chemicals (HAS) and synthesised HA from kapur sireh; derived traditionally from natural limestone (HAK), were studied. The HA disc samples were prepared and immersed in simulated body fluid (SBF) for 31-day period. The evaluation conducted focuses on the changes of the pH and the Calcium ion (Ca-ion) and Phosphate ion (P-ion) concentrations in the SBF solution, as well as the XRD and SEM data representing the reactions on the HA materials. From the XRD, it was found that HAK has the smallest crystallite sizes, which in turn affect the pH of the SBF during immersion. The Ca and P-ion concentrations generally decrease over time at different rates for different HA. Upon 1-day immersion in SBF, apatite growth was observed onto all three surfaces, which became more pronounced after 3-day immersion. However, the appetites formed were observed to be different in shapes and sizes. The reasons for the difference in the apatite-crystals and their subsequent effects on cells are still being investigated.

Bone Substitutes↗

Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy.

AIMS/HYPOTHESIS: The pathogenesis of painful diabetic neuropathy remains unknown. As a consequence we still do not have any effective, rational treatments and a greater understanding of the mechanisms is urgently required. Previous studies have shown no consistent morphological differences in the nerves of patients with and without painful neuropathy. The aim of this study was to compare epineurial haemodynamics in patients with chronic painful and painless neuropathy. METHODS: The techniques of microlightguide spectrophotometry and fluorescein angiography were used to measure epineurial intravascular oxygen saturation and blood flow respectively. Eleven patients with painful and eight with painless neuropathy were studied, with the groups matched carefully in terms of severity of neuropathy and diabetes control. RESULTS: Intravascular oxygen saturation was higher in the painful neuropathy group compared to those without pain (median 73.8% vs 67.7%, respectively; p=0.021). Fluorescein rise time was also faster in those with painful symptoms (median 18.3 s vs 53.6 s; p=0.046) indicating higher epineurial blood flow in these subjects. CONCLUSION/INTERPRETATION: These results indicate that there are distinct differences in haemodynamics within the epineurium of the sural nerve in subjects with painful and painless neuropathy. Haemodynamic factors could therefore have an important role in the pathogenesis of neuropathic pain and might offer further insight into potential treatments for this distressing condition.

Blood Flow Velocity↗

Injury to arms protruding through vehicle windows.

Driving with an arm protruding through a window can result in limb threatening injury. A series of seven upper limb injuries sustained during motor vehicle accidents (MVAs) with a limb protruding from the vehicle window is described. The severity and complexity of these injuries are related to the ultimate functional recovery for the limb. This study serves to highlight the severity of injury and morbidity following these modalities of trauma, which although rarely fatal, carry extensive consequences and could be easily prevented with appropriate education programmes and legislation.

Accidents, Traffic↗

Implantation metastasis in a 13-year-old girl: a case report.

We report a case of a 13-year-old girl with an osteosarcoma of the right humerus, which had been diagnosed as an aneurysmal bone cyst at our institution. She underwent curettage and bone grafting of the lesion, which resulted in implantation metastasis of the tumour to the ilium. She died 15 months after presentation owing to pulmonary metastases. This report highlights the possibility of metastasis occurring by direct implantation to a graft donor site. We strongly recommend that a biopsy be performed in cases of presumed benign lesions before proceeding with the definitive surgery.

Adolescent↗

Febrile seizures: factors affecting risk of recurrence in Pakistani children presenting at the Aga Khan University Hospital.

OBJECTIVES: To (a) describe the effect of temperature rise on seizure recurrence in the ER (b) investigate the effect of age, gender, family and developmental history, type, duration and multiple seizures, past history and number of seizures and treatment given (either late or early) on seizure recurrence in the ER and (c) explore prognostic indicators for seizure recurrence. METHODS: Data from 352 children [ages 3-84 months; 220 males (62.5%) 132 females (37.5%)] was taken using chart reviews for the years January 1998-August 2000 inclusive, from the Pediatric department of the Aga Khan University Hospital. Descriptive statistics, Chi-square, and Discriminant Analysis were used. RESULTS: Of the 52 (16%) cases that had seizure recurrence in the ER, majority (36.5%) occurred in > 38.5 degrees < or = 39.5 degrees C temperature range. The percentage declined to 15% at higher temperatures. Bivariate tests showed that age, family and developmental history, type of seizure and treatment given did not affect seizure recurrence in the ER. Past history number of seizures (p = .006), duration of seizure (p < 0.001), past history of seizures (p = 0.004) and multiple seizure (p = 0.024) were factors significantly associated with seizure recurrence in the ER at the bivariate level of analysis. Duration of seizure was the most important prognostic indicator for FS recurrence in the ER at the multivariate level with beta = .79. CONCLUSION: Duration of seizure (> 5 minutes) was the most important prognostic factor for FS recurrence. Early treatment did not affect recurrence,suggesting timely anti-pyretic vs. anti-leptic medication use.

Age Distribution↗

Indigenous knowledge system for treatment of trypanosomiasis in Kaduna state of Nigeria.

A survey was carried out in Kaduna State of Nigeria to establish the indigenous knowledge system for treating trypanosomiasis in domestic animals. Questionnaire and interviews were, respectively, administered to, or conducted with about 200 livestock farmers and traders spread around the state. Data obtained revealed the use of several plants either alone or in combination, for the treatment and management of trypasonomiasis. The most common plants encountered were Adansonia digitata, Terminalia avicennoides, Khaya senegalensis, Cissus populnea, Tamarindus indica, Lawsonia inermis, Boswellia dalzielli, Pseudocedrela kotschi, Syzyium quinensis, Sterculia setigera, Afzelia africana, Prosopis africana, Lancea kerstingii. The method of preparation and mode of administration of some of these plants in the treatment of trypanosomiasis are reviewed and discussed.

Animals↗

Birth asphyxia--analysis of 235 cases.

OBJECTIVE: To look for risk factors leading to birth asphyxia in new borns admitted in a tertiary care unit STUDY DESIGN: Retrospective analysis. SETTING: Neonatal Unit of National Institute of Child Health, Karachi from 1st January, 2001 to 31st August, 2001. PATIENTS AND METHODS: Records of 235 new borns admitted with birth asphyxia during this period were analyzed. Variables studied included antenatal care, period of gestation, place of delivery, mode of delivery, birth weight and age at arrival in the hospital. RESULTS: Majority (71%) of mothers were booked and had antenatal care, similarly most (88%) of the babies were born at term and 75.3% were delivered in maternity homes or hospitals. Caesarian sections were performed in 14% cases and rest were all vaginal deliveries. Fifty seven percent newborns weighed more than 2.5 kg and 22.5% presented to the hospital within 6 hours of birth. CONCLUSION: Birth asphyxia occurring in such a high number of booked cases delivered at term with good weight, reflects the poor perinatal services offered in those maternity homes or hospitals. It is recommended that trained personnel and neonatal resuscitation equipment should be made mandatory in all maternity homes/hospitals.

Asphyxia Neonatorum↗

CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia.

CD38 is a transmembrane glycoprotein expressed on the surface of leukemic cells in a significant percentage of patients with B-cell chronic lymphocytic leukemia (B-CLL). A recent study suggested that CD38 expression has prognostic value in CLL. Peripheral blood samples from 218 patients with B-CLL were analyzed by flow cytometry for CD38 expression on CD5/19(+) leukemic cells. Various patient characteristics were studied including age, sex, Rai and Binet stages, splenomegaly, hepatomegaly, hemoglobin (Hgb) level, beta-2 microglobulin (beta2M) level in the serum, number of nodal sites involved with disease, and length of survival. The Kaplan-Meier method was used to construct survival curves, and the log-rank statistic was used to compare these curves. CD38 was expressed in 20% or more of leukemic cells in 43% of the patients. Patients with high CD38 expression (20% or more) had significantly shorter survival times (P =.00005). Multivariate analyses showed that CD38 expression is an important prognostic factor associated with high incidence of lymph node involvement (P =.004), lower hemoglobin level (P =.001), hepatomegaly (P =.05), and high beta2M level (P =.00005). CD38 expression identified a group of patients with aggressive disease that was considered by Rai staging to be early-stage disease (Rai stages 0-II). Patients with CD38(+) samples have significantly aggressive disease regardless of their clinical stage. Measurement of CD38 expression by flow cytometry should become a routine test in the evaluation of patients with CLL.

ADP-ribosyl Cyclase↗

N-acetyl alpha-D-glucosaminidase from the venom of African puff adder (Bitis arietans).

The activity of N-acetyl-alpha-D-glucosaminidase from venom of the African puff adder (Bitis arietans) has been detected. The enzyme from the venom was purified by chromatography on Q-sepharose, CM-cellulose, and N-acetyl-alpha-D-glucosamine-agarose affinity column. The enzyme has a molecular weight of 102 kDa determined by size exclusion chromatography on Sephacryl 200. It migrated as a 51-kDa band on SDS polyacrylamide gels. The enzyme is maximally active at pH 5.5 and 40 degrees C. The B. arietans NAGase hydrolyzed exclusively terminally linked alpha-(1-4) GlcNAc residues from nonreducing ends of oligosaccharides. It hydrolysed chito-oligosaccharide, MU-GlcNAc and chitobiose with K(M) values of 0.15 mM and 1.22 mM, respectively. Swollen chitin and oligosaccharide above (GlcNAc)(4) were not hydrolysed by the enzyme. B. arietans NAGase was strongly inhibited noncompetitively by Hg(2+), competitively by 1-thio-beta-D-GlcNAc and N-acetyl glucosamine (NAG) with K(i) of 0.55, 0.25 and 8 mM, respectively. Colombin the active component of antivenom preparation from Aristolodia albida inhibited the enzyme competitively with K(i) of 0.6 mM. Delineation of the active site by chemical modification revealed the involvement of His and Trp in the catalysis of the enzyme.

Acetylglucosaminidase↗