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Biomedical subjects

K Abdullah

Publications and source records attributed to K Abdullah.

16 recordsLinked to original sources

Imaging patients with "post-cholecystectomy syndrome": an algorithmic approach.

AIM: To assess the role of ultrasound (US), magnetic resonance cholangiopancreatography (MRCP) and liver function tests (LFTs) in the evaluation of selected patients presenting with late post-cholecystectomy syndrome (PCS) who were referred for endoscopic retrograde cholangiopancreatography (ERCP). MATERIALS AND METHODS: In a retrospective study a final group of 42 patients with PCS referred for diagnostic ERCP underwent MRCP and abdominal US. ERCP and MRCP images were assessed for bile duct diameters and the presence of strictures and stones. A common bile duct (CBD) diameter of < 10mm was considered normal, whereas > or = 10mm was considered abnormal on US. Findings were correlated to LFTs with contingency table results performed for single techniques and combination of methods. RESULTS: In total 14 stones and one stricture were seen. US had a high negative predictive value (86.4%). MRCP had a sensitivity of 100% and specificity of 88.0%. ERCP is the most accurate test but failed in 11 patients, five of whom had a stone. The accuracy of US and LFTs increases to 93.8% if test results agree in either negative or positive outcome. CONCLUSION: US and LFTs are first-line tests in PCS. If the CBD on US is > or = 10mm, but no cause is identified, MRCP should be performed. If US and LFTs are normal then MRCP is not necessary. The availability of LFTs raises the diagnostic value of imaging.

Adult↗

Twenty cases of adult-to-adult living-related liver transplantation: single-center experience in Saudi Arabia.

BACKGROUND: The deceased donor organ shortage has forced surgeons to implement innovations, including living-related liver transplantation (LRLT). OBJECTIVE: To present the first 20 cases of adult LRLT in a single center in Saudi Arabia. METHODS: From November 2000 to May 2004, we performed 20 cases of LRLT. Eighteen donors were men and 2 were women. Their median age was 27 years. Seventeen of the recipients were men and 3 were women of median age 55 years. One patient received combined liver and kidney grafts. RESULTS: All cases had liver cirrhosis. Seven had hepatitis C; six, hepatitis B and C; three, hepatitis B; one, alcoholic cirrhosis; one, Bylar disease, one hepatic schistosomiasis, and one cryptogenic cirrhosis. Three cases had associated hepatocellular carcinomas. There was no donor mortality. In the recipients, the overall patient and graft survival was 85%. While 10 donors presented uneventful postoperative courses, 8 experienced minor complications and 2, major complications: biliary stricture and portal vein thrombosis. Recipients complications included biliary complications (35%), acute rejection (20%), hepatitis C reactivation (20%), hepatic vein stenosis (10%), hepatic artery stenosis (5%), and hepatocellular carcinoma recurrence (5%). CONCLUSIONS: LRLT has become a standard option in adults with end-stage liver failure in our center.

Adult↗

Incidence and management of biliary complications after orthotopic liver transplantation: ten years' experience at King Fahad National Guard Hospital.

BACKGROUND: Despite technical modifications and application of various surgical techniques, biliary tract complications remain a major source of morbidity after orthotopic liver transplantation. We sought to assess the incidence and management of biliary complications at a single liver transplant unit. METHODS: Among 184 consecutive deceased donor liver transplants performed between February 1994 and July 2004, 66 were female patients and 118 male patients of age range 2(1/2) to 69 years. We retrospectively reviewed the data regarding biliary complications in liver transplant recipients, after 115 duct-to-duct anastomoses and 65 hepaticojejunostomy. We analyzed the incidence and type of biliary complications, management sequence, and success rate. We analyzed the correlation between the modality of biliary reconstruction and the type/incidence of biliary complications. RESULTS: Thirty-two patients developed biliary complications, giving an overall incidence of 17.4%. There was a higher incidence of complications among patients in the hepaticojejunostomy group (21.5%) than the duct-to-duct technique (15.1%). Bile leakage occurred in 12 patients, including eight successful cases (66.6%) of endoscopic stent insertion/radiological techniques and surgery in four cases (33.3%). Among the 12 patients with initial leaks, six developed a subsequent stricture (50%). There were 26 cases of biliary stricture, including 22 (84.6%) who were initially managed using nonsurgical techniques with a success rate of 59%. CONCLUSION: Biliary complications remain an important cause of morbidity after orthotopic liver transplantation. They can usually be managed percutaneously or endoscopically; however, tight strictures and major leaks frequently required surgical intervention.

Female↗

Neutrophils and lymphoid chimerism after adult living-related liver transplantation from a homozygous donor.

Chimerism and graft-versus-host disease (GVHD) pose significant risks to liver transplant patients. The risk of chimerism and GVHD is higher among cases of living-related liver transplant (LRLT). Donors homozygous at all HLA loci carry a higher risk for GVHD. Herein we present a case of LRLT. The recipient suffered from end-stage liver disease and received a right lobe graft from his son. After 8 months posttransplant, the patient developed profound bone marrow depression. The patient was negative for CMV, Brucella, HHV6, HHV8, HBV, HCV, and parvovirus. No skin or GI signs of GVHD were noted. The patient and donor were HLA typed by SSP. The donor was homozygous for all HLA loci while the patient shared the class II homozygosity and was class I heterozygous. Chimerism studies were prompted after noting that the neutrophil compartment of the patient was homozygous for all HLA loci. This initiated further studies of the PMN and lymphocytes by microsatellite analysis. A total 15 microsatellites were analyzed. The results suggest that the majority (75%) of the PMNs and 45% of the lymphocytes were of donor origin. The patient was treated with G-CSF; his WBC counts returned to normal. At 2.5 years posttransplant the patient had not developed GVHD, despite the large number of donor lymphocytes circulating in his bloodstream. The only complaint he had was severe arthritis, which was treated with steroids. It must be investigated whether this was the result of GVHD.

Bone Marrow↗

Comparison of the effects of nitric oxide synthase, guanylate cyclase and potassium channel inhibition on vascular contractions in vitro in the rat.

1. We have investigated the differences between the nitric oxide synthase inhibitor L-NMMA, the guanylate cyclase inhibitor methylene blue and the potassium channel blockers apamin and charybdotoxin or apamin and iberiotoxin, in their abilities to increase vasoconstrictor responses in rat small mesenteric arterial rings. 2. When administered during the maintained contraction to PGF2alpha (10 microM), L-NMMA (100 microM) or the combination of apamin (0.7 microM) and charybdotoxin (0.1 microM) significantly increased the contractile response. Methylene blue (10 microM) increased the contraction, but this did not reach significance. However, apamin (0.7 microM) and iberiotoxin (0.1 microM) also significantly increased the contractile response. 3. The combination of L-NMMA or methylene blue with apamin/charybdotoxin produced significantly greater increases in the contractile response to PGF2alpha than achieved individually. 4. Relaxations to acetylcholine (10 microM) were significantly reduced by L-NMMA or methylene blue but not by apamin in combination with charybdotoxin or iberiotoxin. 5. Since apamin/iberiotoxin had similar effects to apamin/charybdotoxin, it is likely that the actions of these agents involve direct actions on smooth muscle potassium channels rather than inhibition of endothelium-derived hyperpolarising factor (EDHF). These results suggest that endothelium-derived nitric oxide but not EDHF has a major role in modulating vascular tone under these conditions.

Analysis of Variance↗

Comparison of the effects of nitric oxide synthase inhibition and guanylate cyclase inhibition on vascular contraction in vitro and in vivo in the rat.

We have investigated the differences between the nitric oxide synthase inhibitor (NOSI), L-NMMA, and the guanylate cyclase inhibitors (GCI), methylene blue and LY 83583, in their abilities to increase vasoconstrictor responses in vitro and in vivo. In rat small mesenteric arterial rings, 1 h exposure to the NOSI, L-NMMA (100 microM), and the GCI, methylene blue (10 microM), alone or in combination with L-NMMA, caused a significant reduction in the maximum relaxation to ACh in mesenteric arteries pre-contracted with the thromboxane mimetic U46619 (10 microM). Hence, both NOSI and GCI inhibit endothelium-dependent relaxations to ACh in rat small mesenteric artery. However, 1 h exposure to L-NMMA and L-NNA (both 100 microM), but not methylene blue (10 microM), significantly increased the contractile response to U-46619 (10 microM) in rat small mesenteric artery. It was decided to investigate further this difference between NOSI and methylene blue. In rat small mesenteric arterial rings, L-NMMA (10 microM) and LY 83583 (1-10 microM) significantly increased the contractile response to KCl (40 mM) or to noradrenaline (10 microM), when administered during the contraction. However, methylene blue (1-10 microM) increased the contractile response to KCl but not noradrenaline. In rat aortic rings, L-NMMA (100 microM), methylene blue (1-10 microM) and LY 83583 (1-10 microM) significantly increased the contractile response to KCl (40 mM) or to noradrenaline (1 microM). In the pithed rat preparation, L-NMMA (40.3 micromol kg(-1), i.v.) significantly increased the pressor response both to bolus injection of noradrenaline (3.13 nmol kg[-1]) and to spinal pressor nerve stimulation. However, methylene blue (3.13-15.6 micromol kg[-1]) or LY 83583 (4.0-40.0 micromol kg[-1]), failed to affect pressor responses to either NA or pressor nerve stimulation. Hence, there are differences between NOSI and GCI in their abilities to increase vasoconstrictor responses, especially when comparing responses in vitro and in vivo. This suggests that nitric oxide has actions in addition to activation of guanylate cyclase to modulate vasoconstrictor responses, presumably by membrane hyperpolarisation, and that this action may be more important in vivo.

Acetylcholine↗

Functional identification of the active-site nucleophile of the human 85-kDa cytosolic phospholipase A2.

Ser-228 has been shown to be essential for the catalytic activity of the human cytosolic phospholipase A2 (cPLA2). However, its involvement in catalysis has not yet been demonstrated. Using site-directed mutagenesis, active-site directed irreversible inhibitors, and the novel fluorogenic substrate 7-hydroxycoumarinyl gamma-linolenate, evidence is presented to show that the hydroxyl group of Ser-228 is the catalytic nucleophile of cPLA2. Replacement of Ser-228 by Ala, Cys, or Thr resulted in the inability of these mutants to mediate calcium ionophore induced PGE2 production in COS-7 cells cotransfected with the cPLA2 mutants and cyclooxygenase-1. Cell lysates from these transfected cells also had undetectable levels of cPLA2 phospholipid hydrolyase activity as did the affinity column purified S228A and S228C cPLA2 mutants overexpressed in insect cells. The loss in activity was not due to the inability of the mutant enzymes to translocate to the substrate lipid interface since the purified S228C cPLA2 mutant, like the wild type, translocated to the phospholipid membrane in the presence of calcium as judged by fluorescence energy transfer. However, when an activated substrate, 7-hydroxycoumarinyl gamma-linolenate (pKa approximately 7.8 for its leaving group) was used as substrate, there was a significant level of 7-hydroxycoumarin esterase (7-HCEase) activity (about 1% of wild type) associated with the purified S228CC cPLA2 mutant. The S228A cPLA2 mutant was catalytically inactive. Contrary to wild type cPLA2, the 7-HCEase activity of the thio-cPLA2 was not titrated by the irreversible active-site-directed inhibitor methyl arachidonyl fluorophosphonate, but rather titrated by one equivalent of arachidonyl bromomethyl ketone, an arachidonyl binding site directed sulfhydryl reagent. These results are compatible with the hydroxyl of Ser-228 being the catalytic nucleophile of cPLA2 and that cysteine can replace serine as the nucleophile, resulting ina thiol-cPLA2 with significantly reduced catalytic power.

Amino Acid Sequence↗

Human cytosolic phospholipase A2 expressed in insect cells is extensively phosphorylated on Ser-505.

Cytosolic PLA2 (cPLA2) has been implicated in the release of the arachidonic acid utilized in the inflammatory cascade. Phosphorylation of cPLA2 on Ser-505 by MAP kinase in response to agonist treatment, is thought to be one of the mechanisms required for activation of the enzyme in the cell. In order to obtain enough material for enzymological studies as well as to investigate the role of phosphorylation in the activation of cPLA2, the human enzyme was overexpressed in insect cells using a recombinant baculovirus. We report here on the characterization of the phosphorylation state of cPLA2 overexpressed in Sf9 cells. The level of overexpressed cPLA2 was shown to peak between 48 and 60 h post-infection, by this time the phosphorylated enzyme could easily be detected because of its reduced mobility on polyacrylamide gels. The reduced mobility or gel-shift has been shown to be due to phosphorylation of Ser-505. To determine whether this was also the case for insect cell overexpressed cPLA2, Ser-505 was replaced by Ala, and this mutant (cPLA2S505A) was expressed in Sf9 cells. Analysis of the overexpressed cPLA2S505A showed that it migrated only as the lower unshifted cPLA2 band confirming that the baculovirus overexpressed cPLA2 is extensively phosphorylated on Ser-505. Furthermore, treatment of infected Sf9 cells expressing the wild-type cPLA2 with phorbol 12-tetradecanoate 13-acetate (TPA) shifted all of the overexpressed cPLA2 to the phosphorylated Ser-505 form. When infected Sf9 cells were labelled with [32P], in addition to labelling of Ser-505 other sites were also labelled. Both cPLA2 and cPLA2S505A were purified from infected Sf9 cells and the specific activity for each of the enzymes was measured in a phosphatidylcholine vesicle fluorescence assay using 1-(10-pyrenedecanyl)arachidonyl-sn-glycero-3-phosphocholine as substrate. Under these conditions the specific activity of cPLA2 was, 2 mumol/min per mg, whereas cPLA2S505A was 7-fold less active. These findings suggest that Sf9 cells have a mechanism for phosphorylating cPLA2 similar to that found in mammalian cells which probably proceeds through a MAP kinase. Thus, insect cell overexpressed cPLA2 is a very good source for the Ser-505 phosphorylated enzyme.

Animals↗

Effect of thermal injury and sepsis on neutrophil function.

Burn injury and sepsis have been repeatedly demonstrated to impair the function of circulating (blood) neutrophils. As a result of the difficulty in harvesting and purifying neutrophils from the burn wound, there have been minimal investigations to date on the effect of burn injury and sepsis on the function of neutrophils which have reached the wound. We utilized a sponge matrix model in order to obtain neutrophils from burned and burned-infected rats. Despite having a higher concentration of neutrophils in the blood, both the burned and burned-infected rats were noted to have a decreased number of neutrophils infiltrating the sponge compared with the controls (1.91 +/- 0.30 x 10(6), 2.31 +/- 0.47 x 10(6), and 4.82 +/- 0.64 x 10(6) neutrophils per sponge, respectively). Blood neutrophils from both the burned and burned-infected rats had a greater chemiluminescence capacity than neutrophils from the control group (p < 0.0001). This enhanced capacity was not present with sponge neutrophils obtained from the burned-infected group. The diminished capacity may have been the result of a decreased concentration of prostaglandin E in the sponge fluid of the burned-infected rats compared with that of the burned or control rats (52 +/- 9, 135 +/- 15, and 114 +/- 13 pg/mL of sponge fluid, respectively).

Animals↗

Iatrogenic ureteric injuries.

Damage to the lower ureters during pelvic surgery is a serious and well-recognised complication. This iatrogenic injury, when undetected intra-operatively, continues to give rise to significant patient morbidity. In 1987, this Department was referred 18 cases of iatrogenic ureteric injuries. 16 patients were from gynaecologic surgery and 2 patients were from general surgery. Only 4 cases (24%) were detected and referred intra-operatively. 13 patients presented post-operatively with various symptoms viz., anuria, loin pain and urinary leak per vagina. Good recovery of urinary function was achieved in all cases after urological intervention, usually by ureteric re-implantation.

Female↗