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F H Mourad

Publications and source records attributed to F H Mourad.

At least 19 recordsLinked to original sources
PubMed2003

Interplay between nitric oxide and vasoactive intestinal polypeptide in inducing fluid secretion in rat jejunum.

Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) interact in the regulation of neuromuscular function in the gut. They are also potent intestinal secretogogues that coexist in the enteric nervous system. The aims of this study were: (1) to investigate the interaction between NO and VIP in inducing fluid secretion in the rat jejunum, and (2) to determine whether the NO effect on intestinal fluid movement is neurally mediated. The single pass perfusion technique was used to study fluid movement in a 25 cm segment of rat jejunum in vivo. A solution containing 20 mM L-arginine, a NO precursor, was perfused into the segment. The effect of the NO synthase inhibitors (L-NAME and L-nitroindazole (L-NI)) and the VIP antagonist ([4Cl-D-Phe6,Leu17]VIP (VIPa)) on L-arginine-induced changes in fluid movement, expressed as microl min(-1) (g dry intestinal weight)(-1), was determined. In addition, the effect of neuronal blockade by tetrodotoxin (TTX) and ablation of the myenteric plexus by benzalkonium chloride (BAC) was studied. In parallel groups of rats, the effect of L-NAME and L-NI on VIP-induced intestinal fluid secretion was also examined. Basal fluid absorption in control rats was (median (interquartile range)) 65 (45-78). L-Arginine induced a significant fluid secretion (-14 (-20 to -5); P<0.01). This effect was reversed completely by L-NAME (60 (36-65); P<0.01) and L-NI (46 (39-75); P<0.01) and partially by VIPa (37 (14-47); P<0.01). TTX and BAC partially inhibited the effect of L-arginine (22 (15-32) and 15 (10-26), respectively; P<0.05). The effect of VIP on fluid movement (-23 (-26 to -14)) was partially reversed by L-NAME (24 (8.4-35.5); P<0.01) and L-NI (29 (4-44); P<0.01). The inhibition of VIP or NO synthase prevented L-arginine- and VIP-induced intestinal fluid secretion through a neural mechanism. The data suggest that NO enhances the release of VIP from nerve terminals and vice versa. Subsequently, each potentiates the other's effect in inducing intestinal fluid secretion.

Animals↗
PubMed2002

Effect of oral iron chelation therapy with deferiprone (L1) on the psychosocial status of thalassaemia patients.

Beta-thalassemia requires life-long treatment, including regular blood transfusion and daily iron chelation by desferrioxamine, which places considerable burden on the social and psychological life of patients. It is expected that oral chelation therapy, which is easier to administer, would improve their psychosocial status. In this sutdy, interviews were conducted with a series of 44 patients recently placed on oral chelation therapy to evaluate their reactions to the new treatment. Eighty-six per cent of patients complied better with the oral chelation therapy. Fifty per cent of patients mentioned that relief from the desferrioxamine pump was the major improvement, while 47% felt psychologically better. Fifty per cent of patients noted improvements in their relationships, while 63% noted increased social activities. Evaluation of a larger sample of patients over a longer period of time is needed in order to confirm the favourable results obtained in this study.

Adolescent↗
PubMed2001

Experimental colitis decreases rat jejunal amino acid absorption: role of capsaicin sensitive primary afferents.

Ulcerative colitis and experimental colitis are known to be associated with functional and structural abnormalities of the small intestine. The aim of this study was to determine whether experimental colitis in the rat has any effect on jejunal amino acid absorption and to investigate the neural mechanisms involved. In Sprague Dawley rats, colitis was induced by intracolonic administration of 0.1 ml of 6% iodoacetamide. Alanine absorption in the jejunum was measured using the single pass intraluminal perfusion technique in vivo and the three-compartment model in vitro. Experiments were done in normal and sham treated rats, as well as in rats that underwent neonatal capsaicin treatment, adult capsaicin treatment, or subdiaphragmatic vagotomy. Colitis was more severe in rats subjected to neonatal or adult capsaicin treatment, but was not affected by subdiaphragmatic vagotomy. In rats with colitis, jejunal alanine absorption was reduced by 2% (P>0.05), 28%, 40%, and 18% (P<0.001) at 1, 1.5, 2, and 3 days post rectal iodoacetamide administration. A rebound increase of 12% above baseline was noted at 4 days (P<0.05). Similar results were noted in vitro. In rats that received two consecutive injections of iodoacetamide, the decrease in jejunal alanine absorption occurred earlier, was more severe, and persisted for more than 30 days. Neonatal as well as adult capsaicin treatment aggravated both the colitis and the decrease in jejunal alanine absorption. On the other hand, subdiaphragmatic vagotomy attenuated the decrease in jejunal alanine absorption, but had no significant effect on colitis severity. It is concluded that iodoacetamide induced colitis impairs jejunal amino acid absorption and that this effect involves vagal efferents as well as capsaicin sensitive primary afferents.

Afferent Pathways↗
PubMed2001

Panniculitis and arthritis as the presenting manifestation of chronic pancreatitis.

Although rare, panniculitis and polyarthritis can be the presenting manifestations of pancreatitis. Early recognition of this triad is critical because of the high mortality rate from pancreatic disease when the diagnosis is delayed. We report a patient with chronic alcohol intake whose sole presentation was severe polyarthritis and skin lesions secondary to chronic pancreatitis associated with extra pancreatic pseudocyst. Both arthritis and skin lesions disappeared after partial pancreatectomy and pancreatic stent insertion for a pancreatic duct stricture.

Arthritis↗
PubMed2001

Inferior vena cava obstruction in Budd-Chiari syndrome: successful treatment by radiological stenting followed by a portosystemic shunt.

Surgical decompression by a portosystemic shunt in Budd-Chiari syndrome depends on the caval state. Obstruction of the inferior vena cava (IVC) precludes such an operation due to the risk of reduced blood flow across the shunt and subsequent thrombosis. Similar risks are encountered in more complicated operations such as mesoatrial shunt. We report a patient with Budd-Chiari syndrome in whom obstruction of the intrahepatic IVC by a hypertrophied caudate lobe of the liver precluded the construction of a standard portocaval shunt. A two-step procedure with preoperative radiological stenting of the narrowed IVC followed by a portocaval shunt was successfully performed. This is the fifth case reported in the literature of such an approach.

Adult↗
PubMed2000

Common bile duct obstruction secondary to a balloon separated from a Fogarty vascular embolectomy catheter during laparoscopic cholecystectomy.

Laparoscopic instrumentation of the common bile duct (CBD) via the transcystic route or through direct choledochotomy seems to be safe, but in rare cases, complications such as pancreatitis, bile duct damage, and hemorrhage from cystic artery may occur. We report an unusual complication with this approach. A 62-year-old man with gallbladder stones presented with obstructive jaundice, mild pancreatitis, and a dilated CBD. He underwent laparoscopic cholecystectomy with an intraoperative cholangiogram through the cystic duct. A small stone seen in the CBD was removed using a 6-Fr vascular Fogarty catheter. Two days later, he became jaundiced again with a rising bilirubin. An endoscopic retrograde cholangiogram showed a 1.5-cm round filling defect floating in a dilated CBD. A sphincterotomy was performed, and a balloon catheter was inflated proximally and pulled down. To our surprise, the filling defect was a crystal clear object, which we finally realized was a fully inflated Fogarty catheter balloon. The balloon spontaneously deflated while being caught with a basket. Surgeons should be aware of this possible complication, and every effort should be made to verify that the balloon still is in place after removal of the embolectomy catheter. Whether vascular embolectomy catheter balloons are appropriate for stone removal or more rigid balloons should be used needs further evaluation.

Catheterization↗
PubMed2000

Ticlopidine-induced aplastic anemia and quick recovery with G-CSF: case report and literature review.

We report here a case of ticlopidine-induced aplastic anemia that responded to G-CSF and review the literature. An 83-year-old woman was started on ticlopidine for coronary artery disease after an episode of upper gastrointestinal bleeding secondary to aspirin. She developed aplastic anemia seven weeks after initiation of ticlopidine. She was hospitalised and received empiric antibiotic therapy and granulocyte colony stimulating factor (G-CSF). Her bone marrow started to recover quickly, and white blood cell and platelet counts returned to normal within three weeks. A review of medical literature revealed 20 similar cases of ticlopidine-induced aplastic anemia resulting in death in seven cases. G-CSF has been used previously with variable success. Ticlopidine is associated with serious, sometimes fatal hematological side effects. This risk should be seriously taken into consideration when prescribing ticlopidine. G-CSF may be helpful in the treatment of ticlopidine-induced aplastic anemia.

Aged↗
PubMed2000

Protective effect of the nitric oxide donor molsidomine on indomethacin and aspirin-induced gastric injury in rats.

OBJECTIVE: To study the effect of the nitric oxide donor, molsidomine, on gastric and duodenal injury induced by indomethacin and aspirin. METHODS: Sprague-Dawley rats weighing 180-200 g were used after 24 h fasting. Indomethacin (5 mg/kg) was given subcutaneously as a single dose and followed by multiple injections of histamine. Molsidomine (0.05 mg/kg) or distilled water was given by gavage 30 min before indomethacin and repeated at 3 h intervals for two doses. Rats were killed 2 h after the last dose of molsidomine. Aspirin (500 mg/kg) was given by gavage and repeated 2.5 h later. Molsidomine or distilled water was given 30 min before the initial aspirin dose and repeated after 2 h. Animals were killed 2.5 h after the second dose of aspirin. The severity of the gastric mucosal damage was graded from 0 to 3, and the duodenal bulb ulcer surface area calculated by two independent observers using a dissecting microscope. RESULTS: Indomethacin and aspirin resulted in significant gastric mucosal damage with median scores of 2 (interquartile ranges 1.4-3, n = 16 and 2-3, n = 10, respectively). Molsidomine significantly ameliorated indomethacin- and aspirin-induced damage with median scores of 1 (interquartile ranges 0.5-1.5, n = 19 and 0.6-1.9, n = 10, respectively; P<0.008 and P<0.02, respectively (Mann-Whitney Utest)). Molsidomine had no effect on duodenal bulb ulcerations caused by indomethacin. CONCLUSION: Oral molsidomine has a protective effect on gastric mucosa against damage induced by ulcerogenic agents. This could have an important clinical benefit, especially in cardiac patients taking aspirin in addition to a nitric oxide donor such as molsidomine.

Administration, Oral↗
PubMed2000

Effect of vasoactive intestinal polypeptide (VIP) antagonism on rat jejunal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.

BACKGROUND: The enteric nervous system is important in the pathophysiology of intestinal fluid secretion induced by cholera toxin (CT), Escherichia coli heat labile (LT), and heat stable (STa) toxins. The neurotransmitters involved are not fully elucidated. Vasoactive intestinal polypeptide (VIP), a potent intestinal secretagogue present in the enteric nervous system, is increased after exposure of the cat intestine to CT. Whether VIP is involved in the pathogenesis of cholera and other toxins in not known. AIM: To study in vivo the effect of VIP antagonism on jejunal fluid secretion induced by CT, LT, and STa. METHODS: CT, LT (25 microg), or 0.9% NaCl was instilled in an isolated 25 cm segment of rat jejunum, and the VIP antagonist (VIPa) [4Cl-D-Phe(6), Leu(17)]-VIP (0.2 or 2 microg/kg/min) or 0.9% NaCl was given intravenously. Two hours later, single pass in vivo jejunal perfusion was performed to assess fluid movement. In STa experiments, intravenous VIPa or 0.9% NaCl was given and 30 minutes later the jejunal segment was perfused with a solution containing STa 200 microg/l. RESULTS: VIPa had no effect on basal intestinal fluid absorption. CT induced net fluid secretion (median -68 microl/min/g dry intestinal weight (interquartile range -80 to -56)) which was dose dependently reversed by VIPa (6.2 (-16 to 34) and 29 (17 to 42); p<0.01). Similarly, LT induced secretion (-63 (-73 to -30)) was attenuated by VIPa (0.2 microg/kg/min) (-15 (-24 to -1); p<0.01) and totally reversed to normal levels by VIPa (2 microg/kg/min) (37 (28-56); p<0. 01 compared with LT and not significant compared with normal controls). STa induced secretion (-17 (-19 to -2)) was also reversed by VIPa (12 (9-23) and 14 (0-26); p<0.01). CONCLUSION: VIP plays an important role in CT, LT, and STa induced intestinal secretion and may be the final putative neurotransmitter in the pathophysiology of these toxins.

Animals↗
PubMed1999

Proabsorptive and prosecretory roles for nitric oxide in cholera toxin induced secretion.

BACKGROUND: Cholera toxin causes small intestinal hypersecretion by inducing a coordinated response from enterocytes, enterochromaffin cells, enteric neurones, and the vascular supply. Nitric oxide has been implicated in the function of these separate components. AIMS: To explore the role of nitric oxide in the totality of cholera toxin induced secretion in vivo. METHODS: One group of adult male Wistar rats was treated with the nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME; subcutaneously or intraluminally), NG-methyl-L-arginine (L-NMA), or 7-nitroindazole. A second group of rats was treated with L-arginine (intraperitoneally or intraluminally) or D-arginine. The small intestine was isolated between two cannulae and instilled with 75 microg cholera toxin or saline for two hours. Small intestinal perfusion of a plasma electrolyte solution containing [14C]-PEG was undertaken to determine net water and electrolyte movement. After the experiment macroscopic and microscopic intestinal appearances were noted and jejunal 5-hydroxytryptamine concentrations were determined. RESULTS: Both L-arginine and L-NAME induced secretion in the basal state, but only when administered intraluminally. Systemically applied L-NAME caused a dose dependent reduction in cholera toxin induced secretion. This was paralleled by L-NMA but not by 7-nitroindazole or by intraluminally applied L-NAME. Systemically applied L-NAME caused notable cyanosis of the intestine, consistent with mesenteric ischaemia, but no microscopic abnormalities. Systemically applied L-arginine but not D-arginine also reduced cholera toxin induced secretion and inhibited 5-hydroxytryptamine release. CONCLUSION: Nitric oxide has a duality of roles in cholera toxin induced secretion, acting both as an absorbagogue and a secretagogue. Its mechanisms of action include the maintenance of mucosal perfusion and enterochromaffin cell stabilisation.

Animals↗
PubMed1999

Cisplatin impairs fluid and electrolyte absorption in rat small intestine: a role for 5-hydroxytryptamine.

BACKGROUND: The antineoplastic drug cisplatin has been widely used for the treatment of cancer in humans but its use has been limited by vomiting and diarrhoea. Cisplatin releases 5-hydroxytryptamine into the gut which is thought to be the major mediator of cisplatin induced vomiting. AIM: To determine whether cisplatin affects fluid and electrolyte transport in rat jejunum and whether this change can be modulated by the 5-hydroxytryptamine3 receptor antagonist, ondansetron. METHODS: Jejunal perfusion in rats in vivo was performed one hour after intraperitoneal cisplatin (5 and 10 mg/kg) administration. The effect of pretreatment with subcutaneous ondansetron 300 microg/kg was investigated. RESULTS: Median net fluid absorption after cisplatin 10 mg/kg (67 microl/min/g dry intestinal weight (interquartile range 46 to 100); n = 15) was reduced compared with controls (120 (107 to 151) microl/min/g; n = 13; p<0.001). Ondansetron reversed the impairment of jejunal fluid absorption produced by cisplatin to normal (161 (130 to 176) microl/min/g; n = 11; p<0.001). Electrolyte movement paralleled fluid movement. Jejunal histological examination of sections from cisplatin treated animals showed villus damage, which was not prevented by pretreatment with ondansetron. CONCLUSION: These findings suggest that diarrhoea during cisplatin therapy may be due to altered fluid transport in the small bowel. The reversal of fluid transport to normal in the presence of a 5-hydroxytryptamine3 receptor antagonist suggests that 5-hydroxytryptamine is a local mediator in the small intestine.

Animals↗
PubMed1999

Adrenoleukodystrophy associated with vitiligo and ulcerative colitis.

Adrenoleukodystrophy (ALD) is an X-linked inherited disorder of lipid metabolism usually presenting in childhood or early adolescence. It is a progressive disease with symptoms of adrenal insufficiency and central nervous system demyelination. The pathology results from the accumulation of very long-chain fatty acids and an inflammatory reaction in the brain white matter. We report a case of ALD associated with adrenal insufficiency and two autoimmune diseases: vitiligo and ulcerative colitis.

Addison Disease↗
PubMed1999

Efficacy and side effects of deferiprone (L1) in thalassemia patients not compliant with desferrioxamine.

We report our experience with deferiprone (L1) (DFP) in 17 thalassemic patients, followed up in one center in Lebanon, who were initially on desferrioxamine and then shifted to DFP at a dose of 50-75 mg/kg/day as the sole chelator during 1-year follow-up. All 17 patients were compliant with therapy and there was no change in physical examination over the study period. Eight patients (47.1%) were positive for hepatitis C virus (HCV) antibodies. Urinary iron excretion was 21.8 +/- 14 mg/24 h (mean +/- SD) 1 week after starting DFP and dropped 12 months later to 13 +/- 7.4 mg/24 h (p = 0.009, paired t test). The initial serum ferritin level was 3,863 +/- 2,344 microg/l which dropped to 3,179 +/- 2,075 at 12 months after starting therapy (p = 0.07). HCV-negative patients as a group exhibited a significant decrease in serum ferritin after 6 and 12 months of DFP therapy (3,942 +/- 2,739 vs. 2,341 +/- 1,179 and 2,681 +/- 1,519 microg/l; p < 0.03 and p < 0.05, respectively). The most frequent side effects were joint pain, stiffness or swelling in 6 patients (35.3%), and nausea in 7 patients (41.2%), but these were well tolerated and did not require stopping treatment.

Adolescent↗
PubMed1998

Crucial role for 5-HT in cholera toxin but not Escherichia coli heat-labile enterotoxin-intestinal secretion in rats.

BACKGROUND & AIMS: Many consider cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) to be functionally identical. Both increase intracellular adenosine 3',5'-cyclic monophosphate concentration; however, differences between the two and the severity of the diseases they cause have been reported. The secretagogue 5-hydroxytryptamine (5-HT) is implicated in CT-induced secretion, but its role in LT-induced secretion is unclear. We tested the hypothesis that LT fails to recruit 5-HT in its secretory processes. METHODS: In vivo small intestinal perfusions were undertaken in adult male Wistar rats after incubation with equipotent doses of CT or LT, or saline. Small intestinal 5-HT release and the effect on net small intestinal water and electrolyte transport of (1) pharmacological depletion of 5-HT; (2) blockade of 5-HT type 2, 3, and 4 receptors; and (3) pretreatment with lidocaine, hexamethonium, and atropine were determined. RESULTS: CT- but not LT-induced secretion was accompanied by 5-HT release, reduced by 5-HT depletion, and inhibited by each 5-HT antagonist. By contrast, lidocaine and hexamethonium inhibited secretion induced by both toxins. CONCLUSIONS: LT induces secretion without recruiting a 5-HT-dependent cascade. This may account for differences in clinical severity of the diseases CT and LT cause and has implications for the development of antisecretory therapies.

Animals↗