bluuebunny/crossref_metadata_2025 huggingface dataset:
Barium and 4-Aminopyridine Inhibit Flow-Initiated Endothelium-Independent Relaxation
Authors: Xie Hui , Bevan John A.
Published: April 2003

Although much is known about the underlying mechanism of endothelium-dependent flow-induced vasorelaxation, the cellular processes responsible for the endothelium-independent flow-induced relaxation observed in some vessels is unknown. As there is evidence for the participation of K+ channels in the endothelium-dependent response, the present study was designed to determine whether such channels are involved in the endothelium-independent response and if so, which ones. We examined the effects of various selective K+ channel blockers on endothelium-independent relaxation initiated by intraluminal flow (10–80 µl/min), and by an endothelium-independent vasodilator sodium nitroprusside (SNP, 1 nmol/l to 3 µmol/l) in segments of the rabbit facial vein under isometric conditions. Flow-initiated relaxation was abolished by 25 and 40 mmol/l K+ as well as 10 mmol/l tetraethylammonium (TEA), significantly inhibited by 100 µmol/l Ba2+, 5 mmol/l Cs+ and 7.5 mmol/l 4-aminopyridine (4-AP), but unaffected by 5 µmol/l glibenclamide and 50 nmol/l charybdotoxin. Relaxation induced by SNP was reduced by 7.5 mmol/l 4-AP, but not by any of the above drugs in their listed concentrations. The inhibitory effect of 100 µmol/l Ba2+ on the relaxation caused by low concentrations of K+ (15–20 mmol/l) supports the presence of inward rectifier K+ channels in the vascular smooth muscle cells of this tissue. We speculate that endothelium-independent flow-initiated relaxation of the rabbit facial vein may be associated with activation of inward rectifier and voltage-dependent K+ channels. The latter may also contribute to the vasorelaxation initiated by SNP.
Angiostatin Diminishes Activation of the Mitogen-Activated Protein Kinases ERK-1 and ERK-2 in Human Dermal Microvascular Endothelial Cells
Authors: Redlitz Alexander , Daum Guenter , Sage E.Helene
Published: April 2003

Angiostatin is an endogenous inhibitor of angiogenesis that was isolated from tumor-bearing mice. It has been established that angiostatin inhibits endothelial cell proliferation; however, the underlying mechanisms remain to be elucidated. Here we report that angiostatin reduces transiently the phosphorylation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular cells, but not in human vascular smooth muscle cells or human dermal fibroblasts. We demonstrate that angiostatin diminishes ERK activation by basic fibroblast growth factor and vascular endothelial growth factor. Dephosphorylation of ERK and other tyrosine-phosphorylated proteins was blocked by pretreatment of the cells with sodium meta-vanadate, an inhibitor of protein tyrosine phosphatases, indicating that angiostatin signaling may require the activity of a tyrosine phosphatase. Concentrations of angiostatin that inhibited ERK activation also inhibited basic fibroblast growth factor-stimulated collagen gel invasion by endothelial cells, but did not affect endothelial cell proliferation. We thus show that angiostatin inhibits primarily the invasion of endothelial cells and exerts minimal (if any) effects on their proliferation. Invasion is a process that involves proteolysis, adhesion and migration, all of which have been linked to ERK signaling.
Leukocyte Sequestration in Pulmonary Microvessels and Lung Injury following Systemic Complement Activation in Rabbits
Authors: Kuhnle Gerhard E.H. , Kiefmann Rainer , Sckell Axel , Kuebler Wolfgang M. , Groh Joachim , Goetz Alwin E.
Published: April 2003

Inflammatory reactions are associated with sequestration of leukocytes in the lung. Complement activation leads to accumulation of leukocytes in alveolar septa and alveoli, to lung edema and hemorrhage. Although in organs other than the lung leukocytes interact with the vascular endothelium only in postcapillary venules, alveolar capillaries are considered to be the site of leukocyte sequestration in the lung. However, pulmonary venules and arterioles have not been investigated systematically after complement activation so far. A closed thoracic window was implanted in anesthetized rabbits; leukocytes and red blood cells were stained, and the movement of these cells was measured in superficial pulmonary arterioles, venules and alveolar capillaries using fluorescence video microscopy before and 30 and 60 min after infusion of cobra venom factor (CVF). Erythrocyte velocity and macrohemodynamic conditions did not change after CVF infusion and were not different from the sham-treated controls. The number of sticking leukocytes increased significantly compared to baseline and control: by 150% in arterioles and in venules and by 740% in alveolar capillaries within 60 min after CVF infusion. The width of alveolar septa in vivo was significantly enlarged after CVF infusion, indicating interstitial pulmonary edema. At the end of the experiments, myeloperoxidase activity was higher in the CVF group, showing leukocyte sequestration in the whole organ. It is concluded that complement activation by CVF induces leukocyte sequestration in lung arterioles, venules and alveolar capillaries and leads to mild lung injury.
Characterization of Major Phosphoproteins in the cGMP-Mediated Protein Phosphorylation System of Vascular Smooth Muscle Membranes
Authors: Fujita Satoru , Yoshida Yutaka , Islam Omedul , Ma Xin , Fujioka Masaki , Ito Masaaki , Nakano Takeshi , Aizawa Yoshifusa , Imai Shoichi , Higuchi Hiroshi
Published: April 2003

G₀ (215–250 kD) and G1 (120–140 kD), the unidentified major phosphoproteins in the cGMP-mediated protein phosphorylation system of vascular smooth muscle membranes, were compared for biochemical and immunological properties with the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R, 240 kD) and the myosin-binding subunit (MBS, 138 kD) of myosin phosphatase, both of them substrates for cGMP-dependent protein kinase. Two microsomal proteins that were immunoreactive with antibodies to InsP3R and MBS were detected, and comigrated with G₀ and G1, respectively, on SDS-PAGE. When thiophosphorylated G₀ and G1 were subjected to immunoprecipitation, MBS antibody induced the precipitation of a 138-kD phosphoprotein, but did not significantly affect the amount of G1 remaining in the supernatant, while InsP3R antibody precipitated G₀ almost completely. Unexpectedly, InsP3R antibody coprecipitated a large portion of G1, which did not cross-react with either antibody to MBS or InsP3R. Just like InsP3R, G₀ bound to the calmodulin column in a Ca2+-dependent manner, and, again, a large portion of G1 was copurified with G₀. These results suggest that G₀ is identical to InsP3R, while G1 consists of several phosphoproteins, including the 138-kD protein associated with InsP3R as a major component. MBS is not G1 or may represent only a minor component of it.
Aquaporin-1 Is Expressed by Vascular Smooth Muscle Cells and Mediates Rapid Water Transport across Vascular Cell Membranes
Authors: Shanahan Catherine M. , Connolly Derek L. , Tyson Kerry L. , Cary Nathaniel R.B. , Osbourn Jane K. , Agre Peter , Weissberg Peter L.
Published: April 2003

The aquaporins are a rapidly expanding family of highly conserved proteins which function as transmembrane water channels. We have previously shown that the gene for aquaporin-1 (AQP-1) is expressed in rat, aortic vascular smooth muscle cells (VSMCs) implying a specific role for AQP-1 in vascular function. In this study we set out to document the expression of AQP-1 in human arteries and found mRNA and protein in normal endothelial and VSMCs of human arteries and capillaries and in a subset of VSMCs in human atherosclerotic plaques. Secondly, we examined the regulation of AQP-1 gene expression during vascular development and following vascular injury. Studies in the rat demonstrated that AQP-1 mRNA is induced in the neonatal aorta at week 2 of postnatal development and that the protein is present in neointimal VSMCs following balloon injury. Finally, by measuring the rate of change in cell size induced by changes in external osmolarity and demonstrating that water transport can be inhibited with mercuric chloride, we show that AQP-1 is responsible for water transport across human VSMC membranes. Thus, this study provides evidence for a hitherto unrecognised role for aquaporins in mediating rapid water transport across human VSMC membranes. By analogy with other tissues, these data argue for an important role for AQP-1 in regulating transcellular fluid flow and tissue hydration.
Human Vascular Reactivity and Polymorphisms of the Angiotensin-Converting Enzyme and the Angiotensin Type 1 Receptor Genes
Authors: Steeds R.P. , Toole L.O. , Channer K.S. , Morice A.H.
Published: April 2003

The D allele of the insertion (I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the C allele of the A1166-C polymorphism in the angiotensin II type 1 receptor (AGT1R) gene have been associated with altered vascular structure and with an increased risk of myocardial infarction. The aim of this study was to determine whether differences in vascular function could be demonstrated to link the previously described changes in structure and the disease outcome. 70 subjects were recruited at random from patients undergoing colonic resection, resistance arteries were excised and were mounted in a small vessel wire myograph. Vasomotor responses to potassium chloride, noradrenaline, prostaglandin F2α, angiotensin I, angiotensin II, acetylcholine and substance P were performed in 30 subjects. Genotype was established in a blinded fashion after completion of myography. To exclude the possibility of masking of genetic influence by non-ACE conversion of angiotensin I, vasomotor responses were then performed to proline10-angiotensin I in a further 30 subjects and to angiotensin I in the presence of chymostatin in a further 10 subjects. No significant effect of the I/D polymorphism of the ACE gene was seen on vasomotor function. The C allele of the AGT1R gene was associated with an increase in sensitivity to prostaglandin F2α but not with alteration to the other vasoactive agents studied. The I/D ACE and A1166-C AGT1 receptor polymorphism do not appear to result in differences in vasomotor function in isolated human mesenteric resistance arterioles in subjects without evidence of underlying hypertensive or cardiovascular disease.
Sensitive Superoxide Detection in Vascular Cells by the New Chemiluminescence Dye L-012
Authors: Sohn Hae-Young , Gloe Torsten , Keller Matthias , Schoenafinger Karl , Pohl Ulrich
Published: April 2003

The detection superoxide production in vascular cells is usually limited by a low sensitivity of available assays. We tested the applicability of the luminol derivate L-012 [8-amino-5-chloro-7-phenylpyridol[3,4-d]pyridazine-1,4(2H,3H)dione] to measure superoxide production in cultured endothelial cells (human umbilical vein endothelial cells) and rat aortic segments. Following stimulation with the protein kinase stimulator phorbol 12-myristate 13-acetate (PMA, 1 μM) there was an 2.8-fold increase of L-012 chemiluminescence, whereas incubation with angiotensin II (100 nM) did not result in a measurable increase. Addition of vanadate (100 μM) considerably increased the chemiluminescence (up to 17-fold) after PMA and made possible the detection of an enhanced superoxide production after stimulation with angiotensin II (by 1.7-fold). This was due to a ∼9-fold increase in signal intensity of L-012 in the presence of vanadate. Prolonged incubation with vanadate also led to a tyrosine phosphorylation-dependent increase in superoxide formation which was predominantly produced by an NAD(P)H oxidase. Short-term vanadate-enhanced L-012 chemiluminescence represents a highly sensitive assay making it possible to detect small changes of superoxide formation in intact vascular cells.
Contractility and Endothelium-Dependent Relaxation of Resistance Vessels in Polycystic Kidney Disease Rats
Authors: Wang Dan , Iversen Jens , Strandgaard Svend
Published: April 2003

Hypertension and vascular disease are common complications in autosomal-dominant polycystic kidney disease (ADPKD). The role of changes in morphology and reactivity of resistance vessels in this disease have not previously been studied. Mesenteric resistance arteries were dissected from 8- to 14-week-old heterozygous Han:SPRD polycystic kidney disease (PKD) rats, homozygous normal Han:SPRD littermates (HSPRD) and Sprague-Dawley rats (SD). The morphology, noradrenaline (NA) contractility, endothelium-dependent acetylcholine (ACh) relaxation before and after incubation with LG-nitro-L-arginine methyl ester (L-NAME), and endothelium-independent 3-morphollino-sydnonimine (SIN-1) relaxation were studied with the Mulvany-Halpern myograph. Blood pressure and morphology of vessels were the same in all groups of rats, apart from a slightly higher media/lumen ratio in heterozygous PKD rats (p < 0.05). Active wall tension and contractile sensitivity to NA were higher in both heterozygous PKD rats and HSPRD than SD rats (p < 0.05). The maximum endothelium-dependent relaxation rate was markedly decreased in heterozygous PKD (19 ± 9%) and HSPRD (34 ± 12%) compared to SD rats (75 ± 11%) (p < 0.05). After incubation with L-NAME, ACh-induced relaxation was significantly attenuated in SD rats, less attenuated in HSPRD, and not significantly changed in heterozygous PKD rats. SIN-1-induced endothelium-independent relaxation was similar in all three groups. In conclusion, hyperreactivity to NA and impaired endothelium-dependent relaxation were present in resistance vessels from Han:SPRD rats, especially in animals with PKD. These abnormalities in resistance vessels from PKD rats may be important for the development of hypertension and vascular disease.
The Mitogenic Effect of 17β-Estradiol on in vitro Endothelial Cell Proliferation and on in vivo Reendothelialization Are Both Dependent on Vascular Endothelial Growth Factor
Authors: Concina P. , Sordello S. , Barbacanne M.A. , Elhage R. , Pieraggi M.T. , Fournial G. , Plouet J. , Bayard F. , Arnal J.F.
Published: April 2003

In addition to their actions on reproductive function, estrogens have important effects on endothelial cells. The present study was designed to evaluate the mechanism(s) by which 17β-estradiol (E2) promotes endothelial cell proliferation. The potential involvement of vascular endothelial growth factor (VEGF) was investigated by the coadministration of polyclonal anti-VEGF antibody. First, the effect of E2 on the proliferation of cultured foetal bovine aortic endothelial cells (FBAEC) was studied. E2 stimulated this proliferation with an EC50 between 10–11 and 10–10 M and this effect was inhibited by the anti-VEGF antibody. The effect of a physiological dose of E2 was then studied in the rat model of carotid injury. After deendothelializing balloon injury, reendothelialization of the denuded surface may influence the growth of the underlying smooth muscle cells. Male Sprague-Dawley rats were castrated and then received E2 from subcutaneously implanted pellets that released 3.2 μg/kg/day. Endothelial regrowth (Evans blue staining) and neointimal thickening were evaluated 2 weeks after the carotid injury. In comparison to the placebo group, E2 increased the extent of reendothelialization (p = 0.0002) and reduced neointimal thickening (p = 0.0007). Anti-VEGF antibody abolished the effect of E2 on reendothelialization as well as on neointimal thickening. Thoracic aorta VEGF content was increased in E2-treated rats compared to control rats. In conclusion, the present study demonstrates that E2 increases endothelial cell proliferation in vitro and reendothelialization in vivo by means of a mechanism dependent on endogenous VEGF. This effect could contribute to the antiatherogenic effect of a physiological dose of E2.
The Interaction between Oxidised Chylomicron Remnants and the Aorta of Rats Fed a Normocholesterolaemic or Hypercholesterolaemic Diet
Authors: Grieve David J. , Avella Michael A. , Elliott Jonathan , Botham Kathleen M.
Published: April 2003

The effects of oxidised chylomicron remnants on endothelium-dependent relaxation and lipoprotein uptake were studied in both the normocholesterolaemic and hypercholesterolaemic rat aorta in vitro. Incubation of aortic rings taken from normocholesterolaemic animals with oxidised (by treatment with copper sulphate) chylomicron remnant particles resulted in a reduction in both vessel sensitivity and maximum percent relaxation in response to carbachol (CCh) and ATP, without affecting responses to A23187 and S-nitroso-N-acetylpenicillamine (SNAP). Studies comparing control vessels and those taken from fat-fed rats confirmed that hypercholesterolaemia significantly decreased relaxations in response to CCh and potentiated contractions in response to phenylephrine (PE) via a nitric oxide (NO)-dependent mechanism. Perfusion of the aorta of these hypercholesterolaemic rats for 2 h with 125I-labelled oxidised chylomicron remnants showed that significantly greater amounts of lipoprotein became associated with the artery wall, as compared to control normocholesterolaemic animals. However, there was no significant difference in the uptake of native chylomicron remnant particles between control and hypercholesterolaemic vessels. Taken together, the findings of this study suggest that incorporation of lipoproteins of dietary origin into the arterial wall may contribute to endothelial dysfunction and that their contribution may be enhanced by hypercholesterolaemia. These data also support the putative involvement of oxidative modification in the atherosclerotic process, although the presence of oxidised chylomicron remnants in vivo and their role in atherogenesis remains to be established.
Mg2+-Induced Vasodilation in Human Forearm Vasculature Is Inhibited by NG-Monomethyl- L-Arginine but Not by Indometacin
Authors: Dawes Matthew , Ritter James M.
Published: April 2003

We have investigated the mechanism of the vasodilator action of Mg2+ in human forearm resistance vasculature. Venous occlusion plethysmography was used to measure vasodilator responses to Mg2+ infused via the brachial artery in healthy men, and to determine effects on Mg2+ responses of indometacin (an inhibitor of cyclo-oxygenase) and of NG-monomethyl-L-arginine (L-NMMA, an inhibitor of the L-arginine/nitric oxide, L-arg/NO, pathway). Magnesium sulphate infusion (0.05, 0.1, 0.2 mmol·min–1) increased plasma Mg2+ concentration to 1.57 ± 0.16 mmol·l–1 in venous blood from the infused arm at the highest dose. There was a dose-related increase in forearm blood flow in the infused arm to a maximum of 6.37 ± 1.37 ml·min–1·dl forearm–1 at the highest dose corresponding to an increase of 159 ± 25% in blood flow relative to the non-infused arm. There was no tachyphylaxis during a second infusion following a 21-min recovery period. Indometacin had no effect on vasodilator responses to Mg2+, whereas L-NMMA inhibited Mg2+ responses (area under the dose-response curve) by 43 ± 6% (p = 0.0003 by repeated-measures ANOVA). Therefore the L-arg/NO pathway is responsible, in part, for the vasodilator action of Mg2+ in human forearm resistance vasculature.
Haemopoietic Origin of Myofibroblasts Formed in the Peritoneal Cavity in Response to a Foreign Body
Authors: Campbell Julie H. , Efendy Johnny L. , Han Chih-Lu , Girjes Adeeb A. , Campbell Gordon R.
Published: April 2003

This study utilized both in vivo and in vitro techniques to investigate whether cells of bone marrow origin can differentiate into smooth muscle-like cells (myofibroblasts) with contractile filaments and proteins. Female C57BL/6 mice expressing the Ly5.2 antigen on the surface of their haemopoietic cells had four pieces of silastic tubing (3 × 0.5 mm outer diameter) or boiled blood clot (2–3 mm diameter) placed in their peritoneal cavity. After 3, 5, 7 and 14 days (n = 4/group) the implants were removed and those that had remained free-floating were processed for light microscopy, immunohistochemistry and electron microscopy. In the first 3–5 days, rounded cells adhered to the entire surface of the tubing then flattened. These cells stained with fluoresceinated antibodies to Ly5.2 showing that they were derived from haemopoietic cells. By 14 days the cells had become elongated and multilayered in a collagen matrix, forming a thick tissue capsule around the tubing or boiled clot. They contained contractile filaments and stained with antibodies to α-smooth muscle actin but no longer stained for Ly5.2. A separate set of female C57BL/6 Ly5.2 mice were X-irradiated to destroy bone marrow then immediately transfused with 106 nucleated bone marrow cells taken from the femur and tibia of a congenic strain of male mice expressing the Ly5.1 allele. Eight of the female mice with successful engraftment (80–99%) had silastic tubing implanted in the peritoneal cavity. After 14 days, in situ hybridization with Y chromosome probe confirmed the male donor, and thus bone marrow, origin of the elongated cells that formed the capsule. In vitro studies showed that cells of the murine macrophage cell lines RAW 264.7 and J774 express α-smooth muscle actin after exposure to the cytokine γ-interferon in vitro. These data show that bone marrow-derived cells can differentiate into smooth muscle-like cells and raises the possibility that blood-derived cells may contribute to the development of fibro-proliferative vascular diseases such as atherosclerosis.
Effects of the AT1 Antagonist HR 720 in Comparison to Losartan on Stimulated Sympathetic Outflow, Blood Pressure, and Heart Rate in Pithed Spontaneously Hypertensive Rats
Authors: Häuser W. , Dendorfer A. , Nguyen T. , Dominiak P.
Published: April 2003

It has been demonstrated in isolated organs that angiotensin II mediates catecholamine release via presynaptically located AT1 receptor subtypes. In the present study, the relevance of AT1-mediated noradrenaline and adrenaline release in a whole-animal model, which reflects the peripherally sympathetic system (pithed rat), was investigated. Furthermore, the effects of a new AT1 antagonist, HR 720, are demonstrated with respect to its pre- and postsynaptic actions in comparison to the AT1 antagonist losartan. Dose-response curves to angiotensin II of blood pressure show a tenfold higher potency for HR 720 to compete for angiotensin II, thereby decreasing the maximum effects when compared with losartan. The electrically induced sympathetic outflow resulted in a dose-dependent increase after angiotensin II infusions. It could markedly be reduced with both AT1 antagonists, whereby HR 720 again was ten times more potent than losartan. Neither with HR 720 nor with losartan an agonistic activity could be demonstrated. The results indicate an AT1 receptor subtype mediated release of catecholamines in a whole-animal model. HR 720 is ten times more potent than the AT1 antagonist losartan and acts in a noncompetitive manner.
Autosomal Recessive Early-Onset Nephropathy with Progressive Focal Glomerulosclerosis
Authors: Amirlak I. , Al-Gazali L.I.
Published: April 2003

We report an inbred Arab family from Oman with 5 children affected with an early-onset nephropathy and an early progression to renal failure. All patients presented with eyelid swelling, proteinuria and microscopic haematuria associated with growth failure. The patients did not present gross oedema or clinical nephrotic syndrome in spite of massive proteinuria and hypoproteinaemia, and there was no response to steroid. Renal biopsy showed progressive focal glomerulosclerosis in 2 of them and an unusual appearance in the 3rd child with deposition of electron-dense immune complexes in the mesangium and subendothelial position. It may be that this is a new type of nephropathy leading to focal glomerulosclerosis. Mapping the gene for this type of nephrosis should be possible in this family using the concept of homozygosity mapping.
Granulocyte Colony-Stimulating Factor Potentiated Severe Atypical Vincristine-Induced Neuropathy
Authors: Al-Bahar Soad , Pandita Ramesh , Savani Bipin N. , Bavishi Ketan G.
Published: April 2003

We report a patient with acute lymphoblastic leukemia who developed severe atypical neuropathy (SAN), distinct from classical vincristine neuropathy, following the use of vincristine and granulocyte colony-stimulating factor (G-CSF). SAN was characterized by acute onset of severe pain, exquisite tenderness on even light touch and profound motor weakness involving predominantly the lower limbs. The upper limbs were spared. Imaging studies and cerebrospinal fluid examination were normal. Electrophysiological studies showed axonal sensorimotor neuropathy. Potentiation of vincristine-induced neuropathy by G-CSF should be considered when formulating protocols using both these agents, and concomitant use of both the agents should be avoided.
Mental Deficiency and Unstable Bladder in a Case ofMarfan’s Syndrome
Authors: Mavra Milica , Henein Moheb M. , Chadha Geeti , Darne R.D. , Behbehani Jaafar
Published: April 2003

We report a case of Marfan’s syndrome in a 23-year-old Arab man presenting with unstable bladder, and who was also found to have a mental deficiency. Familial occurrence of marfanoid habitus and heart abnormalities were detected. This is the first report of Marfan’s syndrome in a patient from Kuwait and the Gulf region.
Primary Cystic Duct Carcinoma
Authors: El-Sayed M. Afifi , Juma T.H.
Published: April 2003

Primary cystic duct carcinoma is rare. To date only 27 cases have been reported in the English literature, and 17 cases in the Japanese literature. This paper reports another case of primary cystic duct carcinoma. A 70-year-old male presented with signs and symptoms of acute calcular cholecystitis and dilated extrahepatic bile ducts. An ERCP failed technically. An ultrasound-guided aspiration was performed to drain an obstructed gall bladder and an adjacent pyogenic liver abscess. A cholecystogram showed an obstructed cystic duct. On table a tumour was suspected at the junction of the cystic duct and common hepatic duct (CHD). En masse excision of the gall bladder, cystic duct, tumour, part of the CHD and the supraduodenal part of the common bile duct was performed with a Roux-en-Y hepatico-jejunostomy. Histopathologically the tumour fulfills all of Farrar’s criteria for primary cystic duct carcinoma. Our case is of interest since it is the 2nd case to present with Mirrizzi-like syndrome.
Bovine Spongiform Encephalopathy (BSE) – Mad Cow Disease
Authors: Campbell Peter N.
Published: April 2003

The background to the epidemic of bovine spongiform encephalopathy (BSE) among cattle in the United Kingdom is described as the possible origin of the disease and its relationship to scrapie in sheep. Although the epidemic in cattle is virtually over there is evidence of the transmission of the infectious agent to humans to produce a new variant of Creutzfeldt-Jakob disease. The current status of our understanding of the molecular biology of the infectious agent is described as is the evidence in support of the protein-only, prion, hypothesis. Study of the glycoforms of the prions supports the view that BSE has been transmitted to humans.
Systemic and Portal Hemodynamic Response to Propranolol in Patients with Portal Hypertension Due to Hepatitis C Virus
Authors: Koshy Abraham , Al-Nakib Basil , Al-Mufti Siham , Hasan Fuad
Published: April 2003

Objective: Propranolol, a β-adrenergic blocker, has been reported to reduce portal pressure in patients with alcoholic cirrhosis and thereby might be useful in the prophylaxis of variceal bleeding. Since it is not known if the response of patients with portal hypertension due to hepatitis C virus is similar, systemic and portal hemodynamic response to propranolol was evaluated in 10 patients with portal hypertension and hepatitis C virus infection. Methods: Patients were studied before the intravenous infusion of 0.15 mg/kg propranolol, and 30 min after the infusion. Results: Propranolol induced highly significant systemic hemodynamic effects, reducing heart rate from 65 ± 6 to 57 ± 5 (p < 0.0001) and cardiac output from 6.7 ± 1.6 to 5.0 ± 1.1 (liters/min, p < 0.0005). The effect on the pulmonary circulation was a mild increase in diastolic pulmonary artery pressure. Propranolol induced a mild and insignificant decrease in wedged hepatic vein pressure (WHVP), from 32 ± 6 to 29 ± 5 mm Hg, and hepatic venous pressure gradient from 18 ± 3 to 16 ± 5 mm Hg (p > 0.05). Decrease of WHVP of more than 5 mm Hg occurred only in 3 out of 10 patients. Conclusion: It is suggested that propranolol may be useful only in some patients with portal hypertension associated with hepatitis C virus infection.
Comparative Study of Meloxicam and Indomethacin on Ovine Ureteral Motility
Authors: Yousif Mariam H. , Thulesius Olav
Published: April 2003

Objective: To test the potentially toxic urinary tract effects of indomethacin in comparison with a novel COX-2 inhibitor, meloxicam. Method: In vitro experiments were performed using isolated ring segments of sheep ureter mounted in organ-baths. Changes in isometric tension and frequency of rhythmic contractions were assessed in control and lipopolysaccharide (LPS)-treated preparations prior to and after administration of the tested drugs. Results: Sheep ureteral rings displayed reproducible spontaneous rhythmic contractions which were abolished by indomethacin (10–6 M) and not by meloxicam (10–6 M) under control conditions. However, in LPS-treated preparations, to induce COX-2, meloxicam produced a slight inhibitory action. Conclusion: Indomethacin blocks normal motility through inhibition of COX-1, while meloxicam does not interfere with ureteral peristalsis. Meloxicam only exerts a slight inhibition in inflammation-induced preparations due to the specific action as an inhibitor of COX-2. Further studies are needed to evaluate and compare the effects of meloxicam and indomethacin from other measures of effects of COX-1 and COX-2.
Molecular Analysis of the G6PD-Mediterranean Mutation in Kuwait
Authors: D’Souza Brendan , Samilchuk Elena , Al-Awadi Sadika
Published: April 2003

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been reported to be quite common in Kuwait, though neither the underlying biochemical variants nor the mutations involved have ever been analyzed. The 563C→T mutation underlies one of the most common G6PD-deficient variants, G6PDMed. It is observed on two different haplotypes (Mediterranean and Asian), as judged by a 1311C → T polymorphism. The objective of this study was a population and haplotype analysis of the 563C→T mutation in Kuwait. Methods: DNA was extracted from the peripheral blood of 110 unrelated individuals (population group) and 20 family members of G6PDMed-positive probands. The population group comprises native Kuwaitis and Bedouins residing in Kuwait (63 males and 47 females). Detection of both 563C → T and 1311C → T was carried out by using the PCR/RFLP technique. Results: Seven individuals (4 hemizygotes, 2 heterozygotes and 1 homozygote) were identified in the population group, giving a G6PDMed frequency of 0.0509 (0.0635 for males and 0.0425 for females). Haplotype analysis of the G6PDMed chromosomes was informative for all cases except for 1 heterozygous female. Of the 7 unrelated G6PDMed chromosomes from Kuwait, 6 had the Mediterranean and 1 had the Asian haplotype.
Ruptured Hepatoma: Report of 5 Cases in Arabs
Authors: Farghaly Medhat M. , Abdul-Ghaffar Naser Uama , SaadAlmanee Mohammed
Published: April 2003

Objective and Importance: Ruptured hepatic tumours are common among South East Asians. They are rare in whites and in Arabs. Arab cirrhotics who develop acute abdominal pain associated with hypovolaemia and evidence of intra-abdominal bleeding ought to be suspected of ruptured hepatocellular carcinoma. Clinical Presentation: Five cases of ruptured hepatocellular carcinoma in Arabs are reported. All patients had liver cirrhosis, and radical surgery was not possible due to the advanced stage of the tumour. Two patients who underwent common hepatic artery ligation survived for more than 9 months after the acute episode. The other 3 died in the hospital due to liver failure. Conclusion: Hepatic dearterialization was found effective in controlling bleeding from ruptured hepatoma. Other modalities of management such as hepatic artery embolization or intratumoural alcohol injection have been found effective in controlling bleeding.
Anterior Cruciate Ligament Reconstruction by Combined Intra-Articular (K. Lambert) and Extra-Articular Iliotibial Band Tenodesis (MacIntosh; Autologous Grafts)
Authors: Ibrahim Samir Abdul-Razik
Published: April 2003

Objective: To assess the results of anterior cruciate ligament reconstruction in a group of sports players. Methods: A total of 153 sports players were reviewed 70 months (range 39–84 months) after they had anterior cruciate ligaments reconstruction by autologous patellar tendon graft (K. Lambert intra-articular reconstruction) combined with extra-articular tenodesis using iliotibial band (MacIntosh tenodesis). Results: We found all the patients were able to return to their normal active life and 131 atheletes were able to return to full sports activities, while 21 patients were not able to go back to their sports or had to modify their sports activities. The knees were assessed using Lysholm knee score, Shino grading system and clinical examination for anterior drawer, Lachman and pivot shift signs. The mean Lysholm knee score was 94.9 (range 71–100) while Shino grading for 64 knees was very good, for 68 knees good, and 21 knees fair. None of the patients had poor results. Conclusions: Depending on the type and degree of functional instability, we recommend anterior cruciate ligament reconstruction by autologous tendon graft and in all cases, extra-articular procedures are required.
Role of Human Lymphocytes Bearing αβ and γδ T-Cell Receptor in Malaria Infection
Authors: Iqbal Jamshaid , Robina J.
Published: April 2003

Objective: To investigate the role of γδ T cells in the regulation of immune response in Plasmodium falciparum infection. Methods: γδ and αβ T cells were purified from peripheral mononuclear blood cells (PMBC) by positive selection method using monoclonal antibodies. The PMBC were obtained from normal healthy donors. The role of various T cell subsets was investigated by observing their capacity to inhibit the growth of P. falciparum parasites. Results: By positive selection using monoclonal antibodies we were able to obtain a relatively pure fraction (>95%) of γδ T cells from PMBC. The parasite growth inhibitory capacity of activated γδ T cells ranged between 6 and 55%, however, activated αβ T cells failed to inhibit the growth. It was also observed that the inhibitory capacity of γδ T cells was dose-dependent and required physical contact with the organism. Conclusion: Activated γδ T cells have the capacity to inhibit the growth of P. falciparum parasites and thus may act as a first line of defense in controlling the blood stage infection. The significance of γδ T cells in influencing various bacterial infections is discussed.
A Case of Angiotropic Large Cell Lymphoma Primarily Discovered in Biopsy Specimens from Liver and Bone Marrow
Authors: Kahvic M. , Nayak N.C. , Mokhtar S. , Dhamer A.S. , Lulu A.R.D.
Published: April 2003

Objective and Importance: We describe an unusual site for angiotropic large cell lymphoma (ALCL) diagnosed from liver and bone marrow biopsy specimens. ALCL is a rare, multifocal, exclusively intravascular and generally fatal disorder of high-grade non-Hodgkin’s lymphoma. Clinical Presentation: The patient, a 70-year-old woman, presented with hepatosplenomegaly, anaemia, and disturbed liver function tests. Conclusion: As far as we know, and according to the available literature, liver and bone marrow biopsies have never been reported as being primary sites of ALCL.
Adhesion of Staphylococcus epidermidis to a Human Cardiac Cell Line Mediated by Lipoteichoic Acid
Authors: Chugh T.D. , Burns G. , Bahr G.M.
Published: April 2003

Objective: Staphylococcus epidermidis is a common cause of endocarditis. This study was carried out to examine the early steps of its pathogenesis, i.e. bacterial adhesion. Methods: Adherence of S. epidermidis to human, bovine and murine endothelial cell lines with and without pretreatment of cell lines with lipoteichoic acid (LTA) and pretreatment of bacteria with polyclonal anti-LTA antibodies, human albumin and lipase was carried out. Results: S. epidermidis binding to human continuous endocardial cell line was ∼3% of the inoculum. This was blocked with LTA (∼65%), polyclonal anti-LTA antibodies (∼50%), human albumin (∼60%) and lipase (∼60–70%). Conclusion: LTA is an important though not the sole adhesin for bacterium host cell receptor interaction in this experimental model.
Survey of Drug Use in Labour in a Kuwaiti Hospital: A Pilot Study
Authors: Makhseed Ma’asoumah , Nandakumaran Moorkath , Ahmed MohammadAbrar , Lakshmi Vijaya , AlShimalee Iman , AlQallaf Khalida
Published: April 2003

Objective: To study the trends of drugs used in labour in Kuwait. Methods: A drug survey of a total of 326 mothers was conducted in the labour room of the Maternity Hospital, Kuwait. Data were collected from the prescription sheets and patient files by four doctors from the labour room based on a 4-day duty rotation schedule. Results: Percentages of the prescribed drugs were: analgesics 59.5, tranquilizers 25.5, uterotonics 7.4, antibiotics 5.5, anticonvulsants 0.9, antihypertensives 1.5, and H2 receptor blockers 38.96. Conclusion: Our survey has shown that analgesics, H2 receptor blockers and tranquilizers constitute the most commonly used drugs in labour.
Rate of and Risk Factors Associated with Retinopathy of Prematurity: A Prospective Study from Kuwait
Authors: Al-Essa Mazen , Azad R.V. , Rashwan Nabil
Published: April 2003

Objective: To determine the rate of retinopathy of prematurity (ROP) among a population of preterm infants in Kuwait, and to review the risk factors associated with the disease. Methodology: A prospective cohort study of all preterm infants of less than 2,000 g birth weight and/or 36 weeks gestational age who were screened for ROP during 1995 at the neonatal unit of the Maternity Hospital in Kuwait. The rate of and some of the possible risk factors associated with the disease were determined. Results: A total of 130 babies were screened of which 59 (45.4%) developed some stage of ROP. The frequency of blindness was 3 (2.3%). Low birth weight, oxygen therapy, patent ductus arteriosus, intraventricular hemorrhage and blood transfusion were the risk factors found to be associated with the disease. However, with logistic regression analysis, only low birth weight and oxygen were independently associated with ROP. Conclusion: The rate of ROP in our unit is not different from that of the other centers, and low birth weight and oxygen therapy are the main risk factors associated with the disease.
The Introduction of Laparoscopic Appendectomy in a Teaching Hospital
Authors: Khoursheed M. , Sobhi W. , Al-Sharaf K. , Aman S. , Behbehani A. , Dashti H.
Published: April 2003

Objectives: A retrospective study of laparoscopic appendectomy (LA) versus open appendectomy (OA) was performed on patients with suspected acute appendicitis. Patients were selected for OA or LA according to the clinical evaluation, and preference of the surgeon. Methods: Over a 2-year period 180 patients were included, of whom 94 patients underwent OA, and 86 patients underwent LA. Results: LA was successfully completed in 76 patients (88.3%). The mean hospital stay in OA was 3.2 days versus 2.7 days in LA. The mean operative time was shorter in OA than in LA (51.6 versus 59.8 min). There was no significant difference in convalescence between both the groups, however, there was a tendency towards less narcotic requirement among the LA group. Postoperative complications in patients who underwent OA included: chest infection (3 patients), wound infection (4 patients), thrombophlebitis (1 patient). Complications after LA included: pelvic collection (1 patient), chest infection (1 patient), ileus (1 patient). There was no wound infection in the LA group. There was no death in either groups. Conclusion: LA is a safe procedure comparable to OA, however, it requires skills in laparoscopy and prospective randomized trials are needed to confirm its advantages over conventional appendectomy.
Postoperative Thrombocytosis after Coronary Artery Bypass Grafting: A Potential Danger even after Hospital Discharge
Authors: Christenson JanT. , Simonet François , Schmuziger Martin
Published: April 2003

Objective: Thrombocytosis (platelet counts >400 × 103/mm3) following coronary artery bypass grafting has been described to occur frequently (20–30%) and to be associated with thrombotic complications postoperatively. The purpose of the present study is to establish when the peak value of platelet count occurs, and how high it is, as well as to determine the duration of thrombocytosis. Methods: Thirty consecutive patients undergoing elective coronary artery bypass grafting, who subsequently developed postoperative thrombocytosis (group 1) were considered for the study. Another 30 patients with platelet counts within normal limits postoperatively served as controls (group 2). Platelet count was monitored on a weekly basis during 5 weeks postoperatively. Patient characteristics, operation data and cardiopulmonary bypass data in group 1 did not differ from group 2 patients, except for a higher incidence of hyperlipidemia, i.e., 97% (29/30 patients) in group 1 compared to 40% (12/30) in group 2 (p < 0.001). Results: Neither deaths nor nonfatal myocardial infarctions occurred during the study period. Postoperative thrombocytosis was diagnosed on 6.1 ± 1.5 days postoperatively, and peak platelet count reached 14 ± 4.0 days postoperatively (6–21 days). The highest platelet count observed was 905,000/mm3. Platelet counts returned to normal values within 5 weeks. Three late vein graft occlusions occurred in all groups, and thus coinciding with the maximum platelet count observed. Conclusions: Postoperative thrombocytosis is a potentially dangerous complication, with an increased risk for vein graft occlusion. Postoperative thrombocytosis, when it occurs, is diagnosed around the 6th postoperative day, reaches its peak 2 weeks postoperatively and may last as long as 5 weeks. Close surveillance of patients with postoperative thrombocytosis is emphasized.
Down’s Syndrome in Kuwait: Recurrent Familial Trisomy 21 in Sibs
Authors: Al-Awadi S.A. , Naguib K.K. , Bastaki L. , Gouda S. , Mohammed F.M. , Abulhasan S.J. , Al-Ateeqi W.A. , Murthy D.S.Krishna
Published: April 2003

Objective: To study the families with recurrent trisomy 21 in sibs, and to understand the increased risk of recurrence in some selected families. The importance of parental mosaicism as a cause for non-disjunction or the possibility of genetic predisposition to non-disjunction is addressed. Methods: Three young unrelated Kuwaiti families each confirmed to have 3 sibs with regular trisomy 21 were investigated. Detailed chromosome analysis of the peripheral blood culture in Down’s syndrome children and their parents was carried out. At least 100 cells in each of the cases were scored to exclude low grade mosaicism. Results: Regular trisomy 21 was confirmed in all the sibs in the three families. Mosaicism was not detected in parents. However, gonadal tissue mosaicism could not be excluded, as it is not practical to study the gonadal biopsy in the parents. Conclusion: Though parental mosaicism (gonadal, more often maternal), has been reported in familial recurrent trisomy 21 cases, no mosaicism could be confirmed in our study. Our finding suggests that the possibility of a genetic predisposition to non-disjunction parental mosaicism should be considered in counselling families having sibs with trisomy 21.
Changes in Acidic Amino Acid Efflux from Rat Brain with Maturation
Authors: Al-Sarraf Hameed
Published: April 2003

Objective: Our previous studies have shown a greater uptake of acidic amino acids from the blood into the brain of neonatal when compared to that of adult rats. The aim of this study is to investigate whether a developmental change exists in the brain to blood efflux of this group of amino acids. Methods: The whole brain was perfused in situ with Ringer’s solution containing 14C-aspartate or 14C-glutamate for 10 min. The perfusion was then continued with 14C-free perfusate for a further 20 min and samples of jugular venous outflow were taken at 30-second intervals. The amount of radioactivity (in ln dpm) in each sample was then plotted against the sampling time, and the half-time (t½) for 14C-efflux was calculated. Results: Paper chromatography of the outflow samples revealed that more than 91% of the 14C-labelled acidic amino acid present in the effluent samples for up to 30 min of perfusion was chemically intact. The t½ for aspartate efflux in neonatal rats was 16.16 ± 0.76 min which was significantly slower (p < 0.05) than that for the adults, 10.06 ± 0.46 min (means ± SEM, n = 3 and 4). The t½ for glutamate efflux was also small in the adult brain where it was 50% the value seen in the neonates. Conclusion: The above results indicate that the systems involved in the efflux of acidic amino acids out of the brain favour retention and increased levels of this group of amino acids in the developing brain.
The Influence of Gender and Personally Knowing a Victim on Medical Students’ Attitudes towards Female Victims of Interpersonal Violence
Authors: Nayak Madhabika B.
Published: April 2003

Objective: The purpose of this study was to assess medical students’ attitudes towards female victims of interpersonal violence and to examine associations between these attitudes and gender, personally knowing a victim, and knowledge of interpersonal violence issues. Methods: One hundred and two students completed a survey adapted from established attitudinal scales that included an assessment of knowledge of interpersonal violence. Multivariate analyses were conducted using attitude scores as the dependent variables, gender and personally knowing a victim as independent variables, and knowledge of interpersonal violence as a covariate. Results: Both gender and personally knowing a victim had significant associations with attitudes towards victims of violence. Women were found to have lower blaming scores for victims of both rape and domestic violence. With regard to rape victim blaming, personally knowing a victim of interpersonal violence reduced scores for both men and women. However, for domestic violence victim blaming, knowing a victim reduced scores for women only. No significant association was found between knowledge of interpersonal violence and attitudes towards victims of violence. Conclusions: Clinical training that focuses on information alone is unlikely to influence medical student attitudes towards victims of interpersonal violence. Female gender and personally knowing a victim positively influence attitudes towards victims of violence, however the impact of these variables may be specific to the type of violence. Training programs on interpersonal violence must take into account attitudinal differences due to student gender and prior experiences with victims of violence.