bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Nitric Oxide in Pathogenesis of Aspirin-Induced Gastric Mucosal Damage in Rats
Authors: Takeuchi Koji , Yasuhiro Tetsuya , Asada Yoko , Sugawa Yasunari
Published: April 2003

We examined the effect of NO synthase inhibitor on the functional and ulcerogenic responses to aspirin (ASA) in rat stomach. The animals were given ASA (20–80 mM) orally with or without HCl (10–50 mM) and killed 2 h later. NG-nitro-L-arginine methyl ester (L-NAME) was given i.v. 5 min before aspirin. In the functional study, a rat stomach was mounted on an ex vivo chamber under urethane anesthesia, perfused with saline, and transmucosal potential difference (PD), luminal pH, acid secretion and mucosal blood flow (GMBF) were measured simultaneously. ASA alone caused gastric damage in a dose-related manner; mostly nonhemorrhagic lesions. Pretreatment with L-NAME worsened such lesions and caused severe hemorrhagic lesions. Coadministration of HCl with ASA also potentiated gastric lesions in a concentration-dependent manner, changing nonhemorrhagic into hemorrhagic damage, and the worsening effect of L-NAME disappeared when 80 mM ASA was given together with HCl at >20 mM. In chambered stomachs, the mucosal application of ASA (80 mM, 30 min) caused a marked reduction in PD and a slight decrease in acid secretion, with minimal change in GMBF. L-NAME blocked the reduced acid response following ASA and caused stimulation of acid secretion with no effect on PD and GMBF. These effects of L-NAME were all antagonized by coadministration of L-arginine and significantly mitigated by sensory deafferentation or pretreatment with cimetidine or FPL-52694. These results suggest that (1) intragastric administration of ASA causes a release of NO, which reduces the development of hemorrhagic lesions by decreasing acid secretion, and (2) L-NAME worsens gastric damage by increasing acid secretion in ASA-treated stomachs, the process being dependent on endogenous histamine and sensory neurons.
Primary Hepatic Neuroendocrine Tumor: Successful Hepatectomy in Two Cases and Review of the Literature
Authors: Rückert Ralph I. , Rückert Jens C. , Dörffel Yvonne , Rudolph Birgit , Müller Joachim M.
Published: April 2003

Background/Aims: Primary hepatic neuroendocrine tumor represents an extremely rare clinical entity with only very few cases having been reported to date. Methods: The case histories of 2 patients with presumably primary hepatic neuroendocrine tumor were analyzed and a complete follow-up obtained. The literature was reviewed to provide comprehensive data collection. Results: Both patients underwent partial hepatic resection. Histomorphologic diagnosis revealed a neuroendocrine tumor in both cases. Extensive preoperative as well as intra- and postoperative search for the primary tumor did not identify another site of neuroendocrine tumor tissue. Six and ten years after hepatic segmentectomy, the 2 patients are alive and show no clinical signs of malignancy. Their most recent thorough follow-up included computed tomography and somatostatin receptor scintigraphy. Neither a nonhepatic primary neuroendocrine tumor site nor recurrent disease was found in the 2 patients. The literature review resulted in a complete survey of all previously reported cases of primary hepatic neuroendocrine tumors. Conclusion: We conclude that the liver was the primary site of the neuroendocrine tumor in both patients. Radical surgery was successfully performed as the only treatment option with curative intention.
Cigarette Smoke Increases Apoptosis in the Gastric Mucosa: Role of Epidermal Growth Factor
Authors: Ma Li , Wang Hong Y. , Chow Jimmy Y.C. , Cho Chi H.
Published: April 2003

Background/Aims: Apoptosis is a common mechanism for the regulation of cell loss. It is associated with both tissue atrophy and metaplasia. Cigarette smoking has tremendous adverse effects on the stomach and also increases the risk of gastric cancer. This action may be through the change in apoptosis in the stomach. The aim of this study was to examine the effect of cigarette smoking on apoptosis in the gastric mucosa and the possible role of epidermal growth factor (EGF) in this action. Methods: Gastric blood flow was assessed by the laser Doppler technique. Serum and gastric mucosal EGF levels were measured by RIA. Gastric mucosal apoptosis was determined using TdT-mediated dUTP-biotin nick end labeling (TUNEL). Results: Cigarette smoke exposure decreased serum EGF which was accompanied by a reduction in gastric blood flow. Meanwhile, gastric mucosal cell apoptosis was increased. Administration of EGF (20 μg/kg i.v.) before each cigarette smoke exposure reversed these actions. Removal of salivary glands induced similar effects on the gastric blood flow, apoptosis, and serum EGF level as with cigarette smoke exposure. Conclusion: A reduction in serum EGF was involved in the decrease in gastric blood flow and increase in gastric mucosal apoptosis caused by cigarette smoking.
Unusual Manifestation of an Ampullary Tumor Presenting with Severe Upper Gastrointestinal Bleeding
Authors: Ashkar Khalil , Deeb LilianeS. , Bikhazi Kamal , Arnaout M. Samir
Published: April 2003

Ampullary tumors can occasionally ulcerate and present as frank gastrointestinal bleeding. The most common clinical presentation is jaundice like in other tumors of the biliary tree. We report on a 68-year-old man who presented with severe upper gastrointestinal hemorrhage secondary to an asymptomatic mass of the ampulla of Vater. An endoscopic biopsy specimen revealed a villous adenoma with moderate dysplasia. A curative resection was performed, and pathological work-up revealed the presence of an infiltrating, moderately differentiated ampullary adenocarcinoma.
Increased Mitogen-Activated Protein Kinase Activities Stimulated with Interleukin-1-Beta and Mechanism(s) of the Kinase Signaling Pathways in Rat Gastric Epithelial Cells
Authors: Tominaga Kazunari , Arakawa Tetsuo , Tsuno Miho , Kim Shokei , Iwao Hiroshi , Kuroki Tetsuo
Published: April 2003

Interleukin (IL)-1β, a multifunctional cytokine, is associated with inflammatory gastric mucosa, but the responses of gastric epithelial cells stimulated by IL-1β are not known. We determined whether IL-1β activates the two subfamilies of mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs), in rat gastric epithelial cells (RGM1) using in-gel kinase assays. In addition, we examined the mechanism(s) underlying their signaling pathways and the effect on proliferation of these cells. IL-1β (0–5 × 103 pg/ml) dose dependently induced activation of ERKs (p44ERK and p42ERK) and JNKs (p46JNK and p55JNK) in RGM1 cells; maximal activities were attained with 1,000 pg/ml of IL-1β. These activities were increased with time, and were maximal 20 min after stimulation with IL-1β (100 pg/ml). Pretreatment with neutralizing antibody against IL-1β inhibited IL-1β-induced activation of ERKs and JNKs. Genistein (100 μM), a tyrosine kinase inhibitor, and GF109203X (2 μM), a protein kinase C inhibitor, inhibited the IL-1β-induced activation of ERKs and JNKs. Six- hour pre-incubation with IL-1β inhibited proliferation of these cells by 40% at 24 h of incubation, but the inhibition was recovered at 48 h. These findings suggest that IL-1β activated ERKs and JNKs in rat gastric epithelial cells and inhibited cell proliferation, possibly via the specific receptor for IL-1β. Activation of MAP kinases by IL-1β may be mediated by tyrosine kinase and protein kinase C.
Neurofibrillary Tangles and Alzheimer’s Disease
Authors: Brion J.-P.
Published: April 2003

The neuropathological diagnosis of Alzheimer’s disease relies on the presence of both neurofibrillary tangles and senile plaques. The number of neurofibrillary tangles is tightly linked to the degree of dementia, suggesting that the formation of neurofibrillary tangles more directly correlates with neuronal dysfunction. The regional pattern of areas affected by neurofibrillary tangles formation during the course of the disease is relatively stereotyped. Neurofibrillary tangles are composed of highly phosphorylated forms of the microtubule-associated protein tau. Phosphorylated tau proteins accumulate early in neurons, even before formation of neurofibrillary tangles, suggesting that an imbalance between the activities of protein kinases and phosphatases acting on tau is an early phenomenon. The latter might be related to changes in signalling through transduction cascades, since many of the protein kinases generating phosphorylated tau species participate in signalling pathways. The accumulation of neurofibrillary tangles and phosphorylated tau species is associated with disturbances of the microtubule network and, as a consequence of the latter, of axoplasmic flows. The mechanistic relationship between the formation of neurofibrillary tangles and senile plaques is still little understood and in vivo formation of neurofibrilllary tangles in experimental models has not yet been achieved. Future animal models, e.g. transgenic animals expressing combined key human proteins, will hopefully reproduce faithfully all the major cellular lesions of the disease.
COMT Inhibition by Tolcapone Further Improves Levodopa Pharmacokinetics when Combined with a Dual-Release Formulation of Levodopa/Benserazide
Authors: Gasser U.E. , Jorga K. , Crevoisier C. , Hovens S.E.L. , van Giersbergen P.L.M.
Published: April 2003

The objective of the study reported here was the investigation of the effect of catechol-O-methyl transferase (COMT) inhibition by tolcapone on the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after administration of a new dual-release formulation (dual-RF) of levodopa/benserazide (200/50). The study had a double-blind, placebo-controlled, randomized, crossover design and was conducted in 18 healthy young subjects. On the 2 treatment days, separated by a washout period of 7 days, the dual-RF was administered in combination (blinded) with tolcapone (200 mg) or placebo. Both treatment combinations were well tolerated. Tolcapone increased the bioavailability (AUC0–∞) and apparent elimination half-life (t½) of levodopa by 80 and 40%, respectively, compared to placebo. The maximal plasma concentration (Cmax) was slightly elevated by tolcapone. In the presence of tolcapone, formation of 3-OMD was substantially reduced. In conclusion, the effect of tolcapone on levodopa pharmacokinetics after administration of the dual-RF is similar to the one observed after immediate- and slow-RFs and leads to a marked improvement in levodopa pharmacokinetics and subsequently to an optimization of levodopa therapy.
Effect of Long-Term Oxygen Therapy on Cognitive and Neurological Dysfunction in Chronic Obstructive Pulmonary Disease
Authors: Hjalmarsen Audhild , Waterloo Knut , Dahl Arve , Jorde Rolf , Viitanen Matti
Published: April 2003

The aim of this study was to assess effect of long-term oxygen therapy (LTOT) on the function of central and autonomic nervous system in patients with hypoxaemic chronic obstructive pulmonary disease (COPD). A battery of neuropsychological tests was used together with the Short Test of Mental Status in addition to transcranial Doppler ultrasonography, and five cardiovascular tests as well as a questionnaire on autonomic function. Ten COPD patients, 4 males and 6 females, with a mean age of 65.9 ± 7.3 (SD) years, were studied at the beginning and after 3 months of LTOT. At start PaO2 was 6.7 ± 1.1 kPa without oxygen and 9.9 ± 1.5 kPa after 3 months with oxygen. Our results demonstrate that neuropsychological function, cerebral blood flow velocity and autonomic function were positively influenced after 3 months of LTOT although the changes did not reach statistical significance. The COPD patients were cognitively impaired as compared to age-matched healthy controls. Our findings were consistent with the previous notion of improvement of hypoxic cognitive dysfunction by LTOT.
Effect of Bilateral Subthalamic Nucleus Stimulation and Dopatherapy on Oral Control in Parkinson’s Disease
Authors: Gentil Michèle , Tournier Claire-Lise , Pollak Pierre , Benabid Alim Louis
Published: April 2003

This study focuses on the speech organs of a parkinsonian patient who initially had been treated with levodopa for 13 years, and had become severely disabled by motor fluctuations. This patient has been treated with bilateral chronic stimulation of the subthalamic nucleus (STN) for the last 2 years. Upper lip, lower lip and tongue force production were examined before surgery under off and on medication conditions, and 2 years after surgery under off and on stimulation conditions. We compared the effect of stimulation and dopatherapy on the speech organs. L-Dopa had a poor effect whereas bilateral stimulation improved oral control and speech intelligibility. These results suggest that STN stimulation influences speech organs in a different way from the dopaminergic system and similarly affects oral and limb motor systems.
Long-Term Follow-Up after Extracranial Internal Carotid Artery Dissection
Authors: Engelter S.T. , Lyrer P.A. , Kirsch E.C. , Steck A.J.
Published: April 2003

Objective: To evaluate long-term outcome after extracranial internal carotid artery dissection (eICAD) in consideration of the applied antithrombotic therapy. Material and Methods: Among 33 consecutive eICAD patients initially treated either with anticoagulation (n = 25) or with antiplatelets (n = 8), a standardized interview was performed after 28 ± 22.1 months to analyze risks and benefits of both agents. Ischemic and hemorrhagic complications, occurrence of seizure and rates of arterial recanalization were compared and long-term clinical outcome was assessed using the modified Rankin Scale (mRS) and Barthel Index (BI). Results: Among anticoagulated patients, 1 died due to brain herniation. In 3 patients stroke (n = 2) or TIA (n = 1) recurred. In the antiplatelet group, none died and no subsequent ischemic events happened. Hemorrhagic complications were noted in neither treatment group. Functional outcome among anticoagulated patients was BI 92 ± 21.6 and mRS 1.48 ± 1.50, which did not differ from patients initially treated with antiplatelets (BI 89 ± 18.9, mRS 1.50 ± 1.41, p > 0.05). Four anticoagulated patients developed seizures, compared to 2 patients with antiplatelets (p > 0.05). Arterial recanalization occurred in 16 of 22 antico- agulated patients with ultrasound follow-up, compared to 6 of 6 patients with antiplatelets (p > 0.05). Conclusion: In the absence of iatrogenic side effects, both anticoagulation and antiplatelets seem to be safe for eICAD. The rates for death and stroke were low and outcome ratings did not differ between both agents. These findings may indicate that a controlled randomized trial comparing anticoagulation and antiplatelets is ethically justified.
Augmentation of Mitochondrial Reduced Glutathione by S-Adenosyl-L-Methionine Administration in Ischemia-Reperfusion Injury of the Rat Steatotic Liver Induced by Choline-Methionine-Deficient Diet
Authors: Kaneshiro Y. , Nakano H. , Kumada K. , Boudjema K. , Kitamura N. , Shimura H. , Barama A. , Kigawa G. , Tatsuno M. , Fujiwara Y. , Baek Y. , Sasaki J. , Nagasaki H. , Yamaguchi M.
Published: April 2003

We examined whether warm ischemia-reperfusion (I/R) damage of the rat steatotic liver can be reduced by administration of S-adenosyl-L-methionine (SAMe). We examined the effect of SAMe on the mitochondrial reduced-glutathione (GSH) pool. Sixty minutes of partial left lobar vascular clamping followed by 2 h of reperfusion were employed for a model of hepatic warm ischemia. Either 5% dextrose or SAMe was injected intraperitoneally 2 h before I/R in steatotic rats (S-D5% or S-SAMe group). Serum liver enzyme concentrations 2 h after reperfusion were significantly lower in the S-SAMe group than in the S-D5% group. The cytosolic and mitochondrial GSH concentrations after I/R were significantly higher in the S-SAMe group than in the S-D5% group (p < 0.05). The cytosolic and mitochondrial oxidized-glutathione/GSH ratios after I/R were significantly greater in the S-D5% group than in the S-SAMe group (p < 0.01). The adenosine triphosphate concentration was higher in the S-SAMe group than in the S-D5% group (p = 0.0515). These results show that hepatocellular and mitochondrial oxidative stress after I/R in the steatotic liver can be reduced by administration of SAMe. The results also show that mitochondrial function and hepatocellular integrity can be restored by administration of SAMe in steatotic rats.
Effect of Surgery on Neutrophil Leukotriene B4 Generation and Arachidonic Acid Content
Authors: Sane S. , Baba M. , Kusano C. , Shirao K. , Kamada T. , Aikou T.
Published: April 2003

The effect of surgery on neutrophil leukotriene B4 (LTB4) generation and arachidonic acid content was examined in 9 patients undergoing major surgery for esophageal cancer and 10 patients undergoing lesser surgery. Plasma IL-8 and neutrophil LTB4 generation was increased significantly 6 h after surgery regardless of the extent of surgery. This finding was associated with a decrease in neutrophil arachidonate content. In patients who underwent major surgery, neutrophil LTB4 generation decreased progressively on the 1st, 2nd, and 4th postoperative days, and this decrease paralleled a further decrease in neutrophil arachidonate content. These findings suggest that neutrophils are activated by surgery, thereby consuming their arachidonic acid, and that neutrophil LTB4 generation is influenced by postoperative arachidonate levels.
Prolonged Function of Hepatocytes Transplanted into the Spleens of Nagase Analbuminemic Rats
Authors: Ikebukuro H. , Inagaki M. , Mito M. , Kasai S. , Ogawa K. , Nozawa M.
Published: April 2003

Hepatocytes isolated from F344 rats were transplanted into the spleens of congenic Nagase analbuminemic rats (NARs). The morphology and function of the transplanted hepatocytes were investigated after 18 months. The hepatocytes had formed nodules that occupied approximately 35% of the area of the splenic parenchyma on microscopic examination. Ultrastructural examination demonstrated that the organelles of the transplanted cells were indistinguishable from those of normal hepatocytes. The serum albumin level in NARs at 18 months after intrasplenic transplantation (HCTx) was about 3.6 % of that in normal rats. We confirmed that the hepatocytes in the spleen produced albumin and increased the serum albumin level in NARs with HCTx. The NAR model demonstrates the effect of HCTx and prolonged changes in the morphology of the hepatized spleen.
Pre-Emptive Analgesia: How Important Is It in Clinical Reality?
Authors: Filos K.S. , Vagianos C.E.
Published: April 2003

Surgical trauma induces nociceptive sensitization leading to amplification and prolongation of postoperative pain. In experimental studies, preinjury (e.g. pre-emptive) neural blockade using local anaesthetics or opioids has been shown to prevent or to reduce postinjury sensitization of the central nervous system, while similar techniques applied after the injury had less or no effect. Several clinical studies have evaluated possible pre-emptive analgesic effects by administering prior to surgery a variety of analgesic drugs both systemically or epidurally. These treatment modalities were compared to the same treatment following surgery or to control groups not given such treatment. In general, the results from these studies have been disappointing, although some clinical studies have confirmed the impressive results from animal studies. The present paper discusses deficiencies in study design of clinical trials, since the question regarding the effectiveness of pre-emptive analgesic regimens lies not so much in the timing of analgesic administration (e.g. preinjury vs. postinjury treatment), but in the effective prevention of altered central sensitization. Recent evidence suggests that administration of analgesics in order to effectively pre-empt postoperative pain should start before surgery and furthermore, this treatment should be extended into the early postoperative period.
Does Effective Postoperative Pain Management Influence Surgical Morbidity?
Authors: Rosenberg J. , Kehlet H.
Published: April 2003

It has been assumed that adequate postoperative pain relief will improve outcome from surgery, but several controlled trials have demonstrated that pain treatment with nonsteroidal anti-inflammatory drugs, patient-controlled analgesia or epidural techniques will not significantly improve outcome after major procedures. In lower body procedures, however, intra- and early postoperative pain relief with epidural or spinal anaesthesia reduces blood loss and thromboembolic complications. It is hypothesized that effective postoperative pain relief may significantly improve outcome only if integrated into a multimodal rehabilitation program.
Airway Anastomotic Healing in the Rat Tracheal Autograft
Authors: Hyytinen T. , Paavonen T. , Inkinen K. , Ahonen J. , Mattila S.
Published: April 2003

The healing of airway anastomoses after tracheal autotransplantation was studied in a rat model. Tracheal autotransplantation in length of five tracheal cartilaginous rings was performed in 46 PVGr1 female rats. The animals were sacrificed and divided into six groups as follows: 0-day control group, and 3-, 7-, 14-, 21- and 28-day study groups (n = 6–7/group). In laser Doppler measurements, blood flow was significantly increased in the lower anastomosis after day 7 and in the upper anastomosis after day 21 compared with the control group (p < 0.05). The breaking strength of the tracheal autograft increased after day 7 compared with the control group (p < 0.05). The total collagen content of the lower anastomosis was significantly decreased on days 3 and 7 compared with the control group (p < 0.05), but thereafter it increased constantly. In the upper anastomosis on days 3 and 7, there were significant histological alterations, especially in the tracheal epithelium, compared with the control group (p < 0.05). Tracheal anastomosis is most vulnerable during the first 7 days.
Secretion of IL-6, Monocyte Chemoattractant Protein-1, Macrophage Inflammatory Protein-1α, and TNFα by Cultured Intact Human Peritoneum
Authors: Riese Jutta , Denzel C. , Zowe M. , Mehler C. , Hohenberger W. , Haupt W.
Published: April 2003

The peritoneum is an important site of host defence. The mesothelial cells, lining the peritoneum, and the fibroblasts found in the layers below are potent sources of a variety of mediators. Furthermore, granulocytes, mast cells, and macrophages, either resident or attracted by inflammatory processes, are interspersed within the tissue. We investigated the production of mediators by samples of fresh human peritoneum. The method described here has the advantage that the cellular composition of the human peritoneum remains intact. Samples of peritoneum were excised at the beginning of elective abdominal operations in infection-free patients. The tissue was placed across the wells of a microtitre plate, fixed in place by the plate cover and incubated with culture medium with or without lipopolysaccharide (LPS) for up to 5 h. The accumulation of IL-6, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and TNFα in culture supernatants was measured by ELISA. Production of MCP-1 and IL-6 occurred spontaneously during incubation and was enhanced by as much as 4-fold in the presence of different concentrations of LPS (0.5–500 ng/ml) in a dose-dependent manner. MIP-1α and TNFα were detected in culture supernatants of LPS-stimulated samples with concentrations about 8 times as high as those of samples cultured with no such stimulus. The addition of IL-1β resulted in an increase in the release of IL-6 and MCP-1, similar to that observed with LPS stimulation, but failed to increase the production of TNFα. MIP-1α production was only marginally enhanced by IL-1β. In conclusion, our experimental system is suitable for the investigation of chemokine and cytokine production by the human peritoneum, with the aim of assessing aspects of local immunocompetence.
Endothelin-Induced Contraction of the Portal Vein in Cirrhosis
Authors: Petrowsky H. , Schmandra T. , Lorey T. , Hanisch E. , Herrmann G.
Published: April 2003

Endothelin (ET) is one of the most potent vasoconstrictors known so far. It has been proposed that the ET-induced contraction of hepatic stellate cells (Ito, endothelial cells) is an important mechanism for the development of portal hypertension. The purpose of this study was to investigate in an in vitro model whether ET causes a contraction of the portal vein which can contribute to portal hypertension in cirrhosis. Portal veins from normal and cirrhotic rats were used for experiments. Measurements were performed in vitro for cumulative concentrations of ET-1 and ET-3 (1, 5, 10, 50 and 100 nM). Both ETs caused a dose-dependent increase in portal venous tension; the maximal tension (Tmax) was measured at 50 nM. The measured Tmax was higher for cirrhotic (ET-1: Tmax = 189%; ET-3: Tmax = 175%) than for normal rats (ET-1: Tmax = 130%; ET-3: Tmax = 151%). ET-3 produced a higher tension of portal veins in normal rats than ET-1. In conclusion, this study shows that portal veins from cirrhotic rats react more sensitively to ET than those from normal rats. Besides the ET-induced contraction of hepatic stellate cells, contraction of the portal vein and its intrahepatic branches, especially in cirrhotic individuals, has to be considered as a further mechanism of ET contributing to portal hypertension.
Pancreatic Regeneration after Subtotal Distal Resection in Rats
Authors: Bufalari A. , Ferri M. , Sidoni A. , Alberti P. , Giustozzi G. , Moggi L.
Published: April 2003

Forty male Wistar rats were randomly allocated to four treatment groups after 90% distal pancreatectomy: group A (control) received saline (0.5 ml subcutaneously); group B received bombesin (BBS; 10 μg/kg intraperitoneally); group C received octreotide (2.5 μg/kg subcutaneously), and group D received BBS and octreotide. All substances were injected three times a day until sacrifice after 28 days. BBS increased pancreas weight (p = 0.003) and DNA synthesis (p < 0.001), as measured by a bromodeoxyuridine nuclear-labeling index (BrdU LI). The simultaneous administration of octreotide significantly decreases the remnant pancreas weight (p = 0.016) as compared to group B rats; however the BrdU LI is not significantly reduced in group D as compared to group B. BBS administration promotes regeneration of the remnant pancreas in terms of hypertrophy and hyperplasia. Although octreotide appears to significantly reduce the pancreatic weight increase induced by BBS, it does not reduce DNA synthesis and cell proliferation.
Effect of Experimental Diabetes and Growth Hormone Administration on the Strength of Colonic Anastomoses in Rats
Authors: Seyer-Hansen M. , Andreassen T.T. , Christensen H. , Oxlund H.
Published: April 2003

The influence of growth hormone (GH; 2 mg/kg/day) administration on the mechanical breaking strength of colonic anastomoses in diabetic rats has been investigated on the day of operation (suture binding capacity) and after 4 and 7 days of healing. In diabetic rats, the suture binding capacity was decreased by 26% in both ultimate load and relative failure energy. After 4 days of healing, no difference was observed between control and diabetic animals. After 7 days, relative failure energy in the diabetic animals was reduced by 33%. GH administration to diabetic animals did not alter strength during the first week of healing. We found an increased circumference (33%) and defatted dry weight (22%) of the colon in diabetic rats. In conclusion, diabetes impairs the suture-binding capacity of the colon in rats, while there is only little influence on healing in the following week. GH administration could not influence the strength of colonic anastomoses in diabetic animals.
Expression of the Extracellular Matrix Proteins Collagen I, Collagen III and Fibronectin and Matrix Metalloproteinase-1 and -13 in the Skin of Patients with Inguinal Hernia
Authors: Klinge U. , Zheng H. , Si Z. , Schumpelick V. , Bhardwaj R.S. , Muys L. , Klosterhalfen B.
Published: April 2003

Although abnormal collagen metabolism has been ascribed an important role in the high recurrence rates after surgical hernia repair, knowledge on tissue sampled in the region affected by inguinal hernias is poor. In the present study, we determined collagen type I and type III in the skin of adult patients with indirect and direct inguinal hernias by both immunohistochemistry and Western blot analysis. In addition, we quantified the immunohistochemical expression of fibronectin and matrix metalloproteinase (MMP)-1 and -13. The results indicated that the ratio of collagen type I/III was significantly decreased in the skin of patients with either indirect (n = 9) or direct hernia (n = 7), with a concomitant increase in collagen type III (p < 0.001 vs. controls, n = 7, without affection of the inguinal region). There was no significant difference between patients with indirect and direct hernia (p > 0.05). MMP-13 was not expressed in any of the skin samples investigated, whereas MMP-1 was found in the epidermis. Fibronectin was predominantly detected at the epidermal-dermal junction. MMP-1, MMP-13 and fibronectin levels were significantly different between patients and controls (p > 0.05). We conclude that in contrast to the unchanged expression of fibronectin and MMP-1 and MMP-13, the decreased ratios of collagen tpye I/III with the basically increased amount of collagen type III could be of significant importance for the pathophysiology of hernias. The specific ratio collagen I/III probably reflects the altered structural integrity and mechanical stability of the connective tissue in both indirect and direct hernias. Moreover, our findings stress that hernias should be regarded as the manifestation of a systemic disease in the inguinal region with a genetic background, explaining the high recurrence rates after repeated suture repair, as well as the usefulness of surgical meshes in this clinical setting.
Stapled versus Hand-Sewn Vascular Anastomoses
Authors: Pauli S. , Lauwers P. , van Hee R. , Discart R.
Published: April 2003

Objective: Narrowing of vascular anastomoses is a frequently encountered surgical problem, with intimal hyperplasia being one of its most important causes. The aim of the present study was to compare in a rabbit model ‘manual’ (hand-sewn) with ‘stapled’ anastomoses (using a staple device) with respect to occurrence and severity of intimal hyperplasia. Materials and Methods: Twenty-four male rabbits (mean weight 2,849 g) were randomly allocated to one of two groups (n = 12). An end-to-end anastomosis of the left femoral artery was performed in all animals under general anesthesia. The anastomosis was hand sewn in group 1, while a vascular closure stapler (VCS) was used in group 2. Both anastomotic time and total operation time were recorded. After 28 days, the rabbits were sacrificed. The femoral artery of operated and nonoperated sides were removed and prepared for anatomopathological examination. The I/M ratio (= difference between tunica intima and tunica media) was determined on hematoxylin-eosin stained slides. All results were analyzed using Student’s t test. Results: Mean anastomotic times were 25 ± 7 min for the ‘manual’ group and 17 ± 9 min for the ‘stapled’ group (p = 0.02). There was no significant difference in the total operation time (55 ± 15 vs. 41 ± 18 min, p = 0.057). All animals survived the anastomosis procedure. In the group of ‘manual’ anastomosis, morbidity was significantly higher. At the moment of sacrifice, all anastomoses were patent. There was no difference in the I/M ratio between the groups. Conclusions: The use of VCS is a promising alternative to hand-sewn anastomoses. It takes less time to perform a stapled anastomosis, the technique has a shorter learning period and morbidity seems to be lower when vascular anastomoses are applied with the VCS in this rabbit model.
Abnormal Collagen I to III Distribution in the Skin of Patients with Incisional Hernia
Authors: Klinge U. , Si Z.Y. , Zheng H. , Schumpelick V. , Bhardwaj R.S. , Klosterhalfen B.
Published: April 2003

The surgical mesh-free repair of incisional hernias has to face recurrence rates of up to 50%. Apart from technical faults this is probably due to collagen metabolic disorders, known to play an important role in the development of inguinal hernia. In particular an altered ratio of collagen types I and III with an increase in collagen type III has been claimed to reduce the mechanical strength of connective tissues. Therefore, we investigated the content of collagen types I and III in the skin of patients with incisional hernia (n = 7) and recurrent incisional hernia (n = 5) in comparison to controls with healthy skin (n = 7) and normal skin scar (n = 7) both by immunohistochemistry and Western blot analysis. Both immunohistochemistry and Western blot analysis revealed a decrease in the ratio of collagen I/III due to a concomitant increase in collagen III. The patients with incisional hernias and with recurrent incisional hernias showed a ratio of 1.0 ± 0.1 and 0.8 ± 0.1, respectively, whereas the controls exhibit a ratio of 2.1 ± 0.2 in healthy skin and of 1.2 ± 0.2 in normal skin scar, respectively. The decrease was highly significant (p < 0.01) between the patients with either primary or recurrent hernia and the controls or the normal scar, as well as between controls and normal scar, whereas there was not any significant difference between primary and recurrent hernia (p > 0.05). Our data for the first time confirmed that the presence of incisional hernia is accompanied by impaired collagen synthesis in the skin. The decreased tensile strength of collagen type III may play a key role in the development of incisional hernias. Furthermore, it might explain the high recurrence rates of hernia repair by simple closure, as a repetition of the primarily failing technique, and the improvement by the additional use of alloplastic material.
Effect of a Novel Immunosuppressant, FTY720, on Allograft Survival after Renal Transplant in Rats
Authors: Ueda H. , Takahara S. , Azuma H. , Kusaka M. , Suzuki S. , Katsuoka Y.
Published: April 2003

FTY720 was developed by chemical modification of ISP-1 which was purified from culture filtrates of an ascomycete, Isaria sinclairii. We evaluated the effect of FTY720 on allograft survival using a rat renal transplantation model in which Wistar King Aptekman Hokkaido rats (WKAH, RT1K) served as the organ donor and Lewis rats (LEW, RT1l) as the recipient. WKAH renal allografts were acutely rejected by the untreated LEW recipients at a mean graft survival ± SD of 7.2 ± 0.4 days (n = 5). Consecutive oral administration of FTY720 following transplantation significantly prolonged allograft survival in a dose-dependent manner over the range of 0.05–3 mg/kg/day. The mean allograft survival of the recipients treated with FTY720 at a doses of 0.05, 0.1, 0.5, 1, and 3 mg/kg/day was 12.2 ± 3.3 (n = 5, p < 0.05, vs. untreated host), 11.2 ± 2.4 (n = 5, p < 0.05, vs. untreated host), 13.6 ± 0.9 (n = 5, p < 0.01, vs. untreated host), 14.6 ± 1.7 (n = 5, p < 0.01, vs. untreated host) and 20.2 ± 0.8 days (n = 5, p < 0.01, vs. untreated host). In the recipients treated with FTY720 (3 mg/kg/day), the number of peripheral blood lymphocytes significantly decreased. From the results of the flow cytometric study, FTY720 significantly diminished the percentage of interleukin-2 receptor (IL-2R)-positive cells in the allografts (6.34 ± 0.81% in the untreated recipients vs. 3.10 ± 0.86% in the recipients treated with FTY720, p < 0.05). As to the CD4/CD8 ratio of splenic cells and graft infiltrate, there was no significant difference between the untreated hosts and the recipients treated with FTY720. In conclusion, FTY720 significantly extended rat renal allograft survival and the immunosuppressive effects of FTY720 may be due to a reduction in not only the number of peripheral lymphocytes but also the percentage of IL-2R-positive cells in the allografts.
Prenatal Diagnosis of Ostium secundum Atrial Septal Defect by M-Mode Fetal Echocardiography
Authors: Salih Mustafa , Demirel L. Cem , Kurtay Gülay
Published: April 2003

Advances in fetal echocardiography enable the prenatal diagnosis of a vast majority of congenital heart defects. On the other hand, ostium secundum atrial septal defect is difficult to diagnose in the fetus. Although a defect of minor clinical significance, this may be the only intrauterine finding of a chromosomal anomaly. We documented an abnormal oscillatory pattern of the foramen ovale flap motion by M-mode fetal echocardiography in 2 fetuses with ostium secundum atrial septal defect. This may be a more consistent finding for the prenatal diagnosis of ostium secundum atrial septal defect than the previously reported bidirectional flow across the foramen ovale on color Doppler sonography.
Conversion of Big Endothelin-1 and Characterization of Its Contractile Effects on Isolated Human Placental Arteries
Authors: Hanson Gunilla C. , Wide-Swenson Dag , Andersson Karl-Erik , Lindberg B. Fredrik
Published: April 2003

Objectives: To study the conversion of human big endothelin-1 (bigET-1) to endothelin-1 (ET-1) and to characterize contractile ET-1 receptors in human placental arteries. Methods: BigET-1 was incubated with artery membranes and the formation of ET-1 was investigated. ET-1 and bigET-1-induced contractile responses were studied in the absence or presence of the metalloprotease inhibitor phosphoramidon, the ETA-receptor antagonist BQ 123, or the ETB-receptor antagonists IRL 1038 and RES 701-1. Results: The artery membranes hydrolysed bigET-1 to ET-1 through a partly phosphoramidon-sensitive pathway. The contractile responses to ET-1 and bigET-1 were similar, with pEC50% values of 8.1 ± 0.2 and 7.8 ± 0.1, respectively (NS; n = 17). Phosphoramidon decreased pEC50% for bigET-1-evoked contractions (p < 0.05; n = 8), without affecting the response to ET-1. A Schild plot of BQ 123 effects on ET-1 and bigET-1-induced contractions resulted in identical pA2 values and a slope of 0.56 ± 0.2 and 0.47 ± 0.01, respectively. IRL 1038 and RES 701-1 did not affect the contractile responses. Conclusion: BigET-1-evoked contractions in isolated human placental arteries depend on a rapid and metalloprotease-dependent hydrolytic conversion to ET-1, which in turn causes a, mainly ETA-receptor-mediated, contraction.
Changes in Polymorphonuclear Leukocytes in the Vagina of Patients with Preterm Labor
Authors: Yamada Tetsuo , Minakami Hisanori , Matsubara Shigeki , Yatsuda Tomomi , Sato Ikuo
Published: April 2003

To evaluate changes in vaginal polymorphonuclear leukocytes (vPMNL) in patients with preterm labor, we obtained vPMNL-rich suspensions from vaginal fluids of 77 women (21 with preterm labor and 56 control women with uncomplicated pregnancy). Total counts of vPMNL and % viability of vPMNL (viable vPMNL:total vPMNL) were significantly higher in patients with preterm labor (37 ± 92 × 105, 23 ± 29%) vs. controls (11 ± 15 × 105, 6.9 ± 8.3%). The concentration of granulocyte elastase in vaginal fluid diluted to 20 ml was also higher in patients with preterm labor than in controls (4,806 ± 3,818 vs. 2,739 ± 2,556 ng/ml). We conclude that PMNL and granulocyte elastase are abundant in the vagina in patients with preterm labor, which suggests that the PMNL may be involved in the pathogenesis of preterm labor.
ABO Blood Group and Expression of Antisperm Antibodies in Infertile Couples in Kuwait
Authors: Omu Alexander E. , Al-Mutawa Mahmoud , Al-Qattan Fawzia
Published: April 2003

Two hundred and fifty infertile couples and 102 fertile controls were evaluated to determine the association between ABO blood group status and seminal blood group substances among infertile couples and expression of circulating antisperm antibodies. Antisperm antibodies occurred in 18.8 and 17.7% of the infertile men and women, compared to 3.9% in the fertile women (p < 0.01). The 23 ABO blood group combinations in the infertile and fertile couples revealed no significant association with infertility except the predominance of B+/O+ spouses in the fertile group (p < 0.03). Although 76.8% of the men were secretors of seminal blood group substances, there was no significant association with development of antisperm antibodies. This shows that ABO blood group is not directly associated with infertility nor antisperm antibody formation.
Endometrial Thermal Coagulation – Degree of Uterine Fibrosis Predicts Treatment Outcome
Authors: Friberg Britt , Joergensen Connie , Ahlgren Mats
Published: April 2003

Objective: To study the uterine cavity after thermal endometrial destruction for the treatment of menorrhagia by means of a balloon catheter, the CavatermTM system. To relate the appearance of the uterine cavity to the outcome of the treatment. Methods: Fifty-one of the first 60 women treated with balloon endometrial destruction were examined with hysteroscopy and saline infusion sonography 11–28 months after treatment. Results: Patients with minimal or no bleeding after thermal endometrial destruction had more uterine fibrosis than patients bleeding more. Conclusion: The greater the degree of fibrosis of the uterine cavity after balloon endometrial destruction by thermal coagulation, the better the effect on menorrhagia.
Antiphospholipid Antibodies in Eclamptic Women
Authors: Kaleli Babür , Kaleli İlknur , Aktan Erdal , Turan Cem , Akşit Filiz
Published: April 2003

Our purpose was to determine the prevalence of antiphospholipid antibodies (APA) in eclamptic women as well as the rates of intrauterine growth retardation (IUGR) and fetal death in APA-positive and -negative eclamptic women. Thirty-six eclamptic and 30 healthy pregnant women were enrolled in this study. APA in those groups were determined. The prevalences of IUGR and fetal death were determined in APA-positive and -negative eclamptic women. In the eclamptic group, APA were positive in 9 out of 36 patients (25%), where as only 2 out of 30 controls (6.7%) were positive (p < 0.05). Fetal death was encountered in 4 out of 9 (44.4%) APA-positive eclamptic women; this was a significantly larger proportion than that for APA-negative eclamptic women (1/27; p < 0.01). The rates of IUGR in APA-positive and -negative eclamptic women were not significantly different (p > 0.05). Similar conclusions about our results could also be made, when weakly positive anticardiolipin antibodies were regarded as negative in our study group and controls. Our study suggests that positive levels of APA in eclamptic women increase the risk for intrauterine fetal death.
Side Effects of Tamoxifen in Oophorectomized Rats
Authors: Kafkaslı Ayşe , Erdem Faruk , Muezzinoglu Bahar , Akbaşak Bülbin , Burak Feza , Aksoy Tijen , Birincioglu Mustafa , Biotech Mehmet Gül , Biotec Fahri Turan
Published: April 2003

Objective: Our objective was to evaluate the direct effect of tamoxifen citrate (TAM) on the endometrium, liver, breast tissue and the lipid profile in oophorectomized (OX) rats. Study Design: An experimental animal study. Material and Methods: Forty-one mature rats (33 OX) were randomly divided into four groups and received either TAM (0.4 or 0.8 mg/kg p.o.) therapy or placebo over 60 days as follows: (1) sham; (2) OX + TAM (0.4 mg/kg); (3) OX + TAM (0.8 mg/kg); (4) OX. All histological changes in the endometrium, liver and breast tissue were evaluated under the light microscope by comparing the TAM-treated groups with the OX and sham-operated groups. Blood total cholesterol and low-density lipoprotein cholesterol levels were also analyzed. Results: TAM-treated rats showed a significant reduction in body weight, blood cholesterol and low-density lipoprotein cholesterol levels, but the wet uterine weight was not affected. Estrogenic effects of TAM were not detected with either dosage on the endometrium. TAM-treated groups showed atrophic breast tissue. No histopathological changes were detected in the liver with TAM treatment. Conclusion: The data suggests that TAM may not act as an estrogen receptor agonist with the given dosage on the endometrium in OX rats. Two different doses of TAM do not cause histological changes in liver over 60 days of treatment.
Symptoms of Defective Emptying and Raised Residual Urine May Arise from Ligamentous Laxity in the Posterior Vaginal Fornix
Authors: Papa Petros P.E.
Published: April 2003

Objectives: To prospectively test the hypothesis that laxity in the posterior ligaments of the vagina may cause raised residual urine and abnormal emptying symptoms. Methods: Eighteen patients, 16 multiparous, and 2 nulliparous, were referred with symptoms of abnormal bladder emptying. All were assessed with standard cystometry and standing resting and straining lateral X-ray films, with the bladder containing a Foley balloon catheter containing 10 ml of radio-opaque dye. Three patients were also assessed with videocystourethrograms, and these were compared to 4 normal controls. A posterior fornix repair was performed. A full thickness horizontal vaginal incision was made using a scalpel. The incision was stretched antero-posteriorly, and the utero-sacral and cardinal ligaments tightened by suturing them side to side. Results: Specific symptoms of defective opening were reduced from a total of 43 pre-operatively to 9 post-operatively. Mean residual urine was reduced from 98.7 to 31.7 ml (p ≤ 0.028). Peak flow increased from 29.7 to 34.2 ml/s, p ≤ 0.08. Mean flow pre-operative was 8.18 ml/s, and post-operative flow 8.6 ml/s (p ≤0.88). Mean emptying time decreased from 65.3 to 60.4 s. Conclusions: Reference to radiographs in normal patients demonstrates that bladder funnelling is associated with a powerful downward force transmitted to the coccyx via the utero-sacral ligaments. Correction of laxity in the utero-sacral ligaments, the effective insertion points of the downward force, improved bladder emptying. This appears to sustain the hypothesis that abnormal bladder emptying in the female may be at least partly caused by ineffectiveness of the opening muscles, because of laxity in their insertion points.
Complications of Radical Hysterectomy: Clinical Experience of 115 Early Stage Cervical Cancers
Authors: Zorlu C. Gürkan , Aydoğdu Tuǧrul , Ergün Yusuf , Kuşçu Esra , Çobanoğlu Ömer , Koçak Sırrı
Published: April 2003

We evaluated the clinical experience of 115 women with early stage cervical cancer who had been operated in our Gynecologic Oncology Clinic. Of these, 85 were in stage I, and 30 in stage II. Intraoperative complications occurred in 16 patients including 3 cases concerning bladder, 1 ureter, 1 aorta, 5 v.cava inferior, 1 internal iliac a., 3 internal iliac v., 1 obturator nerve and 1 recto-vaginal septum hematoma formation. Postoperative complications were observed in 38 patients. These were 14 bladder dysfunctions, 10 lymphocyst formations, 6 urinary infections, 12 wound infections, 3 pelvic infections, 2 eviscerations and 1 incisional hernia. However, no death occurred due to intraoperative or postoperative complications. Pelvic lymph node metastases were observed in 32 patients of whom 17 had only unilateral involvement, most often in the obturator region. Para-aortic lymph node metastases were diagnosed in 4 patients, all of whom were in stage II.