bluuebunny/crossref_metadata_2025 huggingface dataset:
PMN/Platelets Coinfused in Guinea Pig Hearts Exposed to Low-Flow Ischemia Have no Additive Cardiodepressive Effect
Authors: Seligmann Christian , Leitsch Tobias , Kusus Magda , Bock Andreas , Schimmer Mike , Simsek Yusuf , Daniel Werner G.
Published: December 2003

Recent studies revealed an additive cardiodepressive effect of polymorphonuclear granulocytes (PMN) and thrombocytes in hearts exposed to a no-flow ischemia. To find out whether or not this is also true for isolated guinea pig hearts exposed to a low-flow ischemia, the current study was performed. PMN or thrombocytes, together or separately, were applied as a 1-min bolus (1,000/µl or 20,000/µl, respectively) during ischemia or in reperfusion in the presence of thrombin (0.3 U/ml perfusate). Recovery of external heart work and intracoronary cell retention were quantified in percent. Sole application of PMN or platelets during ischemia and reperfusion significantly compromised myocardial function, whereas coapplication of PMN and platelets did not exhibit any further cardiodepressive effect. Coapplication of cells almost prevented intracoronary platelet retention during ischemia and in reperfusion, as opposed to sole platelet application. Known blockers of endogenously released anti-platelet substances like nitric oxide, PGI2 or adenosine did not mediate a further aggravation of myocardial dysfunction. The platelet-activating factor (PAF) antagonist WEB 2170 BS, however, significantly improved recovery of external heart work during ischemia and in reperfusion. This indicates that an additive cardiodepressive effect of PMN and platelets in working guinea pig hearts exposed to a low-flow ischemia, cannot be demonstrated, whereas PAF antagonists seem to be cardioprotective, under these conditions. Even addition of fibrinogen to the perfusate, did not show an additive cardiodepressive effect of coapplication of PMN and platelets.
Idiopathic Stabbing Headache and Experimental Ice Cream Headache (Short-Lived Headaches)
Authors: Selekler H. Macit , Budak Faik
Published: December 2003

Idiopathic stabbing headache (ISH) and ice cream headache occur due to paroxysmal firing of trigeminal pathways and a defect in pain control mechanisms. Any defect in pain control mechanisms appears to be localized to the affected areas. Therefore, we compared ISH and experimentally induced ice cream headache localizations in the same group of migraine sufferers to investigate similarities and differences between these headaches. The percentage of ice cream headache localizations restricted to ‘in front of the vertex/on the vertex’ was 94%, while it was 45% for ISH. The percentage of ice cream headache occurrence behind the vertex was 6% and 55% for ISH. Due to the widespread distribution of ISH in the head, there might be irritation of various branches of the trigeminal nerve, while the restricted localizations of ice cream headache suggest irritation of a certain branch or branches of the trigeminal nerve, e.g. in the oropharynx. Either widespread or restricted irritation of trigeminal pathways causes either ISH or ice cream headache, in which intermittent deficits in central pain control mechanisms seem to be playing the key role.
Serum Insulin-Like Growth Factor 1 and Growth Hormone Levels of Hypoxic-Ischemic Newborns
Authors: Satar Mehmet , Özcan Kenan , Yapıcıoğlu Hacer , Narlı Nejat
Published: December 2003

A number of growth factors, their binding proteins, and their receptors have been shown to be induced in the hypoxic-ischemic (HI) brain. In this prospective study, we aimed at determining the levels of insulin-like growth factor 1 (IGF-1), growth hormone (GH), and cortisol in HI babies and at identifying whether they differ from the levels of control infants. The serum IGF-1 levels were measured after the first 12–24 h of life, and the measurements were repeated on the 5th and 10th days of life for babies with HI encephalopathy (n = 18) and on the 10th day of life for controls (n = 19). Blood samples for measurement of cortisol and GH from both HI and control groups were collected after the first 12–24 h of life. There were 11 babies in the mild-to-moderate (stages I and II) group and 7 babies in the severe (stage III) group according to Sarnat and Sarnat. The IGF-1 levels of the HI group measured after 12–24 h [78.5 ± 27.9 (range 9–123.4) ng/ml] and on the 10th day [72.2 ± 36.8 (range 29.7–159.2) ng/ml] of life were statistically significantly lower than the IGF-1 levels of the control group [121.5 ± 50.4 (range 74.4–280.5) ng/ml and 133.1 ± 34.4 (range 65.9–202) ng/ml, respectively] (p = 0.002 and p = 0.001, respectively). But there was no statistically significant difference between mild-to-moderate HI group and severe HI group in terms of IGF-1 levels after 12–24 h and 5 and 10 days of life (p > 0.05). Also there was no statistically significant difference in IGF-1 values after the first 12–24 h and after 10 days of life between HI subjects who died or survived (p > 0.05). The GH levels of the HI group after the first 12–24 h of life [34.6 ± 32.3 (range 0.1–120) mIU/l] were statistically significantly higher than those in the control group [10.4 ± 4.5 (range 3.7–16.9) mIU/l] (p = 0.005). There was no statistically significant difference in the serum cortisol levels between HI and control groups after the first 12–24 h of life [18.7 ± 17.0 (range 1.6–65.1) µg/dl vs. 10.8 ± 5.4 (range 3.0–23.2) µg/dl] (p > 0.05). No statistically significant correlation was found between IGF-1 levels and GH and cortisol levels of the HI encephalopathy group [r = –0.113 (p > 0.05) and r = 0.108 (p > 0.05), respectively]. In conclusion, this study showed decreased levels of serum IGF-1 and increased levels of GH which may be secondary to serum IGF-1 influx from the circulation to the brain as a protective mechanism or may be due to some cytokines which alter the GH/IGF axis, inhibit the action of IGF-1, and stimulate IGF-binding protein 1.
The Accuracy of Transcutaneous Bilirubin Measurements in Neonates: A Correlation Study
Authors: Nanjundaswamy Shakuntala , Petrova Anna , Mehta Rajeev , Bernstein William , Hegyi Thomas
Published: December 2003

A prospective observational study was conducted on 212 neonates born between 24 and 42 weeks of gestation who required blood sampling to determine total serum bilirubin (TSB) in the first week of life, prior to phototherapy. The transcutaneous bilirubin (TcB) measurements were performed on the infant’s forehead using BiliCheck™ within ±30 min of a blood sample being drawn. There was significant (r = 0.78) correlation between bilirubin levels obtained transcutaneously and those measured in the infant’s blood. The correlation was not affected by birth weight and was dependent on the bilirubin levels. The negative nonsignificant correlation appears when TSB levels are greater than 11 mg/dl. Thus, TcB measurements can accurately predict TSB values lower than 11 mg/dl in a multiracial preterm and term neonatal population.
Selective Inhibition of Nitric Oxide in Hypoxic-Ischemic Brain Model in Newborn Rats: Is It an Explanation for the Protective Role of Erythropoietin?
Authors: Kumral Abdullah , Baskin Huseyin , Gokmen Necati , Yilmaz Osman , Genc Kursad , Genc Sermin , Tatli M. Mansur , Duman Nuray , Ozer Erdener , Ozkan Hasan
Published: December 2003

Erythropoietin (Epo) exerts neuroprotection against neuronal death induced by ischemia and hypoxia in vitro and in vivo. Recent studies suggest that the neuroprotective effects of Epo may depend upon different mechanisms, including the inhibition of nitric oxide (NO). We recently demonstrated that Epo exerts neuroprotection in a model of neonatal hypoxic-ischemic brain damage. In the present study, we directly determined whether systemic administration of recombinant Epo modulates cerebral NO production in a neonatal rat model of hypoxic-ischemic brain injury. Seven-day-old Wistar rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure. Brain nitrite levels were evaluated in both hemispheres (carotid ligated or nonligated) by Griess reagent 72 h after the hypoxic-ischemic insult. Our results show that hypoxic-ischemic insult results a significant increase in NO production as compared with NO levels in hypoxic hemispheres and control animals. A single dose of Epo treatment (1,000 U/kg i.p.) significantly decreased NO overproduction in the hypoxic-ischemic hemisphere, whereas no significant change appeared in hypoxia alone or in controls. These data suggest that the selective inhibitory effect of Epo on NO overproduction could have a neuroprotective effect in neonatal hypoxic-ischemic brain injury.
Reoxygenation with 100 or 21% Oxygen after Cerebral Hypoxemia-Ischemia-Hypercapnia in Newborn Piglets
Authors: Solås Anne-Beate , Kalous Petr , Saugstad Ola D.
Published: December 2003

We tested if reoxygenation with 100% O2 was superior to 21% O2 after combined cerebral hypoxemia-ischemia-hypercapnia (HIH) in newborn piglets. Twenty-eight piglets were randomized to reoxygenation with 100 or 21% O2 following asphyxia. Asphyxia was induced by ventilation with 8% O2, adding CO2, and temporary occlusion of both common carotid arteries. After 20 min, reoxygenation-reperfusion was started with 21% O2 (HIH 21% group, n = 13) or 100% O2 (HIH 100% group, n = 11) for 30 min followed by 21% O2. All piglets were observed for 2 h. We measured mean arterial blood pressure (MABP), changes in microcirculation in the cerebral cortex (laser Doppler), and extracellular concentrations of hypoxanthine in the cortex and amino acids in the striatum (microdialysis). We found significantly higher MABP and better restoration of microcirculation after reoxygenation with 100% compared with 21% O2, but no differences in biochemical markers were found between the groups. This indicates that the brain tolerated reoxygenation with 21% as well as with 100% O2 in the present model of experimental asphyxia in spite of the differences in MABP and cerebral microcirculation.
Expression and Phosphorylation of N-Methyl-D-Aspartate Receptor Subunits during Graded Hypoxia in the Cerebral Cortex of Newborn Piglets
Authors: Fritz Karen I. , Ashraf Qazi M. , Zubrow Alan B. , Mishra Om P. , Delivoria-Papadopoulos Maria
Published: December 2003

The present study tests the hypothesis that during graded hypoxia, N-methyl-D-aspartate (NMDA) receptor expression and phosphorylation are altered in the cerebral cortex of newborn piglets. Studies were performed in anesthetized, ventilated piglets, 6 normoxic and 9 exposed to different lengths of decreased fractions of inspired oxygen to achieve varying biochemical levels of phosphocreatine (PCr). P2 membrane proteins were immunoprecipitated with antiphosphoserine, antiphosphotyrosine, or antiphosphothreonine antibodies and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins were transblotted and probed with NMDA receptor subunit 1 (NR1), NR2A or NR2B antibodies. As tissue PCr levels decreased from 3.5 to 0.5 µmol/g brain during hypoxia, NR1, NR2A and NR2B protein increased by 84, 56 and 38%, respectively. Phosphorylated serine, tyrosine and threonine residues also increased during hypoxia on the three subunits. However, the increase in subunit protein exceeded the increase in phosphorylated residues for all three subunits. Therefore, the ratio of phosphorylated/dephosphorylated serine, tyrosine and threonine residues decreased with worsening hypoxia. We speculate that an alteration in the ratio of phosphorylated/dephosphorylated residues of the NMDA receptor may regulate receptor activation during hypoxia.
Bacterial Translocation of Coagulase-Negative Staphylococci in Rats following Intestinal Ischemia-Reperfusion Injury
Authors: Luo Chih-Cheng , Shih Hsiang-Hung , Chiu Cheng-Hsun , Lin Jer-Nan
Published: December 2003

Many patients with sepsis have bacteremia for which no septic focus is identified either clinically or by autopsy. This study was designed to determine the relationship between the ischemia-reperfusion injury (IRI) and bacterial translocation that might be involved in the pathogenesis of necrotizing enterocolitis. In the first experiment, a total of 32 Sprague-Dawley rats weighing 150–200 g were divided into four groups. The mesentery to isolated loop was occluded for 30, 60, and 90 min following 30-min reperfusion in the three groups of experimental animals with a micro-bulldog clamp. A control group involved the same technique and exposure, without occlusion of the mesentery. Two sets of blood culture were taken through a catheter in the portal vein immediately and 15 min after the reperfusion, respectively. In another experiment, bacteria isolated were fed in different doses to control rats and those after 30- or 60-min ischemia and 30-min reperfusion. Two sets of blood culture were taken following the procedure. Invasion and transcytosis of the bacteria through epithelial cells were studied in vitro using a Madin-Derby canine kidney (MDCK) cell monolayer model. PCR for delta toxin gene was performed on all bacteria isolated, using Staphylococcus epidermidis as the control. Coagulase-negative staphylococci (CoNS) were invariably isolated from mice with prolonged ischemia (90 min) and reperfusion. When bacteria were fed into mice with only 30-min ischemia, an inoculum as low as 5 × 105 CFU/ml could induce bacteremia. No bacterial translocation was found in control mice even fed with a higher dose of bacteria (5 × 108 CFU/ml). In vitro experiments showed that CoNS failed to transcytose MDCK monolayer. These isolates were not cytotoxic to MDCK cells and contained no delta toxin gene. Bacterial translocation of CoNS occurred following severe bowel ischemia and reperfusion injury. Intact mucosa integrity readily prevented bacterial translocation; however, bacterial translocation could occur in rats following mild IRI in the presence of a higher number of CoNS in the gut.
Supplementation of Female Rats with α-Linolenic Acid or Docosahexaenoic Acid Leads to the Same Omega-6/Omega-3 LC-PUFA Accretion in Mother Tissues and in Fetal and Newborn Brains
Authors: Valenzuela Alfonso , von Bernhardi Rommy , Valenzuela Viviana , Ramírez Gigliola , Alarcón Rodrigo , Sanhueza Julio , Nieto Susana
Published: December 2003

Background: Maternal omega-3 fatty acid supplementation has been suggested to provide docosahexaenoic acid (DHA) for the normal brain development during gestation. DHA can be given as such (preformed) or through the omega-3 precursor alpha-linolenic acid (LNA) which is transformed into DHA by elongation and desaturation reactions. Western diet provides low amounts of LNA and DHA; therefore, supplementation with these omega-3 fatty acids has been suggested for pregnant women. However, the bioequivalence of LNA ingestion to DHA supplementation has not been established. Methods: Recently weaning female Wistar rats were fed a diet containing a small amount of LNA and no DHA. The animals were daily supplemented 40 days before mating, during pregnancy, and until delivery with 60 mg/kg of LNA or 6 mg/kg of DHA dissolved in coconut oil. Fatty acids were given as ethyl ester derivatives. Controls received coconut oil. The fatty acid composition of blood plasma, erythrocytes, liver, visceral adipose tissue, and brain segments (frontal cortex, hippocampus, and cerebellum) was analyzed. Brain segments obtained from 16- and 19-day-old fetuses and from 2- and 21-day-old rats were also analyzed for fatty acid composition. Results: Supplementation with LNA and DHA induced a similar accretion of DHA in plasma, erythrocytes, liver, and brain segments of the mothers. The adipose tissue showed a higher DHA accretion after DHA-supplementation. The DHA accretion in frontal cortex, hippocampus, and cerebellum obtained from the fetuses and the newborn rats was similar when the mothers were supplemented with LNA and DHA. Our results show that under our experimental conditions a similar accretion of DHA in the different tissues of the mothers and in the brain segments of fetuses and newborn rats is obtained after LNA and DHA supplementation. Conclusion: LNA and DHA, at the amounts given in this study, show a similar bioequivalence for DHA accretion in different tissues of the mother and in brain segments of fetuses and newborn rats.
Ileocecal Valve-Preserving Ileostomy after Total Proctocolectomy – A Novel Technique for Ileostomy
Authors: Nio Yoshinori , Itakura Masayuki , Yamaguchi Kazushige , Hirahara Noriyuki
Published: December 2003

Background: Although ileoanal anastomosis has become popular for ulcerative colitis, in an emergency situation patients must undergo ileostomy. Aim: A novel ileocecal valve-preserving ileostomy procedure was devised to reduce high output liquid loss. Method: After total colectomy, the ascending colon was clamped and the terminal ileum and ileocecal valve were isolated from the cecum by dissection. The ileum was then brought out through a conventional ileostomy opening in the abdominal wall. Results: Two patients with ulcerative colitis underwent ileostomy in this fashion. The stool became solid within 1 week after the start of solid food and their body weight increased by more than 10% 1 year after surgery. Conclusion: This novel procedure may result in an improvement in the quality of life of patients who undergo total proctocolectomy.
Defense Styles, Impulsivity and Suicide Attempts in Major Depression
Authors: Corruble Emmanuelle , Hatem Nizar , Damy Claire , Falissard Bruno , Guelfi Julien-Daniel , Reynaud Michel , Hardy Patrick
Published: December 2003

Background: The aim of our study was to identify if defense mechanisms are associated with impulsivity and lifetime suicide attempts in depressed patients. Sampling and Methods: The Defense Style Questionnaire, the Impulsivity Rating Scale and the Impulse Control Scale were used in 77 depressed inpatients. Results: Impulsivity was correlated positively with immature and neurotic styles and negatively with mature style. Some but not all defense mechanisms were relevant in this respect. The number of lifetime suicide attempts was positively correlated not only with impulsivity, but also with immature style and to a lesser extent with neurotic style. Several defense mechanisms were involved in these correlations: undoing, projection, passive aggression, acting out, splitting and somatization. Conclusions: Like impulsivity, defense styles may be relevant to discriminate recurrent suicide attempters in depression. Prospective assessment of defense styles and suicide attempts in depression is needed.
Augmented Contractile Response of Vascular Smooth Muscle in a Diabetic Mouse Model
Authors: Okon Elena B. , Szado Tania , Laher Ismail , McManus Bruce , van Breemen Cornelis
Published: December 2003

The vasomotor properties of isolated aortae and mesenteric arteries of insulin-resistant ob/ob and 57CBL/6J mice were compared in organ bath studies. Vessels from ob/ob mice were more sensitive to phenylephrine. Pretreatment with L-NAME caused similar leftward shifts of the phenylephrine concentration response curves in diabetic and non-diabetic vessels. The ob/ob aortae contracted in response to phenylephrine with roughly twice the force while they were not stiffer than control aortae. L-NAME caused a greater percentage increase in maximal force in the control than in the ob/ob tissue. Denudation potentiated force in the control aortae, but not in the ob/ob aortae. Endothelium-dependent relaxation in the ob/ob aortae and mesenteric arteries was impaired as manifested by a decreased sensitivity and maximal relaxation to acetylcholine, while the aortic basal eNOS mRNA levels did not differ between the two strains. In addition, ob/ob aortae were less sensitive to the nitric oxide donor sodium nitroprusside. Inhibition of endogenous prostaglandin synthesis with indomethacin (10 µM) partly normalized the contractile response of the ob/ob aortae and enhanced their endothelium-dependent relaxation. Neither blockade of endothelin-1 receptors (bosentan, 10 µM) nor PKC inhibition (calphostin, 1 µM) affected the contractile response to phenylephrine in the mouse aortae of either strain. In conclusion, vascular dysfunction in the aorta and mesenteric artery of ob/ob mice are due to increased smooth muscle contractility and impaired dilation but not to changes in elasticity of the vascular wall. Endothelium-produced prostaglandins contribute to the increased vasoconstriction.
Estrogen Altered Oral Tolerance Induction in Type II Collagen-Induced Murine Arthritis
Authors: Hosoda Tomoko , Mito Natsuko , Yoshino Haruka , Sato Kazuto
Published: December 2003

Background: Estrogen plays an important modulatory role in the immune system, and is concerned with the pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA), although the mechanism has not yet been clarified. Oral tolerance, a form of specific peripheral tolerance, which is recognized as a new therapeutic strategy, is related to the function of gut-associated lymphoid tissue. Methods: In this study, using collagen-induced arthritis as an animal model of RA, the effects of 17β-estradiol (E2) on oral tolerance induction were investigated. For induction of oral tolerance, mice were fed 60 µg type II collagen (CII) for 10 consecutive days prior to each CII immunization. Mice in the E2 treatment groups were injected with 5 µg (low dose) or 500 µg (high dose) E2 three times during the induction of oral tolerance. Results: Oral tolerance induction suppressed the occurrence of arthritis, the proliferative response of splenocytes to CII and the specific DTH response. However, E2 treatment abrogated the suppression, which might be connected with a change in function of Peyer’s patch (PP) lymphocytes. Conclusion: These results suggest that oral tolerance induction might be affected by estrogen treatment through alteration of intestinal immune responses.
Repeated Aerosol Allergen Exposure Suppresses Inflammation in B-Cell-Deficient Mice with Established Allergic Asthma
Authors: Jungsuwadee Paiboon , Benkovszky Michaela , Dekan Gerhard , Stingl Georg , Epstein Michelle M.
Published: December 2003

Background: Repeated allergen administration is a well-established therapeutic strategy for desensitizing patients with allergic disease. Similarly, repeated inhalation of antigen by mice with established allergen-induced asthma suppresses allergic inflammation. The mechanisms underlying antigen-dependent suppression of allergic immune responses remain unknown. In previous studies, we found that repeated aerosol antigen challenges in sensitized mice reduced eosinophils while increasing plasma cells and antibody in the lungs. We sought to test whether plasma cells and antibody played a role in suppression of allergic disease. Methods: We primed wild-type and B-cell-deficient (µMT) mice with 25 µg ovalbumin (OVA) precipitated in alum on days 0 and 5, nebulized weekly with 1% OVA, 1 h, twice daily, for up to 6 weeks, and assessed lung inflammation, mucus hypersecretion, and IgE/IgG1. Results: Kinetic studies revealed that initial aerosol exposure induced high numbers of eosinophils, lymphocytes, and macrophages within lung infiltrates and increased mucus production in wild-type mice. After 3–4 weeks of antigen exposure, eosinophils diminished while lymphocytes, plasma cells, and macrophages and mucus hypersecretion increased. However, by 6 weeks, lung inflammation and mucus hypersecretion were dramatically reduced. In contrast, repeated aerosol challenges maintained OVA-specific IgG1 and IgE production. Repeated aerosol antigen challenges in µMT mice resulted in reduced lung inflammation and mucus hypersecretion and the development of smooth muscle hypertrophy of the pulmonary microvasculature. Conclusions: B cells and antibody do not appear to play a role in antigen-dependent suppression of allergic responses in mice.
Platelet-Activating Factor Concentration in the Stool of Human Newborns: Effects of Enteral Feeding and Neonatal Necrotizing Enterocolitis
Authors: Amer Michael D. , Hedlund Erik , Rochester Jeremy , Caplan Michael S.
Published: December 2003

Epidemiologic studies have identified enteral feedings as a risk factor for necrotizing enterocolitis (NEC). Enteral feedings provide the substrate for colonization of the newborn gut with gram-negative bacteria with endotoxin production, which may trigger the production of endogenous inflammatory mediators, including platelet-activating factor (PAF). In this prospective study, we examined the effect of enteral feeding on PAF concentration in the stool of preterm and full-term human newborns. The concentration of PAF levels in stool was measured at the following times: at passage of first meconium, within 24 h prior to the onset of feedings, at the 3rd and 14th day of feeding and at any time confirmed NEC developed. Stool samples also were analyzed for levels of acetylhydrolase, the PAF breakdown enzyme. Stool PAF concentration rose significantly following the start of enteral feedings. The mean PAF concentration for day 14 samples was significantly higher than the mean concentration of meconium samples (4.90 ± 1.03 vs. 1.81 ± 0.38 ng/g, p < 0.05) and day 0 samples (4.90 ± 1.03 vs. 1.79 ± 0.39 ng/g, p < 0.05). For the 7 patients diagnosed with definite NEC, the mean stool PAF concentration was 12.42 ± 0.77 ng/g, significantly elevated compared to the mean PAF levels in stool from healthy infants at all sampling times (p < 0.01). There was no significant change in acetylhydrolase activity at any of the sampling times. Stool PAF concentration increases with the provision of enteral feedings and rises further with the development of NEC. Since stool acetylhydrolase activity remained unchanged, we speculate the increase of PAF in stool likely represents increased PAF production at the local level following the provision of enteral feedings or the development of neonatal necrotizing enterocolitis.
von Hippel-Lindau Tumor Suppressor Protein and Hypoxia-Inducible Factor in Kidney Cancer
Authors: Maynard Mindy A. , Ohh Michael
Published: December 2003

The development of hereditary von Hippel-Lindau (VHL) disease and the majority of sporadic kidney cancers are due to the functional inactivation of the VHL gene. The product of the VHL gene, pVHL, in association with elongins B and C, cullin 2, and Rbx1 form an E3 ubiquitin-ligase complex VEC that targets the alpha subunits of hypoxia-inducible factor (HIF) for ubiquitination. Ubiquitin-tagged HIF-α proteins are subsequently degraded by the common 26S proteasome. pVHL functions as the substrate-docking interface that specifically recognizes prolyl-hydroxylated HIF-α. This hydroxylation occurs only in the presence of oxygen or normoxia. Thus, under hypoxia, HIF-α subunits are no longer subjected to degradation and are thereby able to dimerize with the common and constitutively stable β subunits. The heterodimeric HIFs upregulate a myriad of hypoxia-inducible genes, triggering our physiologic response to hypoxia. Inappropriate accumulations of HIF-α in VHL disease are believed to contribute to the pathogenesis via the upregulation of several of these HIF target genes. Our current molecular understanding of the roles of HIF and pVHL in the development of VHL-associated clear-cell renal cell carcinoma (CC-RCC) is the focus of this review.
Three-Dimensional Sonographic Features of Placental Abnormalities
Authors: Hata Toshiyuki , Kanenishi Kenji , Inubashiri Eisuke , Tanaka Hirokazu , Senoh Daisaku , Manabe Atsushi , Miyake Kaoru , Kondoh Shungo , Hata Toshio
Published: December 2003

Objective: To describe three-dimensional (3D) sonographic features of placental abnormalities in utero. Methods: A total of 6 cases with placental abnormalities (1 chorioangioma, 1 subchorionic hematoma, 2 placental cysts, and 2 subplacental fibromas) from 22 to 34 weeks of gestation were studied with transabdominal 3D sonography. Results: Placental abnormalities could be easily imaged with both two-dimensional (2D) and 3D sonography; however, visualization of the continuity and curvature of structures was more easily accomplished with 3D sonography. In the case with chorioangioma, the thick and rough surface of the tumor was clearly depicted. With the use of color Doppler ultrasound, only a case of chorioangioma was shown to have abundant blood flow within the tumor. In cases with placental cyst and subchorionic hematoma, the wall of the cyst becomes a transparent-like structure, so internal textures can be clearly identified. In the case with subplacental fibroma, the location in relation to the placenta was clearly recognized. Conclusion: These results suggest that 3D sonography has the potential to be a supplement to 2D sonography and color Doppler ultrasound in identifying placental masses and provides a novel means of visualizing placental abnormalities in utero.
Medical Fellowship Programme within the Gynaecological Cancer Group of the European Organisation for Research and Treatment of Cancer
Authors: Wagenaar H.C. , Trimbos J.B.M.Z. , Teodorovic I. , Therasse P. , Vergote I.
Published: December 2003

In 1962, the European Organisation for Research and Treatment of Cancer (EORTC) was founded, and in the course of the years it developed into the leading European organisation in cancer research. Currently, the EORTC is organised into (Pre-)Clinical Groups and Task Forces consisting of scientists and/or clinicians. One of these groups with a specific area of interest in cancer research is the Gynaecological Cancer Group (GCG). The EORTC offers fellowship programmes to physicians and scientists from all over the world to create a possibility to be temporarily linked to an EORTC group or a specific research project. Over the past decade, 76 research fellowships have been appointed at the EORTC Data Center. This paper shows an overview of the activities of one EORTC/GCG medical fellow.
Validation of a Reliable Instrument (QUOTE-IBD) for Assessing the Quality of Health Care in Greek Patients with Inflammatory Bowel Disease
Authors: Pallis Athanasios G. , Vlachonikolis Ioannis G. , Mouzas Ioannis A.
Published: December 2003

Given the early onset, the chronic and recurrent nature of their disease and their normal life expectancy, patients with inflammatory bowel disease (IBD) may need considerable health care. The purpose of this study is to validate the Greek translation of the QUOTE-IBD questionnaire (GR-QUOTE-IBD). For that purpose we assessed its construct validity, and reliability. Fifty patients (33 ulcerative colitis, 17 Crohn’s disease) completed the GR-QUOTE-IBD and visual-analogue scales (VAS) for the patients’ evaluation of the quality of separate care dimensions, and of the total care. A subgroup of 33 patients (64%) completed the GR-QUOTE-IBD for a second time. Quality of life was assessed by the short version of the IBDQ. Clinical activity was assessed by Harvey-Bradshaw index and Colitis Activity Index. Correlations among all care dimensions and VAS were positive and highly significant (p < 0.001). The total care and all eight dimensional care scores (quality impact and importance) had no significant differences between the baseline and the follow-up visit. Similarly, the correlation coefficients between the scores of the two occasions were all positive (close to one) and highly significant (p < 0.001). The GR-QUOTE-IBD proved to be a valid and reliable instrument, applicable in international clinical studies.
LOS Function and Obesity: The Impact of Untreated Obesity, Weight Loss, and Chronic Gastric Balloon Distension
Authors: Mathus-Vliegen E.M.H. , van Weeren M. , van Eerten P.V.
Published: December 2003

Background/Aims: In obesity, many gastro-oesophageal reflux promoting factors are present. Weight reduction is advised to symptomatic overweight subjects. The aim of the present study was to investigate the influences of untreated obesity, weight loss, and chronic gastric balloon distension on the lower oesophageal sphincter (LOS) function. Methods: Patients entering a randomized, double-blind, sham-controlled study of balloon treatment, consisting of 4 months of either sham balloon or balloon treatment followed by 4 months of balloon treatment. Manometry and 24-hour pH measurements were performed at the start of the study and after 13 and 26 weeks. Results: Before treatment, LOS dysfunction was present in 7 of 32 patients (21.9%). Increased upright and supine reflux was present in 8 patients (25%). Sham treatment resulted in a weight loss of 9.7% with improved LOS function (a significant 0.6-cm increase in LOS length and a non-significant 2.6 mm Hg higher LOS pressure) and in a significantly decreased upright reflux (acid reflux time decreasing from 8.0 to 5.5% and number of meal-related and postprandial reflux episodes decreasing from 49 to 32). These improved values deteriorated after 4 months of balloon placement, with significantly increasing total, upright, and supine reflux to 7.5, 7.6, and 6.7% of the time, respectively, with oesophageal lesions after an overall 17.8% weight loss. Four months of balloon treatment induced a similar weight loss (9.9%) with significantly increased supine reflux from 1.6 to 6.7% of the time. After a second 4-month balloon period and an overall 13.8% weight loss, LOS and reflux values returned towards baseline values. A comparison of both groups demonstrated the adverse effects of balloon positioning after a period of substantial sham-induced weight loss. Conclusions: Impaired LOS function and increased gastro-oesophageal reflux were observed in one quarter of the untreated obese subjects. Weight loss ameliorated manometry and pH values, but subsequent balloon positioning tended to counteract these beneficial changes. In patients on balloon treatment from the start, adverse effects seemed to wear off with prolonged treatment.
A Monozygotic Conjoined Twin Pregnancy Discordant for Laterality of Cleft Lip
Authors: Masuzaki Hideaki , Miura Kiyonori , Yoshiura Ko-ichiro , Yoshimura Shuichiro , Ishimaru Tadayuki
Published: December 2003

Conjoined twins discordant for phenotype of cleft lip are reported. One had right-sided cleft lip, while the co-twin had left-sided cleft lip. Both twins had a normal 46,XY karyotype. Genotyping at 50 polymorphic loci revealed that the twins were identical (monozygotic). Our analysis suggests that the laterality of cleft lip is more affected by the process of twinning than by genetic factors.
Abnormal Colonic Propagated Activity in Patients with Slow Transit Constipation and Constipation-Predominant Irritable Bowel Syndrome
Authors: Bassotti Gabrio , Chistolini Fabio , Marinozzi Gabriele , Morelli Antonio
Published: December 2003

Background: The pathophysiological basis of constipation is still unclear, and the role of colonic dysfunction is debated, especially in irritable bowel syndrome. Objective data are quite scarce, especially concerning colonic propulsive activity. Aims: To evaluate high- and low-amplitude colonic propulsive activity in constipated patients (slow-transit type and irritable bowel syndrome) in comparison with normal controls. Patients and Methods: Forty-five constipated patients (35 with slow-transit constipation and 10 with constipation-predominant irritable bowel syndrome) were recruited, and their data compared to those of 18 healthy subjects. Twenty-four-hour colonic manometric recordings were obtained in the three groups of subjects, and data concerning high- and low-amplitude colonic propulsive activity were then compared. Results: High-amplitude propagated contractions were significantly (p < 0.05) decreased in patients with slow-transit constipation and constipation-predominant irritable bowel syndrome with respect to controls (1.5 ± 0.4, 3.7 ± 2, and 6 ± 1 events/subject/day, respectively). In slow-transit constipation, a significant decrease of contractions’ amplitude was also observed. Concerning low-amplitude propagated contractions, patients with slow-transit constipation had significantly less events with respect to patients with constipation-predominant irritable bowel syndrome (46 ± 7 vs. 87.4 ± 19, p = 0.015); no differences were found between patients with slow-transit constipation and controls and between patients with constipation-predominant irritable bowel syndrome and controls. All three groups displayed a significant increase of low-amplitude propagated contractions after meals (6.3 ± 2 vs. 18.2 ± 5 for controls, p < 0.005; 6.4 ± 1.4 vs. 16.3 ± 2.4 for slow-transit constipation, p < 0.005; 10.5 ± 3.2 vs. 32.6 ± 7 for constipation-predominant irritable bowel syndrome, p = 0.001). Conclusions: Low-amplitude propagated contractions may represent an important physiologic motor event in constipated patients, reducing the severity of constipation in patients with irritable bowel syndrome and preserving a residual colonic propulsive activity in patients with slow-transit constipation.
Factors Affecting Sexual Life during Pregnancy in Eastern Turkey
Authors: Eryilmaz Gülşen , Ege Emel , Zincir Handan
Published: December 2003

This is a descriptive and cross-sectional study aiming to determine the factors affecting sexual life in pregnant women. The study was carried out in 238 women in Malatya, Turkey. It was found that 61.4% regarded coitus as a risk during pregnancy, 31.9% did not have any knowledge about this matter. In 81.5% sexual life was affected during pregnancy. The mean frequency of intercourse was 2.02 ± 0.7/week before pregnancy and decreased to 1.51 ± 0.6/week during pregnancy. The reasons for this decline are: exhaustion and fatigue (64.3%); waning of sexual desire (55.9%); harmful to the fetus (49.2%); causing abortions in early pregnancy (45%), and inducing preterm labor (34%). There was a significant relationship between changes in sexual life during pregnancy and the duration of marriage (χ2 = 10.8, p < 0.05), education level (χ2 = 18.1, p < 0.05), parity (χ2 = 11.1, p < 0.05), and gravidity (χ2 = 6.8, p < 0.05). The variables such as age, employment status, and number of abortions did not affect sexual life during pregnancy.
Influence of Trans Fatty Acids on Health
Authors: Stender Steen , Dyerberg Jørn
Published: December 2003

The contribution of dietary trans fatty acids (TFAs) on the risk of ischemic heart disease (IHD) has recently gained further support due to the results from large, prospective, population-based studies. Compared to saturated fat, TFAs are, gram to gram, associated with a considerably (2.5- to >10-fold) higher risk increment for IHD. A negative effect on the human fetus and on newborns and an increase in colon cancer risk in adults are possible but, however, still equivocal. Recent findings justify further studies concerning the effect of TFAs on allergic diseases in children and on the risk of type-2 diabetes in adults. The intake of industrially produced TFAs in European countries is decreasing. However, determination of the TFA content in various popular food items collected in Danish shops showed that it is likely that persons with a frequent intake of, e.g., French fries, microwave oven popcorn, chocolate bars, fast food, etc., consume industrially produced TFAs in amounts far exceeding the average intake, and are thereby exposed to an unnecessary health risk. The Danish government has decided that oils and fats containing more than 2% industrially produced TFAs will not be sold in Denmark after the January 1, 2004.
Serum Total Prostate-Specific Antigen Assay in Women with Cushing’s Disease or Alcohol-Dependent Pseudo-Cushing’s State
Authors: Coiro V. , Volpi R. , Galli P. , Manfredi G. , Magotti M.G. , Saccani-Jotti G. , Chiodera P.
Published: December 2003

Background: The distinction between Cushing’s disease (Cushing’s syndrome dependent on adrenocorticotropic hormone (ACTH)-secreting tumors of pituitary origin) and pseudo-Cushing’s states (Cushingoid features and hypercortisolism sometimes present in alcoholic, depressed or obese subjects) can present a diagnostic challenge in clinical endocrinology. Recently, the availability of a highly sensitive immunofluorometric assay for the measurement of total prostate-specific antigen (PSA) provided the possibility to measure serum PSA levels in women. Interestingly, PSA gene expression and protein production has been found to be upregulated by steroid hormones, such as androgens, glucocorticoids, mineral corticoids and progestins. In fact, serum total PSA concentrations appear to be higher in female patients with Cushing’s disease than in normal women. We wondered whether a similar phenomenon also occurs in pseudo-Cushing’s state. Methods: In order to answer this question, we compared the serum total PSA levels measured in 10 female subjects with alcohol-dependent pseudo-Cushing’s state with those observed in 8 female patients with Cushing’s disease and in 15 age-matched healthy women. Serum testosterone, ACTH and cortisol, and 24-hour urinary cortisol levels were measured; cortisol suppression after dexamethasone was also tested in all subjects. Results: The basal serum levels of ACTH and cortisol were significantly lower in normal subjects than in patients with Cushing’s disease or pseudo-Cushing’s state; these latter groups showed similar basal hormonal values. Dexamethasone administration was unable to suppress serum cortisol levels in 5 subjects with Cushing’s disease and 6 subjects with pseudo-Cushing’s state. Serum testosterone values in the group with Cushing’s disease were higher than in the other groups. No differences were observed between pseudo-Cushing’s and normal subjects. Serum total PSA levels were significantly higher in women with Cushing’s disease than in subjects with pseudo-Cushing’s state and normal controls; these latter groups showed similar PSA values. When serum total PSA and testosterone levels were considered together, a significant positive correlation was observed in the group with Cushing’s disease, but not in the other groups. Conclusions: These data indicate that the steroid milieu responsible for the elevation in serum PSA in women with Cushing’s disease is not present in subjects with alcohol-dependent pseudo-Cushing’s state, suggesting the possible use of PSA as a marker of differentiation between these pathological conditions in women.
Prediction of Adverse Neonatal Outcomes in Preeclampsia by Absent or Reversed End-Diastolic Flow Velocity in the Umbilical Artery
Authors: Sezik Mekin , Tuncay Görkem , Yapar Elif Gül
Published: December 2003

To evaluate the independent contribution of absent or reversed end-diastolic umbilical artery Doppler flow (AREDF) in the prediction of subsequent adverse neonatal outcomes, we performed Doppler examinations on 270 preeclamptic women with a singleton pregnancy. The end-point variables were low Apgar scores and adverse neonatal outcomes (respiratory distress syndrome, intracranial hemorrhage, sepsis, seizures, jaundice, hypoglycemia, hypocalcemia, thrombocytopenia, polycythemia, and neonatal mortality). Stepwise logistic regression was used to control for gestational age, oligohydramnios, and fetal growth restriction. Infants with AREDF had an increased frequency of hypoglycemia (odds ratio = 1.7) and polycythemia (odds ratio = 1.7), whereas the remaining neonatal outcomes were explained by gestational age and growth restriction. Therefore, live-born infants of preeclamptic patients with AREDF velocities, independent of prematurity and growth restriction, are prone to hypoglycemia and polycythemia.
Intrauterine Fetal Death Caused by Pit Viper Venom Poisoning in Early Pregnancy
Authors: Nasu Kaei , Ueda Tami , Miyakawa Isao
Published: December 2003

Poisonous snakebite is a rare complication of pregnancy. It has been suggested that snakebite poisoning during pregnancy may cause fetal loss. We report a case of intrauterine fetal death after a poisonous snakebite in the first trimester of pregnancy. A 29-year-old pregnant Japanese woman was admitted to hospital after being bitten by a pit viper on her right heel. The patient was at 10 weeks of gestation. In response to the bite, her right leg became extremely swollen, and paralysis of the right oculomotor nerve was observed. Intravenous administration of cepharanthine, ulinastatin, hydrocortisone sodium succinate, gabexate mesylate and antibiotics was started. Laboratory data suggested the presence of rhabdomyolysis. One week after admission, although she improved clinically and symptomatically, transvaginal ultrasonography revealed intrauterine fetal death. No vaginal bleeding was observed. A dilatation and curettage was performed. The patient made an uneventful recovery and was discharged from hospital 17 days after the snakebite. Consistent with other reports, in the first trimester intrauterine fetal death may especially occur when the mother has systemic symptoms, although its mechanism remains unclear.
Endogenous Nitric Oxide Reduces Microvascular Permeability and Tissue Oedema during Exercise in Cat Skeletal Muscle
Authors: Persson Johan , Ekelund Ulf , Grände Per Olof
Published: December 2003

Based on a proposed increase in the release of the vasodilators nitric oxide (NO) and prostacyclin during exercise, and the fact that these substances have vascular permeability-reducing properties, this study was designed to evaluate (1) possible effects of exercise on hydraulic permeability, (2) whether permeability and muscle swelling are reduced by an increased release of NO and prostacyclin during exercise and (3) whether NO and prostacyclin are involved in exercise hyperaemia. The study was performed on an autoperfused cat calf muscle preparation with ligated lymph vessels, and exercise was induced by somatomotor nerve stimulation. Change in microvascular hydraulic permeability was estimated by a capillary filtration coefficient (CFC) technique. We found that the marked muscle volume increase after the start of the exercise gradually decreased, reaching an isovolumetric state within 25 min where CFC had decreased by about 25% (p < 0.05). CFC recovered completely after exercise was stopped. The decrease in CFC was abolished during blockade of endogenous NO by the NO synthase inhibitor L-NAME, but was preserved during blockade of endogenous prostacyclin by tranylcypromine. The muscle volume increase during exercise was about 60% greater with L-NAME than during vehicle or tranylcypromine (p < 0.01). Neither L-NAME nor tranylcypromine had any effect on exercise hyperaemia. We conclude that microvascular hydraulic permeability is reduced during exercise, that this effect reduces exercise-induced muscle swelling, and that the effects are mediated via release of NO. NO and prostacyclin are not involved in exercise hyperaemia.
Esomeprazole 40 mg Provides Improved Intragastric Acid Control as Compared with Lansoprazole 30 mg and Rabeprazole 20 mg in Healthy Volunteers
Authors: Wilder-Smith Clive H. , Röhss Kerstin , Nilsson-Pieschl Catharina , Junghard Ola , Nyman Lars
Published: December 2003

Aim: To compare the effects of standard-dose esomeprazole with those of standard doses of lansoprazole and rabeprazole on intragastric pH during repeated daily oral dosing in healthy volunteers. Methods: In two standardized, randomized crossover studies, Helicobacter pylori negative healthy volunteers (study A: 19 males, 5 females; study B: 13 males, 10 females) received esomeprazole 40 mg and either lansoprazole 30 mg (study A) or rabeprazole 20 mg (study B) orally once daily in the morning for 5 days. Continuous 24-hour intragastric pH recording was performed on day 5. Results: The intragastric pH was maintained >4 for 65% (95% CI 59.5–71.3) of the 24-hour period with esomeprazole and for 53% of the time (95% CI 47.0–58.9) with lansoprazole in study A (p < 0.001). In study B, the proportion of time with pH >4 was 61% (95% CI 53.6–68.3) with esomeprazole versus 45% (95% CI 37.7–52.5) with rabeprazole (p = 0.005). The 24-hour median pH and the proportion of volunteers with intragastric pH >4 for ≧12 h and ≧16 h were significantly higher with esomeprazole than with either lansoprazole or rabeprazole. Conclusion: Esomeprazole 40 mg provides significantly more effective and more sustained gastric acid control than lansoprazole 30 mg or rabeprazole 20 mg in healthy volunteers.