bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenal and Thyroid Axis Function in Preterm Ventilated Baboons
Authors: Jobe Alan H. , Scott Susan M. , Polk Daniel H. , Seidner Steven R.
Published: April 2003

Cortisol and thyroid hormones are critical to normal fetal development and neonatal transition, and baseline values and stimulation tests are abnormal after preterm birth. To evaluate cortisol and thyroxine (T4) responses that are not influenced by uncontrolled antenatal events associated with human preterm labor, we measured cortisol and T4 after standard-dose adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) stimulation tests, as well as high-dose CRH and thyrotropin-releasing hormone stimulation tests in baboons that were delivered for 3 separate protocols at 125 days of gestation (term is 186 days). The animals were surfactant treated and ventilated for up to 14 days. Some fetuses were exposed to fetal or maternal betamethasone, and some newborns were treated with 10 µg/kg T4 for 9 days after birth. Baseline cortisol levels were in a stress range of 30–60 µg/dl by day 5. Cortisol did not increase consistently until day 11 in response to a high CRH dose or ACTH. T4 treatment for 9 days after birth suppressed the cortisol responses and subsequent baseline T4 levels. The hypothalamic-pituitary-adrenal (HPA) axis was unresponsive to standard dose stimulation tests until 11 days of age in preterm baboons, indicating HPA immaturity.
Neuroprotective Effect of Erythropoietin on Hypoxic-Ischemic Brain Injury in Neonatal Rats
Authors: Kumral Abdullah , Ozer Erdener , Yilmaz Osman , Akhisaroglu Mustafa , Gokmen Necati , Duman Nuray , Ulukus Cagnur , Genc Sermin , Ozkan Hasan
Published: April 2003

Erythropoietin (Epo) prevents ischemia and hypoxia-induced neuronal death in vitro. Recent studies have shown that this cytokine also has in vivo neuroprotective effects in cerebral and spinal ischemia in adult rodents. In this study, we aimed to investigate the effect of systemically administered recombinant human Epo on infarct volume and apoptotic neuronal death in a newborn rat hypoxic-ischemic brain injury model. Our results showed that a single dose of intraperitoneal Epo treatment (1,000 U/kg) significantly decreased the mean infarct volume as compared to the control group. In contrast to the Epo-treated group, histopathological examination by positive terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling of the affected brain in control animals revealed widespread neuronal injury associated with numerous apoptotic cells. Morphometric analysis to determine the extent of damage quantitatively ascertained that the mean infarct volume was significantly lower in the Epo-treated group (p < 0.003). These results suggest the beneficial neuroprotective effect of Epo in this model of neonatal hypoxic-ischemic brain injury. To our knowledge, this is the first study that demonstrates a protective effect of Epo against hypoxia-ischemia in the developing brain.
Antioxidant Protection against Free Radicals Is Reduced in Fetal Plasma after Intrauterine Red Blood Cell Transfusion
Authors: Egberts Johannes , Luykx Lucille M. , Berger Howard M.
Published: April 2003

After intrauterine transfusion for red cell alloimmunization, a 2- to 20-fold increase of plasma Hb, a strong pro-oxidant, was observed. The increase of fetal plasma Hb after transfusion leads to a highly significant reduction of plasma antioxidant capacity, measured as the peroxyl radical trapping capacity. Consequently, the posttransfusion reduced antioxidant protection may enhance the peroxidation of lipids in e.g. donor erythrocyte membranes, leading to the shortened life span of these cells in the fetus.
The Activation of the Retinoic Acid Response Element Is Inhibited in an Animal Model of Congenital Diaphragmatic Hernia
Authors: Chen Miao-hsueh , MacGowan Alice , Ward Simon , Bavik Claes , Greer John J.
Published: April 2003

Defects very similar to those seen in infants born with congenital diaphragmatic hernias can be induced in rodents by the administration of the teratogen nitrofen. There is an interest in understanding the biochemical mechanisms of nitrofen’s actions in hopes of gaining insights into the etiology of congenital diaphragmatic hernia. In this study, we test the hypothesis that nitrofen is acting to perturb the retinoid signaling pathway by utilizing genetically engineered mice that have the lacZ reporter gene linked to a retinoic acid response element (RARE). We demonstrate a pronounced suppression of RARE-lacZ expression by nitrofen in vitro (by approximately 64%) and in vivo (by approximately 43%).
Early Cord Clamping Protects At-Risk Neonates from Polycythemia
Authors: Capasso Letizia , Raimondi Francesco , Capasso Antonio , Crivaro Valeria , Capasso Rachele , Paludetto Roberto
Published: April 2003

Neonatal polycythemia is a potentially lethal, multi-organ disease. We have performed a prospective, open-label study to test the hypothesis that an early cord clamping proximally to the neonate’s abdomen could avert from the neonatal circulation a blood volume critical to the occurrence of polycythemia in at-risk neonates. Newborns were divided into group 1 (clamping time within 10 s) and group 2 (clamping time 11–120 s). Group 1 had statistically significant more blood volume sequestered in the cord and less manifestations of polycythemia. Conclusion: An early cord clamping is an effective and zero-cost way to prevent polycythemia in at-risk neonates.
Transcranial Magnetic Cortical Stimulation Relieves Central Pain
Authors: Canavero S. , Bonicalzi V. , Dotta M. , Vighetti S. , Asteggiano G. , Cocito D.
Published: April 2003

Extradural cortical stimulation for neurogenic pain is a recent addition to the field of functional neurosurgery. About 50% of patients with central pain draw benefit in the long run. However, there is an urgent need for prognostic factors in order to cut the costs of the procedure. In this paper we report a statistically significant correlation between the subhypnotic propofol test, transcranial magnetic cortical stimulation (TMS) and the actual short-term outcome of extradural cortical stimulation in 9 patients. The propofol test and TMS appear to predict short-term effects of extradural cortical stimulation.
Mucosal Tolerance and Immunity: Regulating the Development of Allergic Disease and Asthma
Authors: Akbari Omid , Stock Philippe , DeKruyff Rosemarie H. , Umetsu Dale T.
Published: April 2003

Allergic diseases and asthma are characterized by eosinophilic inflammation induced by Th2 lymphocytes. However, the immunological events and the molecular and cellular mechanisms that protect against and regulate these pathological immune responses are poorly understood. In this review, we discuss the role of immunological tolerance, regulatory T cells, and dendritic cells (DCs) in these protective processes. In addition, we discuss factors like the maturation state of DCs, source and effect of Il-10 production as well as specific combinations of costimulatory molecules in the antigen-presenting cell: T cell synapse, which determine whether tolerance or immunity develops in the respiratory mucosa in response to inhaled allergen.
Influence of Different Variables on the Inter-Municipality Variation in Caries Experience in Danish Adolescents
Authors: Ekstrand K.R. , Christiansen M.E.C. , Qvist V.
Published: April 2003

This investigation sought to estimate the influence a number of variables had on the inter-municipality variation in caries experience across Denmark. Unit of measurement was the municipality with public clinics. Mean DMF-S and %DMF-S = 0 of 15- and 18-year-olds in 1999 were obtained from 204 and 143 municipalities, respectively, out of a total number of 206 municipalities with public clinics. The independent variables were: cost per child per year; children/dentist ratio; auxiliary personal/dentist ratio; fluoride concentration in the water supply [F]; average personal income; % of mothers of the 15- and 18-year-olds with ≤10 years education (EDU-15 or EDU-18); proportion of immigrants; and size of the municipality. Multiple regression analyses disclosed that [F] (p < 0.001) and EDU-15 (p < 0.001) were significant variables among the 15-year-olds explaining 45% of the variation in mean DMF-S and 31% of the variation in % DMF-S = 0. With respect to the 18-year-olds, [F] (p < 0.001) and average personal income (p < 0.001) explained 53% of the variation in mean DMF-S and 30% of the variation in %DMF-S = 0. Few municipalities were characterized as outliers with significantly lower or higher observed caries experience than expected. It is concluded that there is room for other explanatory factors – first and foremost the professional effort made in the individual Public Dental Health Service to control caries.
Laryngeal Stridor in Multiple System Atrophy
Authors: Yamaguchi Mika , Arai Kimihito , Asahina Masato , Hattori Takamichi
Published: April 2003

The purpose of this study was to elucidate the clinical features of laryngeal stridor in 104 patients with multiple system atrophy (MSA) and to predict the hazard risk. Stridor was observed in 36 patients. It occurred in the first year of the disease in 10 cases, and 69% of the cases were diagnosed with stridor within the first 4 years. Dysphagia and hoarseness had a statistically higher frequency in the stridor group, and the onset period of these elements correlated with the onset of stridor. A follow-up study of survival probability was carried out in 83 patients. The median survival period in the stridor group (33 cases) and the non-stridor group (50 cases) was 8.0 and 9.0 years, respectively. Treatment for stridor decreased the relative risk from 2.998 to 0.147. Laryngeal stridor is a common and early clinical symptom in MSA. Early treatment for stridor is advisable to reduce mortality.
Hypersomnia Associated with Bilateral Posterior Hypothalamic Lesion
Authors: Eisensehr I. , Noachtar S. , von Schlippenbach C. , Uttner I. , Kleine J. , Seelos K. , Helmchen C.
Published: April 2003

We examined an obese 58-year-old patient with a bilateral posterior hypothalamic lesion of unknown etiology. A 24-hour polysomnography revealed a markedly increased total sleep time (17.6 h). During daytime, only 3 continuous wake phases occurred. REM periods occurred only between 5 p.m. and 6 a.m. We conclude from our results that, similar to the results from animal experiments, the posterior hypothalamus in humans plays a critical role in the maintenance of wakefulness.
The Relationship of Recurrent Spontaneous Miscarriage with Reproductive Failure
Authors: Diejomaoh Michael , Jirous Jiri , Al-Azemi Magda , Baig Saba , Gupta Madhu , Tallat Alaa
Published: April 2003

Objective: To investigate the reproductive performance of non-pregnant women with recurrent spontaneous miscarriage (RSM) and the association between RSM and polycystic ovary syndrome (PCOS) in reproductive failure. Subjects and Methods: Fifty non-pregnant women with 3 or more consecutive RSM attending our RSM clinic were evaluated prospectively. Detailed history and physical examination were completed. Extensive laboratory investigations, ultrasonographic, radiological and specialized procedures/tests were performed. Those patients who did not achieve pregnancy within the first 6 months of follow-up had appropriate treatment options implemented. The outcome of any subsequent pregnancies was analyzed. Results: The mean age of the patients was 33.8 ± 4.6 years (range 22–43 years). The aetiological factors associated with RSM were chromosome anomaly, uterine abnormality, antiphospholipid syndrome, PCOS and infections; 40% were ‘unexplained’. Thirty patients (60%) were able to achieve viable pregnancies which progressed to term, resulting in live births. Fourteen of the other 20 patients had high body mass index (BMI) >30 and evidence of PCOS. Of these 20 patients, 13 eventually achieved pregnancies which ended again in first-second-trimester abortions (cause undetermined). The remaining 7 patients (4 with high BMI) who had a combination of male factor/protracted PCOS/ovarian failure did not achieve pregnancies. Conclusion: The association of RSM with PCOS resulted in poor reproductive performance, which may progress to reproductive failure.
Evaluation of Nitric Oxide Synthesis in the Optic Nerve Head in vivo Using Microdialysis and High-Performance Liquid Chromatography and Its Interaction with Endothelin-1
Authors: Okuno Takashi , Oku Hidehiro , Sugiyama Tetsuya , Goto Wakana , Ikeda Tsunehiko
Published: April 2003

Purpose: To investigate the relationship between nitric oxide synthesis and endothelin-1 (ET-1) in the optic nerve head in vivo. Methods: A concentric microdialysis probe was inserted into the optic nerve head of a rabbit and was perfused with Ringer’s solution at a constant flow rate of 2 µl/min. The perfused dialysates were collected every 10 min, and levels of nitrite and nitrate in the 10-min dialysate samples were measured after intravitreal injection of ET-1 (100 pmol) using high-performance liquid chromatography based on the Griess method. Results: Basal levels of nitrite and nitrate in the 10-min dialysate were 0.08 ± 0.01 and 3.95 ± 0.50 µM, respectively. We confirmed that these levels were reduced by intravenous L-NAME and restored by L-arginine. Intravitreal ET-1 significantly elevated the levels of nitrate to 189% of baseline 10 min after ET-1 application, which was inhibited by pretreatment of intravenous L-NAME (50 mg/kg). Conclusion: These results indicate that production of nitric oxide is closely connected with the ET-1 signaling pathway.
Does Continuous Venovenous Hemodiafiltration Concomitant with Radiological Procedures Provide a Significant and Safe Removal of the Iodinated Contrast Ioversol?
Authors: Gabutti Luca , Marone Claudio , Monti Matteo , Malfanti Marco , Zwahlen Ugo , Pasotti Elena , Colucci Giuseppe , Schönholzer Carlo
Published: April 2003

Background: The purpose of our study was to investigate whether continuous venovenous hemodiafiltration (CVVHDF) concomitant with radiological procedures (RxP) was feasible, well tolerated and could significantly remove iodinated contrast media (CM). Methods: 26 patients with various degrees of renal insufficiency who were submitted to RxP were included in the study. The CVVHDF session was started immediately before CM administration. All the patients were evaluated for feasibility and tolerability; furthermore a pharmacokinetic study was done on 12 patients to calculate the amount of CM eliminated. The baseline incidence of CM nephropathy was studied in 25 consecutive historical controls. Results: The CM administered was 208 ± 146 g; the fractional removal of CM was 9.2 ± 4.9% during RxP and 30.9 ± 20.7% during the whole CVVHDF session. Hemodynamic tolerance was excellent. The incidence of CM nephropathy in the experimental and control groups was 37 and 24%, respectively. Conclusions: CVVHDF during RxP is feasible and well tolerated but ioversol removal is modest. This fact together with the high incidence of renal function impairment, the complexity of the procedure and its intrinsic risks, and the large amount of resources needed discourage the routine use of CVVHDF as a prophylactic tool to avoid CM nephropathy.
Ärztliche Fortbildung unter Korruptionsverdacht?
Authors: Drack G. , Kuhn H.P. , Haller U.
Published: April 2003

Die standeseigenen und gesetzlichen Auflagen an die ärztliche Fortbildung sind in jüngster Vergangenheit erhöht worden. Der Aufwand an Zeit und Geld für gute Fortbildung ist hoch. Das Sponsoring vor allem der Heilmittelindustrie vermochte die Kosten für den einzelnen Teilnehmer tief zu halten. Es stellt sich die Frage nach einer tarifarischen Abgeltung der obligatorischen Fortbildung. Ansätze zur künftigen Deckung von indirekten Kosten sind gemacht. Bei einer vollständigen tarifarischen Abgeltung der Kosten müssten diverse Nachteile für Teilnehmer wie auch für die Qualität der Fortbildung erwartet werden. Neuerungen im schweizerischen Strafrecht und das neue Heilmittelgesetz verbieten das Sponsoring nicht, verlangen jedoch nach berufsethischen und im öffentlichen Spital personalrechtlichen Regeln für den Umgang mit Sponsorgeldern. Für das Sponsoring sind verschiedene Modelle denkbar mit unterschiedlicher Zuteilung an Veranstalter, Einzelteilnehmer oder Verteilung über ein Poolsystem. Starke Argumente sprechen für eine Fortführung der bisherigen Praxis einer gemischten Finanzierung über Teilnehmer und Sponsoring unter Einhaltung bestimmter Regeln zur Transparenz. Was bisher fehlt ist eine politische Entscheidung über die Finanzierung der ärztlichen Fortbildung.
The Reduced Release of GH by GHRH in 8 Subjects Aged 65–69 Years Is Augmented Considerably by Rivastigmine, a Drug for Alzheimer’s Disease
Authors: Obermayr Rudolf P. , Mayerhofer Lothar , Knechtelsdorfer Maarten , Tragl Karl Heinz , Geyer Georg
Published: April 2003

Background: The growth hormone (GH) secretion declines by 14% with each decade of adult life. Several attempts have been made to reverse the manifestations of the senile GH deficiency, termed somatopause, but GH substitution treatment in old age has not yet developed an established regimen. Cholinesterase inhibitors like pyridostigmine are able to elicit GH secretion when administered alone and to enhance the GH response to growth hormone releasing hormone (GHRH), but its clinical use is limited due to the strong peripheral cholinergic side effects. Objective: The aims of our experiments were to find out whether the GH response to GHRH can be augmented by rivastigmine, a new orally applicable and well-tolerated selective inhibitor of cerebral acetylchoinesterase. Methods: Eight healthy volunteers (age range 65–69 years) were studied. After an overnight fast, GHRH tests were done: 1 µg/kg GHRH was injected as an intravenous bolus. Blood samples for an immunoradiometric GH assay were taken at the time of GHRH injection (time 0) and after 15, 30, 45, 60, and 120 min. First, the baseline experiment was done: it consisted of two subsequent GHRH tests which were carried out within an interval of 120 min. Four weeks later the rivastigmine experiment was done identically, but 60 min before performing the second GHRH test, rivastigmine (4.5 mg) was administered orally. The GH secretory responses were expressed as areas under the curve (AUC; median, interquartile range), Wilcoxon’s signed-rank test was used for statistical comparisons. Results: Baseline experiment: The GH AUC of the first GHRH test was 1,040 (range 420–1,250) ng/ml/h. The repeated GHRH stimulation after 120 min (second GHRH test) showed a 13-fold decrease to 80 (range 60–130) ng/ml/h. Rivastigmine experiment: The GH AUC of the first GHRH test was 950 (range 540–1,430) ng/ml/h and, therefore, similar to that of the baseline experiment. 60 min after ingestion of the single oral dose of rivastigmine (4.5 mg), the following GHRH stimulation (second GHRH test) nearly doubled the GH AUC to 1,580 (range 860–3,330) ng/ml/h. Comparing the ΔGH AUC values (ΔGH AUC = GH AUC of the first GHRH test minus GH AUC of the second GHRH test), baseline experiment versus rivastigmine experiment, there was a 20-fold (p = 0.018) increase in GH AUC after rivastigmine pretreatment. Conclusions: Rivastigmine is a powerful drug to enhance GH release to repeated GHRH stimulation in healthy elderly human subjects. Future investigations are necessary to find out whether rivastigmine can restore the senile decline of the circadian GH secretion in the long term and, therefore, has new implications for patient treatment.
Iron and Folate Status before Pregnancy and Anemia during Pregnancy
Authors: Casanueva Esther , Pfeffer Frania , Drijanski Alejandra , Fernández-Gaxiola Ana Cecilia , Gutiérrez-Valenzuela Verónica , Rothenberg Stephen J.
Published: April 2003

Background: A lack of information about the role that iron and folate stores (erythrocyte folate) play on the anemia incidence in pregnant women. Objective: To evaluate the predictive value of ferritin and erythrocyte folate before pregnancy in relationship to the incidence of anemia throughout pregnancy. Methods: Thirty-five non-anemic non-pregnant women were evaluated 1 or 2 months before the pregnancy. After becoming pregnant they were evaluated every 4 weeks starting in the 8th week of pregnancy until 1 month post-partum. Every evaluation included determination of hemoglobin, ferritin and erythrocyte folate. Results: When the women started gestation with an insufficient iron store (<20 µg/l), the trend was to present anemia at significantly earlier gestational ages, in such a way that at week 20 of gestation almost 60% of the women with an inadequate store had anemia and only 25% of the women with an adequate store had this condition. On the other hand, the pregestational erythrocyte folate did not predict anemia incidence. Conclusions: Pregestational ferritin concentration predicts value of incidence of anemia throughout pregnancy.
Polyphenol Pattern and Antioxidant Activity of Different Tomato Lines and Cultivars
Authors: Minoggio M. , Bramati L. , Simonetti P. , Gardana C. , Iemoli L. , Santangelo E. , Mauri P.L. , Spigno P. , Soressi G.P. , Pietta P.G.
Published: April 2003

Background/Aims: Besides antioxidant vitamins and minerals, fruits and vegetables contain flavonoids and related phenolics. The biological activities of these polyphenols have become well known in recent years evidencing their beneficial effects on human health. In this context, the characterization of the flavonoids present in tomatoes is of great interest. Thus the polyphenol pattern (including flavonols, flavanones and cinnamate derivatives), lycopene and β-carotene concentrations and the total antioxidant activity (TAA) of the phenolic fraction from different tomato lines and cultivars have been determined. Methods: The characterization was obtained by means of spectrophotometry and HPLC analyses. Results: Mean values for single flavonoids were 0.68 ± 0.16 for naringenin, 0.74 ± 0.12 for rutin and 0.32 ± 0.06 for a rutin-pentoside. Mean total polyphenol content was 13.15 ± 1.15 mg/100 g and mean TAA value was 1.3 ± 0.10 mmol/g. The obtained TAA values resulted in good accordance with the total polyphenol content (R2 = 0.7928). The main phenolic acids were chlorogenic (mean ± SE 0.20 ± 0.03) and caffeic acid (mean ± SE 0.03 ± 0.01). Mean levels of lycopene and β-carotene were 5.38 ± 0.90 and 1.18 ± 0.40 mg/100 g, respectively. Conclusions: Almost all the lines characterised by low carotenoid content produce high levels of polyphenols, and consequently have the most powerful antioxidant potential.
Weekly High-Dose Folic Acid Supplementation Is Effective in Lowering Serum Homocysteine Concentrations in Women
Authors: Adank Charlotte , Green Timothy J. , Skeaff C. Murray , Briars Brooke
Published: April 2003

Aims: To compare the efficacy of a weekly high-dose (2,800 µg) folic acid supplement with a daily (400 µg) folic acid supplement in lowering homocysteine concentrations in healthy women of childbearing age. Methods: Free-living healthy women of childbearing age (n = 138) were randomized to receive a weekly (2,800 µg), a daily (400 µg) folic acid supplement, or placebo. Blood samples were collected at baseline and at 12 weeks and analyzed for serum homocysteine and erythrocyte folate. Results: At 12 weeks the mean (95% CI) serum homocysteine concentrations declined significantly (p < 0.05) in women receiving the daily [week 12 – baseline: –1.4 (–2.0, –0.70) µmol/l] and the weekly supplement [–1.3 (–2.1, –0.5) µmol/l] versus placebo [0.0 (–0.5, 0.5) µmol/l]. There was no significant difference between the two folate-treated groups (p > 0.05). At 12 weeks the mean erythrocyte folate concentration increased significantly in both supplemented groups versus placebo (p < 0.001). The increase in erythrocyte folate was significantly greater (p < 0.001) in the daily group than in the weekly group [451 (380, 521) vs. 288 (240, 335) nmol/l]. Conclusion: A weekly high-dose folic acid supplement was as effective as a daily supplement in lowering homocysteine concentrations in healthy women of childbearing age. Further study is needed to determine if weekly folic acid supplementation is effective in lowering homocysteine concentrations in populations with high homocysteine.
Topographical Organization of an Indirect Telencephalo-Cerebellar Pathway through the Nucleus paracommissuralis in a Teleost, Oreochromis niloticus
Authors: Imura Kosuke , Yamamoto Naoyuki , Sawai Nobuhiko , Yoshimoto Masami , Yang Chun-Ying , Xue Hao-Gang , Ito Hironobu
Published: April 2003

The nucleus paracommissuralis (NPC) of teleosts is a relay nucleus of an indirect telencephalo-cerebellar pathway. However, cells of origin in telencephalic subdivisions and terminal patterns of the NPC fibers in the cerebellum remain unclear. We studied these issues by means of tract-tracing methods in a cichlid, tilapia (Oreochromis niloticus). After tracer injections into the NPC, retrogradely labeled cells were found bilaterally in dorsal and ventral regions of the area dorsalis telencephali pars centralis (dDc and vDc) and area dorsalis telencephali pars dorsalis (Dd). Anterogradely labeled terminals were found in a caudal part of the bilateral corpus cerebelli (CC). The labeled terminals were restricted in the granular layer, which can be divided into dorsal and ventral regions based on cytoarchitecture. We injected tracers separately into the three telencephalic portions (dDc, vDc, and Dd) and into the dorsal or ventral regions of granular layer in the caudal CC. The results revealed a topographical organization of the indirect telencephalo-cerebellar pathway. A medial portion of the NPC received fibers from the vDc and projected to the ventral region of the caudal CC. An intermediate portion of the NPC received fibers from the dDc and Dd, and in turn projected to the dorsal region of the caudal CC. A lateral portion of the NPC received fibers from the Dd and in turn projected to the dorsal region of the caudal CC. The Dc is known to receive visual input via the area dorsalis telencephali pars lateralis, and the Dd is presumably a multimodal telencephalic portion. The present study suggests that the indirect telencephalo-cerebellar pathway through the NPC might convey descending visual and multimodal information to the CC in a topographical manner. We also demonstrated other indirect telencephalo-cerebellar pathways through the nucleus lateralis valvulae and the area pretectalis.
How Helicobacter pylori Changed the Life of Surgeons
Authors: Kleeff J. , Friess H. , Büchler M.W.
Published: April 2003

Helicobacter pylori infection has been identified as a pathogenic factor in a number of gastroduodenal diseases, most importantly in gastric and duodenal ulcer disease. This association and the development of H. pylori eradication therapies has had a tremendous influence on the surgical therapy for these disorders. Decades ago, surgery was the therapy of choice for gastric and duodenal ulcers. Now, however, the first line of therapy includes treatment of H. pylori infection, suppression of gastric acid secretion, and protection of gastric mucosal barriers combined with a range of endoscopic procedures. These developments have had a major impact on the indications for surgery in benign gastroduodenal diseases. In addition, advances in our understanding of the pathogenetic mechanisms of H. pylori infection have also changed our views of gastric mucosa-associated lymphoid tissue lymphoma, gastric cancer, and gastroesophageal reflux disease.
Testicular Blood Flow Alterations and Flow Cytometric Analysis in Prepubertal Rats with Experimentally Induced Unilateral Varicocele
Authors: Öztürk H. , Surer I. , Okur H. , Demirbag Suzi , Cetinkursun S.
Published: April 2003

Unilateral testicular pathologies have been accused of causing contralateral damage through a decrease in testicular blood flow. However, the contralateral testicular blood flow in unilateral varicocele has not been studied in detail. Therefore, the present study has been designed to evaluate the effects of a unilateral varicocele on the ipsilateral and on the contralateral testicular blood flow and the flow cytometric alterations in prepubertal rats. Experimental stenosis of the left renal vein in prepubertal rats causes dilation of the testicular vessels after puberty. Partial stenosis of the ipsilateral renal vein during the prepubertal period has no effect on ipsilateral or contralateral testicular blood flow, but does induce significant testicular damage, as determined by flow cytometry.
Perils and Pitfalls in the Interpretation of Clinical Trials: A Reflection on the Recent Experience in Multiple Sclerosis
Authors: Goodin Douglas S.
Published: April 2003

Therapeutic trials in multiple sclerosis, in part because of the marked intra- and inter-individual variability of its clinical course, are prone to serious flaws in both design and interpretation. As a consequence, it has been a common historical pattern that treatment regimens, which are enthusiastically recommended at one point in time, are later proven to be ineffective by more definitive studies. This review considers several recently published therapeutic trials in order to exemplify some of the difficulties that commonly arise in this area of clinical research.
Verbal Working Memory Deficit in Parkinson’s Disease Subjects
Authors: Graceffa Anita M.S. , Carlesimo Giovanni A. , Peppe Antonella , Caltagirone Carlo
Published: April 2003

The aim of the present work was to evaluate verbal working memory in patients affected by Parkinson’s disease (PD). In particular, tests that explore the functionality of the Articulatory Loop and of the Central Executive during verbal tasks were given. PD patients displayed normal phonological similarity, word length and word frequency effects in a Word span task, thus demonstrating adequate retention capacity of the phonological store, normal functioning of the articulatory rehearsal mechanism and a normal contribution of lexical-semantic knowledge to verbal immediate recall. In the Brown-Peterson task, PD patients showed abnormal performance decay on the letter recall task when articulatory rehearsal was inhibited by a serial subtraction concurrent task. These data provide evidence for normal functioning of the Articulatory Loop in PD patients. However, when the verbal recall task is more attention demanding, PD patients show deficient performance levels, presumably due to depleted processing resources by the Central Executive.
Impaired T Lymphocyte Function and Differential Cytokine Response Pattern in Members from Cancer Families
Authors: Shevde Lalita A. , Joshi Narendra N. , Advani Suresh H. , Nadkarni Jayshree J.
Published: April 2003

In an attempt to understand the basis of lowered natural killer (NK) and T cell functions in unaffected members from cancer families, we investigated cytotoxic T lymphocyte function (CD3-directed lysis) and the ability of the lymphocytes to respond to cytokines such as IL-2, IFN-α and IL-12. We observed lower CD3-mediated cytotoxic activity in these individuals supported by significantly lower numbers of circulating CD3+ lymphocytes. The cytokine treatment studies revealed impaired response to IFN-α and IL-12 in unaffected members and breast cancer patients. The observations presented herein not only reinforce our earlier finding that lower NK and T lymphocyte function may be a feature of cancer families, but also suggest that such impaired responses may be one of the factors contributing to lower cytotoxic potential of the circulating lymphocytes.
Clinical Implications of Natural Killer Cytotoxicity in Patients with Squamous Cell Carcinoma of the Penis
Authors: Campos Mércia Mendes , de Souza Maria Helena Ornellas , Pires Virginia , Scheiner Marcos A.M. , Esteves Eliane Barbosa , Ornellas Antonio Augusto
Published: April 2003

Impairment of natural cytotoxicity mediated by natural killer (NK) cells may play a role in the pathogenesis of penile carcinoma. The aim of this study was to examine the NK activity profile and its prognostic significance in patients with squamous cell carcinoma of the penis. The NK activity was measured in peripheral blood mononuclear cells (PBMCs) from 39 patients diagnosed histologically as having invasive squamous cell penile carcinoma and 4 patients with verrucous carcinoma of the penis. Of 39 patients with invasive squamous cell carcinoma, 4 had undergone previous penile amputation. According to the prognosis, the patients with invasive squamous cell carcinoma were divided into two groups: with metastasis and without metastasis. The patients were evaluated in relation to clinicopathologic variables using univariate analyses. NK cell activity was significantly decreased in all patients with penile carcinoma when compared with the control groups (p < 0.0001). There was no statistically significant difference between the groups with and without metastasis. We conclude that there is a decrease in NK activity in PBMCs from patients with penile carcinoma and that the presence of advanced disease or metastatic involvement is not responsible for this reduction.
Selective Fetal Hypophysectomy in utero: Microsurgical Technique and Comparisons with Hypophysectomy by Decapitation
Authors: Enemar Anders
Published: April 2003

A detailed description is given of a surgical technique for selectively removing the pituitary anlage from the intrauterine fetal rat as an alternative to the more generally applied fetal hypophysectomy by decapitation. Fetuses on the 17th day of gestation were approached through a narrow opening in the uterine wall and fetal membranes. The pituitary gland was sucked out with a fine glass tube introduced from the side of the head into the space between the pons and the ventral hypothalamus, where the gland is situated. The female rat was sacrificed on the 22nd day of gestation (the day before delivery) and the surviving fetuses were preserved. On average, 20% of the operated fetuses survived until that day, 20% of which were completely hypophysectomized (microscopical examination). Operated fetuses with intact pituitaries served as surgical controls for the evaluation of selected effects of the total hypophysectomy. Initial comparisons were made with published results based on hypophysectomy by decapitation, evaluated without access to surgical controls. The two methods of fetal pituitary removal provide consistent results as regards the weight increase of adrenal and thyroid glands (retardation), thymus gland (stimulation) and testicles (no effect). On the other hand, body weight increase was not affected by selective hypophysectomy but instead slowed down after decapitation, whereas the growth in length of the humerus bone was stimulated and retarded, respectively.
Association between Arterial Bifurcation Anatomy and Angiographic Plaque Ulceration among 4,627 Carotid Stenoses
Authors: Schulz Ursula G.R. , Rothwell Peter M.
Published: April 2003

Stability of atheromatous plaques is influenced by local mechanical and haemodynamic factors, such as plaque motion and shear stress. However, although blood vessel anatomy is an important determinant of haemodynamics, particularly at bifurcations, there have been no previous clinical studies of the association between arterial anatomy and plaque ulceration. We therefore studied arterial anatomy and plaque ulceration using angiograms of 4,627 carotid bifurcations with atheromatous disease from the European Carotid Surgery Trial (ECST). We studied the vessel diameter and area ratios that have been shown in flow models to affect local haemodynamics and shear stress, and which are known to vary widely between and within individuals (internal to common, external to common, external to internal carotid artery and outflow/inflow area). Angiographic plaque surface morphology was defined as ulcerated or not ulcerated. To avoid any potential bias due to selective inclusion of patients in the ECST, we studied the contralateral, and usually asymptomatic, as well as the symptomatic carotid artery. To correct for the effects of systemic factors that might influence plaque stability, we also studied the relationship between the degree of asymmetry of bifurcation anatomy within individuals and the presence of plaque ulceration. Despite considerable inter-individual variation in carotid anatomy, we found no association between the prevalence of angiographic plaque ulceration and any of the anatomical parameters studied in either symptomatic or contralateral carotid arteries. There were also no associations between ipsilateral bifurcation anatomy and plaque ulceration in individuals with unilateral plaque ulceration. Carotid arterial anatomy does not appear to be an important determinant of plaque stability. Other factors that influence local haemodynamics, such as the anatomy and composition of the plaque itself may be more important.
Relevance of Interleukin-1 Receptor Antagonist Intron-2 Polymorphism in Ischemic Stroke
Authors: Seripa Davide , Dobrina Aldo , Margaglione Maurizio , Matera Maria Giovanna , Gravina Carolina , Vecile Elena , Fazio Vito Michele
Published: April 2003

Evidence of inflammatory phenomena associated with atherosclerotic plaques is extensive. Interleukin-1 (IL-1) is one of the key modulators of the inflammatory response, and its activity is critically regulated by its receptor antagonist (IL-1Ra). A variable number of tandem repeats (VNTR) in intron 2 of the human IL-1Ra shows a common polymorphism that has been related to different production of IL-1Ra and IL-1 proteins. In monocytes, the less common allele 2 has been associated with an increased production of IL-1Ra and a decreased production of IL-1. Moreover, a cooperative effect with a C to T polymorphism in the promoter of IL-1β gene (C–511→T) has been described. In the present study, we investigated the frequency of these polymorphisms in 110 subjects who survived an ischemic stroke, in 101 healthy age-matched individuals, and in a population-based sample of 1,303 healthy Italians. The frequency of the IL- 1Ra 1/1 genotype was significantly higher in stroke survivors with respect to age-matched controls (77.2 and 45.5%, respectively; p < 0.001), and to the wide group of healthy Italians (77.2 and 51.9%, respectively; p < 0.001). As expected, the estimated frequency of the IL-1Ra allele 1 (Ra*1 allele) in stroke survivors was higher than in age-matched controls (0.851 and 0.664, respectively; p < 0.001) and in healthy Italians (0.851 and 0.717, respectively; p < 0.001). Thus, ischemic stroke survivors that carry the Ra*1 allele showed a strong association with the disease with respect to age-matched controls [odds ratio (OR) = 3.905; 95% confidence interval (CI), 2.110–7.229] and healthy Italians [OR = 3.256 (95% CI, 1.971–5.379)]. No significant association was seen for the IL-1β (C–511→T) polymorphism. However, in stroke survivors, an association between the Ra*1 allele and the C allele of the IL-1β (-511) polymorphism was found (p < 0.001). Our results implicate the IL-1Ra gene in the susceptibility to ischemic stroke, and suggest that IL-1Ra genotyping may be useful in the identification of patient subgroups for pharmacological intervention in IL-1 production or actions.
Purification and Characterization of a Cross-Reactive 45-kD Major Allergen of Fusarium solani
Authors: Verma Jyotsna , Singh B.P. , Sridhara Susheela , Gaur S.N. , Arora Naveen
Published: April 2003

Background:Fusarium solani (FS) is an important source of fungal allergen. A 45-kD major allergen of FS showed reactivity with patients’ sera sensitive to many fungi. Objectives: To purify and characterize a 45-kD common allergenic protein from FS, which may be useful for the diagnosis of and therapy for fungal allergy. Methods: FS culture filtrate extract was separated on SDS-PAGE; 45-kD protein was electroeluted and purified on C18 column using reverse-phase high-pressure liquid chromatography (rpHPLC). The purified protein was functionally and biochemically characterized by in vitro and in vivo methods. Results: The 45-kD protein showed a single peak on rpHPLC. The N-terminal amino acid sequence of this protein did not show homology to enolase or known fungal proteins. It showed cross-reactivity with Epicoccum nigrum, Curvularia lunata, Cladosporium herbarum and Alternaria alternata by ELISA and ELISA inhibition using rabbit antibodies raised against these fungi. IgE ELISA inhibition with patients’ sera positive to different fungi demonstrated allergenic cross-reactivity of the 45-kD protein with other fungal extracts. This 45-kD protein released a significant amount of histamine in FS-allergic patients. Conclusion: A cross-reactive 45-kD allergenic/antigenic protein was purified to homogeneity and characterized. It has prospects for use in allergen therapy.
The Simultaneous Presence of α- and β-Thalassaemia Alleles: A Pitfall of Thalassaemia Screening
Authors: Law H.Y. , Chee M.K.L. , Tan G.P. , Ng I.S.L.
Published: April 2003

Objective: To compare the efficacy of routine haematological tests and molecular analysis in the diagnosis of double heterozygous α- and β-thalassaemia. Methods: Screening was carried out in extended family members from 125 families registered in the National Thalassaemia Registry, known to have both α- and β-thalassaemia carriers. Results: Eighty-three individuals from 59 families were identified to be double heterozygous for α- and β-thalassaemia only upon molecular analyses. Among 40 married individuals, 1 was at 25% risk for having β-thalassaemia major children and 6 for having Bart’s hydrops pregnancies. Conclusion: Molecular analysis must be used for the accurate diagnosis of double heterozygous α- and β-thalassaemia for proper risk ascertainment, especially in regions with a high prevalence of both types of thalassaemia.
Attitudes towards Genetic Screening for Predisposition to Colon Cancer among Cancer Patients, Their Relatives and Members of the Community
Authors: Ramsey Scott D. , Wilson Susan , Spencer Anna , Geidzinska Antoinette , Newcomb Polly
Published: April 2003

Objective: To compare knowledge of and interest in genetic testing for hereditary colon cancer syndromes. Methods: Colorectal cancer patients, first-degree relatives of colon cancer patients and controls were recruited from a familial cancer registry. Focus groups explored attitudes about genetic testing. Results: All three groups conveyed interest in testing, but lacked knowledge about testing and its implications. After receiving information regarding the potential benefits and costs of testing (including insurance and employment issues) all three groups were disinclined to be tested. The reasons varied among risk groups. Conclusions: When informed about the costs and implications of testing, individuals may be reluctant to undergo genetic testing, regardless of baseline risk. Barriers to testing will vary depending on the perceived risk of carrying a mutation
Genebanks: A Comparison of Eight Proposed International Genetic Databases
Authors: Austin Melissa A. , Harding Sarah , McElroy Courtney
Published: April 2003

Objective: To identify and compare population-based genetic databases, or ‘genebanks’, that have been proposed in eight international locations between 1998 and 2002. A genebank can be defined as a stored collection of genetic samples in the form of blood or tissue, that can be linked with medical and genealogical or lifestyle information from a specific population, gathered using a process of generalized consent. Methods: Genebanks were identified by searching Medline and internet search engines with key words such as ‘genetic database’ and ‘biobank’ and by reviewing literature on previously identified databases such as the deCode project. Collection of genebank characteristics was by an electronic and literature search, augmented by correspondence with informed individuals. The proposed genebanks are located in Iceland, the United Kingdom, Estonia, Latvia, Sweden, Singapore, the Kingdom of Tonga, and Quebec, Canada. Comparisons of the genebanks were based on the following criteria: genebank location and description of purpose, role of government, commercial involvement, consent and confidentiality procedures, opposition to the genebank, and current progress. Results: All of the groups proposing the genebanks plan to search for susceptibility genes for complex diseases while attempting to improve public health and medical care in the region and, in some cases, stimulating the local economy through expansion of the biotechnology sector. While all of the identified plans share these purposes, they differ in many aspects, including funding, subject participation, and organization. The balance of government and commercial involvement in the development of each project varies. Genetic samples and health information will be collected from participants and coded in all of the genebanks, but consent procedures range from presumed consent of the entire eligible population to recruitment of volunteers with informed consent. Issues regarding confidentiality and consent have resulted in opposition to some of the more publicized projects. None of the proposed databases are currently operational and at least one project was terminated due to opposition. Conclusions: Ambitious genebank projects have been proposed in numerous countries and provinces. The characteristics of the projects vary, but all intend to map genes for common diseases and hope to improve the health of the populations involved. The impact of these projects on understanding genetic susceptibility to disease will be increasingly apparent if the projects become operational. The ethical, legal, and social implications of the projects should be carefully considered during their development.
Haemodiafiltration: Current Status
Authors: Spalding Elaine , Farrington Ken
Published: April 2003

Haemodiafiltration combines elements of diffusion and convection in a single treatment modality to provide solute removal over a wide range of molecular weights. Theoretically, it represents the best available form of renal replacement therapy but uptake of the technique has been slow. This pattern may change, given the growing acceptance of the potential benefits of the technique, the maturing technology including cost-efficient online production of substitution fluid, and the demonstration of the long-term safety of the technique. Long-term clinical outcome data are awaited.
High Glucose Induces Type 1 Hexokinase Gene Expression in Isolated Glomeruli of Diabetic Rats and in Mesangial Cells
Authors: Henningsen C. , Zahner G. , Thaiss F.
Published: April 2003

Background: Diabetic nephropathy, which is characterized by renal hypertrophy and accumulation of extracellular matrix, is one of the leading causes for end-stage renal disease. Pathophysiological changes, which finally lead to the development of diabetic nephropathy, act through an increase in the intracellular NADH/NAD ratio and the activation of the polyol and protein kinase C pathways. The first rate-limiting enzymes in intracellular glucose metabolism are the hexokinases, which catalyze the phosphorylation of glucose. Therefore, in order to examine a possible link between increased glucose metabolism and the development of diabetic nephropathy mRNA and protein expression as well as enzyme activity of type 1 hexokinase were examined in kidneys of control and diabetic rats and in mesangial cells. Methods: Diabetes in rats was induced by intravenous injection of streptozotocin and animals were treated or not treated with insulin. RNA or protein was extracted from isolated glomeruli at different time intervals. In addition, glomerular mesangial cells were incubated in high glucose medium and hexokinase expression determined along with enzyme activity. Results: The experiments demonstrate a significant increase in gene and protein expression of type 1 hexokinase in glomeruli of diabetic rats throughout a three week observation period. Insulin therapy reduced glomerular type 1 hexokinase mRNA expression. Gene expression and hexokinase enzyme activity were also increased in mesangial cells grown in high glucose medium. Conclusion: The present experiments demonstrate that the expression of type 1 hexokinase is increased in isolated glomeruli of diabetic animals and is regulated by high ambient glucose concentrations. These results add further evidence to the fact that the kidney is one of the tissues most sensitive to high glucose levels in diabetes.