bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Growth Hormone Release in Common Carp Pituitary Cells by Pituitary Adenylate Cyclase-Activating Polypeptide: Signal Transduction Involves cAMP- and Calcium-Dependent Mechanisms
Authors: Xiao Dong , Chu Mable M.S. , Lee Eric K.Y. , Lin Hao-Ran , Wong Anderson O.L.
Published: April 2003

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the glucagon/secretin peptide family and its molecular structure is highly conserved among vertebrates. In this study, the role of PACAP in regulating growth hormone (GH) secretion in fish was examined in vitro using common carp pituitary cells under column perifusion. A dose-dependent increase in GH release was observed after exposing pituitary cells to increasing doses of ovine PACAP38 (oPACAP38) and PACAP27 (oPACAP27), but not vasoactive intestinal polypeptide (VIP). A lack of GH response to VIP stimulation is consistent with the pharmacological properties of PAC-1 receptors, suggesting that this receptor subtype may be involved in PACAP-induced GH secretion in carp species. Although the maximal GH responses induced by oPACAP38 and oPACAP27 were similar, the minimal effective dose and ED50 value for oPACAP38 were significantly lower than that for oPACAP27. These results may indicate that common carp PAC-1 receptors are more sensitive to stimulation by oPACAP38 than by oPACAP27. In parallel studies, oPACAP38 and oPACAP27 were also effective in increasing cAMP release, cellular cAMP content, total cAMP production, and intracellular Ca2+ ([Ca2+]i) levels in common carp pituitary cells. Besides, the rise in [Ca2+]i induced by oPACAP38 was blocked by removing extracellular Ca2+ ([Ca2+]e) or by treatment with nifedipine, an inhibitor of voltage-sensitive Ca2+ channels (VSCC). The dose dependence of PACAP-stimulated GH release in common carp pituitary cells was mimicked by activating adenylate cyclase using forskolin, inhibiting cAMP degradation using IBMX, increasing functional levels of intracellular cAMP using CPT-cAMP, or inducing [Ca2+]e entry using the Ca2+ ionophore A23187. In contrast, the GH-releasing effect of oPACAP38 was suppressed by treatment with the adenylate cyclase inhibitor MDL12330A, protein kinase A inhibitor H89, and VSCC blocker nifedipine, or by perifusion with a Ca2+-free culture medium. These results, as a whole, suggest that PACAP functions as a GH-releasing factor in common carp by activating pituitary receptors resembling mammalian PAC-1 receptors. Apparently, the GH-releasing action of PACAP is mediated through the adenylate cyclase/cAMP/protein kinase A pathway and [Ca2+]e influx through VSCC.
Comparison of Cutaneous Bioavailability of Cosmetic Preparations Containing Caffeine or α-Tocopherol Applied on Human Skin Models or Human Skin ex vivo at Finite Doses
Authors: Dreher Frank , Fouchard Frédéric , Patouillet Claire , Andrian Michèle , Simonnet Jean-Thierry , Benech-Kieffer Florence
Published: April 2003

The use of human skin models for performing cutaneous bioavailability studies has been little investigated. For instance, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration. The present study aimed at evaluating the influence on caffeine’s and α-tocopherol’s cutaneous bioavailability of cosmetic vehicles such as a water-in-oil emulsion, an oil-in-water emulsion, a liposome dispersion and a hydrogel applied at finite dose using the reconstructed human skin models EpiDerm® and Episkin®. The results were compared with those obtained in human skin ex vivo using similar experimental conditions. It was demonstrated that the rank order of solute permeability could be correctly predicted when the preparation was applied at a finite dose in human skin models, at least when solutes with far different physicochemical properties such as caffeine and α-tocopherol were used. If only slight effects of cosmetic vehicle on skin bioavailability were observed in human skin ex vivo, they were less predictable using skin models. Especially, alcohol-containing vehicles seemed to behave differently in EpiDerm as well as in Episkin than on human skin ex vivo. Stratum corneum intercellular lipid composition and organization of human skin models differ to some extent from that of human stratum corneum ex vivo, which contributes to less pronounced barrier properties, together with the increased hydration of the outermost stratum corneum layers of the models. These features, as well as still unknown factors, may explain the differences observed in vehicle effects in human skin ex vivo versus human skin models.
Familial Aggregation of Early-Onset Myocardial Infarction
Authors: Brown David W. , Giles Wayne H. , Burke Wylie , Greenlund Kurt J. , Croft Janet B.
Published: April 2003

Although ischemic heart disease tends to cluster in families, previous studies have reported a modest (2-fold increased risk) to strong (10-fold increased risk) contribution of family history to the explanation of disease occurrence. The authors assessed the familial aggregation of early-onset myocardial infarction in 11,307 adults aged <65 years who participated in the Third National Health and Nutrition Examination Survey. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). A parental history was more common in those with (n = 237) than in those without (n = 11,070) a myocardial infarction (19.8 vs. 7.9%, p ≤ 0.01). Adults with a parental history were also more likely to have multiple risk factors for cardiovascular disease (OR for four or five risk factors compared with none: 2.9, 95% CI: 1.4, 6.3). After multivariate adjustment, the likelihood of myocardial infarction was more than three times greater among adults with a parental history than among those without (95% CI: 1.7, 6.7). A maternal history of myocardial infarction was strongly associated (OR = 6.1, 95% CI: 2.1, 17.4) with an increased likelihood of myocardial infarction, and a paternal history was associated with a 3-fold (95% CI: 1.5, 6.3) increased likelihood of myocardial infarction after adjustment for cardiovascular disease risk factors. These results suggest a familial aggregation of early-onset myocardial infarction and show that family history is strongly associated with cardiovascular disease risk factors.
Prey Capture by Larval Zebrafish: Evidence for Fine Axial Motor Control
Authors: Borla Melissa A. , Palecek Betsy , Budick Seth , O’Malley Donald M.
Published: April 2003

Swimming and turning behaviors of larval zebrafish have been described kinematically, but prey capture behaviors are less well characterized. High-speed digital imaging was used to record the axial kinematics of larval zebrafish as they preyed upon paramecia and also during other types of swimming. In all types of swim bouts, a series of traveling waves of bending is observed and these bends propagate along the trunk in the rostral to caudal direction. The prey capture swim bouts appeared to be more complex than other swim patterns examined. In the capture swim bouts, the initial bends were of low amplitude and were most prominent at far-caudal locations during each individual traveling wave of bending. Later bends in the bout (occurring just prior to prey capture) appeared to originate more rostrally and were of larger amplitude. These changes in bending pattern during capture swims were accompanied by a marked increase in tail-beat frequency. Associated with these axial kinematics were changes in heading and an abrupt increase in velocity close to the moment of prey capture. These changing patterns of bending suggest precise, bend-to-bend, neural control over both the timing and the rostral-caudal locus of bending. This degree of ‘fine axial motor control’ has not previously been described in the teleost behavioral literature and is notable because it occurs in larval zebrafish, where descending control signals are funneled through the roughly three-hundred neurons that project from brain into spinal cord. These findings will necessitate a significant increase in the complexity of current models of descending motor control in fishes.
Pancreatic Panniculitis in an 88-Year-Old Man with Neuroendocrine Carcinoma
Authors: Preiss Jan Christian , Faiss Siegbert , Loddenkemper Christoph , Zeitz Martin , Duchmann Rainer
Published: April 2003

Pancreatic panniculitis is a rare complication that occurs in 0.3–3% of patients with pancreatic diseases. Most of the cases reported to date were associated with adenocarcinoma and acute or chronic pancreatitis. We here present an 88-year-old man who was admitted to our institution with a nonfunctional neuroendocrine carcinoma of the pancreas. He subsequently developed pancreatic panniculitis and arthritis. Treatment with octreotide did not have an effect neither on progression of the carcinoma nor on development of new skin lesions. Two months after the diagnosis of pancreatic panniculitis had been made, the patient died from progressing carcinoma. A review of the literature shows that there is no congruent hypothesis for the pathogenesis of pancreatic panniculitis. Vascular damage seems to induce lipolysis by pancreatic enzymes. This eventually leads to fat necrosis. The diversity of disorders that can go along with pancreatic panniculitis suggests an unspecific damage of pancreatic tissue as a first step in the chain of events.
Factors Regulating the Effect of IL-4 on Intestinal Epithelial Barrier Function
Authors: Di Leo Vincenza , Yang Ping-Chang , Berin M. Cecilia , Perdue Mary H.
Published: April 2003

Background: Inflammatory bowel disease is associated with an imbalance in cytokine production and defective intestinal barrier function. Previous studies indicate that IL-4, a cytokine increased in food allergy and in early Crohn’s disease, enhances epithelial permeability. Here, we characterized the mechanism of action of IL-4 on cultured epithelial cells and examined if the anti-inflammatory cytokines, TGF-β or IL-10, can modulate the effects of IL-4. Methods: Confluent monolayers of human T84 epithelial cells were cultured with IL-4 alone or in combination with IL-10 or TGF-β or with inhibitors of protein synthesis and blockers of IL-4 receptor signalling pathways. Permeability was evaluated by measuring transepithelial resistance (TER), flux of 3H-fMLP (a small bacterial tripeptide) and horseradish peroxidase (HRP) (a macromolecule). Results: T84 cells cultured with IL-4 showed a significant drop in TER as well as an increased flux of 3H-fMLP and HRP. Co-treatment with IL-10 did not improve TER, whereas TGF-β attenuated the resistance drop. However, neither TGF-β nor IL-10 were able to correct the increased 3H-fMLP flux. In contrast, the increased HRP flux caused by IL-4 was inhibited by both IL-10 and TGF-β. TGF-β and IL-10 significantly reduced IL-4-enhanced values for endosomal area and paracellular spaces containing HRP. Inhibitor studies indicated the requirement for protein synthesis and the involvement of phosphatidylinositol 3-kinase. Conclusions: These results provide new insights into the regulation of intestinal barrier function and may suggest a novel approach in the treatment of intestinal inflammation.
Defective Interleukin-10 Synthesis by Peripheral Blood Mononuclear Cells among Hemodialysis Patients
Authors: Perianayagam Mary C. , Jaber Bertrand L. , Guo Daqing , King Andrew J. , Pereira Brian J.G. , Balakrishnan Vaidyanathapuram S.
Published: April 2003

Background: Interleukin-10 (IL-10), a potent regulatory monokine produced by activated mononuclear cells, provides an efficient autocrine mechanism for controlling proinflammatory cytokine synthesis. We hypothesized that defective synthesis of IL-10 could contribute to the inflammatory state in hemodialysis (HD) patients due to impaired feedback inhibition of proinflammatory cytokine production. Methods: We compared peripheral blood mononuclear cell (PBMC) synthesis and transcription of IL-10 and TNF-α in 12 patients with end-stage renal disease on long-term maintenance HD and a control group of 10 healthy subjects. Results: The synthesis of IL-10 by unstimulated PBMC was detectable in 5 of 12 (42%) HD patients as compared to 7 of 10 (70%) controls (p = 0.02). IL-10 synthesis in response to endotoxin (ET) by PBMC from HD patients was significantly lower when compared to the robust response in the control group (p = 0.008). Among the HD patients, there was a positive correlation between ET-stimulated IL-10 synthesis and the duration of time on dialysis. Unstimulated and ET-stimulated synthesis of TNF-α by PBMC did not differ between the 2 groups. In the HD patients, there was an inverse correlation between TNF-α and IL-10 synthesis by ET-stimulated PBMC, suggesting a regulatory effect of IL-10 on PBMC TNF-α synthesis. There was also an inverse correlation between plasma albumin and ET-stimulated TNF-α synthesis by PBMC among HD patients. TNF-α mRNA expression did not differ in HD patients relative to healthy controls. In contrast, when IL-10 mRNA from ET-stimulated PBMC was quantified, there was marked difference between the 2 groups indicating a transcriptional defect in IL-10 synthesis in PBMC from HD patients. Conclusion: Our observations indicate a marked abnormality in IL-10 synthesis by PBMC from HD patients probably related to a transcriptional defect. Low PBMC IL-10 synthesis may contribute to a chronic inflammatory state in these patients by defective feedback inhibition of proinflammatory cytokine production.
Variations in Flow, Duration, and Concentration Do Not Change the Final Lung Concentration of Melphalan after Isolated Lung Perfusion in Rats
Authors: Romijn S. , Hendriks J.M.H. , van Putte B.P. , Guetens G. , De Bruijn E.A. , van Schil P.E.Y.
Published: April 2003

Objective: The influences of flow, perfusion time, and concentration on melphalan (MN) lung levels in a rat model of isolated lung perfusion (ILuP) were studied. Methods: ILuP was performed in WAG/Rij rats by using a single-pass system with 0.5, 0.05, 0.01, and 0.005 mg of MN. Subsequently ILuP with 0.05 mg MN was performed during 30 min with a flow rate of 0.5 ml/min, during 60 min with a flow rate of 0.5 ml/min, and during 30 min with a flow rate of 1.0 ml/min. Results: The lung MN levels of 0.05 mg were significantly lower as compared with 0.5 mg (p = 0.02). In the second experiment, no significant differences were seen in lung levels of MN between the different groups. Conclusion: The final lung MN levels were only determined by the absolute amount administered.
A Brief Descriptive Analysis of Stroke Features in a Population of Patients from a Large Urban Hospital in Richmond, Virginia, a City within the ‘Stroke Belt’
Authors: Williams Carlos A. , Sheppard Tim , Marrufo Manuel , Galbis-Reig David , Gaskill Andrea
Published: April 2003

Purpose: To provide a descriptive analysis of the stroke features in a population of patients from a large urban hospital within the ‘stroke belt’, with the intention of stimulating interest in creating similar comprehensive databases across the country; the differential population features that may contribute to the increased incidence of ischemic and hemorrhagic stroke within the ‘stroke belt’ can thus be better studied and understood. Background: Strokes account for approximately 5–10% of all deaths in the western world. Within a geographically nondescript region in the Southern United States known as the ‘stroke belt’, however, the incidence of stroke is 1.5–2 times greater than in other regions of the country. Despite the relatively high incidence of stroke within the ‘stroke belt’, very little information is available regarding the differential population features that distinguish stroke patients within this region from those in other parts of the country. Design/Methods: During the period September 1, 1995 to August 31, 1998, data for 506 patients meeting criteria for stroke as outlined in the National Survey of Stroke were entered into the ‘Adult Brain Attack Database’ at the Medical College of Virginia Hospitals of Virginia Commonwealth University. The data were analyzed using descriptive statistics. Results: Of the 506 patients entered into the database 281 experienced their first stroke during the data collection period. Of these individuals, 60.5% (n = 170) were female (mean age 60.6). The mean age in men presenting with new stroke (n = 111) was 62.5. African-Americans represented the predominant ethnic group making up 63.3% (n = 178) of all first stroke patients. The three most common risk factors among deceased ischemic stroke patients (3.2%; n = 9) included hypertension (58.3%), alcohol abuse (41.6%) and cigarette smoking (33.3%). Among ischemic stroke survivors, the three most common risk factors included hypertension (53.6%), prior neurovascular disease (36.2%) and cigarette smoking (28.0%). Risk factors among hemorrhagic stroke patients included hypertension (42.0%), cigarette smoking (26.3%) and alcohol abuse (21.1%). The most common complication associated with stroke across all subtypes was hypertension with an overall prevalence of 9.3%. The use of antiplatelet and antihypertensive therapy at discharge among stroke patients in whom such data was recorded was 58.8% (179/289) and 48.9% (132/270), respectively. Discussion: Future studies comparing data from the Richmond, Va. stroke database with data from other regions of the country outside the ‘stroke belt’ may allow for differentiation of the population features that contribute to the increased prevalence of stroke within the ‘stroke belt’.
The Use of Standardized Incidence and Prevalence Rates in Epidemiological Studies on Multiple Sclerosis
Authors: Zivadinov Robert , Iona Leo , Monti-Bragadin Luisa , Bosco Antonio , Jurjevic Ante , Taus Cristina , Cazzato Giuseppe , Zorzon Marino
Published: April 2003

Objective: To demonstrate whether or not the age and sex adjustment of incidence and prevalence rates in multiple sclerosis (MS) could allow more reliable comparison between epidemiological studies performed in different areas of the world and to establish if the latitude gradient theory could be confirmed after the standardization for age and sex distribution. Methods: A meta-analysis of population-based incidence and prevalence studies on MS from 1980 through 1998 using the terms ‘multiple sclerosis’, ‘prevalence’ and ‘incidence’ in the bibliographic databases MEDLINE and EMBASE was performed. We included studies that reported the diagnostic criteria, number of cases and the population studied, the date of the study, the latitude, and the age- and sex-specific crude incidence and prevalence rates. According to the inclusion criteria, 69 of 127 papers on prevalence and 22 of 70 papers on incidence were considered for age adjustment and 27 prevalence and 8 incidence studies for sex adjustment. The mean incidence and prevalencerates and the 95% confidence intervals age- and sex-adjusted to the World and the European standard populations were calculated. Results: The Spearman rank correlation and the multiple regression analyses indicated that age adjustment to standard populations could overcome the limitations in comparing the crude prevalence and incidence rates of different epidemiological studies on MS. When the mean crude and age- and sex-adjusted prevalence and age-adjusted incidence rates were stratified by latitude (from south to north), the latitudinal gradient, which was highly significant for the crude rates, became less remarkable for the age- and sex-adjusted prevalence rates and not significant for the age-adjusted incidence rates. Conclusions: The crude incidence and prevalence rates in epidemiological studies on MS should be age- and sex-adjusted to a common standard population to permit a more reliable comparison among studies performed in different countries. Our findings support the opinion that the latitude does not play a key role in determining the onset of MS. Whenever possible, the crude incidence and prevalence rates should be adjusted to the ethnic origin and migration characteristics.
Administration of Nonionic Iodinated Contrast Medium Does Not Influence the Outcome of Patients with Ischemic Brain Infarction
Authors: Palomäki Heikki , Muuronen Antti , Raininko Raili , Piilonen Anneli , Kaste Markku
Published: April 2003

Some reports indicate that exposure to iodinated contrast medium (CM) could worsen the outcome of patients with brain infarction. In this prospective study, we compared the outcome of 77 patients receiving and 128 not receiving nonionic iodinated CM. Stroke severity was assessed by the Scandinavian Prognostic Stroke Score, and outcome by the Rankin Scale. All radiological studies using intravenous or intra-arterial CM were registered. Two nonionic iodinated CM (iopamidol and iohexol) were used. Exposure to CM did not influence case fatality, ability to live at home, ability to walk, disability and stroke severity. Initial stroke severity and arterial hypertension were independent determinants of poor neurological recovery or death. Large infarct, age, male gender, and baseline stroke severity were independent determinants of major disability or death. CM enhancement on CT did not show any harmful effect on stroke severity or outcome. As a conclusion, intravascular administration of nonionic iodinated CM did not influence stroke severity or outcome of our patients.
Complaints of Poststroke Insomnia and Its Treatment with Mianserin
Authors: Palomäki Heikki , Berg Anu , Meririnne Esa , Kaste Markku , Lönnqvist Riitta , Lehtihalmes Matti , Lönnqvist Jouko
Published: April 2003

We assessed the prevalence and associations of symptoms of insomnia in patients with acute ischemic stroke, and evaluated whether mianserin as a sedative antidepressant is beneficial in the treatment of poststroke insomnia. One hundred consecutively hospitalized patients were randomized to receive 60 mg/day of mianserin (n = 51) or placebo for 1 year in a double-blind trial with a 6-month follow-up after the therapy. Symptoms of insomnia were assessed with the three insomnia-related items of the Hamilton Depression Scale; patients were defined as insomniacs if any of these items was positive. Complaints of insomnia occurred in 68% of patients on admission, and in 49% at 18 months, and they were as frequent in all subgroups of patients. From 2 months, symptoms of insomnia were associated independently with depression. Living alone before stroke (at 0 and 2 months) and age (at 12 months) were other independent predictors of insomnia. The rate of recovery as evaluated by the insomnia score was more rapid in patients on mianserin than in those on placebo. At 2 months, the scores were significantly different favoring mianserin treatment (1.3 vs. 0.8, p = 0.02). We conclude that insomnia is a common complaint after ischemic stroke. Mianserin had a beneficial influence on the recovery from symptoms of insomnia, even though the intensity of poststroke depression was low.
Percutaneous Transluminal Angioplasty for Symptomatic Middle Cerebral Artery Stenosis: Long-Term Follow-Up
Authors: Lee Ju H. , Kwon Sun U. , Lee Jae H. , Suh Dae C. , Kim Jong S.
Published: April 2003

Background and Objective: Although percutaneous transluminal angioplasty (PTA) is an effective treatment modality in the coronary and peripheral arterial diseases, its efficacy for intracranial atherosclerotic stenosis has not been verified. We assessed the long-term outcome of PTA for symptomatic middle cerebral artery (MCA) stenosis. Methods: We performed PTA in 10 patients with symptomatic high-grade stenosis (>70%) on M1 segment of MCA, who had either recurrent transient ischemic attacks (TIAs) resistant to medical therapy or perfusion problems. PTA was performed with a microballoon (2–2.5 mm diameter and 10–13 mm length) without insertion of a stent. After PTA, we evaluated the possible occurrence of restenosis, which was defined as >50% stenosis on follow-up conventional angiogram or increased M1 flow velocity on follow-up transcranial doppler up to the baseline value. Results: PTA was successfully performed in 9 patients without any serious complications. One patient had asymptomatic dissection. Residual stenosis was less than 50% in diameter in all the patients. During follow-up period (mean 34.5 months), TIAs did not recur in 6 of 7 patients who had had intractable TIAs.Two patients developed strokes, which were not referable to the index MCA lesions. Among the 6 patients who underwent follow-up conventional angiography or serial TCD, restenosis was noticed in 3 patients (50%). Conclusion: Although restenosis is not uncommon, PTA for symptomatic MCA stenosis is a relatively safe procedure, and can be used to prevent recurrent TIAs or strokes in selected patients.
Sensitivity of the Dementia Rating Scale in Vascular Dementia: Comparison between Two Sets of Criteria to Define Cognitive Impairment
Authors: Paul Robert H. , Cohen Ronald A. , Moser David J. , Browndyke Jeff N. , Davis Kelly , Gordon Norman , Sweet Lawrence , Lawrence Jeffrey J. , Zawacki Tricia
Published: April 2003

Background:  The Dementia Rating Scale (DRS) is a common measure of cognitive function, but its sensitivity to identify deficits across cognitive domains in vascular dementia (VaD) remains unclear. Methods: We compared the sensitivity and specificity of two recommended cutoff scores of the DRS. Thirty-eight patients diagnosed with VaD participated in the current study. Results: The original recommendations resulted in poor sensitivity for the DRS total score and attention, construction, and memory subscales. The more recent recommendations greatly improved the sensitivity of the subscales and the total DRS score, but resulted in decreased specificity. Correlations between the specific DRS subscales and criterion measures of cognitive function revealed good convergent and divergent validity for most subscales. Conclusions: The DRS is a valid measure of cognitive dysfunction in VaD, but clinicians should consider using the more recent recommendations developed for AD to determine impaired performances in VaD.
Roles of Microtubule Dynamics and Small GTPase Rac in Endothelial Cell Migration and Lamellipodium Formation under Flow
Authors: Hu Ying-Li , Li Song , Miao Hui , Tsou Tsui-Chun , del Pozo Miguel Angel , Chien Shu
Published: April 2003

Endothelial cell (EC) migration is required for vascular development and wound healing. We investigated the roles of microtubule (MT) dynamics and the small GTPase Rac in the fluid shear stress-induced protrusion of lamellipodia and enhancement of migration of bovine aortic ECs (BAECs). Shear stress increased lamellipodial protrusion and cell migration. Treating BAECs with paclitaxel (Taxol), an MT-stabilizing agent, inhibited lamellipodial protrusion and reduced migration speed in both the static and sheared groups. After Taxol washout, both lamellipodial protrusion and cell migration increased in the flow direction. Taxol treatment also decreased the shear-induced Rac activation. Transfection of BAECs with a dominant negative mutant of Rac1 inhibited lamellipodial protrusion and cell migration under static and shear conditions. Transfection with an activated mutant of Rac1 induced lamellipodia in all directions and attenuated the shear-induced migration, suggesting that an appropriate level of Rac activity and a polarized lamellipodial protrusion are important for cell migration under static and shear conditions. Our findings suggest that MT dynamics and optimum Rac activation are required for the polarized protrusion of lamellipodia that drives the directional EC migration under flow.
Natural History and Predictors of Temporary Epicardial Pacemaker Wire Function in Patients after Open Heart Surgery
Authors: Elmi Farhad , Tullo Nicholas G. , Khalighi Koroush
Published: April 2003

Study Objectives: To assess the short-term reliability of temporary epicardial pacing wires in patients after open heart surgery and to determine the influence of preoperative factors on the performance of these wires. Patients and Methods: In this prospective, longitudinal cohort study, 60 patients (41 men) with a mean age of 66.8 ± 8.9 years were studied for 5.3 ± 1.1 days postoperatively. Each patient’s history, physical findings, hemodynamics and echocardiographic data were analyzed. Postoperatively, capture threshold, the electrogram amplitude and slew rate, and the lead impedance were determined daily in both chambers. Results: Both atrial and ventricular thresholds increased significantly (p < 0.001) by the 4th postoperative day. The P-wave amplitudes were consistently less than half of the R-wave amplitudes. Both P- and R-wave amplitudes deteriorated significantly by the 2nd postoperative day (p < 0.001 and p < 0.02, respectively). Atrial and ventricular slew rates and lead impedance decreased significantly during the observation period (p < 0.002). Conclusion: Although both atrial and ventricular temporary epicardial leads are reliable for short-term use, their function deteriorates on a daily basis. Perioperative factors are generally not helpful in predicting the performance of temporary epicardial pacing wires.
Goblet Cell Hyperplasia in the Airway of Nippostrongylus brasiliensis-Infected Rats
Authors: Tomita Masaki , Kobayashi Takahiko , Itoh Hiroshi , Onitsuka Toshio , Nawa Yukifumi
Published: April 2003

Background: In rats, the intestinal parasite Nippostrongylus brasiliensis is recognized as a strong inducer of intestinal goblet cell hyperplasia. Although this parasite migrates through the airways during the course of its infection, airway goblet cell response remains unknown. Objective: This study was designed to examine airway goblet cell response during the course of N. brasiliensis infection in rats and to characterize these goblet cells. Methods: Airway goblet cells were stained with Alcian blue and periodic acid-Schiff. To characterize the goblet cells, mebendazole treatment, lectin histochemistry, and RNA blot analysis using probes for rat MUC2 and trefoil peptides were examined. Results: Airway and small intestinal goblet cell hyperplasia were observed at days 14 and 21 after infection but not at day 7. In rats treated with mebendazole, goblet cell hyperplasia was not present in the small intestine, but was observed in the lung on day 14. These results indicate that airway goblet cell hyperplasia may be induced by local pulmonary factors. By lectin histochemistry, the stainability of airway goblet cells at day 21 was similar to that of small intestine goblet cells even though rat MUC2 and trefoil peptide mRNA were not detected in the lung. Conclusions: Airway goblet cell hyperplasia observed at days 14 and 21 after N. brasiliensis infection may be induced by local factors. Airway goblet cells have characteristics that differ from those of the small intestine.
Endoscopic Ultrasound in Pancreatic Diseases
Authors: Kahl Stefan , Glasbrenner Bernhard , Zimmermann Sandra , Malfertheiner Peter
Published: April 2003

There are many indications for the use of endoscopic ultrasound (EUS) in the management of patients with pancreatic diseases. High-resolution imaging of the pancreas is achievable due to the close proximity between luminal structures and the pancreas. Since its introduction, EUS has had a significant impact on the diagnosis of pancreatic diseases. The detection of small lesions and neuroendocrine pancreatic tumors as well as the preoperative staging of pancreatic adenocarcinoma have been improved employing EUS. For the detection of small pancreatic tumors <2 cm in diameter, EUS appears to be the most sensitive method. EUS adds significant information to the differential diagnosis between pancreatic cancer and chronic pancreatitis, and it may be further enhanced by EUS-guided fine-needle aspiration. While the role of EUS in distinguishing between benign and malignant cystic pancreatic tumors is under discussion, EUS-guided drainage of pancreatic pseudocysts is an accepted treatment option for symptomatic individuals. One of the most important advantages of EUS apart from tumor staging is the early detection of chronic pancreatitis. EUS is as good as endoscopic retrograde cholangiopancreatography in diagnosing chronic pancreatitis in advanced stages. In early stages of the disease, when the ductal system remains normal, EUS appears to be a superior diagnostic modality because it can detect features of chronic pancreatitis in the parenchyma not visible by other techniques.
Stenting of the Gastrointestinal Tract
Authors: Mergener Klaus , Kozarek Richard A.
Published: April 2003

Self-expandable metal stents are being increasingly used to palliate malignant stenoses of the gastrointestinal tract. These prostheses have made it possible to reestablish luminal continuity in patients with malignant obstruction of esophagus, gastric outlet, small bowel, or colon who are at high risk of surgical intervention. Despite technologic refinements in the stents and their delivery systems, and an increasing number of studies related to self-expandable metal stents, data regarding their long-term efficacy, side effect profile, and true cost efficacy in comparison with other treatment modalities remain incomplete. This article reviews the available technology, placement techniques, indications, and outcomes relating to the use of self-expandable metal stents in esophagus, stomach, small bowel, and colon.
Are ‘Micrometastases’ of the Peritoneum Equivalent to Distant Metastases?
Authors: Kienle Peter , Koch Moritz
Published: April 2003

Tumor progression after curative resection of gastrointestinal cancer is probably caused by disseminated tumor cells that can be detected in different body compartments, e.g. the peritoneum. The clinical importance and prognostic significance of gross peritoneal metastasis is well known whereas the prognostic relevance of disseminated tumor cells in the peritoneum of patients with gastrointestinal cancer is still unclear. Disseminated tumor cells in the peritoneal cavity are generally detected by cytology, immunohistochemistry or polymerase chain reaction-based molecular methods. A consensus on the most adequate detection method has not yet been found making the comparison of different data difficult. The prognostic relevance of tumor cell dissemination has, at least in part, been shown for gastric, pancreatic and colon cancer, and the prognostic data regarding gastric cancer are most convincing. Peritoneal ‘micrometastases’ are obviously not equivalent to distant metastases as the evidence for their prognostic significance is clearly less than that for gross peritoneal metastases. This article gives a critical review of the detection and prognostic significance of disseminated tumor cells in the peritoneum of patients with gastrointestinal cancer.
Ethical Considerations in Gastroenterology and Endoscopy
Authors: Axon Anthony
Published: April 2003

Previously doctors decided what was right or wrong in medicine, today our individual freedom is more limited. External influences including the human rights act, government initiatives, management protocols, professional guidelines, multi-disciplinary decision-making and financial restrictions intervene between the doctor and the patient. Furthermore the move away from paternalism in the doctor–patient relationship to patient empowerment (informed consent) has put patients in charge of their medical destiny. Increased public expectations leading to health screening, genetic profiling and treatment of unwanted physiological changes mean that doctors now manage healthy patients for ‘potential’ or ‘virtual’ disease. This implies a greater ethical burden than treatment of the sick. Finally, death is no longer regarded by many as a physiological process, but a consequence of disease. The investigation and management of patients with incurable conditions can lead to difficult ethical dilemmas. Gastroenterology and endoscopy generate specific ethical problems which among others include training in endoscopy, percutaneous endoscopic gastrostomy placement, informed consent and live endoscopy demonstrations. This article addresses some of these issues in order to draw attention to potential difficulties in modern ethical practice. It should be read in conjunction with the other publications stemming from the 1st Symposium on Ethics in Gastroenterology and Endoscopy, Kos, June 2002.
What Information Should Be Given to Patients Undergoing Therapeutic Endoscopy?
Authors: Isaacs Peter E.T.
Published: April 2003

Doctors and other health professionals should always offer information to patients about the risks, benefits and alternatives to the treatment or examination proposed. Such information should be offered in a timely fashion and in a form understandable to the patient. The professional should assess the patients’ ability to comprehend and to make a judgement if their consent is to be valid. Patients occasionally may refuse the offer, but this refusal does not exonerate the doctor from pointing out serious hazards. Discussions of risk must be made in a friendly manner and the patient’s questions invited.
Indications for Percutaneous Endoscopic Gastrostomy Insertion: Ethical Aspects
Authors: Niv Yaron , Abuksis Galia
Published: April 2003

Percutaneous endoscopic gastrostomy (PEG) is a popular technique for long-term enteral nutrition. However it is not beneficial in all cases, and may even prolong the process of dying. The present article discusses the main indications for PEG insertion, and the ethical considerations involved. Three main questions need to be answered: (1) for what purposes should PEG be used; (2) for what type of patients, and (3) when should PEG be inserted in the natural history of the patient’s illness? PEG is used in patients unable to maintain sufficient oral intake. It has been found to improve quality of life and/or to increase survival in patients with head and neck cancer, acute stroke, neurogenic and muscle dystrophy syndrome, growth failure (children) and gastric decompression. It led to no improvement in nutritional or functional status in patients with cachexia, anorexia, aspiration (and aspiration pneumonia), and cancer with a short life expectancy. Several court decisions have stipulated that PEG need be offered in patients in a persistent vegetative state or patients with senile dementia who have lost the ability for self-determination. Since the 30-day mortality after PEG insertion is very high for patients hospitalized in a general medical center, a ‘cooling off’ period of 30–60 days should be scheduled from the time of the PEG request to actual insertion.
Dissatisfaction with Consent for Diagnostic Gastrointestinal Endoscopy
Authors: Bassi A. , Brown E. , Kapoor N. , Bodger K.
Published: April 2003

Introduction: Little is known about patients’ perspectives on the amount of information they receive prior to diagnostic gastrointestinal endoscopies. Our unit’s policy for obtaining consent consists of initially posting an information leaflet to the patient followed by subsequent explanation of the procedure on arrival for the test. The consent form is signed by the patient immediately prior to the test. Methods: A questionnaire survey was conducted to assess patient perception and satisfaction with the amount of information received before diagnostic endoscopy. Results: The information was obtained from 127 of the 175 questionnaires that were distributed. Whereas 97% had read the information leaflet, only 52% had read the consent form before signing it. 64/127(51%) felt dissatisfied because they would have wanted more information while 3% were dissatisfied because they would have liked less information relating to one or more aspects of the test. Dissatisfaction was higher in patients who had not read the consent form (p < 0.001) and those with some formal education (p = 0.01). Conclusions: Patients who did not read the consent form were more dissatisfied. Strategies to improve the rate of reading this document may increase patient satisfaction.
Informed Consent for Gastrointestinal Endoscopy: A 2002 ESGE Survey
Authors: Triantafyllou K. , Stanciu C. , Kruse A. , Malfertheiner P. , Axon A. , Ladas S.D.
Published: April 2003

Background/Aim: Gastroenterologists are required to obtain informed consent before undertaking any endoscopic examination. Published data indicate that in practice there are many deficiencies in this process. The aim of this survey was to determine the quality of information given to patients before the endoscopic procedures in countries that are members of the European Society of Gastrointestinal Endoscopy (ESGE). Methods: A structured questionnaire was sent to representatives of endoscopic societies that are members of ESGE regarding the quality of informed consent. Results: The response rate was 59% (26/44). The endoscopist is responsible for giving the required information prior to written consent in only 23.1% (6/26) of the countries. Although information about the procedure is given to the patients in 96% of the responding countries, in only 77% is there sufficient time for the patients to ask questions about the nature of the procedure. In 15% (4/26) of the countries neither the diagnostic or therapeutic alternatives to endoscopy are discussed nor the potential complication rates. Finally, the procedure-related mortality is provided in only 23% (6/26) of countries. Conclusion: The procedure of obtaining informed consent for endoscopy varies considerably and may need reevaluation.
Assessment of Depression in Patients with Chronic Viral Hepatitis: Effect of Interferon Treatment
Authors: Koskinas J. , Merkouraki P. , Manesis E. , Hadziyannis S.
Published: April 2003

Introduction/Aim: Chronic viral hepatitis and its treatment with interferon (IFN) have an impact on patients’ quality of life. The purpose of this study was to evaluate the degree of depression in patients with chronic viral hepatitis before and during IFN therapy. Patients/Methods: Our study group comprised 132 patients, 38 with chronic hepatitis C (26 males, 12 females), 36 with chronic hepatitis B (29 males, 7 females), and 58 individuals with no chronic disease (24 males, 34 females). Depression was assessed using the Zung Self-Rating Depression Scale and the corresponding SDS index. Results: At baseline, patients with viral hepatitis and healthy controls had similar SDS indexes. During treatment, a significant increase in the SDS index was observed in both HBV and HCV patients (p < 0.001), which returned to the baseline levels after treatment. During IFN therapy, the SDS indexes were higher in HCV compared to HBV patients and women compared to men (p = 0.001 and p = 0.008, respectively), and there was a >5- fold increased frequency to develop severe depression. Conclusions: IFN-induced depression occurs more frequently in HCV than HBV patients and in women than men. Monitoring during treatment is mandatory in order to maximize treatment adherence.
Ring-Enhanced Malignant Meningioma Mimicking a Brain Metastasis from a Renal Cell Carcinoma
Authors: Yashi Masahiro , Sasaki Masahiro , Ono Tsuyoshi
Published: April 2003

We report a case of ring-enhanced malignant meningioma mimicking a solitary brain metastasis in a patient with renal cell carcinoma. This misleading situation is rarely encountered and has not been documented previously. Considering the low incidence of brain metastases from a renal cell carcinoma staged T1–2 without systemic metastases, a clinical diagnosis requires circumspection, and both primary and metastatic tumors should be considered when a solitary brain lesion is encountered.
Recommendations for the Treatment of Localized Prostate Cancer by Permanent Interstitial Brachytherapy
Authors: Hakenberg O.W. , Wirth M.P. , Hermann T. , Alken P. , Kovacs G. , Müller R.P. , Ahlemann L. , Schalkhäuser K.
Published: April 2003

The increasing use of interstitial brachytherapy for the treatment of prostate cancer has made it necessary to discuss and establish guidelines for the application of this treatment modality. A group of experts representing the four professional and scientific societies of urologic surgeons and radiation oncologists in Germany was formed by the German Society of Urology (Deutsche Gesellschaft für Urologie, DGU), the Association of German Urologists (Berufsverband der Deutschen Urologen e.V., BDU), the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) and the Association of German Radiotherapists (Berufsverband der Deutschen Strahlentherapeuten, BVDSt). This group has formulated a consensus statement consisting of recommendations and guidelines for the indications, planning, implementation and follow-up of permanent interstitial brachytherapy by seed implantation for the treatment of localized prostate cancer. These recommendations also define the responsibilities of the two medical disciplines involved in the use of this interdisciplinary treatment.
Augmentation Cystoplasty in Patients with Multiple Sclerosis
Authors: Zachoval Roman , Pitha Jiri , Medova Eva , Heracek Jiri , Lukes Martin , Zalesky Miroslav , Urban Michael
Published: April 2003

Introduction: Augmentation cystoplasty is an effective approach to the detrusor hyperreflexia which is refractory to conservative treatment. Sporadic data have been published in patients with progressive diseases such as multiple sclerosis (MS). Materials and Methods: Augmentation ileocystoplasty (Goodwin ‘cup-patch’) was performed in 9 patients (7 females, 2 males). The average Expanded Disability Status Scale score was 4.1 (range 3.0–6.5); 7 patients had relapse-remitting MS and 2 patients secondary-progressive MS. The indication was a detrusor hyperreflexia refractory to conservative treatment in 8 patients and a detrusor hyperrefluxia with third degree bilateral vesico-ureteral reflux and renal insufficiency in 1 patient. Pre- and postoperative objective parameters were evaluated by urodynamic examination, imaging methods and laboratory examination. Subjective evaluation was performed using a questionnaire on micturition symptoms (score 0–5) and on quality of life (score 0–6). Results: With a follow-up of 6–19 months, we recorded an average increase of the maximum detrusor capacity from 105 to 797 ml and decrease of maximum detrusor pressure from 53 to 30 cm H2O. Postmicturition residual urine >25% of the maximum capacity was present in 6 patients who performed clear intermittent autocatheterization postoperatively (2 patients preoperatively). In all patients there was a significant improvement in the irritation micturition symptomatology (pollakisuria, nycturia, urgency and urge incontinence) and the quality of life score improved on average from 5 to 0.7. In the case of the patient with renal insufficiency, the creatinine level decreased from 286 to 150 µmol/l; in the other patients renal function remained normal. Conclusions: Augmentation cystoplasty is a safe and effective method for indicated patients, which significantly enhances their quality of life.
The Impact of Biomarkers and Surrogate End Points on Regulatory Approval of New Drugs
Authors: Kleist Peter
Published: April 2003

Biomarkers are becoming increasingly important in the process of development of new drugs. However, as they are often not able to reflect the actual clinical value and safety of a drug, their role in the framework of the licensing of drugs is limited. For the health authorities, proof of a positive benefit/risk ratio based on hard clinical end points is generally the decisive factor. Only in very few indications do validated surrogate end points exist that show a high predictive value for a relevant clinical end point – the granting of marketing authorization on the basis of a surrogate end point alone is therefore the exception. In principle, this is also true for drugs for the treatment of serious, life-threatening diseases, as the present accelerated approval procedures for the granting of a license on the basis of provisional data and without direct proof of a clinical benefit are used by the authorities only in isolated cases. Only if new biomarkers can be validated as surrogate end points for hard clinical end points can their value for the licensing of new drugs increase in the future.