bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Bub1 Gene Correlates with Tumor Proliferating Activity in Human Gastric Carcinomas
Authors: Shigeishi Hideo , Oue Naohide , Kuniyasu Hiroki , Wakikawa Atsuko , Yokozaki Hiroshi , Ishikawa Takenori , Yasui Wataru
Published: April 2003

Bub1 plays an important role at the spindle assembly checkpoint to prevent cell cycle progression following spindle damage. We examined the expression of human Bub1 mRNA in 20 gastric carcinoma tissues and corresponding nonneoplastic mucosas by reverse transcriptase-polymerase chain reaction and analyzed the relation with proliferative activity monitored by the expression of proliferating cell nuclear antigen (PCNA) on Western blotting as well as Ki-67 labeling index by immunohistochemistry. Increased expression of Bub1 mRNA was detected in 8 (40%) of the gastric carcinomas in comparison with their nonneoplastic counterparts, while 4 (20%) expressed Bub1 at lower levels. The expression of Bub1 mRNA was confirmed by in situ hybridization. The expression levels of Bub1 mRNA were well correlated with the levels of PCNA protein in 16 (80%) gastric carcinoma cases. The examination of Ki-67 labeling indices proved the close correlation between the expression levels of Bub1 and proliferating activity. These findings suggest that mRNA expression of human Bub1 gene is closely associated with the tumor-proliferating activity. Since genetic alterations of human Bub1 rarely occur in gastrointestinal cancers, the functional machinery of Bub1 to prevent cell cycle progression into anaphase might be well preserved in gastric carcinomas even with high proliferative activity.
Dyspepsia Management in Primary Care in The Netherlands: To What Extent Is Helicobacter pylori Diagnosis and Treatment Incorporated?
Authors: Weijnen Catherine F. , de Wit Niek J. , Numans Mattijs E. , Quartero A. Otto , Verheij Theo J.M.
Published: April 2003

Background: Many guidelines on the management of Helicobacter pylori (HP)-related dyspepsia have been launched over the past decade. The suggested policies in these guidelines are often more consensus- than evidence-based (test-and-treat policy, test and endoscope), which may cause confusion among primary-care physicians. Aim: To determine the current management of HP-related dyspepsia by Dutch general practitioners (GPs). Methods: A random sample of 5% of all Dutch GPs (n = 355) were sent a questionnaire on the diagnosis and treatment of HP infections in dyspepsia management. Results: The response rate was 66.2% (n = 235). Almost 80% of the responding GPs stated they had conducted HP testing (via endoscopy or serology) during the previous 12 months. In the same time period, more than 94% had actually prescribed a HP eradication therapy. A total of 70% of the GPs stated that they used endoscopy to test for HP infection, 54% used serology (ELISA); whole-blood tests and carbon urea breath tests were not used. Patients with a history of peptic ulcer disease, those on chronic acid-suppressive drugs and patients with recurrent ulcer-like complaints were most frequently tested for HP infection. Conclusions: Given the frequency of consultations for dyspepsia in primary care in the Netherlands (150 new dyspeptic patients per average practice per year), and the reported average number of HP tests perfomed (1–5 per GP per year), HP diagnosis plays a modest role in the management of dyspepsia in Dutch general practices. Neither the ‘test-and-treat’ policy recommended in the Maastricht guidelines, nor its advice regarding the choice of diagnostic tests (carbon urea breath test or serology), is being followed. The majority of GPs uses endoscopy for the detection of HP infection.
Mutations of the Cationic Trypsinogen Gene in Hereditary and Non-Hereditary Pancreatitis
Authors: O’Reilly Derek A. , Yang Bing-Mei , Creighton Jane E. , Demaine Andrew G. , Kingsnorth Andrew N.
Published: April 2003

Background/Aims: Mutations in the cationic trypsinogen gene have been detected in patients with hereditary pancreatitis (HP). This study investigates the prevalence of the R122H, N29I, A16V and –28delTCC mutations in the common, non-hereditary forms of chronic pancreatitis and in a HP family. Methods: DNA was prepared from blood samples of 53 patients with chronic pancreatitis (36 alcoholic, 14 idiopathic and 3 hereditary), 20 alcoholic controls and 20 healthy, ethnically matched controls. The R122H and A16V mutations were identified by the polymerase chain reaction (PCR) and restriction enzyme digestion. A nested-PCR was used to identify the N29I mutation. The –28delTCC deletion and the C133807T polymorphism were sought by direct sequencing. Results: The R122H mutation was detected in 1 patient with alcoholic chronic pancreatitis and all 3 affected members of a HP family. The N29I, A16V and –28delTCC mutations were not detected in any of the study subjects. At the C133807T polymorphism, the C allele and C/C genotype were significantly increased in alcoholic chronic pancreatitis (p = 0.001 and p = 0.0004, respectively) while the T allele and CT genotype were significantly reduced (p = 0.001 and p = 0.004, respectively) compared to healthy controls. Conclusions: Mutations of the cationic trypsinogen gene are rarely found in chronic pancreatitis patients of typical aetiology. Screening for these mutations should be considered in those with a family history consistent with hereditary pancreatitis but may also be appropriate in a well-defined subgroup of patients with non-hereditary chronic pancreatitis, i.e. those who have developed the disease before the age of 30.
Limited Heat-Shock Protein 72 Induction in Caco-2 Cells by L-Glutamine
Authors: Lindemann G. , Grohs M. , Stange E.F. , Fellermann K.
Published: April 2003

Background/Aims:L-Glutamine (L-gln) is a conditionally essential amino acid which is consumed by certain tissues like the intestine in large amounts as energy source during critical illness. Apart from nutritive action, recent data suggest a link to heat-shock protein (hsp) induction. We investigated the effect of L-gln on hsp72 expression in the intestinal cell line Caco-2 under basal and heat-shock conditions and compared it with related amino acids. Methods: Total cellular protein was extracted and separated by SDS-PAGE. Immunoblots were performed with anti-hsp72 followed by chemiluminescence detection and densitometric scanning. Results: Following heat shock, hsp72 protein expression increased by 72 and 53% at 2 and 4 mmol/l L-gln, respectively, compared to heat shock alone (p < 0.05). Under basal conditions a limited increase occurred only at 8 mmol/l L-gln (p < 0.01). Levels remained unaffected when related amino acids including alanine, glutamate or glycine were supplemented under basal and heat-shock conditions. Similarly, the nonmetabolizable glutamine analogue DON or the toxic metabolite L-pyroglutamate did not induce hsp72. Conclusion: We conclude that the glutamine-mediated effect may be specifically attributed to the metabolic action of L-gln.
Screening of First Degree Relatives of Patients Operated for Colorectal Cancer: Evaluation of Fecal Calprotectin vs. Hemoccult II
Authors: Kristinsson J. , Nygaard K. , Aadland E. , Barstad S. , Sauar J. , Hofstad B. , Stray N. , Stallemo A. , Haug B. , Ugstad M. , Tøn H. , Fuglerud P.
Published: April 2003

Fecal calprotectin (CPT) is elevated in the majority of patients with known colorectal cancer (CRC), but the specificity is not clarified. Aim: To evaluate if a CPT test (PhiCal ELISA) was more sensitive than Hemoccult II test in detecting colorectal neoplasia, and to obtain reference values in subjects with normal colonoscopy. To evaluate a possible relation between number and extent of dysplasia of adenomas in first degree relatives of patients with CRC and the stage of the carcinoma in the index casus. Further to study the prevalence of CRC and adenomas in the first degree relatives of patients operated for CRC. Method: In a multicenter study, 253 first degree relatives of patients with CRC, aged 50–75 years (mean age 60 years) underwent colonoscopy after having delivered stool samples and three Hemoccult II slides. Results:  In 237 first degree relatives from 148 patients with CRC, polyps were found in 118 (50%). Seventy three (31%) had adenomas and 17 had adenomas ≧10 mm. Five had asymptomatic cancers. The specificity of fecal CPT for adenomas at cut off levels ≤10, ≤15 and ≤20 mg/l were 47.4, 59.6 and 71.1%, respectively (max of three samples). The sensitivity at same cut off levels was 56.2, 45.2 and 31.5% and 4/5 of patients with carcinoma had CPT values >15 mg/l. The sensitivity of Hemoccult II for adenomas was 8%, and 4/5 of patients with carcinoma had negative Hemoccult II. The specificity for adenomas was 95%. Conclusion: Fecal CPT test was more sensitive than Hemoccult II in detecting colorectal neoplasia but the specificity was lower. In a high risk group like first degree relatives of patients with CRC, there are good reasons to consider fecal CPT as a first test in selecting patients for endoscopy.
Effect of Electrical Stimulation on Acupuncture Points in Diabetic Patients with Gastric Dysrhythmia: A Pilot Study
Authors: Chang Chi-Sen , Ko Chung-Wang , Wu Chun-Ying , Chen Gran-Hum
Published: April 2003

Background/Aims: Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis and are associated with impaired antral motor activity. In this study, we aimed at evaluating the effect of acupuncture on gastric slow waves in diabetic patients with symptoms suggesting gastric motor dysfunction. Methods: Fifteen patients with type II diabetes who had had dyspeptic symptoms for more than 3 months were enrolled. Two acupuncture needles were inserted into the subjects’ legs at the Zusanli points, and electrical stimulation (2-Hz pulses) was delivered for 30 min. Cutaneous electrogastrography was performed for 30 min at baseline, for 30 min during acupuncture, and for an additional 30 min after acupuncture. Serum gastrin, motilin, and human pancreatic polypeptide levels were also measured. Results: There was a significant increase in the percentages of normal frequency during and after acupuncture (baseline vs. acupuncture and after acupuncture 21.99 ± 19.38% vs. 45.93 ± 19.72 and 48.92 ± 19.56%; p < 0.01). In addition, the percentage of tachygastric frequency was decreased significantly during and after acupuncture. The dominant frequency was also changed significantly. There was an increase of serum human pancreatic polypeptide during acupuncture (baseline vs. acupuncture 56.96 ± 27.64 vs. 73.11 ± 22.37 pmol/l; p < 0.05). Conclusions: The results of this study revealed that electrical stimulation at the Zusanli points could increase the percentage of normal electrogastrography frequency and decrease the percentage of tachygastric frequency in diabetic patients. The data indicate that acupuncture may enhance the regularity of gastric myoelectrical activity in diabetic patients.
An Unusual Metastatic Motilin-Secreting Neuroendocrine Tumour with a 20-Year Survival
Authors: Fiasse R. , Deprez P. , Weynand B. , De Clercq P. , Wibin E. , Pauwels S. , Rahier J. , Peeters T.
Published: April 2003

Motilin-secreting neuroendocrine tumours have been rarely described. Immunohistochemical, biochemical and motility investigations were performed in a 62-year-old man with liver and bone metastases of a motilin-secreting neuroendocrine tumour originating from a rectal polyp removed 14 years previously. Symptoms related to liver metastases were reduced by a right hepatectomy whereas plasma motilin levels were decreased. The patient also underwent two operations for spinal cord decompression and survived 6 more years under medical treatment, mainly octreotide. Immunohistochemistry revealed predominant expression of motilin-containing cells, with rare cells expressing somatostatin and pancreatic polypeptide, and staining for only one panendocrine marker, neurone-specific enolase. A liver tumour extract contained 17.9 µg motilin per gram of tissue, which permitted to isolate and characterize human motilin, which was identical to porcine motilin. Plasma column gel chromatography revealed a main peak corresponding apparently to porcine motilin. The patient had no symptoms of disturbed motility. Gastric emptying and gastroduodenojejunal motility were found within normal limits. The absence of alterations of gut motility was perhaps related to sustained autonomous motilin production. The long evolution of this type of tumour suggests that plasma motilin determination should be added to the investigations for neuroendocrine tumours.
L-Arginine: A Unique Amino Acid for Improving Depressed Wound Immune Function following Hemorrhage
Authors: Angele Martin K. , Nitsch Stefan M. , Hatz Rudolf A. , Angele Peter , Hernandez-Richter Thomas , Wichmann Mathias W. , Chaudry Irshad H. , Schildberg Friedrich W.
Published: April 2003

Objective: To determine whether L-arginine has any salutary effects on wound immune cell function following trauma-hemorrhage. Background: Depressed wound immune function contributes to an increased incidence of wound infections following hemorrhage. Although administration of L-arginine has been shown to restore depressed cell-mediated immune responses following hemorrhage potentially by maintaining organ blood flow, it remains unknown whether L-arginine has any salutary effects on the depressed local immune response at the wound site. Methods: Male mice were subjected to a midline laparotomy and polyvinyl sponges were implanted subcutaneously in the abdominal wound prior to hemorrhage (35 ± 5 mm Hg for 90 min and resuscitation) or sham operation. During resuscitation mice received 300 mg/kg body weight L-arginine or saline (vehicle). Sponges were harvested 24 h thereafter, wound fluid collected and wound immune cells cultured for 24 h in the presence of LPS. Pro- (IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines were determined in the supernatants and the wound fluid. In addition, wounds were stained for IL-6 immunohistochemically. In a separate set of animals, skin and muscle blood flow was determined by microspheres. Results: The capacity of wound immune cells to release IL-1β and IL-6 in vitro was significantly depressed in hemorrhaged mice receiving vehicle. Administration of L-arginine, however, improved wound immune cell function. In contrast, in vivo the increased IL-6 release at the wound site was decreased in L-arginine-treated mice following hemorrhage. Moreover, IL-10 levels were significantly increased in the wound fluid in hemorrhaged animals receiving L-arginine compared to vehicle-treated mice. In addition, the depressed skin and muscle blood flow after hemorrhage was restored by L-arginine. Conclusions: Thus, L-arginine might improve local wound cell function by decreasing the inflammatory response at the wound site. Since L-arginine protected wound immune cell function this amino acid might represent a novel and useful adjunct to fluid resuscitation for decreasing wound complications following hemorrhage.
Correct Identification and Explanation of Age-Related Changes Are Always Possible
Authors: Molenaar Peter C.M.
Published: April 2003

In this commentary, it is argued that the definition of the time or the age variable in the models presented by Hofer and Sliwinski is ambiguous, and a standard interpretation of this time of age variable is proposed instead. Some simulation studies are presented, the results of which indicate that, even with age-heterogeneous cross-sectional data, correct identification of the true sources of age-dependent variation is possible. An important qualification, based on new methodological work in progress, is given of the scope of longitudinal designs. It is concluded that all kinds of age-related changes are potentially interesting and can be correctly identified and explained.
Age-Related Effect of Aluminium on the Catalase Activities of the Brains of Two Species of Poikilothermic Vertebrates
Authors: Jena B.S. , Nayak S.B. , Patnaik B.K.
Published: April 2003

Background: Although aluminium (Al) has been implicated in various neuropathological states with aging due to its involvement in neurotoxicity, the exact role of the metal ion is still unclear. Objective: The aim of the present study is to ascertain whether the antioxidant enzymes of the brain protecting from oxidative damages which accumulate with aging are regulated by Al in an age-dependent manner. Method: The inhibitory effect of Al on the catalase activity of brain homogenates of two species of poikilothermic vertebrates was studied in vitro using a spectrophotometric method. Results: At a final concentration of 666 µM, the metal ion inhibited the enzyme activity of the brain in both species. In fish brain the degree of inhibition was not age-dependent. On the other hand, the rate of inhibition increased between young and middle-aged lizards followed by a decline in the old counterparts. Conclusion: Al inhibits catalase activity but this effect may not be a major contributing factor in the aging of the brain in the two species capable of maintaining their antioxidant capacity until old age.
Non-Compliance with Drug Treatment and Reading Difficulties with Regard to Prescription Labelling among Seniors
Authors: Moisan Jocelyne , Gaudet Michel , Grégoire Jean-Pierre , Bouchard Réjeanne
Published: April 2003

Background: The link between experiencing difficulties in reading or understanding and non-compliance with drug treatment among seniors is not clearly established. Objectives: We measured the effect of both difficulties in reading, as well as difficulties in understanding prescription labelling, on non-compliance with drug treatments among seniors. Since the use of a pill organizer prepared by a pharmacist may compensate for the problems in reading, we also checked the potential modifying effect of the use of a pill organizer on these two associations. Method: Data on non-compliance with drug treatment, comprehension of prescription labelling and on the factors potentially linked to non-compliance, were collected during face-to-face interviews with 325 seniors. Results: In all, 126 respondents (38.8%) were not able to read all the prescription labels and 218 (67.1%) did not fully understand all the information. 153 respondents were non-compliant with their drug treatment. After adjusting for sex, age, living alone or not, having had help with taking the medication, use of a pill organizer, having had sufficient funds to procure his medicine during the previous month, belief in the efficacy of his medication, perception of his state of health, satisfaction with physician-given and pharmacist-given information, as well as the complexity of the treatment, the two associations remained statistically non-significant. The use of a pill organizer was not a modifying factor. Conclusion: Our results did not demonstrate the existence, among seniors, of an association between non-compliance and difficulty in reading and understanding prescription labelling.
Changes in Serum Cortisol with Age in Critically Ill Patients
Authors: Beale Elizabeth , Zhu Jay , Belzberg Howard
Published: April 2003

Background: Mortality in the intensive care unit (ICU) rises with age, a high basal serum cortisol and a small response to adrenocorticotropin (ACTH) stimulation. Even slight impairment of the adrenal response during severe illness can be lethal. Objectives: To determine if age is associated with changes in basal or stimulated serum cortisol in critically ill patients. Methods: We studied 2 groups of surgical ICU patients with hypotension despite ≧6 h of catecholamine therapy. Group 1 comprised 7 patients aged <30 (mean 22.9 ± 3.7) years, and group 2 comprised 8 patients aged >60 (mean 75.8 ± 10.3) years (p < 0.001). We compared baseline serum cortisol levels and the serum cortisol response 30 and 60 min after stimulation with low-dose (1 µg) and 2 h later standard-dose (250 µg) ACTH. We also determined the incidence of adrenal insufficiency in each group using standard criteria and compared selected clinical variables. Results: There was no significant difference in the mean serum cortisol at baseline although it tended to be higher in older patients. Group 2 patients had a significantly smaller response to the low-dose test at 30 min (p = 0.002), and to the standard-dose test at both 30 (p = 0.02) and 60 min (p = 0.04). There was no significant difference in the incidence of adrenal insufficiency between the 2 groups: 1/7 or 14.3% in group 1 vs. 1/8 or 12.5% in group 2 (p = 1.0). There was no significant difference between the 2 groups in the mean acute physiology score, blood pressure, serum albumin, dopamine, or dobutamine dose (p > 0.05). Creatinine clearance was significantly lower in group 2 (p > 0.001) and endogenous ACTH significantly higher (p = 0.04). Significantly more patients in group 1 (5/7, 72%) than group 2 (1/8, 12.5%) had a diagnosis of trauma on admission (p = 0.04). Seven of the eight patients (88%) in group 2 vs. 1/7 (14%) of patients in group 1 died in the ICU, but this difference was not statistically significant (p = 0.18). Conclusion: In this small exploratory study, baseline serum cortisol tended to be higher in older patients and older patients had a significantly smaller response to ACTH stimulation on both low-dose and standard-dose tests. In view of the high death rate in the older ICU patients, the findings in this study need to be confirmed in a larger study. The mechanism and clinical significance of these findings remain to be determined but may be related to deterioration in renal function with age.
Impact of Age, Gender and Cognitive Functioning on Pain Perception
Authors: Pickering Gisèle , Jourdan Didier , Eschalier Alain , Dubray Claude
Published: April 2003

Background: Experimental data on nociception in the elderly have so far been contradictory and most of these have been obtained using psychophysical methods with little attention paid simultaneously to the state of cognition and the psychometric performance of the subjects. Objective: The aim of this study was twofold: (1) to evaluate the impact of age on experimental nociception thresholds, and (2) to investigate the interactions of age, sex, cognition and psychometric performance with nociception thresholds. Methodology: (1) Two groups, one young and one elderly, of 42 healthy participants each, 21 males and 21 females, were compared as regards nociception thresholds with thermal and mechanical stimuli (heat and pressure detection and tolerance thresholds). (2) The elderly group took cognitive (mini-mental test), psychometric (choice reaction time) and psychophysical tests in auditory (sensibility, tolerance, discrimination) and nociceptive fields. Results: This study shows that (1) pressure nociception decreases with age especially in males, while thermal thresholds are not modified, and (2) correlations exist between cognitive function, psychometric performance, tolerance to loud sounds and tolerance to mechanical noxious stimuli. Conclusion: Our results suggest that cognitive and psychomotor parameters have to be taken into account when assessing experimental nociception in the elderly. Further studies are needed to evaluate possible report biases and to assess these interactions in old patients with pain and in mildly sensory, cognitive or motor impaired elderly subjects.
Evidence-Based Medicine: How to Read an Article about a Diagnostic Test
Authors: Glenck Urs , Pewsner Daniel , Bucher Heiner C.
Published: April 2003

Against the background of the technological progress in medicine which has produced a multitude of new diagnostic possibilities, doctors nowadays are in danger of using misdirected tests for diagnostic workup that are useless in certain cases or even dangerous because they make healthy people appear sick. As economic resources are limited, the use of diagnostic tests has to be rational and carefully directed. In this article the authors show how trials with diagnostic tests can be critically appraised using the tools of evidence-based medicine. The starting point is a clinical example of daily practice, i.e. the exclusion of deep vein thromboses in the case of a swollen leg. The appropriate clinical question is formulated and a literature search in Medline is done to find the answer. The general criteria of quality in diagnostic studies are explained and applied to a specific study of a rapid D-dimer test which is easy to use in the general practice. Gold standard, pre- and posttest probabilities and properties of tests such as sensitivity, specificity and likelihood ratios are explained in detail. The value of clinically estimating the probability of a disease is shown with the model for the estimation of the pretest probability of deep vein thrombosis according to Wells.
Current-Induced Vasodilation during Water Iontophoresis (5 min, 0.10 mA) Is Delayed from Current Onset and Involves Aspirin Sensitive Mechanisms
Authors: Durand S. , Fromy B. , Bouyé P. , Saumet J.L. , Abraham P.
Published: April 2003

Study of the microcirculation by iontophoresis is potentially confounded by any non-specific effects of current application. Laser Doppler flow (LDF, mean ± SD; arbitrary units; AU) was recorded on the forearms of healthy volunteers during and 20 min following application of 0.10-mA current for 1, 3 and 5 min, using deionised water as a vehicle. Local heating to 44°C was then applied for 24 min to assess maximal vasodilation. Cathodal current applications resulted in delayed and prolonged vasodilation (peak values: 78 ± 29, 75 ± 19, 80 ± 37 AU) whereas anodal peak LDF was 13 ± 6, 27 ± 34 and 72 ± 40 AU for 1-, 3- and 5-min periods of current applications, respectively. From current onset, inflexion points in the responses to 3- and 5-min anodal current applications occurred at 4.5 and 6.5 min, respectively, and at ∼1.5 min for all cathodal current applications. For 5-min current applications: a preliminary tourniquet ischaemia neither changed the time course nor the amplitude of the response to current application. In this situation, local anaesthesia abolished the current-induced vasodilation. Chronic capsaicin pretreatment decreased the amplitude of the vasodilation. Pretreatment with 500 mg oral aspirin decreased the cathodal vasodilation and abolished the anodal vasodilation, even in the absence of preliminary ischaemia. We conclude that vasodilation to prolonged application of 0.10-mA continuous monopolar current after transient tourniquet ischaemia cannot be exclusively the result of an axon reflex initiated by current onset. This current-induced vasodilation is at least partly dependent on capsaicin-sensitive afferent fibres and relies on aspirin-sensitive mechanisms at both polarities.
Changes in the Actin Cytoskeleton of Cardiac Capillary Endothelial Cells during Ischaemia and Reperfusion: The Effect of Phalloidin on Cell Shape
Authors: Glyn Matthew C.P. , Ward Barbara J.
Published: April 2003

A reduction in capillary dimensions has been demonstrated in postischaemic reperfusion in the heart. The aim of this study was to demonstrate that in ischaemia and ischaemia followed by reperfusion, the change in shape of the constituent endothelial cells can be inhibited by phalloidin which stabilises the actin microfilament system. Isolated, perfused rat hearts were made globally ischaemic both with and without reperfusion and in the presence or absence of phalloidin. Changes in ischaemic endothelial cell dimensions were quantified by measuring whole capillary and luminal cross-sectional areas, abluminal and luminal membrane lengths. The distribution of β-actin within the endothelial cells was determined by immunocytochemistry. In control hearts, β-actin is distributed throughout the endothelium with a slight increase towards the luminal membrane. In ischaemia, this was more marked and other patterns of actin distribution were also observed. After reperfusion, a ‘double ring’ of actin could be distinguished. With phalloidin, the actin staining was more regular and the ring pattern was not observed. Morphometry showed that phalloidin was more effective in reducing endothelial cell shape change after reperfusion than after ischaemia alone. We conclude that endothelial cell shape change on reperfusion can be modified by agents which target the contractile proteins.
Physiological Concentrations of Dopamine Inhibit the Proliferation and Cytotoxicity of Human CD4+ and CD8+ T Cells in vitro: A Receptor-Mediated Mechanism
Authors: Saha Baisakhi , Mondal Amal Chandra , Majumder Jahar , Basu Sujit , Dasgupta Partha Sarathi
Published: April 2003

Objective: Dopamine, a catecholamine neurotransmitter, influences growth and proliferation of lymphocytes. Pharmacological doses of dopamine have been shown to modulate T cell functions significantly, but no information is available on the effect of physiological concentrations of circulating dopamine on CD4+ and CD8+ T cell functions. This information may be of importance since significantly elevated plasma dopamine levels were observed in humans during uncoping stress, and suppression of T cell functions during stress is a well-known phenomenon. However, the mechanism inducing the suppression of T cell functions during stress is not yet clear. In the present investigation, we evaluated the effect of the dopamine level attained in the plasma of individuals with uncoping stress on the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. Methods: T cell subpopulations were separated by panning. The effect of dopamine on IL-2-induced cell proliferation in vitro was evaluated by [3H]thymidine incorporation and cytotoxicity by 51Cr release, receptors by radioligand binding, cAMP by an assay kit and apoptosis by DNA fragmentation. Results: At these elevated physiological concentrations, dopamine was found to inhibit significantly the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. This dopamine-mediated inhibition of proliferation was more marked on CD8+ T cells than on CD4+ T cells. The underlying mechanism was found to be D1 class of dopamine-receptor-mediated stimulation of intracellular cAMP. Conclusion: Results may be of significance to understand the role of peripheral dopamine in human neuroimmune communication in terms of physiological homeostasis in health and disease.
Strain Differences in the Expression of Corticotropin-Releasing Hormone Immunoreactivity in Nerves That Supply the Spleen and Thymus
Authors: Bellinger Denise L. , Brouxhon Sabine M. , Lubahn Cheri , Tran Lily , Kang Joey I. , Felten David L. , Lorton Dianne
Published: April 2003

The existence of nerve fibers containing corticotropin-releasing hormone (CRH) immunoreactivity in primary and secondary lymphoid organs from three strains of young adult male rats was examined. Spleens and thymuses from Fischer 344 (F344), Sprague-Dawley (SD) and Lewis (LEW) rats were prepared for immunocytochemistry using antisera directed against CRH. In F344 and SD rats, we were unable to demonstrate CRH-immunoreactive nerves in either the thymus or the spleen. Despite the lack of CRH-containing nerves, CRH immunoreactivity was present in pleotropic cells in the septum, cortex and medulla of the thymus, and in the red and white pulp of spleens from F344 and SD rats. In contrast, CRH+ nerves were found in thymuses and spleens from LEW rats. CRH+ nerves coursed in the interlobular septa, capsule, cortex and medulla of the LEW rat thymus. Large CRH-immunoreactive nerve bundles were present in the hilar region of the LEW rat spleen, and individual CRH+ fibers coursed in the capsule, trabeculae, red pulp, venous sinuses and marginal zone of the white pulp of the spleen. These findings indicate strain differences in neurotransmitter-specific nerves that innervate the rat spleen and thymus under basal conditions.
Intravenous Immunoglobulin G in the Treatment of Patients with Chronic Glomerulonephritis: Clinical Experience Lasting 15 Years
Authors: Monova Daniela , Belovezhdov Nicolay , Altunkova Iskra , Monov Simeon
Published: April 2003

In our study, we collected data on 116 patients with biopsy-proven idiopathic or lupus glomerulonephritis who were treated with high doses of intravenous immunoglobulin G (IVIG) (Veinoglobuline or Immunovenin-intact). In all patients a severe nephrotic syndrome (edema, proteinuria >6 g/24 h, serum albumin <22 g/24 h) had been observed. 34 patients had renal failure (serum creatinine up to 504 µmol/l) and 96 hypertension. 98 patients were previously for a long time treated with corticosteroids, immunosuppressors and anticoagulants without any effect. 18 patients had no therapy before IVIG. IVIG had been applied in a dose of 85 mg/kg/24 h 3 times every other day. Depending on the clinical improvement afterwards (in case of therapy resistance or relapse) these boli had been repeated in 84 patients after 1 month (and every 3 months for maintenance of remission) to 7 years. Proteinuria disappeared and full remission occurred in 36 patients. Partial remission was present in 48 patients. 32 patients went into end-stage renal failure and/or died (15 of them of a nonrenal cause). In 13/34 patients with impaired renal function serum creatinine levels go back to normal after treatment. Our results suggested that IVIG therapy may be recommended in patients unresponsive to aggressive conventional treatment.
Changes in Mac-1 and CD14 Expression on Monocytes and Serum Soluble CD14 Level during Push/Pull Hemodiafiltration
Authors: Kawabata Kenji , Nakai Shigeru , Miwa Masamiki , Sugiura Tatsuki , Otsuka Yuka , Shinzato Toru , Hiki Yoshiyuki , Tomimatsu Ikuko , Ushida Yumi , Hosono Fumiko , Maeda Kenji
Published: April 2003

Background/Aim: Employment of treated dialysate as replacement fluid raises concerns about exposure of patients to pyrogenic substances. This study was undertaken to evaluate the safety of treated dialysate as the replacement fluid for push/pull hemodiafiltration. Methods: In the present study, changes in the expressions of Mac-1 and CD14 on monocytes, which are upregulated by monocyte activation, were analyzed by flow cytometry, and the serum level of sCD14 which elevates by monocyte activation was measured by enzyme-linked immunosorbent assay (ELISA) during treatment in 7 patients on hemodialysis with regenerated cellulose (RC) membrane, polysulfone (PS) membranes and by push/pull hemodiafiltration (HDF) with PS membranes in a cross-over fashion. Results: During hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration with PS, both Mac-1 and CD14 expressions on monocytes significantly increased by passing through the artificial kidneys, and, accordingly, the respective values downstream of the artificial kidneys were significantly higher than the predialysis values, even when the lipopolysaccharide level in dialysate was not detectable by Limulus assay. There was no significant variation in serum sCD14 levels during any of the hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration. However, during hemodialysis with PS or push/pull hemodiafiltration with PS, changes in Mac-1 and CD14 expression on monocytes were significantly smaller than those during hemodialysis with RC. Conclusion: Monocytes are activated to a greater extent during hemodialysis with RC membranes than during push/pull HDF with PS membranes. We consider that push/pull HDF may be safer than hemodialysis with RC membrane and that it is as safe as hemodialysis with the PS membrane in terms of monocyte activation, when pyrogen-free dialysate is employed.
Reflex Anuria from Unilateral Ureteral Obstruction
Authors: Catalano C. , Comuzzi E. , Davì L. , Fabbian F.
Published: April 2003

Renal function is usually normal or only marginally affected in patients with unilateral ureteral obstruction due to the vicarious function of the contralateral kidney. Few reports exist in which unilateral renal obstruction is associated with anuria (reflex anuria, RA) and acute renal failure. We report the clinical case of a female patient who was referred to the emergency department due to anuria of 72 h duration and acute renal failure (serum creatinine 9 mg/dl) associated with several episodes of violent right flank pain with hematuria following extracorporeal shock wave lithotripsy (ESWL). A few weeks before ESWL, urography showed a 2-cm stone located in the right pelvis whilst the left kidney was functionally normal. On admission, renal ultrasound documented a normal left kidney, whilst the right pelvis was hydronephrotic and there were two indwelling stones at the right pyeloureteral junction. After the patient passed a urinary stone, diuresis restarted and acute renal failure was resolved. Thereafter, urography confirmed that the left kidney, the left ureter and bladder were functionally and morphologically normal. RA with acute renal failure has been so scarcely documented that it is considered to be legend by many clinicians. Major textbooks do not discuss RA with acute renal failure. Vascular or ureteral spasm related in part to a peculiar hyperexcitability of the autonomic nervous system may explain RA. We suggest that nephrologists should always consider RA when evaluating acute renal failure. On the other hand, RA might be relatively common and we cannot rule out that only the most severe and/or better-documented cases have been reported in the medical literature.
Isolation of Guinea Pig Inner Hair Cells Using Manual Microsurgical Dissection
Authors: Yang Shi-Ming , Jing Shen , Doi Tadashi , Kaneko Toshihiko , Yamashita Toshio
Published: April 2003

Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) show distinctive morphological features that are usually sufficient to distinguish these two species in vitro. However, OHCs may sometimes resemble IHCs when they are mechanically distorted or begin swelling at their basal end. As a result, accurately discriminating the cells based on morphology was thought to be problematic. An objective method that allows us to clearly and unambiguously distinguish these two cell types is therefore of continued interest. We describe a protocol in which solitary IHCs were harvested from guinea pig cochlea using a manual microsurgical dissection.
The Mouse (Mus musculus) T Cell Receptor Delta Variable (TRDV), Diversity (TRDD) and Joining (TRDJ) Genes
Authors: Bosc Nathalie , Contet Valérie , Lefranc Marie-Paule
Published: April 2003

‘The Mouse (Mus musculus) T Cell Receptor Delta Variable (TRDV), Diversity (TRDD) and Joining (TRDJ) Genes’, the 15th report of the ‘IMGT Locus in Focus’ section, comprises 7 tables entitled: (1) ‘Number of mouse (Mus musculus) germline TRDV genes at 14D1–D2 and potential repertoire’; (2) ‘Mouse (Mus musculus) germline TRDV genes at 14D1–D2’; (3) ‘Mouse (Mus musculus) TRDV allele table’; (4) ‘Mouse (Mus musculus) germline TRDD genes and alleles’; (5) ‘Mouse (Mus musculus) germline TRDJ genes’; (6) ‘Mouse (Mus musculus) TRDJ allele table’, and (7) ‘Correspondence between the different mouse (Mus musculus) TRDV gene nomenclatures’. These tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines. fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France.
Serial Magnetic Resonance Imaging of Global and Regional Left Ventricular Remodeling during 1 Year after Acute Myocardial Infarction
Authors: Schroeder Anne Pauline , Houlind Kim , Morre Pedersen Erik , Toftegaard Nielsen Torsten , Egeblad Henrik
Published: April 2003

Biplane long-axis cine MRI was performed in 51 patients 1, 13, 26, and 52 weeks after their first AMI. LV mass index (LVMI) was significantly increased 1 week after AMI (84.3 ± 16.9 vs. 68.1 ± 11.4 g/m2 controls, n = 48, p < 0.001), presumably owing to edema of the infarcted myocardium. Six months after AMI, LVMI decreased to 76.5 ± 16.4 g/m2, but had again augmented after 1 year (81.8 ± 17.3 g/m2, p < 0.05), suggesting late, compensatory left ventricular hypertrophy. In patients treated with primary percutaneous transluminal coronary angioplasty, LVMI decreased 5% over 1 year, while LVMI increased 10% in patients receiving thrombolysis (p < 0.05). In the entire population, the global increase in LVMI 1 year after AMI seemed to reflect global cavity dilatation with unchanged thickness of the vital myocardium. In conclusion, in patients receiving contemporary treatment, LV remodeling only partially complied with the classical patho-anatomical concept.
Neurosonology in Cerebral Ischemia: Future Application of Transcranial Doppler in Acute Stroke
Authors: Egido Jose A. , Sánchez Carmen
Published: April 2003

Transcranial Doppler (TCD) has become a general practice in recent years in the diagnostic study of patients with cerebral ischemia. This is due to the fact that it is a rapid, noninvasive, reproducible and dynamic examination of intracranial circulation. In the acute phase of cerebral infarction, it can detect MCA occlusion with a good correlation with angiographic findings and, what is even more important, the patients who will later suffer lacunar infarctions almost always show a normal Doppler examination. Acute abnormalities can also demonstrate the mechanism of the clinical signs; the examination informs us of the existence of collaterals and severe occlusions or stenoses of the extracranial arteries, and can change the priority in the search for the etiological diagnosis. The diagnosis of intracranial stenoses as a cause of clinical signs is another immediate application of TCD, right from the acute phase. If in the future anticoagulation is shown to be an optimum treatment for secondary prophylaxis in intracranial stenoses, TCD will probably become the diagnostic technique of choice. The ability to predict the prognosis based on parameters obtained by TCD opens up the possibility of using it as an auxiliary technique for the selection of patients for reperfusion treatment, having in its favor that it is quick and easy to perform, and therefore suitable for treatment monitoring. It seems clear that the data obtained by Doppler in the first 6 h are a good predictor of both spontaneous improvement and early impairment, which could help to avoid treatment in patients in whom a rapid improvement can be expected. Finally, the hemodynamic data of the TCD could be of inestimable value in the assessment and monitoring of intracranial hypertension treatments and for hemodynamic management of the patient, allowing the treatment margins of the acute phase of arterial hypertension to be reliably established without compromising the perfusion pressure. In conclusion, TCD will possibly be more widely used in the future in the acute phase of cerebral infarction as a guide to diagnostic procedures, for treatment selection and for monitoring of cerebral hemodynamics.
Antithrombotic Therapy in the Acute Phase: New Approaches
Authors: Sherman David G.
Published: April 2003

Both anticoagulants and antiplatelet agents have been advocated, used and studied for the treatment of acute ischemic stroke. Randomized trials of unfractionated heparin, low-molecular-weight heparin and heparinoids have failed to show an overall benefit to these agents largely because the benefits in reducing thromboembolic events are offset by the increased risk of bleeding complications. The International Stroke Trial, the Trial of ORG 10172 Acute Stroke Treatment and studies of fraxaripine all failed to show an overall benefit to anticoagulation in the patients studied. Aspirin has been shown to offer a modest benefit when studied in patients treated within 48 h of stroke onset. Ancrod is an antithrombotic agent that acts by reducing circulating fibrinogen levels. Patients treated within 3 h of stroke symptom onset had a better functional outcome at 90 days compared to placebo-treated patients with both the benefits and the risk of intracerebral bleeding related to the fibrinogen lowering achieved. Abciximab is a blocker of the platelet GPIIb/IIIa receptor. A dose finding safety study suggests that in doses up to that typically given in patients with acute coronary occlusion syndromes, there is no increased risk of symptomatic intracerebral bleeding and suggestions of potential benefits on neurological outcome.
The Palliative Effects of Octreotide in Cancer Patients
Authors: Dean Andrew
Published: April 2003

Octreotide is an extremely useful compound for palliative care physicians. It appears to be active in a number of different pain states and may be given by the spinal and intraventricular route. Its actions in reducing gut motility and secretions make it a valuable adjunct in the management of inoperable bowel obstruction. The same actions make it a potent antidiarrheal agent. Octreotide will often succeed where other antidiarrheal agents fail. Its ability to reduce gut secretions has led to its use in the treatment of fistulae. It has also been proposed as a useful drug in the management of cachexia and ascites. Most of the existing evidence is based on small numbers of case reports and further larger trials are necessary.
Somatostatin Analogs in Oncology: A Look to the Future
Authors: Jenkins Spencer A. , Kynaston Howard G. , Davies Nick , Baxter John N. , Nott David M.
Published: April 2003

In the past 15 years considerable advances have been made in our understanding of the molecular pharmacology of the mechanisms whereby somatostatin and its analogs mediate their direct and indirect antineoplastic effects. However, some important issues remain to be resolved, in particular the functional roles of the individual somatostatin receptors (SSTR-1–5) in tumor tissue and up- or downregulation of the hSSTRs with prolonged administration of somatostatin analogs. Answers to these questions are essential before we can maximize the therapeutic efficacy of somatostatin analogs in cancer. For example, is continuous administration more or less effective than intermittent therapy? The role of somatostatin analogs in the management of acromegaly and to a lesser extent neuroendocrine tumors is firmly established. The development of depot preparations of all 3 somatostatin analogs currently available for clinical use will undoubtedly improve both patient compliance and quality of life in patients with these conditions. There are only likely to be minor differences in the therapeutic efficacy of octreotide, lanreotide and vapreotide since all three analogs exert the majority of their antineoplastic effects via hSSTR-2 and hSSTR-5 and at the end of the day, price may well dictate which of these drugs oncologists use to provide symptomatic palliation of acromegaly and neuroendocrine tumors. Apart from some notable exceptions, somatostatin analog therapy has proven to be very disappointing in the management of advanced malignancy. Improvements in the management of solid tumors are likely to come only from combination therapy of somatostatin analogs with cytotoxic agents or other hormones in both advanced malignancy and in the adjuvant setting. Clinical trials with clear-cut objective outcome measures and health-related quality of life assessment are needed to evaluate the therapeutic efficacy of combination treatment in advanced malignancy and as an adjuvant to surgery. Particular attention needs to be paid to possible adverse effects of somatostatin analog therapy on the immune response to cancer. Further studies are required to establish whether the adverse effects of somatostatin analog therapy alone or in combination with cytotoxics or other hormones can be reversed with appropriate immunomodulatory treatment. Targeted somatostatin analog radiotherapy and chemotherapy are currently being investigated and the results of these studies are awaited with interest. Novel approaches using combinations of somatostatin analogs with antiangiogenic drugs or gene therapy are of particular interest and may provide important advances in the management of cancer in the not too distant future.