bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Findings in Barrett’s Epithelium
Authors: Tannapfel Andrea
Published: September 2004

Barrett’s metaplasia is a premalignant condition and remains the number one risk factor for developing adenocarcinoma. The histologic changes leading to adenocarcinoma are accompanied by genetic disturbances of the epithelial cells itself as well as the surrounding stroma. Genetic and epigenetic events affect the cell cycle, leading to growth self-sufficiency and ignoration of antigrowth signals. The balance of cell turnover is instable by avoidance of apoptosis and a general limitless of the replicative potential of the (mutated) stem cells. Sustained angiogenesis, not only a consequence of chronic inflammation, may precede invasion of genetically instable (aneuploid) cells. The principal genetic changes in Barrett’s carcinogenesis are comparable to those known from other epithelial malignancies. Loss of p16 gene expression (by deletion or hypermethylation), the loss of p53 expression (by mutation and deletion), the increase in cyclin expression, and the losses of Rb, APC as well as various chromosomal loci have been reported. Since these genetic or epigenetic alterations are neither tumor nor stage specific, they could not gain diagnostic significance as biomarkers until now.
Chromoendoscopy and Magnifying Endoscopy in Patients with Gastroesophageal Reflux Disease
Authors: Kiesslich Ralf , Neurath Markus F. , Galle Peter R.
Published: September 2004

Gastroesophageal reflux disease (GERD) is common in the Western world. Upper endoscopy is needed to characterize the disease. Barrett’s esophagus as a complication of GERD is an established precancerous condition which can lead to adenocarcinoma in the distal esophagus. This review summarizes recent advances in the endoscopic characterization of Barrett’s esophagus using magnification endoscopy and chromoendoscopy. Methylene blue, indigo carmine and acetic acid are commonly used dyes to facilitate diagnosis of Barrett’s esophagus. Methylene blue is absorbed in the specialized columnar epithelium, which is pathognomonic for Barrett’s esophagus. Indigo carmine and acetic acid are used as contrast stains to highlight the surface architecture. Currently, different dyes are used in conjunction with magnifying endoscopes to characterize specific surface patterns of Barrett’s epithelium. However, the current proposed classifications are too complex relative to their clinical value. Nevertheless, simplification of these systems will occur over time with increased use of magnifying chromoendoscopy. The value of magnifying chromoendoscopy for clinical practice is not determined yet and currently under investigation. However, these techniques have significant potential to improve diagnostic accuracy in patients with Barrett’s esophagus.
Treatment of Gastroesophageal Reflux Disease in Adults: An Individualized Approach
Authors: Galmiche Jean Paul , Stephenson Kate
Published: September 2004

Until the 1990s, most therapeutic trials in gastroesophageal reflux disease (GERD) focussed upon endoscopic lesions. In fact the correlation between patient symptoms and both the presence and grade of esophagitis is very poor. The classical criteria for the assessment of therapeutic efficacy in GERD have therefore been revised, and there is now a consensus that the relief of symptoms and the long-term control of the disease are the primary aims of therapy for the majority of patients. Proton pump inhibitors (PPIs) represent the mainstay of therapy for patients with non-erosive reflux disease (NERD) as well as esophagitis. Although a stepwise strategy has been recommended in the past, a step-down strategy (starting with a full-dose PPI) appears to be a more cost-effective approach. There are as yet insufficient data to establish the clear superiority of one PPI over others. PPIs have a number of limitations. Symptom relief is significantly inferior in NERD than in erosive esophagitis. The heterogeneity of the NERD group may be one of the most influential factors, but the role of esophageal hypersensitivity has been suggested especially in patients with normal acid exposure. The role of non-acid reflux should also be scrutinized. Long-term control of the disease can be achieved by drug therapy, anti-reflux surgery and now with a variety of endoscopic procedures. The different drug management strategies can be divided into (i) continuous maintenance therapy and (ii) discontinuous therapy which can again be divided into two categories, intermittent and on-demand drug therapy. A case-by-case approach is recommended to determine the personal therapeutic needs and preferences of each individual. Many patients with NERD or mild esophagitis do not require continuous maintenance therapy and recent studies have shown excellent results with different PPI on-demand therapy regimens. Finally when making a choice between different long-term strategies both the clinician and the informed patient have to consider efficacy, safety, tolerability and cost. The potential efficacy of new drugs, especially the GABA(B) agonists and the fast onset acid suppressors, as well as the cost-effectiveness of non-drug strategies (surgery and endoluminal therapies) should be further evaluated.
Surgery of Gastroesophageal Reflux Disease: A Competitive or Complementary Procedure?
Authors: Lundell Lars
Published: September 2004

The management of chronic gastroesophageal reflux disease (GERD) has both been simplified and immensely improved by the development of modern medical therapies. These are built entirely on the concept of profound acid inhibition, which is very successful in a substantial proportion of GERD patients. Despite the efficacy of proton pump inhibitors (PPIs) some failures are unavoidable, and some patients experience incomplete control of major GERD symptoms on ordinary dosing of PPIs. Although the safety profile of PPIs is very reassuring, some people express some concern about the safety of drug treatment extending beyond 10 years especially when alternative therapeutic strategies are available. Some patients complain of alleged respiratory complications to severe reflux, and in those situations as well as in cases with e.g. Barrett’s esophagus, a complete control of reflux also incorporating the duodenal components in the refluxate may be warranted. In all those situations antireflux surgery can be considered indicated for the treatment of chronic GERD and thus be looked upon as complementary to medical therapy. Furthermore, some patients who have their GERD symptoms under control on PPIs still want to have an operation to avoid dependency on drugs. Hence in none of these clinical situations does antireflux surgery play a competitive role in relation to medical therapy. However, in the very few randomized clinical trials in which a head-to-head comparison has been completed between medical and surgical therapy, the latter has been found to be somewhat more effective in terms of reflux control. The other side of the coin is that antireflux surgery has some side effects that signify the importance of this surgery being performed in specialized centers.
Ablative Procedures for Prevention and Treatment of Esophageal Adenocarcinoma
Authors: Peitz U. , Kahl S. , Malfertheiner P.
Published: September 2004

Ablation of Barrett’s mucosa by endoscopic resection, photodynamic therapy or thermoablative methods in combination with adequate acid suppression leads to mucosal replacement largely by squamous epithelium. In appropriately selected cases, these methods have the potential to cure superficial Barrett’s neoplasia. Endoscopic resection is an alternative to surgical resection of high-grade intraepithelial neoplasia or early esophageal adenocarcinoma, if the tumor is less than 20 mm in size, is not ulcerated, and does not exhibit differentiation grade 3 or lymph vessel infiltration on histological examination. In the presence of submucosal infiltration, the likelihood of lymph node infiltration is related to the infiltration depth. The risk of a noncurative endoscopic ablative approach has to be weighted against the general risk of surgery. With photodynamic or thermoablative treatment, the completeness of destruction of neoplastic tissue can only be judged at follow-up. These methods are therefore restricted to cases that have an increased surgical risk. Ablation of non-neoplastic Barrett’s mucosa is currently not indicated.
What Parameters Are Relevant for the Histological Diagnosis of Gastroesophageal Reflux Disease without Barrett’s Mucosa?
Authors: Vieth M. , Peitz U. , Labenz J. , Kulig M. , Nauclér E. , Jaspersen D. , Meyer-Sabellek W. , Willich S. , Lind T. , Malfertheiner P. , Stolte M.
Published: September 2004

Background/Aims: There are still ongoing controversies as to which histological parameters allow the diagnosis of gastroesophageal reflux disease (GERD). The aim of the present analysis was to relate histological changes of the esophageal squamous epithelium to different severities of GERD. Methods: Data were obtained from patients participating in the ProGERD study, who had either erosive reflux disease (ERD, n = 3,245) or non-erosive reflux disease (NERD, n = 2,970). 1,475 patients fulfilled our requirement of having complete biopsy data from two sites (2 cm above the z-line and at the z-line). Changes in the squamous epithelium were assessed by measuring the thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness and counting interepithelial inflammatory cells. Results: The most useful parameters for histological assessment of GERD (given as means, 2 cm above the z-line and at the z-line, respectively) were elongation of the papillae: NERD 40.7 and 48.9%; ERD 46.1 and 54.9% and basal cell hyperplasia: NERD 12.7 and 17.9%; ERD 15.7 and 23.0%. The occurrence of intraepithelial lymphocytic infiltrates, however, is dependent on the severity of GERD, and they are more common than neutrophilic and eosinophilic granulocytes. Conclusion: This study shows that both NERD and ERD can be diagnosed histologically if biopsies are obtained from the distal esophagus or from the z-line. Intraepithelial inflammatory cells are rare and show a high specificity, but very low sensitivity.
Surgical Treatment of Oesophageal Cancer
Authors: Hartel Mark , Wente Moritz N. , Büchler Markus W. , Friess Helmut
Published: September 2004

Various reconstructive conduits and routes of reconstruction have an impact on operative morbidity and foregut function in patients undergoing oesophagectomy. Advantages of a fundus rotation gastroplasty are the better blood supply and the greater length of the gastric tube and its possible impact on anastomotic complications. For a subgroup of patients with oesophageal carcinoma limited to the lamina propria vagal-sparing oesophagectomy seems to be a good alternative in terms of quality of life to preserve gastric secretory, motor, and reservoir function. Posterior mediastinal reconstruction is usually preferred when complete resection (R0) has been accomplished. Anterior mediastinal reconstruction may secondary prevent dysphagia after incomplete resections due to tumour recurrence (R0, R1). However, for all presently available surgical approaches in the treatment of oesophageal cancer qualified studies (prospective randomised) are needed. In addition, randomized trials are needed to identify the specific subgroups of patients who benefit from neoadjuvant or adjuvant radiochemotherapy.
Long-Term Follow-Up of Spontaneous Development in a Boy with Familial Male Precocious Puberty
Authors: Partsch Carl-Joachim , Krone Nils , Riepe Felix G. , Gromoll Jörg , Sippell Wolfgang G.
Published: September 2004

Background/Aims: Limited data are available about spontaneous growth, pubertal growth spurt and the long-term outcome of patients suffering from familial male precocious puberty (FMPP). We report on a boy with FMPP whose growth pattern and pubertal development was studied longitudinally without treatment. Methods: Long-term prospective follow-up without treatment of a 6.2-year-old boy with FMPP having inherited a mutation of the LH receptor gene (A568V) from his father. Results: The pubertal growth spurt was of unusual maximal amplitude (growth rate 12.4 cm/year at the age of 5–6 years) and of extraordinary duration lasting for 5.2 years from age 3.8 to 9.0 years. No deterioration of height potential was observed. Height (174 cm) was within target height range (171.5–188.5 cm) at age 13 years. No central precocious puberty occurred. Conclusion: FMPP is an experiment of nature demonstrating that the amplitude and duration of the pubertal growth spurt are much more variable than previously described. Furthermore, this case emphasizes that the indication for treatment is highly dependent on intrafamilial and individual factors.
Characterization of Glucose Uptake by Cultured Rat Podocytes
Authors: Lewko Barbara , Bryl Ewa , Witkowski Jacek M. , Latawiec Elżbieta , Gołos Magdalena , Endlich Nicole , Hähnel Brunhilde , Koksch Claudia , Angielski Stefan , Kriz Wilhelm , Stepinski Jan
Published: September 2004

The nonmetabolizable glucose analogue [3H]-2-deoxy-D-glucose (3H-2DG) was used to study glucose transport in cultured rat podocytes. Intracellular accumulation of 3H-2DG was linear up to 20 min and was inhibited by cytochalasin B (80% inhibition) and by phlorizin (20% inhibition). Pretreatment with insulin stimulated the 3H-2DG uptake 1.5-fold. A Hill analysis of the rate of glucose transport yielded a Vmax value of approximately 10 mM and S0.5 of 7.8 mM. The value h = 1.0 for a Hill coefficient confirmed that glucose uptake exhibited a Michaelis-Menten kinetics. Transporters GLUT2 and GLUT4 were expressed in over 90% podocytes. Of the GLUT2- and GLUT4-expressing cells, approximately one-fourth expressed the membrane-bound fraction. We conclude that cultured rat podocytes possess a differentiated glucose transport system consisting chiefly of facilitative GLUT2 and GLUT4 transporters. It seems likely that a sodium-dependent glucose cotransporter may also be present in these cells.
Effects of Thyroid Hormone and Hypoxia on 2,3-Bisphosphoglycerate, Bisphosphoglycerate Synthase and Phosphoglycerate Mutase in Rabbit Erythroblasts and Reticulocytes in vivo
Authors: González-Cinca Nuria , Pérez de la Ossa Pablo , Carreras José , Climent Fernando
Published: September 2004

Objectives: The effects of triiodothyronine (T3) and hypoxia on 2,3-bisphosphoglycerate (2,3-BPG) studied in vitro are unclear. To clarify these effects we selected a more physiologic approach: the in vivo study in rabbits. We also present the changes produced by T3 and hypoxia on phosphoglycerate mutase (PGAM), which requires 2,3-BPG as a cofactor, and 2,3-BPG synthase (BPGS), the enzyme responsible for 2,3-BPG synthesis in erythroblasts and reticulocytes. Methods: Hyperthyroidism was induced by daily T3 injection (250 µg/kg), hypoxia by a mixture of 90% nitrogen and 10% oxygen and hypothyroidism by propylthiouracil (PTU) added to drinking water. Results: Both T3 administration and hypoxic conditions increased 2,3-BPG levels and BPGS mRNA levels and activity in erythroblasts but not in reticulocytes. Unlike BPGS, both PGAM mRNA levels and activity were increased in erythroblasts and reticulocytes under hyperthyrodism and hypoxia. The antihormone PTU produced opposite effects to T3. Conclusion: The results presented here suggest that both hyperthyroidism and hypoxia modulate in vivo red cell 2,3-BPG content by changes in the expression of BPGS. Similarly, the changes in PGAM activity are also explained by changes in its expression.
Calcitonin-Secreting Tumor of the Pancreas
Authors: Mullerpatan Prashant M. , Joshi Shashank R. , Shah Rajiv C. , Tampi Chandralekha S. , Doctor Vatsala M. , Jagannath Palepu , Modlin Irvin M.
Published: September 2004

Pancreatic endocrine tumors (PETs) are unusual tumors arising from cells belonging generically to the amine precursor uptake and decarboxylation systems. We present a case of a calcitonin-secreting PET in a 56-year-old female who presented with watery diarrhea, dehydration and hypokalemia. Investigation revealed hypercalcemia, hyperphosphatemia, hypercalcitonemia and a well-defined mass in the head of the pancreas on CT scan. Following a pancreaticoduodenectomy her serum calcitonin levels returned to normal and diarrhea disappeared. The identification of this particularly rare presentation of a calcitonin-secreting PET provides the opportunity to examine this pathological entity within the context of the very few previously reported instances of this disease.
Is There Any Mediterranean Diet Not Affecting Bilitec Assessment of Bile Reflux?
Authors: Zacharioudakis George , Chrysos Emmanuel , Athanasakis Elias , Tsiaoussis John , Karmoiris Konstandinos , Xynos Evaghelos
Published: September 2004

Background: Colored food substances may interfere with Bilitec system that uses bilirubin as a marker for the detection of duodeno-gastro-esophageal reflux, causing false positive results. Therefore, diets have been suggested for consumption during Bilitec studies that contain minimal amounts of pigments. Aim: To enrich the list of suitable foods for Bilitec measurements with dishes common in Mediterranean diets, and improve subject’s compliance. Methods: Ninety substances were in vivo tested for ‘bilirubin absorbance’. ‘Dry’ substances were blended after being diluted in water, while ‘floppy’ substances and cooked foods were blended undiluted. Blended mixtures and ‘liquids’ were tested for bilirubin without further dilution and after being mixed with hydrochloric acid. The procedure was repeated to assess reproducibility of the measurements. Results: Measurements are highly reproducible. Thirty five foods exhibited ‘bilirubin absorbance’ values safely below the threshold, and are considered to be suitable for Bilitec studies. On the contrary some vegetables and fruits, legumes, tomato sauce preparations, red wine, coffee, tea and jams showed high absorbance values, and are not recommended. Conclusion: Menus containing part of the variety of Mediterranean food preparations are safely recommended for consumption during Bilitec studies, enriching food lists available at present.
ErbB2 without ErbB3 Expression in Metaplastic Columnar Epithelium of Barrett’s Esophagus
Authors: Nishigaki Hitoshi , Wada Ken , Tatsuguchi Atsushi , Sueoka Nobuo , Futagami Seiji , Gudis Katya , Miyake Kazumasa , Tsukui Taku , Sakamoto Choitsu
Published: September 2004

Background/Aims: ErbB2 expression in esophageal adenocarcinoma has been shown to correlate with its clinicopathological features. However, expression levels for EGF receptor, erbB2 and erbB3 in specialized columnar epithelium (SCE) of Barrett’s esophagus have yet to be determined. To investigate the relationship between EGF family receptors and Barrett’s esophagus, we examined expression levels for EGF receptor, erbB2 and erbB3 in SCE of Barrett’s esophagus. Methods: 10 consecutive patients with short- and long-segment Barrett’s esophagus, and 10 control subjects without organic esophago-gastric diseases were enrolled. Biopsy samples of Barrett’s mucosa stained or not stained with methylene blue applied endoscopically were used for histological evaluation and Western blot analysis of EGF receptor, erbB2 and erbB3 proteins. Results: Mean length of Barrett’s esophagus was 2.6 cm (range 1–8 cm) and all tissue samples from methylene blue stained Barrett’s mucosa consisted of non-dysplastic SCE. In the Barrett’s group, Western blot analysis showed that EGF receptor and erbB2 were equally and strongly expressed in SCE and squamous epithelium; in contrast, erbB3 expression in SCE was considerably weaker. In control subjects, all proteins showed strong expression for all samples. Immunohistochemical analysis of SCE in Barrett’s esophagus showed positive EGF receptor and erbB2 expression, and no erbB3 expression. Conclusions: ErbB2 is strongly expressed in both non-dysplastic SCE and squamous epithelium, whereas erbB3 expression is essentially limited to the squamous epithelium.
The Efficacy of Levonorgestrel-Releasing Intrauterine Device in Selected Cases of Myoma-Related Menorrhagia: A Prospective Controlled Trial
Authors: Soysal Seyide , Soysal Mehmet E.
Published: September 2004

Background/Aims: To determine the efficacy of levonorgestrel-releasing intrauterine device (LNG-IUD) insertion in menorrhagic patients who have at least one type II myoma according to the European Society of Hysteroscopy. The primary outcome measures were menstrual blood flow reduction and increase in hemoglobin values. The secondary outcome measures were hysterectomy rates and patient satisfaction. Methods: In menorrhagic women (documented by a validated pad scoring system) with a myomatous uterus <380 ml at ultrasonography, LNG-IUD was inserted after the diagnostic triage. Patients were evaluated at 3, 6 and 12 months after the insertion. The primary outcome measures were compared to those of a matched group of historical controls that underwent thermal balloon ablation (TBA). Results: Following LNG-IUD insertion, statistically significant decreases in menstrual blood flow and increases in hemoglobin values were noted. LNG-IUD insertion was found to be as effective as historical controls of TBA applications. Conclusion: This prospective controlled trial demonstrates the effectiveness of LNG-IUD in this setting and equivalent results are obtained as compared to TBA.
Differential Diagnosis of Smooth Muscle Tumors Utilizing p53, pTEN and Ki-67 Expression with Estrogen and Progesterone Receptors
Authors: Gökaslan Hüsnü , Türkeri Levent , Kavak Zehra Neşe , Eren Funda , Şişmanoğlu Alper , İlvan Şennur , Durmuşoğlu Fatih
Published: September 2004

Background/Aim: To investigate the expression and value for diagnosis of the genes, p53 and pTEN, the protein, Ki-67, and the receptors, estrogen and progesterone, in differentiating smooth muscle tumors of the uterus. Material and Method: Seventeen samples of leiomyosarcoma, 2 smooth muscle tumors with uncertain malignant potential (STUMP), 9 atypical myomas and 15 leiomyomas were stained immunohistochemically. The χ2 test was used for the statistical analysis of the data. Results: The malignant side of the spectrum was strongly stained for Ki-67 and p53 while uniformly decreasing toward the benign tumors. The results were found to be statistically significant (p < 0.0001). The staining for progesterone receptor was also statistically significant, but the tumors that were considered benign, such as leiomyoma and atypical myoma, were the ones strongly stained (p = 0.005). The expression of estrogen receptor was significant in these tumors, but the p value was very close to the cut-off value (p = 0.07). As the degree of differentiation of the tumor increased, the trend showed stronger staining for estrogen receptor. However, no difference was detected in the staining properties of the tumors for pTEN (p = 0.2457). Conclusion: The expression of Ki-67, p53 and progesterone receptors is promising in immunodifferentiation of smooth muscle tumors of the uterus with malignant potential.
Eosinophilic Esophagitis: Red on Microscopy, White on Endoscopy
Authors: Straumann Alex , Spichtin Hans-Peter , Bucher Kathleen A. , Heer Pius , Simon Hans-Uwe
Published: September 2004

Background/Aims: The presenting symptom of eosinophilic esophagitis, a chronic TH2-type inflammatory disease, is uniform dysphagia attacks. Histology reveals a dense mucosal infiltration with eosinophils. Unfortunately, endoscopic findings are often unremarkable or misleading. This study characterizes the endoscopic manifestations of eosinophilic esophagitis and analyzes the nature and clinical features of the frequently observed white alterations. Methods: Thirty adult patients (22 males, 8 females; mean age 40.6 years) with previously confirmed EE prospectively underwent a structured interview, physical examination, laboratory tests and upper endoscopy with histomorphometric examination of the esophageal mucosa. Results: On endoscopy, all patients showed mucosal abnormalities in the esophagus. Findings included an unspectacular loss of vascular pattern (93.3%) and white exudates (53.3%). Biopsies demonstrated significantly increased eosinophilia in the white exudates (108.4 vs. 14.0 cells/hpf). A significant correlation was found between white exudates and dysphagia frequency (<1 attack/week = 20%; >1 attack/ week = 70%). Conclusion: Eosinophilic esophagitis evokes at least 12 different signs resulting in an individually unique endoscopic pattern, but no disease-specific picture. White exudates correspond to foci of dense eosinophilic infiltration reflecting inflammatory activity and are associated with significantly more frequent dysphagia attacks. Both the lack of a typical endoscopic picture as well as the heterogeneity of the eosinophilic infiltration impede diagnosis.
Uremic Toxins Adsorbed by AST-120 Promote Tubular Hypertrophy and Interstitial Fibrosis in Nephrectomized Rats
Authors: Okada Kazuyoshi , Matsumoto Koichi , Takahashi Susumu
Published: September 2004

Background: Uremic toxins have been shown to promote glomerular hypertrophy. The present study was performed to elucidate the relation between uremic toxins and tubulointerstitial changes. Methods: Sixty male Sprague-Dawley rats underwent 2/3 nephrectomy (Nx; n = 30) and 4/5 Nx (n = 30). Experiments were initiated 2 weeks after surgery, and were performed over an 8-week period. Half of each group (Nx-A) was administered 1 g/day of an oral carbonaceous adsorbent, AST-120, with pair-feeding, and the other half (Nx-C) served as controls. All rats were sacrificed at week 8 after a clearance study. Results: The shortest diameter of proximal tubules (PTD) and interstitial fibrosis area (IFA) at week 8 in 2/3 Nx-A rats was significantly decreased compared to that in 2/3 Nx-C rats (similar body weights, systolic blood pressures, glomerular filtration rates, and urinary protein excretion levels). The values of PTD and IFA, glomerular filtration rate and urinary protein excretion level at week 8 in 4/5 Nx-A rats were significantly decreased compared to those in 4/5 Nx-C rats (similar body weights and systolic blood pressures). Conclusion: Administration of AST-120 minimized the appearance of proximal tubular hypertrophy and interstitial fibrosis, and subsequently prevented the occurrence of proteinuria and decreased renal function. The present study indicates that uremic toxins adsorbed by AST-120 promote tubular hypertrophy and interstitial fibrosis in nephrectomized rats.
Rivastigmine as a Modulator of the Neuronal Glutamate Transporter rEAAC1 mRNA Expression
Authors: Andin Josefine , Enz Albert , Gentsch Conrad , Marcusson Jan
Published: September 2004

Alzheimer’s disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.
Motivational Symptoms of Depression Mask Preclinical Alzheimer’s Disease in Elderly Subjects
Authors: Bartolini Marco , Coccia Michela , Luzzi Simona , Provinciali Leandro , Ceravolo M. Gabriella
Published: September 2004

Background: Althoughthe relationship between depressive disorders and Alzheimer’s disease (AD) is debated, there is evidence that depression may be an early symptom of dementia. Objective: To evaluate depression features prospectively in elderly subjects with a view to identifying a subgroup affected by preclinical AD. Methods: We performed a cohort study on cognitive performances with a 12-month follow-up in out-patients referred to the local Neuropsychology Clinic complaining of memory problems. Two hundred and twenty-two consecutive non-demented subjects were studied using a neuropsychological battery and the Beck Depression Inventory (BDI) and assessed again 1 year later for the possible onset of cognitive impairment. Multivariate analysis was performed to detect independent predictors of dementia development among age, education, neuropsychological test scores and BDI scores and subscores. BDI subscores were obtained by dividing items into three domains corresponding to mood-related, somatic and motivation-related symptoms. Results: At the time of the first evaluation, 124 of the 222 subjects were depressed according to DSM-III-R criteria. At 1 year, 31 of the 124 depressed subjects and 2 non-depressed ones had AD according to NINCDS-ADRDA criteria. Stepwise logistic regression analysis indicated that the subjects who went on to develop dementia had significantly higher total BDI scores and motivational BDI subscores. Among depressed subjects, the probability of being diagnosed with dementia during follow-up was significantly associated with a motivational BDI subscore ≧7 (odds ratio: 3,885, 95% Cl 154–97,902). Comment: Close neuropsychological follow-up of depressed elderly subjects complaining of memory failure and showing apathy is recommended to detect the early stage of AD.
Perception of Emotion on Faces in Frontotemporal Dementia and Alzheimer’s Disease: A Longitudinal Study
Authors: Lavenu I. , Pasquier F.
Published: September 2004

Frontotemporal dementia (FTD) is a neurodegenerative disease characterised by behavioural disorders that suggest abnormalities of emotional processing. In a previous study, we showed that patients with Alzheimer’s disease (AD) and with FTD were equally able to distinguish a face displaying affect from one not displaying affect. However, recognition of emotion was worse in patients with FTD than in patients with AD who did not differ significantly from controls. The aim of this study was to follow up the perception of emotions on faces in these patients. The poor perception of emotion could worsen differently in AD and in FTD, with the progression of atrophy of the amygdala, the anterior temporal cortex and the orbital frontal cortex, structures that are components of the brain’s emotional processing systems. Methods: Patients with AD or with FTD had to recognise and point out the name of one of seven basic emotions (anger, disgust, happiness, fear, sadness, surprise and contempt) on a set of 28 faces presented on slides at the first visit and 3 years later. Results: Thirty-seven patients (AD = 19, FTD = 18) performed the tests initially. The two patient groups did not differ for age, sex and duration of the disease. During the follow-up, 12 patients died, 4 patients refused to perform the tests and 8 could not be tested because of the severity of the disease. Finally, 7 patients with AD and 6 patients with FTD performed the two tests at a mean delay of 40 months. All patients with AD had worse results at follow-up on the perception of emotion despite the prescription of inhibitors of cholinesterase in all patients and of selective serotonin reuptake inhibitors (SSRIs) in 4 patients. As a whole, patients with FTD had better results in the second than in the first assessment (however, 3 of them had worse results) independently of the prescription of trazodone (n = 2), other SSRIs (n = 2), or the absence of treatment (n = 2), and of possible cognitive change. Conclusions: Recognition of emotion on faces in AD decreases with the progression of dementia and could be related to the progression of the degeneration of the structures implicated in emotional processing systems. Inconsistency of the results in FTD may be related to impulsiveness, lack of consistency of the patients and to heterogeneity of the progression of the lesions.
Lower Limb Compression Bandaging Is Effective in Preventing Signs and Symptoms of Seating-Induced Postural Hypotension
Authors: Gorelik Oleg , Fishlev Gregory , Almoznino-Sarafian Dorit , Alon Irena , Weissgarten Joshua , Shteinshnaider Miriam , Chachashvily Shulamit , Modai David , Cohen Natan
Published: September 2004

Background and Aims: Data concerning postural hypotension (PH) induced by transition from supine to sitting position are scarce and measures for its prevention have not been investigated. Our objective was to assess the preventive role of lower limb compression bandaging on PH and associated manifestations in older inpatients when seated from lying position. Methods: In a randomized crossover study, 61 patients aged >65 years were enrolled. Following bed rest lasting >36 h, each patient was seated and studied for 2 consecutive days, unbandaged or bandaged. PH was defined as a fall of ≧20 mm Hg and/or ≧10 mm Hg in systolic/diastolic blood pressure, respectively. Compression bandages were applied along both legs before seating; the pressure was approximately 30 mm Hg. Blood pressure, heart rate, O2 saturation, dizziness and palpitations were recorded prior to and 1, 3, and 5 min following seating. Results: Prevalence of PH was identical in the unbandaged versus bandaged state (55.7%). However, dizziness, palpitations, accelerated heart rate and decreased O2 saturation over 5 min were more prevalent in the unbandaged versus bandaged state (p < 0.01, <0.001, <0.05, <0.001, respectively). In the unbandaged state, presence versus absence of PH was associated with significantly greater incidence of palpitations, tachycardia and decline of O2 saturation over time (p < 0.04, <0.03, <0.03, respectively). In the bandaged state, O2 saturation over 5 min tended to rise irrespective of PH, but mean values were higher in patients without PH (p < 0.02). Conclusions: Lower limb compression bandaging does not reduce the incidence of PH. However, associated manifestations are largely prevented.
Glycoprotein IIb/IIIa Inhibitor-Associated Thrombocytopenia: Clinical Predictors and Effect on Outcome
Authors: George Benjamin J. , Eckart Robert E. , Shry Eric A. , Simpson Daniel E.
Published: September 2004

Glycoprotein IIb/IIIa inhibitors are used as an adjunct to antiplatelet therapy in percutaneous coronary intervention to reduce postprocedural enzyme elevations. Previous studies have shown a risk for thrombocytopenia that is associated with these agents. We sought to evaluate the incidence and outcomes of glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia in an unselected series of patients undergoing percutaneous coronary intervention. We reviewed 984 interventions performed on 908 subjects over a specific time period. Glycoprotein IIb/IIIa inhibitors were used in 58.8% of cases. Their use increased from 38 to 82% during the study period (p < 0.0001). The incidence of glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia was 5.4%. The occurrence of thrombocytopenia was not associated with higher age, gender or ethnicity. The preprocedural platelet count was not associated with induced thrombocytopenia (237 ± 76 vs. 209 ± 68 × 103, p > 0.05). The occurrence of thrombocytopenia was not associated with increased in-hospital mortality, 1-year mortality, myocardial infarction or revascularization, but was associated with a hospital stay twice as long as in those patients without thrombocytopenia (5.6 ± 11.3 vs. 2.1 ± 2.2 days, p < 0.001). Of the 5.4% of patients who developed thrombocytopenia, only 2 patients (7.1%) required platelet or blood cell transfusion.
Diurnal Variation of Soluble E- and P-Selectin, and Intercellular Adhesion Molecule-1 in Patients with and without Coronary Artery Disease
Authors: Osmancik Pavel , Kvasnicka Jan , Widimsky Petr , Tarnok Attila
Published: September 2004

Background: The more frequent onset of acute coronary syndromes (ACS) in the morning has been known for a long time. Diurnal changes of fibrinolysis such as lower activity of tissue plasminogen activator and higher activity of plasminogen activator inhibitor-1 (PAI-1) in the morning has been demonstrated previously and correspond with the manifestation of ACS. Less is known about the diurnal variation of soluble adhesion molecules as markers of endothelial or platelet activity in patients with coronary artery disease (CAD). Patients and Methods: 80 patients with a history of myocardial infarction and/or chest pain with positive exercise testing admitted for elective coronary angiography were studied. 10 had normal findings on coronary angiography (control group), 70 patients had at least one or more stenoses ≧50% of the diameter of an epicardial vessel. None of the patients suffered from acute inflammation, connective or tumor disease. Blood samples were drawn at 7:00 a.m. and at 7:00 p.m. at rest and plasma concentration of soluble P-selectin (sP-selectin), E-selectin (sE-selectin), intercellular adhesion molecule-1 (sICAM-1) and acute-phase proteins were measured by ELISA. Results: In both groups, no diurnal variation was found in sE-selectin and sICAM-1. sP-selectin levels were significantly higher in the evening (CAD group: 149.8 ± 54.5 vs. 172.2 ± 68.8 ng/ml, p < 0.001; control: 148.7 ± 75.5 vs. 187.5 ± 96.3 ng/ml, p = 0.001, Wilcoxon test). Conclusion: We have demonstrated diurnal variation of sP-selectin in patients with CAD. We conclude that high sP-selectin values in the evening represent the shed forms of the morning membrane-bound P-selectin.
Effects and Safety of Intracoronary Thrombectomy Using Transradial Application of the PercuSurge Distal Balloon Protection System in Patients with Early or Recent Myocardial Infarction
Authors: Chen Yen-Hsun , Wu Chiung-Jen , Chang Hsueh-Wen , Fang Chih-Yuan , Chen Chien-Jen , Yu Teng-Hung , Chen Shyh-Ming , Hung Wei-Chin , Cheng Cheng-I , Yip Hon-Kan
Published: September 2004

Background: Distal embolization and no reflow are likely during primary percutaneous coronary intervention (PCI) on the large infarct-related artery (IRA), which mostly contains high-burden thrombus formation (HBTF) and plaque burden. Mechanical devices to prevent distal atheroembolism may be of importance for preserving reperfusion and microvascular integrity in IRA. Methods and Results: Between May 2002 and December 2002, transradial application (TRA) of the PercuSurge GuardWire™ device with 7-french arterial sheath was performed in 39 consecutive patients who experienced early (>12 h and ≤7 days) or recent (>7 days and <14 days) myocardial infarction (MI) associated with large IRA (vessel size ≧3.5 mm with HBTF; group 1). Between January 2001 and April 2002, 64 consecutive patients who had early or recent MI associated with HBTF in IRA of a vessel size ≧3.5 mm received TRA of PCI with adjunctive tirofiban therapy but without using the adjunctive PercuSurge GuardWire device (group 2). The angiographic and clinical outcomes of both groups were compared in a chronologically consecutive manner. The procedural success rate and post-PCI myocardial blush grades were significantly higher in group 1 than in group 2 patients (all p values <0.05), whereas a combined incidence of vascular and bleeding complications and 30-day major adverse cardiac events (defined as death, reinfarction and repeated PCI of IRA) were significantly higher in group 2 than in group 1 patients (all p values <0.05). Conclusions: Our data suggested that TRA using the PercuSurge GuardWire device during PCI for patients with early or recent MI and HBTF in IRA was safe and feasible. This mechanical device provided more additional benefit to patients in this clinical setting than a combination of conventional PCI and tirofiban therapy.
Clinical Association between Renal Insufficiency and Positive Troponin I in Patients with Acute Coronary Syndrome
Authors: Al Badr Wisam , Mukherjee Debabrata , Kline-Rogers Eva , Mani Obli , Hussain Sabiha , Mehta Rajendra , Cooper Jeanna V. , Eagle Kim A.
Published: September 2004

Background: Whether renal insufficiency (RI) influences troponin levels in patients with acute coronary syndromes (ACS) is controversial. We attempted to determine whether there is an association between RI and troponin I (TnI) elevation in patients presenting with ACS. Methods: We studied 764 consecutive patients with ACS admitted to our institution from January 1999 to June 2000. Patients were identified prospectively and data were collected through chart review of all cases with an admission diagnosis of ACS. In order to assess the relationship of TnI and RI, we calculated the creatinine clearance (Cr-Cl) for all patients. We conducted an analysis of variance comparing TnI in quintiles of patients with lowest to highest Cr-Cl. Results: Among 764 patients, 173 patients had a discharge diagnosis of ST elevation myocardial infarction and 591 had non-ST elevation myocardial infarction. There was no correlation between peak TnI levels and renal function as measured by Cr-Cl in the entire cohort with ACS and in the subgroups with ST elevation myocardial infarction and non ST elevation myocardial infarction. Conclusions: This large cohort study demonstrates that there appears to be no association between RI and positive TnI in patients with ACS.
Angiotensin II Receptor Modulation of Renal Vascular Resistance and Neurotransmission in Young and Adult Spontaneously Hypertensive Rats
Authors: Stegbauer Johannes , Vonend Oliver , Oberhauser Vitus , Sellin Lorenz , Rump Lars Christian
Published: September 2004

Background/Aims: Angiotensin (Ang) II modulates vascular resistance and sympathetic neurotransmission through Ang II type 1 (AT1) receptors. Recent studies reported an involvement of AT2 receptors. We investigated whether AT2 receptors participate in modulation of vascular resistance and sympathetic neurotransmission in spontaneously hypertensive rats (SHR). Methods: Kidneys of 6- and 16-week-old normotensive (WKY) and SHR were isolated and perfused. Results: Noradrenaline release induced by renal nerve stimulation (RNS) was increased in SHR (WKY: 1,837 ± 128, SHR: 2,310 ± 192 pg/g). Ang I- and II-induced pressor responses and enhancement of noradrenaline release were greater in SHR than in WKY. Pressor responses to Ang I and II were greater in adult compared with young SHR. The AT1 receptor antagonist EXP3174 (0.1 µM) blocked Ang I- and II-induced renal vasoconstriction and noradrenaline release to RNS in both strains. In contrast, the selective AT2 receptor antagonist PD 123319 (1 µM) had no influence in young and adult WKY and SHR. Conclusion: Ang I and II had a greater impact on renal vascular resistance and neurotransmission in SHR, which was more pronounced in adult SHR. All effects are mediated by the AT1 receptor and no modulatory influence of the AT2 receptor could be found.
Epidemic West Nile Virus Encephalitis in Tunisia
Authors: Feki Imed , Marrakchi Chakib , Ben Hmida Mohamed , Belahsen Faozi , Ben Jemaa Mounir , Maaloul Imed , Kanoun Fakher , Ben Hamed Sonia , Mhiri Chokri
Published: September 2004

West Nile fever (WNF) is a mosquito-borne flavivirus infection. It is epidemic in Africa and Asia. In autumn 1997, a WNF epidemic occurred in the Sfax area (southeastern Tunisia). Fifty-seven patients were hospitalized with aseptic meningitis and/or encephalitis. Search for specific anti-West Nile virus (WNV) antibodies in serum and cerebrospinal fluid (CSF) was performed using an ELISA test. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the WNV genome in CSF and brain specimens. Recent central nervous system (CNS) infection by WNV was confirmed in 30 patients, probable infection in 17 and it was excluded in 10. In the confirmed subgroup, patients with encephalitis were older than those with meningitis. CSF showed pleocytosis, high protein (47%) and normal glucose levels. Brain computed tomography-scan (CT-scan) and magnetic resonance imaging (MRI) were normal. RT-PCR disclosed WNV genome in the CSF in two cases and in a brain specimen in one. Three patients died rapidly, the remaining cases had favorable prognosis. Autopsy was performed in two cases and showed nonspecific lesions of encephalitis. No viral inclusions were seen with light microscopy. Seropositivity rate in patients’ proxies for WNV was 23.4%. Prognosis of CNS involvement during WNF seemed to be poor in older patients. This is the first WNV encephalitis epidemic report in the Sfax area of Tunisia.
Epidemiological Study of Creutzfeldt-Jakob Disease Death Certificates in Canada, 1979–2001
Authors: ElSaadany Susie , Semenciw Robert , Ricketts Maura , Mao Yang , Giulivi Antonio
Published: September 2004

Introduction: A descriptive epidemiological analysis to update trends of Creutzfeldt-Jakob disease (CJD) deaths, from 1979–2001, was undertaken. Methods: Cases with CJD as underlying cause were extracted. Age-adjusted death rates by age, sex, and province were calculated. Information on birthplace, autopsy indications and type of work were examined for death certificates from 1979 to 1997. Results: 462 cases were identified between 1979 and 1997. The average annual age-standardized mortality rate was 0.93 deaths per million persons during this period and 1.03 for 1998–2001. Persons 60 years or older demonstrated the highest average annual mortality rate. Rates were slightly higher among males and increased with age. Persons born in Canada accounted for 72% of deaths. Cause of death was verified by autopsy for 9.1% of patients while 21% of deaths indicated that additional information relating to underlying cause was expected. The service industry occupation represented the largest mortality (Quebec does not capture these data). Conclusions: Canadian rates are consistent with those of the United States and slightly higher than those of certain European countries. Approximately 44% of CJD cases had an autopsy record, though many were incomplete. We are unable to determine a relation with occupation. We recommend annual analysis of CJD death registrations for updated surveillance of trends, as mortality data are an efficient tool for monitoring incidence.
Seasonal Variation in Hospitalization and Case Fatality of Subarachnoid Hemorrhage – A Nationwide Danish Study on 9,367 Patients
Authors: Fischer Thomas , Johnsen Søren P. , Pedersen Lars , Gaist David , Sørensen Henrik T. , Rothman Kenneth J.
Published: September 2004

Seasonal variation in the occurrence of cerebrovascular disease has been reported, but data about subarachnoid hemorrhage (SAH) are few and inconclusive. We conducted a nationwide population-based study in Denmark to examine any seasonal pattern of hospitalization and case fatality of SAH. We identified 9,367 patients with SAH and found a modest indication of overall seasonal variation for the risk of hospitalization with this diagnosis. The seasonal pattern, with the highest incidence in January and the nadir in July, was mostly apparent for subjects aged >65 years (peak-to-trough ratio = 1.18; 95% CI 1.04–1.32). There was little difference by sex. The overall 30-day case fatality rate was 38% and showed less seasonal variation. We found evidence of weak seasonal variation in hospitalization for SAH and almost no seasonal variation in a 30-day case fatality rate after SAH.