bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Detection of Pancreatic Cancer following the Diagnosis of Chronic Pancreatitis
Authors: Talamini G. , Bassi C. , Falconi M. , Sartori N. , Pasetto M. , Salvia R. , DiFrancesco V. , Frulloni L. , Vaona B. , Bovo P. , Pederzoli P. , Cavallini G.
Published: April 2003

Aim: To assess whether patients with misdiagnoses of chronic pancreatitis (CP), followed at an early stage by a diagnosis of pancreatic cancer (PCr), present different epidemiological characteristics from patients suffering either from CP alone or from CP with late degeneration to PCr. Methods: We arbitrarily subdivided our patient series into three groups: (1) 12 CP who developed PCr within 4 years after onset of symptoms; (2) 12 CP developing PCr after the 4th year, and (3) 701 CP with no subsequent development of PCr. The variables studied were age, sex, drinking and smoking habits, tumor localization, and presence of intraductal calcifications and diabetes mellitus at the time of diagnosis of CP. Results: There were no significant differences between CP and ‘late’ PCr in any of the study variables considered. As compared with the CP group, the ‘early’ PCr cases were older (58.7 vs. 40.7 years; p < 0.0001), with a lower proportion of males (58 vs. 88%; p < 0.01), smaller proportions of both smokers (42 vs. 88%; p < 0.0001) and subjects drinking more than 40 g of alcohol/day (42 vs. 86%; p < 0.0001), and a greater incidence of non-insulin-dependent diabetics at the time of diagnosis of CP (25 vs. 3.7%; p < 0.012). As compared with the ‘late’ PCr group, the malignancies in the ‘early’ PCr cases were more often located in the head of the pancreas (100 vs. 50%; p < 0.01). Multivariate logistic regression analysis selected age over 50 (odds ratio OR 13.5, 95% confidence interval CI 2.79–65.5; p < 0.001), smoking habits (OR 0.14, 95% CI 0.04–0.49; p < 0.002), and non-insulin-dependent diabetes (OR 5.91, 95% CI 1.20–29.1; p < 0.028) as variables identifying subjects with ‘early’ PCr. Conclusions: A high suspicion of a pancreatic tumor is necessary when CP is diagnosed in a patient with atypical epidemiological characteristics for this condition, possibly female, aged over 50, who is not a smoker or drinker, and suffers from non-insulin-dependent diabetes.
In Search of Immunogenic Helicobacter pylori Proteins by Screening of Expression Library
Authors: Łazowska Izabella , Trzeciak Lech , Godlewska Renata , Hennig Ewa , Jagusztyn-Krynicka Katarzyna , Popowski Janusz , Reguła Jarosław , Ostrowski Jerzy
Published: April 2003

Background: Prevention of Helicobacter pylori infection may help to control related gastritis, peptic ulcer and cancer. Of the possible preventive measures, immunization was successfully employed in various animal studies. However, no immunization protocol has been accepted for humans. A better characterization of the immune response against the pathogen may be required before a human vaccine is developed. Aim: To identify bacterial proteins which induce an immune response in infected humans or H. pylori-immunized rabbits. Methods: An expression library of H. pylori genes was screened with sera from infected humans and from immunized rabbits. Positive clones were partially sequenced and identified on the basis of a homology search of a H. pylori genome database. Encoded proteins were expressed directly from positive clones and analyzed by SDS-PAGE/Western blot techniques. Results: 114 positive clones were isolated: 79 by screening with human sera and 35 by screening with rabbit sera. Western blot analysis demonstrated that selected clones encoded one or more strongly immunoreactive proteins. 64 clones selected with human sera had no counterparts among clones from screening with rabbit serum. 13 of these clones encoded a total of 21 unknown H. pylori proteins. 17 clones selected with rabbit sera were not immunostained with human sera. They represent 2 various regions of the H. pylori genome which encoded 3 bacterial proteins of unknown function. Conclusions: Screening of H. pylori expression library identified immunogenic proteins – potential vaccine antigens.
Retreatment with Interferon-Alpha and Ribavirin in Primary Interferon-Alpha Non-Responders with Chronic Hepatitis C
Authors: Teuber Gerlinde , Berg Thomas , Hoffmann Robert M. , Leifeld Ludger , Lafrenz Michael , Spengler Ulrich , Pape Gerd R. , Hopf Uwe , Zeuzem Stefan
Published: April 2003

Background/Aims: Combination therapy with interferon-α (IFN-α) plus ribavirin is more efficacious than IFN-α monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-α relapse. Only limited data are available in IFN-α non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-α-resistant chronic hepatitis C. Methods: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-α-2a (3 × 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-α dose of 3 × 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. Results: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-α dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). Conclusions: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-α non-responders. Higher IFN-α induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1.
Continuous Monitoring of Nitric Oxide Release Induced by Cholecystokinin from the Choledochal Sphincter in Guinea Pigs
Authors: Shima Yasuo , Mori Masanobu , Takakura Norihisa , Tanaka Noriaki , Yokoi Isao , Kabuto Hideaki , Yamazato Teruhiro
Published: April 2003

Background/Aims: Many in vitro studies in the choledochoduodenal junction of the guinea pig have shown that cholecystokinin (CCK) contracts the sphincter of Oddi (SO). This study, using the choledochal sphincter of the guinea pig as the SO, evaluates the hypothesis that effects of CCK on the SO were mediated by nitric oxide (NO). Methods: Spontaneous motility and effects of CCK on the choledochal sphincter were recorded using a constant-perfusion technique, and direct measurement of NO release using a specific NO sensor was performed at the same time. Results: CCK-8 decreased the phasic wave amplitude of the choledochal sphincter, and increased NO release. NG-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthase, increased the spontaneous motility and converted the CCK-induced inhibitory response into an excitatory response. L-NAME also reduced NO release and abolished the increase of NO that had been caused by CCK-8. These effects were reduced by treatment with L-arginine (L-Arg). L-Arg application enhanced NO release, and recovered the increase of NO by CCK-8. Conclusion: These studies demonstrate that CCK relaxes the choledochal sphincter and this relaxant response is mediated by NO.
In vitro Responses of Gallbladder Muscle from Patients with Acalculous Biliary Pain
Authors: Ahmed Rosina , Bird Nigel C. , Chess-Williams Russell , Thomas William E.G. , Johnson Alan G.
Published: April 2003

Background: Diagnosis and identification of patients with acalculous biliary pain, who would benefit from surgery, remains a significant clinical problem. The cholecystokinin (CCK) provocation test helps diagnosis, but lack of consistency limits its usefulness. Aim: To characterize the response of gallbladder muscle strips, from patients with acalculous biliary pain, to hormonal and muscarinic stimulation and to compare these with strips from gallstone patients and normal controls. Patients: Eleven patients with acalculous biliary pain were studied, 5 had a positive CCK test. Eight gallbladders from gallstone patients and 6 from partial hepatectomies were used for comparison. Methods: Muscle strips from the body and neck of the gallbladder were suspended in organ baths and dose-response curves were constructed for CCK-8 and carbachol. Results: In the acalculous group the strips from the body were less sensitive to carbachol than those of the neck. Conclusion: Since we found no differences in the CCK responses for the groups, it casts doubt over the effectiveness of the CCK test to diagnose acalculous biliary pain. Since carbachol sensitivity was different, it might be that a similar test using muscarinic stimulation would help in the diagnosis of this difficult group of patients.
Retractile Mesenteritis Presenting as Fever of Unknown Origin and Autoimmune Haemolytic Anaemia
Authors: Papadaki Helen A. , Kouroumalis Elias A. , Stefanaki Kalliopi , Roussomoustakaki Maria , Daskalogiannaki Maria E. , Reppa Despina , Eliopoulos George D.
Published: April 2003

Retractile mesenteritis is an extremely rare disease characterised by a non-specific inflammatory and fibrotic process of the mesenteric adipose tissue, which is usually accompanied by pain and a variety of other abdominal symptoms. We describe here the case of a patient with retractile mesenteritis presenting with prolonged high-grade fever and autoimmune haemolytic anaemia without abdominal symptoms. The patient’s illness was complicated by chylous ascites. Diagnosis was suspected by computed tomography and confirmed histologically following exploratory laparotomy. The patient was treated with prednisone and azathioprine, and he had a rapid improvement in anaemia and fever relief, but no substantial change in the mesenteric lesions. Our case adds autoimmune haemolytic anaemia to the wide spectrum of manifestations of retractile mesenteritis and implies the possible involvement of immune mechanisms in the pathogenesis of the disease.
Structure and Composition of Common Bile Duct Stones in Relation to Duodenal Diverticula, Gastric Resection, Cholecystectomy and Infection
Authors: Sandstad Olav , Osnes Terje , Skar Viggo , Urdal Petter , Osnes Magne
Published: April 2003

Background: Common bile duct stones represent a clinical problem often involving severe infection, cholangitis and cholestasis. Stasis and infection are thought to play a part in the pathogenesis of choledocholithiasis. Investigations on the etiology of common bile duct stones are, however, scarce because of the difficult access to common bile duct stones and bile. In a clinical series of common bile duct stones, we studied the gross appearance of stones extracted endoscopically from the common bile duct and measured the cholesterol and bilirubinate content in order to elucidate factors of importance to etiology. Methods: In 135 patients treated endoscopically for bile duct stones, the stones or parts of the stones were collected. Appearances of the cut surface of the stones were studied and described. Cholesterol and bilirubinate content were analyzed enzymatically and with infrared spectroscopy. The growth in bile of gas-producing bacteria previously shown to be correlated with enterobacteriacea was investigated. Results: Seventy-five percent of the stones were pigment stones, the majority with concentric pigmented layering. There was good agreement between cholesterol measurements. With a cutoff at 50% for the infrared measurements and 25% for the enzymatic assay only 3 stones were discordant between cholesterol measurements and visual inspection. Twenty-one of 23 patients with a previous Billroth-II gastric resection had pigment stones (p < 0.05). Gas-producing bacteria were significantly more prevalent in the bile from patients with layered pigment stones. Conclusion: Pigment stones with concentric layering highly suggestive of a cyclic process of crystallization were recovered from the common bile duct in 70% of the patients in our series.
Lymphocyte Subsets and Cellular Immunity in Patients with Chronic Pancreatitis
Authors: Ockenga J. , Jacobs R. , Kemper A. , Benschop R.J. , Schmidt R.E. , Manns M.P.
Published: April 2003

Background: An abnormal immune response may play a pathogenetic role in chronic pancreatitis. However, to date characterization of the systemic immunological changes in patients with chronic pancreatitis has not been undertaken. Methods: Lymphocyte phenotypes and proliferation (3H-thymidine) after stimulation with mitogens and interleukin-2 were studied in peripheral mononuclear cells from 11 patients with chronic pancreatitis (alcohol-induced n = 6; idiopathic pancreatitis n = 5). The natural killer cell activity was investigated in a 51Cr release cytotoxicity assay. In vitro cytokine release of stimulated mononuclear cells was measured. Results: Flow cytometric studies showed a significant decrease in the percentage of circulating CD8+, CD56+ and CD25+ cells in patients with chronic pancreatitis independent of the etiology. Comparing all patients with chronic pancreatitis to controls, the proliferation rate was not significantly increased, but patients with pain (n = 5) showed increased proliferation in comparison to patients without pain (n = 6). No significant difference in natural killer cytotoxicity was observed. The in vitro release of tumor necrosis factor-α and interleukin-10 by stimulated mononuclear cells was increased. Conclusions: Chronic pancreatitis is accompanied by systemic immune dysregulation. The observed changes in peripheral mononuclear cells reveal additional evidence that the cell-mediated immune response may contribute to the development of pain and tissue destruction in chronic pancreatitis.
End Expiration Is More Accurate than Mid Respiration in Measuring Lower Esophageal Sphincter Pressure
Authors: Allen Melvin L. , Denuna-Rivera Susie , DiMarino Jr. Anthony J.
Published: April 2003

Background/Aims: Two ways popularly used to measure lower esophageal sphincter pressure are the mid-respiratory and end-expiratory methods. The aim of this study was to compare the suitability of these methods in the manometric assessment of patients with endoscopically documented esophagitis. Methods: Manometry was performed on 22 consecutive patients to determine whether medical therapy or surgery was the more appropriate treatment strategy. Lower esophageal sphincter pressure was measured during a slow station pull-through. End-expiratory lower esophageal sphincter pressure was assessed by measuring the highest trough which coincided with end expiration. Mid-respiratory lower esophageal sphincter pressure was assessed by bracketing the highest pressure over ≥3 respiratory cycles and measuring the mid point. Results: Mid-respiratory lower esophageal sphincter pressure (25.6 mm Hg) was higher (p < 0.0001) than end-expiratory lower esophageal sphincter pressure (15.7 mm Hg). Nine (41%) end-expiratory lower esophageal sphincter pressures were abnormally low (i.e., <10 mm Hg), whereas three (14%) mid-respiratory lower esophageal sphincter pressures were abnormally low (i.e., <14 mm Hg; p = 0.042). Conclusion: Mid-respiratory lower esophageal sphincter pressure measurement includes respiratory artifact and does not accurately measure lower esophageal sphincter pressure. End-expiratory sphincter pressure better identifies potential surgical candidates.
Nongastrointestinal Disorders in the Irritable Bowel Syndrome
Authors: Azpiroz Fernando , Dapoigny Michel , Pace Fabio , Müller-Lissner Stefan , Coremans George , Whorwell Peter , Stockbrügger Reinhold W. , Smout André
Published: April 2003

A large proportion of irritable bowel syndrome (IBS) patients also complain of other functional disorders, such as headache, noncardiac chest pain, low back pain, and dysuria. Some of these features, particularly headache, may have a negative influence on the outcome of IBS. In a large proportion of female IBS patients, sexual intercourse triggers the symptoms, and frequently IBS symptoms exacerbate during menses. These gynecological-type symptoms often mislead the patients to the gynecological clinic, which may imply unnecessary investigations and inappropriate treatments. The diagnostic criteria of the fibromyalgia syndrome include IBS, and hence, the apparent relationship of both syndromes is difficult to analyze. On the other hand, no convincing evidence has been produced to date to sustain an association between IBS and the chronic fatigue syndrome.
Helicobacter pylori-Associated Gastric Ulcer Exhibits Enhanced Mucosal Chemokine Activity at the Ulcer Site
Authors: Shimizu Tatsuji , Kusugami Kazuo , Ina Kenji , Imada Akira , Nishio Yuji , Hosokawa Takehiko , Ohsuga Masahiro , Shimada Masaaki , Noshiro Mitsuhiro , Kaneko Hiroshi , Ando Takafumi
Published: April 2003

Background and Aim: Although mucosal α- and β-chemokines are considered to be involved in the pathogenesis of Helicobacter pylori-associated gastritis, little is known how these chemokines are related to the ulcerogenesis in peptic ulcer patients. We examined the levels of interleukin (IL)-8 and macrophage inflammatory protein-1α (MIP-1α) in organ cultures and the numbers of inflammatory cells infiltrating the lamina propria by using the mucosal tissues obtained from gastric ulcer (GU) patients with and without H. pylori infection. Methods: Levels of IL-8 and MIP-1α secreted in organ cultures were measured by an enzyme-linked immunosorbent assay. Numbers of myeloperoxidase-positive neutrophils, CD68-positive macrophages, and mononuclear cells were determined in tissue sections. Results: The mucosal tissues of both the gastric antrum and the ulcer site obtained from patients with H. pylori-positive GU showed significantly higher levels of IL-8 and MIP-1α and increased numbers of inflammatory cells compared with the corresponding mucosal tissues from those with H. pylori-negative GU or the antral mucosal tissues from H. pylori-negative controls. When the values were compared between the mucosal tissues from the gastric antrum and those from the ulcer site, the latter group of tissues showed significantly higher levels of IL-8 and MIP-1α and increased numbers of neutrophils and macrophages than the former group regardless of its healing process in patients with H. pylori-positive GU. Conclusion: Mucosal α- and β-chemokines may be important to the ulcerogenesis in H. pylori-associated GU disease.
Helicobacter pylori Infection: Protection against Barrett’s Mucosa and Neoplasia?
Authors: Vieth M. , Masoud B. , Meining A. , Stolte M.
Published: April 2003

Background: Since Helicobacter pylori (Hp) infection provokes intestinal and gastric metaplasia, the question arises whether the specialized metaplasia (Barrett’s mucosa (BM)) and dysplasia or carcinoma in Barrett’s epithelium seen in gastro-oesophageal reflux disease (GORD) might not also be correlated with Hp infection, or whether the latter offers protection against Barrett’s oesophagus and Barrett’s adenocarcinoma. Patients: Gastric and oesophageal biopsies obtained from a total of 2,201 patients were analysed retrospectively. 297 of these patients had GORD (age 53.5 ± 13.4 years; m:f ratio 2.1:1), 1,192 patients had BM (age 62.8 ± 14.6 years; m:f 2.3:1) with or without neoplasia. 1,054 of these patients were diagnosed as having BM alone, 138 patients having BM neoplasia (high-grade dysplasia or adenocarcinoma). Patients with BM and low-grade dysplasia were excluded from this study because of the uncertainty in differentiating low-grade dysplasia from regenerative epithelium. A total of 712 patients with non-ulcer dyspepsia (NUD; average age 40.0 ± 16.1 years; m:f 0.3:1) served as a control group. Results: The percentage of Hp infection did not differ between patients with GORD with (53.3%)/without BM (51.4%) and neoplasia (47.8%), but is statistically significantly lower than in patients with NUD (65.7%). Conclusion: Our analysis shows that patients with GORD and Hp infection have no increased risk for the development of BM or neoplasia in BM. Since Hp infection is significantly less frequent in GORD than in NUD patients, a protective effect of the Hp infection is a possibility worth discussing.
Characterisation of Acute Murine Dextran Sodium Sulphate Colitis: Cytokine Profile and Dose Dependency
Authors: Egger Bernhard , Bajaj-Elliott Mona , MacDonald Thomas T. , Inglin Roman , Eysselein Viktor E. , Büchler Markus W.
Published: April 2003

Background/Aims: In our experience with the acute murine dextran sodium sulphate (DSS) model of experimental colitis, we noted both interstrain and interanimal variations in daily water consumption. One might critically question whether observed differences in injuries are just a dose dependency phenomenon reflecting variations in DSS intake. To clarify this important topic, we performed a dose and concentration dependency study of DSS in Balb/c mice. We also determined Th1 and Th2 cytokine levels to compare the cytokine profile to that from inflammatory bowel disease (IBD). Methods: In four groups (14 animals each group) different concentrations of DSS (0, 2.5, 5 and 7.5%) were given for 7 days ad libitum. Mucosal injury of the entire colon was histologically assessed and graded. Cytokine levels were determined by competitive quantitative RT-PCR. Results: A linear increase in the crypt damage score was noted with increasing concentrations (0, 4.9 ± 0.7, 11.9 ± 0.5 and 18.9 ± 1.3, respectively), but the total dose of DSS intake did not correlate with mucosal damage. Progressive upregulation in the transcripts for Th1 cytokines (IL-12, IFN-γ, IL-1, TNF-α) was observed with increasing dosage of DSS. Interestingly, an increase in IL-10, but not IL-4 mRNA transcripts was also noted. Discussion: Acute DSS-induced mucosal injury is dependent on the administered DSS water concentration but not on the consumed DSS dose. The cytokine profile is a classic Th1 response and is similar to that of various inflammatory conditions in the colon. Conclusions: Minor variations in fluid consumption do not affect the severity of DSS-induced injury in mice. The acute murine DSS colitis model is useful for studying the pathophysiological aspects of colonic inflammatory diseases as IBD and for evaluating new potential therapeutic agents
A Practical Approach to theUse of Intravenous Immunoglobulin in Neurological Disease
Authors: Wills A.J. , Unsworth D.J.
Published: April 2003

Intravenous immunoglobulin is now used in a wide range of neurological conditions. However, side effects are relatively common, treatment is expensive and sustained benefit unusual without repeated administration. This article aims to provide clinicians with an overview of the potential benefits and drawbacks of intravenous immunoglobulin in neurological practice and concludes with suggested guidelines for its use in adults.
A Neurological Evaluation of Adult Phenylketonuria in Northern Ireland
Authors: McDonnell G.V. , Esmonde T.F. , Hadden D.R. , Morrow J.I.
Published: April 2003

To investigate the extent of neurological disease in adults with phenylketonuria and also their requirement for specialist medical services, we assessed 27 such patients in Northern Ireland. Most had been diagnosed early and with one exception had dietary relaxation by early adolescence. Abnormal neurological features were elicited in 21/27 cases with significant delay of visual evoked potentials and somatosensory evoked potentials occurring in 63.6 and 13.6% of cases respectively. Periventricular white matter abnormalities were observed in 5/12 patients undergoing magnetic resonance imaging, whilst phenylalanine levels were high (mean 1,226 µmol/l). These data accord with the observation that even early treated patients with phenylketonuria can have significant neurological morbidity in adulthood, although the correlation with current or recent dietary control is unclear and requires further study.
Progressive Loss of Speech: A Neuropsychological Profile of Premotor Dysfunction
Authors: Didic Mira , Ceccaldi Mathieu , Poncet Michel
Published: April 2003

Several patients with ‘progressive loss of speech output’ or ‘progressive anarthria’ of degenerative origin have been reported in the literature. We report 5 clinical cases with slowly progressive loss of speech output and initially no deficit in other cognitive domains. The early clinical features were analysed in an attempt to identify the anatomo-functional systems implied in the degenerative process. The first phase of the disorder was characterised by impaired articulation consistent with speech apraxia, telegraphic style and a difficulty to elaborate a series of orofacial or hand movements. It is argued that these symptoms result from an impairment of complex motor processing due to dysfunction of the ventral premotor system. In the second phase, a decrease in spontaneous speech and self-initiated action was combined with exaggerated dependency on external stimuli, interpreted as dysfunction of the dorsal premotor system. We suggest that the neuropsychological profile of the disorder may result from progressive degeneration of the premotor cortex.
Hypertrophy of the Inferior Olivary Nucleus in Patients with Progressive Supranuclear Palsy
Authors: Hanihara Tokiji , Amano Naoji , Takahashi Tatsuya , Itoh Yoji , Yagishita Saburo
Published: April 2003

Hypertrophic changes in the inferior olivary nuclei have been occasionally described in patients with progressive supranuclear palsy (PSP). To elucidate the incidence of olivary hypertrophy, we investigated morphologically the olives and their associated pathways in 20 autopsied cases: 11 cases of PSP, 3 cases of Machado-Joseph disease and 6 cases of dentatorubropallidoluysian atrophy (DRPLA) as control diseases that usually exhibited lesions of the cerebellofugal pathway. Olivary hypertrophy was observed in 5 of 11 PSP cases, but not in the other diseases, except for 1 case of DRPLA with an old infarct in the dentate nucleus. In the olivopetal pathway, grumose degeneration of the dentate nucleus and mild neuronal loss in the red nucleus were observed in all patients with PSP and in the control subjects. Atrophy and fibrillary gliosis of the tegmentum of the pons, including that of the bilateral central tegmental tracts, were observed in all patients with PSP, more severe in the cases with hypertrophic neurons in the olives. We speculate that a lesion that involves the central tegmental tracts may play a major role in inducing hypertrophy of the olives in patients with PSP.
Pharmacokinetic Studies with a Dual-Release Formulation of Levodopa, a Novel Principle in the Treatment of Parkinson’s Disease
Authors: Dingemanse J. , Kleinbloesem C.H. , Crevoisier Ch. , Lankhaar G. , Gasser U.E.
Published: April 2003

The objectives of the two studies reported here were the investigation of the influence of tablet breaking and food on the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after administration of a new levodopa/benserazide formulation with a biphasic drug delivery profile (Madopar® DR). Both studies had an open-label, randomised, two-way crossover design and were conducted in 12 healthy young subjects. The pharmacokinetics of levodopa and 3-OMD after one intact or two halved tablets were very similar with average Cmax and tmax 1.9 mg·l–1 and 1.2 h, respectively. Administration of the formulation after a standard breakfast did not influence the extent of levodopa absorption but increased the absorption rate. Cmax and tmax were on average 2.1 mg·l–1 and 1.3 h, respectively, in the fed condition and 1.5 mg·l–1 and 2.5 h in the fasted condition. The presence of food did not markedly affect the plateau in levodopa levels between about 1 and 3 h after intake. In conclusion, the release characteristics in healthy subjects of the new levodopa/benserazide formulation are influenced only to a minor extent by concomitant intake of food or by tablet breaking.
Isolated So-Called Apraxia of Eyelid Opening: Report of 10 Cases and a Review of the Literature
Authors: Defazio G. , Livrea P. , Lamberti P. , De Salvia R. , Laddomada G. , Giorelli M. , Ferrari E.
Published: April 2003

So-called apraxia of eyelid opening (scAEO) has been described chiefly in the context of extrapyramidal disorders. We described 10 new patients with scAEO developing in the absence of any other CNS sign and reviewed the 11 cases with isolated scAEO reported in the literature. Combining our patients and those from the literature, peak age at onset was in the 6th decade and there was a female preponderance of 2:1. The characteristic inability to initiate lid elevation was frequently associated with failure to sustain lid elevation, thus suggesting that eyelid motor control may be abnormal in isolated scAEO. Antecedent events included ocular signs and symptoms consistent with diseases of eyes or face (4 cases in our series and 2 in the literature), chronic treatment with flunarizine (1 case), and family history of dystonia (1 case). Flunarizine discontinuation led to sustained remission of the eyelid disturbance. Overall, these clues suggest the involvement of the extrapyramidal system in the pathophysiology of isolated scAEO. Familial clustering of isolated scAEO in one of our patients may be in favor of a genetic contribution. In our series, botulinum toxin administration close to the pretarsal part of the orbicularis oculi muscle significantly improved scAEO in 8/10 cases, whereas orbital/preseptal injection had no effect. We conclude that the term ‘apraxia’ may not be the correct descriptive term even when the eyelid disturbance occurs without any other CNS disease.
Brain Metabolic Profiles Obtained by Proton MRS in Two Forms of Mitochondriopathies: Leber’s Hereditary Optic Neuropathy and Chronic Progressive External Ophthalmoplegia
Authors: Salvan Anne-Marie , Vion-Dury Jean , Confort-Gouny Sylviane , Sangla Iban , Pouget Jean . , Cozzone Patrick J.
Published: April 2003

The status of brain metabolism has been evaluated using monovoxel short echo time (20 ms) 1H magnetic resonance spectroscopy in 6 patients with two forms of mitochondrial disorders without clinical cerebral involvement: 2 patients with Leber’s hereditary optic neuropathy (LHON) and 4 patients with chronic progressive external ophthalmoplegia (CPEO). Patients with LHON displayed normal spectra. In all patients with CPEO, the brain metabolic profiles were abnormal, with no single uniform pattern. No typical cerebral metabolic profile was found even when these disorders were classified either by syndrome or by biochemical defect. No lactate signal was detected. The metabolic alterations observed in CPEO patients contrasted with the absence of clinical signs of encephalopathy. The absence of a typical metabolic profile reflects the large variability in the clinical expression of biochemical defects in mitochondriopathies, and the lack of convergence between genetic deletions, biochemical anomalies and clinical syndromes.
Safety, Pharmacokinetics and Biological Activity of Enlimomab (Anti-ICAM-1 Antibody): An Open-Label, Dose Escalation Study in Patients Hospitalized for Acute Stroke
Authors: Schneider D. , Berrouschot J. , Brandt T. , Hacke W. , Ferbert A. , Norris S.H. , Polmar S.H. , Schäfer E.
Published: April 2003

Background and Purpose: To obtain information on the safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody) in stroke patients. Methods: An open, uncontrolled, dose titration study was conducted in 32 patients hospitalized for stroke. Patients received one of four fixed dose regimens of enlimomab. A loading dose of enlimomab administered within 24 h of the onset of stroke symptoms was followed by four daily maintenance doses; total doses ranged from 140 to 480 mg. Results: The pharmacokinetic target levels (enlimomab serum levels of ≥10 µg/ml) were consistently achieved in all patients receiving dose regimens III and IV. Non-serious adverse events thought to be causally related to enlimomab administration included headache, vomiting and extrasystoles. Serious events occurred in 14 patients, including pneumonia, sepsis, cardiac failure and cardiac arrest. The only serious adverse event considered to be related to enlimomab administration was an anaphylactoid reaction, in a patient who received an unfiltered loading dose of antibody; the patient recovered. The overall mortality in the study was 15.6% and the 30-day mortality was 12.5%. There was no increase in the frequency of adverse events with increasing doses of enlimomab. Conclusions: Doses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 ± 10 days. A loading dose of 160 mg followed by four daily maintenance doses of 40 mg appears to be suitable for further study.
Contribution of the Supplementary Motor Area and Anterior Cingulate Gyrus to Pathological Grasping Phenomena
Authors: Hashimoto Ritsuo , Tanaka Yasufumi
Published: April 2003

To investigate the relationship between the site of brain damage and characteristics of the pathological grasping phenomena, we examined different varieties of the reaction in a consecutive series of 28 patients with unilateral hemispheric damage due to stroke. Patients with a lesion relatively confined to the supplementary motor area (n = 4) constantly exhibited a grasp reflex, mainly in the hand contralateral to the lesion, but they never showed a groping reaction. By contrast, patients with damage primarily involving the anterior cingulate gyrus (n = 3) developed the groping reaction in the hand contralateral to the lesion, but they had only a very mild grasp reflex in that hand. Patients with damage involving both the supplementary motor area and the anterior cingulate gyrus (n = 12) showed the grasp reflex and groping reaction mainly in the hand contralateral to the lesion. Patients with damage to the medial parietal lobe (n = 2), those with damage to the lateral convexity of the hemisphere (n = 6), and a patient with damage confined to the corpus callosum did not exhibit such grasping phenomena. From these observations, we conclude that the grasp reflex is closely related to a lesion of the supplementary motor area, whereas the groping reaction is bound to a lesion of the anterior cingulate gyrus.
CAG Repeat Expansion in an Italian Family with Spinocerebellar Ataxia Type 2 (SCA2): A Clinical and Genetic Study
Authors: Malandrini Alessandro , Galli Lucia , Villanova Marcello , Palmeri Silvia , Parrotta Emma , DeFalco Danilo , Cappelli Michela , Salvatore Grieco Gaetano , Renieri Alessandra , Guazzi Giancarlo
Published: April 2003

We report an Italian family in which molecular genetic analysis showed expansion of CAG repeats indicative of the SCA2 genotype. This family confirms that ataxia, ophthalmoparesis and sensory peripheral neuropathy are the salient features of the SCA2 phenotype. In the present cases, early onset and mental deterioration were important additional findings. Nerve biopsy findings were compatible with a chronic axonopathy. We found a direct correlation between length of triplet expansion and severity of the clinical symptoms. Of particular interest is the late-onset phenotypical expression in a patient with 34 repeats.
Transcranial Doppler Monitoring of Intracranial Pressure Therapy with Mannitol, Sorbitol and Glycerol in Patients with Acute Stroke
Authors: Treib Johannes , Becker Susanne Christiane , Grauer Markus T. , Haass Anton
Published: April 2003

Introduction: The noninvasive management of the conservative therapy for intracranial pressure (ICP) with hyperosmolar substances is a central problem in the treatment of brain edema. Using transcranial Doppler (TCD), a continuous monitoring of ICP is now possible, because the TCD pulsatility index (PI) intraindividually closely correlates with the level of ICP. Patients and Methods: We administered an ICP-lowering treatment 113 times in 10 patients with intracranial bleeding or ischemic stroke who also had signs of elevated ICP in the computer tomogram. The treatment was carried out over a period of 9 days, using 50 g each of intravenous sorbitol (n = 38) and mannitol (n = 32) or oral glycerol (n = 43). Results: PI was significantly lowered between 20.0 and 23.9% (p < 0.01) by all substances in the affected and unaffected sides. The differences between the three substances and the differences between the affected and unaffected sides were not significant. The duration of the therapeutic effect of glycerol (190 ± 41 min) was significantly longer (p < 0.01) than that of sorbitol (150 ± 28 min) or mannitol (130 ± 20 min). The duration of the therapeutic effect was also significantly shorter (p < 0.01) in patients with a high PI (> 1.5). All three substances led to a significant increase (p < 0.01) in minimal (= diastolic) flow velocity (Vmin). The increase was highest for glycerol (56.3 ±72.6%). Summary: The decrease in PI under therapy was caused by an increase in Vmin. This indicates that ICP therapy with hyperosmolar substances improves brain edema and does not suggest a therapy-induced vasoconstriction.
Dolicho-Vertebrobasilar Abnormality and Migraine-Like Attacks
Authors: Zambrino Carlo Alberto , Berardinelli Angela , Martelli Adelaide , Vercelli Paola , Termine Cristiano , Lanzi Giovanni
Published: April 2003

This is a study of two children with neuroradiologically diagnosed dolichobasilar anomaly: in both cases, the diagnosis was based on magnetic resonance imaging and magnetic resonance angiography findings. We examined the first child (R., aged 6 years and 8 months) following four episodes of intense pain in the left orbit, lasting between 10 and 30 min and accompanied by photophobia and vomiting. The second child (S., aged 9 years and 2 months), suffering from Marfan’s syndrome, was examined following recurrent episodes of intense pain that started above the left orbit, moving to the homolateral orbit after a few minutes. These episodes, which lasted between 20 and 30 min, took place mainly at night and were accompanied by phono-photophobia and vomiting. In both cases, the pain attacks can be interpreted as a result of compression of the root of the trigeminal nerve caused by an arterial malformation.
Impaired Visual Function in Focal Idiopathic Dystonia
Authors: Büttner T. , Kuhn W. , Dietz M. , Müller T. , Postert T. , Przuntek H. , Welter F.L.
Published: April 2003

Visual dysfunctions have previously been reported in Parkinson’s disease and Huntington’s chorea. To further characterize the pathophysiology of vision in basal ganglion diseases, we studied visual functions in focal dystonic syndromes. Colour discrimination and visual contrast perception were investigated in 37 patients with focal idiopathic dystonia (ID; 20 spasmodic torticollis, 17 blepharospasm) and in age- and sex-matched healthy volunteers using the Farnsworth-Munsell 100-hue test and stationary contrast targets (Vistech plates). The mean total error score as well as the partial scores for the ‘red-green’ and the ‘blue-yellow’ axes in the Farnsworth-Munsell 100-hue test of the patients with ID were significantly elevated as compared to controls (spasmodic torticollis mean total error score 90.9 ± 67.6, controls: 16.6 ± 10.2; blepharospasm mean total error score 119.4 ± 78.6, controls: 22.7 ± 7.9). Additionally, the spatial contrast sensitivity was impaired in patients as compared to controls. The results indicate that the visual system is affected in ID. The visual disorder may be related to an imbalance of certain neurotransmitters in the visual system of patients, e.g. in the catecholaminergic pathways.
n-Hexane Neuropathy Caused by Addictive Inhalation: Clinical and Electrophysiological Features
Authors: Kuwabara Satoshi , Kai MargarethReiko , Nagase Hitoshi , Hattori Takamichi
Published: April 2003

To assess the clinical and electrophysiological features of n-hexane neuropathy caused by addictive inhalation, 4 patients were studied in the progressive phase. The neurological manifestations were characterized by subacute predominantly motor polyneuropathy and disease progression despite discontinuance of the chemicals, which were similar to those reported in industrial exposure, although with a severer degree associated with anorexia and body weight loss. Electrophysiological studies showed that all showed multifocal conduction block and profound conduction slowing, as well as features of axonal degeneration. Sural nerve biopsy showed axonal loss, axonal swelling, and thin myelin probably due to retraction by axonal swelling. n-Hexane abuse causes severe subacute polyneuropathy. The mixed axonal and demyelinating electrophysiological features were consistent with peculiar pathological findings. Conduction block, probably due to paranodal myelin retraction or ongoing wallerian degeneration, is very frequent and could be responsible for the clinical deficits, especially in the early phase of illness.
Regional Specific Changes of Cerebral Metabolism in Systemic Lupus erythematosus Identified by Positron Emission Tomography
Authors: de Jong B.M. , Pruim J. , Sinnige L.G.F. , Beintema K.D. , Spronk P.E. , Bootsma H. , Kallenberg C.G.M. , van Zomeren A.H. , Haaxma-Reiche H.
Published: April 2003

In order to test the hypothesis whether the pathogenesis of cerebral systemic lupus erythematosus (SLE) may include an immune-mediated deficit in specific vulnerable brain regions, the regional cerebral metabolism in 9 patients with diffuse as well as focal cerebral symptoms was compared with that of 10 age-matched control subjects. The cerebral distribution of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake was measured by means of positron emission tomography. Subsequently performed statistical parametric mapping showed (i) a relative increase in metabolism in the striatum and (ii) regional decreases in the premotor cortex as a common feature in the patient group. Region of interest measurements of absolute FDG uptake confirmed these findings. The increased striatal activity may support the presence of a direct immune response against neuronal tissue in SLE, similar to the cross-reaction against inhibitory components in striatal tissue provoked by streptococcal antigens.
Late-Onset Epilepsy Associated with Regional Brain Cortical Dysplasia
Authors: Bartolomei F. , Gavaret M. , Dravet C. , Guye M. , Bally-Berard J.Y. , Genton P. , Raybaud C. , Régis J. , Gastaut J.L.
Published: April 2003

Rationale: Cortical dysplasia (CD) designates a diverse group of malformations resulting from one or more abnormalities in the development of the cerebral cortex. The clinical manifestations of CD are varied, probably depending on the type, location and extent of CD. Epilepsy is a potential late manifestation of any cortical malformation. To our knowledge, however, no study has focused specifically on late onset of epilepsy in patients with localized CD. Material and Methods: We studied patients with localized CD confirmed by MRI. Patients were divided into 2 groups according to age at onset of epilepsy. Group 1 included patients in whom the first seizure occurred up to the age of 12 (early-onset group) and group 2 included patients in whom the first seizure occurred after the age of 12 (late-onset group). The two groups were compared with regard to the type of CD, clinical findings and EEG findings. Results: Thirty-three patients with various forms of CD were studied. Onset of epilepsy occurred in adolescence or adulthood in 9 cases (37%). In 6 of these (17% overall), the first seizure occurred in adulthood. CD were posterior bilateral pachygyria (1), unilateral polymicrogyria (3), focal dysplasia with subcortical gray matter heterotopia (1), perisylvian bilateral polymicrogyria (1), bioccipital polymicrogyria (1) and bilateral nodular periventricular gray matter heterotopia (2). The incidence of neurological signs was lower in the late-onset group. Mental retardation was moderate or absent, thus allowing a fairly normal lifestyle. All patients presented partial seizures with a lower incidence of drug resistance (p < 0.01). EEG demonstrated preservation of background activity and absence of diffuse or multifocal abnormalities. Conclusion: Onset of epilepsy with various forms of CD may be delayed until adolescence or adulthood. Prognosis of epilepsy is usually more favorable in these cases.
Sensory Dysfunction in HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis
Authors: Castillo José L. , Cea José G. , Verdugo Renato J. , Cartier Luis
Published: April 2003

We performed a comprehensive clinical and neurophysiological evaluation of function of the large- and small-caliber afferent pathways in 29 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Sensory symptoms, particularly cutaneous paresthesias, were present in 11 (37.9%) patients. On examination, a mild distal impairment of vibration and sense of position were found in 14 (48.2%) and 5 (17.2%) patients, respectively. Ten (34.4%) patients had distal tactile hypoesthesia and 7 (24.1%) presented pinprick hypoesthesia. Quantitative somatosensory thermotest showed cold hypoesthesia in 58.6% of patients. Nerve conduction studies and electromyography were normal. Tibial somatosensory evoked potentials were abnormal in 88.5% of patients. All of the sensory abnormalities found were restricted to sensations carried by myelinated (A-beta and A-delta) fibers. Unmyelinated C fibers mediating warm sensation and thermal pain appeared unimpaired. Our findings indicate that the sensory dysfunction in HAM/TSP patients is probably due to a lesion restricted to the central nervous system.
Comparison of Rizatriptan 10 mg vs. Naratriptan 2.5 mg in Migraine
Authors: Bomhof Martin , Paz Jose , Legg Nigel , Allen Christopher , Vandormael Kristel , Patel Krupa
Published: April 2003

Rizatriptan (MAXALTTM, Merck & Co., Inc.) is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action for the acute treatment of migraine. This randomized, double-masked, double-dummy, placebo-controlled study compared rizatriptan 10 mg to naratriptan (NARAMIGTM, AMERGETM, both Glaxo Wellcome plc) 2.5 mg in 522 patients treating a single migraine attack. Rizatriptan was more effective than naratriptan. Rizatriptan provided earlier headache relief than naratriptan (hazard ratio 1.62, p < 0.001), acting as early as 30 min. More patients were pain free at 2 h on rizatriptan than on naratriptan (44.8 vs. 20.7%, p < 0.001). Rizatriptan also provided earlier relief of associated migraine symptoms within 2 h than naratriptan and more patients had normal function at 2 h (39.3 vs. 22.6%, p < 0.001). Both active treatments were effective compared to placebo. Both active treatments were well tolerated. The most common side effects with rizatriptan were dizziness, asthenia/fatigue, nausea and somnolence, while the most common side effects with naratriptan were dizziness and asthenia/fatigue.
Magnetic Resonance Signal Abnormalities and Neuropsychological Deficits in Elderly Compressed-Air Divers
Authors: Tetzlaff Kay , Friege Lars , Hutzelmann Alfred , Reuter Michael , Höll Doris , Leplow Bernd
Published: April 2003

We investigated the association between MR signal abnormalities of the central nervous system, neuropsychologic performance and exposure indices in 20 experienced elderly compressed-air divers who had no history of neurological decompression illness (DCI). Results of MRI of the brain and psychometric testing were compared with 20 matched healthy commercial employees who never dived: 60% of the divers and 45% of the controls had hyperintense MR abnormalities. Among divers, both the number and the size of abnormalities correlated with hours diving in the deep air-diving range of 40–60 m (p < 0.05). Divers’ mental flexibility and visual tracking performance were decreased in comparison with controls (p < 0.05 and p < 0.01). Divers thus are at risk of detrimental long-term effects of compressed-air diving on the central nervous system even in the absence of a history of neurological DCI.