bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Approaches to White Matter Disease
Authors: Pantoni Leonardo
Published: April 2003

The study of the cerebral white matter (WM) in experimental models of hypoxia and ischemia has been for a long time neglected, the interest of investigators being focused on the response of the neuronal population. The increasing frequency with which modern neuroimaging techniques disclose alterations of the WM of possibly vascular origin has called some attention to other components of the cerebral parenchyma, namely oligodendrocytes and myelinated axons. The studies here reviewed show that it is possible to investigate the WM alterations in appropriate models of cerebral ischemia. In rodents, chronic ischemia produces extracellular fluid accumulation in the WM, moderate loss of oligodendroglial cells and reactive astrogliosis, all of which contribute to the rarefied appearance under the light microscope. These changes are similar to those found in many patients with leukoencephalopathy of possibly vascular origin. The results of experiments using a rat model of focal brain ischemia show that oligodendrocytes and myelinated fibers are extremely sensitive to ischemic insults with alterations of the subcortical WM detected at a very early time. Opportune modifications of these animal models may represent a valuable source of information on the pathogenesis and pathophysiology of human vascular disease of the WM.
Update on Diagnostic Methods, Natural History and Outcome Variables in Alzheimer’s Disease
Authors: Gauthier S.
Published: April 2003

The diagnosis of Alzheimer’s disease (AD) currently relies on history obtained from family or friends and on mental status assessment matched to National Institute of Neurological and Communicative Disorders and Stroke criteria. Progression over time may or may not be typical, suggesting alternate diagnoses such as Lewy body or frontotemporal dementias. Apolipoprotein E genotype does not appear to be useful as a diagnostic marker. The usefulness of brain imaging in AD must be reexamined. Critical events in the natural history of AD, such as institutionalization and loss of ability for self-care, could be used as end points. Loss of ability for instrumental tasks, such as driving, traveling alone, or managing finances, would be preferable for early-stage stabilization studies. Different symptomatic domains of AD (mood, cognition, functional autonomy, behavior, motoricity) can be quantified using specific outcome measures. Although cognitive loss has been considered a core symptom of AD from a regulatory perspective, loss of functional autonomy and behavioral disinhibition are considered more important by clinicians and families. Recently, the availability of new scales has led to an interest in all of these domains. Results from symptomatic drug studies suggest a differential effect of cholinesterase inhibitors on cognition versus muscarinic agonists on functional autonomy and behavior. Hence there is a need to measure these domains separately and, eventually, to attempt combination therapy. Quality of life is a difficult but important dimension of AD therapeutic research, and it requires further methodological research.
The Emergence of the Frontal Lobe and Its Morbidity, as Opposed to the Central Lobe
Authors: Brun Arne
Published: April 2003

The prevailing anatomical definition of the frontal lobe has resulted in a lobe that is heterogeneous with respect to structure, function and developmental features and at the same time splits up the motor and sensory cortices which have strong functional and developmental bonds, assigning them to different lobes. This topographical map also ignores disease patterns evidently related to developmental principles as illustrated by primary degenerative dementing disorders such as frontotemporal dementia and Alzheimer’s disease. It is therefore suggested that the frontal lobe is restricted to prefrontal structures, in front of the precentral fissure, whereas the motor and sensory cortex together form a central lobe, posteriorly followed by the parietal lobe. These lobes thereby gain in anatomical, functional and developmental purity as well as with respect to disease patterns. This division, thus based on structure, function, phylogeny, ontogeny makes for a better understanding of topographic patterns shown by degenerative disorders.
The Clinical Picture of Frontotemporal Dementia: Diagnosis and Follow-Up
Authors: Pasquier Florence , Lebert Florence , Lavenu Isabelle , Guillaume Bénédicte
Published: April 2003

Frontotemporal dementia (FTD) was diagnosed in 74 outpatients with a standardized assessment including neuropsychological tests, behavioural scale, structural and functional imaging. Clinical characteristics were consistent with the literature data. The cohort was followed for 2–6 years to determine the reliable variable for evaluating the progression of FTD. Every fourth patient died after a mean duration of 7 years. At first, FTD manifests itself in behavioural changes with relatively stable global cognition although language, verbal fluency and memory tests were reliable tools to follow the progression of the disease. Below 18 of Mini-Mental State Examination, mutism and apathy prevented from neuropsychological testing within the next 6 months. Behavioural disorders evolved with time but restlessness and hyperorality were long-lasting. Imaging showed the progression of a consistent pattern of anterior abnormalities with frequent leukoaraiosis.
Frontotemporal Dementia and Alzheimer’s Disease:Differential Diagnosis
Authors: Duara Ranjan , Barker Warren , Luis Cheryl A.
Published: April 2003

This report addresses the clinical differentiation of Alzheimer’s disease (AD) from frontotemporal dementia (FTD), including Pick’s disease. The accuracy of a clinical diagnosis of a dementing disorder is determined in part by the prior probability (base rates) of the disorder, which predicts an overwhelming likelihood of a diagnosis of AD, because the prevalence of AD is much greater than FTD. The clinical features of the disorder also determine the accuracy of diagnosis. Recent studies have reported an improvement in the differential diagnosis of FTD, utilizing the Lund-Manchester criteria. Patients with FTD typically have early noncognitive behavioral changes with relatively spared cognition, frontal atrophy and enlargement of the Sylvian fissures on CT and MRI scans, and frontal-temporal deficits on SPECT or PET scans. In contrast, AD patients have early cognitive changes with relatively preserved personality and behavior, hippocampal and medial-temporal lobe atrophy on CT or MRI scans, and parietotemporal SPECT or PET deficits.
Clinical and Pathological Overlap between Frontotemporal Dementia, Primary Progressive Aphasia and Corticobasal Degeneration: The Pick Complex
Authors: Kertesz Andrew , Davidson Wilda , Munoz David G.
Published: April 2003

A substantive overlap between the clinical syndromes of frontal lobe dementia (FLD), frontotemporal dementia (FTD), or primary progressive aphasia (PPA), and corticobasal degeneration syndrome (CBDS) has been demonstrated in a population of 55 patients followed for more than 3 years in a cognitive neurology clinic. Patients presenting with the personality behavior disorder (FLD) often develop progressive aphasia (PA) and vice versa. CBDS is often associated with FLD and PA, and the extrapyramidal-apractic syndrome of CBDS often appears in FLD and PPA. The histopathological variations do not predict the clinical phenotype. The term Pick complex is suggested to indicate that these clinical and pathological variations are related and they were first described by Pick as clinical manifestations of fronotemporal atrophy. This term will avoid the confusion of using FLD or FTD or for the whole complex and also for the personality behavioral presentation. The relationship of the various clinical presentations has been strengthened by the discovery of chromosome 17 linkage in families manifesting them.
Outcome Measures in Alzheimer’s Disease: Do They Go Far Enough?
Authors: Winblad Bengt , Wimo Anders , Almkvist Ove
Published: April 2003

As the interest in Alzheimer’s disease (AD) and its treatment has grown, so has the sophistication of clinical trials of potential drug therapies. In particular, interest has focused on outcomes used to assess the severity of the illness and the effectiveness of treatment. This paper reviews the assessments that are used frequently in trials of AD therapy and describes further measures that may be of value in determining effective treatments for the disease. The review concludes that it is important that evaluation of drug effects on AD is not confined solely to the assessment of cognitive function. To gain a true overview of the impact of AD on patients, carers and society, areas such as activities of daily living, caregiver burden, quality of life, behavioural symptoms and resource utilization need to be comprehensively determined.
Galantamine: Additional Benefits to Patients with Alzheimer’s Disease
Authors: Lilienfeld Sean , Parys Wim
Published: April 2003

Galantamine, a novel treatment for Alzheimer’s disease (AD), has a dual mechanism of action, combining allosteric modulation of nicotinic acetylcholine receptors with reversible, competitive inhibition of acetylcholinesterase. In the Phase III clinical trial programme, over 3,000 patients with mild-to-moderate AD were enrolled in one of five randomized, controlled, double-blind studies. Using the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) to assess memory and other cognitive functions, galantamine was found to be significantly superior to placebo in all five studies at doses of 16, 24 and 32 mg/day. In all studies, galantamine-treated patients maintained their cognitive function, whereas the placebo-treated patients experienced a significant deterioration in ADAS-cog scores. The 32-mg/day dose was not associated with any additional cognitive benefit. Pooled data from two 6-month studies (n = 1,269), which were of identical design, show that the therapeutic benefits of galantamine are sustained for the duration of treatment. The treatment effect (galantamine-placebo difference on ADAS-cog) for the pooled data was approximately 4 points. Clinical benefit was seen in all levels of disease severity, with a 7-point advantage over placebo on ADAS-cog for patients with moderately severe disease. Galantamine was well tolerated, with most patients completing the 6-month studies. The long-term effects of galantamine have been evaluated in a 12-month study. Patients who completed one of the pivotal 6-month studies (n = 353) were entered into a 6-month open-label extension. Cognitive and daily function were maintained throughout the 12 months in patients who received galantamine 24 mg/day. This sustained level of benefit may reflect galantamine’s dual effect on the cholinergic system. Data from a 5-month, placebo-controlled study have also shown that galantamine produces significant benefits on behavioural symptoms. The persistence and range of therapeutic effects produced by galantamine suggest that it may provide additional benefits for patients with AD.
The Gottfries-Bråne-Steen Scale: Validity, Reliability and Application in Anti-Dementia Drug Trials
Authors: Bråne G. , Gottfries C.G. , Winblad B.
Published: April 2003

Neuropsychological investigation using a comprehensive rating scale is important for the diagnosis and evaluation of dementia patients over time. Requirements for such a scale include accuracy, reliability, sensitivity of the scale over the disease course and simplicity for clinical use by a wide range of healthcare professionals. Ideally, the scale should also be capable of assessing the impact of pharmacological and non-pharmacological treatment regimens on the management of dementia patients. The Gottfries-Bråne-Steen (GBS) Scale is a comprehensive global assessment tool for evaluating dementia symptoms and is based on a semi-structured interview and observation of the patient. The scale consists of subscales measuring intellectual (12 items), emotional (3 items) and activities of daily living, primarily items of self-care (6 items); as well as 6 items of behavioral and psychological symptoms of dementia. This review describes the reliability, validity and sensitivity of the most recent version of the GBS scale since its original publication in 1982.
White Matter Lesions Impair Initiation of FAS Flow
Authors: Fernaeus Sven-Erik , Almkvist Ove , Bronge Lena , Östberg Per , Hellström Åke , Winblad Bengt , Wahlund Lars-Olof
Published: April 2003

Word fluency performance is known to rely on left frontal cortical regions and has also been shown to be affected by lesions in the white matter, which may be seen as white matter hyperintensities (WMH) on magnetic resonance imaging. However, word fluency may be divided into two independent components, initial and late performance, separated in time [J Clin Exp Neuropsychol 1998;20:137–143]. The purpose of the current study was to investigate the relationship between the two components of FAS fluency performance and WMH. Patients varying in degree of memory impairment participated: Alzheimer’s disease, mild cognitive impairment and subjective memory disorder. WMH were rated with the Scheltens scale in the periventricular and deep subcortical areas. Results demonstrated that WMH in this sample of patients may be summarized in two indices according to a principal factor analysis, one anterior factor mainly related to WMH in the frontal lobes and adjacent to ventricles, and a second posterior factor related to parietal and occipital WMH. The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH.
Dementia with Impaired Temporal Glucose Metabolism in Late-Onset Metachromatic Leukodystrophy
Authors: Johannsen Peter , Ehlers Lise , Hansen Hans Jacob
Published: April 2003

An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and attention deficits with a slow psychomotor speed. MR brain imaging displayed confluent hyperintensities of periventricular and subcortical white matter. Low levels of arylsulfatase A confirmed the diagnosis. Impaired cortical glucose metabolism especially of the medial temporal and frontal cortices was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism.
Abnormal Localization of Two Neuronal Calcium Sensor Proteins, Visinin-Like Proteins (VILIPs)-1 and -3, in Neocortical Brain Areas of Alzheimer Disease Patients
Authors: Braunewell K.-H. , Riederer P. , Spilker C. , Gundelfinger E.D. , Bogerts B. , Bernstein H.-G.
Published: April 2003

The anatomical distribution of the neuronal calcium sensor proteins visinin-like protein-1 and -3 (VILIP-1 and -3) was investigated in various neocortical areas of Alzheimer’s disease (AD) patients and controls. In AD and normal brains their cellular localization was confined to pyramidal and non-pyramidal neurons. In AD brains the intracellular immunostaining for VILIP-1 and to a lesser extent for VILIP-3 was found to be reduced in comparison to controls. Also, significantly less VILIP-1-immunoreactive neurons were found in the temporal cortex of AD patients as compared to normal brains. Accordingly, Western blot analysis revealed that immunoreactivity for VILIP-1 is less concentrated in tissue extracts of the temporal cortex of AD patients compared to controls. Extracellularly, VILIP-1 and VILIP-3 immunoreactive material was detected in close association with typical pathologic hallmarks of AD such as dystrophic nerve cell processes, amorphous and neuritic plaques, and extracellular tangles. In control brains an extraneuronal localization of VILIP-1 or VILIP-3 was never observed. Our morphological and neurochemical findings point to an involvement of these two neuronal calcium sensor proteins in pathology and possibly pathophysiology of changed calcium homeostasis in AD.
Excess Functional Disability among Demented Subjects?
Authors: Thomas Vince Salazar
Published: April 2003

Dementia has been recognized as the strongest determinant for developing functional disability. However, dementia patients typically present with concomitant illness, thereby making difficult a determination of the fraction of disability due to dementia. The objective of this study was to estimate the prevalence of functional disability among demented and nondemented people and to estimate the excess disability in demented subjects net of conditions independently associated with disability in older people, using data on nearly 2,900 subjects from the clinical examination of the 1991 Canadian Study of Health and Aging. Unadjusted specific disability prevalence (in bathing, dressing, grooming, toileting and stool and urinary incontinence) is considerably greater among demented subjects than among cognitively normal or cognitively impaired but not demented subjects. After adjustments, specific disability in demented subjects is somewhat reduced in comparison to nondemented and cognitively impaired but not demented subjects. Thus, even when one considers the influence of a history of physical illnesses that typically result in disability, the link between disability and dementia is only marginally attenuated.
Decreased Levels of Intrathecal Interleukin 1 Receptor Antagonist in Alzheimer’s Disease
Authors: Tarkowski Elisabeth , Liljeroth Ann-Marie , Nilsson Åsa , Minthon Lennart , Blennow Kaj
Published: April 2003

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of brain damage in dementia. In previous studies, we have demonstrated intrathecal production of the proinflammatory cytokine tumor necrosis factor (TNF)α in patients with Alzheimer’s disease (AD). The aim of the present study was to investigate the downstream products of TNF-α expression including interleukin (IL)1β and its naturally occurring antagonist IL-1 receptor agonist (ra) in patients with AD. The cytokine levels were related to neuronal damage, as measured by intrathecal τ and β-amyloid concentration and certain clinical features of the disease. Fifty-two patients with AD and 25 healthy controls were analyzed with respect to cerebrospinal fluid (CSF) levels of IL-1β and IL-1ra. CSF IL-1β was neither detectable in CSF of AD nor in control CSF. In contrast, a significantly lower (p < 0.01) number of patients (24 of 49) than of controls (20 of 24) showed detectable levels of IL-1ra in the CSF. The intrathecal levels of IL-1ra were significantly lower in patients with AD than in the controls. Our study demonstrates a decreased production of the anti-inflammatory compound IL-1ra, suggesting a propensity towards inflammation in patients with AD.
Innovative Dementia Care: Functional Status over Time of Persons with Alzheimer Disease in a Residential Care Centre Compared to Special Care Units
Authors: Warren Sharon , Janzen Wonita , Andiel-Hett Corinna , Liu Lili , McKim H. Robert , Schalm Corinne
Published: April 2003

Residential care centres (RCCs) for persons with Alzheimer disease are increasing worldwide, but there are few studies that compare the functional outcomes of RCC residents to residents of other types of continuing care settings. This study compared residents of the first Canadian RCC on physical, cognitive, behavioural and emotional functioning 6, 12 and 18 months after admission to residents of special care units (SCUs) operated by the same continuing care provider. SCU residents were initially functioning lower than RCC residents on most outcome measures and these differences persisted over time. Resident functioning declined over time regardless of care setting and, when the initial status was controlled for, the rates of decline were similar. However, RCC residents experienced greater independence/freedom of choice, fewer physical or psychotropic medication restraints and were more active, which may have enhanced their quality of life.
Critical Review of Acid Suppression in Nonvariceal, Acute, Upper Gastrointestinal Bleeding
Authors: Yacyshyn B.R. , Thomson A.B.R.
Published: April 2003

Nonvariceal, upper gastrointestinal (GI) bleeding is a very common source of morbidity and mortality. The concept of ulcer clot dissolution being facilitated by a low gastric pH has allowed us to better understand the pathophysiology of nonvariceal upper GI bleeding. Placebo-controlled trials have shown the benefit of oral proton pump inhibitor administration in contrast to H2 receptor antagonists. Furthermore, our recent experience with intravenous proton pump inhibitors has reinforced these observations.
Selection of Patients for Laparoscopic Antireflux Surgery
Authors: Glaser Karl , Wetscher Gerold , Klingler Anton , Klingler Paul , Eltschka Bernard , Hollinsky Christian , Achem Sami , Hinder Ronald
Published: April 2003

Since the first laparoscopic fundoplication was performed, the frequency of antireflux surgery has increased rapidly with some centers now having an experience of about 1,000 procedures. The question arises whether this increase is due to a change in indications for the surgical treatment of gastrointestinal reflux disease (GERD) despite the simultaneous appearance of powerful antisecretory medications. Adequate knowledge of the pathophysiology of GERD is necessary in order to establish selection criteria for patients suitable for laparoscopic antireflux surgery. In this article, we review the epidemiology and pathophysiology, and provide a rationale for medical and surgical treatment. We also offer an approach to patient selection for antireflux surgery.
Update on Noncardiac Chest Pain
Authors: Shrestha Sanjeeb , Pasricha Pankaj Jay
Published: April 2003

Patients with recurrent angina-like chest pain with normal coronary vessels are deemed to have the syndrome of noncardiac chest pain (NCCP). These patients, despite having significant cardiac disease ruled out, often spend a restricted lifestyle believing they have cardiac disease. These recurrent episodes of chest pain may be related to gastroesophageal reflux disease (GERD), spastic motility disorders of the esophagus and esophageal (visceral) hyperalgesia. These disease entities are often difficult to diagnose and treat except for GERD and achalasia. Recent prospective double-blind studies have shown that about 44% of these patients may have underlying GERD. There is now more evidence to support the practice of empiric use of proton pump inhibitors (PPIs) as the first step in therapy. Newer modalities for diagnosis like endoscopic ultrasonography (EUS) showed that this group of patients had sustained muscular contractions of longer that 68 s during chest pain. These sustained contractions noted on EUS were secondary to isometric contraction of the circular muscle which did not cause luminal constriction nor was related to contraction of the longitudinal muscles which cannot be recorded by pressure manometry. Treatment is difficult if patients do not respond to high-dose PPIs. Other medications which are known to alter visceral hyperalgesia in low doses, such as tricyclic antidepressants like imipramine and desyrel, can be tried. Psychological intervention may be useful in the management of some of these patients.
Role of Thrombotic Vascular Risk Factors in Inflammatory Bowel Disease
Authors: Koutroubakis I.E.
Published: April 2003

Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). It is recognized that a hypercoagulable state exists in IBD which involves all components of the clotting system. It has been suggested that this hypercoagulable state is closely linked to the disease pathogenesis. Recent studies have shown that genetic defects such as factor V Leiden mutation and C677T methylenetetrahydrofolate reductase polymorphism associated with hyperhomocysteinemia seem to interfere in the thrombotic manifestations of IBD. Acquired factors such as antiphospholipid antibodies could also participate in the development of the thrombotic process. Deficiencies of other anticoagulant factors play a less important role in the thrombosis, and therefore it is not surprising that the results on these factors in IBD are contradictory. In conclusion the resultant gene–gene and gene–environment interactions between risk factors are the key to the understanding of why an IBD patient develops thrombosis at a specific point in time.
Epidemiology and Significance of Barrett’s Esophagus
Authors: DeVault Kenneth R.
Published: April 2003

Barrett’s esophagus (BE) is of interest because of its recognized association with esophageal adenocarcinoma. While BE develops in a minority of patients with gastroesophageal reflux disease, its diagnosis has markedly increased over the last 30 years. Although a concurrent increase in the number of endoscopies performed annually has improved the ability to diagnose BE, the increase in prevalence appears to be a true finding. Conflicting data in the literature confound an accurate assessment of the risk for adenocarcinoma in patients with BE. Certain factors associated with BE also hold for esophageal adenocarcinoma: greater severity of reflux symptoms, specific pattern of symptoms (particularly nocturnal), longer duration of symptoms, white race, and male gender. One report has suggested a 45-fold increase in cancer risk for patients with frequent, severe and long-standing heartburn symptoms. New cases of esophageal adenocarcinoma are also increasing, especially in white males, with over 6,000 new cases diagnosed in 1995. BE can progress to esophageal dysplasia and adenocarcinoma; hence, early diagnosis and surveillance of BE and treatment of high-grade dysplasia leads to improved survival. The reported risk of developing cancer in BE ranges from 0.4 to 1.9%/year of follow-up. Most recent studies have tended to report rates of 0.5%/year or lower. Despite these data and concerns, at least two actuarial studies have suggested that the risk of death in patients with BE does not differ from that of a control population. This review of the literature focuses on the epidemiology of BE and the associated incidence of its sequelae.
Pathogenesis of Acute Hepatic Encephalopathy
Authors: Butterworth Roger
Published: April 2003

Hepatic encephalopathy (HE) is a major neuropsychiatric complication of chronic liver disease. Depending upon the duration and severity of the liver disorder and of the presence of precipitating factors, HE may present as one of two major types. Portal-systemic encephalopathy (PSE) results from portal-systemic shunting of venous blood that arises either spontaneously or due to surgical portacaval anastomosis or transjugular intrahepatic shunts (TIPS) aimed at reducing portal hypertension.
Diagnosis of Encephalopathy
Authors: Weissenborn Karin
Published: April 2003

The features of hepatic encephalopathy (HE) are various. Slight ataxia combined with hypomimia, dysarthria and flapping tremor may represent HE just as minimal changes in personality or psychomotor slowing. Diagnosis of HE is made difficult by the fact that there is no symptom or serum biochemical test result that may produce evidence for the presence of HE. Thus we are forced in each case to exclude other possible causes for the patient’s neuropsychiatric symptoms before diagnosing HE. The diagnosis of HE requires to put together clinical findings, serum test results, neuropsychological and neurophysiological test results and in some cases even cerebral imaging results like pieces of a puzzle. But, ultimately HE is proven only in case that the symptoms disappear with adequate therapy.
Pathogenesis of Hepatocellular Carcinoma
Authors: Caselmann Wolfgang
Published: April 2003

Hepatocellular carcinoma (HCC) represents about 4% of all malignancies worldwide. There are up to 1 million new cases per year and its relative frequency is increasing. Hepatocarcinogenesis is a multistep process and a multifactorial event. The major risk factors for HCC development have been identified. They are chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, aflatoxin B1 uptake as well as metabolic disorders such as hemochromatosis, α1-antitrypsin deficiency or other more rare genetic disorders. Although HCC can develop without preexisting cirrhosis, it occurs in over 80% on the grounds of liver cirrhosis. Regardless of its etiology, cirrhosis is an independent factor that increases significantly the risk of HCC development [for review, see 1]. However, diVerent pathogenic mechanisms contribute to malignant hepatocyte transformation depending on the underlying disease.
Imaging for Diagnosis of Hepatocellular Carcinoma
Authors: Kreft Burkhard , Schild Hans
Published: April 2003

The role of radiology in the evaluation of liver cirrhosis is twofold. First, imaging is used to visualize and characterize the morphologic manifestations of the disease including the hepatic and extrahepatic vasculature and to assess the effects of portal hypertension. The second very important task is the detection of hepatocellular carcinoma (HCC) due to its high incidence in liver cirrhosis [1]. Furthermore, benign nodular lesions in patients with liver cirrhosis should be differentiated from malignant or potentially malignant lesions with high accuracy. The following article describes the value of various imaging modalities which can be used for the detection and characterization of HCC.
Chronic Pancreatitis at Manchester, UK
Authors: McCloy Rory
Published: April 2003

The Manchester ‘oxidant stress’ hypothesis for the development of pancreatitis accommodates published information on both chronic pancreatitis and acute pancreatitis. Oxidant stress, mainly from reactive xenobiotic metabolites, is perceived as the pivotal pre-morbid problem in chronic pancreatitis and, by depleting glutathione, targets the exocytosis mechanism of the pancreatic acinar cell. Inhalation exposure to petrochemical products is identified as an independent risk factor in patients at Manchester Royal Infirmary, where some 50% of patients referred have non-alcoholic disease. This paper describes the development of antioxidant therapy, using supplements of methionine, vitamin C and selenium, and its validation in a placebo-controlled trial, followed by a retrospective cross-sectional study in 94 consecutive patients for an average of 30 months. Antioxidant therapy emerges as a safe and effective medical alternative to surgery for painful chronic pancreatitis.
Operative vs. Nonoperative Therapy in Necrotizing Pancreatitis
Authors: Bradley,III EdwardL.
Published: April 2003

Anecdotal and uncontrolled recommendations for programmatic surgical intervention in necrotizing pancreatitis are gradually being replaced by nonoperative approaches as prospective natural history information becomes available. In patients with sterile pancreatic necrosis, nonoperative managements has now been shown to result in a mortality rate equal or better to surgical debridement. Moreover, since surgical debridement of sterile pancreatic necrosis has not been shown to prevent or ameliorate co-existing organ failure, and given that secondary infection of sterile necrosis occurs as a result of operative debridement in 25% of cases and results in a trebling of mortality risk, it is becoming increasingly clear that surgical debridement in sterile necrotizing pancreatitis will become the exception rather than the rule. However, surgical debridement and drainage remains the preferred approach for infected pancreatic necrosis despite occasional anecdotal reports of successful management by transcutaneous or endoscopic means. While the optimal post-surgical technique of drainage remains controversial, a selective approach is reasonable, with the choice between closed drainage, lesser sac lavage, or schedule re-explorations being based upon extent of the necrotic process.
New Approaches in Surgical Management of Severe Acute Pancreatitis
Authors: Schoenberg M.H. , Rau B. , Beger H.G.
Published: April 2003

Despite many prospective randomized clinical studies a specific pharmacotherapy for severe acute pancreatitis is not in sight. To date, the only possibility to influence the prognosis of this severe illness is early diagnosis and prevention of intra- and extrapancreatic necrosis and its subsequent infection. In severe necrotizing pancreatitis the incidence of infected necrosis amounts to 40–70% of all patients within 3 weeks. Thereby, the clinical picture often varies to large extent. Ultrasonographically or computertomography-guided fine-needle aspiration (FNAC) is a fast and reliable technique for diagnosis with an overall sensitivity of 88% and specificity of 90%. This method should however not be applied too early in the course of necrotizing pancreatitis. Since infection of pancreatic necrosis determines significantly the prognosis of disease, various studies have assessed the efficacy of prophylactic antibiotic treatment in patients. Three prospective randomized studies have shown that prophylaxis significantly minimizes septic complications, only in one study, however, the mortality rate could be improved. Although randomized studies are still mandatory to resolve the controversy, it seems justified to recommend prophylaxis with antibiotics which are capable of penetrating the pancreatic tissue and juice. Sterile necrosis should be treated conservatively, with prophylactic antibiotic treatment for as long as possible. Only if patients worsen despite intensive care medicine, surgical debridement should be considered. In contrast, in patients with infected necrosis immediate surgery is in most cases mandatory. Although in one prospective study conservative treatment did not lead to an enhanced mortality rate, possible delay of surgical treatment may endanger the patient. In order to improve the prognosis of the disease, timely and adequate treatment in specialized units provides the best chances for a good prognosis whereby the severely ill patient should not be treated according to a scheme but to his/her individual needs.
Pathophysiology of Pancreatitis
Authors: Saluja AshokK. , Steer MichaelL.
Published: April 2003

Acute pancreatitis is an inflammatory disease, which varies in severity from mild to severe. Factors determining the severity of pancreatitis are not known. It is generally believed that the earliest events in the evolution of acute pancreatitis lead to premature intra-acinar cell activation of digestive zymogens and that those enzymes, once activated cause acinar cell injury. Recent studies have suggested that the ultimate severity of resulting pancreatitis may be determined by events which occur subsequent to acinar cell injury. These include inflammatory cell recruitment and activation as well as the generation and release of cytokines and other chemical mediators of inflammation. Recently, we have undertaken studies to elucidate the role of various inflammatory agents in determining the severity of pancreatitis. Results from these ongoing studies indicate that substance P acting via neurokinin-1 (NK1) receptors, chemokines interacting with CCR1 receptors and platelet activating factor play an important pro-inflammatory role in regulating the severity of pancreatitis and associated lung injury. On the other hand, complement factor 5a (C5a) acts as an anti-inflammatory agent during the development of pancreatitis.
Effect of IS-741 (A New Synthetic Antiinflammatory Agent) on Acute Necrotizing Pancreatitis in Dogs
Authors: Isaji Shuji , Hayashi Jitsuo , Higashiguchi Takashi , Yokoi Hajime , Ogura Yoshifumi , Noguchi Takashi , Kawarada Yoshifumi
Published: April 2003

IS-741, a new synthetic anti-inflammatory agent, is known to have some inhibitory effect on cytosolic phospholipase A2 (cPLA2), an enzyme which hydrolyzes cellular phospholipids, liberating fatty acids and lysophospholipids and providing the precursor substrates for the biosynthesis of eicosanoids and platelet-activating factor. cPLA2 is therefore an attractive target for the development of novel therapies. During infusion of lactated Ringer’s solution at a rate of 10 ml/kg/h, acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. The dogs were then divided into two groups: group A (nontreatment), no treatment during the experiment, and group B (IS-741), intravenously injected with IS-741 at 6 and 30 h after induction of acute pancreatitis. As a result, the survival rate was significantly higher in group B than in group A. Mean arterial pressure and PaO2 were well maintained in group B as compared with group A. The NAG index, which is known to be markedly increased in renal tubular damage, was significantly lower in group B than in group A. Histological examination of the pancreas, lung, and kidney in group B showed milder changes than in group A. cPLA2 activity in the pancreas, lung and renal cortex was much lower in group B than in group A, but sPLA2 activity in these tissues did not differ significantly between the two groups. In conclusion, IS-741 exerts a potentially therapeutic effect on experimental acute pancreatitis by mitigating the degree of damage in the pancreas, lung, and kidney. The inhibitory effect of IS-741 on cPLA2 may contribute to one of the antiinflammatory mechanisms of actions of this agent.
Pancreatic Exocrine Insufficiency following Pancreatic Resection
Authors: Ghaneh Paula , Neoptolemos John P.
Published: April 2003

Major pancreatic resection can cause pancreatic enzyme insufficiency with fat malabsorption, resulting in symptoms of abdominal pain, steatorrhoea and weight loss which can be extremely debilitating. The most important factors influencing subsequent development of steatorrhoea are the extent and type of surgical resection and the underlying disease process. The resultant steatorrhoea can be marked and difficult to control. There have been relatively few randomised controlled studies which have addressed this particular problem in patients who have had pancreatectomy. The use of effective doses of pancreatic enzyme supplements is essential in those patients who are symptomatic. When stabilised on therapeutically effective doses of pancreatic enzyme supplements, however, over 30% of patients still have evidence of significant levels of steatorrhoea. These results emphasise that the complete eradication of steatorrhoea is still not feasible at the present time, even using the best currently available agents, highlighting the need for further effective therapies.
Octreotide in the Treatment of Refractory Diarrhea
Authors: Fried M.
Published: April 2003

Refractory chronic diarrhea that does not respond to specific antimicrobial therapy or standard unspecific medication may present a challening and serious clinical problem. Octreotide is a candidate drug for the treatment of these patients as it inhibits gastrointestinal motility, pancreatic secretion and inhibits intestinal absorption. Only few mostly uncontrolled studies in small patient groups were published evaluating the efficacy of octreotide in the treatment of patients with chemotherapy-induced diarrhea, short-bowel syndrome, AIDS-associated diarrhea and other conditions with chronic diarrhea not responding to standard treatment. Most of these studies are not conclusive as they yielded either negative or controversial results. Octreotide may be tried in the treatment of refractory diarrhea, in particular AIDS-associated diarrhea if patients do not respond to conventional treatment strategies. Well-designed controlled trials in large patient groups are needed in order to define the place of octreotide in the treatment of patients with refractory diarrhea.
Sows’ Milk Attenuates Dexamethasone-Induced Reductions in Liver Docosahexaenoic Acid
Authors: Petryk Lori , Weiler Hope A.
Published: April 2003

The objective was to determine the effects of dexamethasone (Dex) on growth and arachidonic (AA) and docosahexaenoic (DHA) acid status. Piglets were randomized to suckling or formula feeding plus Dex or placebo treatment for 15 days. Weight and length at the beginning and end of study was used to assess growth. After 15 days, AA and DHA in phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were measured in liver and plasma and total AA and DHA in forebrain and brainstem. Dex treatment significantly reduced weight and length. Dex reduced liver PC and PE DHA in the formula group, but the reduction in the suckled group was not significant. PC AA and DHA were positively related in liver and plasma. A main effect of Dex to reduce AA and DHA was observed in forebrain but not in brainstem. Sows’ milk attenuated the Dex-induced reduction in liver DHA but not forebrain AA and DHA or somatic growth.
Phototherapy of Psoriasis: Comparative Experience of Different Phototherapeutic Approaches
Authors: Karrer Sigrid , Eholzer Christian , Ackermann Günther , Landthaler Michael , Szeimies Rolf-Markus
Published: April 2003

Background: Broad-band UVB alone or in combination with different topical drugs (anthralin, calcipotriol), systemic PUVA and bath-PUVA therapy are very effective and well-established treatment modalities for psoriasis. Objective: The aim of this retrospective study was to assess which of these routinely applied phototherapeutic modalities might be most effective and safe for the treatment of plaque-type psoriasis. Methods: Patients (n = 203) with moderate to severe (pretreatment Psoriasis Area and Severity Index score between 12 and 35) chronic plaque-type psoriasis treated between 1992 and 1998 at our department with either UVB (with/without anthralin or calcipotriol; n = 97), systemic PUVA (n = 19) or bath-PUVA therapy (n = 87) were evaluated for efficacy, duration of treatment, number of treatments necessary for complete remission (CR), cumulative light dose, side effects of therapy and duration of remission after therapy. Results: No statistically significant difference comparing the efficacy of bath-PUVA (CR in 72.4%), PUVA (CR in 89.5%) and UVB phototherapy (CR in 69.1%) was found. Although the duration of therapy was significantly longer for bath-PUVA (66 ± 42 days) as compared to UVB treatment (50 ± 27 days), the mean number of treatments did not differ significantly between bath-PUVA (28 ± 12), UVB therapy (30 ± 12) and PUVA (26 ± 13). Significantly fewer side effects of phototherapy were observed with bath-PUVA (14.9%) therapy compared to UVB treatment (30.9%). Also, the duration of remission after successful therapy was significantly longer for bath-PUVA (8.4 ± 3.5 months) as compared to UVB phototherapy (5.1 ± 4.2 months). Conclusion: Bath-PUVA therapy has some advantages over UVB phototherapy in the treatment of psoriasis: fewer UV-related acute side effects and a longer period of remission after therapy. However, the choice of treatment with either UVB, bath-PUVA or systemic PUVA should also be based on a history of previous response to treatment and patient considerations, including compliance and responsibility for following the precautions to avoid potential side effects.
Efficacy and Safety of Intralesional 5-Fluorouracil in the Treatment of Keloids
Authors: Gupta Somesh , Kalra Amit
Published: April 2003

Background: The treatment of keloids remains challenging. Cryosurgery and intralesional corticosteroids have been considered as the mainstream of therapy; however, the long-term use of corticosteroids has been found to be associated with serious side effects. Intralesional 5-fluorouracil (5-FU) has only been used in one study for the treatment of hypertrophic scars and keloids, mostly in combination with other treatments. The efficacy of 5-FU as an individual therapeutic agent is unknown. Objective: To evaluate the efficacy and safety of intralesional injections of 5-FU in the treatment of small keloid lesions. Methods: Twenty-four (12 male, 12 female) consecutive patients with keloids of 6 cm or less in their maximum dimension were treated with intralesional injections of 50–150 mg 5-FU per week for a maximum of 16 injections. Results: One third (8/24, 33.3%) of the patients showed more than 75% flattening of the keloid. Three out of 8 patients (with >75% flattening) required less than 16 (13, 13 and 15) injections for achieving the desired response. Overall, about half of the patients showed more than 50% flattening of the treated keloid. A correlation with the duration of keloid was found. Six (54.5%) out of 11 patients with keloids of ≤5 years duration, in contrast to only 2 (15.4%) out of 13 patients with keloids of >5 years duration showed more than 75% flattening (p < 0.05). Side effects included pain (all patients), hyperpigmentation (all patients) and ulceration (1 patient). No difference in peripheral blood count was noted before, during and after the therapy. Conclusion: Intralesional 5-FU can be safely used for the management of small keloids of shorter duration.
Fosinopril as a Possible Pemphigus-Inducing Drug
Authors: Parodi A. , Cozzani E. , Milesi G. , Drosera M. , Rebora A.
Published: April 2003

Fosinopril has recently been added to the angiotensin-converting enzyme inhibitors inducing pemphigus. The observation of a patient in whom pemphigus vulgaris (PV) worsened after taking fosinopril prompted us to study an experimental way to assess its responsibility. Slices of normal human skin (NHS) were simultaneously incubated for 2, 6, 12 and 24 h at 4°C with progressively diluted fosinopril and captopril solutions and used as indirect immunofluorescence (IIF) substrates for 2 sera containing anti-desmoglein-3 (anti-Dsg3) antibodies at a dilution of 1/160. With captopril, IIF was negative, irrespective of dilution and time of incubation. Only at 1/40,000 dilution was IIF positive. With fosinopril, IIF was negative for the 2- and 6-hour-long incubations but turned positive after 12 h and so remained with all other solutions and incubation times. IIF negativity with captopril suggests that anti-Dsg3 antibodies contained in the PV sera were unable to find molecules in NHS to bind to. Captopril would therefore induce acantholysis by blocking the adhesion molecules. With fosinopril, instead, a partial block of the adhesion molecules was seen only with the very concentrated solution, unlikely to occur in vivo. Fosinopril, therefore, is probably unable to block the adhesion molecules in vivo. Our method might be used to verify the acantholytic properties of a drug.
Intestinal Proliferation and Delayed Intestinal Transit in a Patient with a GLP-1-, GLP-2- and PYY-Producing Neuroendocrine Carcinoma
Authors: Byrne Maria M. , McGregor Gerard P. , Barth Peter , Rothmund Mathias , Göke Burkhard , Arnold Rudolf
Published: April 2003

Glucagon-like peptides (GLP) 1 and 2 are hormones derived from the post-translational processing of proglucagon in the intestinal L cells that influence intestinal motility and small bowel growth, respectively. We describe a patient with a neuroendocrine tumor of unknown primary origin with peritoneal carcinomatosis and diffuse liver metastases, who presented with constipation and nocturnal itching for over 3 years. Small bowel follow-through showed decreased small intestinal motility and marked intestinal hypertrophy. Biopsies from mesenterial lymph nodes showed, histologically, a well-differentiated neuroendocrine tumor (G1), with positive immunostaining for chromogranin A, GLP-1, GLP-2 and polypeptide YY (PYY). Jejunal biopsy demonstrated marked intestinal mucosal hypertrophy. HPLC analysis combined with RIA of tumor and serum extracts revealed that the tumor was producing and releasing fasting levels of GLP-1 of 738±20.7 pg/ml (normal levels (nl) <100 pg/ml), GLP-2 of 3,150±9 pg/ml (nl <100 pg/ml) as well as PYY 550 pg/ml (nl <100 pg/ml). Octreotide administration decreased levels of GLP-1 and GLP-2 and reduced small intestinal transit time from 150 to 50 min. However, tumor growth was not inhibited by octreotide, interferon or dacarbazine therapy and the patient died 8 months later. This is the first case report demonstrating the overproduction of GLP-1, GLP-2 and PYY from an neuroendocrine tumor, in a patient with intestinal hypertrophy and delayed intestinal transit time.