bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Peripheral Microcirculation Using Computer-Assisted Venous Congestion Plethysmography in Post-Traumatic Complex Regional Pain Syndrome Type I
Authors: Schürmann Matthias , Zaspel Johannes , Gradl Georg , Wipfel Alexander , Christ Frank
Published: April 2003

In complex regional pain syndrome type I (CRPS-I), edema of the affected limb is a common finding. Therefore, the changes in macro- and microcirculatory parameters were investigated to elucidate the underlying pathophysiology. Twenty-four patients with post-traumatic CRPS-I and 25 gender- and age-matched healthy subjects were examined by means of an advanced computer-assisted venous congestion strain-gauge plethysmograph. The recording of the volume response of the forearm to a stepwise inflation of an occlusion cuff placed at the upper arm enabled the calculation of the arterial blood flow into the arm (Qa), the vascular compliance (C), the peripheral venous pressure (Pv), the isovolumetric venous pressure (Pvi; = hydrostatic pressure needed to achieve net fluid filtration) and the capillary filtration capacity (CFC) – an index of microvascular permeability. The study revealed no difference in any of the parameters between the right and left hand of healthy subjects. In CRPS-I patients, however Qa, Pv, Pvi and CFC were significantly (p < 0.01/0.001) elevated in the affected arm (Qa 11.2 ± 7.0 ml min–1 100 ml–1, Pv 20.2 ± 8.1 mm Hg, Pvi 24.7 ± 4.2 mm Hg, CFC 0.0058 ± 0.0015 ml min–1 100 ml–1 mm Hg–1) compared to the unaffected arm (Qa 4.2 ± 2.4 ml min–1 100 ml–1, Pv 10.0 ± 5.1 mm Hg, Pvi 13.2 ± 3.7 mm Hg, CFC 0.0038 ± 0.0005 ml min–1 100 ml–1 mm Hg–1) and the values obtained in healthy controls (Qa 5.1 ± 1.3 ml min–1 100 ml–1, Pv 10.4 ± 4.3 mm Hg, Pvi 15.7 ± 3.3 mm Hg, CFC 0.0048 ± 0.0012 ml min–1 100 ml–1 mm Hg–1). Whereas the values in the unaffected arm of CRPS-I patients revealed no difference in Qa, Pv and Pvi but a lower CFC (p < 0.01) compared to those from healthy controls. These results suggest profound changes in both macro- and microvascular perfusion in the affected arm of CRPS-I patients. The high CFC contributes to the edema formation, and combined with the elevated Pvi, they are in agreement with the hypothesis of an inflammatory origin of CRPS.
Regression of Neointimal Lesions in the Carotid Artery of Nifedipine-Treated SHR and WKY Rats: Possible Role of Apoptosis
Authors: Lemay Jacinthe , Tea Bun Seng , Hamet Pavel , deBlois Denis
Published: April 2003

We previously observed that nifedipine reduces aortic hypertrophy in spontaneously hypertensive rats (SHR) partly by inducing smooth muscle cell (SMC) apoptosis. The present study examined nifedipine regulation of SMC apoptosis in carotids with or without a neointima. A neointima was produced by endothelial denudation of the left carotid of SHR and WKY rats. The contralateral carotid remained uninjured. Beginning at week 6 after injury, rats received nifedipine or placebo for 5 and 7 additional weeks. In situ terminal deoxynucleotidyl transferase (TdT)-mediated DNA labeling was used to mark apoptotic nuclei. Nifedipine reduced blood pressure in SHR but not WKY rats. Nifedipine had antihypertrophic effects in both SHR and WKY rats. In each strain, the greater reduction in cross-sectional area was seen in the neointima. In this tissue, nifedipine significantly increased TdT-positive SMC (4-fold at week 5 in SHR and 5-fold at week 7 in WKY rats) and reduced SMC number (70% in SHR and 29% in WKY rats) at week 7 compared to week 0. The effects were less pronounced in the injured and uninjured media. Thus, the antihypertrophic action of nifedipine is amplified in the neointima of SHR and WKY rat carotids, where histological evidence suggests SMC deletion via apoptosis.
Endothelin-1, a Regulator of Angiogenesis in the Chick Chorioallantoic Membrane
Authors: Cruz Amauri , Parnot Charles , Ribatti Domenico , Corvol Pierre , Gasc Jean-Marie
Published: April 2003

We investigated the angiogenic properties of endothelin-1 (ET-1) using a novel experimental approach involving the constant production and release of ET-1, which was achieved by grafting stably transfected Chinese hamster ovary (CHO) (CHO-ET-1) cell aggregates onto the chorioallantoic membrane (CAM) ectoderm. Macroscopic observation showed that CHO-ET-1 cell aggregates formed highly vascularized nodules surrounded by radially rearranged vessels, with a strong angiogenic response. 5-Bromo-2′-deoxy-uridine (BrdU) studies showed an increase in endothelial cell proliferation in the CAM vasculature around CHO-ET-1 nodules. An angiogenic response was also observed with gelatin sponges containing conditioned medium from CHO-ET-1 cells. The specific involvement of ET-1 in the angiogenic effect mediated by CHO-ET-1 was demonstrated by the reduction or abolition of neovascularized CHO-ET-1 nodules by (1) bosentan, a mixed antagonist of ETA/ETB receptors, (2) an ETA receptor antagonist (Ru69986) and (3) phosporamidon, an inhibitor of endothelin-converting enzyme-1 (ECE-1). We also demonstrated that VEGF was involved in CHO-ET-1-mediated angiogenesis, by using a specific inhibitor of VEGF tyrosine kinase receptor activity (PTK787/ZK 222584), which abolished CHO-ET-1 nodule formation and CAM neovascularization. Thus, our results show that exogenous ET-1 mediates angiogenesis in vivo.
Legal and Policy Issues in Genetics and Insurance
Authors: McGleenan Tony
Published: April 2003

Genetic screening and testing techniques provide a powerful diagnostic tool for the acquisition of predictive information. The potential value of such diagnostic techniques cannot be overstated. However, commercial organisations such as insurance companies and employers are also highly interested in the acquisition and use of genetic information. Concerns about the potential abuse of genetic information have stimulated a countercurrent of public pressure for restrictions on the use which can be made of genetic diagnostic information. In a number of countries this pressure has generated enough concern to stimulate legislatures to enact laws which curtail the use and acquisition of genetic information. This pattern has clearly emerged in the United States of America and there are indications that similar trends are developing in Europe. This paper examines the law and policy issues arising from the interface between genetics and insurance.
Achondroplasia in the Northern Province, South Africa: Case Finding through the Genetic Services System
Authors: de Koomen E. , van Dinther S.P.M. , Venter P.A. , Modiba J. , Hutamo C. , Shimange R. , Ramatumbu N. , Sithole M. , Tshivase O. , Gille J.J.P. , Dijkstra P.F. , ten Kate L.P.
Published: April 2003

Objectives: To assess the feasibility of case finding with regard to genetic disorders through the Primary Health Care Genetic Services System in the rural Northern Province, which is one of the poorest and least developed provinces in South Africa. Methods: Achondroplasia was used as the object of this pilot study. Genetically trained nurses invited patients with known or suspected achondroplasia to attend a clinic. The patients were seen by two medical students and a genetic scientist, who selected cases meeting predefined clinical and anthropometric criteria. X-rays were taken and blood was sampled for mutation analysis. The study took place in the period from March to August 1997. The patients were seen at six local hospitals. Reviewing of the X-rays and mutation analysis took place in Amsterdam, The Netherlands. Results: Thirty-one patients were selected and invited to the clinics. From this group, presented to the medical students, 17 patients were thought to have achondroplasia. The selection was based on clinical features and anthropometrical measurements. After reviewing the X-rays and adding the results from the mutation analysis, 15 out of these 17 patients were diagnosed as having achondroplasia. Conclusion: The genetic nursing system proved to be effective for case finding in this rural setting. The system may serve as a model for genetic services in other underdeveloped regions.
New Developments in Genetics for the New Millennium: The Concept of Clinical Bioinformatics
Authors: Modell Bernadette , Darlison Matthew
Published: April 2003

In the near future, professionals at all levels of health services, including primary health care, will need to be able to inform patients clearly and correctly about the health implications of many different DNA variants. This growing need presents a major information challenge for health systems. We propose that the challenge can be met by bringing together bioinformatics (supporting genetics) and health informatics (supporting clinical services and public health), into a new area of clinical and applied bioinformatics supporting community genetics. We are currently investigating the approach using the model of screening for haemoglobin disorders (see www.chime.ucl.ac.uk/APoGI/).
Testing for Hereditary Risk of Breast and Ovarian Cancer
Authors: Frank Thomas S.
Published: April 2003

Genetic testing provides an opportunity to characterize cancer risks in individuals that previously could only be estimated from epidemiological data. This paper reviews current data and opinions regarding identification and management of women with mutations in BRCA1 and BRCA2. In particular, its objectives are to summarize the risk of breast and ovarian cancer associated with inherited mutations in the genes BRCA1 and BRCA2, criteria to identify patients for whom genetic testing might be helpful, how such genetic tests are interpreted and management of patients with hereditary risk of breast and ovarian cancer. Conclusions indicate that there is increasing evidence that interventions to address hereditary risk of breast and ovarian cancer are effective. Hereditary risk assessment can enhance the health care of women with a personal or family history of ovarian or early-onset breast cancer.
Access to Genetic Tests: A Legal Perspective
Authors: Guillod Olivier
Published: April 2003

Access to genetic testing touches on human rights (self-determination, privacy, equal treatment) and therefore ought to be regulated rather than left to market forces. Developing an appropriate regulatory framework requires combining several types of regulations (legal as well as professional rules) depending on the nature of the standards (substantive or technical). At a time of economic globalisation, however, nations tend to become minor regulatory players on the world scene. They are made even less significant by the increasingly free movement of people and by the spectacular growth of telecommunications and e-commerce. The ‘interconnected global village’ therefore calls for stronger involvement of international and supranational organisations and for promoting international harmonisation. It is suggested that, as a first step, the Council of Europe could play a decisive role by drafting an additional protocol on medical genetics to the 1997 Convention on Human Rights and Biomedicine.
Triple Test Screening for Down Syndrome: Looking Back on a False-Positive Result and Having or Not Having a Triple Test in Subsequent Pregnancies
Authors: Evers-Kiebooms G. , Nys K. , Decruyenaere M. , Witters I. , Fryns J.-P.
Published: April 2003

Objectives:  It was the main aim of the present retrospective study carried out in Flanders to evaluate how women with a false-positive triple test result look back on their experience and decision making and how many of them make use of the triple test in subsequent pregnancies. Methods: All 508 women tested in the Centre for Human Genetics in Leuven in 1995 who had a positive triple test result followed by a normal amniocentesis outcome were invited to participate in a mailed questionnaire study with open and multiple choice questions in 1998. The response rate was 68%. Results: The answers to the multiple choice question assessing how they look back on their initial expectations regarding the exact meaning of the triple test revealed that less than one half reported that it concerned the identification of ‘a higher risk of carrying a child with Down syndrome (DS)’. Reporting correct initial expectations was significantly associated with a higher education level. The same holds for indecisiveness regarding pregnancy termination should the amniocentesis have detected a fetus with DS. As expected, a large majority of the women reported a high level of distress or worry after the communication of the positive triple test result. Overall the findings show that retrospectively most women had the feeling that the decision to have amniocentesis was their own decision rather than a professional’s. Of the subgroup with one or more subsequent pregnancies 70% had another triple test. Conclusions: The overall results of this study clearly reveal a need for a systematic approach aimed at better informing and counselling pregnant women about the implications and limitations of the triple test. Notwithstanding the reported high level of distress caused by a positive triple test result, a large majority of the women with subsequent pregnancies had another triple test; they represent a clearly higher percentage than in another recent study.
The Overlap between Alzheimer’s Disease and Vascular Dementia: The Role of White Matter Changes
Authors: Wallin A.
Published: April 2003

As there is some overlap between Alzheimer’s disease (AD) and vascular dementia (VaD), it can be assumed that some particular features that they have in common are responsible for this overlap. One of the candidates is white matter changes whose presence in variants of the two entities is described in this paper. A common, although much debated, division of AD is into two types, type I usually with early and type II usually with late onset. As to VaD, the division can be based on neuropathological changes and vascular disease mechanisms. In one subtype, ‘subcortical white matter dementia’, white matter lesions are conspicuous features. The overlap between this subtype and AD type I is small, but the overlap is considerable between the same subcortical subtype and AD type II. In the latter, white matter changes and Alzheimer encephalopathy may interact to produce dementia.
The Caregiver’s Role in Alzheimer’s Disease
Authors: Rabins P.V.
Published: April 2003

The majority of persons with Alzheimer’s disease (AD) are cared for by family members in their home. Research from several studies has shown that these care providers have rates of emotional morbidity three times that seen in age-similar individuals. This paper will review the epidemiological data on the incidence and prevalence of emotional disability in caregivers. It will also review the 11 treatment studies in the literature in which blinded intervention was carried out. Nine of these 11 studies show that intervention was more beneficial than the placebo comparison treatment. Both educational and emotional support were effective. However, when compared with each other, emotional support was more effective; the combination may be more effective than either alone. Preliminary evidence suggests that intervention on behalf of caretakers may delay the need for institutionalization of family members with AD.
Overview of Frontotemporal Dementias and the Consensus Applied
Authors: Neary David
Published: April 2003

Frontotemporal dementia, progressive nonfluent aphasia and semantic dementia are distinct clinical syndromes arising from degeneration of the frontotemporal lobes, each syndrome being determined by the distribution of degenerative change within the brain. The Lund-Manchester consensus statement provided diagnostic guidelines for frontotemporal dementia, which were devised to improve its clinical and pathological recognition. The Lund-Manchester groups together with researchers from the United States, Canada and Europe have sought to build on those original criteria to produce a revised set of consensus criteria for each of the major clinical syndromes of frontotemporal lobe degeneration. It is hoped that these new criteria will serve to highlight an important and neglected form of dementia and provide the impetus for clinical and basic scientific research.
Comparative Cognitive Neuropsychological Studies of Frontal Lobe Function: Implications for Therapeutic Strategies in Frontal Variant Frontotemporal Dementia
Authors: Rahman S. , Robbins T.W. , Sahakian B.J.
Published: April 2003

Patients with mild frontal variant frontotemporal dementia (fvFTD) who attend the clinic are usually unaware of the pervasive changes in their personality and behaviour, despite the fact it is these changes which have prompted the referral from the patient’s spouse or carer. Comparative studies across various species offer unique insights into the heterogeneous structure and functions of the prefrontal cortex, and can allow a novel approach to the precise identification of the neuropsychological deficits present in these patients. We have found that they may show marked deficits on tests sensitive to ventromedial prefrontal or orbitofrontal function, in the relative absence of impairments on tests sensitive to dorsolateral prefrontal function. We highlight important differences in the neurocognitive profile of these patients with that of patients with other neurodegenerative conditions, including basal ganglia diseases and dementia of the Alzheimer type. The specific nature of these neuropsychological deficits, together with converging evidence from clinical and neuropathological studies, may provide useful clues about the predominant locus of dysfunction in the early stages of fvFTD and possible underlying neurotransmitter abnormalities. This is important for the successful development of therapeutic intervention strategies for both cognitive and behavioural symptoms in fvFTD. Finally, we evaluate critically the rationales for therapeutic modulation of noradrenergic, serotonergic and dopaminergic neurotransmitter systems at various stages of disease.
Neuropathology of Chromosome-17-Linked Dementia
Authors: Sima Anders A.F. , D’Amato Constance , Foster Norman L.
Published: April 2003

We describe the characteristic neuropathologic changes in chromosome-17-linked dementia. Identified cases to date demonstrate a uniform pathology consisting of neuronal loss, gliosis and vacuolization of frontal, anterior cingulate and temporal cortex and occipital association areas. Similar changes are present in substantia nigra, ventral striatum and amygdala. Hippocampus itself is spared, whereas the afferent perforant tract is consistently affected. Characteristic neuronal inclusions consisting of lattice-like neurofilaments are present in subcortical nuclei and glial cytoplasmic tau-positive inclusions are present throughout the white matter. These pathologic changes appear to be unique for chromosome-17-linked dementia.
Elevated Levels of Fragmented DNA Nucleosomes in Native and Activated Lymphocytes Indicate an Enhanced Sensitivity to Apoptosis in Sporadic Alzheimer’s Disease
Authors: Eckert Anne , Oster Manfred , Zerfass Richard , Hennerici Michael , Müller Walter E.
Published: April 2003

Apoptotic cell death is thought to be the most likely mechanism of cell death contributing to neurodegeneration in Alzheimer’s disease (AD). Here, we provide evidence that in sporadic AD cases the vulnerability of peripheral cells to undergo apoptosis is increased compared to non-demented elderly controls and, very importantly, to patients with subcortical vascular encephalopathy (SVE) as another, but demented control group. Quiescent ‘native’ and ‘activated’ lymphocytes from AD patients that were predisposed to commit apoptotic cell death by priming the cells with interleukin-2, are shown to accumulate apoptosing cells to a significantly higher extent in spontaneous and in oxidative stress-induced in vitro apoptosis. Our results demonstrate robust differences in cell death sensitivity between AD and vascular dementia. In none of the conditions investigated, lymphocytes from SVE patients were significantly different from non-demented controls. The comparable findings of a higher extent of apoptotic features in neurons and in peripheral blood cells of AD patients are remarkable and may suggest a rather general modulation of apoptotic mechanisms by the disease, which even can be picked up at the level of peripheral lymphocytes under specific in vitro conditions.
A Comparison of Medial and Lateral Temporal Lobe Atrophy in Dementia with Lewy Bodies and Alzheimer’s Disease: Magnetic Resonance Imaging Volumetric Study
Authors: Barber R. , McKeith I.G. , Ballard C. , Gholkar A. , O’Brien J.T.
Published: April 2003

Objectives: To compare medial and lateral temporal lobe atrophy on magnetic resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD), and to examine the relationship between volumetric indices and cognitive and non-cognitive symptoms. Methods: T1-weighted 1.0-tesla MRI scans were acquired in elderly subjects with DLB (n = 26; mean age = 75.8 years) and AD (n = 22; 77.3 years) and normal controls (n = 26; 76.2 years). MRI-based volume measurements of the hippocampus, parahippocampus, fusiform gyrus, combined inferior and middle temporal gyri, and superior temporal gyrus were acquired. Results: Hippocampal and parahippocampal volumes were significantly larger in subjects with DLB compared to AD. Differences in hippocampal volumes between DLB and AD were observed across the entire length, and in all subjects with dementia there was a loss of hippocampal asymmetry compared to normal controls. Atrophy of temporal lobe structures correlated with memory impairment in both groups, and with age in DLB. There was no association between atrophy and psychotic symptoms in either group. Conclusions: Subjects with DLB and AD have a different pattern of temporal lobe atrophy with the most striking differences relating to medial rather than lateral temporal lobe structures. These structural differences could explain the relative preservation of memory function in DLB compared to AD.
Comparison of Brain Perfusion in Corticobasal Degeneration and Alzheimer’s Disease
Authors: Okuda Bungo , Tachibana Hisao , Kawabata Keita , Takeda Masanaka , Sugita Minoru
Published: April 2003

To compare brain perfusion between corticobasal degeneration (CBD) and Alzheimer’s disease (AD), we measured regional cerebral blood flow (rCBF) semiquantitatively with single-photon emission computed tomography in 10 patients with CBD and 16 with AD. There was no significant difference in age or illness duration between the patients with CBD and AD. Mini-Mental State Examination scores were significantly lower in the AD patients than in the CBD patients. All CBD patients showed asymmetric akinetic-rigid syndrome and limb apraxia. Four CBD patients were demented, and 1 AD patient had parkinsonism. Compared with 12 age-matched control subjects, the average of the left and right rCBF values for the CBD patients was significantly reduced in the prefrontal, anterior cingulate (AC), medial premotor, sensorimotor (SM), posterior parietal (PP) and superior temporal (ST) cortices as well as in the basal ganglia (BG) and thalamus (Th), while the prefrontal, PP and ST cortices were significantly hypoperfused in the AD patients. In the CBD patients, rCBF was significantly less in the AC and SM cortices, and in the Th and BG, and significantly greater in the PP cortex than in the AD patients. Interhemispheric differences of rCBF in the inferior prefrontal and SM cortices were significantly greater in the CBD patients than the AD patients. It is concluded that rCBF comparison may aid in differentiating CBD from AD.
Apolipoprotein E Genotype, Vascular Risk and Early Cognitive Impairment in an African Caribbean Population
Authors: Stewart Robert , Russ Carsten , Richards Marcus , Brayne Carol , Lovestone Simon , Mann Anthony
Published: April 2003

A reduced risk of Alzheimer’s disease (AD) associated with the apolipoprotein E (APOE) Ε4 allele is reported in populations of African origin. In order to clarify possible reasons for this, we examined the association between APOE genotype and early cognitive impairment in a community-based African Caribbean UK population aged 55–75 years. APOE genotype was available for 202 participants, 57 (28%) of whom were classified as having relative cognitive impairment on a battery of neuropsychological tests. Cognitive impairment was negatively associated with Ε2 and positively but more weakly associated with Ε4. Effects of both alleles increased markedly after age 70. The effect of Ε4 was increased in combination with hypertension, diabetes or lower educational attainment, but these factors did not influence Ε2 effects. Cholesterol and triglyceride levels partially explained effects of Ε2, but did not account for those of Ε4. A reduced association between Ε4 and later AD in populations of African origin is unlikely to be explained by reduced cognitive effects or by differential mortality. However, it may be accounted for by vascular comorbidity. The different patterns of association between Ε2 and Ε4 alleles suggest different pathways of effect.
Retinaldehyde Alleviates Rosacea
Authors: Vienne Marie-Pierre , Ochando Nicole , Borrel Marie-Thérèse , Gall Yvon , Lauze Christophe , Dupuy Patrick
Published: April 2003

Background: Anecdotal observations suggest that retinoic acid may be effective in mild rosacea. Aim: Our aim was to investigate, by an exploratory clinical and instrumental study, the effects of a topical formulation with the retinoic acid precursor retinaldehyde, in patients with vascular signs of facial rosacea. Methods: Female patients were treated with a 0.05% retinaldehyde cream that was applied once daily for 6 months. Clinical assessments of persistent erythema and telangiectasia were performed every month, using a 4-point severity score (absent to severe). The clinical response for each parameter was defined as a decrease of at least 1 grade in the severity score. In addition, erythema was further evaluated by measurement of the a* parameter, using a spectrophotometer on lesional and nonlesional areas. Results: A total of 23 women comprised the study population. At baseline, 10 patients had diffuse erythema, 3 patients had isolated telangiectasia and 10 patients had both. During retinaldehyde treatment, a clinical response was revealed in about 75% of the patients with erythema, after 5 months (p < 0.05). Similarly, isolated telangiectasia responded to retinaldehyde, although to a lesser extent and after a longer period of treatment (46% responders after 6 months, nonsignificant). Using the spectrophotometer, the a* parameter diminished in patients with erythema by about 15%, after 2 months of treatment (p = 0.001). Conclusion: This study indicates that retinaldehyde has beneficial effects on the vascular component of rosacea.
Neuropsychiatric Toxicity of Antiviral Treatment in Chronic Hepatitis C
Authors: Fontana Robert
Published: April 2003

Dose-dependent, reversible neuropsychiatric toxicity is reported in up to 30–40% of chronic hepatitis C patients treated with 6–12 months of interferon-α or interferon-α plus ribavirin combination therapy. Although risk factors remain poorly defined, neuropsychiatric side effects may be severe and dose-limiting in as many as 10–20% of treated patients. Diagnosis relies upon the detection of clinically apparent neuropsychiatric symptoms and the emerging use of self-administered mood inventories and questionnaires. The current stepwise approach to management includes evaluation and treatment of systemic side effects, early use of adjuvant medications, and interferon-α and ribavirin dose reduction or cessation with psychiatric referral in selected cases. Although the cellular basis of the neuropsychiatric toxicity of interferon-α remains unknown, several hypothesis involving changes in central adrenergic, seratonergic, opioid and neuroendocrine pathways have been proposed. Recognition and management of the neuropsychiatric side effects of antiviral therapy will be of growing clinical importance as additional patients with chronic hepatitis C are treated and longer durations of therapy are utilized.
Influence of Chronic Alcohol Abuse on Hepatitis C Virus Replication
Authors: Anand B.S. , Velez Maria
Published: April 2003

Background: Patients with alcoholic liver disease have a high prevalence of hepatitis C virus (HCV) infection. Several workers have shown that HCV-infected alcoholics have more severe biochemical and histological evidence of liver disease than anti-HCV-negative patients. One possible mechanism for the increased liver damage is that alcohol may have a stimulatory effect on HCV replication. The present study was carried out to examine this issue in detail. Methods: Sixty-eight HCV-infected patients, comprising of 50 chronic alcoholics, consuming 80 g or more of alcohol daily for at least 5 years, and 18 completely abstinent subjects were included in the study. Quantitative HCV-RNA was performed by the branched chain DNA (bDNA) technique. Results: There was no significant difference in the mean serum HCV titers in chronic alcoholics compared to nonalcoholic subjects. Linear regression analysis showed no correlation between the daily ethanol consumption and HCV titers. Seven of the chronic alcoholics, 4 of whom were continuing to drink and 3 who had become abstinent, were retested after 6 months. There was no definite trend in the viral titers, either in abstinent individuals or in those who continued to drink. Conclusions: These findings suggest that chronic alcohol abuse does not influence the HCV load in the serum. Therefore, the observation that alcoholics with HCV infection have more severe liver damage requires some other explanation than increased HCV viral titers.
Medical Therapy versus Antireflux Surgery in Barrett’s Esophagus: What Is the Best Therapeutic Approach?
Authors: Klaus Alexander , Hinder Ronald A.
Published: April 2003

We conducted a review of the literature comparing medical treatment with antireflux surgery in patients with Barrett’s esophagus (BE). In particular, we wanted to assess the efficacy of medical and surgical therapies in preventing the progression of Barrett’s epithelium to dysplasia or adenocarcinoma of the esophagus. In general, few BE patients show complete regression of BE epithelium following medical or surgical therapy. The incidence of developing dysplasia or cancer following surgical therapy appears to be less than with medical therapy; however, there is an insufficient number of current, randomized controlled studies to confirm this. Surveillance of BE is required regardless of treatment. This review suggests that there may be a trend in support of surgery being somewhat better than medical therapy in the prevention of BE progression and adenocarcinoma. We suggest that patients with BE should be considered for antireflux surgery – in particular, certain subgroups of BE patients.
Acid Suppression and Reepithelialization after Ablation of Barrett’s Esophagus
Authors: Overholt Bergein F.
Published: April 2003

The role of acid reflux in the development of esophageal columnar epithelium was first described in the early 1970s in the canine esophageal reflux model. In the presence of acid reflux, columnar epithelium developed at the site of induced esophageal mucosal injury. When reflux was suppressed, most epithelium reverted back to squamous mucosa. Similar findings in human patients with Barrett’s esophagus (BE) who were treated with laser ablation were first described in 1993. While acid suppression with antireflux surgery or proton pump inhibitors (PPIs) has proven insufficient to completely reverse BE, ablation of the lesion followed by acid suppression may be a promising option. Although at least one report disputes the importance of complete acid suppression following mucosal ablation of BE, most investigators use full-dose PPI therapy following ablation, in the belief that full acid suppression provides an environment that allows the esophageal progenitor cell to develop squamous mucosa. This article provides a review of the literature to date regarding ablative therapies and acid suppression for patients with BE.
Pathophysiology of Renal Dysfunction in Cirrhosis
Authors: Ginès Pere , Sort Pau
Published: April 2003

The kidney plays a key role in some of the major complications of cirrhosis, specifically the development of ascites, edema and/or pleural effusions and renal failure. Moreover, patients with ascites may develop spontaneous bacterial peritonitis, which is another severe complication of cirrhosis. The most common abnormality of renal function in cirrhosis is sodium retention. Sodium retention is often associated with an impaired ability to eliminate a regular water intake, which may lead to dilutional hyponatremia due to a disproportionate increase in total body water relative to the total sodium content.
Transjugular Intrahepatic Portosystemic Stent Shunt for Acute Variceal Bleeding: An Option?
Authors: Brensing Karl August
Published: April 2003

Hemorrhage from esophageal and/or gastral varices is a major and often fatal complication of portal hypertension caused by liver cirrhosis [1]. Each bleeding episode is associated with a mortality rate in the range of 30–50%, which is much higher than after acute myocardial infarction. Thus, cirrhotics with acute variceal bleeding are high-risk patients and should be treated in experienced intensive care units to provide immediate hemostasis and adequate prevention of early rebleeding and multiorgan complications.
Medical Decompressive Therapy for Prophylaxis of Rebleeding
Authors: Lebrec Didier
Published: April 2003

Among diVerent substances which decrease the degree of portal hypertension, only β-adrenoceptor antagonists are used to prevent recurrent hemorrhage in patients with cirrhosis [1]. Controlled trials comparing endoscopic sclerotherapy with or without β-adrenoceptor antagonists have also been performed.
NO Synthase in the Liver: Prospects of in vivo Gene Transfer
Authors: Fevery J. , Roskams T. , van de Casteele M. , Omasta A. , Janssens S. , Desmet V. , Nevens F.
Published: April 2003

Portal hypertension is a major complication of cirrhosis, portal vein thrombosis, presinusoidal liver diseases such as schistosomiasis and postsinusoidal disorders such as veno-occlusive disease or Budd-Chiari syndrome. The elevated pressure results from enhanced resistance in the portal venous system and from augmented influx of blood due to splanchnic vasodilatation and hypervolemia [1]. The enhanced intrahepatic resistance in cirrhotic livers is partly due to fibrosis [2] and partly to active vasoconstriction, since Bathal and Grossman [3] could demonstrate in the isolated perfused cirrhotic rat liver that the increased portal vascular resistance could be decreased by medication.
Pathology of Hepatocellular Carcinoma
Authors: Pfeifer U.
Published: April 2003

Since hepatocellular carcinoma (HCC) is taken in the context of this workshop as a complication of liver cirrhosis, the old question has to be raised again whether the factors responsible for the development of liver cirrhosis, e.g. viral infection, alcohol damage, metabolic distur- bances, are at the same time causative factors for the development of HCC. As an alternative, cirrhosis itself, i.e. independent of the diVerent causative factors, has been proposed to represent the main precancerous condition.
Screening for Hepatocellular Carcinoma
Authors: Colombo Massimo
Published: April 2003

The medical aim of screening is to improve the health of the general population by early detection and treatment of disease. The economic aims are, in the short term, to save the time of highly trained doctors by using technicians or automated procedures, and in the long run, to treat early disease so as to lengthen the productive life of the persons at risk [1]. Thus, screening has been widely spreading as a practical approach to reducing the mortality rate from hepatocellular carcinoma (HCC).
Paediatric and Hereditary Aspects of Chronic Pancreatitis
Authors: Dodge John A.
Published: April 2003

Cystic fibrosis is by far the commonest cause of chronic pancreatitis in children, but pancreatitis itself is only rarely its presenting feature. In this paper an hypothesis for the development of the pancreatic lesions is presented. Impaired activation of pancreatic proteases in the small intestine is perceived as the pivotal problem that leads to continual feedback release of cholecystokinin, thus, in effect, causing a chronic hyperstimulation pancreatitis with intra-acinar activation of zymogens and, when bicarbonate secretion falls, precipitation of ‘Reg’ and other proteins in the duct system. This position contrasts with that in hereditary pancreatitis in which a mutation in the cationic trypsinogen gene leads to a form of trypsin that resists degradation by mesotrypsin and enzyme Y. A survey of the literature suggests that oxidant stress is a plausible contributor to pancreatic injury in both these diseases and in several other conditions linked with childhood pancreatitis.
Study on Pancreatic Insufficiency (Chronic Pancreatitis) and Steatorrhea in Japanese Patients with Low Fat Intake
Authors: Nakamura Teruo , Tando Yusuke , Yamada Naoko , Watanabe Taku , Ogawa Yoshiji , Kaji Asako , Imamura Ken-ichi , Kikuchi Hiroaki , Suda Toshihiro
Published: April 2003

The incidence of steatorrhea is said to be lower and its grade milder in Japanese because their fat intake is lower than that of Europeans and Americans. Failure to take this into account creates difficulties when attempting to compare data on pancreatic exocrine insufficiency in different countries. The authors examined the incidence and grade of steatorrhea in Japanese chronic pancreatitis (CP) patients whose daily fat intake was <40 g (25 patients) or ≥40 g (35 patients). In addition, 23 CP patients with steatorrhea and daily fecal fat excretion ≥5 g were given a pancreatic enzyme preparation at a dose 3–8 times higher than the usual dose to investigate its effect on fecal fat excretion. Among CP patients whose fat intake was <40 g, the incidence of fecal fat excretion <5 g was 56% and that of fecal fat excretion ≥10 g (severe steatorrhea) was 8%. In CP patients whose fat intake was ≥40 g, the incidences were 27.9 and 34.9%, respecetively; a significant increase in the number of affected patients was noted when fat intake was ≥40 g. The fat absorption rate was 76.2% among patients whose fat intake was <40 g and 77.8% among patients whose fat intake was ≥40 g, revealing no significant difference between the two groups. The proportion of CP patients whose fat absorption rate ≦80% was 32% at a fat intake <40 g and 39% at a fat intake ≥40 g, revealing no significant difference between the two groups.
The Role of Octreotide in the Treatment of Gastroenteropancreatic Endocrine Tumors
Authors: Degen Lukas , Beglinger Christoph
Published: April 2003

Gastrointestinal-endocrine pancreatic (GEP) tumors are rare, occurring in less than 1% of the population. They are usually divided into functionally active or nonfunctioning tumors. Functionally active tumors produce a variety of substances (mainly peptides or serotonin). The tumors are classified according to the dominant clinical syndrome that they cause. Surgery is the treatment of choice in patients with GEP tumors and it should always be considered, even if total tumor excision cannot be achieved. Reduction in tumor mass (debulking) may improve the patients symptoms. Medical treatment is used in patients with advanced malignant endocrine tumors. The most important compounds to control symptoms in these patients are somatostatin analogues. Natural somatostatin is produced in different molecular forms and has inhibitory effects on a number of functions. The observation of potent inhibitory effects on various hormone-secreting cells led to the use of somatostatin for symptomatic treatment of peptide-secreting tumors. Natural somatostatin is not suitable for long-term clinical application; therefore, synthetic somatostatin analogues were developed with improved pharmacokinetic characteristics. The best characterized analogue, octreotide, has been successfully applied to patients with functioning GEP tumors. Octreotide can dramatically ameliorate the debilitating symptoms of patients suffering from the clinical manifestations of endocrine tumors such as diarrhea and flushing. The success of octreotide therapy is best reflected in terms of its impact on the patient''s quality of life as defined by the activity to perform normal daily activities.
Autoimmunity to Keratinocyte Acetylcholine Receptors in Pemphigus
Authors: Grando Sergei A.
Published: April 2003

Pemphigus autoimmunity is not limited to antides- moglein antibodies. Nondesmoglein antibodies induce pemphigus-like lesions in neonatal mice. Acantholytic activity of pemphigus IgG harbors pharmacologic effects on keratinocyte shape and adhesion. Acantholytic antireceptor autoantibodies target: (1) a novel human α9 acetylcholine receptor regulating keratinocyte adhesion, and (2) pemphaxin, a novel keratinocyte annexin-like molecule binding acetylcholine. A ‘multiple-hit’ hypothesis reconciles recent findings of anti-acetylcholine-receptor autoimmunity in pemphigus and the fact that pemphigus patients also develop autoantibodies to adhesion molecules. The antiacantholytic activity of cholinergic agonists suggests a novel avenue for the development of a nonhormonal treatment of pemphigus.
Facial Superficial Porokeratosis
Authors: Navarro V. , Pinazo I. , Martínez E. , Monteagudo C. , Jordá E.
Published: April 2003

A case of exclusively facial superficial porokeratosis occurring in a young man is reported. These lesions were asymptomatic and remarkable because of their location. Histopathology revealed a typical superficial porokeratosis. Exclusively facial porokeratosis is an unusual clinical presentation. To our knowledge, it is the second report of a case with exclusively facial involvement.
Sunscreen and Risk of Osteoporosis in the Elderly: A Two-Year Follow-Up
Authors: Farrerons Jordi , Barnadas Maria , López-Navidad Antonio , Renau Antoni , Rodríguez José , Yoldi Beatriz , Alomar Agustin
Published: April 2003

Background: It has been suggested that the use of sunscreens to prevent skin cancer may put the population at risk of vitamin D deficiency, which in turn may lead to secondary hyperparathyroidism, loss of cortical bone and, ultimately, osteoporotic fractures. Objective: To investigate whether sunscreen SPF15 may lead to loss of bone mass. Methods: We followed 10 sunscreen users and 18 controls over 2 years, including two summers, two winters and a basal period (winter). Bone mass was evaluated each season with dual x-ray absorptiometry. Results: During follow-up, mild fluctuations in bone mass could be seen at Ward’s site in both groups, without a definitive pattern. At the final visit, no significant loss of bone mass was observed in sunscreen users or in the control group. We did not observe any significant differences between groups throughout the study. Conclusion: Although the study samples in this work are small, and a slight variation in bone mass may not be detected, in a clinical setting, sunscreen SPF15 protection does not seem to increase the risk of osteoporosis.
Clinico-Immunological Heterogeneity in Comèl-Netherton Syndrome
Authors: van Gysel D. , Koning H. , Baert M.R.M. , Savelkoul H.F.J. , Neijens H.J. , Oranje A.P.
Published: April 2003

Background: Comèl-Netherton syndrome (CN) is characterized by atopic-eczema-like skin abnormalities combined with linear ichthyotic lesions, hair shaft abnormalities and atopy with high IgE levels. Objective: Five children with CN are described. In 2 of the 3 CN patients still alive, analysis of cytokines regulating IgE synthesis was performed. Methods: In peripheral blood mononuclear cells and cultures of purified T cells, mRNA expression and protein production of interleukin 4 (IL-4), IL-13, IL-5 and interferon γ were analysed. The results were compared with the values in age-matched atopic dermatitis patients and healthy children. Results: The 5 CN patients showed striking differences in disease severity and evolution. Marked differences were found in several cytokines in the 2 analysed CN patients. Low percentages of natural killer cells were observed in both CN patients. Conclusion: The regulation of IgE production in patients with CN is varied and complex. The CN patients were heterogeneous in terms of Th2 skewing.
Widespread Cutaneous Carcinomas Associated with Human Papillomaviruses 5, 14 and 20 after Introduction of Methotrexate in Two Long-Term PUVA-Treated Patients
Authors: Zumtobel Ulf , Schwarze Hartmut P. , Favre Michel , Taïeb Alain , Delaunay Michèle
Published: April 2003

Background: PUVA treatment for patients with severe psoriasis has been demonstrated to be highly effective. However, an increased risk of nonmelanoma and melanoma skin cancers has been reported. It is generally accepted that the risk of squamous-cell carcinoma (SCC) is significantly increased in patients with long-term PUVA therapy. The role of methotrexate (MTX) and infection with oncogenic human papillomaviruses which may act as cocarcinogens is poorly documented. Case Reports: Two cases of multiple SCCs associated with numerous PUVA keratoses and PUVA freckles after long-term PUVA therapy and subsequent treatment with MTX are presented. In 1 case, the tumor progressed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification. Conclusion: These observations support the concept that long-term PUVA treatment is carcinogenic and rise questions concerning an additional influence of MTX in the development and progression of skin cancer. The risk of metastatic SCC seems to be underestimated in high-dose PUVA-treated patients due to longer latency for developing metastases and the small number of studies with long-term follow-up. Treatment with MTX should be considered cautiously in patients previously exposed to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic skin lesions detected only with the highly sensitive nested PCR method is not necessarily a proof of their implication in skin carcinogenesis.
Scytalidium dimidiatum Melanonychia and Scaly Plantar Skin in Four Patients from the Maghreb: Imported Disease or Outbreak in a Belgian Mosque?
Authors: Arrese J.E. , Piérard-Franchimont C. , Piérard G.E.
Published: April 2003

Scytalidium dimidiatum is a geophilic dematiaceous, non-dermatophyte mould that can become a pathogen for plants and humans particularly in tropical and subtropical regions. We report 4 cases of S. dimidiatum onychomycosis presenting clinically as thickened and dark toenails. The skin of the soles was scaly. The time and location of the contaminations were uncertain. Indeed, the patients were ancient immigrants from the Maghreb to Belgium. They were also regularly travelling to their countries of origin. They were also often barefoot in the same Belgian mosque. The disease was unresponsive to current oral antifungal treatments.
Insect Bite Reactions: An Update
Authors: Stibich Adam S. , Carbonaro Paul A. , Schwartz Robert A.
Published: April 2003

Contact with insects may induce cutaneous or systemic reactions, ranging from little more than annoying to life threatening. The diagnosis depends on maintaining a high index of suspicion and being familiar with the insect fauna of the patient’s environment and area of travel.