bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascularization of Developing Human Olfactory Neuroepithelium – A Morphometric Study
Authors: Sangari S.K. , Sengupta P. , Pradhan S. , Khatri K.
Published: April 2003

The present study reveals intraepithelial capillaries in the olfactory neuroepithelium of human fetuses aged between 12 and 24 weeks of gestation, which disappear at birth. The area occupied by the intraepithelial capillaries increases significantly with fetal age (0.047 ± 0.014 μm2/μm2 at 12 weeks and 0.101 ± 0.025 μm2/μm2 at 24 weeks) and with the thickness of the epithelium (45.00 ± 6.74 μm at 8 weeks and 64.10 ± 8.51 μm at 24 weeks). The vascularization of the developing neuroepithelium may suggest increased metabolic demand during development and maturation of the olfactory neuroepithelium, and postnatal retreat of capillaries to the underlying lamina propria may suggest diffusion of nutrients and gases from blood vessels into the lamina propria and direct gaseous exchange from the atmosphere.
The Human Anterior Tympanic Artery
Authors: Wasicky Richard , Pretterklieber Michael L.
Published: April 2003

The variability of the origin of the anterior tympanic artery was investigated in 104 individuals of both sexes. A surprising laterality was found: thus, while the left anterior tympanic artery originated as a singular vessel from either the maxillary or the superficial temporal artery with almost equal frequencies (44.7 and 45.9%, respectively), the right anterior tympanic artery predominantly branched off from the maxillary artery (77.8% of cases). Besides the origin from either the maxillary artery or the superficial temporal artery, also anterior tympanic arteries branching off from the external carotid artery were found to occur (4% on the left and 1% on the right side). Although in the majority of individuals, a singular anterior tympanic artery occurred within the infratemporal fossa, duplications of the anterior tympanic artery were found to be present: in one case on the right and in 8 cases on their left side. In 1 female individual, a triplet of left anterior tympanic arteries was found to supply the tympanic cavity. Also in these cases, the anterior tympanic artery arose from either the external carotid, the superficial temporal or the maxillary artery. In singular cases, even several other branches of the maxillary artery, viz. the deep auricular, middle, and accessory meningeal, as well as the posterior deep temporal, inferior alveolar and masseteric arteries were found to form common trunks with the anterior tympanic artery.
Distribution of Carbonic Anhydrase Isozyme VI in the Developing Bovine Parotid Gland
Authors: Asari Masao , Miura Kohshi , Ichihara Nobutsune , Nishita Toshiho , Amasaki Hajime
Published: April 2003

The distribution of bovine carbonic anhydrase isozyme VI (CA-VI), purified from bovine saliva, was studied immunohistochemically using antiserum against bovine CA-VI in bovine parotid glands during fetal and postnatal development. A weak expression of CA-VI in undifferentiated epithelial cells and ductal cells was observed in a 4- to 5-month-old fetus with a 26-cm crown-rump length. The reaction in both acinar and ductal cells subsequently persisted during late gestation and birth. Although anti-CA-VI reactivity was still seen in both regions immediately following birth, the reactivity had almost completely disappeared from most duct segments by 1 month following birth. Changes in the localization and time-dependent expression of the isozyme in parotid glands may reflect changes in the biological function of structurally closely related isozymes.
Early Bone Healing Events following Rat Molar Tooth Extraction
Authors: Devlin Hugh
Published: April 2003

Healing of the rat tooth extraction socket occurs rapidly, indicating a mechanism for cancellous bone formation occurring swiftly throughout the matrix. The residual periodontal ligament is evident at 2 days after extraction and its rich collagen type III fibre content may form a template for future cancellous bone formation. In the remainder of the early tooth extraction socket, fibronectin staining was generalized. The widespread distribution of fibronectin staining has given rise to speculation that the function of fibronectin may be important in granulation tissue formation, by providing a template matrix for fibroblast migration. Osteoprogenitor cells migrated into the socket from the surrounding bone, and produced decorin and proMMP-13 (procollagenase-3). ProMMP-13 was only expressed at sites of new bone formation, e.g. the border of the recently formed trabecular islands or the periphery of the closing socket. Collagen type I fibres were formed later, and were especially evident at 6 days after extraction. The pattern of distribution of both collagen type I and III fibres were similar as they passed from the bone margin towards the centre of the socket – in the same direction as the forming bone trabeculae. Bone formation occurs by rapid movement of the osteoprogenitor cells along these collagen fibres to allow a rapid healing, rather than that of resorption followed by slow bone deposition.
New Approaches towards ex vivo and in vivo Gene Therapy
Authors: Hauser H. , Spitzer D. , Verhoeyen E. , Unsinger J. , Wirth D.
Published: April 2003

A number of hurdles have to be overcome for efficient and specific gene therapy approaches. Here, we report on two different strategies that should lead to an improvement of current protocols. A strategy is presented to tag unique chromosomal integration sites by means of retroviral infection, which can be reused for exchange with the gene of interest by action of site-specific recombinases. Targeting exchange is achieved in one step with 100% efficiency by a stringent positive selection, which makes further screening superfluous. With this strategy a predictable gene expression is obtained for foreign genes integrated into a predefined chromatin structure. A second approach aims at the stabilization of mouse retroviruses towards human serum which is a prerequisite for in vivo gene therapy protocols. To stabilize murine leukemia virus-based retroviruses against human serum, complement regulatory proteins were fused to the retroviral ENV proteins. This resulted in infectious and human complement-protected particles.
Emerging Therapies in Hepatology: Liver-Directed Gene Transfer and Hepatocyte Transplantation
Authors: Ott M. , Schmidt H.H.-J. , Cichon G. , Manns M.P.
Published: April 2003

Gene transfer and epithelial cell transplantation technologies play an important role in the development of new therapeutic concepts for liver diseases. Although liver organ transplantation has revolutionized the treatment of a wide spectrum of acute and chronic liver diseases, gene- and cell-based therapies are emerging at an astonishing pace, because they promise to be less invasive, less costly and at least as effective as currently established therapy protocols. Experimental gene therapy models have been developed for a wide spectrum of liver diseases, including hereditary liver disorders, malignant liver disease and viral hepatitis. Hepatocyte transplantation (HcTx) is being explored as treatment of severe chronic and acute liver failure as well as for hereditary liver diseases. Most of these procedures and techniques are still experimental or have been applied to a small number of patients only. Rigorous clinical evaluation will finally demonstrate the usefulness of each new procedure in the daily clinical care of patients with liver disease. In this review, we have attempted to provide an introduction and survey of the topics of gene therapy and HcTx with specific examples of laboratory and clinical achievements highlighting potential applications in liver diseases.
Bioartificial Cartilage
Authors: Rudert Maximilian , Hirschmann Frank , Schulze Monika , Wirth Carl Joachim
Published: April 2003

Cartilage is a highly differentiated tissue. Its three-dimensional composition of cells and matrix is able to resist intensive mechanical loads. The capacity of cartilage tissue for regeneration is limited. Chondrocytes are responsible for matrix production of cartilage tissue. Enzymatic isolation and expansion of chondrocytes with cell culture techniques has been improved in the last years. These cells can be cultured on different three-dimensional culture systems suitable for transplantation to repair localized cartilage defects. Two types of bioresorbable polymer fleece matrices (PLLA and a composite fleece of polydioxanone and polyglactin) and lyophilized dura as a biological carrier are tested. Phenotypic and morphological appearance of the cultured articular rabbit chondrocytes is preserved on all three types of transport media. Production of glycosaminoglycans has been shown by Alcian blue staining, production of collagen by azan staining. Chondroitin 4- and 6-sulfate are detected immunohistochemically in the created constructs. The different carriers have specific characteristics regarding their suitability for the creation of bioartificial cartilage. This tissue is transplantable into articular cartilage defects and could, therefore, improve the minor intrinsic healing capacity of cartilage tissue.
Capillarity, Fibre Types and Fibre Morphometry in Different Sampling Sites across and along the Tibialis anterior Muscle of the Rat
Authors: Torrella Joan Ramon , Whitmore Jessica M. , Casas Mireia , Fouces Vicente , Viscor Ginés
Published: April 2003

Capillarity, fibre types, fibre cross-sectional areas and perimeters were studied along and across the rat tibialis anterior muscle. The muscle was sectioned at three different levels (proximal, equatorial and distal) choosing five sampling fields for measurements at each level (from anterior to posterior and lateral to medial zones). Significant differences were found in the percentage of fibre types and capillarity between different fields of the same muscle section. Slow oxidative fibres were confined to the posterior muscle zone with a maximum of 3.7%. The posterior fields also had a greater percentage of fast oxidative glycolytic fibres at proximal (72.3%) and equatorial (61.3%) levels, but a lower value at the distal level (44.8%) and lower capillary density counts in total cross-section means (758 vs. 1,069 capillaries/mm2 in equatorial and 1,035 capillaries/mm2 at proximal levels). The uneven distribution of both fast fibre types and the different degrees of capillarisation along the muscle are statistically significant and may be due to different biomechanical performances along the rat tibialis anterior. Fibre size was significantly larger at the distal level, but no morphometric differences were found across the section of the same level. At the distal level, the mean total fibre area of fast glycolytic fibres (5,130 μm2) and fast oxidative glycolytic fibres (2,493 μm2) contrasted with values at the proximal (fast glycolytic: 4,070 μm2, fast oxidative glycolytic: 1,970 μm2) and equatorial (fast glycolytic: 3,535 μm2, fast oxidative glycolytic: 1,714 μm2) levels. The differences along and across the muscle show the need to design a standardised procedure for sample location when performing comparative studies of morphofunctional adaptive changes in skeletal muscle. A significant difference between individuals (animals) in all parameters was evident and should be taken into consideration when analysing the variability: the factor ‘animal’ should be considered in multiway ANOVAs, especially when low sample sizes are used.
Simulated Microgravity and Hypergravity Attenuate Heart Tissue Development in Explant Culture
Authors: Lwigale Peter Y. , Thurmond Joel E. , Norton William N. , Spooner Brian S. , Wiens Darrell J.
Published: April 2003

Exposure to altered gravity may disturb the cytoskeleton-cell surface-extracellular matrix (ECM) interface of embryonic cells. Development of organs such as the heart depends on dynamic interactions across cell surfaces. Fibronectin (FN), for example, a glycoprotein that links the ECM to the cytoskeleton through integrin surface receptors, is required for normal heart development. Thus, altered gravity may perturb organogenesis. We cultured precardiac explants from chick embryos in a rotating bioreactor vessel to simulate microgravity (μG), or in a tissue culture centrifuge, for 18 h during heart development. Bioreactor μG did not alter external morphology of explants, but did significantly reduce the proportion that developed contractions. Immunostaining for FN of explant sections showed that it also significantly reduced the linear extent of staining present in basement membrane regions. Analysis of ultrastructure revealed a significant reduction in the number of desmosomes per unit area and other differences. Hypergravity dramatically abolished development of contractions and altered morphogenesis. The results indicate a probable sensitivity of cardiomyogenic development involving FN to altered gravity.
The Superficial Anulus Fibrosus Ligament
Authors: Hanson P. , Qvortrup K. , Magnusson S.P.
Published: April 2003

A previously unknown ligament, the superficial anulus fibrosus ligament (SAFL), situated on the ventral part of the L5 intervertebral disc (ID) was observed and described from autopsy material. Twenty-eight cadaveric specimens from 12 black and 16 white persons aged 17–30 years were studied during routine forensic autopsies. The anterior longitudinal ligament was separated from the ID and the ventral part of the SAFL was visualized. The SAFL samples were removed, measured and studied with both conventional histology and examination by transmission electron microscopy. The SAFL was a completely separate ligament at the level of the L5-S1 ID situated between the anterior longitudinal ligament and the anulus fibrosus of the ID. The fibers of the ligament were vertically oriented. A difference in distance between the L5-S1 vertebral bodies ventrally was noted in the two groups studied (18.7 ± 1.2 mm in the black vs. 15.2 ± 1.0 mm in the white, p < 0.001), indicating a difference in the ventral thickness of the intervertebral disc. Also, there was a difference in the length (black: 17.7 ± 1.6 mm vs. white: 14.1 ± 1.1), thickness (black: 3.3 ± 0.3 mm vs. white: 2.1 ± 1.9), and the cross-sectional area (black: 58.2 ± 6.7 mm2 vs. white: 26.5 ± 2.7 mm2, p < 0.001) of the SAFL. Conventional light microscopy revealed no obvious differences. However, transmission electron microscopy revealed notably larger collagen fibril diameter in black than white subjects. In conclusion, the interbody distances were greater in the black group, indicating a greater intervertebral disc thickness, compared to that of the white. Furthermore, the SAFL was significantly longer and thicker in the black than in the white group. Albeit unsubstantiated, these race-specific macroscopic findings may have implications for understanding the etiology of various low back stress problems.
The Dentinal Structure of Equine Incisors: A Light and Scanning Electron-Microscopic Study
Authors: Muylle S. , Simoens P. , Lauwers H.
Published: April 2003

This paper gives an anatomical overview of the dentinal structure in equine incisor teeth with special reference to the three-dimensional organization, the number and the diameter of the dentinal tubules. The spatial arrangement of equine dentine was examined by scanning electron microscopy of occlusal surfaces and longitudinally fractured teeth and by light microscopy of both decalcified and ground sections. The dentinal tubules of the peripherally situated primary dentine were directly continuous with those of the circumpulpal secondary dentine. The tubules had numerous side branches along their entire course and ramified into terminal branches near the dentino-enamel junction. Tubules of tertiary dentine, situated in the centre of the dental star, were few in number and not continuous with those of the surrounding secondary dentine. On non-etched incisors tubular orifices were clogged by an amorphous smear layer that covered the occlusal surface. On etched occlusal surfaces the numerical tubular density was calculated in different zones. The largest number of tubules per unit area was situated in the secondary dentine forming the dark periphery of the dental star, whereas the smallest number was present in the tertiary dentine located in the pale centre of the dental star. Dentinal tubular diameters were measured at various distances from the pulp. They were widest near the pulpal wall and narrowed progressively towards the dentino-enamel junction. Tubular widths measured on etched occlusal surfaces were considerably larger than those measured on undecalcified incisors due to the removal of intratubular dentine during the etching process.
Localization of Sperm Ligand Carbohydrate Chains in Pig Zona pellucida Glycoproteins
Authors: Nakano Minoru , Yonezawa Naoto
Published: April 2003

Neutral N-linked carbohydrate chains from pig ZPB/ZPC mixture are shown to possess sperm ligand activity. Of these complex-type chains, triantennary/tetraantennary chains exhibit the activity stronger than that of diantennary chains. Intact ZPB and ZPC cannot be separated from each other unless acidic N-acetyllactosamine regions of their carbohydrate chains are removed by endo-β-galactosidase digestion. The endo-β-galactosidase-digested ZPB and its N-terminal fragment of 111 residues retain the sperm ligand activity. Three glycopeptides, having one Asn residue to which the carbohydrate chain is linked, are obtained by lysylendopeptidase digestion of the heat-solubilized zonae containing intact ZPB, and lysylendopeptidase and chymotryptic digestions of endo-β-galactosidase-digested ZPB. On the basis of sugar mapping analysis of the N-linked chains from these glycopeptides and comparison with the carbohydrate structures of the main intact neutral N-linked chains of ZPB/ZPC, the triantennary and tetraantennary chains are shown to be localized mainly at Asn220 of ZPB, whereas diantennary chains are present on all the three N-glycosylation sites (Asn203, Asn220 and Asn333). These results suggest that the carbohydrate chains linked to Asn220 of ZPB participate predominantly in sperm-egg binding. ZPC has been shown to support the expression of sperm ligand activity of ZPB. Three glycopeptides, each having one of the N-glycosylation sites, are obtained by tryptic digestion of endo-β-galactosidase-digested ZPC. Triantennary and tetraantennary chains are found mainly at Asn271 of ZPC, whereas diantennary chains are present at all three N-glycosylation sites (Asn124, Asn146 and Asn271). Thus, the localization of triantennary and tetraantennary chains in ZPC is different from that in ZPB.
Ulcerative Colitis and Colon Cancer: More Controversy than Clarity
Authors: Snapper Scott B. , Syngal Sapna , Friedman Lawrence S.
Published: April 2003

Although it is generally accepted that the risk of colorectal cancer in patients with ulcerative colitis is increased compared with the general population, the management of this increased risk remains controversial. Patients with pancolitis of > 8 years duration should consider periodic colonoscopic surveillance or prophylactic colectomy. For patients unwilling to undergo prophylactic colectomy, colonoscopic surveillance annually or biennially is recommended. High-grade dysplasia or low-grade dysplasia in association with a lesion or mass is an indication for colectomy when confirmed by 2 pathologists. Repeat colonoscopic surveillance (in 3–6 months) or colectomy is recommended for confirmed low-grade dysplasia.
Investigative Techniques in the Assessment of Oral-Pharyngeal Dysphagia
Authors: Cook Ian J.
Published: April 2003

Oral-pharyngeal dysphagia is a common problem with a high morbidity and mortality. In general, it is not managed as well as esophageal dysphagia by gastroenterologists. A number of techniques are now available for the assessment of oral-pharyngeal dysphagia. However, a careful clinical assessment followed by a video barium swallow is all that is required for the diagnosis and management in the majority of patients. Pharyngeal manometry is likely to play an increasingly important role in the assessment of difficult or atypical cases in whom it can provide functional information not achievable with videoradiography alone. Videolaryngoscopy is a quick and simple way of detecting structural lesions and of assessing deglutitive airway protection. Videolaryngoscopy is non-invasive and easily performed in an office setting. Ultrasonography is a convenient way of assessing lingual function, but provides no more information than the video barium swallow. Pharyngeal scintigraphy is likely to assume a greater clinical relevance as a means of quantifying swallow efficiency and response to therapy.
Helicobacter Infection in Man: Problems to Be Solved
Authors: Tytgat G.N.J.
Published: April 2003

Helicobacter pylori (Hp) infection in man has several disease outcomes, varying from asymptomatic chronic gastric inflammation to Hp-associated dyspepsia, pepic ulcer disease, gastric adenocarcinoma, and Malt lymphoma. Particularly controversial is the role of Hp infection in the genesis of chronic dyspeptic symptoms. Only a small percentage of chronic dispeptics have long-lasting remission of the complaints after cure of the infection. It is now well established that healing of the inflammation through microbial eradication cures peptic ulcer disease. The high efficacy of bismuth or PPI triple and quadruple therapies is overshadowed by the rising resistance to metronidazole and clarithromycin. The exact role of Hp in gastric carcinogenesis in the various geographical areas needs further study. The results of ongoing trials, evaluating the long-term outcome of Hp cure, on cancer rates are anxiously awaited. The acquisition rate of new knowledge through basal and clinical Hp research has rarely been witnessed in medicine.
Epidemiology, Risk Factors and Treatments for Antibiotic-Associated Diarrhea
Authors: McFarland L.V.
Published: April 2003

Antibiotic-associated diarrhea (AAD) is a common complication of antibiotics and recent findings on the epidemiology, etiologies and treatment strategies are reviewed. Rates of AAD vary from 5 to 39% depending upon the specific type of antibiotic. The severity of AAD may include uncomplicated diarrhea, colitis or pseudomembranous colitis. The pathogenesis of AAD may be mediated through the disruption of the normal flora and overgrowth of pathogens or through metabolic imbalances. The impact of AAD is reflected by increased hospital stays, higher medical costs and increased rates of comorbidity. The key to decreasing these consequences is prompt diagnosis followed by effective treatment and institution of control measures.
Measuring Health-Related Quality of Life in Patients with Upper Gastrointestinal Disease
Authors: Moyer Cheryl , Fendrick A.M.
Published: April 2003

Measurement of health-related quality of life (HRQL) is becoming an increasingly important endpoint to researchers and clinicians. In the context of upper gastrointestinal disorders, understanding the impact of the symptoms and their treatments on physical, psychological, and emotional well-being is crucial. The objective of this review is to provide a background for HRQL assessment for patients with upper GI disease. We assess and critique available generic and disease-specific HRQL instruments, and specify the factors that should be considered when evaluating an instrument. If employed correctly, HRQL assessments for patients with upper GI disease could improve quality of care.
Antibodies in Relation to Gluten Intake
Authors: Mäki Markku , Sulkanen Satu , Collin Pekka
Published: April 2003

Serum reticulin, endomysial and gliadin antibody tests are used in serological screening and case finding of coeliac disease, as well as the novel tissue transglutaminase antibody test. None of these tests are 100% predictive, however. Reticulin/endomysial antibodies predict forthcoming coeliac disease in individuals with normal small-bowel mucosal morphology. The effect of a gluten-free diet can be monitored with serological tests. A positive test result often indicates an inadequate gluten-free diet. However, slight dietary transgressions and minor mucosal damages cannot always be revealed with the serological tests. Therefore, small-bowel mucosal biopsy remains the most sensitive method to monitor the effect of a gluten-free diet.
Genetics of Inflammatory Bowel Disease. The Candidate Gene Approach: Susceptibility versus Disease Heterogeneity
Authors: Peña A.S.
Published: April 2003

Ulcerative colitis and Crohn’s disease are complex diseases of unknown etiology. Several genes are involved in the susceptibility. These genes are necessary to suffer from these diseases but not sufficient. Environmental factors trigger the inflammatory response. Evidence is accumulating that this response is abnormal in these patients. Therefore, the study of genes that are involved in the regulation of the inflammation may help to clarify the pathogenesis of the disease. The working hypothesis is that HLA and cytokine gene polymorphisms, of extreme importance in the regulation of inflammation, contribute to determining the heterogeneity of the disease and the prognosis. In this case, the candidate genes are those involved in the regulation of the immune response of the host. These studies may be of great importance in the tailoring of an appropriate treatment for particular subgroups of patients. A premise for the success of these studies is to use a solid classification, which should take into account the dynamic process and the natural evolution of the disease; to use a carefully selected and ethnically matched group of healthy controls, and to use the advanced molecular biological typing techniques. In the present article, this concept is explored by taking into account some of the recent findings obtained with the HLA and cytokine gene polymorphisms in inflammatory bowel diseases. The results support the concept that these gene polymorphisms are of greater importance in determining the severity of the disease than in determining the susceptibility to suffer from the disease. From this point of view, these studies are complementary and a necessary addition to studies using the whole genome approach in the effort to understand the genetics of these chronic multifactorial diseases.
Genome-Wide Scanning in Inflammatory Bowel Diseases
Authors: Hugot J.P. , Thomas G.
Published: April 2003

Inflammatory bowel diseases (IBD) are multifactorial traits involving both environmental and genetic factors. In order to identify the IBD susceptibility genes, two groups of strategies have been developed. In the candidate gene approach, a specific hypothesis is tested by usually investigating the prevalence of specific alleles in groups of affected and control individuals with no familial relationship. Such association studies are powerful and straightforward. However, they are limited by possible recruitment biases and a multitesting problem due to the large number of posible candidate genes. Furthermore, they rely on the existence of a founder effect. In the genome scanning searches, no prior assumption is made on the susceptibility genes. The studies are based on cosegregation (or linkage) analyses performed on families with several affected members. Their drawbacks are the lack of statistical power and the low resolution of the localization. Nonetheless, using genome-wide screens, two IBD loci have been localized by several independent groups on chromosomes 12 and 16. Additional IBD loci have been proposed by individual groups on chromosomes 1, 3, 4, 7, 11, 15 and X. In order to gain wide acceptance, the latter localizations are to be confirmed by additional independent studies. Identification of IBD susceptibility genes would represent a key step in the understanding of the pathogenic mechanism of these diseases. However, in complex disorders, genes are only a part of the risk factors. Epidemiological studies looking for environmental factors are thus complementary of the genetic approach.
The Role of Antibiotics in Crohn’s Disease
Authors: Cangemi J.R.
Published: April 2003

Antibiotics have been commonly used in Crohn’s disease despite a lack of controlled data to support their use. Review of the histology and histopathology favor an infectious origin and increased infectious complications are witnessed in Crohn’s patients. Enhanced permeability may play a role in providing access of enteric organisms or their cell wall derivatives to the intestinal mucosa. Through an understanding of the pathophysiology and the important role of the fecal stream along with a critical review of the literature, we may gain a better understanding of the role of antibiotics in Crohn’s disease.
Intrahepatic Cholestatic Syndromes: Pathogenesis, Clinical Features and Management
Authors: Qureshi Waqar
Published: April 2003

Intrahepatic cholestasis is characterized by a decrease in bile flow in the absence of overt bile duct obstruction, resulting in the accumulation of bile constituents in the liver and blood. Various etiological factors have been incriminated including drugs, total parenteral nutrition, sepsis, pregnancy, graft-versus-host disease and systemic disorders such as sarcoidosis, amyloidosis and Hodgkin’s disease. The pathogenesis of cholestasis is unclear and several mechanisms have been hypothesized, without convincing evidence that any of these play a role in clinical cholestasis. Despite the uncertainty about the pathophysiology of intrahepatic cholestasis, several forms of therapy have been employed. Ursodeoxycholic acid may relieve pruritus and lethargy, and in some cases may modify disease progression. If cholestasis persists, supportive therapy is important to maintain optimal physical and nutritional well-being. In patients with advanced liver disease associated with hepatocellular failure, liver transplantation is the only viable option.
Fatty Liver and Nonalcoholic Steatohepatitis. Where Do We Stand and Where Are We Going?
Authors: Lonardo Amedeo
Published: April 2003

Background: Fatty liver (FL) is the most common liver disease but its clinical significance remains elusive. Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a cause of liver failure, sometimes recurring following transplantation. Recent data on both conditions are critically reviewed. Methods: A Medline search of the medical literature (1990 to September 1998) and cross-references was performed. Results: FL most commonly affects middle-aged men with obesity, altered glucose metabolism, hyperlipidemia, and hypertension. The link between biology of HCV, iron metabolism and FL should be addressed. Prospective studies should also quantify the rate and the factors involved in the progression of FL to NASH. The clinical spectrum of NASH is currently broader than it was initially recognized. Diagnosis of FL and NASH may involve ultrasonography, liver biopsy, and recognition of related conditions. Treatment of these conditions must be tailored according to patient’s features. Conclusions: The clinical significance of FL is incompletely understood at present. The relationship, if any, of FL and the metabolic syndrome should be carefully investigated.
Adenocarcinoma of the Esophagogastric Junction
Authors: Jenkins Timothy D. , Friedman Lawrence S.
Published: April 2003

Adenocarcinoma of the esophagogastric junction (EGJ) has increased rapidly in incidence in the latter half of the twentieth century. The increase in incidence has affected white men between the ages of 40 and 60 disproportionately. Understanding the etiology and improving treatment requires careful classification of EGJ tumors. A recent consensus conference recognized three types of EGJ adenocarcinomas: distal esophageal, cardia, and subcardia gastric. Distal esophageal adenocarcinomas are associated with Barrett’s esophagus. Heilcobacter pylori infection may play a role in some adenocarcinomas of the subcardia, but the association is unproven. Therapy for all types of EGJ tumors is surgical, but multimodal forms of treatment are commonly used because of the advanced stage at which these tumors often present. Several endoscopic options exist for primary therapy of early-stage tumors and for palliation.
Reduced Intraneuronal Lipofuscin Content in Dementia with Lewy Bodies Compared with Alzheimer’s Disease and Controls
Authors: Drach Lutz M. , Bohl Jürgen , Wach Stefanie , Schlote Wolfgang , Goebel Hans-Hilmar
Published: April 2003

Lipofuscin has been of interest in dementia of Alzheimer’s type (DAT), because of the hypothesis that dementia is a kind of premature ageing. The results of studies on intraneuronal lipofuscin content in DAT are inconsistent. At present no data on intraneuronal lipofuscin in dementia with Lewy bodies (DLB) are available. The amount of lipofuscin in the neurons of the inferior olivary nucleus of 10 brains of DLB patients, 10 of age-matched DAT patients, and 10 of age-matched controls has been measured microfluorometrically. The intraneuronal lipofuscin content in the DLB patients was significantly lower than in the DAT patients and controls. This finding may indicate a general alteration of neuronal cell metabolism in DLB, e.g. a defect of mitochondrial DNA, not confined to neurons developing Lewy bodies.
Inferior Temporal Lobe Atrophy and APOE Genotypes in Alzheimer’s Disease
Authors: Tanaka Seigo , Kawamata Jun , Shimohama Shun , Akaki Hiroshi , Akiguchi Ichiro , Kimura Jun , Ueda Kunihiro
Published: April 2003

The apolipoprotein E (APOE) gene σ4 allele is known to be associated with late-onset familial and sporadic Alzheimer’s disease (AD). We assessed the possible relationship between APOE genotypes and morphological or functional changes in AD brains by x-ray computed tomography (CT), magnetic resonance imaging (MRI) and Xe-133 single photon emission CT (SPECT). First, we estimated the change in size of the whole brain and total ventricular system by using two x-ray CT indices, the cerebral index (CI) and ventricular index (VI), respectively. Neither CI nor VI differed significantly among APOE genotypes. Then, we focused on the inferior temporal lobe regions by introducing new MRI indices, the inferior temporal index (ITI), temporal horn index (THI) and infero-medial temporal index (IMTI). We found a significant difference in each MRI index among APOE subgroups; ITI and IMTI were lower, while THI was higher in AD patients with at least one APOE σ4 allele (σ4+ group) than in those without such an allele (σ4– group). Finally, we compared relative regional cerebral blood flow (rCBF) of Xe-133 SPECT among the AD subgroups. Relative rCBF in the cerebral cortex, particularly in the temporal lobe, was lower in the σ4+ group than in the σ4– group. These results indicate that possession, and thus expression, of the APOE σ4 allele affects preferentially the inferior temporal lobe, encompassing the hippocampus and amygdala, in AD patients.
Vascular Risks and Incident Dementia: Results from a Cohort Study of the Very Old
Authors: Brayne C. , Gill C. , Huppert F.A. , Barkley C. , Gehlhaar E. , Girling D.M. , O’Connor D.W. , Paykel E.S.
Published: April 2003

The contribution of vascular pathology to the manifestation of dementia and the importance of vascular risk to measures of cognitive function is being increasingly recognized. In particular, confirmation of this risk points towards approaches for prevention in large sections of the population. Information on determinants of incident dementia is increasing, but still relatively few studies of risk have been based on incident cases of dementia in very elderly populations. In this study based on incident cases of dementia in a population aged 75 and over, vascular risks were obtained from informants of the respondents with incident dementia. When compared with controls the factors associated with incident dementia were history of heart attack (odds ratio 2.9), transient ischaemic attacks (4.8), cerebrovascular accidents (3.4), family history of first-degree relatives with dementia (4.0), and occupational exposure to vibrating instruments (1.4). If only Alzheimer’s disease, clinically diagnosed, was included, diabetes (1.4) and a history of dementia in first-degree relatives (6.6) emerged. Thus, vascular risk continues to be of importance in the oldest age groups.
Copper, Ceruloplasmin and Superoxide Dismutase in Patients with Alzheimer’s Disease
Authors: Snaedal J. , Kristinsson J. , Gunnarsdóttir S. , Ólafsdóttir Á. , Baldvinsson M. , Jóhannesson T.
Published: April 2003

The copper-containing enzyme superoxide dismutase (SOD) is a key enzyme in suppressing the amounts of superoxide anion radicals. Ceruloplasmin, the copper-transporting protein in plasma, also possesses an important redox capacity. In this study the levels of copper and ceruloplasmin as well as SOD-activity and ceruloplasmin oxidative activity were analyzed in order to throw some light on possible defects in copper mechanisms in patients diagnosed with Alzheimer’s disease (AD). The study included 44 patients with AD and their healthy age- and gender-matched controls. No difference of significance was seen when comparing the copper or ceruloplasmin concentration in plasma of AD patients to that of their paired controls. The SOD activity in red blood cells was significantly lower in the patients than in their controls (p = 0.019). The ceruloplasmin oxidative activity in plasma of Alzheimer’s patients was greatly reduced as compared to that of age- and gender-matched controls and the difference was highly significant (p = 0.0005). Ceruloplasmin activity and SOD activity were not found to be intrinsically correlated. It was postulated that reduced oxidative activity of ceruloplasmin in plasma might be either a cause or a consequence of AD and that reduced SOD activity might further add to the oxidative disturbances in AD due to defective ceruloplasmin activity.
The Stages of Alzheimer’s Disease: A Reappraisal
Authors: Kraemer Helena C. , Taylor Joy L. , Tinklenberg Jared R. , Yesavage Jerome A.
Published: April 2003

‘Stages’, as used in clinical practice and research, are defined, their value described, and criteria are proposed for their evaluation. The specific interest is in staging Alzheimer’s disease (AD). Two staging systems, one based on the Global Deterioration Scale (GDS) and one based on the Mini-Mental State Exam (MMSE), are compared in terms of these criteria, as an illustration of the process involved. We propose that there is not one unique staging system, that different staging criteria might be appropriate to different research or clinical needs, depending on which part of the temporal course of the disease is of primary interest, and on whether the focus is on cognitive, functional, neurological, behavioral, economic, or other issues. GDS staging seems a better choice for the later stages of AD when the focus is on functional change. MMSE staging seems a better choice for tracking the earlier stages of AD when the focus is on cognitive change.
Validation of the Full and Short Forms of the CAMDEX Interview for Diagnosing Dementia: Evidence from a One-Year Follow-Up Study
Authors: Neri M. , Rubichi S. , DeVreese L.P. , Roth M. , Cipolli C.
Published: April 2003

The sensitivity and specificity of the two forms of the CAMDEX interview for dementia diagnosis were assessed in a 1-year follow-up study. At the beginning of the study, 60 patients (22 males and 38 females) who met DSM-IV criteria for dementia and 60 matched controls (15 males and 45 females), were administered the short form of the CAMDEX (short CAMDEX) 3 months after the full one (full CAMDEX). At the follow-up, all patients were administered both the full and short CAMDEX (again with a 3-month interval), whereas controls were administered either CAMDEX form (in any case, at a 12-month interval from initial testing). Upon initial testing, the sensitivity of the full CAMCOG proved to be significantly higher than that of the short CAMCOG, while the opposite trend was observed for specificity, that is the sensitivity of the full Organicity was lower than that of the short Organicity, with specificity remaining equal in the two forms. Upon follow-up, the specificity and sensitivity levels of the two forms did not significantly differ for the CAMCOG and Organicity indices. Moreover, in detecting mildly demented patients, the full CAMCOG proved to be more accurate than the short one, while the opposite trend was observed for Organicity. Among the dementia subjects, significant correlations were found between the homologous indices of the two forms for both test sessions. On the whole, the short CAMDEX appears to maintain most of the psychometric properties of the full version and therefore the two CAMDEX forms can be considered to be interchangeable.
Clinical Aspects of ‘Senile Dementia of the Tangle Type’ – A Subset of Dementia in the Senium Separable from Late-Onset Alzheimer’s Disease
Authors: Ikeda Kenji , Akiyama Haruhiko , Arai Tetsuaki , Oda Tatsuro , Kato Masanori , Iseki Eizo , Kosaka Kenji , Wakabayashi Koichi , Takahashi Hitoshi
Published: April 2003

There is a subset of dementia patients in the senium, in whom abundant neurofibrillary tangles (NFTs) are present mainly in the hippocampal region without significant numbers of senile plaques. This patient group was thought to be separable from those with Alzheimer’s disease based on the results of ApoE allele analysis in addition to the substantial absence of amyloid β deposits and has been designated as senile dementia of the tangle type (SDT). The clinical pictures of 4 autopsied patients with different amounts of NFTs were examined to characterize the clinical aspects of this type of senile dementia. SDT generally occurs in very old patients and was estimated to account for about 4–6% of patients with dementia in the senium excluding vascular dementia. Clinically, long-lasting memory disturbance is more prominent and personality as well as cognitive functions tend to be preserved. Delirium and other psychotic symptoms are often observed. NFTs and accompanying neuronal loss in the limbic, mainly in the hippocampal, region could be responsible for dementia.
Cerebellar Dentate Nucleus in Alzheimer’s Disease with Myoclonus
Authors: Fukutani Yuken , Cairns NigelJ. , Everall IanP. , Chadwick Andrew , Isaki Kiminori , Lantos PeterL.
Published: April 2003

Although myoclonus commonly occurs in a later stage of Alzheimer’s disease (AD), the pathological basis of this symptom is still unclear. In order to elucidate the neuropathological substrate of myoclonus in AD, we quantitatively assessed neuronal density and volume, with a discrimination between small and large neurons, at the rostral and caudal parts in the cerebellar dentate nucleus of 8 AD patients with myoclonus, 10 AD patients without myoclonus and 9 controls, using stereological probes. The neuronal numerical density of the large neurons at the rostral part and of total counts (rostral and caudal parts) in the myoclonic AD group were significantly greater than in the nonmyoclonic AD group. There were no significant differences in the density of small neurons between the two AD groups. The ratio of small neurons to large neurons (S/L ratio) of total counts was significantly lower in AD with myoclonus than in AD without myoclonus. The mean neuronal volume of the large neurons at the rostral part was significantly greater in myoclonic AD than in nonmyoclonic AD. Conversely, the volume of the small neurons at the rostral part was significantly lower in myoclonic AD than in nonmyoclonic AD. This study, for the first time, shows an increase in mean volume of large neurons and a decrease in mean volume of small neurons as well as a change in the S/L ratio in the dentate nucleus in AD with myoclonus. An imbalance in the S/L ratio as well as morphological changes of these neurons in the dentate nucleus may contribute to the pathological substrate of myoclonus in AD.
White Matter Lesions in Alzheimer Patients Are Influenced by Apolipoprotein E Genotype
Authors: Bronge Lena , Fernaeus Sven-Erik , Blomberg Mari , Ingelson Martin , Lannfelt Lars , Isberg Bengt , Wahlund Lars-Olof
Published: April 2003

To analyse the influence of apolipoprotein E (APOE) genotype on the extent of white matter lesions (WMLs) in Alzheimer’s disease (AD), we examined 60 AD patients with magnetic resonance imaging. The WMLs were rated visually in different brain regions. The patients with the APOE genotype σ4/4 had more extensive WMLs in the deep white matter than patients with genotypes σ3/3 and σ3/4. There was a correlation with age for WMLs in the deep white matter in patients with the APOE σ3/3 genotype. In patients carrying at least one σ4 allele, the WMLs showed no age correlation. The results could imply that in APOE allele σ4 carriers, the WMLs represent a pathological process related to the aetiology of the disease.
Simple Standardised NeuropsychologicalAssessments Aid in the Differential Diagnosis of Dementia with Lewy Bodies from Alzheimer’s Disease and Vascular Dementia
Authors: Ballard C.G. , Ayre G. , O’Brien J. , Sahgal A. , McKeith I.G. , Ince P.G. , Perry R.H.
Published: April 2003

Consecutive patients from a dementia case register received a standardised evaluation which incorporated a neuropsychological assessment with the Cambridge Assessment for disorders in the elderly (CAMCOG). Operationalised clinical diagnoses were made (consensus criteria for dementia with Lewy bodies, DLB; NINCDS- ADRDA for Alzheimer’s disease, AD, NINCDS AIRENS for vascular dementia, VaD). Two-hundred and twenty-eight patients were studied (DLB 54, AD102, VaD 72). DLB patients had significantly better performance on recent memory than AD patients, but more impaired visuospatial praxis. DLB patients also had significantly better recent memory than those with VaD. Optimal cut-off points for the recent memory:praxis ratio achieved good discrimination between DLB and both other dementias.
Relationship between Clinical and Radiological Diagnostic Criteria for Alzheimer’s Disease and the Extent of Neuropathology as Reflected by ‘Stages’: A Prospective Study
Authors: Nagy Zs. , Hindley N.J. , Braak H. , Braak E. , Yilmazer-Hanke D.M. , Schultz C. , Barnetson L. , Jobst K.A. , Smith A.D.
Published: April 2003

The distribution of pathology related to Alzheimer’s disease (AD) is not uniform throughout the brain. Sites which have a predilection for the development of Alzheimer-type pathology are the limbic regions and neocortical association areas. The changes in these areas of the brain develop gradually, following a well-determined sequence that allows a pathological staging of the disease process. According to the staging hypothesis, the first pathological alterations develop in the transentorhinal and entorhinal regions. The neurofibrillary pathology then spreads into the hippocampus, but not until the final stages does it affect the neocortex. In this study we analyse the relationship between the pathological stages of AD, according ot the staging hypothesis, and the clinical diagnosis in a prospectively assessed patient group. Prediction of any given pathological stage from the clinical diagnosis was found to be poor. This may be partly due to the fact that additional pathologies can alter the clinical picture and severity of dementia in patients who are only in the initial stages of AD. Nevertheless, the NINCDS-ADRDA clinical criteria had a high sensitivity for detection of AD-related pathology: the ‘probable AD’ category included 22/38 (57.9%) of those in the late isocortical stage, while the ‘possible AD’ category included 19/23 (82.6%) of those in the limbic stage. Using proposed neuro-imaging protocols for improved identification of patients with AD-related pathology, we largely identified subjects in whom the extent of pathology had spread to the neocortex.