bluuebunny/crossref_metadata_2025 huggingface dataset:
The Species Recognition System: A New Corollary for the Human Fetoembryonic Defense System Hypothesis
Authors: Clark Gary F. , Dell Anne , Morris Howard R. , Patankar Manish S. , Easton Richard L.
Published: April 2003

We have previously suggested that the human fetus is protected during human development by a system of both soluble and cell surface associated glycoconjugates that utilize their carbohydrate sequences as functional groups to enable them to evoke tolerance. The proposed model has been referred to as the human fetoembryonic defense system hypothesis (hu-FEDS). In this paradigm, it has previously been proposed that similar oligosaccharides are used to mediate crucial recognition events required during both human sperm-egg binding and immune-inflammatory cell interactions. This vertical integration suggested to us that the sperm-egg binding itself is related to universal recognition events that occur between immune and inflammatory cells, except that in this case recognition of ‘species’ rather than recognition of ‘self’ is being manifested. In this paper, we have designated this component of hu-FEDS as the species recognition system (SRS). We propose that the SRS is an integral component of the hu-FEDS used to enable sperm-egg recognition and protection of the gametes from potential immune responses. Recent structural data indicates that the glycan sequences implicated in mediating murine gamete recognition are also expressed on CD45 in activated murine T lymphocytes and cytotoxic T lymphocytes. This overlap supports our contention that there is an overlap between the immune and gamete recognition systems. Therefore the hu-FEDS paradigm may be a subset of a larger model that also applies to other placental mammals. We therefore propose that the hu-FEDS model for protection should in the future be referred to as the eutherian fetoembryonic defense system hypothesis (eu-FEDS) to account for this extension. The possibility exists that the SRS component of eu-FEDS could predate eutherians and extend to all sexually reproducing organisms. Future investigation of the interactions between the immune and gamete recognition system will be required to determine the degree of overlap.
Relationship of Reproductive Hormones and Neuromuscular Disease of the Gastrointestinal Tract
Authors: Mathias John R. , Clench Mary H.
Published: April 2003

Functional disorders of the gastrointestinal tract comprise a common but ill-defined group of diseases; they primarily afflict women. Although predominantly involving nerve and muscle, the cellular and molecular bases of the pathogenesis of these functional disorders are unknown. Clinical studies indicate that some result from neural dysfunction within the enteric nervous system, others may be due to muscular problems, and the causes of still others remain unknown. Laboratory studies have shown that ovarian products such as progesterone, luteinizing hormone, human chorionic gonadotropin, and relaxin (but not estrogen), are neural antagonists of gastrointestinal motility. The production and secretion of these ovarian substances are controlled by gonadotropin-releasing hormone (GnRH) released from the hypothalamus; they probably act on γ-aminobutyric acid receptors and alter chloride influx into the cell. GnRH analogs are effective drugs that downmodulate the hypothalamic-pituitary-gonadal axis and inhibit the secretion of gonadal products involved in such hormone-dependent diseases as endometriosis and prostate cancer. Acting on the GnRH receptors (seven transmembrane domain receptors) on myenteric neurons, GnRH analogs are also effective neural modulators in such disorders as functional bowel disease. These analogs are a promising new group of compounds that may be used to treat difficult gastrointestinal problems.
Gene Therapy for Liver Disease
Authors: Davern II Timothy J. , Scharschmidt Bruce F.
Published: April 2003

With major advances in biomedical science over the last 2 decades, the possibility of treating human disease at a genetic level has become a tantalizing possibility. As a result, a growing number of investigators are focusing on the development of techniques to deliver therapeutic genes into cells. The liver has been a model organ in the development of this gene transfer technology. This review focuses on the attributes and limitations of the current gene delivery systems that have been explored in the context of liver disease and highlights the obstacles that must be addressed before hepatic gene therapy becomes a clinical reality.
Abnormalities of Liver Regeneration: A Review
Authors: Leevy Carroll B.
Published: April 2003

Structural and functional changes during liver regeneration have been studied extensively in experimental animals following partial hepatectomy or hepatic injury induced by noxious substances. These observations have been extended to evaluate abnormalities of liver regeneration which contribute to chronic hepatitis, cirrhosis and/or liver cancer in man. This is facilitated by the simultaneous perfusion of flash frozen percutaneous biopsies or explanted liver in an acrylic chamber with tritiated thymidine and proline to evaluate DNA and collagen synthesis, respectively. Such investigations indicate that chronic liver damage is associated with replication of mesenchymal, ductular and parenchymal cells, accompanied by increased fibrogenesis. The regenerative response of the liver after noxious injury in experimental animals and man is associated with the release of cytokines, increase of growth response genes and change in telomerase activity. The ability to monitor morphological, genetic and biochemical parameters provides new information on the kinetics of the reparative process in hepatobiliary disease. Abnormal liver regeneration and its untoward effects including tumorigenesis may be modified by altering nutrients, blocking antigens or receptors, and inhibiting metabolites which regulate cell replication and collagen deposition.
Overview of Imaging in Colorectal Cancer
Authors: Ott David J. , Wolfman Neil T. , Scharling Eric S. , Zagoria Ronald J.
Published: April 2003

Accurate staging of colorectal carcinoma (CRC) at initial diagnosis is critical for proper management of this disease. Computed tomography (CT) is often used for preoperative staging and is complementary to the clinical assessment of the patient and to the use of other imaging techniques, such as endoluminal ultrasound (US). CT can identify those patients who may benefit from local radiation therapy, hepatic resection or cryoablation, or intra-arterial chemotherapy. Endoluminal US may detect patients with early disease and alter their course of therapy, especially in those with rectal carcinoma in which limited surgery might be performed. CT is generally the modality of choice for imaging the postoperative patient. CT clearly depicts the operative area, particularly after abdominoperitoneal resection, and can be used to guide percutaneous biopsy of masses. The role of magnetic resonance imaging in CRC remains to be defined. In this review, we discuss the current roles of these various imaging modalities in the management of this disease.
Somatostatin in the Treatment of Non-Variceal Upper Gastrointestinal Bleeding
Authors: Jenkins Spencer A. , Poulianos George , Coraggio Francesco , Rotondano Gianluca
Published: April 2003

The efficacies of somatostatin and octreotide have been widely studied in the control of bleeding from oesophageal varices. It has also been suggested that these drugs may be useful for the control of non-variceal upper gastrointestinal (UGI) bleeding, including that from peptic ulcers. In approximately 80% of patients presenting with non-variceal UGI bleeding, haemorrhage ceases spontaneously and does not recur. However, the remaining 20% of patients require active treatment. Results from recent studies have indicated that somatostatin is an effective treatment for the control of non-variceal UGI bleeding in high-risk patients, i.e. those in whom haemorrhage does not cease spontaneously or is likely to recur. In contrast there is no good evidence available at present to support a role for octreotide in this indication. The efficacy of somatostatin in controlling bleeding in patients with non-variceal UGI bleeding at high risk of mortality upon admission, or rebleeding following endoscopy, coupled with an excellent safety and tolerability profile, suggests that it may be a valuable therapeutic option in the management of non-variceal bleeding.
Management of Acute Liver Failure
Authors: Herrera Jorge
Published: April 2003

Acute liver failure represents one of the most challenging conditions in gastroenterology. In most cases, there is no effective therapy making supportive intensive care the most important management tool. These patients frequently develop multi-organ failure, placing them at risk of systemic infections, cerebral edema, hemodynamic instability, coagulopathy and various renal and metabolic complications. Successful management of the patient with acute liver failure requires an understanding of the pathophysiology and management of these complications. An overview of acute liver failure and its most common complications is presented.
Ingested Foreign Bodies within the Appendix: A 100-Year Review of the Literature
Authors: Klingler Paul , Seelig Matthias , DeVault Kenneth , Wetscher Gerold , Floch Neil , Branton Susan , Hinder Ronald
Published: April 2003

Background/Aim: Appendicitis and its complications remain a common problem affecting patients of all age groups. Foreign bodies are a rare cause of appendicitis. We tried to define potentially dangerous foreign bodies that may cause appendicitis and summarize general guidelines for their clinical management. Methods: A 100-year literature review including 256 cases of ingested foreign bodies within the appendix with emphasis on: (1) objects that are more prone to cause appendicitis or appendiceal perforation; (2) foreign bodies that are radiopaque and may be detected during follow-up with plain abdominal films, and (3) guidelines for clinical management. Results: Complications usually occur with sharp, thin, stiff, pointed and long objects. The majority of these objects are radiopaque. An immediate attempt should be made to remove a risky object by gastroscopy. If this fails, clinical follow-up with serial abdominal radiographs should be obtained. If the anatomical position of the object appears not to change and, most commonly, remains in the right lower abdominal quadrant, an attempt at colonoscopic removal is indicated. If this is unsuccessful, laparoscopic exploration with fluoroscopic guidance should be carried out to localize and remove the objects either by ileotomy, colotomy, or by appendectomy. Conclusion: Foreign bodies causing appendicitis are rare. However, if stiff or pointed objects get into the appendiceal lumen they have a high risk for appendicitis or perforation. These foreign bodies are almost always radiopaque.
Hypersensitivity and Hyperreactivity in the Irritable Bowel Syndrome: An Opportunity for Drug Discovery
Authors: Sanger Gareth J.
Published: April 2003

The gastrointestinal tract of many patients with irritable bowel syndrome (IBS) is hypersensitive to different stimuli. The mechanisms of this hypersensitivity are unclear, but could involve enteric, visceral afferent/efferent, spinal and/or central nervous systems. Such complexity, the absence of animal models or anatomical, molecular or genetic markers of IBS, means that it is difficult to create new types of drugs which specifically treat the condition of IBS. To help in this process, current pre-clinical and early-clinical approaches are evaluated in terms of their ability to intervene within the gut-spinal cord/brain axis and inhibit gastrointestinal ‘hypersensitivity’ and ‘hyperreactivity’. Thus, by developing a rational process the pharmaceutical industry may better understand how to design truly effective drugs for the treatment of IBS.
Success with Intestinal Failure: From Adaptation to Transplantation
Authors: Scolapio James S. , Nguyen Justin H. , Steers Jeffrey , Ukleja Andrzej
Published: April 2003

Intestinal failure can result from large resections of small intestine (short bowel syndrome) and from failure of normal intestinal motility. The medical management of short bowel syndrome centers around appropriate diet and use of specific medications including experimental trophic factors. Enteral tubes and prokinetic medications can be successfully used to treat patients with intestinal failure as a result of abnormal intestinal motility. Small bowel transplantation may be a treatment option in certain patients with intestinal failure. This article reviews the management of intestinal failure with a recent update on small bowel transplantation.
Impact of Inflammatory Bowel Disease on Health-Related Quality of Life
Authors: Casellas F. , López-Vivancos J. , Vergara M. , Malagelada J.-R.
Published: April 2003

Health-related quality of life (HRQOL) has a recognized importance to evaluate, manage and follow patients. Different types of instruments for measuring HRQOL have recently been introduced to evaluate HRQOL in patients with inflammatory bowel disease. Most questionnaires suggest that inflammatory bowel disease has a significant impact in HRQOL. It seems that ulcerative colitis has less profound effects on HRQOL than Crohn’s disease and that some differences in HRQOL status are related to some factors such as the severity of the disease. When patients express their concerns, most important worries are related to surgery. Effective medical treatment appears to improve HRQOL. Effects of surgery on HRQOL can probably be different depending on the type of surgical technique and if it is curative or not. Recent studies suggest that inflammatory bowel disease not only impacts on patient's HRQOL but also on their caregivers. Features such as the impact on HRQOL of different disease variables, such as complications or patient personality, the role of medical or surgical treatments on different dimensions of HRQOL, the cost-utility evaluation of therapy are some of the fields that will probably focus the protagonism in the next years.
Symptom Priority Ranking in the Care of Gastroesophageal Reflux: A Review of 1,850 Cases
Authors: Martinez-Serna Tomas , Tercero Jr. Francisco , Filipi Charles , Dickason Timothy , Watson Patrice , Mittal Sumeet , Tasset Mark
Published: April 2003

Background: Clinical history remains an important part of the medical evaluation of patients with gastroesophageal reflux disease (GERD). Heartburn, regurgitation, and dysphagia are considered typical symptoms of GERD. Priority rankings of these symptoms can be determined with a standardized questionnaire. Objective: To determine whether symptom priority ranking and symptom severity grading can provide useful information in the evaluation of patients with GERD. Methods: From 1,850 patients that were analyzed retrospectively, patients with dysphagia unrelated to GERD were excluded. A standardized questionnaire was applied before each patient underwent any esophageal diagnostic study. Priority of symptoms was determined to be primary, secondary, tertiary, or none based on the patient response to the questionnaire. Presence of a stricture was determined either by endoscopy, esophagraphy, or both studies. Stationary esophageal manometry and 24-hour pH monitoring were performed on all patients. Through bivariate and multivariate analysis, the relationships among typical GERD symptoms, esophageal reflux-related stenosis, lower esophageal sphincter pressure, and composite score were established. Results: High priority ranking of the symptom dysphagia is predictive of the presence of an esophageal stricture, but has a negative association with abnormal manometric and pH studies. In contrast, high priority ranking of the symptom heartburn and regurgitation are positively associated with abnormal manometric and pH results. Conclusions: Priority ranking can be a valuable adjunct to objective testing in the evaluation of GERD. In certain clinical situations it can obviate the need for 24-hour pH monitoring.
KP-1 Is a Marker for Extraneuronal Neurofibrillary Tangles and Senile Plaques in Alzheimer Diseased Brains
Authors: Kobayashi K. , Muramori F. , Aoki T. , Hayashi M. , Miyazu K. , Fukutani Y. , Mukai M. , Koshino F.
Published: April 2003

KP-1 immunostaining with microwave pretreatment in formalin-fixed, paraffin-embedded sections enhanced its immunoreactivity revealing extraneuronal neurofibrillary tangles (NFTs) called ghost tangles, senile plaques (SPs) and perivascular deposits as well as microglial labelling in Alzheimer-diseased brains. KP-1 stained cored and uncored SPs, granules within the SPs, perivascular β-amyloid protein (βAP) and star-like βAP deposits in cortical layer I, which was confirmed in comparison to silver-impregnated structures in the Reusche-stained or Gallyas-Schiff-stained sections. On double immunostaining with KP-1 and ubiquitin, ghost tangles were labelled by KP-1 and intraneuronal NFTs were positive for ubiquitin. A few KP-1-positive granules deposits different from amyloid core were found within the SPs and the outer margin of amyloid cores of SPs were stained by KP-1. KP-1-positive microglia were attached to the ubiquitin-positive intraneuronal NFTs. Microglia were more numerously labelled by CR3/43 than by KP-1, and CR3/43-positive microglia were found to be preferentially attached to SPs. As KP-1 recognizes lysosome-associated antigen CD68, similarities between KP-1 positivity and Reusche-stained structures suggested that lysosomal activity was associated with βAP deposits and ghost tangles were involved in lysosome-associated processes. It is speculated that lysosomes play a role in the process of ghost tangle formation and in βAP deposits leading to SP formation.
Age at Onset and Regional Cerebral Glucose Metabolism in Alzheimer’s Disease
Authors: Yasuno Fumihiko , Imamura Toru , Hirono Nobutsugu , Ishii Kazunari , Sasaki Masahiro , Ikejiri Yoshitaka , Hashimoto Mamoru , Shimomura Tatsuo , Yamashita Hikari , Mori Etsuro
Published: April 2003

This study assessed 46 patients with Alzheimer’s disease and 21 aged controls using positron emission tomography. Repeated analyses using a general linear model examined the effect of age at onset on the pattern of the regional cerebral metabolic rate of glucose (rCMRglc). The results showed significant age effects on the rCMRglc in the fronto-temporo-parietal association cortices and retrosplenial areas. Disease duration, overall cognitive severity or normal aging could not account for the effects. The age effects were delineated as a double dissociation, that is, early-onset patients have a more severe reduction of regional glucose metabolism in the association cortices, while late-onset patients show a more prominent metabolic deficit in the paralimbic area.
Regional Hypometabolism Related to Language Disturbance in Alzheimer’s Disease
Authors: Hirono Nobutsugu , Mori Etsuro , Ishii Kazunari , Ikejiri Yoshitaka , Imamura Toru , Shimomura Tatsuo , Ikeda Manabu , Yamashita Hikari , Takatsuki Yoko , Sasaki Masahiro
Published: April 2003

To elucidate the nature of language disturbance in Alzheimer’s disease (AD) and the cerebral area involved in it, we studied 65 AD patients with the Western Aphasia Battery (WAB) and with 18F-fluorodeoxyglucose and positron emission tomography. Partial correlations were evaluated between the Aphasia Quotient of WAB and regional cerebral glucose metabolism normalized by the mean metabolic rate in the bilateral primary sensorimotor areas after controlling age, sex, education and severity of illness. Language disturbance in AD is accounted for by deficits in the semantic processing of language and is related to glucose hypometabolism in the inferior temporal gyrus and inferior parietal lobule, especially in the dominant side. These results offer further evidence suggesting that the lexico-semantic processing system is mediated in these regions.
Increased Plasma Concentration of Serum Amyloid P Component in Centenarians with Impaired Cognitive Performance
Authors: Nybo Mads , Olsen Hanne , Jeune Bernard , Andersen-Ranberg Karen , Holm Nielsen Ellen , Svehag Sven-Erik
Published: April 2003

Serum amyloid P component (SAP) binds to all amyloid fibrils including those in the plaques and tangles of Alzheimer patients. To investigate whether the plasma SAP concentration correlated to cognitive impairment, we measured SAP levels in blood samples from 41 centenarians and compared these to the cognitive performance evaluated by Mini Mental State Examination (MMSE). We observed a significantly (p < 0.001) increased SAP concentration (48.3 ± 16.9 µg/ml; mean ± SD) in the centenarians compared to gender-matched controls (32.8 ± 11.4 µg/ml). Six severely demented centenarians had an even higher SAP concentration (60.2 µg/ml), while the subgroup of cognitive intact centenarians (MMSE score >24) showed a normal SAP concentration (38.4 ± 9.3 µg/ml). No dehydration or hepatic dysfunction was demonstrable in the centenarians. We conclude that the centenarians with impaired cognitive performance had significantly increased plasma concentrations of SAP, while the values for cognitive intact centenarians were within the normal range.
The Expression of Presenilin-1 mRNA in Skin Fibroblasts from Alzheimer’s Disease
Authors: Ikeda Kazuyuki , Urakami Katsuya , Isoe Kenji , Ohno Kousaku , Nakashima Kenji
Published: April 2003

The presenilin-1 (PS-1) gene was recently identified as one of the causative genes in the early onset of familial Alzheimer’s disease (AD). Analysis of the PS-1 gene is thought to be useful in clarifying the pathogenesis of AD. However, there have been few reports about the expression of the PS-1 gene in AD. In this study, we analyzed the expression of PS-1 mRNA in cultured skin fibroblasts taken from living patients with AD by Northern blot analysis. The subjects consisted of 18 cases with AD and 10 cases of neurological patients without dementia (CTL). We found that the PS-1 mRNA levels in AD were significantly higher than those in CTL (p < 0.01). Moreover, we found that the PS-1 mRNA level increases in the early stages of AD and tends to decrease in the advanced stages. These findings suggest that high levels of PS-1 mRNA may play an important role in developing AD.
Expression of Adult T Cell Leukemia-Derived Factor in Human Brain and Peripheral Nerve Tissues
Authors: Asahina M. , Yamada T. , Yoshiyama Y. , Yodoi J.
Published: April 2003

In both nonneurological and Alzheimer brains, we examined the localization of adult T cell leukemia-derived factor (ADF) by immunohistochemistry, that of its mRNA by in situ hybridization, and its semiquantitative mRNA analyses by RT-PCR. Anti-ADF antibody gave positive staining of white matter astrocytes and Schwann cells in the posterior root. Their intense and abundant staining was seen in Alzheimer brains. In situ hybridization for ADF mRNA showed identical signals in the white matter astrocytes. The evidence was also confirmed by RT-PCR analysis. These results suggest that redox regulation may play a role in Alzheimer pathology.
DNA Polymorphisms of Apolipoprotein B and Angiotensin I-Converting Enzyme Genes and Relationships with Lipid Levels in Italian Patients with Vascular Dementia or Alzheimer’s Disease
Authors: Scacchi R. , de Bernardini L. , Mantuano E. , Vilardo T. , Donini L.M. , Ruggeri M. , Gemma A.T. , Pascone R. , Corbo R.M.
Published: April 2003

The distribution of three DNA polymorphisms (XbaI, EcoRI, and I/D) of the apolipoprotein B (APOB) gene, and of the I/D polymorphism of the angiotensin I-converting enzyme (ACE) gene was investigated in 53 patients with vascular dementia, in 80 patients with late-onset sporadic Alzheimer’s disease, and in 153 age-matched control subjects. Furthermore, plasma total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured in the three groups and the involvement of the genetic variation at APOB locus on lipid levels was determined. Major findings of this work are (1) no genotype or allele of the polymorphisms examined here seemed to be associated with vascular dementia or with Alzheimer’s disease, (2) total cholesterol and LDL cholesterol levels were lower in Alzheimer’s disease patients than in vascular dementia patients and in elderly controls, and (3) the dementia patients with APOB EcoRI R+R– genotype had higher total cholesterol and LDL cholesterol levels than R+R+ homozygotes.
Cognitive and Behavioral Differentiation of Frontal Lobe Degeneration of the Non-Alzheimer Type and Alzheimer’s Disease
Authors: Lindau Maria , Almkvist Ove , Johansson Sven-Erik , Wahlund Lars-Olof
Published: April 2003

Neuropsychological differences between 14 patients with a clinical diagnosis of frontal lobe degeneration of non-Alzheimer type (FLD) and 15 patients with a clinical diagnosis of Alzheimer’s disease (AD) were studied. The most efficient psychometric predictors of FLD were Digit Symbol, estimation tasks, word list recall, and particularly the FAS word fluency test. Behavioral predictors of FLD and AD showed a double dissociation: regression and impulsivity characterized FLD, whereas lack of motivation and slowness were typical of AD. Cognitive and behavioral differences between groups were not related to the degree of dementia, as measured by Mini Mental State Examination, indicating that differences remained during progression of the diseases.
Intracerebroventricular Infusion of Nerve Growth Factor in Three Patients with Alzheimer’s Disease
Authors: Eriksdotter Jönhagen Maria , Nordberg Agneta , Amberla Kaarina , Bäckman Lars , Ebendal Ted , Meyerson Björn , Olson Lars , Seiger Åke , Shigeta Masahiro , Theodorsson Elvar , Viitanen Matti , Winblad Bengt , Wahlund Lars-Olof
Published: April 2003

Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer’s disease. We have treated 3 patients with Alzheimer’s disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.
Epidemiologic and Genetic Studies of Dementia of the Alzheimer Type in Japan
Authors: Urakami Katsuya , Adachi Yoshiki , Wakutani Yosuke , Isoe Kenji , Ji Yong , Takahashi Kazuro , Nakashima Kenji
Published: April 2003

We carried out two separate epidemiological studies on long-term changes, 10 years apart, on the prevalence rate of dementia in the elderly by the same method for the same area in Japan. We also performed a genetic study of patients with dementia of the Alzheimer type (DAT) based on the epidemiological studies. The number of patients with dementia was much larger in 1990 than in 1980. Especially, the number of mildly demented patients was significantly larger in 1990 than in 1980. The 35 patients with DAT did not show any mutations of amyloid-β protein precursor, presenilin 1 and presenilin 2 genes. The frequency of apolipoprotein E (apo E) σ4 allele in DAT was significantly higher than that in control subjects (p < 0.005). This study suggests that the frequency of DAT may increase by aging of the population in the future and we confirm the close association between apoE σ4 allele and DAT in a community-based study in Japan.
In vivo Quantification of Brain Volumes in Subcortical Vascular Dementia and Alzheimer’s Disease
Authors: Pantel J. , Schröder J. , Essig M. , Jauss M. , Schneider G. , Eysenbach K. , von Kummer R. , Baudendistel K. , Schad L.R. , Knopp M.V.
Published: April 2003

Quantitative magnetic resonance imaging (MRI) was used to assess global and regional cerebral volumes in patients with a clinical diagnosis of subcortical vascular dementia (VD) and Alzheimer’s disease (AD). Whole brain volume, cerebrospinal fluid volume, volumes of the temporal, frontal and parietal lobes, the cerebellum and the amygdala-hippocampus complex were determined using a personal computer-based software. Seventeen patients with VD, 22 patients with AD and 13 healthy controls were included. Analysis of covariance using age as covariate demonstrated significant mean differences between controls and dementia groups with respect to all morphological parameters. However, apart from the volume of the cerebellum no significant volumetric differences were found between VD and AD. These results indicate that MRI-based volumetry allows differentiation between AD or VD from normal controls and that measurement of cerebellar volume may be of use to separate vascular and degenerative dementia. However, since the distribution of cerebral atrophy in both dementia groups is very similar, it is suggested that the atrophic changes are not specific to the underlying cause but rather reflect the selective vulnerability of neuronal structures.
Relatively Preserved Hippocampal Glucose Metabolism in Mild Alzheimer’s Disease
Authors: Ishii Kazunari , Sasaki Masahiro , Yamaji Shigeru , Sakamoto Setsu , Kitagaki Hajime , Mori Etsuro
Published: April 2003

The purpose of this study was to clarify the changes in hippocampal glucose metabolism in mild Alzheimer’s disease (AD) using positron emission tomography (PET) and 2-(18F)fluoro-2-deoxy-D-glucose (FDG). Forty-one patients with probable mild AD (age: 69.0 ± 8.0 years; MMSE: 22.6 ± 2.1) and 22 normal volunteers (age: 67.7 ± 7.1 years) were studied. The regional cerebral metabolic rate for glucose (CMRglc) was measured using FDG and PET. Although the mean CMRglc in the parietal region was significantly lower in the AD group (right: 6.35 ± 1.26 mg/100 g/min; left: 6.37 ± 1.21 mg/100 g/min) than in the control group (right: 7.73 ± 1.02 mg/100 g/min; left: 7.63 ± 0.95 mg/100 g/min), the mean CMRglc in the hippocampus did not show a significant difference between the AD group (right: 4.58 ± 0.70 mg/100 g/min; left: 4.63 ± 0.67 mg/100 g/min) and the control group (right: 5.22 ± 0.65 mg/100 g/min; left: 5.22 ± 0.67 mg/100 g/min) by analysis of variance and post-hoc Tukey’s test. The magnitude of the hippocampal CMRglc reduction was not as large as that of parietal CMRglc reduction. Statistical parametric maps (SPM) analysis also did not significantly demonstrate reduced hippocampal CMRglc in AD patients, although it did show a significant reduction in parietal CMRglc in AD patients. Hippocampal CMRglc was not significantly decreased in mild AD. This was unexpected in view of previous studies that have shown atrophy and clinical dysfunction concerning hippocampus in AD, and suggests that the pathophysiology of the hippocampus in AD may be more complex than was previously thought.
Prevalence of Alzheimer’s Disease and Other Dementing Disorders: Assiut-Upper Egypt Study
Authors: Farrag Abdul-Kader F. , Farwiz Hassan M. , Khedr Eman H. , Mahfouz Refaat M. , Omran Safaa M.
Published: April 2003

The aim of this study was to determine the prevalence rate of Alzheimer’s disease (AD) and other types of dementias among the population over the age of 60 years in Assiut governorate. A 3-phase cross-sectional population-based study was carried out to screen 2,000 subjects residing in 11 different locations representing the sociocultural status of the area. We subjected each proband to a modified form of the Mini Mental State Examination test. Subjects scored 21 or less were investigated according to a standardized protocol. We found 90 demented subjects yielding a crude prevalence ratio (case per 100 population over the age of 60) of 4.5. A diagnosis of subtypes of dementia was reached in 83 cases. Prevalence ratios for dementia subtypes were 2.2 for AD, 0.95 for multi-infarct dementia. 0.55 for mixed dementias and 0.45 for secondary dementias. Age-specific prevalence tends to be doubled every 5 years. Occupation, level of education and residence did not affect the prevalence or severity of dementia. Comparison with other studies suggests that dementia of all types is as frequent in Assiut governorate as elsewhere.
Apolipoprotein E and α1-Antichymotrypsin Genotypes and Age of Onset of Familial Alzheimer’s Disease
Authors: Axelman Karin , Basun Hans , Lannfelt Lars
Published: April 2003

Apolipoprotein E (APOE) and α1-antichymotrypsin (ACT) genotype and allele frequency distribution were investigated in 113 familial Alzheimer’s disease (AD) cases. A significantly higher σ4 frequency was observed in patients with an age of onset between 55–64 and 65–74 years compared to individuals with later or earlier onset. No difference in ACT A allele frequency was seen in any onset group, nor was any influence of ACT genotypes on the age of onset observed. However, the mean age of onset was lowered by the presence of the ACT/AA and ACT/TT genotypes among APOE σ3/3 bearers. Possible APOE effects on age of onset were evaluated in 78 affected sib pairs. An earlier age of onset was observed in siblings with an σ4 allele compared to siblings without an σ4 allele. This supports the notion that the σ4 allele promotes an earlier age of onset. However, in siblings with the same APOE genotype, a wide range of onset was seen, indicating that unknown genetic or environmental factors affect the expression of AD.
Dehydroepiandrosterone Sulfate Decreases the Interleukin-2-Mediated Overactivity of the Natural Killer Cell Compartment in Senile Dementia of the Alzheimer Type
Authors: Solerte Sebastiano Bruno , Fioravanti Marisa , Schifino Nicola , Cuzzoni Gianni , Fontana Ilaria , Vignati Giulio , Govoni Stefano , Ferrari Ettore
Published: April 2003

Since dehydroepiandrosterone sulfate (DHEAS) has been involved in the regulation of cellular immunity, the aim of the presence study was to evaluate whether the age-dependent reduction of DHEAS was associated with changes of natural killer (NK) immune function in healthy elderly subjects and in patients with senile dementia of the Alzheimer type (SDAT). Circulating DHEAS was determined throughout 24 h (circadian profile). NK cytotoxic activity was measured as spontaneous and induced cytotoxicity during exposure with DHEAS (10–7 M), interleukin-2 (IL-2; 100 IU) and IL-2 (100 IU) coincubated with DHEAS (10–7 M). DHEAS was significantly reduced in healthy elderly subjects (mesor M ± SD = 2.3 ± 0.5 µmol/l) and SDAT (1.6 ± 0.4 µmol/l) patients compared to healthy young subjects (6.7 ± 0.9 µmol/l; p < 0.001); significant differences were also found when healthy elderly subjects and SDAT patients were compared (p < 0.01). A significant inverse correlation between age and DHEAS levels was demonstrated in SDAT and healthy elderly subjects (p < 0.05). The decrease in 24-hour DHEAS secretion was associated with a higher NK cytotoxic response to DHEAS in the healthy elderly subject group than in healthy subjects of young age (p < 0.01). Increased NK cell activity during IL-2 incubation was found in patients with SDAT in comparison with the healthy elderly subject (p < 0.001). On the contrary, NK cell cytotoxic response of SDAT patients was less pronounced during DHEAS exposure and when DHEAS was coincubated with IL-2 (p < 0.001). These data suggest an immunomodulatory role of DHEAS on NK functional activity in physiological aging and SDAT. The antagonizing effect of DHEAS on NK overactivity during exposure with cytokines might counteract some neuroimmune components related to the pathogenesis and progression of the disease.
Penetrance and Phenotypic Expression of a Mutation Linked to Creutzfeldt-Jakob Disease in the Elderly
Authors: Frenkel Y.R. , Ben-Israel J. , Korczyn A.D. , Chapman J.
Published: April 2003

We have previously reported several carriers of the PRNP E200K point mutation among subjects aged over 65 years. In order to examine the prevalence of this mutation among demented subjects of Libyan and Tunisian origin and the clinical characteristics associated with it, we screened 58 elderly subjects belonging to this ethnic group. Five mutation carriers were identified, all of whom had cognitive deterioration consistent with primary degenerative dementia. All had low Hachinski ischemic scores (0.8 ± 0.8, mean ± SD) as compared with noncarriers (6.7 ± 3.0; p = 0.011, Wilcoxon rank sum test). In addition to the cognitive decline, 4 carriers had additional cerebellar, pyramidal, or extrapyramidal findings compatible with the diagnosis of possible or probable Creutzfeldt-Jakob disease.
Neuroimaging Findings in Twins Discordant for Alzheimer’s Disease
Authors: Pedersen Nancy L. , Miller Bruce L. , Loebach Wetherell Julie , Vallø Jørgen , Toga Arthur W. , Knutson Nathan , Mehringer C. Mark , Small Gary W. , Gatz Margaret
Published: April 2003

Data from computed tomography (CT) scans of 12 twin pairs in which one partner had Azheimer’s disease (AD) and the other partner is cognitively intact were analyzed to study structural brain features associated with AD while controlling for familial factors. Visual ratings and analysis of quantified areas and volumes indicated that AD twins showed more dilation of temporal horns, lateral ventricles and third ventricle, and more atrophy of temporal lobes, particularly in the anterior temporal/perisylvian area, than their healthy cotwins. Demented twins did not have smaller intracranial areas or overall brain volumes than their intact partners. The apolipoprotein σ-4 allele was associated with greater dilation of lateral ventricles and ventricular volume. Significant intrapair correlations were found for total intracranial area and volume, cerebellar area and white matter lesions.
Oxidation of Cytosolic Proteins and Expression of Creatine Kinase BB in Frontal Lobe in Different Neurodegenerative Disorders
Authors: Aksenova M.V. , Aksenov M.Y. , Payne R.M. , Trojanowski J.Q. , Schmidt M.L. , Carney J.M. , Butterfield D.A. , Markesbery W.R.
Published: April 2003

The presence of the biomarkers of oxidative damage, protein carbonyl formation and the inactivation of oxidatively sensitive brain creatine kinase (CK BB, cytosolic isoform), were studied in frontal lobe autopsy specimens obtained from patients with different age-related neurodegenerative diseases: Alzheimer’s disease (AD), Pick’s disease (PkD), diffuse Lewy body disease (DLBD), Parkinson’s disease (PD), and age-matched control subjects. The CK activity was significantly reduced in the frontal lobe of AD, PkD and DLBD subjects, and CK BB-specific mRNA was significantly reduced in AD and DLBD. Protein carbonyl content was significantly increased in AD, PkD and DLBD. The results of this study confirm that the presence of biomarkers of oxidative damage is related to the presence of histopathological markers of neurodegeneration. Our data suggest that oxidative damage contributes to the development of the symptoms of frontal dysfunction in AD, PkD and DLBD. The development of frontal dysfunction in idiopathic PD might be secondary to oxidative damage and neuronal loss primarily located in the nigrostriatal system. The results of CK BB expression analysis demonstrate that the loss of the isoenzyme in different neurodegenerative diseases is likely the consequence of its posttranslational modification, possibly oxidative damage. Changes in CK BB expression may be an early indicator of oxidative stress in neurons.
Alzheimer’s Disease in 22 Twin Pairs – 13-Year Follow-Up: Hormonal, Infectious and Traumatic Factors
Authors: Nee Linda E. , Lippa Carol F.
Published: April 2003

We obtained follow-up data on 22 sets of twins where at least one twin had Alzheimer’s disease (AD). The concordance rate for monozygotic twins (n = 17 pairs) was 59%, whereas that for dizygotic twins was 40%. In our series 8 monozygotic twins had hysterectomies; all had AD. The twins with hysterectomies also had a tendency to develop AD at an earlier age than their co-twin. Five twins with serious systemic infection developed AD, and they tended to have earlier onset than their corresponding twin. We found no strong evidence that head injury predisposed to AD.
Update on the Neuropathogenesis of Delirium
Authors: Trzepacz Paula T.
Published: April 2003

Delirium has been considered a syndrome of generalized dysfunction of higher cortical functions due to its breadth of symptoms and associated diffuse slowing on electroencephalogram. Advances in neuropsychiatry have revealed differences between brain regions, including the hemispheres, which may underlie the constellation of symptoms among different psychiatric disorders. For example, different neural pathways are involved in major depression and obsessive-compulsive disorder, including lateralization to one or the other hemisphere. In this article the author proposes that delirium, too, involves particular neural pathways and that lateralization to the right may be relevant. Structural and functional neuroimaging reports and recent neuropsychological studies support this lateralization. Prefrontal cortices, anterior and right thalamus, and right basilar mesial temporoparietal cortex may play a significant role in subserving delirium symptoms and may be the ‘final common pathway’ for delirium from a variety of etiologies. The final common pathway may be responsible for certain ‘core symptoms’ (disorientation, cognitive deficits, sleep-wake cycle disturbance, disorganized thinking, and language abnormalities), while other symptoms (delusions, hallucinations, illusions, and affective lability) may occur depending on the etiology causing delirium. An imbalance in the cholinergic and dopaminergic neurotransmitter systems is most commonly implicated in causing delirium, and could both account for delirium symptoms and be consistent with the neuroanatomical pathways being implicated.
Clinical Subtypes of Delirium in the Elderly
Authors: O’Keeffe Shaun T.
Published: April 2003

Psychomotor disturbance is common in delirium, with some patients being restless and hyperactive and others lethargic and hypoalert. Although patients with hyperactive delirium may be recognised more readily, hypoactive and mixed forms of delirium are more common on general hospital wards. Recent evidence suggests that hyperactive delirium has a better prognosis than other subtypes. It remains uncertain whether this reflects fundamental differences in the pathophysiology of different subtypes.
No Detected Mutations in the Genes for the Amyloid Precursor Protein and Presenilins 1 and 2 in a Swiss Early-Onset Alzheimer’s Disease Family with a Dominant Mode of Inheritance
Authors: Savioz A. , Leuba G. , Forsell C. , Lilius L. , Rossier C. , Saini K. , Bouras C. , Lannfelt L.
Published: April 2003

Mutations have been found in more than a hundred early-onset families with Alzheimer’s disease (AD) in the genes for the amyloid precursor protein, presenilin 1 and presenilin 2. The object of our investigation was to identify if these mutations or novel ones were operating in a Swiss early-onset AD family (mean age of onset: 53.3 years) with 7 members available, all neuropathologically confirmed. No known or new mutations were detected. Thus, our data support the existence of a yet unknown mutation, or other genes, contributing to familial early-onset AD.
Apolipoprotein E ε4 Is Associated with Neuronal Loss in the Substantia nigra in Alzheimer’s Disease
Authors: Camicioli Richard , Kaye Jeffrey , Payami Haydeh , Ball Melvyn J. , Murdoch Geoffrey
Published: April 2003

Apolipoprotein E ε4 (ApoE ε4) is associated with an earlier age at onset of Alzheimer’s (AD) and possibly Parkinson’s disease, suggesting a general role for ApoE ε4 in neuronal plasticity. Among 31 prospectively assessed subjects with pathologically confirmed AD (without Lewy bodies), ε4+ subjects had a longer duration of disease (by 2.8 years, p = 0.04). Only cell loss in the substantia nigra (p = 0.002) was associated with ε4. Neither neurofibrillary tangles nor plaque counts were associated with ε4. Cell counts of pigmented neurons in single midbrain sections in ε4+ specimens were 72% of those in ε4– substantia nigra (p = 0.04). These findings confirm that cell loss in the substantia nigra is associated with ε4 in AD.
No Association between Apolipoprotein A-IV Codon 360 Mutation and Late-Onset Alzheimer’s Disease in the Japanese Population
Authors: Ji Yong , Urakami Katsuya , Adachi Yoshiki , Nakashima Kenji
Published: April 2003

Human apolipoprotein A-IV (apoA-IV) is genetically polymorphic, the apoA-IV polymorphism being controlled by two alleles, apoA-IV1 and apoA-IV2. The association between the apoA-IV2 allele and late-onset Alzheimer’s disease (LOAD) has been reported in Caucasian populations. We investigated the codon 360 mutation of the apoA-IV gene allele frequency in 173 LOAD and in 158 age-matched control subjects of the Japanese population, and we found that the allele frequency of apoA-IV2 in the Japanese population was very rare and was extremely lower than in Caucasian populations. We conclude that there was no association between apoA-IV genotype and LOAD in the Japanese population.
Evaluation of Serum-Lipid-Related Cardiovascular Risk Factors in Alzheimer’s Disease
Authors: Kálmán J. , Kudchodkar B.J. , Murray K. , McConathy W.J. , Juhász A. , Janka Z. , Lacko A.G.
Published: April 2003

There is now sufficient evidence to suggest that cardiovascular pathology and altered lipid metabolism contribute to the development of late-onset Alzheimer’s disease (AD). In the present study, 24 AD patients and 15 controls were assessed for cardiovascular risk based on serum lipid and lipid oxidation parameters. The AD patients appeared to have a more favorable cardiovascular risk profile than the controls based on high-density lipoprotein cholesterol (HDL-C) values. The levels of thiobarbituric-acid-rective substances and the activity of the enzyme paraoxonase (PON) following copper oxidation indicate that female patients may have better protection against serum and perhaps tissue oxidants than males with AD. While the higher HDL-C values indicate lower cardiovascular risk, additional data on oxidized lipid parameters suggest a lower level of protection against serum oxidants in male AD probands.
Use of Estrogens for the Prevention and Treatment of Alzheimer’s Disease
Authors: Monk Dorota , Brodaty Henry
Published: April 2003

This review examines the biological rationale for the use of estrogen replacement therapy (ERT) and the evidence for the efficacy of ERT in enhancing cognition, preventing Alzheimer’s disease (AD) and treating AD in postmenopausal women. While the biological basis for ERT as a cognition enhancer is strong and multiply mediated, the clinical evidence for its use is not as compelling and must be weighed against possible side effects. Until the results of definitive large trials are available, the use of ERT alone or in combination with other treatments is worthy of consideration.