EPILEPSIA, Issue 4 2003
Beate Diehl
Summary: ,Purpose: Medically intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), with or without cortical dysplasia (CD), is associated with atrophy of the hippocampal formation and regional fluorodeoxyglucose positron-emission tomography (FDG-PET) hypometabolism. The relation between areas of functional and structural abnormalities is not well understood. We investigate the relation between FDG-PET metabolism and temporal lobe (TL) and hippocampal atrophy in patients with histologically proven isolated HS and HS associated with CD. Methods: Twenty-three patients underwent en bloc resection of the mesial and anterolateral neocortical structures. Ten patients were diagnosed with isolated HS; 13 patients had associated microscopic CD. Temporal lobe volumes (TLVs) and hippocampal volumes were measured. Magnetic resonance imaging (MRI) and PET were co-registered, and regions of interest (ROIs) determined as gray matter of the mesial, lateral, and anterior temporal lobe. Results: All patients (HS with or without CD) had significant ipsilateral PET hypometabolism in all three regions studied (p < 0.0001). In patients with isolated HS, the most prominent hypometabolism was in the anterior and mesial temporal lobe, whereas in dual pathology, it was in the lateral temporal lobe. TLVs and hippocampal volumes were significantly smaller on the epileptogenic side (p < 0.05). The PET asymmetries ipsilateral/contralateral to the epileptogenic zone and TLV asymmetries correlated significantly for the anterior and lateral temporal lobes (p < 0.05) in the HS+CD group, but not in the isolated HS group. Mesial temporal hypometabolism was not significantly different between the two groups. Conclusions: Temporal neocortical microscopic CD with concurrent HS is associated with more prominent lateral temporal metabolic dysfunction compared with isolated HS in TL atrophy. Further studies are needed to confirm these findings and correlate the PET hypometabolic patterns with outcome data in patients operated on for HS with or without CD. [source]

Occipitoparietal Epilepsy, Hippocampal Atrophy, and Congenital Developmental Abnormalities

EPILEPSIA, Issue 1 2000
Article first published online: 19 SEP 200
First page of article [source]

Interleukin-2 Gene Polymorphisms Associated with Increased Risk of Gastric Atrophy from Helicobacter pylori Infection

HELICOBACTER, Issue 3 2005
Shozo Togawa
ABSTRACT Background., Gastric atrophy induced by Helicobacter pylori is thought to predispose patients to noncardiac gastric cancer development. However, the host genetic factors that influence the progression of gastric atrophy have not been elucidated. In this study, we examined the effects of cytokine polymorphisms on H. pylori -induced gastric atrophy. Methods., Blood samples were taken from 454 Japanese subjects. The interleukin-2 (IL-2; T-330G), IL-4 (C-33T), and IL-13 (C-1111T) polymorphisms were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Anti- H. pylori IgG antibody and pepsinogen I and II were measured to diagnose H. pylori infection and atrophic gastritis. Results., The odds ratios (ORs) for the association between IL-2 polymorphism [OR = 2.78, 95% CI (confidence interval) = 1.26,6.17 (T/T to G/G)] or IL-4 polymorphism [OR = 2.22, 95% CI = 1.01,4.89 (T/C to C/C)] were increased significantly with gastric atrophy, whereas the corresponding OR of IL-13 polymorphism was decreased with gastric atrophy [OR = 0.61, 95% CI = 0.39,0.96 (C/T and T/T to C/C)]. There were no significant H. pylori seropositivity-related differences between these polymorphisms. We examined the relationship between these polymorphisms and gastric atrophy separately in H. pylori -seropositive and -seronegative groups. In the H. pylori -seropositive group, the IL-2 T/T (OR = 2.78, 95% CI = 1.12,6.93) had a significant association with gastric atrophy. Conclusions., These results reveal that the IL-2 gene polymorphism is associated with an increased risk of gastric atrophy induced by H. pylori infection and might predispose to gastric cancer. [source]

Impact of Helicobacter pylori on the Development of Vitamin B12 Deficiency in the Absence of Gastric Atrophy

HELICOBACTER, Issue 6 2002
Ender Serin
Abstract Background. Cobalamin (vitamin B12) deficiency is associated with Helicobacter pylori infection. This study examined how serum vitamin B12 levels relate to gastric mucosa H. pylori density and histology, and to hematological findings in patients with minimal or no gastric atrophy. A second aim was to confirm that H. pylori eradication therapy increases serum B12. Materials and Methods. Biopsies of the gastric mucosa from a population of dyspeptic patients were graded for level of chronic inflammation, neutrophil activity, atrophy, and H. pylori density. A total of 145 H. pylori -infected patients with minimal or no atrophy were included in the study. Serum cobalamin level, hemoglobin level, and mean corpuscular volume were measured in the 145 patients before eradication therapy, and in 65 of the subjects after treatment. The hematologic findings before and after eradication therapy and correlations between serum vitamin B12 level and histologic parameters, hematologic findings, and patient age were statistically analyzed. Results. There was no significant correlation between serum cobalamin level and patient age. Before treatment all the histopathological scores were inversely correlated with serum vitamin B12 level (p < .01) on univariate analysis. Only H. pylori density was significantly associated with B12 level on multivariate analysis. Serum hemoglobin and cobalamin levels were significantly increased after treatment, regardless of H. pylori eradication status (p < .001). Conclusion. The findings provide strong evidence that H. pylori infection is associated with cobalamin deficiency, and show that this is true even in patients with nonulcer dyspepsia and minimal or no gastric atrophy. [source]

Lichen planopilaris [cicatricial (scarring) alopecia] in a child

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2001
FNASC, FRAS (Lond.), Virendra N. Sehgal MD
A mother of a 12-year-old boy, 2 years ago, noticed that he showed patchy loss of hair on the vertex of the scalp. It was asymptomatic and progressive. Subsequently, similar patches appeared elsewhere on the scalp. Some of these patches joined to form a large bald patch. This was accompanied by dusky blue eruptions over the left upper lip and eyebrows. Later, there was localized loss of hair. A family history of a similar ailment was absent. Examination of the scalp revealed plaques of alopecia with mild to moderate erythema. The skin was smooth, shiny, and atrophic (Fig. 1). Atrophy was apparent by the presence of wrinkles in places, and by holding the skin between the thumb and the index finger. The periphery of the lesions was well demarcated and was occupied by erythematous, scaly, follicular papules. Lesions were also located on the patches of alopecia. In addition, flat-topped, dusky blue, papules/plaques were present over the upper lip. Figure 1. Lichen planopilaris: plaques of alopecia showing smooth, shiny, atrophic skin with erythema A study of hematoxylin and eosin-stained microsections prepared from the upper lip and vertex of the scalp was undertaken. The former revealed hyperkeratosis, hypergranulosis, sawtooth irregular acanthosis, and destruction of the basal cell layer which, in turn, was embraced by a lymphohistiocytic infiltrate disposed in a band-like fashion. A few cells were seen invading the epidermis. Pigment-laden histiocytes were found intermingled with the infiltrate. In the scalp skin, on the other hand, atrophy of the epidermis with punctuation of keratin plugs, together with fibrosis of the dermis, was prominent. The walls of the hair follicles were hyperkeratotic, while their lumina were conspicuous by their dilatation and contained keratotic plugs (Fig. 2a,b). Sebaceous and sweat glands were absent. Figure 2. Lichen planopilaris showing atrophy of the epidermis, fibrosis of the dermis, dilatation of the hair follicle lumina containing keratotic plug(s), and hyperkeratosis of the wall of the follicle (hematoxylin and eosin: a , ×,40; b , ×,100) Response to treatment, comprising ultramicronized griseofulvin (Gris O.D.) 375 mg/day (Sehgal VN, Abraham GJS, Malik GB. Griseofulvin therapy in lichen planus ,- a double blind controlled trial. Br J Dermatol 1972; 86: 383,385; Sehgal VN, Bikhchandani R, Koranne RV et al. Histopathological evaluation of griseofulvin therapy in lichen planus. A double blind controlled study. Dermatologica 1980; 161: 22,27) and prednisolone 20 mg/day for 6 months, was excellent (Fig. 3). Topical betamethasone dipropionate (Diprovate) lotion was used as a supplement. Figure 3. Perceptible decline in band-like lymphohistiocytic inflammatory infiltrate (hematoxylin and eosin, a, × 40; b, ×,100) [source]

Neural correlates of verbal episodic memory in patients with MCI and Alzheimer's disease,,a VBM study

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2008
Dirk T. Leube
Abstract Objective The hippocampus is a key area for episodic memory processes. Hippocampal atrophy is a hallmark feature of Alzheimer's disease (AD). We used a new and automatized morphometric technique to better characterize brain atrophy in subjects with different levels of cognitive deficit. Methods In this study 21 participants with Mild Cognitive Impairment (MCI), 12 patients with early AD and 29 elderly control subjects were subjected to high resolution MRI and a neuropsychological test battery. Brain volume across participants, measured by voxel-based morphometry (VBM), was correlated with verbal memory capacity, measured with a verbal memory test (VLMT). Results Atrophy in the anterior hippocampus, the ento- and perirhinal cortex as well as the parahippocampal gyrus, middle temporal gyrus and anterior cingulate cortex correlated closely with episodic memory performance. Conclusions These brain areas are known to subserve episodic encoding of verbal material. The data contribute to a better understanding of atrophic brain processes in subjects at risk for AD. A combination of neuropsychological testing and voxel-based morphometry may serve as a diagnostic tool in the future. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Effects of age and competence type on the emotions: Focusing on sadness and anger

JAPANESE PSYCHOLOGICAL RESEARCH, Issue 3 2007
TOSHIHIKO HAYAMIZU
Abstract:, The effects of age and competence type on emotional reactions were demonstrated in this study. Participants: (362 junior high-school students, 658 senior high-school students, 407 undergraduates, and 1027 adults) were asked to rate the Assumed-competence Scale, second version (ACS-2) and Rosenberg's Self-esteem Scale, which were prepared to classify the participants into four competence types: Omnipotent, Assumed, Self-respective, and Atrophy. They also rated their perceived emotional reactions toward negative personal and social events, and the responses were compared among age groups and competence types. Remarkable results showed that the Assumed and the Atrophy types were prominent in junior and senior high-school students. They tend to get angry toward negative personal events, and they also tend not to respond emotionally toward social events. Another result was that people in the Assumed and Omnipotent types were likely to get angry toward both personal and social events, and they were also less responsive toward social events. [source]

Malignant Ventricular Arrhythmia in a Case of Adult Onset of Spinal Muscular Atrophy (Kugelberg,Welander Disease)

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2009
MARKUS ROOS M.D.
We present a case of a 43-year-old male patient with adult onset of spinal muscular atrophy (SMA). The patient first came to our attention with atrioventricular (AV) block. A dual-chamber pacemaker (DDD-PM) was implanted. Four years later, the PM data log showed occurrence of frequent episodes of nonsustained ventricular tachycardia (NSVT). The episodes progressed in duration and frequency. An electrophysiological study revealed prolonged His-ventricular (HV) interval duration and induction of sustained ventricular tachycardia. The patient was successfully upgraded to a prophylactic dual-chamber cardioverter defibrillator. Our case is the first description of a patient with adult-onset SMA (Kugelberg,Welander disease [KWD]) and malignant ventricular arrhythmias. [source]

Atrophy and anarchy: third national survey of nursing skill-mix and advanced nursing practice in ophthalmology

JOURNAL OF CLINICAL NURSING, Issue 12 2006
Dip Nursing, Wladyslawa J. Czuber-Dochan MSc
Aims and objectives., The aims of the study were to investigate the advanced nursing practice and the skill-mix of nurses working in ophthalmology. Background., The expansion of new nursing roles in the United Kingdom in the past decade is set against the background of a nursing shortage. The plan to modernize the National Health Service and improve the efficiency and delivery of healthcare services as well as to reduce junior doctors' hours contributes towards a profusion of new and more specialized and advanced nursing roles in various areas of nursing including ophthalmology. Design., A self-reporting quantitative questionnaire was employed. The study used comparative and descriptive statistical tests. Method., The questionnaires were distributed to all ophthalmic hospitals and units in the United Kingdom. Hospital and unit managers were responsible for completing the questionnaires. Results., Out of a total 181 questionnaires 117 were returned. There is a downward trend in the total number of nurses working in ophthalmology. The results demonstrate more nurses working at an advanced level. However, there is a general confusion regarding role interpretation at the advanced level of practice, evident through the wide range of job titles being used. There was inconsistency in the qualifications expected of these nurses. Conclusion., Whilst there are more nurses working at an advanced level this is set against an ageing workforce and an overall decline in the number of nurses in ophthalmology. There is inconsistency in job titles, grades, roles and qualifications for nurses who work at an advanced or higher level of practice. The Agenda for Change with its new structure for grading jobs in the United Kingdom may offer protection and consistency in job titles, pay and qualifications for National Health Service nurse specialists. The Nursing and Midwifery Council needs to provide clear guidelines to the practitioners on educational and professional requirements, to protect patients and nurses. Relevance to clinical practice., The findings indicate that there is a need for better regulations for nurses working at advanced nursing practice. [source]

The emerging role of epigenetic modifications and chromatin remodeling in spinal muscular atrophy

JOURNAL OF NEUROCHEMISTRY, Issue 6 2009
Sebastian Lunke
Abstract As the leading genetic cause for infantile death, Spinal Muscular Atrophy (SMA) has been extensively studied since its first description in the early 1890s. Though today much is known about the cause of the disease, a cure or effective treatment is not currently available. Recently the short chain fatty acid valproic acid, a drug used for decades in the management of epilepsy and migraine therapy, has been shown to elevate the levels of the essential survival motor neuron protein in cultured cells. In SMA mice, valproic acid diminished the severity of the disease phenotype. This effect was linked to the ability of the short chain fatty acid to suppress histone deacetylase activity and activate gene transcription. Since then, the study of different histone deacetylase inhibitors and their epigenetic modifying capabilities has been of high interest in an attempt to find potential candidates for effective treatment of SMA. In this review, we summarize the current knowledge about use of histone deacetylase inhibitors in SMA as well as their proposed effects on chromatin structure and discuss further implications for possible treatments of SMA arising from research examining epigenetic change. [source]

Voxel-Based Morphometry and Voxel-Based Relaxometry in Parkinsonian Variant of Multiple System Atrophy

JOURNAL OF NEUROIMAGING, Issue 3 2010
Loukia C. Tzarouchi MD
ABSTRACT BACKGROUND AND PURPOSE Multiple system atrophy (MSA) is a progressive neurodegenerative disorder divided into a parkinsonian (MSA-P) and a cerebellar variant. The purpose of this study was to assess regional brain atrophy and iron content using Voxel-based morphometry (VBM) and Voxel-based relaxometry (VBR) respectively, in MSA-P. METHODS Using biological parametric mapping the effect of brain atrophy was evaluated in T2 relaxation time (T2) measurements by applying analysis of covariance (ANCOVA) and correlation analysis to the VBM and VBR data. Eleven patients with MSA-P (aged 61.9 ± 11.7 years, disease duration 5.42 ± 2.5 years) and 11 controls were studied. RESULTS In comparison to the controls the patients showed decreased gray matter in the putamen, the caudate nuclei, the thalami, the anterior cerebellar lobes, and the cerebral cortex, and white matter atrophy in the pons, midbrain, and peduncles. VBR analysis showed prolonged T2 in various cortical regions. On ANCOVA, when controlling for gray and white matter volume, these regions of prolonged T2 were shrunk. Negative correlation was demonstrated between T2 and gray and white matter volume. CONCLUSIONS Diffuse brain atrophy, mainly in the motor circuitry is observed in MSA-P. Normalization for atrophy should always be performed in T2 measurements. [source]

Measuring Brain Atrophy in Multiple Sclerosis

JOURNAL OF NEUROIMAGING, Issue 2007
Nicola De Stefano MD
ABSTRACT The last decade has seen the development of methods that use conventional magnetic resonance imaging (MRI) to provide sensitive and reproducible assessments of brain volumes. This has increased the interest in brain atrophy measurement as a reliable indicator of disease progression in many neurological disorders, including multiple sclerosis (MS). After a brief introduction in which we discuss the most commonly used methods for assessing brain atrophy, we will review the most relevant MS studies that have used MRI-based quantitative measures of brain atrophy, the clinical importance of these results, and the potential for future application of these measures to understand MS pathology and progression. Despite the number of issues that still need to be solved, the measurement of brain atrophy by MRI is sufficiently precise and accurate. It represents one of most promising in vivo measures of neuroaxonal degeneration in MS, and it should be used extensively in the future to assess and monitor pathological evolution and treatment efficacy in this disease. [source]

Progressive Cerebral Disease in Lymphomatoid Granulomatosis Causes Anterograde Amnesia and Neuropsychiatric Disorder

JOURNAL OF NEUROIMAGING, Issue 2 2006
Dominic A. Carone PhD
ABSTRACT The authors report neuropsychological (NP) and serial quantitative magnetic resonance imaging (MRI) findings of a 29-year-old woman with lymphomatoid granulomatosis (LG). Disease course was characterized by acute psychosis, tremor, fever, seizures, and progressive cognitive impairment. At the time of symptom onset, brain MRI revealed mild lesion volume and normal parenchymal volume. This was followed by dramatic progression of brain lesions and atrophy over 2 years, at which point the patient expired. Atrophy was most prominent in the mesial temporal lobes. NP testing revealed marked amnesia and mild impairments in other cognitive domains. To our knowledge, this is the first recorded case of LG in which bilateral temporal lobe atrophy is evident and accompanied by anterograde amnesia. We speculate that temporal lobe atrophy was influenced by the established susceptibility of this region in various neurological diseases. [source]

The "Cross" Signs in Patients With Multiple System Atrophy: A Quantitative Study

JOURNAL OF NEUROIMAGING, Issue 1 2006
Kazuo Abe MD
ABSTRACT Patients with multiple system atrophy (MSA) may show the "cross" sign in the pontine base that has been considered as an expression of the degeneration of pontine neurons and transverse pontocerebellar fibers. However, correlations between pontine base atrophy and existence of "cross" sign have not been fully investigated. The authors studied 68 patients with MSA (47 MSA-C [predominantly cerebellar ataxia], 21 MSA-P [predominantly parkinsonism], mean [±SD ] 58.7 ± 10.9 years). T1-weighted (T1W) sagittal and axial images and T2-weighted (T2W) axial images were obtained for all patients and controls. To measure the areas of pontine basis and cerebellar vermis, the authors used midsagittal T1W images and analyzed a bit map transformed on a computer. They classified atrophy in the pontine base into 3 grades. There is significant correlation between atrophies of pontine base and existence of the cross sign. All patients with a smaller area of pontine base 2 standard deviations below those of normal controls had the cross sign. This supports that existence of the cross sign depends only on the extent of pontine base atrophies. [source]

Measurement of Brain and Spinal Cord Atrophy by Magnetic Resonance Imaging as a Tool to Monitor Multiple Sclerosis

JOURNAL OF NEUROIMAGING, Issue 2005
FAAN, Rohit Bakshi MD
ABSTRACT Evaluation of brain and spinal cord atrophy by magnetic resonance imaging (MRI) has become an increasingly important component of understanding the multiple sclerosis (MS) disease process. These destructive aspects of the disease develop early in the disease course. A growing body of data links brain and spinal cord atrophy to clinical impairment more closely than can be linked with conventional measures of overt lesions. Thus, irreversible tissue damage may be a key factor leading to disease progression. In this review, the authors present the proposed mechanisms leading to central nervous system (CNS) atrophy. They describe the available MRI-based techniques to measure regional and global atrophy of the brain and spinal cord. They compare the rate of atrophy among MS phenotypes and summarize the emerging data linking atrophy to neurological and neuropsychological impairment. Finally, they discuss the effect of disease-modifying immunotherapies on the rate of CNS atrophy in patients with MS. Future research to clarify the etiology and pathophysiology of brain and spinal cord atrophy should provide new targets for therapeutic development. [source]

Pathogenesis of Brain and Spinal Cord Atrophy in Multiple Sclerosis

JOURNAL OF NEUROIMAGING, Issue 2004
Alireza Minagar MD
ABSTRACT For more than a century, multiple sclerosis was viewed as a disease process characterized by oligodendrocyte and myelin loss, and research into the pathogenesis of multiple sclerosis was mainly focused on the mechanisms of inflammation. However, with development of more sophisticated neuroimaging and molecular biology techniques, attention has shifted to new aspects of pathogenesis of multiple sclerosis: axonal loss and neurodegeneration. Evidence is increasing that tissue destruction, primarily axonal loss and neurodegeneration, is a key element in the pathogenesis of multiple sclerosis. In addition, it is now known that brain and spinal cord atrophy begins early in the disease process of multiple sclerosis and advances relentlessly throughout the course of the disease. Cumulative data suggest that axonal loss is the major determinant of progressive neuro logic disability in patients with multiple sclerosis. Magnetic resonance imaging and magnetic resonance spectroscopy in patients with multiple sclerosis for < 5 years indicate brain atrophy and loss of axonal integrity. Neurodegeneration and axonal loss in patients with multiple sclerosis are initially accompanied by a local response from oligodendrocyte progenitor cells and some remyelination. However, these repair mechanisms eventually fail, and patients typically develop generalized brain atrophy, cognitive decline, and permanent disability. Although the exact mechanisms underlying central nervous system atrophy in patients with multiple sclerosis are largely unknown, evidence exists that atrophy may represent an epiphenomenon related to the effects of dynamic inflammation within the central nervous system, including demyelination, axonal injury, neuronal loss, Wallerian degeneration, and possibly iron deposition. This article summarizes the potential mechanisms involved in central nervous system atrophy in patients with multiple sclerosis. [source]

Measurement of Whole-Brain Atrophy in Multiple Sclerosis

JOURNAL OF NEUROIMAGING, Issue 2004
Daniel Pelletier MD
ABSTRACT Brain atrophy reflects the net result of irreversible and destructive pathological processes in multiple sclerosis (MS). The gross morphological changes can be accurately quantified using standard magnetic resonance imaging (MRI) acquisitions and various image analysis tools. The current methods used to assess whole-brain atrophy in patients with MS can be classified into 2 groups based on their reliance on segmentation and registration. Segmentation-based methods employed to measure whole-brain atrophy in MS include the brain parenchymal fraction, the index of brain atrophy, the whole-brain ratio, the brain to intracranial capacity ratio, fuzzy connectedness/Udupa's method, 3DVIEWNIX, the Alfano method, and SIENAX. Current registration-based methods used to measure whole-brain atrophy in MS include the brain boundary shift integral, SIENA, statistical parametric mapping, template-driven seg mentation, and voxel-based morphometry. Most of the methods presented here are sensitive to subtle changes in brain structures and have been successfully applied to MS as measures of whole-brain atrophy. Yet comparative studies of these methods are limited and are complicated by the lack of a gold standard for image acquisition, a segmentation algorithm, an image analysis method, or a reproducibility measure. Overall, the measure of whole-brain atrophy from MRI contributes to an appreciation of the dynamics of MS pathology and its relationship to the clinical course of MS. Determination of the relative reproducibility, precision, sensitivity, and validity of these methods will promote the use of whole-brain atrophy measures as components of comprehensive MRI-based outcome assessment in MS clinical trials. [source]

Is Gadolinium Enhancement Predictive of the Development of Brain Atrophy in Multiple Sclerosis?

JOURNAL OF NEUROIMAGING, Issue 4 2002
A Review of the Literature
ABSTRACT Background and Purpose. Several studies have demonstrated that brain atrophy can be detected over relatively short intervals from the earliest stages of multiple sclerosis (MS). Reviewing the published data, the authors highlight some hypothetical pathological mechanisms proposed as determinants of brain atrophy. Methods. Using the terms multiple sclerosis, MRI (magnetic resonance imaging), and brain atrophy, 181 citations were identified. The authors considered only studies with prospective designs with natural-course MS patients and/or placebo-treated patients of therapeutic trials, in which patients under-went baseline and follow-up scans with a T1-weighted gadolinium diethylenetriamine penta-acetic acid sequence (0.1 mmol/kg body weight), and correlation analyses between Gd enhancement activity and brain atrophy progression. Results. Five hundred thirty-two patients of 5 natural history studies and 5 therapeutic trial studies participated in the review process. The main observation was that in patients with a relapsing-remitting (RR) disease course, there was a correlation between Gd enhancement activity and brain atrophy progression. This correlation was not influenced by any other demographic and clinical additional data considered in the review process. Conclusions. Examination of the pathological mechanisms pro-posed in the reviewed studies led the authors to believe that inflammation is only in part responsible for the development of brain atrophy. This conclusion may have an implication for the strategies of tissue protection advocated in the early stages of the RR course and strengthen recent evidence indicating that anti-inflammatory immunomodulatory agents and immunosuppressive treatments, which predominantly act against the inflammatory component of disease activity, may not have similar effects on progressive tissue loss, either in RR or progressive MS. [source]

Procysteine Stimulates Expression of Key Anabolic Factors and Reduces Plantaris Atrophy in Alcohol-Fed Rats

ALCOHOLISM, Issue 8 2009
Jeffrey S. Otis
Background:, Long-term alcohol ingestion may produce severe oxidant stress and lead to skeletal muscle dysfunction. Emerging evidence has suggested that members of the interleukin-6 (IL-6) family of cytokines play diverse roles in the regulation of skeletal muscle mass. Thus, our goals were (i) to minimize the degree of oxidant stress and attenuate atrophy by supplementing the diets of alcohol-fed rats with the glutathione precursor, procysteine, and (ii) to identify the roles of IL-6 family members in alcoholic myopathy. Methods:, Age- and gender-matched Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 35 weeks. Subgroups of alcohol-fed rats received procysteine (0.35%, w/v) for the final 12 weeks. Plantaris morphology was assessed by hematoxylin and eosin staining. Major components of glutathione metabolism were determined using assay kits. Real-time PCR was used to determine expression levels of several genes. Results:, Plantaris muscles from alcohol-fed rats displayed extensive atrophy, as well as decreased glutathione levels, decreased activities of glutathione reductase and glutathione peroxidase, decreased superoxide dismutase (SOD)-2 (Mn-SOD2), and increased NADPH oxidase-1 gene expression,each indicative of significant oxidant stress. Alcohol also induced gene expression of catabolic factors including IL-6, oncostatin M, atrogin-1, muscle ring finger protein-1, and IGFBP-1. Procysteine treatment attenuated plantaris atrophy, restored glutathione levels, and increased catalase, Cu/Zn-SOD1, and Mn-SOD2 mRNA expression, but did not reduce other markers of oxidant stress or levels of these catabolic factors. Instead, procysteine stimulated gene expression of anabolic factors such as insulin-like growth factor-1, ciliary neurotrophic factor, and cardiotrophin-1. Conclusions:, Procysteine significantly attenuated, but did not completely abrogate, alcohol-induced oxidant stress or catabolic factors. Rather, procysteine minimized the extent of plantaris atrophy by inducing components of several anabolic pathways. Therefore, anti-oxidant treatments such as procysteine supplementation may benefit individuals with alcoholic myopathy. [source]

Protective Effect of Vitamin E Against Ethanol-Induced Hyperhomocysteinemia, DNA Damage, and Atrophy in the Developing Male Rat Brain

ALCOHOLISM, Issue 7 2009
Alireza Shirpoor
Background:, Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by clinical investigations and animal experiments. It has been posited that elevated levels of Hcy mediate DNA damage, brain atrophy, and excitotoxicity. The current study sought to elucidate the effect of vitamin E on ethanol-induced hyperhomocysteinemia, DNA damage, and atrophy in the developing hippocampus and cerebellum of rats. Methods:, Pregnant Wistar rats received ethanol with or without vitamin E from gestation day 7 throughout lactation. Weight changes in the brain, hippocampus and cerebellum, DNA damage, and Hcy levels in the plasma, hippocampus, and cerebellum of male offspring were measured at the end of lactation. Results:, The results revealed that along with a significant decrease in brain, cerebellum, and hippocampus weights in animals that received alcohol, the levels of DNA damage and Hcy significantly increased. Significant amelioration of brain atrophy and DNA damage as well as restoration of the elevated level of Hcy to that of controls were found in vitamin E-treated rats. Conclusions:, These findings strongly support the idea that ethanol intake by dams during pregnancy and lactation induces Hcy-mediated oxidative stress in the developing hippocampus and cerebellum of offspring rats, and that these effects can be alleviated by vitamin E as an antioxidant. [source]

The Pathophysiology of ,Brain Shrinkage' in Alcoholics , Structural and Molecular Changes and Clinical Implications

ALCOHOLISM, Issue 6 2005
Clive Harper
This article represents a symposium of the 2004 ISBRA Congress held in Mannheim. The presentations were: Review of the neuropathological and neurochemical changes seen in alcohol-related ,brain shrinkage' by Clive Harper; In Vivo Detection of Macrostructural and Microstructural Markers of Brain Integrity in Human Alcoholism and a Rodent Model of Alcoholism by Adolf Pfefferbaum, Elfar Adalsteinsson and Edith Sullivan; Gene and Protein Changes in the Brains of Alcoholics with ,Brain Shrinkage' by Joanne Lewohl and Peter Dodd; Cross sectional and longitudinal MR spectroscopy studies of chronic adult alcoholics by Michael Taylor; Brain Atrophy Associated with Impairment on a Simulated Gambling Task in Long-Term Abstinent Alcoholics by George Fein and Bennett Landman. [source]

Alteration of histological gastritis after cure of Helicobacter pylori infection

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2002
M. Hojo
Summary Background : It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. Aim : To clarify the histological changes after the cure of H. pylori infection through a literature survey. Methods : Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. Results : Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-up period (> 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow-up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Five of 28 studies described significant improvement of intestinal metaplasia. Conclusions : Activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. Improvement of intestinal metaplasia was difficult to analyse due to methodological problems including statistical power. [source]

Serum pepsinogen and gastrin levels in HIV-positive patients: relationship with CD4+ cell count and Helicobacter pylori infection

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2002
P. Fabris
Background: The relationship between serum parameters of gastric function and Helicobacter pylori infection in human immunodeficiency virus (HIV)-positive patients is almost unknown. Aims: To investigate in HIV-infected patients: (i) the relationship between serum gastrin and serum pepsinogens over the progressive phases of HIV-related disease; (ii) the impact of H. pylori infection on gastrin and pepsinogen serum levels and its relation to antral histology; (iii) the prevalence of parietal cell autoantibodies. Methods: Fifty-nine HIV-positive patients were studied by upper endoscopy plus gastric antral biopsy. Serum samples were tested for gastrin, pepsinogen A, pepsinogen C and parietal cell autoantibodies. Results: In patients without overt acquired immunodeficiency syndrome (AIDS), or with a CD4+ count of > 100 × 106 cells/L, mean serum levels of gastrin and pepsinogen C were higher than in subjects with AIDS or with a CD4+ count of < 100 × 106 cells/L (P < 0.01). Only one patient was found to be positive for parietal cell autoantibodies. H. pylori infection was associated with increased values of gastrin and pepsinogen C only in HIV-positive patients without AIDS or with a CD4+ count of > 100 × 106 cells/L. Atrophy was more frequent in patients with overt AIDS than in those without overt AIDS (57% vs. 33%, P=N.S.), and/or in patients with a CD4+ count of < 100 × 106 cells/L than in those with a CD4+ count of > 100 × 106 cells/L (62% vs. 26%, P < 0.05). Conclusions: HIV-positive patients without overt AIDS have increased serum levels of gastrin and pepsinogen C compared with HIV-positive patients with overt AIDS. [source]

Murine fetal small-intestine grafts: Morphometric and immunohistochemical evaluation

MICROSURGERY, Issue 1 2006
Carlos Eduardo Saldanha De Almeida
We investigated histopathological changes following murine fetal intestinal transplantation. Fetal intestine, obtained from a pregnant C57BL/6 mouse, was transplanted into BALB/c and C57Bl/6 mice. Recipients were divided into three groups: isogeneic, and allogeneic treated with 3 mg/kg/day gangliosides (Allo-a) or 9 mg/kg/day (Allo-b). One week after transplant, all grafts showed good viability, confirmed by cellular mitosis in the mucosa and a well-defined propria muscular layer. Isogeneic grafts showed a thicker muscular layer than in the Allo-a (P = 0.02) and Allo-b (P = 0.004) groups. There was no difference in number of mitotic cells among groups. Goblet cells were significantly reduced in allografts treated with 3 mg gangliosides (P = 0.013) or 9 mg gangliosides (P = 0.002) compared to isografts. Villi height was similar in all studied groups. There was no difference in positivity of the enteric nervous system among groups. Atrophy was more common in the allogeneic groups, suggesting that isografts had better development than allografts treated with gangliosides. © 2006 Wiley-Liss, Inc. Microsurgery 26: 61,64, 2006. [source]

Single muscle fiber size and contractility after spinal cord injury in rats

MUSCLE AND NERVE, Issue 1 2006
Walter R. Frontera MD
Abstract Spinal cord injury (SCI) results in muscle weakness but the degree of impairment at the level of single fibers is not known. The purpose of this study was to examine the effects of T9,level SCI on single muscle fibers from the tibialis anterior of rats. Significant decreases in cross-sectional area (CSA), maximal force (Po), and specific force (SF = Po/CSA) were noted at 2 weeks. Atrophy and force-generating capacity were reversed at 4 weeks, but SF remained impaired. Maximum shortening velocity (Vo) did not change after injury. SCI thus appears to affect various contractile properties of single muscle fibers differently. Normal cage activity may partially restore function but new interventions are needed to restore muscle fiber quality. Muscle Nerve, 2006 [source]

Comparative study of commercially available anti-,-synuclein antibodies

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2006
E. Croisier
Immunohistochemistry for alpha-synuclein has become the histological technique of choice for the diagnosis for Parkinson's disease, Dementia with Lewy bodies and Multiple System Atrophy (http://www.ICDNS.org). Nevertheless, no standardised protocol has been proposed. We have reviewed 242 of the 270 studies published until June 2005 that mentioned immunohistochemistry for anti-alpha synuclein on human tissue and we found that only 75 (31%) used commercial antibodies. We also noted that protocols, particularly dilution and antigen unmasking, varied between studies, even when the same antibody was employed. In order to establish a standardised protocol for alpha-synuclein immunohistochemistry, which can be applied in diagnostic neuropathology we tested seven commercial monoclonal antibodies in brains of subjects with Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, multiple sclerosis with incidental Lewy bodies and aged-matched normal brain and determined for each antibody the best suited protocol for antigen unmasking. We evaluated the intensity of immunolabelling in Lewy bodies, neuropil threads, dendrites, pre-synaptic terminals, granular cytoplasmic positivity, peri-axonal positivity, glial inclusions and non-specific immunolabelling. Although our results showed that all the antibodies detected alpha-synuclein inclusions, differences were noted between antibodies, particularly with regard to the detection of glial inclusions. From our study, the best antibodies of the seven tested appeared to be those directed against amino acids 116,131 and 15,123 and we suggest them to be used in routine diagnostic practice for alpha-synucleinopathies. [source]

Update on the neurology of Parkinson's disease,

NEUROUROLOGY AND URODYNAMICS, Issue 1 2007
Clare J. Fowler
Abstract The differential diagnosis of a patient with apparent Parkinson's Disease (PD) and bladder symptoms is considered and the bladder dysfunction of Multiple System Atrophy (MSA) is reviewed. Recent insights into the progression of the neuropathology of PD have enabled thinking about the stage of the disease at which bladder dysfunction is likely to occur and the expected clinical context of the problem. Bladder symptoms of neurological origin are likely in a patient who has had treated motor symptoms for some years and in whom the ongoing neuropathology has progressed beyond involvement of the basal ganglia, so that symptoms due to cortical dysfunction as well as the adverse effects of dopaminergic medication are also confounding factors. Bladder symptoms in a man with lesser neurological disability should be investigated to exclude underlying outflow obstruction. Possible management options are considered. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source]

Progressive Hemifacial Atrophy with Linear Scleroderma

PEDIATRIC DERMATOLOGY, Issue 5 2005
Emine Dervis M.D.
She had a linear white-colored sclerotic plaque on the right submandibular area of skin. Histologic findings of the lesion were consistent with a diagnosis of scleroderma. The relationship between progressive facial hemiatrophy and linear scleroderma are discussed. We think that linear scleroderma of childhood and hemifacial atrophy have considerable clinical overlap and these two syndromes appear to be manifestations of the same or related pathogenic processes. Recently, the beneficial effects of 1.25-dihydroxyvitamin D3 (calcitriol) were reported in adults and in children with linear scleroderma. We assessed the efficacy of oral calcitriol treatment in our patient. Our result indicates that calcitriol may be an effective agent for treating localized scleroderma in children. [source]