Cortical lesions and cognitive impairment in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system. In the last decade, pathological and magnetic resonance imaging (MRI) studies have shown that a significant portion of inflammatory lesions are located in the grey matter, especially in the cerebral cortex, of MS patients. Cortical inflammatory lesions (CL) can be demonstrated in vivo in MS patients by double inversion recovery (DIR) MRI sequence. Neuropsychological deficits constitute a major clinical aspect of MS, being demonstrated in a percentage ranging from 40 to 65% of patients, and have been shown to be associated with cortical demyelination and atrophy. Recent DIR studies in MS patients having different clinical forms of the disease have disclosed that CL burden not only correlates with the severity of physical disability, but is also one of the major structural changes associated with disease-related cognitive impairment.     

Cardiac infections: focus on molecular diagnosis

The role of different types of infections in heart diseases is more important than commonly thought, with new and re-emerging infections (i.e., Mycobacterium tuberculosis).This review addresses the pathology of infective pericarditis, myocarditis, and endocarditis, mainly focusing on the significance of molecular techniques in the detection of infective agents. Molecular investigations represent important ancillary diagnostic tools and combined with other conventional approaches provide a more precise final diagnosis. A close collaboration and communication among cardiologists, cardiac surgeons, pathologists, and microbiologists is essential to ensure optimal diagnoses and management as well as a favorable impact on patient outcome.     

Biochemical alterations from normal mucosa to gastric cancer by ex vivo magnetic resonance spectroscopy

BACKGROUND AND AIMS: The metabolic profile and morphologic aspects of normal and pathologic human gastric mucosa were studied. The aim of the present research was the application of ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) to the human gastric tissue to get information on the molecular steps involved in gastric carcinogenesis and the identification of biochemical markers useful for the development of in vivo MRS methodologies to diagnose gastric pathologies in clinical situations. METHODS: Twelve normal subjects, five with autoimmune atrophic gastritis, five with Helicobacter pylori infection, and five with adenocarcinoma were examined. Ten biopsies were taken during endoscopy from each patient. Specimens from carcinoma were also obtained during gastrectomy. Of the 10 biopsies, 4 were used for histologic evaluation, 4 were fixed in glutaraldehyde and processed for transmission and scanning electron microscopy, and 2 were immersed in liquid nitrogen and stored at -85 degrees C for monodimensional and bidimensional ex vivo HR-MAS MRS analysis. RESULTS: Ex vivo HR-MAS MRS identified glycine, alanine, free choline, and triglycerides as possible molecular markers related to the human gastric mucosa differentiation toward preneoplastic and neoplastic conditions. Ultrastructural studies of autoimmune atrophic gastritis and gastric adenocarcinoma revealed lipid accumulations intracellularly and extracellularly associated with a severe prenecrotic hypoxia and mitochondria degeneration. CONCLUSIONS: This is the first report of synergic applications of ex vivo HR-MAS MRS and electron microscopy in studying the human gastric mucosa differentiation. This research provides useful information about some molecular steps involved in gastric carcinogenesis. The biochemical data obtained on gastric pathologic tissue could represent the basis for clinical applications of in vivo MRS.     

Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines.

BACKGROUND: Treatment-related neurotoxicity has been recognized as a significant problem in patients with primary central nervous system lymphoma (PCNSL) as effective treatment has increased survival rates. There is, however, a paucity of research on cognitive functions in this population. DESIGN: In a review of the literature, a total of 17 articles that described cognitive outcome in adult PCNSL patients were identified. RESULTS: The studies that assessed cognitive functions after whole-brain radiotherapy combined with chemotherapy reported cognitive impairment in most patients. Patients treated with chemotherapy alone had either stable or improved cognitive performance in most studies. Methodological problems, however, limited the ability to ascertain the specific contribution of disease and various treatment interventions to cognitive outcome. On the basis of the literature review, a battery of cognitive and quality-of-life (QoL) measures to be used in prospective clinical trials was proposed. The battery is composed of five standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (attention, executive functions, memory, psychomotor speed), and QoL questionnaires, and meets criteria for use in collaborative trials. CONCLUSION: The incorporation of formal and systematic cognitive evaluations in PCNSL studies will improve our understanding of treatment-related neurotoxicity in this population.     

Developing a spatial-statistical model and map of historical malaria prevalence in Botswana using a staged variable selection procedure

Background  

Several malaria risk maps have been developed in recent years, many from the prevalence of infection data collated by the MARA (Mapping Malaria Risk in Africa) project, and using various environmental data sets as predictors. Variable selection is a major obstacle due to analytical problems caused by over-fitting, confounding and non-independence in the data. Testing and comparing every combination of explanatory variables in a Bayesian spatial framework remains unfeasible for most researchers. The aim of this study was to develop a malaria risk map using a systematic and practicable variable selection process for spatial analysis and mapping of historical malaria risk in Botswana.     

Predictive value of laboratory tests in "autoimmune" inner ear disease: preliminary report

The purpose of this prospective, controlled study was to estimate the prevalence of immune-mediated (autoimmune) inner ear disease in a high-risk patient population, in order to determine the predictive value of a positive lymphocyte transformation test. The high-risk group was defined as any dizzy patient with unilateral or bilateral-asymmetric sensorineural hearing loss, who had not previously received immunotherapy. From more than 400 consecutive patients with a chief complaint of dizziness, 58 were entered into the study over an 8-month period. The control group consisted of 15 normal volunteers. Thirteen patients (22%) one control (7%) had positive lymphocyte transformation tests. The data suggest that positive results in "high-risk" patients are more common than previously believed. Assuming test sensitivity is 96%, specificity 93%, and disease prevalence 22% in high-risk patients, the predictive value of a positive lymphocyte transformation test using inner ear membranes is 79%. That is, approximately three fourths of all positive results are true positives. Positive results in suspected patients, therefore, should be considered true positives, and treatment recommended. Future research should attempt to refine the putative antigen(s), further define "high risk" patients, and prospectively verify these preliminary results.     

Practical versus theoretical management of autoimmune inner ear disease

Autoimmune inner ear disease is an uncommon but distinct clinical entity. Our ignorance of the immune mediating pathways, need of further animal model experimentation, variability of laboratory test results and of patient treatment responses illustrate how poorly we understand this disorder. The purpose of this review is to compare practical vs theoretical management of autoimmune inner ear disease, based upon our current knowledge of the disease process and upon a review of clinical experience at the Cleveland Clinic Foundation. Representative case histories are presented. The following preliminary conclusions are discussed: Autoimmune inner ear disease can present as a systemic or localized otologic immune disorder. Hearing loss can begin at any age, with unilateral or bilateral sudden onset, fluctuating or progressive symptoms, with or without associated dizziness. The pathogenesis of autoimmune inner ear disease is probably multifactorial (cellular and humoral). The sensitivity and specificity of different laboratory tests vary greatly, but even the most sensitive tests may be falsely normal when symptoms are not acute or when the patient is taking immunosuppressant medication. The mainstay of autoimmune inner ear treatment is steroids: however, cytotoxic drugs are recommended when there is no response to steroid treatment. Apheresis is reserved for selected cases. Hearing improvement can be dramatic even after 2 months of profound deafness. Flare-ups of autoimmune ear disease are best managed by increasing steroid dosage or adding cytotoxic medications. Unfortunately, some patients will develop progressive hearing loss despite vigorous treatment.     

Hormesis and high-risk groups

The concept of hormesis (i.e., biological phenomena characterized by dose-response relationships displaying low-dose stimulation and high-dose inhibition) has important implications for current risk assessment practices because of its generalizability with respect to experimental model, agent, and endpoint measured. This paper addresses the question of whether hormesis is present in high-risk subpopulations and highly susceptible species. Evaluation of published data revealed that hormetic dose-response relationships occur with similar quantitative characteristics among species and individuals that display widely differing susceptibility to various toxicants. This observation suggests that the cause of the differential susceptibility in the more susceptible organisms is not due to the absence of the hormetic response but to some other factor(s). However, despite the recognition that hormetic responses are common and similar in susceptible and resistant organisms there are sufficient examples indicating that some strains/individuals may lack the capacity to produce the low-dose stimulatory response. Thus, the capacity to display hormetic effects is one of a variety of factors affecting differential susceptibility to xenobiotics and needs to be addressed within the hazard assessment process.