Although genetic susceptibility explains the clustering of multiple sclerosis (MS) cases within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the geographic variations in MS frequency and the changes in risk that occur with migration. Epidemiological data provide some support for the "hygiene hypothesis," but with the additional proviso for a key role of Epstein-Barr virus (EBV) in determining MS risk. We show that whereas EBV stands out as the only infectious agent that can explain many of the key features of MS epidemiology, by itself the link between EBV and MS cannot explain the decline in risk among migrants from high to low MS prevalence areas. This decline implies that either EBV strains in low-risk areas have less propensity to cause MS, or that other infectious or noninfectious factors modify the host response to EBV or otherwise contribute to determine MS risk. The role of infectious factors is discussed here; in a companion article, we will examine the possible role of noninfectious factors and provide evidence that high levels of vitamin D may have a protective role, particularly during adolescence. The primary purpose of these reviews is to identify clues to the causes of MS and to evaluate the possibility of primary prevention.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/ana.21117

Environmental risk factors for multiple sclerosis. Part I: the role of infection.

Ultrastructure of malignant rhabdoid tumor of the kidney. A distinctive renal tumor of children

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus In addition, imaging methods as well as biomarkers are not well established Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones This review discusses mechanisms involved in progressive multiple sclerosis, correlations between histopathology and magnetic resonance imaging studies, along with possible new therapeutic approaches

/pdf/progressive-multiple-sclerosis-from-pathogenic-mechanisms-to-2eggo48zl0.pdf

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

The Effect of Intravesical Mitomycin C on Recurrence of Newly Diagnosed Superficial Bladder Cancer: A Further Report with 7 Years of Followup

Thirty-seven Ugandan Africans with Kaposi's sarcoma were studied prospectively and a clinical classification was devised based on the clinical presentation of the disease and the appearance of the cutaneous tumours. The disease could be sub-classified into four major groups. The first consisted of patients with nodular disease which was associated with a relatively benign clinical course. Patients in the next two groups (florid and infiltrative) had more aggressive disease with extensive cutaneous lesions on one or more extremities, generally associated with involvement of adjacent bone. Cutaneous lesions in the florid group were exophytic tumours while in the infiltrative group deep lesions associated with dense fibrosis predominated, Finally, the lymph-adenopathic variety occurred mainly in children where lymph-node involvement was usually the sole manifestation, and in young adults where skin involvement was seen concomitantly. Differing histological patterns were found to correlate with the four clinical types of involvement.

D.J.C. Read

Papers

Insensitivity of respiratory centre to carbon dioxide in the enga people of new guinea