https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71142-9.pdf

Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.

Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice

Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack

The hygiene hypothesis postulates that an environment with a high incidence of infectious diseases protects against allergic and autoimmune diseases, whereas hygienic surroundings increase the incidence of these disorders This review examines the evidence in support of the hygiene hypothesis and offers a number of mechanisms that could explain the relation between sanitary conditions and susceptibility to allergic and autoimmune diseases

https://www.nejm.org/doi/pdf/10.1056/NEJMra020100

The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)17670-8.pdf

External validity of randomised controlled trials: “To whom do the results of this trial apply?”

Neurology 1968;18:671-680

Progressive spinal muscular atrophy, juvenile proximal spinal muscular atrophy (Kugelberg-Welander), and infantile muscular atrophy (Werdnig-Hoffman) comprise a group of diseases by virtue of their pathological similarity Chronic degeneration of the lower motor neurons and neurogenic atrophy of the skeletal muscle are common to all The diseases differ in mode of inheritance, age of onset, distribution of muscular atrophy, and prognosis Some investigators have considered them as a continuum of the same disease, underscoring the pathological similarity, while others have emphasized the clinical differences and prefer to regard them as distinct entities

This report describes 2 families in which 11 members, all male, were affected by an unusual, slowly progressive spinal and bulbar muscular atrophy This disease, apparently inherited as a sex-linked recessive trait, becomes manifest clinically in the fourth and fifth decades and initially involves proximal muscles The proximal weakness gave a clinical picture similar to muscular dystrophy in some patients A full description is made of the prepositus of each family, but only the more striking features or unusual aspects are mentioned in the other cases

Case 1 (V-9) A 57-year-old white meat packer first noted the onset of low back pain at age 30 (Fig 2) Five years later, he began to experience muscle cramps and fasciculations He was able to wield a heavy meat cleaver until age 37 when increasing weakness of the shoulder and pelvic girdle muscles forced him to retire A neurological examination at that time revealed weakness and fasciculations of the proximal limb and girdle muscles





Fig 2 ( Left ) Case 1 (V-9) Member of B family Weakness and atrophy of muscles in extremities, with maximal involvement in girdle musculature Fig 3 ( Right ) Case 7 (V-29) Member of B family Progressive bulbar and limb weakness



He was first examined at the University of …

Progressive proximal spinal and bulbar muscular atrophy of late onset A sex-linked recessive trait

There have been few population-based studies of acute transverse myelitis (ATM). Therefore, incidence and population selectivity of this disorder in different regions is not well known. Data on all Jewish patients with ATM throughout Israel were collected for the period 1955 through 1975. Based on 62 patients who satisfied rigid diagnostic criteria, the average annual incidence rate was 1.34 per million population. No significant difference in incidence was noted between European American-born and Afro/Asian-born populations. There was no significant seasonal or annual fluctuation in frequency. In 37% of the patients, a history of infection prior to ATM was reported, more commonly among younger patients. ATM rarely evolved into multiple sclerosis. More than one-third of the patients with ATM made a good recovery; in another one-third recovery was only fair; 14 patients failed to improve and 3 died. If other population-based studies of ATM were undertaken, comparison with our results might shed further light on the causes of this disorder.

Acute transverse myelitis Incidence and etiologic considerations

MULTIPLE sclerosis tends to be common in temperate latitudes and rare in regions near the equator. 1-4 This geographical distribution suggests that some factor in temperate environments causes the disease, or, conversely, a protective factor is present in tropical regions. If an environmental factor accounts for the difference in frequency between temperate and tropical regions, then migration from one climatic zone to another could affect the risk of developing the disease. Individuals migrating from temperate to tropical areas would be expected to have a decreased risk of acquiring multiple sclerosis whereas those migrating in the opposite direction might increase their risk. An altered risk would be especially evident if migration occurred at a young age before there was adequate opportunity for exposure to the etiological (or protective) factor. Moreover, if risk changed sharply with migration at a particular age, it would suggest that the disease was usually acquired before

Risk of multiple sclerosis related to age at immigration to Israel.

The frequency of multiple sclerosis has been found to increase with increasing latitude. This peculiar geographical distribution has given rise to various hypotheses implicating an environmental factor in the aetiology of the disease (Dean, 1949; Westlund and Kurland, 1953; Kurland and Westlund, 1954; Kurland, Mulder, and Westlund, 1955; Acheson, Bachrach, and Wright, 1960; Mutlu, 1960; Alter, Halpern, Kurland, Bornstein, Leibowitz, and Silberstein, 1962; Kurland and Reed, 1964). Recently, Poskanzer, Schapira, and Miller (1963) have discussed the possibility of an infectious aetiology and have suggested that multiple sclerosis may be an occasional manifestation of a widespread subclinical infection. They think that an enteric infection should be considered because of many similarities in the epidemiological pattern of poliomyelitis and multiple sclerosis. They postulate further that the prevalence of clinically apparent multiple sclerosis might be correlated with the level of sanitation, a situation analogous to that observed in poliomyelitis. Thus, in areas where the sanitary level is high, infection may be acquired later in life, when the individual is more susceptible to the process which produces multiple sclerosis. Conversely, where sanitation is poor, infection may be acquired early when the individual is less susceptible. Although supporting evidence is meagre, these postulates are attractive because they are compatible with the known geographical distribution of the disease. In temperate areas where sanitation is generally on a high level, multiple sclerosis is common; in tropical regions the sanitary level is generally poorer and multiple sclerosis is rare. There are some clinical observations suggesting that the central nervous system of older individuals may be less resistant to the pathological process of

https://jnnp.bmj.com/content/jnnp/29/1/60.full.pdf

Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation.

PROGRESSIVE SPINAL MUSCULAR ATROPHY, juvenile proximal spinal muscular atrophy (Kugelberg-Welander ) , and infantile muscular atrophy ( Werdnig-Hoffman) comprise a group of diseases by virtue of their pathological similarity. Chronic degeneration of the lower motor neurons and neurogenic atrophy of the skeletal muscle are common to all. The diseases differ in mode of inheritance, age of onset, distribution of muscular atrophy, and prognosis. Some investigators have considered them as a continuum of the same disease, underscoring the pathological similarity, while others have emphasized the clinical differences and prefer to regard them as distinct entities. This report describes 2 families in which 11 members, all male, were affected by an unusual, slowly progressive spinal and bulbar muscular atrophy. This disease, apparently inherited as a sex-linked recessive trait, becomes manifest clinically in the fourth and Hth decades and initially involves proximal muscles. The proximal weakness gave a clinical picture similar to muscular dystrophy in some patients. A full description is made of the prepositus of each family, but only the more striking features or unusual aspects are mentioned in the other cases.

Milton Alter

Papers

Progressive proximal spinal and bulbar muscular atrophy of late onset A sex-linked recessive trait

Acute transverse myelitis Incidence and etiologic considerations

Risk of multiple sclerosis related to age at immigration to Israel.

Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation.

Progressive proximal spinal and bulbar muscular atrophy of late onset: a sex-linked recessive trait