Genetic studies are under way for many complex traits, spurred by the recent feasibility of whole genome scans. Clear guidelines for the interpretation of linkage results are needed to avoid a flood of false positive claims. At the same time, an overly cautious approach runs the risk of causing true hints of linkage to be missed. We address this problem by proposing specific standards designed to maintain rigor while also promoting communication.

Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results

The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

SINCE Cohen's review of amyloidosis was published in the Journal in 1967, there have been major advances in our understanding of what was less than a decade ago an untreatable, usually lethal disease complex of unknown nature, cause, and pathogenesis. Much of the mystery about the character of the "waxy, eosinophilic" tissue deposits, which Virchow believed in 1853 to be of polysaccharide composition and consequently designated as "amyloid" (starch-like or cellulose-like) has now yielded to investigations employing a wide variety of chemical and physical techniques. Once it was demonstrated that unique fibrillar components comprised over 90 per cent of amyloid . . .

Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts).

Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease.

Endometriosis

Familial Mediterranean fever. A survey of 470 cases and review of the literature

To determine whether colchicine prevents or ameliorates amyloidosis in patients with familial Mediterranean fever, we followed 1070 patients with the latter disease for 4 to 11 years after they were advised to take colchicine to prevent febrile attacks Overall, at the end of the study, the prevalence of nephropathy was one third of that in a study conducted before colchicine was used to treat familial Mediterranean fever Among 960 patients who initially had no evidence of amyloidosis, proteinuria appeared in 4 who adhered to the prophylactic schedule and in 16 of 54 who admitted non-compliance Life-table analysis showed that the cumulative rate of proteinuria was 17 percent (90 percent confidence limits, 00 and 113 percent) after 11 years in the compliant patients and 489 percent (188 and 790 percent) after 9 years in the noncompliant patients (P less than 00001) A total of 110 patients had overt nephropathy when they started to take colchicine Among 86 patients who had proteinuria but not the nephrotic syndrome, proteinuria resolved in 5 and stabilized in 68 (for more than eight years in 40) Renal function deteriorated in 13 of the patients with proteinuria and in all of the 24 patients with the nephrotic syndrome or uremia We conclude that colchicine prevented amyloidosis in our high-risk population and that it can prevent additional deterioration of renal function in patients with amyloidosis who have proteinuria but not the nephrotic syndrome

Colchicine in the Prevention and Treatment of the Amyloidosis of Familial Mediterranean Fever

A four-month, double-blind, crossover study of 22 patients with familial Mediterranean fever was undertaken to study the effect of colchicine in decreasing acute attacks of that disease. T...

A Controlled Trial of Colchicine in Preventing Attacks of Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an autosomal-recessive disease which affects almost exclusively people of Mediterranean and Middle Eastern origin. We examined the possibility of a dominant inheritance of FMF among our 3,000 patients in Israel. Two hundred forty FMF patients were members of 77 families in which the disease affected more than one generation. In 75 of these families the occurrence of FMF in more than one generation was found to be consistent with a recessive mode of inheritance due to a high gene frequency (q) and consanguinity among parents of the patients. In 2 families, one of Ashkenazi and the other of Georgian Iraqi origin, in which FMF occurred in 4 consecutive generations, the mode of inheritance could be explained only by autosomal-dominant inheritance.

Dominant inheritance in two families with familial Mediterranean fever (FMF).

Three hundred fifty children (younger than age 16) who had familial Mediterranean fever (FMF) were given continuous prophylactic treatment with colchicine (1-2 mg/day) for 6-13 years. Complete remission of febrile attacks was achieved in 64% of the patients, and partial remission in 31%. Protracted attacks of arthritis virtually disappeared. None of the children developed amyloidosis while on the colchicine regimen. Side effects of colchicine were insignificant, and did not prompt permanent discontinuation of treatment in any of the children. Their growth, development, and subsequent fertility were normal. The efficacy of long-term colchicine treatment of children with FMF makes early diagnosis life saving.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780340806

Ezra Sohar

Papers

Familial Mediterranean fever. A survey of 470 cases and review of the literature

Colchicine in the Prevention and Treatment of the Amyloidosis of Familial Mediterranean Fever

A Controlled Trial of Colchicine in Preventing Attacks of Familial Mediterranean Fever

Dominant inheritance in two families with familial Mediterranean fever (FMF).

Long-term colchicine treatment in children with familial mediterranean fever