Familial Mediterranean fever in the colchicine era: the fate of one family.

In order to demonstrate the effect of prophylactic colchicine treatment on the natural history of familial Mediterranean fever (FMF), a family is presented with 6 out of 9 siblings affected by FMF. Each patient represents a different stage of the amyloidotic kidney disease of FMF and the effect of continuous colchicine treatment on its course. Considered together, the members of this family present an almost complete clinical, genetic, and behavioral picture of the disease.

Twin studies in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a genetic disease characterized by recurrent short episodes of fever, accompanied by peritonitis, pleuritis, or arthritis. The disease is almost completely ethnically restricted to patients of Mediterranean descent--Sephardic Jews, Armenians, Anatolian Turks, and Arabs. Although many family studies have been performed, no twin study has been reported as yet. We studied 21 di- and monozygotic twin sets, identified among the 1,943 FMF patients in our registry. Full concordance was observed in all the 10 monozygotic twin sets. In the 11 dizygotic twins, concordance for FMF disease was found in only 3 pairs. Variability in the clinical manifestations and degree of severity have been noted within twins. These findings provide definitive evidence for the genetic cause of FMF. They also support the single gene autosomal recessive model, and provide support for the contention that the lower observed than expected incidence found in FMF is due to genetically affected but clinically undiagnosed patients.

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

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.

The changing face of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a genetic disease characterized by painful febrile "attacks" of serositis and the development of amyloidosis. Although FMF has been extensively studied and described, new data have accumulated during the last decade. This report gives an update, focusing specifically on (1) newly characterized manifestations, such as acute scrotal "attacks," protracted febrile myalgia, and spondyloarthropathy; (2) progress made in the diagnosis and treatment of FMF-amyloidosis; (3) experience acquired with colchicine, establishing its safety in common practice, childhood, conception, and pregnancy; (4) colchicine's role in the prevention and treatment of FMF-amyloidosis; (5) new laboratory findings; and (6) new considerations in the differential diagnosis. The most important achievement in recent years, however, is the mapping of the FMF susceptibility gene to chromosome 16p, a finding that raises hopes for prompt cloning of the gene and elucidation of the mechanisms involved in FMF expression.

Colchicine in the treatment of AA and AL amyloidosis.

Colchicine is an effective medication in the prevention and treatment of amyloidosis of familial Mediterranean fever. Its therapeutic effect depends on the stage of renal disease and the drug dose. To evaluate colchicine effect in AA amyloidosis of other diseases and in primary AL amyloidosis, the literature was reviewed. Findings were that (1) the effect of colchicine in reactive amyloidosis has not been methodically studied, but anecdotal reports suggest it may be beneficial; and (2) the results of studies and case reports on the effect of colchicine in primary amyloidosis are conflicting. Because a therapeutic effect of colchicine in primary and reactive amyloidosis has been shown in sporadic cases, a prospective, controlled, multicenter study assessing the effect of colchicine in all types of amyloidosis appears to be justified. Until such a study is available, the addition of colchicine in an appropriate dose to any therapeutic regimen of patients with AA or AL amyloidosis should be considered.

Incidence and origin of non-systemic microdeposits of amyloid.

In a general hospital, 391 consecutive necropsies in which at least seven organs were available, were examined retrospectively by polarizing microscopy of Congo-red-stained sections for the presence of local amyloid deposits.Non-systemic microdeposits of amyloid were encountered in 72 cases, an overall incidence of 18.4%. They were usually small and frequently detectable only by virtue of polarizing microscopy. There is no indication that these microdeposits of amyloid are of pathogenetic significance. Although they sometimes occur in more than one organ, such deposits can be readily distinguished from those of systemic amyloidosis by their histological features.

Exertional heat stroke: a case series.

UNLABELLED: Exertional heat stroke (EHS) is a state of extreme hyperthermia that occurs when excess heat that is generated by muscular exercise exceeds the body's ability to dissipate it at the same rate. EHS is thought to coincide with previously healthy, highly motivated, and relatively untrained individuals exerting in hot environments for long periods. PURPOSE: To establish this notion, the present study was aimed to follow the trends in the incidence of EHS in the period 1988-1996. METHODS: During these years, 150 cases of male soldiers (age = 20+/-3 yr) were reported to our institute as suffering from heat illnesses. According to the files, 82 cases were definitely diagnosed as EHS. RESULTS: More than 50% of the cases occurred during the first 6 months in service. Most of the cases occurred during the summer season (June-September), but 30% of the cases occurred during the spring. EHS was not related to time in the day. Many cases occurred during the night or early morning, even under mild heat load. Forty percent of the cases occurred during very short activities, and about 60% occurred already during the first 2 h of exercise. The results were discussed in view of the regulations which prevail in the Israeli army. CONCLUSIONS: It seems that almost all EHS cases occurred when regulations were not strictly followed.

Tap water, an efficient method for cooling heatstroke victims--a model in dogs.

Forty experimentally heatstroke dogs were cooled by immersion in water at temperatures varying from 1-25 degrees C. At all water temperatures, cooling occurred at a much slower rate in comatose dogs in conscious ones. Dogs cooled in tap water (15-16 degrees C) had the same cooling rate as those cooled in ice water (1-3 degrees C). At water temperatures above 18 degrees C, cooling rates were considerably decreased. Since tap water cooled as efficiently as ice water, its use may prove the method of choice for human heatstroke victims. Its advantages are ready availability, simplicity of use, and its failure to cause shivering.

[Man in a hot climate--early studies of the Institute of Military Physiology].

In the 1950's many IDF soldiers were hospitalized for heat stroke--about 25% of whom died. Analyzing these cases revealed that commanders misinterpreted human ability to perform in the heat and ignored basic concepts of fluid and electrolyte balance and heat load. In the early 1960's a series of studies was conducted with regard to soldiers' performance in the heat. The first study (1959), which later became a classic, was conducted during a 21-day march from Eilat to Metula, crossing all climatic zones of Israel. The study was followed by other investigations which approached the issues of voluntary dehydration, fluid consumption vs sweat loss, salt additives, and the effect of heat load on performance. Based on these early studies, proper regulations were issued to field officers. Over the years, the lessons learned from these studies saved many lives. The number of cases of heat stroke and of other climate-related injuries was dramatically reduced, and performance was enhanced.

[Physiological responses to heat and effort and complaints of hyperperspiration].

The sensation of hyperperspiration is a common complaint in hot, humid climates. 54 men and 20 women, 18-47 years old, who had this complaint and 27 male control subjects were examined at rest and after 1 hour of mild exercise (40W) under conditions of heat stress (37 degrees C, 50% relative humidity). During exposure to heat rectal and skin temperatures and heart rate were measured every 15 min. Sweat rate was calculated for the entire period of exposure and sweat gland density was measured at 0, 60 and 120 min. Only insignificant deviations from baseline values were noted at rest. During exercise the sweat rate of the men with the complaint was within normal limits and similar to that of the control men (285 +/- 75 ml/m2 vs 272 +/- 48). Matching for age and V02 max revealed no significant differences in physiological responses of men with and those without the complaint. Women with the complaint lost 25-30% less fluid (226 +/- 67 ml/m2) and their concentrations of active sweat glands were lower than in either of the male groups. 2 men and 1 woman with the complaint and 1 control lost 400-425 ml/m2 during exercise, the upper limit of normal. Only 1 subject showed hyperperspiration (855 ml/m2) during the test. All physiological parameters examined in these 5 subjects were within normal limits. It is concluded that the complaint of hyperperspiration in our self-selected group is basically a subjective feeling and has no pathological basis. None of the subjects was heat intolerant.