Ezra Sohar

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

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 1.7 percent (90 percent confidence limits, 0.0 and 11.3 percent) after 11 years in the compliant patients and 48.9 percent (18.8 and 79.0 percent) after 9 years in the noncompliant patients (P less than 0.0001). 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.

A controlled trial of colchicine in preventing attacks of familial mediterranean fever.

Abstract 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...

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 bodys 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.

Colchicine Prevents Kidney Transplant Amyloidosis in Familial Mediterranean Fever

Twenty-one familial Mediterranean fever (FMF) patients who received a kidney transplant for terminal renal failure due to amyloidosis were studied retrospectively to evaluate the prophylactic effect of colchicine on graft amyloidosis. Proteinuria, highly suggestive of kidney transplant amyloidosis, developed in 11 patients within a median of 3 years after transplantation (range 0.5-10 years). In 10 patients, repeated urinalyses for protein were negative during a median of 5 years after transplantation (range 1-13). Patients who developed proteinuria or transplant amyloidosis received smaller colchicine doses than patients without proteinuria--mean 0.69 (range 0-1) versus 1.53 (range 1-2) milligrams per day (p = 0.0002), suggesting that colchicine prevents or delays development of transplant amyloidosis. This prophylactic effect of colchicine was complete at a dose of 1.5 mg/day or more and absent at a daily dose of 0.5 mg or less. In patients who received 1 mg/day, individual variability in the response to colchicine was observed. We conclude that the development of amyloidosis of the kidney transplant in FMF is inevitable at a colchicine dose lower than 1 mg/day, unpredictable at 1 mg/day and usually preventable with 1.5 mg/day or more.

Colchicine Treatment in Conception and Pregnancy: Two Hundred Thirty-one Pregnancies in Patients With Familial Mediterranean Fever

ABSTRACT: The effect of maternal use of colchicine on fetuses is unknown. The children of 116 women with Familial Mediterranean Fever (225 completed pregnancies) were studied. There was no unusual frequency of fetal abnormality among women taking colchicine before or during pregnancy. Colchicine treatment does not apparently harm mother or child.

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.

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.

Diabetic fibrillosis: A report of three cases

Three patients with diabetes are described. Two patients had a mild, well controlled, hyperglycemic syndrome; five years after its detection signs of nephropathy and retinopathy appeared. Both died of renal failure ten years after detection of diabetes. The third patient died at the age of forty-seven of recurrent myocardial infarction. During her terminal hospitalization uremia and hyperglycemia were first discovered. Histologic findings in postmortem material were identical in all three cases. Heavy deposits of pediodic acid-Schiff-positive, colloidal iron and Congo red negative material were found in the blood vessels of virtually all organs examined. The blood vessels involved ranged from capillaries, venules, arterioles to arteries of large size. In some areas the material was seen also in connective tissue outside of blood vessels. Electronmicroscopic examination revealed that the PAS-positive material was composed of fibrils, approximately 100A wide. These findings indicate the presence of a systemic disease of connective tissue in our cases, resembling systemic amyloidosis in extent, location and nature. We suggest the name, diabetic fibrillosis.

Plasma fibrinogen in familial Mediterranean fever.

Excerpt A rise in the plasma fibrinogen level is a nonspecific body response which occurs in many pathological states, resembling in this respect an increase in the erythrocyte sedimentation rate. ...

PLASMA PROTEINS IN FAMILIAL MEDITERRANEAN FEVER.

Abstract 1. 1. Plasma proteins were investigated in FMF patients by paper, starch gel and immunoelectrophoresis. Patients of all stages of the disease (including phenotype II) were examined during and between attacks. 2. 2. CRP, fibrinogen, β2M-globulin, haptoglobins, seromucoid, orosomucoid and lipoproteins were found to be increased in all stages of the disease, including prolonged remissions. Although clinical attacks or amyloid kidney disease accentuated the changes, these were not obligatory factors responsible for this protein pattern.