Joseph Gafni

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...

Review of echocardiographically diagnosed right heart entrapment of pulmonary emboli-in-transit with emphasis on management

2DE permits detection of thromboemboli transiently entrapped in the right heart chambers while en route to the pulmonary arteries. Review of the 49 cases recorded to date reveals that the supple elongated clot produces a 2DE picture--a mass of changing configuration and striking mobility--that is highly characteristic. Since emboli that become entrapped are large, when managed by medical measures alone they have an attendant mortality rate of 50%, usually soon after 2DE diagnosis, upon completion of pulmonary embolization. Death occurred in 8 of 16 patients treated with anticoagulants, thrombolytic agents, or antiaggregants and in 6 of 13 who received supportive measures only. Of 20 patients referred for surgery (cardiotomy and, in 17, pulmonary embolectomy), only three died, two of them failures of preceding anticoagulant treatment. These data indicate that thromboemboli entrapped in the right heart chambers are best handled as a surgical emergency.

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.

Controlled trial of propranolol in intermittent claudication.

Seven patients (5 with arteriosclerosis obliterans and 2 with Buergers disease) completed a two‐phase double‐blind crossover trial of propranolol in intermittent claudication. Performance was measured on a moving treadmill. In the initial phase, the patients were hospitalized in order to determine an “effective” dose of propranolol. Improvement was noted in all: after 1,600 mg in 5 and after 240 mg and 600 mg in the others. The controlled phase was carried out on an outpatient basis over 8 weeks, the patients receiving propranolol and placebo in a random manner, each for two 2‐week periods. Comparison of matched periods of drug and placebo revealed no advantage for propranolol. Patients’ performances deteriorated with time. None of the patients evidenced deterioration of occlusive peripheral arterial disease that could be attributed to propranolol, in spite of the high doses used.

Renal Transplantation in the Amyloidosis of Familial Mediterranean Fever: Experience in Ten Cases

Ten patients with familial Mediterranean fever (FMF) and histologically confirmed amyloidosis received cadaver kidney transplants for treatment of terminal renal disease. Colchicine, 1 mg daily, was included in the routine postoperative regimen from 1974 for amyloidotic patients. Graft and patient survival were compared with ten nonamyloidotic recipients of renal grafts matched for age, sex, type of allograft, and HLA compatibility. In the FMF group, five of ten grafts have survived from 20 to 64 months; in the control group, six of ten. While only recipients with functioning grafts survived in the FMF group, patient survival in the control group is eight of ten after one year. In all five FMF survivors, graft function is satisfactory, proteinuria is absent, and blood creatinine levels are normal. Amyloid involvement of an allograft was documented 16 months after transplantation in the only patient whose maintenance colchicine dosage had been reduced to 0.5 mg daily.

Proximal renal tubular acidosis: association with familial normaldosteronemic hyperpotassemia and hypertension.

Further investigation of a family with normaldosteronemic hyperpotassemia and low-renin hypertension showed seven members from three generations, who ranged in age from 4 to 56 years, to be affected. Results of earlier studies had established a normally functioning renin-aldosterone system and normal renal handling of potassium. Constant, albeit mild and asymptomatic, metabolic acidosis in all those affected prompted bicarbonate loading in both the propositus and his brother, which revealed a maximal renal tubular excretory capacity for bicarbonate reabsorption at serum levels of 18 mmole/liter and proved proximal renal tubular acidosis (PRTA). Further, a linear increase in urinary fractional potassium excretion accompanied that of bicarbonate in both, as in normal individuals. Dextrose-insulin infusion in the brother failed to reduce hyperpotassemia. These data support the hypothesis that a generalized cell membrane defect that specifically impedes potassium influx (as opposed to an isolated renal tubular defect) underlies this autosomal dominant disorder.

Levocardia with partial situs inversus, an incidental finding in a 15-year-old boy

Abstract The purely incidental discovery of an asymptomatic levocardia with ventricular septal defect and partial situs inversus is reported. The possible relationship of the skeletal changes observed in this case and the Marfan syndrome are discussed.

Genetic Heterogeneity of Familial Amyloid Polyneuropathies of Jewish Type

The Jewish SKO amyloid protein is a prealbumin monomer with two amino acid substitutions. Glycine is substituted for Threonine at position 49 and Isoleucine for Phenylalanine at position 33. The distribution of these components is different in thyroid and spleen suggesting tissue specificifity in amyloid disposition. The SKO variant differs from the prealbumin proteins found in the Portuguese, Japanese and Swedish Familial Amyloid Polyneuropathies. Additional prealbumin variants will be expected when the amyloid proteins of the facial and upper limb amyloid neuropathies as well as the Van Allen kinship can be studied.