The kidney in familial Mediterranean fever.
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Amyloidosis↗
Biomedical subjects
M Pras
Publications and source records attributed to M Pras.
Effect of pregnancy on renal function in amyloidosis of familial Mediterranean fever.
OBJECTIVE: To study the effect of pregnancy on kidney function in patients with familial Mediterranean fever (FMF) with amyloidosis. METHODS: A retrospective analysis relating kidney function at term to kidney function at conception and to blood pressure and colchicine treatment before and during pregnancy in 17 patients with 29 pregnancies found among more than 3000 patient files in our FMF clinic. RESULTS: Following pregnancy, 7 patients (24% of pregnancies) experienced a decline in renal function. Urine protein > or = 2 g/24 h at conception was present in all pregnancies which sustained deterioration in contrast to 6 of 22 which did not (p < 0.001). Serum creatinine > or = 1.5 mg/dl at conception was present in 3 patients, all of whom experienced deterioration of renal function during pregnancy (p < 0.01). Neither colchicine dose nor elevated blood pressure correlated with status of renal function at term. CONCLUSION: Our findings suggest a possible deleterious effect of pregnancy on amyloid nephropathy and that this effect may be associated with more advanced renal disease at conception.
Adolescent↗
Total hip replacement in familial Mediterranean fever.
Familial Mediterranean fever (FMF) is a hereditary disorder affecting people of Mediterranean stock, mainly Sephardic Jews and Armenians. It is characterized by attacks of arthritis, either short, self-limited episodes typically lasting 72 hours or protracted attacks lasting from two weeks to one year. The latter form affects mainly the large joints of the lower limb. The hip joint is the most vulnerable and likely to be affected by the protracted attacks, which may result in destruction of the articular cartilage and, in some cases, aseptic necrosis of the femoral head. Eighteen FMF patients (19-52 years) underwent 22 total hip replacements between 1971 and 1985 at our hospital. Six of the 18 initial prostheses experienced aseptic loosening. This relatively high incidence led us to recommend implantation of cementless hip prostheses following meticulous synovectomy as the treatment of choice. The results of these surgeries and the uniqueness of total hip replacement in FMF patients are presented here and discussed.
Adult↗
Expansion of a unique subpopulation of cytotoxic T cells that express a C alpha V delta 1 T-cell receptor gene in a patient with severe persistent neutropenia.
CD8+ T-lymphocyte populations may be expanded in the peripheral blood of patients with chronic idiopathic neutropenia and may be involved in suppression of granulopoiesis. In this report, we have analyzed the T-cell receptor (TCR) used by the T lymphocytes of a patient with chronic severe neutropenia. Using specific oligonucleotides in the polymerase chain reaction (PCR) to amplify cDNA specific for the different families of the V alpha, V beta, and V delta TCR genes, and monoclonal antibodies (MoAbs) to examine T-lymphocyte subsets and their TCR, a persistent expansion of CD3+CD8+ T lymphocytes and a reduced repertoire of TCR V alpha and V beta genes were found in the patient's peripheral blood mononuclear cell (PBMC) preparations. A predominant portion of the T lymphocytes expressed a unique TCR structure. Thus, we found that, despite the fact that 98% of the T cells expressed alpha beta TCR on the surface membrane and less than 2% expressed tau delta TCR, nonetheless, 40% to 60% of the T cells stained positively with anti V delta 1 MoAb. Using the PCR analysis, the V delta 1 gene segment was found to be rearranged to C alpha, rather than to C delta genes. The expanded C alpha V delta 1+ cells, which are found only rarely in normal PB, expressed CD8 and were cytotoxic, and the C alpha V delta 1 receptor was functional in cytotoxicity. This constitutes the first description of an expansion of cytotoxic CD8+ lymphocytes expressing a functional "hybrid" C alpha V delta 1 gene in vivo, and suggests a pathogenic role for CD8+ C alpha V delta 1+ cells in some patients with idiopathic neutropenia.
Antibodies, Monoclonal↗
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.
Adolescent↗
Mapping of a gene causing familial Mediterranean fever to the short arm of chromosome 16.
BACKGROUND: Familial Mediterranean fever is an autosomal-recessive disease characterized by acute attacks of fever with sterile peritonitis, pleurisy, or synovitis. The biochemical basis of the disease is unknown, but determining the chromosomal location of the gene for the disorder should be a first step toward defining the biochemical events. METHODS AND RESULTS: As part of a systematic genome-wide search, we sought evidence of linkage between familial Mediterranean fever and chromosome 16 DNA markers in 27 affected non-Ashkenazi Jewish families from Israel. Two loci from the subtelomeric region of the short arm of chromosome 16 (16p) had lod scores sufficient to establish linkage (a score greater than or equal to 3). One DNA marker (D16S84) gave a maximal lod score of 9.17 (odds of 10(9.17) to 1 in favor of linkage) at a recombination frequency (theta) of 0.04. A probe associated with the hemoglobin alpha complex (5'HVR) gave a maximal lod score of 14.47 at a theta of 0.06. Multipoint linkage analysis indicated that the following was the most likely gene order: the centromere, the gene for familial Mediterranean fever, D16S84, hemoglobin alpha, and the telomere. The maximal multipoint lod score was 19.86. There was a striking degree of homozygosity at chromosome 16p loci in the affected offspring of eight consanguineous couples. CONCLUSIONS: The gene that causes familial Mediterranean fever in non-Ashkenazi Jews maps to the short arm of chromosome 16.
Centromere↗
Isolation and purification of amyloid protein A by sodium dodecyl sulphate polyacrylamide gel electrophoresis and reversed-phase high-performance liquid chromatography.
Sodium dodecyl sulphate polyacrylamide gel electrophoresis and reversed-phase high-performance liquid chromatography (HPLC) were used consecutively for the isolation of amyloid protein A (protein AA) from amyloid fibrils. Highly purified protein AA was obtained and determined by electrophoretic and amino acid analyses. The heterogeneity of protein AA was shown by HPLC. The isoforms of protein AA had different hydrophobicities, although they were equal in size and similar in amino acid composition. Compared with the conventional amyloid separation procedure (gel permeation chromatography), this technique is rapid, requires only small amounts of amyloid fibrils and may provide new information on amyloid proteins.
Amino Acids↗
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.
Adolescent↗
Normal renin-aldosterone-insulin and potassium interrelationship in FMF patients and amyloid nephropathy.
The renin-aldosterone system and plasma insulin were studied in 19 patients with familial Mediterranean fever (FMF). Their relationships to serum potassium level at rest and before and after oral glucose loading are described. An interesting finding is the occurrence of hyperkalemia in the absence of oliguria, in the advanced stages of renal failure. No differences were found in the activity of the renin-angiotensin-aldosterone system to explain these variations in serum potassium found in some of the patients. The response of the renin-aldosterone system to glucose loading showed no abnormality, and the regular relationship between serum potassium, plasma renin activity (PRA), aldosterone, insulin, and plasma pH is maintained. Levels of insulin, potassium, and bicarbonate in serum or plasma pH were found similar in FMF patients with normal renal function with and without proteinuria. Further decrease in renal function due to the progression of the underlying disease is manifested by an increase in FENa+ and FEK+ and a hyperchloremic metabolic acidosis, as is the case in other patients with chronic renal failure.
Adult↗
Treatment of resistant rheumatoid arthritis with minocycline: an open study.
In a 48-week open trial, 18 patients with active rheumatoid arthritis (RA), resistant to second line agents, received 200 mg minocycline daily. Twelve patients completed 48 weeks of therapy. Statistically significant improvement was noted in almost all variables of disease activity. Three patients discontinued therapy because of lack of improvement, 2 patients because of side effects and one patient was lost to followup. Cytofluorographic analysis revealed a significant decrease in expression of a T cell activation antigen (gp 26). Our data suggest that minocycline could be a useful therapeutic agent in RA.
Adult↗
Systemic amyloidosis secondary to chronic leg ulcers.
Chronic leg ulcers due to any cause are almost invariably associated with an inflammatory process. As with any long-standing inflammation, leg ulcers may be complicated by systemic amyloidosis, which occurs in rheumatoid arthritis, cystic fibrosis, tuberculosis, and other disorders. There are, however, very few reports on the association between these two conditions. We report a patient with severe leg ulcers of twenty years' duration in whom reactive systemic amyloidosis presented as a nephrotic syndrome.
Aged↗
[Second line for agents in the treatment of rheumatoid arthritis].
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Arthritis, Rheumatoid↗
[Activity scores in systemic lupus erythematosus].
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Humans↗
Long-term colchicine treatment in children with familial Mediterranean fever.
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.
Adolescent↗
Separation of proteins by consecutive sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and reversed phase high performance liquid chromatography.
A procedure for the preparative separation of proteins was developed by using consecutively sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (SDS-PAGE) and reversed phase high performance liquid chromatography (HPLC). The proteins were separated by SDS-PAGE and afterwards extracted from the gel. The extracted proteins were separated from SDS and other small molecular weight contaminants on a Fractogel TSK HW-40 (F) column in acidic aqueous acetonitrile. The proteins eluted from the Fractogel column were fractionated by HPLC. The identity and purity of the recovered proteins was confirmed by SDS-PAGE analysis.
Chromatography, Gel↗
Exclusion of linkage between familial Mediterranean fever and the human serum amyloid A (SAA) gene cluster.
We studied the relationship between the autosomal recessive trait familial Mediterranean fever (FMF) and the serum amyloid A (SAA) genes by comparing alleles of a highly polymorphic dinucleotide repeat and a conventional restriction fragment length polymorphism (RFLP) in the SAA gene cluster in Israeli FMF kindreds. By haplotype analysis, our data indicate a minimum crossover frequency of 22% between the SAA gene marker and FMF. By conventional linkage analysis this eliminates a minimum of 10.4 cM including and surrounding the SAA gene cluster as the site of the FMF mutation although SAA proteins are prominent physiologic markers of the acute attacks.
Crossing Over, Genetic↗
Expression and functions of very late antigen 1 in inflammatory joint diseases.
In the human immune system, very late antigen 1 (VLA-1), a putative collagen receptor, is expressed on the surface of T lymphocytes that have undergone mitogenic or antigenic stimulation. A new VLA-1-specific monoclonal antibody, 1B3.1, was used to probe the expression and function of VLA-1 on T lymphocytes in patients with arthritis. Synovial mononuclear cells from the joints of patients with rheumatoid arthritis or other joint diseases contained 32.9 +/- 13.8% 1B3.1-positive cells (42.8 +/- 10.4% in patients with rheumatoid arthritis and 28 +/- 12.6% in non rheumatoid patients). In the peripheral blood, patients with active rheumatoid arthritis expressed VLA-1 on 11.7 +/- 6.0% of their mononuclear cells, compared to 1.9 +/- 1.5% in controls (P less than 0.001). Using dual fluorescence analysis, virtually all the 1B3.1-positive synovial cells were CD3+ T lymphocytes and included both CD4+ and CD8+ T cells. When 1B3.1-expressing synovial mononuclear cells or in vitro activated T lymphocytes were triggered with anti-CD3 antibodies, marked augmentation of their proliferation occurred if they were simultaneously cross-linked with mab 1B3.1. Collagen type IV, a putative ligand of VLA-1, also augmented T-cell proliferation to anti-CD3. The data suggest that the VLA-1 molecule could play an important role in the pathophysiology of arthritis by modulating T-cell activation in these diseases.
Antigens, Differentiation, T-Lymphocyte↗
Nodular cutaneous amyloidosis.
A nodular cutaneous amyloidosis biopsy specimen from a solitary nodule of a 75-year-old patient was characterized by amino terminal sequence analysis and was proved to be derived from immunoglobulin kIII light chain. Five years after the diagnosis of amyloidosis in the skin was made, a rectal biopsy demonstrated amyloid deposits in a blood vessel. It is suggested that nodular cutaneous amyloidosis is a slowly progressive systemic disease of the AL type, that manifest itself mainly in the skin.
Aged↗