תרומתי לרפואה

מחקרים קליניים בנושא עמילואידוזס

 

מחקר קליני נרחב בסוגי עמילואידוזס שונים ניתן למצוא ברשימת המאמרים המלאה, במאמרים הבאים: 53, 55, 63, 82, 119, 130, 145, 148, 159, 160, 208, 209, 213, 222, 223, 225, 227, 260, 273, 357, 358, 360, 362, 374, 435, 439, 443, 448, 449, 457, 458, 465, 468 (לרשימת המאמרים המלאה). להלן, מובאים תקצירים של 5 מאמרים נבחרים:

 

Arthritis Rheum. 1994 Dec;37(12):1804-11.
Colchicine treatment of AA amyloidosis of familial Mediterranean fever. An analysis of factors affecting outcome.
Livneh A, Zemer D, Langevitz P, Laor A, Sohar E, Pras M.

 

Abstract
OBJECTIVE: To elucidate factors possibly influencing the outcome of colchicine therapy in patients with amyloidosis of familial Mediterranean fever (FMF).
METHODS: Retrospective analysis of data abstracted from the charts of all 68 FMF patients with amyloidosis who presented during the study period (1974-1992) with proteinuria (> or = 0.5 gm/24 hours) and creatinine values < or = 2.5 mg/dl, received colchicine, and were followed up for > or = 5 years.
RESULTS: At the end of the study period, kidney disease had worsened in 31 patients and remained stable in 22. Proteinuria had regressed in 15 patients. Deterioration was related to initial serum creatinine values > or = 1.5 mg/dl (P < 0.01) and to mean colchicine dosage < or = 1.5 mg/day (P < 0.001). The 3 groups were comparable in terms of initial urinary protein levels, duration of proteinuria, presence of hypertension, occurrence of febrile attacks, sex
distribution, and proportion of non-compliant patients.
CONCLUSION: The therapeutic dosage of colchicine for amyloidosis of FMF is > 1.5 mg/day. This dosage is effective only in patients with initial serum creatinine levels < 1.5 mg/dl.

 

Amyloid. 1999 Mar;6(1):1-6.
MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever.
Livneh A, Langevitz P, Shinar Y, Zaks N, Kastner DL, Pras M, Pras E.

 

Abstract
Familial Mediterranean fever (FMF) is a major cause of AA amyloidosis. Recently, the gene (MEFV) causing this disease was cloned and 16 disease associated mutations have been described. We have analyzed 178 FMF patients, 30 of whom also suffered from amyloidosis, for 4 mutations in MEFV. Mutations were identified in 29 of the FMF amyloidosis patients. 27 FMF amyloidosis patients were homozygous for M694V. One patient was found to be homozygous for both V726A and E148Q. In another patient E148Q and V726A were found on one allele, while V726A was found on the second allele. Amyloidosis was far more common among patients homozygous for M694V compared to patients with other mutations (P < 0.0001). In 3 patients homozygous for M694V, amyloidosis was the sole manifestation of the disease.

 

Amyloid. 2001 Mar;8(1):58-64.
Abdominal CT findings in nephropathic amyloidosis of familial Mediterranean fever.
Apter S, Zemer D, Terhakopian A, Gayer G, Langevitz P, Amitai M, Schwartz T, Atar E, Hertz M, Pras M, Livneh A.

 

Abstract
To evaluate the abdominal CT features of reactive amyloidosis, abdominal CT scans of 20 patients with amyloidosis of familial Mediterranean fever (FMF) were reviewed and compared with abdominal CT scans of 2 control groups: 22 patients with chronic renal failure (CRF) due to non-amyloidotic kidney diseases and 40 patients with normal kidney function. The kidney size of patients with amyloidosis of FMF were found to vary during the course of the disease from normal or slightly larger than normal at the proteinuric phase, to smaller than normal and comparable to kidney size in CRF, at the uremic stage. Compared to
kidney disease of other causes, more patients with FMF-amyloidosis had dense kidneys with coarse parenchymal calcification and calcification in other abdominal organs. Patients with FMF-amyloidosis had fewer aortic calcifications than patients with non-amyloidotic kidney disease. These findings suggest that kidney disease of reactive amyloidosis may have abdominal CT findings distinguishing it from other types of kidney diseases.

 

Arthritis Rheum. 2007 May;56(5):1706-12.
Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever.
Touitou I(1), Sarkisian T, Medlej-Hashim M, Tunca M, Livneh A, Cattan D, Yalçinkaya F, Ozen S, Majeed H, Ozdogan H, Kastner D, Booth D, Ben-Chetrit E, Pugnère D, Michelon C, Séguret F, Gershoni-Baruch R; International Study Group for Phenotype-Genotype Correlation in Familial Mediterranean Fever.

 

Abstract
OBJECTIVE: Familial Mediterranean fever (FMF), the prototype of autoinflammatory disorders, is caused by recessive mutations in the MEFV gene. Some FMF patients develop renal amyloidosis, a potentially fatal condition. This complication has mainly been associated with the M694V mutation, although the different study designs, small numbers of patients, and/or evaluation of few or no covariables calls this association into question. The aim of this study was to examine the controversial issue of amyloidosis susceptibility in FMF by determining the relative contributions of MEFV and numerous epidemiologic factors to the risk of renal amyloidosis.
METHODS: Online questionnaires were completed at the MetaFMF database by patients
at 35 centers in 14 countries. Using a standardized mode of data collection, we retrieved crude initial data from over half of the genetically confirmed FMF patients referred worldwide until May 2003 (2,482 cases, including 260 patients who developed renal amyloidosis). 
RESULTS: Amyloid nephropathy was present in 11.4% of the cases. In the total study population, country of recruitment was the leading risk factor for this manifestation (odds ratio 3.2 [95% confidence interval 1.8-5.9]), followed by M694V homozygosity, proband status, and disease duration. Differing results were found when countries were stratified.
CONCLUSION: Country of recruitment, rather than MEFV genotype, is the key risk factor for renal amyloidosis in FMF. This risk, which parallels infant mortality rates, indicates a possible environmental origin of amyloidosis susceptibility. The patient's country should be considered in addition to MEFV genotype as an indication for prophylactic colchicine, a treatment suggested for asymptomatic individuals who are incidentally discovered to be M694V homozygous.

 

Clin Chem Lab Med. 2007;45(5):625-8.
Transthyretin amyloidosis in a patient of Iranian-Jewish extraction: a second Israeli-Jewish case.
Kaplan B(1), Shinar Y, Avisar C, Livneh A.

 

Abstract
BACKGROUND: We present a patient with late-onset progressive polyneuropathy and a Congo-red positive staining of sural nerve biopsy, where routine immunohistochemical analysis failed to determine the type of amyloid deposited. Since precise determination of the amyloid type has crucial therapeutic implications, we employed our new biochemical micro-techniques, together with molecular biology methods, to characterize the amyloid protein deposited.
METHODS: We used a micro-method for extraction of amyloid proteins, amyloid typing by Western blotting, DNA sequencing, and restriction enzyme site analysis. 
RESULTS: Our new micro-technique for biochemical analysis of fat aspirate demonstrated transthyretin (TTR) amyloid (ATTR) deposition in the patient's tissue. Sequence analysis of the TTR-encoding DNA identified a single mutation, causing a valine to alanine substitution (V32A).
CONCLUSIONS: Although there are approximately 100 known TTR variants associated with peripheral neuropathy, in Israel only one patient with familial amyloid polyneuropathy (FAP), a patient of Ashkenazi origin with ATTR due to an F33I mutation, has been reported so far. Our study identified a second case of ATTR in the Israeli population, this time in a patient of Iranian-Jewish extraction. The study also emphasizes the importance of our new biochemical micro-techniques in elucidating the type of amyloid protein.

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