Suzan Abedat MSc, Simcha Urieli-Shoval PhD, Eli Shapira PhD, Sima Calko, Eldad Ben-Chetrit MD and Yaacov Matzner MD
Background: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF[1] (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients.
Objective: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1b, TNF-a, IFN-a, IFN-g) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures.
Methods: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines.
Results: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR assays enabled estimation of MEFV induction by the cytokines at 10–100-fold and could not be further increased by concomitant addition of colchicine.
Conclusion: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between colchicine ability to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.
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RT-PCR = reverse transcription-polymerase chain reaction
[2] FMF = familial Mediterranean fever
Sydney Benchetrit MD, Jacques Bernheim MD and Eduardo Podjarny MD
Background: Primary aldosteronism is a common cause of non-renal secondary hypertension. A correct diagnosis results in curing the hypertension or targeting appropriate pharmacotherapy. In patients with low renin resistant hypertension (after treatment with three or more different anti-hypertensive drugs the blood pressure remains above 140/90 mmHg), screening for aldosteronism is mandatory.
Objectives: To demonstrate that normal blood levels of potassium in resistant hypertensive patients do not exclude the possible presence of hyperaldosteronism, and to suggest the use of the plasma aldosterone concentration (ng/dl)/plasma renin activity (ng/ml/hour) ratio in screening for hyperaldosteronism.
Methods: Blood tests, suppression and stimulation tests (2 L normal saline IV/4 hours and 20 mg furosemide IV for 60 minutes in a standing position) were systematically performed in 20 low renin normokalemic resistant hypertensive patients. None had renal disorders, known endocrine abnormalities or heart failure. They did not receive anti-hypertensive drugs affecting PAC[1] or PRA[2]. Basal PRA and PAC were measured twice: PAC after saline infusion and PAC/PRA after stimulation.
Results:. PAC/PRA above 50 was used to denote hyperaldosteronism. Serum K was 4 ± 0.07 mM/L, PAC 22.8 ± 1.8 ng/dl, PRA 0.13 ± 0.02 ng/ml/hour, PAC/PRA 190 ± 22 (above 100 in 17). After suppression PAC decreased from 25 ± 1.8 to 11 ± 1 ng/dl (normal <5 ng/dl). Stimulation did not affect PRA and PAC/PRA. Abdominal computed tomography scan revealed normal adrenal glands in 15 patients. Spironolactone (116 ± 60 mg/day) normalized blood pressure in all patients; it was used as a single therapy in 8, and in association with only one anti-hypertensive drug in the remaining 12 patients. In one patient the treatment was discontinued due to the presence of hyperkalemia.
Conclusions: Low renin resistant hypertension associated with normokalemia may be due to hyperaldosteronism. Normal aldosterone levels in the basal condition do not exclude the possibility of hyperaldosteronism. Using a PAC/PRA ratio above 50 as a screening test can aid the physician in deciding when to perform dynamic tests, thus increasing the sensitivity of the diagnosis of hyperaldosteronism. CT scan is frequently normal. Targeted pharmacotherapy leads to a normalization of blood values.
[1] PAC = plasma aldosterone concentration
[2] PRA = plasma renin activity
Rasmi Magadle MD, Paltiel Weiner MD, Marinella Rabner MD, Miri Mizrahi-Reuveni MD and Avi Davidovich MD
Background: The association between coronary and/or other arterial aneurysms and polycystic kidney disease is well known. While myocardial infarction is a possible complication of atheroscletotic coronary aneurysms, it is reasonable to assume that CA[1] in patients with PKD[2] may make them prone them for a similar complication.
Objective: To evaluate the possible occurrence of CA and MI[3] in first relatives of a patient with PKD, CA and MI.
Patients: We studied 12 family members: 2 parents, 8 sisters and 2 brothers of a young woman who was incidentally diagnosed as having a MI, while her mother was known to have PKD. We used electrocardiogram, thallium-image test, and transthoracic echocardiography to determine MI, ultrasonography of the kidney to determine PKD, and coronary angiography and ventriculography to determine CA and MI, respectively.
Results: PKD was detected in seven family members, while CA and MI were found in five and three of them, respectively.
Conclusions: In a family with PKD we detected a high prevalence of CA, with MI as a complication of the latter.
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[1] CA = coronary aneurysms
[2] PKD = polcystic kidney disease
[3] MI = myocardial infarction
Haim Shirin MD, Yaron Davidovitz MD, Yona Avni MD, Paulina Petchenko MD, Zipora Krepel MSc, Rafael Bruck MD and Dina Meytes MD
Background: Epidemiological studies in different parts of the world have revealed controversial results on the association between hepatitis C virus infection and non-Hodgkin’s lymphoma. This discrepancy suggests that HCV[1] lymphotropism or its effect on host lymphocytes may be influenced by regional and racial factors, as well as by genomic variations.
Objective: To determine the prevalence of HCV infection in patients with lymphoproliferative disorders diagnosed and treated in our institute in Israel.
Methods: A total of 212 consecutive patients (95 males and 117 females) treated in our hematology outpatient clinic between August 1997 and September 1999 was screened for anti-HCV antibodies and hepatitis B surface antigen. HCV infection was confirmed by the presence of HCV RNA in the serum. The prevalence of HCV in patients with lymphoproliferative disorders was compared to a control group of patients with myeloproliferative disorders and myelodysplastic syndromes.
Results: HCV infection was more prevalent in the group of LPD] patients than in the control group, but this finding was not statistically significant. The prevalence of HCV among LPD patients was 7.8%, while that in the group with myeloproliferative and myelodysplastic disorders was 1.19% and in the general population 0.64%. Among the different classes of LPD, a significant association with HCV infection was established only in patients with diffuse large B cell lymphoma. Furthermore, HCV infection was significantly more prevalent than HBV infection in the LPD group, but not in the myeloproliferative and myelodysplastic disorders group.
Conclusions: Our finding of a significant association between HCV infection and diffuse large B cell lymphoma leads us to suggest that anti-HCV antibodies be performed routinely in such subjects.
Marina Shargorodsky, MD and Reuven Zimlichman, MD
Philip J. Hashkes, MD, MSc, Orit Friedland, MD and Yosef Uziel, MD, MSc
Kosta Y. Mumcuoglu, PhD, Avi Keysary, PhD and Leon Gilead, MD
Alain Fischer, MD, Salima Hacein-Bey, MD, Franeoise Le Deist, MD, Geneviove De Saint Basile, MD and Marina Cavazzana-Calvo
Ronen Rubinshtein, MD, Eran Bar-Meir, MD, Ahuva Grubstein, MD and Haim Bitterman, MD
Alex Palatnik, MD and Jonathan Benjamin, MD
David G. Mendes, MD, Gilad Barak and Emanuel Mendes