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
Haim Bibi MD, Daniel Weiler-Ravell MD, David Shoseyov MD, Ilana Feigin MD, Yael Arbelli RN and Daniel Chemtob MD MPH DEA
Background: One of the measures adopted in Israel since 1959 as part of the tuberculosis control program was screening children aged 12–13 years old. The screening comprised single-step tuberculin skin testing using the Mantoux method.
Objective: To assess the efficacy of tuberculin skin screening for TB[1] in schoolchildren in southwestern Israel as well as the compliance to treatment for latent tuberculosis infection.
Methods: We retrospectively reviewed the records of children in the Ashkelon region who underwent a tuberculin skin test during the period 1995–99.
Results: Of the 28,016 eligible children, 27,232 were tested. In 923 children, mostly from the former USSR and Ethiopia, an induration of 10 mm or more was found. Only 52 Israeli-born children tested positive. Tuberculosis was found in seven children with a positive test, five of whom were from Ethiopia. All children who tested positive were referred to the local TB clinic; only 266 children (28.8%) presented. Only 151 completed the recommended treatment of isoniazid for 6 months. Thus, although screening included most of the targeted children aged 13, only a third of them presented to a TB clinic, of whom only about half completed treatment of latent infection.
Conclusions: Our results indicate that the current policy of screening for latent TB in our region is ineffective in terms of implementation of the recommended treatment. We suggest that only high risk groups be screened, and that a concerted effort be made to implement treatment.
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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.
Philip J. Hashkes, MD, MSc, Orit Friedland, MD and Yosef Uziel, MD, MSc