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עמוד בית
Sun, 05.05.24

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December 2002
Salvatore De Vita MD, Rosaria Damato MD, Ginevra De Marchi MD, Stefania Sacco MD and Gianfranco Ferraccioli MD

Background: Hepatis C virus infection is presently an exclusion criterion to classify SjoÈ gren's syndrome; however, there are distinct clinicopathologic and biologic similarities between HCV-related and SS-related chronic inflammation of mucosa-associated lymphoid tissue and lymphoproliferation that suggest common pathogenetic pathways.

Objectives: To determine whether a subset of patients with sicca syndrome and HCV infection may present a true primary SS rather than a distinct clinicobiologic entity.

Methods: We extensively characterized 20 consecutive patients with positive anti-HCV antibodies and heavy subjective dry eye and/or dry mouth symptoms, plus positive unstimulated sialometry and/or Shirmer's test. We then compared these features with those in HCV-negative primary SS controls (classified according to the latest American-European Consensus Group Classification Criteria for SS).

Results: Of the 20 HCV-positive patients with sicca manifesta-tions, 12 (60%) had positive anti-SSA/SSB antibodies (3/12 by enzyme-linked immunosorbent assay and 6/12 by immunoblot) and/or positive salivary gland biopsy (at least 1 focus/4 mm2), which met the strict classification criteria for SS, as in the case of HCV-negative SS controls. Comparing the HCV-positive SS subset with HCV-negative SS controls showed similar female to male ratio (11/1 vs. 46/4), major salivary gland swelling (17% vs. 26%), positive antinuclear antibodies (75 vs. 94%) and positive rheumatoid factor (58 vs. 52%). Significant differences (P< 0.05) were seen in mean age (69 vs. 56 years), liver disease (50 vs. 2%), lung disease (25 vs. 0%), anti-SSA/SSB positivity (25 vs. 90%), and low C3 or C4 (83 vs. 36%). HCV-positive SS patients exhibited a trend for more frequent chronic gastritis (50 vs. 22%), fibromyalgia (33 vs. 14%), peripheral neuropathy (33 vs. 18%), purpura (33 vs. 19%) and cryoglobulinemia (33 vs. 6%).

Conclusions: A major subset of HCV-positive patients with definite subjective sicca symptoms and positive objective tests may indeed present a true, though peculiar, subset of SS. There are strict similarities with key clinical, pathologic and immunologic findings of definite HCV-negative SS. Other features appear more characteristic of HCV infection. When also considering that HCV is sialotropic and may be treated, HCV-related chronic sialadenitis represents a unique opportunity to clarify key pathogenetic events occurring in the large majority of HCV-negative SS; and similarities to typical primary SS, rather than differences, should be taken into account.
 

November 2002
Tomas Ganz, PhD, MD

Systemic infection or inflammation causes a decrease in intestinal iron absorption and impairs the release of recycled iron from macrophages. Decreased availability of iron may deny this essential element to invading pathogens and may inhibit their multiplication and other metabolic processes but also results in anemia of chronic disease. This article reviews recent discoveries that shed light on the regulation of iron metabolism during infection and iron overload, and point to the central role of a newly discovered peptide, hepcidin. Evidence to date indicates that hepcidin is a negative regulator of intestinal iron absorption, placental iron transport, and the release of iron from macrophages that recycle iron from senescent red cells. It may also be the central mediator of iron sequestration during infections and inflammatory states and the mediator of anemia of chronic disease. Rapid progress in this area is a good example of the beneficial effects of improvements in peptide analysis and chemistry, advances in genomics, and the increasing use of transgenic mice to determine the function of newly discovered genes and proteins.

October 2002
Judith Barash, MD, Doron Dushnitzky, MD, Dalia Sthoeger, MD, Rita Bardenstein, MSc and Yigal Barak, MD,

Background: Human parvovirus B19 is responsible for a variety of clinical syndromes, such as erythema infectiosum, non-immune hydrops fetalis, transient aplastic anemia, and arthropathies. HPV is also suspected of playing a role in the pathogenesis of various chronic inflammatory and autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Kawasaki disease and multiple sclerosis.

Objectives: To study the age distribution and clinical presentation of patients hospitalized for human parvovirus B19 infection.

Method: We reviewed the case records of all pediatric patients with serologic evidence of HPV infection who were admitted during a 20 month period to a major community hospital

Results: Of 128 children tested for HPV, 48 had evidence of acute infection based on the presence of immunoglobulin M antibodies; 8 patients who also had positive IgM for other viruses were excluded, thus 40 case records were studied. The mean age of the patients was 5.21 years, but 22 patients were under 4: The clinical presentations included 25 patients with fever, either recurrent or prolonged, accompanied in some by enlarged spleen, liver and lymph nodes, skin rash and arthropathy; the remaining patients were investigated for anemia, skin rash, joint complaints and hepatitis. In addition; HPV infection was documented in several well-defihed clinical conditions, such as SLE, vasculitic skin lesions, acute lymphoblastic leukemia, pure red cell aplasia, and optic neuritis.

Conclusions: In a group of 40 pediatric patients exhibiting anti-HPV IgM antibodies, a younger age and less common clinical presentations were observed, furthermore 5 patients had clinical syndromes in which the causative role of HPV infection was not clear.

Abraham Benshushan, MD, Avi Tsafrir, MD, Revital Arbel, MD, Galia Rahav, MD, Ilana Ariel, MD and Nathan Rojansky, MD

Background: Although Listeria monocytogenes is widely distributed in nature, it rarely causes clinical infection in previously healthy people. This microorganism. however, may cause severe invasive disease in pregnant women and newborns.

Objectives: To investigate – in our pregnant population – the impact, severity and outcome of listeriosis on both mother and fetus.

Method: The study was carried out at a level III, university two-hospital complex, In a retrospective chart review of 65,022 parturients during a 10 year period (1990-1999), we identified and: evaluated 11 pregnant patients and their offspring with Listeria infection;

Results: Chorioamnionitis with multiple. placental abscesses were observed in all five placentae examined. Clinically 4 of 11 parturients had a cesarean section for fetal distress (36.3%), as compared to the 14% mean CS rate in our general population. Two of 11 had a fate abortion (18.1%), as compared with the 4% rate in our hospital. Four of 11 had premature labor (36%), which was about four times the rate in our population. Finally, although no intrauterine feta1 death was recorded in our series, there was one neonatal death of a term infant. (1/11, 9%), which is about 10 times higher than our corrected perinatal mortality rate.

Conclusions: If not promptly and adequately treated, listeriosis in pregnancy may present serious hazards to the fetus and newborn through direct infection-of the placenta and chorioamnionitis.
 

Aharon Klar, MD, Ariel Halamish, MD, David Shoseyov, MD, Pascal Cassinotti, PhD, Gunter Siegl, Chaim Springer, MD, Gila Shazberg, MD and Haggit Hurvitz, MD
January 2002
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.

_______________________


[1] TB = tuberculosis

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[2] 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.  

________________________

 [1]LPD = lymphoproliferative disorders

[2] HCV = hepatitis C virus

November 2001
Haim Ashkenazi, MD, Bernard Rudensky, PhD, Esther Paz, MA, David Raveh, MD, Jonathan A. Balkin, MBBCh, Dan Tzivoni, MD and Amos M. Yinnon, MD

Background: Recent studies have suggested a possible association between Chlamydia pneumoniae infection and coronary heart disease.

Objectives: To determine titers of antibodies to Chlamydia pneumoniae in patients with acute  myocardial infraction compared with titers in several control groups.

Methods: This prospective case-control study investigated 209 individuals. We assessed the serum IgG antibody titers to Chlamydia pneumoniae in 57 consecutive patients admitted with AMI to our intensive coronary care unit during a 4 month period. A serum sample was drawn upon admission after 6 weeks. Results were compared with those of four control groups: a) patients admitted with community-acquired pneumonia (n=18), b) patients with community-acquired urinary tract infection (n=42), c) patients with angiographically normal coronary artery disease (n=44), and d) patients with stable coronary artery disease (n=48). Serum immunoglobin G antibody titers to C. pneumoniae were determined using standard micro-immunofluorescene technology.

Results: Of 57 patients with AMI, 32 (56%) had a high lgG titer to C. pneumoniae (>=1:256) on the initial test, which remained unchanged (62%) after 6 weeks. The percentage of patients with high titers was significantly lower in the control groups: 5 of 18 patients (28%) in the pneumonia group (P<0.01), 11 of 42 (26%) in the urinary tract infection group (P<0.01), 11 of 44 (25%) with normal coronary arteries (P<0.01), and 17 of 48 (35%) with stable chronic ischemic heart disease (P<0.05).

Conclusion: The detection of high titers of lgG antibodies to C. pneumoniae in many patients with AMI, compared to control groups, suggest that chronic Chlamydia pneumoniae infection plays a role in the pathogenesis of atherosclerosis and acute ischemic events.

Mariana Munichor, MD, Daniel Gold, PhD, Jacob Lengy, PhD, Ran Linn, MD and David Merzbach, PhD
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