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July 2009
N. Agmon-Levin, B. Gilburd, S. Kivity, B.S. Porat Katz, I. Flitman-Katzevman, N. Shoenfeld, D. Paran, P. Langevitz and Y. Shoenfeld

Background: Anti-ribosomal-P antibodies have been associated with central nervous manifestations of systemic lupus erythematosus. However, inconsistencies in their prevalence and clinical correlations have become an obstacle to their use as a diagnostic marker of the disease. This lack of consistency might stem from several factors, such as the lag period between clinical manifestations and the time blood was drawn, or the different methods used for antibodies detection.

Objectives: To evaluate three different enzyme-linked immunosorbent assay tests for the detection of anti-Rib-P Abs[1] in patients with SLE[2] and normal controls.

Methods: Sera from 50 SLE outpatients and 50 healthy subjects were tested with three ELISA[3] kits: Kit-1, which uses synthetic peptide comprising the 22 C-terminal amino-acids; Kit-2, which uses native human ribosomal proteins (P0, P1, P2); and Kit-3, which is coated with affinity-purified human ribosomal proteins. ELISA studies were performed according to the manufacturers' instructions.

Results: The prevalence of anti-Rib-P Abs in SLE patients and controls was 30% vs. 0%, 17% vs. 21%, and 30% vs. 14% in kits 1-3 respectively. Anti-Rib-P Abs detected by Kit-1 correlated with the SLEDAI score (SLE Disease Activity Index). No correlation between prior CNS[4] manifestations and anti-Rib-P Abs was observed.

Conclusions: A significant difference was documented between the ELISA kits used for the detection of anti-Rib-P Abs. A correlation was found between these antibodies (evaluated by Kit-1) and concurrent SLEDAI scores, in contrast to the lack of correlation with previous CNS manifestations. This supports the notion of "active serology" that is evaluated at the same time manifestations are present, as well as the need for standardization of laboratory assays in the future that enable a better assessment of anti-Rib-P Abs presence and clinical correlation. 



 




[1] anti-Rib-P Abs = anti-ribosomal-P antibodies

[2] SLE = systemic lupus erythematosus

[3] ELISA = enzyme-linked immunosorbent assay

[4] CNS = central nervous system

 



 
February 2009
N. Agmon-Levin, B. Porat Katz and Y. Shoenfeld

Primary biliary cirrhosis is an autoimmune cholestatic liver disease characterized by humoral and cellular response directed at mitochondrial autoantigens, mainly the E2 component of the pyruvate dehydrogenase complex. The etiology of PBC[1], like most polygenic autoimmune diseases, belongs to the "complex" category, including genetic elements and environmental factors. Many environmental factors, such as xenobiotics, smoking, hormonal therapy, toxins, oxidative stress and recurrent urinary tract infections, are associated with PBC. Infectious agents can trigger autoimmunity via several mechanisms and are associated with various autoimmune diseases. A relationship between PBC and several infectious agents, and a possible role for Escherichia coli in the pathogenesis of PBC has been suggested. The identification of a culprit agent that induces or exacerbates PBC might have diagnostic and therapeutic implications. This review evaluates the evidence for an infectious agent role in the pathogenesis of PBC.






[1] PBC = primary biliary cirrhosis


October 2008
G. Katz, R. Durst, E. Shufman, R. Bar-Hamburger and L. Grunhaus

Background: In recent years, mother to child transmission of human immunodeficiency virus in the west has decreased markedly due to the advent of antiretroviral drugs given during pregnancy, cessation of lactation and careful monitoring of viral load in the perinatal period.

Objective:
To assess mother to child transmission of HIV[1] among Ethiopian immigrants and non-Ethiopians in the Jerusalem area.

Methods:
We conducted a prospective analysis of all deliveries of HIV-positive women in the Jerusalem district over a 10 year period.

Results:
Between 1996 and 2006, 35 HIV+ women gave birth to 45 infants. Thirty-one (88%) of these women were of Ethiopian origin and gave birth to 39 infants. Of the 35 HIV+ women, 30 were aware of being HIV positive. They gave birth to 40 infants. Another 5 women (14%) were not aware of being HIV+ during delivery. They gave birth to five infants. Of the group of known HIV+ women, 26 (87%) were Ethiopian immigrants who delivered 34 infants and 4 were non-Ethiopians who delivered 6 infants. In the group of five women not aware of being HIV+, all were Ethiopians. Breast-feeding data were available for 32 of the 35 women. Only 2 women (6.2%) breast-fed their babies. Neither was aware of being HIV+. In the Ethiopian immigrant group (both known and unknown HIV status), 11 deliveries (28%) were vaginal, 18 (46%) were elective cesarean section and 10 (26%) were delivered by emergency cesarean section. Of the 26 known HIV+ Ethiopian women, 3 (12%) refused to take antiretroviral treatment despite repeated counseling. In the non-Ethiopian group, all deliveries were elective cesarean sections. Mother to child transmission of HIV occurred in 4 of the total 45 deliveries (8.8%). Of the 4 transmission cases, 2 occurred among 40 deliveries of known HIV+ women (5%), and 2 occurred among the 5 deliveries of women not aware of being HIV+ (40%, P = 0.05). In the group of Ethiopian women only, HIV transmission occurred in 4 of 39 deliveries (10%), of which 2 occurred among 34 deliveries (5.8%) of women know to be HIV+ and 2 among 5 deliveries (40%) of women not aware of being HIV+ (P = 0.08).

Conclusions:
Pregnant Ethiopian immigrants whose HIV status was known during pregnancy were at relatively high risk of HIV transmission despite the availability of antiretroviral drugs and counseling. This is likely due to inadequate adherence to ART[2] preventive regimens and is not dissimilar to the poor adherence observed among other immigrant groups in western countries. The substantial proportion of women, all Ethiopians, unaware of being HIV+ at delivery, together with the significantly higher HIV transmission in that group compared to women who knew their HIV status, call for a revision of the current Ministry of Health opt-in policy for prenatal HIV screening.

 






[1] HIV = human immunodeficiency virus

[2] ART = antiretroviral therapy


G. Katz, R. Durst, E. Shufman, R. Bar-Hamburger and L. Grunhaus

Background: The co-morbidity rate of illicit substance abuse and major mental problems in Israel is far from clear.

Objectives: To investigate the extent of drug abuse in a sample of psychiatric patients hospitalized in a psychiatric hospital and in the psychiatric department of a general hospital in Israel, to compare demographic and other background factors in dual-diagnosis patients with those of abuse-free mental inpatients, and to examine the time correlation between drug abuse and the appearance of major mental problems.

Methods: Our data were derived from self-report and urine tests. The study population comprised 470 consecutively admitted patients – 250 patients in the mental health center and 220 patients in the psychiatric department of the general hospital.

Results: The lifetime prevalence of drug abuse was 24%; cannabis abuse was found in 19.7%, opiates in 5.7%, cocaine in 2.7%, amphetamines in 3.4% and methamphetamine in 1.1%. Active abuse of drugs (during the last month) was registered in 17.3%, cannabis in 11.5%, opiates in 4.9%, amphetamine in 3.8%, cocaine in 1.3% and methamphetamine in 1.1%. We also found that 28.2% of active abusers used two or more substances. In 41.6% the drug abuse appeared prior to symptoms of the mental disorder; in 37.1% the duration of the mental disorders and the drug abuse was relatively similar, and in 21.3% of cases the duration of mental problems was longer than the duration of drug abuse. Dual-diagnosis patients were younger than non-abusers, more often male, unmarried, and of western origin.

Conclusions: Substance abuse (especially cannabis) among hospitalized psychiatric patients in Israel is a growing problem.

September 2008
M. Shuvy, J. E. Arbelle, A. Grosbard and A. Katz

Background: Heart rate variability is a sensitive marker of cardiac sympathetic activity.

Objectives: To determine whether long-term hyperthyroidism induced by thyroxine suppressive therapy affects HRV[1].

Methods: Nineteen patients treated with suppressive doses of thyroxin for thyroid cancer and 19 age-matched controls were enrolled. Thyroid function tests and 1 minute HRV were performed on all subjects and the results were compared between the groups. The 1 minute HRV was analyzed during deep breathing and defined as the difference in beats/minute between the shortest and the longest heart rate interval measured by eletrocardiographic recording during six cycles of deep breathing.

Results:  One minute HRV during deep breathing was significantly lower among thyroxine-treated patients compared to healthy controls (25.6 ± 10.5 vs. 34.3 ± 12.6 beats/min, P < 0.05). There were no significant differences in mean, maximal and minimal heart rate between the groups

Conclusions: Thyroxine therapy administered for epithelial thyroid cancer resulted in subclinical hyperthyroidism and significantly decreased HRV due to autonomic dysfunction rather than basic elevated heart rate.






[1] HRV = heart rate variability


February 2008
A Shiyovich, I. Munchak, J. Zelingher, A. Grosbard and A. Katz

Background: Syncope is a common clinical problem that often remains undiagnosed despite extensive and expensive diagnostic evaluation.

Objectives: To assess the diagnostic evaluation, costs and prognosis of patients hospitalized for syncope in a tertiary referral center according to discharge diagnosis.

Methods: We retrospectively reviewed the medical records of patients with a diagnosis of syncope discharged from a tertiary referral center in 1999. In addition, mortality data were obtained retrospectively a year after discharge for each patient.

Results: The study group comprised 376 patients. Discharge etiologies were as follows: vasovagal 26.6%, cardiac 17.3%, neurological 4.3%, metabolic 0.5%, unexplained 47.3%, and other 4%. A total of 345 patients were admitted to the internal medicine department, 28 to the intensive cardiac care unit, and 3 to the neurology department. Cardiac and neurological tests were performed more often than other tests, with a higher yield in patients with cardiac and neurological etiologies respectively. The mean evaluation cost was 11,210 ± 8133 shekels, and was higher in the ICCU[1] than in internal medicine wards (19,210 ± 11,855 vs. 10,443 ± 7314 shekels, respectively; P = 0.0015). Mean in-hospital stay was 4.9 ± 4.2 days, which was longer in the ICCU than in medicine wards (7.2 ± 5.6 vs. 4.6 ± 3.5 days, respectively; P = 0.024). Short-term mortality rates (30 days after discharge) and long-term mortality rates (1 year after discharge) were 1.9% and 8.8% respectively, and differed according to discharge etiology. LTM[2] rates were significantly higher in patients discharged with cardiac, neurological and unknown etiologies (not for vasovagal), compared with the general population of Israel (1 year mortality rate for the age-adjusted [65 years] general population = 2.2%). The LTM rate was higher in patients discharged with a cardiac etiology than in those with a non-cardiac etiology (15.4% vs. 7.4%, P = 0.04). Higher short and long-term mortality rates were associated with higher evaluation costs.

Conclusions: Hospitalization in a tertiary referral center for syncope is associated with increased mortality for most etiologies (except vasovagal), cardiac more than non-cardiac. Despite high costs of inpatient evaluation, associated with more diagnostic tests, longer in-hospital stay and higher mortality rates, nearly half of the patients were discharged undiagnosed. Outpatient evaluation should be considered when medically possible.






[1] ICCU = Intensive Cardiac Care Unit

[2] LTM = long-term mortality


January 2008
Y. Shoenfeld, B. Gilburd, M. Abu-Shakra, H. Amital, O. Barzilai, Y. Berkun, M. Blank, G. Zandman-Goddard, U. Katz, I. Krause, P. Langevitz, Y. Levy, H. Orbach, V. Pordeus, M. Ram, Y. Sherer, E. Toubi and Y. Tomer
Y. Shoenfeld, G. Zandman-Goddard, L. Stojanovich, M. Cutolo, H. Amital, Y. Levy, M. Abu-Shakra, O. Barzilai, Y. Berkun, M. Blank, J.F. de Carvalho, A. Doria, B. Gilburd, U. Katz, I. Krause, P. Langevitz, H. Orbach, V. Pordeus, M. Ram, E. Toubi and Y. Sherer
Y. Shoenfeld, M. Blank, M. Abu-Shakra, H. Amital, O. Barzilai, Y. Berkun, N. Bizzaro, B. Gilburd, G. Zandman-Goddard, U. Katz, I. Krause, P. Langevitz, I.R. Mackay, H. Orbach, M. Ram, Y. Sherer, E. Toubi and M.E. Gershwin
Y. Katz, M.R. Goldberg, G. Zadik-Mnuhin, M. Leshno and E. Heyman

Background: Immunoglobulin E-mediated allergy to cow’s milk protein represents a major problem for infants who are not breast fed. A search for substitute milks revealed a cross-allergenicity to milk derived from goat and sheep but not to milk from a mare. We noted that the cow, goat and sheep species are both artiodactyls and ruminants, defining them as kosher animals, in contrast to the mare.

Objectives: To determine whether patients with IgE[1]-mediated cow’s milk allergy are cross-sensitized to milk from other species such as the deer, ibex, buffalo, pig and camel.

Methods: Patients with a clinical history consistent with IgE-mediated cow's milk protein allergy were tested by skin prick test to validate the diagnosis. They were then evaluated by skin-prick test for cross-sensitization to milk-derived proteins from other species.

Results: All patients allergic to cow's milk tested positive by skin-prick test for cross-reactivity to deer, Ibex and buffalo (n=24, P = 0). In contrast, only 5 of the 24 patients (20.83%) tested positive to pig milk and only 2 of 8 (25%) to camel’s milk. Cross-sensitization to soy milk was noted in 4 of 23 patients (17.39%), although they all tolerated oral ingestion of soy-containing foods.

Conclusions: A significant cross-sensitization to milk proteins derived from kosher animals exists in patients allergic to cow's milk protein, but far less so compared to the milk proteins from non-kosher animals tested. Patients with proven IgE-mediated allergy to cow’s milk can utilize the above findings to predict suitable alternative sources of milk.






[1] Ig = immunogloublin



December 2006
E. Zimlichman, M. Szyper-Kravitz, U. Katz and Y. Shoenfeld
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