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Sat, 23.11.24

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May 2014
Donato Rigante MD PhD, Aurora Rossodivita MD PhD and Luca Cantarini MD PhD
Miriam E. Pepys Vered MB BS and Mark B. Pepys MD PhD FRCP FRCPath FRS FMedSci
Bonaguri Chiara PHD, Orsoni Jelka Gabriella MD, Russo Annalisa PHD, Rubino Pierangela MD, Bacciu Salvatore MD, Lippi Giuseppe MD Melegari Alessandra PHD, Zavota Laura MD, Ghirardini Stella AO and Mora Paolo MD

Background: Cogan’s syndrome (CS) is a rare autoimmune vasculitis characterized by ocular inflammation and sensorineural hearing loss. CS is divided into a “typical” form with non-syphilitic interstitial keratitis and audiovestibular symptoms, and an “atypical” form with ocular involvement affecting structures other than the cornea. Anti-Hsp70 antibodies were found at variable levels in patients presenting with various forms of autoimmune sensorineural hearing loss (ASNHL).

Objectives: To assess the correlation between anti-Hsp70 antibodies and specific ASNHL subgroups.

Methods: We divided 112 subjects into four groups: 14 subjects with typical CS, 24 with atypical CS, 55 with ASNHL, and 19 control subjects (healthy subjects and patients with systemic autoimmune diseases but no sensorineural hearing or audiovestibular alterations). Patients were tested for serological autoimmunity markers including anti-Hsp70.

Results: Positivity of the anti-Hsp70 antibody test was highest in the typical CS group (92.9%) and lowest in the control group (5.2%). The test was positive in 52.7% of patients in the ASNHL group and 16.6% in the atypical CS group. The paired comparison analysis between groups showed that sensitivity of anti-Hsp70 in the typical CS group was significantly higher, as compared to the other three study groups.

Conclusions: Anti-Hsp70 antibodies can be considered a serological marker of “typical” CS. “Atypical” CS is conceivably a sort of “melting pot” of different forms of autoimmune diseases still characterized by ocular inflammation and sensorineural hearing loss but whose antigenic characteristics need to be further defined.

Dorit Blickstein MD, Rima Dardik PhD, Esther Rosenthal MsC, Judith Lahav PhD, Yair Molad MD and Aida Inbal MD
Background: A 75 year old patient presenting with mucocutaneous bleeding was diagnosed with acquired thrombastheniaThe diagnosis was based on lack of platelet aggregation with adenosine diphosphate (ADP), arachidonic acid and collagen, and normal aggregation induced by ristocetin.

Objective: To study the mechanism of platelet function inhibition in a patient with acquired thrombasthenia.

Methods: Aggregation assays of platelets from the patient and healthy controls were performed. In addition, anti-glycoprotein (GP) IIbIIIa antibodies binding to normal platelets in the presence or absence of the patient’s serum was studied by flow cytometry.

Results: Aggregation of normal platelets in the presence of patient's plasma was inhibited four- and 2.5-fold in the presence of ADP and arachidonic acid respectively, while collagen-induced aggregation was completely abolished. Ristocetin-induced aggregation was normal. The patient's serum inhibited binding of commercial anti-glycoprotein IIbIIIa antibodies to normal platelets twofold by flow cytometry. Treatment with anti-CD20 monoclonal antibody (rituximab) normalized the patient's platelet aggregation.

Conclusions: These results suggest that the patient developed inhibitory anti-GPIIbIIIa autoantibodies that caused acquired thrombasthenia. 

May 2014
April 2014
Eyal Bercovich MD, Lital Keinan-Boker MD PhD and Shaul M. Shasha MD
 Background: Previous studies suggest that exposure to starvation and stress between conception and early infancy may have deleterious effects on health later in life; this phenomenon is termed fetal origin of adult disease.

Objectives: To determine whether exposure to the Holocaust from preconception to early infancy is a cause of chronic morbidity in adulthood.

Methods: This pilot study involved 70 European Jews born in countries under Nazi rule (exposed group) during the period 1940–1945 who were interviewed to determine the presence of chronic diseases. A control group of 230 Israeli-born individuals of the same descent, age, and gender distribution were extracted from the Israel National Health Interview Survey-2 (unexposed group). The prevalence of selected risk factors and chronic diseases was compared between the groups.

Results: The prevalence of cardiovascular risk factors and morbidity was significantly higher in the exposed group: body mass index (BMI) (29.06 ± 3.2 vs. 26.97 ± 4.42, P = 0.015), hypertension (62.9% vs. 43%, P = 0.003), dyslipidemia (72.9% vs. 46.1%, P < 0.001), diabetes (32.9% vs. 17.4%, P = 0.006), angina pectoris (18.6% vs. 4.8%, P = 0.001) and congestive heart failure (8.6% vs. 1.7%, P = 0.013). The prevalence of cancer (30.0% vs. 8.7% P < 0.001), peptic ulcer disease (21.4% vs. 7%, P = 0.001), headaches/migraines (24.3% vs. 12.6%, P < 0.001) and anxiety/depression (50.0% vs. 8.3%, P < 0.001) was also higher in the exposed group.

Conclusions: These results suggest that exposure to Holocaust conditions in early life may be associated with a higher prevalence of obesity, dyslipidemia, diabetes, hypertension, cardiovascular morbidity, malignancy and peptic diseases in adulthood. These findings set the stage for further research, which might define those exposed as a high risk group for chronic morbidity.

George M. Weisz MD FRACS MA and William R. Albury BA PhD
 Reinhard Heydrich, architect of the “Final solution of the Jewish problem,” had a meteoric career in the SS. He organized the Wannsee Conference and created the SS killing squads. Under his leadership as Reich Protector of Bohemia and Moravia, the suppression of the Czech community was brutal. An attempt on his life in Prague was unsuccessful but it left him severely injured and he died eight days later. Reviewing the available information on his hospital treatment and the autopsy report, it is suggested that Heydrich received substandard medical treatment, quite likely a result of political interference from rival members of the SS hierarchy.

Sarah Kraus PhD, Inna Naumov PhD, Shiran Shapira PhD, Dina Kazanov MSc, Ilan Aroch MSc, Arnon Afek MD PhD, Oded Eisenberg PhD , Jacob George MD, Nadir Arber MD MSc MHA and Ariel Finkelstein MD
 Background: Atherosclerosis is a complex vascular inflammatory disease. In the last decade it was suggested that non-steroidal anti-inflammatory drugs (NSAID) and in particular inhibition of cyclooxygenase (COX)-2 are associated with an increase in cardiovascular morbidity and mortality. Aspirin is known to reduce the incidence and mortality from ischemic heart disease and is a mainstay in the prevention of vascular complications of atherosclerosis.

Objectives: To examine the effect of meloxicam, a selective COX-2 inhibitor, or low dose aspirin on the development of experimental atherosclerosis in apoE knockout (KO) compared to wild-type (WT) mice. We aimed to test the hypothesis that meloxicam, a potential vasculitis inducer, would exacerbate atherosclerotic lesions while aspirin, which is known to reduce the incidence of thrombosis occlusive events, would increase protection in this model.

Methods: We randomly divided 36 male apoE KO and 36 WT mice, 8 weeks old. Mice were treated for 10 weeks with 0.1 mg/ml aspirin, or 0.05 mg/ml meloxicam, dissolved in their drinking water. Control groups received regular drinking water. At sacrifice, the hearts were removed for histochemical staining and plaque size and composition were examined.

Results: Aspirin-treated animals displayed a decreased atherosclerotic lesion area compared to the untreated control mice, while meloxicam had a null effect on the extent of atherosclerosis in Apo E KO mice.

Conclusions: These results suggest that low dose aspirin reduces early atherosclerosis, while inhibition of COX-2 by meloxicam is not associated with an increase in atherosclerotic plaque size in this mouse model.

February 2014
Arnon D. Cohen MD MPH PhD, Israel D. Andrews MD, Evgeny Medvedovsky MD, Roni Peleg MD, and Daniel A.Vardy MD MSc
Background: Localized itch of non-pruritoceptive origin is often neuropathic and may be referred to as neuropathic itch syndrome.

Objectives: To describe the results of nerve conduction studies in patients with anogenital pruritus, brachioradial pruritus and scalp dysesthesia, and compare these sites to typical sites of lichen simplex chronicus (LSC).

Methods: The study summarizes previously published data combined with unpublished data of patients with scalp dysesthesia. Nerve conduction studies included measurements of distal sensory and motor latency, conduction velocity and F-responses.

Results: A neuropathy was demonstrated in 29 of 36 patients with anogenital pruritus (80.5%), 8/14 with brachioradial pruritus (57.1%) and 4/9 with scalp dysesthesia (44.4%). The typical sites overlapped with some but not all LSC sites.

Conclusions: A considerable proportion of patients with brachioradial pruritus, anogenital pruritus and scalp dysesthesia have abnormal nerve conduction findings, suggesting a neuropathic origin. The skin sites overlap with some common LSC sites, suggesting that in some cases of LSC a local neuropathy could be a possible cause.

June 2013
G. Barkai, A. Barzilai, E. Mendelson, M. Tepperberg-Oikawa, D. Ari-Even Roth and J. Kuint
 Background: Congenital cytomegalovirus (C-CMV) infection affects 0.4–2% of newborn infants in Israel, most of whom are asymptomatic. Of these, 10–20% will subsequently develop hearing impairment and might have benefitted from early detection by neonatal screening.

Objectives: To retrospectively analyze the results of a screening program for C-CMV performed at the Sheba Medical Center, Tel Hashomer, during a 1 year period, using real-time polymerase chain reaction (rt-PCR) from umbilical cord blood.

Methods: CMV DNA was detected by rt-PCR performed on infants’ cord blood. C-CMV was confirmed by urine culture (Shell-vial). All confirmed cases were further investigated for C-CMV manifestations by head ultrasound, complete blood count, liver enzyme measurement, ophthalmology examination and hearing investigation.

Results: During the period 1 June 2009 to 31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105 (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them (96%) were confirmed by urine culture. Two additional infants, who had not been screened, were detected after clinical suspicion. All 24 infants were further investigated, and 3 (12.5%) had central nervous system involvement (including hearing impairment) and were offered intravenous ganciclovir for 6 weeks. Eighteen (82%) infants would not otherwise have been diagnosed.

Conclusions: The relatively low incidence of C-CMV detected in our screening program probably reflects the low sensitivity of cord blood screening. Nevertheless, this screening program reliably detected a non-negligible number of infants who could benefit from early detection. Other screening methods using saliva should be investigated further.

 

January 2012
Ronit Lubetzky, MD, Galit Zaidenberg-Israeli, MD, Francis B. Mimouni, MD, Shaul Dollberg, MD, Eyal Shimoni, PhD, Yael Ungar, PhD and Dror Mandel, MD

Background: Human milk produced during prolonged lactation (> 1 year) is extraordinarily rich in fat and has a higher energy content than human milk produced during short lactation.

Objectives: To estimate the fatty acid (FA) profile of human milk and to test the hypothesis that the proportion of C12 and C14 (two dietary saturated FA known to most promote hypercholesterolemia) in human milk during prolonged lactation is similar to that in short lactation.

Methods: We conducted a cross-sectional study of 30 mothers of term infants lactating for more than 1 year as compared with 25 mothers of full-term infants who lactated for 2–6 months. Milk was collected by manual expression in mid-breastfeeding.

Results: The two groups did not differ in maternal height, weight, body mass index, diet, infant birth weight and gestational age, but mothers in the prolonged lactation group were significantly older. There was a significant correlation between lactation duration and C12 or C14. The percentage of all FA combined (except for C12 and C14) decreased significantly over time. In contrast, C12:0 and C14:0 combined increased significantly during lactation (R2 = 10.0%, P < 0.03).

Conclusions: Women who lactated for more than 1 year had higher C12 and C14 FA percentages in their milk than women who lactated for 2–6 months.

Antonella Cianferoni, MD, PhD, Jackie P. Garrett, MD, David R. Naimi, MD, Karishma Khullar, BS and Jonathan M. Spergel, MD, PhD.

Background: Skin-prick tests (SPT), food-specific immunoglobulin E level (sIgE) and clinical history have limited value individually in predicting the severity of outcome of the oral food challenge (OFC). 

Objectives: To develop a score that accounts for SPT, sIgE and clinical history to predict the risk of severe reaction to the OFC. 

Methods: A 5 year retrospective chart review was performed on 983 children who underwent OFC to egg, milk and peanut. 

Results: Using multilogistic regression, four major indicators were found to be independently associated with failed OFC: sIgE (odds ratio = 1.04, P < 0.0001) , wheal size of the SPT (OR = 1.23, P < 0.0001), a history of any prior reaction to the food (OR = 1.13, P < 0.01), and a history of a prior non-cutaneous reaction (OR = 1.99, P < 0.01)  and three were independently associated with anaphylaxis: wheal size (OR = 1.16, P < 0.001), a history of a prior non-cutaneous reaction (OR = 4.24, P < 0.01), and age (OR = 1.07, P < 0.03). A Food Challenge Score (0–4) was developed which accounted for SPT wheal, sIgE, a history of a prior non-cutaneous reaction, and age. A score of 0–1 had a negative predictive value for multisystem reaction to the OFC: 95% for milk, 91% for egg and 93% for peanut. A score of 3–4 had a positive predictive value for anaphylaxis:  62% for milk, 92% for egg and 86% for peanut.

Conclusions: Severe reaction to milk, egg and peanut OFC can be predicted using a simple score that takes into account clinical data that are commonly available prior to the challenges.

Michael B. Levy, MD, Michael R. Goldberg, MD, PhD, Liat Nachshon, MD, Elvan Tabachnik, MD and Yitzhak Katz, MD

Background: Most reports in the medical literature on food allergy mortality are related to peanuts and tree nuts. There is limited knowledge regarding these reactions and often only a partial medical history is described.

Objective: To record and characterize all known cases of mortality due to food allergy in Israel occurring during the period 2004–2011.

Methods: All cases of food allergy-related mortality that were known to medical personnel or were published in the Israeli national communications media were investigated. We interviewed the parents and, when feasible, physicians who treated the final event.

Results: Four cases of food-related mortality were identified: three cases were due to cow’s milk and one to hazelnut. All were exposed to a hidden/non-obvious allergen. All four had a history of asthma but were not on controller medications, and all had experienced previous non-life threatening accidental reactions. Three of the four patients had not been evaluated by an allergist, nor were they prescribed injectable epinephrine. The one patient who had been prescribed injectable epinephrine did not use it during her fatal anaphylactic attack.

Conclusions: Fatal reactions to cow’s milk and hazelnut but not to peanut are the only reported food mortality cases in Israel. Although these patients had previous reactions following accidental exposures, none had experienced a life-threatening reaction. Patients at risk are not adequately evaluated by allergists, nor are they prescribed and instructed on the proper use of injectable epinephrine. Cow’s milk should be considered a potentially fatal allergen.




 



 
Pedro Ojeda, MD, MPH, Isabel Ojeda, MD, Gema Rubio, MD and Fernando Pineda, PhD.

Background: In the last decade the use of different types of oral immunotherapy for food-allergic patients has increased with generally satisfactory outcomes. Cow’s milk and hen’s egg, a common element in the daily diet, have received the main interest. Most of these immunotherapy regimens are performed in the hospital, causing inconvenience for both children and their parents.

Objectives: To assess the efficacy and safety of a home-based oral immunotherapy regimen with raw pasteurized egg.

Methods: The study group comprised children aged 6 years and older with allergy to hen’s egg proteins, proven by positive skin prick-tests (SPT) and/or specific immunoglobulin E (sIgE) and positive open oral food challenge (OOFC) with boiled or raw egg. Patients who met the inclusion criteria and signed the informed consent form underwent egg immunotherapy according to an established schedule.

Results: The treatment was given to 31 of the 36 recruited patients: 80.6% of the intention to treat population achieved complete tolerance to the maximum dose equivalent to one raw hen’s egg, 3.2% achieved incomplete tolerance, and 16.2% did not achieve an acceptable tolerance dose. Most of the latter patients had a positive baseline OOFC with low doses of boiled egg. The average number of reactions per treated patient was 5.8, most of them grades 1 and 2 there were no grade 4 reactions.

Conclusions: This home-based oral immunotherapy protocol proved to effectively induce tolerance to hen’s egg in most of the egg-allergic children and its safety profile was acceptable.

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