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עמוד בית
Thu, 28.11.24

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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.

Mauro Calvani, MD, Iride Dello Iacono, MD, Valentina Giorgio, MD, Stefano Miceli Sopo, Valentina Panetta, MD and Salvatore Tripodi, MD.

Background: The diagnostic gold standard for food allergy is an oral food challenge (OFC) with the suspected food. Usually, an OFC is stopped at the onset of mild objective symptoms for fear of severe reactions. However, there is no consensus on this issue.

Objective: To investigate the effectiveness and side effects of a new model of oral milk challenge in order to increase the diagnostic accuracy of cow¡¯s milk protein allergy and reduce the number of many useless elimination diets. This model is characterized by a conservative diagnostic protocol and ¡°step-up cow’s milk administered dosing.¡± The secondary aim was to investigate possible factors influencing severe reactions.   

Methods: Sixty-six children (median age 1 year, range 1¨C18) with suspected immunoglobulin E (IgE)-mediated cow’s milk allergy performed a conservative oral food challenge (OFC), i.e., the OFC was continued even in the presence of subjective, even repeated, or mild local or multiple organ objective symptoms. If the first objective reaction occurred when the quantity of milk was > 10 ml, the investigator would decide whether to continue the OFC or prescribe a gradual increase in milk feeding at home.

Results: Symptoms developed during the OFC in 42.4% of the children. Local, generalized and severe generalized reactions developed in 11 (16.7%), 11 (16.7%) and 6 (9.1%) children, respectively. Only 14/28 (50%) who developed objective symptoms during the OFC were considered to be affected by cow’s milk allergy. In the remaining 14 both subjective and objective symptoms developed and the OFC was continued without the emergence of additional symptoms. Epinephrine was administered to 6 of the 28 children (21.4%) who developed objective symptoms. All but one had subjective symptoms following the early doses of milk, whereas all children who later tolerated milk had their first subjective or mild symptoms following doses ¡Ý 10 ml.

Conclusions: This new model of oral milk challenge criteria led to frequent severe allergic reactions hence its use in daily practice seems inadvisable. However, our study provides evidence that a severe allergic reaction does not invariably occur if the offending food continues to be administered after the onset of symptoms. If mild symptoms appear at doses higher than 10 ml, continued milk administration, on the same day or in subsequent days, seems to facilitate the development of tolerance and may reduce the number of useless elimination diets.


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.

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.

Michael D. Keller, MD, Michele Shuker, RD, Jennifer Heimall, MD and Antonella Cianferoni, MD, PhD.

Background: Alternatives to cow’s milk and soy milk are often necessary for children with food allergies. Although hydrolyzed and elemental formulas are appropriate replacements, other milk products such as rice and almond milk are insufficient protein sources for children under 2 years of age. A chart review on three patients treated for protein malnutrition in association with multiple diagnosed food allergies that resulted in refractory eczema revealed adverse outcomes that resulted from elimination diets. The use of rice milk resulted in hypoalbuminemia and poor weight gain in all cases, and multiple secondary infections in one patient. These cases illustrate the need for careful nutritional guidance in the management of food allergy, as well as the importance of cautious use and interpretation of testing for food allergies in the absence of a clear clinical history of reaction.

Intan H. Ismail, MD, MMed and Mimi L.K. Tang, MB, BS, PhD

Food allergies have increased significantly over recent decades, and are the most common cause of admissions for anaphylaxis in childhood, particularly in children under 5 years of age. Current management of food allergy is limited to strict food allergen avoidance together with education on the recognition and emergency management of allergic reactions, and in some cases provision of self-injectable adrenalin. Although this supportive management approach is generally effective, it is burdensome for patients and families, and in turn leads to reduced quality of life. Patients with food allergy would benefit greatly from a definitive treatment that could achieve long-term tolerance. Recent studies demonstrate that oral immunotherapy (OIT) can induce desensitization and modulate allergen-specific immune responses. However, it remains uncertain whether long-term tolerance can be achieved with current OIT regimens. Increased allergen dose, duration of OIT and/or inclusion of an immune modifying adjuvant may enhance the tolerogenic potential of OIT. Allergic reactions during OIT are common, although severe reactions are infrequent. Oral immunotherapy holds promise as a novel approach to the definitive treatment of food allergy.

December 2011
G. Goodman and M. Eric Gershwin

Physicians have a great interest in discussions of life and its origin, including life's persistence through successive cycles of self-replication under extreme climatic and man-made trials and tribulations. We review here the fundamental processes that, contrary to human intuition, life may be seen heuristically as an ab initio, fundamental process at the interface between the complementary forces of gravitation and quantum mechanics. Analogies can predict applications of quantum mechanics to human physiology in addition to that already being applied, in particular to aspects of brain activity and pathology. This potential will also extend eventually to, for example, autoimmunity, genetic selection and aging. We present these thoughts in perspective against a background of changes in some physical fundamentals of science, from the earlier times of the natural philosophers of medicine to the technological medical gurus of today. Despite the enormous advances in medical science, including integration of technological changes that have led to the newer clinical applications of magnetic resonance imaging and PET scans and of computerized drug design, there is an intellectual vacuum as to how the physics of matter became translated to the biology of life. The essence and future of medicine continue to lie in cautious, systematic and ethically bound practice and scientific research based on fundamental physical laws accepted as true until proven false.
 

G.A. Weiss, Y. Goldich, E. Bartov and Z. Burgansky-Eliash

Background: Comorbid depression may play an important role in non-compliance with medical treatment among patients with chronic illnesses. Glaucoma is a potentially blinding chronic disease requiring life-long commitment to medical therapy. Patient's failure to adhere to anti-glaucoma treatment may lead to disease progression and visual loss.

Objectives: To assess the prevalence of depressive symptoms in glaucoma patients and the association between these symptoms and non-compliance with anti-glaucoma therapy.

Methods: This was a cross-sectional observational study. Compliance with pharmacotherapy was assessed with the Morisky Medication Adherence questionnaire (eight items). Screening for depression was performed by means of the CES-D scale (Center for Epidemiologic Studies Depression scale). The association between depression and compliance rates was analyzed.

Results: The study group comprised 76 glaucoma patients; 19.7% of the subjects were classified as "non-compliant" (Morisky cutoff < 10) and 21.1% suffered from depression (CES-D cutoff ≥ 16). We found a similar level of non-compliance when comparing depressed with non-depressed glaucoma patients. However, a significant correlation was observed between the level of depression and the level of non-compliance (P = 0.04).

Conclusions: Our study revealed a similar rate of depression in glaucoma patients and the general Israeli population. The presence of depression was not associated with the presence of non-compliance, yet the level of depression was associated with the level of non-compliance.

T. Fuchs, A. Torjman, L. Galitzkaya, M. Leitman and R. Pilz-Burstein

Background: Sudden death in athletes can occur during sport activities and is presumably related to ventricular arrhythmias. There are no guidelines concerning athletes who develop ventricular arrhythmias during an exercise test. It is unclear whether they should be allowed to continue with their competitive activity or not.

Objectives: To investigate the long-term follow-up of athletes with ventricular arrhythmias during an exercise test.

Methods: From a database of 56,462 athletes we identified 192 athletes, less than 35 years old, who had ventricular arrhythmias during an exercise test. Ninety athletes had ≥ 3 ventricular premature beats (group A) and 102 athletes had ventricular couplets or non-sustained ventricular tachycardia during an exercise test (group B). A control group of 92 athletes without ventricular arrhythmias was randomly selected from the database (group C).

Results: All athletes, except one who died from a dilated cardiomyopathy, were alive during a follow-up period of 70 ± 25 months. An abnormal echocardiogram was obtained in seven athletes from group A (10%), four from group B (5%), and one from group C (3%) (not significant). An abnormal echocardiogram was more likely to be present in competitive athletes (P = 0.001) and in female athletes (P = 0.01).

Conclusions: Our results showed that ventricular arrhythmias during exercise are more commonly associated with cardiovascular abnormalities in young competitive athletes and in female athletes. When present, they necessitate a thorough investigation and follow-up.
 

M. Zoabi, Y. Keness, N. Titler and N. Bisharat

Background: The compliance of hospital staff with guidelines for the active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) in Israel has not been determined.

Objectives: To evaluate the compliance of hospital staff with guidelines for the active surveillance of MRSA and assess its impact on the incidence of nosocomial MRSA bacteremia.

Methods: We assessed compliance with MRSA surveillance guidelines by assessing adherence to the screening protocol and reviewing medical and nursing charts of patients colonized with MRSA, and observed hand hygiene opportunities among health care workers and colonized patients. Rates of nosocomial MRSA bacteremia and of adherence with hand hygiene among overall hospital staff were obtained from archived data for the period 2001–2010.

Results: Only 32.4% of eligible patients were screened for MRSA carriage on admission, and 69.9% of MRSA carriers did not receive any eradication treatment. The mean rate of adherence to glove use among nurses and doctors was 69% and 31% respectively (P < 0.01) and to hand hygiene 59% and 41% respectively (P < 0.01). The hospital overall rate of adherence to hand hygiene increased from 42.3% in 2005 to 68.1% in 2010. Rates of nosocomial MRSA bacteremia decreased by 79.2%, from 0.48 (in 2001) to 0.1 (in 2010) per 1000 admissions (P < 0.001).

Conclusions: The compliance of medical and nursing staff with guidelines for active MRSA surveillance was poor. The encouraging increase in adherence to hand hygiene and concomitant decrease in nosocomial MRSA bacteremia is gratifying. The deficiencies in compliance with MRSA infection control policy warrant an adjusted strategy based on the hospital resources.

R. Dabby, M. Sadeh, O. Herman, L. Leibou, E. Kremer, S. Mordechai, N. Watemberg and J. Frand

Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.

Objectives: To describe the clinical, electrophysiologic and pathologic findings in patients with myotonic dystrophy 2.

Methods: We evaluated 10 patients genetically, clinically and electrophysiologically during the years 2007 to 2008.

Results: All patients were of Jewish European ancestry. Among affected individuals, eight patients had symptoms of proximal muscle weakness, two had muscle pain, and two exhibited myotonia. On physical examination six patients had severe weakness of hip flexor muscles. Seven individuals underwent cataract surgery, and cardiac involvement was seen in one case. On the initial electromyographic (EMG) examination five patients demonstrated myotonic discharges; repeated studies showed these discharges in nine cases. Six muscle biopsies showed non-specific pathological changes. Seven patients had an affected first-degree relative with either a diagnosed or an undiagnosed muscular disorder, consistent with an autosomal dominant trait.

Conclusions: DM2 may often present with proximal muscle weakness without myotonia. EMG may initially fail to show myotonic discharges, but these discharges may eventually show in most cases on repeated EMG. Thus, DM2 may be underdiagnosed and should be included in the differential diagnosis of adult patients of Jewish European ancestry presenting with proximal lower limb weakness.
 

A.Ben-Haroush, J. Farhi, I. Ben-Aharon, O. Sapir, H. Pinkas and B. Fisch

Background: Adjuvant/neoadjuvant chemotherapy in breast cancer patients may be associated with amenorrhea and a marked reduction in ovarian reserve.

Objectives: To assess the use of letrozole with follicle-stimulating hormone (FSH) in gonadotropin-releasing hormone (GnRH) analogue protocols, based on reported attempts to avoid the estradiol (E2) increase during controlled ovarian hyperstimulation for embryo cryopreservation in breast cancer patients using a combination of low dose FSH and aromatase inhibitor (letrozole) in a GnRH-antagonist protocol.

Methods: Twenty-four breast cancer patients were treated with recombinant FSH (150–450 U/day) and letrozole (5 mg/day) in a long GnRH-agonist (n=7) or GnRH-antagonist (n=17) protocol. After oocyte retrieval, insemination and/or intracytoplasmic sperm injection was performed. The embryos were frozen.

Results: The average interval from surgery to oocyte retrieval was 40 days. Average duration of treatment was 9.6 days and mean peak E2 level 1342 ± 1091 pmol/L, yielding 16.0 ± 16.3 oocytes (range 0–82). Mean fertilization rate was 69.5 ± 20.4% and mean number of embryos cryopreserved 10.3 ± 9.3. More oocytes were retrieved with the long GnRH protocol, but the difference was not statistically significant (24.8 ± 24.6 vs. 12.0 ± 8.8 pmol/L, P = 0.07).

Conclusions: As previously reported, ovarian stimulation with letrozole and FSH, in both the long GnRH-agonist and GnRH-antagonist protocols, is apparently effective in breast cancer patients and spares them exposure to high E2 levels.
 

I. Grodman, D. Buskila, Y. Arnson, A. Altaman, D. Amital and H. Amital
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