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December 2008
A. A. Wanderer

The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA[1] and COPD[2], which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These stimuli in combination with other danger-related biochemical signals are capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3) and cause interleukin-1β secretion with subsequent neutrophilic inflammation. There is evidence to suggest that the mechanisms and pathobiology associated with chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit similarities to the biphasic pathobiology involved in ischemia-reperfusion injury. A rationale is suggested for trials of IL-1β[3] targeted therapies as an adjunct strategy to control neutrophilic inflammation in these conditions.






[1] SPA = severe persistent asthma

[2] COPD = chronic obstructive pulmonary disease

[3] IL = interleukin


M. Rottem, D. Shostak, S. Foldi

Background: Cow's milk allergy is the most prevalent food hypersensitivity, affecting 2–3% of infants, but it tends to resolve with age. Cow’s milk-specific immunoglobulin E in the serum is an important measure in the diagnosis and follow-up of infants and children with cow's milk allergy.

Objectives: To examine the relation between CmsIgE[1] and the probability of resolution of milk allergy.

Methods: CMsIgE was determined in the serum of 1800 infants and children referred for the evaluation of possible milk allergy. All children with CmsIgE of 1 kU/L or above were followed at the allergy clinic and, according to their condition, underwent milk challenge. The diagnosis of cow's milk allergy was made on the basis of a significant and specific history or a positive oral food challenge. Subsequently, oral tolerance was defined as an uneventful oral challenge.

Results: A total of 135 infants and children had milk-specific IgE greater than 1 kU/L. Forty-one percent of children still had clinical milk allergy after the age of 3 years. Sixty-eight percent of children older than 3 years with persistence of cow's milk allergy had milk-specific IgE > 3 IU/ml before the age of 1 year. Furthermore, 70% of children who at 3 years old had resolved their cow's milk allergy had milk-specific IgE that was lower than 3 IU/ml before the age of 1 year. The positive predictive value of CmsIgE > 3 IU/ml to persistent cow's milk allergy at age 3 years was 82.6% (P = 0.001), with a sensitivity of 67.9% and specificity of 70.4%.

Conclusions: Milk-specific IgE concentration in the first year of life can serve as a predictor of the persistence of milk allergy.

 






[1] CmsIgE = cow’s milk-specific immunoglobulin E


S. Halevy, N. Grossman

Background: Multiple drug allergy syndrome is a rarely reported clinical condition characterized by an adverse reaction to more than one different class of pharmacologically and structurally unrelated drugs. The pathogenesis may involve immediate-type or delayed-type hypersensitivity.

Objectives: To further characterize patients with MDA[1] in terms of the type of CADR, drug intake and clinical drug suspicion.

Methods: The study group comprised 12 patients (6 males, 6 females) with CADRs[2] showing in vitro drug-induced IFNγ[3] release for multiple drugs, suggesting the presence of MDA. The diagnostic role of in vitro IFNγ release in identifying the culprit drugs was evaluated in terms of clinical data and the results of in vivo tests (withdrawal and/or challenge tests) with the offending drugs.

Results: Clinical relevance was attributed to in vitro drug-induced IFNγ release towards multiple drugs in this series of 12 patients with a variety of CADRs, implying MDA. The results of in vivo tests for the offending drugs confirmed the diagnosis. The main causative agents responsible were antibiotics and non-steroidal anti-inflammatory drugs.

Conclusions: The study further supports the role of a T cell-mediated mechanism in the pathogenesis of MDA. The in vitro drug-induced IFNγ release test may serve as a laboratory tool to identify the culprit drugs associated with this allergy.  






[1] MDA = multiple drug allergy

[2] CADR = cutaneous adverse drug reaction

[3] IFNg = interferon-gamma


A. Bleich, M. Gelkopf, R. Berger, Z. Solomon

Background: Detrimental effects of military service among the civilian Palestinian population have been reported in soldiers.

Objectives: To examine the frequency and type of stressors encountered by soldiers in close contact with the CPP and its relationship with post-traumatic symptomatology. We also investigated coping methods and the preferred types of professional help.

Methods: Using random digit dialing methodology we conducted a phone survey of veteran soldiers, men (n=167) and women (n=59) in close contact with the CPP; the comparison group comprised male veteran soldiers with no CPP exposure (n=74). We used focus groups to develop context-related measures to assess exposure to violent incidents, coping modes and preferred modes of professional assistance. We included measures of traumatic exposure, post-traumatic stress symptoms and post-traumatic stress disorder.

Results: Soldiers who served among the CPP had greater exposure to traumatic events and to civilian-related violent incidents (more than half as victims, and a third as perpetrators); and 17.4% perceived their behavior as degrading civilians. Primary traumatic exposure, perceived health problems and avoidance coping were found to be risk factors for PTS[1] and PTSD[2]. Involvement in incidents that may have degraded Palestinian civilians predicted PTS.
Conclusions: Friction with the CPP in itself does not constitute a risk factor for psychopathology among soldiers. However, contact with this population entails more exposure to traumatic events, which may cause PTS and PTSD. Furthermore, a relative minority of soldiers may be involved in situations that may degrade civilians, which is a risk factor for PTS. To avoid violent and sometimes degrading behaviors, appropriate psycho-educational and behavioral preparation should be provided.|



 



[1] PTS = post-traumatic stress symptoms

[2] PTSD = post-traumatic stress disorder
 
 

A. Vivante, R. Bilik, I. S. Eisen, J. Kuint

Background: Over the last two decades, the epidemiology, treatment strategy and mortality rate for congenital diaphragmatic hernia have changed.

Objectives: To retrospectively analyze our experience with CDH[1] of the last 22 years.

Methods: We reviewed the charts of all infants suffering from CDH between 1985 and 2007. Prenatal and maternal as well as perinatal and neonatal data were collected, including outcome parameters. The 71 infants that we identified were divided them into two historical groups: from 1985 to 1995 (group 1, 123 patients) and from 1996 to 2007 (group 2, 45 patients).

Results: We found an increase in the incidence of prenatal diagnosis and a subsequent significant decrease in gestational age at diagnosis in group 2 (25 weeks gestation, compared with 30 weeks gestation in group 1, P = 0.018). In addition, we noted a trend toward a reduced number of infants with right-sided hernia and associated cardiac anomalies. The timing to post-delivery surgery was significantly longer in group 2 (20 hours in group 1 vs. 53 hours in group 2, P < 0.001). A significant reduction in postoperative mortality was demonstrated in group 2 compared with group 1 (13.5% vs. 38.7% respectively, P = 0.04),

Conclusion: Our data suggest a higher survival rate for operated infants in group 1 during the last decade, probably due to changes in preoperative methods of treatment as well as later surgery timing compared to group 1. We speculate that today’s cases of congenital diaphragmatic hernia are probably milder than in the past due to earlier and more detailed prenatal diagnosis and subsequent termination of pregnancies for the more severe forms of the disorder. 






[1] CDH = congenital diaphragmatic hernia


Y. Michowitz, S. Kisil, H. Guzner-Gur, A. Rubinstein, D. Wexler, D. Sheps, G. Keren, J. George

Background: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress.

Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure.

Methods: Baseline serum MPO[1] levels were measured in 285 consecutive CHF[2] patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality.

Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 ± 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP[3] was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values.


Conclusions: MPO levels are elevated in CHF and correlate with disease severity. MPO has an additive predictive value on mortality in patients with intermediate NT-proBNP levels.

 


 


[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

[3] NT-proBNP = N-terminal pro-brain natriuretic peptide

A. Hadary, I. Dashkovsky, A. Rapaport, J.C. Cozakov

Background: Non-traumatic rupture of the spleen is a rare condition. It can occur in a pathological spleen caused by any of a variety of diseases. For yet unknown reasons this condition may sometimes involve an apparently normal spleen as well.

Objectives: To examine the incidence, symptoms, causes, therapy and prognosis of "spontaneous" splenic rupture.

Methods: We conducted a retrospective study of seven patients diagnosed with splenic rupture not related to any traumatic event, who had been treated in the surgical department of a community hospital within the last 19 years.

Results: The male to female ratio was 5:2. In some patients, no background disease that could explain increased friability of splenic tissue could be identified. In some cases, where hemodynamic stability and absence of peritoneal signs afforded observation, splenectomy was delayed. In one case it was avoided altogether.

Conclusions: “Spontaneous” rupture of spleen should be suspected when abdominal symptomatology occurs against a background of an acute infectious disease, especially in young males, or a disease known to affect target organs of the reticular endothelial system. Preoperative use of imaging studies in hemodynamically stable patients can sometimes obviate surgery, or in cases of massive hemoperitoneum reduce intraoperative time.

Click here for article written by Orly Tamir, MHA, MSc, Joshua Shemer, MD, Mordechai Shani, MD, Sharona Vaknin, MSc and Miriam Ines Siebzehner, PhD, MPA, RN. IMAJ 2008: 12: December: 901-905
The Israeli Center for Technology Assessment in Health Care (ICTAHC) was established in 1998 at the Gertner Institute for Epidemiology and Health Policy Research, on foundations set in 1992 by the Medical Technology Assessment Unit. The Center is defined as an independent multidisciplinary research center, whose main aims are to assist in developing processes for the adoption of new technologies, identify and propose health priorities, and serve as an educational center for all stakeholders. Moreover, the Center promotes working relations with overseas counterparts as an essential component for expansion and advancement of the field of health technology assessment. Throughout the years, ICTAHC had contributed significantly to the development of the discipline of health technology assessment in Israel and to actual decision making in the health care system. The Center had outlined the principles, guidelines and overall framework for technology assessment in the country, as well as substantiating the discipline through various research areas, which materialized into a variety of technology-related policy accomplishments. Today, the Center serves as a national focal point in the health care system in Israel, as well as maintaining an active position in the international milieu. It has been a decade since the establishment of ICTAHC. This paper reviews the evolution of the center, describes changes in the HTA[1] field in Israel, identifies areas of focus and main research accomplishments, and illustrates the breadth of potential research scope and projections for the future.





[1] HTA = health technology assessment

November 2008
Y. Bentur et al

Background: The Israel National Poison Information Center, Rambam Health Care Campus, provides telephone consultations on clinical toxicology as well as drug and teratogen information around the clock. The Center participates in research, teaching and regulatory activities, and also provides laboratory services.

Objectives: To analyze data on the epidemiology of poisonings and poison exposures in Israel.

Methods: We conducted computerized queries and a descriptive analysis of the medical records database of the IPIC[1] during 2007.

Results: Overall, 26,738 poison exposure cases were recorded, a 118.5% increase compared to 1995. Children under 6 years old were involved in 45% of cases; 73% of the calls were made by the public and 25.5% by physicians; 74.4% of exposures were unintentional and 9.2% intentional. Chemicals were involved in 37.9% of cases, pharmaceuticals in 44.2%, bites and stings in 4.3% and poisonous plants in 1.2%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.5%. Substances most frequently involved in moderate/major exposures were insecticides, drugs of abuse and corrosives. Eight fatalities were recorded – three unintentional exposures (all chemicals) and five intentional (chemicals, medications, drugs of abuse).

Conclusions: The rates of poison exposures and poisonings in Israel have increased significantly, contributing substantially to morbidity and mortality. The IPIC database is a valuable national resource for collecting and monitoring cases of poison exposure and can be used as a real-time surveillance system. It is recommended that reporting to the IPIC become mandatory and that its activities be adequately supported by national resources.

 






[1] IPIC = Israel National Poison Information Center


A. F. Sawalha

Background: The Palestinian Poison Control and Drug Information Center was established in 2006 to provide up-to-date information on medications and to help in the early diagnosis and management of poisoning cases.

Objectives: To summarize the activities carried out by the PCDIC[1] in the past 2 years.

Methods: Documented inquires received at the PCDIC were analyzed and the Center's activities were extracted from the files.

Results: During the first 2 years of the Center's existence, 323 inquiries were received, mainly (67.2%) from physicians; 70% of the calls were from the city of Nablus. Unintentional poisoning was the leading type of call (62.8%) followed by suicidal poisoning (20.7%). Medications were the major category of toxicants encountered (48.9%), followed by pesticides (23.5%). In 67.9% of the cases, the calls were initiated before any treatment was provided. The advice provided by the PCDIC was based on the nature of the call. During these 2 years the PCDIC has conducted several academic and non-academic activities. The Center introduced the concept of poison prevention weeks in Palestine and has conducted two so far. The PCDIC has published several articles in the fields of toxicology, rational drug use, complementary and herbal therapy, pharmacoepidemiology, and self-medication.

Conclusions: Documentation of all inquiries is mandatory for analysis, evaluation, comparative purposes, and quality assurance. More information campaigns are needed to encourage people to use the services provided by the PCDIC.






[1] PCDIC = Poison Control and Drug Information Center


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