Israel Medical Association Journal

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.

Hereditary angioedema is a rare genetic disorder, manifested by recurrent edema leading to disfigurement, organ dysfunction and life-threatening respiratory impairment that may become fatal. The hallmark of HAE is a C1 esterase inhibitor deficiency, but recent evidence points at bradykinin as the main mediator that causes hyperpermeability of small vasculature, leading to accumulation of edema fluid. Current therapeutic options for HAE[1] are limited, and consist of drugs, replacement therapy, and supportive treatment. In view of many disadvantages of the current therapeutic modalities new approaches to the treatment of HAE are now being offered. This review summarizes our experience with a new line of medications developed for the treatment of acute exacerbations and prophylaxis of HAE – icatibant: bradykinin receptor antagonist, ecallantide: kallikrein inhibitor, and two C1 INH[2] preparations: Berinert-P, human plasma-derived concentrate, and Rhucin: novel recombinant C1-INH produced in transgenic rabbits. Preliminary results of these studies are encouraging and may bring new hope to the patients with this distressing condition. The exact number of HAE patients in Israel is unknown and because patients are treated individually and comprehensive laboratory assessment is partial, many cases might be missed or not treated according to accepted guidelines. We offer a new specialty center for HAE patients, addressing the medical and psychosocial needs of patients and their families.

The pollen of Ambrosia (ragweed) is one of the major causes of pollen-induced allergy worldwide. This family of plants has apparently evolved in North America but was later spread into Europe and Asia. Flowering of the Ambrosias starts in mid-July and continues throughout the autumn and is a cause of major morbidity to allergic sensitized patients. The invasion of new species of Ambrosia into Israel is still in progress. Plants of Ambrosia artemisiifolia (American short ragweed), Ambrosia trifida (American giant ragweed), Ambrosia confertifolia, Ambrosia grayi and Ambrosia tenuifolia are increasingly found in Israel, mainly in the Hula valley in the eastern Galilee and near the Alexander River in the Sharon plain. From experience it is known that the time it takes to eradicate a new invasive species is limited. Action should be taken immediately or this new invasion will spread and cause a significantly increased burden of morbidity and increased health costs in Israel.

Background: Insulin-dependent diabetes mellitus is dominated by a Th1 response whereas atopic diseases such as asthma, eczema and allergic rhinitis are characterized by a Th2 response. Because it is known that Th1 and Th2 cells reciprocally counteract each other, it can be speculated that the prevalence of Th2-mediated diseases is lower in patients with a Th1-mediated disease.

Objectives: To compare the prevalence of atopic diseases among children with IDDM[1] and age-matched controls.

Methods: The study group comprised 65 children with IDDM attending the pediatric endocrinology clinic at the Wolfson Medical Center. The control group consisted of 74 non-diabetic children who presented at the emergency room due to an acute illness (burns, abdominal pain, fever, head trauma). Patients were asked to complete a detailed questionnaire on their history of personal and familial atopic and autoimmune diseases. In addition, a total serum immunoglobulin E concentration and the presence of IgE[2] antibodies to a panel of relevant inhalant allergens were analyzed.

Results: Children with IDDM and their first-degree relatives had a significantly higher prevalence of other autoimmune diseases such as thyroiditis and celiac as compared to controls. The two groups had a similar prevalence of atopic diseases with respect to history, total serum IgE, or the presence of IgE antibodies to a panel of relevant inhalant allergens.

Conclusions: The prevalence of atopic diseases in IDDM patients was similar to that in the normal population. Our results suggest that the traditional Th1/Th2 theory to explain the complexity of the immune response is oversimplified. 

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.  

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
 
 

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.

[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

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

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.

Organophosphate and carbamate are mainly used to kill insects, thereby protecting livestock, crops, homes and communities. Yet, these compounds also convey great danger. OP[1] and CRB[2] poisoning is an important clinical problem, often life-threatening, especially in the pediatric population in rural areas where reaching a physician or hospital on time is difficult. We present a summary of accumulated toxicological knowledge as well as clinical and laboratory experience from a medical center serving a relatively vast rural area and pediatric population. We stress the importance of knowing how to recognize the classic signs of OP and CRB poisoning and when it is appropriate to investigate for such poisoning even in the absence of those signs. Like any medical emergency, OP and CRB poisoning requires prompt resuscitation and use of antidotes. Atropine, oxygen and fluids are the mainstay of therapy. Oximes, which were found useful in some cases of OP poisoning and useless in some cases of CRB poisoning, are absolutely safe as empiric treatment, which is often needed since the major differential diagnosis of OP poisoning is CRB poisoning that is clinically indistinguishable. We hope that continuing research will offer further insights into the management of such events, and we are confident that improved medical management of OP and CRB poisoning will result in a reduction of morbidity and other complications associated with intensive care procedures and hospitalization.