Israel Medical Association Journal

In this issue of IMAJ, two articles discuss and review the roles of chronic airway infection (1) and inflammation (2) respectively in cystic fibrosis lung disease.

Multidetector-row computed tomography has been validated as a useful non-invasive diagnostic method in patients with various cardiac diseases.

Background: There are no national data on the burden and management of acute cerebrovascular disease in Israel.

Objectives: To delineate the burden, characteristics, management and outcomes of hospitalized patients with acute cerebrovascular disease in Israel, and to examine adherence to current guidelines.

Methods: We prospectively performed a national survey in all 28 hospitals in Israel admitting patients with acute cerebrovascular events (stroke or transient ischemic attacks) during February and March 2004.

Results: During the survey period 2,174 patients were admitted with acute cerebrovascular disease (mean age 71 ± 13 years, 47% women; 89% ischemic stroke or TIA[1], 7% intracerebral hemorrhage and 4% undetermined stroke). Sixty-two percent of patients were admitted to departments of Medicine and a third to Neurology, of which only 7% were admitted to departments with a designated stroke unit. Head computed tomography was performed during hospitalization in 93% of patients. The overall rate of urgent thrombolytic therapy for acute ischemic stroke was 0.5%. Among patients with ischemic stroke or TIA, 94% were prescribed an antithrombotic medication at hospital discharge, and among those with atrial fibrillation about half were prescribed warfarin. Carotid duplex was performed in 30% and any vascular imaging study in 36% of patients with ischemic events. The mean length of hospital stay was 12 ± 27 days for ICH[2] and 8 ± 11 days for ischemic stroke. Among patients with ICH, 28% died and 66% died or had severe disability at hospital discharge, and for ischemic stroke the corresponding rates were 7% and 41% respectively. Mortality rates within 3 months were 34% for ICH and 14% for ischemic stroke.

Conclusions: This national survey demonstrates the high burden of acute stroke in Israel and reveals discordance between existing guidelines and current practice. The findings highlight important areas for which reorganization is imperative for patients afflicted with acute stroke.

Background: In Japan, helicopters have rarely been used for emergency medical services. The use of helicopters not only ensures rapid evacuation but may also serve to provide emergency management to patients with life-threatening injuries in the prehospital setting.

Objectives: To evaluate a Japanese helicopter-based emergency medical system including an onboard physician, particularly in terms of probability of survival.

Methods: We conducted a retrospective review of trauma victims, and calculated two estimates of PS[1] – at the scene and on arrival at the emergency department – based on patient age, Injury Severity Score, and Revised Trauma Score.

Results: We identified trauma victims who had an ISS[2] above 15 and were transported from the scene by helicopter. Excluding cardiopulmonary arrest at the scene, 151 cases were studied. Thirty-two patients had hemodynamic instability with systolic blood pressures below 90 mmHg, caused by hemorrhagic shock (29 cases) or obstructive shock (3 cases). Their PS values were 0.56 ± 0.38 in the prehospital setting and 0.65 ± 0.38 on arrival at the ED[3], representing a significant difference (P = 0.0003). Twenty-four of these patients survived, reflecting successful resuscitation during prehospital and ED management.

Conclusions: A doctor-helicopter system was shown to improve probability of survival for life-threatening trauma in the Japanese emergency medical system.

Background: Phototherapy is considered the standard of care for neonatal jaundice. However, its short term cardiorespiratory effects have not been studied thoroughly.

Objectives: To assess the cardiorespiratory effect of phototherapy during sleep in term infants with physiologic jaundice.

Methods: We performed two polysomnography studies during 3 hours sleep in 10 healthy term infants with physiologic jaundice; each infant served as his/her own control. The first study was performed just prior to phototherapy and the second study during phototherapy 24 hours later. Heart and respiratory rates, type and duration of apneas, and arterial oxygen saturation were analyzed during active and quiet sleep.

Results: Term infants (gestational age 38.6 ± 1.4 weeks, birth weight 3.2 ± 0.5 kg) underwent the two polysomnography studies within a short time interval and had a comparable bilrubin level (3.6 ± 0.8 and 4.5 ± 0.8 days; 14.5 ± 1.4 and 13.8 ± 2.1 mg/dl, P = NS, respectively). There was no difference in sleeping time or the fraction of active and quiet sleep before or during phototherapy. During active sleep under phototherapy there was a significant decrease in respiratory rate and increase in heart rate (54.3 ± 10.3 vs. 49.1 ± 10.8 breaths/minute, and 125.9 ± 11.7 vs. 129.7 ± 15.3 beats/minute, respectively, P < 0.05), as well as a decrease in respiratory effort in response to apnea. These effects were not found during quiet sleep. Phototherapy had no significant effect on oxygen saturation, apnea rate or periodic breathing in either sleep state. No clinical significant apnea or bradycardia occurred.

Conclusions: Phototherapy affected the cardiorespiratory activity during active sleep but not during quiet sleep in term infants with physiologic jaundice. These effects do not seem to have clinical significance in "real-life" conditions.

At the WHO meeting on primary immunodeficiency held in Orvetto, Italy in 1994, mutations in the genes involved in the classical PID disorders, such as X-linked agammaglobulinemia (Bruton).

The autoimmune lymphoproliferative syndrome is a recently described human disorder that affects lymphocyte programmed cell death (apoptosis).

Although the airway granulomata in Wegener's granulomatosis were stressed initially by Friedrich Wegener himself, in the last few decades systemic lesions mainly caused by acute vasculitis have received the most attention. However, recently, the implication of granulomatous manifestations in WG[1] has raised much interest. The present data suggest that an aberrant Th1-type response might play a role in the initiation of WG, clinico-pathologically characterized by granulomatous inflammation rather than vasculitis. Disease progression to generalized WG with the predominance of vasculitic manifestations is associated with a “switch” or further complexity of the collective T cell response with the appearance of another subset of Th2-type cells and a less prominent Th1-type cytokine production in the granulomatous lesions of the upper respiratory tract. However, the clinical significance of the granulomatous inflammation is not yet completely understood. Further research will also have to focus on the role of the granulomata during relapsing disease. We review present knowledge of granulomatous inflammation in WG. Morphologic aspects, the scale of cytokine alterations as well as the variety of clinical manifestations are discussed.

Background: Heat shock proteins are highly conserved immunodominant antigens found in various species. Humoral immune responses to mycobacterial HSP65[1] and human HSP60 have been established in a number of human autoimmune diseases.

Objective: To assess the prevalence of antibodies to HSP60 kDa and HSP65 kDa in patients with Sjogren's syndrome as compared to normal subjects.

Methods: Thirty-seven patients with SS[2] were compared with normal controls. The antibodies against human HSP60 were measured by the Anti-Human (IgG/IgM) HSP60 ELISA kit. IgGs[3] and IgMs to mycobacterial HSP65 were determined using an enzyme-linked immunosorbent assay with mycobacterial recombinant HSP65 antigens.

Results: The levels of both anti-HSP60 and -HSP65 were lower among patients compared with controls. IgG autoantibodies to HSP60 were significantly different between groups: 162 ± 55.1 ng/ml in controls versus 112.3 ± 30.6 ng/ml in SS patients (P < 0.001). The levels among controls of anti-HSP65 IgM isotype were also significantly higher than among patients: 111.6 ± 33.4 U/ml versus 96.1 ± 8.9 U/ml (P = 0.01).

Conclusions: The results of the present study show that the levels of different isotypes of anti- HSP60 and HSP65 antibodies were lower in patients with SS than in normal subjects. Additional studies on larger patient populations are required to evaluate the prevalence of these autoantibodies in SS patients.

Background: Dyspnea may be a presenting symptom of type I food hypersensitivity, and bronchial hyper-reactivity, without known asthma, can coexist in patients with food allergy.

Objective: To evaluate airway involvement in young adult patients with food allergy and no asthma and compare the findings to those of patients with food allergy and asthma, with food allergy and allergic rhinitis, with asthma and no food allergy, and of apparently healthy controls.

Methods: The evaluation involved prick skin test to food (65 allergens) and inhalants (24 allergens), spirometry, methacholine inhalation challenge, and induced sputum for cell analysis. The five groups consisted of 18 patients with food allergy alone, 11 with food allergy and asthma, 13 with food allergy and allergic rhinitis, 10 with asthma alone, and 10 controls.

Results: Patients with food allergy alone were mainly (86%) skin sensitive to pollens. Those with either asthma or allergic rhinitis were mainly (95%) sensitive to mites. BHR was detected in 40% of the patients with food allergy alone, 55% of the patients with allergic rhinitis, and 100% of the patients with asthma. Cell counts in the sputum of patients with asthma and in those with food allergy and asthma showed higher eosinophil counts compared to those with food allergy and allergic rhinitis. Patients with food allergy and no asthma, regardless of BHR status, had mainly neutrophils in the sputum.

Conclusions: Patients with food allergy are highly likely to have concomitant asymptomatic BHR. Mite sensitivity in patients with food allergy predicts respiratory allergy (either asthma or allergic rhinitis). High eosinophil levels in the sputum of food allergy patients predict respiratory involvement.

Background: In the last decade there has been an increase in asthma morbidity. Hospital admission rates for childhood asthma are influenced by the prevalence of asthma and the quality of asthma care.

Objective: To assess trends in hospital admission and readmission rates for childhood asthma in the Jezreel Valley in Israel in the last decade, and to evaluate the possible effect of changes in asthma treatment upon hospitalization for acute asthma during this period.

Methods: All records from pediatric patients from the central hospital in the Jezreel Valley in northeastern Israel over a 10 year period from 1990 through 1999 who were diagnosed as having asthma were thoroughly reviewed and analyzed for admissions, re-admissions, and treatment before and during admissions

Results: There were 1584 admissions, 1208 were first-time admissions and 374 were re-admissions. The number of first-time admissions increased significantly over time (P < 0.0001), with a significant decrease of re-admissions (P < 0.005); this finding was more significant in children under the age of 8 years (P < 0.005). The length of hospital stay decreased significantly from 3.3 days to 2.7 days (P < 0.002). Significant changes in the use of medications included an increase in inhalant glucocorticoids and a decrease in the use of sodium cromoglycate and theophylline. Controller medication use was concomitant with a significant decrease in the re-admission rates.

Conclusions: The increase in the admission rate and the decrease in the rate of re-admissions and the length of hospital stay probably reflect the increase in the prevalence of asthma and changes in its treatment, respectively. It is essential that asthma be recognized as a significant cause of morbidity and that controller medications be administered to decrease the asthma's severity, morbidity, and resultant hospital admissions.
 

Non-steroidal anti-inflammatory drugs, mainly ibuprofen, are extensively used in children as analgesics and antipyretics.

Background: The anti-inflammatory effect of montelukast, a leukotriene receptor antagonist, in patients with bronchial asthma is not entirely clear. Basophils can release a variety of mediators, including histamine and leukotriens, which most likely play an active part in the late allergic response.

Objectives: To study the effect of montelukast (10 mg/day) on histamine and cysteinyl leukotriene release from basophils taken from 12 mild atopic asthmatic patients who were given the drug for 4 weeks.

Methods: Basophils were withdrawn at baseline, and after 48 hours, 1 week, and 4 weeks of therapy. Histamine was measured by a radioenzymatic method and leukotrienes by immunologic assay. Histamine and cysLT release was measured spontaneously and following stimulation with interleukin-3 and anti-immunoglobulin E. Spirometry and symptom score were measured before and during treatment.

Results: During the treatment with montelukast there were no significant changes in spontaneous, IL-3 and anti-IgE‑induced histamine release. cysLT release decreased significantly only after 4 weeks of treatment (from 2899 ± 550 pg/ml at baseline to 2225 ± 430 pg/ml at 4 weeks, P = 0.02).

Conclusions: Montelukast does not seem to affect the release of histamine from basophils but mildly inhibits the cysLT release seen after 4 weeks of treatment.

Background: Food allergies in children are often very serious and can lead to anaphylactic reactions. Observations that camel milk ameliorates allergic reactions were noted over the years. The effect of the camel milk is probably related to its special composition.

Objectives: To investigate the effect of camel milk in several children with severe food (mainly milk) allergies.

Methods: We studied eight children with food allergies who did not benefit from conventional treatment. Their parents, or their physicians, decided to try camel milk as a last resort. The parents were advised by the authors – who have considerable experience with the use of camel milk – regarding how much and when the children should drink the milk. The parents reported daily on the progress of their children.

Results: All eight children in this study reacted well to the milk and recovered fully from their allergies.

Conclusions: These encouraging results should be validated by large-scale clinical trials.

Background: Since 1984, several waves of Ethiopian immigrants have settled in Israel. On arrival they were found to be highly infected with intestinal parasites and to have increased serum immunoglobulin E and eosinophilia. 

Objectives: To study serum IgE [1] levels in Ethiopian children growing up in the environment of Israel . 

Methods: We assessed four groups of children of Ethiopian origin: a) adolescents examined on their arrival to Israel (group 1, n=11); b) adolescents born in Ethiopia and living in Israel for more than 7 years (group 2, n=10); c) children of Ethiopian origin born in Israel, without a history of allergy or asthma (group 3, n=15); and d) asthmatic children of Ethiopian origin born in Israel (group 4, n=8). A thorough clinical interview and examination as well as serum IgE levels, stool parasites and absolute eosinophil count were performed. 

Results: Group 1 (11 newly arrived Ethiopian adolescents) had a mean eosinophil count of 688 cells/ml (0–1739) and a mean serum IgE of 1043 IU/ml (253–2932), P < 0.0009 as compared to group 2. Helminthic parasites were observed in 8/11 individuals; after 1 year of follow-up and anti-parasitic treatment, serum IgE levels did not change significantly. Group 2 (10 Ethiopian born adolescents living in Israel for on average 10 years, 7–15 years) had a normal leukocyte count, MEC [2] 192 cells/ml (range 54–289), serum IgE 142 IU/ml (range 14–399 IU/ml) and no parasites in stool. Group 3 (15 Ethiopian children born in Israel) had a normal leukocyte count, MEC 128 cells/ml (0–324), serum IgE 55 IU/ml (7–189 IU/ml), similar to age-matched Israeli controls. In group 4 (8 Israeli born children of Ethiopian descent diagnosed with asthma), serum IgE showed significant elevation compared to Israeli age-matched asthmatic children (P < 0.005).  

Conclusions: High levels of IgE found in Ethiopian children on arrival to Israel declined to Israeli control levels after several years of living in the new environment. Ethiopian children born in Israel had normal levels of IgE, suggesting that environment is the main factor affecting IgE levels in this population. Israeli born Ethiopian children with asthma had significantly increased serum IgE levels compared to asthmatics of Israeli origin. These findings suggest that both environmental and genetic factors determine the level of serum IgE in these children. 

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 [1] Ig = immunoglobulin

 [2] MEC = mean eosinophil count