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.

Asthma is an airway disease, yet that airway extends all the way to the alveolar tissue area. Pathohistiological as well as physiological and clinical studies have recently documented this aspect of asthma. The implications of this are important for all asthmatic patients, but particularly for those whose asthma is more difficult to control. Many of the inhaled preparations used as therapy for asthma are of relatively large particle size. 

Thus, the deposition of these medications is mainly in the central and medium sized airways and very little of a given actuation gets to the distal airways. Ultrafine inhaled steroid particles have been shown to reach the more peripheral portions of the airway, and improvement in outcome variables such as air trapping as well as symptomatic outcomes have been demonstrated. This review focuses on anatomic airway changes, physiological changes of the distal airways, clinical outcome data, and particle size of inhaled preparations.

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.

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: 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: 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.

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. 

Background: Medication errors are a common cause of morbidity and mortality.

Objectives: To evaluate the rate of acknowledgment of medication errors as reported by physicians working in the community and in hospitals.

Methods: An anonymous questionnaire was sent to 9320 active physicians (about 48% community physicians, 17% hospital physicians and 35% working in both places), with questions on the rate and type of medication errors that they had encountered during their professional career. The questions specified errors in dosage, type of medicine (wrong indication), route of administration and drug interactions.

Results: Only 627 physicians (6.7%) responded. Of these, nearly 79% admitted having made an error in prescribing medication; the majority admitted to more than one error. Physicians with fewer years of experience admitted having made a mistake more than did physicians with more experience (P = 0.019). Pediatricians and geriatricians made more dosage mistakes (P = 0.02), while family physicians and psychiatrists made more mistakes in drug interactions (P = 0.001).

Conclusions: It is possible that indifference, fear of identification, or lack of awareness may have contributed to the low response rate despite the fact that the questionnaire was anonymous. Educational programs should be implemented in medical schools to encourage physicians to report errors before the onset of adverse reactions.
 

Background: Infections with blood-borne viruses are a major health problem among illicit drug users. There is little information about infection rates and risk factors for hepatitis virus B, C or the human immunodeficiency virus in drug users in Israel.

Objectives: To determine the prevalence of HCV[1], HBV[2] and HIV[3] infections in a large cohort of drug users in Israel; to compare rates of HCV, HBV and HIV between injecting versus non-injecting drug users and between different origin countries; and to identify risk factors for HCV among illicit drug users.

Methods: We conducted a cross-sectional interviewer-administered questionnaire and serological screening for HCV, HBV and HIV in 1443 consecutive drug users diagnosed at the Israeli National Center for Diagnosis of Drug Addicts between January 2003 and December 2005.

Results: Fourteen (0.9%), 51 (3.5%) and 515 (35.7%) subjects tested positive for HIV, HBV and HCV, respectively. All three infections (HIV, HBV and HCV) were significantly more common among injecting drug users and immigrants from the former Soviet Union and other East European countries compared to native Israelis. Multivariate analysis showed that HCV infection was associated with age (> 40 years) (OR=2.06, 95% CI 1.40–3.03), immigration from East European countries and the former Soviet Union (OR=4.54, 95% CI 3.28–6.28), and injecting drug use (OR=16.44, 95% CI 10.79–25.05).

Conclusions: HIV, HBV and HCV prevalence among drug users in Israel is significantly lower than in North America and West Europe. Risk factors for HCV infection in this population include injecting drug use, older age, and immigration from the former Soviet Union.

Background: Due to extensive activity at sea, certain human populations, especially fishermen, are exposed to direct contact with the sea's inhabitants, including dangerous marine animals.

Objectives: To characterize and assess the extent of injuries caused by marine organisms along the Mediterranean coast of Israel, their type, severity and medical treatment given.

Methods: Data were obtained from a survey on injuries from marine organisms conducted among professional fishermen along the Mediterranean coast of Israel and from medical records reporting toxicological consultations provided by the Israel Poison Information Center.

Results: Injuries caused by marine organisms are not rare in Israel, but most cases are not severe. The most common injuries reported by fishermen were caused by stingrays (30%), weaver fish (22%), rabbit fish, (13%) and marine catfish (10%) – a new Red Sea immigrant. Most fishermen tend to treat such injuries themselves and sought medical help only when an unknown venomous fish was involved. Most cases of severe toxicity were due to secondary infection. Data from the IPIC[1] indicated that 64% of the calls were from the general public and the rest came from physicians in health care facilities. Four sources of injuries were identified: cleaning and preparing fish for consumption, during leisure water sport activities, handling marine aquaria, and fishing. Most cases from the IPIC were graded as minor severity (85%) and were treated symptomatically.
Conclusions: We recommend that medical facilities be installed at the fishing anchorages and that a separate category be established for injuries by marine organisms to facilitate epidemiological data collection from health care facilities

Background: Cardiac computed tomography scans influde several extra-cardiac structures such as mediastinum, lung parenchyma and upper abdominal organs. A variety of abnormalities in those structures might be clinically important and in some cases might explain the patient's complaints.

Objectives: To analyze consecutive cardiac computed tomography examinations for the prevalence and clinical significance of extra-cardiac findings.

Methods: Cardiac CT scans of 134 sequential patients (104 males, 30 females) aged 20–77 years (mean 54 years) with suspected coronary artery disease were prospectively and independently reviewed by a consensus of two radiologists for the presence of lung, mediastinal, pleural, upper abdominal and skeletal abnormalities. CT scans with extra-cardiac abnormalities were divided into two groups: group A – defined as "clinically significant" or "potentially significant findings" – consisted of patients requiring further evaluation or follow-up, and group B – "clinically non-significant findings."

Results: Extra-cardiac abnormalities were found in 103 of the 134 patients (76.8%). Group A abnormalities were found in 52/134 patients (39%), while group B abnormalities were seen in 85/134 (63%). The most common abnormalities in group A were non-calcified lung nodules (> 4 mm) noted in 17/134 patients (13%), followed by enlarged mediastinal lymph nodes (> 10 mm) in 14/134 (10%), diaphragmatic hernia (2 cm) in 12/134 (9%), moderate or severe degenerative spine disease in 12/134 (9%), and emphysema and aortic aneurysm in 6 patients each (4.5%). A malignant lung tumor was noted in one patient.

Conclusions: There is a high prevalence of non-cardiac abnormalities in patients undergoing CCT[1]. Clinically significant or potentially significant findings can be expected in 40% of patients who undergo CCT, and these will require further evaluation and follow-up. The reporting radiologist should be experienced in chest imaging and aware of the large variety of non-cardiac findings in CCT that might explain the patient's complaints.