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עמוד בית
Wed, 13.11.24

November 2008


Toxicology
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


G. Markel, A. Krivoy, E. Rotman, O. Schein, S. Shrot, T. Brosh-Nissimov, T. Dushnitsky, A. Eisenkraft
The relative accessibility to various chemical agents, including chemical warfare agents and toxic industrial compounds, places a toxicological mass casualty event, including chemical terrorism, among the major threats to homeland security. TMCE[1] represents a medical and logistic challenge with potential hazardous exposure of first-response teams. In addition, TMCE poses substantial psychological and economical impact. We have created a simple response algorithm that provides practical guidelines for participating forces in TMCE. Emphasis is placed on the role of first responders, highlighting the importance of early recognition of the event as a TMCE, informing the command and control centers, and application of appropriate self-protection. The medical identification of the toxidrome is of utmost importance as it may dictate radically different approaches and life-saving modalities. Our proposed emergency management of TMCE values the “Scoop & Run” approach orchestrated by an organized evacuation plan rather than on-site decontamination. Finally, continuous preparedness of health systems – exemplified by periodic CBRN (Chemical, Biological, Radio-Nuclear) medical training of both first responders and hospital staff, mandatory placement of antidotal auto-injectors in all ambulances and CBRN[2] emergency kits in the emergency departments – would considerably improve the emergency medical response to TMCE.

 


[1] TMCE = toxicological mass casualty event

[2] CBRN = chemical, biological, radio-nuclear 
T. Leibson and M. Lifshitz

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. 






[1] OP = organophosphonate

[2] CRB = carbamate


B. Bar-Oz, M. Goldman, E. Lahat, R. Greenberg, M. Avgil, A. Blay, A. Herman, M. Berkovitch

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.
 

R. Loebstein et al

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.






[1] HCV = hepatitis C virus

[2] HBV = hepatitis B virus

[3] HIV = human immunodeficiency virus


Eran Kozer, MD, Rachel Bar-Hamburger, MD, Noa Y. Rosenfeld, MD, Irena Zdanovitch, MD, Mordechai Bulkowstein, MD and Matitiahu Berkovitch, MD.

Background: Clinicians’ impression of adolescents' alcohol or drug involvement may underestimate substance-related pathology.

Objectives: To describe the characteristics of adolescents presenting to the pediatric emergency department due to substance abuse and to determine whether physicians can reliably identify these patients.

Methods: We conducted a prospective cohort study of all patients aged 12–18 years presenting to a pediatric emergency department between 1 January 2005 and 31 December 2006 for whom a urine drug screen or ethanol blood levels was ordered. According to departmental protocol urine drug screen and ethanol levels are taken for specific indications. Based on the history and clinical findings the pediatrician in the ED[1] assessed on a 5-point likelihood scale the possibility that the patients’ symptoms were related to substance abuse.

Results: Of the 139 patients in the study group 40 (30%) tested positive for ethanol or drugs of abuse. The median age was 16. Compared with patients who tested negative, there were more patients with decreased level of consciousness among patients who tested positive for ethanol or drugs (5% vs. 33% respectively, P < 0.001). The median physician estimate for the likelihood of substance abuse was 5 in patients who tested positive and 2 in patients who tested negative (P < 0.001). The likelihood of a positive drug/ethanol test was not affected by age or gender.
Conclusions: Since the likelihood of substance abuse is higher in patients presenting with a low level of consciousness, physicians may accurately assess the likelihood of substance abuse in these patients





[1] ED = emergency department

S. Gweta et al.

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







[1] IPIC = Israel Poison Information Center


Ophir Lavon, MD, Yael Lurie, MD and Yedidia Bentur, MD

Background: Scombroid fish poisoning is an acute illness caused by consumption of fish containing high concentrations of histamine. Improper handling of fish leads to bacterial contamination. Bacterial enzymes convert histidine to histamine. Symptoms develop quickly and resemble an immunoglobulin E-mediated allergic reaction. The diagnosis is often missed. Serious complications (e.g., bronchospasm, hypotension) are infrequent.

Objectives: To evaluate the prevalence and characteristics of scombroid fish poisoning in Israel as reported to the National Poison Information Center.

Methods: We conducted a retrospective poison center chart review from January 2005 to December 2007.

Results: During the study period, 21 events of scombroid poisoning involving 46 patients were recorded. Tuna was the commonest fish consumed (84.7%). Clinical manifestations developed within 20 minutes in 65.2% of the patients. The main clinical manifestations included rash (41%), flushing (37%), gastrointestinal complaints (37%) and headache (30.4%). About 25% had abnormal vital signs; two patients developed hypotension. Treatment was supportive and included mainly H1-antagonists (65.2%) and fluids (13%). Five patients were initially misdiagnosed as having an allergic reaction and were treated with corticosteroids (four patients) and epinephrine (one patient).

Conclusions: Scombroid fish poisoning should be suspected in patients with histamine-like manifestations that are temporally related to fish (mainly tuna) consumption, especially in outbreaks. Although scombroid poisoning is often self-limited and responds well to antihistamines, prolonged observation may be required as severe toxicity can supervene. Proper handling of fish and urgent notification of the Ministry of Health are mandatory in order to prevent this potentially serious public heath problem.
 

Yoram Finkelstein, MD PhD, Na Zhang, PhD, Vanessa A. Fitsanakis, PhD, Malcolm J. Avison, PhD, John C. Gore, PhD and Michael Aschner, PhD

Background: Manganism is a central nervous system disorder caused by toxic exposure to manganese. Manganism has been related to occupational exposures, liver diseases, prolonged parenteral nutrition, and abuse of illicit drugs. Initially manifested by a reversible neuropsychiatric syndrome (locura manganica), the main symptoms and signs of manganism are emotional lability, compulsive behavior and visual hallucinations. Locura manganica is followed by an irreversible extrapyramidal syndrome, the onset of which occurs years after chronic exposure.

Objectives: To characterize the regional distribution of Mn[1] in the rat brain after subchronic exposure to Mn. This animal model holds special clinical relevance, reflecting the earlier clinical stages of manganism before chronic exposure to Mn exerts its irreversible effects.

Methods: Sprague-Dawley rats were intravenously injected with MnCl2 weekly, for a total of 14 weeks – approximately 1/10 of the lifetime of the rat. T1-weighted magnetic resonance imaging was used to detect the distribution of Mn deposition in brain tissues, as evidenced by areas of T1-weighted hyperintense signals.

Results: A consistent region-specific pattern of T1-weighted hyperintensities was observed in the brains of Mn-treated rats. Cortical hyperintensities were prominent in the hippocampus and dentate gyrus. Hyperintensities were also observed in the olfactory bulbs, pituitary gland, optic nerves and chiasma, pons, midbrain tegmentum, habenula, lentiform and caudate nuclei, thalamus, chorioid plexus and cerebellar hemispheres.

Conclusions: Prominent Mn depositions, evidenced by T1-weighted hyperintensities in the hippocampus after subacute exposure to Mn, are compatible with the clinical picture of manganism during its early stages; and may explain its pathophysiology 






[1] Mn = manganese


Ophir Lavon, MD, Yael Lurie, MD, Benjamin Abbou, MD, Bishara Bishara, MD, Shlomo Hanan Israelit, MD PhD and Yedidia Bentur, MD.
Shaden Salameh, MD, Teddy Weiss, MD and Yona Amitai, MD MPH
Original Articles
I. Greenberg-Wolff et al

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. 






[1] CCT = coronary computed tomography


Michal Tenenbaum, Shahar Lavi, Nurit Magal, Gabrielle J. Halpern, Inbal Bolocan, Monther Boulos, Michael Kapeliovich, Mordechai Shohat, Haim Hammerman

Background: Long QT syndrome is an inherited cardiac disease, associated with malignant arrhythmias and sudden cardiac death.

Objectives: To map and identify the gene responsible for LQTS[1] in an Israeli family.

Methods: A large family was screened for LQTS after one of them was successfully resuscitated from ventricular fibrillation. The DNA was examined for suspicious loci by whole genome screening and the coding region of the LQT2 gene was sequenced.

Results: Nine family members, 6 males and 3 females, age (median and interquartile range) 26 years (13, 46), who were characterized by a unique T wave pattern were diagnosed as carrying the mutant gene. The LQTS-causing gene was mapped to chromosome 7 with the A614V mutation. All of the affected members in the family were correctly identified by electrocardiogram. Corrected QT duration was inversely associated with age in the affected family members and decreased with age.
Conclusions: Careful inspection of the ECG can correctly identify LQTS in some families. Genetic analysis is needed to confirm the diagnosis and enable the correct therapy in this disease







[1] LQTS = long QT syndrome


R. Shaoul et al

Background: Patients with non-inflamed appendix have been reported to have had more hospitalizations and emotional disorders before and after the operation than patients with acute appendicitis.

Objectives: To compare abdominal pain characteristics, as well as demographic and psychosocial data in children with histologically confirmed appendicitis compared to non-inflamed appendices.

Methods: Charts of children with suspected appendicitis who had undergone appendectomy were retrospectively reviewed for relevant clinical and laboratory data. The patients or their parents were then contacted by phone and were asked to respond to a detailed questionnaire on abdominal symptoms as well as demographic and psychosocial data.

Results: The study group comprised 156 children: 117 with histologically confirmed appendicitis and 39 with normal appendices. Eighty-two patients (53.2%) were located and interviewed: 62 (54%) with appendicitis and 20 (51%) with normal appendices. Of the 82 children, 16 reported recurrent episodes of abdominal pain before or after surgery: 11 (17.7%) in the appendicitis group and 5 (25%) in the normal appendix group. Only six patients fulfilled the formal criteria for the diagnosis of recurrent abdominal pain: 5 (8%) from the appendicitis group and 1 (5%) from the non-inflamed appendix group (not significant). In addition, no significant statistical differences were found between the groups regarding school performance, behavior and social interaction with peers.

Conclusions: We could not demonstrate an increased incidence of recurrent abdominal pain, nor could we identify significant psychosocial morbidity in those children undergoing a non-inflamed appendectomy.

Reviews
Eyal Shteyer, MD and Michael Wilschanski, MD.
Management of inflammatory bowel disease in childhood poses great challenges. Apart from the disease complications, the drugs' adverse affects, especially corticosteroids, are significant. In the past decade there was major progress in elucidating the pathogenesis of IBD[1], which led to new treatment options aiming to achieve better control of the disease and decrease the various complications of therapy currently used. In this review we provide an overview of novel therapies for IBD, their efficacy, safety and their current use in children.





[1] IBD = inflammatory bowel disease


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