Ariel Hourvitz

Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate plasma acetylcholinesterase and paraoxonase activities

The 5.5u2003Mb chromosome 7q21–22 ACHE/PON1 locus harbours the ACHE gene encoding the acetylcholine hydrolyzing, organophosphate (OP)‐inhibitable acetylcholinesterase protein and the paraoxonase gene PON1, yielding the OP‐hydrolyzing PON1 enzyme which also displays arylesterase activity. In search of inherited and acquired ACHE–PON1 interactions we genotyped seven polymorphic sites and determined the hydrolytic activities of the corresponding plasma enzymes and of the AChE‐homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE, arylesterase, BChE and paraoxonase activities in plasma displayed 5.4‐, 6.5‐, 7.2‐ and 15.5‐fold variability, respectively, with genotype‐specific differences between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase but not paraoxonase activity increased with age, depending on leucine at PON1 position 55. In contrast, carriers of PON1u2003M55 displayed decreased arylesterase activity independent of the −u200a108 promoter polymorphism. Predicted structural consequences of the PON1u2003L55M substitution demonstrated spatial shifts in adjacent residues. Molecular modelling showed substrate interactions with the enzyme variants, explaining the changes in substrate specificity induced by the Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities displayed inverse association with AChE activity. Our findings demonstrate that polymorphism(s) in the adjacent PON1 and ACHE genes affect each others expression, predicting for carriers of biochemically debilitating ACHE/PON1 polymorphisms adverse genome–environment interactions.

Lessons learned from cross-border medical response to the terrorist bombings in Tabba and Ras-el-Satan, Egypt, on 07 October 2004

INTRODUCTIONnLarge-scale, terrorist attacks can happen in peripheral areas, which are located close to a countrys borders and far from its main medical facilities and involve multi-national casualties and responders. The objective of this study was to analyze the terrorist suicide bombings that occurred on 07 October 2004, near the Israeli-Egyptian border, as representative of such a complex scenario.nnnMETHODSnData from formal debriefings after the event were processed in order to learn about victim outcomes, resource utilization, critical events, and time course of the emergency response.nnnRESULTSnA total of 185 injured survivors were repatriated: four were severely wounded, 13 were moderately injured, and 168 were mildly injured. Thirty-eight people died. A forward medical team landed at the border towns airport, which provided reinforcement in the field and in the local hospital. Israeli and Egyptian search and rescue teams collaborated at the destruction site. One-hundred sixty-eight injured patients arrived at the small border hospital that rapidly organized itself for the mass-casualty incident, operating as an evacuation staging hospital. Twenty-three casualties secondarily were distributed to two major trauma centers in the south and the center of Israel, respectively, either by ambulance or by helicopter.nnnCONCLUSIONnLarge-scale, terrorist attacks at a peripheral border zone can be handled by international collaboration, reinforcement of medical teams at the site itself and at the peripheral neighboring hospital, rapid rearrangement of an evacuation hospital, and efficient transport to trauma centers by ambulances, helicopters, and other aircraft.

Who should worry for the "worried well"? Analysis of mild casualties center drills in non-conventional scenarios.

INTRODUCTIONnA mass toxicological event (MTE) caused by an act of terrorism or an industrial incident can create large numbers of ambulatory casualties suffering from mild intoxication, acute stress reaction (ASR), and exacerbation of chronic diseases or iatrogenic insult (such as atropine overdose). The logistical and medical management of this population may present a challenge in such a scenario. The aim of this article is to describe the concept of the Israeli Home Front Command (HFC) of a Mild Casualties Center (MCC) for a chemical scenario, and to analyze the results of two large-scale drills that have been used to evaluate this concept.nnnMETHODSnTwo large-scale drills were conducted. One MCC drill was located in a school building and the second MCC drill was located in a basketball stadium. These medical centers were staffed by physicians, nurses, and medics, both military (reservists) and civilian (community, non-hospital teams). Two hundred simulated patients entered the MCC during each of the drills, and drill observers assessed how these patients were managed for two hours.nnnRESULTSnOf the casualties, 28 were treated in the medical treatment site, 10 of which were relocated to a nearby hospital. Only four casualties were treated in the large mental care site, planned for a much higher burden of worried well patients. Documentation of patient data and medical care was sub-optimal.nnnCONCLUSIONnA MCC is a logistically suitable solution for the challenge of managing thousands of ambulatory casualties. The knowledge of the medical team must be bolstered, as most are unfamiliar with both nerve gas poisoning and with ASR. Mild casualties centers should not be located within hospitals and must be staffed by non-hospital, medical personnel to achieve the main task of allowing hospital teams to focus on providing medical care to the moderate and severe nerve gas casualties, without the extra burden of caring for thousands of mild casualties.

Validity of self-assessment of skin reaction after smallpox vaccination.

Methods. We conducted a prospective, double-blinded, paired-measurement validation study of 174 non-naive adult vaccinees and their physician evaluators. Subjects provided paired, blinded, independent assessments of take 7–9 days after vaccination. Results. Overall, vaccinees and evaluators agreed on 157 of 174 (90.2%) take assessments. Sensitivity of the tool was 99.1%, and specificity was 75%. The positive predictive value of self-assessment was 87.2% and the negative predictive value was 98%. Specificity of the tool and measures of agreement were significantly modified by age, education, and occupation. When adjusted for the expected take rate among a population including naive vaccinees, positive predictive value and overall agreement increased significantly. Conclusions. Self-assessment may be a feasible option for evaluation of take in the event of mass smallpox vaccination. The predictive values and overall agreement of the tool are satisfactory, and can be expected to increase when used in a largely naive population.

A four-step approach for establishment of a national medical response to mega-terrorism.

A simplified, four-step approach was used to establish a medical management and response plan to mega-terrorism in Israel. The basic steps of this approach are: (1) analysis of a scenario based on past incidents; (2) description of relevant capabilities of the medical system; (3) analysis of gaps between the scenario and the expected response; and (4) development of an operational framework. Analyses of both the scenario and medical abilities led to the recommendation of an evidence-based contingency plan for mega-terrorism. An important lesson learned from the analyses is that a shortage in medical first responders would require the administration of advanced life support (ALS) by paramedics at the scene, along with simultaneous, rapid evacuation of urgent casualties to nearby hospitals by medics practicing basic life support (BLS). Ambulances and helicopters should triage casualties from inner to outer circle hospitals secondarily, preferentially Level-1 trauma centers. In conclusion, this four-step approach based on scenario analysis, mapping of medical capabilities, detection of bottlenecks, and establishment of a unique operational framework, can help other medical systems develop a response plan to mega-terrorist attacks.