Lack of toxicity from pediatric beta-blocker exposures.

The risk of toxicity in a child who is unintentionally exposed to a beta-blocking drug remains uncertain. The current study further defines this risk, particularly in the common scenario of ingestion of one or two tablets. A prospective cohort of 208 pediatric patients, 6 months to 6 years of age, reported to two regional poison centers serves as the study population. Data were collected with a standardized instrument during the care of each patient and for a minimum of 24 hours after exposure. No instances of serious toxicity typical of beta-blocker intoxication, such as 'shock-like' states, arrhythmias or seizures were observed in this series. Furthermore, there were no reported episodes of hypoglycemia, symptomatic bradycardia or bronchospasm. Nine instances of altered mental status or behavioral changes were reported. All appeared to be minor in nature. The most serious outcome was charcoal aspiration during gastrointestinal decontamination. This study adds to a growing body of evidence suggesting that exposure to one or two beta-blocker tablets places children at very little, if any, risk of toxicity.

Do poison center triage guidelines affect healthcare facility referrals?

BACKGROUND: The purpose of this study was to determine the extent to which poison center triage guidelines influence healthcare facility referral rates for acute, unintentional acetaminophen-only poisoning and acute, unintentional adult formulation iron poisoning. METHODS: Managers of US poison centers were interviewed by telephone to determine their center's triage threshold value (mg/kg) for acute iron and acute acetaminophen poisoning in 1997. Triage threshold values and healthcare facility referral rates were fit to a univariate logistic regression model for acetaminophen and iron using maximum likelihood estimation. RESULTS: Triage threshold values ranged from 120-201 mg/kg (acetaminophen) and 16-61 mg/kg (iron). Referral rates ranged from 3.1% to 24% (acetaminophen) and 3.7% to 46.7% (iron). There was a statistically significant inverse relationship between the triage value and the referral rate for acetaminophen (p < 0.001) and iron (p = 0.0013). The model explained 31.7% of the referral variation for acetaminophen but only 4.1% of the variation for iron. CONCLUSION: There is great variability in poison center triage values and referral rates for iron and acetaminophen poisoning. Guidelines can account for a meaningful proportion of referral variation. Their influence appears to be substance dependent. These data suggest that efforts to determine and utilize the highest, safe, triage threshold value could substantially decrease healthcare costs for poisonings as long as patient medical outcomes are not compromised.

Mechanical and electromagnetic induction of protection against oxidative stress.

Cells and tissues can be protected against a potentially lethal stress by first exposing them to a brief dose of the same or different stress. This "pre-conditioning" phenomenon has been documented in many models of protection against oxidative stress, including ischemia/reperfusion and ultraviolet (UV) light exposure. Stimuli which induce this protective response include heat, chemicals, brief ischemia, and electromagnetic (EM) field exposures. We report here that constant mechanical vibration pre-conditions chick embryos, protecting them during subsequent stress from hypoxia or UV light exposure. Continuously mechanically vibrated embryos (60 Hz, 1 g (32 ft/s2), 20 min) exhibited nearly double the survival (67.5%, P < 0.001) after subsequent hypoxia as compared to non-vibrated controls (37.6%). As a second set of experiments, embryos were vibrated and then exposed to UV light stress. Those embryos that were vibrated prior to UV had nearly double the survival 3 h after UV exposure (66%, P < 0.001) as compared to controls (35%). The degree of protection, however, was dependent on the constancy of the vibration amplitude. When vibration was turned on and off at 1-s intervals throughout exposure, no increase in hypoxia protection was noted. For 50 s on/off vibration intervals, however, hypoxia protection comparable to continuous vibration was obtained. In contrast, random, inconstant mechanical vibration did not induce protection against subsequent UV exposure. These data suggest that to be an effective pre-conditioning agent, mechanical vibration must have a degree of temporally constancy (on/off intervals of greater than 1 s). Further experiments in both models (hypoxia and UV) indicated an interaction between vibration and EM field-induced protection. Vibration-induced hypoxia protection was inhibited by superposition of a random EM noise field (previously shown to inhibit EM field-induced protection). In addition, EM field-induced UV protection was inhibited by the superposition of random mechanical vibration. Thus, the superposition of either vibrational or EM noise during pre-conditioning virtually eliminated protection against hypoxia and UV. This link between EM field exposures and mechanical vibration is consistent with the hypothesis that cells sense these stimuli via a similar mechanism involving counter ion displacement.

Thresholds for electromagnetic field-induced hypoxia protection: evidence for a primary electric field effect.

We have recently reported that weak electromagnetic (EM) field exposure of chick embryos induces a response that can be used to protect against subsequent hypoxic insult. This work is continued here with an exposure response study using 20-min exposure to 60 Hz magnetic fields over a range of 2-10 microT. Once again, the biomarker used was induction of hypoxia protection. A sigmoidal response curve was found, with exposures to magnetic field strengths > or = 4 microT inducing maximum hypoxia protection (68% survival). We also attempted to determine whether the magnetic or induced electric component of the EM field was responsible for the observed protection. This was accomplished by making measurements with two different orientations of the magnetic fields (perpendicular and parallel to the major axis of the egg). Owing to the configuration of the embryo in the egg, the induced electric field at the embryo was lower when the magnetic field was parallel to the major axis even though the magnetic field strength was the same for each orientation. Exposure of the embryos to the parallel orientation resulted in a reduced protective response. An exposure-response curve generated for this orientation of the field also showed a more "drawn-out" appearance, consistent with the observed distribution of embryo positions within the egg. Our results suggest that the induced electric, not the applied magnetic field, plays a primary role in the protective effect observed in this chick embryo model.

Electromagnetic field-induced protection of chick embryos against hypoxia exhibits characteristics of temporal sensing.

We previously studied the response of mammalian cultured cells to weak, 60 Hz-electromagnetic (EM) fields. Two time constants, similar to those observed in chemotaxis, were found to govern the cellular response to the field. We concluded that a system of temporal sensing, similar to that employed in chemotaxis by motile bacteria, was operative. We termed the shorter time (approximately 0.1 s) the "sensing" time, and the longer time (approximately 10 s) the "memory" time. To investigate the possibility that temporal sensing was a general property of EM field-cell interaction, the temporal properties of another EM field-induced effect was studied. The EM field-induced protection against the effects of extreme hypoxia was examined in chick embryos. Embryos were exposed to 60 Hz-magnetic fields, the amplitudes of which were regularly altered throughout the 20-min exposure. Alteration was accomplished either by turning the field off and on at regular intervals (1-50 s), or by introducing brief (10 or 100 ms), zero amplitude gaps, once each second, throughout exposure. When the field was turned on and off at 0.1 s intervals, the protective effect conferred by a constant field was lost. At progressively longer on/off intervals, protection was progressively restored, maximizing at intervals of 10-30 s. Gapping the magnetic field for 10 ms, each second of exposure conferred the same protection as that observed for an uninterrupted field, but gapping the field at 100 ms each second produced a significant reduction in protection. These data exhibit remarkable consistency with those obtained in similar temporal studies of the magnetic field-induced enhancement of ornithine decarboxylase activity in L929 fibroblasts. It appears that temporal sensing is a general feature of the EM field-cell interaction.

Acute beta blocker overdose: factors associated with the development of cardiovascular morbidity.

OBJECTIVE: To identify factors in exposures to beta blockers (beta-adrenergic receptor antagonists) that are associated with the development of cardiovascular morbidity and contribute to disposition decisions from the emergency department. METHODS: Prospective cohort of 280 beta blocker exposures reported to 2 regional poison centers. Multiple logistic regression was used to determine association of various clinical factors and outcome. RESULTS: In this series of beta blocker exposures, 41 (15%) developed cardiovascular morbidity and 4 (1.4%) died. A history of cardioactive coingestant was the only factor significantly associated with the development of cardiovascular morbidity (p < .05). When cases reporting cardioactive coingestants were excluded, a history of ingesting a beta blocker with membrane stabilizing activity was significantly associated with the development of cardiovascular morbidity (p < .05). All those in whom the timing of symptoms could be determined, developed symptoms within 6 hours of ingestion. CONCLUSIONS: The single most important factor associated with the development of cardiovascular morbidity in beta blocker ingestion is a history of a cardioactive coingestant, primarily calcium channel blockers, cyclic antidepressants, and neuroleptics. In the absence of such coingestion, exposure to a beta blocker with membrane stabilizing activity is associated with an increased risk of cardiovascular morbidity. Beta blocker ingestion is unlikely to result in symptoms if the patient remains asymptomatic for 6 hours after the time of ingestion.

Characterization of US poison centers: a 1998 survey conducted by the American Association of Poison Control Centers.

A 1998 survey of all 73 US poison centers, including 52 certified centers and 21 noncertified centers, is presented. Despite a continued decline of the number of poison centers operating in the US, the volume of calls has steadily increased. In 1997 these centers handled 3.65 million telephone consultations, including 2,475,010 human poison exposure cases, 134,646 animal poison exposures, and 1,036,148 information calls. Nearly the entire US population had access to a poison center (99.9%), although only 78.5% of the US population was served by a certified center. Certified poison centers handled 83.6% of human poison exposure cases reported to US poison centers. Calls to certified centers were twice as likely to be handled by staff who were certified as specialists in poison information. On average, poison center utilization was 9.2 human exposure consultations/1,000 population. Total national poison center expenses approached $81 million. The average cost/human exposure case was $33.30 in certified centers, a substantial savings when compared with the alternative of emergency department management. State governments provided the single largest source of funding. Poison center funding remains unstable, with 41% of centers reporting a possible or definite budget reduction anticipated in the next budget year. In the past 5 y, 47.9% of centers faced threat of closure. Center certification and increased public education activity, especially the distribution of poison prevention materials and number of media contacts, were associated with greater utilization of the poison center in the region served.

Dose-response of electromagnetic field-enhanced ornithine decarboxylase activity.

Alteration of ODC activity in animals or cultured cells exposed to extremely low frequency electromagnetic fields, or to modulated microwave fields, has been documented by several laboratories. However, an evaluation of the dose-response relationship in these experiments has not been done. We examined ODC activity in L929 fibroblasts exposed for 4 h to 60 Hz magnetic fields of different amplitudes. Our results show a clear threshold response which could be fitted to a sigmoidal function, with the 50% point occurring at approximately 5 microT. This sigmoidal response is characteristic of biological responses which are governed by ligand-receptor binding, and has been previously observed in the incidence of magnetic-field induced morphological abnormalities in chick embryos. The implications of this study are discussed in terms of environmental exposures to EM fields.

Is genetics the unrecognized confounding factor in bioelectromagnetics? Flock-dependence of field-induced anoxia protection in chick embryos.

Work in bioelectromagnetics has long been plagued by problems with replication. This includes experiments done on electromagnetic (EM) field-induced effects in chick embryos. Our laboratory investigated responses of embryos from two flocks of White Leghorn hens. Both flocks were studied simultaneously, and it was found that they responded differently to EM field exposures. Embryos were exposed to 60 Hz, 8 microT EM fields prior to placement in an anoxic chamber. Following re-oxygenation, survival in controls was 34.6%, exposed flock 1 survival was 62% (P < 0.0001) and exposed flock 2 survival was 43% (P < 0.0136). P values are from comparison of data between EM field exposed embryos (flocks 1 and 2) versus controls. In order to induce maximum protection in flock 2, (approximately 62% survival), embryos required a longer exposure time at higher magnetic field strengths. These results reinforce the concepts that genetics are important in determining whether or not chick embryos will respond to EM field stimulation. A broader look at the role of genetic factors emphasizes that these variations in response to external stimuli (e.g., drugs, radiation, and EM fields) are found in all areas of biological research (cell culture, chick, rat, and human studies). The present study suggests that genetics may be a prime cause of the difficulties encountered in replication studies in the field of bioelectromagnetics. We conclude that replication studies should not be undertaken unless care is taken to insure that exactly the same strains of cells or animals are used. Researchers should also first confirm that the responses of their model to non-EM field stimuli are similar to that obtained in the original study.

Myocardial protection conferred by electromagnetic fields.

BACKGROUND: It has been reported that electromagnetic (EM) fields induce stress proteins in vitro. These proteins have been shown to be important in recovery from ischemia/reperfusion. It was, therefore, hypothesized that EM fields could activate stress responses in vivo and protect myocardial tissue during anoxia. METHODS AND RESULTS: Chick embryos were exposed to 4-, 6-, 8-, and 10- microT and 60-Hz EM fields for 20 minutes followed by a 1-hour rest period before placement in an anoxic chamber. Embryos were reoxygenated when survival of controls dropped to <40%, and final observations were made 30 minutes later. Data from 80 experiments (>500 EM field-exposed embryos) indicated that EM field protection was extremely significant (P<0.0001). Survival rates were 39.6% in controls and 68.7% in field-exposed embryos. In a second set of experiments, embryos were exposed for 20 minutes to several pretreatments: (1) hyperthermia (43 degreesC), (2) 60-Hz, 8- microT EM fields, or (3) 60-Hz, 8- microT EM fields plus a random EM noise field (8 microT). Embryo survival was 37.7% (control), 57.6% (heated), 69% (60-Hz EM field only), and 41.5% (60-Hz EM field plus EM noise). To confirm that heating resulting from field exposures did not occur, thermocouples were placed into several eggs at the site of the embryo during exposure; no increase in temperature was noted. CONCLUSIONS: We conclude that athermal EM field exposures induce stress responses that protect chick embryo myocardium from anoxia damage. These results suggest that EM field exposures may be a useful, noninvasive means of minimizing myocardial damage during surgery, transplantation, or heart attack in humans.

Short-term magnetic field exposures (60 Hz) induce protection against ultraviolet radiation damage.

PURPOSE: To investigate the ability of electromagnetic (EM) field pre-exposures to induce protection in chick embryos against subsequent ultraviolet (UV) light exposure. MATERIALS AND METHOD: Chick embryos in the 4th day of gestation were exposed for 20 minutes (short term) or 96 hours (long term) to 60 Hz, 8 microT magnetic or sham fields (controls) followed by 30 minutes rest. They were then exposed to UV radiation of either low (30J/m2) or high (45J/m2) intensity (long term was exposed only to 30J/m2) for 75 minutes. Mortality measurements were made every 30 minutes following UV exposure. RESULTS: At both UV intensities, short-term, EM field-exposed embryos showed significantly higher post-UV survival (p<0.05) at each time point as compared to controls. Long-term EM field exposures, however, offered no protection against low intensity UV light, in fact, 96 hour-EM field-exposed embryos were significantly less protected than non-EM field-exposed controls (p<0.05). CONCLUSIONS: Results of the present study demonstrate that EM field exposures of appropriate duration induce protection against damage from UV light exposure. Because EM field exposures have been reported to activate stress protein response pathways and protect against anoxia/re-oxygenation damage, stress proteins are thought to play a role in the observed UV protection.

A simple experiment to study electromagnetic field effects: protection induced by short-term exposures to 60 Hz magnetic fields.

Stress proteins are important in protection during cardiac ischemia/reperfusion (cessation and return of blood flow) and are reportedly induced by electromagnetic (EM) fields. This suggests a possible ischemia protection role for EM exposures. To test this, chick embryos (96 h) were exposed to 60 Hz magnetic fields prior to being placed into anoxia. Survival was 39.6% (control), and 68.7% (field-exposed). As a positive control, embryos were heated prior to anoxia (57.6% survival). We conclude that: 1) 60 Hz magnetic field exposures reduce anoxia-induced mortality in chick embryos, comparable to reductions observed following heat stress, and 2) this is a simple and rapid experiment to demonstrate the existence of weak EM field effects.

The TESS database. Use in product safety assessment.

The Toxic Exposure Surveillance System or TESS is a comprehensive poisoning surveillance database maintained by the American Association of Poison Control Centers. It now includes data on more than 20.3 million human poison exposures reported to US poison centres. TESS data are submitted by 67 of the 75 US poison control centres, covering 87% of the US population. Reports to US poison centres included in TESS originate both from the general public and from health professionals (12.9%) and include both patients managed at home or at the site of the exposure (73.6%) and those managed in hospitals, emergency departments, or other healthcare facilities (22.8%). TESS data are used by the pharmaceutical industry to monitor or defend product safety, by regulatory agencies proposing new regulations or considering new approvals or over-the-counter switches, and by clinical researchers attempting to characterise toxicity profiles or determine treatment protocols. TESS is a key component of an effective post-marketing surveillance programme, allowing early identification of previously unsuspected hazards, and early changes in formulations, labelling, or packaging when needed, thereby minimising injuries, deaths and product liability. Deaths, severe outcomes and comparisons of poisoning outcomes and hospitalisation rates between products or product categories are used to identify safety outliers. TESS data for each case of poisoning include identification of the substances implicated (including brand and formulation where known), patient age, outcome, specific clinical effects, exposure route, reason for the exposure (unintentional, suicidal, therapeutic error, etc.), antidotes used and the level of healthcare intervention utilised. Pharmaceuticals are implicated in 42% of TESS poisoning cases. About 53% of all cases of poisoning occur in children under 6 years of age. Of the more than 2.1 million cases reported to TESS in 1996, 123,095 (5.7%) were therapeutic errors and 32,866 (1.5%) were adverse reactions to pharmaceuticals. TESS is an essential but under-utilised resource for product-specific toxicity and safety data. Use of TESS data to identify hazards, followed by remedial action to reformulate, repackage, re-label, or recall, will protect patients and consumers from needless hazards, and prevent unnecessary product-related morbidity and mortality.

The superposition of a temporally incoherent magnetic field inhibits 60 Hz-induced changes in the ODC activity of developing chick embryos.

Previously, we have shown that the application of a weak (4 microT) 60 Hz magnetic field (MF) can alter the magnitudes of the ornithine decarboxylase (ODC) activity peaks which occur during gastrulation and neurulation of chick embryos. We report here the ODC activity of chick embryos which were exposed to the superposition of a weak noise MF over a 60 Hz MF of equal (rms strength). In contrast to the results we obtain with a 60 Hz field alone, the activity of ODC in embryos exposed to the superposition of the incoherent and 60 Hz fields was indistinguishable from the control activity during both gastrulation and neurulation. This result adds to the body of experimental evidence which demonstrates that the superposition of an incoherent field inhibits the response of biological systems to a coherent MF. The observation that a noise field inhibits ODC activity changes is consistent with our speculation that MF-induced ODC activity changes during early development may be related to MF-induced neural tube defects at slightly later stages (which are also inhibited by the superposition of a noise field).