Report on a study of fires with smoke gas development : determination of blood cyanide levels, clinical signs and laboratory values in victims.

BACKGROUND: This is a report on an international non-interventional study of patients exposed to fires with smoke development in closed rooms. The objective of the study was to document clinical symptoms, relevant laboratory values and blood cyanide concentrations from fire victims in order to confirm or rule out presumptive correlations between the individual parameters. MATERIALS AND METHODS: The study was conducted in five European countries with patients being included if they presented with the characteristic clinical signs, such as soot deposits and altered neurological status. Venous blood samples were taken from victims prior to administration of an antidote in all cases and determination of cyanide concentration was performed in a central laboratory using high performance liquid chromatography. RESULTS: Data from 102 patients (62 % male, average age 49 years) were included in the evaluation with no blood samples being available for analysis from 2 patients. In 25 patients the blood cyanide concentration was below the limit of detection of 1.2 µmol/l. Cyanide levels between 1.2 and 10 µmol/l were measured in 54 patients, 7 patients had values between 10 and 20 µmol/l, 4 patients between 20 and 40 µmol/l while levels above 40 µmol/l were determined in 10 patients. The results of the study could not demonstrate that the cyanide level was influenced either by the interval between smoke exposure and blood sampling or the duration presence at the fire scene. The following clinical signs or laboratory values were recorded as relevant for increased and possibly toxic cyanide levels: respiratory arrest, dyspnea, resuscitation requirement, tracheal intubation, respiratory support measures, low Glasgow coma scale (GCS) score and respiratory frequency. A correlation between cyanide concentration and the total amount of soot deposits on the face and neck, in the oral cavity and in expectoration was confirmed. A correlation between cyanide and carboxyhemoglobin (COHb) levels in the blood of fire victims was also confirmed. CONCLUSIONS: As long as it is not possible to immediately determine the blood cyanide concentration in patients exposed to fire with smoke development, a decreased GCS score, soot deposits particularly in expectoration, dyspnea and convulsions are to be regarded as risk markers for intoxication. In their presence immediate administration of hydroxocobalamin as an antidote is recommended.

Acute renal failure by ingestion of Cortinarius species confounded with psychoactive mushrooms: a case series and literature survey.

Mushrooms of the Cortinarius species are nephrotoxic and can cause severe acute renal failure. The toxic effect is due to orellanine. It is suspected that the cytotoxic damage is caused by the production of oxygen-free radicals. Renal pathology shows tubular necrosis with interstitial nephritis. In addition to accidental intoxications as a consequence of mushroom meals, recent cases are often due to voluntary abuse of natural drugs like magic mushrooms. We report 4 current cases of acute renal failure from intoxication by Cortinarius species by confusing it with psychoactive fungi. Typical for the Cortinarius poisoning is the long latency period from ingestion until the onset of clinical symptoms (3 - 20 days). Diagnosis is based on microscopical identification of the mushroom spores, and detection of the orellanine toxin in leftover mushrooms. In renal biopsy tissue, orellanine is detectable by thin-layer chromaography technique up to 6 months after poisoning. There is no causative therapy, and treatment is symptomatic with adequate hemodialysis. In cases of otherwise unexplained acute renal failure, intoxication with nephrotoxic mushrooms should be considered.

Treatment of health complaints attributed to amalgam.

The aim of the present study was to compare the reduction of subjective complaints by 3 treatment strategies in 90 "amalgam patients" whose complaints could not be explained by a medical or psychological disorder. The individuals were randomly assigned either to removal of dental amalgam only (removal group), or removal in combination with a "biological detoxification" therapy with high doses of vitamins and trace elements (removal-plus group), or participation in a health promotion program without removal of dental amalgam (no-removal group). Between baseline and month 12, the sum score of main complaints decreased by 3.5 (SD=2.2) points on average in the removal group as well as in the removal-plus group, and by 2.5 (SD=2.4) points in the no-removal group (p=0.152). Both removal groups showed a significant decrease in steady-state levels of inorganic mercury compared with the no-removal group. Thus, all 3 interventions were associated with clinically relevant improvements.

Cerebellar effects after consumption of edible morels (Morchella conica, Morchella esculenta).

Morchella esculenta and Morchella conica are well known edible morels, which seldom induce clinical symptoms. We report six persons who developed cerebellar effects 6-12 hours after consumption of these mushrooms. The symptoms were self-limited and disappeared after one day.

Withdrawal from high-dose tranylcypromine.

A 34-year-old man with a history of multiple substance abuse (now abstinent for six years) became addicted to tranylcypromine, consuming up to 240 mg/day. After discontinuing the drug, he developed thrombocytopenia (52,000/ul) and delirium; there were no other anticholinergic signs. The delirium was unresponsive to haloperidol and diazepam. Intravenous administration of physostigmine (2 mg) on hospital day 6 resulted in prompt, but temporary, clearing of the delirium. Following a recurrence of the delirium after 30 minutes, he was started on an intravenous infusion of physostigmine (2 mg/hr) with good results. Physostigmine administration did not produce any cholinergic signs. By hospital day 8, he did not require any more physostigmine. Thrombocytopenia resolved on hospital day 9 without therapeutic intervention. On hospital day 10, the patient was asymptomatic and left the hospital on his own recognizance.

Lessons to be learnt from organophosphorus pesticide poisoning for the treatment of nerve agent poisoning.

The increasing threat of nerve agent use for terrorist purposes against civilian and military population calls for effective therapeutic preparedness. At present, administration of atropine and an oxime are recommended, although effectiveness of this treatment is not proved in clinical trials. Here, monitoring of intoxications with organophosphorus (OP) pesticides may be of help, as their actions are closely related to those of nerve agents and intoxication and therapy follow the same principles. To this end, the clinical course of poisoning and the effectiveness of antidotal therapy were investigated in patients requiring artificial ventilation being treated with atropine and obidoxime. However, poisoning with OP pesticides shows extremely heterogeneous pictures of cholinergic crisis frequently associated with clinical complications. To achieve valuable information for the therapy of nerve agent poisoning, cases resembling situations in nerve agent poisoning had to be extracted: (a) intoxication with OPs forming reactivatable OP-AChE-complexes with short persistence of the OP in the body resembling inhalational sarin intoxication; (b) intoxication with OPs resulting rapidly in an aged OP-AChE-complex resembling inhalational soman intoxication; (c) intoxications with OPs forming a reactivatable AChE-OP complex with prolonged persistence of the OP in the body resembling percutaneous VX intoxication. From these cases it was concluded that sufficient reactivation of nerve agent inhibited non-aged AChE should be possible, if the poison load was not too high and the effective oximes were administered early and with an appropriate duration. When RBC-AChE activity was higher than some 30%, neuromuscular transmission was relatively normal. Relatively low atropine doses (several milligrams) should be sufficient to cope with muscarinic symptoms during oxime therapy.

Dysfunctional cognitions in idiopathic environmental intolerances (IEI)--an integrative psychiatric perspective.

Idiopathic environmental intolerances (IEI) - formerly multiple chemical sensitivities (MCS) - are characterized by diffuse symptoms reported after exposure to low doses of everyday chemicals. Previous theories about the origin of IEI have emphasized either biological or psychological factors, neglecting a probable interplay. Many have suggested classifying IEI as a somatoform or an anxiety disorder, irrespective of some incongruities. By focusing on dysfunctional cognitions we discuss obvious parallels of IEI with somatoform disorders, and also indicate overlaps with anxiety and delusional disorders. To propose a hypothetical psycho-neurobiological basis of IEI, recent evidence about cortically represented symptoms in the absence of peripheral stimuli is briefly summarized. We conclude that IEI can serve as an illustrative example for the impact of cognitive, representational processes in symptom generation.

[Poisoning by the autumn crocus plant]. / Verwechslungsgefahr im Frühjahr: Bärlauch und Herbstzeitlose. Warnen Sie lhre Patienten vor dem tödlichen Salat!

Confirmed cases of poisoning resulting from the ingestion of Colchicum autumnale in mistake for Allium ursinum were analysed retrospectively. The study included 32 patients between 27 and 90 years. The severity of the intoxication was graded on the basis of the poisoning severity score (PSS). All the patients developed diarrhea and/or vomiting after a latency period of between 2 and 24 h. All those patients with a latency of > 9 h suffered only mild poisoning. If the leaves were boiled before being eaten, 64% of the patients suffered moderate, severe or fatal poisoning; when the leaves were eaten raw, only 33%. It is presumed that heating may promote the liberation of colchicines from the plant. Eight of the nine patients with severe or fatal poisoning were older than 65 years. A possible cause of the more serious course in the elderly may be a decrease in renal clearance. In addition, a diminished sense of smell may allow the absence of the typical garlic smell and taste of Allium ursinum to go unrecognised.

Modern strategies in therapy of organophosphate poisoning.

Considering the various microscopic reactions as well as toxicokinetic and pharmacokinetic principles in therapy of organophosphate poisoning, the administration of obidoxime by an initial bolus dose followed by continuous infusion appears rational. Using this protocol, six patients each with parathion or oxydemeton methyl poisoning were treated. In parathion poisoning, reactivation was possible up to 7 days. At paraoxon concentrations > 0.1 microM obidoxime only partially reactivated acetylcholinesterase (AChE) of erythrocytes in vivo although reactivation could be assessed in vitro, which roughly fitted theoretical calculations. AChE-inhibitory material was detected up to 5 days. Cholinergic signs soon subsided when AChE was above 20% of normal, and atropine plasma levels could be kept below 7 ng/ml. In one patient brain damage persisted. Oxydemeton methyl poisoning responded to obidoxime therapy only when the oxime was instituted shortly after poisoning. Out of six patients one died. No intermediate syndrome and no signs of permanent hepatic dysfunction were found in the 12 patients.

Cholinesterase status, pharmacokinetics and laboratory findings during obidoxime therapy in organophosphate poisoned patients.

1 The effectiveness of oxime therapy in organophosphate poisoning is still a matter of debate. It appears, however, that the often cited ineffectiveness of oximes may be due to inappropriate dosing. By virtue of in vitro findings and theoretical considerations we concluded in the preceding paper that oximes should preferably be administered by continuous infusion following an initial bolus dose for as long as reactivation of inhibited acetylcholinesterase (AChE) can be expected. This conclusion has called for a clinical trial to evaluate such oxime therapy on the basis of objective parameters. 2 Before transfer to the intensive care unit (ICU), 5 patients received primary care by an emergency physician. In the ICU, atropine sulphate was administered i.v. upon demand according to the endpoints: no bronchorrhoea, dry mucous membranes, no axillary sweating, heart rate of about 100/min. Obidoxime (Toxogonin) was given as an i.v. bolus (250 mg) followed by continuous infusion of 750 mg/24 h. 3 Intoxication and therapy were monitored by determining erythrocyte AChE (eryAChE) activity, reactivatability of the patient's eryAChE ex vivo, plasma cholinesterase activity, the presence of AChE inhibiting compounds, as well as the concentrations of obidoxime and atropine in plasma. 4 Obidoxime was effective in life-threatening parathion poisoning, in particular when the dose absorbed was comparably low. In mega-dose poisoning, net reactivation was not achieved until several days after ingestion, when the concentration of active poison in plasma had declined. Reactivatability in vivo lasted for a longer period than expected from in vitro experiments. 5 Obidoxime was quite ineffective in oxydemetonmethyl poisoning, when the time elapsed between ingestion and oxime therapy was longer than 1 day. When obidoxime was administered shortly after ingestion (1 h) reactivation was nearly complete. 6 Obidoxime levels of 10-20 microM were achieved by our regimen, and atropine could rapidly be reduced to approx. 20 microM, as attained by continuous infusion of 1 mg atropine sulphate/h. Maintenance of the desired plasma levels was not critical even when renal function deteriorated. 7 Signs of transiently impaired liver function were observed in patients who showed transient multiorgan failure. In the present stage of knowledge, we feel it advisable to keep the plasma concentration of obidoxime at 10-20 microM, although the full reactivating potential of obidoxime will not then be exploited. Still, the reactivation rate, with an apparent half-time of some 3 min, is twice that estimated for a tenfold higher pralidoxime concentration.

Internal biokinetic behaviour of molybdenum in humans studied with stable isotopes as tracers.

Although molybdenum is considered to be an essential trace metal for humans, the knowledge about its metabolism is rather limited. The present study was aimed at the assessment of biokinetics following intravenous injection of trace amounts of 95Mo or 96Mo into five healthy volunteers. In a total of 11 investigations, the plasma clearance up to eight hours and the urinary excretion for at least three days after the injection were evaluated. The tracer concentrations were determined by proton nuclear activation analysis in blood plasma and by thermal ionization mass spectrometry in urine samples respectively. In all subjects, the plasma clearance is much faster than expected from the literature. The data obtained for the plasma clearance of the tracer can reasonably be fitted by a two exponential equation. The half times of the fast component range between 4 and 70 minutes and for the slow component between 3 and 30 hours. The urinary excretion of the injected tracer seems also to be faster than expected and the fractions lost are higher for larger doses administered. For the smallest dose given, 34% of the injected tracer were excreted within one day whereas for the four times larger dose about 60% were lost. These findings on urinary excretion are in agreement with recently published results.

Assessment of intestinal absorption of trace metals in humans by means of stable isotopes.

This study is aimed to demonstrate the feasibility of stable isotopes for the assessment of reliable data on fractional intestinal absorption of trace metals in healthy humans. Among the various methods available, the double isotope technique, i.e. one isotope given orally together with the test substance to be investigated and another isotope injected intravenously to correct for retention and endogenous excretion of the particular trace metal, provides quantitative figures of intestinal absorption at reasonable expenses with regard to costs for materials and number of samples to be evaluated. The trace metals exemplarily included in this study, i.e. iron, cobalt and molybdenum show diverging relations between absorbed fractions and amounts administered which are indicative for different regulatory mechanisms of their body content. Food ligands influence the fractional absorption significantly so that the uptake from a composite meal cannot be derived from results on uptake from particular foodstuffs. Therefore, validated data on the behaviour of intestinal absorption will significantly contribute to a better understanding of human trace metal metabolism.

[Adder bites in humans]. / Kreuzotterbisse beim Menschen.

In Germany the common viper (Vipera berus) and very seldom Vipera aspis are the only in freedom normally existing snakes. In general, bites by the common viper cause slight local symptoms, sometimes strong swellings of the extremities, but only rarely severe perilous general symptoms such as shock and angioneurotic edema. Mortal progresses despite of medical treatment are the exceptions. The most important therapeutic measure is the immobilization of the bitten extremity and the transport in a recumbent position to the next surgeon or clinic. The perilous shock and the angioneurotic edema often react on the administration of antihistaminica and corticosteroids, whereas the increase of the swelling of the extremity cannot be influenced by this treatment. The corresponding antisera have an advantageous and fast effect on all general symptoms and seem to favourably influence the swelling of the extremities. Because of the allergic reactions against the sera from horses, which do not occur seldom, in severe cases only Beritab--which is not yet admitted in Germany--with purified Fab-fragment antibodies from sheep should be used.

[Psychiatric aspects of multiple chemical sensitivity (MCS)]. / Psychiatrische Aspekte der Multiple Chemical Sensitivity (MCS).

Patients with multiple chemical sensitivity (MCS) react to low levels of common environmental chemicals with various health complaints. The etiology and pathogenesis of MCS is not clear. Objective criteria for diagnosis are lacking. Usually there are no pathological somatic findings, while psychiatric morbidity is considerably high. Somatoform, mood and anxiety disorders are diagnosed most frequently. A subgroup of MCS patients may suffer from a special form of somatoform disorders related to the environment. Critics of a psychogenic model of MCS argue that psychiatric diagnoses are descriptive, and causality can not be derived from them. However, clinicians are expected to evaluate the most probable cause of the complaints and give therapeutic recommendations. There are promising therapeutic concepts for somatoform and other psychiatric disorders, but not for MCS. Double-blind challenge tests, but also therapy evaluation studies could contribute to a better understanding of the pathogenesis of MCS in the future.

[Alcohol withdrawal syndrome and delirium tremens. Diagnosis and therapy]. / Alkoholentzugssyndrom und Delirium tremens. Diagnose und Therapie.

The alcohol withdrawal syndrome can be classified into three degrees of severity on the basis of the symptomatology, autonomic withdrawal, predelirium and delirium tremens. In American literature the severity of withdrawal is recorded using the CIWA-A scale (Clinical Institute Withdrawal Assessment--Alcohol). The pathophysiological causes lie in an imbalance between the inhibitory and excitatory neurotransmitters after giving up alcohol. This results in predomination by the excitatory system. Therapeutic intervention is possible here. Clomethiazole has effective sedative actions, stabilises the autonomic nervous system, and is an anticonvulsant. It is the drug of choice for autonomic withdrawal and predelirium. The benzodlazepines have a similar effect, but cannot be controlled so accurately. Carbamazepine can prevent withdrawal convulsions and progression of delirium. Clonidine acts on autonomic withdrawal and, together with neuroleptics and benzodiazepines, is easy to use parenterally for delirium tremens, while parenteral clomethiazole harbours dangers.

[Multiple chemical sensitivity. Is the patient suffering as a result of environmental pollutants or psychological problems?]. / V. a. Multiple Chemical Sensitivity. Leidet Ihr Patient an Umweltgiften oder an der Seele?

Multiple chemical sensitivity (MCS) poses a medical challenge. Proposed etiologies are as numerous as they are contradictory, direct and indirect costs are high, and patient suffering considerable. In the absence of objective diagnostic criteria, estimation of its prevalence is difficult. Nevertheless, establishment of the diagnosis is frequently strikingly uncritical. We support an holistic approach that gives consideration both to psychological and physical aspects, as well as taking account of the high level of comorbidity, and we warn against "over-diagnosis". Therapeutical approaches should consider carefully the risk of avoidance and social withdrawal.

Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds.

OBJECTIVES: Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Maximal oxime effects are expected when effective doses are administered as soon as possible and as long as reactivation can be anticipated. An obidoxime plasma level in the range of 10-20 microM was estimated as appropriate. The achievement of this target was assessed in 34 severely OP-poisoned patients. METHODS: After admission to the intensive care unit (ICU) the obidoxime regimen (250 mg i.v. as bolus, followed by 750 mg/24h) was started and maintained as long as reactivation was possible. Plasma concentrations of obidoxime were determined by HPLC. RESULTS: A total amount of 2269+/-1726 mg obidoxime was infused over 65 h+/-55 h resulting in a steady state plasma concentration of 14.5+/-7.3 microM. Obidoxime was eliminated with t(1/2(1)) 2.2 and t(1/2(2)) 14 h. The volumes of distribution amounted to 0.32+/-0.1L/kg (V((1))) and 0.28+/-0.12 (V((2)))L/kg. Postmortem examination of tissue in one patient showed obidoxime accumulation in cartilage, kidney and liver and pointed to brain concentrations similar to plasma concentration. CONCLUSIONS: Using the suggested obidoxime regimen, the targeted plasma concentration could be achieved. Obidoxime was eliminated biphasically and was well tolerated. This result allows the recommendation of using this definite regimen for adults also in case of mass casualties.