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T Zilker

Publications and source records attributed to T Zilker.

At least 19 recordsLinked to original sources
PubMed2001

Internal standard high-performance liquid chromatography method for the determination of obidoxime in urine of organophosphate-poisoned patients.

Obidoxime is an antidote approved for reactivation of inhibited acetylcholinesterase in organophosphate poisoning. HPLC methods were described for its determination in blood or aqueous solutions but not for the determination in urine. Since data for renal obidoxime excretion ranged from 2.2 to 84% of administered dose in healthy volunteers depending on the route of administration and little is known about pharmacokinetics of obidoxime in severely intoxicated patients we developed an internal standard (HI 6) reversed-phase HPLC method for determining obidoxime in urine. The mobile phase consisted of methanol, the counter ion 1-heptane sulfonic acid and tetrabutylammonium phosphate, the stationary phase involved a 5 microm reversed-phase column (125x4 mm). Obidoxime was detected spectrophotometrically at 288 nm. The limit of quantification (LOQ) was 1 microM, the limit of detection (LOD) 0.5 microM. Linear calibration curves were obtained in a concentration range from 1 to 1000 microM. Intra- and inter-day precision C.V.s were below 4%. Accuracy was 95.9% in the LOQ range. Using this method, we were able to quantify obidoxime in urine of an organophosphate poisoned patient. Based on this data we calculated that 58% of the administered dose was excreted in the urine.

Cholinesterase Reactivators↗
PubMed2000

[Psychiatric and somatic morbidity of patients with suspected multiple chemical sensitivity syndrome (MCS)].

Multiple chemical sensitivity (MCS) or idiopathic environmental intolerance (IEI) is understood as an acquired disorder with multiple recurrent symptoms that cannot be traced to any well-known medical or psychiatric condition and is associated with diverse environmental influences that are well tolerated by the majority of people. In a prospective study, we investigated 120 consecutive patients admitted a university-based outpatient department for environmental medicine during 1 year. Apart from routine medical examination and special toxicological diagnostic procedures, a structured clinical interview for DSM-IV psychiatric disorders was performed with every patient. At least one psychiatric diagnosis was found in 100 patients. The diagnostic criteria for somatoform disorders were filled by 53 patients. We found lifetime or current affective disorders in 39 patients, anxiety disorders in 29, and substance dependency or abuse in 25. In 16 patients, personality disorders were diagnosed. Nine suffered from psychotic disorders. This is the largest prospective study with standardized psychiatric diagnostic methods concerning psychiatric morbidity and MCS. The data show that many patients with environmental health problems obviously suffer from somatoform disorders but also from other, well-known psychiatric conditions.

Adolescent↗
PubMed2000

Intoxication with huperzine A, a potent anticholinesterase found in the fir club moss.

BACKGROUND: Herbs from Lycopodium are generally reputed to be nontoxic and are occasionally used for preparing a salubrious tea. In Europe, the common Lycopodium clavatum can be easily confused with Lycopodium selago, the fir club moss. CASE REPORT: We report 2 patients who drank a tea, erroneously prepared from dried herbs of Lycopodium selago, which resulted in sweating, vomiting, diarrhea, dizziness, cramps, and slurred speech. These symptoms were suggestive of a cholinergic mechanism. To elucidate the active principle, aqueous extracts of Lycopodium selago were checked for their suspected anticholinesterase activity using human erythrocytes as an enzyme source in a modified Ellman assay. The extracts did exhibit significant anticholinesterase activity. The anticholinesterase(s) were most effectively extracted with dichloromethane and isolated by high-performance liquid chromatography. The major compound with anticholinesterase activity co-chromatographed with authentic huperzine A, but had a 2-3-fold higher inhibitory potency than the racemic standard. The amount of huperzine A found in the Lycopodium selago sample used for the tea preparation was calculated to be sufficient for a relevant acetylcholinesterase inhibition. CONCLUSION: The signs and symptoms of Lycopodium selago poisoning are consistent with the anticholinesterase activity of huperzine A and should favorably respond to atropine therapy. This report demonstrates once more that laymen should not be encouraged to gather their remedies from "Mother Nature" without advanced botanical knowledge.

Alkaloids↗
PubMed1999

[Alcohol withdrawal syndrome and delirium tremens. Diagnosis and therapy].

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.

Alcohol Withdrawal Delirium↗
PubMed1999

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.

Acetylcholinesterase↗
PubMed1999

[Idiopathic environmental intolerance (IPI)--formerly multiple chemical sensitivity (MCS)--from the psychiatric perspective].

The term "idiopathic environmental intolerances" (IEI)/"multiple chemical sensitivities" (MCS) is used to describe a complex of heterogeneous somatic symptoms without a diagnosable organic disease. Symptoms are believed to be triggered by exposure to low levels of environmental chemicals that are usually well tolerated by the general population. There is no widely accepted definition for the phenomenon. A number of contradictory etiologic hypotheses and therapeutic concepts are discussed. One of the crucial questions is whether IEI/MCS should be understood as an own entity of disease. It has been demonstrated that a majority of patients with IEI/MCS meet diagnostic criteria for psychiatric diseases. Most frequently, somatoform, affective and anxiety disorders can be diagnosed. Therefore, psychiatric and psychotherapeutic therapy seems appropriate. The present paper provides a review of the different case definitions, etiologic and therapeutic concepts and of studies examining the frequency of psychiatric morbidity in patients with IEI/MCS. Additionally, a diagnostic algorithm and a concept of behavioral therapy for IEI/MCS patients with somatoform disorders are described.

Humans↗
PubMed1999

Opiate detoxification under anesthesia: no apparent benefit but suppression of thyroid hormones and risk of pulmonary and renal failure.

INTRODUCTION: The new technique for opiate detoxification using anesthesia and high, repetitive doses of opiate-antagonists claims to detoxify addicts without withdrawal symptoms within 24-48 hours. We studied the method with 12 opiate addicts (5 L-polamidone, 4 dihydrocodeine, 3 heroin), using general anesthesia and the antagonists naloxone 0.5 mg/kg and naltrexone > 150 mg. Objective and subjective withdrawal symptoms were measured until urine was free of drugs and patients had no withdrawal symptoms. Thyroid hormones were measured before, during, and after the anesthesia period. RESULTS: All patients had moderate to severe opiate withdrawal symptoms. No detoxification was finished within 48 hours. The dihydrocodeine subjects were compared with conventionally detoxified controls; no difference was seen. The method suppressed thyroid hormones TT3, TT4, and TSH. The study was terminated because of side effects: 1 pulmonary failure and 2 renal failures. All patients survived without sequelae. CONCLUSION: There is no obvious benefit from this method, whereas the risks are high.

Acute Kidney Injury↗
PubMed1999

Opiate detection in saliva and urine--a prospective comparison by gas chromatography-mass spectrometry.

UNLABELLED: There is an increasing interest in saliva as an alternative analytic body fluid. OBJECTIVE: This study sought to determine the correlation of opiates analyzed in saliva and corresponding urine. METHODS: A total of 130 adequate and 24 inadequate samples were collected from patients participating in drug withdrawal therapy. To obtain saliva from the oral cavity, a newly developed collection device (Clin Rep), consisting of a treated cotton roll and a centrifugation vial with a filter inset, was tested. For the preparation of a purified solution of urine, liquid extraction was used. Solid phase extraction was utilized to prepare the saliva samples. For the detection by gas chromatography-mass spectrometry, an appropriate derivatization was necessary using N-methyl-N-(trimethylsilyl)trifluoroacetamide. The retention times were compared with defined standard solutions. The obtained mass spectra showed a characteristic fragmenting pattern and offered a reliable identification. RESULTS: The concordance of the analytic results of the saliva samples with urine was 93% for a decision limit of 100 ng/mL and 98% for a decision limit of 300 ng/mL (DHHS opiate cutoff) in urine. CONCLUSIONS: Saliva, of adequate amount in 85% of samples, may be appropriate for analysis of drugs of abuse.

Gas Chromatography-Mass Spectrometry↗
PubMed1998

Cocaine increases the endothelial release of immunoreactive endothelin and its concentrations in human plasma and urine: reversal by coincubation with sigma-receptor antagonists.

BACKGROUND: Cocaine-associated vascular events are not completely explained by adrenergic stimulation. The purposes of this study were to investigate whether vasoconstrictive endothelin-1 is released by cocaine and to elucidate the mechanisms involved. METHODS AND RESULTS: Endothelin-1 was measured by radioimmunoassay and high-performance liquid chromatography (1) in the supernatant of porcine aortic endothelial cells after treatment with cocaine (10(-7) to 10(-4) mol/L) and a sigma-receptor antagonist, haloperidol (10(-6) mol/L) or ditolylguanidine (10(-5) mol/L) and (2) in plasma and urine of 12 cocaine-intoxicated patients and 13 healthy control subjects. Radioligand binding assays were performed on endothelial membrane preparations. In cell culture, cocaine significantly increased endothelin accumulation above baseline at 3 to 24 hours; endothelin release rates per hour increased dose-dependently, reaching a plateau of 175+/-23% of control at hour 4 to 5. Coincubation of cocaine with haloperidol or ditolylguanidine abolished or reduced cocaine-induced endothelin release. Endothelial membrane preparations specifically and displaceably bound the highly selective sigma-ligand [3H]ditolylguanidine (25x10(-9) mol/L), with 1400 binding sites estimated per cell. Endothelin-1 levels in plasma (22.7+/-5.6 versus 7.3+/-0.8 pmol/L) and urine (41.5+/-10.1 versus 12.7+/-3.8 pmol/L) of cocaine-intoxicated patients were significantly increased compared with control values. CONCLUSIONS: The data suggest that cocaine increases the endothelin-1 release in vitro and in vivo. The cocaine-induced vasoconstriction/vasospasm may therefore be facilitated by the release of endothelin-1. Cocaine appears to be an exogenous stimulator at endothelial sigma-receptors. The endogenous ligands of this antiopioid system may prove to play a role in vasospastic angina, acute myocardial infarction, and sudden cardiac death.

Acute Disease↗
PubMed1998

[Adder bites in humans].

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.

Adolescent↗
PubMed1997

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.

Acetylcholinesterase↗
PubMed1996

Clinical course of severe poisoning with thiomersal.

CASE REPORT: A 44-year-old man ingested 83 mg/kg Thiomersal. He developed gastritis, renal tubular failure, dermatitis, gingivitis, delirium, coma, polyneuropathy and respiratory failure. Treatment was symptomatic plus gastric lavage and the oral chelating agents dimercaptopropane sulfonate and dimercaptosuccinic acid. The patient recovered completely. Maximum mercury concentrations were blood 14 mg/L, serum 1.7 mg/L, urine 10.7 mg/L, and cerebrospinal fluid 0.025 mg/L. Mercury concentration in blood declined with two velocities: first with half-time 2.2 days, then with half-time 40.5 days. The decline of mercury concentration in blood, urinary mercury excretion, and renal mercury clearance were not substantially influenced by chelation therapy.

Administration, Oral↗
PubMed1996

[A case of malignant neuroleptic syndrome. Case report].

We report on a woman patient with organophosphate poisoning resulting from a psychotically motivated suicide attempt. After detoxification and during treatment with haloperidol and levomepromazine, she developed acute malignant neuroleptic syndrome (MNS) in which dyspnea requiring assisted ventilation was the main symptom. Discontinuation of the neuroleptics was enough to effect sufficient recovery. With this case report, we would first like to emphasize that MNS can evolve within a very short time into a severe and life-threatening situation requiring intensive medical care, and secondly to illustrate the implications of organophosphate poisoning and the consequent cholinesterase blocking far the differential diagnosis of MNS.

Adult↗