bluuebunny/crossref_metadata_2025_split huggingface dataset:
?-adrenoceptor Blocker Intoxication: Epidemiological Data. Prenalterol as an Alternative in the Treatment of Cardiac Dysfunction
Authors: Kulling P. , Eleborg L. , Persson H. 
Published: December 2008

1 During the three years 1978-1980 the Swedish Poison Information Centre received reports of 184 patients hospitalized due to ?-adrenoceptor blocker overdosage. Of the 35 patients who developed signs of severe cardiac dysfunction (HR < 50 beats/min, systolic blood pressure < 80 mm Hg), 23 had ingested propranolol, 10 metoprolol and 2 alprenolol. 2 The mean value of the defined daily doses (DDD) per 1000 inhabitants per day in Sweden during these years were 11.97 for propranolol, 8.02 for alprenolol and 7.74 for metoprolol. The incidence of severe poisoning due to alprenolol overdosage is lower than expected according to DDD. 3 During 1979 19 persons died from overdosage with ?-adrenoceptor blockers in Sweden: 15 due to propranolol (non-selective, lacks intrinsic sympathomimetic activity), 2 to metoprolol (cardioselective, lacks intrinsic sympathomimetic activity) and 2 to alprenolol (non-selective, intrinsic sympathomimetic activity). These findings indicate that severe and even fatal poisoning may occur regardless of the type of ?-blocking agent. 4 The usefulness of prenalterol, a cardioselective ?-adrenoceptor partial agonist, in reversing unwanted cardiac effects of ?-adrenoceptor blocking agents is illustrated by two cases of massive propranolol intoxication (maximal plasma concentrations of propranolol 7.2 and 7.8 ?mol/l respectively). Prenalterol in high doses (130 and 280 mg/24 h respectively) restored cardiac function.
Myoglobinuric Renal Failure due to Drug-induced Rhabdomyolysis
Authors: Hampel G. , Horstkotte H. , Rumpf K.W. 
Published: December 2008

1 Two cases of drug-induced rhabdomyolysis, one of them presenting with acute myoglobinuric renal failure are described. 2 The pathogenesis of rhabdomyolysis and renal failure in our cases is discussed with reference to work published by other authors. 3 Whereas there seems to be obvious evidence for direct toxic drug-muscle interaction, the mechanism for the development of myoglobinuric renal failure remains unclear.
Experience with a Screening Method for Laxative Abuse
Authors: de Wolff F.A. , Edelbroek P.M. , de Haas E.J.M. , Vermeij P. 
Published: December 2008

1 Abuse of laxatives may lead to a variety of serious disorders which are usually difficult to recognize because of the heterogenicity of the toxic effects. 2 In order to facilitate the diagnosis of chronic laxative poisoning, a laboratory screening method for the detection of colonic stimulants in urine has been designed and has been applied in practice over a three-year-period. 3 During this period, 157 samples from 81 patients were sent to the laboratory. Fifteen patients (18.5%) were definitely shown to use self-prescribed laxatives. 4 Next to the diphenolic compounds: bisacodyl, phenolphthalein and bisoxatin, the anthraquinone derivative rhein, a metabolite of vegetable laxatives, was found in several cases. In the urine of three patients a substance resembling rhein was found, which was shown to be aloe-emodin. 5 It is concluded that chronic self-poisoning with laxatives is a fairly common disorder that can easily be overlooked. Laboratory screening of the urine of suspected patients is an economic and reliable method for its diagnosis.
Determination of Amphetamine and Methylamphetamine by Gas-liquid Chromatography (Head Space)
Authors: Martinez D. , Gimenez M.P. 
Published: December 2008

1 A method for determining amphetamine and methylamphetamine in urine by gas-liquid chromatography is described. 2 Chromatography is performed on a 10% Apiezon L, 10% KOH column with alkali-flame detection (NPD). This method avoids the losses of these volatile substances which are known to occur when solvent extraction is used. An alkalinized urine sample (1 ml) is introduced into a sealed vial which is heated in a water bath at 70°C for 20 min. A 1 ml portion of the gas phase in equilibrium with the liquid phase is chromatographed. 3 Amphetamine and methylamphetamine can be detected and measured in urine samples after single therapeutic doses of the drugs.
The Mechanism of Paracetamol-induced Hepatotoxicity: Implications for Therapy
Authors: Huggett A. , Blair I.A. 
Published: December 2008

1 The reactive metabolite responsible for paracetamol-induced hepatotoxicity, postulated to be N -acetyl- p-benzoquinoneimine reacts with N-acetyl cysteine.2 An adduct is formed by an SN2 mechanism and paracetamol is produced by a redox reaction.3 The adduct produced is capable of further oxidation by N-acetyl- p-benzoquinoneimine.4 Methionine does not react with the reactive metabolite to any great extent.
A Collection of Therapeutic, Toxic and Fatal Blood Drug Concentrations in Man
Authors: Stead A.H. , Moffat A.C. 
Published: December 2008

1 In order to assess the significance of drug concentrations measured in clinical and toxicological investigations, it is essential that good collections of data are readily available. As a guide to interpreting findings, the present work provides a compilation of therapeutic, toxic and fatal blood concentration ranges of 298 drugs of interest to clinical pharmacologists, clinical toxicologists, and forensic toxicologists.2 Wherever possible, ranges are expressed concisely in terms of the maximum blood concentrations which account for 10, 50 and 90% of the data collected. They provide easy access to the most reliable information which relates the blood drug concentration to the biological response it produces. Where appropriate, the different toxic effects of a drug and/or the different degrees of severity of toxic symptoms associated with different drug levels are clearly defined.3 The original sources of all data used are provided to allow the analyst to obtain further analytical, pharmacokinetic and toxicological information should this be necessary.4 Those factors (e.g. age, capacity for drug metabolism, drug interactions, etc) which can modify the relationship between a drug concentration and the response it produces are briefly discussed.
Autoradiographic Studies of the Distribution of Radium-226 in Rat Bone: Their Implications for Human Radiation Dosimetry and Toxicity
Authors: Priest N.D. , Howells G. , Green D. , Hainesl J.W. 
Published: December 2008

A solution containing 226Ra chloride was injected into young female rats via the saphenous vein. Subsequently, the distribution and retention of the 226Ra in the skeleton was studied. The results show that: 1226Ra is initially deposited in the rat femur as a volume deposit and is fairly evenly distributed throughout the bone matrix. 2 Much of the 226Ra initially deposited in the skeleton is lost within a few days of its administration. 3 During the first week 226Ra gradually accumulates at sites of bone deposition including accreting surfaces. 4 Subsequent bone growth results in the burial of contaminated bone surfaces and 5 Following bone resorption some of the 226Ra released from individual bones is recycled systemically so that all skeletal components tend towards a uniform 226Ra concentration per unit of bone mineral. Of the two models conventionally used for radiation dosimetry purposes, the results reported here for rats suggest that though neither is ideal, the volume distribution model is preferable to the surface model at all times after the uptake of radium by the skeleton.
A Toxicology Databank—The Registry of Human Toxicology
Authors: Gomm P.J. 
Published: December 2008

1 The Registry of Human Toxicology is a databank designed to assist in the interpretation of results obtained from the analysis of human body organs for toxic substances. 2 The present Registry contains over 16,000 analyses from 4309 cases giving details of 282 compounds and 360 preparations. 3 Computer facilities are provided for collating, storing and disseminating the information.
Acute Dapsone Poisoning: Clinical Features and Pharmacokinetic Studies
Authors: Woodhouse K.W. , Henderson D.B. , Charlton B. , Peaston R.T. , Rawlins M.D. 
Published: December 2008

1 A case of acute dapsone poisoning in a 57 year old man is reported. Peak plasma dapsone concentrations of 18.8 mg/l were observed 20 hours after ingestion, and methaemoglobin concentrations fell in parallel with dapsone. 2 Plasma dapsone concentrations declined mono-exponentially with time, and the half-life (29.7 hours) was similar to that described in subjects receiving conventional doses. Moreover, the ratio of monoacetyl-dapsone (MADDS) to dapsone remained constant as plasma concentrations fell. These observations suggest that N-acetylation of dapsone was not saturated even at the toxic concentrations observed.
Importance of Membrane Stabilizing Effect in Massive Overdose of Propranolol: Plasma Level Study in a Fatal Case
Authors: Hong C.Y. , Yang W.C. , Chiang B.N. 
Published: December 2008

1 Plasma propranolol levels were measured in a woman who took 3120 mg of propranolol in a suicide attempt.2 Highest plasma level, measured at the 12th hour, was 1475 ng/ml. Elimination half life was prolonged to 13.8 h.3 She suffered from coma and profound hypotension, then died on the 20th day.4 By estimating brain propranolol concentration from the plasma level, and reviewing the clinical pictures of previously reported cases, we propose that central nervous suppression by propranolol, with membrane stabilizing effect as its pharmacological basis, may cause life threatening abnormalities in patients with massive overdose of propranolol.
Nephrotoxicity of Phenazopyridine
Authors: Tomlinson B. , Cohen S.L. , Smith M.R. , Fisher C. 
Published: December 2008

1 A young man developed reversible acute renal failure after a large overdose of phenazopyridine.2 The renal failure was treated by peritoneal dialysis.3 Analysis of blood and urine samples failed to demonstrate the parent drug but a metabolite with similar ultraviolet absorption was detected.4 No parent drug or metabolites were detected in the peritoneal dialysate.
Animal Studies on the Treatment of Poisoning by Amitraz (a Formamidine Pesticide) and Xylene
Authors: Turnbull G.J. 
Published: December 2008

1 In Charles River CD rats the pesticide MITAC 20 EC (containing amitraz and 75% xylene) given orally at an LD80 dose caused toxicity featuring hypothermia, reduced spontaneous activity, episodes of increased activity and minor signs of general debilitation. Recovery in survivors was complete within about 8 days. 2 Therapies including absorption retardants, diuretics, reduction of urine pH, thermal support and treatment with phentolamine or nikethamide were given to groups showing these signs of poisoning. 3 None of the therapies gave consistent evidence of benefit during acute poisoning in terms of reduced intensity or duration of symptoms or reduced mortality. 4 Comparison with animals given amitraz alone suggested that the hypothermia and the later phase of reduced spontaneous activity were attributable to the pharmacological effects of amitraz. While the product was apparently more acutely toxic by the oral route than xylene alone, the evidence was that xylene caused the early signs of poisoning. 5 This work indicates that any case of poisoning by ingestion of MITAC 20 EC should initially be treated for the xylene exposure. There is no specific therapy or antidote for the subsequent possible pharmacological effects of amitraz. Many other pesticides also contain high proportions of aromatic solvents and the importance of the solvent in cases of ingestion is seen to be applicable to a variety of pesticides as well as MITAC 20 EC.
Extrapolation from Safety Data to Management of Poisoning with Reference to Amitraz (a Formamidine Pesticide) and Xylene
Authors: Bonsall J.L. , Turnbull G.J. 
Published: December 2008

1 Many pesticides are formulated in organic solvents. An example is amitraz, one of the formamidine group of pesticidal chemicals. As a contingency against the possibility of poisoning cases occurring, the toxicity and pharmacology of amitraz were reviewed in order to recommend medical management procedures. 2 Amitraz has pharmacological activity, including monoamine oxidase inhibition, α-adrenergic agonist activity and it inhibits prostaglandin synthesis. Extrapolating from acute studies in animals, the likely signs of poisoning in humans may include bradycardia, hypotension, hyperglycaemia, CNS depression, and hypothermia. 3 Despite the presence of amitraz, it appears that the xylene is the more aggressive component in the formulation tested, and treatment for overexposure by the oral route is generally as for xylene ingestion, but the presence of amitraz is an indication for gastric lavage. 4 Few cases of poisoning have occurred and these are presented.
Psychological and Physical Complaints of Subjects with Low Exposure to Lead
Authors: Zimmermann-Tansella C. , Camparal P. , D'Andrea F. , Savonitto C. , Tansella M. 
Published: December 2008

1 The relationship between lead uptake level and subjective psychological and physical symptoms was investigated in two groups of occupationally exposed workers with PbB levels between 45 and 60 μg/100 ml and below 35 μg/100 ml respectively. Findings were compared with those of a non-exposed control group. 2 Psychological symptomatology as defined by the GHQ proved unsensitive to low levels of lead exposure, while physical symptomatology as defined by the SSQ, in particular neurological symptoms, showed a significant tendency towards an uptake response relationship. 3 The minimum uptake level for neurological symptoms in this study was below 35μg/100 ml.
Hardness of Domestic Water and Blood Lead Levels
Authors: Elwood P.C. , Phillips K.M. , Lowe N. , Phillips J.K. , Toothill C. 
Published: December 2008

1 The effect on the blood lead levels of residents in an area in which a soft plumbo-solvent water was hardened is examined. 2 Water lead levels fell after hardening was introduced whereas there was a small rise in water lead levels in a control area monitored over the same time. 3 The blood lead levels of residents fell after hardening and the fall was slightly greater than would have been predicted on the basis of the change in water lead levels. This suggests that lead is less well absorbed from hard water than from soft water. 4 Following hardening there was a significant fall in mean blood lead level of subjects living in houses which had initially had negligible amounts of lead in the water. This suggests that hard water may interfere with the absorption of lead from sources other than water.
Urinary Excretion of Cadmium, Protein, Beta-2-Microglobulin and Glucose in Individuals Living in a Cadmium-Polluted Area
Authors: Sangster B. , de Groot G. , Loeber J.G. , Derks H.J.G.M. , Krajnc E.I. , Savelkoul T.J.F. 
Published: December 2008

1 Urine was collected from 289 inhabitants of a cadmium-polluted quarter of Stadskanaal. The excretion of cadmium, protein, beta-2-microglobulin and glucose were determined. After being divided according to sex and to smoking habits, the results of the inhabitants were compared with those of 293 controls. 2 In inhabitants as well as controls, cadmium excretion was age-dependent. Cadmium excretion in females increased faster with age than in males. 3 In male-smoker controls, cadmium excretion was significantly higher (p < 0.001) than in male-non-smoker controls. 4 In male-non-smoker inhabitants, cadmium excretion (p = 0.05), protein excretion (p <0.01) and glucose excretion (p <0.01) were significantly higher than in corresponding controls. In male-smoker inhabitants, protein excretion (p < 0.01) and glucose excretion (0.01 < p < 0.05) were significantly higher than in corresponding controls. In female-non-smoker inhabitants glucose excretion was significantly higher (0.01 < p < 0.05) than in corresponding controls. 5 For some categories, living in the polluted area was associated with an increased cadmium excretion in urine and a slight difference in renal function, possibly related to a difference in cadmium body burden. It was concluded that, considering the actual values of each parameter, the observed differences were not relevant in terms of potential health hazards.
Transplacental Carcinogenesis with Radioactive Phosphorus: The Effects of Promoting Agents
Authors: Berry C.L. , Nickols C. , Swettenham K.V. 
Published: December 2008

1 In a previous experiment, using 32P as a potential transplacental carcinogen in rats, we found that the isotope caused life-span shortening, reduced growth and caused ante-dating of the time of the tumour occurrence. 2 Liver cell changes (nuclear atypia, variation in cell size) were noted and suggested liver cell damage, possible 'initiation'. 3 A phorbol ester (TPA) and a high fat/high protein diet were used as promoting agents on further transplacentally irradiated rats. 4 The results were identical to the previous experiment; no evidence of promotion was found.
Evaluation of Genotoxicity of Ampicillin and Carbenicillin on Human Lymphocytes in vitro: Chromosome Aberrations, Mitotic Index, Cell Cycle Kinetics, Satellite Associations of Acrocentric Chromosomes and Sister Chromatid Exchanges
Authors: Jaju Manjula , Jaju Madhuri , Ahuja Y.R. 
Published: December 2008

A large number of drugs have been introduced into man's environment in recent years, many of which have been shown to have mutagenic, teratogenic and carcinogenic effects. Keeping in view the potential hazardous effects of drugs and chemicals, it is desirable to test new drugs for their genotoxic effects prior to widespread use. 1 In the present investigation genetic effects of ampicillin and carbenicillin were studied in vitro in human lymphocytes using a number of end-points. 2 These drugs were added at a range of concentrations and times during a 72h culture period. Concentrations corresponding to the plasma level after receiving therapeutic doses as well as concentrations higher than the plasma levels were examined. 3 Neither drug affected the frequency of chromosome aberrations, satellite associations, mitotic index and cell turnover rate at plasma level concentrations. However, all these parameters were affected at higher concentrations. 4 The frequency of SCEs was not increased with both the drugs irrespective of the concentrations or durations of treatment, suggesting that the mechanisms leading to the formation of SCEs and chromosome aberrations are different. 5 Both ampicillin and carbenicillin were genetically non-toxic for the end points measured and non-clastogenic in vitro at therapeutic doses. However, previous studies have shown ampicillin to be clastogenic in vivo. 6 For evaluation of genetic toxicity, drugs should be tested both in vitro and in vivo.
Lead Poisoning: Hair Analysis Shows the Calendar of Events
Authors: Grandjean P. 
Published: December 2008

1 A woman was given frequent oral doses of lead nitrate over an extended time period. Diagnosis was finally made about 6 months after the first symptoms appeared. Analysis of hair taken at 2 different times was used as evidence in court. 2 The hair lead concentrations exhibited rapid changes and normalised shortly after chelation treatment had been instituted. This finding suggests that the hair lead level may reflect a current absorption level rather than the lead content of whole blood which, in this case, changed much more slowly. 3 Despite the extremely high blood lead levels and the severe clinical lead poisoning, lead concentrations in hair were relatively low in comparison to the concentrations found in hair of workers exposed to high levels of airborne lead. This observation suggests that a large proportion of the lead content of hair from individuals with respiratory lead exposure may be exogenous.
Adverse Reactions to N-Acetylcysteine
Authors: Bateman D.N. , Woodhouse K.W. , Rawlins M.D. 
Published: December 2008

1 Clinical details of seven patients who suffered adverse reactions to N-acetylcysteine as Parvolex are documented. 2 Skin testing was carried out to diluted Parvolex, and its individual components N-acetylcysteine and ethylenediaminetetra-acetate, in five reacting patients and five patients who had received Parvolex with no ill-effects. 3 Weal responses to high concentrations (20 mg/ml) of acetylcysteine as Parvolex were significantly greater ( p < 0.02) in reactors. There were no other significant differences between the groups. 4 In two patients who reacted, the effects of intradermal Parvolex could be inhibited by prior therapy with the antihistamine terfenadine. 5 These results suggest a 'pseudo-allergic' rather than an immunological aetiology for adverse reactions to Parvolex.
Long-term Behaviour of 239Pu, 241Am and 233U in Different Bones of One-year-old Rats: Macrodistribution and Macrodosimetry
Authors: Sontag W. 
Published: December 2008

1 Female and male rats of the Sprague-Dawley strain, aged about 13 months, were injected intravenously with monomeric 239Pu-(30.7 kBq/kg), 241Am-(54.8 kBq/kg) or 233U-citrate (56.6 kBq/kg) and killed between 7 and 540 days after injection. 2 In both sexes the wet skeletal weight was proportional to body weight; however, the skeletal weight of female rats remained constant, whereas the skeletal weight, and body weight, of male rats increased as a function of age. 3 The initial skeletal deposition decreased in the order 239Pu > 241Am > 233U and for americium and uranium was greater in male rats. The 'half-time' of retention of plutonium and americium was considerably greater than 1 year but the corresponding values for uranium were 140 (females) and 80 (males) days. 4. The relative concentration of the radionuclides in the skeleton varied between 0.2 and 2.0, the variation was greatest for plutonium and lowest for americium and decreased with increasing time after injection. 5 For calculation of the nuclide content of the whole skeleton the most suitable reference bone was found to be the humerus in the case of uranium, and the femur and humerus for plutonium and americium. 6 The cumulative mean skeletal absorbed radiation dose 1 year after injection decreased in the order 239Pu > 241 Am > 233U; for plutonium it was equal for both sexes, whereas for americium and uranium it was 1.5 times higher in male than in females rats. In the individual bones the cumulative dose was greatest in the vertebral column, except the tail, and lowest in the paws.
Urinary Metabolic Profile of Isoniazid in Patients who Develop Isoniazid-related Liver Damage
Authors: Timbrell J.A. , Wright J.M. 
Published: December 2008

1 The urinary metabolite profile of isoniazid has been studied in patients receiving the drug as therapy for tuberculosis and the profile in patients suffering liver damage due to isoniazid compared with that in control patients.2 There were no consistent differences between control patients and those suffering liver damage in the excretion of isoniazid metabolites.3 It may be that susceptibility to the hepatotoxicity of isoniazid is not due to metabolic differences, although a number of other possible explanations are discussed.4 It is not at present possible to predict which patients will be susceptible from metabolic studies.
Fatal Self-poisoning with Benoxaprofen
Authors: Fancourt G.J. , Adams H. , Walls J. , Ward J.W. 
Published: December 2008

1 A report of the first fatal self-poisoning due to primary toxicity of benoxaprofen. 2 Benoxaprofen is toxic in acute overdosage to the central nervous system, myocardium and kidneys, but appears to spare the liver.