bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study on the Neurotoxicity of Broxyquinoline and Brobenzoxaldine Combination in Therapeutic Doses
Authors: Swain R. , Bapna J.S. , Das A.K. , Chandrasekar S. , Swaminathan R.P. , Bosco B. , Veliath S. , Thombre D.P.
Published: December 2008

1 The neurotoxicity of a combination of broxyquinoline and brobenzoxaldine (Intestopan Forte, containing 500 mg and 100 mg of the drugs respectively per capsule) was investigated by prospective clinical and electrophysiological studies in patients and volunteer subjects given the drugs in therapeutic doses (two capsules three times a day for 5 days).

2 Of 16 patients with intestinal amoebiasis given the drugs (study A), 13 (81.25%) were cured. Adverse effects were mild and did not affect treatment. No neurological adverse effect was reported. Neurological examinations revealed no abnormality in any patient after treatment.

3 Seven volunteer subjects underwent medical, neurological and ophthalmological examinations, and electrophysiological studies of ulnar and peroneal nerve conduction before and after treatment with the drugs in therapeutic doses (study B). Transient parasthesiae were reported by one subject on the fourth day of treatment. No medical, neurological or ophthalmological abnormality was detected in any subject after treatment. There was no significant change in motor nerve conduction velocities. There was a significant (P<0.001) increase in the stimulus strength for distal ulnar stimulation and a significant (P<0.01) decrease in stimulus duration for proximal and distal ulnar stimulation. No significant changes were seen in the peroneal nerves in these parameters. No qualitative abnormality was seen in the oscilloscopic patterns of nerve conduction after treatment. 4 Literature on the neurotoxicity of the halogenated hydroxyquinolines is reviewed.

5 It is concluded that broxyquinoline and brobenzoxaldine (and probably other halogenated hydroxyquinolines as well) are safe and effective in therapeutic doses; neurotoxicity is unlikely to occur when these drugs are used according to therapeutic recommendations.
Encephalopathy Associated with Sulindac
Authors: Neufeld M.Y. , Korczyn A.D.
Published: December 2008

Sulindac (Clinoril) is a non-steroidal anti-inflammatory drug. It is an indene derivative with therapeutic efficiency comparable with that of indomethacin. We report a case of encephalopathy associated with the intake of sulindac.
Impairment of Exercise Tolerance due to Broxyquinoline-Brobenzoxaldine Combination
Authors: Swain R. , Bapna J.S.
Published: December 2008

1 A case report of impaired exercise tolerance during administration of broxyquinoline-brobenzoxaldine combination in therapeutic doses is presented.

2 The first author of this paper, a 28-year-old healthy male, volunteered as a subject for a prospective study on the neurotoxicity of halogenated hydroxyquinolines and took a course of broxyquinoline-brobenzoxaldine combination.

3 The author, who is a karate enthusiast, observed impairment of exercise tolerance during the course of treatment with the drugs.

4 A challenge course of treatment with the same drugs in the same doses produced similar effects.

5 Since halogenated hydroxyquinolines are still used widely in many countries, such an adverse effect would be of practical relevance, particularly in asymptomatic cyst-passers of Entamoeba histolytica whose occupations involve physical labour.
Choice Reaction Time in Workers Exposed to Styrene Vapour
Authors: Mackay C.J. , Kelman G.R.
Published: December 2008

1 Behavioural effects of occupational exposure to vapour from styrene-based resin were investigated in 10 female workers with a portable test of choice reaction time. Testing was carried out both at the beginning and end of the day's shift.

2 Uptake and metabolism of styrene were assessed by monitoring post-shift urinary mandelic acid excretion rates. By using these data workers were allocated to three groups reflecting zero, low )r high exposure.

3 After exposure slowing of reaction times was found in those with the highest mandelic acid excretion rates, whereas a slight improvement or no change was found in those with low or zero exposure.

4 Subsequent improvements in extraction and ventilation in the workroom were shown to be associated with both decreased mandelic acid excretion and absence of long reaction times in those previously most heavily exposed.
Potato Steroidal Alkaloids and Neural Tube Defects: Serum Concentrations Fail to Demonstrate a Causal Relation
Authors: Harvey M.H. , Morris B.A. , McMillan M. , Marks V.
Published: December 2008

Spoiled potatoes and, in particular, steroidal alkaloids have been proposed as an aetiological factor in the pathogenesis of neural tube defect (NTD). The present study involves the measurement of potato (solanum) steroidal alkaloid concentrations in serum by radioimmunoassay. Serum solanidine and total potato alkaloid concentrations were measured in two groups of women: one group pregnant with a fetus, subsequently shown to be affected by a NTD, the other with a healthy fetus. Serum alkaloid concentrations were, contrary to expectations, lower in the NTD group. They lend no weight therefore to the theory that potato alkaloids are responsible for NTD, but are consistent with the opinion that some water-soluble vitamins lessen the risk.
Influence of Dosing Interval and In-patient Versus Out-patient Status on Incidence of Side-effects of Niridazole
Authors: Abdu-Aguye I. , Sambo-Donga L.
Published: December 2008

The side-effects of niridazole used for urinary schistosomiasis were studied prospectively over a 3-month period in male patients receiving the standard dose of 25 mg day-1 kg-1 for 7 days. Side-effects were detected in 80% of in-patients but only in 33% of out-patients. The range of side-effects was greater in in-patients taking their daily doses in two portions than in those taking theirs in three. Cure rates and degree of schistosoma egg suppression were significantly lower in out-patients suggesting that compliance with treatment was poorer.
Charcoal and Isoniazid Pharmacokinetics
Authors: Scolding N. , Ward M.J. , Hutchings A. , Routledge P.A.
Published: December 2008

Activated charcoal (10 g) administered 1 h after a 600 mg oral dose of isoniazid to six healthy subjects did not reduce the area under the plasma concentration-time curve for isoniazid significantly. Charcoal administration is unlikely to be of value in isoniazid poisoning if delayed by an hour or more after the overdose.
Kinetics of Methaemoglobin Production (2). Kinetics of the Cyanide Antidote p-Aminopropiophenone During Oral Administration
Authors: Bright J.E. , Marrs T.C.
Published: December 2008

The kinetics of methaemoglobin production by orally administered p-aminopropiophenone (PAPP) was studied by using a kinetic model previously developed to describe methaemoglobinaemia consequent on intravenous injection of PAPP. Both ISIS, a simulation package, and NONLIN, a non-linear least-squares regression analysis program, were used to analyse the data. Some modification of the model was necessary to describe oral profiles and 40-50% of the administered PAPP appeared to be being metabolized at first pass to a non-active metabolite.
Asthma and Rhinitis after Exposure to Glutaraldehyde in Endoscopy Units
Authors: Corrado O.J. , Osman J. , Davies R.J.
Published: December 2008

1 Four nurses working in endoscopy units complained of respiratory symptoms on exposure to alkaline glutaraldehyde used as a disinfectant for fibre-optic endoscopes.

2 A provocation test was positive in two of these patients.

3 This is the first report to use provocation testing to confirm a relation between exposure to alkaline glutaraldehyde and respiratory disease.
Comparison of Effects of Lysine Aspirin, Soluble Aspirin and Conventional Aspirin on Buccal Potential Difference in Healthy Volunteer Subjects
Authors: Shah K. , Jackson S.H.D. , Hedges A. , Turner P.
Published: December 2008

The effects of aspirin, soluble aspirin and lysine aspirin on buccal mucosal potential difference (p.d.) were compared in a double-blind trial. Placebo and three doses of each preparation containing 150, 300 and 600 mg of aspirin were allocated according to a latin square design. Six volunteer subjects were studied; each received a total of 10 treatments at least 24 h apart. All doses of each preparation considered, a significant treatment effect was seen [F (d.f. = 2,306) = 6.2, P<0.003]. Lysine aspirin showed the least effect of the active treatments on buccal p.d. with a change from baseline of +8.5 mV compared with +13.3 for soluble aspirin +14.4 for conventional aspirin and —5.2 mV for placebo.
Poisoning Associated with Potassium
Authors: Chaturvedi A.K. , Rao N.G.S. , Moon M.D.
Published: December 2008

A suicidal poisoning by intravenous administration of concentrated solution of potassium (K+) (chloride) is described in the study. A 30-year-old Caucasian female health professional was found dead in a motel. An intravenous needle was found inserted in the antecubital area in a right arm vein of the deceased. Attached to the needle, by a flexible tubing, was a 50 ml syringe four-fifths full of a clear liquid. Autopsy on the victim revealed pulmonary oedema and congestion. A routine toxicological analysis of biological samples ruled out the possibility of a drug overdose. However, the liquid from the syringe contained 1468 mmol of K+/1. Chloride ions were also present in high concentration in the liquid. The concentrations of K+ in the clear plasma and vitreous humour were 54 and 9.2 mmol/l respectively. It is suggested that the elevated level of K+ in the plasma or vitreous humour does not indicate necessarily a death due to the electrolyte. The evidence in this case is circumstantial and apparently can be expected to be so in any case where death is due to the intravenous infusion of a concentrated K+ solution.
Paracetamol Toxicity: is Enzyme Induction Important?
Authors: Smith J.A.E. , Hine I.D. , Beck P. , Routledge P.A.
Published: December 2008

A female patient receiving carbamazepine developed severe liver damage after an overdose of paracetamol. Antidotal therapy was not administered because her plasma paracetamol concentration was below that normally indicating the need for such therapy. Subsequently, carbamazepine was readministered and resulted in marked induction of the metabolism of a single dose of paracetamol. Antidotal therapy may be indicated if the plasma paracetamol concentrations are 70% or more of those shown in the conventional treatment line, if the patients are also receiving enzyme-inducing drugs.
Seventh-nerve Palsy and Hepatitis Associated with Nitrofurantoin
Authors: Thomson R.G. , James O.F.W.
Published: December 2008

Adverse hepatic reactions to nitrofurantoin therapy are well reported and range from acute cholestatic or hepatitic injury to chronic active hepatitis [R. G. Penn & J. P. Griffin (1982) Br. Med. J., 284, 1440-1442]. Neurological side-effects, predominantly sensorimotor peripheral poly-neuropathy, have also been documented [R. G. Penn & J. P. Griffin (1982)]. We report the first case of combined neurological and hepatic reaction to nitrofurantoin; this occurred during repeated treatment with the drug.
Uses and Usefulness of Paraquat
Authors: Sagar G.R.
Published: December 2008

1 Paraquat was discovered in 1955 and introduced to the market place in 1962. During the 23 years between introduction and the present day numerous successful practical uses of the herbicide have been developed. In addition the characteristics of the chemical have allowed significant changes to be made in the ways that some crops are grown.

2 Paraquat is a relatively non-selective foliage-applied contact herbicide. It is inactivated on contact with almost all naturally occurring soils and it was this property, perhaps above all others, that provided the greatest breakthrough in chemical weed control at the time of its discovery.

3 Inactivation on contact with soil means that no biologically active residues remain in the soil, thus allowing planting or sowing to be carried out almost immediately after spraying. Although the non-systemic (contact) property of paraquat makes it less than ideal for the long-term control of perennial weeds, the same property is of real advantage when parts of crop plants are sprayed accidentally, for usually only the part receiving the spray is affected.

4 Total annual usage of all herbicides in agriculture and horticulture in England and Wales, UK, over the period of 1980-1983 has been estimated at 26 360 tonnes used on 12 402 x 103 ha (1 hectare = 1 x 104 m2). For paraquat (not including its mixtures with diquat and monolinuron) 270 tonnes were sprayed over 392 218 ha/year. It is estimated from sales records that in Europe 5 x 106 ha are sprayed annually with paraquat.

5 The paper reviews the need for the use of herbicides and the properties that are important for particular crop-weed situations, but concentrates on the properties of paraquat that make it an essential agent of weed control in many areas of agriculture, horticulture and forestry.
Mechanism of Paraquat Toxicity in Lung and its Relevance to Treatment
Authors: Smith L.L.
Published: December 2008

1 The symptoms of paraquat poisoning depend largely on the amount of compound consumed, although in many cases the most characteristic feature of poisoning is lung damage, causing severe anoxia which leads to death.

2 Studies in experimental animals have demonstrated that paraquat produces an acute damaging phase in the lung, followed by a reparative phase dominated by an extensive fibrosis. The latter is a major contributor to the lung lesion that causes anoxia. The specific toxicity in the lung can be explained in part by the selective accumulation of paraquat into this organ in comparison with other tissues. The accumulation is energy-dependent and probably specific to certain lung cells.

3 It is now known that paraquat is accumulated into the lung by a recently described diamine transport process located in the alveolar epithelial cells and the Clara cells of the airways. When accumulated, paraquat undergoes a NADPH-dependent one-electron reduction to form its free radical which almost instantly reacts with molecular oxygen to reform the cation and concomitantly produce superoxide anion. This species of oxygen radical can contribute to the formation of more toxic species of radical which may directly damage vital cellular constituents.

4 Paraquat has been shown to stimulate rapidly the pentose phosphate pathway and inhibit the synthesis of fatty acids in the lung in a dose-dependent manner. In addition there is a rapid increase in the pulmonary levels of mixed disulphides and the eventual reduction of NADPH levels in the lung.

5 These results are consistent with the suggestion that paraquat causes a rapid and pronounced oxidation of NADPH which initiates compensatory biochemical responses in the lung.

6 With toxic levels of paraquat the compensatory biochemical processes are insufficient to maintain levels of NADPH consistent with cell viability. Thus, cell death may result from NADPH depletion, or the loss of this vital co-factor may render the lung more susceptible to free-radical attack and thereby peroxidation of vital cellular constituents.
Paraquat Poisoning: The Rationale for Current Treatment Regimes
Authors: Davies D.S.
Published: December 2008

1 The critical events leading to death from the ingestion of paraquat are absorption from the gastrointestinal tract, active accumulation in the lung almost certainly preceded by acute renal failure and redox cycling in the lung which initiates certain, as yet unidentified, biochemical events leading to cell death with subsequent destruction of the lung and death from anoxia.

2 Present evidence suggests that absorption of paraquat is rapid and the use of adsorbents more than 6 hours after ingestion is likely to be ineffective. Further work is needed to characterize the mechanism of absorption and to identify an innocuous chemical which could be added to formulations of paraquat to inhibit absorption; this approach may be the best solution to the problem of paraquat poisoning.

3 Steps to actively remove paraquat from the systemic circulation will probably only succeed in a small number of patients taking moderate doses and developing early renal failure. The 'window' for such treatment may be as narrow as 6-18 h after ingestion. This 'window' would also operate for chemicals designed to inhibit the pulmonary uptake of paraquat.

4 The biochemical events leading to paraquat-induced cell death are not sufficiently defined to permit the design of treatments to prevent or reverse these processes.
Paraquat poisoning: clinical features and immediate general management
Authors: Vale J.A. , Meredith T.J. , Buckley B.M.
Published: December 2008

1 In contrast to 10-15 years ago most cases of paraquat poisoning are now due to deliberate self-poisoning with parasuicidal or suicidal intent rather than to accidental ingestion. Less commonly, poisoning may follow careless handling of paraquat during occupational use. Although paraquat can be absorbed through the skin if improperly handled, poisoning usually follows ingestion and has rarely been reported after subcutaneous, intravenous or intraperitoneal injection.

2 Clinically, three degrees of intoxication may be distinguished. (a) Mild poisoning occurs after the ingestion or injection of less than 20 mg of paraquat ion/kg body weight. In these cases patients are either asymptomatic or symptoms are confined to the gastrointestinal system. All patients recover fully. (b) Moderate to severe poisoning usually follows the ingestion (rarely injection) of 20-40 mg of paraquat ion/kg body weight. Non-specific symptoms of ill health together with local gastrointestinal symptoms precede the development of renal failure (which may recover spontaneously) and pulmonary fibrosis which may not be manifest for days or weeks. Death occurs in the majority of cases but is usually delayed for 2-3 weeks. (c) Acute fulminant poisoning follows the ingestion of substantial quantities of paraquat (> 40 mg of paraquat ion/kg body weight). In addition to local symptoms, multiple organ (cardiac, respiratory, hepatic, renal, adrenal, pancreatic, neurological) failure occurs. Death may supervene within hours and is never delayed for more than a few days.

3 Initial general management has four priorities. Firstly, fluid loss should be replaced; secondly, the prognosis should be determined by measurement of the plasma paraquat concentration; thirdly, symptoms due to ulceration of the oropharynx must be relieved; fourthly, supportive care for patients and relatives must be provided.

4 Experience suggests that management of the terminally ill patient with acute fulminant poisoning is a far greater clinical challenge to medical and nursing expertise than simply the employment of methods to prevent absorption or increase elimination of paraquat.
Treatment of Paraquat Poisoning in Man: Methods to Prevent Absorption
Authors: Meredith T.J. , Vale J.A.
Published: December 2008

Theoretically, absorption of an ingested dose of paraquat may be reduced by (1) gastric lavage, (2) induced emesis, (3) whole-gut lavage or (4) by the oral administration of adsorbent substances.

1 Animal experiments suggest that paraquat is absorbed poorly from the stomach and absorbed incompletely (< 5%) from the small intestine over a 1-6-h period. Although gastric lavage would therefore seem a logical way to ameliorate the toxicity of an ingested dose of paraquat, peak plasma concentrations are attained rapidly and evidence for the efficacy of gastric lavage in man is poor.

2 In 1977, a potent emetic (PP796) was added to liquid and solid formulations of paraquat because experiments in primates had demonstrated a fivefold reduction in toxicity. In man, ingestion of formulations containing an emetic is more likely to cause spontaneous vomiting within 30 min than non-emetic preparations. However, definite evidence of benefit, as judged by improved patient prognosis, has yet to be established.

3 Gut lavage has been shown to remove only a small proportion of an ingested dose of paraquat. At the flow rates employed in man (75 ml/min), approximately 0.5-1.0 litres of lavage fluid/h may be absorbed across the intestinal wall. Since there is a theoretical risk of increasing paraquat absorption, the use of whole-gut lavage cannot be recommended.

4 Bipyridilium herbicides are adsorbed by soil and clay minerals, and montmorillonite in particular has been shown to be a strong binding agent in vitro. Accordingly, the use of Fuller's Earth (calcium montmorillonite) and Bentonite (sodium montmorillonite) for the treatment of poisoning has been investigated in animal models. Both agents reduce plasma paraquat concentrations and mortality in animals when administered after an oral dose of paraquat. Recently, other adsorbent materials have been found to have high maximum adsorption capacities for paraquat. In particular, activated charcoals and cation-exchange resins have attracted interest. Unfortunately, as yet, there is no evidence that the use of adsorbents in man is of therapeutic value.
Prognostic Value of Plasma and Urine Paraquat Concentration
Authors: Scherrmann J.M. , Houze P. , Bismuth C. , Bourdon R.
Published: December 2008

1 A non-exponential mathematical equation was used to extrapolate the 'predictive line' for plasma paraquat concentrations beyond 24 h. Plasma paraquat concentrations were measured in 30 patients who were admitted more than 24 h after overdose. The extrapolated line accurately predicted the outcome in 27 of these 30 patients.

2 Urine paraquat concentrations were measured in 53 patients. All patients with urine paraquat concentrations of less than 1 mg/l (colourless or light blue test result using the colorimetric test) within 24 h of overdose survived. In contrast, patients with urine paraquat concentrations of more than 1 mg/l had a high probability of death.

3 Even if plasma paraquat concentrations have a higher predictive value, urine data may contribute to a more rapid evaluation of prognosis.
Poisoning with Dextropropoxyphene in Denmark
Authors: Segest E.
Published: December 2008

The sale of dextropropoxyphene is rising in Denmark, and the number of both fatal and non-fatal cases of poisoning with dextropropoxyphene is similarly rising. A total of 124 fatal and 297 non-fatal hospitalized cases of poisoning caused by dextropropoxyphene were reported to the National Board of Health in 1984. These figures are judged to be minimum figures. There is an accumulation of cases in the municipality of Copenhagen as compared to the remainder of the country. Cases of poisoning with dextropropoxyphene occur more frequently in socially and mentally encumbered groups.

It is often difficult to determine with certainty the method of poisoning, but it is considered that the distribution is roughly one-third suicide or attempted suicide, about the same from accidental or simple over-dosage, while the remainder are uncertain. It is judged that the number of suicides or attempted suicides in normal persons is small, while the numbers in persons not entirely normal or carried out as an impulsive act are considerably higher.

Other intoxicants, most frequently alcohol, have in more than one half of the cases been consumed together with dextropropoxyphene.

The mortality rate for those cases reaching medical aid has been found to be 3.6% which is lower than the figure reported in other investigations. Very many of the cases of poisoning, however, are fatal at the time of discovery. Serious sequelae after non-fatal cases of poisoning are extremely rare.

The steps being taken by the National Board of Health to reduce the number of cases of poisoning are mentioned, and the possibilities of reducing the number of cases are also discussed.
Effect of Dietary Fish Oil on Hyperlipidaemia due to Isotretinoin and Etretinate
Authors: Marsden J.R.
Published: December 2008

Treatment with retinoids results in increased serum triglyceride and cholesterol and reduced HDL-cholesterol; dietary supplementation with fish oil lowers serum lipids. Therefore combining retinoids with fish oil may reduce retinoid hyperlipidaemia. Increased triglyceride due to isotretinoin was reduced by 70% (P < 0.05) and cholesterol by 45% (P < 0.05) after addition of fish oil; placebo oil had no effect. These decreases were not associated with changes in levels of HDL-cholesterol or reduction of increased levels of apoprotein B. Increased triglyceride due to etretinate was reversed after the addition of fish oil (P < 0.01), but cholesterol levels did not change. Therefore fish oil inhibits hypertriglyceridaemia due to isotretinoin and etretinate and reduces increased cholesterol levels due to isotretinoin; this effect is likely to be due to altered lipoprotein composition.
Effect of Gentamicin on Human Blood Cells Metabolism as Measured by Microcalorimetry
Authors: Nässberger L. , Monti M.
Published: December 2008

The effect of gentamicin on overall metabolism in human blood cells was studied by microcalorimetry. At concentrations above therapeutic levels, the drug induced an increase in heat production rate in red cells, whereas no effect was found at lower concentrations. The Na/K-pump was unaffected at any gentamicin concentration. A slight increase in heat production rate was noted in granulocytes when incubated with gentamicin at concentrations above therapeutic levels, otherwise no effect was recorded at lower concentrations. Lymphocytes were unaffected by gentamicin at any concentration. Microcalorimetry seems to be a suitable method for studying the effect of drugs on overall cell metabolism, and for evaluating the Na/K-pump activity.
Aminoglutethimide as Second-line Hormonal Therapy in Advanced Breast Cancer: Response and Toxicity
Authors: Rowell N.P. , Gilmore O.J.A. , Plowman P.N.
Published: December 2008

Seventy-nine postmenopausal patients received aminoglutethimide (AG; 750 mg daily) and hydrocortisone therapy for metastatic or locally recurrent breast cancer following the failure of other hormonal therapy. Fourteen of 64 patients, tolerating the drug and assessable for response, achieved a complete or partial response. Disease stabilisation occurred in a further 2 patients giving a response rate of 25% in these patients. Median duration of response was 10 months. Response rates to AG were not significantly different whether or not there had been a response to previous hormonal therapy but a trend to higher response rates in ER rich tumours was observed. Those with a longer interval from first relapse to the start of AG appeared more likely to respond. Side-effects were noted in 35 patients overall (44%) and in 70% of those over the age of 65 years. Treatment was discontinued because of toxicity in 10 patients and there was one death due to agranulocytosis.

AG is active in postmenopausal breast cancer following failure of first-line hormonal therapy, toxicity limiting its use earlier in the disease.
Carbamazepine and Carbamazepine-10,11-epoxide Pharmacokinetics in an Overdose Patient
Authors: Patsalos P.N. , Krishna S. , Elyas A.A. , Lascelles P.T.
Published: December 2008

1 A case report on a 13-year-old girl with idiopathic grand mal epilepsy who ingested 34 g carbamazepine (CBZ) and 80 mg clonazepam is presented.

2 The patient survived but suffered severe temporary neurological toxicity characteristic of CBZ.

3 CBZ was 79.6 ± 2.8% bound to serum protein and carbamazepine-10,11-epoxide (CBZ-E) binding was essentially concentration dependent.

4 CBZ and CBZ-E elimination half-lives were 26 and 16.5 h respectively. An inhibitory metabolic interaction with the co-ingested clonazepam is suggested.
Evaluation of the BTS Approach to the Testing of Substances and Preparations for their Acute Toxicity
Authors: van den Heuvel M.J. , Dayan A.D. , Shillaker R.O.
Published: December 2008

This study has shown that the new approach to acute oral toxicity testing proposed by the British Toxicology Society

1 provides the information on the toxic effects of materials necessary for human risk assessment,

2 can be used to rank materials for regulatory purposes on the basis of their acute toxicity,

3 provides advantages for animal welfare by requiring the use of fewer animals than conventional acute oral toxicity tests and by subjecting those animals used to less chance of experiencing pain or distress.
Accidental Poisoning in Childhood: A Multicentre Survey. 1. General Epidemiology
Authors: Wiseman H.M. , Guest K. , Murray V.S.G. , Volans G.N. ,   NPIS Monitoring Group
Published: December 2008

1 As background to a study of the effectiveness of packaging in preventing childhood poisoning, the National Poisons Information Service coordinated a prospective survey, in which 9 Accident and Emergency (A & E) departments and 5 paediatric departments, between July 1982 and February 1984, recorded 2043 cases of suspected accidental poisoning in children aged 0-60 months.

2 The products implicated were drugs (59%), household products (37%) and plants (3%). The drugs most frequently implicated were analgesics, anxiolytics, cough medicines, oral contraceptives and drugs to supplement diet or treat dietary disorders. The most frequently implicated household products were cleaners such as bleach, detergent and disinfectant, and petroleum distillate.

3 Seventy-five per cent of the children were 2 and 3-year-olds. Fifty-six per cent were male.

4 Only 22% of the children had signs or symptoms on admission. In only 2 cases were these serious. Treatment other than ipecacuanha and/or oral fluids was seldom required. Of the cases where outcome was recorded, 56% were discharged from A & E. The rest were admitted to a ward; only 7 children were admitted to intensive care units. No child died.

5 Comparison with HASS and other epidemiological surveys shows that these results are representative of national trends.
Poisoning with Over-the-Counter Doxylamine Preparations: An Evaluation of 109 Cases
Authors: Köppel C. , Tenczer J. , Ibe K.
Published: December 2008

One hundred and nine cases of monointoxication with doxylamine were evaluated with respect to age distribution, amount ingested, plasma level, and clinical symptomatology. The age of 60% of the patients ranged between 16 and 30 years. In about 60% of the cases 10 to 40 times a single therapeutic dose (25 mg) was ingested. Doxylamine plasma concentrations exceeded the maximum plasma level after a therapeutic dose by a factor of 10 to 40 in two-thirds of cases. The most frequent symptoms included impaired consciousness, seizures, tachycardia, mydriasis and a 'psychosis' similar to that in catatonic stupor. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. No symptoms were observed in 39% of the patients. No correlation was found between the amount ingested or doxylamine plasma level and the clinical symptomatology. Primary detoxication included gastric lavage, administration of activated charcoal and sodium sulfate. Regarding the high frequency of doxylamine overdose and its possible complications the question arises as to whether doxylamine-containing preparations should be subjected to prescription.
Studies on the Metabolic Behaviour of Industrial Actinide-bearing Aerosols after Deposition in the Rat Lung: An Experimental Basis for Interpreting Chest Monitoring Data and Assessing Limits on Intake for Workers
Authors: Stradling G.N. , Stather J.W. , Gray S.A. , Moody J.C. , Bailey M.R. , Hodgson A. , Collier C.
Published: December 2008

The metabolism of 239Pu and 241Am in 3 site-specific industrial dusts has been studied after their deposition in the rat lung. A comparative experiment has also been carried out with a mixture of these actinides inhaled as their nitrates. The aim of this study was to provide an experimental basis for assessing limits on intake and to establish whether the 239Pu content in the lungs could be interpolated from measurements of 241Am. The results:

1 demonstrate the wide differences in the lung retention kinetics of the actinides and in the absolute and relative amounts translocated to the blood that can occur for industrially produced materials;

2 show that the annual limits on intake (ALIs) for the different materials vary between those postulated for class W and Y compounds by the International Commission on Radiological Protection;

3 indicate that acute intakes of 239Pu equivalent to the ALI can, depending on the nature of the dust, be estimated from 241Am chest monitoring data at times from a few days up to about 3 years after exposure.
Mianserin and Complete Heart Block
Authors: Hla K.K. , Boyd O.
Published: December 2008

Cardiac complications are common in tricyclic antidepressant poisoning, but are rare with overdose of mianserin, which is a tetracyclic antidepressant. We report a case in which repeated episodes of complete heart block occurred following overdose with mianserin.
A Case of Acute Poisoning with Fenitrothion (Sumithion)
Authors: Yoshida M. , Shimada E. , Yamanaka S. , Aoyama H. , Yamamura Y. , Owada S.
Published: December 2008

A 56-year-old male attempted suicide by ingestion of about 60 ml of 50% fenitrothion (Sumithion) emulsion. Five hours later, combined hemoperfusion and hemodialysis (HP-HD) treatment was performed for 60 min and consequently the toxic symptoms improved gradually. However, cholinergic symptoms recurred 4 days after ingestion. Although HP-HD was immediately performed for 180 min, it had no effect on the clinical symptoms. He died of respiratory insufficiency 6 days after the ingestion of fenitrothion.

Fenitrothion concentration in the organs and tissues showed the highest values in the fat tissue, followed in decreasing order by the pancreas, muscle, lung and brain. The results indicate that fenitrothion has high lipid solubility and deposits in the fat tissue. Furthermore, we believe that when HP-HD therapy is used in the treatment of acute insecticide poisoning it is important that it be performed continuously and in as early a stage as possible.
Exposure of the Skin to Methyl Bromide: A Study of Six Cases Occupationally Exposed to High Concentrations during Fumigation
Authors: Zwaveling J.H. , de Kort W.L.A.M. , Meulenbelt J. , Hezemans-Boer M. , van Vloten W.A. , Sangster B.
Published: December 2008

1 The effects of exposure of the skin to high concentrations of methyl bromide were studied in 6 cases, who had been unintentionally exposed.

2 Exposure to high concentrations of methyl bromide (approximately 40 g/m3) for 40 min can lead to redness and blistering of the skin. This cannot be prevented by wearing standard protective clothing.

3 Skin lesions show a preference for relatively moist skin areas.

4 Plasma bromide levels were highest immediately following exposure (mean 9.0 ± 1.4 mg/l) and fell in subsequent hours (mean 6.8 ± 2.3 mg/l 12 h after the exposure), suggesting absorption of (methyl) bromide through the skin.

5 No systemic effects were noted in this series.

6 Fumigation with methyl bromide should not be done in such a way as to require the presence of workers inside closed areas, where methyl bromide is released.
Isoniazid Overdose: Pharmacokinetics and Effects of Oral Charcoal in Treatment
Authors: Siefkin A.D. , Albertson T.E. , Corbett M.G.
Published: December 2008

The pharmacokinetics of isoniazid following overdose in two patients is described. One patient was treated with haemodialysis for seizures and persistent coma without obvious immediate clinical improvement. In addition, three volunteer subjects were given isoniazid orally on two separate occasions. Isoniazid elimination pharmacokinetics were determined with and without concominant charcoal. Oral activated charcoal totally prevented the absorption of isoniazid. Current recommendations for treatment of isoniazid overdoses include intravenous pyridoxine (one gram IV pyridoxine for each gram of ingested isoniazid), intravenous diazepam or phenobarbital for continued seizures, and gastric decontamination with lavage and activated charcoal (1 g/kg). Extraordinary measures such as early haemodialysis and haemoperfusion should be reserved for those patients with persistent coma or refractory seizures.
Terbutaline Concentrations in Self-Poisoning: A Case Report
Authors: Heath A. , Hultén B.-Å.
Published: December 2008

A young female patient was admitted twice within two months, each time after an overdose of 500 mg terbutaline. Clinical features included nausea, tachycardia, tremor, hyperglycemia and hypokalemia. Although plasma concentrations of terbutaline were at least 50 times the normal therapeutic level, after potassium substitution the outcome was uneventful.
Contac 400: A Possible Cause of Aspiration Under Anaesthesia
Authors: Wilkinson D.J.
Published: December 2008

Patients often take proprietary medicines which they do not report to their anaesthetist. One such case is reported in which a self administered high dosage of such a medication can be linked with a potentially life threatening anaesthetic complication. Pre-anaesthetic assessment should include specific questioning on over-the-counter medication.
Paraquat Poisoning by Skin Absorption: A Review
Authors: Smith J.G.
Published: December 2008

All reported cases of paraquat poisoning by absorption through the skin are briefly reviewed. It is concluded that, while paraquat cannot be absorbed significantly through intact human skin, damage to the skin, either by paraquat itself or by other means, will permit greater systemic absorption and possibly poisoning. The lowest known concentration of paraquat to result in fatal poisoning through the skin is 5 g/l.

Animal experiments with paraquat are also reviewed. The fact that the reported lethal dermal dose of paraquat in rats is slightly less than the oral dose is probably due to the lack of head restraint on the rats in the dermal dosing experiments.

In vivo and in vitro tests on human skin at concentrations of 9 g/l and 5 g/l did not result in significant absorption of paraquat through the skin but in these experiments the skin was intact.
Effects of Extended Feeding of Decocainized Erythroxylon Coca Leaves on Growth and Selected Organs in Rats and Rabbits
Authors: Valentine J.L. , Fremming B.D. , Chappell R.H. , Stephen P.M.
Published: December 2008

Erythroxylon coca leaves from the Trujillo area of Peru were extracted with methylene chloride to remove most cocaine-like alkaloids. The decocainized leaves were formulated in a honey-water vehicle and fed on a chronic basis to female rats for 32 weeks and female rabbits for 13 weeks. Rabbits fed decocainized leaves at doses of 21 or 210 mg demonstrated no significant change in growth (weight gain) when compared with those receiving vehicle. Histological findings were unremarkable except for fatty islands in the myocardium. Rats fed the decocainized leaves at doses of 1.5 and 15 mg demonstrated no significant changes in weight, whereas those receiving 150 mg had a significant decrease in weight gain when compared with control animals receiving vehicle. Necropsy findings in rats demonstrated pyometra in all groups receiving decocainized leaves as well as in some of the controls. Those rats with pyometra often exhibited endometrial metaplasia. Renal tubular calcification and proteinaceous material were consistently noted at all dose levels. Portal triaditis was also found in the livers of most rats.
Fatal Paracetamol Poisoning in an Epileptic
Authors: Minton N.A. , Henry J.A. , Frankel R.J.
Published: December 2008

Treatment nomograms are used in paracetamol poisoning for indicating when antidotes should be given to prevent hepatic or renal damage.1We report a fatal case of paracetamol poisoning in an epileptic taking phenytoin, in whom no antidotal treatment was given because it was not indicated.
Blood Cadmium Concentrations in the General Population of British Middle-aged Men
Authors: Pocock S.J. , Delves H.T. , Ashby D. , Shaper A.G. , Clayton B.E.
Published: December 2008

Blood cadmium concentrations were determined for 6919 men aged 40-59 randomly selected from general practice registers in 24 British towns. The mean and median blood cadmium were 1.9 and 1.4 μg/1 respectively and the distribution was highly skewed. The mean levels in non-smokers was 1.0 μg/l and current smokers showed a marked gradient with the daily amount smoked, with a mean of 3.9 μg/l in men smoking 40 or more cigarettes per day. Whereas 95% of men who never smoked had blood cadmium < 2.0 μg/l, 80% of men smoking 20 or more cigarettes a day exceeded this figure. 1% of the men had blood cadmium concentrations ≥ 7 μg/l virtually all of whom currently smoked cigarettes. Blood cadmium levels in ex-smokers were much lower than in current smokers even for those who had stopped within the past year. However, the mean levels in ex-smokers remained higher than the 'never smoked' for several years after stopping. There was little evidence that age, social class, or alcohol consumption were associated with blood cadmium levels after allowance for cigarette smoking.

There is substantial geographic variation in mean blood cadmium for middle-aged men which could not be completely accounted for by smoking differences. Towns in the south and east of England all had mean levels under 2.0 μg/l whereas the majority of towns in other parts of Britain had mean levels greater than 2.0 μg/l. Possible reasons for this geographic pattern (e.g. geochemistry, industrial exposure, dietary differences) need further exploration.
Lead Toxicity on Endocrine Testicular Function in an Occupationally Exposed Population
Authors: Rodamilans M. , Osaba Ma J. Mtz. , To-Figueras J. , Fillat F. Rivera , Marques J. Ma , Pérez P. , Corbella J.
Published: December 2008

The hypothalamo-pituitary-testicular axis was evaluated in a group of 23 men who worked in the lead smelting industry and had a history of occupational inorganic lead exposure. The endocrine status of the workers was related to lead poisoning biological markers. According to the duration of their lead exposure they were divided into three groups: group 1 < 1 year, n = 5; group 2 between 3 and 5 years, n = 8; group 3 > 5 years, n = 10.

Serum testosterone (T), steroid binding globulin (SBG), free testosterone index (T/SBG), serum luteinizing hormone (LH), follicle stimulating hormone (FSH), Blood lead levels, and blood zinc protoporphyrin (ZPP) were measured in all workers.

Groups 2 and 3 showed a decrease in serum testosterone levels, an increase in SBG levels, and a decrease in T/SBG index, suggesting a correlation between testicular dysfunction and duration of exposure. There was an increase in serum LH in group 1, which was not progressive. This suggests that prolonged lead exposure initially produces a direct testicular toxicity followed by hypothalamic or pituitary disturbance when longer periods of exposure take place.
The Effects of Soman on Human Isolated Uterine Arteries
Authors: Hu C.-Y. , Robinson C.P.
Published: December 2008

1 The effects of soman on the resting contractile tension of human uterine arteries, and on contractions of these arteries to vasoactive agents were investigated.

2 Soman did not alter the resting tension of helically-cut strips of human uterine arteries.

3 Soman did not alter concentration-response curves of the strips to noradrenaline, serotonin, potassium chloride or histamine.

4 Soman increased contractile tension of human uterine artery strips to subsequently added 1 μM noradrenaline.

5 It is possible that this enhancement may be involved in decreased regional blood flow following soman administration.
Comparative Effects of Several Chelating Agents on the Toxicity, Distribution and Excretion of Aluminium
Authors: Domingo J.L. , Gómez M. , Llobet J.M. , Corbella J.
Published: December 2008

The relative efficacy of citric, malic, malonic, oxalic and succinic acids, and deferoxamine mesylate (DFOA) on the toxicity, distribution and excretion in mice exposed to aluminium were compared. Chelating agents were administered intraperitoneally at a dose equal to one-fourth of their respective LD50. To determine the effect of the various chelators on the toxicity of aluminium, various doses of aluminium nitrate (938-3188 mg/kg) were administered intraperitoneally, followed by one of the chelators. Survival was recorded at the end of 14 days. Malic and succinic acids were the most effective.

Malic acid and DFOA were the most effective in increasing the urinary excretion of aluminium. Citric acid was the most effective in increasing the faecal excretion of aluminium. Malonic, oxalic and succinic acids had no overall beneficial effects. Citric acid would appear to be the most effective agent of those tested in the prevention of acute aluminium intoxication. However, before the use of these compounds in human aluminium intoxication is possible, further investigations including the effects of these chelators after chronic aluminium intoxication are required.
The Toxic Effects of Alpha-Chloralose
Authors: Thomas H.M. , Simpson D. , Prescott L.F.
Published: December 2008

1 Alpha-chloralose, formed by the condensation of glucose with chloral, is used as a rodenticide and in the control of bird pests.

2 In two cases of poisoning with alpha-chloralose the clinical features included coma and generalized convulsions resembling the effects of strychnine more than those of chloral hydrate.

3 The principles of management are the support of vital functions in the unconscious patient and removal of unabsorbed poison by gastric lavage. Diazepam may be used to control convulsions.
Acute MCPP Intoxication: Report of Two Cases
Authors: Meulenbelt J. , Zwaveling J.H. , van Zoonen P. , Notermans N.C.
Published: December 2008

1 Two cases of serious intoxication with phenoxy herbicides (MCPP) are reported.

2 Both patients had central nervous system involvement, became unconscious and had an inadequate respiration. Muscle cramps and rhabdomyolysis with renal failure were noted in both. Shortly after admission both patients developed a serious decrease in arterial blood pressure (160/ 80 mmHg to 80/45 mmHg). In one patient this was demonstrated to be caused by a reduction in peripheral vascular resistance.

3 Plasma concentration of MCPP in patient 2 was 298 mg/l (3-4 h after ingestion). The plasma t½ was about 17 h. MCPP plasma elimination probably follows first-order kinetics.
Studies of the 'Adaptive' Repair Response in Human Lymphocytes and V79 Cells after Treatment with MNNG and MNU
Authors: Anderson D. , Fisher P. , Jenkinson P.C. , Phillips B.J.
Published: December 2008

In bacteria, there is evidence that a damage inducible repair response system known as the adaptive response exists since pretreatment with low doses of a simple monofunctional alkylating agent leads to a decrease in both the lethal and mutagenic effects of a subsequent challenge dose of the agent. The evidence for an analagous system in mammalian cells has proved to be inconsistent to date. The induction of chromosome repair mechanisms in human cells by low-dose radiation from tritiated thymidine has been shown to make the cells refractory to the induction of chromosome aberrations by X-rays. The present communication investigates the induction of an adaptive response in human lymphocytes from four donors and V79 cells using SCE and mutation as endpoints and MNNG and MNU for the adapting and challenging treatment. It is clear that a reproducible model of the adaptive response in human lymphocytes is difficult to establish because of the variability between different donors and different culture times. In V79 cells, assays with much larger cell numbers are required to detect a reproducible response with such small changes in mutant frequency. To demonstrate an adaptive response conclusively in mammalian cells will probably require the use of more sensitive experimental protocols and alternative methods of administration of adaptive doses of mutagen.