bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Prospective Study of Self-poisoned Patients in Trondheim, Norway between 1978 and 1987: Epidemiology and Clinical Data
Authors: Rygnestad T.
Published: December 2008

1 In a prospective study of patients hospitalized for deliberate self-poisoning between 1978 and 1987 the number of admissions increased from 303 to 425. The annual incidence increased significantly for both women (P < 0.05) and men (P < 0.01). The mean age decreased significantly in the male group (P < 0.05), but increased in the female group (P < 0.05).

2 The median latency time for patients presenting at the hospital was short; 3.7 h in 1978 and 2.9 h in 1987.

3 There was a significant reduction in the percentage using barbiturates (9% in 1978 and 1% in 1987; P < 0.001) and the use of benzodiazepines increased (18% in 1978 and 32% in 1987; P < 0.05). The percentage of unconscious patients did not change significantly.

4 In 1987 N-acetyl-cysteine was the most frequently used antidote. Physostigmine has almost been abandoned since 1978.

5 Significantly more patients were hypotensive in 1978: 24% vs 11% in 1987; (P < 0.001) and significantly less patients needed treatment in the central intensive care unit (2% in 1987 and 5% in 1978; P < 0.05). Complications were few (8-10%) and the mortality low (approximately 1%) in both years studied.

6 The mean duration of hospitalization in 1978 was 65 h vs 30 h in 1987, (P < 0.001).
Comparison of the binding of 59Fe- and 239Pu-transferrin to rat liver cell membranes
Authors: Planas-Bohne F. , Rau W.
Published: December 2008

The binding of the 59Fe and 239Pu complexes of transferrin and 125I labelled transferrin [Tf (125I) ] to isolated cell membranes of rat liver has been studied. Transferrin forms a complex with an integral protein of the membrane which has an apparent molecular weight of about 180 kDa and is stable only at pH 7.4. Iron-59 is eluted from Sephacryl S 300 columns together with Tf (125I) or the Tf-membrane protein complex while 239Pu seems to be bound to different membrane protein(s).

After isolation of the Tf-binding protein from 35S-labelled membranes and incubation with one of the metal-Tf complexes 59Fe elutes from a Sephacryl S 300 column together with 35S at an apparent molecular weight of ca. 250 kDa while 239Pu is found in fractions of lower molecular weight. It is concluded from these results that there are Tf-receptors in the liver cell membrane to which iron transferrin may bind. Plutonium, however, seems to be dissociated from Tf and bound directly to other membrane proteins.
Post-mortem Serum Concentration of Cantharidin in a Fatal Case of Cantharides Poisoning
Authors: Hundt H.K.L. , Steyn J.M. , Wagner L.
Published: December 2008

A patient admitted to hospital died shortly after admission without a proper diagnosis having been made. Symptoms as well as the presence of a brown powder found in the possession of the deceased indicated the possibility of cantharidin intoxication.

Cantharidin was positively identified by means of a GC/MS analysis, utilizing the selected ion monitoring technique (SIM), for m/z = 197.0813, (M+H+) for cantharidin, under positive chemical ionization conditions at a resolution of 7000 and a mass window of 30 ppm. Quantitation was done by means of a GC/MS SIM analysis of a toluene extract of acidified post-mortem serum under El+ conditions at a resolution of 3000, using clofibrate as internal standard and monitoring m/z = 128.0473 and 128.0029 for cantharidin and clofibrate respectively.

The post-mortem serum was found to contain cantharidin at a concentration of 72.3 ng/ m l whilst the cantharides powder contained 0.87% cantharidin.
Vaginal Absorption of Polyvinyl Alcohol in Fischer 344 Rats
Authors: Sanders J.M. , Matthews H.B.
Published: December 2008

Polyvinyl alcohol (PVA) is a polymer with a wide range of molecular weights and uses. Recently, low molecular weight formulations of PVA have been used as components of contraceptive products designed for intravaginal administration in human females. Previous studies in animals have determined that little or no absorption of PVA occurs from the gastrointestinal (GI) tract. However, there is some concern that PVA of lower molecular weights might be absorbed across membranes of the reproductive tract. Consequently, this work has investigated the absorption of low molecular weight PVA across biological membranes of the reproductive and GI tracts of Fischer 344 rats. Oral administration of ten consecutive daily doses of14C PVA resulted in little apparent absorption of the dose from the GI tract. In contrast, intravaginal administration of14C PVA resulted in increasing concentrations of PVA-derived radioactivity in major tissues following one, three or ten daily doses of the estimated human dose of 3 mg/kg. PVA-derived radioactivity was concentrated mainly in the liver, reaching a peak greater than 1750 ng equivalents/g tissue 24 hours following ten daily doses. Over 300 ng equivalents/g tissue were still present in the liver 30 days following the last dose.
Severe Oxprenolol Poisoning: The Importance of Glucagon Infusion
Authors: O'Mahony D. , O'Leary P. , Molloy M.G.
Published: December 2008

We describe a case of severe oxprenolol poisoning (8 g overdose) where restoration of normal blood pressure depended critically on high-dose glucagon infusion after several bolus injections of glucagon had failed. We stress the importance of infusion delivery of glucagon in severe beta-blocker poisoning.
National Poisons Information Centre in a Developing Asian Country - The First Year's Experience
Authors: Fernando Ravindra
Published: December 2008

The National Poisons Information Centre (NPIC) in Sri Lanka was established in January 1988. It received 353 enquiries in the first year of which 37% concerned pesticide poisoning. More than half the instances were of self-poisoning; consistent with the high suicide rate in the island. Over a quarter of poisoning episodes were among 19-25 year olds. Follow-up of enquiries showed 31 (9%) deaths. Collaboration with developed countries helped in the formation of the NPIC, fulfilling a long felt need among doctors in the island.
Specific Anti-digoxin Fab Fragments: an Available Antidote for Proscillaridin and Scilliroside Poisoning?
Authors: Sabouraud A. , Urtizberea M. , Cano N. , Garnier R. , Scherrmann J.M.
Published: December 2008

The purpose of this study was to evaluate the capacity of specific anti-digoxin Fab fragments to bind to and neutralize scilliroside and proscillaridin in acute poisoning. Apparent affinity constants were determined with values of 2.6 108M -1 for scilliroside and 3.8 107M-1 for proscillaridin. These results are in accordance with a possible in-vivo neutralization of these toxins.
The Effect of the ?-Particle Emitter Astatine-211 in the Mouse at the Minimum Toxic Dose
Authors: Cobb L.M. , Butler S.A. , Harrison A.
Published: December 2008

The radioactive halogen astatine-211 was injected into mice in an amount producing minimal toxicity. Histopathological examination of tissues at intervals between 3 d and 16 weeks showed the following changes:

1 Radiation-induced necrosis and progressive fibrosis of the thyroid gland. The gland was reduced to 25% of its original mass with only a few relatively normal follicles persisting.

2 A small, temporary, reduction in peripheral blood lymphocytes, platelets and red cells and a significant persistant increase in polymorphs.

3 Severe reduction in reproductive cells in the testis with some signs of recovery at 16 weeks.
Photopic luminance does not always predict perceived room brightness
Authors: Berman S.M. , Jewett D.L. , Fein G. , Saika G. , Ashford F.
Published: December 2008

The perception of room brightness over photopic luminances ranging from 30 cd m-2 to 67 cd m-2 was judged by 12 subjects in an almost uniformly white experimental chamber. Two different illuminants were compared which had different spectral compositions, but were colour matched. Brightness judgements were often opposite to large differences in photopic luminance. These results are inconsistent with models of brightness perception that depend solely on cone receptors. At the luminance levels considered here subjective evaluation of light intensity depends upon both photopic and scotopic spectral contributions. These results imply that aspects of the visual system operate mesopically under most interior lighting conditions.
Showlight 89
Authors: Ackerman K.R.
Published: December 2008

The Colloquium on Television, Theatre and Film Lightin~-`~hawlight 89a--was held in Amsterdam and Hilversum from 15-17 May. It was organised by the British NIC panel on Television, Theatre and Film Lighting. Hosts for the event were NOB (Netherlands Broadcasting Services Corporation). This was the third such Colloquium organised under CIE auspices. 'Showlight 89' proved to be an outstanding success with over 250 delegates coming from 27 countries in four continents and exhibitors, in the accompanying comprehensive exhibition, representing the entertainment industry of six countries.
Zenith luminance and total horizontal illuminance of the tropical clear sky
Authors: Sastri V.D.P. , Manamohanan S.B.
Published: December 2008

Data on zenith luminance and total horizontal illuminance obtained for tropical clear sky at Delhi showed strong turbidity-related seasonal dependance. A comparison of the variability of these parameters with solar height for the Delhi sky with variabilities for other locations, as given by data-based empirical equations and as calculated theorectically, revealed significant differences. The best approximation to zenith luminance and its variability for different locations was obtained with the formula of Dogniaux. A similar approximation was obtained for the total horizontal illuminance of different locations with the values and variabilities as derived, combining Dogniaux's formula for zenith luminance with the luminance distribution of Kittler. Exceptions to this type of approximation may be noticed for locations with special atmospheric conditions and ground reflectance.
HI-6 in Man: Efficacy of the Oxime in Poisoning by Organophosphorus Insecticides
Authors: Kusic R. , Jovanovic D. , Randjelovic S. , Joksovic D. , Todorovic V. , Boskovic B. , Jokanovic M. , Vojvodic V.
Published: December 2008

The efficacy of the oxime HI-6 was studied as a treatment for organophosphorus poisoning. HI-6 was given four times daily as a single intramuscular injection of 500 mg accompanied by atropine and diazepam therapy. Oxime treatment was started on admission and continued for a minimum of 48 h and a maximum of 7 d. HI-6 rapidly reactivated human blood acetylcholinesterase inhibited by diethoxy organophosphorus compounds, while the dimethoxy-inhibited enzyme was mainly resistant to the treatment by HI-6. Although both HI-6 and pralidoxime chloride reactivated the red blood cell cholinesterase in quinalphos-poisoned subjects, the return of enzyme activities was more rapid following the use of HI-6. The general improvement of poisoned patients, which was sometimes more rapid than the rise of acetylcholinesterase activity, pointed to direct pharmacological effects of HI-6. No undesirable side-effects were noted in patients when HI-6 plasma concentrations were maintained at levels far above the 'therapeutic' concentration for up to 7 d.
Poisoning with a Traditional Remedy Containing Potassium Dichromate
Authors: Michie C.A. , Hayhurst M. , Knobel G.J. , Stokol J.M. , Hensley B.
Published: December 2008

A fatal case of potassium dichromate ingestion is documented. A retrospective review of serum and organ levels of chromium demonstrates that charcoal haemoperfusion, peritoneal and haemodialysis are ineffective therapies for the toxin. Other treatments for this poisoning are reviewed, the poor prognosis of dichromate ingestion, and the paucity of effective therapy underlined. The application of dichromates in traditional medications is briefly discussed; this is a toxin which may be more prevalent than previously thought. It is proposed that the exposure limits of dichromate be more widely publicised.
Possible Risk Considerations for Toxic Risk Assessment
Authors: Illing H. Paul A.
Published: December 2008

The concepts of 'negligible', 'tolerable' and 'unacceptable' risk are considered in the context of 'voluntary' and 'involuntary' risks. Levels of risk for different ill health consequences are examined in relation to the various types of risk associated with standard setting and, in particular, for standards relevant to workplace ill-health.
Efficacy of Flumazenil in Acute Alcohol Intoxication: Double Blind Placebo-Controlled Evaluation
Authors: Lheureux P. , Askenasi R.
Published: December 2008

Flumazenil acts as an antidote for pharmacological and toxic effects due to benzodiazepines. Several isolated observations and short uncontrolled series have also suggested a possible effect against the impairement of consciousness induced by pure alcohol intoxication.

Patients admitted in the emergency department with coma related to acute alcohol (ALC) or pure benzodiazepine (BZD) intoxication were randomized and treated blindly with either placebo or 1 mg flumazenil. A modified Glasgow score was used to observe the evolution of consciousness. In the 18 ALC patients, 1 mg flumazenil was not more effective than placebo, whereas it appeared to be very active in the BZD group. However, an open administration of higher doses of flumazenil (2-5 mg) in 11 ALC patients, whose condition had not initially improved, was followed by clear improvement of consciousness in five of them. Flumazenil, administered at a dose usually active against BZD sedation, does not improve CNS depression induced by ALC intoxication. Higher doses could be more effective in some patients, but it should also be verified in a placebo-controlled trial.
The Consequences of Iron Overdose and its Treatment with Desferrioxamine in Pregnancy
Authors: McElhatton P.R. , Roberts J.C. , Sullivan F.M.
Published: December 2008

A study was carried out to assess the effect on the outcome of pregnancy of iron overdose and its treatment with desferrioxamine. Sixty-eight cases were drawn from those reported to the United Kingdom National Poisons Information Centre and the Teratology Information Service at Guy's Hospital, London, and follow-up was obtained in 51 of these. Two were subsequently reported not to be pregnant and there were 49 records of pregnant patients who took iron overdoses and where outcome of the pregnancy was known. Twenty-five of these patients were treated with desferrioxamine.

In 48 of the 49 patients the dose of iron allegedly taken was known and in 28 (60%) was over 20 mg kg-1, sufficient to put them at risk of toxicity. In the 36 whose serum iron levels were measured, 20 patients had levels in excess of 60 μmol l-1, indicating a risk of moderate or severe toxicity. Of the 49 pregnancies, 43 resulted in live babies, two had spontaneous abortions and there were four elective terminations. Of the live babies, three were premature, two of whom had problems, and there were three other babies with abnormalities. All babies with malformations were associated with overdoses after the first trimester and so the malformations cannot be directly related to the overdose. A total of 25 patients received desferrioxamine of whom two had malformed babies, but the desferrioxamine can be excluded as a cause. There was no correlation between the serum iron levels and the birthweights.

In conclusion, iron overdose in pregnancy can be fatal and antidote treatment if appropriate should not be withheld. The majority of second and third trimester iron overdoses, treated with desferrioxamine or other antidotes, will have a normal pregnancy outcome. The risk of spontaneous abortion is low but cannot be excluded.
The Clinical and Biochemical Study of Pesticide Sprayers
Authors: Srivastava A.K. , Gupta B.N. , Mathur A.K. , Mathur N. , Mahendra P.N. , Bharti R.S.
Published: December 2008

Clinical, haematological and biochemical studies of 34 subjects, occupationally exposed to different types of pesticides, were conducted. The findings have been compared with those observed in 14 control subjects. Inhibition of cholinesterase activity was observed in the exposed group. Serum alkaline phosphatase was also found to be raised. Radiological examination revealed pneumonitic patches in the chest skiagrams of three exposed subjects. Paraesthesia with hyporeflexia was also found in 8.8% of exposed subjects. The findings suggest that exposure to multiple pesticides over many years affects the normal functioning of different organ systems and may produce characteristic clinical effects.
Persistent Ethanol Drinking Increases Liver Injury Induced by Trinitrotoluene Exposure: An In-plant Case-Control Study
Authors: Li Jie  , Jiang Quan-Guan , Zhong Wei-Dong
Published: December 2008

On the basis of a general survey conducted in a munitions plant, a case-control study was made on the various risk factors of liver damage induced by trinitrotoluene (TNT) exposure in the plant.

One-hundred male cases with occupational TNT liver damage were paired with 100 male controls, one-by-one, for occupation, age and duration (years) of employment. A total of 55 possible risk factors were statistically analysed with a single factor analysis. On the basis of the single analysis, nine factors including drinking, smoking and education were further analysed with a conditional logistic regression model. A calculation was made on the odds ratio (OR) of each factor selected into the model. According to the estimated parameter of the established logistic model, the relative risk of the risk factors could be worked out. Finally, two factors, the amount of ethanol drunk on each occasion and the frequency of drinking every week were selected into the model at the level of a = 0.05. The result showed that these two factors have a dose-response relationship with their OR of occupational TNT liver damage, but there is no connection between smoking and occupational TNT liver damage and no interaction between drinking and smoking.

The above results have revealed that people exposed to TNT and with a long history of heavy drinking, have a greater risk of suffering from chronic liver impairment than those that do not drink.
Calculation of reflecting and refracting optical elements
Authors: Stanioch W.
Published: December 2008

The paper describes a calculation method for the design of optical elements to be used in luminaires and light sources. The method enables the design by IBM PC of mirror profiles and refracting prismatic structures producing any light distribution from radiation incident at any angle. Typical calculations are given and compared with those of mathematical and physical models.
Elevation of Lead in Human Blood from its Controlled Ingestion in Beer
Authors: Newton D. , Pickford C.J. , Chamberlain A.C. , Sherlock J.C. , Hislop J.S.
Published: December 2008

1 Nine volunteers ingested high levels of lead in beer over a 28-d period. The increase in blood lead varied by a factor of about two. There was a similar two-fold variability in the whole-body uptake (mean 14%) of a single oral dose of the short-lived tracer 203Pb.

2 The average elevations led to estimates of the potential increment from consumption of alcoholic beverages which accord broadly with epidemiological observation and which, if relevant to intakes of lead in table wine, raise the possibility of considerably elevated levels in the blood of avid consumers.

3 Rate constants inferred for removal of stable lead from blood were lower than reported following intake of the tracer, reflecting feedback of lead from other compartments.
Immunotoxic Effects of MPT-IP Containing 60% Methylparathion in Mice
Authors: Institóris L. , Siroki Olga , Tóth S. , Dési I.
Published: December 2008

The effects of a single large and repeated small doses of MPT-IP (the industrial product used to produce Wofatox EC 50) containing 60% methylparathion, on the humoral and cellular immunoreactivity of CFLP mice were investigated.

Administration of a single LD50/2 dose 3 d prior to immunization caused a 40% increase in the number of splenic PFC on the 5th day but no significant increase in serum antibody titre on the 7th day after immunization.

Treatment for 4 weeks with an LD50/40 dose resulted in a 100% increase in splenic PFC, also not associated with a change in serum antibody titre. Under the same conditions and LD50/20 dose had no effect on these parameters.

Neither the single large nor the repeated small doses had any effect on the intensity or time course of a DTH reaction.

The results show that MPT-IP has an immunotoxic potential in mice under certain experimental conditions.
Assessment of Pentachlorophenol Exposure in Humans using the Clearance Concept
Authors: Reigner Bruno G. , Bois Frédéric Y. , Tozer Thomas N.
Published: December 2008

1 Pentachlorophenol (PeCP), a widely-used wood preservative, is a ubiquitous compound which has been found to be carcinogenic in mice. The objective of this study is to assess the average net daily intake of PeCP in cohorts of individuals who are: (1) not specifically exposed to PeCP, (2) residents of homes made of PeCP-treated logs and (3) occupationally exposed to PeCP.

2 The average net daily intake was calculated using a basic pharmacokinetic principle, the clearance (CL) concept: net daily intake equals CL (in 1 d-1) times the average steady-state concentration of PeCP in plasma ( Css). Css values reported in the literature were used for the calculations.

3 Because the two definitive studies on PeCP toxicokinetics in humans have given conflicting results, kinetic information from human exposure to PeCP was reviewed. Plasma clearance was estimated from retrospective analysis of urine and plasma concentrations measured in people after long-term exposure to PeCP. An overall clearance of 0.425 1 d-1 was obtained.

4 In groups of individuals who are not specifically exposed to PeCP, net daily intake estimated in eight countries varied from 5 μg (Nigeria) to 37 μg (The Netherlands). Net intake was between 51 μg d-1 and 157 μg d-1 in residents of homes made of PeCP-treated logs. In individuals occupationally exposed to PeCP, net daily intake varied widely (from 35 μg to about 24 000 μg) depending on the type of work.
Dangerous Mixture of Household Detergents in an Old-style Toilet: a Case Report with Simulation Experiments of the Working Environment and Warning of Potential Hazard Relevant to the General Environment
Authors: Minami Masayasu , Katsumata Masao , Miyake Kazumasa , Inagaki Hirofumi , Fan Xiao-Hui , Kubota Hideo , Yamano Yoko , Kimura Osamu
Published: December 2008

A housewife cleaned toilet porcelain connected directly to a sewage storage tank with a mixture of cleaning agents; sodium hypochlorite (NaOCl) and hydrochloric acid (HCl) solutions. She complained of insomnia on the night after cleaning and suffered from severe metabolic acidosis with extremely low blood pH, PCO2 and bicarbonate values. She recovered from the acidosis after bicarbonate transfusion, plasmapheresis and plasma exchange. Permanent blindness ensued, however, from the third day after the event. These clinical symptoms suggested that the toxic substances responsible were chloramine and methyl chloride. Their generation was confirmed by in-vitro experiments, mixing NaOCl, HCl and pooled urine from normal people. In the simulation, the methyl chloride level far exceeded (100 000 ppm) the maximal allowable concentration recommended (ca 400 ppm) by the American Conference of Governmental Industrial Hygienists (ACGIH). Chloramine's toxic actions were confirmed using purified enzyme assay, and the inhibition of carbonic anhydrase and aldehyde dehydrogenase and the enhancement of superoxide dismutase activity were confirmed in neutral pH. The patient's clinical symptoms suggested that insomnia and permanent blindness seemed to be partly ascribable to chronic repetitive exposure to methyl chloride; catching a cold, drug intake and alcohol intake, in addition, precipitated the patient's visual loss. The possibility of this kind of intoxication with such a mixture of agents may lie latent in any situation where sewage or garbage are exposed to the open air.
Aldrin and Dieldrin Residues in Human Fat, Milk and Blood Serum Collected from Delhi
Authors: Nair Amit , Dureja P. , Pillai M.K.K.
Published: December 2008

1 Aldrin and dieldrin residues were monitored in the fat, breast milk and blood serum from female residents of Delhi.

2 The average aldrin and dieldrin contents were 0.048 and 0.099 ppb in adipose tissue, 0.003 and 0.060 ppb in breast milk and 0.004 and 0.002 ppb in blood serum, respectively.

3 The older donors contained higher levels of aldrin and dieldrin in their adipose tissue.

4 Primagravidae contained more of these chemicals in their breast milk.

5 A positive correlation was observed between the aldrin concentration in adipose tissue and breast milk, and that in adipose tissue and blood serum. Similarly, a significant correlation was found between dieldrin in adipose tissue and blood serum.

6 The levels of aldrin and dieldrin were low in samples from residents of Delhi when compared to those in developed countries.
Cardiac Toxicity Following Short-Term Exposure to Methomyl in Spraymen and Rabbits
Authors: Saiyed H.N. , Sadhu H.G. , Bhatnagar V.K. , Dewan A. , Venkaiah K. , Kashyap S.K.
Published: December 2008

A health surveillance study in 22 healthy spraymen showed significent T-wave changes (including inversion) in most of the limb leads and chest leads following 5 d exposure to methomyl, a carbamate pesticide. Significant changes in plasma cholinesterase and lactic dehydrogenase activities were also noticed. The ECG changes could be reproduced in rabbits and were dose dependent. This type of ECG change following exposure to a carbamate compound is reported for the first time in occupationally-exposed subjects. The study results indicate that these changes are probably directly related to methomyl rather than its toxicity through cholinesterase inhibition. The significance of these changes remain to be investigated.
Drug Interaction between Rifampicin, Isoniazid and Cotrimoxazole in Rabbits
Authors: Malhi R. , Uppal R. , Sharma P.L.
Published: December 2008

1 The results of cotrimoxazole (CTZ) co-administration (15 mg kg-1 trimethoprim + 40 mg kg-1 sulphamethoxazole) on plasma concentration and various pharmacokinetic parameters of rifampicin (RIF, 24 mg kg-1) and isoniazid (INH, 14 mg kg-1) were studied.

2 In the test group ( n = 6), CTZ was administered on the 24th day of antitubercular treatment (ATT) and given for 7 d.

3 At the end of concurrent treatment with CTZ, RIF half-life ( t½) and plasma concentration were both increased. However, there was no effect on INH half-life and plasma concentration.
High-Dose Cyclophosphamide and Dexamethasone in Paraquat Poisoning: A Prospective Study
Authors: Perriëns J.H. , Benimadho S. , Lie Kiauw I. , Wisse J. , Chee H.
Published: December 2008

Between March 1986 and March 1988, 47 consecutive patients, whose paraquat intoxication was confirmed by urine testing, were enrolled in a prospective study on the treatment of paraquat poisoning. Fourteen received a standard treatment regimen consisting of fluid replacement and oral absorbents, and 33 received high-dose cyclophosphamide and dexamethasone, in addition to standard therapy.

The case fatality rate in both treatment groups (63 and 61%) was similar. In addition, all 26 patients whose paraquat serum concentrations were measured and who had a probability of survival of less than 65% according the survival curve of Hart et al. died, regardless of therapy. These included four in the cyclophosphamide/dexamethasone group and two in the standard treatment group who had prior survival probabilities between 50 and 65%. This indicated that the cut-off curve relating mortality and paraquat serum concentrations was similar in both treatment groups.

High-dose cyclophosphamide/dexamethasone treatment is unlikely to improve the prognosis of paraquat poisoning.
Clinical Features and Treatment of Elapidae Bites: Report of Three Cases
Authors: Coelho L.K. , Silva E. , Espositto C. , Zanin M.
Published: December 2008

This report describes two accidents, involving snakes of the Micrurus corallinus species, where compromising respiratory function was not observed and the specific anti-elapidic serum was the single therapy used, and a third incident, probably involving Micrurus frontalis, where neostigmine was used to remedy respiratory failure.
An International Appraisal of the Minimum Duration of Chronic Animal Toxicity Studies
Authors: Lumley Cynthia E. , Parkinson Christopher , Walker Stuart R.
Published: December 2008

1 There are international differences in regulatory guidelines for the appropriate duration of chronic, two species repeat-dose animal tests for new medicines intended for long-term use in man, ranging from 6 months in Europe to 12 months in Japan and the USA.1

2 An adequate data base is necessary to support any challenge to the scientific rationale behind regulatory guidelines with regard to the design, duration and relevance of toxicity tests of new medicines.

3 The Centre for Medicines Research has established an international toxicology data base which has been expanded to enable a comparison of data obtained within 6 months, with information from longer periods, for 154 studies.

4 Although new findings were revealed after 6 months for 9/75 cases for which pathology data are available at 6 and 12 months or longer, and 21/80 with data at 1 or 3 (but not 6 months) and 12 months or longer, in no instance did these influence the decision to drop or further develop the compounds in question.

5 These data suggest that a 6-month period of dosing is all that is routinely required for evaluating the chronic toxic (excluding carcinogenic) potential of a new chemical entity intended for therapeutic use.
Rat Model to Investigate the Treatment of Acute Nitrogen Dioxide Intoxication
Authors: Meulenbelt J. , Dormans J.A.M.A. , Marra M. , Rombout P.J.A. , Sangster B.
Published: December 2008

1 The pulmonary toxic events induced by acute nitrogen dioxide (NO)2 exposure were studied in the rat to develop an inhalation model to investigate therapeutic measures.

2 A good correlation was observed between the lung weights and severity of the atypical pneumonitis. The pulmonary effects observed, became more pronounced with increasing NO 2 concentrations (0, 25, 75, 125, 175 or 200 ppm, 1 ppm NO2=1.88 mg m-3 NO2) and exposure times (5, 10, 20 or 30 min).

3 An adequate NO 2 concentration is 175 ppm, because it can induce a severe lung injury without mortality. This makes it possible to investigate suitable therapeutic interventions for several days.

4 Following acute inhalatory NO2 intoxication, transformation of NO2 to nitrate is presumably more notable than transformation to nitrite.

5 The transformation of NO2 to nitrate in lung tissue causes a slight increase in the serum nitrite concentration, which does not induce measurable formation of methaemoglobin. 6 Presumably, methaemoglobin does not contribute to the toxicity of NO2 intoxication.
Elemental Mercury Vapour Toxicity, Treatment, and Prognosis After Acute, Intensive Exposure in Chloralkali Plant Workers. Part I: History, Neuropsychological Findings and Chelator effects
Authors: Bluhm Renata E. , Bobbitt Robert G. , Welch Larry W. , Wood Alastair J.J. , Bonfiglio J. Frank , Sarzen Christopher , Heath Andrew J. , Branch Robert A.
Published: December 2008

Mercury poisoning occurred after the acute, prolonged exposure of 53 construction workers to elemental mercury. Of those exposed, 26 were evaluated by clinical examination and tests of neuropsychological function. Patients received treatment with chelation therapy in the first weeks after exposure. Eleven of the patients with the highest mercury levels were followed in detail over an extended period. Observations included the evaluation of subjective symptoms of distress, using the 'Symptom Check List 90-Revised' (SCL-90R) and tests of visual-motor function such as 'Trailmaking Parts A and B', 'Finger Tapping', 'Stroop Colour Word Test' and 'Grooved Pegboard.' On day 85 ± 11 (mean±s.d.) after exposure, these 11 men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L-penicillamine (NAP) in a short-term study designed to compare the potential to mobilize mercury and the incidence of drug-induced toxicity of these two chelating agents.

Rapidly resolving metal fume fever was the earliest manifestation of symptoms. CNS symptoms and abnormal performance on neuropsychological tests persisted over the prolonged period of follow-up. There were significant correlations between neuropsychological tests and indices of mercury exposure. Serial mercury in the blood and urine verified the long half-life and large volume of distribution of mercury. Chelation therapy with both drugs resulted in the mobilization of a small fraction of the total estimated body mercury. However, DMSA was able to increase the excretion of mercury to a greater extent than NAP. These observations demonstrate that acute exposure to elemental mercury and its vapour induces acute, inorganic mercury toxicity and causes long-term, probably irreversible, neurological sequelae.
Changes in Antioxidant Lung Protection after Single Intra-tracheal Cadmium Acetate Instillation in Rats
Authors: Salovsky P. , Shopova V. , Dancheva V. , Marev R.
Published: December 2008

One-hundred male white rats were given a single intratracheal dose of 0, 5 mg kg-1 cadmium acetate. There was a fall in catalase (CAT) and superoxide dismutase (SOD) in lung homogenate throughout the 30 d after treatment. Non-protein sulphhydryl (NPSH) content, glucose-6-phosphate dehydrogenase (G-6-PD) and glutathione peroxidase (GP) were all increased from days 5 to 15. There was an increase in lactate dehydrogenase (LDH) and protein in bronchoalveolar lavage fluid (BALF) and in the relative weight of the lungs which provide evidence of severe toxic lesions of the lungs. Increased lipid peroxidation provoked by the reduced lung antioxidant protective capacity may be an important mechanism in the pulmonary damage caused by cadmium.
Pharmacokinetics of Fluazifop-butyl in Human Volunteers II: Dermal Dosing
Authors: Ramsey J.D. , Woollen B.H. , Auton T.R. , Batten P.L. , Leeser J.E.
Published: December 2008

1 The absorption of the herbicide fluazifop-butyl (f-b), has been determined from plasma and urine measurements in groups of six male volunteers following dermal administration of 2.5, 25 and 250 ?g cm-2 from standardized formulations containing 0.05, 0.5 and 5.0% (w/v) fluazifop-butyl to a skin area of 800 cm2.

2 Urinary excretion rate of the principal metabolite fluazifop, following dosing with the 5% formulation, was described by a two-compartment pharmacokinetic model; the average elimination half-lives of initial and terminal phases were 18 h and approximately 70 h, respectively. For the other dose levels the elimination half-life was estimated to be 17 h; urine concentrations at later time points were too low to characterize a second compartment.

3 The estimated total fluazifop-butyl absorbed was 8.0, 3.4 and 1.6% of the applied dose for the 0.05, 0.5 and 5.0% formulations, respectively.

4 Up to 50% of the applied fluazifop-butyl was readily removed by skin washing and the majority of the remainder was transferred to clothing during the 24 h following application.

5 When six volunteers were given a daily dermal dose of the 0.5% formulation for five consecutive days, the plasma and urinary excretion kinetics of fluazifop could be accurately predicted by simple mathematical extrapolation of the kinetic data from the single exposure study at the equivalent daily dose.

6 It is concluded that fluazifop-butyl is only slowly and poorly absorbed through human skin and has a low potential to accumulate in man.
Chronic Low-Dose Exposure of Sodium Nitrite in VM-Strain Mice: Central Nervous System Changes
Authors: Hawkes C.H. , Cavanagh J.B. , Darling J.L. , Watkins B.A. , Thomas D.G.T.
Published: December 2008

1 There is suggestive evidence that nitrite may be a causative factor in cerebral glioma.

2 To test this hypothesis we selected the VM mouse strain, known for its susceptibility to spontaneous glioma formation, and exposed 300 animals to 0.2% sodium nitrite in their drinking water. One hundred of this group were exposed both in utero and throughout their adult lives. The remaining 200 animals received nitrite from the time of weaning. A further 200 mice were used as controls and received distilled water.

3 All animals were maintained until their natural death and were then subjected to autopsy and routine histological examination.

4 There was no excess of nervous system tumours in the experimental groups.
Anterograde Amnesia in Triazolam Overdose Despite Flumazenil Treatment: A Case Report
Authors: Hung Dong-Zong , Tsai Wei-Jen , Deng Jou-Fang
Published: December 2008

Anterograde amnesia, possibly accompanied by acute brain syndrome, is a potential side-effect of certain benzodiazepines, particularly triazolam. Flumazenil is a benzodiazepine antagonist that is highly effective in reversing the central nervous system effects of benzodiazepine overdose. We report a case of triazolam overdose resulting in anterograde amnesia after flumazenil administration had restored clear consciousness. The defect in memory may have been due to too little flumazenil being given or failure of memory consolidation affected by the character of triazolam during the induced lucent period. We feel that physicians should be aware of the potential occurrence of acute brain syndrome in patients with benzodiazepine overdose despite treatment with flumazenil.
Individual Differences in Activity of Glutathione Peroxidase and Catalase Studied in Monozygotic Twins Discordant for Smoking
Authors: Björkman Lars , Svartengren Magnus , Nordberg Monica
Published: December 2008

1 Cigarette smoke contains free radicals. The enzymes glutathione peroxidase (GSH-px) and catalase are important parts of the anti-oxidative protecting system.

2 Ten pairs of monozygotic twins, who were discordant for smoking, were analysed in order to determine their erythrocyte glutathione peroxidase and catalase activities and their plasma concentrations of selenium.

3 Analysis of variance (ANOVA) revealed that the difference in activities of catalase and glutathione peroxidase was much less within pairs than between pairs, indicating a large individual variation due to genetic expression or shared environment and no major effect from smoking.

4 The plasma selenium levels of the investigated twins revealed sufficient intake of selenium to maintain maximal activity of GSH-px in erythrocytes. The mean±s.d. selenium concentration in plasma for smokers was 98 ± 16 μg 1-1 and for non-smokers 111 ± 16 μg 1-1. There was no correlation between plasma selenium and glutathione peroxidase in erythrocytes.
Sudden Infant Death Syndrome (SIDS) and the Toxic Gas Hypothesis: Microbiological Studies of Cot Mattresses
Authors: Kelley Joan , Allsopp Dennis , Hawksworth David L.
Published: December 2008

1 Fifty infants' mattresses were studied to investigate the occurrence of viable fungal and bacterial propagules, with particular reference to Scopulariopsis brevicaulis which had been suggested to be implicated in SIDS cases. A total of 19 SIDS cases mattresses, 1 non-SIDS death, 20 used controls, and 10 new unused controls were examined.

2 Differences were found between SIDS and used controls in the variety of fungal species isolated and the numbers isolated from fillings; bacterial numbers were similar.

3 S. brevicaulis was isolated from only four mattresses, three of which were SIDS cases. It was not found in most of those on which death had occurred.

4 A number of potentially pathogenic or allergenic fungi, including Aspergillus fumigatus, were isolated more frequently from SIDS cases mattresses than new or used controls.

5 Scanning electron microscopy of mattress covers and fillings showed microbial 'biofilms' in the head areas of all SIDS cases examined. This was not seen on other samples.

6 The limited number of mattresses studied and the use of unmatched controls precludes the drawing of any general conclusions as to the significance of the biofilms or other fungi isolated.

7 Reports of the existence of a dimorphism in general growth forms of S. brevicaulis were investigated by growing and transferring authentic strains between a variety of growth media.

8 No 'slimy' state of this fungus was observed and dimorphism was not confirmed.
Persistence of metaldehyde during acute molluscicide poisoning
Authors: Moody J.P. , Inglis Fraser G.
Published: December 2008

A case is presented in which a 37-year-old man took an overdose of Slugit, liquid containing metaldehyde. Significant concentrations were found in his serum and urine for several days afterwards. Acetaldehyde and ethanol were not detected. The significance of these findings is discussed.
Toxicology of Sensory Systems: A Perspective
Authors: Lock E.A. , Harpur E.S.
Published: December 2008

This brief review is the result of a recent meeting of the British Toxicology Society (Toxicology of Sensory Systems, University of York, April 2-3, 1992). The meeting provided the opportunity to discuss the anatomy, physiology and function of the eye, ear, nasal epithelium and peripheral sensation and the methods that are available to detect injury or dysfunction both in the preclinical and clinical situation. In addition, the mechanism whereby certain chemicals can perturb some of these organs was discussed. The aim of this short article is to highlight some of the recent advances in understanding in these areas with regard to their relevance or impact on toxicology. For convenience the areas will be discussed under separate headings.
Artificial sky for use with large-scale architectural daylight models
Authors: Lioutsko K.V. , Spiridonov A.V.
Published: December 2008

The Research Institute for Building Physics (NIISF) has developed a unique installation - a successfully functioning large 'Artificial sky'. The paper gives a detailed description of its structural features and facilities.
Natural lighting under translucent domes
Authors: Wilkinson M.A.
Published: December 2008

Expressions for the illuminance on inclined planes from uniform diffuse and CIE overcast skies are used to determine the total flux incident upon a class of domes. An accurate model of flux transfer is then employed to predict the average daylight factor within translucent domes, but it is concluded that under most circumstances a simple approximation is adequate.
The CSP index: A practical measure of office lighting quality as perceived by the office worker†
Authors: Bear A.R. , Bell R.I.
Published: December 2008

Opinion surveys have shown that far too many workers are dissatisfied with the quality of their artificial lighting, despite the fact that, in many cases, their lighting meets the basic requirements of the CIBS Code for interior lighting. Lighting designers find it difficult to obtain a suitable balance between the various design elements. The Comfort, Satisfaction and Performance index (CSP) has been developed, based upon existing data, current Code recommendations and detailed studies of over 650 individual workers and their offices (44). The CSP index is designed to be used in conjunction with the Code and takes a value from 0 to 100 which relates to the probability that office workers will be satisfied with their visual environment.
The No-Effect Level of Sodium Bromide in Healthy Volunteers
Authors: van Gelderen C.E.M. , Savelkoul T.J.F. , Blom J.L. , van Dokkum W. , Kroes R.
Published: December 2008

1 A total of 0, 4 and 9 mg kg-1 body weight sodium bromide was administered orally to 45 healthy female volunteers.

2 The experiment lasted for six menstrual cycles: only during the first three cycles was bromide administered;

3 At the start, at the end of the administration period and at the end of the experiment a physical examination and haematological and routine clinical chemistry tests were performed. Except for nausea in relation to the intake of bromide, no adverse effects were observed.

4 The bromide concentration in plasma rose to 3.22 ± 0.93 mmol kg-1 in the 4 mg kg-1 group and to 7.99 ± 1.89 in the 9 mg kg-1 group by the end of the administration period.

5 Before and at the end of the experiment the thyroid hormones (T4, FT4, TBG, T3 and TSH) were analysed. No significant differences were observed between the groups.

6 Before, after three menstrual cycles and at the end of the experiment an EEG with a Visual Evoked Response was recorded. At the 4 and 9 mg kg-1 dose level in the α1-band and the β-bands significant changes were found (P < 0.1 and P < 0.05, respectively). The Visual Evoked Response showed no significant differences between the three groups.

7 From this experiment and previous experiments a no-effect level in humans for sodium bromide of 4 mg kg-1 body weight is proposed.
The Use of the Dog in Toxicity Tests on Pharmaceutical Compounds
Authors: Parkinson C. , Grasso P.
Published: December 2008

1 The preclinical animal safety testing strategy used in pharmaceutical development is generally successful, with the large majority of new medicines not causing serious toxicity in man. The use of the dog has significantly contributed to this achievement by aiding the selection of safe compounds for human trials.

2 The dog should be selected as the non-rodent species for pharmacodynamic, pharmacokinetic, metabolic and other scientific reasons, not solely for practical considerations.

3 The dog is an extremely useful laboratory animal, particularly for procedures requiring extensive handling, detailed observation or biological sampling.

4 Refinements in the use of the dog have been achieved, but further progress is desirable. Retrospective analysis of pharmaceutical toxicity data could encourage the regulatory flexibility necessary for further progress.
Intoxication from Veratrum album
Authors: Quatrehomme G. , Bertrand F. , Chauvet C. , Ollier A.
Published: December 2008

Two new cases of Veratrum poisoning are described. Clinical symptoms occurred quickly, within 30 min. Vomiting, a fall in blood pressure and bradycardia were observed. The outcome was favourable in both cases, producing a cure without sequellae. Examination of the literature showed that such cases are nearly always accidental, resulting from the difficulty in distinguishing Veratrum album and Gentiana.
Interaction of Cimetidine with Cytochrome P450 and Effect on Mixed-Function Oxidase Activities of Liver Microsomes
Authors: Faux S.P. , Combes R.D.
Published: December 2008

The histamine H2-receptor antagonist drug, cimetidine (CM), was investigated to determine its effect on the metabolism of 'model' alkoxyphenoxazone substrates ethoxyresorufin (ER) and pentoxyresorufin (PR). The investigation was carried out under different conditions in rat liver microsomes from rodents pretreated with various classical cytochrome P450 inducers. CM exerted a dual effect on uninduced and PB-induced liver microsomal ethoxyresorufin-O-de-ethylase (EROD) activities; it was initially stimulatory but became inhibitory. However, when 3-MC-induced preparations were used, CM only exerted an inhibitory effect on EROD activity over the whole concentration range (0.01 μM-20 mM). Pre-incubating PB-induced and uninduced liver microsomes with NADPH before the addition of ER and CM decreased the stimulatory effect of CM and increased the inhibitory effect in the concentration range (5-20 mM). With 3-MC-induced preparations, the inhibition of EROD was only marginally potentiated. Overall conclusions for the diphasic effects of CM on biological activities were due to CM binding with differing affinities to different P450s. Subsequent decreases and increases in stimulation and inhibition, respectively, on pre-incubation with NADPH were thought to be due to an increased affinity of CM for reduced cytochrome P450.