Lethal Intoxication Research Articles

Lethal intoxications with morphine in Sweden 1966?1974

Fatal intoxications with morphine derivatives have become increasingly common in Sweden. Toxicologic data and pathologic findings in 34 cases of morphine intoxications from 1966 to 1974 in Sweden are presented. From 1972 on when morphine the black market, lethal intoxications with centrally stimulation amines.

Lethal intoxications with centrally stimulating amines in Sweden 1966-1973.

Fatal intoxications with centrally stimulating amines (CSA) have become increasingly common in Sweden. Toxicological data and pathological findings of 32 cases of amphetamine and phenmetrazine intoxications which occurred from 1966-1973 in Sweden are described. Furthermore, 13 cases where these drugs were not the cause of death, but found in urine and organs, are reported.

Report on a lethal antazoline intoxication.

A lethal antazoline intoxication is reported and a method for isolation and determination of this compound and two hydrolysis products in autopsy material is described. Analytical findings in liver tissue, kidney tissue and blood are given. Definite identification of the compounds found was obtained by mass spectrometry.

Evaluation of the cause of death in cases of acute alcohol poisoning

During the 10-year period 1959–1968 the amount of acute lethal poisonings (in the full sense of the word) with ethyl alcohol recorded in the Poznań centre was an average of 2.5% of all autopsies. The increase of this number during the last period is alarming: 3.1% during 1964–1967, compared to 1.6% in 1960–1963. The increased frequency of acute lethal poisonings with ethyl alcohol presents proof of the constant necessity of a systematic fight against alcoholism by all attainable means and especially by the education of society as a whole. In persons who died from acute ethanol poisoning the concentration of the alcohol in blood was usually lower than in the urine; it is very likely that death occurs some time after the peak concentration of alcohol in the blood has occurred. Only in a few cases was the concentration of alcohol in the blood higher than in the urine (death during the phase of absorption). Data from the inquiry must be taken into consideration with the results of autopsy and laboratory investigations when evaluating deaths due to alcohol poisoning.

Lethal orphenadrine intoxications. A report of five cases.

Five cases of lethal orphenadrine intoxications are reported. The concentration of the drug in liver ranged from 17 to 41 mg per 100 g. The results are compared with findings in fatal intoxications with phenothiazines and other tricyclic amines.

Effects of ouabain on spontaneous afferent activity in the aortic and carotid sinus nerves of cats

Spontaneous afferent traffic over aortic and carotid sinus nerves was studied in cats subjected to progressive, lethal intoxication with ouabain. Neural activity was enhanced by the glycoside administration in 80% of aortic nerves and in 86% of carotid sinus nerves. While chemoreceptor activity was not separated from baroreceptor activity with certainty, the results suggested that both types of function were increased.

Hemoglobin and Escherichia coli , a Lethal Intraperitoneal Combination

Intraperitoneal injection into mice of approximately 8 x 10(6) washed cells of Escherichia coli suspended in a lysate of washed human red blood cells or an aqueous solution of crystalline hemoglobin was lethal. E. coli suspended in washed intact erythrocytes, whole blood, plasma, or saline was innocuous. Fractionation of non-hemoglobin proteins from hemoglobin in lysates showed that only hemoglobin promoted a lethal infection. Overwhelming intraperitoneal growth of E. coli was attained in about 12 hr in lethal infections. The polymorphonuclear leukocytic response was ineffective against this rapid growth. The lethal mechanism is hypothesized to center on a unique role for free hemoglobin in inhibiting peritoneal absorption and stimulating an intraperitoneal exudate which supports luxuriant bacterial growth. Death is attributed to a lethal intoxication from bacterial endotoxins. This role for hemoglobin involves neither enhanced bacterial virulence nor lowered host resistance, and it would be of importance not only in peritonitis but also in problems where hemolysis and infection coexist.

Effect of compound 48/80 on toxicity of histamine and of serotonin in mice.

Summary(1) Compound 48/80 appears to have an additive effect on toxicity of histamine and a synergistic effect on toxicity of serotonin in the mouse. (2) Heparin interferes with this compound 48/80 effect on lethal intoxication with histamine or serotonin by direct interaction with compound 48/80 but does not appear to alter individual toxicities of respective amines. (3) It is suggested that degranulation of mast cells in response to compound 48/80 is a protective function of connective tissue in which the releaser drug is sequestered by heparin of the mast cell. The associated release of amines is thought to be a manifestation of this interaction between mast cells and compound 48/80 and only indirectly related (if at all) to lethal effects of this drug.

PROTECTION AGAINST LETHAL ORGANOPHOSPHATE POISONING BY QUATERNARY PYRIDINE ALDOXIMES

The effect of 18 pyridinium aldoximes on diethylphosphoryl-acetocholinesterase in vitro and the protection against lethal poisoning by ethyl pyrophosphate (TEPP) in mice pretreated with 0.095 m.mole/kg. of these oximes was investigated. Monoximes and dioximes of polymethylenebispyridinium compounds were studied in greater detail since they were up to 22 times more potent than pyridine-2-aldoxime methiodide (2-hydroxyiminomethyl-N-methylpyridinium iodide) in reactivating diethylphosphoryl-acetocholinesterase in vitro and protected mice against lethal poisoning by up to 15 LD100 of ethyl pyrophosphate. These oximes were also up to 52 times more potent than pyridine-2-aldoxime methiodide in reactivating di-isopropylphosphoryl-acetocholinesterase in vitro and were effective in preventing lethal poisoning by dyflos (di-isopropyl phosphorofluoridate). The antidotal action against diethyl phosphostigmine (Ro 3-0340) was even greater than that against ethyl pyrophosphate. Some of the most effective oximes had antidotal actions in poisoning by ethyl pyrophosphate, diethyl phosphostigmine and dyflos when given in 0.0095 m.mole/kg. and this effect was enhanced by 1 mg./kg. atropine sulphate. In vivo reactivation of diethylphosphoryl-acetocholinesterases by 0.0095 or 0.095 m.mole/kg. of oximes of polymethylenebispyridinium compounds was demonstrated in blood but not in brain. Atropine-like and neuromuscular blocking activities were studied on isolated organs and protection against lethal doses of neostigmine and related anticholinesterases were also investigated. Some of the oximes of polymethylenebispyridinium compounds have, relative to pyridine-2-aldoxime methiodide, a higher therapeutic ratio in mice and considerably greater water-solubility. The possible advantages to be gained from their use in preference to pyridine-2-aldoxime methiodide are discussed.

Protection by oximes of bis-pyridinium ions against lethal diisopropyl phosphonofluoridate poisoning.

THE monoximes and dioximes of bis-pyridinium ions are considerably more effective than any other known compound in re-activating acetocholinesterase inhibited by tetraethyl pyrophosphate and in protecting mice against lethal tetraethyl pyrophosphate poisoning1. Equally favourable results have now been obtained in experiments in which diisopropyl phosphonofluoridate was used instead of tetraethyl pyrophosphate. Tables 1 and 2 show the effectiveness (relative to pyridine-2-aldoxime methiodide) of four oximes of bis-pyridinium ions in restoring the activity of acetocholinesterase freshly inhibited by diisopropyl phosphonofluoridate, and the protection given by 0.095 m.mole/kgm. of the same compounds against lethal poisoning by diisopropyl phosphonofluoridate in mice. Results obtained with three other compounds, a monoxime (n = 5) and two dioximes (n = 2 and 5), are not included in Tables 1 and 2 because they are inferior to compounds 1–4 as regards therapeutic ratio or water solubility.

A case of photo-imaging agent poisoning

Acute lethal poisonings with photoprothylene ("metol") are described extremely rarely. In the available literature we found only one work devoted to the clinic and morphology of this poisoning (T.A. Savelieva). This issue is also insufficiently covered in manuals on occupational and domestic poisonings, which affects the provision of effective care. From this point of view, our case can be of interest for clinicians, forensic physicians and pathologists.

The effect of cortisone upon typhoid intoxication in rabbits

The introduction of cortisone in the dose of 5 mg per kilogram of body weight to rabbits twice a day in lethal typhoid intoxication prolonged the life of these animals up to 38 hours, on the average. However, it had no effect on the disturbance of the sugar concentration, blood level of adrenalin and the level of ascorbic acid in the blood and suprarenal glands. It had a certain retarding effect on depletion of adrenalin in the suprarenal glands.

The effect of water and potassium chloride ingestion on the level of urinary 17-ketosteroids in the rabbit.

MUCH evidence indicates that adrenal cortical extracts and desoxycorticosterone acetate promote the excretion of ingested water and provide protection against lethal water intoxication in both normal and adrenaleetomized animals (Gaunt, Birnie, and Eversole, 1949). Furthermore desoxycorticosterone has been found to be an effective stimulant for potassium excretion in the adrenalectomized animal. In view of these facts one might expect the normal experimental animal to respond to excessive quantities of potassium or water with an increased production of adrenal cortical hormones facilitating water or potassium excretion. McHenry et al. (1947) observed such a correlation between urine volume and the excretion of 17-ketosteroids in patients with carcinoma of the prostate as well as in normal subjects although thorough study of the effect of the administration of large quantities of water upon the level of urinary 17-ketosteroids was made in but one instance.

Effects of dihydrogenated alkaloids of argot on the experimental pulmonary edema caused by adrenalin, methyl-salicylate and thiourea

In all known cases, rabbits that have been injected intravenously with dihydrogenated alkaloids of ergot and subsequently injected intravenously with 2 mg of adrenaline (d. l. 100) (irrespective of animal weight) do not manifest any sign whatever of pulmonary edema and, in fact, acquire immunity against the acute lethal intoxication normally called forth by adrenaline.

Protection of Normal Rats Against Death from Water Intoxication with Adrenal Cortical Substances.

SummaryLarge doses of adrenal cortical extract or desoxycorticosterone acetate will protect normal rats from doses of water which otherwise produce lethal water intoxication.

NICOTINE POISONING IN A CHILD

Nicotine is one of the most lethal poisons known to man. Some conception of its extreme toxicity may be gained by comparing it with hydrocyanic acid, which is of approximately equal potency. Nicotine is present in appreciable quantities in tobacco (ranging from 0.6 to 8 per cent),¹the poorer grades containing relatively more than the better grades. Since tobacco is used so widely both for smoking and for chewing (including snuff), it is amazing that so few instances of fatal poisoning from nicotine have been recorded. As far as smoking is concerned, a possible explanation may be the destruction of the drug by combustion and also its expulsion with the smoke. Then too, marked tolerance acquired by the habitual use of tobacco is undoubtedly an important factor. Consequently, in a majority of instances nicotine poisoning among adults has been traced to the ingestion of some strong solution of the

THE TOXIC PROPERTIES OF SERUM EXTRACTS OF HEMOLYTIC STREPTOCOCCI

1. A method is described whereby toxic substances may be extracted from hemolytic streptococci with inactivated serum. 2. Such extracts contain large amounts of hemotoxin and leucocidin. 3. Their intravenous injection into mice causes marked hemoglobinuria, anemia, and death. 4. There is evidence that this anemia is not the only cause of death of these animals. 5. Incomplete work seems to indicate that the hemotoxin and the lethal poisons are not antigenic. 6. Certain biological properties of the extract are described.

A COMPREHENSIVE PLAN OF TREATMENT FOR THE SO-CALLED INTESTINAL INTOXICATION OF INFANTS

Intestinal intoxication, while perhaps less frequently seen now than formerly, is still not an uncommon condition, and one greatly feared because of incomplete knowledge in regard to pathogenesis and inadequate measures of treatment. The clinical picture is well known, and is in many respects similar to that reported in inanition fever of the new-born, 1 Asiatic cholera, 2 severe burns, 3 high intestinal obstruction, 4 traumatic and histamine shock, 5 lethal war-gas poisoning, 6 certain cases of influenza 7 and induced dehydration in animals. 8 The basis for correspondence in symptoms is probably to be found in increased blood concentration, a condition common to all of these otherwise unrelated maladies. Since morbid states such as these, wholly diverse in etiology, may present a similar clinical picture, pediatricians ought to recognize the probability that intestinal intoxication, so-called, is but a symptomcomplex dependent largely on abnormal concentration of the blood, a condition

ROENTGEN RAY INTOXICATION

Roentgen radiation of the thorax (abdomen shielded) in dogs, even with large doses (up to 512 milliampere minutes), gives no clinical evidence of intoxication. There may be a transient leucopenia and a slight rise in urinary nitrogen. Roentgen radiation of the abdomen (thorax shielded) in dogs, with a dose of 350 milliampere minutes, will almost certainly cause a fatal intoxication. Smaller doses may be survived but usually with signs of gastrointestinal intoxication. This lethal intoxication due to abdominal radiation presents a remarkably uniform clinical and anatomical picture. There is a latent period of 24 to 36 hours, during which the dog is perfectly normal clinically. The 2nd day usually shows the beginning of diarrhea and perhaps some vomitus. The 3rd and 4th days show progressive intoxication with increasing vomiting and bloody diarrhea until the dog becomes stuporous. Death is almost always on the 4th day. Anatomically the only lesions of significance are to be found in the small intestine. The epithelium of the crypts and villi shows more or less complete necrosis, and this condition may involve almost all of the small intestine. The epithelium may vanish completely except for a few cells here and there which have escaped and are often found in mitosis, probably an effort at repair and regeneration. We are forced to the conclusion that this remarkable injury of the epithelium of the small intestine is responsible for the various abnormal reactions and final lethal intoxication which follow a unit dose of Roentgen radiation over the abdomen of a normal dog. This sensitiveness of the intestinal epithelium to x-rays is not appreciated and should be given proper consideration in clinical work.