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Case 1 was a 59-year-old female who had been taking distigmine bromide 20 mg/day for 2 years. She had concurrently developed pneumonia and was admitted to the hospital. Her pupil diameter was 1.0 mm, serum ChE value was decreased at 25 IU/L. Case 2 was a 72-year-old male who had been taking distigmine bromide 15 mg/day for 8 months. He was transported to the hospital with a chief complaint of dyspnea. His pupil diameter was 2.0 mm, serum ChE value was decreased at 75 IU/L, and he had concurrent pyothorax. Case 3 was a 74-year-old male who had been taking distigmine bromide 10 mg/day for 4 years. He was transported to the hospital with a chief complaint of disturbance of consciousness. His pupil diameter was 2.0 mm, and serum ChE value was decreased at 55 IU/L. He had concurrent aspiration pneumonia. In Case 1, the distigmine bromide concentration was elevated at 13.2 ng/mL at admission. However, it decreased from the following day. The two other patients had low concentrations of distigmine bromide. In all patients, ChE levels recovered after discontinuing distigmine bromide, and respiratory conditions also improved. Distigmine bromide was no longer detected in blood before ChE levels recovered.

Distigmine bromide (Ubretid) is a long-acting anti-cholinesterase, widely used for the treatment of underactive neurogenic bladder and myasthenia gravis. Our study concerns a 73-year-old man treated with a potentially life-threatening cholinergic state due to distigmine bromide. He had been administered distigmine bromide orally for over two years at a daily dosage of 10 mg as a treatment for underactive neurogenic bladder. He suddenly developed diarrhea and consciousness disturbance during treatment of his urinary tract infection. Bradycardia and miosis were noted. Blood examination revealed extremely low levels of the plasma cholinesterase activity. The condition was diagnosed as distigmine bromide intoxication. All cholinergic symptoms disappeared in several days after the administration of distigmine bromide was terminated. Cholinergic crisis due to overdosage with anticholinesterases is well known, and the myasthenic patients are usually supervised in the early stages of dosage regulation to guard against the possibility of cholinergic crisis. However the use of oral distigmine bromide, even in therapeutic doses for urinary retention, could result in cholinergic crisis. We therefore conclude that extreme caution must be used in administering distigmine bromide.

Severe cases of poisoning with pesticides, especially suicidal ones, continue to be a diagnostic and therapeutic problem in Regional Toxicological Centre in Lublin. The present author describes the pathomechanism of poisonings with dipyridil herbicides basing on the literature on the subject. The present article presents our own observations of the treatment of acute poisonings with the above herbicides, the clinical course, and complications from various internal organs, outcome and prognosis in this type of poisoning cases in the Lublin macro-region basing on the comprehensive material gathered. Our observations confirm high toxicity of dipyridil, especially in the cases of suicidal poisoning with changes in many internal organs and often a lethal outcome. High mortality rate in these cases motivates for finding better prevention methods not only when they are produced and distributed but also when they are used on fields.

Diquat dibromide is a commonly used herbicide. The product label cautions against allowing the material to contact the skin as severe skin irritation is possible as well as absorption of the material into the systemic circulation. Waterproof footwear and clothing should be worn to minimize skin contact. A case of full thickness burns of the feet requiring skin grafting occurred following prolonged exposure of the soles of the feet to diquat dibromide.

A patient developed high fever, cough, changing consolidations on chest roentgenograms, jaundice, and skin rash following inhalation of diquat aerosol. To our knowledge this is the first report of diquat inhalation and only the second report of aerosol damage from any part of the dipyridyl herbicides.

Histoenzymatic changes in cells of the reticulo-endothelial system of liver and spleen and in hepatocytes were studied in the course of acute poisoning with Morfamquat dichloride, without and under the screen of vitamin E (to mice tissue restrictive respiration compound). This herbicide was given to mice in single, intraperitoneal injection of 100 mg/kg b.w. The choice of the enzymes was based on the so-called markers of the lysosomes structures of a cell (acid phosphatase-APh-EC. 3.1.3.2. and beta-glucuronidase-beta-GU-EC. 3.2.1.31) and Golgi apparatus (thiamin pyrophosphatase-TPP-EC. 3.5.99.2) It was stated that Morfamquat dichloride caused clear stimulation in the reticuloendothelial system of the organism, with occurrence of the high activity of APh and beta-GU in the lysosome and phagolysosome structures, growth of the lysosome membranes permeability and passing their content to cytoplasm. Furthermore, the increased activity of TPP-ase in Golgi apparatus hepatocytes of animals liver may point to disturbances of the pirogroniam decarboxylation and also to disturbances of the pentose-phosphate cycle. The application of vitamin E to mice for 5 days before the poisoning, protects animals distinctly against the toxic activity of the herbicide.

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents. Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1-2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1-2 ppm, the clearance values for hemoperfusion were some 5-7 times higher than those for hemodialysis. In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquats less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

Animal experiments have suggested that diquat is less toxic than the more widely used paraquat. In this paper, nine previously reported cases of diquat intoxication are reviewed, together with the description of our personal observations in two additional patients. These two patients, like four other patients described in the literature, died from complications involving the gastrointestinal tract, brain and kidneys. Thus, diquat intoxication is apparently not as innocent as was originally thought. In this paper, special attention has been given to the major clinical differences between diquat and paraquat intoxication. In contrast with the latter, severe diquat intoxication induces gastrointestinal fluid sequestration and is associated with cerebral hemorrhagic lesions and a higher incidence of severe acute renal failure. Despite an asymptomatic clinical interval of up to 48 hours after ingestion, hemoperfusion should be started as soon as possible to prevent toxic levels of diquat in tissue.

Extracorporeal hemodialyses were carried out in a female patient with severe diquat intoxication. Diquat clearance was on average, 3.17 ml/min. Only 0.84 mg diquat could be eliminated from the blood serum by 11.5 hrs of dialysis. Hemodialysis is therefore not an efficient technique for removing amounts of diquat from the organism that are toxicologically relevant one day after ingestion.

A 2 1/2 year old boy accidentally ingested the herbicide diquat. Progressive neurologic dysfunction preceded his death 143 hours after poisoning. Brain stem infarction and purpura were noted at post mortem and closely resembled the brain stem pathology in 3 of 7 adults who died after diquat ingestion. Renal, gastrointestinal and pulmonary involvement in this child also resembled that seen in adults after ingestion of diquat. Hemoperfusion was performed six times in an effort to lower the body diquat burden. Cellulose-coated, activated charcoal was first employed 40 hours postingestion and removed diquat from serum with clearances of 104 and 39 ml/minute at the initiation of hemoperfusion and 6 hours later, respectively. Serum diquat concentrations decreased rapidly during charcoal hemoperfusion. However, marked rebound in serum diquat concentrations were noted between charcoal treatments, indicating extensive sequestration of diquat by tissues. Thrombocytopenia and hypocalcemia, the major complications of charcoal hemoperfusion, were easily treated. Unlike charcoal, Amberlite XAD-4 resin hemoperfusion did not remove diquat from serum. Charcoal hemoperfusion may temporarily reduce serum diquat concentrations. Whether the early institution and daily performance of charcoal hemoperfusion will minimize diquat-induced damage to brain and other organs is not clear from this case and will only be determined in future studies.

A 33-year old farmer ingested approximately 300 ml of a 20% solution of diquat along with about 80 mg flunitrazepam. The patient presented neurological (coma grade I), digestive (oro-pharyngeal erosions, ileus), hepatic (cytolysis), hematological (thrombopenia) and renal (tubular dysfunction) signs. Plasma creatinine did not exceed 1.22 mg/dl (upper normal value), but retinol binding protein level in urine (a marker of renal tubular dysfunction) reached a value of 337 mg/d (normal values less than 300 micrograms/d). Its level returned to normal value 18 days after the ingestion. Four hours after the poisoning, diquat level in blood amounted to 10.4 mg/l, but its level was below the detection limit (0.2 mg/l) 6 hours later. In urine, however, diquat was detected until day 13. The following therapy was applied: ventilation (FiO2:0.21), gastro-intestinal lavage, hemoperfusion, anti-oxidants and prolonged forced diuresis. The patient made an uneventful recovery. intestinal washout must be applied with caution since an ileus is a classical complication of diquat poisoning. Hemoperfusion was found to be of little value. The interest of prolonged application of forced diuresis is suggested by the detection of diquat in urine for about 2 weeks along with the presence of biological signs of renal tubular dysfunction.

Parkinson's disease is characterized especially by a degeneration of pigmented brain regions, like substantia nigra. These changes are accompanied by a variety of biochemical disturbances of dopaminergic and noradrenergic systems. Also the reduction of serotonin can be related to degenerative processes occurring in subareas of the raphe. Furthermore amino acid transmitters like GABA and a variety of peptidergic neuromodulators are changed. Additional cholinergic hypofunction due to degeneration of the nucleus basalis Meynert is able to impair the quality of life due to loss of intellectual capacity. A variety of biochemical mechanisms compensate for a long time the progression of neuronal loss. Modern treatment strategies (combined L-dopa therapy, dopaminergic agonists, MAO-B inhibitors, amantadine) are able to substitute the deficiency especially of the catecholamines. For the development of more causal therapies, a new animal model has been developed 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism after peripheral administration and leads to denervation of the dopaminergic nigrostriatal system. It is the hope that this new model, which is described here in detail, will lead to decisive data underlying the cause of Parkinson's disease.

A 24-year old man was exposed to a diquat aerosol and developed systemic symptoms and mild non-oliguric renal failure. A method of measurement of diquat was later developed and serial diquat levels during and after haemoperfusion showed that the technique was relatively ineffective in removing diquat.

Reported is the case of a 23-year-old man who ingested 300 mL of Reglone. He developed vomiting five to 10 minutes after ingestion. Shortly thereafter, he developed renal and central nervous system manifestations of toxicity, followed by cardiovascular collapse and death 14 hours after admission. Autopsy findings revealed esophagitis, tracheitis, gastritis, and ileitis. Prompt, aggressive therapy that included fluid replacement and removal of the toxin was unsuccessful.