Late treatment of paracetamol poisoning with mercaptamine.

Forty patients who had taken overdoses of paracetamol were treated with mercaptamine. Twenty-three patients given mercaptamine within 10 hours of poisoning had normal liver function tests at follow-up, and one could not be traced. In 16 patients mecraptamine was begun more than 10 hours after ingestion of paracetamol ("late" mercaptamine). Eight of these patients developed severe liver damage, which in six was moderate or severe before mercaptamine administration. Acute renal failure occurred in two patients; in one other renal function was temporarily severely impaired. At follow-up two patients were not available, and one admitted moribund had died soon after admission. The remaining 13 all had normal liver function tests. It is concluded that late mercaptamine is not dangerous and may prevent further liver damage.     

Predicting outcome of paracetamol poisoning by use 14C-aminopyrine breath test.

The 14C-aminopyrine (14C-amidopyrine) breath test, carried out within 24-36 hours of an overdosage of paracetamol, was used to predict the extent of liver damage in 30 seriously poisoned patients. Mean 14CO2 excretion was 4.4% in 20 healthy control subjects; 5.5% in six patients who escaped injury; and 2.9%, 1.5%, and 0.2% in those with mild to moderate (12 patients), severe (eight patients), and fatal (four patients) liver damage respectively. This test proved to be a more reliable predictor of the extent of liver damage than plasma paracetamol concentration or half life or the results of conventional liver function tests and may enable treatment of hepatic failure to be started at an early stage.     

Acute Paracetamol Poisoning

Of 41 cases of acute paracetamol poisoning one died of gastrointestinal haemorrhage and acute massive necrosis of the liver, three became jaundiced, and 13 others had biochemical evidence of hepatocellular damage. Liver damage is a toxic effect which is present in most patients who ingest more than 15 g. of paracetamol. One patient with liver damage survived renal failure due to acute tubular necrosis. It is suggested that the renal lesion was also the result of paracetamol overdosage.Profound hypoglycaemia and metabolic acidosis may also complicate severe poisoning. Plasma levels of para-aminophenol fall rapidly, and procedures currently used to enhance the elimination of the drug cannot be expected to prevent development of hepatic damage.     

Lipid peroxidation and covalent binding in the early functional impairment of liver Golgi apparatus by carbon tetrachloride

The onset of the lipoprotein secretory block provoked by CCl4 in the whole animal was monitored after purification of liver Golgi membranes. Both lipid transit through the apparatus and hexosylation of the lipoprotein are markedly inhibited 5-15 min after poisoning. Pre-treating the animal with alpha-tocopherol, shown to prevent lipid peroxidation without modifying the covalent binding due to CCl4 metabolites, affords little protection against lipid accumulation in the Golgi, but total preservation of galactosyl transferase activity. While haloalkylation therefore appears to be the major mechanism of damage in the early phases of CCl4-induced derangement of lipid secretion, lipid peroxidation is probably more involved later; this is indicated by the marked, though never complete, protection against fatty liver afforded at 24 h after CCl4 poisoning by supplementation of the membrane with alpha-tocopherol.     

Biochemical and histologic presentations of female wistar rats administered with different doses of paracetamol/methionine

This study was carried out to compare the hepatoprotective effect of methionine on paracetamol treated rats at both the peaks of toxicity and absorption. Female Wistar rats were divided into 17 groups consisting of eight rats per group and treated with different doses of paracetamol/methionine (5:1). Each control rat received 5 ml of physiologic saline. The study was terminated at two different end points -the 4th and 16th hours. Results show that rats administered with toxic doses (1000 mg/kg, 3000 mg/kg, 5000 mg/kg BW) of paracetamol exhibited significant increases in the levels of ALT, AST, γ- GT compared with controls. These increases were much higher at the 16th than 4th hour but serum total protein, albumin and globulin were significantly decreased by the end of the 16th hour. Histology results of rats in the 3000 and 5000 mg/kg (by the end of the 16th hour) confirmed hepatic damage, light microscopic evaluation of liver showed remarkable centrilobular necrosis. Moreover, the presence of mononuclear cells in liver section of rats intoxicated with APAP (5000 mg/kg) suggests a possible involvement of inflammatory process which resulted in regurgitation of bilirubin leading to its elevated level as well as increase activity of ALP. The hepatoprotective effect of methionine, on the other hand, was demonstrated in these rats at the 4th and 16th hours, and both results were comparable and therefore not significantly different but elevation in GGT level still persisted. In conclusion, data obtained from this study suggest that these agents may be capable of inducing GGT, although further study is required to establish a possible relationship between methionine and this enzyme in some other animal species.     

Antioxidant and hepatoprotective activity of Aphanizomenon flos-aquae Linn against paracetamol intoxication in rats

Paracetamol caused liver damage as evident by significant increase in the activities of aspartate and alanine transferases. There were general statistically significant losses in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione transferase and an increase in thiobarbituric acid reactive substances in the liver of paracetamol treated group compared with the control group. However, treatment with ethanol extract of A. flos-aquae (EEAFA) was able to counteract these effects. Protection offered by silymarin (standard reference drug) seemed relatively greater. The results suggest that EEAFA can act as hepatoprotective agent against paracetamol induced toxicity as an antioxidant.     

血浆置换联合血液灌流治疗急性重度有机磷农药中毒的疗效及对患者肝功能的影响

目的:探讨血浆置换联合血液灌流治疗急性重度有机磷农药中毒的临床疗效及对患者肝功能的影响。方法:选择我院于2014年1月至2017年9月收治的66例急性重度有机磷农药中毒患者,按照随机原则分为血液灌流组(n=30)、联合治疗组(n=36),两组均接受急性重度有机磷农药中毒常规治疗,在此基础上血液灌流组和联合治疗组分别接受血液灌流、血浆置换联合血液灌流治疗。观察两组治疗效果,治疗前、治疗1周后血浆丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素水平。观察治疗过程中的不良反应发生情况。结果:与血液灌流组比较,联合治疗组胆碱酯酶(CHE)恢复时间较短,而长托宁用量较少,住院时间较短,且抢救成功率较高(P0.05)。治疗1周后联合治疗组血浆ALT、AST、总胆红素显著低于血液灌流组(P0.05)。治疗过程联合治疗组出现1例皮疹,不良反应发生率为2.78%,血流灌注组无不良反应发生,两组不良反应发生率比较无差异(P0.05)。结论:血浆置换联合血液灌流能明显提高急性重度有机磷中毒患者的抢救成功率,同时改善患者肝功能,且安全性良好,值得临床推广。     

Antipyrine,paracetamol, and lignocaine elimination in chronic liver disease.

The plasma half lives of antipyrine, paracetamol, and lignocaine given by mouth were measured in 23 patients with stable chronic liver diseases of varying severity. Fifteen patients received all three drugs and 19 at least two. The half life of paracetamol was abnormally prolonged in nine out of 17 patients (mean 2-9 hours, normal 2-0 hours), of antipyrine in 10 out of 19 patients (mean 30-4 hours, normal 12-0 hours), and of lignocaine in 19 out of 21 patients (mean 6-6 hours, normal 1-4 hours). Prolongation of the half lives of all three drugs was significantly correlated with an increase of the vitamin-K1-corrected prothrombin time ratio and a reduction in serum albumin concentration. There was no correlation with serum bilirubin concentration or serum alanine aminotransferase activity. This suggests that impaired drug elimination was related to depressed hepatic protein synthesis. Considerable prolongation of the half life of one drug was invariably associated with delayed elimination of the others. The half life of lignocaine, however, was always the most prolonged and was a highly sensitive indicator of hepatic dysfunction. The pharmacokinetic characteristics of a drug as well as the severity of liver disease should be taken into account when considering drug dosage in patients with chronic liver disease.     

Plasmapheresis in the treatment of hepatic coma]

Fourteen patients, including 6 with viral hepatitis B and 8 with liver cirrhosis were treated with plasmapheresis for hepatic coma. Altogether 29 plasmaphereses were carried out. Complete recovery was achieved in one patient with viral hepatitis B and in 3 patients with liver cirrhosis. Plasmapheresis should be performed in patients with severe lesions to the liver. Classification of patients to the treatment should include clinical examination, biochemical and enzymatic tests, and evaluation of liver reserve with isotope hepatography. In case of the acute poisoning with hepatotoxic agents indications to plasmapheresis should be evaluated from the toxicologic point of view.     

Acute Hepatic Coma Successfully Treated by Extracorporeal Baboon Liver Perfusions

Two patients in deep hepatic coma due to fulminant viral hepatitis were treated by extracorporeal baboon liver perfusion after failing to respond to medical treatment and three consecutive exchange transfusions. Both patients recovered full consciousness after one liver perfusion, made a complete recovery, and were leading normal lives seven and eight months after treatment. Perfusions were maintained for 13½ and 16½ hours without complication, and neither clinical immunological reactions nor antibaboon serum antibodies developed as a result of treatment.Whereas normal consciousness could be restored only by liver perfusion, both exchange transfusion and liver perfusion were effective in clearing bilirubin and in raising the level of clotting factors. Extracorporeal baboon liver perfusion provides a safe and effective method for the treatment of acute hepatic coma.     

Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine.

OBJECTIVE: To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients. DESIGN: Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks. SETTING: Multicentre outpatient study at secondary referral centres in five European countries. PATIENTS--297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal anti-inflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial. INTERVENTIONS: Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal anti-inflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator''s discretion. END POINT: Frequency of gastric and duodenal ulceration or lesions, or both. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of peptic ulceration by eight weeks was 10.3% (27/263); 2 out of 135 (1.5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency of gastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection. CONCLUSIONS: Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.     

Use of acyclovir in the prevention of herpes infections after allogenic bone marrow grafts

In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.     

Factors contributing to mortality in paracetamol-induced hepatic failure.

Fifty patients with fulminant hepatic failure from paracetamol overdose were reviewed retrospectively to determine whether there had been any avoidable delays in treatment with protective agents, or other preventable factors which could contribute to the high mortality. Only nine were admitted to the local hospital early enough (within 12 hours) to benefit from protective agents, and only three of these were treated. Treatment was delayed in two patients while the results of plasma paracetamol concentrations were awaited. Signs of grade 3 hepatic encephalopathy were never found until 72 hours after the overdose, and sudden deterioration in consciousness at an earlier stage was due either to the sedative effects of drugs or to hypoglycaemia, which in one patient went unrecognised for 24 hours. A rapid deterioration in prothrombin time, which became prolonged by at least 25 seconds at 48 hours, preceded the onset of grade 3 encephalopathy, and this is the time at which transfer should be arranged to avoid the danger of brain-stem coning. This occurred more rapidly in those transferred at a later stage of their illness.     

Mushroom poisoning

In the research we included a total of 207 subjects with the dismissal diagnosis of "mycetismus", who were treated at the Department of Infectious Diseases, General Hospital Osijek, during the 1983-1992 period. 32 of them were children. There were 44.93% of men, 39.61% of women and 15.45% of children. The latent time > 6 hours was determined in 51 (25%) and < 6 hours in 75% of subjects. In 156 of patients with the latent time > 6 hours, "false" poisoning occured, while 51 patients experienced real mushroom toxins poisoning. At the admission to the hospital, in patients with the latent time > 6 hours, a pathological PT (protrombine time) was established only in women, leukocytosis in both women and children, increased concentration of GGT (gamma-glutamin-transferase) in men, increased AST (aspartate-aminotransferase) and ALT (alanin-aminotransferase) only in women, and increased urea in both women and children. After 24 hours, control measuring established high values of AST and ALT extended PT uremia and exalted amount of ammonia in blood in 11 of patients (2 men, 7 women and 2 children). They had severe liver and kidney damage, the most probably caused by Amanita phalloides toxins. The latent time lasted 9 to 13 hours. Of the 11 above mentioned patients, 2 women, aged 74 and 43, and one girl, aged 6, died. No pathological laboratory parameters were established in 40 of subjects with the latent time of 6 and more hours, and the disease manifested through vomiting and diarrhea that lasted for several days. These subjects most probably suffered from mushroom toxins poisoning. Mushroom toxins irritate the mucuous membrane of the gastrointestinal tract, and there are many such poisonous mushrooms. There were no mortalities in this group of subjects.     

Morbidity from Acute Carbon Monoxide Poisoning at Three-year Follow-up

Seventy-four survivors of acute carbon monoxide poisoning were followed up for an average of three years. In eight patients gross neuropsychiatric damage was directly attributable to the poisoning. Three patients had committed suicide and eight had died from other causes. Morbidity and mortality in those deliberately and accidentally poisoned was approximately equal.Of 63 patients alive at follow-up eight showed an improvement and 21 (33.3%) a deterioration of personality after poisoning, and 27 (43%) reported a subsequent impairment of memory. Deterioration of personality and memory impairment were highly correlated. The level of consciousness on admission to hospital in the acute phase of poisoning correlated significantly with the development of gross neuropsychiatric sequelae. These findings emphasize the importance of prompt and efficient treatment of carbon monoxide poisoning and the need to follow-up all cases in the anticipation of a relapsing course or the development of sequelae.     

Intramuscular loading dose of quinine for falciparum malaria: pharmacokinetics and toxicity.

In a study of intramuscular injection of quinine eight adults with moderately severe falciparum malaria resistant to chloroquine were treated with quinine dihydrochloride, being given a loading dose of 20 mg salt (16.7 mg base)/kg followed by three or four eight hourly maintenance doses of 10 mg salt (8.3 mg base)/kg injected into the anterior thigh. All patients responded to treatment. Fever and parasite clearance times (mean (SD) 60 (23) h and 53 (22) h respectively) were comparable with those obtained with intravenous quinine. The mean peak plasma quinine concentration of 11.0 mg/l (34.4 mu mol/l) [corrected] was reached a median of five hours after administration of the loading dose. In all patients plasma quinine concentrations exceeded the high minimum inhibitory concentration for Plasmodium falciparum malaria prevalent in Thailand within four hours of the start of treatment but did not cause toxicity other than mild cinchonism. When intravenous infusion is not possible an intramuscular quinine loading dose is an effective means of starting treatment in patients with moderately severe falciparum malaria who cannot swallow tablets.     

急性一氧化碳中毒致心肌损害临床研究

目的研究急性一氧化碳（CO）中毒对心脏的损害。方法选择急诊入院的急性CO中毒患者102例,分为轻度、中度和重度中毒组,同时在健康体检人群中随机选择100例健康人为对照组。中毒组的病例入院24h采静脉血测定心肌酶及行心电图检查;对照组清晨抽空腹静脉血．测定心肌酶并完成12导联心电图描记。结果急性CO中毒患者中有63例血清心肌酶谱改变,占61.77％。中、重度中毒者多有不同程度的心肌酶升高,与健康对照组相比,差异有统计学意义（P〈0．01）;重、中度中毒组相比。差异亦有统计学意义（P〈0．01）。心电图异常改变有70例．占68．63％。经治疗,除2例病重无康复外．其余100例均康复出院．在CO中毒纠正后心肌酶和心电图均恢复正常。蛄论急性CO中毒不仅对神经系统造成损害．对心脏的损害也较严重,需要给予相应的治疗.     

Successful treatment of experimental B virus (Herpesvirus simiae) infection with acyclovir.

The efficacy of the new nucleoside analogue acyclovir against B virus (Herpesvirus simiae) was investigated in rabbits and Vero cells infected with 2-136 and 0.3-1.0 TCD50 of the virus respectively. In the Vero cells 1 mg of acyclovir/1 reduced the yield of virus by 90%, which was slightly less than the effect on herpes simplex virus. Results in the rabbits varied with the interval between doses, duration of treatment, and delay before starting treatment. Acyclovir controlled an otherwise lethal infection when given not less than eight-hourly for 14 days. Withdrawing treatment after 9-10 days resulted in late-onset fatal disease in some rabbits. Treatment begun within 24 hours after infection gave complete protection, and rabbits first treated up to five days after infection showed a significant reduction in mortality (p less than 0.001). The plasma half life of acyclovir is twice as long in man as in rabbits and progression of the disease is much slower. Hence acyclovir may be useful for post-exposure prophylaxis against B virus infection in man and possibly also for treatment of the disease.     

Liver Damage due to Methotrexate in Patients with Psoriasis

Liver function and histological changes in liver biopsies were studied in 37 patients who had been treated for psoriasis with methotrexate. Cirrhosis was found in seven (19%) and hepatic fibrosis of varying severity in 10 (27%). Minor abnormalities in another 17 (46%) consisted of fatty change, round cell infiltration, and extensive vacuolation of liver cell nuclei. In only three (8%) was hepatic histology entirely normal. The severity of liver damage was related to the duration of methotrexate treatment. Minor abnormalities of liver function tests and liver histology were also found in eight control psoriatic patients. Standard liver function tests were of little value in predicting the degree of liver damage. It appears that methotrexate, in the doses normally used to control psoriasis, may cause cirrhosis if treatment is prolonged and that liver biopsy is necessary for evaluation of liver damage in these patients.     

Electrophysiological Follow-Up of Patients with Chronic Peripheral Neuropathy Induced by Occupational Intoxication with n-Hexane

The aim of this study is to characterize and dynamically monitor the progress of peripheral neuropathy induced by n-hexane by electromyography and nerve conduction velocity (NCV-EMG). Twenty-five patients with n-hexane poisoning from an electronic company were investigated in the year 2009. The occupational history of these workers was collected, and toxic substance exposure was identified. Neurologic inspection and regular NCV-EMG inspection were performed for all patients upon hospital admission and after 3, 6, and 12 months of treatment. NCV-EMG results shown that patients with n-hexane poisoning have simultaneous damage on motor and sensory nerves, of which sensory nerve damage was more severe. Motor nerves of the lower limbs were severe damaged than those of the upper limbs; whereas injury of sensory nerve in the upper limbs was more severe than that of the lower limbs. After treatment, clinical signs and symptoms of the patients were significantly improved. NCV-EMG result showed a delayed worsening at 3 months then gradually recovered after 12 months. Recovery of the motor nerve was better compared with sensory nerve, with upper limbs faster than that of the lower limbs.