Differentiation between organophosphate and carbamate poisoning.

We propose a novel and simple assay for the real-time differentiation between carbamate and organophosphate inhibition of cholinesterase, based on our observations of the kinetic behavior of inhibited enzyme. The assay of carbamylated cholinesterase activity over time follows a non-linear kinetic pattern, whereas that of phosphorylated enzyme activity is linear. This feature can be exploited to differentiate between carbamate and organophosphate cholinesterase inhibition. The non-linear pattern characteristic of carbamates is easily discernible at degrees of inhibition of 40% or more. In this setting, cholinesterase activity ought to be measured continuously for about 1 h to obtain the kinetic pattern of enzyme activity. The initial activity, measured during the first 5 min of assay, represents the activity of enzyme in vivo. In vitro reactivation of inhibited cholinesterase allows the estimation of full potential activity of enzyme prior to poisoning, so that percentage of inhibition can be calculated. Reactivation of carbamylated cholinesterase is obtained by the incubation of diluted enzyme at 37 degrees C for 2.5 h prior to assay, whereas phosphorylated (non-aged) enzyme is reactivated by a 30 min incubation with oximes. In cases of mild exposure to cholinesterase inhibitors (< 40% inhibition), the response of enzyme to in vitro reactivation serves as a complementary test for exposure and for the nature of the inhibitor. All the results presented in this work refer to plasma cholinesterase. Erythrocyte cholinesterase was found to behave very similarly to plasma enzyme and its results have not been reported here.

Decreased serum cholesterol level after snake bite (Vipera palaestinae) as a marker of severity of envenomation.

In 44 patients bitten by snakes (Vipera palaestinae), admission serum cholesterol levels were negatively correlated with severity of envenomation (mean +/- SD, 175 +/- 49, 137 +/- 36, and 96 +/- 40 mg/dl, respectively, in cases with mild, moderate, and severe clinical manifestations [p < 0.0001]). Concomitant decreases in serum albumin were not significant. These findings were supported by experimental results in rabbits, in which low, medium, and high doses of purified V. palaestinae venom (all in the non-lethal range), led to dose-dependent decreases in serum cholesterol, at 180 minutes, of 9.5% +/- 8.9%, 18.6% +/- 10.1%, and 32.7% +/- 11.8%, respectively (p < 0.01). This rapid decrease in serum cholesterol level is only partially explained by transcapillary lipoprotein leakage and probably indicates changes in lipoprotein transport and metabolism caused by the phospholipase A2 component of V. palaestinae venom. Admission total serum cholesterol level may serve as an indicator of severity of envenomation in patients bitten by snakes of the Vipera genus before full development of the clinical syndrome.

Use of flumazenil in the diagnosis and treatment of patients with coma of unknown etiology.

OBJECTIVES: To evaluate the use of single-dose flumazenil in the diagnosis of coma of unknown etiology, and of continuous flumazenil infusion in the treatment of benzodiazepine-induced coma. DESIGN: Prospective study. SETTING: Emergency room and general medicine ward of a teaching hospital. PATIENTS: A total of 42 comatose adults in whom metabolic, neurologic, or traumatic causes of coma were excluded. INTERVENTIONS: a) Intravenous bolus injections of 0.25 mg flumazenil were given at 1-min intervals, either until improvement by two coma grades or a total dose of 2.0 mg was reached. b) Loading doses as in (a) followed by a maintenance infusion administered as long as indicated by repeated coma grade evaluation. MEASUREMENTS AND MAIN RESULTS: a) Of 34 patients, 28 received only the flumazenil loading dose responded promptly. Twenty-one of 25 available urine samples of the responding patients contained only benzodiazepine metabolites. Four urine samples contained benzodiazepines in combination with other drugs. Six patients did not respond to the flumazenil loading dose. The urine of three patients contained a combination of benzodiazepines and another coma-exerting drug; the remaining three were negative. A total of 24 patients, who initially responded to flumazenil loading, deteriorated to their previous coma state and were admitted to the general medical ward. Six (25%) patients developed complications related to hospitalization and their bedridden state. b) Eight other patients, who deteriorated after an initial loading dose, received a second iv bolus of flumazenil, followed by maintenance infusions over 5 to 24 hrs. Their hospital course was uneventful. CONCLUSIONS: These findings indicate that flumazenil is safe and effective in the diagnosis of benzodiazepine-induced coma. Furthermore, the use of continuous flumazenil maintenance infusion is of considerable therapeutic value in patients who exhibit deterioration after initial response to the single loading dose.

Acute pyridostigmine overdose: a report of nine cases.

Pyridostigmine is known as a pre-treatment drug against intoxication with organophosphorus nerve agents. During the Persian Gulf war, we encountered a cluster of nine cases of pyridostigmine self-poisoning, of which three presented with mixed drug poisoning. The clinical and laboratory features of pyridostigmine toxicity are presented. Doses ranged between 390 and 900 mg. Pyridostigmine ingestion resulted in mild to moderate cholinergic symptoms such as abdominal cramps, diarrhea, emesis, nausea, hypersalivation, urinary incontinence, fasciculations, muscle weakness and blurred vision. No central nervous system manifestations were evident. The symptoms developed within several minutes and lasted up to 24 h. All patients underwent gastric emptying followed by administration of activated charcoal. Atropine (1-8 mg) was required in only three patients. Measurement of serum cholinesterase inhibition was found to be a reliable and sensitive diagnostic tool in pyridostigmine poisoning. No clear correlation was found between the extent of cholinesterase inhibition and the incidence or severity of the cholinergic signs. The clinical recovery was faster than the spontaneous recovery of the enzyme. Pyridostigmine intoxication is self-limited and well tolerated by young healthy adults.

Fatal accidental inhalation of bromochlorodifluoromethane (Halon 1211).

Bromochlorodifluoromethane (Halon 1211) is a widely used fire extinguishing agent. Several cases of sudden death in teenagers associated with BCF abuse have been reported. BCF is used as a fire extinguisher in battle tanks. Two young previously healthy male soldiers were accidentally exposed to BCF in a battle tank. The tank driver died, but the gunner survived the event with no medial complications. It is concluded that BCF should be used in confined chambers only after the evacuation of all personnel.

[Lead poisoning in two families from a car battery workshop].

Lead poisoning resulting from exposure to lead in a domestic car battery workshop is reported in 10 children in 2 families. 2 girls, aged 2 10/12 and 1 8/12 years, respectively, from 1 of the families were hospitalized for investigation of nausea, vomiting, progressive muscular weakness and peripheral neuropathy. Serum lead levels were 52 and 49 mcg/dl, respectively. Subsequent screening of all members of this family, as well as those of the other family who lived in the same house, revealed abnormally elevated levels of serum lead in all the members of both families. The 2 girls were treated with chelating agents and improved clinically and their serum lead levels decreased to 29 and 34 mcg/dl, respectively. The domestic workshop was closed and the 2 families moved to another neighborhood. These cases illustrate the need to screen all family members and contacts of patients with lead poisoning, as well as the hazards of the uncontrolled use of lead in domestic workshops.

Effect of alpha-methyldopa excreted in human milk on the breast-fed infant.

A nursing infant whose mother took alpha-methyldopa (alpha-MD) was followed for 3 months. Analysis of maternal serum and milk as well as the infant's serum and urine for alpha-MD revealed that the drug was excreted into maternal milk, absorbed by the infant and excreted in her urine, but no adverse clinical effects were noted during the follow-up period. alpha-MD is excreted in human milk in concentrations that probably do not harm the breast-fed infant.

The Arjenyattah epidemic. A mass phenomenon: spread and triggering factors.

A massive epidemic of psychogenic aetiology occurred in three districts of the West Bank over two weeks in March-April, 1983. It affected 949 individuals, 727 (77%) of them adolescent females. The symptoms were not accompanied by positive physical signs or by laboratory findings. The epidemiological pattern was pathognomonic of that of a psychogenic disorder. The initial trigger was probably the odour of H2S escaping from a faulty latrine in the schoolyard of the first affected school. Subsequent spread of the disease was due to psychological and extra-medical factors, including publicity by the mass media. Spread was stopped immediately after closure of schools.

Methyldopa poisoning.

A case of methyldopa overdose, confirmed by quantitative blood analysis, is presented. The clinical manifestations were coma, hypothermia, hypotension, bradycardia, and dry mouth. This combination of clinical findings, previously considered characteristic of phenothiazines or tricyclic antidepressants poisoning, should also raise the suspicion of methyldopa overdose. Methyldopa is a commonly used antihypertensive agent. Surprisingly, reports on overdose are exceedingly rare [1, 2]. We have recently treated a case of methyldopa overdose in which the presenting signs resembled those of psychotropic drug poisoning.

The chemically abused child.

The case of an 18-month-old child poisoned by her mother with chlorpromazine is described. Fifteen other cases of child poisoning have been previously reported. In all of these cases the assailant was the mother (who in 11 cases was described as mentally disturbed); in 14 cases the presenting sign was a change in the level of the child's consciousness; and in ten cases the agent was a psychotropic drug. These poisonings were always well planned and manipulative, usually of long duration (1 1/2 to 48 months), and often continued during hospitalization, but lacked homicidal intent. Three children died. It is suggested that this subgroup of child abuse be more rigidly defined and possibly be named "the chemically abused child." A higher degree of suspicion and alertness to this problem would increase the number of cases identified and the number of children who receive professional care.