Propofol and green urine.
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Anesthesia, Intravenous↗
Biomedical subjects
S Almog
Publications and source records attributed to S Almog.
Evaluation of the decarbamylation process of cholinesterase during assay of enzyme activity.
The activity of carbamylated cholinesterase increases continuously during assay, suggesting that progressive decarbamylation takes place. The following effects of assay conditions on the observed decarbamylation were studied: the effect of the sulfhydryl group of nitrobenzoate produced in the course of Ellman assay, the effect of substrate and the effect of sample dilution during assay. This study indicates that sample dilution is the main trigger to the decarbamylation observed during assay of cholinesterase activity. The process was described as a first-order reaction during which the inhibited enzyme gives place to the active form. Kinetic constants for decarbamylation of human pseudocholinesterase (EC 3.1.1.8) at 30 degrees C were approximately 0.005 min-1 for dimethylcarbamates and 0.010 min-1 for monomethylcarbamates, when 1 mmol/l propionylthiocholine was used as substrate.
Aldicarb↗
Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
In this study, we report the isolation from canine intestines of 2-arachidonyl glycerol (2-Ara-Gl). Its structure was determined by mass spectrometry and by direct comparison with a synthetic sample. 2-Ara-Gl bound to membranes from cells transiently transfected with expression plasmids carrying DNA of either CB1 or CB2--the two cannabinoid receptors identified thus far--with Ki values of 472 +/- 55 and 1400 +/- 172 nM, respectively. In the presence of forskolin, 2-Ara-Gl inhibited adenylate cyclase in isolated mouse spleen cells, at the potency level of delta 9-tetrahydrocannabinol (delta 9-THC). Upon intravenous administration to mice, 2-Ara-Gl caused the typical tetrad of effects produced by THC: antinociception, immobility, reduction of spontaneous activity, and lowering of the rectal temperature. 2-Ara-Gl also shares the ability of delta 9-THC to inhibit electrically evoked contractions of mouse isolated vasa deferentia; however, it was less potent than delta 9-THC.
Animals↗
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.
Adolescent↗
Interrelationships among measures of autonomic activity and cardiovascular risk factors during orthostasis and the oral glucose tolerance test.
Overstimulation of sympathetic nervous system activity is related to atherosclerotic cardiovascular disease risk, but the role of parasympathetic activity in this association is not clear. This study evaluated sympathetic and parasympathetic function by spectral analysis of heart rate variability and plasma levels of norepinephrine (NE) epinephrine (EPI), dihydroxyphenylglycol (DHPG), dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC). It also examined the interrelationships among these parameters and established atherosclerotic cardiovascular disease risk factors in 53 men (mean age 59.5 years). During supine rest, low-frequency power correlated positively with high-frequency power (r = 0.58, p < 0.001), plasma NE correlated with plasma DHPG (r = 0.41, p < 0.001) and plasma DOPA with DOPAC (r = 0.47, p < 0.001) but neither low- nor high-frequency power was correlated with plasma levels of any catechol. Among risk factors, plasma NE correlated with fasting insulin and mean arterial blood pressure, and urine NE correlated with body mass index. Both low- and high-frequency power correlated positively with insulin levels. Orthostasis decreased high-frequency power and increased low-frequency power and plasma NE levels. During the oral glucose tolerance test, both high- and low-frequency power increased, plasma NE levels were unchanged, and plasma EPI levels decreased [88.5 +/- 18 (SEM) versus 52.5 +/- 12 pM, p = 0.001]. The results suggest that orthostasis decreases and the oral glucose tolerance test increases parasympathetic outflows, whereas both stimuli increase sympathetic outflows. Among all atherosclerotic cardiovascular disease risk factors, hyperinsulinaemia showed the strongest association with autonomic nervous system activity, especially parasympathetic activity. Estimates of sympathetic responses obtained from power spectral analysis of heart rate variability agree poorly with those from plasma levels of catechols, possibly because of a parasympathetic contribution to low-frequency power and independence of sympathoneural outflows to the arm and heart.
Aged↗
Insulin resistance and autonomic function in traumatic lower limb amputees.
This study examined plasma insulin response to oral glucose load and autonomic nervous system activity in male lower limb amputees (n = 52) aged 50-65 years, compared to matched controls (n = 53). The groups had similar body mass index, blood pressure and plasma lipid levels. The amputees had higher mean fasting plasma insulin levels (18.4 +/- 9.7 (SD) versus 13.7 +/- 5.1 mU/l, p = 0.005) and during an oral glucose tolerance test (OGTT) (1 h levels 88.1 +/- 45.3 versus 62.1 +/- 42.7, p = 0.016) with similar plasma glucose levels, indicating insulin resistance. At baseline with the subjects supine, there were no group differences in low- or high-frequency power of heart rate variability or in plasma levels of norepinephrine (NE) or epinephrine (EPI). In response to orthostasis, the groups had similarly increased plasma NE levels. During the OGTT, amputees had significantly larger increments in low-frequency power than did controls (2.2 +/- 1.3 versus 1.6 +/- 0.9 (beats/min)2 respectively, p < 0.01) and plasma NE levels increased significantly in amputees (1595 +/- 849 versus 1941 +/- 986 pM, p = 0.0008) but not in controls. At 1 h after glucose administration, plasma EPI levels were decreased significantly from baseline in both groups; at both 1 and 2 h after glucose administration, plasma EPI levels were higher in the amputees than controls. Amputees appear to have a combination of enhanced sympathoneural responsiveness and attenuated suppression of adrenomedullary secretion during glucose challenge. As catecholamines antagonize insulin effects, one possible explanation for insulin resistance in amputees is hyperglycaemia-induced sympathoneural activation and a failure of hyperglycaemia to decrease adrenomedullary secretion.
Aged↗
Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy.
PURPOSE: We have previously found thiamine (vitamin B1) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in doses of 80 mg/d or more for at least 3 months. PATIENTS AND METHODS: Thirty patients were randomized to 1 week of double-blind inpatient therapy with either i.v. thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography. RESULTS: TPPE, diuresis, and LVEF were unchanged with i.v. placebo. After i.v. thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/- 800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01). CONCLUSIONS: Thiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving longterm furosemide therapy.
Aged↗
Ocular effects of hyoscine in double dose transdermal administration and its reversal by low dose pyridostigmine.
The potential of low dose (30 mg t.i.d) pyridostigmine to reduce the ocular side effects of double dose transdermal controlled release hyoscine was evaluated by the study of near visual acuity, accommodation amplitude and pupil diameter in a placebo controlled, double masked study. We studied 47 healthy men (age 18-21 yr) in 3 groups: 16 assigned to placebo hyoscine and placebo pyridostigmine, 15 assigned to double dose hyoscine and placebo pyridostigmine, and 16 to double dose hyoscine and pyridostigmine. Subjects were tested during 48 h of treatment and 48 h of washout period. Blood cholinesterase inhibition level and amount of hyoscine released from the patches were used as parameters of reliability. Difference between groups was assessed using change from baseline scores. Double dose hyoscine caused decrease in near visual acuity to a mean of 14/18. Accommodation amplitude was decreased in the double dose transdermal hyoscine group from 9.19 +/- 1.04 to 4.83 +/- 1.97 diopters of accommodation. This decrease was significant when compared to the placebo group (p < 0.05) and to the pyridostigmine-protected group (p < 0.05). Pyridostigmine, however, did not significantly change the hyoscine-induced mydriasis of 1.47 + 0.15 mm change from baseline (p < 0.05). These results suggest that pyridostigmine administration may be beneficial in shortening recovery time when near vision impairment is experienced following single and double dose transdermal hyoscine administration.
Adolescent↗
Carbamate poisoning and oxime treatment in children: a clinical and laboratory study.
OBJECTIVE: (1) Retrospective evaluation of the clinical course of carbamate poisoning and the effect of oxime therapy in children. (2) In vitro study of the effect of oximes on the reactivation of carbamylated cholinesterase. DESIGN: (1) Clinical survey: The records of 26 children intoxicated with carbamates were examined retrospectively. The poisoning agents in all cases were positively identified as methomyl or aldicarb by gas chromatography-mass spectrometry. (2) Laboratory study: The direct effect of obidoxime and of pralidoxime on acetylcholinesterase activity in vitro was investigated in normal human packed red blood cells pretreated with an organophosphate (paraoxon) or a carbamate (aldicarb or methomyl). CLINICAL SETTING: Pediatric intensive care unit of a teaching hospital. PATIENTS: Twenty-six infants and young children (aged 1 to 8 years) admitted to the pediatric intensive care unit with severe carbamate intoxication. INTERVENTIONS: All cases had been treated with repeated doses of atropine sulfate (0.05 mg/kg) administered every 5 to 10 minutes until muscarinic symptoms disappeared. Obidoxime chloride (Toxogonin, 6 mg/kg) was administered on admission, and again after 4 to 5 hours. RESULTS: Predominant symptoms were related to central nervous system and nicotinic effects. All the patients showed marked improvement within several hours and recovered completely within 24 hours. None of the children deteriorated and none showed exacerbation of cholinergic symptoms after obidoxime treatment. In vitro, oximes reactivated acetylcholinesterase inhibited with paraoxon, whereas no significant effect of oximes on carbamylated enzyme activity was observed. CONCLUSIONS: Based on the recovery of all cases, as compared with other reports of carbamate poisoning treated with atropine alone, it is concluded that, in the case of aldicarb or methomyl poisoning, oxime therapy apparently does not contribute to the recovery of poisoned patients. In cases of poisoning by an unknown pesticide or of mixed poisoning, oxime therapy can prove beneficial because no negative effects of the therapy can be discerned.
Aldicarb↗
Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor.
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Animals↗
Quinidine enhances digitalis toxicity at therapeutic serum digoxin levels.
OBJECTIVE: To determine the effect of the digoxin-quinidine interaction on rate of in-hospital digitalis toxicity. METHODS: This was a prospective observational study over 9 months, set in two general medical wards. We studied consecutive patients (n = 141) who were receiving digoxin. Measurements included digitalis toxicity, defined by ECG criteria and resolution after stopping digoxin; all additional medications (including antiarrhythmics) continued. The observer was "blinded" to serum digoxin level and to concomitant drugs. RESULTS: Digitalis toxicity rates were as follows: digoxin alone, 4.9% (5 of 101 patients); with amiodarone or verapamil, 5.0% (1 of 20 patients); with quinidine, 50% (10 of 20 patients) (p < 0.01). No toxicity was seen at digoxin levels < 1.0 ng/ml. Toxicity at 1.0 to 2.0 ng/ml was as follows: digoxin alone, 1 of 41 patients; with quinidine, 4 of 15 patients (p = 0.014). Toxicity was similar at levels > 2.0 ng/ml: 4 of 8 patients and 7 of 11 patients, respectively. Independent relative risks and 95% confidence intervals (CI) of digitalis toxicity were as follows: serum digoxin, 9.1 (95% CI, 2.9 to 13.0); concurrent quinidine, 24.3 (95% CI, 3.4 to 124). There was a significant (p < 0.01) interaction between concurrent quinidine, serum digoxin of 1.0 to 2.0 ng/ml, and digitalis toxicity. CONCLUSION: The digoxin-quinidine interaction significantly increases digitalis toxicity, even in the therapeutic range of serum digoxin levels.
Aged↗
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.
Adolescent↗
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.
Adult↗
Atropine poisoning in children during the Persian Gulf crisis. A national survey in Israel.
OBJECTIVE: To evaluate the effects of high doses of atropine in children accidentally injected with automatic atropine injectors. These were distributed in Israel during the Persian Gulf Crisis as an antidote for chemical warfare agents. DESIGN AND SETTING: A national survey in pediatric emergency departments in Israel, involving 22 medical centers, with prospective data collection in 14 centers. PATIENTS: Children (n = 268) presenting to emergency departments following misuse of automatic atropine injectors. MAIN OUTCOME MEASURES: Documentation of atropine dose and clinical manifestations; determination of a clinical severity score and its correlation with atropine dose; measurements of serum atropine levels in six patients. RESULTS: Over a period of 4 months, 268 cases were reported, of which 240 were clinically evaluated. The most common site of injection (75%) was the finger or palm. Doses were up to 17-fold higher than standard doses for age. In 116 children (48%), systemic effects of atropine were observed, and 20 (8%) had severe atropinization. Seizures and life-threatening arrhythmias were not reported, and there were no fatalities. The severity of atropinization was correlated with the dose following a classic nonlinear, dose-response relationship. Serum atropine levels (6.2 to 61.0 ng/mL) were much higher than those observed after administration of therapeutic doses. CONCLUSIONS: The high incidence of injection in the hand implies accidental use of automatic atropine injectors among children. The lack of mortality or life-threatening complications from injection of large doses of atropine attests to its relative safety in children. The low risk from atropine injections weighed against expected benefit as a lifesaving antidote justifies the distribution of personal atropine injectors to children at risk of organophosphorus nerve agent attack.
Accidents↗
Computer assisted design of a theophylline dosing regimen in acute bronchospasm: serum concentrations and clinical outcome.
The effect of intravenous theophylline on the outcome of inhospital treatment of acute bronchospasm has been assessed, comparing the results achieved by computer-assisted dosing, designed to achieve and maintain a serum theophylline level of 16 micrograms.ml-1 (10 patients) with those of unaided physicians (15 control patients). The outcome measures compared were clinical improvement, peak expiratory flow rate and serum theophylline concentration. Loading doses of theophylline in the control and computer groups were: 167 and 437 mg, respectively. Initial serum theophylline concentrations, measured 20 min after the loading dose, were 13.6 and 17.0 micrograms.ml-1 in the control and computer groups, respectively. In patients who had not received theophylline prior to admission, loading doses and initial concentrations were: 200 mg and 9.4 micrograms.ml-1 in the control group (n = 5) versus 613 mg and 15.7 micrograms.ml-1 in the computer group (n = 4), respectively. During maintenance therapy, serum theophylline concentrations were kept in the therapeutic range (10-20 micrograms.ml-1) throughout 51% and 77% of the hospitalisation period, in the control and computer groups, respectively. There were no differences between the two groups in the rate or extent of clinical improvement or in change in peak expiratory flow rate. The computer assisted theophylline dosing regimen outperformed that of the unaided physicians in achieving and maintaining therapeutic serum theophylline concentrations in acute bronchospasm. There was no correlation between clinical outcome and serum theophylline concentration, but this may have been due to the small sample size and modest difference in serum theophylline between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Seizures after flumazenil administration in a case of combined benzodiazepine and tricyclic antidepressant overdose.
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Adult↗
Prevention of peripheral side-effects of transdermal hyoscine by adjunctive therapy with low dosage of pyridostigmine.
1. The value of low dosage of pyridostigmine (30 mg three times daily) in preventing peripheral anti-muscarinic side effects of a transdermal controlled-release formulation of hyoscine, was tested in a double-blind placebo-controlled study, involving 47 healthy subjects. 2. Salivary excretion was repeatedly measured during 48 h of combined therapy of two transdermal hyoscine patches with pyridostigmine and 14 h after its cessation. Blood acetylcholinesterase activity was also measured, serving as an index of pyridostigmine bioavailability. 3. The adjunctive therapy with pyridostigmine was highly effective in preventing the substantial impairment in salivary flow caused by the transdermal formulation. An associated 23% inhibition of blood acetylcholinesterase activity was observed. 4. Small doses of pyridostigmine may therefore have a role in increasing the tolerability of transdermal hyoscine therapy. In some patients this drug combination might also allow some increment of the hyoscine dose.
Acetylcholinesterase↗
A submicron emulsion as ocular vehicle for delta-8-tetrahydrocannabinol: effect on intraocular pressure in rabbits.
delta 8-Tetrahydrocannabinol (delta 8-THC), a known antiglaucoma lipophilic drug, was incorporated in a submicron emulsion for ocular administration. The mean droplet size of the emulsion was 130 +/- 41 nm, and no droplet was larger than 400 nm. No change in pH, particle size distribution or zeta potential was noted after sterilization by steam autoclaving or long-term storage over 9 months. An intense and long-lasting intraocular pressure (IOP)-depressant effect was observed after ocular application (50 microliters) of the THC emulsion, 0.4% (w/w), to rabbits with ocular hypertension (chymotrypsin model). Lesser effects were observed in normotensive rabbits. No irritation effect of either the emulsion vehicle or THC emulsion on the rabbit eyes was detected. These results underline the promising properties of submicron emulsions as vehicles for lipophilic ophthalmic drugs. The mechanism by which the emulsion induced the marked delta 8-THC antiglaucoma effect remains unclear. However, the possible involvement of delta 8-THC systemic absorption in the hypotensive effect induced by the emulsion cannot be excluded and will be the subject of further investigation.
Animals↗