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Biomedical subjects

S Almog

Publications and source records attributed to S Almog.

At least 37 records · Page 2Linked to original sources
PubMed1995

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs.

Responsiveness to antihypertensive medications was investigated cross-sectionally in 559 individuals comprising all treated hypertensive patients identified within a representative sample (n = 3,532, aged 40-70 years) of the Jewish population in Israel. A rate of dosage score (a summed ranking of dosages of all drugs taken) of two or more increased significantly with increasing levels of body mass index (BMI) from 37.5% in levels less than 23, 54.9% in levels 23.0-29.9, and 76.4% in levels of 30 or greater (p less than 0.0001). Multivariate analyses, adjusting for age, gender, arm circumference, and ethnic group, confirmed the independent effect of BMI on dosage score (p less than 0.001). At each level of dosage score, mean blood pressure levels were equivalent at all levels of BMI after adjusting for potential confounders. This indicates that achieved blood pressure level and not BMI itself was the main determinant of the higher dosing regimens prescribed at higher levels of BMI. In representative subgroups, glucose tolerance (n = 372) and hyperinsulinemia (n = 190) were determined and were found to be positively associated with a dosage score of two or more (p less than 0.05) independently of BMI. These effects could not be accounted for by poor compliance or by altered drug absorption or disposition since overnight urinary drug excretion and plasma drug concentrations 2 hours after ingestion, measured in 80 randomly selected patients from the study group, were not different across BMI categories at similar dosages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

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.

Accidents, Occupational↗
PubMed1990

States of aggregation and phase transformations in mixtures of phosphatidylcholine and octyl glucoside.

The result of mixing varying concentrations of the nonionic detergent octyl glucoside (OG) with small unilamellar vesicles (SUV) of egg phosphatidylcholine (PC) made by sonication depends on the ratio between OG and PC in the mixed aggregates. When this molar ratio (Re) is lower than 1.4, the detergent partitions between the PC vesicles and the aqueous medium with a partition coefficient of K = 0.033 mM-1. As a consequence of introduction of OG into the bilayers, the vesicles grow in size. The resultant vesicles have a mean diameter that is an increasing function of Re and is independent of the total PC concentration. Experiments in which the vesicles were loaded with high molecular weight dextran prior to being exposed to OG suggest that the mechanism responsible for the size growth involves lipid transfer rather than fusion. Mixtures with Re values within the range of 1.4-3.2 separate into two macroscopic phases: The lower phase is clear but very viscous. It contains constant OG and PC concentrations and is characterized by an Re value of 3.2, independent of the composition of the whole dispersion. The upper phase contains vesicles of varying concentrations of OG and PC, but a constant Re of 1.4. When the saturating level of 1.4 OG molecules per PC molecule is approached, the concentration of OG monomers in the aqueous medium reaches the value of 16.6 +/- 0.3 mM, which is the apparent cmc of OG in the lipid-containing medium. OG-PC mixed micelles contain at least 3.2 OG molecules per PC molecule. The mixed micelles present at Re = 3.2 apparently have the shape of oblate ellipsoids with a minor axis of about 2 nm and two major axes of about 25 nm. The surface area of the mixed micelles at this point is just sufficient for them to undergo conversion into the smallest possible spherical vesicles of a radius of 12 nm. At Re values above 3.2, the major axis of the mixed micelles becomes smaller as Re increases, while at values of Re below 3.2 the micelles would have been expected to grow very rapidly with decreasing Re. This may explain the partial vesicle closure occurring below Re = 3.2.

Detergents↗
PubMed1990

The effect of repeated doses of 30 mg pyridostigmine bromide on pilot performance in an A-4 flight simulator.

The effect of repeated doses of 30 mg pyridostigmine bromide every 8 h on flight skills in an A-4 simulator was tested in this crossover double-blind placebo-controlled study on 10 pilots experienced in actual and simulated A-4 flights. The pilots flew two test simulator flights 2 h after the fourth dose of pyridostigmine or placebo. The flight profile included navigation, rapid ascent, 360 degrees turns, and instrument landing. Each flight lasted approximately 20 min. Flight parameters measured included indicated air speed, true heading, barometric altitude, vertical velocity, and bank. The mean whole blood cholinesterase inhibition level was 29%. There was no decrement in performance under treatment with pyridostigmine in the percent of deviation time from the prescribed limits or in the average duration or magnitude of the deviation in each of the flight parameters. We conclude that pyridostigmine bromide in repeated doses of 30 mg every 8 h does not appear to influence pilot performance during short A-4 missions.

Adult↗
PubMed1990

Stability of mixed micellar systems made by solubilizing phosphatidylcholine-cholesterol vesicles by bile salts.

Complete solubilization of phosphatidylcholine and cholesterol by bile salts in the form of stable mixed micelles requires that the effective ratio of bile salt/lipids in the mixed micelles (Re = ([bile salt] - critical micellar concentration)/([phosphatidylcholine] + [cholesterol]) will exceed a critical value. This equilibrium solubilizing ratio is an increasing function of the cholesterol/phosphatidylcholine ratio. In contrast, the concentration of sodium cholate required for solubilization of vesicles made of phosphatidylcholine and cholesterol does not increase by increasing the cholesterol/phosphatidylcholine ratio. Consequently, the latter solubilization procedure yields metastable mixed micelles whenever the cholate concentration is higher than that required for vesicle solubilization but lower than that needed for establishing a micellar equilibrium. These metastable mixed micelles undergo partial revesiculation to form cholesterol-rich vesicles that subsequently aggregate. Cholesterol crystallization appears to occur through its reorganization within these aggregated vesicles. The overall rate of the above series of processes increases sharply with the total lipid concentration and with the cholesterol/phosphatidylcholine ratio. The dependence of the rate on the effective ratio of bile salts/lipids is very complex: at any given ratio of cholesterol/phosphatidylcholine within the range of 0.3 to 0.5, increasing the cholesterol/phosphatidylcholine ratio requires higher cholate concentrations for the formation of stable mixed micelles (higher equilibrium solubilizing ratio). On the other hand, the metastable mixed micellar larsystems are long-lived whenever the effective ratio of cholate/lipids is lower than a critical value.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1988

Hydrolysis of phosphatidylcholine in phosphatidylcholine-cholate mixtures by porcine pancreatic phospholipase A2.

Pancreatic phospholipase A2 (PLA2)-catalyzed hydrolysis of egg yolk phosphatidylcholine (PC) in mixed PC-cholate systems depends upon composition, structure, and size of the mixed aggregates. The hydrolysis of PC-cholate-mixed micelles made of an equal number of PC and cholate molecules is consistent with a Km of about 1 mM and a turnover number of about 120 s-1. Increasing the cholate/PC ratio in the micelles results in a decreased initial velocity. Hydrolysis of cholate-containing unilamellar vesicles is very sensitive to the ratio of cholate to PC in the vesicles. The hydrolysis of vesicles with an effective cholate/PC ratio greater than 0.27 is similar to that of the mixed micelles. The time course of hydrolysis of vesicles with lower effective ratios is similar to that exhibited by pure dipalmitoyl-phosphatidylcholine (DPPC) large unilamellar vesicles in the thermotropic phase transition region. In the latter two cases, the rate of hydrolysis increases with time until substrate depletion becomes significant. The reaction can be divided phenomenologically into two phases: a latency phase where the amount of product formed is a square function of time (P(t) = At2) and a phase distinguished by a sudden increase in activity. The parameter A, which describes the activation rate of the enzyme during the initial phase in a quantitative fashion, increases with increasing [PLA2], decreasing [PC], decreasing vesicle size, and increasing relative cholate content of the vesicles. The effect of [PLA2] and [PC] on the hydrolysis reaction is similar to that found with pure DPPC unilamellar vesicles in their thermotropic phase transition region. The effect of cholate on the hydrolysis reaction is similar to that of temperature variation within the phase transition of temperature variation within the phase transition of DPPC. These results are consistent with our previously proposed model, which postulates that activation of PLA2 involves dimerization of the enzyme on the substrate surface and that the rate of activation is directly proportional to the magnitude of lipid structural fluctuations. It is suggested that large structural fluctuations, which exist in the pure lipid system in the phase transition range, are introduced into liquid crystalline vesicles by the presence of cholate and thus promote activation of the enzyme.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

Effect of calcium on kinetic and structural aspects of dilution-induced micellar to lamellar phase transformation in phosphatidylcholine-cholate mixtures.

Previously, we have shown [Almog, S., Kushnir, T., Nir, S., & Lichtenberg, D. (1986) Biochemistry 25, 2597-2605] that the distribution of cholate between phosphatidylcholine (PC) vesicles and aqueous media apparently obeys a single distribution coefficient, K. In PC-cholate mixed micellar systems, the monomer concentration does not rise much above the cholate's critical micelle concentration (cmc). Consequently, for vesicular systems, the cholate:PC molar ratio in the mixed aggregates (Re) is given by Re = [cholate]/([PC] + 1/K) whereas for mixed micellar systems Re = ([cholate] - cmc)/[PC]. Dilution of mixed micellar systems results in a decrease of Re, due to an increase in the fraction of monomeric PC. If the decrease in Re is to values lower than 0.3, micellar to lamellar transformation occurs. This process involves a sequence of three steps, namely, micellar equilibration followed by vesiculation and subsequent vesicle size growth via a lipid transfer mechanism. The ultimate size of the resultant vesicles is an increasing function of Re. This work is devoted to the effect of calcium on the dilution-induced vesicle formation. Its major findings and conclusions are as follows: (i) Calcium reduces the cmc of the detergent and raises its distribution coefficient between PC vesicles and the aqueous medium. Thus, for any given cholate and PC concentrations, calcium causes an increase of Re. (ii) The rate of all the steps which ultimately lead to an apparent equilibrium vesicle size distribution increases dramatically with increasing calcium concentration. Thus, equilibration is attained in seconds to minutes rather than many hours required in the absence of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗