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Biomedical subjects

U Taitelman

Publications and source records attributed to U Taitelman.

At least 19 recordsLinked to original sources

Postmortem digoxin-like immunoreactive substances (DLIS) in patients not treated with digoxin.

Endogenous digoxin-like immunoreactive substances (DLIS) cross-react in immunoassays of digoxin. The postmortem rise in digoxin levels in patients treated with the drug may be due to its redistribution. It is unclear what is the contribution of DLIS to this increase and whether DLIS are present postmortem in patients not treated with digoxin. The objectives of this study were to determine whether DLIS are present after death in patients not treated with digoxin, whether a postmortem increase in DLIS is detectable and whether sampling site can affect DLIS concentrations. DLIS (measured as digoxin, TDx Abott) were determined in blood samples drawn antemortem from ICU patients; postmortem samples from femoral artery and cardiac chambers were taken at least 12 h after the death of these same patients. DLIS concentrations > or = 0.2 ng/ml were measured in 44 and 40% of patients antemortem and postmortem (femoral), respectively. No difference was found in DLIS levels between antemortem and postmortem femoral and cardiac samples. Age, ICU stay and postmortem sampling time did not affect the postmortem increase in DLIS. None of the levels was in the toxic range. DLIS may be present after death and their concentration does not increase postmortem. The interpretation of postmortem digoxin concentrations that fall in the therapeutic range should be done cautiously; such measurable levels do not necessarily indicate misuse or malicious intent even in patients who had not been treated with the drug.

Adolescent↗

[Hyperbaric oxygen for carbon monoxide poisoning].

Severe cases of carbon monoxide (CO) poisoning from all over Israel are treated at the Israel Naval Medical Institute with hyperbaric oxygen (HBO). Between 1.11.94 and 15.2.95. 24 cases of CO poisoning were treated. Poisoning was usually due to domestic gas-fired heating systems, CO being the only toxin involved. Since delay between termination of CO exposure and arrival at the emergency department averaged 55 minutes, the level of carboxyhemoglobin measured on presentation did not always reflect the true severity of the poisoning. Poisoning was defined as severe and requiring HBO treatment when 1 or more of the following indications was present: evidence of neurological involvement, cardiographic signs of acute ischemic injury, metabolic acidosis, carboxyhemoglobin level greater than 25%, and pregnancy. 20 (84%) recovered consciousness during the course of 1 session (90 min.) of HBO treatment (pO2 2.8 ATA) or immediately thereafter, with resolution of other signs of CO poisoning. 3 required a second treatment session before their symptoms resolved. A patient who arrived in deep coma with severe cerebral edema died. HBO is an important element in the combined treatment of severe CO poisoning. There should be greater awareness of the danger of CO poisoning and the means of preventing it, both among medical staff and the population as a whole, mainly in areas in which cold weather requires use of heating systems, which may be gas-fired.

Carbon Monoxide Poisoning↗

N-acetylcysteine increases the glutathione content and protects rat alveolar type II cells against paraquat-induced cytotoxicity.

A protective effect of N-acetylcysteine in oxidative lung damage was reported by a number of workers; however, the mechanism underlying this effect was not thoroughly elucidated. The present research investigates the protection by N-acetylcysteine against paraquat-induced cytotoxicity to alveolar type II cells, which are known to be specific targets of paraquat toxicity in vivo. We found that addition of 1 mM N-acetylcysteine to alveolar type II cells incubated with 1 mM paraquat reduced the cytotoxic index from 17.4 +/- 1.3% to 9.3 +/- 1.5%. This effect could not be explained by the interference of N-acetylcysteine with the active uptake of paraquat by type II cells. Incubation of these cells with N-acetylcysteine enhances their glutathione content, thus reducing the paraquat- induced depletion of glutathione in these cells. These results suggest that N-acetylcysteine exerts its protective effect by acting as a precursor for glutathione in alveolar type II cells.

Acetylcysteine↗

Potassium-wasting nephropathy in an outbreak of chronic organic mercurial intoxication.

An outbreak of organic mercurial intoxication in a peasant family from the Jordan West Bank is reported. Extrapyramidal symptoms, muscular wasting, oral ulcerations, and renal tubular dysfunction were the main manifestations. Hpyokalemia (1.9-2.7 mEq/l) due to urinary potassium wasting was present in all 4 patients. Type II RTA was observed in 2 cases. Urinary ammonium excretion was increased over the range predicted by the given urinary pH in all the patients. Intrinsic tubular damage, nonreabsorbable anions of catabolic origin, increased prostaglandin synthesis inducing renin-angiotensin axis activation, and, consequently, inappropriate relatively high levels of aldosterone, are advanced as an explanation for potassium wasting.

Adolescent↗

Evaluation of a liposome system for the delivery of desferrioxamine to lungs in rats.

Liposomes with various lipid composition and sizes, prepared by two different techniques were evaluated for their potential to deliver desferrioxamine to lungs as a treatment against oxidative lung damage. Multilamellar vesicles (MLV) and reverse evaporation vesicles were prepared out of a lipid mixture containing dipalmitoyl phosphatidylcholine, stearyl amine, cholesterol and vitamin E. The administration of desferrioxamine-encapsulated liposomes to rats by the intravenous route at a dose of 100 mg kg-1, significantly prolonged the presence of desferrioxamine in all the tested organs when compared with the administration of free desferrioxamine. The injection of reverse evaporation vesicles extruded through a 2 microns polycarbonate membrane exhibited a longer residence time of the desferrioxamine and of liposomal vitamin E in lungs compared with the other types of liposomes tested. The examination of liposome components in the bronchoalveolar lavage fluid (BALF) and the alveolar macrophages recovered from BALF revealed that about 7 x 10(-3)% of the administered desferrioxamine dose was recovered by this technique at 3 and 17 h after liposome administration. This high residual concentration in the alveolar space confirms the hypothesis that liposomes can be delivered to the lung tissue when encapsulated in alveolar macrophages.

Animals↗

N-acetylcysteine delays the infiltration of inflammatory cells into the lungs of paraquat-intoxicated rats.

We investigated a possible role for N-acetylcysteine (NAC), a well-known antioxidant and free radical scavenger, against oxidative lung damage as observed in the in vivo model of paraquat-intoxicated rats. The administration of two ip doses of 50 mg/kg NAC to paraquat-intoxicated animals did not change the glutathione status of the lungs, as determined by the measurement of nonprotein sulfhydryl (NP-SH) groups. The administration of NAC did however suppress the paraquat-induced release of chemoattractants for neutrophils in the bronchoalveolar fluid when the lavage was carried out 12 hr after the administration of 30 mg/kg paraquat. Also, in the intoxicated NAC-treated animals, the infiltration of inflammatory cells was significantly reduced, as demonstrated by the examination of the cell composition of the bronchoalveolar lavage (BAL), 24 hr after paraquat. Phorbol myristate acetate-stimulated superoxide anion production from the AM isolated from the BAL of paraquat-intoxicated nontreated animals was lower than that of controls, whereas in the NAC-treated animals, it was close to that of the controls. The obtained results indicate that NAC has a protective effect against oxidative lung damage by delaying inflammation. It also prevents the paraquat-induced reduction of superoxide anion production by stimulated AM. In the present model, however, the NAC administration regimen did not affect the survival rate of paraquat-intoxicated rats.

Acetylcysteine↗

Pharmacokinetics of obidoxime in organophosphate poisoning associated with renal failure.

Obidoxime is an oxime used in several countries as an antidote in organophosphate intoxication. Its pharmacokinetics were studied in a 20 year-old female with severe and complicated methamidophos intoxication. Obidoxime elimination half life was 6.9 h, volume of distribution 0.845 L/kg, total body clearance 85.4 mL/min, and renal clearance 69 mL/min (creatinine clearance 54 mL/min). Eighty percent of the dose was excreted in the urine over 5 h. Possible reasons for the different pharmacokinetic values as compared with values previously reported in healthy volunteers are discussed. Obidoxime dose should be adjusted according to renal function. More studies are needed to establish the therapeutic window of obidoxime in patients with organophosphate intoxication.

Acute Kidney Injury↗

Effect of phosphamidon and obidoxime on the QT-RR relationship of isolated rat heart.

We studied the effects of phosphamidon (an organophosphate compound), obidoxime (a cholinesterase reactivator), and their combination, phosphamidon/obidoxime (PD/OB) on cardiac cycle length (RR), QT interval, and on QT-RR relationship of isolated rat heart. Cardiac cycle length did not change significantly following perfusion with phosphamidon or obidoxime alone; however, following perfusion with PD/OB, RR significantly increased at high concentrations (10(-3) M) of both drugs. The QT interval lengthened by 5% following perfusion with phosphamidon, did not change following perfusion with obidoxime, and increased by 10% following perfusion with PD/OB. The QT-RR relationship without drugs was positive and linear. Following perfusion with phosphamidon alone, the slope of the relationship decreased significantly, while perfusion with obidoxime alone did not change the QT-RR relationship. Perfusion with PD/OB at low concentrations decreased the slope of the relationship; however, at the highest concentration (10(-3) M) the QT-RR relationship was inverted and became negative. Ventricular arrhythmias as premature ventricular beats, or bigeminies, were noted with increasing frequency following perfusion with increasing doses of phosphamidon. Perfusion with obidoxime did not cause arrhythmias, whereas perfusion with PD/OB caused premature ventricular beats, bigeminies, and ventricular tachycardias at high doses. We suggest that obidoxime modulates the direct effects of phosphamidon on the cardiac repolarization process. PD/OB at high concentrations invert the normal depolarization-repolarization coupling and may therefore potentiate arrhythmias.

Animals↗

Obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.

The present study was designed to determine modulation of the direct inotropic effect of an anticholinesterase organophosphorus compound, phosphamidon, by the reactivator obidoxime. We investigated the effects of phosphamidon (n = 9), obidoxime (n = 5), and their combination (n = 5) on the mechanical and energetic indices of left ventricular function, in the isolated working rat heart model. Phosphamidon at a concentration range of 10(-6)-10(-3) M had a positive inotropic effect. Obidoxime at a concentration range of 10(-6)-10(-3) M had no significant effect on heart rate, but did have a statistically significant positive inotropic effect on end-systolic pressure, cardiac output, mean left ventricular pressure, and maximal time derivative of left ventricular pressure (dP/dtmax) (P less than 0.01). Perfusion with 10(-3) M obidoxime caused a 19% increase in left ventricular stroke work and a 31% increase in total pressure-volume area. Perfusion with phosphamidon and obidoxime at concentrations ranging from 10(-6) to 10(-3) M resulted in a more intense inotropic response than the separate drug effects. At the highest combined concentrations tested, cardiac output increased by 60%, left ventricular stroke work increased by 100%, and left ventricular total pressure volume area increased by 111% of their control values (P less than 0.001). We conclude that obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.

Animals↗

The administration of desferrioxamine to paraquat-intoxicated rats.

We investigated the effect of desferrioxamine, an effective iron chelator, on animal survival and on plasma vitamin E levels after administration of paraquat doses close to the LD50. Male Sprague-Dawley rats received 20 mg paraquat/kg followed by 300 mg desferrioxamine/kg/d given ip over 2 d at 3 equal intervals. The results suggested that desferrioxamine prevented the paraquat-induced depletion of vitamin E, but did not improve the mortality due to paraquat. In ancillary in vitro experiments with a paraquat-based free radical system, where glutathione reductase and NADPH were used as sources of enzymic activity for the redox cycling of paraquat, desferrioxamine effectively prevented the formation of hydroxyl radicals, as determined by deoxyribose degradation.

Animals↗

Parathion transfer and acetylcholinesterase activity in an in-vitro perfused term human placenta.

Organophosphate transport through the placenta was investigated in an in-vitro placental perfusion system. The system consisted of maternal and fetal reservoirs in which Krebs Ringer bicarbonate buffer with heparin, albumin and glucose was circulated at a constant pH, temperature and pO2. Parathion was analysed by means of gas chromatography with a N-P detector. 14C Antipyrine, a lipid soluble salt, was used as an internal standard, which allowed for the difference in placental size and permeability. A certain amount of parathion passed the placenta and reached the fetal compartment. Glucose consumption was not influenced by the introduction of parathion; neither was the water content of the placental tissue. Acetylcholinesterase activity in placental tissue decreased 50%. The amount of parathion transferred was not negligible and could have caused damage to a fetus.

Acetylcholinesterase↗

Direct effects of phosphamidon on isolated working rat heart electrical and mechanical function.

Phosphamidon (2-chloro-3-(diethylamino)-1-methyl-3-oxopropanyldimethyl phosphate) is widely used in agriculture as an organophosphate insecticide. It is a water-soluble cholinesterase inhibitor whose estimated rat LD50 is 9.2 mg/kg, ip. Mechanical and electrophysiologic direct effects of phosphamidon were studied in an isolated working rat heart model. Phosphamidon caused a positive inotropic effect, as indicated by increased maximum time derivative of left ventricular pressure and increased cardiac output. Stroke work and total pressure-volume area increased in a dose-dependent manner following perfusion with phosphamidon. Phosphamidon had in this preparation a biphasic effect on heart rate: at 10(-6) M concentration, heart rate increased, but at higher concentrations (10(-4)-10(-3) M) heart rate decreased significantly. High concentrations of phosphamidon caused a significant prolongation of the Q-T interval. We conclude that phosphamidon has potent cardiotoxic effects, both mechanical and electrophysiologic, on the isolated rat heart.

Animals↗

Efficiency of arsenic clearance from human blood in vitro and from dogs in vivo by extracorporeal complexing haemodialysis.

In vitro dialysis using human blood and in vivo extracorporeal haemodialysis trials with dogs, in the presence and absence of various chelating agents, showed that haemodialysis alone facilitated efficient removal of the metal, even in the absence of any of the chelating agents. In vitro haemodialysis for 5 hr without chelating agents caused the removal of 85% of the arsenic (As) added to the blood 1 hr before the beginning of the treatment. Ten-33% of the single dose given to the dogs, were removed into the dialysate during the first treatment and 8-15% during the second. The amounts of As excreted in the urine of dogs given 0.25 mg As/kg b.wt./day for 6 days were 6.8-7.4 mg As/24 hr, while the same amounts of the metal were removed into the dialysate during haemodialysis for 5 hr. This demonstrates the advantage of employing haemodialysis over the conventional treatment for the enhanced removal of As from the body.

Animals↗

Extracorporeal complexation haemodialysis for the treatment of cadmium poisoning. II. In vivo mobilization and removal.

The purpose of this study was to apply our earlier in vitro findings for extracorporeal complexation combined with haemodialysis to in vivo conditions, for the enhancement of cadmium (Cd) removal from dogs. The results showed that ethylenediaminetetraacetic acid (EDTA), glutathione (GSH) and combination of the two agents (EDTA + GSH) facilitated efficient elimination of cadmium. GSH, EDTA and EDTA + GSH treatments brought about the clearance of 2.2, 14.7 and 18.2 micrograms Cd/kg body weight/hr haemodialysis, respectively. Treatment with EDTA + GSH brought about the most rapid extravascular redistribution of the metal.

Animals↗

Exposure to paraquat through skin absorption: clinical and laboratory observations of accidental splashing on healthy skin of agricultural workers.

Data concerning 15 consecutive cases of single exposures of the skin or eyes during work to paraquat solutions are presented. Urine and serum were analysed for paraquat in all these cases at the laboratory of the Israel Poison Information Center. From these data it is apparent that a single exposure of healthy skin to paraquat solutions caused only local lesions. No systemic effect was detected in these patients.

Administration, Topical↗

CNS involvement in acute organophosphate poisoning: specific pattern of toxicity, clinical correlates and antidotal treatment.

The present review was designed to integrate both experimental and clinical data and to focus on the problems of management of severe cases of acute organophosphate poisoning, which always show CNS involvement. AChE activity, in discrete regions of the human brain, was studied by quantitative histochemistry of 40 mu thick sections. The regional effects of AChE inhibition by organophosphates was examined in a comparative study of the brains of two victims and two control brains, matched for age and sex. The pattern of AChE inhibition was regionally selective. The most significant decreases were observed in the neocerebellum, thalamic nuclei and the cortex. This specific distribution of AChE inhibition may be correlated with some of the clinical characteristics of acute organophosphate poisoning. The diagnostic value of blood AChE levels was examined in a personal series of 53 patients, who needed artificial ventilation, intensive care monitoring and antidotal treatment. The effects and side-effects of the antidotal treatment were reassessed. Recommended regimen of therapy was outlined, based upon experience in this series and in recent animal studies. The logical therapy would be and almost always in the co-administration of an anticholinergic drug (usually atropine) and an AChE reactivator (oximes) in order to rapidly obtain the most beneficial effect in the critically ill patient. Seizures that do not respond to the specific antidotal therapy, should be treated with I.V. benzodiazepines. Artificial respiration and supportive measures are essential for patient' survival. They enable the patient to gain the necessary time for sufficient recovery of AChE activity.

Acetylcholinesterase↗

Systemic manifestations of erucism: a case report.

Larvae of the caterpillar Thaumetopoea wilkinsoni are widely distributed in pine groves throughout Israel. Erucism is defined as urtication by Lepidoptera larvae. Both irritating effects on contact with skin and eyes and toxic effects on ingestion have been described after exposure to several species of Lepidoptera. We report the case of a 4-year-old child who vomited repeatedly and developed symmetrical swelling of both hands after touching a larva of Thaumetopoea wilkinsoni.

Animals↗

Meso-2,3-dimercaptosuccinic acid in the diagnosis and treatment of lead poisoning.

Lead poisoning remains one of the hazards of industrialized civilization. CaNa2 EDTA and dimercaprol, the usual therapeutic measures, have many side effects and can be given by parenteral route alone. The authors present a case of chronic lead poisoning caused by ingestion of contaminated flour ground in a primitive flour mill. The diagnosis was confirmed by the CaNa2 EDTA provocative test. Dimercaptosuccinic acid (DMSA) was given orally as a further provocation and resulted in an 11-fold increase in urinary lead excretion. A 5-day course of treatment with DMSA was instituted, during which symptoms abated, urinary lead excretion increased and the blood lead level decreased. No side effects were noticed. There has been no relapse over several months of follow-up. The authors conclude that the oral use of DMSA is effective, safe and convenient both as a provocative test in establishing the diagnosis of lead poisoning and as a therapeutic tool.

Adult↗