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Biomedical subjects

E Geller

Publications and source records attributed to E Geller.

At least 55 records · Page 3Linked to original sources

Fenfluramine effects on serotonergic measures in vervet monkeys.

Chronic fenfluramine treatment reduced whole blood serotonin and CSF 5-hydroxyindoleacetic acid, but increased aggressive and locomotor behavior, in adult male vervet monkeys (Cercopithecus aethiops sabaeus). Following a drug-free washout period to monitor the drug recovery course, we initiated a second period of fenfluramine treatment in the same animals. When whole blood serotonin concentrations were reduced by about 40% from predrug baseline levels, we examined 11 cortical and subcortical brain regions for their content of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, norepinephrine, and dopamine. We observed correspondence between the reduction in whole blood serotonin and the reduction in brain 5-hydroxytryptamine. Similarly, there was a correspondence between the reduced 5-hydroxyindoleacetic acid levels observed in CSF and brain. No alterations were noted in the concentrations of norepinephrine or dopamine. These observations suggest that the behavioral effects observed in monkeys after chronic fenfluramine treatment result from reduced central serotonin.

Animals↗

Risks and benefits of therapy with flumazenil (Anexate) in mixed drug intoxications.

Flumazenil, the first specific benzodiazepine (BZD) antagonist, is one of the most innovative drugs to become available within the last few years. Flumazenil is indicated for the reversal of the centrally depressant effects of BZDs, in BZD-induced anaesthesia, in BZD sedation in intensive care and in patients comatose after drug overdoses including BZDs. A conference of experts experienced in the treatment of mixed drug overdoses by various means, including flumazenil, was held in order to try to reach a consensus regarding the safe use of flumazenil in this indication. From the knowledge and experience gained to date, it was concluded that flumazenil may be useful and safe in the treatment of suspected BZD and mixed drug overdoses, provided that the appropriate precautions are observed.

Antidepressive Agents, Tricyclic↗

Cardiorespiratory effects of antagonism of diazepam sedation with flumazenil in patients with cardiac disease.

The specific benzodiazepine antagonist flumazenil is currently under intense study. Despite much clinical experience, no detailed invasive hemodynamic studies of its use in cardiac patients have been published. In the present study, hemodynamic and respiratory variables were measured in 10 cardiac patients undergoing catheterization of the right and left sides of the heart, before and after sedation with intravenous diazepam, and after reversal of sedation with flumazenil. A sleep dose of diazepam (12.2 +/- 5.1 mg, mean +/- SD) caused only slight decreases in mean arterial pressure (103 +/- 12 to 98 +/- 14 mm Hg; P less than 0.05), pulmonary capillary wedge pressure (13.2 +/- 6.3 to 11.7 +/- 6.6 mm Hg; P less than 0.05), and left ventricular end-diastolic pressure (20.8 +/- 7.5 to 17.3 +/- 10.0 mm Hg; P less than 0.05), with no significant changes in respiratory gas homeostasis. Intravenous flumazenil (0.22 +/- 0.07 mg) resulted in spontaneous awakening and return to full orientation, yet caused no significant alteration in either hemodynamic or respiratory variables measured. Reversal of diazepam-induced sedation by flumazenil in cardiac patients appears safe and effective.

Aged↗

Paraparesis following emergency room thoracotomy: case report.

Spinal cord ischemia complicating resuscitative aortic occlusion is reported in a patient requiring emergency thoracotomy and aortic cross-clamping following a stab wound to the heart. Paraparesis and ischemic myelopathy were documented in the absence of associated injury. The possible contribution of systemic hypotension to spinal cord ischemia following aortic occlusion is suggested.

Adult↗

The respiratory effects of reversing midazolam sedation with flumazenil in the presence or absence of narcotics.

The purpose of this study was to determine the effects of reversal of sedation with flumazenil (F), in the presence or absence of opiates, on arterial oxygen saturation (SaO2) and end-tidal CO2 (ETCO2). Twenty-four patients undergoing surgery and epidural anaesthesia were studied. Twelve patients (Group A) were orally premedicated with diazepam and 0.1 mg.kg-1 morphine i.m. Intraoperative sedation consisted of midazolam 0.1 mg.kg-1 and pethidine 0.7 mg.kg-1 i.v. Twelve patients (Group B) were premedicated with diazepam and sedated intraoperatively with 0.1 mg.kg-1 midazolam. In the recovery room, six patients in each group were randomly allocated to receive 1 mg of flumazenil while the others were allowed to awaken spontaneously (control). Sedation (eyes open vs closed), SaO2, ETCO2, respiratory rate, blood pressure and pulse were non-invasively monitored for 90 min. Administration of flumazenil resulted in a statistically significant increase in the number of patients with eyes open in both groups at 5 min, lasting 15 min in Group A and 30 min in Group B patients. An increase in SaO2 from 15-45 min after injection of flumazenil was observed only in Group B. No significant difference between groups in any other parameter was found. We concluded that reversal of benzodiazepine (BZ) sedation with flumazenil improved SaO2 in patients sedated with only BZ; in the presence of BZ and opiates, flumazenil did not affect respiratory parameters.

Anesthesia, Epidural↗

A benzodiazepine receptor antagonist improves emergence of mice from halothane anaesthesia.

The benzodiazepine receptor antagonist, flumazenil, at a dose of 10 mg/kg given intraperitoneally to mice, had no effect on the minimum air concentration (MAC-50) of halothane causing anesthesia in 50% of the animals and which was 1.0% by volume of the inhaled air. Diazepam, 10 mg/kg, potentiated the effect of halothane. When the mice had been pretreated with diazepam and flumazenil, 10 mg/kg or 20 mg/kg, partial but not complete reversal of the potentiating effect of diazepam was observed, minimum air concentration values being 0.6% after diazepam alone and 0.8% after diazepam and flumazenil. However, mice pretreated intraperitoneally with flumazenil, in the concentration range 1-10 mg/kg, delivered as a solution in polyethylene glycol-Intralipid vehicle or as a suspension in saline, recovered control levels of spontaneous motor activity much faster than in the absence of flumazenil, on emergence from halothane-induced anaesthesia. In this range, the effect was not dose-dependent. These findings suggest that some of the effects of halothane are mediated at the level of the benzodiazepine receptor.

Anesthesia↗

Acute poisoning treated in the intensive care unit: a case series.

A retrospective study on patients with acute poisoning admitted to the Intensive Care Unit (ICU) of the Ichilov Hospital over a 3-year period (1982-84) is presented. Of 419 patients seen in the Emergency Room for intoxication during these years, 71 (17%) required intensive care upon admission. Suicide attempts accounted for 90% of the ICU admissions, with drugs of the benzodiazepine (BDZ) group being the most commonly used (51%). Mixed-drug overdose was seen in 55% of the patients. There was a poor correlation between the drugs suspected on admission and those actually detected in the blood. Although the total number of admissions due to poisoning increased in 1984 (21 in 1982 vs. 37 in 1984), mechanical ventilation was required by fewer patients (92% in 1982 vs. 51% in 1984) and for a shorter period of time (3.1 days in 1982 vs. 2.1 days in 1984), which resulted in a shorter ICU stay (4.8 days in 1982 vs. 3.1 days in 1984). The introduction of the new BDZ antagonist flumazenil may have partially accounted for this positive trend.

Acute Disease↗

Postherpetic neuralgia: clinical experience with a conservative treatment.

Ninety-seven consecutive cases of postherpetic neuralgia (PHN) were retrospectively reviewed. Patients comprised 49 women and 48 men with a mean age of 71.6 years. The most common painful locations were the chest and upper back (34%), abdomen and lower back (25.2%), and face (20.2%). Burning pain was the most common type of pain (61.3%). Lancinating pain was reported by 40% and throbbing pain by 22.6%. Treatments included drugs (mainly tricyclic antidepressant, anticonvulsant, and neuroleptic drugs), transcutaneous electrical nerve stimulation (TENS), and dry needling of muscles in the affected dermatomes. Positive response to treatment occurred in 18.5% of the patients after one visit. In 9.3% of the patients, the pain still could not be controlled after 10 visits of 2-week intervals. TENS proved to be effective in patients whose skin sensation was preserved. It was concluded that in most PHN cases, pain can be effectively controlled by conservative noninvasive therapy.

Adult↗

Success of contact chemolysis in calcified cholesterol gallstones.

Contact dissolution of cholesterol gallstones has emerged as a viable alternative in patients at high risk for surgery. The newest dissolution agent methyl tertiary butyl ether (MTBE) has undergone a series of successful clinical trials and has compared favorably with its predecessor, monooctanoin (MO). Previous studies have demonstrated the utility of MTBE in the setting of a large solitary gallstone impacted within the cystic duct as well as with multiple non-obstructing gallstones. We present a case of MTBE contact dissolution in the face of combined non-obstructing and obstructing gallbladder calculi. Whereas others have recommended restricting its use to those gallstones that are radiolucent, we have shown that MTBE may be used, and excellent results obtained, even with calculi that are calcified, so-called "Type 1" cholesterol gallstones.

Cholelithiasis↗

RO 15-1788 produces naloxone-reversible analgesia in the rat.

Intraperitoneal and intracerebroventricular administration of the benzodiazepine antagonist RO 15-1788 produced analgesia to both thermal and mechanical pain. This effect was reversed by pretreatment with the opioid antagonist naloxone but was unaffected by pretreatment with the benzodiazepine agonist midazolam. Furthermore, administration of the benzodiazepine antagonist RO 15-3505 was without analgesic effect. It is, therefore, proposed that the intrinsic action induced by RO 15-1788 is exerted via the indirect activation of endogenous opioid systems and that the observed effect is not due to the action of the antagonist on the benzodiazepine receptor.

Analgesics↗

Platelet size, number, and serotonin content in blood of autistic, childhood schizophrenic, and normal children.

Platelet volumes were measured in 19 autistic, 26 normal, and 6 schizophrenic children with similar blood serotonin concentrations. The groups did not significantly differ in platelet volumes, nor did platelet volumes and blood serotonin concentrations correlate. These results do not support the hypothesis that the hyperserotoninemia in some autistics reflects increased platelet volume.

Autistic Disorder↗

Midazolam infusion and the benzodiazepine antagonist flumazenil for sedation of intensive care patients.

ICU patients often require sedation. Midazolam (M), a new imidazobenzodiazepine, features rapid onset and rapid elimination time. Flumazenil (Ro 15-1788) is a new benzodiazepine antagonist. We studied the efficacy and safety of M by continuous infusion in 28 ICU patients: 16 post major surgery, and 12 medical patients, aged 20-77 years. M was administered as a loading dose of 0.05-0.15 mg/kg per min followed by continuous infusion of 0.05-0.1 mg/kg per h titrated to maintain patients asleep but arousable. M was administered for up to 14 days in doses of 1-15 mg/h and cumulative doses of up to 1915 mg. No untoward effects were noted except for slight decreases in blood pressure following the loading dose. ACTH challenge tests performed before and 24 h or more following the start of M showed no depression of adrenal responsivity. All patients meeting weaning criteria were weaned off mechanical ventilation while still on M. In 13 patients extubation was performed immediately after M was stopped, and flumazenil (0.38 +/- 0.27 mg, i.v.) given until full awakening. Patients remained awake yet calm. Vital signs remained stable after flumazenil. Midazolam by continuous infusion appears to be a safe and effective mode of sedation in ICU patients. Flumazenil may increase the flexibility and safety of this mode of sedation.

Adult↗

Early clinical experience in reversing benzodiazepine sedation with flumazenil after short procedures.

Flumazenil (Flu) (Ro 15-1788, Anexate) is a newly synthetized specific benzodiazepine (BZD) antagonist which was recently introduced for clinical study. The drug was intravenously injected, in titrated doses, to patients undergoing diagnostic or therapeutic procedures in order to reverse the sedative effects of BZDs. A total of 63 patients undergoing hand surgery under i.v. regional block, lower abdominal surgery under epidural anesthesia, cardiac catheterization, intracardiac catheter ablation, cardioversion, gastroscopy and bronchoscopy were studied. Flu in a dose ranging from 0.1 to 0.42 mg effectively reversed BZD-induced sedation in all patients 1-2 min following i.v. injection. Patients were fully awake and oriented yet calm and in good mood. Flu was well tolerated even in the high risk cardiac patients, with no significant changes in vital signs nor any sign of local irritation at the site of Flu injection. No significant resedation was observed. Thus Flu was very useful in reversing BZD-induced sedation or unconsciousness in a variety of clinical situations.

Aged↗