A magnetic resonance spectroscopic imaging study of adult nonhuman primates exposed to early-life stressors.

BACKGROUND: Long-term behavioral, immunologic, and neurochemical alterations have been found in primates exposed to adverse early rearing. METHODS: Bonnet macaque (Macaca radiata) mother-infant dyads were exposed to uncertain requirements for food procurement (variable foraging demand, VFD) for a few months. Ten years later, these offspring and age- and gender-matched control subjects were studied using proton magnetic resonance spectroscopic imaging (MRSI). RESULTS: In anterior cingulate, VFD-reared subjects displayed significantly decreased N-acetylaspartate (NAA) resonance and significantly increased glutamate-glutamine-gamma-aminobutyric acid (Glx) resonance relative to the stable neurometabolite creatine (Cr). Across all subjects, NAA/Cr and Glx/Cr ratios in the anterior cingulate were negatively correlated (r = -.638, p =.014). In the medial temporal lobe, the ratio of choline-containing compounds to Cr was significantly increased in VFD subjects. CONCLUSIONS: These findings indicate that adverse early rearing in primates has an enduring impact on adult MRSI measures considered reflective of neuronal integrity and metabolism, membrane structure and glial function, and cerebral glutamate content, and that these alterations occur in the same brain regions implicated in trauma-related psychiatric disorders.

A simple electrophoretic technique for the estimation of complement C3 conversion: specific application to the investigation of anaphylactoid response to I.V. agents.

A simple electrophoretic technique employing commercially available agarose films is described for the routine estimation of plasma complement C3 conversion. This technique has particular value in the investigation of anaphylactoid responses in patients following the administration of intravenous hypnotic drugs, plasma substitutes or radio-contrast media.

Continuous EEG and ICP monitoring as a guide to the administration of althesin sedation in severe head injury.

The effects of 142 intravenous boluses of althesin (0.05 ml/kg) on cerebral perfusion pressure (CPP) were studied in twelve head injured comatose patients. The data were divided into those where the mean pre-bolus intracranial pressure (ICP) was above or below 20 mmHg and then subdivided into those where the minimum pre-bolus voltage of the cerebral function monitor (CFM) was above or below 5 microV (representing marked reduction in cortical electrical activity). The pre-bolus ICP influenced the extent of the fall in ICP and thus the direction of the resulting change in CPP. A mean reduction in CPP was observed in both groups in which ICP was below 20 mmHg irrespective of the CFM voltage. In the subgroups with high ICP, CPP increased when CFM was not depressed and fell when CFM was below 5 microV. The effects of individual boluses varied within and between the subgroups and, occasionally, severe and unpredictable hypotension occurred. If althesin administration had been restricted to the high CFM and high ICP group, 90% of the episodes of reduced CPP would have been avoided. In fact, when cortical electrical activity is already severely depressed, further administration of hypnotic anaesthetic agents produces only small reductions in ICP and usually a fall in CPP. These findings suggest that the minimum voltage of the CFM trace is a clinically useful guide to the administration of intravenous anaesthetic agents and offers a relevant prediction of their effects on CPP.

Effects of inhalation and intravenous anesthetic agents on pressor response to NG-nitro-L-arginine.

The effects of anaesthetic agents on pressor effect of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide (NO) synthesis, were examined in rats. I.v. bolus of L-NNA (1-32 mg/kg) in conscious rats dose dependently increased mean arterial pressure (MAP) to a maximum value of 53 +/- 2 mmHg at 16 mg/kg with ED50 value of 4.7 +/- 0.9 mg/kg. The effects of a single i.v. bolus dose (32 mg/kg) of L-NNA were examined in conscious rats and rats anaesthetised with pentobarbital, chloralose, ketamine, althesin (mixture of alphaxalone and alphadolone), urethane, enflurane or halothane. In conscious rats, peak MAP (51 +/- 3 mmHg) was reached 10 min after i.v. injection and the effect lasted more than two hours. The magnitudes of peak MAP differed under the influence of anaesthetic agents with the following rank order: althesin greater than conscious = pentobarbital = chloralose = ketamine = urethane greater than enflurane much greater than halothane (in which there was negligible change in MAP). The onsets were delayed in rats anaesthetised with pentobarbital, althesin, chloralose and enflurane but not altered with ketamine and urethane compared to that in conscious rats. Therefore, L-NNA caused intense and prolonged pressor response in conscious rats and rats anaesthetised with the i.v. anaesthetic agents pentobarbital, chloralose, ketamine, althesin and urethane. MAP effect of L-NNA was markedly attenuated by the inhalation anaesthetics halothane and enflurane.

Althesin in the management of head injuries: a preliminary report.

The aggressive treatment of major craniocerebral trauma has received recent attention. Barbiturate administration has been beneficial in some cases of sustained, uncontrolled intracranial hypertension. One major disadvantage of pentobarbital narcosis is the long half-life of the drug (15 to 48 hours). We have used Althesin, an intravenous steroid anesthetic (alfaxalone and alfadolone acetate; Glaxo Laboratories Ltd., Greenford, Middlesex, England), in eight seriously head-injured patients. Althesin combines the theoretical advantages of pentobarbital in the management of head trauma with almost immediate reversibility (serum half-life, 1.6 minutes). Raised intracranial pressure and clinical outcome seem to be influenced favorably and the side effects are negligible when the drug is administered by continuous intravenous infusion over several days. Further study of this compound in the management of head trauma seems warranted.

["In situ" anesthetics and experimental cryotumorectomy]. / Anesthesiques "in situ" et cryotumorectomies experimentales.

Some similarities have been found between the actions of anesthetics and freezing on biological membranes. Therefore, it has been thought that these agents could potentiate the destructive effect of cryosurgery. Experiments on cryopreservation of HeLa cells in vitro using three anesthetics--thiopental sodium, lignocaïne and CT 1341--indicate enhancement of "cryosensitivity". When using in vivo the same anesthetics injected in an experimental carcinoma (KDMC) of the Sprague-Dawley rat, cryosurgically treated, the results are: --no tumoricidal effect nor antitumoral activity of these agents when used alone,--the simultaneous use of anesthetics and cryosurgery gives better (but no significant results than cryosurgery alone,--the best agent in regard to this possible adjuvant effect seems to be thiopental sodium, it also facilitates tumoral dissemination. The authors conclude from these preliminary results that they need further experiments to assess this findings with smaller tumors, more numerous animals, same and others anesthetics at different concentrations. They attempt to define some caracteristics of potentiative agents during physical phase of cryodestruction.

A clinical comparison of CT1341, ketamine, and xylazine in cats.

The new anesthetic agent CT1341 was compared to ketamine and xylazine in experimental and clinical situations with cats. Anesthesia with CT1341 was characterized by fast recovery times, good muscle relaxation, eyelid closure, occasional vomition, defecation, or urination during induction and recovery, generally smooth induction, and occasional hyperreflexive recoveries with much sneezing. The agent was moderately hypotensive, but caused little change in heart rate, central venous pressure, arterial pH, or blood gases.

Alphaxolone-alphadolone anaesthesia in laboratory animals.

The anaesthetic steroid combination alphaxolone-alphadolone is a well-established short-acting injectable agent for cats and primates. It can be recommended for intravenous administration to rats, rabbits, neonatal pigs, mice and hamsters. It has limited value in mice and hamsters by the intraperitoneal route, but provides sedation in ferrets and neonatal pigs when injected intramuscularly. It can be given repeatedly or continuously to maintain anaesthesia for long periods without the development of tolerance or cumulation.

Anaesthesia of the common marmoset (Callithrix jacchus) using continuous intravenous infusion of alphaxalone/alphadalone.

A safe means of anaesthetizing common marmosets (Callithrix jacchus) for a study using magnetic resonance imaging (MRI) to investigate cerebral ischaemia was required. Continuous infusion of alphaxalone/alphadalone was used to anaesthetize 37 marmosets for non-recovery and recovery experiments. This was found to give safe, reliable anaesthesia when coupled with pulse oximetry and electrocardiographic (ECG) monitoring.

Neuroleptanalgesic drug combinations in the anaesthetic management of small laboratory animals.

Trials of different drug combinations for use in rabbits, guinea-pigs, rats, hamsters and mice are described in detail and experience over a 5-year period evaluated. Combinations of fentanyl citrate, fluanisone and diazepam provided exceptionally good anaesthesia in each species and were considered superior to other injectable agents.

[The use of althesin in endoscopy]. / Utilizzazione dell'Althesin nelle pratiche endoscopiche.

Althesin was used on account of its pharmacokinetic and pharmacodynamic properties and its high therapeutic index in a search for a narcotic drug displaying minimal interference with metabolic and functional parameters in the aged. Continuous perfusion of the anaesthetic proved an extremely flexible method bearing in mind the varying length of the operations concerned. Stress is laid on the need for clinical control, especially at the moment of induction to ensure that timely action can be taken in the event of complications.

Anaesthesia for transcervical thymectomy in myasthenia gravis.

A modified technique of total intravenous anaesthesia was used in the management of 22 patients with myasthenia gravis of varying severity undergoing therapeutic transcervical thymectomy. The relatively short-acting intravenous hypnotics, Althesin and etomidate were compared for induction of anaesthesia and for maintenance as a supplement to 50% nitrous oxide in oxygen. Moderately high doses (20 or 25 micrograms/kg) of the potent, synthetic opiate, fentanyl provided analgesia and a level of respiratory depression sufficient to facilitate control of respiration. The induction of anaesthesia was rapid and smooth, completed in under 5 minutes. Reflex response to surgical stimulation was suppressed for extremely variable periods. Complete recovery of consiousness, or adequate spontaneous respiration and of muscle tone was readily achieved, but was more rapid after Althesin (p less than 0.05). Postoperative problems were few. It is suggested that this technique of anaesthesia can provide optimum operating conditions with rapid, complete recovery and consequently low morbidity; the primary requirements of anaesthesia for therapeutic thymectomy.

Effects of Saffan administered intravenously in the horse.

Saffan was injected intravenously on 41 occasions in 11 horses and ponies to investigate its possible use in clinical equine anaesthesia. The optimum dose for induction was 1-90 mg per kg. This dose was divided into two halves, the first half given in five seconds and the second half, containing suxamethonium chloride 0.1 mg per kg, in the next 10 seconds. Induction was associated with excitement for up to 30 secs after the assumption of recumbency. At this dose rate anaesthesia lasted five to eight minutes. Muscle relaxation was poor. Recovery was associated with marked tactile and audible hyperaesthesia. Slight stimulation resulted in twitching and violent kicking movements lasting up to 15 mins. Maintenance with halothane was satisfactory and recovery from this regime was uneventful. Anaesthesia could be maintained with Saffan alone. This agent would appear to offer no advantage over currently used anaesthetic agents in equine practice and to display several marked disadvantages.

[Anesthetic induction with Althesin or diazepam in patients undergoing an aortocoronary bypass]. / Induction anesthésique avec Alfatésine ou diazépam chez des patients opérés pour pontage aorto-coronarien.

The haemodynamic effects of induction of anaesthesia with diazepam (group D) and Althesin (group A) were studied in 25 coronary patients under betablockers with good myocardial function. Haemodynamic variables monitored were vascular pressures, cardiac output and systolic time intervals. The effects of both drugs were observed when used alone (time I) and in combination with fentanyl, pancuronium and nitrous oxide (time II). The results seemed to show that Althesin (12.51% fall in SI and 10.79% increase in PEP/LVET) depressed myocardial function more than diazepam (no significant difference), but the introduction of fentanyl, pancuronium and nitrous oxide removed the differences between the drugs as to their effect on myocardial performance. These drugs added a depressant effect to diazepam (13.83% fall in SI and 15.77% increase in PEP/LVET) without increasing Althesin's negative inotropic effect. However, in group A at time II, the pulmonary arterial pressure, the wedge pressure and the pulmonary vascular resistance were significantly reduced, while they remained stable in the diazepam group.

[Althesin or CT 1341 as a drug to induce balanced anesthesia with ethrane or fluothane associated with type II NLA in dental, maxillofacial and plastic surgery of the head area]. / L'Althesin o CT 1341 come farmaco di induzione alla narcosi bilanciata con ethrane o fluothane associati alla N.L.A. tipo II in chirurgia stomatologica, maxillo-facciale e plastica dell'estremo cranio-cefalico.

The Authors have tried Althesin as a medicine for the induction and maintainement of the narcosis in the stomatological, maxillo-facial and extra and intra-oral surgery. They have deduced that CT 1341 does not constitute to the anaesthetics Ethrane and Fluothane because of the anaesthetic-level instability (restlessness of the patient and clonic movements of the limbs during the most painful operations in particular). The Authors, supporters of the balanced anaesthesia, suggest using Althesin in the narcosis induction, the maintaining of which is carried on by the N.L.A. type II medicine and by the Ethrane or Fluothane. The latest ones are to be given in very small, not dangerous quantities. The Authors have so obtained a remarkable oxygenation of the patient, a ready, calm and lucid awakening without any collateral and dangerous consequences.

[Blood histamine level and anaphylactic reaction under alphadione]. / Histaminémie et réactions anaphylactoïdes sous alfadione.

Histamine release is generally thought to play a major role in anaesthetic-induced anaphylactoid reactions. In 12 patients who were developing such a reaction at the start of a slow rate intra-venous infusion of alphadione, serum histamine was measured using the enzyme-isotopic assay from a blood sample drawn within the first 5 minutes following the onset of clinical signs. Histaminemia above normal value was noted in 3 patients only without clear clinical correlation. These results would suggest that histamine release is unlikely to be principally involved in this kind of adverse reaction.

[On the toxicity of CT-1341 evoked by long-term administration. II. Subacute and chronic toxicities of alphaxalone in rats (author's transl)].

Alphaxalone, an anesthetic steroid dissolved in 20% Cremophor solution was administered intraperitoneally to test the subacute toxicity (administration for one month) and chronic toxicity (administration for 3 months). In daily doses less than 8 mg/kg, alphaxalone did not show any particular toxic sign after administered for three months. Rats tolerated to daily administration of 20 mg/kg for three months, without showing severe toxic signs in body weight curve, blood cells and biochemical data obtained in blood and urine. However, some female rats receiving 50 mg/kg/day of alphaxalone, died by paralysis of respiratory center at the second day. Main histo-pathological changes induced by subacute and chronic administrations of the larger doses than 20 mg/kg, were swelling of cells in the liver and kidneys, but severe pathological changes were not seen in any organs.

[On the toxicity of CT-1341 evoked by long-term administration. I. Subacute toxicity of the intravenous anesthetic, CT-1341 in rats (author's transl)].

CT-1341, an intravenous anesthetic was given in various daily doses in rats for a period of one month to test the subacute toxicity. The drug was administered intraperitoneally in rats. Rats tolerated to daily administration of CT-1341 at doses of less than 1.8 ml/kg without showing other particular toxic signs than anesthesia. Main pathological findings were swelling of cells in the liver and renal tubules, and perivascular cuffing in lungs. No severe patho-histological changes were observed in any organs. Mortal cases were seen in the group of rats, in which CT-1341 was given in a daily dose of 5.4 ml/kg. A paralysis of respiratory center was suggested to be cause of death, because no severe patho-histological changes were observed in any organs of mortal rats. Survivals of this group showed no particular symptom except anesthesia, but an inhibition of the growth curve was seen in male rats only.