Interaction of pregnanolone and pregnenolone sulfate with ethanol and pentobarbital. 3-alpha-Hydroxy-5-beta-pregnan-20-one [pregnanolone (PA)] and 3-beta-hydroxy-5-pregnen-20-one 3-sulfate [pregnenolone sulfate (PS)] are steroids that have been shown in biochemical studies to be active at the GABA-benzodiazepine-chloride receptor complex, Pa as a "barbiturate-like" agonist and PS as a "picrotoxin-like" antagonist. Since other compounds that are active at this site interact with the effects of pentobarbital and ethanol, the behavioral effects of these steroids alone and in combination with pentobarbital and ethanol were tested. Pa blocks the convulsions caused by pentylenetetrazole (PTZ) and increases motor activity when given alone in low doses. In combination with either pentobarbital or ethanol, it enhances the depression in motor activity, hypothermia, and hypnosis. In contrast, PS has no effect on PTZ convulsions and depresses motor activity by itself. With pentobarbital, PS enhances the depression in motor activity but has no effect on hypothermia or hypnosis. With ethanol, PS enhances the hypothermia but does not affect motor activity or hypnosis. Therefore, Pa and PS show different but not opposite effects in interacting with compounds active at the GABA-benzodiazepine-chloride receptor complex.


Potentiation of the dorsal immobility response following intrastriatal injections of enkephalins. The effects of bilateral intrastriatal injections (1.0 microgram/side) of leucine5- and methionine5-enkephalins and their related nonopiate fragments upon three measures of immobility over a time course were investigated. Both leucine5-enkephalin and des-Tyr1-leucine-enkephalin potentiated the duration of the dorsal immobility response (DIR) 15 min postinjection and over a 1-h time course. On the other hand, methionine5-enkephalin and des-Tyr1-methionine-enkephalin potentiated the duration of the DIR at 5 and 15 min. These enkephalins and their fragments had no effect upon vertical cling and bar catalepsy. In a second study, an SC injection of 4 mg/kg naloxone 15 min prior to the central injections blocked the potentiation of the DIR effects of the enkephalins.


Direct microinjection of cathinone into the rat brain produces discriminative stimuli. Rats were trained to discriminate IP administration of 800 micrograms/kg cathinone using a food-motivated, two-lever discrimination procedure. Following training, 800 micrograms/kg cathinone discrimination was produced (generalized) by lower cathinone doses in a dose-responsive manner after IP administration; an ED50 value of 330 micrograms/kg was calculated. Subsequently, guide cannulae were implanted into the lateral ventricle and bilaterally into the nucleus accumbens. After recovery, injections were made via cannulae that extended 0.5 mm past the tip of the guide cannulae. ICV administration of 256 micrograms cathinone/rat produced discriminative responding on the cathinone-appropriate lever to the same degree as did the peripherally administered training dose of cathinone. Decreasing ICV doses produced decreased discriminative performance and allowed the calculation of an ED50 value of 90.5 micrograms. Likewise, administration of 64 micrograms cathinone/nucleus accumbens (for a total of 128 micrograms/rat) substituted for the IP training dose of cathinone. These results evidence the central mediation of the cathinone-induced discriminative stimulus cue and show that administration of cathinone into the nucleus accumbens is sufficient to produce these stimuli. Thus, these data suggest that receptors in the nucleus accumbens are important for the discrimination of this psychostimulant.


Phencyclidine does not disrupt latent inhibition in rats: implications for animal models of schizophrenia. Latent inhibition (LI) is a behavioral paradigm in which prior exposure to a stimulus not followed by reinforcement retards subsequent conditioning to that stimulus when it is paired with reinforcement. The development of LI reflects a process of learning to ignore, or tune out, irrelevant stimuli. Three experiments investigated the effects of phencyclidine (PCP) on LI. The investigation was carried out using a conditioned emotional response (CER) procedure consisting of three stages: preexposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; conditioning, in which the preexposed stimulus was paired with shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 h apart. In Experiment 1, 1 mg/kg PCP was administered either in the preexposure or in the conditioning stage or in both. Experiment 2 used 5 mg/kg PCP in the same procedure. In Experiment 3, 5 mg/kg PCP was administered throughout the LI procedure, including the test stage. In all three experiments, PCP did not affect LI. The implications of these findings for the development of animal models of schizophrenia are discussed.


Oral caffeine consumption by rats: the role of flavor history, concentration, concurrent food, and an adenosine agonist. Some determinants of caffeine consumption by rats were examined using the two-bottle choice test. To describe the role of flavor history, groups of eight rats each received one of three fluids as their only source of fluid beginning at 29 days of age and continuing throughout the experiments. One group ("water") received tapwater, a second group ("caffeine") received 0.5 mg/ml caffeine in tapwater, and a third group ("quinine") received 0.01 mg/ml quinine in tapwater. Two-bottle choice tests began when rats were 40 days old. In the initial tests, caffeine rats drank more caffeinated water than water rats. Quinine rats were midway between these two groups. On a second block of tests, quinine and water rats' caffeine consumption increased so that the three groups were indistinguishable. When 0.5 mg/ml caffeine was available for 24 h, about one third of the total fluid consumption was of caffeinated water for all three groups. The presence of food greatly increased both caffeine and water consumption across a range of caffeine concentrations spanning 0.125-4.0 mg/ml. Increasing caffeine concentration generally increased consumption of plain water and decreased that of caffeinated water (but not total caffeine consumed) for water rats. Caffeine rats generally drank more caffeine than water rats, largely due to a tendency toward increased consumption of the 0.5-mg/ml concentration. Consumption of caffeinated water peaked at 0.5 mg/ml and showed graded decreases at higher and lower concentrations. Caffeine consumption showed dose-related increases with presession administration of l-phenylisopropyl adenosine. The serines of experiments characterize some of the determinants of caffeine consumption in rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Naltrexone, serotonin receptor subtype antagonists, and glucoprivic intake: 1. 2-Deoxy-D-glucose. Inhibition of deprivation-induced intake by naloxone was significantly enhanced by the 5-hydroxytryptamine3 (5-HT3) antagonist ICS-205,930. Interactions between naloxone and either the general 5-HT antagonist methysergide or the 5-HT2 antagonist ritanserin or ketanserin produced smaller effects. The present study evaluated whether 2-deoxy-D-glucose (2DG, 400 mg/kg) hyperphagia was affected by methysergide (0.5-5 mg/kg), ritanserin (0.25-2.5 mg/kg), or ICS-205,930 (0.5-5 mg/kg) alone or in combination with naltrexone (0.25 and 2.5 mg/kg). Only ICS-205,930 stimulated spontaneous intake for up to 4 h in the light cycle. Only ritanserin (1.25 mg/kg) transiently reduced 2DG hyperphagia. The dose-dependent decreases in 2DG hyperphagia by naltrexone were significantly enhanced by the dose range of ICS-205,930. The inhibition of 2DG hyperphagia by the low naltrexone dose was enhanced by methysergide (5 mg/kg) and ritanserin (1.25 mg/kg). These data suggest that the 5-HT3 receptor primarily interacts with opioid systems to modulate 2DG hyperphagia and that one possible locus of interaction is in the caudal brainstem.


Naltrexone, serotonin receptor subtype antagonists, and glucoprivic intake: 2. Insulin. Opiate antagonist inhibition of deprivation-induced intake and 2-deoxy-D-glucose (2DG) hyperphagia is significantly enhanced by the 5-hydroxytryptamine3 (5-HT3) antagonist, ICS-205,930. Interactions between opiate antagonists and either 5-HT or 5-HT2 antagonists produced smaller effects. The present study evaluated whether insulin (5 U/kg) hyperphagia was affected by methysergide (0.5-5 mg/kg), ritanserin (0.25-2.5 mg/kg), and ICS-205,930 (0.5-5 mg/kg) alone or in combination with naltrexone (2.5-10 mg/kg). Whereas ICS-205,930 stimulated insulin hyperphagia across the 6-h time course, ritanserin and, to a lesser degree, methysergide reduced insulin hyperphagia. Naltrexone marginally (19-33%) reduced insulin hyperphagia. Pairing naltrexone with either ICS-205,930 or ritanserin significantly suppressed insulin hyperphagia after 2 h. Pairing naltrexone with each of the serotonin antagonists significantly enhanced insulin hyperphagia after 4 and 6 h. These data suggest that 5-HT2 and 5-HT3 receptor subtypes interact with opioid systems to modulate insulin hyperphagia. Given that central insulin reduces food intake and body weight, the interaction between serotonergic and opioid systems may occur peripherally.


Reduction of flurazepam's antiseizure efficacy persists after stress. Twenty-four hours after mice were forced to swim for up to 10 min in cold (6 degrees C) water, the ability of flurazepam to antagonize the electrical precipitation of seizures was reduced. This stress-induced reduction in flurazepam's antiseizure efficacy persisted for at least 72 h; but was absent 1 week after the single session of swim stress. The data may be relevant to stress-related psychiatric disorders and suggest that the therapeutic efficacy of benzodiazepines may be altered after a severe stress.


A-71623, a selective CCK-A receptor agonist, suppresses food intake in the mouse, dog, and monkey. The anorectic actions of cholecystokinin (CCK)-8 and of a selective CCK-A agonist, A-71623, were examined in CD1 mice, beagle dogs, and cynomolgus monkeys. A-71623 suppressed intakes in all species tested, and the effects were blocked by a selective CCK-A antagonist, A-70104. In the dog only, CCK-8 was more potent on a molar basis compared to A-71623, although the effects of both CCK agonists were more short-lived in the dog compared to the other species tested. Our results support other evidence suggesting that the anorectic actions of exogenous application of CCK-8 in these species are mediated via stimulation of the CCK-A receptor subtype.


Effects of d-amphetamine on the recovery of function following cerebral ischemic injury. Amphetamine with appropriate motor experience has been found to facilitate the recovery of motor function after several different types of brain injuries. We investigated whether amphetamine would hasten the recovery of spatial mapping ability in gerbils previously subjected to a 3-min episode of forebrain ischemia. Amphetamine did not promote behavioral recovery, nor did it attenuate ischemic cell damage of hippocampal CA1 neurons. The beneficial effects of amphetamine after brain injury may be limited to restoration of sensorimotor ability and not to cognitive functions such as memory.


Behavioral performance, brain histology, and EEG sequela after immediate combined atropine/diazepam treatment of soman-intoxicated rats. It is known that rats poisoned with near-lethal doses of pinacolyl methylphosphonofluoridate (soman) develop brain lesions, particularly when convulsions are induced. When rats were intoxicated with a LD50 of soman and treated immediately thereafter with a combination of low doses of atropine and diazepam (LOW AS/DZ treatment), large decrements in performance of an earlier acquired shuttle-box task were found 6 days after intoxication. In contrast, no such decrements were found in soman-intoxicated animals treated similarly with a combination of high doses of these drugs (HIGH AS/DZ treatment). Surprisingly, surviving LOW AS/DZ animals acquired the same task again at a speed that was almost as fast as before intoxication. Similarly treated animals were examined light-microscopically 24 h after intoxication; in LOW-AS/DZ-treated animals, neuropathology was only observed in animals that had exhibited convulsions, whereas in HIGH AS/DZ animals neither convulsions nor brain damage were observed. Power spectra, obtained from electroencephalograms (EEGs) 6 days after intoxication, revealed significant differences between both treatment groups, particularly in the delta-, theta-, and beta-frequencies. After the HIGH AS/DZ treatment, a significant increase in delta activity was found compared to control values, suggestive of neuropathology. It is concluded that, in contrast with the LOW AS/DZ combination, HIGH AS/DZ prevents active avoidance deficits, convulsions, and light-microscopically detectable neuropathology after soman intoxication. However, the results of EEG measurements suggest that some aberrations may still remain even after the HIGH AS/DZ treatment.


Effects of bifemelane on discrimination learning of serotonergic-dysfunction rats. To investigate the effect of bifemelane hydrochloride on learning achievements of serotonin-deficient rats, animals were fed with tryptophan-deficient diets and operant type discrimination learning tests were performed. In general, serotonin-deficient rats show hyperactivity. In this study, total number of responses in reverse learning experiments was lower in rats that received 50 mg/kg bifemelane compared to the other serotonin-deficient groups. The ratio of correct responses to the total number of responses revealed low learning achievements in the control and low-dose groups, whereas the ratio in the high-dose group was nearly the same as in normal rats in the final few sessions of both the primary and reverse learning experiments. Throughout this study, the high-dose group showed a better improvement in learning achievement than the low-dose group. Therefore, bifemelane has certain effects on learning achievement from a) the functional activation of the serotonergic nervous system and b) changes in neurotransmitter levels in the brain (e.g., acetylcholine, noradrenaline) and overall energy metabolism.


beta-Carboline and pentylenetetrazol effects on conflict behavior in the rat. The beta-carbolines and the convulsant agent pentylenetetrazol (PTZ) have been reported as "anxiogenic" in several animal models for anxiety. The present study examined the effects of the beta-carboline noreleagnine (NOR) and PTZ, administered alone and in combination with the benzodiazepine antagonist, Ro 15-1788, on behavior in the conditioned suppression of drinking (CSD) conflict procedure. In daily 10-min sessions, water-deprived female SD rats were trained to drink from a tube that was electrified (0.25 mA). Electrification was signaled by a tone. Acute (20-min) treatment with NOR or PTZ resulted in a dose-dependent decrease in both punished responding (shocks received) and unpunished responding (water intake). Both NOR and PTZ decreased punished responding only at doses that also depressed unpunished responding. Coadministration of Ro 15-1788 (2 mg/kg) reduced the effects of NOR on punished, but not unpunished, responding; this Ro 15-1788 cotreatment reduced the effects of PTZ on both punished and unpunished responding. These data suggest that both PTZ and NOR produce benzodiazepine receptor-mediated anxiogenic-like effects on conflict behavior.


Neonatal treatment with clomipramine increased immobility in the forced swim test: an attribute of animal models of depression. The forced swimming test in rats has been identified as a suitable model for detecting antidepressant activity of several drugs regardless of their mode of action. On the other hand, a number of animal models of human endogenous depression have been proposed. Recently, it has been reported that perinatal administration of clomipramine in rats elicits behavioral changes in adulthood that resemble human endogenous depression. In the present study, we showed that in this new animal model of depression immobility was increased when animals were submitted to the forced swimming test. This finding supports the notion that the amount of immobility during the forced swimming test is directly proportional to a depressive state in the rat.


Neonatal brain dopamine depletion and the cortical and behavioral consequences of enriched postweaning environment. This study investigated the effects of neonatal intraventricular administration of 6-hydroxydopamine (6-OHDA, 15 micrograms total with and without desmethylimipramine pretreatment) on the cortical thickening and behavioral effects of 35 days of enriched postweaning housing (ENR) in the rat. The 6-OHDA treatment depleted cortical dopamine (DA) to about 40% of control. It did not affect the thickness of the cerebral cortex nor did it affect the capacity for the cortex to be thickened by ENR. In addition, it did not alter the superior performance on two spatial water maze tasks that was caused by ENR. Thus, the potential for neurobehavioral plasticity was not changed by neonatal DA depletion. ENR eliminated the spatial learning/memory deficits that were caused by neonatal DA depletion and that were manifested when the rat was raised in standard (impoverished) laboratory conditions. Hence, environmental factors can modulate the cognitive effects of neonatal DA depletion. ENR did not attenuate the hyperactivity of the neonatal DA-depleted rat. This may reflect the subcortical mediation of this behavioral abnormality.


Memory deficits following chronic alcohol consumption in mice: relationships with hippocampal and cortical cholinergic activities. Chronic ethanol consumption (12% v/v for 12 months) produced an accelerated decay of T-maze spontaneous alternation (SA) rates as the interval that elapsed between forced trials, used as acquisition, and a free test trial, used as a retention test, increased. Thus, alcohol-treated mice that exhibited normal SA rates at a short interval (5 min) were impaired at the longer one (6 h) relative to controls. This alcohol-induced deficit was almost completely reversed by physostigmine (0.05 mg/kg, IP) given only before the test trial. Parallel neurochemical analysis showed that chronic alcohol intake produced a significant decrease in hippocampal and cortical sodium-dependent high-affinity choline uptake. In particular, the significant cholinergic activation produced by a T-maze exploration in controls was attenuated in experimental subjects so that the between-groups differences already present in the quiet condition were amplified in the active (exploration) state. These findings suggest that the memory deficits induced by chronic ethanol consumption stem from a failure of some cholinergic-dependent retrieval processes. An attempt is made to relate the present results with our previous ones that emphasized the importance of diencephalic damage in alcohol-induced retrieval deficits.


Effects of lorazepam on psychomotor performance: a comparison of independent-groups and repeated-measures designs. The purpose of this study was to compare the sensitivity to the effects of lorazepam (2.5 mg) of a design using independent groups (random allocation of subjects to either a placebo or a lorazepam treatment) with a repeated-measures design (subjects tested both before and after lorazepam treatment). With both designs, it was possible to demonstrate significant and equal effects of lorazepam in tests based upon speed of responding: Lorazepam significantly increased simple reaction time and significantly decreased performance in number cancellation and symbol copying tasks. The independent-groups design was more sensitive (i.e., showed effects at a higher level of significance) to the lorazepam-induced impairment in episodic memory, as assessed in a picture recognition task, and to the lorazepam-induced impairment in a word completion task. Comparisons between the two control condition scores indicated that there were unlikely to be significant group differences with random allocation of a relative homogeneous group of volunteers, such as medical students. While either design would be appropriate for homogeneous populations, for a heterogeneous clinical population where groups cannot be matched the repeated-measures design would be preferable.


Naloxone reduces amphetamine-induced stimulation of locomotor activity and in vivo dopamine release in the striatum and nucleus accumbens. This study tested the possibility that naloxone (NX), an opioid antagonist, reduces the behavioral effects of amphetamine (AMPH) in rats by attenuating the dopaminergic response to AMPH. In the first experiment, adult, male rats were injected SC with either NX (5.0 mg/kg) or saline and 30 min later received doses of AMPH (0.0, 0.1, 0.4, 1.6, and 6.4 mg/kg) cumulatively at 30-min intervals. Gross locomotor counts following AMPH administration were significantly lower for rats pretreated with NX than for rats pretreated with saline. In the second experiment, the same drug treatments were given while performing microdialysis in either the striatum (STR) or nucleus accumbens (NACC). STR rats treated with vehicle showed a larger percentage increase in DA levels following AMPH treatment than did NACC rats treated with vehicle. NX pretreatment did not affect dopamine concentrations in either brain region. However, compared to pretreatment with saline pretreatment with NX significantly decreased the dopaminergic response to AMPH in the STR. There was no difference between the two groups in the peak dopaminergic response to AMPH in the NACC, but there was a significant AMPH x treatment x time interaction due to differences between the groups during the later portion of the response to 6.4 mg/kg AMPH. There was also a difference in locomotor activity following AMPH treatment between NX- and saline-treated subjects during dialysis. These findings suggest that a decrease in the dopaminergic response to AMPH is the mechanism by which NX attenuates behavioral stimulant effects of AMPH. In addition, there is a difference between the STR and NACC in dopaminergic responsiveness to AMPH.


Cocaine euphoria, dysphoria, and tolerance assessed using drug-induced changes in brain-stimulation reward. The time course of cocaine-induced changes in self-stimulation thresholds were used to evaluate cocaine euphoria and dysphoria as a function of the chronicity of drug treatment, dosage level, and the spacing of injections. It was assumed that cocaine-induced decreases in thresholds were indicative of cocaine euphoria, while increases in thresholds reflected rebound dysphoric responses to cocaine administration. Three experiments were performed using self-stimulating rats implanted with ventral tegmental area electrodes. Cocaine's threshold-lowering effects were evident 15 min postinjection (IP) with thresholds returning to baseline by approximately 3.0 h after treatment. Little evidence for cocaine-induced increases in thresholds was observed during periods of chronic cocaine treatment. However, thresholds were slightly elevated upon withdrawal from chronic cocaine treatment in Experiments 2 and 3. No evidence of tolerance or sensitization to cocaine-induced shifts in thresholds was noted with single daily injections, while multiple daily injections produced tolerance to cocaine's threshold-lowering effects. It is concluded that cocaine's ability to enhance brain-stimulation reward is highly reliable and robust, while decreases in brain-stimulation reward associated with chronic cocaine treatment are less reliable and difficult to demonstrate. The possible influence of drug dosage on the induction of cocaine dysphoria and the ability of various self-stimulation procedures to measure dysphoric effects are discussed.


Oxiracetam prevents haloperidol-induced passive avoidance impairment in mice. The nootropic drug oxiracetam (50 mg/kg) prevented passive avoidance impairment induced by posttraining administration of haloperidol (0.25 and 0.5 mg/kg). Conversely, oxiracetam did not antagonize either locomotor depression or suppression of active avoidance responses induced by the dopamine receptor blocking agent. The results indicate that prevention of haloperidol-induced retention impairment, by oxiracetam, may be due to a not yet defined protective action, common to other nootropic agents, on different types of experimental amnesias, rather than to a specific interaction with dopaminergic mechanisms.


Upregulation of postsynaptic dopamine receptors in the striatum does not influence haloperidol-induced catalepsy in mice. The incidence of haloperidol-induced catalepsy was investigated in mice whose postsynaptic dopamine (DA) receptors in the striatum had been upregulated by denervation with 6-hydroxydopamine (6-OHDA). In nonupregulated mice, which were injected with 6-OHDA 4 days before, DA in the striatum fell to 21% of the level found in vehicle-injected mice but [3H]spiperone binding to the membrane of the striatum did not increase. In upregulated mice, which were injected with 6-OHDA 28 days before, DA was at 24% and [3H]spiperone binding increased by 15%. The ED50 values (with 95% confidence limits) for haloperidol-induced catalepsy in nonupregulated mice and that in upregulated mice was 0.40 mg/kg (0.25-0.65 mg/kg) and 0.29 mg/kg (0.16-0.51 mg/kg), respectively. There was no significant difference in the incidence of catalepsy between the two groups of mice. This suggests that the intensity of catalepsy produced by the DA receptor blockade may be unaltered even when the density of receptors increases.


Reversal of testosterone-induced dominance by the serotonergic agonist quipazine. Anabolic steroids and other androgens, such as testosterone propionate (TP), have a facilitatory role in the expression of aggressive behavior. Based upon literature indicating an inverse relationship between aggression and the central neurotransmitter serotonin (5-HT), the present study was undertaken to investigate the role of 5-HT in androgen-induced aggression. In this study, an animal model of aggression involving competition between male rat pairs for sugar pellets was used to investigate the effects of TP. When TP was administered daily (30 mg/kg) to nondominant rats, these animals became dominant. Dominant behavior was found to be stable throughout the study with continued daily administration of TP. To test the serotonergic component of TP-induced aggression, the serotonergic agonist 2-(1-piperazinyl) quinolone dimaleate (quipazine) was administered acutely to TP-dominant rats. Quipazine dose dependently reduced aggressive dominance in TP-dominant rats, as well as in naturally dominant rats. When the serotonergic antagonists pirenpirone or pizotyline were coadministered with quipazine to either group of dominant rats, they blocked the effect of quipazine in reducing dominance. However, when 1-[1H-Indol-4-yloxy]-3-[isopropylamino]-2-propanol (pindolol), a drug that acts at both beta-adrenergic receptors and at 5-HT1A and 5-HT1B receptors, was coadministered with quipazine there was a reversal of the quipazine effect on aggression only in TP-dominant rats. These results indicate that androgen-induced aggression may involve a complex alteration in serotonergic neurotransmission.


Effects of chronic morphine administration and naloxone on EEG, EEG power spectra, and associated behavior in two inbred rat strains. Utilizing behavioral and electroencephalographic (EEG) assessments, two inbred rat strains, Lewis (LEW) and Fischer 344 (F344), were exposed to morphine (IV) over a period of 7 days to discern differences in tolerance development. Following morphine injection, the LEW group demonstrated a greater mean total amount, as well as a greater rate of reduction, of stuporous behavior across the 7 days tested. Differences in patterns of latency to onset of slow-wave sleep between the two strains were also exposed. EEG analysis of spectral parameters utilizing an analysis of variance with repeated measures revealed that peak frequency, mean frequency, and edge frequency differed as a function of inbred rat strain. All spectral parameters differed as a function of duration of morphine injection; linear trends were indicated for both strains. Naloxone was administered (IV) following the 7 days of morphine to delineate dependence differences. LEW animals reflected a greater amount of behavioral responses, for example, wet-dog shakes, diarrhea, body stretch, and sluggish behavior. However, F344 rats demonstrated a greater alteration in two spectral parameters assessed: peak frequency and total power. Genetic variability appears to play a major role in both morphine tolerance and dependence as indicated by differences in EEG and behavioral responses.


Embryonic differentiation of sexual dimorphism in vasotocin and mesotocin levels in chickens. Chicken embryos of both sexes were injected on the tenth day of incubation with either estradiol benzoate (EB), aromatase inhibitor [1,4,6-androstatrien-3, 17-dione (ATD)], antiestrogen [tamoxifen (TAM)], antiandrogen [flutamide (FLU)], or the oil vehicle as control (C). At adulthood, at the age of 26 weeks, 10 chickens of each sex were killed and the amounts of immunoreactive arginine vasotocin (AVT) and mesotocin (MT) in the anterior hypothalamus (AHA), posterior hypothalamus (PHA), neurohypophysis (NHP), and pineal gland (PNL) were determined. Control hens had significantly more AVT in PNL and less MT in AHA and NHP than the corresponding roosters. This sexual dimorphism was affected by the embryonic treatments; TAM increased AVT in AHA of cockerels but not of hens. In both sexes, TAM and FLU increased AVT content in NYP. In males, but not in females, ATD also increased AVT content in the NHP. TAM and FLU administration to the female embryo reduced PNL AVT to the amount present in normal males. None of the treatments effected AHA MT in hens, while in cockerels TAM increased it. In females, TAM and FLU significantly increased NHP MT to the level of C males. In roosters, ATD, TAM, and FLU increased NHP MT further. In hens, but not roosters, FLU reduced MT in PNL. These results indicate that embryonic differentiation of the MT and AVT systems is affected by gonadal steroids in chickens.


Daily dose of ethanol and the development and decay of acute and chronic tolerance and physical dependence in rats. Using behavioral and physiological measures, we compared the rates of development and decay of acute and chronic tolerance to ethanol (ET) and the severity of the withdrawal syndrome. Male rats were treated with 6, 9, or 12 g/kg/day ET or equicaloric dextrin maltose, delivered intragastrically. Although treatment duration varied, the total dose of ET was kept constant at 162 g/kg/rat for the three groups. The effects of a cumulative test dose of ET or equicaloric dextrin maltose, after exposure to a total of 0, 42, 83, 126, and 162 g/kg ET, and at 3, 5, and 7 days after termination of the chronic treatments, were evaluated on rectal temperature, dowel performance, and tail-flick and startle responses. After the initial five tolerance tests, chronic treatments were discontinued and rats were tested in a modified open-field apparatus and for their startle response to an auditory stimulus at 8, 12, 16, 20, 32, and 40 h later. With all measures, little tolerance developed in the 6-g/kg/day group. On the other hand, development of chronic tolerance was fastest in rats treated with the 12-g/kg/dose of ET. Chronic tolerance did not develop to ET's depressant effect on the startle response. Acute tolerance declined with chronicity of treatment in animals given the largest daily dose of ET. During withdrawal, and in contrast to the dextrin maltose-treated animals, there was impairment in all measures taken during the modified open-field test and hypersensitivity of the startle response for all three chronic ET-treated animals. Greatest behavioral impairment occurred in animals treated with 12 g/kg/day, and some impairment was still evident 40 h after the last dose of ET. Thus, the severity of the withdrawal syndrome was greatest in the group displaying the most acute and chronic tolerance.


Facilitative effect of carbamazepine on previously induced hippocampal long-term potentiation. The effects of carbamazepine (CBZ) on previously induced hippocampal long-term potentiation (LTP) were examined. Acute experiments were performed on 33 adult, male rabbits. Field potentials in the dentate gyrus were elicited by single shocks to the perforant path, and LTP was induced by tetanic stimulation to the pathway without induction of seizure discharge. At a CBZ serum level of about 5 micrograms/ml (value +/- SD = 5.40 +/- 1.28 micrograms/ml), the previously induced LTP in population spikes (PSs) and population excitatory postsynaptic potentials (EPSPs) was facilitated. At a CBZ serum level of about 15 micrograms/ml (value +/- SD = 14.28 +/- 1.29 micrograms/ml), the LTP in PS alone was decreased. The effects of carbamazepine on synaptic inhibition were examined by the paired-pulse test. The inhibition was enhanced with induction of LTP. After administration of CBZ, at a CBZ serum level of about 5 micrograms/ml the inhibition was further enhanced, while it was attenuated at a CBZ serum level of about 15 micrograms/ml. These results suggest that CBZ has a facilitative effect on previously induced LTP.


Administration of dexfenfluramine in pregnant rats: effect on brain serotonin parameters in offspring. Dexfenfluramine (DFEN) was infused SC at doses of either 6 or 12 mg/kg/day during the last week of pregnancy in rats. Compared with untreated controls, weight gain of dams was attenuated by DFEN without effect on the number or birth weight of offspring. Brain serotonin (5-HT) concentration and/or paroxetine binding to the 5-HT uptake carrier was reduced by 20% on the day after birth in one study but not in two other studies. No decreases in brain 5-HT parameters were observed on or after the sixth postnatal day. In contrast, mothers sustained large depletions of brain 5-HT when measured at least 3 weeks after giving birth. These data indicate that fetal brains either are protected from or recover rapidly from the 5-HT-depleting actions of high-dosage regimens of DFEN in rats.


Effects of piracetam on retention and biogenic amine turnover in albino rats. The chronic effects of orally administered 2-pyrrolidone acetamide (piracetam) on one-trial, passive avoidance task were studied in albino rats. The effects on the contents of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in the brain and on the levels of their metabolites both in the brain and urine were also assessed. Significant improvement was observed in the retention ability compared with saline-administered controls. The contents of NE, DA, and 5-HT and their metabolites in the brain were significantly decreased after piracetam administration. The urinary metabolite levels were also significantly decreased except total 3-methoxy-4-hydroxyphenyl glycol (MHPG). These data indicate that piracetam causes an overall decrease in the turnover of central monoamines. Thus, the results of this study implicate the involvement of NE, DA, and 5-HT systems in learning and memory processes. Piracetam did not exert any GABAergic effect as shown by the absence of change in the brain GABA levels.


Effects of d-amphetamine and ethosuximide on responding under delayed-matching-to-sample procedures with differential and nondifferential outcomes. Pigeons were exposed to delayed-matching-to-sample (DMTS) procedures in which food or a flash of the feeder light followed correct responses. When these consequences were correlated with a particular stimulus (e.g., food followed matching responses to red and a flash of the feeder light followed matching responses to green), accuracy was higher (i.e., stimulus control was greater) than when discriminative stimuli and consequences were not correlated. Although stimulus control in the absence of drug appeared to be weaker under the uncorrelated procedure, neither d-amphetamine (0.5-3.0 mg/kg) in Experiment 1 nor ethosuximide (40-160 mg/kg) in Experiment 2 disrupted accuracy to a greater extent under that procedure. These results, like those of a prior investigation, suggest that drug effects are similar under DMTS procedures regardless of whether correlated or uncorrelated outcomes are arranged.


Muscimol facilitates sexual receptivity in hamsters when infused into the ventral tegmentum. Progestogenic stimulation of both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) within the midbrain is critical for normal receptivity in female hamsters. However, few estrogen-induced progestin receptors have been found in the midbrain. In addition, recent evidence suggests that progestin's action in the VTA is mediated nongenomically at the membrane. The present experiment investigated the possible role of GABAA receptors in mediating the effects of progesterone in this brain region. Ovariectomized female hamsters were bilaterally implanted with chronic cannulae aimed toward the ventral mesencephalon. Five days after surgery, animals were injected with 10 micrograms estradiol benzoate SC. Forty hours later, the same animals were injected with either 25 or 100 micrograms progesterone and at hour 43.5, 50 ng muscimol was infused in 0.5 microliters. Control animals received 0.5 microliters vehicle, sterile saline, or no infusion. At hour 44, animals were tested for sexual receptivity by placing them in an observation arena with a sexually experienced male for 10 min, during which lordosis duration was recorded. The following week, the same regimen was given with the alternate dose of progesterone. Histology revealed that only those animals that were infused with muscimol into the VTA had total lordosis durations that were significantly longer than the controls. Implants that missed the ventral tegmental area were much less effective. These results indicate that GABA might play a facilitatory role in enhancing the efficacy of threshold doses of progesterone. Whether this interaction is due to a direct effect of progestins on the GABAA receptor complex awaits further study.


Cocaine's colocalized effects on synaptic serotonin and dopamine in ventral tegmentum in a reinforcement paradigm. The effect of subcutaneous (SC) cocaine (20 mg/kg) on synaptic concentrations of the biogenic amines, dopamine (DA), and serotonin (5-HT) in Ventral Tegmental Area, (VTA-[A10]) was studied in freely moving and behaving rats (rattus norvegicus) with in vivo voltammetry (in vivo electrochemistry). The actual detection of the biogenic amines was on-line and within a temporal resolution of seconds. Simultaneously, the psychostimulant behavior induced by cocaine was studied by infrared photocell beam detection. The results show that cocaine concurrently and significantly increased synaptic concentrations of DA (p less than 0.0001) and 5-HT (p less than 0.004) in VTA. Serotonin changes were accompanied by a notable oscillatory pattern. Importantly, DA and 5-HT changes in VTA were significantly and positively correlated (p less than 0.01). Moreover, psychostimulant behaviors induced by cocaine were significantly increased over control values (p less than 0.0001). Psychostimulant behaviors were significantly correlated with concurrently changing synaptic concentrations of DA (p less than 0.01) and also with 5-HT to a lesser degree. Additionally, behavioral data indicate that cocaine may exhibit an anxiolytic effect during acute administration because agoraphobic behavior, as shown by increased central ambulatory behavior, was dramatically reduced by cocaine. Summarily, the present findings show that cocaine increased synaptic concentrations of DA in VTA, an action that is correlated with cocaine-induced psychostimulant behavior. The DA-ergic effect appears to be tonically maintained. Furthermore, new findings demonstrate a colocalized, cocaine induced 5-HT-ergic effect in VTA, which keeps pace with cocaine-induced alterations in DA-ergic neurotransmission. Thus, 5-HT may be a relay or a gating mechanism for a DA reward signalling pathway for cocaine.


Anticonvulsant effect of allopurinol on hippocampal-kindled seizures. This study assessed the anticonvulsant effect of allopurinol (5 and 50 mg/kg, IP) on seizures kindled from the feline hippocampus. Allopurinol at a higher dose significantly reduced the behavioral seizures stage, but not afterdischarge duration, without producing any behavioral toxicity. The present results lend experimental support to the contention that allopurinol possesses anticonvulsant efficacy in the treatment of human epilepsy.


Mobilization and location of the genetic determinant of chloramphenicol resistance from Lactobacillus plantarum caTC2R. The mobilization of a nonconjugative plasmid (pCaT) that mediates chloramphenicol resistance in Lactobacillus plantarum caTC2R was achieved by comobilization with the conjugative plasmid pAM beta 1. The conjugation studies confirmed that the 8.5-kb pCaT in L. plantarum caTC2R contains the gene responsible for chloramphenicol resistance and that the plasmid has several unique restriction sites which make it useful for genetic studies in Carnobacterium spp. Cloning studies showed that the gene responsible for chloramphenicol resistance is located in the 2.6-kb EcoRV-SalI region of pCaT. This was confirmed by probing the 3.0-kb BglII fragment of pCaT with a biotin-labeled 1.6-kb BstEII-HpaII fragment from the streptococcal-derived plasmid pVA797(Cmr). Expression of chloramphenicol resistance in Carnobacterium as well as in other Lactobacillus species was achieved by electrotransformation using donor DNA from pCaT.


Use of differential agar media for detection of cloned DNA fragments in the tetracycline and chloramphenicol resistance genes of pBR322. A method for detecting newly cloned DNA fragments in pBR322-based vectors was devised for use in DNA probe production. Escherichia coli strain DH5 containing plasmids with different resistance patterns to tetracycline (Tc) and chloramphenicol (Cm) were grown on nonpigmented media, blotted, transferred, and incubated for 2 h on MacConkey agar containing Tc or Cm. Resistant colonies changed color to pink as they began fermenting the lactose on the agar, while sensitive colonies remained white but were still viable and could be subcultured. This method can be applied to the detection of other plasmids with insertional inactivation of Tc or Cm resistance marker genes following successful cloning experiments, especially if pUC18 or M13 is not a possible vector. It eliminates 1 day of culture and the labor involved in individually transferring hundreds of colonies.


Genetic and molecular analysis of pIP417 and pIP419: Bacteroides plasmids encoding 5-nitroimidazole resistance. This report describes a genetic and molecular analysis of two transferable Bacteroides plasmids, pIP417 and pIP419, which carry genetic determinants conferring low-level resistance to 5-nitroimidazoles. The restriction endonuclease cleavage sites for each plasmid were localized. The NiR genetic determinants of pIP417 and pIP419 plasmids have been cloned into the Bacteroides cloning vector pBI191 (C.J. Smith, J. Bacteriol. 164, 294-301, 1985) as PvuII and Sau3A fragments, respectively. Both inserts had different restriction sites and did not cross-hybridize by Southern blot analysis. Genetic data obtained by cloning into pBI191 clearly show that the PvuII-generated fragments A (Rep) and B (Mob) of pIP417 are involved in plasmid replication and transfer, respectively. Although encoding resistance to the same antibiotic, both plasmids appeared different with regard to the 5-nitroimidazole resistance and replication genetic determinants. However, they share a homology in a region involved, at least in one case, in plasmid transfer. Considering the spontaneous high level of resistance to 5-nitroimidazole in Escherichia coli, this work, based on direct gene cloning into Bacteroides, demonstrates the value of such an approach.


Construction of a cassette enabling regulated gene expression in the presence of aromatic hydrocarbons. A high-level expression cassette has been constructed from a TOL plasmid derived from Pseudomonas putida carrying all cis- and trans-acting regulatory elements necessary for transcriptional gene activation in the presence of aromatic hydrocarbons such as toluene. Foreign DNA can be inserted at unique KpnI, SacI, and EcoRI sites 7, 13, and 15 nucleotides downstream of a ribosome binding site. The cassette, flanked by BamHI and EcoRI restriction sites, was inserted into a broad-host-range vector and its efficacy demonstrated in various purple bacteria by monitoring the expression of a reporter gene spectrophotometrically and by SDS-PAGE. High-level induction (80- to 600-fold) was detected in Enterobacteriaceae and in Pseudomonas but was absent or low in Agrobacterium tumefaciens and Rhizobium leguminosarum.


Construction of a sequenced Clostridium perfringens-Escherichia coli shuttle plasmid. A new Clostridium perfringens-Escherichia coli shuttle plasmid has been constructed and its complete DNA sequence compiled. The vector, pJIR418, contains the replication regions from the C. perfringens replicon pIP404 and the E. coli vector pUC18. The multiple cloning site and lacZ' gene from pUC18 are also present, which means that X-gal screening can be used to select recombinants in E. coli. Both chloramphenicol and erythromycin resistance can be selected in C. perfringens and E. coli since pJIR418 carries the C. perfringens catP and ermBP genes. Insertional inactivation of either the catP or ermBP genes can also be used to directly screen recombinants in both organisms. The versatility of pJIR418 and its applicability for the cloning of toxin genes from C. perfringens have been demonstrated by the manipulation of a cloned gene encoding the production of phospholipase C.


Location of the origin of replication for the 7.5-kb Chlamydia trachomatis plasmid. The hypothetical origin of replication for the 7.5-kb plasmid common to Chlamydia trachomatis is believed to be in a region of the plasmid that contains four 22-bp tandem repeats preceded by an A-T-rich region. To test this hypothesis, replication of plasmid DNA in metabolically active reticulate bodies of the Lymphogranuloma venereum biovar of C. trachomatis was examined by electron microscopy. The results presented show that the origin of replication appears to be near the tandem repeats of pCHL2. In addition, replication of the 7.5-kb plasmid is unidirectional, and the copy number during replication is 7-10. The evidence presented suggests that C. trachomatis has a homologue to the Escherichia coli dnaA gene and that this homologue might be involved in replication of the C. trachomatis 7.5-kb plasmid.


New plasmid vector and host system for genetic engineering in Bacillus sphaericus. A new plasmid, pNQ116, was constructed in Bacillus sphaericus by cloning a promoter fragment from B. sphaericus Ts-1 into pNQ112. The plasmid (CmrKmr, 5.23 kb) contains a restriction endonuclease polylinker used for cloning foreign genes, and its cat-86 gene is expressed at high levels from the Ts-1 promoter. This plasmid vector has been transformed into B. sphaericus AS 1.270, AS 1.465, AS 1.469, and 2362, at frequencies of 10(2)-10(3) transformants per microgram of DNA, and is maintained stably under nonselective conditions in these host strains. The presence of pNQ116 in B. sphaericus 2362 does ot interfere with the mosquito larvicidal activity of the organism.


Molecular analysis of a gene from Bacteroides fragilis involved in metronidazole resistance in Escherichia coli. The region of Bacteroides fragilis DNA on the recombinant plasmid pMT100 responsible for conferring metronidazole resistance in Escherichia coli strains was characterized. An open reading frame (ORF1) of 195 bp encoded a protein of 64 amino acids with a predicted M(r) of 7.3 kDa. Deletion analysis indicated that ORF1 conferred the metronidazole resistance phenotype and encoded a protein with an apparent M(r) of approximately 8-10 kDa.


Auricular repair with autogenous rib cartilage grafts: two decades of experience with 600 cases. The purpose of this paper is twofold: to present a sound approach to auricular construction using methods that have evolved through two decades of my personal experience with 600 cases and to discuss pertinent information I have gleaned from a questionnaire sent to my operated patients. This series comprises 546 completed ears in 500 microtia patients (46 bilateral) and 75 completed ears in acquired deformities. Follow-up ranges from 1 to 17 years. Major complications such as infection, hematoma, or skin loss with cartilage exposure occurred in only 1.6 percent of cases and were limited to the perioperative period of 12 days. None have occurred in the last 9 years (481 frameworks). This paper describes the evolution and rationale for my current management of total ear repair and covers preoperative planning, how to fabricate the rib cartilage framework, how to modify the framework for specific deformities, and how to cover the framework, i.e., how to assess and use local skin and vestiges or when to supplement the coverage by recruiting fascial flaps or using tissue expansion. When considering fascial flaps, patient selection was found to be particularly important because of long-term effects on the donor scalp; expansion was found to be most useful intraoperatively. This paper also covers how to manage the hairline, how to stage the surgery, when to combine procedures, and how to manage bilateral microtia in a team approach. The survey revealed that autogenous cartilage frameworks grow, are durable, retain their detail over the years, and withstand trauma well. More than 40 severe traumas occurred in surgically constructed ears, and all healed without incident. Ears constructed in young patients generally grew to keep pace with the opposite normal side; 41.6 percent actually overgrew by several millimeters. Emotional and psychological benefits were universal, and patient satisfaction was high. Among patients who were classified as "severely affected" by the original deformity, 100 percent were pleased with the result. When considered "moderately disturbed" by the microtic defect and operated on by age 14, 95.5 percent of patients were satisfied with the surgical repair; 83.3 percent of adolescents between the ages of 15 and 20 who did not consider themselves "severely affected" by the deformity were pleased with the outcome, and the rest were "undecided."


Intracranial pressure and intracranial volume in children with craniosynostosis. Intracranial volume and intracranial pressure have been measured in 66 children with craniosynostosis, 48 boys and 18 girls. The premature fusion of skull sutures is assumed to restrict skull growth and predispose to elevated intracranial pressure. Thirteen children (20 percent) had raised intracranial pressure and demonstrated a significant restriction of skull growth. In this series, volume measurement alone, however, did not serve as a reliable predictor that the intracranial pressure was raised.


Primary reconstruction of major human bite wounds of the face. Primary reconstruction of 36 major human bite wounds of the face without clinical infection has been carried out successfully as late as the fourth day after the initial injury. Primary healing was achieved in all patients. The postoperative period was free from major infection in all patients except one, including the latecomers. Extensive bacteriologic studies reveal that the infection in human bite wounds occurs secondarily as invasion to devitalized tissue. We therefore consider that debridement of wound edges to eliminate the crushed devitalized tissue is the key to success.


Reconstruction of the lacrimal excretory system. Primary surgical repair of the lacrimal drainage apparatus may not be feasible in patients with maxillofacial injuries involving extensive structural damage. If secondary restoration of the tear duct is not possible, reconstruction of an aberrant passage then will be necessary for tear drainage. Although the Pyrex conjunctivorhinostomy has been considered to be the most effective modality of treatment in managing patients with tear-duct dysfunction, this procedure can be plagued with problems of tube dislodgment, infection, and cicatricial tract obliteration. The patients are, furthermore, required to wear the device for the remainder of their lives. Autologous material is therefore best suited for reconstructing a conduit. A medially based mucosal flap fashioned in the lower palpebral conjunctiva, 5 mm in anteroposterior dimension and 15 mm in horizontal length, can be used to form a conduit. This is then sutured to a flap mobilized from the nasal cavity, the lacrimal sac, or the maxillary antrum. In the past 15 years, a total of 24 fistulous tracts utilizing this technique were reconstructed in 20 patients with tear-duct obstruction. The experience accumulated from managing this group of patients forms the basis of this report.


Distant effects of dorsal and tip grafting in rhinoplasty. Grafts to the nasal dorsum and tip, whose local effects are well known, also have distant effects that may not be as readily obvious but that nevertheless are just as real. Dorsal and tip grafts can shorten or lengthen the nose (relatively and absolutely), affect nasal symmetry, preserve or alter nasal ethnic characteristics, and alter dorsum/tip relationships. Each of these properties increases the utility of cartilage and bone grafts in treating a variety of nasal configurations.


A new intraoral flap: facial artery musculomucosal (FAMM) flap. By combining the principles of nasolabial and buccal mucosal flaps, we have designed a new axial musculomucosal flap based on the facial artery. This flap has been designated the facial artery musculomucosal (FAMM) flap. The flap has proven to be reliable either superiorly based (retrograde flow) or inferiorly based (antegrade flow). It is versatile and has been used 18 times in 15 patients, with one failure and two partial losses. It has been used successfully to reconstruct a wide variety of difficult oronasal mucosal defects, including defects of the palate, alveolus, nasal septum, antrum, upper and lower lips, floor of the mouth, and soft palate.


Argon laser treatment of port-wine stains: the patients' evaluations of the result. The argon laser is now a well-established method of treating port-wine stains (PWS) in the face and neck areas. Satisfactory results are reported in 44 to 75 percent of cases, but criteria for that classification and the patients' perceptions of the result are seldom given. In the present paper, a sample of 58 patients was used to assess the patients' own perceptions of the degree of lightening and scarring. Three felt the results were excellent, 23 good, 18 fair, and 14 poor. The treatment was considered as unpleasant by 76 percent, and 55 percent of the patients asked for a new consultation. Scarring was noticed by 50 percent. The patients' perceptions of the results and physicians' rating were the same in 69 percent. The best results were obtained in older patients with small port-wine stains. Such lesions also can be treated surgically with good results.


Cryosurgery of lentigo maligna.

Cryosurgery of lentigo maligna. Lentigo maligna denotes flat, pigmented lesions predominantly in areas of actinic damage that have the propensity to become malignant. More than 10 years may pass before lentigo maligna evolves into an invasive neoplasma. As an invasive process, it is termed lentigo maligna melanoma (LMM), and it has the potential for both lymphatic and hematogenic metastases. Because of the size and location of the lesions, cosmetically unsatisfactory scars may result from conventional surgery. Therefore, alternative means of treatment, including cryosurgery, have been employed. We report on 12 patients suffering from lentigo maligna who had been treated successfully by cryosurgery between 1984 and 1990. The average follow-up period was 51.4 months, and the recurrence rate was 8.3 percent. Knowing that microinvasive components can be demonstrated in 15 percent of lentigo maligna lesions, we retrospectively reassessed our patients by immunohistochemical procedures with S-100 protein. Although intradermal microinvasion could be confirmed in one patient, no recurrence had been observed within 61 months of follow-up. Provided that patients are selected properly and extension of cryonecrosis is monitored, cryosurgery may prove an efficient alternative to conventional surgery in the treatment of lentigo maligna.


Acute intraoperative arterial lengthening for closure of large vascular gaps. This study demonstrates the feasibility of acute extraluminal expansion to elongate arteries intraoperatively in order to overcome defects too large to be repaired primarily. Twenty Sprague-Dawley rats were divided into two groups: an expander-elongation group and a nonexpanded control group of 10 rats each. Arterial resections were performed ranging from 6 to 22 mm. A miniaturized tissue expander was used to stretch vessels in three consecutive cycles over a 15- to 20-minute period (expander-elongation group). Defects twice as long as those which could be overcome by mobilization alone (nonexpanded control group) could be closed following the application of this technique without thrombosis. Initial laboratory findings and the application of this method in a clinical case are presented.


Progressive hemifacial atrophy associated with Lyme disease. A case is described of progressive hemifacial atrophy occurring in a child with Lyme disease. Borrelial infection may have been an etiologic factor in the progressive hemifacial atrophy, which was ultimately treated with an SIEA free-flap transfer.


Pseudomeningocele: an unusual complication of craniofacial surgery. A previously unreported complication of pseudomeningocele following monoblock frontofacial advancement is described. The defect was repaired by means of an extracranial approach with a satisfactory outcome.


Bilateral rotated buttock flaps for vaginal atresia in severely masculinized females with adrenogenital syndrome. The addition of large bilateral rotated buttock flaps to the flap vaginoplasty enhances the introitus in severely masculinized patients with high vaginal atresia. The flaps are rotated medially to create the distal aspect of the lateral and anterior vaginal wall. The inferior advancement of the labioscrotal folds aids in closing the donor defect, while at the same time creating the appearance of labia majora. Finally, the use of these local tissues will result, in later life, in a vaginal reconstruction free of unwanted hair. This reconstruction technique should obviate dilatation in the older child and prevent further stenosis.


Technique of foot lengthening and shaping with free vascularized iliac osteocutaneous flap. The iliac osteocutaneous flap has been used widely to replace bony defects of the mandible and the extremities. We report a further application of this flap in foot reconstruction. The iliac osteocutaneous flap proved to be of value to augment both soft tissue and bone in a transmetatarsally amputated foot. This resulted in satisfactory function and an appealing cosmetic result, allowing the patient to wear normal shoes. Flap design and secondary contouring procedures are described for the success of this reconstruction.


An unusual pediatric lymphoma.

An unusual pediatric lymphoma. The diagnosis of true histiocytic lymphoma is complex. Since clinical findings are nonspecific and histopathology is only suggestive, misdiagnosis is likely. Using appropriate cytochemical and immunologic markers incorporated into a panel of studies, the diagnosis of true histiocytic lymphoma may be secured. Only with accurate diagnosis and further study can long-term, disease-free survival and curability be determined.


Maximizing gain from rectangular tissue expanders. Three different options are proposed to cut the flap after expansion of rectangular tissue expanders. Each method, when used effectively, allows the expander to deliver the full punch of the expansion process.


Multipurpose anthropometric facial anglemeter. We have developed a multipurpose anglemeter for measuring the face that enables us to determine accurately the size of six profile angles by both direct and indirect anthropometry in markedly reduced time.


Silicone genital prosthesis for female-to-male transsexuals. In the case of a female-to-male transsexual who has not yet undergone phalloplasty, one of the greatest concerns is how to give the appearance of having male external genitals. Many methods have been attempted by patients. We helped develop a silicone prosthesis after obtaining information on the demands of female-to-male transsexuals through a questionnaire sent to 120 of them. Three different models of the prosthesis were designed to enable three different methods of fixation. One of the methods of fixation involves the creation of a bipedicled skin flap in the pubic area. Thus this is the first of such prostheses that can be worn directly fixed to the body. It seems that the prosthesis developed in close cooperation with our department fulfills most of the needs of our patients.


Vulva reconstruction with a tissue expander. A patient with exstrophy of the bladder in whom we performed vulva reconstruction using a tissue-expansion technique and local flaps was presented. The ultimate result was in concert with the anatomic characteristics of normal external genitalia with regard to type of skin, pigmentation, hair pattern, quality of circulation, and sensory supply.


The role of the gastrointestinal tract in the development of burn sepsis. Conceptualization of the gastrointestinal tract as the "motor" that drives sepsis and multiple-system organ failure has only recently been appreciated. Most of the investigation into the pathophysiology of gut-derived sepsis involves using animal models; however, some of the findings are already being corroborated in human studies. The gastrointestinal tract is a dynamic organ whose function as a front-line defense against infection needs to be appreciated. The development of lethal sepsis is a function of the microbial load and virulence, the status of the gastrointestinal barrier, and the magnitude of the host defense response. In assuming care of a critically ill patient, we must be judicious in the use of antibiotics in order to prevent intestinal overgrowth of potential pathogens. Providing proper nutrition by an enteral route (when possible) not only satisfies caloric needs but regulates the microflora and maintains the integrity of the mucosal barrier. Burn patients should receive enteral nutrition early, the first day if possible. This not only will protect the intestinal mucosa but also will blunt the hypermetabolic response following thermal injury. Lastly, the patient should not receive an excessive amount of narcotic or sedative, for these drugs have an inhibitory effect on gastrointestinal motility, encouraging bacterial overgrowth. In the near future, new therapeutic modalities may soon become available to protect and treat the compromised gastrointestinal barrier. These modalities may include, but certainly are not limited to, the use of glutamine and xanthine oxidase inhibitors to prevent stress-related injury to the gastrointestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)


[The right to treatment of the institutionalized mentally ill in the United States]. In his epochmaking article, Birnbaum proposed that courts should recognize a right to treatment of institutionalized psychiatric patients based on the substantive due process. His proposal was adopted in Rouse v. Cameron as a statutory right. Wyatt v. Stickney decision was the first to hold that there was a constitutionally based right to treatment for involuntarily committed patients. The Supreme Court, though reluctantly, held in Youngberg v. Romeo that the institutionalized mentally retarded were entitled to minimally adequate training, which was drawn in the Fourteenth Amendment.


Cognitive behavior therapy and relapse of nonbipolar depression: parallels with pharmacotherapy. The risk of relapse was studied in 44 major depressives following successful acute treatment with cognitive behavior therapy (CBT). Patients entered a 1-year prospective followup with independent clinical assessments at 1, 3, 6, 9, and 12 months. Of these patients, 15 (34%) relapsed; correlates included marital status, recurrent subtype, higher initial and residual ratings of depressive severity, and slower response to therapy. Both married status (p = .008) and fully recovered status (p = .02) were significantly and independently related to decreased risk of relapse using the Cox proportional hazard method. These findings provide further documentation of a relationship between residual symptomatology and relapse after cessation of active treatment and closely parallel findings pertaining to risk of relapse after acute antidepressant pharmacotherapy of unipolar depression. As in pharmacotherapy, a longer period of continuation treatment may be indicated for patients at risk for relapse after an initial course of time-limited therapy with CBT.


Pharmacotherapy observed in a large prospective longitudinal study on anxiety disorders. Data concerning 331 subjects participating in a longitudinal study on anxiety disorders were collected over the first 6 months of the study. Preliminary analyses of somatic treatment according to diagnoses and study site were conducted. The comorbidity of one anxiety disorder with other DSM-III-R diagnoses and other types of anxiety disorders was extensive. Patients with panic disorder received significantly more treatment with a benzodiazepine than patients without panic disorder. Fewer than five percent of the sample were treated with a monoamine oxidase inhibitor. Comorbid depression increased the likelihood of treatment with a newer non-MAOI (non-monoamine oxidase inhibitor), nontricyclic antidepressant. Results suggest a strong effect of treatment site on the pharmacotherapy offered.


Fluoxetine for trichotillomania: an open clinical trial. Of 17 adult patients with long-standing trichotillomania, 13 completed an 8- to 12-week open trial of fluoxetine, up to 80 mg per day. No patient had obsessive-compulsive disorder or major depression. We used the compulsions subscale of the Yale-Brown Obsessive-Compulsive Scale (YBOCS) to rate patients' hair-pulling behavior. The 13 completing patients' mean YBOCS score decreased significantly from 10.15 at baseline to 5.92 at the completion visit (Student's paired t = 4.82, df = 12, two-tailed p less than .001). Of these 13 patients, 5 experienced a 50 percent or greater decrease in their pulling behavior as measured by the YBOCS; 4 experienced between a 25 percent and 50 percent decrease. Three of the patients stopped pulling entirely, as did 2 of the 4 noncompleting patients. Three noncompleting patients discontinued treatment because of side effects, and 1 insisted on early use of behavior therapy. Comparative treatment trials elucidating the indications, risks, and expectable benefits of psychotherapeutic and pharmacological treatments are needed.


The efficacy of psychotropic drugs: implications for power analysis. The estimation of the correct sample size to successfully test a hypothesis has become critical. A common approach to this problem is for the investigating team to complete a pilot study of a few patients to establish the "active drug-placebo" difference, using this "effect size" to perform the power analysis for sample size estimation. Given the variability evident in the effect size from completed and published studies, the pilot study approach may not be entirely dependable. The authors propose a method to obtain this initial "active drug-placebo" difference, in the field of psychotropic drug research. They apply meta-analysis to statistically summarize effect sizes obtained from an exhaustive review of the literature for a specific psychotropic drug in a given clinical condition. All double-blind, random assignment studies are used to calculate the effect size; therefore, no selection bias exists. These literature-based effect sizes are then used to perform the traditional power analysis for sample size estimation. The authors propose these estimations as a convenient reference source for future clinical investigators.


Predictors of placebo response: a retrospective analysis. This retrospective evaluation involved 197 patients from independent clinical investigations of four antidepressant medications. Six variables were analyzed for their discriminative utility in predicting placebo response rates: gender; marital status; age; education; duration of illness; and severity of depressive symptomatology, as measured by Hamilton Rating Scale for Depression (HAM-D or HDRS) scores. Men were slightly more responsive to placebo than were women (29.8%, n = 94 vs. 24.3%, n = 103). Married patients demonstrated the highest probability of a positive placebo response (38.15%, n = 76), as compared with widowed/separated/divorced (21.9%, n = 73) or single (16.7%, n = 48) patients. A trend toward an increased probability of placebo response was detected for patients aged 60 and above (35.7%, n = 14). Educational level achieved and duration of illness were not predictive. Severity of illness proved most noteworthy, with the placebo response rate higher in the more mild patients (40.8%, n = 27 vs. 23.4%, n = 77).


Debrisoquine hydroxylation phenotyping in geriatric psychopharmacology. The metabolic ratios (MRs) between debrisoquine (DBQ) and 4-hydroxydebrisoquine in urine after a single dose of 10 mg DBQ was determined in 175 unmedicated, healthy subjects older than age 59 (mean of 75 years). Creatinine clearance was determined on the same 8-hour urine collection. Test procedures were well tolerated in all cases. Although age was significantly correlated with creatinine clearance (r = -.38), there was no relationship between age and MR. Analysis by kernel density estimation revealed a bimodal distribution of MRs with an antimode of 11.6. Six subjects (3.4%) were categorically slow DBQ metabolizers (MR greater than 11.6). The proportion of elderly slow metabolizers approaches the lower range determined in a younger population. Our findings, that DBQ oxidative metabolism does not necessarily change with aging, alone, and that (genetic) slow DBQ metabolizers endure into old age, remaining at risk for treatment with many commonly used psychotropics, suggests the need to study the relevance of metabolic phenotyping in elderly psychiatric patients.


Low dose oral haloperidol and blood levels in Alzheimer's disease: a preliminary study. Nineteen patients with probable Alzheimer's disease who manifested psychosis or behavioral disturbance received 0.5 to 5 mg per day of oral haloperidol, with blood levels drawn on a stable daily dose. Oral dose correlated strongly with haloperidol blood levels assessed by radioimmunoassay (r = 0.82, p = .0001). The stronger correlation observed between oral dose and blood level compared with most studies in schizophrenia may be related to the fact that virtually all the Alzheimer's patients were neuroleptic naive, without the alterations in absorption and metabolism known to occur in schizophrenics receiving long-term neuroleptic treatment. Compared with oral dose, blood levels showed stronger relations to changes in symptoms and to changes in severity of extrapyramidal side effects. These preliminary data suggest that the utility of monitoring haloperidol blood levels in patients with Alzheimer's disease merits further investigation.


Blocking the Ca(2+)-activated cytotoxic mechanisms of cholinergic neuronal death: a novel treatment strategy for Alzheimer's disease. The major neuropathological finding in Alzheimer's disease (AD) is the death of cholinergic cell bodies originating in the nucleus basalis of Mynert. This paper will review the data suggesting that a pharmacologic strategy designed to slow the rate of cholinergic neuronal death (CND) should be of palliative value in the treatment of AD. Recent data on the biology of cell death (CD) show that there are two patterns of CD: necrosis and apoptosis or genetically controlled, programmed cell death. Regardless of whether cells die by necrosis or apoptosis, four Ca(2+)-activated cytotoxic mechanisms are triggered. Cytosolic free [Ca2+]i increases with aging. After 75 years, this rise may lead to the activation of a putative apoptotic gene in AD that results in CND. Since the increase in cytosolic [Ca2+]i may be mediated by the voltage operated L-type Ca2+ channel on the neuronal cell body, chronic treatment with an L-channel blocker, like nimodipine, might palliate the progression of and possibly prevent the majority of cases of AD.


Haloperidol in schizophrenic children: early findings from a study in progress. This report presents preliminary findings in an ongoing double-blind, placebo-controlled study of the safety and efficacy of haloperidol in hospitalized schizophrenic children. The subjects are diagnosed schizophrenic by DSM-III-R criteria and admitted to the Bellevue Hospital Children's Inpatient Psychiatric Unit. The study is 10 weeks in duration and employs a crossover design. After a 2-week placebo baseline period, the subjects enter double-blind treatment for 8 weeks, by random assignment receiving either haloperidol for 4 weeks followed by placebo for 4 weeks, or alternatively, placebo for 4 weeks followed by haloperidol for 4 weeks. Dosage, regulated individually, ranges from 0.5 to 10.0 mg/day. To date, of an anticipated 20 subjects, 12 have completed the study. These children, 9 boys and 3 girls, were ages 5.5 to 11.75 years upon study entry. Haloperidol was superior to placebo for reduction of target symptoms with optimal haloperidol dose of 0.5 to 3.5 mg/day (0.02-0.12 mg/kg/day).


Pimozide in autistic children.

Pimozide in autistic children. This open pilot study explored the efficacy and safety of pimozide, over a 3-week period, in hospitalized autistic children. Eight males, ages 4.2 to 8.3 years, completed the study. Intellectual functioning ranged from moderate to profound mental retardation. Symptoms included severe withdrawal, stereotypies, hyperactivity and/or hypoactivity, aggressiveness, and temper tantrums. Therapeutic daily doses of pimozide ranged from 3.0 mg to 6.0 mg with a mean of 4.9 mg (0.12-0.32 mg/kg; mean, 0.22). Laboratory studies including electrocardiogram and liver function tests remained within normal limits. Untoward effects were minimal and transient. Decreases of behavioral symptoms were evidenced on all measures including the Children's Psychiatric Rating Scale, Clinical Global Impressions, and Global Clinical Judgments Scale (consensus rating). Of the 5 hypoactive children, 4 showed a decrease in hypoactivity, whereas 1 child showed worsening. These findings are promising and indicate the need for further study.


Carbamazepine in hospitalized aggressive conduct disorder children: an open pilot study. Ten subjects completed an open pilot study of carbamazepine in hospitalized aggressive and explosive children diagnosed as having conduct disorder. The subjects (9 boys, 1 girl) ranged in age from 5.25 to 10.92 years (mean = 8.27). Ratings were done at the end of a 1-week baseline period and after 3 weeks of treatment with carbamazepine. Ratings were carried out by multiple raters in several settings, using various rating instruments. The optimal daily doses of carbamazepine ranged from 600 to 800 mg (mean = 630); plasma levels at post-treatment rating ranged from 4.8 to 10.4 micrograms/mL (mean = 6.2). Administration of carbamazepine was associated with clinically and statistically significant declines in the target symptoms of aggressiveness and explosiveness. These results are promising and suggest that a critical assessment of the efficacy and safety of carbamazepine is warranted under double-blind and placebo-controlled conditions in this population.


Profile of a sample of subjects admitted to an acute care psychiatric facility with manic symptoms. A prospective survey was conducted on 155 consecutive subjects with manic symptoms admitted to an inpatient psychiatric facility to identify possible reasons for rehospitalization. Approximately one third were previously hospitalized at the same facility within the past month. Over half (57%) of the sample were admitted because of aggressive episodes. On admission, 80 percent were receiving carbamazepine or lithium for a mood disorder, and 52.3 percent were receiving multiple medications, of which antipsychotics accounted for over half. Forty-four percent of the sample had comorbid substance use on admission, with marijuana and stimulants accounting for the majority of illicit drug use. Medication noncompliance in 64 percent, and identifiable psychosocial stressors in 55 percent, were also likely contributors to rehospitalization. The data highlights specific treatment issues in the care of patients with a manic component to their illness, and suggests the need for individualized discharge planning with careful followup and continual patient education to assist in the transition from inpatient to society.


Effects of nitrous oxide on psychological performance. Thirty healthy volunteers took part in this double-blind crossover study comparing 15 percent nitrous oxide in oxygen with 100 percent oxygen. They received each treatment for 45 minutes, in counter-balanced order, with no break between treatments. Central nervous system (CNS) effects of nitrous oxide were assessed by a battery of performance tests and by the Visual Analog Scales. The Digit-symbol Substitution Test showed significant slowing with nitrous oxide as did Symbol-digit Substitution and Sentence Verification. Subjects rated themselves as more drowsy, dizzy, abnormal, drunk, and muzzy on nitrous oxide than on oxygen. Significant carryover effects were seen only for the Alert-Drowsy scale at 2.5 minutes after the start of treatment, and not at any later time point. These results show that the onset and offset of the CNS effects of 15 percent nitrous oxide are sufficiently rapid to permit the study of two treatment periods within a single experimental session.


Mechanisms of cocaine-induced sensitization. Rats pretreated with repeated footshock demonstrated an augmentation in cocaine-induced locomotor activity and extracellular dopamine concentrations in the nucleus accumbens. Pertussis toxin injections into the A10 region also led to cocaine- induced enhancement in extracellular dopamine levels in the nucleus accumbens and a strong trend towards elevated locomotor activity. Repeated treatment with cocaine led to a blockade of the footshock-induced increase in extracellular dopamine in the medial prefrontal cortex. Prior treatment with pertussis toxin microinjection into the A10 region resulted in enhanced levels of tissue dopamine metabolites in the medial prefrontal cortex following footshock stress. The pertussis toxin- and daily stress-induced behavioral and neurochemical sensitization suggest that behavioral sensitization to these stimuli involves a loss of inhibitory tone on A10 dopamine cells.


Biological markers of depression: WHO multi-center studies and future perspective. Dexamethasone suppression test (DST), imipramine platelet binding and sleep EEG in depressed patients were studied by the network of WHO Collaborating Centers. DST and sleep EEG indicated abnormalities characteristic to depression, but imipramine platelet binding failed to show difference between depressed and normal subjects. 20 papers related to markers of depression were presented at the 17th Congress of CINP, Kyoto, 1990. They were introduced under 5 headings: 1) DST and its modifications, 2) serotonergic functions, 3) platelet studies, 4) ocular potentials and melatonin, and 5) brain imaging. There are reviewed here.


Rodent models of aggressive behavior and serotonergic drugs. Various models of rodent agonistic behaviour are described, which differentiate between offensive and defensive/flight models. Particular attention is given to one male and one female paradigm for offensive aggression, viz. resident-intruder or territorial (RI) and maternal aggression (MA). After an overview of the serotonin (5-HT) system in the CNS, a description is given of the ligands available. Subsequently the effects of various drugs affecting serotonergic transmission in the RI- and MA-paradigms are described. The 5-HT1A agonists buspirone, ipsapirone and 8-OH-DPAT decreased aggression in RI and MA, but simultaneously led to a marked decrease in social interest and activity, indicative of a non-specific anti-aggressive profile. Non-selective 5-HT1 agonists, such as RU 24969, eltoprazine (DU 28853), and TFMPP reduced aggression quite specific and did not decrease social interest or exploration, but sometimes even increased these behaviours. In RI and MA the behavioural effects of these drugs were roughly similar. In contrast, MA was more sensitive to the treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression only non-specifically at the highest dose. DOI, a 5-HT2 and 5-HT1C agonist, decreased aggressive behaviour and increased inactivity, without affecting social interest and exploration in RI as well as MA. This was, however, accompanied by 'wet dog shaking', characteristic of 5-HT2-receptor stimulation. The non-specific 5-HT agonist (and 5-HT3 antagonist) quipazine also induced 'wet dog shaking' at doses which suppressed aggression, social interest and exploration but increased inactive behaviours (sitting and lying). The discussion attempts to delineate a role for 5-HT receptor subtype involvement in the modulation of aggression, with the restrictions we clearly face with regard to the lack of specific serotonergic agonists and antagonists for certain receptor subtypes. By and large, male and female rats react similarly to treatment with serotonergic drugs stressing the consistent role of 5-HT in different forms of aggression.


Variation in evoked potential measures over the menstrual cycle: a pilot study. The P3 component of a visual event related potential (ERP) was studied for five consecutive weeks in six women with normal menstrual cycles. Serum concentrations of luteinizing hormone (LH), estradiol (E2) and progesterone were studied during the same period. Increases in P3 amplitude, although nonsignificant, were noted in the week preceding onset of menses. No significant changes in reaction times to target/nontarget stimuli were noted over the same time period.


Endocrine study of the maternity blues.

Endocrine study of the maternity blues. The relationship between several psychological variables and adrenocortical function of the blues is examined in a prospective study of 47 Japanese women. Psychological measures, including the psychiatric interview and assessment of the Schedule for Affective Disorders and Schizophrenia (SASD), the Research Diagnostic Criteria (RDC) and self-rating scales, were administered at the 36th week of pregnancy, on the 3rd or 4th day postnatal and one month after delivery. Twelve subjects (25.5%) were diagnosed as having the blues on the Stein's scale. Women who developed the blues had significantly higher serum bound cortisol than the non-blues group. No significant correlation was obtained between the incidence of the blues and obstetric variables. At one month after delivery, four women (8.5%) were diagnosed as postpartum depression according to the RDC. Our finding that there was no consistent obstetric factor which predisposes women to develop the blues support the hypothesis that hyperadrenocorticalism is important in the genesis of this syndrome.


A preliminary study of serotonergic antidepressants in treatment of dysthymia. There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on follow-up at five months. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.


Genetic analyses in neurons and neural crest-derived post mitotic cells. Cationic lipids are shown to be efficient DNA carriers for gene transfer into neurons and chromaffin cells. Chimeric genes containing the coding sequence for the bacterial gene chloramphenicol acetyl transferase (CAT), under various promoter sequences were used to estimate transfection efficiency and to analyse transcriptional mechanisms. Using a ubiquitously expressed construct (RSV-CAT), and an anti-CAT antibody to identify CAT positive cells transfection efficiency was found to be approximately 70% in cultures of hypothalamic neurons. Proenkephalin gene expression was studied in chromaffin cells by employing a chimeric gene containing the rat pro-enkephalin promoter fused to the CAT reporter gene. Using this model we show that the transfected gene is inducible by neurotransmitters and second messengers. The contribution of a specific kinase (protein kinase A, PKA) to proenkephalin gene regulation is analysed using this model system, and expression vectors coding for the catalytic subunit of PKA.


Reducing the time needed to conduct conditioned place preference testing. The objective of the present experiment was to demonstrate whether four days of twice-a-day conditioned place conditioning produces a preference that is equivalent to that produced by using eight days of once-a-day training. Two doses of the amphetamine-like stimulant drug cathinone (0.2 and 1.6 mg/kg) were selected to demonstrate the effectiveness of twice-a-day (morning-vehicle; afternoon-drug pairings) conditioning. The 0.2 mg/kg dose of cathinone failed to affect the expression of place preference, whereas the 1.6 mg/kg dose produced a significant (p less than 0.002) shift in CPP from baseline when compared to previous measurements. These results demonstrate that twice-a-day pairings over four days effectively shorten the total duration of training without changing the development of place preference produced by once-a-day over eight conditioning day schedule.


Effects of disulfiram, phenoxybenzamine and propranolol on the behaviors evoked by apomorphine and amphetamine in adult cats. The aim of this work was to study the role that the noradrenergic system could play in the mechanism of production of the behaviors evoked by parenteral injection of apomorphine and amphetamine in adult cats. Ten cats were injected s.c. with 2 mg/kg of apomorphine and 2.5 mg/kg of amphetamine in separate sessions. The behaviors were recorded, until control conditions were again attained. In a second stage, disulfiram was administered ip., followed by apomorphine and amphetamine in the same doses as cited above. The effects on behaviors produced by disulfiram and those of apomorphine and amphetamine were recorded by three independent observers. Comparisons of the pre- and post-disulfiram behavioral results were analyzed with the help of the non-parametric Wilcoxon signed rank test. In another group of ten cats a similar procedure was carried on employing the alpha and beta noradrenergic blocking agents, phenoxybenzamine and propranolol. The noradrenergic blocking drugs, especially disulfiram and phenoxybenzamine produced by themselves a decrease in motility, in alertness and an increase in indifference and inappetence. Apomorphine and amphetamine administered after the blocking drugs showed slight behavioural modifications, reflection most of them the changes produced by the three blocking drugs. It is concluded that probably the nor-adrenergic system could be involved in the hypomotility elicited by amphetamine. NA is not involved in the induction of the other behaviors evoked by apomorphine and amphetamine.


[Application of high frequency jet ventilation during microsurgery of the larynx under suspending laryngoscopy]. This study describes the results obtained with high frequency jet ventilation (HFJV) in 19 patients who underwent laryngeal microsurgery under suspending laryngoscopy. After premedication and anesthetic induction with propofol (Diprivan R, ICI-Farma), we performed an endotracheal intubation (28F tube) under succinyl-choline facilitation. Conventional ventilation was started at a rate of 14-16 cpm with a minute volume of 8-10 l, and a FiO2 of 0.4 (air-oxygen). The endotracheal tube was replaced by an insufflation catheter of 2 mm internal diameter and HFJV was initiated at a rate of 100 cpm, inspiratory time equal to the 33% of the total cycle, generator pressure of 2.5-3.6 kg/cm2, and similar FiO2. We used an Ergojet CVT (Temel SA) respirator that allowed continuous monitoring of the injector released volume during each cycle (Vjet) as well as the air way pressure. Anesthesia was maintained with continuous propofol perfusion. During HFJV there were no significant hemodynamic alterations and surgeons considered that the condition of the surgical field was excellent. Air way pressure was maintained at low levels in all cases, although brief hypertensive episodes occurred during laryngeal manipulation. Oxygenation was satisfactory in all except one patient with chronic obstructive pulmonary disease. Conventional ventilation and HFJV did not induce significant differences in alveolar ventilation nor in PaCO2. However, during HFJV oxygenation and ventilatory levels suffered a high degree of interindividual variability. This phenomenon could be due to the existence of variable degrees of gas reflux during insufflation. We conclude that HFJV is a very useful technique for anesthesia in laryngeal microsurgery. However, an appropriate monitoring of ventilatory dynamics and a detailed knowledge of the influences of patient's characteristics on HFJV are required.


[Effect of isoflurane on gas exchange and systemic and pulmonary hemodynamics in man during single lung ventilation]. We studied the effect of 1.5% isoflurane end expiratory fraction on arterial oxygenation and on systemic and pulmonary hemodynamics during nonsurgical single lung ventilation. The study includes 6 patients undergoing surgical thoracotomy. In all cases a double lumen endotracheal tube was inserted and pulmonary ventilation was performed with a FiO2 = 1. Patients were placed on lateral decubitus position. The following variables were measured: mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), central venous pressure (CVP), capillary pulmonary pressure (CPP), cardiac output (CO), and Qs/Qt. Measurements were taken at three different situations. The first was done under bilateral pulmonary ventilation and intravenous anesthesia with thiopental, fentanyl, and diazepam. The nondependent lung was collapsed by means of a selective ventilation of the dependent lung, and the second series of measurements was done 20 min after intravenous anesthesia. The third block of data was obtained after 15 min of respiratory ventilation with 1.5% isoflurane. Single lung ventilation induced a significant decrease of Pa O2 (379 +/- 96 mmHg vs 208 +/- 93 mmHg) and a significant increase in Qs/Qt (20 +/- 8% vs 30 +/- 10%). However, during isoflurane ventilation there were no significant changes in PaO2 (208 +/- 93 mmHg vs 204 +/- 94 mmHg) nor in Qs/Qt (30 +/- 10 vs 28 +/- 8). Isoflurane elicited a significant decrease of the CO, whereas MPAP, RVS, and PvO2 did not show significant variations. We conclude that 1.5% isoflurane end expiratory concentrations did not significantly affect pulmonary oxygenation during single lung ventilation.


[Continuous intradural anesthesia in geriatric patients undergoing orthopedic and traumatologic surgery]. The aim of the study was to prospectively evaluate the results of continuous intradural anesthesia with 18G Tuohy needle and 20G catheter in geriatric patients. We studied 70 patients with a mean age of 75.9 +/- 10.8 years who were subjected to orthopedic or traumatologic surgery of the lower extremities with a duration of 104.6 +/- 53.6 min. Success index was 95.7%. The initial dose of 1% tetracaine was 10.36 +/- 3.96 mg, the second dose in 29 patients was 7.2 +/- 2.7 mg, the third in 7 cases was 7.40 +/- 2.47 mg, and the total dose was 14.56 +/- 5.6 mg. The metameric level was between T8 and T11 in 80.32% of patients. Peroperative complications were limited to paresthesia in 5 cases (7.14%) during insertion of the catheter, difficulties in catheter placement in one case (1.42%), and accidental catheter extraction during withdrawal of the needle in 2 cases (2.85%). Ten patients (14.28%) presented arterial hypotension (pressure decrease greater than 30% of baseline systolic arterial pressure). During the postoperative phase there were 3 cases of slight headache after dural puncture (4.28%) that recovered with conservative treatment, and one case of lumbalgia at the puncture zone (1.42%). Continuous intradural anesthesia with the material used in this study is technically easy. It allows to accurately reach the desired metameric level, avoiding massive sympathetic blockade, and providing a steady hemodynamic condition. All these effects are essential for anesthesia in geriatric patients.


[Incidence of headache following intradural anesthesia with 26 gauge needles depending on whether the punction is done with the bevel perpendicular or parallel to the dura mater fibers]. To determine the incidence of headache after lumbar puncture, we prospectively studied 270 patients who underwent intradural anesthesia for programmed urologic, traumatologic, general, and gynaecologic surgery. The mean age of the patients was 55.6 +/- 16.9 years. There were significant differences between the age of women (54.8 +/- 15.5 years) and men (56.4 +/- 18.4 years). Intradural anesthesia was performed with a Becton-Dickinson 26G needle with a Quincke tip. Patients were randomly divided into two groups according to that puncture was directed parallel (group 1) or perpendicular (group 2) to the dura-mater fibers. When the spinal liquid dripped through the needle, 2 ml of a 0.75% (15 mg) solution of bupivacaine and 0.2 ml of a 50% (100 mg) solution of glucose were injected. No special measures were undertaken during the postoperative phase. The incidence of headache was analyzed 72 hours after puncture. One patient of group 1 (0.66%) and 6 patients of group 2 (5%) presented headache. This difference was not statistically significant. Differences between the incidence of headache in women (4.05%) and in men (2.15%) were also not significant.


[Patient-controlled analgesia (PCA) with variable doses: an alternative to conventional PCA?]. We have prospectively studied the effects of three types of patient controlled anesthesia (PCA) in 30 patients who underwent elective upper abdominal surgery. Patients were allocated into three groups of 10. The first group received postoperative anesthesia by means of intravenous conventional PCA at fixed demand doses (PCADF). A second group was treated with demand doses that were varied in each bolus according to the intensity of pain (PCADV). A third group received continuous infusion with additional demand doses in variable bolus (PCAC + DV). The analgesic agent used in this study was morphine chloride. The total accumulated doses of morphine in PCADV group were lower than those of the other two groups. These differences were statistically significant when they were compared with PCADF group (p less than 0.01 at 2 and 6 hours; p less than 0.05 at 12 and 24 hours) and with PCAC + DV group (p less than 0.01 at 2, 6, 12, and 24 hours). Differences in morphine consumption during the different time intervals were markedly significant between 0 and 2 hours after the onset of PCA. PCADV required lower doses (p less than 0.01). After the first 2 hours, patients of PCADV group continued using lower morphine doses, but these differences were not significant when compared with PCADF group, although were present with respect to patients of PCAC + DV group (p less than 0.01). The incidence of secondary effects was not significantly different among the three groups. Based on these results we propose a modification in present PCA pumps.


[The morphine-scopolamine combination in chloroform anesthesia]. After introduction of surgical anesthesia with general agents such as ether and chloroform, a large number of deaths due to anesthetic toxicity were reported. With the aim to reduce toxicity several types of mixtures were devised. One of the most important was the association of opioids and scopolamine. This technique was compiled in a thesis on the use of morphine and scopolamine during anesthesia with chloroform which was presented by Dr. José Blasco Reta at the University of Madrid the 27th of June of 1907. Claude Bernard was the first to use this technique. He was based on the assumption that a previous injection of 1 cg of morphine acetate will decrease both, the needs and the risk of chloroform since this procedure shortened the excitation period, decreased ether-induced bronchial congestion, and prolonged for several hours the analgesic effect in the postoperative phase. The first who applied this technique in Spain was Dr. Losada, and Dr. Emilio Ruiz observed the rapid action of the mixture. After 1900, Schneiderlein added scopolamine in order to decrease the excitation and to reduce vomiting secondary to the association morphine-chloroform. Scopolamine was administered in 2 or 3 injections. Jun our country Dr. Lozano Monzón and Dr. Recasens used this pharmacologic association and considered it of beneficial effects when applied during labour. In a total number of 4,240 anesthetic procedures using the same technique, Dr. Blasco Reta reported 24 deaths, among them the first that occurred to Mr. Víctor Escribano between 1902 and 1903. Mortality was considered to be 1/1,000 cases.