Hazard potential ranking of hazardous waste landfill sites and risk of congenital anomalies.

BACKGROUND: A 33% increase in the risk of congenital anomalies has been found among residents near hazardous waste landfill sites in a European collaborative study (EUROHAZCON). AIMS: To develop and evaluate an expert panel scoring method of the hazard potential of EUROHAZCON landfill sites, and to investigate whether sites classified as posing a greater potential hazard are those with a greater risk of congenital anomaly among nearby residents relative to more distant residents. METHODS: A total of 1270 cases of congenital anomaly and 2308 non-malformed control births were selected in 14 study areas around 20 landfill sites. An expert panel of four landfill specialists scored each site in three categories-overall, water, and air hazard-based on readily available, documented data on site characteristics. Tertiles of the average ranking scores defined low, medium, and high hazard sites. Calculation of odds ratios was based on distance of residence from the sites, comparing a 0-3 km "proximate" with a 3-7 km "distant" zone. RESULTS: Agreement between experts measured by intraclass correlation coefficients was 0.50, 0.44, and 0.20 for overall, water, and air hazard before a consensus meeting and 0.60, 0.56, and 0.53 respectively after this meeting. There was no evidence for a trend of increasing odds ratios with increasing overall hazard or air hazard. For non-chromosomal anomalies, odds ratios by water hazard category showed an increasing trend of borderline statistical significance (p = 0.06) from 0.79 in the low hazard category, 1.43 in the medium, to 1.60 in the high water hazard category. CONCLUSIONS: There is little evidence for a relation between risk of congenital anomaly in proximate relative to distant zones and hazard potential of landfill sites as classified by the expert panel, but without external validation of the hazard potential scoring method interpretation is difficult. Potential misclassification of sites may have reduced our ability to detect any true dose-response effect.

Microdialysis in mice for drug delivery research.

Intracerebral microdialysis was first performed in the mouse at the end of the 1980s. Most microdialysis studies on mice were confined to neuropharmacology and changes in neurotransmitter concentrations up to 1995, although pharmacological studies were done on other tissues like the skin, kidney and implanted tumors. The use of microdialysis in mice for pharmacokinetic and drug delivery studies owes much to the recent availability of genetically engineered mice, such as mice in which the genes encoding multiple drug resistance have been knocked out. The quantitative microdialysis of blood and various tissue fluids of the mouse is now feasible and the recent development of specific microdialysis devices for use in mice should facilitate its use in these small animals. This review covers the technical aspects of microdialysis in the mouse and includes references to many of the published studies on pharmacokinetics and drug delivery.

Elevated concentrations of morphine 6-beta-D-glucuronide in brain extracellular fluid despite low blood-brain barrier permeability.

1 This study was done to find out how morphine 6-beta-D-glucuronide (M6G) induces more potent central analgesia than morphine, despite its poor blood-brain barrier (BBB) permeability. The brain uptake and disposition of these compounds were investigated in plasma and in various brain compartments: extracellular fluid (ECF), intracellular space (ICS) and cerebrospinal fluid (CSF). 2 Morphine or M6G was given to rats at 10 mg kg(-1) s.c. Transcortical microdialysis was used to assess their distributions in the brain ECF. Conventional tissue homogenization was used to determine the distribution in the cortex and whole brain. These two procedures were combined to estimate drug distribution in the brain ICS. The blood and CSF pharmacokinetics were also determined. 3 Plasma concentration data for M6G were much higher than those of morphine, with Cmax and AUC 4-5 times more higher, Tmax shorter, and VZf-1 (volume of distribution) and CL f(-1) (clearance) 4-6 times lower. The concentrations of the compounds in various brain compartments also differed: AUC values for M6G were lower than those of morphine in tissue and CSF and higher in brain ECF. AUC values in brain show that morphine levels were four times higher in ICS than in ECF, whereas M6G levels were 125 higher in ECF than in ICS. 4 Morphine entered brain cells, whereas M6G was almost exclusively extracellular. This high extracellular concentration, coupled with extremely slow diffusion into the CSF, indicates that M6G was predominantly trapped in the extracellular fluid and therefore durably available to bind at opioid receptors.

Influence of various combinations of specific antibody dose and affinity on tissue imipramine redistribution.

1. This study was designed to evaluate the distribution kinetics of imipramine (Imip) in the brain and the main peripheral organs (heart, kidney, liver and lung) of rats, and to establish the relationship between the redistribution of Imip from these tissues and the immunoreactive capacity (dose and affinity) of anti-TCA IgG. 2. [3H]-Imip (1 nmol kg(-1) body weight) was injected intravenously 6 min before the i.v. injection of antibodies. At this time, the concentrations of Imip and its main metabolites in plasma were determined. The radioactivity measured corresponded to 91.7% Imip, indicating that the pharmacokinetics reflected essentially Imip. Plasma and tissue Imip contents were measured over the interval 1 to 90 min in control and in treated rats. The antibodies used were a murine monoclonal IgG1 (Ka=3.8 10(7) M(-1)) at an IgG1/Imip molar ratio of 1000 (IgG1 1000), and a sheep polyclonal IgG (TAb, Ka=1.3 10(10) M(-1)) at IgG/ Imip molar ratios of 1, 10 and 100 (TAb1, TAb10 and TAb100). 3. The anti-TCA IgG increased the plasma [3H]-Imip concentrations: the AUC1-->60 min for [3H]-Imip were 4 (IgG1 1000), 9 (TAb1), 33.9 (TAb10) and 41.4 (TAb100) times higher in the treated groups than in the controls. The opposite effect occurred in the brain, heart and lungs, with large, rapid decreases in Imip. The increase in plasma Imip and the decrease in tissue Imip depended on the immunoreactive capacity (NKa) of the antibody, where N=molar concentration of IgG binding sites and Ka=IgG affinity constant. Maximal plasma and tissue redistribution occurred when NKa=33.8 x 10(4). 4. Imip redistribution can be controlled using various doses or affinities of specific antibodies, and the resulting rapid, extensive Imip redistribution from the main target organs could be very promising for TCA detoxification.

Epidemiology and treatment of otitis media with effusion in children in the first year of primary school.

In this multicentre study we evaluated the prevalence and risk factors of otitis media with effusion (OME) in Italian school-children and the effectiveness of medical treatment of chronic OME with a new cephalosporin, ceftibuten. During two winter periods, 3413 children, aged 5 to 7 years, were examined for the presence of OME by means of pneumotoscopy and a portable, hand-held tympanometer. The prevalence of asymptomatic OME was 14.2%, with no difference as regards sex, age, month of examination or geographic area. Younger children had significantly more bilateral than unilateral effusion. A recent episode of acute otitis media and previous tonsillectomy or adenoidectomy were associated with an increased risk of OME in multivariate logistic regression models. The presence of OME was unrelated to such factors as birthweight, prematurity, sibling or parental history of allergy, duration of daycare attendance, family history of ear infections. After 12 weeks, 26.6% of children with OME still had middle-ear fluid: 52 were randomized to ceftibuten (9 mg/kg q.d. for 14 days) and 59 to no treatment (nasal saline drops allowed). Children treated with ceftibuten had a significantly better resolution of middle-ear effusion after 4 and 8 weeks. As mass screening programmes for OME in the year of school entry are questioned, a focus only on children with known risk factors seems advisable. Ceftibuten can be useful in reducing the duration of middle-ear effusion.

Simultaneous microdialysis in brain and blood of the mouse: extracellular and intracellular brain colchicine disposition.

A simultaneous brain and blood microdialysis system was developed to study the passage of colchicine through the blood-brain barrier in the mouse. Colchicine was administered as a bolus in the jugular vein (1.5 mg kg-1) and its hippocampal extracellular fluid (ECF) and blood kinetics were determined over a 4 h period using two microdialysis probes, one in the dorsal hippocampus, the other in the inferior vena cava. Colchicine rapidly diffused into the hippocampus (maximum concentration in the first dialysate sample) and brain and blood concentrations declined in parallel, suggesting rapid equilibration between these two compartments. However, only 6. 7% of total blood colchicine, 14% of unbound colchicine was present in the hippocampus suggesting that the P-glycoprotein efflux pump limits colchicine uptake by the brain. We also found, using conventional tissue homogenate analysis in parallel, that the concentration of colchicine in the hippocampal ECF was 10 times less than that in the intracellular space and that the hippocampus colchicine concentration was 2.8 times higher than that of the rest of the brain. This study shows that the simultaneous brain and blood microdialysis can be used to measure the passage of colchicine through the blood-brain barrier and to estimate the brain extra- and intracellular distribution of colchicine.

Redistribution of imipramine from regions of the brain under the influence of circulating specific antibodies.

The kinetics of brain-to-blood redistribution of imipramine (IMI) was assessed in nine brain regions of control rats and rats given anti-tricyclic antidepressant (anti-TCA) antibody. Two antibodies were given intravenously 6 min after intravenous [3H]IMI (1 nmol/kg). One was a murine monoclonal IgG1 (Ka = 3.8 x 10(7) M(-1)) at an IgG/IMI molar ratio of 1,000 (IgG1,000), and the other was a sheep polyclonal IgG (TAb; Ka = 1.3 x 10(10) M(-1)) at IgG/IMI molar ratios of 1, 10, and 100 (TAb1, TAb10, and TAb100). In the control rats, IMI was rapidly taken up by the brain (Cmax at 5 min) with no significant differences among the brain regions (4.1 +/- 0.4 to 5.4 +/- 0.6 pmol/ g), and brain IMI then declined monoexponentially with a half-life of 44.2 min (cerebellum) to 77.3 min (hippocampus). The greatest IMI content was in the frontal cortex and the lowest in the cerebellum. The antibodies (except TAb1) stimulated the extent and rate of IMI redistribution from all the brain regions depending on the immunoreactive capacity (NKa) of the antibody. The antibody with the highest NKa (TAb100) had the greatest effect. The fraction of IMI removed from the brain was 58-74%, and the redistribution half-life was 7.9-15.6 min; the mean residence time was reduced by 66-75% (11.8-23.9 min). These results demonstrate that circulating anti-TCA IgG rapidly and reliably removes IMI from the brain, indicating that immunotoxicotherapy could be an efficient procedure for accelerating the removal of TCA from the brain.

Facilitation of imipramine efflux from the brain by systemic specific antibodies.

1. This study investigated the capacity of circulating anti-tricyclic antidepressant (TCA) IgG to increase the efflux of imipramine (Imip) from the rat brain. 2. A tracer amount of [3H]-Imip (40 pmol) was injected into the cerebral lateral ventricle and its efflux was determined in control rats and in rats given anti-TCA antibody. The monoclonal anti-TCA IgG1 was injected i.v. 48 h before Imip at 4 IgG:Imip molar ratios (10, 100, 1000 and 10,000). The [3H]-Imip in arterial and venous plasma was measured for up to 60 min, and in the brain and peripheral organs (heart, liver, lung, kidney) 5 and 60 min after Imip injection. 3. The arterial plasma concentration of Imip in control rats was significantly higher (26.7 +/- 2.1 pM) than the venous one (17.7 +/- 2.0 pM) at 5 min, indicating that Imip released from brain becomes distributed in peripheral tissues. These concentrations were not significantly different at 60 min suggesting that Imip was, at this time, redistributing from extravascular tissues to the blood. In rats given anti-TCA IgG, any Imip leaving the brain was immediately bound by the circulating antibody at 5 min. This greatly reduced the Imip in the heart (63.9%) and lung (61.3%) at the highest IgG:Imip ratio. The brain Imip was markedly lower at 60 min (31.5% with an IgG Imip ratio of 1000 and 57.5% at a ratio of 10,000). The two lowest IgG:Imip ratios had less effect on the plasma Imip because of the relative low affinity of the anti-TCA IgG (3.8 x 10(7) M-1). 4. These data indicate that the anti-TCA IgG facilitated the efflux of Imip from the brain, even though these antibodies cannot cross the blood-brain barrier. This may be an efficient system for increasing drug organ clearance, as more than half the Imip in the brain was actively removed by the antibody in 1 h.

[Urban air pollutant exposure among traffic policemen]. / Esposizione agli inquinanti dell'aria urbana dei vigili municipali.

Exposure to dusts and benzene was studied in 65 traffic policemen. Samples of total dusts showed that mean personal exposure was 0.44 (SD = 0.30) mg/m3, with peaks of about 2 mg/m3. Exposure to 1-nitropyrene (1-NP), the main compound occurring in emissions from diesel engines, which was estimated from concentrations in dusts collected with high-flow samplers, was 0.28 (SD = 0.19) ng/m3 (range: 0.06-1.24 ng/m3). The mean concentration of benzene in the breathing zone was 41 (SD = 20) micrograms/m3, although a level of 100 micrograms/m3 was slightly exceeded in one subject. In urine samples collected before and after workshifts, two biological indicators of exposure to benzene were measured, urinary benzene and urinary trans, trans-muconic acid (MA). The mean values of urinary benzene before and after workshift were similar (98, SD = 81 and 83, SD = 55 ng/l; n = 63; Wilcoxon's T-test = not significant), while a moderate increase in the metabolite was observed (MA = 0.08, SD = 0.11; 0.11, SD = 0.09 mg/g creatinine, in pre- and post-shift samples respectively; Wilcoxon's T-test, z = 3.00; p < 0.01). The levels of exposure to dusts and 1-NP deriving from diesel engine emissions were comparable to those of other occupational groups with this type of risk (garage mechanics, workers operating diesel engine machinery, etc.). Traffic police exposure to benzene was similar to that of the whole population of Padova (40 micrograms/m3, mean annual 24-hour value). However, the values of urinary MA, like those reported by other authors for non-smoker controls, increased after the workshift, indicating low occupational exposure to this pollutant. It should be noted that traffic police exposure to benzene is much lower than that of other occupational categories, e.g., fuel pump distributors.

Dose-dependent delivery of colchicine to the rat hippocampus by microdialysis.

The time courses of the colchicine delivery and diffusion rate in the brain were studied by microdialysis in the rat. Microdialysis allowed the exposure of the brain tissue to colchicine to be regulated, unlike a bolus injection. Colchicine was infused directly into the dorsal hippocampus at 40 ng/ml and 40 micrograms/ml, for 8 h. The amount of colchicine delivered to the brain and the diffusion rate from the probe were dose-dependent: colchicine diffusion into the brain was linear at 40 ng/ml but tended to plateau after 4 h at 40 micrograms/ml. The drug actually delivered with the higher dosage was only about 50% of that predicted from a constant diffusion. The total amount delivered at 40 ng/ml was 3.73 +/- 0.14 ng and at 40 micrograms/ml, it was 2.06 +/- 0.20 micrograms. Thus tissues surrounding the infusion site were saturated at high concentration and no more colchicine was diffused. Postmortem measurements of colchicine concentration in the forebrain confirmed these findings. Hence, the way in which colchicine is delivered to the brain is a critical factor for induction of its neurotoxic effects. These data open the way to a research on the correlation between local brain concentrations of colchicine and neurodegenerescence.

Brain microdialysis in the mouse.

Microdialysis of small brain areas of OF1 mice is shown to be feasible using the smallest commercially available probes (CMA/11). The brain areas studied were the dorsal hippocampus and nucleus accumbens. The basal concentrations of biogenic amine metabolites in dialysate samples were measured by HPLC with electrochemical detection (ED). The basal levels of MHPG, DOPAC, and HVA in the dorsal hippocampus were obtained immediately after probe insertion, whereas the basal 5-HIAA concentration gradually declined. The stable levels of DOPAC, HVA, and 5-HIAA in the nucleus accumbens were reached in 80 min. Histological controls showed the tract of the dialysis membrane within the studied sites. This procedure could allow simultaneous correlation of the neurobiochemical changes and pharmacological responses, and could facilitate further biochemical and pharmacokinetic research in the mouse.

Involvement of hydroxylated metabolites in amphetamine-induced hypothermia in mice.

1. The hydroxylated metabolites of amphetamine, p-hydroxyamphetamine (p-OHA) and p-hydroxynorephedrine (p-OHN), were administered intracerebroventricularly in mice in order to evaluate their ability to elicit hypothermia. 2. Intracerebroventricular (i.c.v.) administration of p-OHA and p-OHN (1, 3 and 9 micrograms/mouse) induced maximal hypothermia 30 min after injection. p-OHA and p-OHN (9 micrograms, i.c.v.) produced maximal decreases in rectal temperature of -6.48 +/- 0.44 degrees C and -3.82 +/- 0.42 degrees C, respectively. Both metabolites are more effective than amphetamine (at 9 micrograms, i.c.v., -3.32 +/- 0.75 degrees C). 3. Pretreatment with haloperidol (5 micrograms, i.c.v.) suppressed the fall in temperature produced by p-OHA (3 micrograms, i.c.v.) and reduced that produced by p-OHN (3 micrograms, i.c.v.), respectively. The selective dopaminergic D1 receptor antagonist, SCH 23390, and the D2 receptor antagonists, sultopride and metoclopramide, were without effect on the hypothermia induced by either metabolite. Similarly, amphetamine-induced hypothermia was only inhibited by haloperidol. Apomorphine (0.1 mg kg-1, i.p.) did not potentiate the hypothermia induced by either metabolite, whereas the selective dopaminergic D2 agonist, quinpirole (0.2 mg kg-1, i.p.) did. Amphetamine-induced hypothermia was potentiated by apomorphine and quinpirole. 4. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the 5-HT receptor agonist, quipazine, modified metabolite-induced hypothermia. In contrast, amphetamine-induced hypothermia was affected by these 5-HT drugs. 5. The neuropeptide CCK-8 (0.04 mg kg-1, i.p.) and gamma-butyrolactone (40 mg kg-1, i.p.) potentiated the hypothermia produced by amphetamine and its metabolites. Conversely, desipramine (20 mg kg-1, i.p.) antagonized it.(ABSTRACT TRUNCATED AT 250 WORDS)

Facilitation of amphetamine-induced hypothermia in mice by GABA agonists and CCK-8.

1. Amphetamine-induced hypothermia in mice is facilitated by dopaminergic stimulation and 5-hydroxytryptaminergic inhibition. The present study was designed to investigate: (a) the involvement of other neuronal systems, such as the gamma-aminobutyric acid (GABA), the opioid and the cholecystokinin (CCK-8) systems; (b) the possible contribution of hydroxylated metabolites of amphetamine to the hypothermia; (c) the capacity of dopamine itself to induce hypothermia and its mechanisms, in order to clarify the resistance of amphetamine-induced hypothermia to certain neuroleptics. 2. Pretreatment with the GABA antagonists, bicuculline and picrotoxin, did not inhibit amphetamine-induced hypothermia. The GABAB agonist, baclofen (2.5 mg kg-1, i.p.) potentiated this hypothermia, whereas the GABAA agonist, muscimol, did not. gamma-Butyrolactone (GBL) (40 mg kg-1, i.p.) and the neuropeptide CCK-8 (0.04 mg kg-1, i.p.) also induced potentiation. The opioid antagonist, naloxone, was without effect. 3. Dopamine itself (3, 9, 16 and 27 micrograms, i.c.v.) induced less hypothermia than the same doses of amphetamine. Sulpiride did not block dopamine-induced hypothermia, but pimozide (4 mg kg-1, i.p.), cis(z)flupentixol (0.25 mg kg-1, i.p.) and haloperidol (5 micrograms, i.c.v.) did. The direct dopamine receptor agonist, apomorphine, did not alter the hypothermia. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the inhibitor of 5-HT synthesis, p-chlorophenylalanine (PCPA), modified dopamine-induced hypothermia. Fluoxetine, an inhibitor of 5-HT reuptake, had no effect, whereas quipazine (6 mg kg-1, i.p.), a 5-HT agonist, totally prevented the hypothermia. Hypothermia was unaffected by pretreatment with CCK-8. 4. These data indicate that the hypothermia induced by amphetamine involves not only dopaminergic and 5-hydroxytryptaminergic systems which are functionally antagonistic, but is also facilitated by direct or indirect GABA and CCK-8 receptor stimulation. This facilitation could result, in part, from modulation of dopaminergic neurotransmission. This may explain the apparent resistance of amphetamineinduced hypothermia to some neuroleptics, while dopamine-induced hypothermia is not resistant. The possible action of hydroxylated metabolites of amphetamine may also help to explain these differences.

[Possible interpretation errors in studying the pelvis in children. Description of 2 clinical cases]. / Possibili errori interpretativi nello studio del bacino pediatrico. Descrizione di due casi clinici.

The Authors describe two clinical cases in which the report of an abnormal conformation of the pubic bones required a careful differential diagnosis between a pathological condition and physiological variants of the normal ossification. Considering the different ways of this process of ossification, the pediatrician and the radiologist can avoid a wrong diagnosis with considerable consequences for the little patient.

Predominant cytosolic distribution of serotonin in rat pineal gland in contrast to biogenic monoamine localization in midbrain and adrenal gland.

The subcellular distribution of serotonin and norepinephrine in the rat pineal gland was studied by tissue fractionation and compared with that of biogenic monoamines in the adrenal gland and midbrain. Homogenized tissues were fractionated by ultracentrifugation or by filtration through cellulose ester membranes. Most of the epinephrine (70-80%) and norepinephrine (62-82%) present in the adrenal glands was detected in the particulate fraction. The same distribution was found for serotonin (68.5%) and norepinephrine (59%) in the midbrain and for norepinephrine (62.5%) in the pineal gland. However, most of the serotonin in the pineal was found in the soluble fraction (89.5-98%). This suggests that the great majority of serotonin in the rat pinealocytes is cytosolic and thus is not stored in subcellular vesicles, in contrast to the biogenic monoamines in the midbrain or adrenal gland.

Time required for transmitter accumulation inside monoaminergic storage vesicles differs in peripheral and in central systems.

Monoamine storage vesicles accumulate transmitters via an active transport process which presents similar pharmacological and bioenergetic properties in all monoaminergic systems. Using [3H]reserpine, a specific ligand of the vesicular monoamine transporter on isolated storage vesicles, we have determined the molecular turnover number of the monoamine transporter and found in various monoaminergic systems an identical value of 135 molecules of substrate transported per min. Using high performance liquid chromatography-electrochemical monoamine determination and the binding of [3H]dihydrotetrabenazine, a specific ligand of the vesicular monoamine transporter in tissue homogenates, we have measured the ratio of transmitter molecules per transporter in various rat tissues containing high amounts of monoamines. This ratio is about 500 in brain regions (striatum, hypothalamus, midbrain) and in the maxillary gland, it varies from 2000 to 7000 in sympathetic nerve terminals in the heart, brown adipose tissue and vas deferens, and it is 6000 in platelets and 280,000 in the adrenal medulla. The minimal time required in vivo for biogenic amine accumulation inside storage vesicles could be derived from these data. Values of 2-4 min were found for brain or maxillary gland synaptic vesicles, 15-50 min for heart, brown adipose tissue or vas deferens sympathetic vesicles and for platelet granules, and 35 h for adrenal medulla chromaffin granules. Thus the maturation time of monoaminergic vesicles, in terms of monoamine accumulation, is highly variable, being short in the brain and maxillary glands, 5-20-fold longer in the sympathetic nervous system and in platelets, and much increased in adrenals.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuroleptic-induced hypothermia in mice: lack of evidence for a central mechanism.

The present study investigated the ability of neuroleptic drugs to induce hypothermia in mice when they were administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). Twelve neuroleptics belonging to five chemical classes including phenothiazines, butyrophenones, benzamides, thioxanthenes and diphenylbutylpiperidines were injected i.p. All of them, except benzamides, induced a dose-dependent decrease in rectal temperature. Neuroleptics were administered i.c.v. via cannulae previously implanted in mice to determine whether this response might have a central origin. None of the drugs tested induced hypothermia at doses which did not produce toxic effects. These negative results suggest that neuroleptics act to elicit hypothermia via a peripheral, rather than a central mechanism. Since some neuroleptics possess alpha-adrenolytic properties which could induce hypothermia by promoting vasodilatation, we attempted to antagonize the hypothermia produced by peripheral administration of two neuroleptics with phenylephrine, an alpha-adrenoceptor agonist that does not cross the blood-brain barrier. The hypothermia induced by both chlorpromazine and haloperidol was attenuated by phenylephrine, supporting the view that peripheral alpha-adrenoceptors may mediate neuroleptic-induced hypothermia.

The regionalization of [3H]dihydrotetrabenazine binding sites in the mouse brain and its relationship to the distribution of monoamines and their metabolites.

[3H]Dihydrotetrabenazine binding was measured in 8 areas of the mouse brain. In all areas, binding occurred on a homogeneous class of sites (Kd approximately equal to 2.6 nM). The density of [3H]dihydrotetrabenazine binding sites strongly varied between the different brain structures; it was compared to endogenous levels of biogenic monoamines and their metabolites: the density is independent of the nature of the monoamine and of neuronal activity, but is highly correlated to the total amount of monoamines present in each structure.

[The technic of sub-vigil anesthesia in plastic-reconstructive surgery]. / La tecnica di anestesia sub-vigile in chirurgia plastico-ricostruttiva.

The personal experience in plastic-reconstructive surgery with 395 cases of sub-vigil anaesthesia (neuroleptanalgesia + benzodiazepine in 124 patients (group A); ketamine + benzodiazepine in 138 patients (group B); neuroleptanalgesia + ketamine + benzodiazepine in 133 patients (group C) is described by the authors in the present study. They conclude that the sub-vigil anaesthesia is usually free from complications and a very safe, tolerable, expedient technique for plastic surgical procedures; furthermore, the result is good patient acceptance, a stable blood pressure and heart rate.