Intravenous cocaine discrimination in humans.

Ten cocaine-dependent participants were trained to discriminate between intravenous saline and 20 mg/70 kg cocaine. During the first session, saline and cocaine injections were alternated twice, with each separated by 1 hr. The injections were identified by letter codes. During the next 3 sessions, 12 trials were conducted, with saline and cocaine administered 6 times each in pseudorandom order. Thirty minutes following each injection, participants were asked to identify the injection by letter code. Seven of the 10 learned the discrimination (at least 10 trials correct). To evaluate sensitivity, the investigators tested participants with different doses of cocaine in test sessions. In the next phase, methamphetamine (5 and 10 mg/70 kg) and pentobarbital (50 and 100 mg/70 kg) were given intravenously during test sessions to determine whether the discrimination exhibited pharmacological class selectivity. During the evaluation of sensitivity and selectivity, training sessions were interspersed. As dose of cocaine increased, the number of participants identifying the test dose as cocaine increased, demonstrating sensitivity. The higher doses of methamphetamine and pentobarbital substituted for cocaine. The physiological and subjective effects of cocaine and methamphetamine were stimulant-like and dose related. Pentobarbital produced no physiological changes but increased Visual Analog Scale ratings of Sedation, Good Drug Effect, and High. This failure to demonstrate pharmacological selectivity may be related to participants' learning a drug-vs.-no-drug discrimination, and thus it may be necessary to alter training procedures in future studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contralateral auditory stimulation alters acoustic distortion products in humans

It is now generally accepted that otoacoustic emissions (OAE) represent the only objective and non-intrusive means of functional exploration of the active micromechanical characteristics of the outer hair cells of the organ of Corti. Previous studies showed a decrease of the transiently evoked otoacoustic emissions and spontaneous otoacoustic emissions in humans, during acoustic stimulation of the contralateral ear, and attributed this effect to the medial efferent system. Such an effect has been shown on acoustic distortion product otoacoustic distortion emissions (DPOAE) in guinea pigs, but has not been investigated for DPOAEs recorded in humans, although DPOAEs represent the easiest means of exploring active micromechanical cochlear properties both in humans and in laboratory animals. The present study sought to investigate the existence and characteristics of a contralateral auditory stimulation effect on DPOAEs recorded in humans. This study shows that contralateral broad-band noise (BBN) has a suppressive effect on DPOAEs recorded from 0.5 kHz to 5 kHz. This effect is not due to air conduction, as no change in the noise floor occurred under increasing contralateral stimulation, and as no reduction in DPOAE amplitude was obtained in subjects whose contralateral ear was sealed with a plastic ear plug. Moreover, cross-over attenuation by bone transmission has been ruled out, as no change in DPOAE amplitude was recorded in the healthy ear of total unilaterally deaf patients during acoustic stimulation of the deaf ear. The effect seen was not entirely due to the acoustic reflex, as it was found and could indeed be even greater in subjects with no acoustic reflex. Results presented here show that the contralateral BBN effect is greater at low levels of ipsilateral stimulation, which leads us to discuss the involvement of both passive and active mechanisms in DPOAE generation at high stimulation levels. The contralateral BBN effect seems to be greater in mid frequency cochlear regions. There is strong evidence that the medial efferent system is involved and that afferent and efferent inputs are, at least partly, integrated at a brainstem level in order to ensure cochlear interaction. DPOAEs provide an interesting model for functional exploration of the efferent system, since they seem to be the only type of otoacoustic emission that can be recorded in both humans and in the majority of animals, and since results are obtained in the same way from both animals and humans, which allows experimental animal models very close to the human model.     

Cardiac autonomic patterns preceding occasional vasovagal reactions in healthy humans

BACKGROUND: The wide range of clinical presentation of orthostatic vasovagal syncope suggests different underlying changes in the cardiac autonomic modulation. METHODS AND RESULTS: To evaluate the beat-by-beat modifications in the neural control of heart period preceding a syncopal event, we studied RR interval variability in 22 healthy subjects who experienced fainting for the first time during a 90 degrees head-up tilt and in 22 control subjects by means of time-variant power spectral analysis. Sympathetic and vagal modulations to the sinoatrial node were assessed by the normalized power of the low-frequency (LF, approximately 0.1-Hz) and high-frequency (HF, approximately 0.25-Hz) oscillatory components of RR variability. When the patients were supine, no differences were observed in the hemodynamic and spectral parameters of the 2 groups. During the tilt procedure, RR, LFNU, and HFNU (NU=normalized units) values were relatively stable in control subjects. During early tilt (T1), subjects with syncope had reduced RR intervals compared with control subjects. In 13 subjects with syncope, RR decreased while LFNU and LF/HF increased in the last minute of tilt before syncope (T2). Conversely, in the remaining 9 fainters, LFNU and LF/HF decreased from T1 to T2 and HFNU increased slightly. CONCLUSIONS: Two different patterns may be recognized in the cardiac autonomic changes preceding an occasional vasovagal event, namely, one characterized by a progressive increase of the marker of cardiac sympathetic modulation up to the onset of syncope, the other by a sympathetic inhibition with an impending vagal predominance. The recognition of different pathophysiological mechanisms in fainters may have important therapeutic implications.     

A laboratory model of cocaine withdrawal in humans: Intravenous cocaine.

Seven adult intravenous (IV) cocaine users completed a protocol investigating changes in behavior after the self-administration of cocaine. During sessions, the participants could self-administer up to 6 doses of IV cocaine (32 mg/70 kg) twice each day. Both 2- and 3-day binge conditions were tested. At 39 hr after the 3-day but not the 2-day binge of cocaine use, total Beck Depression Inventory scores were increased and participants reported increased ratings of Irritable and decreased ratings of I Want Cocaine. Exposure to stimulus cues associated with IV cocaine increased ratings of I Want Cocaine during periods of abstinence after both 2- and 3-day binges and increased ratings of Depressed only after the 3-day binge of cocaine use. The cessation of binge cocaine use produced modest changes in mood and cocaine craving that were related to the length of the binge and varied as a function of time since last cocaine use. Responsiveness to cocaine cues also varied as a function of the length of the previous cocaine binge. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperventilation alters colonic motor and sensory function: effects and mechanisms in humans

BACKGROUND & AIMS. Hyperventilation-induced hypocapnia affects hemodynamic function and enhances colonic motility. The aims of this study were to determine the effects of hypocapnic hyperventilation on colonic motility and sensation in health and to explore the putative neurohumoral mechanisms. METHODS: In experiment 1, colonic tone, sensation, plasma levels of cortisol, beta-endorphin, selected gut neuropeptides, norepinephrine, epinephrine, and splanchnic blood volume were measured during two sequences of hypocapnic hyperventilation. In experiment 2, colonic tone and sensation were assessed during eucapnic hyperventilation and abdominal compression. RESULTS: Hypocapnic hyperventilation, but not eucapnic hyperventilation or abdominal compression, significantly increased colonic tone and sensitivity to balloon distention (P = 0.017) without altering humoral mediators or splanchnic blood volume. Plasma norepinephrine level increased (P = 0.017) and splanchnic blood volume decreased (P = 0.028) during 5 minutes after hyperventilation, consistent with homeostatic responses. CONCLUSIONS: Increased colonic tone and sensation during hypocapnic hyperventilation are not caused by colonic compression. These effects of hyperventilation are not mediated humorally but may result from direct metabolic effects of hypocapnia on colonic muscle or from changes in central autonomic control of colonic smooth muscle.     

Extent of autonomic activation following cerebral ischemia is different in hypertensive and normotensive humans

OBJECTIVES: To evaluate whether the extent of autonomic activation following brain infarction differs between hypertensive and normotensive humans, and to investigate the role of the insular cortex for this sympathetic activation. DESIGN: Prospective, hospital-based study. SETTING: Department of Neurology of a university medical center. SUBJECTS: Forty-two patients with essential hypertension and 45 patients who were normotensive. MAIN OUTCOME MEASURES: Extent of autonomic activation following stroke as indicated by circadian blood pressure patterns, serum norepinephrine levels, and cardiovascular variables. RESULTS: Normotensive patients with insular infarction showed a significantly reduced circadian blood pressure variation and a higher frequency of nocturnal blood pressure increase compared with patients suffering from essential hypertension and insular stroke. These findings were also associated with higher serum norepinephrine concentrations and more frequent electrocardiographic abnormalities. No significant changes in these variables were seen between normotensive and hypertensive patients without insular involvement. CONCLUSIONS: Our findings suggest a difference in cortical control of autonomic function between hypertensive and normotensive patients after stroke and point to a possible role of the insular cortex in the pathogenesis of essential hypertension.     

Cardiac psychophysiology and autonomic space in humans: Empirical perspectives and conceptual implications.

Contemporary findings reveal that autonomic control of dually innervated visceral organs does not lie along a single continuum extending from parasympathetic to sympathetic dominance. Rather, a bivariate autonomic space bounded by sympathetic and parasympathetic axes is the minimal representation necessary to capture the modes of autonomic control. A quantitative bivariate model for the chronotropic control of the heart in humans is empirically instantiated. This model provides a more comprehensive characterization of psychophysiological response than simple measures of end-organ state and permits a differentiation of behavioral states and processes that would otherwise remain obscure. The model also illuminates and subsumes general principles such as the law of initial values and reveals a fundamental physiological rationale for the selection of heart period over heart rate as a metric for cardiac chronotropy. The present article also considers strategies for psychophysiological investigations within the autonomic space model, the limitations of these methods, and analytical tools for assessing their validity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hunger alters the expression of acquired hedonic but not sensory qualities of food-paired odors in humans.

To test whether expression of hedonic and sensory odor qualities acquired by association with sweet and bitter tastes depend on hunger state, hungry volunteers experienced odors paired with sucrose, quinine, or water and then were tested under different hunger states manipulated with energy preloads. Acquired liking for sucrose-paired odors was evident following a low-energy or control preload but not a high-energy preload; however, odor sweetness increased in all preload conditions. Acquired dislike and increased bitterness of quinine-paired odors were independent of preloading. These data demonstrate hunger-dependent expression of acquired liking for flavors through flavor-flavor associations in humans and demonstrate independence between acquired hedonic and sensory qualities of odors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motilin induces gall bladder emptying and antral contractions in the fasted state in humans

BACKGROUND: Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying. AIMS: To explore the effect of increasing doses of exogenous motilin on gall bladder volume and antral contractility in the fasted state in humans. METHODS: After an overnight fast, eight healthy men received increasing intravenous doses of Leu13-motilin (KW-5139) or 0.9% NaCl in a double blind, randomised fashion. Gall bladder volume and antral contraction frequency were determined by ultrasonography. RESULTS: Infusion of motilin increased plasma motilin levels. Motilin induced a reduction in gall bladder volume of 8.0 (5.0)%, 17.1 (5.0)%, 18.5 (4.7)%, and 16.1 (4.9)% of baseline volume at the end of infusion of 2, 4, 8, and 16 pmol/kg/min respectively, compared with mean stable gall bladder volumes during placebo infusion (p < 0.05). Antral contraction frequency increased during motilin infusion, but not during placebo infusion (p < 0.05). CONCLUSIONS: Exogenous motilin reducted fasting gall bladder volume and increased antral contractions. After reaching maximal reduction, the gall bladder volume did not decrease further during continuous motilin infusion at higher doses and stayed at the same reduced volume. The degree of gall bladder volume reduction during motilin infusion mimicked gall bladder emptying preceding antral phase III activity of the migrating motor complex in humans. This study indicates that motilin may play a physiological role in the regulation of gall bladder emptying in the fasted state.     

Biomedical instrumentation in the Soviet Union

A modified technique for vaso-vasostomy is described with the aim to achieve better results in operative recanalization and restoration of fertility after vasectomy. Vaso-vasostomy is a success when the man is able to produce fertile semen. Criteria for a fertile semen are mentioned. Fertile semen was obtained in all 5 patients treated by this modified technique.     

Delta-opioid stimulation by BW373U86 promotes autonomic reactivity to stressors and alters attention-related cardiac responses in rabbits.

The nonpeptide δ-opioid agonist BW373U86 (3 to 300 μg/kg) was tested in rabbits for effects on heart rate, cardiac orienting and Pavlovian conditioned responses to tones, and unconditioned cardiac and somatomotor responses to signaled and unsignaled shocks. BW373U86 did not alter shock-evoked somatomotor reflexes and had few effects on the development or retention of Pavlovian conditioned heart rate discrimination. However, BW373U86 appeared to modulate cardiac conditioning indirectly, by facilitating sympathetic reflexes evoked by the signaled stressor, and the dose effect was ∪-shaped within the dose range tested. The pronounced tachycardiac effect of BW373U86 was completely blocked, or rapidly reversed, by the selective δ-opiate antagonist naltrindole. BW373U86 was more potent in increasing signaled than unsignaled shock-evoked tachycardia, suggesting release of an endogenous substance (e.g., a δ-opioid) because of the Pavlovian conditioning contingency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Erythrocytes participate significantly in blood transport of amino acids during the post absorptive state in normal humans

To investigate the participation of erythrocytes in the blood transport of amino acids during the course of intestinal absorption in humans, erythrocyte and plasma amino-acid concentrations were determined following ingestion of an oral load of amino acids. In addition to baseline plasma and erythrocyte amino acid concentrations in 18 subjects, plasma and erythrocyte amino acids kinetics during the 125 min following an oral amino acid load were further determined in 9 of the 18 subjects. The results showed that human erythrocytes contained most amino acids at similar or higher concentrations than plasma. Furthermore, the correlations observed between plasma and erythrocyte contents clearly indicated that erythrocytes were involved in the transport of amino acids by the blood. For some amino acids erythrocyte transport sometimes exceeded that of plasma. Significant correlation coefficients showed that strong plasma-erythrocyte relationships existed for alanine, valine, methionine, isoleucine, leucine, phenylalanine, and ornithine. In conclusion, our data supported the hypothesis that both blood compartments, plasma and erythrocytes, are involved significantly in the blood transport of amino acids in humans during the postabsorptive state.     

Age-related changes in the autonomic ganglia

Debridement of nonviable tissue is crucial to optimal wound healing, which can be impaired unless all necrotic tissue, exudate, and metabolic wastes have been removed from the wound. Debridement methods are classified as sharp, mechanical, chemical, and autolytic. This article describes methods of debridement and their outcomes.     

Spinal instrumentation in the management of adolescent scoliosis

A multitude of posterior and anterior segmental spinal instrumentation systems are now available for the treatment of idiopathic scoliosis. As a consequence, fixation strategies are more complex than they were with Harrington instrumentation. The newer systems provide better sagittal control and more stable fixation, allowing quicker mobilization of the patient. On thin patients, the bulk of these implants may be a problem. The techniques of fusion and the fusion levels remain constant.     

A heroin-, but not a cocaine-expecting, self-administration state preferentially alters endogenous brain peptides

The effects of L-type voltage-dependent Ca2+ channel blockers on apomorphine, bromocriptine and morphine-induced changes in locomotor activity were examined in mice. Apomorphine (4 mg/kg) and morphine (20 mg/kg) produced locomotor stimulation. Bromocriptine (8 mg/kg) produced a biphasic effect on motor behaviour, an early depressant phase, followed by locomotor stimulation. Amlodipine (2.5 mg/kg), nicardipine (10 mg/kg), diltiazem (10 mg/kg) and verapamil (10 mg/kg), which by itself did not affect locomotor activity, inhibited the stimulant phase of bromocriptine without altering the depressant phase, while they did not affect apomorphine- and morphine-induced locomotor stimulation. Apomorphine, bromocriptine and morphine-induced locomotor stimulation was decreased by SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7- ol) (0.05 mg/kg) or haloperidol (0.1 mg/kg). These results indicate that L-type voltage-dependent Ca2+ channels are involved in the motor stimulant effect of bromocriptine, but not in apomorphine- and morphine-induced locomotor stimulation. The effects of Ca2+ channel blockers on the dopaminergic system appears not to be directly related to dopamine receptor blockade.     

Anterior instrumentation in the management of thoracolumbar burst fractures

Anterior instrumentation in the treatment of thoracolumbar fractures has progressed significantly during the past 2 decades. These fixation systems have evolved to meet the anatomic, biomechanical, and imaging challenges associated with internal fixation of the thoracolumbar spine. The evolution of these devices will be reviewed, and from this, the indications and surgical techniques necessary for the safe and effective use of the device will be discussed. This study also reports the authors' initial clinical experience using the Z plate anterior thoracolumbar plating system in the treatment of thoracolumbar burst fractures. The study consists of 12 consecutive adult patients who underwent a 1-stage anterolateral decompressive and stabilization procedure for burst fractures from T9-L3. The indications for surgery included neurologic deficits, deformity, progressive kyphosis, and late pain. Ten of the 12 patients maintained their postoperative sagittal alignment or a significant portion of their kyphosis reduction. Two patients with severe kyphotic deformities greater than 50 degrees lost 10 degrees and 20 degrees of their reduction at last followup. All 3 patients with neurologic deficits recovered. There were no neurologic or perioperative complications. Eleven of the 12 patients obtained a good or excellent functional outcome. Anterior arthrodesis using instrumentation stabilization after a 1-stage anterolateral decompression and reduction procedure can yield successful clinical results in the treatment of thoracolumbar burst fractures.     

Role of automation in new instrumentation

In recent years there has been an unprecedented increase in the development of automated instrumentation for ophthalmic diagnostic and assessment purposes. An important part of this growth in automated clinical ophthalmic instrumentation has been directed to perimetry and visual field testing. In less than 15 years automated perimetry has advanced from a laboratory curiosity to become the standard for clinical visual field testing. This paper will provide a brief overview of the impact that automated perimetry has had on current clinical ophthalmic practice and patient management. It is presented as a general example of the influence that automated instrumentation has exerted on the clinical environment.     

Domestic dogs (Canis familiaris) are sensitive to the attentional state of humans.

Twelve domestic dogs (Canis familiaris) were given a series of trials in which they were forbidden to take a piece of visible food. In some trials, the human continued to look at the dog throughout the trial (control condition), whereas in others, the human (a) left the room, (b) turned her back, (c) engaged in a distracting activity, or (d) closed her eyes. Dogs behaved in clearly different ways in most of the conditions in which the human did not watch them compared with the control condition, in which she did. In particular, when the human looked at them, dogs retrieved less food, approached it in a more indirect way, and sat (as opposed to laid down) more often than in the other conditions. Results are discussed in terms of domestic dogs' social-cognitive skills and their unique evolutionary and ontogenetic histories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrophysiological tests of autonomic function in patients with idiopathic autonomic failure syndromes

Three electrophysiological tests of autonomic function were performed in patients with autonomic nervous system dysfunction to define test sensitivities and specificities. The skin sympathetic response, Valsalva ratio, and heart rate variation with deep breathing were studied in 10 patients with multiple system atrophy (MSA) and in 7 patients with pure (also called progressive or primary) autonomic failure (PAF); control subjects were 17 normal individuals of similar age. Thirteen patients had abnormal skin sympathetic responses, and 16 had abnormal Valsalva ratios. Fourteen patients had an abnormal variation of the heart rate with deep breathing. Taking the three tests together, binary logistic regression for distinguishing between patients and normal subjects correctly classified 91% of the 33 individuals for whom there were complete data with sensitivity of 88% and specificity of 94%. However, only 69% of the patients could be correctly classified by a logistic regression for discriminating between MSA and PAF. Electromyography (EMG) studies showed that 7 of 8 patients with MSA but only 2 of 7 patients with PAF (both multiparous women) had denervation of the rectal sphincter muscle. The EMG study is, therefore, valuable in men, but has a high false positive rate in women, probably because of pudendal nerve injury from parturition.