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Biomedical subjects

S L Rauch

Publications and source records attributed to S L Rauch.

107 records · Page 6Linked to original sources

Recognition and management of benzodiazepine dependence.

Primary care physicians prescribe the majority of benzodiazepines and thus may see most patients who are dependent on these drugs. The diagnosis of benzodiazepine misuse is based on the history, the physical examination and drug use patterns. The treatment of benzodiazepine misuse can be a challenging process that requires the physician's patience, caution and sound clinical judgment. Patients who misuse benzodiazepines may have coexisting psychiatric problems that require treatment, such as depression or panic disorder. Family physicians can manage these patients but should be prepared to refer them for hospitalization when habituation and withdrawal reactions are complicated by medical instability, noncompliance or clinical deterioration.

Ambulatory Care↗

Neuropsychiatric considerations in the treatment of hypertension.

Algorithms have been developed to guide the treatment of simple hypertension. The basic algorithms are modified in the face of concurrent medical conditions, taking into account the various pharmacological effects of antihypertensive agents. This article reviews the neuropsychiatric effects of the major classes of antihypertensive agents (ganglionic blockers, centrally acting agents, diuretics, vasodilators, beta-blockers, calcium channel blockers and angiotensin converting enzyme inhibitors). The purported efficacy of some antihypertensive agents in the treatment of psychiatric conditions is also discussed. Beneficial as well as adverse neuropsychiatric effects are reviewed. In this way, guidelines for the treatment of hypertension are suggested which take into account a broad spectrum of neuropsychiatric considerations.

Antihypertensive Agents↗

Prenatal phenytoin exposure decreases neuronal membrane order in rat offspring hippocampus.

Pregnant Sprague-Dawley CD rats were administered 0 or 200 mg/kg of phenytoin by gavage on days 7-18 of gestation, with controls pair-fed to the phenytoin exposed dams. At birth, litter sizes were standardized to 10, balancing for sex, and were reared by their biological dams until either day 3 or 28. At each of these ages half of the litters from each group were used to determine synaptic plasma membrane order in selected brain regions (cerebellum, cortex, hippocampus) by fluorescence polarization using the probe 1,6-diphenyl-1,3,5-hexatriene (DPH). No significant differences in membrane anisotropy were noted in 3-day-old phenytoin offspring, but a reduction in anisotropy in 28-day-old phenytoin offspring hippocampal regions was observed. The effect was specific in that no changes were found in the cerebellum or cortex at this age. The magnitude of the change corresponded to an approximately 3-5 degrees C increase in temperature and to changes produced by other known membrane disordering agents, such as ethanol. The data, together with previous findings of memory impairments in phenytoin offspring, support an association between the hippocampal membrane disordering effect and functional impairments produced by prenatal phenytoin exposure.

Aging↗

TS prognosis and ADD.

Explore the source record for details and available documents.

Attention Deficit Disorder with Hyperactivity↗

Developmental changes in synaptic membrane order: a comparison of regions in the rat brain.

Developmental changes in synaptic membrane order were followed in 5 regions of the rat brain, the cortex (Cx), cerebellum (Cb), brainstem (BS), lateral subcortex (LSCx) and midline subcortex (MSCx). Membrane order was assessed by the fluorescence polarization technique, using 1,6-diphenyl-1,3,5-hexatriene (DPH) as the probe. The results illustrate that the developmental increase in membrane order proceeds from caudal to rostral brain regions. Thus, at the earliest time point examined (day 3) steady-state anisotropy (rs) in the BS was significantly higher than in the Cx and reached adult values by day 14 while the Cx values were still significantly less than the adult value even at day 30. The thermotropic behavior of the membranes was investigated over the range of 20-37 degrees C. The Arrhenius slopes among the Cx, BS, LSCx and MSCx were similar across all ages studied, suggesting that the developmental increase in order primarily results from a change in entropy. In contrast, the Arrhenius slopes for the Cb increase greater than 100% during development, suggesting that a change in enthalpy is important for the increase in membrane order. Multilamellar liposomes prepared from membrane lipid extracts generally showed the same developmental changes in order as the intact membranes. These data indicate that the increase in membrane order results from a marked change in bulk lipid composition rather than a secondary lipid matrix change (e.g. in membrane asymmetry) and/or from the developmental increase in the protein/lipid ratio.

Animals↗

Cholinergic mediation of spatial memory in the preweanling rat: application of the radial arm maze paradigm.

These experiments assessed spatial memory capabilities in the developing rat by the radial arm maze paradigm. Subjects were trained and tested in the maze beginning at 16 days until they were 25 days of age. Results showed that animals that received training performed significantly better than those naive to the task, and better than chance, which suggests an early capacity for this type of learning. The second experiment investigated the neural mechanism that underlies spatial memory at this age as measured by the radial arm maze. In order to distinguish between the working and the reference memory components of the task, a modification of the basic radial arm maze paradigm was used. Subjects trained from 16 days received drug injections of saline, methylscopolamine, scopolamine, or arecoline prior to testing at age 25 days. Results indicated that central cholinergic antagonism severely impairs working memory while sparing reference memory. This finding is consistent with the existing literature that suggests a role for acetylcholine in adult learning and memory, specifically in working memory. Most important, these experiments document that (a) the radial arm maze paradigm can be used effectively for the developmental study of learning and memory in the rat and (b) cholinergic system(s) mediate working memory at an early age.

Animals↗

Prenatal valproic acid exposure decreases neuronal membrane order in rat offspring hippocampus and cortex.

Sprague-Dawley rats were administered 0 or 200 mg/kg of valproic acid (VPA) on days 7-18 of gestation. Controls were pair-fed. On postnatal day 28, analyses of brain tissues were performed on enriched neuronal membrane fractions from cerebellum, hippocampus, and cortex for anisotropy using the membrane probe 1,6-diphenyl-1,3,5-hexatriene (DPH). No significant differences in membrane anisotropy were noted in the cerebellum, but a significant reduction in anisotropy in the hippocampus and cortex was observed. This change corresponds to a 3-5 degrees C increase in temperature or that produced by other membrane disordering agents (ethanol, phenytoin). An association between membrane anisotropy and functional effects of prenatal VPA exposure is discussed.

Animals↗

Neurosurgical treatment of Tourette's syndrome: a critical review.

Some patients with Tourette's syndrome (TS) remain disabled despite conventional treatment. Recently, neurosurgical procedures have been reported to be potentially effective interventions for such intractable cases. Clinicians are now being asked to make recommendations to patients about these candidate operations. This review explores the reported experience with neurosurgical treatment of TS to assess critically the evidence regarding risks and benefits. Toward that end, the rationale for the various procedures and the relevant neuroanatomy are outlined and recommendations for patient selection and management of future cases are discussed. We reviewed all available published reports on this subject and two unpublished cases, totaling 36 patients. Although a variety of operations have been used to treat TS, there is limited evidence pertaining to the risks or benefits of any surgical procedure. Neurosurgical treatment of TS remains experimental, since there is only anecdotal experience with these operations. Furthermore, there is no compelling evidence that any neurosurgical procedure is superior to all others. If these experimental neurosurgeries are to continue, guidelines should be developed regarding patient and operation selection, and interdisciplinary assessment committees should implement such guidelines at institutions where these operations are performed. Moreover, future cases should be prospectively studied using contemporary technologies to assess lesion placement and size and validated clinical instruments to characterize patients and assess outcome, including adverse effects.

Brain↗

Neurobiological models of obsessive-compulsive disorder.

The authors review current neurobiological models of obsessive-compulsive disorder (OCD). The rationale for anatomically based models is outlined and selected brain regions of interest are discussed. The authors conclude that there is abundant evidence to implicate multiple brain regions as sites of abnormality in OCD. A review of neuropharmacological concepts related to the serotonergic (5-HT) hypothesis of OCD is also presented. The authors conclude that anti-obsessional agents may well have therapeutic effects via the 5-HT system, yet there is little unequivocal evidence to suggest an underlying abnormality in the 5-HT system. A comprehensive neurobiological model of OCD must acknowledge the interrelationship between multiple transmitter systems and integrate anatomical with neuropharmacological concepts.

Brain↗

Chronic benzodiazepine treatment decreases postsynaptic GABA sensitivity.

Benzodiazepines exert most of their pharmacological effects by a selective facilitation of the postsynaptic actions of GABA. Clinical, behavioural and electrophysiological studies have shown reduced drug response following chronic benzodiazepine administration. We present here electrophysiological evidence for decreased postsynaptic sensitivity to GABA following chronic benzodiazepine administration as measured by the direct iontophoretic application of GABA and serotonin onto serotonergic cells in the midbrain dorsal raphe nucleus (DRN), known to receive GABAergic input. The subsensitivity to GABA was found to be dose dependent and was seen when diazepam administration was three weeks or longer. Further, acute injection of the specific benzodiazepine antagonist, Ro15-1788, was found to reverse rapidly the decrease in GABA sensitivity observed in chronically diazepam-treated animals without altering GABA sensitivity in vehicle-treated rats. Decreased response to chronic benzodiazepines does not appear to be consistently related to alterations in the number or affinity of receptors for benzodiazepines. Our studies of radioligand-binding showed a decrease in the ability of GABA to enhance benzodiazepine binding in cerebral cortical membranes from chronic diazepam-treated animals without significant changes in benzodiazepine binding site density or affinity.

Action Potentials↗

Tourette's disorder and related problems: a review and update.

Tourette's disorder is a complex, multifaceted condition of neurological origin with psychiatric symptomatology characterized by multiple motor and vocal tics. It begins during childhood and has a waxing and waning course. Coexisting obsessive-compulsive symptoms, attentional problems, and other behavioral features are common. Pathophysiology involves dysfunction in basal ganglia and related corticothalamic circuits. Many patients who present in clinical settings have mild to moderate symptoms and require only education, monitoring, and long-term follow-up. Those with more-severe symptoms require treatment, typically including both pharmacotherapy and nonmedication approaches. In addition to traditional neuroleptic treatment, a variety of agents such as clonidine, serotonin-reuptake inhibitors, and tricyclic antidepressants can be used. Further investigation is needed in a variety of areas, including longitudinal follow-up studies of children, adolescents, and adults with Tourette's disorder; systematic investigation of psychiatric comorbidity and the heterogeneity of the disorder; clarification of the phenomenological similarities and differences between Tourette's disorder and obsessive-compulsive disorder; and neuroimaging and neuropsychological studies of Tourette's disorder and related problems.

Antidepressive Agents, Tricyclic↗

Clinical neuroimaging in psychiatry.

The practical aspects of contemporary neuroimaging techniques relevant to clinical psychiatry are reviewed. In particular, the structural imaging modalities of computed axial tomography (CT) and magnetic resonance imaging (MRI) are described and compared. Likewise, functional neuroimaging modalities including the nuclear imaging techniques of positron emission tomography (PET) and single photon emission computed tomography (SPECT), as well as the newer magnetic resonance techniques of functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS), are reviewed. Although structural imaging techniques are most useful for ruling out medical etiologies of mental status disturbances, functional neuroimaging techniques currently have an adjunctive role in the evaluation of dementia and seizure disorders and show promise for the evaluation of primary psychiatric disorders in the future. Specific guidelines are suggested regarding the use of these neuroimaging studies.

Brain Diseases↗

Neuroimaging and neurobiological models of depression.

We review the data from structural neuroimaging studies (computed tomography and magnetic resonance imaging) related to depressive disorders. In addition, we review the relevant functional neuroimaging research, including studies of normal emotional processing, studies of the functional neuroanatomy of major depression, and neurochemical neuroimaging studies of depression. Finally, we discuss existing neurobiological models of depression and offer modifications based upon the body of neuroimaging research we have presented.

Depressive Disorder↗