SEARCH · PubMed Health

Results for “synaptic dysfunction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,477 records · Page 82Linked to original sources

PubMed2004

Sequence analysis of ADARB1 gene in patients with familial bipolar disorder.

BACKGROUND: The ADARB1 gene is located in 21q22.3 region, previously linked to familial bipolar disorder, and its product has a documented action in the editing of the pre-mRNA of glutamate receptor B subunit. Dysfunction of glutamatergic neurotransmission could play an important role in the pathophysiology of bipolar disorder (BD). Glutamate excitatory neurotransmission regulation is a possible mechanism of the initial effect of anticonvulsants in regulating mood. METHODS: To investigate the hypothesis of an involvement of ADARB1 gene in the BD, the ADARB1 cDNA has been cloned and sequenced in seven selected bipolar I disorder patients with evidence of familiarity of mood disorders. A detailed investigation of the gene nucleotide sequence in the open reading frame has been performed. RESULTS: No alteration in the sequence of the ADARB1 gene cDNA was found in any patient, except a common neutral polymorphism in three out of seven patients. CONCLUSIONS: Mutations in ADARB1 gene are not commonly associated with bipolar I disorder, therefore other genes in the 21q22 region could be associated with bipolar illness in some families, likely in the context of a multifactorial transmission model.

Adenosine Deaminase↗

PubMed2004

Comparative effects of glycine and D-cycloserine on persistent negative symptoms in schizophrenia: a retrospective analysis.

Phencyclidine (PCP), ketamine and other N-methyl-D-aspartate (NMDA) antagonists induce schizophrenia-like symptoms in normal volunteers, suggesting that endogenous dysfunction or dysregulation of NMDA receptors may contribute to the pathophysiology of schizophrenia. Glycine and D-cycloserine are potential treatments for persistent negative symptoms of schizophrenia. Seventeen patients were identified who participated in double-blind trials of both agents. Significant clinical improvement was observed during both trials. However, the degree of improvement was significantly larger during glycine, than D-cycloserine, treatment on both an individual subject and group level. Previous analyses have documented effectiveness of glycine, and to a lesser extent D-cycloserine, within separate patient populations. This analysis provides the first direct comparison of glycine and D-cycloserine effects within the same population, and suggests first, that NMDA agonists are effective in treatment of persistent negative symptoms of schizophrenia, and, second, that full agonists, such as glycine and D-serine, may be more effective than partial agonists such as D-cycloserine. Similar findings are apparent when data are considered from all trials with NMDA agonists performed to date. Overall, the findings indicate that agents which potentiate NMDA transmission may be therapeutically beneficial in treatment of persistent symptoms of schizophrenia.

Adult↗

PubMedDate not supplied

Incidence of phrenic neuropathy after isolated lung transplantation. The Loyola University Lung Transplant Group.

BACKGROUND: Isolated lung transplantation is a viable therapeutic option for many patients with end-stage pulmonary disease. Other intrathoracic surgical procedures have a well documented incidence of phrenic nerve dysfunction, although the incidence after lung transplantation has not been studied. METHODS: Thirty-one patients who underwent lung transplantation were evaluated for evidence of phrenic nerve dysfunction and subsequent recovery. Risk factors contributing to the incidence of injury were examined. Phrenic nerve injury was defined by two separate diagnostic tests (Transcutaneous Phrenic Nerve Conduction Studies and Fluoroscopic evaluation of diaphragmatic movement) used in combination. RESULTS: Of the 27 patients who were completely evaluated after the operation, eight had defining criteria for nerve injury--an incidence of 29.6%. Of those affected, the majority of injuries (89%) resulted in complete paralysis of the affected hemidiaphragm. The highest incidence of injury occurred in patients who underwent bilateral single lung transplantation (41%), with the right phrenic nerve being injured most often (78%). Fortunately, no significant postoperative morbidity was attributable to the occurrence of phrenic nerve injury when compared with those patients who did not sustain injury. CONCLUSIONS: The analysis of possible risk factors resulted in the hypothesis that the likely mechanism of injury in these patients was due to stretching or direct instrumentation of the nerve, and thus measures should be instituted to minimize the possibility of injury.

Adult↗

PubMed2004

Mania as a dysfunction of reentry: application of Edelman's and Tononi's hypothesis for consciousness in relation to a psychiatric disorder.

The concept of reentry as the most important element in a hypothesis for consciousness proposed by Edelman and Tononi is reviewed. Reentry, is a process of ongoing parallel and recursive signalling between separate neuronal groups along parallel reciprocally fibers that link these groups anatomically. Reentry alters the activity of the target areas it interconnects until a synchronous activity across these areas is created, this may be the direct biological mechanism of consciousness. The repetitive process of reentry may explain how the millisecond time scale of neural signalling is turned into the time scale of seconds characterizing our impression of the duration of a given content of consciousness. It is suggested that reentry may be faster in mania, and specifically that the repetitive recursive signalling is faster in mania, hereby allowing reentry to produce a conscious state, faster than usual. Faster reentry may on a molecular level be caused by faster propagation of nerve impulses, which may be in accordance with a number of hypotheses where mania is seen as a disorder of ionic conductance, nerve cell excitability, action potential firing, membrane abnormalities, and cortical instability. Also the antiepileptic drugs used to treat mania may point to reentry as a factor in this disorder. On a more integrated level faster reentry processes may explain several of the core symptoms of the manic state. Also the drug induced switch from depression to mania in bipolar patients may be explained by the concept of reentry.

Bipolar Disorder↗

PubMed2000

Effects of antidepressants in adrenergic neurotransmission of human vas deferens.

OBJECTIVES: To evaluate the effects of sertraline, fluoxetine, and amitriptyline on the contractile responses of the human vas deferens muscle elicited by norepinephrine, electrical field stimulation, and KCl, because the therapeutic action of antidepressants may be accompanied by sexual dysfunction related to the contractility of the vas deferens smooth muscle. METHODS: Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of sertraline, fluoxetine, and amitriptyline on the neurogenic and agonist-induced contractile responses. RESULTS: Amitriptyline caused concentration-dependent inhibition of neurogenic and norepinephrine-induced contractions. In contrast, only the highest concentration (10(-5) M) of sertraline and fluoxetine reduced the adrenergic contractions. The dihydropyridine calcium antagonist nifedipine (10(-6) M) completely prevented the inhibitory effect of sertraline and fluoxetine on neurogenic and norepinephrine-induced contractions but did not change the inhibition caused by amitriptyline. Sertraline, fluoxetine, and amitriptyline (all at 10(-5) M) attenuated contractions elicited by KCl and reduced contractions induced by CaCl(2) in KCl-depolarized preparations. CONCLUSIONS: The results indicate that sertraline and fluoxetine inhibit vas deferens motility through inhibition of Ca(2+) entry, with no effect on the adrenergic receptors, and amitriptyline acts as an adrenoceptor antagonist and inhibitor of the entry of calcium.

Amitriptyline↗

PubMed2002

Effects of ketamine on leading saccades during smooth-pursuit eye movements may implicate cerebellar dysfunction in schizophrenia.

OBJECTIVE: Ketamine has proved a useful probe in the study of schizophrenia. Recent studies have shown that ketamine causes abnormalities in eye tracking similar to those seen in patients with schizophrenia. The authors examined the effects of ketamine on leading saccadic eye movements, a specific component of the smooth-pursuit response shown to be abnormal in schizophrenia patients and their relatives. METHOD: Twelve normal healthy volunteers received a 0.1 mg/kg bolus injection of ketamine or placebo in double-blind fashion during a smooth-pursuit eye-movement task. The number of leading saccades and the ratios of leading saccades to smooth-pursuit response time and to total saccadic eye-movement time were measured. RESULTS: Ketamine significantly increased the number of leading saccades and increased the leading saccade ratios for more slowly moving targets. Similar nonsignificant effects were noted at higher target speeds. Ketamine-induced abnormalities were similar to those observed in relatives of schizophrenia patients under drug-free conditions. CONCLUSIONS: These results suggest that neurotransmission mediated by N-methyl-D-aspartate (NMDA) is involved in eye-tracking abnormalities. The generation of disruptive leading saccades during smooth pursuit is thought to be mediated by frontal-thalamic-cerebellar circuitry. Evidence that the locus of this and other ketamine-induced smooth-pursuit eye-movement deficits involves NMDA receptor functioning in the cerebellum is suggested.

Adult↗

PubMed1980

Diagnostic capacity of sinus node recovery time after inhibition of autonomous neural tone.

Symptomatic arrhythmias often occur intermittently in patients with sinus node dysfunction. A diagnostic test with ability to reveal latent sinus disease has therefore been much sought for. Determinations of sinus node recovery time (SNRT) and corrected sinus node recovery time (CSNRT) have been attempted but limitations in their diagnostic power are well recognized. To eliminate a possible masking effect of autonomous neural tone, propranolol 0.1 mg/kg and atropine 0.02 mg/kg was administered to 30 patients with established symptomatic sinus bradydysrhythmias (SSBD) and to a control group of 18 age-matched healthy volunteers. In addition the same procedure was applied to 9 patients with symptoms suggesting SSBD in whom, however, this cause was later excluded. The upper normal limit of CSNRT defined by the control group was 545 msec before and 505 msec after drugs. In the SSBD group, CSNRT was falsely negative in 8 of the 30 patients. Repeated testing after drug inhibition reduced this number to 2 patients. Thus, the sensitivity increased from 73% to 93%. CSNRT determinations were normal in the non-SSBD patients, specificity remaining at 100%. Thus, the discriminative power of electrophysiologic testing for sinus node disease was found to be high when CSNRT determinations were performed both before and after drug inhibition of autonomous neural tone.

Aged↗

PubMed2005

Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin.

OBJECTIVE: While both thalamic abnormalities and dopaminergic dysregulation have been separately implicated in the pathophysiology of schizophrenia, little is known about the possible dysfunction of molecules associated with dopaminergic neurotransmission in the thalamus in this illness. In this study, the authors studied this question by measuring in postmortem brain the expression of molecules associated with dopaminergic neurotransmission. METHOD: Using in situ hybridization and receptor autoradiography, the authors determined in schizophrenia and comparison subjects 1) thalamic expression of the transcripts encoding the five dopamine receptors; 2) binding to the dopamine D(1), D(2), and D(3) receptors; 3) monoaminergic innervation as assessed by binding to the vesicular monoamine transporter; and 4) transcripts encoding three dopamine receptor-associated intracellular proteins (calcyon, spinophilin, and DARPP-32) that mediate integration of dopaminergic signaling with other neurotransmitter systems. RESULTS: Both calcyon and spinophilin transcripts were significantly elevated in schizophrenia subjects. Monoaminergic innervation, as well as dopamine receptor transcripts and binding sites, were unaffected in this illness. CONCLUSIONS: These data indicate that there are dopaminergic abnormalities in the thalamus in schizophrenia but that they are at the level of intracellular integration of dopamine signaling with other neurotransmitter systems, likely including glutamate, in thalamic neurons.

Aged↗

PubMed1999

Measurement of GABAergic parameters in the prefrontal cortex in schizophrenia: focus on GABA content, GABA(A) receptor alpha-1 subunit messenger RNA and human GABA transporter-1 (HGAT-1) messenger RNA expression.

The hypothesis that the pathophysiology of schizophrenia may be associated with a dysfunction in GABA transmission in the human prefrontal cortex was investigated. Human post mortem brain tissue from 10 control cases and six cases of schizophrenia were processed for amino acid analysis and for radioactive in situ hybridization. Laminae III and V of three prefrontal cortical areas were examined in detail, namely Brodmann areas 9, 10 and 11. Of these three areas significant changes in GABAergic markers were found only in areas 9 and 10. Of note, a significant decrease in the tissue content of GABA was observed and this was accompanied by a marked increase in the cellular expression of the GABA(A) receptor alpha-1 subunit messenger RNA and a marked decrease in the expression of human GABA transporter-1, the messenger RNA encoding the neuronal GABA transporter protein. The amino acid analysis data provided in this study coupled with the detailed cellular study of several GABAergic markers in the human prefrontal cortex provide direct evidence in support of a disturbance in GABA transmission in the prefrontal cortex, which may be loosely termed "hypofrontality".

Aged↗

PubMed1987

Pharmacology of Reye syndrome.

Reye syndrome, a reversible metabolic encephalopathy and hepatopathy, offers a unique opportunity to investigate the pharmacologic mechanisms by which a toxic-metabolic insult to mitochondria is translated into neurochemical and neurologic dysfunction. Similarity of some clinical and metabolic abnormalities between certain inborn errors of organic acid, ammonia, and carbohydrate metabolism and Reye syndrome suggests a common pathophysiologic mechanism at some level. The primary metabolic aberration in Reye syndrome is unknown. Viral, drug, and toxic precipitants in a conductive host alter glial and neuronal function, possibly by direct toxic effects or by altered transmitter metabolism and signal transduction. These events translate into a rather stereotyped progression of the clinical syndrome. Increased ICP, which is a life-threatening epiphenomenon, is the focus of conventional therapy. Investigational treatments, still in preliminary stages, are aimed at early correction of instigating metabolic abnormalities or correction of their consequences on central neurotransmission. Our fragmentary knowledge of neurotransmitter abnormalities in this disorder, which have suggested disparate interpretations, does not allow a cohesive pharmacologic theory of Reye syndrome. The greatest difficulties in interpretation of possible central mechanisms from existing data, which derive largely from peripheral tissues, is in the differentiation of primary from compensatory changes. The unitarian notion that a single pharmacologic disturbance is the source of the encephalopathy is perhaps too simplistic. It is hoped that future studies of disorders such as Reye syndrome will elucidate the intricate relationships between biochemical pathways and neurotransmitter metabolism.

Amino Acids↗

PubMed2000

Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis.

Patients with long-standing diabetes commonly suffer from gastric neuromuscular dysfunction (gastropathy) causing symptoms ranging from postprandial bloating to recurrent vomiting. Autonomic neuropathy is generally believed to be responsible for diabetic gastropathy and the underlying impairments in gastric emptying (gastroparesis) and receptive relaxation, but the specific mechanisms have not been elucidated. Recently, it has been recognized that interstitial cells of Cajal generate electrical pacemaker activity and mediate motor neurotransmission in the stomach. Loss or defects in interstitial cells could contribute to the development of diabetic gastroparesis. Gastric motility was characterized in spontaneously diabetic NOD/LtJ mice by measuring gastric emptying and by monitoring spontaneous and induced electrical activity in circular smooth muscle cells. Interstitial cells of Cajal were studied by Kit immunofluorescence and transmission electron microscopy. Diabetic mice developed delayed gastric emptying, impaired electrical pacemaking, and reduced motor neurotransmission. Interstitial cells of Cajal were greatly reduced in the distal stomach, and the normally close associations between these cells and enteric nerve terminals were infrequent. Our observations suggest that damage to interstitial cells of Cajal may play a key role in the pathogenesis of diabetic gastropathy.

Animals↗

PubMed2004

M4 muscarinic receptors regulate the dynamics of cholinergic and dopaminergic neurotransmission: relevance to the pathophysiology and treatment of related CNS pathologies.

Dopaminergic dysfunction is an important pathogenetic factor for brain pathologies such as Parkinson's disease, ADHD, schizophrenia, and addiction as well as for metabolic disorders and anorexia. Dopaminergic neurons projecting from the midbrain to forebrain regions, such as the nucleus accumbens and the prefrontal cortex, regulate motor and cognitive functions and coordinate the patterned response of the organism to sensory, affective, and rewarding stimuli. In this study, we showed that dopaminergic neurotransmission is highly dependent on M4 cholinergic muscarinic receptor function. Using in vivo microdialysis, we found elevated dopamine (DA) basal values and enhanced DA response to psychostimulants in the nucleus accumbens of M4 knockout mice. We also demonstrated impaired homeostatic control of cholinergic activity that leads to increased basal acetylcholine efflux in the midbrain of these animals. Thus, loss of M4 muscarinic receptor control of cholinergic function effectuates a state of dopaminergic hyperexcitability. This may be responsible for pathological conditions, in which appetitive motivation as well as affective and cognitive processing is impaired. We propose that M4 receptor agonists could represent an innovative strategy for the treatment of pathologies associated with hyperdopaminergia.

Acetylcholine↗

PubMed1994

Effects of nefiracetam on deficits in active avoidance response and hippocampal cholinergic and monoaminergic dysfunctions induced by AF64A in mice.

The effects of nefiracetam [DM-9384; N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide] and of phosphatidylcholine on a step-up active avoidance response, locomotor activities and regional brain cholinergic and monoaminergic neurotransmitters in AF64A-treated mice were investigated. Intracerebroventricular (i.c.v.) injection of AF64A (ethylcholine mustard aziridinium ion; 8 nmol/ventricle) impaired acquisition and retention of the avoidance task, and increased vertical and horizontal locomotor activities. Regional levels of acetylcholine, noradrenaline, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly decreased and homovanillic acid (HVA) levels were increased in the hippocampus but not in the septum, cerebral cortex or striatum of AF64A-treated animals. Administration of nefiracetam (3 mg/kg, p.o.) twice daily for 9 days to AF64A-treated animals ameliorated the deficit in active avoidance response in addition to attenuating the increase in locomotor activities. In parallel with these behavioural effects, nefiracetam reversed AF64A-induced alterations in the hippocampal profiles of cholinergic and monoaminergic neurotransmitters and their metabolites. In contrast, administration of phosphatidylcholine (30 mg/kg, p.o.) twice daily for 9 days had no significant effect on the deficit in active avoidance response, despite significantly reversing the decrease in acetylcholine levels in the hippocampus. These results indicate that the effects of nefiracetam on AF64A-induced behavioural deficits are probably due to its ability to facilitate both cholinergic and monoaminergic neurotransmitter systems.

Acetylcholine↗

PubMed1990

No impairment of sympathetic neurotransmission in stunned myocardium.

Reversibly injured myocardium after short periods of ischemia is characterized by a prolonged depression of contractile function which can, however, be enhanced by inotropic interventions. Thus, a lack of inotropic stimulation due to ischemic damage of cardiac sympathetic nerves has been suggested as a mechanism underlying postischemic myocardial dysfunction. We tested this hypothesis in nine anesthetized, vagotomized dogs with left cardiac sympathetic nerve stimulation (CSNS) at 1, 2, 5, 10, and 20 Hz and compared this response to that of intravenous norepinephrine infusion (NE, 0.5-1 microgram/kg.min). Regional myocardial wall thickness was measured using sonomicrometry, and mean systolic wall thickening velocity (MSTV) was determined. CSNS was performed before and at 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24 h after release of a 15 min occlusion of a left circumflex coronary artery branch. Before coronary artery occlusion MSTV was increased in a frequency-dependent way from 7.5 +/- 2.7 (S.D.) (rest) to 8.1 +/- 3.1 (1 Hz), 9.4 +/- 3.2 (2 Hz), 11.4 +/- 2.7 (5 Hz), 13.4 +/- 2.4 (10 Hz), and 16.8 +/- 2.1 (20 Hz) by CSNS, and to 12.6 +/- 3.4 mm/s by NE. Immediately upon reperfusion CSNS increased MSTV from 2.9 +/- 2.0 to 2.9 +/- 2.8, 4.1 +/- 3.0, 5.4 +/- 4.6, 6.9 +/- 4.5 and 9.4 +/- 5.9, and NE increased MSTV to 7.8 +/- 1.9 mm/s. Baseline function recovered over 24 h, as did the response to CSNS and NE. Since the recovery of baseline function paralleled the increases in regional contractile function achieved by CSNS or NE, we conclude that there is no impairment of sympathetic neurotransmission in the stunned myocardium.

Animals↗

PubMed1995

Antisocial tendencies and cortical sensory-evoked responses in alcoholism.

Alcohol-dependent patients with antisocial, aggressive, and impulsive behaviors form a subgroup, in which a dysfunction of the brain serotonin system is discussed as a pathogenetic factor. Early onset and a transmission from fathers to sons (type II alcoholism; Cloninger, 1987) are supposedly further characteristics of this subgroup. The response pattern of primary auditory cortices to auditory stimuli with different intensities is discussed as a noninvasive indicator of the level of central serotonergic neurotransmission. A strong intensity dependence of these responses is supposed to indicate low serotonergic neurotransmission and vice versa. A strong intensity dependence is therefore expected to characterize patients with antisocial tendencies. Auditory-evoked potentials (N1/P2 component) to stimuli in five different intensities were recorded in 53 hospitalized patients after 1 week of withdrawal. Dipole source analysis was performed to separate responses of primary and secondary auditory cortices. Patients with antisocial tendencies showed a significantly stronger intensity dependence of their evoked responses of primary auditory cortices (tangential dipoles). Age at onset and family history were not related to the intensity dependence of the evoked responses. The results support the notion that alcohol-dependent patients with strong intensity dependence and antisocial tendencies form a subgroup with a serotonergic hypofunction. These patients may respond favorably to a relapse prevention with serotonergic drugs.

Adult↗

PubMed1996

In vivo assessment of neurotransmitter system in cardiovascular diseases. Clinical issues.

Cardiac neurotransmitter systems, especially the adrenergic receptor pathway, are impaired in heart diseases. In patients with heart failure, these abnormalities contribute to arrhythmogenesis and to progression of cardiac dysfunction. The use of MIBG with single photon imaging has provided useful information on the mechanisms of ventricular arrhythmias, and on the causes of death in patients with heart failure or hypertrophic cardiomyopathy. It has been suggested as a prognostic indicator in patients with heart failure. Positron Emission Tomography (PET) now allows us to obtain noninvasively the quantitative determination of regional receptor density and affinity in humans as well as innervation integrity and functioning. These measurements are based upon the synthesis of a radioligand, usually either a selective receptor antagonist or a false neurotransmitter labeled with a positron-emitting radioisotope. Mathematical compartmental models are fitted to activity-versus-time curves obtained during saturation or displacement experiments in order to calculate the rate constants and the receptor density in the myocardium. PET has only recently begun to be applied to the study of cardiac physiology and disease. PET and SPECT cardiac neuroimaging techniques are able to demonstrate the physiological regulation of receptors, and to provide the possibility of studying regional abnormalities of cardiac neurotransmission, especially in arrhythmogenic cardiomyopathy. Furthermore these non invasive techniques could be useful in exploring the alteration of neurotransmission in the early stage of heart disease and could allow repeated scintigraphic examinations in order to evaluate the effects of cardiac medications.

Animals↗

PubMed2005

Neuropharmacology of cognition and memory: a unifying theory of neuromodulator imbalance in psychiatry and amnesia.

The case of HM, a man with intractable epilepsy who became amnesic following bilateral medial temporal lobe surgery nearly half a century ago has instigated ongoing research and theoretical speculation on the nature of memory and the role of the hippocampus. Neuropsychological testing showed that although HM had extensive anterograde memory loss he could still acquire motor and cognitive skills implicitly, but could not remember the context of this learning. This has lead to declarative and procedural descriptions of the memory process. Cholinergic and monoaminergic neurotransmitter systems have also been implicated in the memory process and anticholinergic drugs traditionally have been associated with impairment of declarative memory. The cholinergic hypothesis of Alzheimer's disease is a classic example of an application of these neuropharmacological findings. In schizophrenia, preattentive deficits have been amply demonstrated by unconscious priming studies. Memory processes are also impaired in these patients. Dopamine, glutamate and even cholinergic dysfunction has been implicated in the clinical picture of schizophrenia. The present paper will attempt to bring together both the anatomical and pharmacological data from these disparate fields of research under a cohesive theory of cognition and memory. A hypothesis is presented for an inverse relationship between monoaminergic and cholinergic systems in the modulation of implicit (unconscious) and explicit (conscious) cognitive processes. It is postulated that muscarinic cholinergic receptors and monoaminergic systems facilitate unconscious and conscious processes, respectively, and they disfacilitate conscious and unconscious processes, respectively (the purported inverse relationship). In fact, the muscarinic and monoaminergic modulations of a neural network are proposed to be finely balanced such that, if, the activity of one receptor system is modified then this by necessity has effects on the other system. It takes into account receptor subtypes and their effects mediated through excitatory and inhibitory G-protein complexes. For example, m1/D2 and D1/m4 paired receptor subtypes, colocalized on separate neurons would have opposing functional effects. A theory is then presented that the critical underlying pathophysiology of schizophrenia involves a hypofunctional muscarinic cholinergic system, which induces abnormal facilitation of monoaminergic subsystems such as dopamine (e.g., a decrease in m1R function would potentiate D2R function). This extends the idea of an inverted U function for optimal monoaminergic concentrations. Not only would this impair unconscious preattentive processes, but according to the hypothesis, explicit cognition as well including memory deficits and would underlie the mechanism of psychosis. Contrary to current thinking a different view is also presented for the role of the hippocampus in the memory process. It is postulated that long-term explicit memory traces in the neocortex are laid down by phasic coactivation of forebrain projecting monoaminergic systems above some basal firing rate, such as the rostral serotonergic raphe, which projects diffusely to the cortex and according to a modified Hebbian principle. This is the proposed principal function of the hippocampal theta rhythm. The phasic activation of the cholinergic basal forebrain is mediated by projections from a separate cortical structure, possibly the lateral prefrontal cortex. Phasic muscarinic receptor activation is proposed to strengthen implicit memory traces (at a synaptic level) in the neocortex. Thus, the latter are spared by medial temporal surgery explaining the dissociation of explicit from implicit memory.

Amnesia↗

PubMed1992

Carpal tunnel syndrome: a review.

Carpal tunnel syndrome involves classic symptoms of numbness and paresthesias in the radial 3-1/2 digits, most frequently nocturnal, and pain associated with this distribution. Thenar weakness and autonomic dysfunction rarely are seen in this syndrome except in advanced cases. Provocative tests on physical examination such as the wrist flexion test and the local percussion sensitivity test over the median nerve can be extremely helpful in determining and confirming the diagnosis. Nerve conduction velocity and electromyographic studies of the median nerve and its compression can be helpful especially in difficult cases involving a complex differential diagnosis. It has been clearly documented that a negative NCV/EMG study by itself, does not exclude the possibility of carpal tunnel syndrome. The hallmark of the diagnosis remains the history and a careful physical examination. Treatment initially consisting of wrist splint immobilization and steroid injection into the carpal canal can provide initial relief and elimination of symptoms on a long-term basis in several patient groups. Patients without any resolution of symptoms after two to three months of conservative treatment or those with symptoms of greater than one year's duration generally can be considered candidates for surgical decompression of the carpal canal. The likelihood of operative treatment being required for resolution of symptoms is heightened if the patient is involved in daily manual repetitive activities of the hand and/or wrist. Surgical decompression can be accomplished by either a limited open technique or the new endoscopic released technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Carpal Tunnel Syndrome↗