Vagus nerve stimulation magnet activation for seizures: a critical review.

Some patients receiving VNS Therapy report benefit from manually activating the generator with a handheld magnet at the time of a seizure. A review of 20 studies comprising 859 subjects identified patients who reported on-demand magnet mode stimulation to be beneficial. Benefit was reported in a weighted average of 45% of patients (range 0-89%) using the magnet, with seizure cessation claimed in a weighted average of 28% (range 15-67%). In addition to seizure termination, patients sometimes reported decreased intensity or duration of seizures or the post-ictal period. One study reported an isolated instance of worsening with magnet stimulation (Arch Pediatr Adolesc Med, 157, 2003 and 560). All of the reviewed studies assessed adjunctive magnet use. No studies were designed to provide Level I evidence of efficacy of magnet-induced stimulation. Retrospective analysis of one pivotal randomized trial of VNS therapy showed significantly more seizures terminated or improved in the active stimulation group vs the control group. Prospective, controlled studies would be required to isolate the effect and benefit of magnet mode stimulation and to document that the magnet-induced stimulation is the proximate cause of seizure reduction. Manual application of the magnet to initiate stimulation is not always practical because many patients are immobilized or unaware of their seizures, asleep or not in reach of the magnet. Algorithms based on changes in heart rate at or near the onset of the seizure provide a methodology for automated responsive stimulation. Because literature indicates additional benefits from on-demand magnet mode stimulation, a potential role exists for automatic activation of stimulation.

Symptoms and esophageal motility based on phenotypic findings of scleroderma.

Scleroderma esophagus is characterized by ineffective peristalsis and reduced esophageal sphincter pressure. Esophageal disease in scleroderma can precede cutaneous manifestations and has been associated with Raynaud's phenomenon (RP) and pulmonary fibrosis (PF). The objective of the study is to evaluate the impact of cutaneous findings, RP, and PF on demographics, symptoms, and esophageal motility in patients with scleroderma. Scleroderma patients with esophageal involvement were included after review of esophageal manometries and charts over a 6-year period. High-resolution esophageal manometry was performed. Patients completed a symptom questionnaire. The study enrolled 28 patients (22 females; mean age 50.3 ± 12.8 years) with scleroderma esophagus. Patients without skin involvement (n= 12) reported more severe heartburn (P= 0.02), while those with cutaneous findings (n= 16) had more frequent dysphagia with solids (P= 0.02). Patients with RP (n= 22) had lower amplitude of distal esophageal contractions (P= 0.01) than those without RP (n= 6). Patients with PF (n= 11) reported more severe coughing and wheezing (both P= 0.03) than those without lung disease (n= 17). This study highlights subgroups of patients with scleroderma esophagus according to phenotypic findings of dermatologic changes, RP, and PF. Heartburn and dysphagia are important symptoms that may be associated with different stages of disease progression based on skin changes in scleroderma. RP was associated with greater esophageal dysmotility. Coughing and wheezing were more severe in patients with PF.

Epithelial cell volume regulation: bicarbonate dependence.

When Necturus gallbladder epithelial cells are osmotically shrunken, they rapidly return to their original volume despite the continued presence of a hypertonic bathing solution. This volume-regulatory process requires bicarbonate ions in the bathing solutions and is associated with the uptake of chloride ions. Volume-regulatory increase by epithelial cells in probable due to the parallel operation of sodium-hydrogen and chloride-bicarbonate exchangers in the apical cell membrane.

Group therapy for patients with psychogenic nonepileptic seizures: a pilot study.

Great advances have been made in the diagnosis of people with psychogenic nonepileptic seizures (PNES) since the advent of video/EEG monitoring. However, treatment options for this population have lagged significantly. This pilot study was undertaken to evaluate whether group therapy done with a psychodynamic focus would offer a useful intervention. Twelve patients entered the study and seven completed at least 75% of the 32 weekly sessions. The Beck Depression Inventory and the Global Severity Index of the Symptom Checklist-90 showed improvement as well as an overall decrease in PNES frequency. The data suggest that group therapy focusing on interpersonal issues may benefit patients with PNES.

The hormonal regulation of pyloric sphincter function.

The purpose of this study was to evaluate the hormonal control of pyloric sphincter function. Studies were performed on both pyloric circular muscle, in vitro, and the human pylorus, in vivo. Full dose-response curves to gastrin I, cholecystokinin, and secretin were constructed for the pyloric muscle of the opossum studied at its length of optimal tension development, Lo. Both cholecystokinin and secretin were potent agonists on the muscle but gastrin I gave no increase in muscle tension. The combination of cholecystokinin and secretin was additive at submaximal concentrations but potentiation of the maximal responses was not observed. Gastrin I produced a surmountable, competitive-like antagonism to the effect of cholecystokinin on the pyloric muscle. The octapeptide of cholecystokinin was a more potent agonist than the whole molecule of cholecystokinin on the pyloric muscle. In man, the pyloric pressure rose significantly during intravenous infusion of either cholecystokinin or secretin. The combination of maximal doses of both hormones did not show significant potentiation. Gastrin I did not significantly increase pyloric pressure but did antagonize the pyloric response to duodenal acidification. These studies suggest that: (a) Both secretin and cholecystokinin augment pyloric sphincter pressure while gastrin I is an antagonist inhibiting their effects. (b) The hormonal responses of pyloric sphincter circular muscle, in vitro, can be correlated with human sphincter function, in vivo.

High-resolution solid-state manometry of the antropyloroduodenal region.

Manometric recording from the pyloric channel is challenging and is usually performed with a sleeve device. Recently, a solid-state manometry system was developed, which incorporates 36 circumferential pressure sensors spaced at 1-cm intervals. Our aim was to use this system to determine whether it provided useful manometric measurements of the pyloric region. We recruited 10 healthy subjects (7 males:3 females). The catheter (ManoScan(360)) was introduced transnasally and, in the final position, 15-20 sensors were in the stomach and the remainder distributed across the pylorus and duodenum. Patients were recorded fasting and then given a meal and recorded postprandially. Using pressure data and isocontour plots, the pylorus was identified in all subjects. Mean pyloric width was 2.1 +/- 0.1 cm (95% CI: 1.40-2.40). Basal pyloric pressure during phase I was 9.4 +/- 1.1 mmHg, while basal antral pressure was significantly lower (P = 0.003; 95% CI: 2.4-8.4). Pyloric pressure was always elevated relative to antral pressure in phase I. For phases II and III, pyloric pressure was 7.7 +/- 2.3 mmHg and 9.4 +/- 1.1 mmHg, respectively. Pyloric pressure increased similarly after both the liquid and solid meal. In addition, isolated pressure events and waves, which involve the pylorus, were readily identified.

Regional gastric emptying abnormalities in functional dyspepsia and gastro-oesophageal reflux disease.

To characterize proximal and distal stomach emptying in functional dyspepsia (FD) and gastro-oesophageal reflux disease (GORD). Eighty-three patients underwent gastric emptying (GE) scintigraphy and symptom scoring for the evaluation of upper gastrointestinal symptoms and were divided into three groups: FD (n = 25), GORD (n = 20) and FD + GORD (n = 38). Total, proximal and distal gastric retention were determined scintigraphically and compared with normal controls. Delayed total GE was observed in each subgroup: FD (56%), GORD (45%) and FD + GORD (55%). Greater proximal gastric retention was observed after meal ingestion in GORD compared to FD. Greater distal gastric retention was observed in FD and FD + GORD but it was only mild in GORD. Nausea, vomiting, early satiety, distention and regurgitation were associated with proximal gastric retention whereas there was no symptom associated with distal gastric retention. Multiple regression demonstrated total gastric retention at 30 min and 1 h was positively correlated with regurgitation whereas early proximal gastric retention was positively correlated with regurgitation and negatively correlated with nausea. Selective abnormalities of proximal and distal stomach emptying were demonstrated in GORD and FD. GORD and FD symptoms were associated with proximal gastric retention suggesting that proximal stomach motor function may be important in the pathogenesis of symptoms associated with these disorders.

K+ secretion across frog skin. Induction by removal of basolateral Cl-.

We examined the development of K+ secretion after removing Cl- from the basolateral surface of isolated skins of Rana temporaria using noise analysis. K+ secretion was defined by the appearance of a Lorentzian component in the power density spectrum (PDS) when Ba2+ was present in the apical bath (0.5 mM). No Lorentzians were observed when tissues were bathed in control, NaCl Ringer solution. Replacement of basolateral Cl- by gluconate, nitrate, or SO4- (0-Clb) yielded Lorentzians with corner frequencies near 25 Hz, and plateau values (So) that were used to estimate the magnitude of K+ secretion through channels in the apical cell membranes of the principal cells. The response was reversible and reproducible. In contrast, removing apical Cl- did not alter the PDS. Reduction of basolateral Cl- to 11.5 mM induced Lorentzians, but with lower values of So. Inhibition of Na+ transport with amiloride or by omitting apical Na+ depressed K+ secretion but did not prevent its appearance in response to 0-Clb. Using microelectrodes, we observed depolarization of the intracellular voltage concomitant with increased resistance of the basolateral membrane after 0-Clb. Basolateral application of Ba2+ to depolarize cells also induced K+ secretion. Because apical conductance and channel density are unchanged after 0-Clb, we conclude that K+ secretion is "induced" simply by an increase of the electrical driving force for K+ exit across this membrane. Repolarization of the apical membrane after 0-Clb eliminated K+ secretion, while further depolarization increased the magnitude of the secretory current. The cell depolarization after 0-Clb is most likely caused directly by a decrease of the basolateral membrane K+ conductance. Ba2(+)-induced Lorentzians also were elicited by basolateral hypertonic solutions but with lower values of So, indicating that cell shrinkage per se could not entirely account for the response to 0-Clb and that the effects of 0-Clb may be partly related to a fall of intracellular Cl-.

Microelectrode studies of the active Na transport pathway of frog skin.

When the outer surface of short-circuited frog skin was penetrated with microelectrodes, stable negative potentials that averaged near -100 mV were recorded consistently, confirming the results of Nagel (W. Nagel. 1975. Abstracts of the 5th International Biophysics Congress, Copenhagen. P-147.). The appearance of these stable potentials, V(O), concurrent with the observations that (a) a high resistance outer barrier R(O) accounting for approximately 75 percent or more of the transcellular resistance of control skins had been penetrated and that (b) 10(-5) M amiloride and reduced [Na] outside caused the values of V(O) to increase towards means value near -130 mV while the values of percent R(O) increased to more than 90 percent. It was of relationships were the same as the values of E(1) observed in studies of the current-voltage relationships were the same as the values of E'(1) defined as the values of voltage at the inner barrier when the V(O) of the outer barrier was reduced to zero by voltage clamping of the skins. Accordingly, these data are interpreted to mean that the values of E(1), approximately 130 mV, represent the E(Na) of the sodium pump at the inner barrier. 2,4-DNP was observed to decrease the values of transepithelial voltage less than E(1) the V(O) was negative. These data can be interpreted with a simple electrical equivalent circuit of the active sodium transport pathway of the frog skin that includes the idea that the outer membrane behaves as an electrical rectifier for ion transport.

Intracellular voltage of isolated epithelia of frog skin: apical and basolateral cell punctures.

Isolated epithelia of frog skin were prepared with collagenase, and the cells were punctured with intracellular microelectrodes across their apical (outer) and basolateral (inner) surfaces. Regardless of the route of cell puncture, the intracellular voltage (Vosc) in short-circuited isolated epithelia was markedly negative, averaging -70.4 mV for apical punctures and -91.6 mV for basolateral punctures. As in intact epithelia, amiloride outside caused the Vosc to become more negative (means of -96.7 and -101.8 mV), with a concomitant increase in the resistance of the apical barrier. Increasing the [K)i of the basolateral solution from 2.4 to 8.0 or 14.4 mM caused rapid step depolarization (5-10 s) of the Vosc under transepithelial Na transporting and amiloride-inhibited conditions of Na transport, with the delta Vosc ranging between 23.9 and 68.3 mV per decade change of [K]i. The finding that the Vosc of isolated epithelia of frog skin is independent of the route of cell penetration is consistent with the notion that the cells of the stratified epithelium are electrically coupled (functional syncitium). Moreover, the isolated epithelium can serve as a useful preparation, especially in studies designed to investigate the properties of the basolateral surfaces of cells.

Ouabain on active transepithelial sodium transport in frog skin: studies with microelectrodes.

Studies were done with isolated frog skin to determine the effects of 10(-4) M ouabain on the electrophysiological parameters of outer and inner barriers of the Na-transporting cells. Microelectrodes were used to impale the skins from the outer surface to determine the intracellular voltages (Vsco) under conditions of short-circuiting and under conditions where a voltage clamp was used to vary the transepithelial voltage, VT. From this, the electrical resistances of outer (Rfo) and inner (RI) barriers were estimated. In addition, the driving force for active transepithelial Na transport (ENa = E'1) was estimated from the values of VT when the Vo = 0 mV (Helman and Fisher. 1977. J. Gen. Physiol. 69: 571-604). Studies were done with skins bathed with the usual 2.4 meq/liter [K]i in the inner solution as well as with reduced [K]i of 0.5 and 0 meq/liter. Characteristically, the responses to ouabain could be described by an initial rapid phase (5-10 min) during which time the Ri was increased markedly and the E'1 was decreased from control values. Thereafter, during the slow phases of the response, the resistances of both outer and inner barriers increased continuously and markedly with time leading ultimately to essentially complete inhibition of the short-circuit current. Similar studies were done with skins exposed to 10(-4) M amiloride in the outer solution. Although estimates of Ri could not be obtained under these conditions, the effects on the Vsco and E'1 were similar to those observed for the Na-transporting skins. However, the magnitudes of the effects were less and relatively slower than observed for the Na-transporting skins. The results of these studies were analyzed within the context of a proposed electrical model that takes into account the observation that the magnitude of the voltage at the inner barrier appears to exceed the equilibrium potential for K especially when transepithelial Na transport is inhibited at the apical barrier of the cells.

The effect of rabeprazole on regional gastric acidity and the postprandial cardia/gastro-oesophageal junction acid layer in normal subjects: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Postprandial intragastric acidity is not uniform. Postprandial proximal gastric acid pockets have been described in the present study. AIM: To determine the effects of rabeprazole on regional intragastric acidity and proximal acid pockets. METHODS: Ten normal subjects underwent two 8-day oral dosing regimens with placebo or rabeprazole 20 mg each morning in a randomized, double-blind protocol. Oesophago-gastric pH monitoring was performed on days 1 and 8. RESULTS: Rabeprazole increased fasting and postprandial gastric pH to above 4 in each area of the stomach on days 1 and 8. With placebo, acid pockets were identified at the cardia/gastro-oesophageal junction in 62 and 50 of 150 pull-throughs on days 1 and 8, respectively. Acid pockets were detected postprandially 3.1 +/- 0.2-5.8 +/- 0.1 cm below the proximal border of the lower oesophageal sphincter with a mean pH drop from 4.6 +/- 0.1 to 1.5 +/- 0.1. Rabeprazole decreased the number of acid pockets to 30 and 27 on days 1 and 8, respectively. Rabeprazole also decreased their length and magnitude of the pH drop. CONCLUSIONS: Rabeprazole increased intragastric pH on day 1 and 8 and maintained an elevated pH during and after meals. Postprandial acid pockets, identified in the region of the cardia/gastro-oesophageal junction area postprandially, were decreased in number, length and magnitude by rabeprazole.

Biorhythms and highway crashes. Are they related?

Biorhythm, a theory that purports to identify periods of increased individual susceptibility to accident or misfortune on the basis of recurring biological cycles, is currently enjoying world-wide popularity. In view of the implications of such a theory for both public health and safety, the present study was undertaken as an empirical test of its validity. Using data from 205 carefully investigated highway crashes (135 fatal; 70 nonfatal) in which the drivers were clearly at fault, the authors computed specific points in drivers' biorhythm cycles at which the accidents occurred. The observed frequencies of accidents occurring during so-called critical and minus periods were then compared with the frequencies to be expected on a chance basis alone. The results provided no evidence for a relationship between purported biorhythm cycles and accident likelihood.

Electroencephalographic features of moyamoya in adults.

OBJECTIVE: Electroencephalography is useful for evaluating transient neurological events in the setting of moyamoya disease. METHODS: EEG findings of adults with moyamoya seen at a large moyamoya referral center are summarized. Patients were identified by retrospective chart review. RESULTS: EEGs were ordered after cerebral revascularization for altered mental status, aphasia, limb shaking, or facial twitching. Among the study population of 103 patients having EEGs, 24% of adults with moyamoya had a history of clinical seizures. Ischemic or hemorrhagic strokes were associated with a twofold relative risk of seizures. Overall, 90% of EEGs were abnormal, most commonly focally (78%), or diffusely slow (68%). Epileptiform EEG discharges were seen in 24%. Whereas hemispheres with an ischemic stroke had a 19% risk of epileptiform discharges and an 8% risk of seizures on EEG, hemispheres with hemorrhagic stroke had a 35% risk of epileptiform discharges and 19% risk of seizures on EEG. Focal amplitude attenuation was seen in 19%, breach rhythm in 15%, rhythmic delta in 14%, and electrographic seizures in 12%. CONCLUSIONS: Seizures and epileptiform EEG changes are common in patients with moyamoya disease. SIGNIFICANCE: Transient events in patients with moyamoya can result from seizures as well as ischemia.

Sensory, motor and cognitive alterations in aged cats.

These experiments were designed to assess some of the sensory, motor and cognitive alterations that occur in aged cats. Three groups of cats (1-3, 5-9 and 11-16 years of age) were tested in four behavioral tasks to assess age-dependent changes in locomotor activity, fine motor coordination, reactivity to auditory stimuli and spatial reversal learning. In tests of locomotor activity, 11-16 year old cats displayed altered patterns of habituation compared to 1-3 and 5-9 year cats. There were no decrements in fine motor coordination in the 11-16 year cats as measured by their ability to traverse planks of varying width or by their scores on a neurological examination. The 11-16 and 5-9 year cats both displayed increased reactivity to auditory stimuli. On tests of spatial reversal learning, 11-16 year cats displayed superior performance compared to 5-9 or 1-3 year animals, making fewer errors and requiring fewer trials to reach criterion. These findings indicate that a series of age-related behavioral changes occurs in the cat. Some of these may be related to morphological and neurophysiological alterations in neurons in the caudate nucleus.

Quantitative morphology of medium-sized caudate spiny neurons in aged cats.

These studies were designed to assess some of the morphological alterations that occur in medium-sized spiny neurons of the caudate nucleus in aged cats. Computer assistance was used to quantify in three dimensions the extent of the dendritic trees of 164 neurons from 11 cats (5 1-3 years and 6 over 10 years of age) stained by the rapid Golgi technique. In all animals beyond 10 years of age there was a decrease in the density of spines on distal dendritic segments. This decrease was moderate (16%) in 13 year old cats and reached about 50% in 15 and 18 year old animals. In addition, there was an increase in the frequency of occurrence of spines with enlarged heads in all aged cats. In cats over 13 years there was a marked loss of portions of distal dendritic segments. All measures of dendrite length displayed statistically significant decreases of 30-40% in cats 15 and 18 years of age. There were no significant age-related alterations in numbers of dendrites, number of branches per dendrite or soma diameter. These morphological results indicate that there is a sequence of age-related changes that occurs in caudate medium-sized spiny neurons and provides a basis from which to assess functional alterations.

Suicide by vehicular crash.

The authors evaluated data on 182 fatally injured and 96 nonfatally injured drivers involved in vehicular crashes over a 6-year period. Only 1.7% of the total fatal crashes were considered to have been suicides, and 1% of the nonfatal crashes were deemed suicide attempts. Neither group of drivers had unusually high incidences of previous suicidal ideation or behavior, but both groups tended to be socially deviant, with above average levels of psychopathology and social aggressiveness. Crash victims in both groups also had poor driving records and high rates of alcohol abuse, findings that have important implications for accident prevention.

Social adjustment profiles of female drivers involved in fatal and nonfatal accidents.

Previous research by the authors has shown that male drivers involved in fatal and nonfatal accidents can be differentiated from the general population on the basis of background, behavior, and social adjustment. The results of the present study suggest that female drivers involved in serious crashes do not differ from the overall female driving population.

Sources of neostriatal cholecystokinin in the cat.

The objective of this study was to determine the sources of cholecystokinin within the neostriatum of the cat. Cholecystokinin-immunoreactive cells and fibers were detected by means of the peroxidase antiperoxidase immunohistochemical technique. This method was combined with intrastriatal injections of the retrograde marker horseradish peroxidase conjugated with wheat-germ agglutinin to survey the possible afferent sources of cholecystokinin to the feline neostriatum. Intrinsic, apparently aspiny cholecystokinin-immunoreactive neurons organized in a pericapsular pattern were found within both the caudate and putamen of the cat. In addition, both thalamostriatal and mesostriatal projections containing cholecystokinin were observed. These results indicate that cholecystokinin within the neostriatum of the cat arises from both intrinsic and extrinsic sites.

GABAergic basal forebrain neurons project to the neocortex: the localization of glutamic acid decarboxylase and choline acetyltransferase in feline corticopetal neurons.

Our objective was to determine whether GABAergic and cholinergic basal forebrain neurons project to the neocortex. The retrograde connectivity marker wheat germ agglutinin lectin-bound horseradish peroxidase was injected into the neocortex of adult cats. Histo- and immunohistochemical methods were combined to label sequentially connectivity and transmitter markers (glutamic acid decarboxylase; choline acetyltransferase) in forebrain neurons. The labels of each marker were identified by correlative light and electron microscopy. Two principal types of doubly labeled neurons were demonstrated. The connectivity marker was colocalized with glutamic acid decarboxylase or choline acetyltransferase. The neurons were located in the basal forebrain. Their ultrastructural, cellular, and regional organization supported 2 conclusions. (1) GABAergic basal forebrain neurons project to the neocortex. This is important new morphological evidence for the origin of inhibitory neocortical afferents from a subcortical brain site. (2) The GABAergic and cholinergic basal forebrain neurons projecting to the neocortex exhibit remarkable structural similarities. The transmitter diversity of these intertwined neocortical afferents may be significant for the pathology and treatment of human neurological disorders such as Alzheimer's disease.