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Biomedical subjects

M S Levine

Publications and source records attributed to M S Levine.

At least 19 recordsLinked to original sources

Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex.

The responses of human neocortical neurons to iontophoretic application of excitatory amino acids and their modulation by dopamine (DA) were studied in vitro. Brain slices were obtained from children undergoing surgery for intractable epilepsy. Application of N-methyl-D-aspartate (NMDA) to the slices induced slow depolarizations accompanied by decreased input conductances and sustained action potentials in cortical neurons. Glutamate produced rapid depolarizations and firing with few changes in input conductances. Quisqualate also induced depolarization and firing, but input conductances increased during the rising phase of the membrane depolarization. Iontophoretic application of DA alone produced no change in membrane potential or input conductance. However, when DA was applied in conjunction with the excitatory amino acids, it produced contrasting effects. With either bath application of DA or when iontophoresis of DA preceded application of NMDA, the amplitude of the membrane depolarizations and the number of action potentials were increased, whereas the latency of these responses decreased. In contrast, DA decreased the amplitude of the depolarizations and the number of action potentials evoked by glutamate or quisqualate. The fact that DA affects responses to NMDA and glutamate or quisqualate in opposite directions is of considerable importance to the understanding of cellular mechanisms of neuromodulation and the role of DA in cognitive processing and in epilepsy.

Adolescent

Gastric carcinoma after gastrojejunostomy for benign disease: radiographic findings.

Although it is not well recognized in the radiologic literature, gastric carcinoma has been reported to occur as a late complication of gastrojejunostomy for benign disease, even in the absence of partial gastrectomy. We present the radiographic findings in two patients with this complication and review clinical and experimental data supporting the role of gastrojejunostomy in the subsequent development of gastric carcinoma.

Aged

Massive gastric distention due to duodenal involvement by retroperitoneal tumors.

We present three patients with retroperitoneal tumor involving the duodenum in whom upper gastrointestinal (GI) studies revealed delayed gastric emptying and massive gastric dilatation out of proportion to the degree of duodenal dilatation. While the radiographic findings mimicked acute gastric outlet obstruction, delayed films demonstrated narrowing and encasement of the duodenum at the site of obstruction in all three patients. Thus, the duodenum should be carefully evaluated radiographically in patients with acute gastric dilatation, particularly if there is a known history of malignancy.

Acute Disease

Age-induced changes in electrophysiological responses of neostriatal neurons recorded in vitro.

The present studies were undertaken to determine whether the major electrophysiological characteristics of neostriatal neurons are altered during aging. The passive and active membrane properties of 130 neostriatal neurons obtained from young (three to five months, N = 65) and aged (24-26 months, N = 65) Fischer 344 rats were compared using an in vitro slice preparation. The results indicated that in a population of aged neostriatal neurons the majority of the electrophysiological changes that occurred resulted in decreases in cellular excitability. These changes included increased threshold to induce action potentials by intracellular current injection and decreased negativity of membrane potentials at which such action potentials were induced. In addition, there were increases in the amplitude of the action potential afterhyperpolarization and increases in the frequency of occurrence of accommodation when trains of action potentials were induced. These two latter effects can limit the frequency of action potential generation. The thresholds to elicit synaptically evoked depolarizing responses and action potentials were increased. The results also indicated that a number of basic electrophysiological parameters were unchanged by the aging process. These included action potential amplitude, rise time and duration, resting membrane potential, input resistance and time constant. Although thresholds for the induction of synaptic and action potentials by extracellular stimulation were increased, the latency, amplitude and duration of the evoked depolarization remained unchanged. These findings suggest that the ability of neostriatal neurons to integrate spatiotemporal inputs must be severely compromised in this population of aged cells. Furthermore, the present findings, when compared with age-induced electrophysiological alterations in neurons in other brain areas, indicate that age may differentially alter electrophysiological properties of neurons in separate nuclei. Profiles of age-related changes in neurophysiological properties of neurons provide important information that can be related to the contributions of individual neural areas to the behavioral effects of aging.

Action Potentials

Herpes esophagitis in otherwise healthy patients: clinical and radiographic findings.

The authors report the clinical and radiographic findings in five otherwise healthy male patients with herpes esophagitis who had no underlying immunologic problems. The patients all presented with onset of acute odynophagia after a flulike prodrome of fever, sore throat, or myalgias. In all five patients, double-contrast esophagograms revealed innumerable punctate or linear areas of ulceration, predominantly located in the midesophagus near the level of the left main bronchus. Four patients received viscous lidocaine and antacids, and one patient, intravenously administered acyclovir. All five patients had an acute, self-limited illness with complete resolution of symptoms 10-12 days from the time of presentation. It is concluded that, if the characteristic clinical prodrome is present in patients with typical findings on double-contrast esophagograms, such patients can receive conservative treatment without need for endoscopic intervention.

Adolescent

Focal spiculation of the upper thoracic esophagus: normal variant at double-contrast esophagography.

A review of 100 routine biphasic upper gastrointestinal examinations revealed focal spiculation of the upper thoracic esophagus as a transient finding in 11 patients (11%) who otherwise had no clinical or radiographic signs of esophageal disease. All 11 patients had remarkably similar findings, with thin (1-2 mm wide), transverse folds or striations above the level of the aortic arch, producing a spiculated or serrated appearance in profile. This focal spiculation should be considered a normal variant in the esophagus on double-contrast radiographs. It is suspected that this phenomenon is related to weakening of peristalsis or localized contraction of the longitudinally oriented muscularis mucosae at the junction of the striated- and smooth-muscle portions of the esophagus. Whatever the explanation, radiologists should be familiar with this finding, so that it is not mistaken for a focal area of esophagitis.

Adolescent

Enhanced responses to NMDA receptor activation in the developing cat caudate nucleus.

An in vitro slice preparation was used to assess the effects of N-methyl-D-aspartate (NMDA) receptor activation in the developing cat caudate nucleus. Removal of Mg2+ from the bathing medium, in the presence of 10 microM bicuculline, increased the amplitude and duration of the excitatory postsynaptic potential induced by local extracellular stimulation at all ages tested. In neurons younger than 35 days of age, removal of Mg2+ in the presence of bicuculline produced an increase in excitatory postsynaptic potential amplitude and duration as well as bursts of action potentials when local extracellular stimulation was applied. The effects of Mg2+ removal were reversibly attenuated by the specific NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid. These findings are important because they demonstrate that NMDA receptor-mediated responses can be induced in developing caudate neurons by local extracellular stimulation and these responses are enhanced in early postnatal periods at ages when motor control is being established.

Animals

Iontophoretic application of NMDA produces different types of excitatory responses in developing human cortical and caudate neurons.

The effects of iontophoretically applied N-methyl-D-aspartate (NMDA) were assessed in human neocortical and caudate neurons. NMDA depolarized cell membranes, decreased input conductances and induced firing. The discharge patterns differed in the two areas studied. In neocortex, NMDA produced repetitive spikes or bursts. In caudate, it induced slow, rhythmic plateau depolarizations accompanied by an initial burst of action potentials, followed by low amplitude, long duration spikes. After hyperpolarizations were seen after each depolarization in the caudate. These variations in patterns of excitation may relate to differences in local circuits intrinsic to each region, and/or to membrane conductances specific to each type of cell.

Adolescent

Neurophysiological maturation of cat caudate neurons: evidence from in vitro studies.

The membrane properties and synaptic physiology of developing cat caudate (Cd) nucleus neurons were studied in in vitro slice preparations. Recordings were obtained from 98 cells in kittens from fetal day (F) 56 to postnatal day (P) 90. With increasing age, the following maturational changes occurred; resting membrane potentials became more negative, action potential rise times decreased, action potential amplitudes increased, and action potential durations and input resistances decreased. The frequency of occurrence of afterhyperpolarizations and of anomalous rectification increased with age. The primary response to local extracellular stimulation was a depolarization usually accompanied by an action potential. Evoked hyperpolarizing responses were seen after P28 but only occurred if the membrane was depolarized by intracellular current injection. Cells identified by intracellular injection of Lucifer yellow were primarily medium-sized spiny neurons although it was not always possible to determine the cell type in slices from animals less than P5. Somatic diameter, dendritic length, and spine density increased with age. Dye-coupling occurred in slices less than P20. Its frequency decreased with age. These results show that Cd neurons undergo significant maturation during late prenatal and early postnatal periods. In contrast, substantia nigra neurons mature more rapidly and should be capable of influencing the less mature Cd neurons during development.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

Neurophysiological maturation of cat substantia nigra neurons: evidence from in vitro studies.

The membrane properties and synaptic physiology of developing cat substantia nigra (SN) neurons were studied in in vitro slice preparations. Stable intracellular recordings were obtained from 46 neurons in 20 kittens ranging in age from fetal day (F) 51 to postnatal day (P) 120. Only two of these properties changed with development. The percentage of cells displaying inward rectification and the percentage of cells that generated low-threshold Ca++ spikes increased with age. Properties that did not change included resting membrane potentials, action potential amplitudes and durations, and input resistances. At all ages locally evoked synaptic responses consisted of sequences of excitatory postsynaptic potentials followed by inhibitory postsynaptic potentials. Most of the cells recorded had the electrophysiological properties which have been attributed to SN dopamine-containing neurons. To identify neurons morphologically, and verify the recording site, cells were filled with Lucifer yellow at the end of each experiment. Somatic shapes varied widely from oval to fusiform to triangular. Somatic diameters and dendritic length increased with development. Filopodial processes and growth cones were present up to the first postnatal month. Dye-coupling occurred only in the fetal group. These results indicate that cat SN neurons have many mature physiological properties during late fetal and early postnatal development. This contrasts with the significant maturation that occurs in cat caudate neurons during the same developmental period.

Action Potentials

Duodenitis: a reliable radiologic diagnosis?

The authors performed a retrospective study of 50 patients with endoscopically diagnosed duodenitis who had undergone double-contrast upper gastrointestinal (GI) examinations. Duodenitis was diagnosed on the original radiographic reports in six of 37 patients (16%) with mild-to-moderate duodenitis, five of 13 patients (38%) with severe duodenitis, and 11 of 50 patients (22%) with all grades of duodenitis on endoscopy. Subsequent analysis of the films revealed one or more radiologic signs of duodenitis (including folds more than 4 mm in thickness, mucosal nodularity, bulbar deformity, and erosions) in 18 of 37 patients (49%) with mild-to-moderate duodenitis, eight of 13 patients (62%) with severe duodenitis, and 26 of 50 patients (52%) with all grades of duodenitis on endoscopy. In a separate part of the study, the authors identified another 20 patients with radiographically diagnosed duodenitis who had undergone endoscopic examinations. Nine of those 20 patients (45%) had duodenitis on endoscopy. Subsequent analysis of the films revealed one or more signs of duodenitis in 17 patients from this group. Nine of the latter patients (53%) had duodenitis on endoscopy. Using established radiologic criteria for duodenitis, our rate of false-positive and false-negative radiologic diagnoses still was about 50%. Thus, the double-contrast upper GI examination is a relatively unreliable technique for diagnosing duodenitis.

Adult

Extrusion of PEG tube from the stomach with fistula formation: an unusual complication of percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) has become an accepted technique for providing long-term enteral feeding. We report two cases of extrusion of the PEG tube into a short fistulous tract that communicates with the stomach. Although this unusual complication led to difficulty with tube feedings, both patients were asymptomatic, and, in one case, it was possible to reposition another catheter in the stomach via the fistula.

Adult

Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat.

A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis which is characterized by ataxia, tremor and hind limb rigidity. Brains of affected rats and unaffected littermate controls were transected at the mesencephalon into rostral and caudal portions (the caudal portion contained the cerebellum and brainstem). Poly(A)+ mRNA was isolated from pooled rostral or caudal portions and injected into Xenopus oocytes. The oocytes were voltage-clamped and exposed to 1 mM L-glutamate, 500 microM kainate, 500 microM quisqualate, 200 microM N-methyl-D-aspartate (NMDA) or 1 mM gamma-aminobutyric acid (GABA). Oocytes injected with mRNA isolated from the caudal portions of the affected rat brains exhibited statistically significant increases in glutamate and kainate peak current responses compared to oocytes injected with mRNA from other brain samples. No differences were noted in the responses of the groups when exposed to quisqualate, NMDA or GABA. Cerebellar and brain stem mRNA were also isolated separately in different groups of mutants and unaffected littermates. Only oocytes injected with cerebellar mRNA from mutants displayed statistically significant increases in responses to glutamate and kainate. In parallel morphological studies changes in the cerebellum of mutants were also observed. These consisted of a loss of Purkinje cells and an asymmetrical disarrangement of the granule cell layer of cerebellar cortex. Taken together, the physiological and morphological results suggest that alterations in glutamate/kainate receptors in the cerebellum are phenotypic manifestations of the Han-Wistar mutation. The results are consistent with the hypothesis that this mutant rat might serve as a model of glutamate/kainate excitotoxicity in the brain.

Animals

Radiology of esophagitis: a pattern approach.

This article presents a pattern approach for diagnosing esophagitis at double-contrast esophagography. In patients with nodular elevations of the mucosa, discrete plaques should suggest Candida esophagitis, whereas poorly defined nodules should suggest reflux esophagitis and a distinctive reticular pattern of the mucosa should suggest Barrett esophagus, particularly if adjacent to the distal aspect of a high stricture. In patients with ulceration, one or more shallow ulcers at or near the gastroesophageal junction should suggest reflux esophagitis, whereas discrete, superficial ulcers in the midesophagus should suggest herpes or drug-induced esophagitis, depending on the clinical setting. In contrast, one or more giant, relatively flat ulcers should suggest cytomegalovirus esophagitis, particularly in patients with acquired immunodeficiency syndrome. Finally, thickened longitudinal folds may be caused by esophagitis, varices, or, rarely, "varicoid" carcinoma, but these conditions usually can be differentiated on radiologic grounds. By carefully analyzing the appearance and location of nodules, plaques, ulcers, or abnormal folds in the esophagus, one can usually suggest a cause of the disease.

Barrett Esophagus

Giant, human immunodeficiency virus-related ulcers in the esophagus.

Human immunodeficiency virus (HIV) infection of the esophagus has recently been implicated as a cause of giant esophageal ulcers in HIV-positive patients with odynophagia. The authors examined four patients in whom esophagograms (one single-contrast and three double-contrast studies) revealed giant, HIV-related ulcers indistinguishable from those of cytomegalovirus (CMV) esophagitis. All four patients had severe odynophagia, one had an associated maculopapular rash, and two became HIV-positive at approximately the time of clinical presentation. In all patients, biopsy samples, brushings, and cultures obtained with endoscopy were negative for CMV or herpes simplex. One patient had positive brushings for candidiasis, but this may have resulted from fungal superinfection of the ulcer. Two patients were treated with orally administered steroids, and all four had swift clinical improvement; symptoms disappeared during an average period of 8.3 days from presentation. HIV-related esophageal ulcers should be distinguished from CMV ulcers, so that appropriate treatment can be initiated in these patients.

Adult

Diagnosis of pneumoperitoneum on supine abdominal radiographs.

A blinded, retrospective study was performed to determine the value of supine abdominal radiographs in diagnosing pneumoperitoneum. Supine films from 44 cases of pneumoperitoneum were randomly interspersed among supine films from 87 control subjects without free air, and the films were reviewed for the presence or absence of various signs of pneumoperitoneum, including Rigler's sign (gas on both sides of the bowel wall), the falciform ligament sign (gas outlining the falciform ligament), the football sign (gas outlining the peritoneal cavity), the inverted-V sign (gas outlining the medial umbilical folds), and the right-upper-quadrant gas sign (localized gas in the right upper quadrant). One or more of these signs were present in 26 cases (59%) of pneumoperitoneum, including the right-upper-quadrant gas sign in 18 cases (41%), Rigler's sign in 14 cases (32%), and the falciform ligament and football signs in one case each (2%). Unfortunately, there were frequent errors in the interpretation of the right-upper-quadrant gas sign and Rigler's sign, with a total of 11 false-positive cases (13%). Further analysis of the true-positive right-upper-quadrant gas signs showed that these gas collections were always triangular or linear with an inferolateral to superomedial orientation and, if triangular, a concave superolateral border. In the true-positive Rigler's signs, the bowel wall thickness ranged from 1 to 8 mm, whereas the false positives all had a bowel wall thickness of 1 mm or less. Proper interpretation of the various signs of pneumoperitoneum on supine films should lead to more accurate diagnosis of this condition.

False Positive Reactions