N400-like magnetoencephalography responses modulated by semantic context,word frequency,and lexical class in sentences

Words have been found to elicit a negative potential at the scalp peaking at approximately 400 ms that is strongly modulated by semantic context. The current study used whole-head magnetoencephalography (MEG) as male subjects read sentences ending with semantically congruous or incongruous words. Compared with congruous words, sentence-terminal incongruous words consistently evoked a large magnetic field over the left hemisphere, peaking at approximately 450 ms. Source modeling at this latency with conventional equivalent current dipoles (ECDs) placed the N400 m generator in or near the left superior temporal sulcus. A distributed solution constrained to the cortical surface suggested a sequence of differential activation, beginning in Wernicke's area at approximately 250 ms, spreading to anterior temporal sites at approximately 270 ms, to Broca's area by approximately 300 ms, to dorsolateral prefrontal cortices by approximately 320 ms, and to anterior orbital and frontopolar cortices by approximately 370 ms. Differential activity was exclusively left-sided until >370 ms, and then involved right anterior temporal and orbital cortices. At the peak of the N400 m, activation in the left hemisphere was estimated to be widespread in the anterior temporal, perisylvian, orbital, frontopolar, and dorsolateral prefrontal cortices. In the right hemisphere, the orbital, as well as, weakly, the right anterior temporal cortices were activated. Similar but weaker field patterns were evoked by intermediate words in the sentences, especially to low-frequency words occurring in early sentence positions where there is little preceding context. The locations of the N400 m sources identified with the distributed solution correspond well with those previously demonstrated with direct intracranial recordings, and suggested by functional magnetic resonance imaging (fMRI). These results help identify a distributed cortical network that supports online semantic processing.     

A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate- or ranitidine-treated intensive care unit patients

OBJECTIVE: To compare the frequency of acute stress ulceration and secondary pneumonia caused by aerobic Gram-negative bacilli in ICU patients treated with either sucralfate or ranitidine. DESIGN: Prospective, randomized study. SETTING: ICU, university hospital. PATIENTS: Sixty adult patients who were mechanically ventilated and at risk of developing stress ulceration. INTERVENTION: The patients were randomized to receive either sucralfate (1 g every 6 hrs) via the nasogastric tube or iv ranitidine (50 mg every 6 hrs). If the gastric pH was less than 3.5 in the latter group, 30 mL of 0.3M sodium citrate was given via the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: On admission, the frequency rate of erosion/ulceration (assessed with the endoscope) was 13.5%. After 4 days, this rate had increased to 18% in sucralfate-treated patients and 36% in ranitidine-treated patients (NS). Mean gastric pH was more alkaline in the ranitidine-treated patients (5.50) compared with the sucralfate-treated patients (4.26) (p less than .01). This pH permitted a higher occurrence rate of gastric colonization by aerobic Gram-negative bacilli in ranitidine-treated patients (64.3%) compared with sucralfate-treated patients (23.8%) (p less than .01). Retrograde bacterial colonization from the stomach to oropharynx and trachea occurred more frequently in ranitidine-treated patients compared with sucralfate-treated patients. Ultimately, the occurrence rate of pneumonia was greater in the ranitidine-treated (35.7%) than in the sucralfate-treated patients (10.3%) (p less than .05). CONCLUSION: Based on our findings, we recommend the adoption of sucralfate for routine prophylaxis against stress ulceration.     

A postsynaptic inhibitory histamine H2-receptor in the mouse isolated vas deferens

The effect of histamine on adrenergic neurotransmission in the mouse isolated vas deferens preparation was investigated. Concentrations of histamine ranging from 0.2 to 650 M depressed, in a dose-related manner, not only the contractile response elicited by field stimulation but also the response caused by the addition of exogenous noradrenaline and acetylcholine. However, the release of [³H]-NA evoked by field stimulation or by high K⁺ remained unchanged in the presence of these concentrations of histamine. The inhibitory effect of histamine on the contractile responses caused by various stimuli was reduced or completely antagonized by cimetidine, a histamine H₂-receptor antagonist but not by mepyramine, a conventional antihistamine. The inhibitory effect of histamine was found to be inversely proportional to both the Ca²⁺ concentration in the bathing medium and to the frequency of field stimulation. Further, the inhibitory effect of histamine was markedly reduced when Mg²⁺ was omitted from the bathing medium. It is concluded that the mouse vas deferens preparation contains a post-junctional inhibitory H₂-receptor. The stimulation of H₂-receptors by histamine inhibits the contractile response of the vas deferens, possibly by decreasing the availability of Ca²⁺ required for contraction by depressing the influx of Ca²⁺.     

His bundle electrogram in patients with acute myocardial infarction complicated by atrioventricular or intraventricular conduction disturbances.

Seventy-two patients with acute myocardial infarction complicated by atrioventricular or bundle-branch block or a combination of both had His bundle electrogram studies performed during their stay in the coronary care unit. In 19 of the 72 patients a repeat His bundle electrogram was performed before discharge from hospital. These studies demonstrated that 30 of the 32 patients with atrioventricular block and narrow QRS complexes had a block above the origin othe His spike (proximal block). Eleven patients in this group had repeat His bundle electrograms performed before discharge and in 3 patients there was evidence of residual atrioventricular nodal dysfunction. Both the hospital and follow-up mortality in this group was low and there was no evidence to suggest that permanent pacing would benefit these patients. Of the 18 patients with bundle-branch block and a normal PR interval, 9 had prolongation of the HV interval, but there was no difference in mortality in patients with normal or prolonged HV intervals. Twenty-two patients with bundle-branch block also developed atrioventricular block. In 5 of these patients the site of the AV block was proximal and in 14 it was distal, while 3 patients had both proximal and distal block. The hospital mortality in those patients who progressed to second- or third-degree atrioventricular block was considerably higher than in those patients who remained in first-degree atrioventricular block.     

His bundle electrogram in patients with acute myocardial infarction complicated by atrioventricular or intraventricular conduction disturbances.

Seventy-two patients with acute myocardial infarction complicated by atrioventricular or bundle-branch block or a combination of both had His bundle electrogram studies performed during their stay in the coronary care unit. In 19 of the 72 patients a repeat His bundle electrogram was performed before discharge from hospital. These studies demonstrated that 30 of the 32 patients with atrioventricular block and narrow QRS complexes had a block above the origin othe His spike (proximal block). Eleven patients in this group had repeat His bundle electrograms performed before discharge and in 3 patients there was evidence of residual atrioventricular nodal dysfunction. Both the hospital and follow-up mortality in this group was low and there was no evidence to suggest that permanent pacing would benefit these patients. Of the 18 patients with bundle-branch block and a normal PR interval, 9 had prolongation of the HV interval, but there was no difference in mortality in patients with normal or prolonged HV intervals. Twenty-two patients with bundle-branch block also developed atrioventricular block. In 5 of these patients the site of the AV block was proximal and in 14 it was distal, while 3 patients had both proximal and distal block. The hospital mortality in those patients who progressed to second- or third-degree atrioventricular block was considerably higher than in those patients who remained in first-degree atrioventricular block.     

Effect of coexistent coarctation of pulmonary trunk in natural history of complete absence of pulmonary valve with ventricular septal defect.

A case of complete absence of the pulmonary valve in association with a ventricular septal defect and a pulmonary artery coarctation is described. Despite these defects the patient had minimal symptoms, probably because the pulmonary artery coarctation acted as a natural banding and limited the pulmonary regurgitant flow and reduced the left-to-right shunt across the ventricular septal defect. The patient was operated on at the age of 40 and the ventricular septal defect was closed but the pulmonary artery coarctation was left alone. In view of the long-term survival in this case, it is suggested that pulmonary artery banding would reduce the symptoms and increase the life expectancy of patients with congenital absence of the pulmonary valve and a ventricular septal defect.     

Metastatic germ cell tumor to the heart presenting with syncope.

Malignant nonseminomatous germ cell tumors (NSGCT) rarely metastasize to the heart. The first such case presenting with syncope is described. Eight previously described cases of NSGCT with intracaval metastasis to the heart are reviewed and the literature to date is discussed. Transesophageal echocardiography is the diagnostic study of choice and treatment consists primarily of platinum-based chemotherapy followed by surgical resection of residual deposits.     

Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms.

We investigated the basis for a novel form of the slow-channel congenital myasthenic syndrome presenting in infancy in a single individual as progressive weakness and impaired neuromuscular transmission without overt degeneration of the motor endplate. Prolonged low-amplitude synaptic currents in biopsied anconeus muscle at 9 years of age suggested a kinetic disorder of the muscle acetylcholine receptor. Ultrastructural studies at 16 months, at 9 years, and at 15 years of age showed none of the typical degenerative changes of the endplate associated with the slow-channel congenital myasthenic syndrome, and acetylcholine receptor numbers were not significantly reduced. We identified a novel C-to-T substitution in exon 8 of the delta-subunit that results in a serine to phenylalanine mutation in the region encoding the second transmembrane domain that lines the ion channel. Using Xenopus oocyte in vitro expression studies we confirmed that the deltaS268F mutation, as with other slow-channel congenital myasthenic syndrome mutations, causes delayed closure of acetylcholine receptor ion channels. In addition, unlike other mutations in slow-channel congenital myasthenic syndrome, this mutation also causes delayed opening of the channel, a finding that readily explains the marked congenital weakness in the absence of endplate degeneration. Finally, we used serial morphometric analysis of electron micrographs to explore the basis for the progressive weakness and decline of amplitude of endplate currents over a period of 14 years. We demonstrated a progressive widening and accumulation of debris in the synaptic cleft, resulting in loss of efficacy of released neurotransmitter and reduced safety factor. These studies demonstrate the role of previously unrecognized mechanisms of impairment of synaptic transmission caused by a novel mutation and show the importance of serial in vitro studies to elucidate novel disease mechanisms.     

Management of neutropenic colitis.

Neutropenic colitis is recognized as a rare complication of chemotherapy in haematological malignancies. By contrast, the complication is less well known in relationship to chemotherapy for solid malignancies. There are very few examples reported and this paper adds three further cases and reviews the literature. We emphasize that although some cases of neutropenic colitis may be managed medically, full thickness involvement of the bowel wall may lead to perforation and require surgery. The pathogenesis of this progression is discussed and it is concluded that clinical awareness is important in the diagnosis. The signs of peritonitis or septicaemia are indications for excisional surgery with the formation of a temporary ileostomy.