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This study examined global resting‐state functional connectivity of neural oscillations in individuals with chronic tinnitus and normal and impaired hearing. We tested the hypothesis that distinct neural oscillatory networks are engaged in tinnitus with and without hearing loss. In both tinnitus groups, with and without hearing loss, we identified multiple frequency band‐dependent regions of increased and decreased global functional connectivity. We also found that the auditory domain of tinnitus severity, assayed by the Tinnitus Functional Index, was associated with global functional connectivity in both auditory and nonauditory regions. These findings provide candidate biomarkers to target and monitor treatments for tinnitus with and without hearing loss.

In patients with gliomas, changes in hemispheric specialization for language determined by magnetoencephalography (MEG) were analyzed to elucidate the impact of treatment and tumor recurrence on language networks. Demonstration of reorganization of language networks in these patients has significant implications on the prevention of postoperative functional loss and recovery. Whole-brain activity during an auditory verb generation task was estimated from MEG recordings in a group of 73 patients with recurrent gliomas. Hemisphere of language dominance was estimated using the language laterality index (LI), a measure derived from the task. The initial scan was performed prior to resection; patients subsequently underwent surgery and adjuvant treatment. A second scan was performed upon recurrence prior to repeat resection. The relationship between the shift in LI between scans and demographics, anatomic location, pathology, and adjuvant treatment was analyzed. Laterality shifts were observed between scans; the median percent change was 29.1% across all patients. Laterality shift magnitude and relative direction were associated with the initial position of language dominance; patients with increased lateralization experienced greater shifts than those presenting more bilateral representation. A change in LI from left or right to bilateral (or vice versa) occurred in 23.3% of patients; complete switch occurred in 5.5% of patients. Patients with tumors within the language-dominant hemisphere experienced significantly greater shifts than those with contralateral tumors. The majority of patients with glioma experience shifts in language network organization over time which correlate with the relative position of language lateralization and tumor location.

Objective: The goal of the current study was to examine the dynamics of language lateralization using magnetoencephalographic (MEG) imaging, to determine the sensitivity and specificity of MEG imaging, and to determine whether MEG imaging can become a viable alternative to the intracarotid amobarbital procedure (IAP), the current gold standard for preoperative language lateralization in neurosurgical candidates. Methods: MEG was recorded during an auditory verb generation task and imaging analysis of oscillatory activity was initially performed in 21 subjects with epilepsy, brain tumor, or arteriovenous malformation who had undergone IAP and MEG. Time windows and brain regions of interest that best discriminated between IAP-determined left or right dominance for language were identified. Parameters derived in the retrospective analysis were applied to a prospective cohort of 14 patients and healthy controls. Results: Power decreases in the beta frequency band were consistently observed following auditory stimulation in inferior frontal, superior temporal, and parietal cortices; similar power decreases were also seen in inferior frontal cortex prior to and during overt verb generation. Language lateralization was clearly observed to be a dynamic process that is bilateral for several hundred milliseconds during periods of auditory perception and overt speech production. Correlation with the IAP was seen in 13 of 14 (93%) prospective patients, with the test demonstrating a sensitivity of 100% and specificity of 92%. Interpretation: Our results demonstrate excellent correlation between MEG imaging findings and the IAP for language lateralization, and provide new insights into the spatiotemporal dynamics of cortical speech processing. ANN NEUROL 2012

Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear.In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from 13 patients and matched controls.Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength.There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD.Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning-based sensorimotor interventions.

ObjectiveAsymmetric large-amplitude slow activity is sometimes observed on interictal electroencephalography (EEG) in epilepsy. However, few studies have examined slowing during magnetoencephalography (MEG) recordings, which are performed primarily to localize interictal spikes. Also, no prior investigations have compared the sensitivity of MEG to scalp EEG in detecting slow rhythms.MethodsWe performed a retrospective cohort study of focal epilepsy patients who received MEG followed by surgical resection at our institution. We examined MEG, simultaneous EEG, and long-term EEG recordings for prominent asymmetric slow activity (delta-range, 1-4 Hz), and evaluated post-operative seizure outcomes.ResultsWe studied 132 patients with ≥ 1 year post-operative follow-up (mean, 3.6 years). Mean age was 27 (range, 3-68) years, and 55% of patients were male. Asymmetric large-amplitude slow wave activity was observed on interictal MEG in 21 of 132 (16%) patients. Interictal slowing lateralized to the hemisphere of resection in all but one (95%) patient. Among the 21 patients with interictal MEG slowing, 11 (52%) individuals had similarly lateralized EEG slowing, 7 patients had no EEG slowing, and 3 had bilateral symmetric EEG slowing. Meanwhile, none of the 111 patients without lateralized MEG slowing had asymmetric EEG slowing, suggesting significantly higher sensitivity of MEG versus EEG in detecting asymmetric slowing (χ(2)=63.4, p

© Wiley Periodicals, Inc. © 2015 International League Against Epilepsy. Objective The efficacy of epilepsy surgery depends critically upon successful localization of the epileptogenic zone. Magnetoencephalography (MEG) enables noninvasive detection of interictal spike activity in epilepsy, which can then be localized in three dimensions using magnetic source imaging (MSI) techniques. However, the clinical value of MEG in the presurgical epilepsy evaluation is not fully understood, as studies to date are limited by either a lack of long-term seizure outcomes or small sample size. Methods We performed a retrospective cohort study of patients with focal epilepsy who received MEG for interictal spike mapping followed by surgical resection at our institution. Results We studied 132 surgical patients, with mean postoperative follow-up of 3.6 years (minimum 1 year). Dipole source modeling was successful in 103 patients (78%), whereas no interictal spikes were seen in others. Among patients with successful dipole modeling, MEG findings were concordant with and specific to the following: (1) the region of resection in 66% of patients, (2) invasive electrocorticography (ECoG) findings in 67% of individuals, and (3) the magnetic resonance imaging (MRI) abnormality in 74% of cases. MEG showed discordant lateralization in ~5% of cases. After surgery, 70% of all patients achieved seizure freedom (Engel class I outcome). Whereas 85% of patients with concordant and specific MEG findings became seizure-free, this outcome was achieved by only 37% of individuals with MEG findings that were nonspecific to or discordant with the region of resection (χ2 = 26.4, p < 0.001). MEG reliability was comparable in patients with or without localized scalp electroencephalography (EEG), and overall, localizing MEG findings predicted seizure freedom with an odds ratio of 5.11 (95% confidence interval [CI] 2.23-11.8). Significance MEG is a valuable tool for noninvasive interictal spike mapping in epilepsy surgery, including patients with nonlocalized findings receiving long-term EEG monitoring, and localization of the epileptogenic zone using MEG is associated with improved seizure outcomes.

© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning.

ObjectiveLesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation (nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS.MethodsSubjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared.ResultsnTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects.ConclusionMaps of language function generated with nTMS correlate well with those generated by DCS. Negative nTMS mapping also correlates with negative DCS mapping. In our study, MEGI lacks the same level of correlation with intraoperative mapping; nevertheless it provides useful adjunct information in some cases. nTMS may offer a lesion-based method for noninvasively interrogating language pathways and be valuable in managing patients with peri-eloquent lesions.

Traumatic brain injury (TBI) is one of the leading causes of morbidity worldwide. One mechanism by which blunt head trauma may disrupt normal cognition and behavior is through alteration of functional connectivity between brain regions. In this pilot study, the authors applied a rapid automated resting state magnetoencephalography (MEG) imaging technique suitable for routine clinical use to test the hypothesis that there is decreased functional connectivity in patients with TBI compared with matched controls, even in cases of mild TBI. Furthermore, they posit that these abnormal reductions in MEG functional connectivity can be detected even in TBI patients without specific evidence of traumatic lesions on 3-T MR images. Finally, they hypothesize that the reductions of functional connectivity can improve over time across serial MEG scans during recovery from TBI.Magnetoencephalography maps of functional connectivity in the alpha (8- to 12-Hz) band from 21 patients who sustained a TBI were compared with those from 18 age- and sex-matched controls. Regions of altered functional connectivity in each patient were detected in automated fashion through atlas-based registration to the control database. The extent of reduced functional connectivity in the patient group was tested for correlations with clinical characteristics of the injury as well as with findings on 3-T MRI. Finally, the authors compared initial connectivity maps with 2-year follow-up functional connectivity in a subgroup of 5 patients with TBI.Fourteen male and 7 female patients (17-53 years old, median 29 years) were enrolled. By Glasgow Coma Scale (GCS) criteria, 11 patients had mild, 1 had moderate, and 3 had severe TBI, and 6 had no GCS score recorded. On 3-T MRI, 16 patients had abnormal findings attributable to the trauma and 5 had findings in the normal range. As a group, the patients with TBI had significantly lower functional connectivity than controls (p0.01). Three of the 5 patients with normal findings on 3-T MRI showed regions of abnormally reduced MEG functional connectivity. No significant correlations were seen between extent of functional disconnection and injury severity or posttraumatic symptoms (p0.05). In the subgroup undergoing 2-year follow-up, the second MEG scan demonstrated a significantly lower percentage of voxels with decreased connectivity (p0.05) than the initial MEG scan.A rapid automated resting-state MEG imaging technique demonstrates abnormally decreased functional connectivity that may persist for years after TBI, including cases classified as "mild" by GCS criteria. Disrupted MEG connectivity can be detected even in some patients with normal findings on 3-T MRI. Analysis of follow-up MEG scans in a subgroup of patients shows that, over time, the abnormally reduced connectivity can improve, suggesting neuroplasticity during the recovery from TBI. Resting state MEG deserves further investigation as a prognostic and predictive biomarker for TBI.

BackgroundThe removal of brain tumors in perieloquent or eloquent cortex risks causing new neurological deficits in patients. The assessment of the functionality of perilesional tissue is essential to avoid postoperative neurological morbidity.ObjectiveTo evaluate preoperative magnetoencephalography-based functional connectivity as a predictor of short- and medium-term neurological outcome after removal of gliomas in perieloquent and eloquent areas.MethodsResting-state whole-brain magnetoencephalography recordings were obtained from 79 consecutive subjects with focal brain gliomas near or within motor, sensory, or language areas. Neural activity was estimated using adaptive spatial filtering. The mean imaginary coherence between voxels in and around brain tumors was compared with contralesional voxels and used as an index of their functional connectivity with the rest of the brain. The connectivity values of the tissue resected during surgery were correlated with the early (1 week postoperatively) and medium-term (6 months postoperatively) neurological morbidity.ResultsPatients undergoing resection of tumors with decreased functional connectivity had a 29% rate of a new neurological deficit 1 week after surgery and a 0% rate at 6-month follow-up. Patients undergoing resection of tumors with increased functional connectivity had a 60% rate of a new deficit at 1 week and a 25% rate at 6 months.ConclusionMagnetoencephalography connectivity analysis gives a valuable preoperative evaluation of the functionality of the tissue surrounding tumors in perieloquent and eloquent areas. These data may be used to optimize preoperative patient counseling and surgical strategy.

Object Direct cortical stimulation (DCS) is the gold-standard technique for motor mapping during craniotomy. However, preoperative noninvasive motor mapping is becoming increasingly accurate. Two such noninvasive modalities are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) imaging. While MEG imaging has already been extensively validated as an accurate modality of noninvasive motor mapping, TMS is less well studied. In this study, the authors compared the accuracy of TMS to both DCS and MEG imaging. Methods Patients with tumors in proximity to primary motor cortex underwent preoperative TMS and MEG imaging for motor mapping. The patients subsequently underwent motor mapping via intraoperative DCS. The loci of maximal response were recorded from each modality and compared. Motor strength was assessed at 3 months postoperatively. Results Transcranial magnetic stimulation and MEG imaging were performed on 24 patients. Intraoperative DCS yielded 8 positive motor sites in 5 patients. The median distance ± SEM between TMS and DCS motor sites was 2.13 ± 0.29 mm, and between TMS and MEG imaging motor sites was 4.71 ± 1.08 mm. In no patients did DCS motor mapping reveal a motor site that was unrecognized by TMS. Three of 24 patients developed new, early neurological deficit in the form of upper-extremity paresis. At the 3-month follow-up evaluation, 2 of these patients were significantly improved, experiencing difficulty only with fine motor tasks; the remaining patient had improvement to 4/5 strength. There were no deaths over the course of the study. Conclusions Maps of the motor system generated with TMS correlate well with those generated by both MEG imaging and DCS. Negative TMS mapping also correlates with negative DCS mapping. Navigated TMS is an accurate modality for noninvasively generating preoperative motor maps.

The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–55 Hz) bands. Global connectivity (GC) was defined as synchronization between a region and the rest of the brain. In AgCC individuals, alpha band GC was significantly reduced in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto-occipital cortices (PO). No significant differences in GC were seen in either the beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional reduction in functional connectivity is explained primarily by a specific reduction in interhemispheric connectivity. However, our data suggest that reduced connectivity in these regions is driven by faulty coupling in both inter- and intrahemispheric connectivity. We also assessed whether the degree of connectivity correlated with behavioral performance, focusing on cognitive measures known to be impaired in AgCC individuals. Neuropsychological measures of verbal processing speed were significantly correlated with resting-state functional connectivity of the left medial and superior temporal lobe in AgCC participants. Connectivity of DLPFC correlated strongly with performance on the Tower of London in the AgCC cohort. These findings indicate that the abnormal callosal development produces salient but selective (alpha band only) resting-state functional connectivity disruptions that correlate with cognitive impairment. Understanding the relationship between impoverished functional connectivity and cognition is a key step in identifying the neural mechanisms of language and executive dysfunction in common neurodevelopmental and psychiatric disorders where disruptions of callosal development are consistently identified.

OBJECTIVE Resection of brain tumors adjacent to eloquent areas represents a challenge in neurosurgery. If maximal resection is desired without inducing postoperative neurological deficits a detailed knowledge of the functional topography in and around the tumor is crucial. The aim of the present work is to evaluate the value of preoperative magnetoencephalography (MEG) imaging of functional connectivity to predict the results of intraoperative electrical stimulation (IES) mapping the clinical gold standard for neurosurgical localization of functional areas. METHODS Resting state whole cortex MEG recordings were obtained from 57 consecutive subjects with focal brain tumors near or within motor sensory or language areas. Neural activity was estimated using adaptive spatial filtering algorithms and the mean imaginary coherence between the rest of the brain and voxels in and around brain tumors were compared to the mean imaginary coherence between the rest of the brain and contralesional voxels as an index of functional connectivity. IES mapping was performed in all subjects. The cortical connectivity pattern near the tumor was compared to the IES results. RESULTS Maps with decreased resting state functional connectivity in the entire tumor area had a negative predictive value of 100 for absence of eloquent cortex during IES. Maps showing increased resting state functional connectivity within the tumor area had a positive predictive value of 64 for finding language motor or sensory cortical sites during IES mapping. INTERPRETATION Preoperative resting state MEG connectivity analysis is a useful noninvasive tool to evaluate the functionality of the tissue surrounding tumors within eloquent areas and could potentially contribute to surgical planning and patient counseling.

Object The goal of this study was to examine the sensitivity and specificity in preoperative localization of hand motor cortex by imaging regional event-related desynchronization (ERD) of brainwaves in the β frequency band (15–25 Hz) involved in self-paced movement. Methods Using magnetoencephalography (MEG), the authors measured ERD that occurred before self-paced unilateral index finger flexion in 66 patients with brain tumors, epilepsy, and arteriovenous malformations. Results The authors applied an adaptive spatial filtering algorithm to MEG data and found that peaks of the tomographic distribution of β-band ERD sources reliably localized hand motor cortex compared with electrical cortical stimulation. They also observed high specificity in estimating contralateral hand motor cortical representations relative to somatosensory cortex. Neither presence nor location of tumor changed the qualitative or quantitative location of motor cortex relative to somatosensory cortex. Conclusions An imaging protocol using ERD obtained by adaptive spatial filtering of MEG data can be used for extremely reliable preoperative localization of hand motor cortex.

OBJECTIVE: The spatial distribution of functional connectivity between brain areas and the disturbance introduced by focal brain lesions are poorly understood. Based on the rationale that damaged brain tissue is disconnected from the physiological interactions among healthy areas, this study aimed to map the functionality of brain areas according to their connectivity with other areas. METHODS: Magnetoencephalography recordings of spontaneous cortical activity during resting state were obtained from 15 consecutive patients with focal brain lesions and from 14 healthy control subjects. Neural activity in the brain was estimated using an adaptive spatial filtering technique. The mean imaginary coherence between brain voxels was then calculated as an index of functional connectivity. RESULTS: Imaginary coherence was greatest in the alpha frequency range corresponding to the human cortical idling rhythm. In healthy subjects, functionally critical brain areas such as the somatosensory and language cortices had the highest alpha coherence. When compared with healthy control subjects, all lesion patients had diffuse or scattered brain areas with decreased alpha coherence. Patients with lesion-induced neurological deficits displayed decreased connectivity estimates in the corresponding brain area compared with intact contralateral regions. In tumor patients without preoperative neurological deficits, brain areas showing decreased coherence could be surgically resected without the occurrence of postoperative deficits. INTERPRETATION: Resting state coherence measured with magnetoencephalography is capable of mapping the functional connectivity of the brain, and can therefore offer valuable information for use in planning resective surgeries in patients with brain lesions, as well as investigations into structural-functional relationships in healthy subjects.

We analyzed oral behavior from food intake until terminal swallow for mastication and swallowing under a freely eating condition with a natural food. Measurements, including movement of the mandible and tongue, the size of the gape, different sequences involved in the oral aspect of the swallowing action, and bolus size and movement were carried out in five "freely eating subjects" using videofluorography. During food intake, the tongue moved forwards and backwards to introduce food into the mouth, to compress the food against the hard palate, and to transport food to the occlusal surface of the molar teeth. Most of the food was swallowed in the first swallow, and any residual food was aggregated by the tongue into a bolus and then swallowed in the last swallow. These findings suggest that 1) tongue manipulation plays an important role in recognizing and evaluating the volume of bite taken, 2) the intra-oral compression of food has a role in the recognition of food texture, 3) stage I transport is closely bound to the texture recognition process, 4) humans need at least two swallows, even with one bite of food, when ingesting food freely, and 5) the duration time of the oral stage of swallowing may depend on the bolus volume and be longer for smaller volumes unlike those measured under the command swallow.

We report a 34-year-old man with evident family history of paralysis and myotonia. He has noticed episodic morning paralysis alternating with muscle myotonia since the age of 10 years. When an episode of paralysis occurred, his serum potassium level decreased to 2.3 mEq/L and tended to increase to about 4.0 mEq/L when he complained myotonia. This case is obviously different from several already-known diseases, as it is perhaps the first case thermo-sensitive disorder of muscle activity in that the myotonia is induced by warm environment but paralysis occurs in the setting of cold ambient temperature and hypokalemia. Therefore, we are underway to perform molecular genetic analysis of ion channels since paramyotonia/hyperkalemic periodic paralysis is known to be associated with Na(+)-channel missense mutations, while hypokalemic periodic paralysis is with Ca(++)-channel. Addendum: After submission of the manuscript, we identified a novel mutation in Na+ channel alpha subunit. The detail of molecular aspect will be reported elsewhere.

A 42-year-old man with pulmonary disease caused by Mcobacterium xenopi is described. He had a history of alcohol use of over 20 years. He was admitted to another hospital for evaluation of an abnormal chest shadow. A chest X-ray showed a cavitary shadow with infiltration in the right upper lung field. Acid-fast organisms were recognized in sputum and M. xenopi was identified by DNA-DNA hybridization. Although he had been treated with isoniazid, rifampicin, and ethanbutol for 5 years, sputum remained positive on culture and chest X-ray findings did not improve. He was later admitted to our hospital for surgery, and right upper lobectomy was performed. He has remained well for 18 months since the operation. In Japan, cases of the pulmonary infection with M. xenopi are rare. Surgical resection is required when chemotherapy is unsuccessful.

A double blinded clinical trial was conducted in which the efficacy and safety of pulse methylprednisolone (400 mg/day) was compared with oral prednisolone (50 mg/day), a control drug for a period of 3 months. One-hundred and two (102) patients were enrolled in the study, of which 91 patients were determined as eligible for analysis of efficacy. Patients on pulse methylprednisolone had more favorable response to therapy with regard to laboratory value changes from baseline such as CH50 and anti-DNA antibody titers. In terms of anti-DNA antibodies, a significant difference was detected at one week after treatment. With regard to time course changes in laboratory values, CH50 at one and two weeks after treatment showed a significantly higher elevation in the pulse methylprednisolone group than in the control group. There was no significant difference noted in incidence of adverse reactions between both treatment groups. No serious adverse reaction was encountered in the pulse methylprednisolone group. The physician's assessment of final global improvement significantly favored the pulse methylprednisolone-treated group. The above results suggest that the pulse therapy with methylprednisolone leads to more rapid onset of drug effect than the conventional oral prednisolone in the treatment of lupus nephritis.

Recently, in Japan, auranofin (6 mg/day) has been demonstrated to be a useful treatment for patients with moderate to severe asthma in a double-blind clinical trial. Therefore, to investigate the mechanism of auranofin on bronchial asthma, we examined pulmonary functions and bronchial responsiveness to inhaled methacholine in well-controlled asthmatics after 12 wks of treatment with auranofin, in a double-blind, placebo-controlled fashion. Twenty-five adult patients with asthma received orally 3 mg of auranofin or inactive placebo twice daily for 12 weeks. Bronchial responsiveness, pulmonary function tests and concentrations of gold in the blood were measured before and 6 and 12 wks after the therapy. Bronchial responsiveness (PD35-Grs) was significantly decreased after 12 wks of treatment with auranofin, compared with that 12 wks after treatment with inactive placebo. We suggest that inhibition of bronchial hyperresponsiveness by auranofin is one of the mechanisms by which auranofin is effective against bronchial asthma.

Described is a case of infarctions in fibroadenomas of the breast that occurred during pregnancy, with a review of the pertinent literature and a brief discussion on the difficulty of achieving a cytologic diagnosis. A 24-year-old female presented tender lumps that increased in size in her breast during the 7 months of her pregnancy. A subsequent cytologic examination revealed many typical cells with clustered nude nuclei. The cytologic diagnosis indicated a Group V, poorly differentiated adenocarcinoma. Following delivery of her infant, the lumps were excised. Microscopic examination revealed extensive infarcted fibroadenomas with lactational changes.

Cefotaxime (CTX) was used for 129 cases in respiratory tract and other infections; 57 cases of pneumonia, 20 cases of bronchopneumonia, 20 cases of acute bronchitis, 14 cases of chronic bronchitis, 7 cases of acute exacerbation of bronchiectasia or pulmonary emphysema, 4 cases of suppurative diseases of the lung, 1 case of pyothorax, 1 case of retropharyngeal abscess, 3 cases of pleurisy and 1 case of urinary tract infection. (A case was excepted on clinical evaluation.) CTX was administered by intravenous injection or drip infusion at a daily dose ranging from 0.5 to 8 g, for a term of 2 to 61 days. The total dose patients received ranged from 3 to 226 g. The results obtained were as follows. Clinical effects; excellent in 45 cases, good in 63 cases, fair in 9 cases, poor in 7 cases and unevaluable in 4 cases. The efficacy rate was 87.1% (108/124). Bacteriological effects; eliminated in 30 cases, decreased in 8 cases, unchanged in 2 cases and replaced in 1 case. The elimination rate was 75.6% (31/41). Side effects and abnormal laboratory findings; general itching, fatigue in lower extremities and albuminuria in 1 case each, and anemia in 2 cases. Increased number of eosinophiles and elevated GOT in 1 case each, elevated GOT and GPT in 3 cases and elevated GOT, GPT and A1-P in 2 cases. These symptoms or abnormal laboratory findings disappeared after the discontinuation or termination of CTX therapy. In view of the above, CTX may be considered to be a clinically useful antibiotic against respiratory tract infections.

This is a clinical and pathological study of malignant germ tumors in the lung or mediastinum. Germ cell tumors may be considered to originate from primitive germ cells with totipotency. One of 3 cases showed clinical and pathological findings suggesting that a part of the tumor differentiated into many kinds of tissue, such as growing and metastasizing. Initial diagnosis was performed radiographically and pathologically with difficulty. But finally, the first patient was diagnosed as malignant teratoma, the second as yolk sac tumor and the third as choriocarcinoma, in consideration of the tumor markers and clinical process.

A case of an adenomatoid tumor of the epididymis is reported. The patient, a 41-year-old male, had a total right orchiectomy of his testicular mass. The tumor was located in the inferior portion of the right epididymis and was a well-circumscribed solitary mass, measuring 3 X 3 X 3 cm. Microscopically, the tumor contained plump acidophilic cells arrange in cords and trabecula with fibrous connective tissue. Immunohistochemical studies for keratin and vimentin in the tumor cells were positive. Electron microscopical findings of the tumor were similar to those of a benign mesothelioma. These findings suggest that adenomatoid tumors are of mesothelial origin.

To elucidate the pathophysiology of dilated cardiomyopathy (DCM), the relationship of two-dimensional echocardiographic wall motion abnormalities (asynergy) to histopathological findings was evaluated in autopsied patients including seven with DCM, five with old myocardial infarction (OMI) and three with the normal heart. The DCM cases were classified morphologically in two groups, namely four of type I and II and three of type III, according to Shozawa's classification. Three short-axis views of the left ventricle were divided into 19 segments; the wall motion was assessed visually and classified as normal motion, hypokinesis, akinesis and dyskinesis. The postmortem specimens were immersed in 10% formalin; transverse sections and wall divisions were prepared corresponding to the two-dimensional echocardiographic views, and the area of each segment was determined by a computer planimetry excluding the papillary muscles and trabeculae. Fibrosis (%) was measured histologically by the point counting method with light microscopy. The results were as follows: In DCM, fibrosis (%) increased with increasing severity of asynergy: 17.1% fibrosis in normal motion; 28.7% in hypokinesis; 40.7% in akinesis and dyskinesis. In OMI, fibrosis (%) also increased with increasing severity of asynergy. On comparison of DCM with OMI, no difference was established relating to fibrosis (%) in the asynergic segments; moreover, in both groups, asynergy was detected more frequently in the segments in which fibrosis (%) exceeded 21%. On comparison of type I+II DCM with type III DCM, fibrosis (%) of type III was significantly less than that of type I+II in the same degree of asynergic segments. Moreover, fibrosis (%) of type I+II tended to be greater in the outer layer than in the inner layer, while fibrosis (%) of type III was evenly distributed throughout the myocardium, or greater in the inner layer than in the outer layer. In type I+II, wall thinning was marked with increasing severity of asynergy; in contrast, these correlations were not observed in type III. In type I+II, a higher fibrotic rate was observed in the left ventricular free wall and an abnormal Q wave appeared frequently on ECG. This tendency was not found in type III. These findings indicate that fibrosis is one of the most important factors in decreasing cardiac muscular contractility in DCM, and suggest that there is a different pathogenesis between type I+II and type III fibrosis.

Eight cases of primary malignant lymphoma of the brain were examined clinically and immunohistopathologically. According to the LSG classification the patients were subclassified into 5 with diffuse large cell type, 2 with diffuse medium-sized cell type and one with diffuse mixed cell type. Immunohistological stainings demonstrated that all of them were of B lymphocyte origin. Two cases had multiple lesions which were seen in the periventricular area. Tumor response for the treatment consisted of surgery followed by radiation therapy was excellent except for one. Only 2 patients were alive and well at 24 months and 27 months.

We have measured the rise in plasma cyclic AMP induced by glucagon and adrenaline in manic patients on lithium therapy. Glucagon-induced increases in the concentration of plasma cyclic AMP were larger, but the adrenaline-induced increases were smaller, in lithium-treated manic patients than in normal controls. In 3 manic patients, the enhanced response to glucagon was normalized 3 weeks after the cessation of lithium treatment. Though the underlying mechanism is unknown, the unusual plasma cyclic AMP responses may reflect altered receptor sensitivity which would be closely related to the curative effect of lithium on symptoms of mania.