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Objective: This study undertook neuropharmacological research on the clinical course of controlled medication discontinuation to guide practitioners who are considering stopping medications for youths with attention-deficit hyperactivity disorder (ADHD)., Methods: This study analyzed the data for 14 ADHD children (12 male and 2 female) in two datasets: The children prescribed methylphenidate (MPH) were at an initial mean age of 7.5 years (SD = 1.70, range: 6-11) with a mean ADHD-Rating Score (ADHD-RS) of 26.6 (SD = 8.64, range 15-40). The children who discontinued MPH based on clinical judgment were at a mean age of 12.21 years (SD = 2.12, range: 8-15) with a mean ADHD-RS of 15.9 (SD = 6.86, range 5-27). The go/no-go task was used to assess response inhibition, while functional near-infrared spectroscopy (fNIRS) was used to measure cerebral hemodynamics. Oxygenated hemoglobin (Oxy-Hb) values from fNIRS data were analyzed for each subject, focusing on past and current measurements. Baseline was set at 10 s pre-task, with interval means from 4 to 24 s analyzed. One-sample t-tests were used to evaluate brain activity magnitude., Results: The results of the study demonstrate that the children who had discontinued the medication exhibited activation in specific brain regions including the frontopolar cortex and the right ventrolateral prefrontal cortex. Activation (t = 2.363, p = 0.034, Cohen's d = 0.632) was found especially in the right dorsolateral prefrontal cortex during the performance of the go/no-go task. These activated areas were consistent with those observed in a previous study comparing brain activity during a go/no-go task between children with ADHD and healthy children., Conclusion: The present study showed differences in cerebral hemodynamics before and after discontinuation of MPH in ADHD children whose ADHD symptoms did not recur after MPH was discontinued. In the near future, further investigations that include control groups will be conducted to demonstrate the effects of MPH prior to discontinuation based on the changes in cerebral blood flow in the right prefrontal cortex, which is involved in behavioral inhibition, as observed in this study. This and future research will facilitate the development of criteria for discontinuing treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced or appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The pathogenesis of acute encephalopathy (AE) remains unclear, and a biomarker has not been identified., Methods: Levels of 49 cytokines and chemokines, including osteopontin (OPN), were measured in serum and cerebrospinal fluid (CSF) of children with AE (n = 17) or febrile convulsion (FC; n = 8; control group). The AE group included acute necrotizing encephalopathy (n = 1), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 3), clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS; n = 4), and unclassified acute encephalopathy (UCAE; n = 9) that does not meet the criteria of syndrome classification. Five individuals with AE had neurological sequelae or death (poor prognosis), whereas 12 were alive without neurological sequelae (good prognosis)., Results: The CSF:serum ratios of OPN, CC chemokine ligand (CCL)4, and interleukin (IL)-10 were significantly higher in AE than in FC. The CSF levels of macrophage inhibitory factor (MIF) and leukemia inhibitory factor (LIF) were significantly higher in the poor-prognosis group than in the good-prognosis group. The CSF:serum ratios of OPN were significantly higher in AESD and in MERS than in FC. The CSF:serum ratios of MIF and OPN were higher in MERS than in UCAE or FC., Conclusion: Our results suggest that microglia-related cytokines and chemokines such as OPN, MIF, and LIF could be novel biomarkers of AE, in addition to the previously reported IL-10 and CCL4, and that MIF and LIF may be markers of poor prognosis., (Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: The effect of rituximab on acute disseminated encephalomyelitis (ADEM) followed by recurrent optic neuritis (ON) is not yet known., Patient: We are reporting the case of a 4-year-old Japanese girl who was diagnosed with anti-myelin oligodendrocyte glycoprotein (MOG) antibody positive ADEM followed by recurrent ON. She developed altered mental status, left facial paralysis, left paresis, and experienced three episodes of ON. She was treated with rituximab and azathioprine (AZA) as prevention for recurrent ON. She relapsed under treatment with AZA when CD19 cells reappeared 6 months after the first rituximab infusion. However, she has not relapsed since her CD19 count was reduced and kept low with rituximab infusion., Conclusions: It is conceivable that anti-MOG antibodies are involved in the pathology of "ADEM followed by recurrent ON," and that the early introduction of rituximab, which is involved in the suppression of antibody production and has effects on CD20 T lymphocytes, may be a feasible treatment for ON. Due to the small number of patients, additional reports on prospectively followed patients are needed., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Alexander disease (AxD) is a progressive neurodegenerative disease caused by a mutation in the glial fibrillary acid protein (GFAP) gene. A 4-year-old boy presented several times with hemiclonic seizures with eye deviation for a few minutes at 28 days after birth. Electroencephalogram showed independent sharp waves in the right and left temporal area. Magnetic resonance imaging showed high intensity T1-weighted images in the white matter of the frontal lobe and basal ganglia. He showed no head control at 4 years of age, and his weight gain was insufficient. He did not show macrocephaly. At 4 years of age, he died of bacterial pneumonia and septic shock. He was diagnosed with AxD, and direct sequencing revealed a de novo known mutation, c. 239 T > C, p.(F80S), in GFAP. Hela and U2-OS cells transfected with GFAP cDNA with c. 239 T > C showed dot-like cytoplasmic aggregation, similar to R239C, a common mutation found in severe infantile AxD. Aggregation in the cytoplasm caused by a GFAP mutation is a hallmark of AxD. Although there is only one previous report of a patient with an F80S mutation, our data support that F80S can cause the severe, infantile form of AxD., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Leigh syndrome, which is a common phenotype of pediatric mitochondrial disease, is a progressive neurodegenerative disease. The typical neuroimaging findings of Leigh syndrome include bilateral symmetric lesions in the basal ganglia and/or the brainstem. However, there are a few reports on spinal cord involvement in patients with Leigh syndrome. In the present case, magnetic resonance imaging (MRI) obtained during infancy revealed symmetric lesions in the substantia nigra of a patient with Leigh syndrome with an NDUFA1 mutation; lesions of the bilateral putamen and brainstem were subsequently observed. Additionally, our patient presented large and extended spinal cord lesions. Therefore, this case is suggesting that we should consider the occurrence of spinal cord lesions as an atypical finding in Leigh syndrome., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We report the case of a 19-year-old female patient who had progressive chorea associated with a GNAO1 mutation. Chorea was refractory to multiple anticonvulsants, and the patient suffered from tiapride-induced neuroleptic malignant syndrome. After identification of a GNAO1 missense mutation at the age of 18years, topiramate treatment was initiated and the frequency of chorea decreased dramatically. The efficacy of topiramate may have been related to the inhibitory modulation of voltage-activated Ca 2+ channels. Given the side effects and complications associated with neuroleptics and deep brain stimulation, respectively, topiramate is recommended for the first-line management of severe chorea associated with a GNAO1 mutation., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We are reporting on a case of pediatric anti-NMDAR encephalitis with autonomic instability. The patient showed little response to first-line treatment of steroid and IVIG. We initiated plasma exchange, also a first-line treatment. This worsened his autonomic instability, resulting in hypotensive shock. He responded well to rituximab and cyclophosphamide, second-line therapies. Anti-NMDAR encephalitis is often accompanied by autonomic instability. Our and other reported cases, raise the question of plasma exchange as a first-line therapy for pediatric NMDAR encephalitis, which is frequently accompanied by autonomic instability. Plasma exchange should be performed cautiously in such patients., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

While a growing body of neurocognitive research has explored the neural substrates associated with attention deficit hyperactive disorder (ADHD), an objective biomarker for diagnosis has not been established. The advent of functional near-infrared spectroscopy (fNIRS), which is a noninvasive and unrestrictive method of functional neuroimaging, raised the possibility of introducing functional neuroimaging diagnosis in young ADHD children. Previously, our fNIRS-based measurements successfully visualized the hypoactivation pattern in the right prefrontal cortex during a go/no-go task in ADHD children compared with typically developing control children at a group level. The current study aimed to explore a method of individual differentiation between ADHD and typically developing control children using multichannel fNIRS, emphasizing how spatial distribution and amplitude of hemodynamic response are associated with inhibition-related right prefrontal dysfunction. Thirty ADHD and thirty typically developing control children underwent a go/no-go task, and their cortical hemodynamics were assessed using fNIRS. We explored specific regions of interest (ROIs) and cut-off amplitudes for cortical activation to distinguish ADHD children from control children. The ROI located on the border of inferior and middle frontal gyri yielded the most accurate discrimination. Furthermore, we adapted well-formed formulae for the constituent channels of the optimized ROI, leading to improved classification accuracy with an area under the curve value of 85% and with 90% sensitivity. Thus, the right prefrontal hypoactivation assessed by fNIRS would serve as a potentially effective biomarker for classifying ADHD children at the individual level.

The object of the current study is to explore the neural substrate for effects of atomoxetine (ATX) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS). We monitored the oxy-hemoglobin signal changes of sixteen ADHD children (6-14 years old) performing a go/no-go task before and 1.5 h after ATX or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Sixteen age- and gender-matched normal controls without ATX administration were also monitored. In the control subjects, the go/no-go task recruited the right inferior and middle prefrontal gyri (IFG/MFG), and this activation was absent in pre-medicated ADHD children. The reduction of right IFG/MFG activation was acutely normalized after ATX administration but not placebo administration in ADHD children. These results are reminiscent of the neuropharmacological effects of methylphenidate to up-regulate reduced right IFG/MFG function in ADHD children during inhibitory tasks. As with methylphenidate, activation in the IFG/MFG could serve as an objective neuro-functional biomarker to indicate the effects of ATX on inhibitory control in ADHD children. This promising technique will enhance early clinical diagnosis and treatment of ADHD in children, especially in those with a hyperactivity/impulsivity phenotype.

We report the case of a boy with myoclonic epilepsy with ragged-red fibers (MERRF) who had astatic seizures since 2 years of age and later developed ataxia, absence seizures, and myoclonus. Almost homoplasmic A8344G mutation of mitochondrial DNA (m.8344A>G mutation) was detected in lymphocytes. He developed late-onset Leigh syndrome (LS) when he contracted pneumonia at 6 years. He developed bulbar palsy and deep coma. MRI demonstrated lesions in the brainstem, basal ganglia, and cerebral cortex. Three similar cases have been reported; two carried the almost-homoplasmic m.8344A>G mutation in muscle tissue. These suggested that almost homoplastic m.8344A>G mutation developed clinical phenotype of MERRF in the early stage and late-onset Leigh syndrome in the late course of the disease., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

An objective biomarker is a compelling need for the early diagnosis of attention deficit hyperactivity disorder (ADHD), as well as for the monitoring of pharmacological treatment effectiveness. The advent of fNIRS, which is relatively robust to the body movements of ADHD children, raised the possibility of introducing functional neuroimaging diagnosis in younger ADHD children. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 16 ADHD children (6 to 13 years old) performing a go/no-go task before and 1.5 h after MPH or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. 16 age- and gender-matched normal controls without MPH administration were also monitored. Relative to control subjects, unmedicated ADHD children exhibited reduced activation in the right inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during go/no-go tasks. The reduced right IFG/MFG activation was acutely normalized after MPH administration, but not after placebo administration. The MPH-induced right IFG/MFG activation was significantly larger than the placebo-induced activation. Post-scan exclusion rate was 0% among 16 right-handed ADHD children with IQ > 70. We revealed that the right IFG/MFG activation could serve as a neuro-functional biomarker for monitoring the acute effects of methylphenidate in ADHD children. fNIRS-based examinations were applicable to ADHD children as young as 6 years old, and thus would contribute to early clinical diagnosis and treatment of ADHD children.

Objective: Attention Deficit Hyperactivity Disorder (ADHD), a common developmental syndrome with inattention, hyperactivity, and impulsivity, is typically treated with the psychostimulant drug, methylphenidate (MPH). We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to search for a clinically implementable biological marker for the acute MPH effect on ADHD children., Methods: Following an MPH washout period, twelve ADHD children performed a go/no-go task before and 1.5 h after MPH intake. fNIRS was used to monitor the lateral prefrontal cortical hemodynamics of ADHD children performing a go/no-go task., Results: There was no significant activation in the lateral prefrontal cortices examined before MPH intake. However, after MPH intake, significant MPH-elicited activation (oxygenated hemoglobin signal increase) was detected in the right lateral prefrontal cortex (LPFC) implicated with response inhibition functions. There was a large significant correlation between increases in task performance and activation in the right LPFC., Conclusions: The improved cognitive performance was associated with activation in the right LPFC, which might serve as a biological marker to monitor the effect of MPH in ADHD children., Significance: MPH-effect assessment in ADHD children using fNIRS can be performed within a 3 h stay at a hospital during a single visit, and thus may be integrated into clinical practice., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The patient was a 14-year-old male diagnosed with acute disseminated encephalomyelitis (ADEM) with acute onset of multifocal central nervous system symptoms. He showed increased cerebrospinal fluid cell counts and high myelin basic protein levels, which responded well to steroid pulse therapy. Spinal MRI showed a centrally-located long spinal cord lesion (LCL) involving 17 vertebral bodies from C2 to T11 that later expanded into the white matter, and lesions on the ventral side of the medulla. The cause of LCL has been reported to be heterogeneous. In this case, LCL is considered to be associated with ADEM, an acute autoimmune response to myelin, and vascular inflammation of the gray matter of the spinal cord., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Postprandial hyperlipidemia (PPHL) is an independent risk factor for coronary heart disease (CHD) which is based on the accumulation of chylomicrons (CM) and CM remnants containing apolipoprotein B-48 (apoB-48). Since atherosclerotic cardiovascular diseases are frequently observed even in subjects with normal serum triglyceride (TG) level, the correlation between fasting apoB-48 containing lipoproteins and carotid intima-media thickness (IMT) was analyzed in subjects with normal TG levels., Methods: From subjects who took their annual health check at the Osaka Police Hospital (n=245, male), one-hundred and sixty-four male subjects were selected to take part in this study; the excluding factors were: systolic blood pressure ≥ 140 mmHg, intake of antihypertensive or antihyperlipidemic drugs, or age >65 years. The association between biochemical markers and IMT was analyzed and independent predictors of max-IMT were determined by multiple regression analysis in all subjects and in groups N-1 (TG<100mg/dl, n=58), N-2 (100 ≤ TG<150 mg/dl, n=53) and H (150 ≤ TG mg/dl, n=53), respectively., Results: Fasting total cholesterol, LDL-cholesterol, HDL-cholesterol, apoB-100 and lnRemL-C (remnant lipoprotein-cholesterol) levels were not correlated with max-IMT, but lnTG and lnapoB-48 were significantly correlated with max-IMT in all subjects. LnapoB-48 and apoB-48/TG ratio were significantly correlated with max-IMT in group N-2. By multiple regression analysis, age and lnapoB-48 were independent variables associated with max-IMT in group N-2., Conclusion: Serum apoB-48 level might be a good marker for the detection of early atherosclerosis in middle-aged subjects with normal-range levels of blood pressure and TG., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat., Methods: Fifteen male, bred, 12-week-old Jcl-Wister rats were used. A pellet of strontium chromate were inserted into the bronchus of the rats. The rats were sacrificed 9 months after the pellet was inserted. We pathologically examined the region of the bronchi to which the pellet was attached. We quantified the amount of chromium accumulation in the bronchial lesions using a microscopic X-ray fluorescence analyzer., Results: Of the 15 rats, 1 rat had a lesion of squamous cell carcinoma (SCC), 7 rats had carcinoma in situ (CIS) or dysplasia, 8 rats had squamous metaplasia, and 5 rats had goblet cell hyperplasia. The amounts of chromium accumulation in normal epithelium (n=24), goblet cell hyperplasia (n=14), squamous metaplasia (n=8), and dysplasia plus CIS plus SCC (n=9) were 500+/-1354, 713+/-1062, 941+/-1328, and 3511+/-4473 (mean+/-SD) counts/s/mA, respectively. The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium (Spearman's correlation coefficient by ranks, rs=0.454, P<0.01)., Conclusions: The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium. Examining the genetic alterations of histologic changes in this model was helpful in elucidating the process of carcinogenesis of chromium in the lung.

Background: The thymus or thymoma plays a role in the pathogenesis of myasthenia gravis (MG). Although previous studies have reported that the presence of MG in thymoma patients is an indicator of poor prognosis, recent reports have shown that the presence of MG no longer influences the prognosis or indicates a more favorable prognosis in thymoma patients., Methods: To clarify the difference in tumor behavior between thymoma with MG and that without MG, we compiled 1,089 thymomas treated between 1990 and 1994 from 115 institutes in Japan and analyzed the clinical characteristics of thymoma with MG compared with thymoma without MG., Results: MG was associated with 270 cases (24.8%) of thymoma. The total resection cases comprised 94.6% and 91.4%, and the recurrent cases comprised 6.4% and 8.3% in the groups with and without MG, respectively. The 5-year survival rates for thymoma with and without MG in stage III were 85.7% and 89.3%, respectively; and those in stage IV were 85.1% and 63.9%, respectively. The prognosis of thymoma with MG in stage IV tended to be better than that of thymoma without MG (p = 0.0523). The thymoma with MG group had fewer stage IVb thymomas than did the thymoma without MG group (15% vs 34%). The resectability rate in the thymoma with MG group was higher than that in the thymoma without MG group (60% vs 38%)., Conclusions: Thymoma with MG is equally or less malignant than that without MG. The infrequency of stage IVb thymomas and the high resectability rate had an influence on the favorable prognosis of stage IV thymoma with MG.

Study Objectives: To evaluate how serum lidocaine concentrations (SLC) rise when lidocaine is administered by a Bronchofiberscopic Catheter Spray Device (BCSD), and to demonstrate the effect on the aspiration speed of a substitute for sputum when a catheter spray remains in the channel of the bronchofiberscope (BF)., Methods: This is a prospective randomized clinical study. After lidocaine ultrasonic nebulizer, the BF was inserted orally. During the procedure patients received 4% lidocaine by two methods. In Group 1, 11 patients received lidocaine by bronchofiberscopic (BF) injection. In Group 2, 15 patients received lidocaine by spraying from the diameter 1.06 mm catheter through the BF channel. SLC were measured at 40 min from onset of nebulization. Separately, we examined how effectively sputum was aspirated through the BF channel with a catheter., Results: Total lidocaine dose (TLD) is the total dose used for nebulization and for the BF injection or spray. The TLD for Groups 1 and 2 were 698.2+/-162.1 mg (mean+/-SD) and 498.7+/-103.8 mg, respectively (P = 0.03). The SLC for Groups 1 and 2 were 1.28+/-0.72 and 1.48+/-0.70 mg/l, respectively (P = 0.49)., Conclusions: Using BCSD allows easier in administration of lidocaine and is not associated with a significant increase in SLC in comparison with BF injection. Although sputum aspiration using the BF inserted with our catheter was somewhat slow, we did not feel inconvenient so much. Compared to the conventional method, using BCSD may be preferable for patients and bronchoscopists.

Background: The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus., Methods: We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance., Results: There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 (p = 0.0436), and between type B3 and type C (p = 0.042). By multivariate analysis, only Masaoka clinical stage (p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively., Conclusions: The current study confirmed the World Health Organization histologic classification as a good prognostic factor.

Background: A TNM classification has been established for various tumors. However, the TNM classification of thymic epithelial tumor has not been established yet., Methods: We received replies to a questionnaire on thymic epithelial tumors from 115 institutes. We compiled a database of 1,320 patients with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41 thymic carcinoids) who were treated between 1990 and 1994. We used a tentative TNM classification of thymoma presented by Yamakawa and associates in 1991. The regional lymph nodes of the thymus were classified into three groups: anterior mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic lymph nodes (N3)., Results: The rate of lymphogenous metastasis in thymoma, thymic carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma, 69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2, and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis demonstrated that survival of patients with thymoma was dependent on the clinical stage of Masaoka and complete resection. In thymic carcinoma, survival was dependent on lymph node metastasis and complete resection., Conclusions: The N factor was one of the predictors of survival in thymoma and thymic carcinoma. However, M factor showed less influence on survival than T or N factors.

Background: Surgery remains the mainstay of treatment for thymic epithelial tumors, and radiation and chemotherapy also have been applied widely as adjuvant and palliative procedures., Methods: We compiled records of 1,320 patients with thymic epithelial tumors who were treated from 1990 to 1994 in 115 institutes certified as special institutes for general thoracic surgery by The Japanese Association for Chest Surgery., Results: Patients with stage I thymoma were treated with only surgery, and patients with stage II and III thymoma and thymic carcinoid underwent surgery and additional radiotherapy. Patients with stage IV thymoma and thymic carcinoma were treated with radiation or chemotherapy. The Masaoka clinical stage is an excellent predictor of the prognosis of thymoma and thymic carcinoma, but not thymic carcinoid. In stage III and IV thymoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 93%, 64%, and 36%, respectively. On the other hand, in thymic carcinoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 67%, 30%, and 24%, respectively. Prophylactic mediastinal radiotherapy could not prevent local recurrences effectively in patients with totally resected stage II and III thymoma. Adjuvant therapy including radiation or chemotherapy did not improve the prognosis in patients with totally resected III and VI thymoma and thymic carcinoma., Conclusions: Total resection is the most important factor in the treatment of thymic epithelial tumors. There is value in debulking surgery in invasive thymoma, but not in thymic carcinoma. We doubt that adjuvant therapy is valuable for patients with totally resected invasive thymoma and thymic carcinoma.

Human gastrointestinal neoplasms are mostly developed from the mucosa, not from the adjacent muscle layer. DNA adducts in the mucosa and adjacent muscle layer of the non-tumoral part of stomach from 19 patients with gastric neoplasms and from six newborns were analyzed by 32P-postlabeling, and then compared them with those of representative colon or small intestine sample. Five kinds of mucosa-specific DNA adducts (G1-5) were found in all of the adult stomach samples, but were entirely absent from the adjacent muscle layers and from the newborn stomachs. In addition, several common background adducts were also present in both the mucosa and muscle layer. G2 was the same DNA adduct as Si2 in the small intestine and C1 in the colon, and G3 was the same as Si1 in the small intestine. Thus, it was demonstrated that the mucosa of the stomach was exposed to DNA-reactive substances.

Objective: We developed low-concentration homogenized castor oil eye drops for the treatment of patients with noninflamed obstructive meibomian gland dysfunction (MGD), a major cause of lipid-deficiency dry eye, and assessed the safety, stability, and efficacy of the eye drops., Design: Randomized, double-masked, placebo-controlled crossover clinical trial., Participants: Forty eyes of 20 patients with noninflamed MGD., Methods: After a preliminary study of eye drops containing castor oil, 2% castor oil and 5% polyoxyethylene castor oil (emulsifier) were mixed to formulate homogenized oil eye drops. The patients were assigned randomly to receive oil eye drops or placebo six times daily for 2 periods of 2 weeks each., Main Outcome Measures: At the end of each treatment period, we assessed symptoms, tear interference grade, tear evaporation, fluorescein and rose bengal scores, tear break-up time (BUT), and meibomian gland orifice obstruction. Safety and stability tests were also performed., Results: Symptom scores, tear interference grade, tear evaporation test results, rose bengal scores, tear BUT, and orifice obstruction scores after the oil eye drop period showed significant improvement compared with the results after the placebo period. No complications attributable to the eye drops were observed. The oil eye drops were stable when stored at 4 degrees C., Conclusions: The results indicate that castor oil eye drops are effective and safe in the treatment of MGD. The possible mechanisms of this treatment are improvement of tear stability as a result of lipid spreading, ease of meibum expression, prevention of tear evaporation, and the lubricating effect of the oil eye drops.

A 61-year-old woman, who had been diagnosed as having Sjögren's syndrome, developed an anterior mediastinal mass. She was diagnosed with Sjögren's syndrome with thymoma, preoperatively. Extended thymectomy was performed. Macroscopically, the mediastinal mass showed thick-walled multiloculated cavities filled with turbid yellow fluid. Microscopically, the cyst lining was continuous with thymic lobules in the wall with inflammatory process, cholesterol granuloma formation, and prominent lymph follicular hyperplasia. She was diagnosed with multilocular thymic cysts associated with Sjögren's syndrome.

Background and Methods: We established a new, patientlike orthotopic model of lung cancer metastasis with human non-small cell lung cancer cell lines. In this report, we describe the progressive stages of development of lymphogenous mediastinal metastasis in the Ma44-3 cell line from day 3 to day 15 after implantation in severe combined immunodeficiency mice and the process of lymphogenous metastasis., Results: All mice killed after day 12 had perivascular and peribronchial tumor growth. Micrometastasis to the mediastinum was first observed on day 5. On days 5 through 9, 10 of 13 mice had metastasis to the mediastinum, and all mice had one by day 12. When perivascular and peribronchial tumor growth was present by day 5, metastasis to the mediastinum developed in all mice., Conclusions: This study demonstrates the lymphogenous spread of human lung cancer in severe combined immunodeficiency mouse using an orthotopic implantation model. Our model was thought to be an artificial lymphogenous metastasis model, owing to forced tumor inoculation into lymphatic vessels.

We have previously purified an extracellular polysaccharide, D-galactan sulfate associated with L(+)-lactic acid, produced from a marine microalga Dinoflagellate Gymnodinium sp. A3 (GA3). The GA3 polysaccharide, irrespective of presence or absence of lactic acid, exhibited significant cytotoxicity, which is based on an induction of apoptotic cell death, toward human myeloid leukemia K562 cells. Furthermore, we found that the GA3 polysaccharide with or without lactic acid possesses an inhibitory effect on topoisomerase-I (topo-I). The potent cytotoxic effect of GA3 polysaccharide may result from its inhibitory effect on topo-I, because the topo-I inhibition is known to trigger apoptotic cell death.

8-Hydroxyguanine (8-OH-G) is the site of a frequent mutagenic lesion of DNA, produced by oxidative damage. MutM of E. coli and OGG1 of Saccharomyces cervisiae are known to possess 8-OH-G glycosylase activity and apurinic (AP) site lyase activity to repair 8-OH-G lesions. Recently, cDNA clones of human OGG1 homologues (hMMH) of four isoforms (type 1a, type 1b, type 1c, and type 2) were isolated. However, it is unknown whether expression of endogenous hMMH proteins actually occurs in mammalian cells. Here using hMMH type 1a-specific antibody and cells overexpressing tag-fused hMMH type 1a, we show the expression of hMMH type 1a protein in many types of human cells and show that endogenous hMMH type 1a protein has 8-OH-G glycosylase/AP lyase activity. Furthermore, we show that upon depletion of hMMH type 1a protein in a whole cell extract by its antibody, most of the AP lyase activity is lost, indicating that hMMH type 1a protein is a major enzyme for repair of 8-OH-G lesions in human cells., (Copyright 1999 Academic Press.)

Two cases of repeatedly recurrent thymoma with myasthenia gravis are detailed here. A 41-year-old woman had 5 recurrent thymomas, including local recurrences and lumbar and lung metastases; she was alive at the time of this writing, which was 22 years after her first surgery. A 36-year-old man had 3 recurrent thymomas, including local recurrence, dissemination, and lung metastasis; he was alive at the time of this writing, which was 16 years after his first surgery. Both recurrent lesions were diagnosed as "atypical thymoma" with moderate nuclear atypia. The patients with atypical thymoma must be followed up carefully due to a possible recurrence. Surgical treatment with chemoradiotherapy can lengthen their survival.

We examined p53 mutations in 20 cancer samples from 19 chromate workers with lung cancer by Polymerase chain reaction-Single strand conformation polymorphism analysis and direct sequencing. Six missense mutations were identified in 4 (20%) of the 20 chromate lung cancer samples. Fewer mutations were found in the patients with lung cancers who had been exposed to chromate than in those who had not. However, the pattern of p53 mutations in lung cancer patients exposed to chromate differed from that of common lung cancers in 3 respects. There were no apparent G to T transversions, which are common base changes in lung cancers. Half of the mutational sites (3/ 6) had changes of AT base-pairs, and 2 of 4 mutational tumor samples had double missense mutations. Our results suggested that chromate exposure may induce point mutation of the p53 gene.

Rho proteins have been implicated in a variety of cytoskeletal functions, but it is unclear how Rho proteins regulate these cellular functions and how Rho proteins are regulated. In this study, we cloned the rhoB gene from the mouse genome and characterized its promoter region. The predicted amino acid sequence was identical to that encoded by the human rhoB gene. A site for initiation of transcription was found at position -376 relative to the site for initiation of translation. Deletion analysis of the 5'-flanking region of the rhoB gene revealed that the minimum region of the promoter was located between positions -507 and -376. Northern blotting analysis showed that the expression of the mouse rhoB gene was induced by serum, suggesting that expression of the rhoB gene might be controlled by some signal-responsive element(s).

Background: Since 1973 we have performed extended thymectomy for myasthenia gravis because of the presence of thymic tissue in the anterior mediastinal fatty tissue. Follow-up results were reviewed and influencing factors were investigated., Methods: Three hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point., Results: Remission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome., Conclusions: Extended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.

We examined the binding of various steroid hormones to DNA in vitro by means of 32P-postlabeling. Seventeen steroid hormones and cholesterol (CS) were incubated with human liver DNA at 37 degrees C for 1 h under aerobic conditions in the absence of catalysis. The reaction mixtures were analyzed by the nuclease P-1 version of 32P-postlabeling. The results showed that cortexolone (CX), prednisolone (PS), cortisone (CN), cortisol (CL), tetrahydrocortisol (TC), corticosterone (CC), 11-deoxycorticosterone (DC), dexamethasone (DX), dihydrocortisol (DL), and aldosterone (AL) covalently bound with DNA. However, progesterone (PG), 17 alpha-hydroxyprogesterone (HG), estrone (E1), estradiol (E2), estriol (E3), testosterone (TS), cortol (CR) and the original compound for biosynthesis, CS, did not form adducts. In absence of DNA, the steroids themselves did not give rise to any spot on TLC under the same conditions. The dose-responses of DNA binding by DC, DL, CC, CL and CN were linear. The relative adduct labeling of reactive steroids at a concentration of 2 mM were as follows: 68.8 (CX), 53.2 (PS), 39.6 (CN), 29.9 (CL), 20.9 (TC), 12.9 (CC), 12.3 (DC), 7.5 (DX), 4.7 (DL), 1.2 (AL) adducts per 10(8) nucleotides. Reactive and nonreactive steroids were distinguishable by the presence or absence of the carbonyl group (-CO-CH2OH) at carbon seventeen (C17) of the cholesterol skeleton. This implies that the electrophilic carbonyl or a neighboring group perhaps involved in the formation of covalent bond with DNA. To investigate the nature of target base(s) of these DNA reactive steroids, mononucleotides of all four bases of DNA were reacted with CN, CL, CC and cochromatographed with the obtained spots of DNA reactions. The results of which stated that these steroids and guanine reaction gave the same spots as observed in DNA reaction, indicating guanine is the main target of these DNA reactive steroids. Hep G2 human hepatocellular carcinoma cells were used as an alternative model. Although nine steroids (CL, DL, TC, PS, DX, PG, E2, TX, CR) did not react with intracellular DNA under our experimental conditions, our findings suggested that some hormonal steroids can form covalent DNA adducts in vivo.

The electrical impedance of a pulmonary mass was measured in 53 patients of whom 44 had primary lung cancer, 5 had metastatic lung tumor, and 4 had organizing pneumonia. Because biologic tissue can be regarded, electrically, to consist of extracellular resistance (Re), intracellular resistance (Ri), and the electrical capacitance of the cell membrane (Cm), these three parameters were calculated from the measured electrical impedance of tissue by a curve-fitting technique using a computer program. The Re of lung tissue was significantly greater (p < 0.01) and the Cm of lung tissue was significantly less (p < 0.01) than that of a pulmonary mass. The Re of malignant tumors (both lung cancer and metastatic tumors) was significantly greater (p < 0.01) and the Cm of malignant tumors was significantly less (p < 0.01) than that of organizing pneumonia. With this information, we used a biopsy needle to diagnose nine intrathoracic lesions. This technique additionally allowed us to confirm the proximity of the needle tip of the mass. The electrical impedance of the lung mass was measured through the biopsy needle using a modified impedance analysis system before the biopsy was performed. There were no false-negative results, and one false-positive result. The rapid measurement of the electrical impedance of a pulmonary mass, preoperatively, may be of value in the clinical evaluation of a pulmonary mass both by facilitating needle guidance and by permitting diagnosis based on electrical impedance.

We examined the phenotypes of lymphocytes in the pleural cavity of 23 lung cancer patients without malignant effusion. The ability of those lymphocytes to develop lymphokine-activated killer (LAK) activity and the regulation of LAK by pleural cavity macrophages were also compared with their counterparts in the peripheral blood. Mononuclear cells (MNC) were obtained simultaneously from the blood and by lavage of the pleural cavity of patients with lung cancer. The proportion of the T-cell subset of HLA-DR+ cells was significantly higher in the pleural cavity than in the peripheral blood, but the proportions of CD3+ and CD8+ cells in the pleural cavity were similar to the corresponding proportions in the blood. The proportions of CD4+ and CD16+ cells were lower in the pleural cavity than in the blood. The LAK activity could be developed by MNC from the pleural cavity following incubation with interleukin 2 (IL-2), but the LAK activity of pleural cavity MNC was significantly less than that of peripheral MNC. Pleural cavity lymphocytes alone also developed LAK activity following incubation with IL-2. Pleural macrophages from the patients were regulated to augment in vitro induction of LAK activity by IL-2 from autologous blood lymphocytes and pleural cavity lymphocytes. Lymphocytes in the pleural cavity without malignant pleural effusion could be developed by LAK activity and this activity was augmented by pleural cavity macrophages. The LAK activity developed by pleural cavity lymphocytes was significantly lower than that developed by peripheral blood lymphocytes. However, they can change their population to include cells with higher activities on exposure to IL-2 against the invasion of lung cancer cells into the pleural cavity. Thus, the population of lymphocytes in the pleural cavity of patients with lung cancer without malignant pleural effusion was different from that in malignant pleural effusion.

The reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis and sequencing were used to examine p53 gene alterations in 18 surgical specimens of primary lung cancers obtained in Japan. Somatic mutations resulting in amino acid changes were found in eight of the 18 cases (44%). Seven missense mutations were located in amino acid-conserved domains or their vicinities (codons 110 to 307). Most mutations were found at G-C pairs, suggesting that specific carcinogens are involved in the etiology of lung cancer. The p53 mutations showed a significant association with a history of smoking (P = 0.0294). We suggest that the p53 mutations may be associated with smoking-induced lung carcinogenesis.

Immunohistochemical reactivity with OKT9 (antitransferrin receptor) monoclonal antibody was studied in 58 surgically resected adenocarcinomas of the lung. The cell surface and cytoplasm of the tumor cells were stained in 44 cases (76 percent). The expression of the transferrin receptor (TrfR) in tumor cells was compared with histopathologic prognostic factors, such as TNM factors, degree of histologic differentiation, degree of nuclear atypia, and frequency of mitotic figures. The expression of TrfR showed significant correlation with the degree of histopathologic differentiation (p less than 0.025), degree of nuclear atypia (p less than 0.025), and frequency of mitotic figures (p less than 0.001). However, there was no definite correlation with TNM factors. These results indicate that the expression of the TrfR in pulmonary adenocarcinoma corresponds to the elevated proliferative activity of the tumor cells, and that immunohistochemical reactivity with OKT9 can be used as one of the histopathologic indicators of prognosis of pulmonary adenocarcinoma.

A 6-month-old girl was not to have fever and stridor. Investigations revealed an abnormal lung that communicated with the esophagus and had a systemic arterial supply from the abdominal aorta. Resection of the abnormal lung was performed successfully. We have termed this disorder total lung ectoplasia. Ten patients from the literature were reviewed.

To evaluate the significance of the blood lactate threshold as a predictor of postthoracotomy hospital mortality resulting from pulmonary complications, a 3-minute incremental exercise test was administered to 33 lung cancer patients who underwent thoracotomy between October, 1981, and May, 1984. The oxygen consumption/body surface area at an arterial lactate level of 20 mg/dl (VO2/BSA at La-20) was adopted as the blood lactate threshold. Age and pulmonary function parameters such as forced expiratory volume in one second (FEV1)/body surface area (BSA), FEV1/forced vital capacity, diffusing capacity for the carbon monoxide/lung volume, and maximum ventilatory volume/BSA revealed significant differences between patients with postthoracotomy pulmonary complications and those without such complications. However, there was no difference in pulmonary function test results between the surviving and deceased patients. In contrast, although VO2/BSA at La-20 did not differ between the patients with and without pulmonary complications, it differed significantly between the surviving and deceased patients. We concluded that postthoracotomy pulmonary complications depended on the severity of preoperatively associated pulmonary function disorders and that the blood lactate threshold expressed by VO2/BSA at La-20 was an important indicator of the risk of hospital mortality.

Nineteen patients with giant bulla were followed for more than 1 year after bullectomy. They were divided into two groups according to their postoperative symptoms. Group 1 consisted of 16 patients who had no problems in their postoperative clinical course, while Group 2 included 3 patients who complained of severe dyspnea at 5 to 6 years of follow-up. Prior to operation, the forced expiratory volume in 1 sec over vital capacity (FEV1%) was 66.8 +/- in Group 1 and 27.6 +/- 5.4% in Group 2. Differences in preoperative and postoperative FEV1% were statistically significant within Group 1 and between the two groups. Postoperative FEV1% (Y) correlated significantly with preoperative FEV1% (X) (Y = 0.74X + 25.4; r = 0.836; p less than 0.001). Thus, we were able to predict the postoperative FEV1% from the preoperative value. Regional ventilation over volume was computed from the washout curve of xenon 133 after reaching equilibrium with rebreathing in a closed circuit (V/V dynamic). Group 2 had significantly lower regional ventilation over volume in all regions, both before and even after bullectomy, compared with normal subjects or Group 1 patients. Preoperative V/V dynamic was below 0.5 in all regions of Group 2. Furthermore, postoperative V/V dynamic (Y) correlated significantly with preoperative V/V dynamic (X) in the upper region (Y = 0.46X + 0.40; r = 0.638; p less than 0.02) and in the lower region (Y = 0.72X + 0.33; r = 0.869; p less than 0.001). We conclude that functional indications of bullectomy for giant bulla are that FEV1% should be greater than 40%, and that regional V/V dynamic should be greater than 0.5. On the other hand, symptomatic and functional improvement following bullectomy was reduced in patients whose FEV1% was less than 35% in whose V/V dynamic was remarkably disturbed in all regions of the involved hemithorax.

A 23-year-old man with pulmonary arteriovenous fistulas of the right middle lobe is described. During the incremental exercise test, the shunt fraction dropped from 19 percent to 12 percent as the cardiac output increased. We discuss the mechanism of this fall in shunt fraction in this patient during exercise.

Factors influencing the recurrence or persistence of thymoma after therapy were investigated in 127 patients with thymoma, including 75 with thymoma and myasthenia gravis. The rate of recurrence or persistence was 19% (24 of 127 patients) overall, 11% (8 of 75 patients) in myasthenic thymoma, and 31% (16 of 52 patients) in nonmyasthenic thymoma. The more advanced the clinical stage, the higher the rate of recurrence or persistence. The recurrence/persistence rate for patients with the same clinical stage was higher in those with nonmyasthenic thymoma (8% in Stage I, 11% in Stage II, 36% in Stage III, and 75% in Stage IV) than in those with myasthenic thymoma (0 in Stage I, 13% in Stage II, 18% in Stage III, and 20% in Stage IV). The prognosis for patients having subtotal resection of tumor was good in myasthenic thymoma (recurrence/persistence rate, 17%) in contrast with nonmyasthenic thymoma (recurrence/persistence rate, 78%). These results suggest that nonmyasthenic thymoma is more malignant than myasthenic thymoma. Postoperative radiotherapy was effective in preventing the recurrence or persistence of thymoma after therapy.

In 80 patients with type II nonthymomatous myasthenia gravis who underwent extended thymectomy, we investigated preoperative duration of symptoms, prognosis after thymectomy, immunological findings, and germinal center formation in the thymus. Our findings included the following. First, the palliation rate after thymectomy ranged from 73 to 100% and was independent of the preoperative duration of symptoms. The remission rate was high in patients with a short preoperative duration. Second, the lymphocyte count of peripheral blood decreased as preoperative duration increased. Third, the percentage of positive reactions to purified protein derivative of tuberculin decreased as preoperative duration increased: 100% in the one-year group, 78% in the two-year group, 75% in the three-year group, and 56% in the four-year group. Fourth, the degree of germinal center formation in the thymus was higher in patients with a longer preoperative duration. The correlation between germinal center formation and preoperative duration was significant. Finally, the T-cell population in peripheral blood and immunoglobulin, and antibody to acetylcholine receptor in serum, had no significant relationship with the preoperative duration of myasthenia gravis.

A 49-year-old woman who had previously undergone hysterectomy was found to have multiple pulmonary masses and cysts and experienced respiratory failure. Bronchoscopic study revealed an endobronchial mass obstructing the left main bronchus and protruding into the trachea. She was treated with an endoscopic laser to eliminate the airway obstruction. After recovery from the respiratory failure, two-stage thoracotomies were performed at six-month intervals. The endobronchial mass originated from a tumor in the left basal segment. The histologic findings on the cysts and nodules of both lungs were compatible with fibroleiomyoma. The final diagnosis was pulmonary leiomyomatosis with myoma uteri.

The binding to hemoglobin of synthetic 2-hydroxyamino-6-methyldipyrido[1,2-a: 3',2'-d] imidazole from the carcinogenic product of L-glutamic acid pyrolysis 2-amino-6-methyldipyrido[1,2-a: 3',2'-d] imidazole were investigated in vitro. The hydroxylamine required oxidation to its nitroso derivative to bind to rat hemoglobin through thiol groups. Oxidation of the hydroxylamine to the nitroso form was found to be enhanced by oxyhemoglobin and superoxide dismutase at pH 7.4 under aerobic conditions. Since these conditions might also enhance this oxidation in vivo, the conversion of the DNA-reactive arylhydroxylamines to the DNA-non-reactive nitroso compounds and their subsequent binding to highly abundant thiol groups of proteins could be considered as a process for detoxification of toxic arylhydroxylamines.

We predicted the postoperative forced expiratory volume in 1 second (FEV1) with a formula based on the premise that the total number of subsegments was 42: postop FEV1 = [1 - (b - n)/(42 - n)] (preop FEV1), where n and b are the number of obstructed subsegments and total subsegments, respectively, in the resected lobe. It was assumed that b was 6, 4, and 12 in the right upper, middle, and lower lobes, respectively, and 10 each in the left upper and the left lower lobes. The obstructed subsegments, n, were obtained from the findings on bronchography or bronchofiberscopy or both before operation. The linear regression line derived from the correlation between predicted (x) and measured (y) FEV1 was y = 0.850x + 0.286 +/- 0.296 (standard error) (N = 52; r = 0.821; p less than 0.001). We calculated the predicted postoperative FEV1 in 188 patients with primary lung cancer. The predicted values were corrected with the regression equation just mentioned and then normalized by the patient's height and sex (%FEV1(p,c). The correlation between %FEV1(p,c) and the surgical risk was studied. Postoperative respiratory complications were inversely related to %FEV1(p,c), and a significantly high incidence of complications (p less than 0.05) was observed in those whose %FEV1(p,c) was less than 60% of predicted normal. In aged patients (65 years old or more) without complications, %FEV1(p,c) was 67.3 +/- 18.0%; it was 52.2 +/- 12.8% in those with respiratory trouble and 53.3% +/- 9.6% in those with circulatory complications. The difference between groups with and without complications was significant (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Of 277 patients with myasthenia gravis (MG) who underwent thymectomy, including 78 with thymomatous MG, 33 patients had other autoimmune diseases. The clinical characteristics of MG with other autoimmune disease were investigated. Graves's disease and rheumatoid arthritis were the most common autoimmune diseases seen. The association rate of autoimmune disease in patients with thymomatous MG (3.8%) was significantly lower than that in patients with nonthymomatous MG (15.1%). The positive rate for a germinal center in the thymus was significantly higher in patients with other autoimmune disease than in those without such disease. Thymectomy was effective for MG in patients with an associated disease as well as in those without such a complication. The clinical course of the associated autoimmune disease did not seem to be adversely affected by thymectomy. Therefore, thymectomy should be performed in MG patients with other autoimmune disease.

A simple technique for drainage for a giant bulla with balloon catheter using chemical irritants and fibrin glue is described. This method allows physical and functional improvement without major surgery in compromised patients with giant bullae.

Sixty-five patients with thymomatous myasthenia gravis were investigated. Thymomas were present in 44% of the male patients and 19% of the female patients with myasthenia gravis. The incidence of thymomatous disease in male patients was higher than in female patients in all age groups. Eighty percent of men more than 50 years old and women more than 60 years old had myasthenia gravis with thymoma. Germinal center formation in the thymus of patients with thymomatous myasthenia gravis was positive in 91% and was high grade. The prognosis for patients undergoing extended thymectomy of thymomatous myasthenia gravis was significantly better than in those having transsternal simple thymectomy, but it was worse than the prognosis for patients with nonthymomatous myasthenia gravis. No increase in the rate of remission or palliation was seen one year after thymectomy. It is concluded that early thymectomy is effective in control of myasthenia gravis in thymomatous myasthenia gravis.

The clinical features and the effect of thymectomy were compared between 27 elderly patients (Group 2) and 119 young adult patients (Group 1) with myasthenia gravis (MG). In the elderly group, MG was type I in 3 patients, type IIA in 6, type IIB in 17, and type III in 1; and in the young group, type I in 6, type IIA in 36, type IIB in 73, and type III in 4. The association rate with autoimmune disease in patients without thymoma was 12.5% (1/8) in Group 2 and 21.3% (20/94) in Group 1. Autoimmune diseases were not seen in any patients with thymoma. The clinical stage of thymoma was not significantly different between the two groups. The rates of remission and of palliation at 3 years after thymectomy were 18.2% and 72.7%, respectively, in Group 2 patients with thymoma, 21.4% and 78.6% in Group 1 patients with thymoma, 50% and 100% in Group 2 patients without thymoma, and 50% and 98.1% in Group 1 patients without thymoma.