[MERRF/MELAS overlap syndrome].
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Biomedical subjects
Publications and source records attributed to Y Goto.
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We report a case of intractable lymphedema of the left leg following radical prostatectomy. The 69-year-old male patient complained of difficulty walking, caused by severe lymphedema. Intraarterial autologous lymphocyte transfusion therapy was performed because of failure of conventional conservative therapy, and the leg edema resolved almost completely. However, the treatment did not improve the penoscrotal edema necessitating excision of the edema and skin graft in a separate procedure. The post-operative course was excellent and the patient's performance status improved to 1 from 3.
Perioperative mortality and morbidity in Japan for the year 1999 were analyzed retrospectively with special reference to operative regions. The total number of analyzed cases was 701,940. The percentages for each operative region were as follows, craniotomy 4.5%, thoracotomy 3.3%, heart and great-vessels 3.9%, thoracotomy with laparotomy 0.8%, laparotomy except caeserian-section 31.7%, ceserian-section 3.2%, head-neck and otolarynx 14.5%, chest-abdomen-perineum 11.1%, spine 3.5%, extremity including peripheral-vessel 16.5%, and others 6.9%. The incidence of serious events, including cardiac arrest and severe hypotension and hypoxemia suggesting impending cardiac arrest was 34.58 per 10,000 cases in all operative regions. The events were observed more frequently in heart and great-vessels 247.26, thoracotomy with laparotomy 128.91 and thoracotomy 61.55, and less frequently in chest-abdomen-perineum 13.52 and extremity including peripheral-vessel 16.99. Regarding the prognosis of events, the cases with no sequela were 69.9% in all operative regions. While there were fewer cases with no sequela in craniotomy 50.4%, thoracotomy with laparotomy 54.3% and heart and great-vessels 58.6%, there were more cases in head-neck and oto-larynx 95.2% and chest-abdomen-perineum 90.5%. The incidence of serious events totally attributable to anesthetic management was 7.79 per 10,000 cases in all operative regions. The events were observed more frequently in thoracotomy 12.82, heart and great-vessels 12.29 and spine 11.06, and less frequently in extremity including peripheral-vessel 5.17 and chest-abdomen-perineum 6.05. Regarding the prognosis of events, the cases with no sequela were 93.1% in all operative regions. There were fewer cases with no sequela in thoracotomy with laparotomy 80.0% and craniotomy 81.8%. The main cause of events in thoracotomy and spine was the inadequate airway management, and in heart and great-vessels was the overdose or miss-selection of drugs. Although the incidence of serious events totally attributable to anesthetic management was one fourth of all events, most of them resulted from human factors. Thus, the more efforts are necessary to improve the outcomes. While the total deaths from 701,940 cases, including death on the operation day or within 7 days after it, were 528 cases (7.52 per 10,000 cases), the deaths totally attributable to anesthesia were 7 cases (0.10 per 10,000 cases).
Anesthetic mortality and morbidity in Japan Society of Anesthesiologists (JSA) Certified Training Hospitals (CTH) for the year 1999 were reported as continuation of annual studies started in 1993. The JSA Committee on Operating Room Safety (CORS) sent confidential questionnaires to 774 CTH and received valid responses from 60.3% of hospitals. A total number of 793,840 anesthetics were documented. The respondents were asked to report all cases of cardiac arrests and other critical incidents (serious hypotension, serious hypoxemia and others), and their outcomes (death in operating room, death within 7 days, transfer to vegetative state and rescue without sequelae) as well as one principal cause for each incident from list of 52 items. They were also requested to submit the tabulation of patients by ASA physical status, age distribution, surgery sites and anesthetic methods. Analysis was made by total incidents under anesthesia/surgery, and also by incidents totally attributable to anesthetic management (AM), due to preoperative complications (PC), due to intraoperative pathological events (IP) and due to surgery (SG), with special reference to each of four tabulation groups and the whole group of patients. This paper focused analysis on all patients, as analyses with special reference to ASA physical status, age distribution, surgery sites and anesthetic methods were previously reported. Total incidence of cardiac arrest under anesthesia/surgery was 6.53 per 10,000 anesthetics. PC, IP and SG represented principal causes in 42.9%, 22.0% and 21.4% causes of total cardiac arrest cases, respectively. AM was noted as the principal cause in 12.0% of cases, with an incidence rate of 0.78 per 10,000. In 52 more detailed classification of principal causes, the most frequent cause of cardiac arrest was preoperative hemorrhagic shock, 20.3% of all cardiac arrests. The second cause was massive hemorrhage and/or hypovolemia due to surgical procedures (13.1%), and the third was intraoperative myocardial infarction/coronary ischemia/coronary spasm (9.5%). Prognoses of cardiac arrest cases declined due to PC: 71.1% of cardiac arrests died in the operating room or within 7 days after surgery and only 19.8% survived without sequelae. The best prognoses were found in cardiac arrest cases due to AM: 69.4% survived without sequelae and 12.9% died. The mortality rate post-cardiac arrest was 3.44 per 10,000 anesthetics, of those 0.10 due to AM, 0.57 due to IP, 1.99 due to PC and 0.76 due to SG. The mortality rate after critical incidents other than cardiac arrest such as severe hypotension and severe hypoxemia was 3.75, of those 0.03 due to AM, 0.28 due to IP, 2.31 due to PC and 1.13 due to SG. The final mortality rate attributable to anesthesia/surgery including deaths post-cardiac arrest and after other critical incidents was 7.19 per 10,000 anesthetics and very close to 7.18 [6.22, 8.13], that of mean [95% C.I.] in 1994-1998. The final mortality rate totally attributable to anesthesia was 0.13 per 10,000 anesthetics, which was significantly improved from 0.21 [0.15, 0.27], that of mean [95% C.I.] in 1994-1998. IP, PC and SG showed the final mortality rate of 0.84, 4.30 and 1.89, respectively. Five major causes of all critical incidents were massive hemorrhage due to surgical procedures (20.8%), preoperative hemorrhagic shock (10.7%), surgical technique (8.0%), inappropriate airway management (5.2%) and intraoperative myocardial infarction and coronary ischemia (4.5%). Drug overdose or selection error (3.9%) and overdose of main anesthetic (2.9%) as a result of human error occupied the 7th and 10th places. As far as anesthetic management to reduce mortality and morbidity related to anesthesia is concerned, we should increase vigilance to avoid human errors in addition to improving preanesthetic preparations and assessment of cardiovascular status as well as intraoperative management of cardiovascular events.
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To understand the mechanism of the interaction between human beta(2)-glycoprotein I (beta(2)-GPI) and negatively charged phospholipids, we determined the three-dimensional solution structure of the fifth domain of beta(2)-GPI by heteronuclear multidimensional NMR. The results showed that the molecule is composed of well-defined four anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop. Backbone dynamic analysis demonstrated significant mobility of the flexible loop on a subnanosecond time scale. Structural modeling of the nicked fifth domain, in which the Lys317-Thr318 peptide bond was specifically cleaved, revealed the importance of this long C-terminal loop for the interaction between beta(2)-GPI and negatively charged phospholipids. A titration experiment with the anionic surfactant SDS showed that this highly mobile loop, as well as the short beta-hairpin between betaC and betaD strands, which is rich in positively charged residues, specifically interact with the surfactant. The mobile loop, together with the surrounding positively charged residues, probably construct the binding site for negatively charged phospholipids such as cardiolipin.
We studied the time course of central nervous system (CNS) involvement after the termination of methylmercury exposure to rats, in order to investigate whether or not the involvement still progresses even after the termination of exposure. Methylmercury chloride (MMC), at a dose of 2 mg/kg/day, was subcutaneously injected for 25 consecutive days in 12 adult male Sprague-Dawley rats. Six of them were sacrificed on the final day of exposure (group A) after completing the observations of behavioral changes and determining the local cerebral glucose utilization (LCGU) as an indicator of cerebral neuronal activities. Histological examinations of the brain and the sciatic nerve were done. The other six rats were further followed up for 90 days after the termination of exposure (group B). In addition, six rats that received physiological saline served as a control. Group A showed a significant reduction of LCGU without any accompanying cerebral histological alterations and a moderate loss of myelinated fibers in the sciatic nerve. Group B showed normal LCGU rates while severe axonal degeneration of the sciatic nerve was found on the final day of the 90-day follow-up period. The present results demonstrate that a transient involvement of the CNS can occur after MMC exposure. In addition, a complete recovery may occur when the process is mild enough not to cause histological alterations. In contrast, the involvement of the peripheral nerve is much more severe than that of the CNS and it was observed to progress even after the cessation of MMC exposure. Therefore, it seems unlikely, at least in rats, that a steadily progressive course occurs in the CNS but not in the peripheral nerves over a long period of time after MMC exposure.
We studied the effects of the long-term and small-dose administration of methylmercury chloride (MMC) on the cerebral function in rats. MMC, at a dose of 0.7 mg/kg/day, was subcutaneously injected for 85 consecutive days in nine adult male Sprague-Dawley rats. They were then sacrificed on the final day of exposure (MMC group) after both completing observations on behavioral changes and also determining the local cerebral glucose utilization (LCGU) as an indicator of the cerebral neuronal activities. Histological examinations of the brain and the sciatic nerve were also performed. In addition, seven rats who received physiological saline also served as a control. LCGU significantly decreased in the visual cortex, lateral geniculate nucleus and medial geniculate nucleus without any accompanying histological alterations. Severe axonal degeneration of the sciatic nerve was also observed, which corresponded to the previously described crossed leg phenomenon. The present results suggest that the damage to the peripheral nerve was much more severe than that to the brain, which caused behavioral changes. Although no cerebral morphological changes were observed, brain dysfunction showed a selective involvement of the visual and auditory systems. This finding suggests that LCGU is a sensitive method for detecting the subclinical cerebral dysfunction caused by long-term and small-dose MMC intoxication in the rat brain.
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To evaluate the early molecular events of oxidant-induced pulmonary fibrosis, rats were continuously exposed to 0.4 ppm ozone and 7 ppm nitrogen dioxide. The early responses to the combined gases could be divided into three phases. Acute pulmonary inflammation indicated by an increase in pulmonary edema as well as an influx of neutrophils into the airspaces first occurred on days 1 to 3 of the exposure. The pulmonary inflammation was reversed by day 8, and no biochemical or morphologic aspects of tissue responses were detected from days 15 to 45, suggesting that rats adapted to the stimuli during that period. Pulmonary fibrosis could be detected by an increase in the biomarker of lung collagen content at day 60 and by histopathologic evaluation by day 90. Enhanced expression of macrophage inflammatory protein-2 was observed only at day 1, whereas the pulmonary expression of transforming growth factor-beta was upregulated on days 60 and 90 of the exposure. Macrophage expressions of interleukin-1beta and interleukin-6 were enhanced during acute pulmonary inflammation; however, macrophage expression of tumor necrosis factor-alpha was elevated at both day 1 and days 60-90. Activation of nuclear factor-kappa B and increased expression of thioredoxin in the lungs was also observed at day 1 and days 60-90. The expression of antioxidant enzymes, such as manganeous superoxide dismutase and glutathione peroxidase, was not altered during exposure. These results indicate that macrophage activation and the expression of macrophage-derived cytokines may play an important role in the early pulmonary responses against the combined gases.