Effects of different speeds of induction with sevoflurane on the EEG in Man

The effects of two kinds of induction speed of sevoflurane anesthesia on the EEG pattern were compared in the same individual using medical student volunteers: a first exposure of 4% was given, followed after full recovery, by incremental doses of 1, 2 and 4% successively, each being administered for 10min. The arterial blood level of the anesthetic was measured using gaschromatograph. The changes of EEG pattern during fast induction with 4% were not represented by the abbreviation of those observed during the slow induction with the incremental doses. The administration of 4% induced a sudden appearance of high voltage, rhythmic slow waves of 2–3Hz at 1–3min when the arterial blood anesthetic level increased maximally, which was then followed by a pattern of faster activities of 10–14Hz mixed with 5–8Hz slow waves. In contrast, the administration of incremental doses induced an increase in frequency and amplitude of EEG activities in the light plane, followed by their decreases in deeper planes. The final EEG patterns were identical for both these methods of induction. These findings confirmed our previous hypothesis that not only the arterial blood level of anesthetics but the rate of its increase are important factors determining the EEG pattern of anesthesia.(Avramov MN et al.: Effects of different speeds of induction with sevoflurane on the EEG in man. J Anesth 1: 1–7, 1987)     

Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma

BackgroundExtrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection.MethodsThe participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping.ResultsExtrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively.ConclusionWe have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.     

Deuterium chemical shift imaging for the estimation of cerebral perfusion in rabbit infarction model

In order to develop a new technique for the measurement of local cerebral blood flow (CBF), the deuterium chemical shift imaging (²H-CSI) technique, an application of in vivo nuclear magnetic resonance (NMR), was used for the estimation of cerebral perfusion in rabbit infarction model. The ²H chemical shift images of rabbit brain were obtained every 30 seconds before and after intravenous injection of deuterated saline. The changes in ²H NMR signal intensity documented that the cerebral perfusion in the damaged area due to infarction decreased obviously compared to that in the intact area. These findings indicate that the ²H-CSI technique can be applied to the measurement of local CBF. The readily availability and limited toxicity of deuterated water may make possible to use this method in clinical cases.(Kito K, Arai T, Mori K, et al.: Deuterium chemical shift imaging for the estimation of cerebral perfusion in rabbit infarction model. J Anesth 7: 447–453, 1993)     

Molecular basis of carotid body tumor and associated clinical features in Japan identified by genomic,immunohistochemical, and clinical analyses

Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.     

Boron neutron capture therapy: Preliminary study of BNCT with sodium borocaptate (Na2B1 2H1 1SH) on glioblastoma

To plan the optimal BNCT using BSH for glioblastoma patients, the¹⁰B concentration in tumor and blood was investigated in 11newly diagnosed glioblastoma patients. All patients received 20 mg BSH/kgbody weight 2.5–16 hrs prior to tumor removal. The quantitativedistribution of ¹⁰B was determined by prompt gamma rayspectrometry and/or -track autoradiography. ¹⁰Bdistribution in tumors was heterogeneous, ± 25% of scatteringat the microscopic level, and the distribution was also heterogeneous at thetissue level. ¹⁰B concentration in blood decreased inbi-exponential decay as a function of the time after the end of theadministration. The T/B ratio showed non-exponential increase with largevariation. The maximum T/B ratio would be around 1. The tumor/normal brain(T/N) ratio of ¹⁰B concentration was 11.0 ± 3.2. The¹⁰B content in normal brain is originated in vascular¹⁰B in parenchyma, since the ¹⁰B content innormal brain to blood (N/B ratio) being compatible with the blood content inparenchyma. These values allow for BNCT, using thermal neutrons, on braintumors located less than approximately 3.3 cm in depth from the brainsurface of neutron incidence, providing that the dose on the normalendothelium is controlled to less than the tolerance limit. In ourpreliminary study of BNCT, a 31% 3-year survival was achieved overall for 16 glioblastoma patients and a 50% 2-year survival wasachieved on 8 glioblastoma patients in our recent dose escalation studybased on these data.     

Surgical treatment of the so-called "galloping type" small size carcinoma of the lung]

We experienced twelve cases of non-small cell carcinoma of the lung of the so-called "galloping type" small size carcinoma (less than or equal to 2 cm). Ten cases presented with mediastinal lymph node metastasis and two cases with distant metastasis. Solitary lymph node metastasis observed in almost half of the cases and lymph node metastasis in peculiar lymphatic regions (#3 a) seen in two cases, were the prominent characteristics of the lymphatic pathway dissemination showed by this type of cancer in advanced clinical stage. The prognosis was good, with 3 years and 5 years survival rate of 72.2% and 54.1% respectively. According to these results, we consider that, if the clinical stage is favorable, the surgical treatment must be indicated in all cases of these advanced small size carcinoma of the lung.     

Concurrent deletion of BMP4 and OTX2 genes,two master genes in ophthalmogenesis

BMP4 and OTX2 are master genes in ophthalmogenesis. Mutations of BMP4 and OTX2 often lead to eye defects, including anophthalmia–microphthalmia. A significant degree of variable expressivity has been reported in heterozygous individuals with BMP4 or OTX2 mutation. Interestingly, both BMP4 and OTX2 reside on 14q22, being only 2.8 Mb apart. Previous studies reported that among three patients with 14q22 deletion involving BMP4 and OTX2, all had severe eye defects. The minimal degree of variable expressivity among these individuals who were doubly deleted for BMP4 and OTX2 could be attributed to the combinatorial relationship of the two genes observed in animal models. We herein report a patient with a concurrent deletion of BMP4 and OTX2 who exhibited bilateral microphthalmia, more specifically, anterior segment dysgenesis with microcornea. Evolutionarily conserved physical linkage of Bmp4 and Otx2 loci may suggest an advantage of the proximal alignment of the two genes. Another striking feature in the propositus was the progressive white matter loss observed by serial neuroimaging. A review of twelve previously reported patients with 14q22 microdeletion revealed decreased white matter volume in half of the patients. It remains to be elucidated whether the white matter lesion is age-dependent and progressive. In conclusion, anterior segment defects of the eyes, especially when accompanied by decreased white matter volume on neuroimaging, should raise the clinical suspicion of 14q22 microdeletion.