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This study, along with our previous studies (Yuguchi et al. 2015, 2019a), reveals the hydrothermal alteration processes in a pluton, with a focus on the mass transfer between minerals and hydrothermal fluid. It also depicts the sequential variations in fluid chemistry as alteration progresses. Hydrothermal alteration of the Toki granite in Tono, Japan—the study area of this research—progressed through the successive processes of chloritization, plagioclase alteration, and precipitation of a carbonate. This paper describes the alteration processes of hornblende chloritization, K-feldspar chloritization, and the formation of fracture-filling chlorite through petrography and mineral chemistry. A set of singular value decomposition analyses was conducted to obtain reaction equations for the chloritization processes, which facilitates the quantitative assessment of mass transfer between the reactant and product minerals, and the inflow and outflow of components through the hydrothermal fluid. Several types of chloritization reactions (including biotite chloritization) can be characterized by their reaction with the inflow of Al3+, Fe2+, Mn2+, and Mg2+ and the outflow of H4SiO4, Ca2+, K+, and F–. The age and thermal conditions of hornblende chloritization (64–54 Ma and 330–190 °C), K-feldspar chloritization (68–53 Ma and 350–210 °C), and precipitation of fracture-filling chlorite (66 and 63 Ma, 340 and 320 °C) overlap with those of biotite chloritization (68–51 Ma and 350–180 °C). The chloritization reactions (this study and Yuguchi et al. 2015) and plagioclase alteration (Yuguchi et al. 2019a) represent sequential variations in fluid chemistry at temporal conditions from 68 to 51 Ma as the temperature decreased from 350 to 180 °C. As the alteration proceeds, the concentrations of aluminum, iron, manganese, and magnesium ions in the hydrothermal fluid decrease gradually, and those of calcium, hydrogen, and fluorine ions increase gradually. Hornblende chloritization is associated with formation of magnetite and ilmenite. The thermal conditions of the hydrothermal fluid yielding the formation of magnetite and ilmenite can be interpreted by the chemical characteristics of chlorite around their associated minerals. The formation temperature of magnetite was higher than that of ilmenite, implying a decrease in oxygen fugacity in the hydrothermal fluid with the decrease in temperature from 280–310 to 220–250 °C.

Thalidomide is a TNF-alpha inhibitor and has been administrated for erythema nodosum leprosum (ENL, Type II leprosy reaction) which is one of leprosy reactions and can cause serious illness to patients oflepromatous pole among the immune spectrum. Twenty live cases (at May, 2011) were identified to whom thalidomide had been administrated since 1978 for their ENL reactions. Data were collected from their clinical records in order to evaluate the usage and effectiveness of thalidomide in National Sanatorium Oku-Komyoen, Okayama, Setouchi-city, Japan. Individual data includes bacillary index (BI), total dose, average daily dose, maximum daily dose, minimum daily dose, methods of thalidomide administration and change of symptoms of ENL. Results: No adverse effect was found among 20 cases. Average daily dose of 20 cases was 19 mg. Regarding to the maximum daily dose, in 3 cases (15%) more than 100 mg, in 3 cases (15%) 50 mg, and in 14 cases (70%) less than 40 mg was administrated. Dose was gradually tapered in most cases. From clinical records, thalidomide was found effective for ENL in 19 cases and clinicians concerned were trying to adjust the proper dose of the drug carefully depending on the current symptoms, because there was no guideline of thalidomide administration for ENL. This data suggests that even less than 50-100 mg as the initial daily dose was still effective, though 50-100 mg daily dose is recommended in the current guideline of Japan (2011) and more dose had been administrated in USA and India.

We have examined in leprosy in Bangladesh the change in the rate of peripheral nerve damage before and after the treatment. In the well-organized NGO program where the early diagnose is given, the damage rate improves slightly during the treatment. But among the MB cases, it has been found that the damage rate taken at the time of patient's first check-up still stays high. Furthermore, during the treatment of MB cases, 72% cases show the episode of neuritis, and even during two years of observation period after treatment, 15% cases show the same episode. Among the recurrent cases of last ten years in Oku-Komyo-en, we have looked into the ways of drugs prescribed for the treatment of previous recurrent term in the double recurrent cases. In these prescription, the amount of each dosage was relatively a little and the prescription period was rather long. In RFP, prescription frequency was relatively high, and in DDS and CLF, they were low. We think that the treatment of leprosy in Japan should be based on WHO's regimen. However before making Japanese regimen, it is necessary to discuss more when to finish the treatment.

Spherical bodies, roughly 10 micro m in diameter, which have not been reported before, were found in the peripheral nerve axons of specimens collected during post-mortem examination of leprosy patients. These bodies were found in the fascicles of all peripheral nerves of the extremities examined (median, radial, ulnar, peroneal and sciatic nerves). Their incidence was not related to the type of leprosy. The area immediately below the thickened perineurium, a feature associated with leprosy, often showed a large number of spherical bodies. When observed under a transmission electron microscope, the spherical lesions often showed a lamellar structure, although some of them were amorphous. No structure resembling organelles was seen within the bodies. Observation with the merge technique showed a clearly lamellar structure in most of the spherical bodies. These bodies and the surrounding myelin sheaths were partially polarized. The axonal spherical bodies observed in our study seem to represent lesions gradually formed due to glycoprotein denaturation over long periods of time and to be associated with leprosy-caused thickening of the perineurium of peripheral nerves.

From clinical experiences with the Fontan operation in six cases, a few practical contrivances and operative steps are described. We stress that meticulous care should be taken not to cause any stenotic complication in the outflow tract toward the pulmonary artery, particularly by traction of the right atrial appendage only to achieve a direct anastomosis. Conduit repair would be necessitated by cases in order to expand the indicative criteria vertically as well as horizontally. For conduit material, we used consecutively nonvalved polytetrafluoroethylene that was reinforced by handmade stainless steel wire ring (Gore-Tex, Inc) or by spirally built-in stent (IMPRA, Inc). The latter was eventually useful in obtaining natural curving of the conduit without kinking or compression. Some contrivances in anastomosing a conduit were also proposed to achieve an excellent result. We believe diese practical contrivances will serve for expansion of the indicative criteria and promise improved operative outcome.