Considerations on the Factors Influencing Living Kidney Donors' Autonomous Decision-Making: A Systematic Literature Review.

As outcomes of organ transplantation have improved with advances in medicine, managing medical ethics issues has become increasingly more important. Although a basic consensus has been formed on the respect of autonomy in decision-making by prospective donors regarding living kidney transplantation, concrete and practical measures at the clinical site are required to ensure donor autonomy. The aim of the study was to identify elements related to autonomy in the kidney donor decision-making process. METHODS: We systematically collected relevant studies from multiple databases in and out of Japan and conducted qualitative and inductive analyses. RESULTS: The identified elements were categorized into 12 subcategories and then regrouped into the following 4 categories based on the similarity of the contents: donor personality and values, inability to fully understand the implications of donation, possibility of direct pressure on donor's decision-making process, and donor's environment and situation. DISCUSSION: The autonomy-related elements were highly diverse, including obvious pressure upon the donor and their values as well as influences from health care professionals. Some elements had room for change, such as the informed consent procedure, while some elements were unchangeable. Other elements were changeable by intervention, but discussion is required about the appropriateness of the intervention itself. Further, a classification of clinical approach was suggested by the development of an analytical framework using 2 axes of "site where the element arises" and "room for change" based on the practical viewpoint of clinical circumstances.

Twenty Years After Enactment of the Organ Transplant Law in Japan: Why Are There Still So Few Deceased Donors?

BACKGROUND: Twenty years have passed since the 1997 enactment of the Organ Transplant Law in Japan, but the number of deceased donors remains extremely low. In this study we examine why deceased donation has continued to remain so infrequent. METHODS: This investigation was a secondary analysis of published data from the Japan Organ Transplant Network, 2016 Fact Book of Organ Transplantation in Japan, and International Registry on Organ Donation and Transplantation. RESULTS: In the past 20 years, donation intent declarations, knowledge, and respect for family member's wishes have increased, whereas resistance toward transplantation has decreased. Despite this, the traditional perspective on corpses of gotai manzoku (ie, the soul cannot be put to rest without being physically intact and without defect), the family-centricism, and reward-seeking altruism have not changed much. Living organ transplants have alleviated the organ deficiency somewhat, and the law requiring family consent seems to have contributed to the observed small increase in deceased donors. CONCLUSION: The number of deceased donors is unlikely to increase suddenly. However, 8 strategies are proposed to increase the number of deceased donors, including: increasing the number of donor procurement coordinators and establishing a training system; increasing the number of organ procurement facilities; creating hub transplant centers and training transplant surgeons; implementing radical reform in public education; reducing workload and improving education of emergency physicians, neurosurgeons, and pediatricians; revisiting the stringent standards of brain-death determination; revisiting the registration process; and considering development of a Japanese version of organ procurement organizations as well as revisions to the Organ Transplant Law. The Japanese government and academic societies must work together to increase the number of deceased donors in Japan.

A case of minimal change nephrotic syndrome with acute renal failure complicating Hashimotoâs disease.

A 63-year-old man was admitted to our hospital for evaluation of generalized edema. Coexistence of severe hypothyroidism and nephrotic syndrome was detected by laboratory examination. High titer of both antimicrosomal antibody and antithyroid peroxidase antibody indicated Hashimotoâs disease. Renal biopsy showed minimal change glomerular abnormality, but no findings of membranous nephropathy. A series of medical treatments, including steroid therapy, thyroid hormone and human albumin replacement therapy, were administered. However, acute renal failure accompanied by hypotension, was not sufficiently prevented. After 9 sessions of plasmapheresis therapy, the severe proteinuria and low serum albumin levels were improved. Even after resting hypotension was normalized, neither renal function nor thyroid function were fully recovered. After discharge, renal function gradually returned to normal, and the blood pressure developed into a hypertensive state concomitant with the normalization of thyroid function. This report is a rare case of autoimmune thyroid disease complicated with minimal change nephrotic syndrome. In most cases of nephritic syndrome, acute renal failure (ARF) has been reported to coexist with hypertension. Although pseudohypothyroidism is well-known in nephrotic pathophysiology, complications of actual hypothyroidism are uncommon. It is suggested that the development of hypotension and ARF could be enhanced not only by hypoproteinemia, but also by severe hypothyroidism.

The efficiency of X-ray microanalysis in low-vacuum scanning electron microscope: deposition of calcium on the surface of implanted hydrogel intraocular lens (IOL).

To examine the calcification of implanted hydrogel IOL by X-ray microanalysis, we compared conventional transmission electron microscopy (TEM) with low-vacuum scanning electron microscopy (SEM). We also compared metal coating with non metal coating in low-vacuum SEM. Calcification of IOL showed deposits which were located in the superficial substance of lens. In conventional TEM and X-ray microanalysis, calcium, phosphate and silicon were detected in the deposits. In low-vacuum SEM, the deposits detected in metal coating were calcium, phosphorus, sodium and magnesium, but not silicon. However, in non metal coating, the deposits contained not only calcium, phosphorus, silicon, sodium and magnesium, but also fluoride, aluminum and argentums. It was concluded that in conventional TEM where a specimen is fixed and dehydrated in ethanol, various elements leak out. On the other hand, when a specimen is coated with carbon and gold palladium for SEM, light elements might not be detected in X-ray microanalysis. Low-vacuum SEM preparation does not need metal coating and low-vacuum SEM appears to provide a highly efficient method for X-ray microanalysis.

Combined treatment with nafamostat mesilate and aspirin prevents heparin-induced thrombocytopenia in a hemodialysis patient.

We report on the management of a 36-year-old hemodialysis patient with heparin-induced thrombocytopenia (HIT, type II) and clot formation in extracorporeal circulation. Platelet aggregation test and measurement of anti-platelet factor 4/heparin complex antibody by enzyme-linked immunosorbent assay revealed to us that our patient had developed HIT. Instead of heparin, we used nafamostat mesilate (NM) as an anticoagulant during hemodialysis, but could not completely prevent HIT-induced thrombocytopenia or clot formation in the extracorporeal circuit. Combined use of NM and aspirin completely inhibited platelet aggregation, decrease in platelet count and clot formation in the extracorporeal circuit.

[Effect of paclitaxel on cisplatin resistant head and neck squamous multicellular tumor spheroids].

Paclitaxel has been reported to be effective for the treatment of CDDP resistant tumors. Thus, the efficacy of paclitaxel on CDDP resistant HEp-2 and KB head and neck squamous carcinoma cell lines was evaluated in monolayer and multicellular tumor spheroids (MTS). Cell lines with a tenfold resistance to CDDP were used in this study (Tanaka, K. et al, Keio J Med, 70. 1993). MTS were developed using the liquid overlay culture technique. After exposure to graded concentrations of drugs and different exposure time, the cells were subjected to a clonogenic assay. The effect of paclitaxel on both monolayer and MTS was dependent on the drug concentration and related to the exposure time. For HEp-2 MTS, 10(-7) M/L of paclitaxel resulted in a cell death rate of approximately 90% in both parent and resistant cells. For KB MTS, the cells were more resistant to paclitaxel than the HEp-2 cells, and a 72 hour exposure time was needed to achieve a cell death rate of approximately 90%. These data suggest that paclitaxel may be effective for treating CDDP resistant head and neck cancer.

Glucose-6-phosphate dehydrogenase cytochemistry using a copper ferrocyanide method and its application to rapidly frozen cells.

We describe an improved copper ferrocyanide-based method for cytochemical detection of glucose-6-phosphate dehydrogenase (G6PD), which was used to localize the enzyme within the ultrastructure of rat hepatocytes and adrenocortical cells. With this method, glutaraldehyde fixation and the addition of exogenous electron carriers (for example, phenazine methosulfate) to the cytochemical reaction medium were essential. Copper ferrocyanide reaction product showing the distribution of G6PD was readily recognized at the light microscopic level as Hatchett's brown staining and at the electron microscopic level as electron-dense deposits. Within stained regions, enzyme cytochemical G6PD activity was found to be associated with ribosome-like structures. Because G6PD is a soluble, cytosolic enzyme, its displacement or extraction may occur during conventional fixation. We, therefore, combined a rapid-freezing technique with G6PD enzyme cytochemistry. The resultant rapid-freezing enzyme cytochemistry enabled us to show the subcellular distribution of G6PD in a more life-like state; the localization of G6PD in rapidly frozen cells was in substantial agreement with that in conventionally fixed cells.

Ultrastructural observations of astrocyte end-feet in the rat central nervous system.

Astrocytic end-feet in the rat CNS were studied by thin section electron microscopy. Astrocyte processes that enclose neuronal elements extended to blood vessels and the pia mater, where the processes expanded to form end-feet or glial limiting membranes. At the end-feet, cell junctions such as gap junctions and desmosome-like junctions were formed between the astrocyte processes. The end-foot plasma membrane facing the basal lamina was undercoated with electron-dense, layered materials, with an internal substructure of filamentous networks, with which bundles of glial filaments (GFs) appeared to be closely associated via fine filamentous structures, often showing a hemi-desmosome-like appearance. In specimens treated with Triton X-100, the internal substructure of the undercoat was better visualized and the association with GFs was well preserved. At the end-feet, some unique tubular structures were found in spatial relationship to the plasmalemmal undercoat. Plectin visualized by immunofluorescence was localized to astrocytes and their processes, especially at the end-feet facing the pia mater. Immunoelectron microscopy located plectin on fine filamentous structures lying between GFs and the plasmalemmal undercoat. These observations suggest that plasmalemmal undercoats at the astrocyte end feet may serve as attachment sites of GFs to the plasma membrane and that plectin may be involved in such attachment.

Immobilization of rat hepatocytes on multiporous microcarriers with larger pores and their metabolic activity.

We have investigated the availability of multiporous microcarriers (MCs) for immobilizing isolated rat hepatocytes, but the pore size of MCs was too small (35 microns) for hepatocyte immobilization. In this study, we immobilized isolated rat hepatocytes on MCs with larger pores, and evaluated their metabolic activity. Isolated hepatocytes were immobilized on MCs precoated with collagen by the intermittent stirring method and by aspiration, and the cell-protein content per 100 mg MCs was determined for comparison of these methods. Metabolic activity was evaluated by analyzing NH3 metabolism, urea nitrogen synthesis and glucose synthesis. The aspiration method immobilized significantly more of hepatocytes on MCs than the intermittent stirring method (p < 0.05). A stationary culture of hepatocytes immobilized on MCs showed a similar NH3 metabolism to monolayer cultured hepatocytes, and hepatocytes immobilized on MCs in a floating culture showed significantly higher NH3 metabolism than those in a stationary culture (p < 0.01). However, monolayer cultured hepatocytes showed higher glucose synthesis than hepatocytes immobilized on MCs in a stationary culture (p < 0.01). In conclusion, hepatocytes immobilized on MCs proved to be useful as a bioreactor in a hybrid artificial liver.

[Chemotherapy of head and neck cancer].

Squamous cell carcinoma of the head and neck is a chemotherapeutically responsive tumor. Methotrexate, cisplatin, 5-fluorouracil and bleomycin in various combinations have achieved tumor regression, with complete or partial response, in 60-90% of previously untreated patients. The response to chemotherapy, however, is often short-lived, and conventional treatment has produced little impact on survival. To date, neo-adjuvant and/or adjuvant chemotherapy have also failed to demonstrate any impact on the survival rate, although subset analysis has indicated a possible survival benefit. Furthermore, larynx preservation and reduction in incidence of metastasis have been demonstrated. Concomitant chemoradiotherapy has some positive results in disease free survival and/or overall survival. In this report, we reviewed the literature on neoadjuvant chemotherapy, adjuvant chemotherapy, salvage chemotherapy and concomitant chemoradiotherapy for advanced head and neck cancer, and analyzed their efficacy.

Occurrence of fasciculated microtubules at nodes of Ranvier in rat spinal roots.

Fascicles of microtubules, previously considered to be unique to the initial segments of myelinated axons, were found at nodes of Ranvier of sensory and motor axons in rat spinal roots, though their occurrence was limited to the proximal portion of the axons. No fasciculated microtubules were noticed in the internodes of myelinated axons or in unmyelinated axons. In transverse sections, microtubules in fascicles were characteristically cross-linked by short filamentous strands at a centre-to-centre distance of 36-40 nm. In sensory axons, the density of fasciculated microtubules at the node of Ranvier was 45-48% at the level of the dorsal root ganglion and decreased progressively as thin sections were made more distal to the ganglion in both directions. In motor axons, microtubule-fascicles involved about 24% of the microtubules in the ventral rootlets, but they were rarely seen in distal portions of the ventral roots. No fasciculation of microtubules was discerned in the sciatic and saphenous nerves. These findings suggest that cross-linking protein(s) for fasciculation, which are synthesized in the perikaryon and primarily used for the initial segment, may be further transported to fasciculate microtubules at some proximal nodes of Ranvier.

Induction chemotherapy with cisplatin, etoposide, and mitomycin-C (PEM) regimen in advanced cases with cancer of pharynx and oral cavity.

With the aim of improving survival rate in advanced head and neck cancer, we scheduled 26 patients to receive PEM regimen. This regimen consisted of cisplatin (CDDP)(P), etoposide (VP-16)(E), and mitomycin-C (MMC)(M) (CDDP 60 mg/ m2/2 hr infusion on day 1; VP-16 40 mg/m2/1 hr infusion on days 1-3; MMC 7 mg/m2 iv bolus on day 1). Of 25 patients evaluable for response, 8 complete response (CR), 14 partial response (PR) were achieved, with an overall response rate (RR) of 88%. Myelosuppression was major side effect and thrombocytopenia (23% greater than WHO grade) was dose limiting toxicity. Other adverse reactions including mucositis were all mild and transient. Since limited mucosal toxicity, full course of following treatment including radiotherapy and/or surgery could be done satisfactorily. We concluded that this regimen produced beneficial effect as the adjuvant setting in patients with cancer in pharynx and oral cavity because of limited mucosal toxicity.