Search PubMed⌕ Search

Biomedical subjects

H Kubo

Publications and source records attributed to H Kubo.

At least 163 records · Page 9Linked to original sources

Clinical significance and time course of antibodies to glutamic acid decarboxylase in Japanese children with type I (insulin-dependent) diabetes mellitus.

Although anti-glutamic acid decarboxylase antibodies (GADAb) have been reported to be a useful diagnostic and predictive marker of insulin-dependent diabetes mellitus (IDDM, type 1 DM) in Caucasians, a precise analysis of GADAb in Japanese children has not been reported. We examined the clinical significance and time course of GADAb in Japanese IDDM children, who have different genetic backgrounds from Caucasians. Twenty-three of 34 (67.6%) sera from recent-onset (< 6 months) IDDM, and 16 of 49 (32.7%) sera from long-standing (> or = 2 years) IDDM patients were positive for GADAb. This prevalence of GADAb in IDDM patients was significantly higher than in normal controls and the other groups including non-insulin-dependent DM, autoimmune thyroid disease and congenital hypothyroidism, and was also significantly higher in recent-onset than in long-standing IDDM. Time course analysis suggested that autoimmune response against GAD could follow different courses in individual cases after the initiation of insulin therapy. The incidence of GADAb was significantly higher in females than in males in the older age group (11-15 years). Other clinical features including residual pancreatic beta-cell function after diagnosis were demonstrated to be similar between GADAb-positive and -negative patients. In conclusion, this study using the newly established radioimmunoassay (RIA) for GADAb revealed a high prevalence of autoimmune reactivity to GAD in Japanese IDDM children. These results, using this RIA procedure, might assist in laying the groundwork for future trials of immunomodulation therapy for IDDM in Japan.

Adolescent↗

Enhancement of oral bioavailability and pharmacological effect of 1-(3,4-dimethoxyphenyl)-2,3-bis(methoxycarbonyl)-4-hydroxy-6,7,8- trimethoxynaphthalene (TA-7552), a new hypocholesterolemic agent, by micronization in co-ground mixture with D-mannitol.

To improve the bioavailability of the sparingly water-soluble drug, 1-(3,4-dimethoxyphenyl)-2,3-bis(methoxycarbonyl)-4-hydroxy-6,7,8- trimethoxynaphthalene (TA-7552), the usefulness of the co-grinding method with D-mannitol was investigated. The co-grinding was performed at various weight ratios of TA-7552 and D-mannitol using a ball mill. The particle size was markedly reduced with increasing amount of D-mannitol. A mixture ratio greater than or equal to 1:3 of the drug and D-mannitol produced submicron-sized particles. In dogs, bioavailability increased with increasing amount of D-mannitol. The 1:9 co-ground mixture gave complete absorption, as did a lecithin solution of the drug. Even co-ground powders with lower amounts of D-mannitol provided relatively high bioavailability in comparison with ground drug powder alone of a similar particle size. Further, pharmacological examination using rats indicated that the inhibition of cholesterol absorption was intestified with the reduction of particle size. These findings suggest that the co-grinding method with D-mannitol is useful for enhancing the bioavailability and pharmacological effectiveness of this sparingly water-soluble drug.

Animals↗

The usefulness of ultrasonic microprobe imaging for endoscopic variceal ligation.

OBJECTIVES: This study investigated whether ultrasonic microprobe (UMP) imaging was useful in judging the therapeutic effect of endoscopic variceal (EVL) on varices as well as assessing varices and surrounding vessels before and after EVL. METHODS: UMP imaging was performed repeatedly safely and easily via the biopsy channel of an endoscope in 20 patients with esophageal varices. Using this modality in combination with our method of "intensive ligation," we treated esophageal varices successfully. RESULTS: Before EVL, UMP imaging displayed esophageal varices, periesophageal collaterals, and the azygous vein as echo-free lumens. In 15 of 20 patients, UMP imaging clearly detected the perforating vein, one of the optimal ligation sites for EVL, connecting the varix and collateral vein. Just after EVL, UMP imaging revealed a hyperechoic change ("snow ball" sign or "snow channel" sign), indicating blood flow stasis in the esophageal varices. On subsequent EVL, UMP imaging showed the cross-sectional area of varices was undetectable (occluded) or partially detectaable. After repeated EVL (2.9 treatment sessions on average), UMP imaging, as well as endoscopy, indicated that almost all varices were eradicated (undetectable). However, UMP imaging demonstrated that neither collaterals nor the azygous vein had significantly changed in size. CONCLUSIONS: This modern diagnostic modality provided a clinical adjunct to current endoscopy when observing esophageal varices and surrounding vessels before and after EVL to determine the need for additional therapy.

Aged↗

The effect of ultra-low sodium dialysate in CAPD. A kinetic and clinical analysis.

In peritoneal dialysis, sodium (Na) passes through the peritoneal membrane to a lesser extent than H2O and thus hypotonic fluid is removed indicating that Na removal is inefficient. Therefore we developed an ultra-low Na dialysate (ULNaD) [Na 98 mmol/liter, osmolality 340 mOsm/kg, glucose (G), 2.48%] to facilitate trans-peritoneal Na removal. The aim of the study was to examine (a) the fluid and Na kinetics of this solution, and (b) the clinical effect in the overhydrated patient. Regarding the former, in six cases, changes in the effluent Na levels during a 240-minute dwell of ULNaD were measured at 60-minute intervals. In eighteen cases, the transperitoneal net-Na removal (Na removal) and drained ultrafiltration (UF) volume after a 240-minute dwell of ULNaD were measured and compared to two types of standard Na dialysate (SNaD) [Na 132 mmol/liter, 1.36% G (348 mOsm/kg) and 2.27% G (396 mOsm/kg)]. The effluent Na levels increased gradually until the end of the dwelling. Drained UF volume of ULNaD (224 +/- 25 ml) was more than 1.36% G SNaD (77 +/- 33 ml, p < 0.01), but it was less than 2.27% G SNaD (341 +/- 32 ml, p < 0.01). However, a significant increase in Na removal by ULNaD (78.1 +/- 5.6 mmol) was found compared with both SNaD solutions (12.6 +/- 6.4 mmol in 1.36% G solution, p < 0.001; 27.8 +/- 5.1 mmol in 2.27% G solution, p < 0.001, respectively). Regarding the latter study aim, in six overhydrated patients with a Na excess, SNaD was replaced with ULNaD once a day for 7 consecutive days. At the end of the study as compared to the pre-values, a significant reduction in body weight (-2.5 +/- 1.0%, p < 0.05) and mean arterial pressure (-12.3 +/- 3.5%, p < 0.001) was observed. An increased drainage of daily UF volume (+86.5 +/- 31.1%, p < 0.05) and a markedly increased daily Na removal (+131.1 +/- 24.2%, p < 0.01) were also observed. The results of this study suggest that ULNaD actually facilitates trans-peritoneal Na removal mainly by diffusion force, and that ULNaD could benefit overhydrated patients with a Na excess.

Adult↗

Is atherosclerosis accelerated by CAPD?

Cardiovascular complications in renal replacement therapy remain prevalent today. The question, "Is atherosclerosis accelerated in peritoneal dialysis (PD) patients," has not been resolved. Many cross-sectional studies have revealed that there are more atherogenic lipid profiles in continuous ambulatory peritoneal dialysis (CAPD) than in other dialytic modalities. However, it is not certain that CAPD per se may contribute to lipid abnormalities in continuing PD for a long time. Therefore, we tried to assess whether CAPD itself may change lipid profiles in the long-term period on CAPD. We measured conventional lipid profiles in 16 stable CAPD patients in whom total cholesterol (T.chol.) levels remained under 240 mg/dL at the time of starting observation. Diabetic end-stage renal disease (DMESRD) patients were excluded from this study. Blood sampling was performed under strict conditions indicating overnight fasting with 10 hours dwell of 2 L of 1.5% Dianeal. Plasma levels of T.chol., triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and atherogenic lipoprotein (apo B/A-I) did not show significant changes by serial measurements from the sixth month to the thirtieth month following the commencement of CAPD as their initial dialysis treatment. Recently it is reported that high plasma levels of Lp(a) lipoprotein are an independent risk factor in cardiovascular events in renal replacement therapy because Lp(a) has a close relation to intravascular thrombosis and acceleration of atherosclerosis. We found that the incident of vascular accidents was five episodes among 33 patients with higher (> 31 mg/dL) Lp(a) levels, while there was only one episode in 45 patients with lower (< 30 mg/dL) Lp(a) levels (p < 0.05, odds ratio: 7.9). However, severity of aortic calcification and incidence of positive treadmill test showed no difference in these two groups. No significant correlation was observed between duration on CAPD and plasma Lp(a) levels. From the fact mentioned above, we speculate that CAPD does not essentially affect lipid profiles if determined under the strict condition of blood sampling. In order to evaluate the atherosclerosis noninvasively, we have measured aortic pulse wave velocity (AoPWV) in 33 stable CAPD patients excluding those with DMESRD by two years' interval. Fifteen cases (46%) increased in AoPWV, however, lipid profiles did not differ from those of nonadvanced patients. Calcification of arteries is further evidence of acceleration in atherosclerotic change. Therefore, we have graded severity of abdominal aortic calcification into three categories: grade I denoted nil calcification, grade II denoted patchy calcification, and grade III denoted calcification along the entire abdominal wall, having a lead-pipe shape by lateral view of plain abdominal x-ray film. There were significant differences in the duration of CAPD (grade I: 41 months, grade II: 60 months, grade III: 68 months). AoPWV showed least in the grade I group, faster in grade II, and fastest in grade III, while lipid profiles did not show significant differences in three categories. From the analysis of serial changes of lipid profiles, AoPWV and aortic calcification, CAPD may present some risk of accelerating atherosclerosis, at least in some patients on long-term treatment. Risk factors contributing to acceleration of atherosclerosis is result not from lipid abnormalities, but from other factors which remained to be seen, for example, abnormalities in calcium metabolism.

Adult↗

Low calcium (1.25 mmol/L) dialysate can normalize relative hypoparathyroidism in CAPD patients with low bone turnover.

Recently, several reports have suggested that there is a higher incidence of low turnover bone in the absence of aluminium exposure in peritoneal dialysis patients than in hemodialysis patients. Relative hypoparathyroidism with mild hypercalcemia, induced by a positive calcium balance, is considered to be one of the major causes of this disorder. Thus, we recruited 9 continuous ambulatory peritoneal dialysis (CAPD) patients with relative hypoparathyroidism and low bone turnover [intact parathyroid hormone (iPTH) < 50 pg/mL, intact osteocalcin < 10.0 ng/mL] who had been prescribed 1.75 mmol/L calcium (Ca) dialysate for 5.0 +/- 0.3 years. They were then treated by low Ca (1.25 mmol/L) dialysate for nine months without vitamin D and aluminum administration. Intact PTH and bone metabolic markers [intact osteocalcin, alkaline phosphatase (ALP)] were measured every three months. Intact PTH levels increased from 21.1 +/- 3.8 to 159.2 +/- 32.8 pg/mL after the first three months; thereafter, those levels were maintained at around 150 pg/mL. On the other hand, intact osteocalcin levels rose consecutively from 6.7 +/- 1.2 to reach 22.0 +/- 3.8 ng/mL after nine months. Interestingly, the pattern of time course changes between PTH and intact osteocalcin was different. ALP activity did not change during the nine-month period. Corrected serum calcium was significantly decreased (p < 0.001) to approximately 0.25 mmol/L within one month, and the level remained almost the same thereafter. The serum phosphate level did not change without adjusting the original dose of calcium carbonate as a phosphate binder. We concluded that low Ca dialysate (1.25 mmol/L) is effective for the treatment of CAPD-related hypoparathyroidism with low bone turnover.

Aged↗

[Function testing of bronchial responsiveness].

Asthma patients have bronchial hyperreactivity compared with normal subjects. The pathophysiological characteristics of bronchial asthma show the reversible bronchial obstruction (air-flow limitation) caused by several physical and chemical stimuli. Thus, it is important to verify the bronchial responsiveness for diagnosis of bronchial asthma. Function testing of bronchial responsiveness is one of the bronchial reactivity tests which is important for the diagnosis of bronchial asthma as well as the judgment of severity, therapeutic effect and the differential diagnosis. Function testing of bronchial responsiveness consists of 2 major parts : 1) standard method of acetylcholine or histamine inhalation test 2) direct-writing recorder of the dose-response curves of the airway to methacholine test (Astograph).

Acetylcholine↗

[Continuous ambulatory peritoneal dialysis ameliorated metabolic disturbances of a patient with chronic renal failure caused by glycogen storage disease type I].

A 30-year-old woman with chronic renal failure (CRF) due to glycogen storage disease Type I (GSD I) was admitted for dialysis. Hemodialysis (HD) was introduced as the primary therapeutic modality. However, maintenance HD was very difficult to conduct because of hypotension during the HD sessions. Furthermore, hypoglycemia and metabolic disturbances persisted. After changing from HD to CAPD, fasting blood sugar was significantly elevated through a continuous glucose supply from the dialysate. The values of ketone, non-esterified fatty acid, blood urea nitrogen/creatinine (BUN/ Cr), and glucagon were improved. CAPD not only controlled uremia, but also ameliorated the metabolic disturbances of GSD I. Therefore, we conclude that CAPD is superior to HD as a dialytic modality for patients with CRF due to GSD I.

Adult↗

[Evaluation of nutritional status of patients on continuous ambulatory peritoneal dialysis (CAPD) by dual photon energy X-ray absorptiometry (DEXA)].

Malnutrition is a serious complication in patients on long-term CAPD treatment. Accordingly, quantitative evaluation of nutritional status is a critical issue. This study aimed to assess nutritional status by dual photon energy x-ray absorptiometry (DEXA) in CAPD patients. Total lean body mass (D-TBM), right arm lean mass (D-RAM) and body fat percent (D-% FAT) measured by DEXA were compared with mid-arm muscle circumference (MAMC) and body fat percent (AP-% FAT) measured by anthropometrics (AP) in 51 CAPD patients. The subjects were stratified into groups by gender, age, duration on CAPD, and diabetes mellitus or non-diabetes. There was significant correlation between D-TBM, D-RAM and MAMC (r = 0.519, p = 0.001, r = 0.545, p = 0.001) or D-% FAT and AP-% FAT (r = 0.763, p = 0.0001). However, in the groups of females with over 50 years and over 48 months of dialysis duration, there was no correlation between D-TBM, D-RAM and MAMC. The DEXA method is useful in the quantitative evaluation of nutritional status of dialysis patients serially.

Absorptiometry, Photon↗

Neutrophil emigration in the lungs.

Neutrophil emigration into the lung occurs in response to inflammatory mediators in the interstitium and the airspace. Emigration through the pulmonary microvasculature occurs through two pathways, one that requires CD11/CD18 and ICAM-1 and one that does not: Which pathway is utilized is determined by the stimulus. The ability of a stimulus to upregulate ICAM-1 by inducing the production of pro-inflammatory cytokines including TNF-alpha appears to determine the selection of the CD11/CD18, ICAM-1, ICAM-1-dependent pathway Recently, a third pathway has been identified that requires CD11/CD18 but not ICAM-1. The ligand for this pathway, as well as the ligands for CD11/CD18, ICAM-1-independent adhesion have not been identified. During recurrent pneumonia, the adhesion molecules required for emigration are different than those utilize during acute inflammation in previously normal lung tissue. For example, studies investigating the role of CD11/CD18 in recurrent pneumonia induced by P. aeruginosa, a stimulus which elicits CD11/CD18-dependent emigration initially, showed that when the organisms are instilled at the same site 7 days after the initial instillation, most emigration occurs through CD11/CD18-independent mechanisms. These studies suggest that when an acute stimulus is placed at a site of resolving inflammation, new pathways of adhesion are recruited. Whether these molecules are the same ones mediating acute CD11/CD18-independent adhesion remains to be determined. In summary, neutrophil emigration in the lung can occur through several adhesion pathways, which pathway is utilized can change during the inflammatory process, and cytokines participate in the selection of the pathway.

Animals↗

Structural analysis of mono- and bis-sulfated glycosphingolipids by negative liquid secondary ion mass spectrometry with high- and low-energy collision-induced dissociation.

Several underivatized mono- and bis-sulfated glycosphingolipids having gangliotriaose or gangliotetraose core structure were analyzed by negative liquid secondary ion mass spectrometry (LSIMS) with high- and low-energy collision-induced dissociation (CID). In the normal negative LSIMS spectra, each mono-sulfated glycolipid gave abundant [M - H]- ions and each bis-sulfated glycolipid gave abundant [M + Na - 2H]- ions as well as the hydrogen sulfate anion [OSO3H]-. In high-energy CID spectra of the deprotonated molecule, only ions containing a sulfate ester were clearly observed. When a sulfate was present on the non-reducing terminal saccharide residue, a series of ions corresponding to sulfated mono- to tetra-saccharides, resulting from sequential cleavage of glycosidic bonds, were observed. If the sulfate was attached to an internal hexose of the sugar chain, the product ions corresponding to the non-sulfated, non-reducing terminal residue were absent. In contrast, the low-energy CID resulted in extremely simple spectra that contained only one or two major product ions characteristic of each sulfated glycolipid. These results provided clear information on the overall sugar and ceramide compositions, and allowed saccharide structures differing in location and number of sulfate esters to be distinguished.

Animals↗

Expression, purification, and characterization of the recombinant proform of eosinophil granule major basic protein.

The cDNA for the highly toxic eosinophil granule major basic protein (MBP) encodes a 25-kDa acidic precursor (proMBP) that is processed to form the 14-kDa mature MBP. To characterize the biochemical and biological properties of proMBP, and compare these to the known properties of MBP, we expressed recombinant proMBP in Chinese hamster ovary cells and purified the secreted form from supernatants. We developed a mAb specific for proMBP, J163-15E10, and by using a proMBP-specific RIA we found that recombinant proMBP was expressed quite efficiently at levels between 10 and 100 mg/l. By SDS-PAGE and immunoblotting analyses of bulk Chinese hamster ovary supernatants, recombinant proMBP was electrophoretically heterogeneous with an apparent molecular mass ranging from 3 x 10(4) to 1 x 10(5) daltons. Despite difficulties encountered because of the extreme molecular heterogeneity of the proform, two methods for purification of a predominant 33-kDa form of recombinant proMBP are presented. Glycosylation analysis of purified 33-kDa proMBP indicated that approximately 5 kDa is likely accounted for by the addition of one glycosaminoglycan group, three O-linked, and one N-linked complex type carbohydrate groups. Functional studies of purified recombinant proMBP were also conducted. Using amounts of proMBP determined to be optimal for MBP activity, it was shown that proMBP not only lacked the ability to inhibit protein synthesis in K562 cells, but it also lacked the ability to stimulate basophil histamine release or generate neutrophil superoxide anion release. Furthermore, proMBP inhibited in a dose-responsive manner the basophil histamine release and superoxide anion generation stimulated by MBP. The development of a mAb and RIA specific for proMBP will now make it possible to analyze biologic fluids for the presence of this protein, especially in pregnancy, when proMBP is increased.

Amino Acid Sequence↗

Localization of neurovirulence determinant for rats on the S1 subunit of murine coronavirus JHMV.

A cloned virus of murine coronavirus JHMV, cl-2, was shown to be highly neurovirulent for rats in comparison with other JHMV variants. We have isolated cl-2-derived variant viruses resistant to neutralization by monoclonal antibodies (MAbs) specific for the spike (S) protein of cl-2. The variants MM6 and MM13, selected by the MAbs specific for the JHMV S protein, were revealed to have a point mutation located within the N-terminal 100 amino acids (aa) of the S1 protein. The variants MM56, MM85, and MM78, selected by MAbs specific for the larger S protein of JHMV, were shown to have a deletion composed of about 150 aa located in the middle of the S1 subunit (MM56 and MM85) or one amino acid deletion, aspartic acid at number 543 from the N-terminus of the S1 (MM78). These five MAb-resistant variants were not different from cl-2 in growth pattern on cultured DBT cells. MM6 and MM13 were shown to be highly neurovirulent for 4-week-old Lewis rats, growing to high titers in the brain and causing as high an incidence of neurological disease and death as the parental cl-2. In contrast, MM56 and MM85 were nonneurovirulent for rats. They did not cause any central nervous system disorders nor did they multiply in the rat brains. MM78 showed intermediate neurovirulence as well as intermediate growth potential in the rat brain. However, there was no apparent difference in neurovirulence between the parental and the MAb-resistant variants for mice; all of these viruses showed high neurovirulence for mice. These results suggest that the domain composed of about 150 aa in the middle of the S1 is critical for high neurovirulence of JHMV for rats. Furthermore, it is suggested that the neurovirulence of cl-2 for mice is controlled by a different viral factor.

Animals↗

Neurovirulence for rats of the JHMV variants escaped from neutralization with the S1-specific monoclonal antibodies.

We have studied the neurovirulence for rats of the MAb-resistant variants isolated from a highly neurovirulent JHMV, cl-2. The variants, MM6 and MM13, with point mutation located within the N terminal 100 amino acids (aa) of the S1 protein showed no alteration in neurovirulence in comparison with cl-2, showing high neurovirulence. The variants, MM65 and MM85, with a deletion composed of about 150 aa located in the middle of the S1 subunit were revealed to be non-neurovirulent. A variant MM78 with one aa deletion, asparagic acid at number 543 from the N terminus of the S1, was shown to be low-virulence. The neurovirulence of these viruses paralleled with the viral growth potential in the rat brain. However, all of these variants as well as parental cl-2 showed high neurovirulence for mice. These results suggest that the domain composed of about 150 aa in the middle of the S1 is critical for high-neurovirulence of JHMV for rats.

Animals↗

Localization of neutralizing epitopes and receptor-binding site in murine coronavirus spike protein.

To identify the localization of the epitopes recognized by monoclonal antibodies (MAbs) against the S1 subunit of the murine coronavirus JHMV spike protein, we have expressed the S1 proteins with different deletions from the C terminus of the S1. All of MAbs in groups A and B recognized the S1N(330) composed of 330 amino acids (aa) from the N terminus of the S1 and the larger S1 deletion mutants, but failed to react with the S1N(220) composed of 220 aa. MAbs in group C reacted only with the S1utt protein without any deletion. These results indicated that the S1N330 comprised the cluster of epitopes recognized by MAbs in groups A and B. These results together with the fact that all the MAbs in group B retained the high neutralizing activity suggested that the N terminus 330 aa are responsible for binding to the MHV-specific receptors. In pursuit of this possibility, we have expressed the receptor protein and examined the binding of each S1 deletion mutants to the receptor. It was demonstrated that the S1N(330) protein as well as other S1 deletion mutants larger than S1N(330) bound to the receptor. These results indicated that a domain composed of 330 aa at the N terminus of the S1 protein is responsible for binding to the MHV-specific receptor.

Animals↗

Combination therapy with cisplatin and nifedipine induces apoptosis in cisplatin-sensitive and cisplatin-resistant human glioblastoma cells.

We attempted to determine whether calcium channel blockers (CCBs) enhance the anti-tumour activity of cis-diamminedichloroplatinum (cisplatin) against both cisplatin-sensitive human glioblastoma U87 MG cells and cisplatin-resistant U87-MG-CR cells, the latter of which we developed for resistance to cisplatin. Nifedipine, a dihydropyridine class CCB, significantly enhanced the anti-tumour effect of cisplatin on these two cell types in vitro and in vivo. Our findings also indicated that, in the absence of normal extracellular Ca2+ nifedipine was capable of enhancing the cytotoxicity of cisplatin. In addition, this anti-tumour activity was partially inhibited by actinomycin D and cycloheximide, suggesting that it is possibly dependent upon new RNA and protein synthesis. Interestingly, ultrastructural analysis, DNA fragmentation assay and cell cycle analysis demonstrated that synergism between cisplatin and nifedipine results in apoptosis (programmed cell death) at a relatively low concentration of cisplatin, which when tested alone did not induce apoptosis. Furthermore, we demonstrated that nuclei from these cells lack a Ca(2+)-dependent endonuclease that degrade chromatin in the linker region between nucleosomes. In conclusion, our studies suggest that the non-cytotoxic agent nifedipine is able to synergistically enhance the anti-tumour effects of cisplatin on U87-MG and U87-MG-CR cells lacking a Ca(2+)-dependent endonuclease and subsequently to induce apoptosis via interaction of nifedipine with an as yet uncharacterised functional site other than a calcium channel on target cells.

Animals↗

Current issues of continuous ambulatory peritoneal dialysis.

This paper concerns the overall median technical survival of chronic continuous ambulatory peritoneal dialysis (CAPD) patients and treatment in the 6 years since the commencement of CAPD at the Jikei University Hospital. Diabetic end-stage renal disease (ESRD) patients showed 5 years' survival, apparently shorter than that of nondiabetic ESRD which was 7 years. From this fact, the question of whether CAPD is the best dialytic option in diabetic ESRD should be reevaluated. Although a remarkable reduction in the incidence of peritonitis has been seen, generally ranging from 1 episode/40 patient months to 60 patient months or more in Japan, one serious issue still to be addressed is exit site/skin tunnel infection. The incidence is around 1 episode/30 patient months in our hospital. Discovering how to prevent this infection is a matter of some urgency. Peritoneal dialysis is a limiting dialytic modality as far as the biomembrane used. Although the precise mechanisms deteriorating the peritoneal function are still obscure, the treatment of sclerosing encapsulated peritonitis is also an urgent matter. Regarding bone disease and metastatic calcification, adynamic bone disease is frequently observed in ESRD patients: However, the pathogenesis of this morbidity has not been clarified. Treatment of extraosseous calcification in vessels and periarticular, and visceral organs should be developed. New dialytic alternatives to glucose and/or lactate-based solutions have been under experimental study. Until a new solution is delivered commercially, CAPD will remain a transient therapy. Our large study of CAPD patients revealed that 26% were malnourished. The biochemical parameters, amount of daily protein intake, and KT/V did not show significant differences between those patients identified as well nourished versus malnourished. The causes of malnutrition should be considered from other points of view such as endocrinological circumstances. Newer therapeutic approaches to malnutrition are also required.

Adult↗