Association between evacuation and becoming overweight after the Great East Japan Earthquake: a 7-year follow-up of the Fukushima Health Management Survey.

OBJECTIVES: Disaster evacuation increases the risk of becoming overweight or obese owing to lifestyle changes and psychosocial factors. This study evaluated the effect of evacuation on becoming overweight during a 7-year follow-up among residents of Fukushima Prefecture during the Great East Japan Earthquake. STUDY DESIGN: This was a prospective cohort study. METHODS: We analysed data collected from 18,977 non-overweight Japanese participants who completed the 'Comprehensive Health Checkup Program' and 'Mental Health and Lifestyle Survey', as part of the Fukushima Health Management Survey, between July 2011 and November 2012. An evacuation was defined as the moving out of residents of municipalities designated as an evacuation zone by the government or having a self-reported experience of moving into shelters or temporary housing. Follow-up examinations were conducted in March 2018 to identify patients who became overweight. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using a Cox proportional hazards regression model. RESULTS: Among 15,875 participants (6091 men and 9784 women; mean age 63.0 ± 11.1 years) who received follow-up examination (mean follow-up, 4.29 years), 2042 (856 men and 1186 women) became overweight. Age-, baseline body mass index-, lifestyle-, and psychosocial status-adjusted HRs (95% CIs) for becoming overweight after evacuation were 1.44 (1.24-1.66) for men and 1.66 (1.47-1.89) for women. CONCLUSION: Evacuation was associated with the risk of becoming overweight 7 years after the disaster. Thus, maintaining physical activity, healthy diet, and sleep quality and removing barriers to healthy behaviour caused by disasters, including anxiety concerning radiation, may prevent this health risk among evacuees.

Cumulative incidence of femoral localized periosteal thickening (beaking) preceding atypical femoral fractures in patients with rheumatoid arthritis.

The incidence of localized periosteal thickening (LPT, also termed beaking) of the lateral cortex that often precedes an atypical femoral fracture (AFF) was not high in patients with rheumatoid arthritis (RA) but incomplete AFFs developed in two patients. Higher-dose prednisolone was a significant risk factor for LPT in patients with RA. INTRODUCTION: Atypical femoral fractures (AFFs) are stress fractures; bisphosphonate (BP) use is a major risk factor for the development of such fractures. Localized periosteal thickening (LPT, also termed beaking) of the lateral cortex often precedes a complete or incomplete AFF. We evaluated the incidence of latent LPT in patients with rheumatoid arthritis (RA), to evaluate LPT progression, and to define LPT risk factors. METHODS: A total of 254 patients with RA were included; all underwent annual X-ray evaluation, dual-energy X-ray absorptiometry, and analyses of serum and bone metabolic markers for 2-3 years. LPT of the lateral cortex was sought in femoral X-rays. RESULTS: The incidence of LPT was 2.4% (6/254). Among patients on both BP and prednisolone (PSL) at enrollment, the incidence was 2.3% (3/131). Two femurs of two patients with LPT developed incomplete AFFs; LPT was extensive and associated with endosteal thickening. One patient had been on BP and PSL and microscopic polyangiitis was comorbidity. The other was on a selective estrogen receptor modulator and PSL. A daily PSL dose >5 mg (OR 11.4; 95%CI 2.15-60.2; p = 0.004) and higher-dose methotrexate (OR 1.22; 95%CI 1.01-1.49; p = 0.043) were significant risk factors for LPT. CONCLUSIONS: The incidence of latent LPT was not high (2.4%) but incomplete AFFs developed in two RA patients. Higher-dose PSL because of a comorbid disease requiring glucocorticoid treatment other than RA or refractory RA were risk factors for LPT; X-ray screening for latent LPT would usefully prevent complete AFFs.

High and pointed type of femoral localized reaction frequently extends to complete and incomplete atypical femoral fracture in patients with autoimmune diseases on long-term glucocorticoids and bisphosphonates.

Once a localized reaction (beaking) was detected, discontinuation of bisphosphonates (BPs) and switching to vitamin D supplementation or teriparatide therapy effectively improved its shape. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete atypical femoral fracture increased and consideration of prophylactic fixation for such patients was required. INTRODUCTION: Femoral localized reaction (localized periosteal thickening of the lateral cortex, beaking) is reported to precede atypical femoral fractures (AFFs) and to develop in 8-10% of patients with autoimmune diseases taking BPs and glucocorticoids. The aims of the present study were to retrospectively investigate the shapes of localized reaction to consider how to manage the condition. METHODS: Twenty femora of 12 patients with autoimmune diseases who were on BPs and glucocorticoids exhibited femoral localized reaction. The heights of localized reaction were measured and the shapes classified as pointed, arched, and other. Localized reaction changes were divided into three categories: deterioration, no change, and improvement. A severe form of localized reaction was defined; this was associated with prodromal pain, de novo complete AFF, or incomplete AFF with a fracture line at the localized reaction. RESULTS: The mean height of localized reaction was 2.3 ± 0.8 mm (range, 1.0-3.7 mm) and the pointed type was 35%. Localized reaction was significantly higher (3.3 ± 0.8 vs. 2.1 ± 0.7 mm; p = 0.003) and the pointed type more common (78 vs. 27%; p = 0.035) in those with the severe form of localized reaction. Seven patients with localized reactions discontinued BPs just after localized reaction was detected, but five continued on BPs for 2 years. Localized reaction deterioration was more common in patients who continued than discontinued BPs (100 vs. 29%; p = 0.027). After 2 years, all patients had discontinued BPs and localized reaction did not deteriorate further in any patient. CONCLUSIONS: Once a localized reaction was detected, discontinuation of BPs and switching to vitamin D supplementation or teriparatide therapy effectively improved it. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete AFF increased and consideration of prophylactic fixation for such patients was required.

The cumulative incidence of and risk factors for latent beaking in patients with autoimmune diseases taking long-term glucocorticoids and bisphosphonates.

SUMMARY: The incidence of beaking, which has been reported to precede atypical femoral fracture, was high and increased over 2 years in patients with autoimmune diseases who were taking bisphosphonates and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking, and bisphosphonate drug holidays should be considered. INTRODUCTION: Atypical femoral fractures (AFFs) have been recently recognized as complications associated with bisphosphonate (BP) use. AFFs are considered to be stress fractures; localized periosteal thickening of the lateral cortex is often present at the fracture site; this thickening is termed "beaking." Beaking has been reported to precede AFF. The aims of the present study were to evaluate the incidence of latent beaking in patients with autoimmune diseases taking BPs and glucocorticoids and to identify risk factors for beaking. METHODS: A total of 125 patients with autoimmune diseases who were taking BPs and glucocorticoids was included; 116 patients underwent X-rays and analysis of serum and urine bone metabolic markers annually for 2 years. Mean patient age was 54.5 years; there were 105 (90.5%) females and the mean duration of disease was 13.2 years. Focal lateral cortical thickening in femoral X-rays was defined as beaking. RESULTS: Beaking was detected in 15 femora of 10 patients (8.0%) at the time of recruitment. Over the 2-year observation period, the incidence of beaking increased to 21 femora of 12 patients (10.3%), and a complete AFF at the location of beaking occurred in one patient. Beaking was associated with a longer duration of BP treatment (6.1 ± 1.0 years vs. 5.0 ± 2.9 years, p = 0.01). Age 40-60 years, BP therapy ≥4 years, and diabetes mellitus were significantly associated with beaking. CONCLUSIONS: The incidence of beaking was high, and increased over 2 years, in patients with autoimmune diseases who were taking BPs and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking. Long-term BP/glucocorticoid use was a risk factor for beaking in patients with autoimmune diseases; BP drug holidays should be considered.

Patients undergoing dialysis therapy for 30 years or more survive with serious osteoarticular disorders.

AIMS: Increasing numbers of patients are undergoing long-term dialysis therapy. It is crucial for their quality of life to overcome dialysis-related complications, such as dialysis-related amyloidosis (DRA) and other osteoarticular disorder. The aim of the study was to investigate the characteristics, such as dialysis-related complications, in chronic kidney disease (CKD) Stage 5D patients undergoing dialysis therapy for more than 30 years or more. METHODS: From 2003 to 2006, 359 CKD Stage 5D patients who were admitted to a single tertiary-care center. The age and the duration of dialysis therapy, the purpose for hospital admission, and history of osteoarticular disorder, such as carpal tunnel syndrome (CTS), destructive spondyloarthropathy (DSA) and joint arthropathy, were studied. RESULTS: The proportions of the patients undergoing dialysis therapy for 20 - 24, 25 - 29 years and 30 years or more were 8.9, 5.6, and 4.5% of all admitted patients, respectively. DSA was a major cause of hospital admissions in long-term dialysis patients, especially in those treated for 30 years or more. The rate of surgery for osteoarticular disorder, such as CTS, DSA and joint arthropathy, which may show the presence of DRA, was 25.0, 66.0 and 77.8% in 20 - 24 years, 25 - 29 years and 30 years or more after the initiation of dialysis therapy, respectively. The frequency and severity of osteoarticular disorder accelerated with the duration of dialysis therapy, especially in those treated for 30 years or more. The rate of parathyroidectomy for secondary hyperparathyroidism was performed for 37.5% in 22.1 +/- 2.1 years after the initiation of dialysis treatment in the patients treated for 30 years or more. Mean age at the initiation of dialysis therapy was 27.3 +/- 8.0 years, and primary cause of CKD was mainly chronic glomerulonephritis in the patients undergoing dialysis therapy for 30 years or more. CONCLUSION: CKD stage 5D patients undergoing dialysis therapy for 30 years or more survive with characteristics of younger age at initiation of dialysis therapy, chronic glomerulonephritis as a primary cause of CKD, and serious complication of osteoarticular disorders.

The making of a bone in blood vessels: from the soft shell to the hard bone.

Vascular calcification, particularly of the medial layer of arteries, is one of the key determinants of survival in patients with chronic kidney disease. This abnormality is not merely a simple process of precipitation of calcium and phosphate but also includes several mechanisms similar to those of bone formation within the vessel wall.

Basic and clinical aspects of parathyroid hyperplasia in chronic kidney disease.

Marked parathyroid hyperplasia develops in patients with chronic kidney disease, especially those with long dialysis vintage. Although progression of hyperplasia is associated with downregulation of vitamin D receptor and calcium-sensing receptor, initial abnormality that triggers and maintains parathyroid cell proliferation, as well the critical abnormality for the progression of diffuse hyperplasia to nodular hyperplasia, still remains to be elucidated. It is quite important for the optimal management of renal osteodystrophy to recognize the development of nodular hyperplasia, because the cells in nodular hyperplasia are usually resistant to medical therapy and further treatment of such patients often leads to vascular calcification. For this purpose, size and blood supply of enlarged parathyroid glands have been used as good clinical markers. Furthermore, we have recently shown that the serum fibroblast growth factor 23 level can be used for predicting refractory hyperparathyroidism. Once nodular hyperplasia develops in any of the enlarged parathyroid glands, such patients need to be treated by parathyroid intervention including percutaneous ethanol injection therapy. In addition, as direct vitamin D injection therapy has been shown to induce regression of hyperplasia, it may become possible to reverse or normalize established nodular hyperplasia if we can develop new agents with such effects in the near future.

Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients.

Although uremia is well known as the most common cause of pruritus, the mechanisms of pruritus in chronic hemodialysis patients remain unclear. The purpose was to characterize uremic pruritus in more detail and to investigate whether severe pruritus is a marker for poor prognosis. A total of 1773 adult hemodialysis patients were studied. A questionnaire was given to each patient to assess the intensity and frequency, as well as pruritus-related sleep disturbance. We analyzed the relationship between clinical and laboratory data and the severity of pruritus in hemodialysis patients and followed them for 24 months prospectively. In total, 453 patients had severe pruritus with a visual analogue scale (VAS) score more than or equal to 7.0. Among them, more than 70% complained of sleep disturbance, whereas the majority of patients with a VAS score of less than 7.0 had no sleep disturbance. Male gender, high levels of blood urea nitrogen, beta2-microglobulin (beta2MG), hypercalcemia, and hyperphosphatemia were identified as independent risk factors for the development of severe pruritus, whereas a low level of calcium and intact-parathyroid hormone were associated with reduced risk. During the follow-up, 171 (9.64%) patients died. The prognosis of patients with severe pruritus was significantly worse than the others. Moreover, severe pruritus was independently associated with death even after adjusting for other clinical factors including diabetes mellitus, age, beta2MG, and albumin. Severe uremic pruritus caused by multiple factors, not only affects the quality of life but may also be associated with poor outcome in chronic hemodialysis patients.

Maxacalcitol therapy decreases circulating osteoprotegerin levels in dialysis patients with secondary hyperparathyroidism.

BACKGROUND: Osteoprotegerin is a natural glycoprotein which plays a critical role in osteoclast physiology. Elevated levels of circulating osteoprotegerin may account for the development of bone and mineral metabolic abnormalities in uremia. Little is known about the effects of vitamin D therapy on the circulating osteoprotegerin levels in dialysis patients. PATIENTS AND METHODS: Fifty chronic dialysis patients whose plasma intact PTH levels were greater than 300 pg/ml were analyzed for the study. Following a four-week washout time during which all vitamin D administration was halted, 10 microg of maxacalcitol was intravenously injected thrice a week. RESULTS: The circulating intact PTH, bone-specific alkaline phosphatase and intact osteocalcin levels were significantly lowered, while the serum calcium levels were elevated after the therapy. The osteoprotegerin levels significantly decreased after the therapy (p < 0.0001). CONCLUSION: Maxacalcitol therapy reduced the circulating osteoprotegerin levels and improved secondary hyperparathyroidism. The observed effects were the opposite of those expected from previous in vitro studies. Osteoprotegerin may mediate and/or modify the effect of active vitamin D therapy in dialysis patients.

Development of hungry bone syndrome after rapid lowering of PTH with intravenous maxacalcitol therapy in a patient with non-uremic secondary hyperparathyroidism.

A 41 year-old woman complained of general bone pain and polyuria. She did not have Albright hereditary osteodystrophy. Laboratory examination revealed hypokalemia, hypocalcemia, and an elevation of serum intact PTH concentration. The patient was polyuric and relatively hypercalciuric, though her glomerular filtration rate (GFR) was normal. Neither urinary Pi nor cAMP excretion was remarkably promoted by an exogenous PTH load. An iliac bone biopsy revealed osteopenia, active osteoclastic bone resorption, fibrous transformation in bone marrow tissue, and severely disturbed calcification. Although the oral administration of alfacalcidol showed no effects, 3 weeks of intermittent intravenous injection of maxacalcitol therapy decreased the serum intact PTH concentration from 597 pg/ml to 40 pg/ml, and the bone pain was greatly relieved. However, plasma Ca concentration also decreased and symptoms of tetany appeared. Pseudohypoparathyroidism type Ib was the most likely diagnosis in this patient. In conclusion, maxacalcitol therapy satisfactorily suppressed parathyroid function in a patient with secondary hyperparathyroidism without uremia. Appropriate Ca supplementation was required to perform it safely.

Pathophysiology of gastric acid secretion in patients with chronic renal failure: influence of Helicobacter pylori infection.

OBJECTIVES: The incidence of gastroduodenal diseases is high in patients with chronic renal failure (CRF). However, gastric acidity in CRF has been reported to range in level from low to high. Moreover, it remains unknown whether Helicobacter pylori infection influences gastric acidity in such patients. Thus, we aimed to clarify the pathophysiological perturbation in gastric acidity and to determine the influence of H. pylori infection in CRF. DESIGN: Case-control study. SETTING: A university hospital. SUBJECTS: Twenty-seven patients with CRF and 24 control patients, presenting with either gastrointestinal symptoms, positive faecal occult blood, or anaemia (haemoglobin <10 g dL(-1)). MEASURES: The patients underwent gastroduodenal endoscopy with simultaneous determination of H. pylori infection. Gastric ammonium concentration, serum pepsinogen I and II, and basal gastrin level were measured. Thereafter, gastric acid secretion was monitored by 24-h intragastric acidity measurement with calculation of pH-3 holding time (%) (hours showing pH>3/24 h). RESULTS: In the CRF group, pH-3 holding time of H. pylori (+) subgroup was significantly greater than that of H. pylori (-) subgroup (71.2 +/- 32.4% vs. 32.8 +/- 30.0%, mean +/- SD; P=0.03). Pepsinogen I/II ratio was inversely correlated with pH-3 holding time in the control and CRF groups. Gastric ammonium concentration in CRF/H. pylori (+) subgroup (14.1 +/- 9.2 mmol L(-1)) was significantly higher than in CRF/H. pylori (-) (2.5 +/- 2.7 mmol L(-1); P=0.002) and control/H. pylori (+) subgroups (6.1 +/- 4.2 mmol L(-1); P=0.01). Serum gastrin level was significantly higher in the CRF group than in the control group (297 +/-343 pg mL(-1) vs. 116 +/- 69 pg mL(-1); P=0.02) as a whole. However, there was no significant correlation between serum creatinine and gastrin levels in the CRF group. Gastrin level in CRF/H. pylori (+) subgroup was significantly higher than in CRF/H. pylori (-), control/H. pylori (+), and control/H. pylori (-) subgroups (423 +/-398 pg mL(-1) vs. 113 +/- 79, 124 +/- 78, and 96 +/-43 pg mL(-1), respectively; P=0.01-0.03). Significant positive correlations amongst pH-3 holding time, ammonium and gastrin concentrations were found in the CRF group, but not in the control group. CONCLUSIONS: CRF without H. pylori infection primarily shows a tendency for high gastric acidity, but without hypergastrinaemia. Persistent H. pylori infection in CRF leads to decreased acidity and, consequently, to fasting hypergastrinaemia via a feedback mechanism. The hypoacidity in CRF with H. pylori infection appears to result from neutralization of acid by ammonia as well as from gastric atrophy. Thus, H. pylori infection status critically determines perturbation in gastric acidity and fasting gastrin level in CRF.

Successful perioperative blood purification therapy in patients with maintenance hemodialysis therapy who underwent living donor liver transplantation.

Living donor liver transplantation (LDLT) is a treatment for end-stage liver failure, and was developed to overcome the distinct insufficiency of cadaveric donors. Case 1 is a 56-year-old man who had undergone maintenance hemodialysis therapy for 4 years. An LDLT was performed for the treatment of advanced liver cirrhosis and hepatocellular carcinoma. Continuous hemodiafiltration (CHDF) was performed from the 2nd to 5th days after the operation. Case 2 is a 55-year-old man with primary amyloidosis and chronic renal failure. An LDLT was performed for the treatment of severe abdominal distention caused by a large liver volume. Although CHDF was started at the 3rd day after the operation, it was discontinued within 24 hours because of an increased urinary volume. CHDF was required again from the 6th-8th days, after which the blood purification mode was switched to regular intermittent hemodialysis. Meanwhile, no major problems occurred in either case. In conclusion, CHDF was required for about 5 days from the 2nd day after the operation. The application of careful and aggressive blood purification therapy during the perioperative period is a key to successful LDLT in dialysis patients.

High-level expression of naked DNA delivered to rat liver via tail vein injection.

BACKGROUND: High levels of foreign gene expression in mouse hepatocytes can be achieved by rapid tail vein injection of a large volume of a naked DNA solution, the 'hydrodynamics-based procedure'. Rats are more tolerant of the frequent phlebotomies required for monitoring blood parameters than mice, and thus are better for some biomedical research. METHODS: We tested this technique for the delivery of a therapeutic protein in normal rats, using a rat erythropoietin (Epo) expression plasmid vector, pCAGGS-Epo. RESULTS: We obtained maximal Epo expression when the DNA solution was injected in a volume of 25 ml (approximately 100 ml/kg body weight) within 15 s. We observed a dose-response relationship between serum Epo levels and the amount of injected DNA up to 800 microg. Using quantitative real-time PCR, the vector-derived Epo mRNA expression was mainly detected in the liver. When a lacZ expression plasmid was injected similarly, beta-galactosidase was exclusively detected in the liver, mainly in hepatocytes. Toxicity attributable to the technique was mild and transient, as assessed by histochemical analysis. Epo gene expression and erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 12 weeks, the last time point examined. Repeated administration of the plasmid DNA also effectively led to erythropoiesis. CONCLUSIONS: These results demonstrate that gene transfer into the liver via rapid tail vein injection can easily be achieved in the rat, which is more than 10 times larger than the mouse, and has significant value for gene function analysis in rats.

Skeletal resistance to pth as a basic abnormality underlying uremic bone diseases.

Skeletal resistance to parathyroid hormone (PTH) was suggested initially as a mechanism of PTH hypersecretion in uremia. Because of the effective suppression of PTH by recently developed therapeutic modalities, this background abnormality has been uncovered and currently recognized as relative hypoparathyroidism in terms of its relation to bone turnover. Thus, PTH levels two to three times greater than normal are usually required to keep bone turnover normal in uremia. Recent studies suggested that PTH activity may be overestimated using the conventional intact PTH assay. In addition, several steps to osteoclastogenesis are suspected to be disturbed in uremia. Additional studies at cellular and molecular levels are needed to establish preventive and therapeutic modalities for this abnormality.

Osteoclastogenesis and osteoclast activation in dialysis-related amyloid osteopathy.

Dialysis-related amyloid osteopathy (DRAO) is characterized by local osteoarticular lytic lesions, which sometimes cause a pathological fracture and reduce the quality of life in affected patients. In DRAO, active osteoclastic bone resorption is found at the bone surface facing the invaded synovial tissue and/or intervertebral disc, whereas reactive bone formation is absent. The eroded bone surface is covered with osteoclasts, suggesting the local promotion of osteoclastogenesis and osteoclast activation around DRAO. Inflammatory cells infiltrating the synovial tissue are likely to promote inflammatory osteolysis. Three possible pathways can be considered for the osteoclastogenesis and/or osteoclast activation in inflammatory osteolysis in DRAO: (1) indirect action of the inflammatory cytokines through the receptor activator of nuclear factor-kappaB ligand/osteoprotegerin ligand (RANKL/OPGL) expression in osteoblasts, (2) direct action of inflammatory cytokines, and (3) RANKL/OPGL expression in inflammatory cells. To apply antiosteoclastic agents as another therapy for DRAO, we have to clarify the roles of those pathways in local osteoclastogenesis and/or osteoclast activation.

Comparison of intact PTH assay and whole PTH assay in long-term dialysis patients.

Adynamic bone disease has become a major problem in long-term dialysis patients. It has been suggested that higher levels of parathyroid hormone (PTH) are needed to maintain normal bone turnover in uremia. PTH levels currently are evaluated routinely by intact PTH assay, which may detect inactive 7-84 PTH fragments as well as 1-84 PTH. We examined the efficacy of whole PTH assay, which detects 1-84 PTH exclusively, in 99 nondiabetic patients on maintenance dialysis for more than 10 years, without any residual renal function. PTH levels determined by whole PTH assay were lower than those determined by intact PTH assay in all cases. Serum markers of bone metabolism, such as serum activity of bone alkaline phosphatase, correlated well with whole PTH levels. Because 7-84 PTH has been shown to inhibit the effects of 1-84 PTH, the biologic activity of circulating PTH in uremic patients may be much lower than the values assayed by conventional intact PTH assay. Despite an attempt to correlate 1-84 PTH/7-84 PTH ratio with bone histology, we could find only 1 patient out of 99 with 1-84 PTH/7-84 PTH ratio less than 1, which has been suggested to be indicative of low turnover bone. A cutoff value of this ratio should be set in the future for patients with a long hemodialysis history, with various modes of medical therapy.

Osteoprotegerin levels before and after renal transplantation.

Osteoprotegerin (OPG) is a newly identified glycoprotein that belongs to the tumor necrosis factor receptor superfamily and regulates bone mass by inhibiting osteoclastic bone resorption. The regulatory mechanism of OPG is still unclear after successful renal transplantation (RTX), however, resulting in resolution of uremia. The present study was designed to clarify the potential role of OPG in uremia and after RTX under immunosuppressive therapy. We evaluated circulating OPG levels by measuring them before and after RTX (postoperative days 2, 14, and 28). Our protocol of immunosuppressive drugs was dual therapy using cyclosporine and steroids. Serum OPG was quantitated using enzyme-linked immunosorbent assay. After successful RTX, serum OPG levels decreased significantly on day 14 and day 28 compared with the baseline level (P < 0.05). Creatinine clearance dramatically increased until day 14 and decreased thereafter. Serum OPG declines for the first 2 weeks after RTX owing to functioning allograft and decreases again for the next 2 weeks because of steroids and possible immunosuppressive agents.

Pharmacokinetics of paclitaxel and cisplatin in a hemodialysis patient with recurrent ovarian cancer.

This is the first report that the combination of paclitaxel and cisplatin is feasible in a patient with recurrent ovarian cancer undergoing hemodialysis. Paclitaxel at a dose of 150 mg/m(2) was administered as a 3-h continuous i.v. infusion. Thirty minutes after paclitaxel administration, cisplatin was administered at a dose of 30 mg/m(2) for 30 min. Hemodialysis was started 30 min after completion of the cisplatin infusion and performed for 5 h. The maximum plasma concentrations of paclitaxel, total platinum and free platinum were 3.26, 2.44 and 1.84 microg/ml, respectively. The AUC of paclitaxel and free platinum were 15.3 and 1.76 microg x h/ml, respectively. The pelvic tumor size was reduced by 42% on MRI after the second course of this therapy. Grade IV neutropenia and grade III thrombopenia were observed. We conclude that paclitaxel and cisplatin combination chemotherapy is efficacious and feasible for an ovarian cancer patient under hemodialysis.

Reduction of circulating beta2-microglobulin level for the treatment of dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA) is a common complication associated with long-term haemodialysis therapy. The elimination of beta2-microglobulin (beta2m), the major constituent of the amyloid fibrils in DRA, from circulation has been expected to bring some clinical benefit. Recently, a direct haemoperfusion method using selective beta2m absorption column to eliminate circulating beta2m has been introduced into clinical practice. According to a recently performed, prospective, multicentre study, joint pain, stiffness and daily activities were significantly improved in patients with established DRA after the introduction of selective beta2m absorption therapy. Meanwhile, although osteoarticular lesions progressed in the control group, there was no significant progression in the selective beta2m absorption therapy group. The absorptive affinity of the column for beta2m is not quite specific and therefore some other unknown uraemic toxins might be removed also. However, the improvement of joint pain and the ability to undertake daily activities showed reversed correlations against plasma beta2m clearance. Symptoms associated with the increased amount of extracorporeal circulation and increased economical burden are areas of concern for this therapy. In conclusion, selective beta2m absorption therapy was suggested to have the potential to ameliorate established DRA symptoms and simultaneously prevent its local development. The mechanism by which DRA symptoms are ameliorated remains obscure.

[Osteoprotegerin and adynamic bone disease].

"The skeletal resistance to PTH" which is receiving much attentions especially after the break through in the field of osteoclastogenesis/activation research, is a practical pathogenesis of adynamic bone diseases. Serum osteoprotegerin (OPG) levels increase along with the deteriorations of glomerular filtration rate, and that in dialysis patients would be high enough to demonstrate a osteoclastogenesis inhibitory action in vitro. In fact, the parameters for bone resorption in biopsied iliac bone from dialysis patients showed a negative correlation with serum OPG levels. Moreover, serum OPG concentration increases with aging even among dialysis patients. Therefore "the skeletal resistance to PTH" in aged dialysis patients should be greater than that in younger ones, that possibly explains why adynamic bone disease is more common in aged patients. Thus, circulating OPG in uremic patients may promote the development of adynamic bone disease through the osteoclastogenesis inhibitory action.