Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 796
Filter
1.
Sci Rep ; 14(1): 14552, 2024 06 24.
Article in English | MEDLINE | ID: mdl-38914593

ABSTRACT

We have reported that an environmental pollutant, cadmium, promotes cell death in the human renal tubular cells (RTCs) through hyperactivation of a serine/threonine kinase Akt. However, the molecular mechanisms downstream of Akt in this process have not been elucidated. Cadmium has a potential to accumulate misfolded proteins, and proteotoxicity is involved in cadmium toxicity. To clear the roles of Akt in cadmium exposure-induced RTCs death, we investigated the possibility that Akt could regulate proteotoxicity through autophagy in cadmium chloride (CdCl2)-exposed HK-2 human renal proximal tubular cells. CdCl2 exposure promoted the accumulation of misfolded or damaged proteins, the formation of aggresomes (pericentriolar cytoplasmic inclusions), and aggrephagy (selective autophagy to degrade aggresome). Pharmacological inhibition of Akt using MK2206 or Akti-1/2 enhanced aggrephagy by promoting dephosphorylation and nuclear translocation of transcription factor EB (TFEB)/transcription factor E3 (TFE3), lysosomal transcription factors. TFEB or TFE3 knockdown by siRNAs attenuated the protective effects of MK2206 against cadmium toxicity. These results suggested that aberrant activation of Akt attenuates aggrephagy via TFEB or TFE3 to facilitate CdCl2-induced cell death. Furthermore, these roles of Akt/TFEB/TFE3 were conserved in CdCl2-exposed primary human RTCs. The present study shows the molecular mechanisms underlying Akt activation that promotes cadmium-induced RTCs death.


Subject(s)
Autophagy , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Cadmium , Proto-Oncogene Proteins c-akt , Humans , Proto-Oncogene Proteins c-akt/metabolism , Autophagy/drug effects , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Cell Line , Cadmium/toxicity , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/pathology , Phosphorylation/drug effects , Cadmium Chloride/toxicity , Heterocyclic Compounds, 3-Ring/pharmacology , Kidney Tubules/metabolism , Kidney Tubules/drug effects , Kidney Tubules/cytology , Kidney Tubules/pathology
2.
J Physiol Pharmacol ; 73(1)2022 Feb.
Article in English | MEDLINE | ID: mdl-35793766

ABSTRACT

Statins and fibrates are frequently used to treat hyperlipidemia; however, these drugs may have adverse effects such as rhabdomyolysis. The incidence of rhabdomyolysis due to fibrates and statins is low (0.0028-0.0096%) when administered as monotherapy, however it increases to 0.015-0.021% when the drugs are used in combination. The mechanism underlying myotoxicity induced by the combination of statins and fibrates is yet unclear. Here, we investigated the mechanisms underlying induced myotoxicity in rat myoblasts L6 and differentiated L6 cells (myotubes) using a combination of statins and fibrates. We found that cell death induced by a combination of fluvastatin or simvastatin with bezafibrate or fenofibrate in L6 myoblasts and myotubes was mediated by inhibition of geranylgeranyl pyrophosphate (GGPP) production. Additionally, the drug combination inhibited Rho activation in L6 myoblasts and myotube cells. In L6 myoblasts, the combination of statins and bezafibrate enhanced p27 expression and induced G1 arrest and apoptosis. Furthermore, combined treatment suppressed Akt activation and enhanced Bim expression in L6 myotubes but did not affect extracellular regulated protein kinase 1/2 activation. These results suggested that combined administration of statins and fibrates induced death of L6 myoblasts and myotube cells by inhibiting GGPP biosynthesis and Rho pathway activation. Supplementation with GGPP may be therapeutically beneficial for preventing myotoxicity associated with combined statin and fibrates treatment.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Rhabdomyolysis , Animals , Bezafibrate/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Muscle Fibers, Skeletal , Myoblasts , Myotoxicity , Polyisoprenyl Phosphates , Rats , Rhabdomyolysis/chemically induced , Rhabdomyolysis/drug therapy
3.
Jpn J Clin Oncol ; 51(4): 544-551, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33324967

ABSTRACT

AIM: The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. METHODS: Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon's minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. RESULTS: For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55-86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4-84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%-69.3%), median prostate-specific antigen-progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). CONCLUSIONS: Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen-progression-free survival was shorter than that reported in previous studies. Considering the benefit-risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.


Subject(s)
Abiraterone Acetate/adverse effects , Abiraterone Acetate/therapeutic use , Androgens/deficiency , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prednisolone/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Metastasis , Prednisolone/administration & dosage , Progression-Free Survival , Treatment Outcome
4.
Diabet Med ; 37(12): 2143-2152, 2020 12.
Article in English | MEDLINE | ID: mdl-32276289

ABSTRACT

AIMS: Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. METHODS: This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy-proven diabetic nephropathy, with a median follow-up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. RESULTS: Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow-up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan-Meier analysis than those without these lesions (P = 0.005, log-rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. CONCLUSIONS: Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy.


Subject(s)
Arterioles/pathology , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/pathology , Hyalin , Kidney/pathology , Renal Artery/pathology , Tunica Intima/pathology , Aged , Amputation, Surgical/statistics & numerical data , Arrhythmias, Cardiac/mortality , Cardiovascular Diseases/mortality , Cause of Death , Cohort Studies , Death, Sudden/epidemiology , Diabetic Nephropathies/etiology , Female , Heart Failure/epidemiology , Hospitalization/statistics & numerical data , Humans , Kidney/blood supply , Kidney Failure, Chronic/epidemiology , Male , Middle Aged , Mortality , Myocardial Infarction/epidemiology , Myocardial Infarction/mortality , Myocardial Revascularization/statistics & numerical data , Proportional Hazards Models , Retrospective Studies , Stroke/epidemiology , Stroke/mortality
6.
Transplant Proc ; 50(10): 3321-3328, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30577202

ABSTRACT

BACKGROUND: There have been few studies that have reported the influence of kidney transplantation on the quality of life (QOL) of patients of preemptive kidney transplantation (PKT) and nonpreemptive kidney transplantation (NPKT). MATERIAL AND METHODS: Fifty patients of PKT and 49 patients of NPKT were employed as study subjects. A questionnaire survey using Short Form 36 and Kidney Disease QOL on patients' physical and psychological QOL was performed for these patients prior to transplantation and 1 month, 3 months, and 1 year after transplantation. RESULTS: The analysis of results has revealed that transplantation clearly has improved the physical and psychological QOL in patients with end-stage renal disease. For the items regarding physical burdens incurred by the transplantation, patient QOL deteriorated on a single occasion 1 month after the transplantation while it was improved 1 year after the transplantation. For the items regarding psychological burdens, the mental condition of the patients was improved overall without deterioration over time. Concerning the "Effect of Kidney Disease" and "Burden of Kidney Disease," QOL was significantly better in PKT than NPKT at baseline before transplantation, although the significant difference gradually decreased 1 month and 3 months after the transplantation and disappeared after 1 year. CONCLUSION: Transplantation certainly improved the QOL of patients with end-stage renal disease. Before transplantation, PKT was clearly better than NPKT in the QOL items associated with "Burden of Kidney Disease." This indicated that patients of PKT have improved QOL compared to patients of NPKT, and that the overall awareness of kidney disease is decreased. A postoperative gap in mental and bodies was observed especially in PKT, however, could be overcome by nursing interventions.


Subject(s)
Kidney Transplantation/methods , Kidney Transplantation/psychology , Quality of Life , Adult , Female , Humans , Kidney Failure, Chronic/surgery , Male , Middle Aged
7.
Transplant Proc ; 50(8): 2338-2341, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30316354

ABSTRACT

INTRODUCTION: With the increasing number of elderly kidney donor candidates due to the lack of available donors, prostate cancer has sometimes been detected in these candidates during pretransplant screening examinations. There are currently no guidelines or consensus on prostate cancer screening and treatment in donors. We retrospectively evaluated the clinical course of donor candidates with prostate cancer. METHODS: Between January 2006 and December 2016, 9 donor candidates for living related kidney transplantation were incidentally diagnosed with prostate cancer at our institution. All male kidney transplant donor candidates routinely received prostate-specific antigen (PSA) testing. The patients with PSA levels > 4.0 ng/mL underwent prostate biopsies. For future kidney transplantation, treatment for localized prostate cancer was prostatectomy. RESULTS: Seven low- or intermediate-risk patients according to the D'Amico risk classification underwent endoscopic prostatectomy, while 2 high-risk patients underwent high dose-rate brachytherapy to prioritize prostate cancer treatment. Of the 7 who underwent surgery, 3 patients ultimately became living related kidney transplantation donors for their wives. There was no recurrence of PSA elevation after treatment. CONCLUSION: This study showed that donor candidates with prostate cancer could safely donate a kidney after a thorough evaluation to exclude those with high-risk prostate cancer. Transmission of prostate cancer through kidney transplantation seems unlikely and robot-assisted laparoscopic prostatectomy may be feasible for donor candidates with localized prostate cancer.


Subject(s)
Kidney Transplantation/methods , Living Donors , Prostatic Neoplasms , Aged , Follow-Up Studies , Humans , Living Donors/supply & distribution , Male , Middle Aged , Retrospective Studies
8.
Transplant Proc ; 50(8): 2439-2442, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30316374

ABSTRACT

BACKGROUND: In patients eligible for organ transplantation, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines specifically recommend avoiding red blood cell transfusions (RBCT) when possible to minimize the risk of allosensitization. OBJECTIVE: To assess the effect of perioperative RBCT on outcomes in living-related kidney transplantation (LRKT) recipients. METHODS: We retrospectively assessed 97 patients who underwent LRKT and whose data were evaluable at our institution between March 2009 and May 2016. We measured serum creatinine levels and calculated the estimated glomerular filtration rate (eGFR) at 3 months, 6 months, and 1 year after kidney transplantation (KTx). We evaluated the rejection rate within a year after KTx. We compared the renal function and rejection rate between those who received blood transfusions (n = 21) and those who did not (n = 76) during the perioperative period. RESULTS: Among patient characteristics, the rate of ABO-incompatible KTx and the mean hemoglobin levels before KTx differed significantly between the groups. The serum creatinine levels and eGFR within 1 year after KTx did not differ significantly between the two groups. The rejection rate in those who received blood transfusions and those who did not was 28.6% (6/21 patients) and 25.0% (19/76 patients) (P = .741), respectively. CONCLUSIONS: We found that the rejection rate was slightly higher in patients who received perioperative RBCT than in those who did not, but the difference was not significant within a year after KTx. Perioperative RBCT may not affect renal function within a year after KTx.


Subject(s)
Blood Transfusion , Graft Rejection/blood , Kidney Transplantation , Adult , Female , Humans , Living Donors , Male , Middle Aged , Retrospective Studies , Treatment Outcome
9.
Transplant Proc ; 50(8): 2443-2446, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30316375

ABSTRACT

BACKGROUND: Among infectious diseases, influenza is the most common cause of infection in Japan and worldwide. We aimed to evaluate the effect of influenza vaccination in kidney transplantation (KTx) recipients. METHODS: We retrospectively evaluated the records of 98 participants who underwent KTx at our institution between March 2009 and May 2016. All patients received tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone for maintenance immunosuppression after KTx. In accordance with the criteria of our institution, everolimus was administered for the maintenance of immunosuppression after KTx. We compared the rate of influenza infection during the 2016-2017 season (8 months, from October 2016-May 2017) between KTx patients treated with 1 or 2 doses of influenza vaccine (treatment group, n = 71) and KTx patients who did not receive a vaccine (nontreatment group, n = 27). RESULTS: Among patient characteristics, only the prevalence of diabetes mellitus differed significantly between the groups (treatment group: 9.9%, 7 of 71 patients; nontreatment group: 29.6%, 8 of 21 patients; P = .02). Influenza infection occurred at similar rates in the 2 groups (treatment group, 5.63% 4 of 71 patients; nontreatment group: 3.70%, 1 of 27 patients; P = .70). CONCLUSIONS: Among KTx patients managed in our institution, treatment with 1 or 2 doses of influenza vaccine did not reduce the rate of influenza infection in the 2016-2017 season, suggesting that influenza vaccination may currently be ineffective in KTx patients.


Subject(s)
Influenza Vaccines/therapeutic use , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Kidney Transplantation , Adult , Cyclosporine/therapeutic use , Everolimus/therapeutic use , Female , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Influenza Vaccines/immunology , Influenza, Human/immunology , Japan , Kidney Transplantation/adverse effects , Male , Methylprednisolone/therapeutic use , Middle Aged , Mycophenolic Acid/therapeutic use , Retrospective Studies , Tacrolimus/therapeutic use
10.
Transplant Proc ; 50(8): 2539-2544, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30316394

ABSTRACT

OBJECTIVES: We aimed to evaluate the feasibility and efficacy of surgical prostatectomy in renal transplant recipients (RTRs). METHODS: Between January 2008 and February 2017, we identified 13 RTRs who were diagnosed with localized prostate cancer and underwent radical prostatectomy. We reviewed all available clinicopathologic data for these 13 patients. RESULTS: The median patient age was 61 years and median serum prostate-specific antigen (PSA) was 8.79 ng/mL. The mean period between transplantation and diagnosis of prostate cancer was 136 months. The sources for the kidney transplants included 10 living and 3 deceased donors. Biopsies indicated that the Gleason scores were 7 in 10 patients and 8 to 10 in 3 patients. Meanwhile, the D'Amico risk classification indicated an intermediate risk in 9 patients and a high risk in 4 patients. Eight patients were at stage cT1 and 5 were at stage cT2. The surgical procedure was retropubic radical prostatectomy in one recipient, laparoscopic radical prostatectomy in 3 recipients, and robot-assisted radical prostatectomy in 9 RTRs. Intraoperative complications were not noted in any patient, although one patient demonstrated postoperative complications (Clavien grade ≥ 3). An indwelling urinary catheter was required in 3 patients for over 3 weeks due to delayed wound healing. Biochemical recurrence evaluated by PSA monitoring occurred in four patients. Postoperative graft function was stable in all but one patient who required resumption of dialysis before prostatectomy; however, all patients are alive at the time of publication with 12 patients showing well-functioning renal allografts. CONCLUSION: Prostatectomy may be a feasible and effective technique as an initial treatment for RTRs with localized prostate cancer.


Subject(s)
Kidney Transplantation , Prostatectomy/methods , Prostatic Neoplasms/complications , Prostatic Neoplasms/surgery , Transplant Recipients , Aged , Humans , Male , Middle Aged , Prostate-Specific Antigen/blood , Prostatic Neoplasms/pathology , Retrospective Studies
11.
Transplant Proc ; 50(8): 2562-2564, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30173850

ABSTRACT

We report a case of living related renal transplantation that used the recipient's saphenous vein as a graft to extend the length of the right donor renal vein. A 41-year-old woman underwent ABO-incompatible living related renal transplantation from her 74-year-old mother in November 2014. A retroperitoneal laparoscopic right donor nephrectomy was performed, because the right kidney showed a cyst on preoperative computed tomography. As the right kidney after donor nephrectomy had a short renal vein and the kidney was large at 280 g, anastomosis with the external iliac vein was difficult. Therefore, we obtained the recipient's 15-cm-long right saphenous vein and created a 1 cm saphenous vein graft. We anastomosed 1 side of the saphenous vein graft to the allograft renal vein in bench surgery and performed end-to-side anastomosis of the other end to the recipient's external iliac vein. The allograft renal artery was used to perform end-to-end anastomosis to the recipient's internal iliac artery. Allograft kidney function was good after transplantation. When the longer axis of the renal graft vein is short, as in the right kidney, a saphenous vein graft may be useful.


Subject(s)
Kidney Transplantation/methods , Living Donors , Nephrectomy/methods , Renal Veins/transplantation , Saphenous Vein/transplantation , Adult , Anastomosis, Surgical , Female , Humans , Kidney/surgery , Tissue and Organ Harvesting/methods
12.
Transplant Proc ; 49(10): 2251-2255, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29198655

ABSTRACT

BACKGROUND: We performed a clinical and pathological analysis of cases of acute vascular rejection (AVR), characterized by intimal arteritis and transmural arteritis (Banff v score) after kidney transplantation, in an attempt to clarify the mechanisms underlying the development and prognostic significance of AVR. METHODS: AVR (Banff score: v >0) was diagnosed in 31 renal allograft biopsy specimens (BS) obtained from 31 renal transplant patients receiving follow-up care at the Department of Urology, Tokyo Women's Medical University, between January 2010 and April 2016. RESULTS: AVR was diagnosed at a median of 124.6 days after transplantation. Among the 31 BS showing evidence of AVR, AVR was mild (v1 in Banff's classification) in 25 cases, moderate (v2) in 6, and severe (v3) in none. We classified the 31 BS with evidence of AVR by their overall histopathological features as follows: isolated v lesions were observed in 6 BS, acute antibody-mediated rejection (AAMR) in 7, acute T-cell-mediated rejection (ATCMR) in 12, and both ATCR and AAMR in 6. Loss of the renal allograft occurred during the observation period in 3 patients, and, of the remaining cases with functioning grafts, deterioration of renal allograft function after biopsy occurred in only 2 patients. CONCLUSIONS: The results of our study suggest that ATCMR contributes to AVR in 40% to 60% of cases, AAMR in 20% to 40% of cases, and isolated v lesions in 20% of cases. The prognosis of the patient with the graft that had AVR was relatively good under the present immunosuppression protocol and current anti-rejection therapies.


Subject(s)
Arteritis/pathology , Graft Rejection/pathology , Kidney Transplantation/adverse effects , Kidney , Postoperative Complications/pathology , Tunica Intima/pathology , Acute Disease , Adult , Arteritis/etiology , Biopsy , Female , Follow-Up Studies , Humans , Kidney/blood supply , Kidney/physiopathology , Male , Middle Aged , Postoperative Complications/etiology , Prognosis , Retrospective Studies , T-Lymphocytes/immunology
13.
J Med Humanit ; 38(4): 541-547, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28975579

ABSTRACT

Fourth-year medical students at the University of Colorado School of Medicine distributed cards to patients in the emergency department asking, "What Worries You Most?" The patients' responses provided insight about their most pressing concerns, often unrelated to their "chief complaints."


Subject(s)
Emergency Service, Hospital , Patients/psychology , Stress, Psychological , Female , Humans , Male , Primary Health Care , Surveys and Questionnaires
14.
Transplant Proc ; 49(5): 1183-1186, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28583552

ABSTRACT

BACKGROUND: Sarcoidosis is a chronic systemic disease that is characterized by the formation of noncaseating granuloma and whose etiology is unclear. It is unclear whether patients with sarcoidosis are suitable organ donors. CASE: We treated a 56-year-old woman with pulmonary sarcoidosis who donated her kidney. She was previously in good health and was diagnosed with pulmonary sarcoidosis during her preoperative examination. Because she presented with no symptoms and was otherwise in good condition, donor nephrectomy was performed. RESULTS: Baseline biopsy examination showed no evidence of sarcoidosis. One year after transplantation, both the donor and the recipient had not developed kidney dysfunction or recurrence of sarcoidosis. CONCLUSION: This is a rare case in which a patient with pulmonary sarcoidosis donated a kidney for transplantation, and both the recipient and the donor were clinically healthy. A patient with sarcoidosis and no kidney lesion can donate a living kidney, because transplantation appears to be safe for both the recipient and the donor.


Subject(s)
Kidney Transplantation , Living Donors , Sarcoidosis, Pulmonary , Female , Humans , Middle Aged
15.
Ann Oncol ; 28(8): 1876-1881, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28486692

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. CONCLUSIONS: Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoadjuvant Therapy , Stomach Neoplasms/drug therapy , Adult , Aged , Cisplatin/administration & dosage , Docetaxel , Drug Combinations , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Oxonic Acid/administration & dosage , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Taxoids/administration & dosage , Tegafur/administration & dosage
16.
Transplant Proc ; 49(1): 78-83, 2017.
Article in English | MEDLINE | ID: mdl-28104164

ABSTRACT

BACKGROUND: Previously, we explored the histopathologic characteristics of medullary ray injury (MRI) inducing interstitial fibrosis and tubular atrophy (IF/TA) to determine its etiologies, which include calcineurin inhibitor (CNI) toxicity and urologic complications. However, we did not examine the effects of these etiologies on long-term kidney allograft prognosis, because biopsy timing differed among cases. AIM: We examined the influence of early MRI on kidney allograft prognosis using protocol biopsies taken within a 3-month time frame. METHODS: We defined early MRI as tubular degeneration with interstitial edema or mild fibrosis localized to the medullary ray. We divided 53 protocol biopsies into 2 groups, with and without early MRI. Early MRI+ cases with isometric vacuolization were classified as CNI toxicity; those with Tamm-Horsfall protein in the interstitium and a thyroidlike appearance were classified as urinary tract system abnormalities; remaining cases were classified as "others." We compared changes in serum levels of creatinine (sCr) over 3 years and fibrosis extent at 1 year. RESULTS: The sCr levels were significantly higher in the MRI+ group than the MRI- group at 3 years (P = .024). Examining the 3 MRI+ subgroups, only the MRI+ urinary tract system abnormalities group had significantly high sCr levels compared to the MRI- group (P = .019). The MRI+ group showed significant signs of IF/TA at 1 year. CONCLUSIONS: Early MRI after kidney transplantation was significantly more likely to develop IF/TA at 1 year and had higher sCr levels at 3 years. In such cases, intervention might preserve graft function over the long term.


Subject(s)
Graft Rejection/pathology , Kidney Transplantation/adverse effects , Kidney/pathology , Adult , Biopsy , Creatinine/blood , Female , Fibrosis/pathology , Humans , Male , Middle Aged
17.
Int J Obstet Anesth ; 29: 34-38, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27789074

ABSTRACT

BACKGROUND: Maternal hypotension is a common complication during cesarean section performed under spinal anesthesia. Changes in maternal heart rate with postural changes or values of heart rate variability have been reported to predict hypotension. Therefore, we hypothesized that changes in heart rate variability due to postural changes can predict hypotension. METHODS: A total of 45 women scheduled to undergo cesarean section under spinal anesthesia were enrolled. A postural change test was performed the day before cesarean section. The ratio of the power of low and high frequency components contributing to heart rate variability was assessed in the order of supine, left lateral, and supine. Patients who exhibited a ⩾two-fold increase in the low-to-high frequency ratio when moving to supine from the lateral position were assigned to the postural change test-positive group. RESULTS: According to the findings of the postural change test, patients were assigned to the positive (n=22) and negative (n=23) groups, respectively. Hypotension occurred in 35/45 patients, of whom 21 (60%) were in the positive group and 14 (40%) were in the negative group. The incidence of hypotension was greater in the positive group (P<0.01). The total dose of ephedrine was greater in the positive group (15±11 vs. 7±7mg, P=0.005). The area under the receiver operating characteristic curve was 0.76 for the postural change test as a predictor of hypotension. CONCLUSION: The postural change test with heart rate variability analysis may be used to predict the risk of hypotension during spinal anesthesia for cesarean section.


Subject(s)
Anesthesia, Obstetrical/adverse effects , Anesthesia, Spinal/adverse effects , Cesarean Section , Heart Rate/physiology , Hypotension/diagnosis , Posture/physiology , Adult , Elective Surgical Procedures , Female , Humans , Hypotension/physiopathology , Intraoperative Complications/diagnosis , Intraoperative Complications/physiopathology , Pregnancy
18.
Phys Rev Lett ; 117(3): 037204, 2016 Jul 15.
Article in English | MEDLINE | ID: mdl-27472134

ABSTRACT

We report the experimental observation of Snell's law for magnetostatic spin waves in thin ferromagnetic Permalloy films by imaging incident, refracted, and reflected waves. We use a thickness step as the interface between two media with different dispersion relations. Since the dispersion relation for magnetostatic waves in thin ferromagnetic films is anisotropic, deviations from the isotropic Snell's law known in optics are observed for incidence angles larger than 25° with respect to the interface normal between the two magnetic media. Furthermore, we can show that the thickness step modifies the wavelength and the amplitude of the incident waves. Our findings open up a new way of spin wave steering for magnonic applications.

19.
Transplant Proc ; 48(3): 734-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27234724

ABSTRACT

BACKGROUND: An equation for the estimated glomerular filtration rate (eGFR) is generally used for evaluating renal function in Japan. OBJECTIVE: To assess the accuracy of the preoperative eGFR for estimating kidney donors' measured glomerular filtration rate (mGFR). METHODS: Between April 2009 and August 2014, 91 Japanese living kidney donors were included in this study. The eGFR was calculated as follows: eGFR = 194 × serum creatinine(-1.094) × Age(-0.287) (and × 0.739 for women), and the mGFR was evaluated using inulin clearance. The preoperative eGFR was then compared with the mGFR. RESULTS: Patients included 27 men and 64 women with a mean age of 56.8 ± 9.5 years (range, 36-79 years), mean body surface area of 1.56 ± 0.14 m(2) (range 1.27-1.92 m(2)), mean body mass index of 22.3 ± 2.3 kg/m(2) (range 14.0-27.0 kg/m(2)), and mean serum creatinine level of 0.66 ± 0.14 mg/dL (range 0.39-0.97 mg/dL). The mean eGFR was 81.3 ± 14.2 mL/min/1.73 m(2) (range 45.5-125.9 mL/min/1.73 m(2)), and the mean mGFR was 89.0 ± 15.5 mL/min/1.73 m(2) (range 45.4-130.7 mL/min/1.73 m(2)). The eGFR was significantly lower than the mGFR (P < .001). The correlation coefficient for the relationship between the eGFR and mGFR values was 0.503, and the mean difference between the 2 values was -7.8 (8.7%). CONCLUSIONS: Although the eGFR correlated with the mGFR, the eGFR values did not accurately estimate the mGFR in living kidney donors. Therefore, it is necessary to evaluate the mGFR, especially in marginal kidney donors.


Subject(s)
Glomerular Filtration Rate , Kidney Transplantation , Living Donors , Adult , Aged , Creatinine/blood , Female , Humans , Japan , Male , Middle Aged , Preoperative Care
20.
Transplant Proc ; 48(3): 827-30, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27234745

ABSTRACT

BACKGROUND: Studies have revealed that patients who undergo preemptive kidney transplantation (PKT) have favorable prognoses compared with those who undergo kidney transplantation after the initiation of dialysis. The number of PKT cases performed worldwide has been increasing. The goal of this study was to determine the clinical characteristics of patients who may successfully receive PKT. METHODS: A single-center, case-control study was conducted to determine the clinical factors that lead to referral for PKT. RESULTS: Between April 1, 2009, and August 1, 2015, a total of 118 patients underwent living donor kidney transplantation. Thirty of these patients had not undergone dialysis before their initial visit to the study hospital. Of these, 20 received kidney transplantation before and after dialysis initiation, respectively (group PKT+, successful PKT; group PKT-, failed PKT). The baseline characteristics at the primary visit were compared between groups. The median duration from the first visit to the study institution to PKT was 5.6 ± 0.7 months. Serum creatinine (Cr) levels differed significantly between groups (PKT+ vs PKT-, 6.0 ± 0.3 mg/dL vs 7.5 ± 0.5 mg/dL; P = .03). The receiver-operating characteristic curves revealed that a serum Cr level >5.7 mg/dL at the initial visit to the unit was a cutoff point for predicting the success of PKT (area under the curve, 0.721; P = .02). CONCLUSIONS: Our results indicate that PKT should be performed within ∼6 months of the initial visit to the transplant center. Serum Cr levels <5.7 mg/dL predict successful PKT.


Subject(s)
Graft Survival , Kidney Transplantation , Adult , Case-Control Studies , Creatinine/blood , Female , Humans , Living Donors , Male , Middle Aged , Prognosis , Renal Dialysis
SELECTION OF CITATIONS
SEARCH DETAIL
...