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Find video protocols related to scientific articles indexed in Pubmed.
[Updates on Lifestyle-Related Diseases and Bone Metabolism. CKD-related osteoporosis].
Clin Calcium
PUBLISHED: 10-31-2014
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Chronic kidney disease (CKD) has a high mortality rate of cardiovascular disease (CVD) . As CKD-mineral and bone disorder (CKD-MBD) is the one of the major risk factors in CVD, it is necessary that CKD patients are controlled CKD-MBD appropriately as early as possible. However, it is difficulty that CKD-MBD condition is exactly diagnosed and controlled, because it presents various conditions according to the difference of patient's background such as having diabetes or stage of CKD. We will give an outline of the mechanism in CKD-MBD according to patient's condition and the association between CKD-MBD and vascular calcification.
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Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors.
PLoS ONE
PUBLISHED: 08-25-2014
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Basic studies have shown that brain-derived neurotrophic factor (BDNF) has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system.
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[Classification of Diabetic Nephropathy 2014].
Nihon Jinzo Gakkai Shi
PUBLISHED: 08-19-2014
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The Committee on Diabetic Nephropathy revised the classification of diabetic nephropathy in view of the current status of eGFR and CKD in Japan. To make revisions for the classification of diabetic nephropathy 2014, the Committee carefully evaluated the report of the Research Group on Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. The major revisions made were as follows: 1. eGFR can be used for the evaluation of GFR; 2. In stage 3 (overt nephropathy), A and B were combined; 3. Stage 4 (renal failure) was defined as GFR less than 30 mL/min/1.73 m2, regardless of albuminuria; and 4. The importance of differential diagnosis was stressed in all stages.
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Plasma polyunsaturated fatty acid profile and delta-5 desaturase activity are altered in patients with type 2 diabetes.
Metab. Clin. Exp.
PUBLISHED: 08-07-2014
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The association between imbalance of polyunsaturated fatty acids (PUFAs), especially low plasma n-3 to n-6 PUFA ratio, and risk of cardiovascular diseases is well known. A balance of plasma PUFAs is determined not only by dietary fatty acid intake, but also by the endogenous fatty acid metabolism, which could be dysregulated by diabetes. In this study, we investigated the plasma n-3 and n-6 PUFA profile and fatty acid desaturase activity in patients with type 2 diabetes (T2D).
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Relationship between serum sclerostin, bone metabolism markers, and bone mineral density in maintenance hemodialysis patients.
J. Clin. Endocrinol. Metab.
PUBLISHED: 08-05-2014
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Sclerostin, which is secreted exclusively by osteocytes, is a negative regulator of bone formation. The role of sclerostin in chronic kidney disease-mineral and bone disorder is not well known. In the present study, we examined the relationship between serum sclerostin levels, bone turnover markers, and bone mineral density (BMD) of the radius in maintenance hemodialysis patients.
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Significant association between bone-specific alkaline phosphatase and vascular calcification of the hand arteries in male hemodialysis patients.
Kidney Blood Press. Res.
PUBLISHED: 07-18-2014
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Bone-specific alkaline phosphatase (BAP) hydrolyzes pyrophosphate, which inhibits vascular calcification. We examined association between serum BAP and vascular calcification of male hemodialysis patients.
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Advantage of Insulin Glulisine Over Regular Insulin in Patients With Type 2 Diabetes and Severe Renal Insufficiency.
J Ren Nutr
PUBLISHED: 06-30-2014
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To compare the efficacy and safety of insulin glulisine over regular insulin in patients with type 2 diabetes and severe renal insufficiency.
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Data from the Dialysis Outcomes and Practice Patterns Study validate an association between high intravenous iron doses and mortality.
Kidney Int.
PUBLISHED: 06-13-2014
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Intravenous (IV) iron is required for optimal management of anemia in the majority of hemodialysis (HD) patients. While IV iron prescription has increased over time, the best dosing strategy is unknown and any effect of IV iron on survival is unclear. Here we used adjusted Cox regression to analyze associations between IV iron dose and clinical outcomes in 32,435 HD patients in 12 countries from 2002 to 2011 in the Dialysis Outcomes and Practice Patterns Study. The primary exposure was total prescribed IV iron dose over the first 4 months in the study, expressed as an average dose/month. Compared with 100-199?mg/month (the most common dose range), case-mix-adjusted mortality was similar for the 0, 1-99, and 200-299?mg/month categories but significantly higher for the 300-399?mg/month (HR of 1.13, 95% CI of 1.00-1.27) and 400?mg/month or more (HR of 1.18, 95% CI of 1.07-1.30) groups. Convergent validity was proved by an instrumental variable analysis, using HD facility as the instrument, and by an analysis expressing IV iron dose/kg body weight. Associations with cause-specific mortality (cardiovascular, infectious, and other) were generally similar to those for all-cause mortality. The hospitalization risk was elevated among patients receiving 300?mg/month or more compared with 100-199?mg/month (HR of 1.12, 95% CI of 1.07-1.18). In light of these associations, a well-powered clinical trial to evaluate the safety of different IV iron-dosing strategies in HD patients is urgently needed.Kidney International advance online publication, 30 July 2014; doi:10.1038/ki.2014.275.
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Effect of Chair Stand Exercise on Activity of Daily Living: A Randomized Controlled Trial in Hemodialysis Patients.
J Ren Nutr
PUBLISHED: 05-07-2014
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Muscle atrophy and weakness impair activity of daily living (ADL). We examined whether chair stand exercise can improve ADL of hemodialysis patients.
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Clinical efficacy of oral risedronate therapy in Japanese patients with Paget's disease of bone.
J. Bone Miner. Metab.
PUBLISHED: 04-16-2014
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Paget's disease of bone (PDB) is a chronic disorder characterized by localized bone regions with excessive bone turnover. Although oral risedronate (17.5 mg daily for 8 weeks) was recently approved in Japan, its efficacy is not well understood. We retrospectively examined the efficacy of oral risedronate in PDB patients in a clinical setting. Eleven patients whose serum alkaline phosphatase (ALP) level exceeded the upper limit of the normal range were treated. Patients whose ALP levels normalized and remained so for 12 months after therapy initiation were defined as responders. Treatment was repeated if bone pain recurred or if serum ALP levels increased at least 25% above the nadir. Six patients (55%) were responsive to the therapy. A higher prevalence of skull lesions, higher serum calcium levels at treatment initiation and antecedent treatments of bisphosphonates were predictors of resistance against the therapy. Fresh frozen serum samples obtained from some treatment sessions were evaluated for metabolic bone markers such as bone-specific ALP (BAP), type I procollagen N-terminal pro-peptide (PINP), N-treminal crosslinking telopeptide of type I collagen and C-treminal crosslinking telopeptide of type I collagen (CTX). A significant reduction of P1NP preceded that of serum ALP levels in the responders, which was followed by a similar occurrence for BAP and osteocalcin (BGP) levels. A temporary decrease in CTX levels was noted. No significant changes in markers (including ALP level) were observed in non-responder and repeat-treatment groups. P1NP levels may be more useful than ALP levels in assessing treatment efficacy. Repeat treatment effectiveness for the repeat-treatment group was limited.
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Immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with diabetes mellitus: with special reference to age, body mass index, and HbA1c.
Hum Vaccin Immunother
PUBLISHED: 04-09-2014
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Subjects with diabetes mellitus are considered to be at high risk of influenza infection and influenza-associated complications. To evaluate the immunogenicity of the influenza A(H1N1)pdm09 vaccine among these subjects, we performed a prospective cohort study and measured hemagglutination inhibition antibody titers at baseline and 3 weeks after vaccination in 49 patients. No serious adverse events were reported. We were able to perform analyses for 48 patients, after excluding one patient with suspected infection. The vaccine induced a rise of about 9-fold in the mean antibody level. The sero-response proportion was 79%, and the sero-protection proportion was 73%. Patients with older age and lower body mass index tended to show lower immune response. Multivariate analysis indicated an independent negative effect of hemoglobin A1c level on the sero-protection proportion. A single A(H1N1)pdm09 vaccination achieved a sufficient level of immunity among diabetic patients, but both clinicians and patients should be aware of the potential for reductions in immune response.
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Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study.
J. Nucl. Med.
PUBLISHED: 03-24-2014
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Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia or astrocytes is related to neuroinflammation. (11)C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide ((11)C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used (11)C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients.
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Dialysate sodium prescription and blood pressure in hemodialysis patients.
Am. J. Hypertens.
PUBLISHED: 03-20-2014
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Diffusive sodium removal has been recommended to control hypertension in hemodialysis patients. Recent evidence on hospitalizations and mortality, however, challenged the benefit of lower dialysate sodium prescriptions and ignited a debate in the dialysis community. We therefore studied the relationship between dialysate sodium and blood pressure over the longer term.
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Association of blood pressure with all-cause mortality and stroke in Japanese hemodialysis patients: the Japan Dialysis Outcomes and Practice Pattern Study.
Hemodial Int
PUBLISHED: 03-14-2014
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The association of low blood pressure (BP) with high mortality is a characteristic for hemodialysis patients. This analysis clarifies the association of BP with mortality and stroke in Japanese hemodialysis (HD) patients and examines the association separately for patients with and without antihypertensive medication (BP meds). We analyzed 9134 patients from Japan in phases 1-4 (1999-2011) of the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective cohort study of in-center HD patients. The association of patient systolic (SBP) and diastolic (DBP) blood pressure with all-cause and cause-specific mortality was assessed using adjusted Cox regression. A U-shaped association between BP and all-cause mortality was observed, with lowest mortality for baseline SBP 140-159?mmHg and DBP 65-74?mmHg. Both SBP and DBP were positively and monotonically associated with stroke-related death: hazard ratio (95% confidence interval) was 1.24 (1.01-1.53) per 20?mmHg higher SBP and 1.23 (1.05-1.44) per 10?mmHg higher DBP. No evidence of interaction was found between SBP and use of BP meds regarding all-cause mortality (P for interaction?=?0.97); the association between SBP and stroke-related death was slightly stronger among patients not on BP meds than patients on BP meds (P for interaction?=?0.09). In Japanese HD patients, both low and high BP are associated with all-cause mortality. This analysis also documents a positive and monotonic association of BP with stroke-related deaths. Although our analysis indicates that the prescription of BP meds to hypertensive patients might protect against stroke-related death, additional study is warranted.
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Comparison of effects of pioglitazone and glimepiride on plasma soluble RAGE and RAGE expression in peripheral mononuclear cells in type 2 diabetes: randomized controlled trial (PioRAGE).
Atherosclerosis
PUBLISHED: 03-01-2014
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The receptor for advanced glycation end-products (RAGE) is involved in vascular complications in diabetic patients. Pioglitazone, in contrast to glimepiride, has been shown to be protective against atherosclerotic disorders. In this study, we directly compared the effects of those drugs on RAGE system.
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[Prediction by early change of bone metabolic markers of the efficacy of anti-osteoporotic drugs on bone mass in osteoporotic patients].
Clin Calcium
PUBLISHED: 03-01-2014
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The importance of measurement of bone metabolic markers has been increasingly recognized in the treatment of osteoporosis. Bone is a dynamic organ in which bone formation and resorption continuously occurs. Biochemical marker for bone metabolism is an non-invasive measure to assess bone metabolic state. Although the purpose of its measurement was initially hypothesized to predict rate of bone loss, the increase of bone marker by itself provides a clinically relevant marker for bone fragility. Furthermore, measurement of bone marker is known to help improve drug compliance. Recent sophistication of bone marker measurement and the increasing kinds of bone markers increase the importance of its measurement to improve osteoporosis treatment.
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Quantitative analysis of abdominal aortic calcification in CKD patients without dialysis therapy by use of the Agatston score.
Kidney Blood Press. Res.
PUBLISHED: 02-20-2014
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The aim of the present study was to quantitatively examine factors associated with aortic calcification in non-dialysis CKD patients.
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Serum ?2-Microglobulin Correlates Positively with Left Ventricular Hypertrophy in Long-Term Hemodialysis Patients.
Nephron Clin Pract
PUBLISHED: 02-19-2014
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Background/Aims: ?2-Microglobulin (?2-MG) is a major protein component of dialysis-related amyloidosis. In long-term hemodialysis (HD) patients, ?2-MG amyloid deposits not only in osteoarticular tissues, but also in systemic tissues, including the heart. The purpose of this study was to investigate the relationship between serum ?2-MG concentrations and echocardiographic parameters in long-term HD patients in a cross-sectional study. Methods: Measurement of serum ?2-MG concentrations and echocardiography were performed in 251 patients who had undergone HD therapy for more than 10 years. Results: The left ventricular mass index (LVMI) of the higher serum ?2-MG (?30 mg/l) group was significantly higher than that of the lower serum ?2-MG (<30 mg/l) group (151.5 ± 45.7 vs. 137.0 ± 44.5 g/m(2), p = 0.020). In simple regression analyses, serum ?2-MG concentrations correlated significantly and positively with interventricular septum thickness (IVST) (r = 0.215, p < 0.001), posterior left ventricular wall thickness (PWT) (r = 0.249, p < 0.001), left ventricular wall thickness (LVWT) (r = 0.252, p < 0.001), relative wall thickness (RWT) (r = 0.153, p = 0.015) and LVMI (r = 0.171, p = 0.007). Multiple regression analyses revealed that serum ?2-MG concentrations correlated significantly and positively with IVST, PWT, LVWT and RWT. Conclusion: Serum ?2-MG concentrations correlated significantly and positively with the echocardiographic parameters of left ventricular hypertrophy (LVH) in long-term HD patients. Thus, deposition of ?2-MG amyloid in the heart may be associated with LVH progression. © 2014 S. Karger AG, Basel.
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The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study.
Trials
PUBLISHED: 01-09-2014
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Hyperuricemia is a risk factor for the onset of chronic kidney disease (CKD) and is significantly associated with the progression of CKD. However, there is no sufficient evidence by interventional research supporting a cause-effect relationship. Hyperuricemic patients without gouty arthritis, whose serum urate (SUA) concentration is ?8.0 mg/dL and who have a complication, are treated by pharmacotherapy in addition to lifestyle guidance. Nevertheless, there is no evidence that rationalizes pharmacotherapy for patients with hyperuricemia who have no complication and whose SUA concentration is below 9.0 mg/dL.
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Leptin is associated with vascular endothelial function in overweight patients with type 2 diabetes.
Cardiovasc Diabetol
PUBLISHED: 01-08-2014
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The adipocyte-derived hormone leptin plays a key role in the regulation of appetite and body weight. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-related atherosclerosis and cardiovascular disease. In this study, we investigated the association of plasma leptin levels with vascular endothelial function in lean and overweight patients with type 2 diabetes.
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Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR) ?, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPAR?activation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.
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Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus.
J. Atheroscler. Thromb.
PUBLISHED: 12-10-2013
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Aim: Remnant lipoproteins are atherogenic and increased in patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus far, information is limited regarding the synthesis and absorption of cholesterol in CKD patients and a possible link to the remnant levels. We examined possible alterations in serum markers of cholesterol synthesis and absorption and their potential associations with remnant lipoproteins in patients with CKD. Methods: The subjects included 146 consecutive patients with T2DM in various stages of CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C), lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated glomerular filtration rate (eGFR) were used to describe the degree of CKD. Results: The median (interquartile range) levels of RemL-C, lathosterol and campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) ?g/mL and 2.3 (1.7-3.0) ?g/mL, respectively. The RemL-C level was positively correlated with the U-ACR and inversely correlated with the eGFR. The RemL-C level was positively correlated with both the lathosterol and campesterol levels. The lathosterol level was not significantly correlated with the U-ACR, although it was positively correlated with the eGFR. In contrast, the campesterol level was positively correlated with the ACR and inversely with the eGFR. In the multiple regression analysis, both lathosterol and campesterol were positively associated with the RemL-C level, independent of the U-ACR, eGFR and other variables. Conclusions: The serum campesterol concentrations are higher in patients with a greater degree of albuminuria and a lower renal funtion. In this study, the markers of cholesterol absorption and synthesis were independent determinants of the RemL-C level. Increased intestinal cholesterol absorption may be an additional mechanism for remnant accumulation in T2DM patients with CKD.
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Strategy of operative treatment of hyperparathyroidism using US scan and (99m)Tc-MIBI SPECT/CT.
Endocr. J.
PUBLISHED: 12-10-2013
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We evaluated the efficacy of (99m)Tc-MIBI SPECT/CT for planning parathyroidectomy in cases with primary hyperparathyroidism (pHPT), comparing with planar scintigraphy and US, in an aim to establish the proper surgical strategy according to the preoperative imaging studies. A retrospective review of consecutive 75 pHPT patients who had been operated on was conducted. The results of preoperative imaging modalities and the operative finding were analyzed. Seven cases were found to have multiple hyperplastic glands, and no responsible gland was found in three cases. Four cases underwent only US scan for preoperative imaging. Remaining 61 cases were found to have single adenoma, and were included in the evaluation of localization imaging. US scan, (99m)Tc-MIBI planar scan and (99m)Tc-MIBI SPECT/CT showed accurate localization in 77.0% (47/61), 75.4% (46/61) and 88.5% (46/52) of the evaluable cases, respectively. US and (99m)Tc-MIBI planar scan demonstrated consistent result in 42 cases (68.9%), and those cases showed accurate localization in 90.5% (38/42). When both US and (99m)Tc-MIBI SPECT/CT was consistent, all 37 lesions had been correctly indicated. No clinico-pathological features were suggested to influence in demonstrating the localization, other than only (99m)Tc-MIBI SPECT/CT exhibited 100% sensitivity in ectopic glands. Combination of US and (99m)Tc-MIBI SPECT/CT certainly contributes to the planning of minimally invasive operation in cases with pHPT by indicating correct localization of single adenoma.
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Association between glycemic control and morning blood pressure surge with vascular endothelial dysfunction in type 2 DM patients.
Diabetes Care
PUBLISHED: 12-02-2013
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ObjectiveMorning blood pressure surge (MBPS) is an independent predictor of cardiovascular events. However, little is known on the association between glycemic control and MBPS and its effect on vascular injury in patients with type 2 diabetes mellitus (T2DM). The present study examined the association between glycemic control and MBPS and the involvement of MBPS in the development of vascular dysfunction in T2DM patients.Research Design and MethodsWe examined MBPS in T2DM patients (M/F; 25/25, age; 60.1±13.2 years, n=50) by 24-hour ambulatory blood pressure monitoring, and assessed vascular function by brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD).ResultsHbA1c (?=0.373, p=0.009) and triglyceride (?=0.375, p=0.009) correlated significantly and positively with MBPS. In multiple regression analysis including triglyceride and HbA1c in addition to age, 24-hour systolic blood pressure (24h-SBP) as independent variables, HbA1c (?=0.328, p=0.016) and triglyceride (?=0.358, p=0.014) associated significantly in a positive manner with MBPS. In non-insulin user, when HOMA-R was included in place of TG, HOMA-R emerged as a significant factor. MBPS (?=-0.289, p=0.043), and HbA1c (?=-0.301, p=0.035) correlated significantly and negatively with FMD, while 24h-SBP correlated with both FMD (?=-0.359, p=0.012) and NMD (?=-0.478, p=0.004). In multiple regression analysis, including age, gender, 24h-SBP, MBPS, LDL-cholesterol, and HbA1c, MBPS (?=-0.284, p=0.044) alone associated significantly in a negative manner with FMD, but not with NMD.ConclusionsThe present study demonstrated that poor glycemic control and insulin resistance are independently associated with the occurrence of MBPS in T2DM patients, which might be significantly associated with endothelial dysfunction.
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Poor glycemic control is a major factor in the overestimation of glomerular filtration rate in diabetic patients.
Diabetes Care
PUBLISHED: 10-15-2013
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ObjectiveSerum creatinine levels are lower in diabetic patients compared with their non-diabetic counterparts. Therefore, estimated glomerular filtration rate (eGFR) is higher in the former than in the latter group. Factors associated with overestimation of renal function in diabetic patients were examined, and new formulae reflecting precise eGFR were created.Research Design and MethodsEighty subjects (age 56.5±15.4 years; 35 males (43.8%); 40 diabetics and 40 non-diabetics subjects) were enrolled. GFR was evaluated by inulin clearance (Cin). eGFR values were calculated based on serum creatinine and/or serum cystatin C levels. The factors related to the dissociation between eGFR and Cin in diabetic patients and the agreement between each of three eGFR and Cin were compared.ResultsAlthough Cin was not significantly different between the diabetic and non- diabetic subjects (p=0.2866), each of three eGFR measures from the diabetic patients was significantly higher than that of the non-diabetic subjects (p<0.01). There were significant and positive correlations between the ratio of each eGFR/Cin, hemoglobin A1c and glycated albumin. The intraclass correlation coefficients in diabetic patients were weaker than those in the non-diabetic subjects, and the intercepts of the regression lines between each eGFR measure and Cin in the diabetic patients were significantly higher than those of the non-diabetic subjects. New formulae for the calculation of eGFR corrected by the glycemic control indices were better than the original eGFR, particularly in diabetic patients.ConclusionseGFR overestimates Cin as glycemic controls worsen. eGFR corrected by hemoglobin A1c is considered to be clinically useful and feasible.
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[A case of gastric metastasis and carcinomatous peritonitis of breast cancer with improved QOL by stent implantation and gemcitabine].
Gan To Kagaku Ryoho
PUBLISHED: 08-30-2013
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A 73-year-old woman had undergone mastectomy for left breast cancer. One year later, bone metastasis was detected. After 7 years, the patient experienced epigastric discomfort, and gastrointestinal endoscopy showed stenosis of the pylorus and enlarged gastric folds. Stomach cancer was suspected at first, but gastric metastasis of breast cancer was diagnosed on the basis of endoscopic reexamination and computed tomography(CT)images. The patient could not drink water, and therefore, gastrointestinal stenting was performed, which facilitated ingestion to some extent. However, at the same time, an elevated serum carcinoembryonic antigen(CEA)level and jaundice were observed. Therefore, biliary tract stenosis due to carcinomatous peritonitis was diagnosed. We attempted to treat the jaundice with endoscopic retrograde cholangiopancreatography( ERCP)or percutaneous transhepatic cholangiography(PTCD), but the treatment was not successful, and an increase in ascites was noted. Accordingly, gemcitabine was administered as systemic therapy. As a result, ascites decreased and jaundice improved. Patients with gastric metastasis of breast cancer have poor quality of life(QOL)because of difficulties in ingestion or vomiting, and poor prognoses, because of frequent concurrent carcinomatous peritonitis. We experienced a case of gastric metastasis and carcinomatous peritonitis, and were able to improve the patients QOL by gastrointestinal stenting and gemcitabine administration.
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Hair magnesium, but not serum magnesium, is associated with left ventricular wall thickness in hemodialysis patients.
Circ. J.
PUBLISHED: 08-23-2013
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Background:?Extracellular magnesium (Mg) accounts for approximately 1% of the total body Mg. Clinically, serum Mg concentration is measured, but it does not necessarily reflect total body Mg status. Although relationships have been reported between reduced Mg and cardiovascular disease in non-dialysis patients, there have been few such studies in hemodialysis patients. It was hypothesized that reduced Mg, as represented by lower Mg concentration in the hair, would be associated with echocardiographic parameters in chronic hemodialysis patients. Methods and Results:?Hair Mg concentration was measured in 79 male hemodialysis patients using inductively coupled plasma mass spectrometry, and the relationships between hair Mg concentration and echocardiographic parameters were investigated. There was no significant correlation between Mg concentration in the hair and in serum. Hair Mg concentration in the patients with high-left ventricular mass index (LVMI) was significantly lower than that in the low-LVMI patients. Hair Mg concentration correlated significantly and negatively with posterior left ventricular wall thickness, interventricular septum thickness, left ventricular wall thickness (LVWT), and relative wall thickness. Serum Mg concentration, however, did not correlate with any of these echocardiographic parameters. Conclusions:?In hemodialysis patients, hair Mg concentration is a biomarker, independent of serum Mg concentration. Hair Mg, but not serum Mg, was significantly and negatively associated with LVWT. Reduced tissue Mg concentration, as measured in the hair, may be associated with left ventricular hypertrophy in hemodialysis patients.??(Circ J?2013; 77: 3029-3036).
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Increased soluble IL-2 receptor levels in serum from a patient with painless thyroiditis.
Thyroid Res
PUBLISHED: 08-15-2013
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Context: Serum concentration of soluble interleukin-2 receptor (sIL-2R) has been established as a reliable marker of T-lymphocyte activation. However, there have been no reports describing the relationship between serum sIL-2R and painless thyroiditis.
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Impact of lanthanum carbonate on cortical bone in dialysis patients with adynamic bone disease.
Ther Apher Dial
PUBLISHED: 04-17-2013
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Among the most serious problems in patients with chronic kidney disease (CKD) is fragility of cortical bone caused by cortical thinning and increased cortical porosity; the cortical fragility is sometimes irreversible, with fractures generally initiating from cortical bone. Therefore, development of treatments for problems of cortical bone is urgently desired. Cortical bone has the three surfaces, including the periosteal surface, intracortical spaces and endocortical surface. Bone turnover at the endocortical surface and intracortical resorption spaces are increased as compared with that at cancellous surface. Bone growth sometimes depends on apposition at the periosteal surface. We treated hyperphosphatemia in two hemodialysis patients with adynamic bone disease with 750-1500?mg/day of lanthanum carbonate, which is a non-calcium containing phosphate binder; the treatment resulted in a decrease of the serum phosphorus levels (P levels), without significant change of the serum intact parathyroid hormone levels. We now report that treatment of these patients with lanthanum carbonate increased mineralization of the periosteal surface, increased bone mass within the intracortical resorption spaces and increased mineralization of the minimodeling surface at the endocortical surface. In addition, woven bone volume in cortical bone was decreased and mineralization of bone units, namely, osteons, was increased. Although these findings were not observed across all surfaces of the cortical bone in the patients, it is expected that lanthanum carbonate would increase the cortical stability in CKD patients, with consequent reduction in the fracture rate in these patients.
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Clinical assessment of delayed gastric emptying and diabetic complications using gastric emptying scintigraphy: Involvement of vascular disorder.
Clin Physiol Funct Imaging
PUBLISHED: 03-21-2013
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Delayed gastric emptying, including gastroparesis, is a common complication in diabetes mellitus. The association between delayed gastric emptying and overall diabetic complications remains to be studied in detail. We analysed this association.
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Autonomic function is associated with health-related quality of life in patients with end-stage renal disease: a case-control study.
J Ren Nutr
PUBLISHED: 02-27-2013
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In the present study, we assessed the associations among fatigue, quality of life (QOL), clinical parameters, and body mass index (BMI) with autonomic function in end-stage renal disease (ESRD) patients undergoing hemodialysis as well as fatigue-free healthy subjects.
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Thyroid heterogeneity, as indicated by the CV of ultrasonographic intensities, correlates with anti-thyroid peroxidase antibodies in euthyroid Hashimotos thyroiditis.
Thyroid Res
PUBLISHED: 02-11-2013
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To prospectively evaluate the heterogeneous appearance of the thyroid gland, reflecting inflammation and destruction in euthyroid Hashimotos thyroiditis (HT), we investigated the clinical utilities of the heterogeneity index (HI) [the coefficient of variance (CV) of the ultrasonographic (US) intensities], focusing on anti-thyroid peroxidase antibodies (TPO-Ab), which represent not only disease activity but also subsequent thyroid destruction of HT.
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Significant positive association between parathyroid hormone and fat mass and lean mass in chronic hemodialysis patients.
J. Clin. Endocrinol. Metab.
PUBLISHED: 02-07-2013
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It has been reported that there is a significant positive relationship between PTH and body weight or body mass index in the general population. However, little is known about this relationship in dialysis patients in whom PTH levels are higher. It is also not known whether fat mass or lean mass is associated with serum PTH among these patients. In the present study, we examined the association of intact PTH with fat mass and lean mass in hemodialysis patients.
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Serum n-3 and n-6 polyunsaturated fatty acid profile as an independent predictor of cardiovascular events in hemodialysis patients.
Am. J. Kidney Dis.
PUBLISHED: 02-05-2013
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Unlike the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), n-3-PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to have beneficial effects on inflammation, thrombosis, and cardiovascular disease (CVD). We examined possible alterations in serum PUFA profiles in patients on maintenance hemodialysis therapy and its association with CVD risk.
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Tumor necrosis factor-related apoptosis-inducing ligand as an independent predictor of mortality in hemodialysis patents.
Cytokine
PUBLISHED: 02-04-2013
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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was originally isolated as an inducer of apoptosis in transformed cells. In addition to tumor surveillance, recent findings suggest that TRAIL and its receptor system have a protective role against infection and cardiovascular disease (CVD). Patients undergoing hemodialysis have a high mortality rate with a unique risk factor profile. Considering that the leading causes of death in these patients are infection and CVD, TRAIL represents an attractive candidate for predicting mortality in this population. We therefore investigated whether TRAIL predicted mortality in hemodialysis patients.
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Greater potency of darbepoetin-? than erythropoietin in suppression of serum hepcidin-25 and utilization of iron for erythropoiesis in hemodialysis patients.
Eur. J. Haematol.
PUBLISHED: 01-04-2013
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The potency of darbepoetin-? (DPO-?) to improve anemia in hemodialysis (HD) patients is greater than that of recombinant human erythropoietin (rHuEPO).
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Relationship between serum TSH levels and intrarenal hemodynamic parameters in euthyroid subjects.
Eur. J. Endocrinol.
PUBLISHED: 01-01-2013
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Low thyroid function may be associated with a reduced glomerular filtration rate (GFR) calculated on the basis of creatinine metabolism. Thyroid hormone directly affects serum creatinine in muscle and low thyroid function might exert a similar direct effect in the kidney. The goal of the study was to evaluate this possibility by assessment of the inulin-based GFR and to examine the mechanism underlying the reduction of GFR.
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Proteome analysis of laser microdissected glomeruli from formalin-fixed paraffin-embedded kidneys of autopsies of diabetic patients: nephronectin is associated with the development of diabetic glomerulosclerosis.
Nephrol. Dial. Transplant.
PUBLISHED: 12-15-2011
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To date, little proteomic information has been available from the glomeruli of diabetic patients, possibly due to the clinical limitations of renal biopsy in diabetic patients and insufficient quantities of such specimens for proteome analysis. The purpose of the present study was to identify altered protein expression profiles in diabetic glomeruli using formalin-fixed paraffin-embedded (FFPE) kidney tissues from diabetic patients.
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Association of endothelial and vascular smooth muscle dysfunction with cardiovascular risk factors, vascular complications, and subclinical carotid atherosclerosis in type 2 diabetic patients.
J. Atheroscler. Thromb.
PUBLISHED: 12-06-2011
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Atherosclerosis and arteriosclerosis are mainly caused by the dysfunction of arterial components, namely, vascular endothelial cells, smooth muscle cells, and the extracellular matrix. Endothelial dysfunction is well established as a predictive surrogate marker of cardiovascular events; however, little is known regarding the clinical implications of vascular smooth muscle dysfunction for cardiovascular disease and microangiopathy. In the present study, we aimed to clarify the association of arterial dysfunction with micro-/macroangiopathy and conventional cardiovascular risk factors in 181 type 2 diabetic patients (T2DM; age ± SD, 64 ± 10 years; duration of diabetes, 12 ± 10 years).
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Dialysate sodium concentration and the association with interdialytic weight gain, hospitalization, and mortality.
Clin J Am Soc Nephrol
PUBLISHED: 11-03-2011
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Recommendations to decrease the dialysate sodium (DNa) prescription demand analyses of patient outcomes. We analyzed morbidity and mortality at various levels of DNa, simultaneously accounting for interdialytic weight gain (IDWG) and for the mortality risk associated with lower predialysis serum sodium (SNa) levels.
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Poor muscle quality as a predictor of high mortality independent of diabetes in hemodialysis patients.
Biomed. Pharmacother.
PUBLISHED: 09-15-2011
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Poor muscle quality provides a clinically relevant measure for mortality in general population, particularly in the elderly people. Our previous reports indicating poorer muscle quality in diabetes mellitus (DM) hemodialysis patients than in non-DM counterparts prompted us to examine the association between two parameters in hemodialysis patients, independent of DM prevalence.
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[Membranous nephropathy with nephrotic syndrome developed after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia].
Rinsho Ketsueki
PUBLISHED: 08-09-2011
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A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bone marrow transplantation from an unrelated donor during the patients first complete remission. After engraftment, he developed acute graft-versus-host disease involving the gastrointestinal tract on day 32. Steroids and mycophenolate mofetil were initiated from day 39. His symptoms improved and the dose of immunosuppressants was tapered and then discontinued on day 421. On day 491, he developed nephrotic syndrome (NS). Based on renal biopsy, membranous nephropathy was diagnosed. There were no apparent symptoms or abnormal laboratory data suggestive of chronic graft-versus-host disease (cGVHD). Steroid therapy was initiated from day 518 and proteinuria improved significantly. NS is very rare following allogeneic hematopoietic stem cell transplantation (allo-HSCT). When there is no concomitant cGVHD, as in this case, allo-HSCT-associated NS is difficult to distinguish from idiopathic NS.
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Comparison of the effect of cilostazol with aspirin on circulating endothelial progenitor cells and small-dense LDL cholesterol in diabetic patients with cerebral ischemia: a randomized controlled pilot trial.
J. Atheroscler. Thromb.
PUBLISHED: 06-24-2011
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A recent clinical trial showed the preventive effect of cilostazol on cerebrovascular diseases. We compared the effects of cilostazol with aspirin on circulating endothelial progenitor cells (EPCs), a surrogate marker for cardiovascular disease, and lipid metabolism in a randomized controlled trial (UMIN000000537).
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Targeted proteomics of isolated glomeruli from the kidneys of diabetic rats: sorbin and SH3 domain containing 2 is a novel protein associated with diabetic nephropathy.
Exp Diabetes Res
PUBLISHED: 06-21-2011
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To evaluate proteins associated with the development of diabetic nephropathy, a major cause of the end-stage renal disease, we analyzed protein expression in isolated glomeruli from spontaneous type 2 diabetic (OLETF) rats and their age-matched control littermates (LETO) in the early and proteinuric stages of diabetic nephropathy using QSTAR Elite LC-MS/MS. Among the 191 and 218 proteins that were altered significantly in the OLETF rats, twenty-four were actin cytoskeleton-associated proteins implicated in the formation of stress fibers, and the impairment of actin polymerization, intermediate filaments and microtubules. Importantly, sorbin and SH3 domain containing 2 (SORBS2), which is involved in the formation of stress fibers, was significantly upregulated in both stages of diabetic nephropathy (1.49- and 1.97-fold, resp.). Immunohistochemical and quantitative-PCR analyses revealed upregulation of SORBS2 in podocytes of glomeruli of OLETF rats. Our findings suggested that SORBS2 may be associated with the development of diabetic nephropathy possibility by reorganization of actin filaments.
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Evaluation of bone markers in hypophosphatemic rickets/osteomalacia.
Endocrine
PUBLISHED: 06-10-2011
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N-terminal propeptide of type I procollagen (PINP) is a marker of newly formed type I collagen. However, its role in hypophosphatemic rickets/osteomalacia has not yet been established. Metabolic bone markers were examined in patients with oncogenic osteomalacia (OOM) and X-linked hypophosphatemic rickets (XLH), and in healthy controls. OOM and XLH patients were found to have hypophosphatemia secondary to elevated levels of serum fibroblast growth factor 23 (FGF-23). OOM patients had reduced levels of 1,25-dihydroxy vitamin D (1,25D) compared with XLH patients and healthy controls, despite attenuation of the reduction in these levels in the XLH patients secondary to active vitamin D supplementation. In contrast to patients with XLH, OOM patients showed a significant increase in serum PINP, which is suggestive of accelerated bone matrix formation. Bone alkaline phosphatase (BAP) and the BAP/PINP ratio were also increased in OOM but not in XLH patients, suggesting the presence of a disturbance in bone mineralization in OOM. Long-term supplementation of active form vitamin D and inorganic phosphate (IP) may have attenuated the defect in bone mineralization in the XLH patients, resulting in the normalization of PINP, BAP, and the BAP/PINP ratio. The present results suggest that, as with BAP, PINP is an appropriate metabolic bone marker in the assessment of hypophosphatemic rickets/osteomalacia.
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Active vitamin D and acute respiratory infections in dialysis patients.
Clin J Am Soc Nephrol
PUBLISHED: 05-26-2011
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Vitamin D has gained attention for its pleiotropic effects in areas other than bone metabolism, and the effects of vitamin D in preventing respiratory infections have been reported as one of its immunomodulating properties. This study assessed the preventive effect of vitamin D receptor activator (VDRA) on respiratory infections in dialysis patients.
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Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis.
J Toxicol Pathol
PUBLISHED: 03-31-2011
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In the present study, modifying effects of diabetes on carcinogenesis induced in type 2 diabetes mellitus model Zucker diabetic fatty (ZDF) rats were investigated using a multiorgan carcinogenesis bioassay. Our re sults demonstrated enhancement of urinary bladder, colon and liver carcinogenesis in ZDF rats treated with five types of carcinogens (DMBDD). Elevated insulin and leptin and decreased adiponectin levels in the serum may be responsible for the high susceptibility of type 2 diabetes mellitus model rats to carcinogenesis in these organs. Possible mechanisms of increased susceptibility of diabetic rats to bladder carcinogenesis could be activation of the PI3K pathway and suppression of p53 in the urothelium in consequence of the above serum protein alterations.
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[Morphological analysis of bone dynamics and metabolic bone disease. A case report of recurrent renal hyperparathyroidism].
Clin Calcium
PUBLISHED: 03-31-2011
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A 39-years-old chronic hemodialysis patient who developed recurrent hyperparathyroidism after total parathyroidectomy with immediate autotransplantation (PTX-AT) is now reported. The patient had undergone bilateral nephrectomy due to bilateral renal cell carcinoma at 4 and 5 years after the initiation of dialysis, followed by the treatment with interleukin-2 administration. Secondary hyperparathyroidism was treated by PTX-AT, followed by confirmation of reduced bone turnover. The parathyroid glands were huge and the total weight of the parathyroid glands was 14.3 gr. Pathological examination revealed nodular hyperplastic parathyroid tissue in all four glands. However, the serum intact parathyroid hormone (iPTH) increased again at 7 years after the PTX, and bone biopsy revealed high turnover bone disease. The recurrent hyperparathyroidism was treated with cinacalcet hydrochloride to reduce the serum iPTH level.
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Higher serum bone alkaline phosphatase as a predictor of mortality in male hemodialysis patients.
Life Sci.
PUBLISHED: 03-18-2011
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Higher serum alkaline phosphatase predicts lower mortality in chronic kidney disease and hemodialysis patients without liver dysfunction because it reflects high bone turnover. The purpose of our study was to compare the significance of serum bone alkaline phosphatase (BAP) with that of other bone markers in prediction of all-cause mortality(ACM) in male hemodialysis patients.
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Fetuin-A: a multifunctional protein.
Recent Pat Endocr Metab Immune Drug Discov
PUBLISHED: 02-07-2011
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Sixty-six years have elapsed since the discovery of fetuin in 1944, but its importance in mammalian physiology has only recently been appreciated. Fetuin, first isolated from fetal bovine serum and now most commonly known as either fetuin-A, alpha-2-HS-glycoprotein (recommended name by UniprotKB and PIR), or ?2-Heremans-Schmid glycoprotein, functions as an important component of diverse normal and pathological processes, including vascular calcification and bone metabolism regulation, insulin resistance, protease activity control, keratinocytes migration, and breast tumor cell proliferative signaling. Fetuin-A has also been identified as a biomarker for neurodegenerative disease. Here, we summarize recent publications focusing on the structural and functional properties of fetuin-A. The emerging importance of fetuin-A for both diagnosis and therapeutics has come to the attention of the pharmaceutical industry. Therefore, we will discuss the status of patents based on fetuin-A.
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Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts.
J. Gastroenterol.
PUBLISHED: 01-19-2011
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Screening and prophylactic treatment for hepatitis B virus (HBV) reactivation is recommended for patients who receive immunosuppressive or cytotoxic therapy. The aim of this study was to clarify the prevalence of HBV reactivation in rheumatoid arthritis (RA) patients who had received more than 1 year of immunosuppressive therapy. This study also evaluated guidelines for determining HBV reactivation in patients with RA.
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Trace elements in the hair of hemodialysis patients.
Biol Trace Elem Res
PUBLISHED: 01-14-2011
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Trace element disturbance is often observed in hemodialysis patients. While trace element concentrations have been reported in blood samples from hemodialysis patients, they have not been well investigated in scalp hair. In the present study, 22 trace elemental concentrations were measured by inductively coupled plasma-atomic emission spectrometry in the scalp hair of 80 male hemodialysis patients and compared with those of 100 healthy male subjects. In hemodialysis patients, the concentrations of beryllium, arsenic, magnesium, chromium, manganese, iron, selenium, molybdenum, iodine, vanadium, and cobalt were significantly higher than those in healthy subjects, while lead, mercury, copper, germanium, and bromine were significantly lower than those in the former group. No significant differences were observed for lithium, aluminum, cadmium, zinc, boron, or nickel. There were significant positive correlations between the duration of hemodialysis and the magnesium and manganese concentrations. There was a significant negative correlation between cadmium concentration and the duration of hemodialysis. There were significant positive correlations between dialysis efficacy (Kt/V) and magnesium, manganese, zinc, and selenium concentrations. In conclusion, trace element concentrations of the scalp hair are different between hemodialysis patients and healthy subjects. Essential trace elements, such as magnesium, manganese, zinc, and selenium, may be affected by the duration of hemodialysis and Kt/V.
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Association of serum TRAIL levels with atherosclerosis in patients with type 2 diabetes mellitus.
Diabetes Res. Clin. Pract.
PUBLISHED: 01-11-2011
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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was originally isolated as an inducer of apoptosis. Recent cross-sectional and prospective studies suggest an inverse association of serum TRAIL levels with the severity of coronary artery disease (CAD) and with an adverse outcome in patients with CAD or heart failure. However, it is unknown whether TRAIL can inversely reflect the progression of atherosclerosis from its early stage. We therefore examined the association between TRAIL measured by ELISA and intima-media thickness (IMT) in carotid and femoral arteries evaluated by ultrasonography as a surrogate marker of atherosclerosis in 416 type 2 diabetic patients without any symptoms of CAD and heart failure. Concurrently, the existence of calcified plaque (CP) was examined. There was no significant association between TRAIL and carotid IMT (?=-0.096, p=0.052) or femoral IMT (?=-0.025, p=0.610), although TRAIL was associated with carotid IMT in a subset of patients with macrovascular diseases (?=-0.174, p=0.034). No difference in TRAIL levels was found between two groups with or without CP. TRAIL may not be a good candidate as a biomarker to evaluate early-stage atherosclerotic lesions.
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Matrix extracellular phosphoglycoprotein is expressed in causative tumors of oncogenic osteomalacia.
J. Bone Miner. Metab.
PUBLISHED: 01-07-2011
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Oncogenic osteomalacia (OOM), or tumor-induced osteomalacia, is a rare disease characterized by renal phosphate wasting and osteomalacia. It arises due to the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Matrix extracellular phosphoglycoprotein (MEPE) is predominantly expressed in odontoblasts, osteoblasts, and osteocytes. Although the presence of MEPE mRNA has been reported in some OOM tumors, little is known about the prevalence of MEPE expression in OOM tumors. In this study, the expression of MEPE and FGF-23 in OOM tumors was investigated at the transcriptional and translational levels. Eleven causative OOM tumors were analyzed by quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry for MEPE and FGF-23 expression. Hemangiopericytomas and giant cell tumors, pathological diagnoses that are common in cases of OOM, were obtained from non-osteomalacic patients and analyzed as controls. The gene expression level of FGF23 and MEPE in OOM tumors was 10(4)- and 10(5)-times higher, respectively, than in non-OOM tumors. Immunohistochemical staining revealed that FGF-23 protein was expressed in all OOM tumors, and MEPE was expressed in 10 out of 11 OOM tumors. Thus, MEPE expression was common in OOM tumors, similar to FGF-23. These results indicate that, in addition to the hypophosphatemic effects of FGF-23, MEPE or the MEPE-derived acidic serine aspartate-rich MEPE-associated motif peptide may contribute to decreased bone mineralization in OOM patients.
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Relationship between fat mass and serum high-sensitivity C-reactive protein levels in prevalent hemodialysis patients.
Nephron Clin Pract
PUBLISHED: 01-06-2011
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Little is known about the relationship between fat mass distribution and chronic inflammation in dialysis patients, in whom chronic inflammation is related to morbidity and mortality.
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Decreased kidney function is a significant factor associated with silent cerebral infarction and periventricular hyperintensities.
Kidney Blood Press. Res.
PUBLISHED: 01-06-2011
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Silent cerebral lacunar infarction (SCI) and periventricular hyperintensities (PVH) have been reported to be markers of ischemic cerebral small-vessel disease and risk factors for future cerebrovascular events in the general population. The relationship between CKD and SCI/PVH is examined.
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Cinacalcet HCl suppresses Cyclin D1 oncogene-derived parathyroid cell proliferation in a murine model for primary hyperparathyroidism.
Calcif. Tissue Int.
PUBLISHED: 01-03-2011
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Cinacalcet HCl (cinacalcet) is a calcimimetic compound, which suppresses parathyroid (PTH) hormone secretion from parathyroid glands in both primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT). We previously reported the suppressive effect of cinacalcet on PTH secretion in vivo in a PHPT model mouse, in which parathyroid-targeted overexpression of the cyclin D1 oncogene caused chronic biochemical hyperparathyroidism and parathyroid cell hyperplasia. Although cinacalcet suppressed parathyroid cell proliferation in SHPT in 5/6-nephrectomized uremic rats, its effect on PHPT has not yet been determined. In this study, the effect of cinacalcet on parathyroid cell proliferation was analyzed in PHPT mice. Cinacalcet (1 mg/g) was mixed into the rodent diet and orally administrated to 80-week-old PHPT mice for 10 days before death. 5-Bromo-2-deoxyuridine (BrdU, 6 mg/day) was infused by an osmotic pump for 5 days before death, followed by immunostaining of the thyroid-parathyroid complex using an anti-BrdU antibody to estimate parathyroid cell proliferation. Compared to untreated PHPT mice, cinacalcet significantly suppressed both serum calcium and PTH. The proportion of BrdU-positive cells to the total cell number in the parathyroid glands increased considerably in untreated PHPT mice (9.5 ± 3.1%) compared to wild-type mice (0.7 ± 0.1%) and was significantly suppressed by cinacalcet (1.2 ± 0.2%). Cinacalcet did not affect apoptosis in the parathyroid cells of PHPT mice. These data suggest that cinacalcet suppressed both serum PTH levels and parathyroid cell proliferation in vivo in PHPT.
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Different effects of diabetic autonomic neuropathy on regional transcutaneous oxygen tension in patients with peripheral arterial disease.
Osaka City Med J
PUBLISHED: 12-06-2010
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Diabetic autonomic neuropathy (DAN) is thought to reduce skin nutritive perfusion through increase of arteriovenous shunting flow, resulting in foot ulceration. However, the correlation between skin tissue oxygenation and DAN has not been fully elucidated. Transcutaneous oxygen tension (TcPO2) is a reliable indicator of skin nutritional microcirculation. The aim of this study was to evaluate the influence of DAN on skin microcirculation by using TcPO2 measurements.
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Different impacts of neck circumference and visceral obesity on the severity of obstructive sleep apnea syndrome.
Obesity (Silver Spring)
PUBLISHED: 08-12-2010
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Our aim was to investigate the significance of neck circumference (NC) on the presence and severity of obstructive sleep apnea (OSA) syndrome independent of visceral fat (VF) obesity. A total of 219 subjects with suspected OSA underwent a complete polysomnography (PSG) study, along with the measurement of NC, and total body fat (TF) and VF levels (VFLs) measured by bioelectrical impedance analysis. We proposed NC divided by height (NC/H) as the simple index for height-corrected NC in Japanese subjects. NC/H exhibited a significantly stronger correlation than NC per se with BMI (r = 0.781 vs. 0.675, P = 0.0178), TF (r = 0.531 vs. 0.156, P < 0.0001), and VF (r = 0.819 vs. 0.731, P = 0.0203), indicating that NC/H is a better indicator of visceral obesity than NC per se. Interestingly, despite the strong correlation between NC/H and VFL, VFL was significantly associated with the apnea-hypopnea index (AHI) ? 5, ? 15, and ? 30, but not with ? 40 or ? 50, whereas NC/H was significantly associated with higher AHI values, i.e., AHI ? 50 but not with lower AHI value. Furthermore, multiple regression analyses revealed that VFL and NC/H were independently associated with the square root of AHI (AHI(0.5)) levels in obese and nonobese patients, respectively. In conclusion, NC is associated with the severity of OSA independently of visceral obesity, especially in nonobese patients.
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The administration of an active vitamin D(3) analogue reduced the serum concentrations of 1-84 and truncated parathyroid hormone in pseudohypoparathyroidism type Ib patients.
Endocr. J.
PUBLISHED: 05-28-2010
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Serum calcium is one of major regulators of PTH amino-terminal (N-terminal) truncation and secretion of full-length (1-84)PTH from parathyroid glands. However, the effect of active vitamin D(3) on PTH truncations remains controversial. To determine whether active vitamin D(3) accelerates the truncation of PTH, the vitamin D(3) analogue alfacalcidol was administered to patients with pseudohypoparathyroidism type Ib (PHP Ib). Both the (1-84)PTH molecule and N-terminally truncated fragments such as (7-84)PTH can be measured by commercially available two-site total PTH (T-PTH) assays. The development of whole PTH (W-PTH) assays specific for full-length (1-84)PTH has enabled us to distinguish between N-terminally truncated PTH and full-length (1-84)PTH. W-PTH/T-PTH ratios were calculated and used as an index of PTH N-terminal truncations. Both serum W-PTH and T-PTH levels were elevated in untreated PHP Ib patients. The administration of alfacalcidol reduced both the W-PTH and T-PTH levels; however, the W-PTH/T-PTH ratios were stable. Serum calcium levels were significantly and negatively correlated with both the W-PTH and T-PTH levels, but not with the W-PTH/T-PTH ratios. Thus, the administration of an active vitamin D(3) analogue did not seem to have a major effect on the rate of PTH N-terminal truncation, even though it did reduce the secretion of both full-length and truncated PTH. Possibly, active vitamin D(3) attenuates the effect of elevated calcium on PTH N-terminal truncation in PHP Ib patients.
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Increased osteocyte death and mineralization inside bone after parathyroidectomy in patients with secondary hyperparathyroidism.
J. Bone Miner. Res.
PUBLISHED: 05-26-2010
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In order to gain insight into the mechanisms underlying the dynamic changes in bone metabolism and bone quality after parathyroidectomy (PTX) in secondary hyperparathyroid patients with high levels of parathyroid hormone (PTH), we performed bone histomorphometric analysis with tetracycline labeling in iliac bone biopsy specimens taken before and after PTX, with special attention paid to osteocytes. At 2 to 4 weeks after PTX, PTH concentrations decreased markedly with evident reductions in bone turnover markers. Histomorphometry revealed that at 2 to 4 weeks following PTX, the osteoclast surface decreased to nearly 0%, with a substantial increase in osteoid volume and a reduction in fibrosis volume. Labeling with tetracycline was observed not only at the mineralization front on the bone surface but also around the osteocyte lacunar walls and canaliculi within both the basic multicellular units (BMUs) and bone structural units (BSUs), suggesting that mineralization was taking place along the lacunocanalicular system after PTX. The tetracycline-labeled area was much greater in the BSUs than in the BMUs and at the mineralization front, and the tetracycline labeling in the BSUs was markedly increased after PTX compared with that in the low- and high-PTH control groups without PTX. The osteocyte number was decreased significantly after PTX, concomitant with an increase in the number of empty lacunae and a reduction of lacunar volume. Thus the increased osteocyte death and mineralization around the lacunocanalicular system in association with a rapid decline in PTH may underlie the changes in bone metabolism and quality that occur following PTX.
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Beneficial effect of risedronate on arterial thickening and stiffening with a reciprocal relationship to its effect on bone mass in female osteoporosis patients: a longitudinal study.
Life Sci.
PUBLISHED: 05-12-2010
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A longitudinal study was performed to examine the effect of risedronate on arterial thickening and stiffening in postmenopausal female osteoporosis patients.
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Fetuin-A is associated with calcified coronary artery disease.
Coron. Artery Dis.
PUBLISHED: 05-04-2010
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Fetuin-A is a circulating glycoprotein that is involved in various stages of atherosclerosis. Despite the fact that emerging evidence suggests fetuin-A acts as a calcification inhibitor that protects against advanced calcified atherosclerosis in dialyzed patients, the role of fetuin-A in cardiovascular disease is still controversial. As diabetes and uremia make the role of fetuin-A in cardiovascular disease uncertain, we investigated the association between fetuin-A and calcified coronary artery disease in participants without diabetes and renal dysfunction.
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Serum C-reactive protein and thioredoxin levels in subjects with mildly reduced glomerular filtration rate.
BMC Nephrol
PUBLISHED: 04-27-2010
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Chronic kidney disease (CKD) is a newly recognized high-risk condition for cardiovascular disease (CVD), and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR).
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Decreases in parathyroid gland volume after cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism.
Nephron Clin Pract
PUBLISHED: 04-23-2010
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Cinacalcet, an allosteric modulator of the calcium-sensing receptor, effectively reduces serum parathyroid hormone (PTH). It was examined whether a regression of parathyroid glands in hemodialysis patients with secondary hyperparathyroidism was induced by cinacalcet treatment.
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Geriatric Nutritional Risk Index, a simplified nutritional screening index, is a significant predictor of mortality in chronic dialysis patients.
Nephrol. Dial. Transplant.
PUBLISHED: 04-16-2010
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Malnutrition is a common complication in haemodialysis patients. Recently, the Geriatric Nutritional Risk Index (GNRI) has been reported as a simple and accurate tool to assess nutritional status of haemodialysis patients. Our objective was to examine the association between GNRI and mortality in chronic haemodialysis patients.
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The levels of somatostatin receptors in causative tumors of oncogenic osteomalacia are insufficient for their agonist to normalize serum phosphate levels.
Calcif. Tissue Int.
PUBLISHED: 04-12-2010
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Oncogenic osteomalacia (OOM) is a rare disease characterized by renal phosphate wasting and osteomalacia and is caused by the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Scintigraphy with octreotide, which binds to somatostatin receptors (SSTRs), is a useful way to locate causative tumors in OOM patients. However, the therapeutic effects of octreotide acetate are still controversial. Two OOM patients were administered octreotide acetate intramuscularly. Ten causative OOM tumors, including two resected from the patients participating in the octreotide administration study, were examined for expression of genes encoding SSTRs by quantitative real-time RT-PCR and immunohistochemistry. Octreotide therapy did not improve hypophosphatemia in either case, despite temporal decreases in FGF-23 levels in one patient. The mean expression levels of SSTR1, SSTR3, and SSTR5 were similar in the OOM and non-OOM tumors. Expression of SSTR2 was significantly higher in the OOM tumors than in the non-OOM tumors. Immunohistochemical examinations revealed the presence of SSTR2A, SSTR2B, and SSTR5 in both the OOM and non-OOM tumors. The expression of SSTR genes in OOM tumors contributes to positive imaging using octreotide scintigraphy. However, the levels of SSTRs seem to be insufficient for the octreotide therapy to improve hypophosphatemia. Further studies are needed to clarify the mechanisms by which FGF-23 secretion from OOM tumors is suppressed by octreotide acetate.
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Regions of arterial stenosis and clinical factors determining transcutaneous oxygen tension in patients with peripheral arterial disease.
J. Atheroscler. Thromb.
PUBLISHED: 03-30-2010
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Despite the clinical usefulness of transcutaneous oxygen tension (TcPO(2)) to assess the severity of limb ischemia, the factors determining TcPO(2) in patients with peripheral arterial disease (PAD) have not been fully clarified. We therefore examined the regions of arterial stenosis and clinical factors affecting lower-extremity TcPO(2).
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