Excerpts from the United States Renal Data System 2006 Annual Data Report.
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Adult↗
Biomedical subjects
Shu-Cheng Chen
Publications and source records attributed to Shu-Cheng Chen.
Atherosclerotic renovascular disease in older US patients starting dialysis, 1996 to 2001.
BACKGROUND: Temporal trends regarding the epidemiology of atherosclerotic renovascular disease (ARVD) in dialysis populations are poorly defined. METHODS AND RESULTS: United States Renal Data System data were used to identify patients aged 67 years or older at dialysis inception between 1996 and 2001 (n=146,973). Medicare claims in the preceding 2 years were used to identify ARVD and revascularization procedures. Prior ARVD rose from 7.1% to 11.2% between 1996 and 2001 (adjusted odds ratio [AOR], 1.68). Other associations included hypertensive end-stage renal disease (ESRD; AOR, 2.21), ESRD network (AOR, 0.44 in network 17 versus 1.00 in network 1), peripheral vascular disease (AOR, 1.65), black race (AOR, 0.44), urologic cause of ESRD (AOR, 0.57), age >85 years (AOR, 0.58), substance dependency (AOR, 0.62), and inability to ambulate or transfer (AOR, 0.67). The proportion of ARVD patients undergoing revascularization rose from 14.6% to 16.7% between 1996 and 2001 (AOR, 1.27). Other associations included hypertension (AOR, 2.10), ESRD network (AOR, 2.07 for network 13 versus 1.00 in network 1), age >85 years (AOR, 0.53), and black race (AOR, 0.54). The rise in ARVD was not reflected in the proportion of patients with renovascular disease listed as cause of ESRD on the Medical Evidence Report at dialysis inception (5.5% in 1996, 5.0% in 2001). CONCLUSIONS: ARVD diagnoses have become more common in older patients beginning dialysis therapy. The association of demographic factors including age, race, and geographic residence with utilization patterns suggests possible barriers to care.
Aged↗
Intradermal pregnenolone sulfate attenuates capsaicin-induced nociception in rats.
We have previously shown that the neurosteroid pregnenolone sulfate (PS) inhibits the capsaicin receptor-mediated current in rat dorsal root ganglion neurons. Here, we examined the effect of intradermal injection of PS into the rat hindpaw on capsaicin-induced nociception. Results revealed that PS co-injected with capsaicin dose-dependently inhibited the capsaicin-induced nocifensive response. In contrast, injections of PS into one hindpaw and capsaicin into the contralateral hindpaw had no effect on the capsaicin-induced nocifensive response, suggesting that PS produced its effect locally but not systemically. Moreover, PS inhibition of the capsaicin-induced nocifensive response was not significantly reduced by a nonselective opioid receptor antagonist or by cannabinoid receptor antagonists, indicating that neither an opioid- nor a cannabinoid-dependent mechanism mediated the effect of PS. These data demonstrate that PS acts peripherally to attenuate capsaicin-induced nociception through an opioid- and cannabinoid-independent mechanism and suggest a new therapeutic potential for PS in pain management.
Animals↗
Characterization of peripheral human cannabinoid receptor (hCB2) expression and pharmacology using a novel radioligand, [35S]Sch225336.
Studies to characterize the endogenous expression and pharmacology of peripheral human cannabinoid receptor (hCB2) have been hampered by the dearth of authentic anti-hCB2 antibodies and the lack of radioligands with CB2 selectivity. We recently described a novel CB2 inverse agonist, N-[1(S)-[4-[[4-methoxy-2-[(4methoxyphenyl)sulfonyl] phenyl]sulfonyl] phenyl]ethyl]methane-sulfonamide (Sch225336), that binds hCB2 with high affinity and excellent selectivity versus hCB1. The precursor primary amine of Sch225336 was prepared and reacted directly with [(35)S]mesyl chloride (synthesized from commercially obtained [(35)S]methane sulfonic acid) to generate [(35)S]Sch225336. [(35)S]Sch225336 has high specific activity (>1,400 Ci/mmol) and affinity for hCB2 (65 pm). Using [(35)S]Sch225336, we assayed hemopoietic cells and cell lines to quantitate the expression and pharmacology of hCB2. Lastly, we used [(35)S]Sch225336 for detailed autoradiographic analysis of CB2 in lymphoid tissues. Based on these data, we conclude that [(35)S]Sch225336 represents a unique radioligand for the study of CB2 endogenously expressed in blood cells and tissues.
Animals↗
Excerpts from the United States Renal Data System 2004 annual data report: atlas of end-stage renal disease in the United States.
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Adolescent↗
Atherosclerotic renovascular disease in United States patients aged 67 years or older: risk factors, revascularization, and prognosis.
BACKGROUND: Although atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology. METHODS: Claims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic renovascular disease in the 2 years preceding December 31, 1999 (N= 1,085,250), followed until December 31, 2001. RESULTS: The incidence of atherosclerotic renovascular disease was 3.7 per 1000 patient-years. Major antecedent associations [P < 0.05, with adjusted hazards ratios (HR) > 1.5] included chronic kidney disease (adjusted HR 2.54), hypertension (2.42), peripheral vascular disease (2.00), and atherosclerotic heart disease (1.70). Adverse event rates after incident atherosclerotic renovascular disease greatly exceeded those in the general population (P < 0.0001): atherosclerotic heart disease, 303.9 per 1000 patient-years (vs. 73.5 in the general population); peripheral vascular disease, 258.6 (vs. 52.2); congestive heart failure, 194.5 (vs. 56.3); cerebrovascular accident or transient ischemic attack, 175.5 (vs. 52.9); death, 166.3 (vs. 63.3); and renal replacement therapy, 28.8 (vs. 1.3). Among atherosclerotic renovascular disease patients, 16.2% underwent a renal revascularization procedure, percutaneously in 96%. Revascularization was not associated with renal replacement therapy, congestive heart failure, or death but was associated with atherosclerotic heart disease (adjusted HR 1.42) (P= 0.004) and peripheral vascular disease (adjusted HR 1.38) (P= 0.002). CONCLUSION: Atherosclerotic renovascular disease is strongly associated with cardiovascular disease, both past and future. Absolute cardiovascular risk exceeds that of renal replacement therapy. Renal revascularization is used selectively and shows inconsistent associations with cardiovascular outcomes, renal replacement therapy, and death.
Aged↗
How to improve communication in dialysis units: a survey of family focus readers.
Future study of communication between dialysis patients and health care providers could not only aid in understanding the survey findings but also advance emphasis on those areas of care needing to be enhanced. By raising awareness about communication in the dialysis unit, it is hoped that health care professionals will embrace the need to encourage patients to be more involved in the educational and treatment process, enabling them to become active partners in their health care.
Communication↗
The fall and rise of parathyroidectomy in U.S. hemodialysis patients, 1992 to 2002.
Although the therapeutic approach to managing hyperparathyroidism has changed dramatically, it is unknown whether parathyroidectomy rates continue to decline in the United States. Parathyroidectomy rates were studied in successive annual national cohorts, prevalent on hemodialysis on January 1 of 1992 to 2002, with Medicare as primary payer. Parathyroidectomy was defined as International Classification of Diseases, Ninth Revision, Clinical Modification code 068. The annual incidence of parathyroidectomy was 11.6 per 1000 patient-years in 1992. The incidence declined progressively after 1994, reaching a low of 6.8 per 1000 patient-years in 1998. Rates increased progressively after 1998, reaching 11.8 per 1000 patient-years in 2002. Using proportional hazards modeling, with adjustment for comorbidity and 1992 as the reference group, the lowest adjusted hazards ratio, 0.32 (P < 0.0001), was seen in 1998, followed by hazards ratios of 0.39 (P < 0.0001) in 1999, 0.41 (P < 0.0001) in 2000, 0.52 (P < 0.0001) in 2001, and 0.53 (P < 0.0001) in 2002. Other antecedents of parathyroidectomy in multivariate models included ESRD network, younger age, female gender, white race, absence of diabetes, longer duration of previous hemodialysis, use of intravenous vitamin D, previous renal transplantation, several comorbid conditions, and parathyroid hormone measurement in the preceding year. With a case-control method, parathyroidectomy was associated with higher mortality rates immediately after surgery, followed, subsequently, by lower long-term rates. Parathyroidectomy rates in U.S. hemodialysis patients increased between 1998 and 2002, a period in which the therapeutic armamentarium for preventing severe hyperparathyroidism expanded considerably.
Aged↗
Mechanism underlying inhibition of the capsaicin receptor-mediated current by pregnenolone sulfate in rat dorsal root ganglion neurons.
The effect of pregnenolone sulfate (PS) on the capsaicin receptor-mediated current was studied in acutely dissociated rat dorsal root ganglion neurons using the whole-cell voltage-clamp technique. PS acted extracellularly to inhibit the capsaicin-induced current in a not competitive but concentration-dependent manner, with an EC50 of 13 microM and a maximal inhibition of 65%. Furthermore, antagonism of the capsaicin response by PS is neither voltage- nor agonist-dependent, indicating that PS did not act as an open-channel blocker. The inhibitory action of PS on the capsaicin-induced current may provide a basis for reducing capsaicin receptor-mediated nociception.
Animals↗
A novel model for lymphocytic infiltration of the thyroid gland generated by transgenic expression of the CC chemokine CCL21.
Lymphocytic infiltrates and lymphoid follicles with germinal centers are often detected in autoimmune thyroid disease (AITD), but the mechanisms underlying lymphocyte entry and organization in the thyroid remain unknown. We tested the hypothesis that CCL21, a chemokine that regulates homeostatic lymphocyte trafficking, and whose expression has been detected in AITD, is involved in the migration of lymphocytes to the thyroid. We show that transgenic mice expressing CCL21 from the thyroglobulin promoter (TGCCL21 mice) have significant lymphocytic infiltrates, which are topologically segregated into B and T cell areas. Although high endothelial venules expressing peripheral lymph node addressin were frequently observed in the thyroid tissue, lymphocyte recruitment was independent of L-selectin or lymphotoxin-alpha but required CCR7 expression. Taken together, these results indicate that CCL21 is sufficient to drive lymphocyte recruitment to the thyroid, suggest that CCL21 is involved in AITD pathogenesis, and establish TGCCL21 transgenic mice as a novel model to study the formation and function of lymphoid follicles in the thyroid.
Adoptive Transfer↗
Competitive inhibition of the capsaicin receptor-mediated current by dehydroepiandrosterone in rat dorsal root ganglion neurons.
The effects of dehydroepiandrosterone (5-androsten-3beta-ol-17-one; DHEA) and related steroids on the capsaicin receptor-mediated current were studied in acutely dissociated rat dorsal root ganglion neurons using the whole-cell voltage-clamp technique. DHEA rapidly and reversibly inhibited the capsaicin-induced current in a concentration-dependent manner, with an EC(50) of 6.7 microM and a maximal inhibition of 100%. DHEA increased the capsaicin EC(50) with little effect on the capsaicin maximal response, suggesting that the blocking action of DHEA is competitive. Neither the capsaicin response nor inhibition of the capsaicin response by extracellularly applied DHEA was significantly affected by inclusion of a saturating concentration of DHEA in the electrode buffer, arguing that DHEA acted at the extracellular surface of the membrane. Moreover, DHEA did not act through protein phosphatases to inhibit the capsaicin-induced current. Furthermore, the stereoisomer of DHEA, 5-androsten-3alpha-ol-17-one, failed to inhibit the capsaicin-induced current, producing instead a potentiating effect on the capsaicin response, demonstrating that the interaction of steroids with the capsaicin receptor is stereospecific. The inhibitory action of DHEA on the capsaicin-induced current may provide a basis for reducing capsaicin receptor-mediated nociception.
Animals↗
Conditional transgenic models to study chemokine biology.
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Animals↗
Expression of a novel murine type I IFN in the pancreatic islets induces diabetes in mice.
IFN-kappa belongs to a recently identified subclass of type I IFNs. In this study, we report the cloning and preliminary characterization of the murine homologue of IFN-kappa. The gene encodes a 200-aa protein which is 38.5% homologous to human IFN-kappa. Murine IFN-kappa contains four cysteines in analogous positions to those observed in the IFN-alpha and an additional fifth unique cysteine, C174. The murine gene is located on chromosome 4, where other type I murine IFN genes, IFN-alpha and IFN-beta, are clustered. This region is syntenic with human chromosome 9 where the gene encoding IFN-kappa and the type I IFN gene cluster are found. Mouse IFN-kappa is expressed at low levels in peritoneal macrophages and its expression is up-regulated by dsRNA and IFN-gamma. Similar to previously reported transgenic mice carrying type I and type II IFNs, transgenic mice overexpressing murine IFN-kappa in the beta cells of the pancreas develop overt diabetes with hyperglycemia. Histological characterization of pancreatic islets from these transgenic mice showed inflammatory infiltrates with corresponding destruction of beta cells.
Amino Acid Sequence↗
Conditional expression of murine Flt3 ligand leads to expansion of multiple dendritic cell subsets in peripheral blood and tissues of transgenic mice.
The analysis of the development and function of distinct subsets of murine dendritic cells (DC) has been hampered by the limited number of these cells in vivo. To circumvent this limitation we have developed a conditional transgenic mouse model for producing large numbers of DC. We used the tetracycline-inducible system to conditionally express murine Flt3 ligand (FL), a potent hemopoietic growth factor that promotes the differentiation and mobilization of DC. Acute treatment (96 h) of the transgenic animals with the tetracycline analog doxycycline (DOX) promoted an approximately 200-fold increase in serum levels of FL without affecting the number of circulating DC. However, within 1 wk of DOX treatment, the relative number of DC in peripheral blood increased from approximately 8 to approximately 40%. Interestingly, both the levels of FL and the number of DC remained elevated for at least 9 mo with continual DOX treatment. Chronic treatment of the mice with DOX led to dramatic increases in the number of DC in multiple tissues without any apparent pathological consequences. Most DC populations were expanded, including immature and mature DC, myeloid (CD11c(+)CD11b(+)CD8a(-)), lymphoid (CD11c(+)CD11b(-)CD8a(+)), and the recently defined plasmacytoid (pDC) subsets. Finally, transplantation of BM from green fluorescent protein-expressing mice into lethally irradiated transgenic mice followed by subsequent DOX treatment led to expansion of green fluorescent protein-labeled DC. The transgenic mice described here should thus provide a readily available source of multiple DC subsets and should facilitate the analysis of their role in homeostasis and disease.
Animals↗
Identification of persons at high risk for kidney disease via targeted screening: the NKF Kidney Early Evaluation Program.
BACKGROUND: More than 340,000 individuals were receiving renal replacement therapy in the United States at the end of 1999; this number is projected to double by the year 2010. Almost half had a primary diagnosis of diabetes mellitus particularly type 2, and more than one quarter a primary diagnosis of hypertension. Studies have demonstrated effective maneuvers to prevent or delay the rate of progression of kidney disease, and decrease morbidity and mortality. The objective of early diagnosis is early detection of asymptomatic disease at a time when intervention has a reasonable potential to have a positive impact on outcome. METHODS: In 1997, the National Kidney Foundation launched KEEP trade mark (Kidney Early Evaluation Program), a free community-based screening that targets first order relatives of persons with hypertension, diabetes or kidney disease, and those with a personal history of diabetes or hypertension. RESULTS: Of the 889 individuals screened in the pilot study, 71.4% had at least one abnormality. The program includes an educational component and referral to a physician for follow-up of abnormal values. CONCLUSIONS: Targeted screenings are an effective means of identifying persons at risk for kidney disease, and can identify individuals at risk early enough in the course of their disease to allow for effective intervention.
Early Diagnosis↗
Chronic kidney disease and cardiovascular disease in the Medicare population.
BACKGROUND: The extent of diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) in the Medicare population is relatively unknown. Also unknown is the effect of these diseases on patient survival before end-stage renal disease (ESRD). METHODS: Prevalent cohorts of Medicare enrollees from 1996 to 2000 were assessed for diabetes and CKD, presence of CVD, and probability of death versus ESRD in the follow-up period. Hospitalization rates and, in diabetics, lipid testing and glycemic control monitoring were also assessed. RESULTS: The prevalence of diabetes in the Medicare population increased at 4.4% per year, reaching 18.9% in the 1999-2000 cohort. Approximately 726,000 elderly Medicare enrollees carry a diagnosis code for CKD. Those with CKD are 5 to 10 times more likely to die before reaching ESRD than the non-CKD group. In CKD patients, CVD is twice as common and advances at twice the rate. Cardiovascular disease advances at a similarly higher rate in CKD patients who die and those who survive to ESRD. Heart failure hospitalizations are 5 times greater in CKD patients and only 30% less than those in dialysis patients. Only half of the CKD patients with diabetes who advance to ESRD had a lipid or glycosylated hemoglobin test done in the year before or after dialysis initiation. CONCLUSION: Diabetes, the leading cause of ESRD, is increasing in the general Medicare population at 4.4% per year. Cardiovascular disease is common, progresses at twice the rate, is associated with death before ESRD, and patients receive suboptimal risk factor monitoring. Active identification and treatment of CKD patients is needed.
Heart Failure↗
Disruption of CCL21-induced chemotaxis in vitro and in vivo by M3, a chemokine-binding protein encoded by murine gammaherpesvirus 68.
Chemokine-binding proteins represent a novel class of antichemokine agents encoded by poxviruses and herpesviruses. One such protein is encoded by the M3 gene present in the murine gammaherpesvirus 68 (MHV-68) genome. The M3 gene encodes a secreted 44-kDa protein that binds with high affinity to certain murine and human chemokines and has been shown to block chemokine signaling in vitro. However, there has been no direct evidence that M3 blocks chemokine activity in vivo, nor has the nature of M3-chemokine interaction been defined. To better understand the ability of M3 to block chemokine activity in vivo, we examined its interaction with a specific subset of chemokines expressed in lymphoid tissues, areas where gammaherpesviruses characteristically establish latency. Here we show that M3 blocks in vitro chemotaxis induced by CCL19 and CCL21, chemokines expressed constitutively in secondary lymphoid tissues. Moreover, we provide evidence that chemokine M3 binding exhibits positive cooperativity. In vivo, the expression of M3 in the pancreas of transgenic mice inhibits recruitment of lymphocytes induced by transgenic expression of CCL21 in this organ. The ability of M3 to block the biological activity of chemokines may represent an important strategy used by MHV-68 to evade immune detection and favor viral replication in the infected host.
Animals↗
Excerpts from the United States Renal Data System 2003 Annual Data Report: atlas of end-stage renal disease in the United States.
Explore the source record for details and available documents.
Adult↗