[Massive rhabdomyolysis associated with the use of cerivastatin monotherapy].
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Anticholesteremic Agents↗
Biomedical subjects
A Cases
Publications and source records attributed to A Cases.
Beta-adrenergic receptor density and function in left ventricular hypertrophy in young essential hypertensives.
A sympathetic overactivity has been reported in the early stages of essential hypertension and has been involved in the pathogenesis of left ventricular hypertrophy (LVH) in essential hypertension. The state of beta2-adrenergic receptors as related to the presence of this complication was investigated in a group of 15 essential hypertensive patients and compared to 10 normotensive control subjects. Left ventricular mass index was determined by bidimensional echocardiography. Plasma catecholamine levels were measured by a radioenzymatic assay. beta2-adrenoceptor density was measured in intact lymphocytes by radioligand binding assay, using the hydrophilic ligand CGP 12177. beta2- adrenoceptor function was assessed by measuring intracellular cAMP levels in isoproterenol-stimulated lymphocytes. Left ventricular mass index (P < 0.05), body mass index (P < 0.01), plasma noradrenaline levels (P < 0.05) and beta2-adrenoceptor density (P < 0.05) were higher in hypertensives than in controls. Left ventricular mass index correlated with body mass index both in normotensives and hypertensives, as well as with plasma noradrenaline levels only in normotensives. Left ventricular mass index also showed a positive correlation with mean arterial pressure and an inverse relationship with beta2-adrenoceptor density and response only in hypertensive patients. In conclusion, left ventricular hypertrophy in young essential hypertensives is associated to a reduced beta2-adrenoceptor density and function, probably as a compensating mechanism of the hypertrophied myocardiocyte secondary to the increased sympathetic outflow. Journal of Human Hypertension (2000) 14, 17-21.
Adrenergic beta-Agonists↗
Abnormal platelet cytoskeletal assembly in hemodialyzed patients results in deficient tyrosine phosphorylation signaling.
BACKGROUND: Uremic patients have a bleeding tendency associated with a platelet dysfunction. We evaluated the impact of a repeated hemodialysis procedure on primary hemostasis by analyzing different aspects of platelet activation in uremic patients. METHODS: Studies were performed in (1) eight patients with end-stage renal disease before the hemodialysis program was initiated and after initiating hemodialysis treatment, and in (2) eight patients on maintenance hemodialysis who were transferred to continuous ambulatory peritoneal dialysis. Studies included routine platelet aggregations and evaluation of platelet-subendothelium interactions under flow conditions. Contractile proteins and tyrosine phosphorylation associated with the cytoskeleton were analyzed, before and after thrombin activation of platelets, by electrophoresis after Triton X-100 extraction. RESULTS: No changes in the clinical parameters analyzed were observed among the different study groups. Aggregation and platelet adhesion only improved when patients were shifted from hemodialysis to continuous ambulatory peritoneal dialysis (P < 0.05 for both percentage of surface covered by platelets and aggregate formation). The association of cytoskeletal proteins in platelets from patients under hemodialysis treatment was statistically decreased with respect to the corresponding values in platelets from patients not subjected to dialysis (P < 0.01 for actin). However, after two months on peritoneal dialysis, these values increased to almost control values (P < 0.001 for actin, vs. hemodialysis). Similarly, translocation of tyrosine-phosphorylated proteins to the cytoskeletal fraction was impaired in platelets from hemodialyzed patients, and it recovered partially after the patients transferred to continuous ambulatory peritoneal dialysis. CONCLUSIONS: Our present data support the concept that repeated platelet stress during hemodialysis has a deleterious effect on the organization of platelet cytoskeleton, which seems to impair the translocation of signal transduction proteins within platelets compromising the platelet function in uremia.
Adult↗
Increased plasma adrenomedullin levels in hemodialysis patients with sustained hypotension.
BACKGROUND: Sustained hypotension in end-stage renal disease patients is characterized, despite an overactivation of the sympathetic and renin-angiotensin systems, by decreased vascular resistance and a blunted vascular response to pressor stimuli. An increased production of one or more vasodilator substances might play a role in the reduced vascular resistance and response to pressor stimuli in these patients. We evaluated the possible role of an increased production of nitric oxide and/or adrenomedullin (ADM) in the pathophysiology of chronic hypotension in hemodialysis (HD) patients. METHODS: Three groups of hypotensive (N = 9), normotensive (N = 10), and hypertensive (N = 9) HD patients were included in the study. Plasma renin activity (PRA) and plasma levels of catecholamines, ADM, nitrite/nitrate (an estimator of nitric oxide production), tumor necrosis factor (TNF), and interleukin-1beta (IL-1beta) were measured. Plasma volume and left ventricular ejection fraction (LVEF) were also evaluated. RESULTS: Plasma levels of nitrite/nitrate and ADM were elevated in HD patients with respect to the reference values in normal subjects. Plasma ADM levels, but not nitrite/nitrate levels, were higher in hypotensive (368.1 +/- 25.4 pg/mL) than normotensive (225 +/- 9.9 pg/mL) and hypertensive HD patients (278.2 +/- 15.5 pg/mL, P < 0.01). When considering hypotensive and normotensive patients together, the mean blood pressure inversely correlated with time on HD (r = -0. 53, P < 0.05) and plasma ADM levels (r = -0.78, P < 0.01). CONCLUSIONS: Plasma ADM and nitrite/nitrate levels are increased in HD patients, but only ADM levels were higher in hypotensive than in normotensive and hypertensive HD patients. The higher plasma levels of this peptide in hypotensive patients and its inverse correlation with mean arterial pressure suggest that ADM may be involved in the pathophysiology of chronic hypotension in HD patients.
Adrenomedullin↗
Doxazosin in a gastrointestinal therapeutic system formulation.
A new formulation of doxazosin, the gastrointestinal therapeutic system (GITS), has been developed to change the drug delivery rate and the pharmacokinetic profile of the drug, allowing a more gradual absorption of doxazosin, thus reducing the plasma doxazosin trough-to-peak ratio and minimizing the need for titration. In patients with hypertension or symptomatic benign prostatic hypertrophy, doxazosin GITS is efficacious as doxazosin standard formulation but has better tolerance and eliminates the need for titration.
Journal Article↗
Recombinant human erythropoietin treatment in chronic renal failure: effects on hemostasis and vasculature.
The use of recombinant human erythropoietin (rhuEPO) for the treatment of renal anemia improves the altered primary hemostasis frequently observed in uremia, through both an increase in hematocrit (rheological effect) and an improvement in uremic platelet function. Although the in vitro vascular effects of rhuEPO are complex and may cause hypertensive and thrombotic complications in patients with end-stage renal disease, in vivo and clinical studies have not confirmed these findings. Therefore, the long-term effects of anemia correction with rhuEPO treatment on endothelial and vascular function in uremic patients merits further investigation.
Journal Article↗
Omapatrilat: clinical pharmacology.
Omapatrilat is the most clinically advanced member of a new class of cardiovascular agents known as vasopeptidase inhibitors. Omapatrilat acts by inhibiting two key enzymes responsible for blood pressure regulation: neutral endopeptidase and angiotensin-converting enzyme. Omapatrilat provides dose-related reductions in systolic and diastolic blood pressure with an excellent trough-to-peak ratio after once-daily administration. The reduction in blood pressure is proportional to baseline blood pressure. Used in monotherapy, omapatrilat controls hypertension in more than 65% of patients treated and reduces blood pressure to a greater extent than existing agents. Furthermore, omapatrilat exhibits an excellent tolerability profile. Therefore, this drug represents an important new approach for treating a wide range of patients, including those who are difficult to control, such as elderly patients with isolated systolic hypertension and patients with diabetes. The results of early clinical trials in patients with congestive heart failure have shown that omapatrilat not only improves symptoms but also reduces the risk of and hospitalization and death when compared with ACE inhibitors alone. These results indicate that vasopeptidase inhibition is a promising new strategy in the treatment of hypertension and cardiac diseases.
Journal Article↗
ASH news on hypertension.
Presentations at the 15th Scientific Meeting of the American Society of Hypertension, held May 16-20, 2000, in New York City, focused on research on basic science and clinical aspects of cardiovascular disease. New findings from several recent large-scale morbidity and mortality clinical trials--HOPE, SECURE, ALLHAT and DASH-sodium--were discussed. The latest clinical findings were reported for omapatrilat.
Journal Article↗
Clinical pharmacology of nebivolol.
Nebivolol is a novel, potent and highly selective beta(1)-adrenergic antagonist, devoid of intrinsic sympathomimetic activity, that induces endothelium-dependent arterial and venous dilatation via the L-arginine-nitric oxide pathway. Nebivolol reduces blood pressure and peripheral vascular resistance and does not depress, but rather maintains or improves, left ventricular function in healthy subjects and in patients with hypertension. It has also been shown to improve large arteries distensibility and compliance and to reduce left ventricular hypertrophy in hypertensive patients. Exercise tolerance is not affected, or may even be improved, by nebivolol treatment. In hypertensive patients, once-daily administration is effective over 24 h, with an excellent trough-to-peak ratio. The response to treatment compares favorably with diuretics, typical beta-blockers, calcium channel blockers and ACE inhibitors. The hypotensive effect is independent of age, weight, smoking, alcohol consumption and presence of diabetes. Nebivolol is effective and safe both in young and elderly patients. Nebivolol also has antianginal properties in patients with coronary artery disease and beneficial hemodynamic effects in patients with stable congestive heart failure.
Journal Article↗
Smoking increases serum levels of transforming growth factor-beta in diabetic patients.
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Adult↗
Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100 ): influence of hematocrit elevation.
BACKGROUND AND OBJECTIVE: Patients with end-stage renal disease or advanced cirrhosis develop bleeding disorders characterized by defective interaction of platelets with damaged subendothelium. The anemia associated with both clinical entities has a negative influence on hemostasis. We evaluated alterations of platelet function in patients suffering from end-stage renal disease (n=21) or hepatic cirrhosis (n=20) using standard aggregometric techniques and the recently developed platelet function analyzer (PFA-100 ). The impact of low hematocrit was also analyzed. DESIGN AND METHODS: The hemostatic capacity of platelets was tested in the PFA-100 using citrated blood and standard cartridges containing collagen-ADP (COL-ADP) or collagen-epinephrine (COL-Epi). The hemodynamic influence of hematocrit was also evaluated in blood aliquots in which hematocrit was experimentally increased by adding red blood cells from the same patient. RESULTS: Aggregation studies demonstrated abnormal responses to several agonists in both group of patients. Closure times obtained by the PFA-100 for control blood samples were 87+/-3 sec for COL-ADP and 113+/-5 sec with COL-EPi cartridges. Closure times in uremic and cirrhotic patients with average hematocrits of 0.26 and 0.27 respectively were significantly prolonged (139+/-12 and 125+/-14 sec, respectively with COL-ADP and 194+/-29 and 151+/-15 sec with COL-Epi cartridges). A 5% increase in the hematocrit caused a reduction in the closure time to 111+/-7 sec (COL-ADP) and 143+/-14 sec (COL-Epi) in the uremic group and to 86+/-4 sec (COL-ADP) and 115+/-16 sec (COL-Epi) in the cirrhotic group. Our studies confirm the platelet dysfunction in uremic and cirrhotic patients. INTERPRETATION AND CONCLUSIONS: The PFA-100 device proved to be useful for testing alterations of primary hemostasis in these acquired disorders and was sensitive enough to detect modifications in hemostasis caused by elevations in hematocrit. Conventional aggregometric tests were able to identify the intrinsic platelet abnormality in uremic and cirrhotic conditions, while the PFA-100 seemed more sensitive in detecting the negative influence of the hematocrit reduction.
Adult↗
Erythropoietin improves signaling through tyrosine phosphorylation in platelets from uremic patients.
Erythropoietin has shown to be effective in the correction of the hemostatic defect present in uremic patients. We have investigated the possible effect of recombinant human erythropoietin (rHuEPO) on the signaling processes occurring in platelets. Platelet suspensions were obtained from hemodialyzed patients before and after at least one month of initiating treatment with rHuEPO. Aliquots of non-activated or thrombin-activated platelets were treated to obtain platelet lysates or processed to extract platelet cytoskeleton. Samples were resolved by 8% SDS-polyacrylamide gel electrophoresis followed by Western blotting. After thrombin activation, proteins p120, p85, p78, p75, pp62, pp60, p59, p58, p56, p54 and p52 associated with the Triton-insoluble cytoskeletal fraction appeared phosphorylated in control profiles. In profiles from platelets obtained from uremic patients before treatment with rHuEPO, only proteins p58 and p56 appeared clearly and p54 was slightly phosphorylated. However, in platelets from the same patients under rHuEPO treatment, thrombin-induced phosphorylation improved to levels even above those observed in control profiles. Specially, the band at 54KDa appeared consistently more phosphorylated in all the patients under rHuEPO treatment. Although it is accepted that part of the hemostatic effect of erythropoietin is mediated by an increase in hematocrit, our study suggests that it enhances platelet signaling in uremic platelets which may explain the improvement of platelet response to activating stimulus before clinically noticeable elevation of hematocrit.
Aged↗
Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution.
BACKGROUND: Twenty percent of patients with multiple myeloma (MM) have renal failure. OBJECTIVE: To analyze the presenting features, the response to therapy, and the factors associated with renal function recovery and survival in 94 patients with MM and renal failure. PATIENTS AND METHODS: Medical records of patients from our institution with MM and renal failure diagnosed between January 1969 and December 1994 were reviewed. The statistical methods consisted of Kaplan-Meier survival curves, the log-rank test, logistic regression analysis, and the Cox proportional hazards model for survival analysis. RESULTS: Renal failure was observed in 94 (22.2%) of 423 patients. Patients with renal failure had more advanced disease than the others. Patients with renal failure had a lower response rate to chemotherapy than those with normal renal function (39% vs 56%; P<.001). However, when patients dying within the first 2 months of treatment were excluded, no significant differences in the response rate were found between patients with renal failure and those with normal renal function. Renal function recovery was observed in 26% of patients. Serum creatinine level (<354 micromol/L [<4 mg/dL]), serum calcium level (> or =2.88 mmol/L [> or = 11.5 mg/dL]), and amount of proteinuria (< 1 g/24 h) were associated with renal function recovery. Patients who recovered renal function had a median survival of 28 months vs 4 months for those with nonreversible renal failure (P<.001). In the multivariate analysis, only serum creatinine level (P=.003) and response to chemotherapy (P<.001) were correlated with survival. CONCLUSIONS: Renal failure was present in almost one fourth of patients with MM. Patients with reversible renal failure had longer survival than those not recovering renal function. When patients dying within the first 2 months of treatment were excluded, the response rate was not affected by renal function. Factors associated with renal function recovery were degree of renal failure, presence of hypercalcemia, and amount of proteinuria. Response to chemotherapy and severity of renal failure were the only independent factors associated with survival.
Adult↗
Effect of recombinant human erythropoietin treatment on circulating reticulated platelets in uremic patients: association with early improvement in platelet function.
Recombinant human erythropoietin improves platelet function in uremia through the correction of anemia, but this effect can be seen also before the hematocrit rise. We studied 12 hemodialyzed patients (seven men, five women) who received recombinant human erythropoietin (40 IU kg(-1)i.v., three times weekly) and were evaluated before treatment and after three doses; 24 control subjects were used. Platelet aggregation induced by adenosine 5'-diphosphate (ADP), epinephrine, collagen, arachidonic acid, and ristocetin, and reticulated platelets determined by flow cytometry after staining with thiazole orange were measured. Platelet aggregation induced by all the agonists were impaired in uremic patients (P < 0.01), but ADP and ristocetin-induced aggregations improved after treatment (P < 0.01). Hemodialyzed patients had less reticulated platelets than controls (P < 0.01). Reticulated platelets increased after three doses of treatment (P < 0.01). In conclusion, improvement of platelet function at early stages of recombinant human erythropoietin treatment may be attributed to the increase in young platelets detected as reticulated platelets.
Adenosine Diphosphate↗
Platelet-leukocyte activation during hemodialysis detected with a monoclonal antibody to leukocyte integrin CD11b.
Platelet activation is commonly monitored with a battery of monoclonal antibodies against different platelet epitopes with controversial results. The transient expression of platelet markers and their role mediating interactions with other cells could easily explain these discrepancies. The present study has evaluated whether the analysis of a leukocyte activation antigen (CD11b) could provide more reliable results than detection of platelet activation markers. Cytometric techniques with specific monoclonal antibodies were used to compare the reliability of platelet and leukocyte markers to detect activation. Modifications in the presence of platelet glycoproteins GPIb (CD42b), GPIIIa (CD41) and GPIV (CD36), expression of specific platelet markers (P-selectin (CD62P) and lysosomal protein (CD63)) and leukocyte integrin (CD11b) were assessed during hemodialysis. Platelet antigens remained in uremic patients at levels similar or slightly above those detected in a group of healthy subjects. Modifications of platelet antigens during hemodialysis produced inconclusive results. However, numbers of leukocytes expressing CD11b increased progressively during hemodialysis (17.2 +/- 5.1% at 15 min and 21.3 +/- 6.6% at 2 h, p < 0.05, vs. baseline 6.9 +/- 0.2%). The hemodialysis procedure caused an increased formation of leukocyte-platelet aggregates. Detection of leukocyte CD11b may be a useful marker of overall cellular activation during the hemodialysis procedure.
Aged↗
Advances in hypertension management: update 1998.
This article briefly reviews some important issues in the management of hypertension recently published or presented in medical congresses. The main results of several large outcome clinical trials, such as the Systolic Hypertension in Europe (Syst-Eur) trial, Hypertension Optimal Treatment (HOT) study and the Captopril Prevention Project (CAPPP) study, are summarized. The results of several retrospective studies dealing with the risk of cancer associated with antihypertensive treatments are presented. Finally, the nephroprotective effects of angiotensin-converting enzyme inhibitors in the progression of nondiabetic renal disease and the controversy surrounding the cardiovascular risk associated with dihydropyridine calcium antagonists are discussed.
Journal Article↗
Recent advances in hypertension research and management.
At the 17th Scientific Meeting of the International Society of Hypertension (Amsterdam, June 7-11, 1998), clinicians and scientists from all over the world exchanged the results of latest research on the pathophysiology, prevention and management of hypertension. Progress in two key areas of basic research was presented at the meeting: ion channels and experimental genetics. In the clinical arena, a number of large, long-term studies were presented on topics that included risk factors of cardiovascular events in male hypertensives; antihypertensive therapy and the risk of cancer; and antihypertensive therapy in dementia. A population-wide approach was stressed as essential in a session on diet intervention and hypertension in the 21st century.
Journal Article↗
Recent advances in nephrology.
The 31st Annual Meeting of the American Society of Nephrology, held in Philadelphia, Pennsylvania, USA, October 25-28, 1998, presented the newest advances in basic and clinical nephrology science. Several presentations discussed the results of studies with the newer immunosuppressants such as tacrolimus, sirolimus, mycophenolate mofetil and the anti-CD25 monoclonal antibodies, with the conclusion that studies on long-term use of these agents are needed. A number of other issues on immunosuppression protocols in renal transplantation were addressed during the meeting, including the subjects of steroid withdrawal and the role of TGF-beta in the development of chronic allograft nephropathy. The use of NESP in the treatment of renal anemia, the use of sildenafil to treat erectile dysfunction in hemodialysis patients, and the use of ACE inhibitors in nondiabetic renal patients were other important issues discussed at this meeting. Newer approaches to the treatment of hypertension discussed at the meeting highlighted the potential role of angiotensin II receptor antagonists in renal disease patients. Researchers also presented the promising results of a trial of a new, hybrid cell vaccine approach to the treatment of renal cell carcinoma.
Journal Article↗