Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aquaporin-2 (AQP-2), a water channel located on the apical membrane of collecting duct cells, regulates water reabsorption under the control of vasopressin (AVP). Using an antibody directed to human AQP-2, a quantitative Western blot analysis was performed to determine the collecting duct responsiveness to an oral, nonpeptide, V2 receptor antagonist (VPA-985) in patients with chronic NYHA II and III heart failure. Standards were derived by conjugating the immunizing peptide to maleimide-activated bovine serum albumin and a standard curve was generated for each blot. Quantification of baseline steady-state AQP-2 excretion was done by collecting urine on the day before study drug administration. The next day patients received either placebo or VPA-985 at one of four different doses and urine was collected every 2 h. Thereafter, urinary AQP-2 excretion was calculated as a ratio of the urine flow and was expressed in pmol/h. During baseline, steady-state excretion did not change significantly (T0-T2, 458 +/- 44; T2-T4, 443 +/- 35; T4-T6, 422 +/- 35; T6-T8, 401 +/- 30). Compared to placebo, urinary AQP-2 excretion decreased significantly and in all groups in a dose-dependent manner during VPA-985 administration. The most impressive decrease was observed in the 250-mg group (T0-T2, 89 +/- 5; T2-T4, 50 +/- 18; T4-T6, 43 +/- 22; T6-T8, 42 +/- 23; P < 0.001 during each period compared with baseline and placebo results). VPA-985 significantly increased solute-free water clearance and urine output and significantly decreased urinary osmolality. Urinary AQP-2 excretion correlated best with solute-free water clearance during T0-T2 and T2-T4 collection, but a correlation with urinary osmolality and urinary output was also found during these periods. In conclusion, AQP-2 urinary excretion, as measured by quantitative Western analysis, is a sensitive biologic marker to assess the short-term responsiveness of the collecting duct to a V2 receptor AVP antagonist in chronic heart failure.
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PMID:Selective V2-receptor vasopressin antagonism decreases urinary aquaporin-2 excretion in patients with chronic heart failure. 1050 93

The purpose of this study was to assess the effect of nutritional supplementation on dietary intake and on pressure ulcer development in critically ill older patients. The multi-center trial involved 19 wards stratified according to specialty and recruitment for critically ill older patients; 9 wards were randomly selected for nutritional intervention (nutritional intervention group), consisting of the daily distribution of two oral supplements, with each supplement containg 200 kcal, for 15 d. Pressure ulcer incidence was prospectively recorded for grades I (erythema), II (superficial broken skin), and III (subcutaneous lesion) for 15 d. Nutritional intake was monitored by using estimates in units of quarters validated by comparison with weight measurement. There were 672 subjects older than 65 y, and 295 were in the nutritional intervention group versus 377 in the control group. The patients were similar for age, sex ratio, and C-reactive protein. In comparison with the control group, the nutritional intervention group included more patients with stroke, heart failure, and dyspnea and fewer with antecedent falls, delirium, lower limb fractures, and digestive disease. The nutritional intervention group had a lower risk of pressure ulcers according to the Norton score but was less dependent (Kuntzman score) and had a lower serum albumin level. During the trial, energy and protein intakes were higher in the nutritional intervention group (day 2: 1081 +/- 595 kcal versus 957 +/- 530 kcal, P = 0.006; 45.9 +/- 27.8 g protein versus 38.3 +/- 23.8 g protein in the control group, P < 0.001). At 15 d, the cumulative incidence of pressure ulcers was 40.6% in the nutritional intervention group versus 47.2% in the control group. The proportion of grade I cases relative to the total number of cases was 90%. Multivariate analysis, taking into account all diagnoses, potential risk factors, and the intra-ward correlation, indicated that the independent risk factors of developing a pressure ulcer during this period were: serum albumin level at baseline, for 1 g/L decrease: 1.05 (95% confidence interval: 1.02 to 1.07, P < 0.001); Kuntzmann score at baseline, for 1-point increase: 1.22 (0.32 to 4.58, P = 0.003); lower limb fracture: 2.68 (1.75 to 4.11, P < 0.001); Norton score < 10 versus > 14: 1.28 (1.01 to 1.62, P = 0.04); and belonging to the control group: 1.57 (1.03 to 2.38, P = 0.04). In conclusion, it was possible to increase the dietary intake of critically ill elderly subjects by systematic use of oral supplements. This intervention was associated with a decreased risk of pressure ulcer incidence.
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PMID:A multi-center trial of the effects of oral nutritional supplementation in critically ill older inpatients. GAGE Group. Groupe Aquitain Geriatrique d'Evaluation. 1067 26

Patients on maintenance hemodialysis therapy for end-stage renal disease have reduced exercise tolerance. Multiple processes related to uremia and hemodialysis have been implicated in the pathophysiology of this impairment. However, limited data are available to identify the separate and combined effects of clinical factors on the degree of impairment for individuals within this population. For this purpose, data from 193 patients who had undergone exercise testing for two clinical trials were retrospectively analyzed. Univariate and multiple linear regression analyses were used to identify demographic and clinical correlates of peak exercise oxygen uptake (VO2). Peak VO2 averaged 18.5 +/- 6.4 mL/min/kg. On univariate analysis, peak VO2 correlated positively with male sex and hemoglobin, serum albumin, and serum creatinine concentrations and correlated negatively with dialytic age and diagnosis of diabetes or chronic heart failure. In a multiple linear regression model, sex, hemoglobin concentration, age, and diagnosis of diabetes each remained statistically significant. Together, factors included in the model accounted for 41% of the variability in peak VO2 (P = 0.0001). Among factors not correlating significantly with peak VO2 were resting blood pressure, serum carnitine level, and urea clearance assessed by Kt/V. Findings show the range of exercise impairment among clinically stable ambulatory hemodialysis patients, which may be sufficient to interfere with normal daily activities for many of these patients. Although this impairment may be broadly attributable to physiological consequences of uremia, the degree of impairment for individual patients is predicted by demographic factors, coexistent disease, and factors potentially modified by medical therapeutics.
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PMID:Clinical and demographic predictors of exercise capacity in end-stage renal disease. 1177 5

In severe hemorrhagic shock, left ventricular (LV) diastolic dysfunction is an early sign of cardiac failure due to compromised myocardial oxygenation. Immediate fluid replacement or, in particular, administration of a hemoglobin-based oxygen carrier (diaspirin cross-linked hemoglobin; DCLHb) improves myocardial oxygenation; therefore, positive effects on LV diastolic function could be expected. The effects of fluid resuscitation from severe hemorrhagic shock with DCLHb were investigated in 20 anesthetized domestic pigs. After generation of a critical left anterior descending coronary artery stenosis (narrowing of the artery until disappearance of reactive hyperemia after a 10-second complete vessel occlusion), hemorrhagic shock (mean arterial blood pressure 45 mm Hg) was induced within 15 min by controlled blood withdrawal and maintained for 60 min. Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). After completion of resuscitation, an observation period of 60 min elapsed. Measurements of central hemodynamics, myocardial oxygenation, and LV diastolic function were performed at baseline, after induction of critical coronary artery stenosis, after 60 min of hemorrhagic shock, immediately after resuscitation, and 60 min later. While 5 out of 10 animals treated with HSA died within the first 20 min after fluid resuscitation from acute LV pump failure, all DCLHb-treated animals survived until the end of the protocol (p < 0.05). Despite superior myocardial oxygenation due to augmentation of the arterial O(2) content as well as of coronary perfusion pressure, no beneficial effects on LV diastolic function were observed after infusion of DCLHb. Peak velocity of LV pressure decrease (dp/dt(min)) did not reveal significant differences between the two groups. Immediately after completion of fluid resuscitation with DCLHb, the time constant of LV diastolic relaxation (tau) was prolonged when compared with HSA-treated animals (p < 0.05), indicating retardation of early LV diastolic relaxation. Our data suggest that DCLHb fails to improve LV diastolic function after fluid resuscitation from severe hemorrhagic shock. However, positive effects on myocardial perfusion and oxygenation result in a significant reduction of the mortality of severe hemorrhagic shock.
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PMID:Diaspirin cross-linked hemoglobin fails to improve left ventricular diastolic function after fluid resuscitation from hemorrhagic shock. 1180 91

Despite improvements in dialysis therapy, the mortality rate of patients with end stage renal disease (ESRD) has remained high. A relatively high proportion of uremic patients dies within one year after the initiation of dialysis treatment. The aim of this study was to evaluate predictors for this early mortality in patients with ESRD. A total of 66 uremic patients were included in the study. Patients were divided in those who survived < 1 year (n = 17) and those who survived > or = 1 year (n = 49). We compared the prevalence of diabetes and hypertension and of vascular diseases as well as the prevalence of heart insufficiency (EF < 30%) and left ventricular hypertrophy (LVH). Additionally, we estimated the laboratory parameters serum creatinine, creatinine clearance, BUN, cholesterol, triglycerides, fibrinogen, serum protein, serum albumin and hemoglobin, and evaluated the indications for the initiation of dialysis therapy in both patient groups. The patients with survival < 1 year were significantly older (64+/-12 vs. 54+/-14 years, p<0.01) and showed a lower BMI (22+/-3 vs. 25+/-3, p<0.01) than those who survived > 1 year. The prevalence of diabetes (70% vs. 31%, p<0.05), cardiac insufficiency (70% vs. 16%, p<0.025), cardiovascular disease (65% vs. 28%, p<0.05) and peripheral vascular diseases (70% vs. 28%, p<0.05) was significantly higher in the patients with early mortality. The prevalence of hypertension was similar in both groups, however, the prevalence of LVH was significantly higher in the patients who survived < 1 year (88% vs. 37%, p<0.05). Laboratory parameters were not significantly different in the two groups of patients, with the exception of serum albumin, which was significantly lower in the patients with early mortality (3.5+/-0.6 vs. 3.9+/-0.4 g/l, p<0.02). Hyperhydration was the most common indication for the start of dialysis in patients with early mortality (59% vs. 13%, p<0.025). Cardiac insufficiency was the most common cause of death in these subjects (n = 10, 59%). Six individuals (12%) died within four weeks after initiating dialysis therapy. Thus, there are several predictors for early mortality in end-stage renal disease patients, including high age, low BMI, the presence of diabetes, coronary heart disease, heart insufficiency and LVH, as well as low serum albumin levels. A relatively high percentage of patients die shortly after the start of dialysis therapy. Heart insufficiency is the most common cause of early death in these patients.
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PMID:Predialysis management and predictors for early mortality in uremic patients who die within one year after initiation of dialysis therapy. 1207 93

Endothelin-1 (ET-1) has been found to be one of the most potent vasoconstrictive peptides known, and is therefore considered to be an important factor in diseases such as hypertension, heart failure, pulmonary hypertension, renal diseases, etc. Thus, the development of ET-receptor antagonists may offer a new therapeutic strategy in these fields. In this article, we summarize the method for assessing our compound as a selective ETA-receptor antagonist. Binding assays and in vitro function assays (isolated vessels) were examined for the assessment of in vitro potency, selectivity of the ETA receptor against the ETB receptor, specificity for ET receptors, agonistic activities for ET receptors and the blocking manner of the compound on ET receptors. Chinese hamster ovary (CHO) cells expressing human ET receptors and tissue membrane preparations from both human and animals were used for the binding assays. The specificity of the compound against ET receptors was demonstrated using 116 and 9 receptor binding and enzyme assays, respectively. The agonistic activity and potency of the compound at tissue levels were examined using isolated vessels. We also demonstrated the effect of protein binding on the potency of the compound by adding a physiological concentration of serum albumin to the tissue baths. In vivo potency and features of the compound as a selective ETA-antagonist were confirmed using mice, rats and dogs exogenously treated with ET-1 or big ET-1. We also demonstrated the compound's duration of action and pharmacokinetics in animal models and intact animals, respectively. From these experiments, we found a nonpeptide, potent, orally active and long-lasting, highly selective ETA-receptor antagonist.
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PMID:Methods for assessing endothelin ETA-receptor antagonists in preclinical studies. 1222 43

This article presents the results of a prospective multivariable study of elderly patients aged over 70 years, hospitalized in an Internal Medicine Department of a Central Lisbon Hospital. The study aimed to identify, at the beginning of hospital admission (HA), predictive factors of hospital mortality (HM) and mortality at 6 months, of duration of HA, of admission to a nursing home at the time of discharge and during a period of 6 months thereafter and of hospital readmission during the 6 months following discharge. The study included 158 patients with a mean hospital stay of 15 days and a hospital mortality of 12%. The main pathologies responsible for hospital admission were cerebrovascular accident (22%), heart failure (20%) and pneumonia (16%). Mortality at 6 months was 29% and hospital readmission in the 6 months thereafter was 24%. When the patient was cared for by the spouse there was a statistically significant correlation with a shorter duration of admission (p = 0.006). Mean hospital stay was not significantly associated with any other variable. A subjective medical evaluation (SME) at the start of HA (p = 0.001), a low Barthel score prior to and at the time of HA, low serum albumin (p = 0.001) and a high leucocyte count (p = 0.005) were correlated with a higher HM. Nursing home admission was only positively correlated with cerebrovascular pathology. Mortality at 6 months was significantly correlated with the SME (p = 0.001), a low Barthel score prior to admission (p < 0.008) and at the time of HA (p < 0.001), nursing home residency (p < 0.005) and a low mental test score (p < 0.01). Hospital readmission at 6 months was influenced by the SME (p < 0.04) and by the reduction in the Barthel score caused by the illness and HA (p = 0.004). These correlations enabled the development of mathematical models that predict HM and mortality at 6 months and admission to a nursing home at the time of discharge and during a period of 6 months thereafter. They could be important in identifying elderly patients' needs early in the hospital admission and in the improvement of the strategy necessary for a successful and dignified hospital discharge.
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PMID:[Predictive factors of hospital and 6-month morbidity and mortality in hospitalized elderly patients]. 1237 94

In renal failure, blood urea nitrogen and serum creatinine usually rise in tandem; the normal BUN: Cr ratio is 10-15: 1. Disproportionate rises in BUN: Cr (> 20: 1) often imply pre-renal azotemia but may be caused by increased protein catabolism or an excessive protein load. In this study we looked at intensive care patients who acutely developed markedly increased BUN (> or = 100 mg/dL) with only modest elevation of Cr (< or = 5 mg/dL) for possible causes of the disproportionate azotemia. There were 19 such cases collected over 6 months, nine women and ten men, with mean age 69.2 +/- 4.4 years (13/19 > 75 years). Peak BUN was 156 +/- 11 mg/dL; peak Cr 4.3 +/- 0.5 mg/dL. Eleven patients expired. Mean serum albumin at the time of consultation was 2.7 +/- 0.2 g/dL; mean total lymphocyte count 1.0 +/- 0.1/mm3. Of possible factors causing the azotemia, nine patients had documented hypovolemia; eight had congestive heart failure; six were in septic or hypovolemic shock, and two received high-dose steroids. As contributing factors, eight patients had Salb < 2.5 g/dL; eight were given a high protein intake > 100 g/d; two had HIV, and two others had gastrointestinal bleeding. Infection was present in 14 patients; seven had sepsis (bacteremia with hypotension). All patients had at least one of these factors present and 16/19 had two or more. Fractional Na excretion was < 1% (consistent with pre-renal azotemia) in only four of the 11 patients in whom it was measured. We conclude that severely disproportionate BUN : Cr is frequently multifactorial and is most common in the elderly, perhaps due to their lower muscle mass, and in ICU patients given a high protein intake. It is often not indicative of uncomplicated renal hypoperfusion, although low renal perfusion (hypovolemia, shock, or heart failure) is common. Mortality is high due to the severe illnesses, especially infection, worsened by decreased renal function and hypercatabolic state.
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PMID:Massive and disproportionate elevation of blood urea nitrogen in acute azotemia. 1254 57

C-reactive protein is the prototype marker of inflammation and has been shown to predict mortality in hemodialysis patients. However, it remains uncertain as to whether a single C-reactive protein level has similar prognostic significance in peritoneal dialysis patients. A single high-sensitivity C-reactive protein (hs-CRP) level was measured in 246 continuous ambulatory peritoneal dialysis patients without active infections at study baseline together with indices of dialysis adequacy, echocardiographic parameters (left ventricular mass index, left ventricular dimensions, and ejection fraction), nutrition markers (serum albumin, dietary intake, and subjective global assessment) and biochemical parameters (hemoglobin, lipids, calcium, and phosphate). The cohort was then followed-up prospectively for a median of 24 mo (range, 2 to 34 mo), and outcomes were studied in relation to these parameters. Fifty-nine patients died (36 from cardiovascular causes) during the follow-up period. The median hs-CRP level was 2.84 mg/L (range, 0.20 to 94.24 mg/L). Patients were stratified into tertiles according to baseline hs-CRP, namely those with hs-CRP < or = 1.26 mg/L, 1.27 to 5.54 mg/L, and > or = 5.55 mg/L. Those with higher hs-CRP were significantly older (P < 0.001), had greater body mass index (P < 0.001), higher prevalence of coronary artery disease (P = 0.003), and greater left ventricular mass index (P < 0.001). One-year overall mortality was 3.9% (lower) versus 8.8% (middle) versus 21.3% (upper tertile) (P < 0.0001). Cardiovascular death rate was 2.7% (lower) versus 5.2% (middle) versus 16.2% (upper tertile) (P < 0.0001). Multivariable Cox regression analysis showed that every 1 mg/L increase in hs-CRP was independently predictive of higher all-cause mortality (hazard ratio [HR], 1.02; 95% CI, 1.01 to 1.04; P = 0.002) and cardiovascular mortality (HR, 1.03; 95% CI, 1.01 to 1.05; P = 0.001) in peritoneal dialysis patients. Other significant predictors for all-cause mortality included age (HR, 1.07; 95% CI, 1.04 to 1.10), gender (HR, 0.49; 95% CI, 0.27 to 0.90), atherosclerotic vascular disease (HR, 2.65; 95% CI, 1.46 to 4.80), left ventricular mass index (HR, 1.01; 95% CI, 1.00 to 1.01) and residual GFR (HR, 0.53; 95% CI, 0.38 to 0.75). Age (HR, 1.06; 95% CI, 1.02 to 1.10), history of heart failure (HR, 3.31; 95% CI, 1.36 to 8.08), atherosclerotic vascular disease (HR, 3.20; 95% CI, 1.43 to 7.13), and residual GFR (HR, 0.57; 95% CI, 0.38 to 0.86) were also independently predictive of cardiovascular mortality. In conclusion, a single, random hs-CRP level has significant and independent prognostic value in PD patients.
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PMID:Is a single time point C-reactive protein predictive of outcome in peritoneal dialysis patients? 1281 48

Heart failure (HF) is the only cardiovascular disease that is increasing in incidence, prevalence, and mortality. One of the major complications associated with HF is malnutrition. Fluctuations due to fluid make weight measurement an inaccurate parameter to identify malnutrition. Therefore, the purpose of this study is to assess clinical parameters that could assist in the recognition of malnutrition in HF patients. A convenience sample of 50 HF patients had anthropometric measurements, a review of their serum chemistry levels, a collection of standard hemodynamic measures plus electrical bioimpedance, and, each subject completed a gastrointestinal symptoms assessment with two meals. Eighteen (36%) subjects were classified as malnourished based on the selected criteria of a serum albumin <3.0 g/dl and/or being less than 90% of ideal body weight. Within this sample of malnourished subjects, 44% of the subjects were found to be obese based on skinfold measurement. A comparison between malnourished/not malnourished groups found that the mean heart rate was higher in the malnourished group (85 vs. 73 beats/min; P<0.017). There were no other parameters that differentiated between these groups. These results demonstrate the need for further research to identify predictive clinical parameters for malnutrition in this vulnerable population.
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PMID:The identification of malnutrition in heart failure patients. 1462 67


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