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Biomedical subjects

A Betriu

Publications and source records attributed to A Betriu.

At least 55 records · Page 3Linked to original sources

Evidence for both abnormal set point of PTH stimulation by calcium and adaptation to serum calcium in hemodialysis patients with hyperparathyroidism.

In vitro studies of parathyroid glands removed from dialysis patients with secondary hyperparathyroidism and hypercalcemia have demonstrated the presence of an increased set point of parathyroid hormone (PTH) stimulation by calcium (set point [PTHstim]), suggesting an intrinsic abnormality of the hyperplastic parathyroid cell. However, clinical studies on dialysis patients have not observed a correlation between the set point (PTHstim) and the magnitude of hyperparathyroidism. In the present study, 58 hemodialysis patients with moderate to severe hyperparathyroidism (mean PTH 780 +/- 377 pg/ml) were evaluated both before and after calcitriol treatment to establish the relationship among PTH, serum calcium, and the set point (PTHstim) and to determine whether changes in the serum calcium, as induced by calcitriol treatment, modified these relationships. Calcitriol treatment decreased serum PTH levels and increased the serum calcium and the setpoint (PTHstim); however, the increase in serum calcium was greater than the increase in the setpoint (PTHstim). Before treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium was r = 0.82, p < 0.001, and between the set point (PTHstim) and PTH was r = 0.39, p = 0.002. After treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium remained significant (r = 0.70, p < 0.001), but the correlation between the set point (PTHstim) and PTH was no longer significant (r = 0.09); moreover, a significant correlation was present between the change in the set point (PTHstim) and the change in serum calcium that resulted from calcitriol treatment (r = 0.73, p < 0.001). The correlation between the residual values (deviation from the regression line) of the set point (PTHstim), derived from the correlation between PTH and the set point (PTHstim), and serum calcium was r = 0.77, p < 0.001 before calcitriol and r = 0.72, p < 0.001 after calcitriol. In conclusion, the set point (PTHstim) increased after a sustained increase in the serum calcium, suggesting an adaptation of the set point to the existing serum calcium; the increase in serum calcium resulting from calcitriol treatment was greater than the increase in the set point (PTHstim); the set point (PTHstim) was greater in hemodialysis patients with higher serum PTH levels; and the correlation between PTH and the set point (PTHstim) may be obscured because the serum calcium directly modifies the set point (PTHstim).

Adaptation, Physiological↗

Association between vitamin D receptor gene polymorphism and relative hypoparathyroidism in patients with chronic renal failure.

To study the influence of vitamin D receptor (VDR) gene polymorphism on parathyroid cell function in chronic renal failure, 85 patients who had serum PTH levels <12 pmol/L (the low intact PTH [iPTH] group) and 46 patients who had serum iPTH levels >60 pmol/L (the high iPTH group) were selected out of a total dialysis population of 170 individuals. As a result of subsequent exclusions based on several criteria in both groups (diabetic patients, serum aluminum levels, serum calcium levels, and time on dialysis), the final low iPTH group consisted of 34 patients and the final high iPTH included 32 patients. A healthy control population (n = 120) and 162 of the 170-patient dialysis population served as control groups. VDR gene polymorphism was determined by digestion with the BsmI enzyme and single-strand conformation polymorphism analysis of PCR amplified fragments. Serum iPTH levels were lower in patients with the BB genotype than in those with the Bb or bb genotype, both in the total dialysis population and when the various exclusion criteria were applied. No differences in genotypic and allelic frequencies were found between the healthy control population and the high iPTH group. However, the genotypic distribution was significantly different in the low iPTH group of patients before and after applying all exclusion criteria (P = 0.037 and P = 0.018, respectively). In the final selected population, the bb genotype was less frequent in the low iPTH group than in the total dialysis population (14.7% versus 36.4%; odds ratio, 0.3; confidence interval, 0.11 to 0.82; P = 0.01). Conversely, the BB genotype was over-represented in the low iPTH group (23.3% versus 19.7%; odds ratio, 1.9; confidence interval, 0.85 to 4.3; P = 0.1). In addition, the bb genotype and the b allele frequencies were lower in the low iPTH group than in the high iPTH group (14.7% versus 34.4%, P = 0.06, and 41.2% versus 60.9%, P = 0.02, respectively), and the BB genotype and the B allele were significantly more frequent in the low PTH group than in the high iPTH group (32.3% versus 12.5%, P = 0.05, and 58.8% versus 39.1%, P = 0.02, respectively). Thus, VDR gene polymorphism influences parathyroid function in chronic renal failure.

Adult↗

[Stents and de novo coronary lesions. Meta-analysis].

OBJECTIVES: The purpose of this investigation was to provide an overview of the effect of coronary artery stent and balloon angioplasty on major clinical outcomes and restenosis from 3 trials (BENESTENT, STRESS and START) comparing the two treatments in the novo lesions. METHODS: The trials included a total of 1,374 patients, 693 of whom were randomized to stent and 682 to conventional angioplasty. Relative risk, 95% confidence interval and p values were calculated for death, infarction and need for revascularization at 6 month follow-up. Restenosis was assessed by using the binary definition. RESULTS: The incidence of combined clinical outcomes was similar to the two treatment strategies (relative risk 0.96; 95% CI 0.64-1.45). However, the odds for needing a new revascularization procedure were reduced by 35% in patients treated with stents (relative risk 0.65; 95% CI 0.51-0.82; p < 0.001). Restenosis rates were 25% and 36.6% (stent vs angioplasty, respectively), which represents a reduction of 31% (relative risk 0.69; 95% CI 0.58-0.81; p > 0.0001). CONCLUSIONS: Compared with balloon angioplasty, coronary stents of de novo lesions in native coronary arteries decreases restenosis at 6 months. This translates into clinical benefit, as shown by a reduction in the number of new revascularization procedures.

Angioplasty, Balloon↗

Thrombolytic therapy for patients with prior percutaneous transluminal coronary angioplasty and subsequent acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

Our purpose was to evaluate the outcomes of patients with prior coronary angioplasty who underwent thrombolysis for new acute myocardial infarction (AMI) in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial. Baseline characteristics and clinical outcomes were compared between patients with (n = 1,647) and without (n = 39,150) previous angioplasty. The relations among prior angioplasty, clinical outcomes, and treatment effects were examined with logistic regression modeling. Patients with previous angioplasty tended to be younger and presented sooner after symptom onset, but had more multivessel disease and lower ejection fractions. Unadjusted mortality was significantly lower in the prior-angioplasty group at 24 hours (1.8% vs 2.7%, p = 0.03) and 30 days (5.6% vs 7.0%, p = 0.036). Although most of the survival advantage was due to low-risk characteristics in this group (lower age and heart rate and fewer anterior wall AMIs), prior angioplasty remained a weak but independent predictor of survival. Recurrent ischemia and reinfarction occurred more often in the prior-angioplasty group, as did bypass surgery (12.2% vs 8.5%) and repeat angioplasty (34.5% vs 21.4%). Patients with prior angioplasty and prior AMI had lower 30-day mortality than those with prior infarction alone (6.3% vs 12.6%, p < 0.01). Treatment effects on 30-day mortality were similar among patients with prior angioplasty (odds ratio 1.2 for accelerated tissue-plasminogen activator v. combined streptokinase arms, 95% confidence interval 0.73 to 1.9). Patients with prior angioplasty who present with AMI have fewer in-hospital adverse events and lower 30-day mortality than those without such a history.

Aged↗

Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy. GUSTO-I investigators.

OBJECTIVE: To compare baseline characteristics, complications, and treatment-specific outcomes of women and men with acute myocardial infarction treated with thrombolytic therapy. DESIGN: Randomized controlled trial. PATIENTS AND SETTING: A total of 10315 women and 30706 men with acute myocardial infarction treated in 1081 hospitals in 15 countries as part of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I). INTERVENTION: One of four thrombolytic regimens: (1) streptokinase with subcutaneous heparin; (2) streptokinase with intravenous heparin; (3) streptokinase plus alteplase (tissue-type plasminogen activator) with intravenous heparin; or (4) accelerated alteplase with intravenous heparin. MAIN OUTCOME MEASURES: Mortality, stroke, and nonfatal complications during 30-day follow-up. RESULTS: Women were on average 7 years older than men and delayed 18 minutes (median) longer after symptom onset before presenting to the hospital. After adjustment for age, women more often had a history of diabetes, hypertension, and smoking than men. Time to treatment was significantly longer in women (1.2 vs 1.0 hours; P<.001). Women had more nonfatal complications after treatment, including shock (9% vs 5%; P<.001), congestive heart failure (22% vs 14%; P<.001), serious bleeding (15% vs 7%; P<.001), and reinfarction (5.1% vs 3.6%; P<.001). Women had twice as many total strokes as men (2.1% vs 1.2%; P<.001), secondary to their older age at presentation. The unadjusted mortality rate was twice as high in women as men (11.3% vs 5.5%; P<.001); the relative risk (RR) of death was greater among women than men after adjustment for differences in baseline characteristics (RR=1.15; 95% confidence interval, 1.0 to 1.31). Although women and men underwent angiography at similar rates, there were small but significant differences in their rates of revascularization procedures (angioplasty: 35% of women and 32% of men; bypass surgery: 7% of women and 9% of men; P<.001 for both). The higher rate of stroke in women after treatment with alteplase (2.0% vs 1.9% with streptokinase and intravenous heparin) was offset by a greater relative reduction in mortality (10.3% vs 11.1%). CONCLUSION: Women who received thrombolytic therapy for treatment of acute myocardial infarction were at greater risk for both fatal and nonfatal complications than men.

Aged↗

Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial.

BACKGROUND: Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. METHODS AND RESULTS: Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. CONCLUSIONS: Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.

Adult↗

Prediction of in-hospital cardiac events using dipyridamole-thallium scintigraphy performed very early after acute myocardial infarction.

BACKGROUND AND HYPOTHESIS: Ischemic complications occur frequently during hospitalization after acute myocardial infarction. Dipyridamole-thallium scintigraphy performed early after admission can detect residual ischemia, may have additional prognostic value and be useful in the management of these patients. METHODS: Dipyridamole infusion and 201thallium imaging were performed on the third day of infarction in 114 consecutive patients. Coronary angiography was performed before hospital discharge in 90% of patients and exercise testing was performed at the time of discharge in patients without contraindications. RESULTS: Side effects occurred in 28 patients, but they were mild and transient or rapidly reversed with intravenous aminophylline. During hospitalization, three patients died and four had a nonfatal reinfarction. Patients with these major cardiac events had previously shown a higher prevalence of reversible perfusion defects during testing (71 vs. 31%, p < 0.05). In addition, 19 patients had early recurrent ischemia requiring early in-hospital revascularization. Overall, cardiac events defined as death, reinfarction, or early myocardial revascularization occurred in 22 patients. Of the patients with these events, 68% had thallium redistribution on initial myocardial scanning compared with 25% of patients without events (p = 0.0001). Patients with cardiac events also showed a higher number of myocardial segments with reversible perfusion defects (1.8 +/- 2.2 vs. 0.6 +/- 1.3, p = 0.001). Logistic regression analysis revealed that among all the other clinical, scintigraphic, and angiographic variables, the presence of thallium redistribution on the dipyridamole-thallium scan was the only independent predictor of cardiac events, increasing the risk by sixfold. Furthermore, during a 1-year follow-up, 14 other patients had ischemic events. Of these, 64% had previously shown thallium redistribution during early dipyridamole testing compared with 19% of patients without cardiac events (p < 0.001). CONCLUSIONS: Intravenous dipyridamole-thallium-scintigraphy performed very early after myocardial infarction is safe and useful to predict in-hospital ischemic events.

Aged↗

Endothelial dysfunction of the non-infarct related, angiographically normal, coronary artery in patients with an acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction and single-vessel disease may have early atherosclerosis in other angiographically normal coronary arteries. METHODS: Coronary endothelial responses were analysed in 20 non-diabetic patients with an acute myocardial infarction and one-vessel disease. In an angiographically normal, non-infarct related, coronary artery serial acetylcholine doses of 10(-7) M, 10(-6) M, 10(-5) M and 10(-4) M and nitroglycerin 40 micrograms were infused over 3 min. The responses of the coronary vessel were measured with quantitative angiography. Coronary blood flow was also measured with a Doppler catheter in 11 of the 20 patients. RESULTS: Four patients showed a trend towards vasodilation during acetylcholine infusion in the proximal and distal segments: from 2.49 +/- 0.23 mm to 2.95 +/- 0.42 mm and 2.43 +/- 0.56 mm to 2.81 +/- 0.66 mm, respectively. Coronary vascular resistance decreased to 57 +/- 4% (P = 0.03). The other 16 patients presented vasoconstriction in the proximal and distal segments: 2.61 +/- 0.75 mm to 2.03 +/- 0.65 mm (P = 0.0001), and 2.40 +/- 0.58 to 1.81 +/- 0.56 mm (P = 0.0036), respectively. Nitroglycerin caused vasodilation in the proximal (2.69 +/- 0.61 mm, P = 0.017, ANOVA) and distal segments (2.48 +/- 0.45 mm, P = 0.009, ANOVA). Coronary vascular resistance increased to 141 +/- 43% (P = 0.03) over the basal value in this group of patients. CONCLUSION: Endothelial dysfunction of the epicardial and resistance vessels was found in angiographically normal coronary arteries of patients with one-vessel disease in 75% of this population.

Adult↗

Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators.

BACKGROUND: The Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial was designed to test whether thrombolytic strategies achieving more complete, early, sustained coronary artery patency would lead to further reductions in mortality in patients with acute myocardial infarction. An angiographic substudy within GUSTO-I provided a unique opportunity to examine the relation between mortality and degrees of patency among the regimens. METHODS AND RESULTS: Four thrombolytic strategies were compared in 41,021 patients in GUSTO-I: streptokinase with subcutaneous or intravenous heparin, accelerated tissue plasminogen activator (TPA) with intravenous heparin, and combination streptokinase plus TPA with intravenous heparin. Accelerated TPA was associated with lower 30-day mortality (6.3%) than the other strategies (7.2%, 7.4%, and 7.0%, respectively). Among the 1210 patients in the angiographic substudy randomized to angiography 90 minutes after starting treatment, there was improved patency, particularly Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, with accelerated TPA over the other regimens (P < .0001). Coronary artery perfusion (TIMI grade 3) at 90 minutes was also a significant predictor of 30-day survival (P < .01). To determine whether differences in mortality among the four strategies matched differences in 90-minute patency, a model was developed for predicting mortality differences in the main trial from the angiographic substudy. The model assumed that any differences in treatment effects on 30-day mortality were mediated through differences in 90-minute patency for the four treatments. The predicted rates were then compared with observed mortality rates of the remaining patients in the main trial for each treatment group. The predicted and observed 30-day mortality rates of the four treatments were streptokinase with subcutaneous heparin, 7.46% versus 7.28%; streptokinase with intravenous heparin, 7.26% versus 7.39%; accelerated TPA, 6.31% versus 6.37%; and streptokinase plus TPA, 6.98% versus 6.96%. The correlation between predicted and observed results was .97, and the proportion of squared error explained (R2) was .92. CONCLUSIONS: The close relation between the predicted and observed 30-day mortality rates supports the concept that an important mechanism for improved survival with thrombolytic therapy is achievement of early, complete perfusion. The close match provides a strong biological explanation for the mortality differences seen in GUSTO-I and a sound rationale for the additional survival advantage of the accelerated TPA regimen. Irrespective of which treatment is used, early and complete restoration of infarct artery perfusion represents an essential goal of myocardial reperfusion therapy.

Coronary Angiography↗

Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators.

BACKGROUND: Despite remarkable advances in the treatment of acute myocardial infarction, substantial early patient mortality remains. Appropriate choices among alternative therapies and the use of clinical resources depend on an estimate of the patient's risk. Individual patients reflect a combination of clinical features that influence prognosis, and these factors must be appropriately weighted to produce an accurate assessment of risk. Prior studies to define prognosis either were performed before widespread use of thrombolysis or were limited in sample size or spectrum of data. Using the large population of the GUSTO-I trial, we performed a comprehensive analysis of relations between baseline clinical data and 30-day mortality and developed a multivariable statistical model for risk assessment in candidates for thrombolytic therapy. METHODS AND RESULTS: For the 41,021 patients enrolled in GUSTO-I, a randomized trial of four thrombolytic strategies, relations between clinical descriptors routinely collected at initial presentation, and death within 30 days (which occurred in 7% of the population) were examined with both univariable and multivariable analyses. Variables studied included demographics, history and risk factors, presenting characteristics, and treatment assignment. Risk modeling was performed with logistic multiple regression and validated with bootstrapping techniques. Multivariable analysis identified age as the most significant factor influencing 30-day mortality, with rates of 1.1% in the youngest decile (< 45 years) and 20.5% in patients > 75 (adjusted chi 2 = 717, P < .0001). Other factors most significantly associated with increased mortality were lower systolic blood pressure (chi 2 = 550, P < .0001), higher Killip class (chi 2 = 350, P < .0001), elevated heart rate (chi 2 = 275, P < .0001), and anterior infarction (chi 2 = 143, P < .0001). Together, these five characteristics contained 90% of the prognostic information in the baseline clinical data. Other significant though less important factors included previous myocardial infarction, height, time to treatment, diabetes, weight, smoking status, type of thrombolytic, previous bypass surgery, hypertension, and prior cerebrovascular disease. Combining prognostic variables through logistic regression, we produced a validated model that stratified patient risk and accurately estimated the likelihood of death. CONCLUSIONS: The clinical determinants of mortality in patients treated with thrombolytic therapy within 6 hours of symptom onset are multifactorial and the relations complex. Although a few variables contain most of the prognostic information, many others contribute additional independent prognostic information. Through consideration of multiple characteristics, including age, medical history, physiological significance of the infarction, and medical treatment, the prognosis of an individual patient can be accurately estimated.

Aged↗

Feasibility of early discharge after acute Q wave myocardial infarction in patients not receiving thrombolytic treatment.

OBJECTIVES: The purpose of this study was to analyze the feasibility of early discharge (4 days) after acute myocardial infarction in patients not receiving thrombolytic therapy by first identifying predictors of short-term prognosis and then testing the derived risk profile in an independent cohort of patients. BACKGROUND: Previous studies have shown that early discharge after acute myocardial infarction is possible. However, physicians are reluctant to shorten the standard 7- to 10-day hospital stay, presumably because of difficulty in selecting low risk patients. METHODS: From January 1985 to November 1986, 358 patients with acute myocardial infarction who did not receive thrombolytic therapy were screened. Those with a Q-wave infarction showing no complications on day 4 were considered candidates for early discharge and were transferred to the ward for a mean of 12 days. During this period, we looked for any event (cardiac or noncardiac) that would have prompted readmission if the patient had been previously discharged. Univariate and multiple regression analysis were performed to identify predictors of these events among 25 baseline variables. The derived risk profile was tested in an independent validation cohort. RESULTS: One hundred five (29.3%) of the 358 patients were free of symptoms on day 4, and 29 (27.6%) had at least one cardiac event, including four deaths and one reinfarction. Multivariate analysis selected diabetes, ejection fraction < 40% and age as independent predictors of events. Using the risk profile, 18 (13.2%) of the 136 validation cohort patients were categorized as low risk, and only 1 of them had a major event (progressive angina). Sensitivity for the risk profile was high (91%), but specificity was low (34%). CONCLUSIONS: The use of simple clinical variables may allow the safe reduction of hospital stay after infarction in selected patients. However because the proportion of candidates for early discharge is small (12.6%), it seems unlikely that the current policies on length of hospital stay will change in the near future.

Cohort Studies↗

[Percutaneous coronary angioscopy].

In the last few years, major advances in catheter technology and miniaturization of fiber optics have allowed percutaneous coronary angioscopy to become a reality. Current angioscopy systems provide an outstanding image quality yielding precise evaluation of coronary atherosclerosis morphology in its various clinical manifestations. However, coronary angioscopy is a new diagnostic tool whose indications and specific role are yet to be delineated. Investigation on the potential roles of this technology are mainly centered in the field of acute coronary syndromes and interventional coronary therapies. In the near future, coronary angioscopy may play an important role in the investigation of the natural history of coronary artery disease, in the field of thrombolysis, and in the selection of specific therapy. In this article, coronary angioscopy system and technique are described and its potential clinical applications discussed.

Angina, Unstable↗