Biomedical subjects

Jan G P Tijssen

Publications and source records attributed to Jan G P Tijssen.

At least 19 recordsLinked to original sources

PubMed2006

Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease.

AIM: To investigate the role of pulmonary arterial hypertension (PAH) in adult patients born with a cardiac septal defect, by assessing its prevalence and its relation with patient characteristics and outcome. METHODS AND RESULTS: From the database of the Euro Heart Survey on adult congenital heart disease (a retrospective cohort study with a 5-year follow-up), the relevant data on all 1877 patients with an atrial septal defect (ASD), a ventricular septal defect (VSD), or a cyanotic defect were analysed. Most patients (83%) attended a specialised centre. There were 896 patients with an ASD (377 closed, 504 open without and 15 with Eisenmenger's syndrome), 710 with a VSD (275, 352 and 83, respectively), 133 with Eisenmenger's syndrome owing to another defect and 138 remaining patients with cyanosis. PAH was present in 531 (28%) patients, or in 34% of patients with an open ASD and 28% of patients with an open VSD, and 12% and 13% of patients with a closed defect, respectively. Mortality was highest in patients with Eisenmenger's syndrome (20.6%). In case of an open defect, PAH entailed an eightfold increased probability of functional limitations (New York Heart Association class >1), with a further sixfold increase when Eisenmenger's syndrome was present. Also, in patients with persisting PAH despite defect closure, functional limitations were more common. In patients with ASD, the prevalence of right ventricular dysfunction increased with systolic pulmonary artery pressure (OR = 1.073 per mm Hg; p<0.001). Major bleeding events were more prevalent in patients with cyanosis with than without Eisenmenger's syndrome (17% vs 3%; p<0.001). CONCLUSION: In this selected population of adults with congenital heart disease, PAH was common and predisposed to more symptoms and further clinical deterioration, even among patients with previous defect closure and patients who had not developed Eisenmenger's physiology.

Adult↗

PubMed2006

C-reactive protein and angiographic characteristics of stable and unstable coronary artery disease: data from the prospective PREVEND cohort.

AIMS: High sensitive-C-reactive protein (hs-CRP) is associated with coronary risk, which may be explained by an association with (unstable) coronary artery disease (CAD). Until now, histopathological and angiographic studies have failed to consistently demonstrate a strong relationship. However, most of these studies were limited by a cross-sectional design. Our aim was to prospectively evaluate the association between hs-CRP and plaque instability. Therefore, firstly, we investigated the relation between hs-CRP measured long before coronary angiography (CAG) and angiographic characteristics of stable and unstable CAD. In addition, we investigated the association with coronary events during follow up in the total PREVEND population. METHODS AND RESULTS: Of the population based Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 8139 subjects without previous documented CAD were followed for the incidence of CAG and coronary events from 1997 to 2003. For the qualitative angiographic analysis, 216 CAGs were available. Mean time to CAG was 37+/-19 months. The 864 coronary vessels were graded as follows: 436 coronary vessels as normal, 175 as non-obstructive CAD, 179 as stable obstructive CAD and 74 as unstable obstructive CAD. Multilevel ordinal regression analysis was performed to study associations between baseline clinical variables and angiographic findings. Hs-CRP contributed significantly to the multivariate model after adjustment for age, gender, smoking, lipids and blood pressure. In 8139 subjects, 201 (2.5%) first coronary events occurred during follow up. Cox survival analysis showed age- and sex-adjusted hazard ratios for hs-CRP 1-3 and >3mg/L of, respectively, 1.26 (95% CI 0.67-2.40) and 3.16 (95% CI 1.26-3.16), relative to hs-CRP <1mg/L. CONCLUSION: In the prospective PREVEND study of subjects without previous documented CAD, hs-CRP levels at baseline were associated with angiographic characteristics and clinical consequences of plaque instability during follow up. This observation supports the concept that hs-CRP significantly contributes to coronary atherogenesis.

Aged↗

PubMed2006

Prediction of treatment response by HPA-axis and glucocorticoid receptor polymorphisms in major depression.

OBJECTIVE: We investigated whether treatment response is predicted by hypothalamus-pituitary-adrenal (HPA) axis parameters, or by genetic polymorphisms in the glucocorticoid receptor (GR), that regulates its feedback. METHODS: Ninety-eight outpatients completed 8 weeks of paroxetine treatment. Treatment response was defined as a 50% decrease in Hamilton Rating Scale for depression (HRSD) ratings. At baseline, 24h urinary cortisol excretion, and cortisol and ACTH concentrations in a DEX/CRH test were measured. The presence of polymorphisms in the GR DNA sequence (BclI, ER22/23EK, N363S) was determined. Prediction of treatment response was analysed by calculating response rates per tertile of an HPA-axis parameter and per GR genotype. RESULTS: The response rate in the high ACTH tertile was significantly lower as compared to the intermediate tertile, but not compared to the low tertile (response rates from high to low tertile: 33%, 67% and 42%). Carriers of the BclI polymorphism had higher ACTH values than non-carriers (baseline ACTH: 3 versus 5ng/l, p=0.02) and showed a trend towards lower decrease of HRSD rates than non-carriers (HRSD decrease: 8 versus 11, respectively, p=0.07). In a subgroup of BclI carriers, patients in the high ACTH tertile had a lower decrease in HRSD and lower response rates than patients in the low ACTH tertiles (HRSD decrease from high to low tertile: 5, 9 and 11, p<0.01). CONCLUSION: The results suggest that hyperactivity of the HPA-axis predict worse treatment outcome. The BclI polymorphism explains, in part, DEX/CRH test results and tends to be associated with worse treatment outcome.

Adolescent↗

PubMed2006

Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention.

BACKGROUND: Drug-eluting coronary-artery stents have been shown to decrease restenosis and therefore the likelihood that additional procedures will be required after percutaneous coronary intervention (PCI). We evaluated the use of a drug-eluting stent in patients undergoing PCI for acute myocardial infarction with ST-segment elevation. METHODS: We randomly assigned 619 patients presenting with an acute myocardial infarction with ST-segment elevation to receive either a paclitaxel-eluting stent or an uncoated stent. The primary end point was a composite of death from cardiac causes, recurrent myocardial infarction, or target-lesion revascularization at 1 year. RESULTS: Baseline clinical and angiographic characteristics in both groups were well matched. There was a trend toward a lower rate of serious adverse events in the paclitaxel-stent group than in the uncoated-stent group (8.8% vs. 12.8%; adjusted relative risk, 0.63; 95% confidence interval, 0.37 to 1.07; P=0.09). A nonsignificant trend was also detected in favor of the paclitaxel-stent group, as compared with the uncoated-stent group, in the rate of death from cardiac causes or recurrent myocardial infarction (5.5% vs. 7.2%, P=0.40) and in the rate of target-lesion revascularization (5.3% vs. 7.8%, P=0.23). The incidence of stent thrombosis during 1 year of follow-up was the same in both groups (1.0%). CONCLUSIONS: Although the use of paclitaxel-eluting stents in acute myocardial infarction with ST-segment elevation reduced the incidence of serious adverse cardiac events at 1 year by 4.0 percentage points, as compared with uncoated stents, the difference was not statistically significant. (Current Controlled Trials number, ISRCTN65027270 [controlled-trials.com].).

Angioplasty, Balloon, Coronary↗

PubMed2006

Impact of multivessel coronary disease on long-term mortality in patients with ST-elevation myocardial infarction is due to the presence of a chronic total occlusion.

In acute ST-elevation myocardial infarction (STEMI), patients with multivessel disease (MVD) are considered to be a subgroup with an increased risk of mortality compared with patients with single-vessel disease (SVD). To evaluate the effect of MVD on 1-year mortality in patients with STEMI, we studied 1,417 consecutive patients with STEMI who were admitted between 1997 and 2002 and treated with primary percutaneous coronary intervention. Further, we hypothesized that the effect of MVD on mortality is due to the presence of a chronic total occlusion in a noninfarct-related artery. Patients with MVD and/or a chronic total occlusion had multiple differences in baseline and angiographic characteristics that were associated with worse outcome. Mortalities in patients with SVD, MVD, and a chronic total occlusion were 8%, 16%, and 35%, respectively. After correction for the baseline differences, MVD was an independent predictor of mortality (odds ratio 1.5, 95% confidence interval 1.1 to 2.1). However, when chronic total occlusion was included in the model, MVD was no longer an independent predictor for mortality, whereas chronic total occlusion was a strong and independent predictor for 1-year mortality in patients with STEMI treated with percutaneous coronary intervention (odds ratio 3.8, 95% confidence interval 2.5 to 5.8). In conclusion, patients with STEMI and MVD have a higher 1-year mortality rate compared with patients with SVD, which is mainly determined by the presence of a chronic total occlusion in a noninfarct-related artery. In the setting of primary percutaneous coronary intervention, the presence of a chronic total occlusion, and not the mere presence of MVD, is an independent predictor of mortality.

Age Factors↗

PubMed2006

Median nerve conduction velocity and central conduction time measured with somatosensory evoked potentials in thyroxine-treated infants with Down syndrome.

OBJECTIVE: The aim of this study was to determine whether thyroxine treatment would improve nerve conduction in infants with Down syndrome. METHODS: A single-center, nationwide, randomized, double-blind, clinical trial was performed. Neonates with Down syndrome were assigned randomly to thyroxine (N = 99) or placebo (N = 97) treatment for 2 years. Daily thyroxine doses were adjusted regularly to maintain plasma thyrotropin levels in the normal range and free thyroxine concentrations in the high-normal range. The outcome measures were nerve conduction velocity and central conduction time, determined through median nerve somatosensory evoked potential recording, at the age of 24 months. RESULTS: At the age of 24 months, somatosensory evoked potential recordings for 81 thyroxine-treated and 84 placebo-treated infants were available for analysis. Nerve conduction velocity and central conduction time did not differ significantly between the 2 treatment groups (nerve conduction velocity: thyroxine: 51.0 m/second; placebo: 50.1 m/second; difference: 0.9 m/second; central conduction time: thyroxine: 8.83 milliseconds; placebo: 8.73 milliseconds; difference: 0.1 milliseconds). CONCLUSIONS: Postnatal thyroxine treatment of infants with Down syndrome did not alter somatosensory evoked potential-measured peripheral or central nerve conduction significantly. The absence of favorable effects suggests that pathologic mechanisms other than mild postnatal hypothyroidism underlie the impaired nerve conduction. The absence of adverse effects suggests that longstanding plasma free thyroxine concentrations in the high-normal range are not harmful to nerve maturation.

Double-Blind Method↗

PubMed2006

Prevalence of myocardial ischaemia as assessed with myocardial perfusion scintigraphy in patients with diabetes mellitus type 2 and mild anginal symptoms.

PURPOSE: To determine the prevalence and predictors of reversible myocardial perfusion defects, indicative of myocardial ischaemia, in patients with mild, stable anginal complaints [Canadian Cardiovascular Society classification (CCS) I-II/IV] and diabetes mellitus type 2 (T2DM). METHODS: A total of 329 patients with T2DM and stable, mild anginal symptoms (CCS I-II/IV) underwent myocardial perfusion scintigraphy. Perfusion images were assessed using a five-point (semi)-quantitative scoring system according to a 17-segment myocardial model. RESULTS: One-hundred and fifty-six (47%) patients showed reversible myocardial perfusion defects defined as a summed difference score of >or=3. Male gender [odds ratio (OR) 2.28, 95% CI 1.4-3.71, p=0.001], previous myocardial infarction (MI) without revascularisation (OR 3.04, 95% CI 1.28-7.24, p=0.01), and the use of two or more classes of anti-anginal medication (OR 2.36, 95% CI 1.48-3.76, p<0.001) were independent predictors for the presence of reversible defects. By contrast, lipid-lowering therapy reduced the possibility of reversible perfusion defects (OR 0.56, 95% CI 0.33-0.95, p=0.03). CONCLUSION: Approximately half of the patients with mild, stable angina pectoris and T2DM showed evidence of myocardial ischaemia. Male gender, previous MI and the use of anti-anginal medication were positive predictors and lipid-lowering therapy was a negative predictor for the results of the scintigraphic stress test.

Adult↗

PubMed2006

Time course of microvascular resistance of the infarct and noninfarct coronary artery following an anterior wall acute myocardial infarction.

Previous studies have suggested that coronary flow velocity reserve (CFVR) in the early phase of acute myocardial infarction (AMI) is abnormal in infarcted and remote regions. This study determined the coronary microvascular resistance of infarct-related arteries (IRAs) and non-IRAs during AMI and at follow-up in patients who were treated with primary percutaneous intervention. In 73 patients with a first anterior wall AMI, baseline and minimal microvascular resistance in IRAs and non-IRAs immediately after reperfusion and at 1-week and 6-month follow-up were calculated as the ratio of mean transvascular pressure gradient to mean baseline and to adenosine-induced hyperemic blood flow velocity, respectively. CFVR in IRAs increased from 1.6 +/- 0.4 after reperfusion to 1.9 +/- 0.5 at 1 week and to 3.0 +/- 0.8 at 6 months (p <0.0001) and in non-IRAs from 2.4 +/- 0.5 to 2.7 +/- 0.6 at 1 week to 3.3 +/- 0.6 at 6 months (p <0.0001). Minimal microvascular resistance in IRAs and non-IRAs (3.2 +/- 1.7 and 2.2 +/- 0.6 mm Hg/second/cm, respectively) decreased significantly at follow-up (2.0 +/- 0.6 and 1.7 +/- 0.6 mm Hg/second/cm at 1 week and 1.8 +/- 0.6 and 1.8 +/- 0.7 mm Hg/second/cm at 6 months, respectively). After correction for rate-pressure product, baseline microvascular resistance after reperfusion and at 6 months did not significantly differ between IRAs and non-IRAs. In conclusion, minimal microvascular resistance is higher in infarcted and noninfarcted regions during AMI than at follow-up. The low CFVR in remote regions during AMI is probably due more to disturbed autoregulation than to increased myocardial workload.

Adult↗

PubMed2006

Safety and feasibility of elective high-risk percutaneous coronary intervention procedures with left ventricular support of the Impella Recover LP 2.5.

Currently, the most used left ventricular (LV) support device is intra-aortic balloon counterpulsation. The percutaneous implantable Impella Recover LP 2.5 system is a novel LV (unloading) assist device. We studied the feasibility and safety of LV support with the percutaneous implantable Impella Recover LP 2.5 system in 19 consecutive high-risk patients with percutaneous coronary intervention. Procedural success using the device and percutaneous coronary intervention was achieved in all 19 patients, who were very poor candidates for surgery. The patients were elderly (84% were >60 years of age), 74% had previous myocardial infarction, 63% had LV ejection fractions of < or =25%, and all had LV ejection fractions of < or =40%. There were no procedural deaths and 2 device-unrelated in-hospital late deaths. Mean decrease in hemoglobin level was 0.7 +/- 0.4 mmol/L. The device did not induce or increase aortic valve regurgitation. There were no important device-related adverse events during LV support with the Impella Recover LP 2.5 system. However, these encouraging findings must be confirmed by larger studies, longer assist times, and in other patient categories.

Aged↗

PubMed2006

RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient versus strict rate control in patients with and without heart failure. Background, aims, and design of RACE II.

BACKGROUND: Recent studies demonstrated that rate control is an acceptable alternative for rhythm control in patients with persistent atrial fibrillation (AF). However, optimal heart rate during AF is still unknown. OBJECTIVE: To show that in patients with permanent AF, lenient rate control is not inferior to strict rate control in terms of cardiovascular mortality, morbidity, neurohormonal activation, New York Heart Association class for heart failure, left ventricular function, left atrial size, quality of life, and costs. METHODS: The RACE II study is a prospective multicenter trial in The Netherlands that will randomize 500 patients with permanent AF (< or = 12 months) to strict or lenient rate control. Strict rate control is defined as a mean resting heart rate < 80 beats per minute (bpm) and heart rate during minor exercise < 110 bpm. After reaching the target, a 24-hour Holter monitoring will be performed. If necessary, drug dose reduction and/or pacemaker implantation will be performed. Lenient rate control is defined as a resting heart rate < 110 bpm. Patients will be seen after 1, 2, and 3 months (for titration of rate control drugs) and yearly thereafter. We anticipate a 25% 2.5-year cardiovascular morbidity and mortality in both groups. RESULTS: Enrollment started in January 2005 in 29 centers in The Netherlands and is expected to be concluded in June 2006. Follow-up will be at least 2 years with a maximum of 3 years. CONCLUSION: This study should provide data how to treat patients with permanent AF.

Anti-Arrhythmia Agents↗

PubMed2006

NT-ProBNP serum levels reflect severity and extent of ischemia in patients admitted with non-ST-elevation acute coronary syndrome.

OBJECTIVE: To explore the relationship between NT-proBNP elevation and prognosis in patients with NSTEACS. BACKGROUND: High NT-proBNP levels are related to a worse prognosis in patients with ACS. The precise mechanism by which is not clear. METHODS: Serial sampling of NT-proBNP, Troponin T and CK-MB was performed in 23 patients admitted with NSTEACS. Using coronary angiography in each patient a culprit lesion was identified. Proximal lesions were located before or at the first major branch of the parent artery. All other lesions localizations were considered distal. To evaluate the influence of left ventricular systolic function on NT-proBNP levels WMSI was measured by echocardiography. RESULTS: Proximal culprit lesion localization was associated with significant higher baseline (mean 506 ng/l, SD 440 ng/l) and peak NT-proBNP levels (mean 1055 ng/l; SD 236 ng/l), as compared to patients with a distal lesion localization. (Baseline: 139 ng/l, SD 140 ng/l, peak: 381 ng/l; SD 64 ng/l). (P = 0.01) NT-proBNP levels were highly correlated to Troponin T and CK-MB peak serum levels. Adjustments for left ventricular dysfunction did not alter these associations. CONCLUSIONS: High peak NT-proBNP levels are independently associated with both proximal culprit localization and elevated biochemical markers of myocardial damage. These findings suggest that NT-proBNP levels reflect the amount of jeopardized myocardium and could signify the integral of the extent and severity of an ischemic event.

Acute Disease↗

PubMed2006

Oral administration of glycine in the prevention of restenosis after coronary angioplasty. A double blind placebo controlled randomized feasibility trial evaluating safety and efficacy of glycine in the prevention of restenosis after angioplasty.

OBJECTIVES: Evaluation of safety, feasibility, and efficacy of oral administered glycine in prevention of angiographic restenosis six months after percutaneous coronary intervention (PCI). BACKGROUND: The amino acid glycine modulates immunological response and enhances the production of endothelial derived nitric oxide (EDNO) factor. This factor has been shown to possess anti-atherosclerotic properties, actions of which are thought to reduce neo-intimal hyperplasia. Furthermore, glycine significantly elevates arginine serum levels. This amino acid has been extensively studied for its effects on the endothelium, nitric oxide (NO) metabolism and effects on several biochemical pathways interfering with the process of restenosis after PCI. METHODS: A prospective double blind placebo controlled randomized study evaluated safety and feasibility of chronic oral administration of glycine. In addition, the efficacy was determined by evaluation of six months angiographic restenosis rates. RESULTS: 214 patients scheduled for elective PCI were randomized to receive glycine or placebo. At follow-up, there was no significant difference in side effects and in major adverse cardiac events (MACE) between both groups. Six-month angiograms revealed similar restenosis rates for the glycine group (17.5%) and for the placebo group (20.2%) (P = 0.82). CONCLUSION: Chronic oral administration of glycine was safe and feasible and had similar side effects compared to placebo. However, chronic oral administration of glycine did not lead to a significant reduction in restenosis rates at six months after elective PCI.

Administration, Oral↗

PubMed2006

Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal origin.

OBJECTIVE AND DESIGN: Lowered neonatal plasma thyroxine (T(4)) and mildly elevated thyrotropin concentrations together with developmental benefits from neonatally started T(4) treatment in a randomized clinical trial demonstrated Down syndrome (DS) neonates to be mildly hypothyroid, at least during their first weeks of life. To prove that this hypothyroid state persists beyond this period in all, and to elucidate its etiology, we evaluated the course of the thyroid function determinants in all DS infants participating in this 24-month trial. MAIN OUTCOME: Mean plasma thyrotropin concentrations and thyrotropin frequency distributions of 97 placebo-treated infants were persistently shifted to substantially higher concentrations, while free T(4) frequency distributions were in the lower two thirds of the reference interval. Mean thyroglobulin concentrations were normal. To normalize plasma thyrotropin, T(4)-treated DS infants (N = 99) needed rather high free T(4) concentrations, like T(4)- treated non-DS children with thyroidal congenital hypothyroidism. At ages 12 and 24 months, thyroid peroxidase antibodies were detected in 1.1% and 5.4% of all DS infants. CONCLUSIONS: These findings suggest that as a group DS infants have a novel type of persistent mild congenital hypothyroidism, presumably of thyroidal origin. The group character suggests a direct relation with the trisomic state of chromosome 21, hypothetically through genomic dosage imbalance of dosage-sensitive genes interfering with thyroid hormone production.

Child, Preschool↗

PubMed2006

Thyrotropin, but not a polymorphism in type II deiodinase, predicts response to paroxetine in major depression.

OBJECTIVE: The determinants of response to antidepressant treatment in major depression are unknown at present. The aim of the present study was to establish whether response is predicted by Hypothalamus-Pituitary-Thyroid (HPT) axis parameters or by a recently discovered polymorphism in the enzyme type II deiodinase (DII), which catalyzes the production of T3 in the brain. DESIGN: We analyzed prediction of response to paroxetine treatment by calculating response rates per tertile of HPT-axis parameters and per DII genotype. METHODS: Ninety-eight outpatients with major depression (DSM-IV) were included. Serum concentrations of TSH, FT4 and delta TSH in a DEX/CRH-TRH test were measured. In addition, the presence of a polymorphism in the DII sequence (Thr92Ala) was determined. RESULTS: The overall treatment response was 48 of 98 patients (49%). After exclusion of patients with subclinical hypothyroidism and/or TPO antibodies (n = 16), higher serum TSH significantly predicted response (response rate per tertile from low to high TSH: 36%, 42%, and 67%). Heterozygous patients for the DII polymorphism (44%) had slightly lower serum TSH (P = 0.03) as compared to patients with the wild-type DII (47%). The polymorphism was unrelated to treatment response. CONCLUSION: Higher serum TSH was associated with response to paroxetine in patients with major depression.

Adult↗

PubMed2006

Comorbidity, hospitalization, and medication use and their influence on mental and motor development of young infants with Down syndrome.

OBJECTIVE: Young infants with Down syndrome have an increased occurrence of several well-known medical conditions such as congenital heart and gastrointestinal disease. The aim of this study was to establish consequences like hospitalization and medication use rates and to determine their possible influence on early neurodevelopment. PATIENTS AND METHODS: This study compared 2 years of thyroxine treatment with placebo in 196 neonates with Down syndrome who were included in a previously reported randomized clinical trial. Parents were interviewed about comorbidity, hospitalization, and medication use at random assignment and regularly thereafter. Data were cross-checked with discharge letters when available. The influence of comorbidity on neurodevelopment at 2 years old (Bayley Scales of Infant Development II) was determined by stepwise multiple linear-regression analysis. RESULTS: Before trial entry, 163 infants with Down syndrome had been admitted to hospital for an average of 14.01 days, whereas during the trial, 95 of 181 infants who completed the trial were hospitalized for an average 19.75 days. Main hospitalization reasons during the trial were lung/airway and congenital heart and gastrointestinal disease. The 48 infants operated on for heart or gastrointestinal disease accounted for 1401 of the total number of 1876 hospital admission days during the trial and for 33 of 62 admissions for lung/airway infection. During their second year of life, approximately 60% of the infants were prescribed drugs, mostly antibiotics and pulmonary. Regression analysis showed infantile spasms, "other" central nervous system disease, and gastrointestinal disease necessitating surgery to be associated with greater developmental age delays at 24 months old (mental: 6.87, 3.52, and 1.69 months; and motor: 3.59, 2.54, and 1.68 months, respectively). CONCLUSIONS: Hospital admission and medication use rates in young infants with Down syndrome are still very high, mainly because of congenital heart and gastrointestinal disease and acquired respiratory disease. Central nervous system disease and gastrointestinal disease necessitating surgery were independently associated with a worse developmental outcome.

Child Development↗

PubMed2005

Glucocorticoids and relapse of major depression (dexamethasone/corticotropin-releasing hormone test in relation to relapse of major depression).

BACKGROUND: Knowledge of pathogenic mechanisms and predictors of relapse in major depressive disorder is still limited. Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is thought to be related to the development and course of depression. METHODS: We investigated whether dexamethasone/corticotropin-releasing hormone (DEX/CRH) test parameters were related to the occurrence of relapse in 45 outpatients with clinically remitted major depression. The DEX/CRH test was administered before and after 8 weeks of antidepressant treatment. RESULTS: Posttreatment maximal adrenocorticotropic hormone (ACTH) and maximal cortisol levels, as well as delta ACTH and delta cortisol levels, were significantly higher (all p < .05) among patients who relapsed (n = 22) compared with patients in whom no relapse occurred (n = 23). Higher posttreatment maximal cortisol response on the DEX/CRH test was associated with shorter "relapse-free survival" (p = .05). CONCLUSIONS: In outpatients with clinically remitted major depression, higher posttreatment maximal cortisol levels on the DEX/CRH test were associated with relapse of major depression.

Adolescent↗

PubMed2005

Early invasive versus selectively invasive management for acute coronary syndromes.

BACKGROUND: Current guidelines recommend an early invasive strategy for patients who have acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level. However, randomized trials have not shown an overall reduction in mortality, and the reduction in the rate of myocardial infarction in previous trials has varied depending on the definition of myocardial infarction. METHODS: We randomly assigned 1200 patients with acute coronary syndrome without ST-segment elevation who had chest pain, an elevated cardiac troponin T level (> or =0.03 mug per liter), and either electrocardiographic evidence of ischemia at admission or a documented history of coronary disease to an early invasive strategy or to a more conservative (selectively invasive) strategy. Patients received aspirin daily, enoxaparin for 48 hours, and abciximab at the time of percutaneous coronary intervention. The use of clopidogrel and intensive lipid-lowering therapy was recommended. The primary end point was a composite of death, nonfatal myocardial infarction, or rehospitalization for anginal symptoms within one year after randomization. RESULTS: The estimated cumulative rate of the primary end point was 22.7 percent in the group assigned to early invasive management and 21.2 percent in the group assigned to selectively invasive management (relative risk, 1.07; 95 percent confidence interval, 0.87 to 1.33; P=0.33). The mortality rate was the same in the two groups (2.5 percent). Myocardial infarction was significantly more frequent in the group assigned to early invasive management (15.0 percent vs. 10.0 percent, P=0.005), but rehospitalization was less frequent in that group (7.4 percent vs. 10.9 percent, P=0.04). CONCLUSIONS: We could not demonstrate that, given optimized medical therapy, an early invasive strategy was superior to a selectively invasive strategy in patients with acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level.

Acute Disease↗

PubMed2005

Repolarization gradients in the canine left ventricle before and after induction of short-term cardiac memory.

BACKGROUND: Questions remain about the contributions of transmural versus apicobasal repolarization gradients to the configuration of the T wave in control settings and after the induction of short-term cardiac memory. METHODS AND RESULTS: Short-term cardiac memory is seen as T-wave changes induced by altered ventricular activation that persists after restoration of sinus rhythm. We studied cardiac memory in anesthetized, open-chest dogs paced from the ventricle for 2 hours. Unipolar electrograms were recorded from as many as 98 epicardial and 144 intramural sites, and activation times and activation-recovery intervals (ARIs) were measured. In separate experiments, epicardial monophasic action potentials were recorded. We found no appreciable left ventricular intramural gradients in repolarization times (activation time+ARI) in either control conditions or after the induction of memory. In controls, there was a left ventricular apicobasal gradient, with the shortest repolarization times in anterobasal regions and longest repolarization times posteroapically. After induction of memory, repolarization times shortened uniformly throughout the ventricular wall. Monophasic action potential duration at 90% repolarization decreased by approximately 10 ms after induction of memory. CONCLUSIONS: In the intact canine left ventricle at physiological rates, there is no transmural gradient in repolarization. Apicobasal gradients in repolarization time, with shortest repolarization times in anterobasal areas and longest repolarization times in posteroapical regions, are important in the genesis of the T wave. Repolarization times and monophasic action potentials at the 90% repolarization level shorten after the induction of memory. The deeper T wave in the ECG after induction of memory may be explained by the more rapid phase 3 of the action potential.

Action Potentials↗