Dynamics of Ventricular Repolarization in Patients with Dilated Cardiomyopathy Versus Healthy Subjects

Background: Patients with impaired left ventricular function have a high risk of developing ventricular arrhythmias and sudden death. Among different markers of risk, the prolongation and regional heterogeneity of repolarization are of increasing interest. However, there are limited data regarding feasibility of analyzing repolarization parameters and their dynamics in 24‐hour Holter ECG recordings. Methods: Dynamic behavior of repolarization parameters was studied with a new automatic algorithm in digital 24‐hour Holter recordings of 60 healthy subjects and 55 patients with idiopathic dilated cardiomyopathy (IDC). Repolarization parameters included the mean value of QT and QTc durations, QT dispersion, and peaks of QT duration and QT dispersion above prespecified thresholds. Results: In comparison to healthy subjects, patients with IDC had lower heart rate variability, longer mean QT and QTc durations, higher content of QTc peaks >500 ms, longer QT dispersion and its standard deviation, and a higher content of peaks >100 ms of QT dispersion (P < 0.01 for all comparisons). These repolarization parameters were significantly higher in IDC patients after adjustment for age, sex, and heart rate variability. The parameters of repolarization dynamics correlated with SDNN in healthy subjects but not in dilated cardiomyopathy patients. Conclusions: The automatic assessment of repolarization parameters in 24‐hour digital ECG recordings is feasible and differentiates dilated cardiomyopathy patients from healthy subjects. Patients with dilated cardiomyopathy have increased QT duration, QT dispersion, and increased variability of QT dispersion reflecting variations in T‐wave morphology, the factors which might predispose them to the development of arrhythmic events.     

Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA)

OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. METHODS: Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. RESULTS: Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable.     

Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder

Background:

Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress.

Methods:

Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded.

Results:

No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027).

Conclusions:

Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life.     

Hepatitis C virus kinetics during and immediately after liver transplantation

The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope -0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope -0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT.     

Left coronary artery spasm causing severe left ventricular dysfunction without myocardial infarction

This report describes a patient with persistent, recurrent left anterior descending coronary artery spasm, which causes marked left ventricular dysfunction in a clinical course that is typical of acute myocardial infarction with hyperacute electrocardiographic changes. However, after emergency coronary artery bypass surgery, the patient had complete reversal of left ventricular dysfunction, with no residual evidence of acute myocardial infarction by electrocardiograph or gated blood pool imaging and no CPK enzyme rise. The patient therefore demonstrates that coronary spasm in some instances clearly precedes the sequence of pathophysiologic events leading to acute myocardial infarction. Our report also demonstrates for the first time in man that massive left ventricular dysfunction may occur in this intermediate coronary syndrome, presenting clinically as impending myocardial infarction. With aggressive surgical intervention and emergency bypass surgery, left ventricular function was restored to normal. Despite the semantic problems of categorizing such patients as having impending myocardial infarction, the severe left ventricular dysfunction and alarming course of this patient's illness was resolved by emergency surgery, suggesting that, in some instances, aggressive therapy is warranted.     

Modulation of the steroidogenic activity of luteinizing hormone by insulin and insulin-like growth factor-I through interaction with the cAMP-dependent protein kinase signaling pathway in the trout ovary

In the salmonid ovary, luteinizing hormone (LH) is the major gonadotropic hormone stimulating the production of steroids during the periovulatory period and its effects are mediated by the cAMP-dependent protein kinase (PKA) signaling pathway. We have previously shown that the in vitro steroidogenic activity of LH in the salmonid ovary is inhibited by insulin-like growth factor I (IGF-I) which, like insulin, has specific receptors in both theca and granulosa layers. In the present study, we have investigated the modulatory effects of insulin on salmon LH (sLH)-stimulated steroid production in preovulatory theca layers of brown trout (Salmo trutta) and the effects of both insulin and IGF-I on the sLH-stimulated cAMP/PKA signaling pathway. Our results show that insulin, like IGF-I, blocked the stimulatory effects of sLH, dibutyryl cAMP and IBMX on testosterone (T) production but not those of sLH on cAMP production. Furthermore, insulin and IGF-I blocked the activation of PKA induced by sLH and these effects were correlated with changes in the total protein content of the catalytic (C) and type II regulatory (RII) subunits of PKA. Interestingly, insulin and IGF-I had different effects on total PKA subunit content since insulin potentiated the sLH-stimulated increase in RII subunit content whereas IGF-I blocked the sLH-stimulated increase in total C subunit content. The effects of insulin and IGF-I in trout theca layers appeared to be mediated by the mitogen-activated protein kinase (MAPK) signaling pathway because inhibition of extracellular signal-regulated kinase 1/2(ERK1/2) activity completely blocked the inhibitory effects of insulin and IGF-I on the sLH-stimulated production of T and because insulin and IGF-I increased the total protein content of ERK1/2 in trout theca layers. Therefore, our results suggest that insulin and IGF-I, probably through the MAPK pathway, block the action of sLH in trout theca layers by modulating the cAMP/PKA signaling pathway.     

Follicular lymphoma international prognostic index

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs 120 g/L), number of nodal areas (> 4 vs 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk ( 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.