Assessing global and regional left ventricular myocardial function in elderly patients using the bidimensional strain method

Biological and anatomical alterations in the elderly result in modifications of the myocardial deformation detected previously by magnetic resonance imaging (MRI) technology and could have consequences on speckle tracking's parameters in this patient population. Aim: To compare left ventricular (LV) 2D strain between elderly patients and young individuals without heart disease. Population and Methods: Patients without history of cardiac disease were enrolled from the geriatric department. After echocardiographic examination, exclusion criteria were LV myocardial abnormality, valve disease, and atrial fibrillation. The control group consisted of healthy subjects from the medical staff. 2D strain values were obtained from 16 segments in four‐, three‐, and two‐chamber apical views for longitudinal and transversal strains, and from six basal segments in short‐axis view for circumferential strain. Results: Forty‐five elderly patients (35 females) with mean age of 83.4 ± 5.0 years (75–95 years) and 45 young subjects (28 females) with mean age of 33.6 ± 7.5 years (17–45 years) were assessed. There was no difference between the two groups considering LV ejection fraction (66 ± 6% vs. 65 ± 4%, P = ns). Feasibility of segmental 2D strain was 55.6% for circumferential strain, 63% for transversal strain, and 82% for longitudinal strain. Global longitudinal strain was significantly lower in elderly patients (–20.9 ± 1.9% vs. –22.2 ± 2.2%, P < 0.01). There was no significant difference in global transversal and circumferential strain. Conclusion: Aging results in a decrease in global longitudinal strain. This should be taken into account in the assessment of pathological myocardial dysfunction. (Echocardiography 2011;28:978‐982)     

Metabolic remodelling of cardiac myocytes during pregnancy: the role of mineralocorticoids

Background

Pregnancy is associated with significant cardiac adaptations. The regulatory mechanisms involved in functional cardiac adaptations during pregnancy are still largely unknown. In pathologic conditions, mineralocorticoids have been shown to mediate structural as well as functional remodelling of the heart. However, their role in cardiac physiological conditions is not completely understood. Here, we examined cardiac cell metabolic remodelling in the late stages of rat pregnancy, as well as mineralocorticoid involvement in this regulation.

Methods

We have applied rapid video imaging, echocardiography, patch clamp technique, confocal microscopy, and time-resolved fluorescence spectroscopy.

Results

Our results revealed that cardiac cells undergo metabolic remodelling in pregnancy. Inhibition of mineralocorticoid receptors during pregnancy elicited functional alterations in cardiac cells: blood levels of energy substrates, particularly lactate, were decreased. As a consequence, the cardiomyocyte contractile response to these substrates was blunted, without modifications of L-type calcium current density. Interestingly, this response was associated with changes in the mitochondrial metabolic state, which correlated with modifications of bound reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H levels. We also noted that mineralocorticoid receptor inhibition prevented pregnancy-induced decrease in transient outward potassium current.

Conclusions

This study demonstrates that in pregnancy, mineralocorticoids contribute to functional adaptations of cardiac myocytes. By regulating energy substrate levels, in particular lactate, in the plasma and metabolic state in the cells, mineralocorticoids affect the contractility responsiveness to these substrates. In the future, understanding cardiac adaptations during pregnancy will help us to comprehend their pathophysiological alterations.     

Effect of chronic hypergastrinemia on human enterochromaffin-like cells: insights from patients with sporadic gastrinomas

BACKGROUND & AIMS: The effect of chronic hypergastrinemia alone on gastric enterochromaffin-like (ECL) cells in humans is largely unknown because in the common chronic hypergastrinemic states (atrophic gastritis, chronic proton pump inhibitor use), it is not possible to separate the effect of hypergastrinemia and other factors, such as gastritis or atrophy. Studies of patients with sporadic Zollinger-Ellison syndrome (ZES) allow this separation. METHODS: In 106 patients with ZES, gastric biopsies were taken, and the qualitative ECL cell pattern/grade and the alpha-subunit of human chorionic gonadotropin (alpha-hCG) expression were determined. RESULTS: In patients with active disease, 99% had ECL hyperplasia and abnormal alpha-hCG staining. Fifty percent had advanced changes in both of these, with 7% having dysplasia and 0% having carcinoids. Advanced ECL cell and alpha-hCG changes were most affected by the level of hypergastrinemia. For ECL cell changes, even mild hypergastrinemia had an effect. Advanced ECL change was also affected by the duration of drug treatment, cure status, and presence of atrophic gastritis, but not by sex or previous vagotomy. The alpha-hCG expression independently predicted dysplasia. CONCLUSIONS: In humans, chronic hypergastrinemia alone causes advanced ECL cell change and abnormal expression of mucosal alpha-hCG. No threshold for this effect was detected, as reported by some, and in contrast to animal studies, sex and vagal tone did not play a major role. The long-term risk of developing gastric carcinoids with chronic hypergastrinemia is low in patients with sporadic gastrinomas (at least 100 times less than in patients with multiple endocrine neoplasia type 1 with ZES) for at least 15-20 years.     

Cytotoxic T lymphocytes directed against a tumor-specific mutated antigen display similar HLA tetramer binding but distinct functional avidity and tissue distribution

We have previously identified an antigen (Ag) recognized on a human large cell carcinoma of the lung by a tumor-specific cytotoxic T lymphocyte clone derived from autologous tumor infiltrating lymphocytes (TILs). The antigenic peptide is presented by HLA-A2 molecules and is encoded by a mutated alpha-actinin-4 (ACTN4) gene. In the present report, we have isolated two anti-alpha-actinin-4 T cell clones from the same patient TIL and from his peripheral blood lymphocytes (PBLs) by using tetramers of soluble HLA-A2 molecules loaded with the mutated peptide. Although all of the clones displayed similar tetramer labeling, those isolated from PBL showed lower avidity of Ag recognition and killed the specific target much less efficiently, indicating that tetramer staining does not correlate with clone avidity/tumor reactivity. T cell receptor (TCR) analysis revealed that alpha-actinin-4-reactive clones used distinct alpha and beta chain rearrangements, demonstrating TCR repertoire diversity. Interestingly, TCR beta chain gene usage indicated that only Ag-specific clones with high functional avidity were expanded at the tumor site, whereas a low-avidity clone was exclusively amplified in patient peripheral blood. Our results point to the existence of distinct but overlapping antitumor TCR repertoires in TIL and PBL and suggest a selective in situ expansion of tumor-specific cytotoxic T lymphocyte with high avidity/tumor reactivity.     

Ovarian tumors associated with pregnancy: a 20-year experience in a teaching hospital

Objective  

Pregnancy associated with ovarian tumors was reviewed over a 20-year period to determine the maternal and fetal outcome in patients undergoing surgery during pregnancy.     

Two medical abortion regimens for late first-trimester termination of pregnancy: a prospective randomized trial

Background

Medical abortion regimens based on the use of either misoprostol alone or in association with mifepristone have shown high efficacy and excellent safety profile in early pregnancy abortion. However, no clear recommendation is available for late first-trimester termination of pregnancy.

Study Design

A prospective randomized controlled trial included 122 women seeking medical abortion at 9 to 12 weeks of gestation. Seventy-three patients were given a fixed protocol of 200 mg of mifepristone followed 48 h later by 400 mcg oral misoprostol (Group 1). The second group of 49 patients was administered 800-mcg intravaginal single-dose misoprostol (Group 2). This study sought to compare safety, efficacy and acceptability of these two nonsurgical abortion regimens.

Results

Fifty-nine (80.8%) women in Group 1 had complete abortion vs. 38 (77.4%) women in Group 2 (p=.66). Abdominal pain was observed significantly more often in Group 2 (35/49 (71.4%) vs. 32/73 (43.8%) in Group 1, p<.0001. Medical abortion was equally acceptable among the two groups [37/49 (75.5%) and 55/73 (75.7%), p=.89].

Conclusion

For late first-trimester termination, a single 800-mcg vaginal dose of misoprostol seems to be as effective as the mifepristone+misoprostol regimen, with acceptable side effects.     

Patients with multiple endocrine neoplasia type 1 with gastrinomas have an increased risk of severe esophageal disease including stricture and the premalignant condition, Barrett's esophagus

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (MEN1/ZES). Although esophageal reflux symptoms are common in these patients, little is known about long-term occurrence of severe peptic esophageal disease including strictures and Barrett's esophagus (BE). OBJECTIVE: The objective of the study was to prospectively analyze the frequency of severe peptic esophageal disease in ZES patients with and without MEN1. SETTING: The study was conducted at a tertiary care research center. PATIENTS: Two hundred ninety-five patients (80 = MEN1/ZES, 215 = sporadic ZES) participated in a prospective study. INTERVENTIONS AND OUTCOME MEASURES: Assessment of MEN1, acid hypersecretion, upper gastrointestinal endoscopy/biopsies, and tumor status were measured initially and at each follow-up. Esophageal manometry was performed in 89 patients. Frequency and type of esophageal disease were correlated with clinical/laboratory/tumoral features of ZES/MEN1. RESULTS: In MEN1/ZES patients, esophageal stricture was 3-fold higher, BE 5-fold higher, and dysplasia 8-fold higher, and one patient died of esophageal adenocarcinoma. Esophageal symptoms were more frequent or severe in MEN1/ZES, but known risk factors for severe esophageal disease and ZES-specific features did not differ between MEN1/ZES and sporadic ZES. In MEN1/ZES, the onset of ZES was 10 yr earlier, and H2-antagonists were used longer and at lower doses. MEN1/ZES patients with esophageal disease differed from those without in that ZES diagnosis was delayed longer, esophageal symptoms were more frequent or severe, hiatal hernias were more frequent, esophagitis or pyloric scarring was more common, basal acid output was higher, and hyperparathyroidism was underdiagnosed. CONCLUSIONS: This study shows that MEN1/ZES patients have a higher incidence of severe esophageal disease including the premalignant condition BE and identifies factors important for their pathogenesis that need to be incorporated into their long-term treatment.