Is there an anatomical substrate for idiopathic paroxysmal atrial fibrillation? A case-control echocardiographic study.

AIM: Idiopathic paroxysmal atrial fibrillation (AF) occurs in patients with apparently normal heart. Its mechanisms may be complex and are poorly understood. The aim of the study was to evaluate whether patients with idiopathic AF have any structural abnormality that may explain the occurrence of AF. METHODS AND RESULTS: A case-control study was undertaken including 60 consecutive patients (mean age 48 +/- 12 years; 75% men) with idiopathic AF admitted to the emergency department. Sixty sex- and age-matched healthy volunteers made up the control group. An echocardiogram was performed in all patients and volunteers to assess the left atrial (LA) and ventricular (LV) dimensions and valvular function. LV diastolic function was also evaluated by analysis of the LV inflow and pulmonary vein flow velocity patterns and tissue Doppler imaging of the mitral annulus. All AF patients showed normal echocardiographic studies with similar LV dimensions, ejection fraction, and diastolic function when compared with normal controls. However, patients with AF had larger LA dimensions (27 +/- 3 vs. 24 +/- 3 mm/m(2)), LA area (10 +/- 2 vs. 8 +/- 2 mm(2)/m(2)), and LA volume (27 +/- 9 vs. 19 +/- 6 mL/m(2)) (P < 0.05 for all). Among patients with AF, there were no differences in LA size between patients with a first episode or recurrent paroxysmal episodes. CONCLUSION: Patients with idiopathic AF showed larger left atria when compared with controls, there being no differences between patients with a first episode or a recurrence. This suggests the presence of an enhanced substrate to develop idiopathic lone AF.     

Incidence of Pulmonary Vein Stenosis in Patients Submitted to Atrial Fibrillation Ablation: A Comparison of the Selective Segmental Ostial Ablation vs the Circumferential Pulmonary Veins Ablation

Introduction: Pulmonary vein (PV) stenosis is an important complication of the AF ablation and could be underestimated if their assessment is not systematically done. Selective Segmental Ostial Ablation (SSOA) and Circunferential Pulmonary Veins Ablation (CPVA) have demonstrated efficacy in atrial fibrillation (AF) treatment. In this study the real incidence of PV stenosis in patients (pts) submitted to both SSOA and CPVA was compared. Methods: Those pts with focal activity and normal left atrial size were submitted to SSOA, remaining pts were submitted to CPVA to treat refractory, symptomatic AF. Contrast enhanced magnetic resonance angiography (MRA) was routinely performed in all patients 4 months after the procedure. Results: A series of 73 consecutive patients (mean age of 51 ± 11 years; 75% male) were included. SSOA was performed in 32 patients, and the remaining 41 patients underwent to CPVA, obtaining similar efficacy rates (72% vs 76% arrythmia free probability at 12 months; log rank test p = NS). Six patients had a significant PV stenosis, all in SSOA group none in CPVA group (18.8% vs 0%; p = 0.005). All patients were asymptomatic and the stenosis was detected in routine MRA. No predictors of stenosis has been identified analysing patient procedure characteristics. Conclusion: PV stenosis is a potential complication of SSOA not seen in CPVA. The study confirms than MRA is useful for identifying patients with asymptomatic PV stenosis. Santiago Nava, A. Berruezo and A. Scalise were supported in part by a Grant from the Fundació Clínic per la Recerca Biomèdica.     

p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis

BACKGROUND: Mutations in p53 and ras genes are frequent in pancreatic carcinoma. Several ras mutations are consistently detected in the pancreatic juice from patients with chronic pancreatitis. The p53 gene mutations have been detected occasionally in chronic pancreatitis tissue. It was the aim of this study to evaluate the presence and clinical significance of p53 and ras mutations in clinical pancreatic juice samples from patients with chronic pancreatitis. METHODS: Pancreatic juice was obtained from 66 patients with chronic pancreatitis and no evidence of pancreatic carcinoma (51 men, 15 women; age 17-86 years [mean 49.6 +/- 12.9]). Patients were followed prospectively for 26 +/- 3 (4-54) months. Detection of p53 gene mutations was by temperature gradient gel electrophoresis (TGGE) and single strand conformation polymorphism (SSCP) for exons 5-8. Analysis of ras mutations was performed by SSCP/polymerase chain reaction, restriction fragment length polymorphism/polymerase chain reaction. All mutations were confirmed by sequencing. RESULTS: Five of 66 (7.5%) pancreatic juice samples contained p53 mutations, and ras mutations were detected in 6 cases (9%). Cytology was negative in all cases. No pancreatic carcinoma developed during follow-up and neither cancer cells nor preneoplastic lesions could be detected histologically in resected specimens. Although no correlation between p53 mutations and duration of pancreatitis or drinking habits was found, K-ras mutations correlated with both heavy smoking and severity of the disease. CONCLUSION: p53 and ras mutations can be detected in a minority of pancreatic juice samples from patients with chronic pancreatitis in the absence of malignancy.     

Electronegative LDL of FH subjects: chemical characterization and induction of chemokine release from human endothelial cells

Electronegative LDL (LDL(-)) constitutes a plasma subfraction of LDL with proinflammatory properties. Its proportion is increased in familial hypercholesterolemia (FH); however, the characteristics of LDL(-) isolated from FH subjects have not been previously studied. In this work, the composition, oxidative status, and inflammatory capacity on endothelial cells of LDL(-) from FH and normolipemic (NL) subjects were evaluated. LDL(-) from FH was relatively enriched in esterified and free cholesterol and triglyceride, and had lower apoB and phospholipid content compared with the non-electronegative fraction (LDL(+)). LDL(-) also contained increased amounts of apoE, apoC-III, sialic acid, and non-esterified fatty acids (NEFAs). The same was observed in NL subjects, except that esterified cholesterol and phospholipid were similar in LDL(-) and LDL(+). No difference was observed between the two fractions concerning malondialdehyde, fatty acid hydroxides, and antioxidants, thereby indicating the absence of increased oxidation of LDL(-) compared with LDL(+). When LDL(-) (100 mg/l) from NL and FH subjects was incubated for 24 h with human umbilical vein endothelial cells (HUVECs), interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) increased twofold in the culture medium compared with LDL(+). Vascular cell adhesion molecule 1 (VCAM-1) expression was not increased by LDL(-). Our data indicate that LDL(-) from FH or NL subjects shows no evidence of increased oxidative modification compared to LDL(+); however, LDL(-) induces twofold the release of chemokines by endothelial cells. This effect, which may contribute to leukocyte recruitment and promote atherogenesis, may be greater in FH subjects in which LDL(-) can be up to eightfold higher than in NL subjects.     

Rituximab in the management of chronic immune thrombocytopenic purpura: an effective and safe therapeutic alternative in refractory patients

Rituximab induces B-cell depletion; therefore, it has been used in the treatment of immune thrombocytopenic purpura (ITP). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 89 patients with chronic ITP refractory to several treatments. All the patients had platelet counts <30×10⁹/l. They had received a median of five (2–13) previous treatments, and 47 had undergone splenectomy. Rituximab was administered i.v. at 375 mg/m² in four weekly doses in 77 patients, and 12 patients received 1–6 doses. Forty-nine patients (55.1%) reached platelet counts >50×10⁹/l; 41 (46%) achieved a complete response (CR; platelets >100×10⁹/l), and eight (9%) obtained a partial response (platelets 50–100×10⁹/l). Overall, 31 patients (35%) maintained response, including 15 patients in whom splenectomy failed, with a median follow-up of 9 months (2–42), 12 for more than 1 year. The unique predictor of a maintained response was to reach a CR. Heavily treated patients (more than three different previous treatments, including any corticosteroids) and those with longer ITP duration (>10 years from diagnosis) had a worse response. Non-splenectomized patients had a better early response rate than those splenectomized. Rituximab was well tolerated, with two fever episodes following infusion and two reports of skin rash. Rituximab induced clinical responses in multi-treated refractory ITP patients with little toxicity and should be considered as an early therapeutic option in this setting, even as an alternative to splenectomy in selected patients.An erratum to this article can be found at     

Follicular lymphoma in early stages: high risk of relapse and usefulness of the Follicular Lymphoma International Prognostic Index to predict the outcome of patients

BACKGROUND AND OBJECTIVES: Patients with follicular lymphoma (FL) in advanced stages are currently deemed incurable with standard treatments. However, FL is considered to be eradicable in the small group of patients presenting with localized disease. The objective of this study was to analyze the clinical features and the outcome of a series of patients with FL in early stages with a long follow-up. PATIENTS AND METHODS: A total of 48 patients (25m/23f; median age: 50 yr) diagnosed consecutively with FL in Ann Arbor stage I (25 cases) or II (23) at a single institution with a median follow-up of 9.5 yr were included in the study. Main biological and clinical characteristics at diagnosis, including Follicular Lymphoma International Prognostic Index (FLIPI) were analyzed; treatment and response were assessed and analyzed for prognosis. RESULTS: The histologic subtypes were: FL type I, 20 cases (42%); type II, 24 (50%); type III, three (6%); and unclassifiable, one (2%). Distribution according to FLIPI was: low risk (36 cases) and intermediate risk (five cases). Treatment mainly consisted of combination chemotherapy (CHOP in 34 cases) plus involved-field radiotherapy in 26 cases. Forty patients (89%) achieved a complete response (CR), three (7%) a partial response, and two (4%) were non-responders; the remaining three patients did not receive therapy. No initial variable predicted CR achievement. About 57% of the patients in CR eventually relapsed with a relapse risk of 46% at 10 yr. Intermediate-risk FLIPI predicted failure-free survival. Histologic transformation was observed in six patients with a 10-yr risk of transformation of 13%. Twelve patients died during follow-up, in two cases as a result of unrelated causes. Overall survival (OS) at 10 yr was 79%. The FLIPI was the sole variable predicting OS. CONCLUSIONS: Although the majority of patients with localized FL achieve CR, the risk of relapse is high. The FLIPI is of prognostic value in these patients.     

Cardiac chimerism in recipients of peripheral-blood and bone marrow stem cells

Multipotent progenitor cells have the ability to differentiate into most somatic cell types, including cardiac myocytes. We sought to investigate cardiac chimerism after peripheral-blood and bone marrow stem cell transplantation. Between 10 and 17 highly polymorphic short tandem repeat (STR) markers were assayed in DNA obtained from donors' peripheral blood, recipients' peripheral blood before transplantation, and the recipient's heart in every patient. Gender and non-gender STR donor alleles were identified in the recipient heart in three patients. Using a highly sensitive PCR assay to determine donor and recipient genotypes, we confirmed the existence of cardiac chimerism in recipients of peripheral-blood and bone marrow stem cells.     

Prevalence and mechanisms of hyperhomocysteinemia in chronic alcoholics

BACKGROUND: Homocysteine (Hcy) is formed as an intermediary in methionine metabolism. Impairment of Hcy remethylation or transulfuration leads to hyperhomocysteinemia, which is considered as a risk factor for atherosclerotic vascular disease and stroke in chronic alcoholics. The aim of the study was to investigate the prevalence of hyperhomocysteinemia in chronic alcoholics and the influence of alcohol consumption, vitamin deficiencies and liver damage on the plasma levels of Hcy. METHODS: 228 chronic alcoholic patients consecutively admitted for detoxication, classified according to clinical and biochemical data in normal liver (n = 117), and in mild to moderate liver disease (n = 111), and 49 healthy controls were studied. Blood levels of Hcy, vitamin B6, vitamin B12 and folate were measured. RESULTS: Plasma Hcy was significantly higher in chronic alcoholics than in controls (9.66 +/- 8.1 vs. 6.93 +/- 2.33 mumol/liter, p < 0.025). Furthermore, plasma Hcy levels were significantly higher in chronic alcoholics with liver injury (12.17 +/- 10.14 mumol/liter) than in those with normal liver and in controls (p < 0.001). The prevalence of hyperhomocysteinemia was also significantly higher in alcoholics with liver damage than in those with normal liver and in controls (29.7%, 5.1%, and 2%, respectively, p < 0.001). Serum folate values were lower in chronic alcoholics than in controls (4.7 +/- 2.6 vs. 7.6 +/- 2.4 nmol/liter, p < 0.001). The lowest values of folate were found in alcoholics with liver disease, especially in those with hyperhomocysteinemia, with a negative correlation between the two parameters. CONCLUSIONS: Moderate hyperhomocysteinemia is common in chronic alcoholics, mainly in those with liver damage, suggesting that, although folate deficiencies may have a contributory role, liver impairment, through changes in methionine metabolism, is the most important mechanism for the elevated plasma Hcy found in these patients.     

Emergency care of patients with upper gastrointestinal bleeding in regional hospitals in Catalonia

Objective

To evaluate the resources available in Catalan regional hospitals for the emergency care of upper gastrointestinal hemorrhage.

Methods

We analyzed a survey sent to 32 hospitals on the availability, composition and resources of a duty endoscopy service for the year 2009.

Results

Responses were obtained from 24 centers, covering 3,954,000 inhabitants. Duty endoscopists were available in 12 hospitals. A total of 1,483,000 inhabitants were unable to access a duty endoscopist in the referral center. Centers with duty endoscopists had more beds and had a larger catchment area. Duty services were composed of 4.5 endoscopists (range 2-11), covering 82.1 (33.2-182.5) duty shifts/year. Seventeen centers reported 1,571 episodes (51%, range: 3-280, 39.68/100,000 inhabitants). Centers with a duty service reported a greater number of cases (76 vs. 43, p = 0.047). Centers without this service referred a greater number of patients (147 vs. 17, p = 0.001). Patients in the emergency department were under the care of the internal medicine department in four centers, the surgery department in 14 centers and under the care of both departments in six. Admitted patients were under the care of the gastroenterology department in only six hospitals. The most widely used procedures were ligation of varicose bleeding and injection therapies in non-varicose bleeding. Twenty-one percent of centers did not perform combined treatment.

Conclusions

A significant proportion of the population does not have access to a duty endoscopist in referral centers. Duty shifts represent significant workload in regional hospitals. Coordination among health professionals and centers would allow the efficient application of therapeutic resources and a duty endoscopy service to be established in centers lacking this resource.     

A new automated method versus continuous positive airway pressure method for measuring pressure-volume curves in patients with acute lung injury

Objective  To compare pressure–volume (P–V) curves obtained with the Galileo ventilator with those obtained with the CPAP method in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Design  Prospective, observational study. Setting  General critical care center. Patients and participants  Patients with ALI/ARDS and receiving mechanical ventilation. Interventions  Pressure–volume curves were obtained in random order with the CPAP technique and with the software PV Tool-2 (Galileo ventilator). Measurements and results  In ten consecutive patients, airway pressure was measured by a pressure transducer and changes in lung volume were measured by respiratory inductive plethysmography. P–V curves were fitted to a sigmoidal equation with a mean R ² of 0.994 ± 0.003. Intraclass correlation coefficients were all >0.75 (P < 0.001 at all pressure levels). Lower (LIP) and upper inflection (UIP), and deflation maximum curvature (PMC) points calculated from the fitted variables showed a good correlation between methods with intraclass correlation coefficients of 0.98 (0.92, 0.99), 0.92 (0.69, 0.98), and 0.97 (0.86, 0.98), respectively (P < 0.001 in all cases). Bias and limits of agreement for LIP (0.51 ± 0.95 cmH₂O; −1.36 to 2.38 cmH₂O), UIP (0.53 ± 1.52 cmH₂O; −2.44 to 3.50 cmH₂O), and PMC (−0.62 ± 0.89 cmH₂O; −2.35 to 1.12 cmH₂O) obtained with the two methods in the same patient were clinically acceptable. No adverse effects were observed. Conclusion  The PV Tool-2 built into the Galileo ventilator is equivalent to the CPAP method for tracing static P–V curves of the respiratory system in critically ill patients receiving mechanical ventilation. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.