PANIC DISORDER, ANXIETY, AND CARDIOVASCULAR DISEASES

Different data indicate that psychological and/or emotional disorders may play an important role in the natural history of heart diseases. Although the major evidence is that related to depression, epidemiological data would indicate that anxiety and panic disorders are highly represented in cardiac patient, thus influencing mortality and morbidity. The diagnosis of panic disorder in patients with chest pain is crucial to a correct therapeutic approach, as well as to reduce the risks and costs of inappropriate treatments. Anxiety and panic may accelerate different direct and indirect processes involved in the pathogenesis of cardiovascular diseases: lifestyle risk factors, arterial hypertension, myocardial perfusion, autonomic nervous system or hypothalamus-pituitary-adrenal axis, platelet activation, and inflammation processes. Panic disorder seems to correlate particularly with sudden death: this suggests that it may be considered one of the main inducers of life-threatening arrhythmias, rather than to be linked to the development and progression of coronary atherosclerosis. Beyond hard outcomes, panic disorders produce negative effects on both global adjustment and life quality that may impair the course of the cardiac diseases. Interestingly, specific antipanic and anxiolytic agents seem to be particularly effective upon life quality. In any case, adequate controlled clinical trials are necessary in order to confirm the possibility of cardiovascular risk reduction by means of anxiety and panic disorder treatment

Effects of ambient temperature, humidity, and other meteorological variables on hospital admissions for angina pectoris.

BACKGROUND: Seasonal peaks in cardiovascular disease incidence have been widely reported, suggesting weather has a role. DESIGN: The aim of our study was to determine the influence of climatic variables on angina pectoris hospital admissions. METHODS: We correlated the daily number of angina cases admitted to a western Sicilian hospital over a period of 12 years and local weather conditions (temperature, humidity, wind force and direction, precipitation, sunny hours and atmospheric pressure) on a day-to-day basis. A total of 2459 consecutive patients were admitted over the period 1987-1998 (1562 men, 867 women; M/F - 1:8). RESULTS: A seasonal variation was found with a noticeable winter peak. The results of Multivariate Poisson analysis showed a significant association between the daily number of angina hospital admission, temperature, and humidity. Significant incidence relative ratios (95% confidence intervals/measure unit) were, in males, 0.988 (0.980-0.996) (p = 0.004) for minimal temperature, 0.990 (0.984-0.996) (p = 0.001) for maximal humidity, and 1.002 (1.000-1.004) (p = 0.045) for minimal humidity. The corresponding values in females were 0.973 (0.951-0.995) (p < 0.017) for maximal temperature and 1.024 (1.001-1.048) (p = 0.037) for minimal temperature. CONCLUSIONS: Environmental temperature and humidity may play an important role in the pathogenesis of angina, although it seems different according to the gender. These data may help to understand the mechanisms that trigger ischemic events and to better organize hospital assistance throughout the year

Human T lymphocytes at tumor sites

CD4(+) and CD8(+) T lymphocytes mediate most of the adaptive immune response against tumors. Naive T lymphocytes specific for tumor antigens are primed in lymph nodes by dendritic cells. Upon activation, antigen-specific T cells proliferate and differentiate into effector cells that migrate out of peripheral blood into tumor sites in an attempt to eliminate cancer cells. After accomplishing their function, most effector T cells die in the tissue, while a small fraction of antigen-specific T cells persist as long-lived memory cells, circulating between peripheral blood and lymphoid tissues, to generate enhanced immune responses when re-encountering the same antigen. A subset of memory T cells, called resident memory T (T-RM) cells, stably resides in non-lymphoid peripheral tissues and may provide rapid immunity independently of T cells recruited from blood. Being adapted to the tissue microenvironment, T-RM cells are potentially endowed with the best features to protect against the reemergence of cancer cells. However, when tumors give clinical manifestation, it means that tumor cells have evaded immune surveillance, including that of T-RM cells. Here, we review the current knowledge as to how T-RM cells are generated during an immune response and then maintained in non-lymphoid tissues. We then focus on what is known about the role of CD4(+) and CD8(+) T-RM cells in antitumor immunity and their possible contribution to the efficacy of immunotherapy. Finally, we highlight some open questions in the field and discuss how new technologies may help in addressing them

HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial.

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 μg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies

Thromboembolic and hemorrhagic risk stratification in patients with atrial fibrillation. Part II: hemorrhagic risk and guidelines recommendations

Robust evidence exists on the efficacy of traditional anticoagulant oral therapy in the prevention of thrombo-embolic risk in patients with non valvular atrial fibrillation, but fears and concerns of hemorrhagic events for the physicians and logistic difficulties related to the periodic International Normalized Ratio evaluation for the patients are at the basis of a noticeable under-utilization of the therapy with vitamin K antagonists in the real world. Stratification of the hemorrhagic risk has, thus, particular importance; for this objective we may use now several score system, among whom the more suggested is the HASBLED, with the principal aim to select and trait modifiable risk factors for bleeding. These score systems have been evaluated in some recent clinical trials. During the last years, a number of national and international guidelines on the prevention of the thrombo-embolic risk in patients with non valvular atrial fibrillation have been updated. These guidelines, generally, recommend the use of the CHA2DS2VaSC score for the evaluation of the thrombo-embolick risk, and of the HAS-BLED score for the evaluation of the hemorrhagic one. The consequent risk stratification is fundamental as a clinical guide for the use of oral anticoagulant therapy

Safety and Immunogenicity of a Genetically Engineered Human Immunodeficiency Virus Vaccine

A phase 1 trial of a candidate human immunodeficiency virus type 1 (HIV-I) vaccine was done in 25 healthy seronegative subjects. The antigen, env2-3 (SF2), was a nonglycosylated polypeptide representing the gp120 region of the env gene of the HIV-l(SF2) isolate. It was produced in genetically engineered yeast as a denatured molecule incapable of binding CD4. A synthetic lipophilic muramyl tripeptide (MTP-PE) was used as an adjuvant. Ten subjects received adjuvant alone and 15 received 50- or 25O-µg doses of env2-3 (SF2) administered intramuscularly in two immunization regimens. In general, adjuvant and vaccine were well tolerated. Antibody responses to both the homologous antigen, env2-3 (SF2), and antigens from other highly divergent HIV isolates were elicited in the majority of vaccine recipients. However, antibody titers were low, without neutralizing activity. In 9 of 11 subjects who received the complete vaccine immunization series, a significant specific T lymphocyte response was observe