Epidemiology of sepsis in Internal Medicine Units of Apulia: results of SEMINA (SEpsis Management in INternal medicine Apulia) study.

Background: The prevalence and mortality of sepsis in Internal Medicine Units (IMUs) is poorly understood as most of the data derive from studies conducted in Intensive Care Units. Aim of SEpsis Management in INternal medicine Apulia (SEMINA) study was to determine the prevalence of sepsis and the characteristics and outcomes of patients with Sepsis-3 criteria admitted in Apulia's Internal Medicine Units for over six months. Methods: The SEpsis Management in INternal medicine of Apulia study was a prospective, multicentre, observational study. Adult admissions to the 13 Apulia Region's Internal Medicine Units between November 15, 2018 and May 15, 2019 were screened for sepsis according to the Sepsis-3 criteria. Medical data were collected in electronic case report form. Results: Out of 7,885 adult patients of the Internal Medicine Units, 359 (4.55%) fulfilled the inclusion criteria, and 65 of them (18.1%) met the septic shock criteria. The patients enrolled were elderly, suffering from chronic poly-pathologies and from cognitive and functional impairment. The respiratory system was the most common site of infection and the most common pathogens isolated from blood cultures were Staphylococcus spp., E. coli, Klebsiella spp., Enterococcus spp. and Acinetobacter spp. The in-hospital fatality rate was 31.2% and was significantly higher for septic shock. Sequential Organ Failure Assessment score, dementia and infections from Acinetobacter spp. were independent risk factors for mortality. Conclusions: A high prevalence of sepsis and a high fatality rate were detected in Apulia Region's Internal Medicine Units. The high fatality rate observed in our study could be related to the underlying diseases and to the vulnerability of elderly patients admitted to our Internal Medicine Units.

In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells.

Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

The SUBITO-DE study: sexual dysfunction in newly diagnosed type 2 diabetes male patients.

INTRODUCTION: No data on the prevalence of erectile dysfunction (ED) in subjects with newly diagnosed Type 2 diabetes mellitus (T2DM) are currently available. AIM: The aim of the present study was to estimate the prevalence of ED and its associated causes in a sample of male patients with recently diagnosed DM (<24 months) attending a diabetes care center. METHODS: The study comprised two phases: a cross-sectional analysis and a longitudinal reassessment of the data collected during the first phase. During the first phase, 1503 subjects (mean age 58.7±8.9 yr) from 27 centers were interviewed: 666 (43.3%) reported experiencing ED, 499 of which (mean age 58.8±8.8 yr) agreed to participate in the study (final enrolment rate, 33.3%). Concurrent morbidities were hypertension (55.3%), dyslipidemia (39.5%), and coronary heart disease (7.8%); chronic complications were neuropathy (8.9%), nephropathy (12.6%) and retinopathy (7.6%) in about one third of the sample at enrolment. RESULTS: Overall, about 20% of the patients reported having used ED drugs, but more than 50% had abandoned therapy because of the drug's ineffectiveness or high cost. The prevalence of hypogonadism was 46.9% (total testosterone level, 3.5 ng/ml). Some 20% of patients reported symptoms suggestive of depression. CONCLUSION: The present study provides data showing a high prevalence of ED, hypogonadism and depressive symptoms among male patients with newly diagnosed T2DM. Further analysis of the data will elucidate the specific determinants of such conditions and their longitudinal significance.

Factors associated with a rapid normalization of HbA1c in newly diagnosed type 2 diabetes patients seen in a specialist setting.

The time to achieve good metabolic control after diagnosis is essential for type 2 diabetes patients because it can influence long-term prognosis. This study aimed to elucidate the predictive role of several clinical and organization factors in normalizing metabolism within 6 months. A multi-centered, retrospective, observational study on 960 patients, with diabetes duration of 12 months or less, consecutively seen in 123 Italian clinics, was undertaken. Information about clinic's organization, along with data abstracted from medical records at enrollment (first visit) and after 6 months (follow-up visit), was collected. At 6 months, HbA1c dropped by -3.1 ± 2.2 points in those who achieved HbA1c <7 % (responders), whereas in non-responders (HbA1c ≥7 %), the mean reduction was -1.8 ± 1.9. The intervention markedly reduced lipids, blood pressure, BMI, and waist circumference, especially in responders. The presence of a diabetes team correlated with a likelihood of HbA1c normalization (OR 1.94, 1.17-3.22). By contrast, indicators of advanced disease such as previous retinopathy (0.53, 0.29-0.98), use of secretagogues (0.40, 0.25-0.64), high levels of HbA1c at first visit and related insulin use emerged as adverse factors. Early detection of diabetes, along with human resources and organization, was found to play a crucial role in rapidly attaining good metabolic control.

Pump blood processing, salvage and re-transfusion improves hemoglobin levels after coronary artery bypass grafting, but affects coagulative and fibrinolytic systems.

Cell saving systems are commonly used during cardiac operations to improve hemoglobin levels and to reduce blood product requirements. We analyzed the effects of residual pump blood salvage through a cell saver on coagulation and fibrinolysis activation and on postoperative hemoglobin levels. Thirty-four elective coronary artery bypass graft (CABG) patients were randomized. In 17 patients, residual cardiopulmonary bypass (CPB) circuit blood was transfused after the cell saving procedure (cell salvage group). In the other 17 patients, residual CPB circuit blood was discarded (control group). Activation of the coagulative, fibrinolytic and inflammatory systems was evaluated pre-operatively (Pre), 2 hours after the termination of CPB (T0) and 24 hours postoperatively (T1), measuring prothrombin fragment 1.2 (PF 1.2), plasmin-anti-plasmin (PAP), plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6). The cell salvage group of patients had a significant improvement in hemoglobin levels after processed blood infusion (2.7 ± 1.7 g/dL vs 1.2 ± 1.1 g/dL; p=0.003). PF1.2 levels were significantly higher after infusion (T0: 1175 ± 770 pmol/L vs 730 ± 237 pmol/L; p=0.037; T1: 331 ± 235 pmol/L vs 174 ± 134 pmol/L; p=0.026). Also, PAP levels were higher in the cell salvage group, although not significantly (T0: 253 ± 251 ng/mL vs 168 ± 96 ng/mL; p: NS; T1: 95 ± 60 ng/mL vs 53 ± 32 ng/mL; p: NS). No differences were found for PAI-1, IL-6, heparin levels or for red blood cell (RBC) transfusions. The cell salvage group of patients had increased chest tube drainage (749 ± 320 vs 592 ± 264; p: NS) and fresh frozen plasma transfusion rate (5 (29%) pts vs 0 pts; p<0.04). Pump blood salvage with a cell saving system improved postoperative hemoglobin levels, but induced a strong thrombin generation, fibrinolysis activation and lower fibrinolysis inhibition. These conditions could generate a consumption coagulopathy.

Global cardiovascular risk management in different Italian regions: an analysis of the Evaluation of Final Feasible Effect of Control Training and Ultra Sensitisation (EFFECTUS) educational program.

BACKGROUND AND AIM: The Final Evaluation Feasible Effect of Ultra Control Training and Sensitization (EFFECTUS) is an educational program, aimed at improving global CV risk stratification and management in Italy. The present study evaluates differences on clinical approach to global CV risk among physicians involved in the EFFECTUS program and stratified in three geographical macro-areas (North, Center, South) of our Country. METHODS AND RESULTS: Physicians were asked to submit data already available in their medical records, covering the first 10 adult outpatients, consecutively seen in the month of May 2006. Overall, 1.078 physicians (27% females, aged 50 ± 7 years) collected data of 9.904 outpatients (46.5% females, aged 67 ± 9 years), among which 3.219 (32.5%) were residents in Northern, 3.652 (36.9%) in Central and 3.033 (30.6%) in Southern Italy. A significantly higher prevalence of major CV risk factors, including obesity, physical inactivity, hypertension and diabetes, was recorded in Southern than in other areas. Accordingly, Southern physicians more frequently prescribed antihypertensive, glucose and lipid lowering agents than other physicians, who paid significantly more attention to life-style changes in their clinical practice. CONCLUSIONS: This analysis of the EFFECTUS study demonstrates a high prevalence of CV risk factors in Italy, particularly in Southern areas, and indicates some important discrepancies in the clinical management of global CV risk among physcians working in different Italian regions.

Myocardial protection during aortic surgery: comparison between Bretschneider-HTK and cold blood cardioplegia.

The ideal cardioplegic strategy in thoracic aorta operations requiring long cardiopulmonary bypass and cross-clamp time has not been established. Suboptimal myocardial protection may lead to myocardial damage and possible post-operative complications. We evaluate post-operative cardiac Troponin I (cTnI) release, low cardiac output syndrome (LCOS) and mortality, using a cold crystalloid single-dose intracellular or cold blood multidose cardioplegia in 112 elective or emergent thoracic aorta operation patients. Fifty-four patients (HTK group) received Custodiol® cardioplegic solution and 58 received cold blood cardioplegia (CB group). Cross-clamp time, cardiopulmonary bypass (CPB) time and cTnI peak release were similar in both groups. No differences were found for atrial and ventricular arrhythmias, inotropic support, LCOS and in-hospital mortality. Two-way ANOVA analysis revealed an interactive effect on cTnI peak (p=0.012) of cardioplegic solution type across the cross-clamp time quintile. In the fifth quintile, cross-clamp time patient (>160 min) cTnI peak value was higher in CB patients (p=0.044). HTK and CB cardioplegic solutions assure similar myocardial protection in patients undergoing thoracic aorta operations. In long cross-clamp times, the lower post-operative cTnI release detected using HTK may be indicative of a better myocardial protection in these extreme conditions.

Impact of physicians' age on the clinical management of global cardiovascular risk: analysis of the results of the Evaluation of Final Feasible Effect of Control Training and Ultra Sensitisation Educational Programme.

AIM: To evaluate the potential impact of physicians' age on global cardiovascular (CV) risk management in the population of the Evaluation of Final Feasible Effect of Ultra Control Training and Sensitisation (EFFECTUS) study. METHODS: Involved physicians were stratified into three age groups (≤ 45, 46-55 and > 55 years), and asked to provide clinical data covering the first 10 adult outpatients, consecutively seen in May 2006. RESULTS: Overall 1078 physicians, among whom 219 (20%) were aged ≤ 45, 658 (61%) between 46 and 55, and 201 (19%) > 55 years, collected data of 9904 outpatients (46.5% female patients, aged 67 ± 9 years), who were distributed into three corresponding groups: 2010 (20%), 6111 (62%) and 1783 (18%), respectively. A higher prevalence of myocardial infarction and stroke was recorded by younger physicians rather than those aged > 46 years. Older physicians frequently recommended life-style changes, whereas a higher number of antihypertensive, antiplatelet, glucose and lipid-lowering prescriptions was prescribed by physicians aged ≤ 45 years. CONCLUSIONS: This analysis of the EFFECTUS study indicates a higher prevalence of vascular diseases among outpatients who were followed by younger physicians, who prescribed a higher number of CV drugs than older physicians. These older physicians have more attitude for prescribing favourable life-style changes than younger physicians.

[Overexpression of laminine-5( LN-5) in peritoneal lavage of colorectal cancer patients preliminary results]. / Overexpression della laminina-5 (LN-5) nel lavaggio peritoneale di pazienti con carcinomi del grosso intestino. Risultati preliminari.

Recent studies show that interaction between LN (heterotrimeric protein formed by a3/b3/g2 chains) and cancer cells plays an important role in tumor invasion, also in colorectal cancer. The overall survival was significantly worse in patients with free peritoneal cancer cells(FPTCs): detection of FPTCs after curative surgery is a challenge, because could improve staging and prognosis. Peritoneal citology is the current standard procedure with very low sensivity. We aimed to study the expression of LN5 in the peritoneal lavage of colorectal cancer pts and in controls with semiquantitative reverse trancriptase-polymerase chain reaction (RT-PCR). LN-5 overexpression was evaluated observing PCR- products intensity at electrophoresis: high intensity is correlated to overexpression. Pre and post-operative peritoneal lavages of 30 pts with colorectal cancer (13M;17F), with median age of 69 (58-84), and of 10 controls, were analyzed by conventional cytology and a semiquantitative RT-PCR. No cancer pts showed pre/postoperative negative cytology and did not express LN-5. In cancer pts. cytology was positive in 2 pts in pre/postoperative lavage. LN-5 overexpression was observed in 56,6% preoperatively and in 76,6% postoperatively. LN-5 g 2 chain was most frequent chain. Our study suggests a relationship between LN-5 and FPTCs, as shown by the low expression of lamimine in controls. LN-5 could be a useful marker to identify a subgroup of early-stage patients at increased risk of recurrence; moreover, mortality seems to correlated to LAMB3 chain. The diagnostic accuracy could be improved by using a quantitative RT-PCR or western-blot and detecting serum laminine. Finally, to validate these findings a larger number of pts with follow-up study is required.

The clinical role of contrast-enhanced ultrasound in the evaluation of renal artery stenosis and diagnostic superiority as compared to traditional echo-color-Doppler flow imaging.

AIM: The purpose of this study was to investigate the feasibility of contrast-enhanced ultrasound (CEUS) in the evaluation of renal artery stenosis as compared with traditional techniques: echo color Doppler (ECD) investigation and selective angiography .CEUS is a technique based on the injection of an intravascular biocompatible tracer, namely an intravenous contrast galactose microparticle suspension containing microbubbles (Levovist), that has a similar rheology to that of red blood cells, allowing quantification of renal tissue perfusion. METHODS: A population of 120 hypertensive patients (82 men, mean age 55) with a systolic abdominal murmur and/or a diagnosis of poly-districtual atherosclerosis was studied by ECD and CEUS (Levovist). Selective angiography was performed in patients with renal artery stenosis demonstrated by one of the two ultrasonographic techniques. RESULTS: Forty of the 120 patients in the study population showed renal artery stenosis at one of the two ultrasound techniques: ECD identified renal artery stenosis in 33 cases and CEUS in 38. Instead, selective angiography had detected renal artery stenosis in 38 patients, the same with renal artery stenosis diagnosed by CEUS. Thus, CEUS sensitivity, specificity and accuracy were similar to those of angiography while six false negatives and two false positives were obtained with ECD. CONCLUSION: Our results suggest that this renal CEUS is a promising, new, non-invasive method for screening patients with suspected renal artery stenosis. This technique appears to be superior to traditional ECD flow imaging for diagnosing renal artery stenosis and so may be an important aid in cardiovascular diagnostics.

Free triiodothyronine is associated with smoking habit, independently of obesity, body fat distribution, insulin, and metabolic parameters.

BACKGROUND: The aim of this study was to examine the relationship between thyroid hormones and smoking and several other parameters like age, gender, insulin, and anthropometric and metabolic parameters in subjects with a wide range of body mass index (BMI). PATIENTS AND METHODS: A total of 931 euthyroid normal weight (BMI<25.0 kg/m2), overweight and obese subjects (BMI ≥25.0 kg/m2), 663 women and 268 men, aged 18-68 yr, were investigated. Fasting TSH, free T3 (FT3), free T4 (FT4), insulin, glucose, and lipid serum levels were determined. Waist circumference was measured as an indirect parameter of central fat accumulation. RESULTS: Smokers were younger (p<0.001) and showed higher FT3 (p<0.01), and triglyceride (p<0.01) levels and lower glucose (p<0.01) and HDL (p<0.001) concentrations than non smoking subjects. FT3 levels were directly associated with BMI (p<0.001), waist circumference (p<0.001), insulin (p<0.001), and triglyceride (p<0.01) levels and negatively correlated with age (p<0.001) and HDL-cholesterol levels (p<0.001). When a multiple regression analysis was performed with FT3 levels as the dependent variable, and smoking, age, gender, and TSH, insulin, triglyceride, and HDL-cholesterol serum concentrations as independent variables, FT3 levels maintained an independent positive association with smoking (p<0.05), age (p<0.001), male sex (p<0.001), waist circumference (p<0.05), and insulin levels (p<0.001). CONCLUSIONS: Smoking increases FT3 levels independently of age, gender, obesity, body fat distribution and metabolic parameters.

Abdominal fat accumulation, and not insulin resistance, is associated to oligomenorrhea in non-hyperandrogenic overweight/obese women.

BACKGROUND: There is a very high prevalence of obese women in the infertile population and many studies have highlighted the link between obesity and infertility. The aim of this study was to evaluate the prevalence of oligomenorrhea in uncomplicated obesity, and to examine whether this menstrual alteration is associated with anthropometric, hormonal, and metabolic parameters. PATIENTS AND METHODS: This is a cross-sectional study of 266 overweight and obese body mass index (BMI) > or =25.0 kg x m(-2)] women, all having apparent normal fertility. Measurements included BMI, central fat accumulation (evaluated by waist circumference), blood pressure levels, and fasting insulin, glucose, and lipid (triglycerides, total and HDL-cholesterol) serum concentrations, and insulin resistance [estimated by (homeostasis model assessment) HOMAIR] during the early follicular phase (days 2-5 of the menstrual cycle). RESULTS: One hundred and seventy-one (64.3%) of 266 women had normal menstrual cycles, 57 (21.4%) had oligomenorrhea, and 38 (14.3%) had hypermenorrhea and/or polimenorrhea. Women with oligomenorrhea had higher waist circumference, BMI, HOMAIR, and insulin levels than women with normal menstrual cycles. When association among oligomenorrhea and other variables (waist circumference, BMI, insulin and HOMAIR) was evaluated by logistic regression, and odds ratio was calculated per unit of SD increase, only waist circumference maintained a significant relationship with oligomenorrhea. CONCLUSIONS: This study shows that more than 20% of women with simple obesity have oligomenorrhea, and suggests that central fat accumulation seems to have a possible direct role in this menstrual alteration, independently of hyperinsulinemia and/or insulin resistance.

Prognostic role of sub-clinical hypothyroidism in chronic heart failure outpatients.

BACKGROUND: It has been suggested that low thyroid hormones levels may be associated with increased mortality in patients with cardiovascular disease. AIM: To evaluate the prognostic role of thyroid function deficiency in patients with chronic heart failure (CHF). METHODS: We evaluated 338 consecutive outpatients with stable CHF receiving conventional therapy, all of whom underwent a physical examination, electrocardiography and echocardiography. Blood samples were drawn to assess renal function, and Na+, hemoglobin, NT-proBNPs, fT3, fT4 and TSH levels. Patients with hyperthyroidism were excluded. RESULTS: During the follow-up (15+/-8 months), heart failure progression was observed in 79 patients (including 18 who died of heart failure after hospitalisation and six who underwent transplantation). Univariate regression analysis showed that TSH (p<0.0001), fT3 (p<0.0001), fT4 (p=0.016) and fT3/fT4 (p<0.0001) were associated with heart failure progression but multivariate analysis showed that only TSH considered as a continuous variable (p = 0.001) as well as subclinical hypothyroidism (TSH > 5.5 mUI/l; p=0.014) remained significantly associated with the events. CONCLUSIONS: In CHF patients TSH levels even slightly above normal range are independently associated with a greater likelihood of heart failure progression. This supports the need for prospective studies aimed at clarifying the most appropriate therapeutic approach to sub-clinical hypothyroidism in such patients.

Gene expression profiling of breast cells induced by X-rays and heavy ions.

Several genetic aberrations and gene expression changes have been shown to occur when cells are exposed to various types of radiation. The integrity of DNA depends upon several processes that include DNA damage recognition and repair, replication, transcription and cell cycle regulation. Ionizing radiation has many sources, including radon decay from the soil and X-rays from medical practice. Epidemiological evidence indicates a risk for cancer by inducing genetic alterations through DNA damage, and molecular alterations have been reported in epidemiological studies of the A-bomb survivors. A spontaneously immortalized human breast epithelial cell model, MCF-10F, was used to examine the gene expression profiling of breast cells induced by X-ray and heavy ion exposure, by a cDNA expression array of DNA damage and repair genes. This cell line was exposed to 10, 50, 100 and 200 cGy of either X-rays or heavy ions and gene expression profiles were studied. Results indicated that out of a total of 161 genes, 38 were differentially expressed by X-ray treatment and 24 by heavy ion (Fe(+2)) treatment. Eight genes were common to both treatments and were confirmed by Northern blot analysis: BRCA1, BIRC2/CIAP1, CENP-E, DDB1, MRE11A, RAD54/ATRX, Wip1 and XPF/ERCC4. A number of candidate genes reported here may be useful molecular biomarkers of radiation exposure in breast cells.

Haptoglobin serum levels are independently associated with insulinemia in overweight and obese women.

BACKGROUND: Obesity is associated with a chronic low-grade inflammatory condition. Haptoglobin is a glycoprotein involved in the acute-phase response to inflammation, and it is increased in obese subjects. The possibility that hyperinsulinemia and/or insulin resistance may directly increase haptoglobin levels has never been tested. The aim of this study was to investigate the associations of haptoglobin serum levels with anthropometric parameters, insulin levels, insulin resistance and related metabolic variables in overweight and obese women. PATIENTS AND METHODS: This is a cross-sectional study of 194 non-diabetic overweight and obese subjects, aged 18-68 yr. Measurements included body mass index (BMI), central fat accumulation [evaluated by waist circumference (WC)], systolic and diastolic blood pressure, and fasting concentrations of haptoglobin, insulin, glucose, lipids (triglycerides, total cholesterol, and HDL-cholesterol), and insulin resistance as estimated by the homeostasis model assessment (HOMAIR). RESULTS: Haptoglobin serum levels showed a positive association with BMI (p<0.001), WC (p<0.001), HOMAIR (p<0.001), and fasting insulin (p<0.001), triglyceride (p<0.001) and glucose (p<0.05) blood levels. However, only insulin maintained a significant independent association with haptoglobin (p<0.001) when a multiple regression analysis was performed and age, BMI (or WC), blood pressure levels, HOMAIR, and fasting insulin, glucose, and lipid blood concentrations were entered as independent variables. CONCLUSIONS: Higher haptoglobin serum levels seem to be a strong marker of hyperinsulinemia, independently of BMI, body fat distribution, insulin resistance and related parameters.

Whole-body bioelectrical impedance analysis in patients with chronic heart failure: reproducibility of the method and effects of body side.

BACKGROUND: Fluid imbalance and malnutrition have an important role in the clinical setting of chronic heart failure (CHF). Recently, tetrapolar bioelectrical impedance analysis has been suggested as an attractive method which may be used in the clinical assessment of the body composition. The aim of this study was to determine the effects of body side on whole bioelectrical impedance analysis parameters and test-retest reliability, prior to its use in a large cohort of patients. METHODS: In 114 consecutive patients with CHF (mean age 65 +/- 10 years, left ventricular ejection fraction 31 +/- 9%, NYHA functional class 2.6 +/- 0.9) we measured the total body resistance, the reactance and the derived angle phase using a single-frequency (50 KHz) tetrapolar plethysmograph device. The evaluations were performed on the left and right sides of the body, in a random order, on two different occasions 30 min apart. The effects of body side were analyzed by the Student's t-test and the test-retest reliability was computed by using the coefficient of variation and intraclass correlation coefficient. RESULTS: In both evaluations, the mean resistance value of the right side was significantly lower (almost 10 ohms) than that of the left side, the reactance was not different, and as a consequence the angle phase was significantly higher (almost 0.1 degrees) in the right than in the left side. The test-retest reliability for all the measurements considered was very high (the intraclass correlation coefficient ranged from 0.95 to 0.99 and the coefficient of variation from 1.7 to 4.3%). CONCLUSIONS: In CHF, the body side is important for the whole-body assessment of the resistance and the angle phase, but not for reactance. In addition, all these measurements are characterized by an excellent test-retest reliability and, consequently, do not necessitate a substantial increase in the sample size for the detection of small differences in experimental studies.

Depression but not anxiety influences the autonomic control of heart rate after myocardial infarction.

AIMS: It has been previously hypothesized that the adverse outcome observed in depressed patients after myocardial infarction might be due to an imbalance in autonomic nervous system activity. The aim of this study was to define the role of depressive and anxious symptoms in influencing autonomic control of heart rate after myocardial infarction. METHODS AND RESULTS: The SD of RR intervals, baroreflex sensitivity, and depression and anxiety (Zung's scales) were assessed before discharge in 103 patients with acute myocardial infarction; 32 were found to be depressed. Among the patients who were not taking beta-blockers, those with depression had significantly lower SDs of RR intervals and baroreflex sensitivity than did those without depression (96.3 +/- 22.2 ms vs 119.5 +/- 37.7 ms, P =.016; 8.6 +/- 6.2 ms vs 11.8 +/- 6.5 ms/mm Hg, P =.01, respectively). No differences were found when anxiety was considered or when beta-blockers were given. Among the patients not taking beta-blockers, there was a significant correlation between depression levels and both the SD of RR intervals (r = -0.47) and baroreflex sensitivity (r = -0.40). CONCLUSIONS: In patients with myocardial infarction, depression but not anxiety negatively influences autonomic control of heart rate. Beta-blockers modify these influences.

Influence of gender and family history of hypertension on autonomic control of heart rate, diastolic function and brain natriuretic peptide.

OBJECTIVE: To verify in a unitary view whether autonomic control of heart rate and cardiac structure and function are modified early in offspring of hypertensive families. METHODS AND RESULTS: We selected 87 age- and sex-matched young normotensive subjects with (n = 45) and without (n = 42) a family history of hypertension who underwent evaluations of arterial pressure, time-domain parameters of autonomic heart rate control (24-h ECG monitoring), spectral baroreflex sensitivity, left ventricular geometry and function (echo-Doppler) and plasma brain natriuretic peptide levels (BNP). The group with a family history of hypertension significantly differed from their counterparts for systolic pressure (119 +/- 11 versus 114 +/- 9 mmHg, P< 0.05), heart rate (RR interval, 766 +/- 64 versus 810 +/- 93 ms, P< 0.05), heart rate variability [the standard deviation of normal RR intervals (SDNN), 147 +/- 29 versus 171 +/- 33 ms, P < 0.051, diastolic function (isovolumetric relaxation time, 65 +/- 9 versus 60 +/- 8 ms, P< 0.05) and BNP (23 +/- 13 versus 37 +/- 10 pg/ml, P< 0.05). Baroreflex sensitivity values did not differ between the two groups. When gender was considered, all the above-mentioned measures, as well as baroreflex sensitivity, were significantly different between males with and without a family history of hypertension but not between females, except for BNP, which was lower in males and females with a history of hypertension (males, 24 +/- 11 versus 38 +/- 8 pg/ml, P< 0.01; females 21 +/- 14 versus 36 +/- 13 pg/ml, P < 0.05). CONCLUSIONS: Male, but not female, hypertensive offspring have modified diastolic function and autonomic control of heart rate; BNP is the only parameter able to characterize hypertensive offspring independently from the influence of gender. This provides the hypothesis that the impaired production of this hormone could play a primary role in the pre-hypertensive state.

pRB and p107 have distinct effects when expressed in pRB-deficient tumor cells at physiologically relevant levels.

A key difference among the three structurally similar pRB family members is that only pRB is a tumor suppressor. Identification of distinctive functional differences between pRB and p107/p130 therefore holds promise for a better understanding of the tumor suppression mechanisms of pRB. Enigmatically, pRB and p107 have been shown to have indistinguishable growth suppression activities when studied in the pRB-deficient Saos-2 cell system. In this study, we discovered that, when expressed at physiologically relevant levels, pRB and p107 had distinctive effects in causing growth suppression. pRB induced cellular p130 levels while p107 repressed them. p107, but not pRB, blocked cells inside S phase in addition to G1 arrest. In contrast, no qualitative differences were identified in their abilities to repress the expression of a set of suspected pRB/E2F repression target genes. These results indicate that pRB and p107 possess different growth suppression effects, despite the fact that they have similar E2F repression effects.

Influence of hydrophilic and lipophilic beta-blockers on heart rate, ventricular repolarization and their interrelationship in normal subjects.

BACKGROUND: It has been hypothesized that hydrophilic and lipophilic beta-blockers have different antiarrhythmic properties because only the latter seem to reduce the rate of sudden death in post-myocardial infarction patients as well as animal models which seem to be independent of their effect on autonomic nervous system modulation. The aim of this study was to evaluate the different effects of a hydrophilic (nadolol) and lipophilic (metoprolol) beta-blocker on ventricular repolarization in normal subjects. METHODS: Seventeen normal subjects entered this randomized, single-blind cross-over study designed to compare the effects of nadolol (80 mg/day) and slow-release metoprolol (200 mg/day) on dynamic ventricular repolarization. The RR intervals, the QT evaluated at the apex (QT apex) and at the end (QT end) of the T wave before and after correction for heart rate, the standard deviation of QT apex and QT end, and the slope of the QT/RR linear relationship (QTa-slope and QTe-slope) were studied using the ELATEC system (ELA Medical, Mountrouge, France), and an evaluation was made of their reproducibility and the effects of each beta-blocker. RESULTS: The most reproducible parameters were QT apex, corrected QT apex and the QTe-slope. Nadolol was associated with a greater adrenergic blockade than metoprolol (lengthening of RR interval +25 +/- 7 and +17 +/- 8% respectively, p = 0.0003) and a lower effect on ventricular repolarization (reduction of corrected QT apex -0.6 +/- 3 and -2.5 +/- 2.1% respectively, p < 0.01; reduction of QTe-slope -5 +/- 16 and -15 +/- 15% respectively, p = 0.03). CONCLUSIONS: At the dosages used in the study, metoprolol showed lower adrenergic blockade but greater effect on ventricular repolarization than nadolol.