A subgroup of light-driven sodium pumps with an additional Schiff base counterion.

Light-driven sodium pumps (NaRs) are unique ion-transporting microbial rhodopsins. The major group of NaRs is characterized by an NDQ motif and has two aspartic acid residues in the central region essential for sodium transport. Here we identify a subgroup of the NDQ rhodopsins bearing an additional glutamic acid residue in the close vicinity to the retinal Schiff base. We thoroughly characterize a member of this subgroup, namely the protein ErNaR from Erythrobacter sp. HL-111 and show that the additional glutamic acid results in almost complete loss of pH sensitivity for sodium-pumping activity, which is in contrast to previously studied NaRs. ErNaR is capable of transporting sodium efficiently even at acidic pH levels. X-ray crystallography and single particle cryo-electron microscopy reveal that the additional glutamic acid residue mediates the connection between the other two Schiff base counterions and strongly interacts with the aspartic acid of the characteristic NDQ motif. Hence, it reduces its pKa. Our findings shed light on a subgroup of NaRs and might serve as a basis for their rational optimization for optogenetics.

Cardiac rupture in embolic myocardial infarction after implantation of a valved aortic conduit.

We report a case of an apical myocardial infarction complicated by left ventricular wall rupture due to coronary artery embolism four years after surgery of an acute type A dissection of an aortic aneurysm with implantation of a valved aortic conduit.

Impairment of survival factor function potentiates chemotherapy-induced apoptosis in tumor cells.

The balance between tumor cell proliferation and apoptosis is a critical determinant of malignant tumor outgrowth. In a transgenic mouse model of beta cell tumorigenesis (Rip1Tag2), insulin-like growth factor II (IGF-II) is up-regulated during the onset of tumor cell proliferation. Disruption of IGF-II expression in these transgenic mice causes a dramatic increase of beta tumor cell (betaTC) apoptosis, indicating that IGF-II acts as a survival factor. Here we report that beta tumor cell lines derived from IGF-II-deficient Rip1Tag2 mice show a higher incidence of apoptosis than their wild-type counterparts. In particular, IGF-II-deficient betaTCs are more sensitive to apoptotic stimuli, such as serum deprivation and staurosporine, and to chemotherapeutic agents, such as daunomycin, etoposide, or vincristine. Thus, the lack of the survival factor IGF-II potentiates chemotherapeutic treatment of betaTCs. Furthermore, normal betaTCs can be sensitized to chemotherapy when transfected with a dominant-negative mutant of the IGF-I receptor. These results demonstrate a pivotal role for IGF-mediated signaling in the survival of tumor cells and, thus, raise the possibility of novel approaches toward cancer therapy by interfering with survival factor function.

An insulin-like growth factor-mediated, phosphatidylinositol 3' kinase-independent survival signaling pathway in beta tumor cells.

Hyperproliferation of tumor cells usually coincides with increased tumor cell apoptosis. To overcome apoptosis, tumor cells frequently induce the expression of growth factors that mediate cell survival. In nontransformed cells, including fibroblasts and neurons, survival factor-mediated signal transduction involves the activation of phosphatidylinositol 3' kinase (PI-3K) and protein kinase B/c-Akt (PKB). Here we demonstrate that tumor cell lines derived from a transgenic mouse model of pancreatic beta cell carcinogenesis use insulin-like growth factors to repress apoptosis independently of PI-3K and PKB. The results indicate that tumor cells can use additional survival signal transduction pathways.

Chronic total occlusion--a definite state?

Successful recanalisation of a chronic coronary occlusion may result in survival advantage. This report describes a 61-year-old man with an initially chronic occluded right coronary artery. A follow-up angiography 2 years later revealed a spontaneous recanalisation.

Catecholamine therapy inducing dynamic left ventricular outflow tract obstruction.

Hypertrophic obstructive cardiomyopathy with significant hypertrophy of the basal septum is the most frequently reported cause of left ventricular outflow tract (LVOT) obstruction. Additionally, other conditions such as dehydration, sepsis, vasodilatation, or mitral valve repair have been associated with LVOT obstruction. In this report, we present a case of a patient without hypertrophy who developed severe dynamic left ventricular outflow tract obstruction during catecholamine stimulation for shock that complicated severe pancreatitis. The present case serves as a reminder that hypovolemia together with a hyperdynamic state resulting from catecholamine administration may result in the development of dynamic LVOT obstruction even if baseline cardiac evaluation is unremarkable. Early detection and intensive efforts to reverse the underlying conditions, including cessation of catecholamine therapy and correction of hypovolemia are essential.

Obesity, body fat and coronary atherosclerosis.

BACKGROUND: Recent prospective studies have provided compelling evidence that obesity is a risk factor for the occurrence of clinical coronary events. However, the link between angiographically determined coronary atherosclerosis and obesity still remains controversial. We conducted this cross-sectional study in a clinical setting to investigate the relation of the obesity and body fat (BF) with angiographically defined coronary atherosclerosis. PATIENTS AND METHODS: Six hundred and seventy-three men (median age 64 years) and four hundred and twenty-eight women (median age 69 years) who underwent coronary angiography for suspected or known coronary heart disease were analyzed. The body mass index (BMI) and the BF were used as main exposure variables, and either the presence of significant (> or =50%) coronary diameter stenosis or a coronary artery disease severity score were defined as outcome variables, in a sex-specific logistic regression analysis. RESULTS: Among male patients, BF was slightly higher with increasing number of vessels involved (adjusted P for trend <0.05). In contrast, BMI showed no association with presence and severity of coronary artery disease (CAD). The odds ratios (ORs) for the presence of significant stenosis across quartiles of BMI were 1.0 (reference), 0.9, 1.1 and 0.7 (adjusted P for trend 0.61). This result did not differ between younger and older men. Among females, however, both BF and BMI were not significantly associated with an increasing number of vessels involved. CONCLUSION: These results suggested that BF may be predictive of an increasing number of coronary vessels involved among male patients, but not among female patients. This study failed to detect a positive association of presence and severity of CAD with BMI.

Postoperative atrial fibrillation independently predicts prolongation of hospital stay after cardiac surgery.

AIM: Postoperative atrial fibrillation (AF) occurs in up to 50% of cardiac surgery patients and represents the most common postoperative arrhythmic complication. A reduction of the length of hospital stay is a desirable goal in preventive strategies of postoperative AF. The aim of the present investigation was to determine whether prolonged postoperative hospital stay associated with AF after cardiac surgery surgery is attributable to the arrhythmia itself or to baseline characteristics of patients who develop AF. METHODS: Patients undergoing elective cardiac surgery in the absence of heart failure and significant left ventricular dysfunction (n = 253; average age 65+/-11 years) were recruited to the present prospective study. Midline sternotomy procedures with standard surgical techniques for normothermic cardiopulmonary bypass in coronary artery bypass grafting and valvular surgery were used. RESULTS: A total of 99 patients (39.1%) of the study population developed AF during the postoperative period. AF patients were older and more likely to have surgery for valvular heart disease and less likely to have antiarrhythmic drugs including beta-adrenergic blockers than patients without AF, but both patients with and without AF had similar body mass index and duration of surgery. Postoperative hospital stays were longer in patients with AF compared to those without AF (14.9+/-5.7 vs 10.6+/-3.6, respectively; P = 0.001). Multivariate analysis, adjusted for age and postoperative complications, demonstrated that postoperative hospital stay was 14.2+/-5.3 days in patients with AF and 10.8+/-3.8 days in patients without AF (P < 0.01). Treatment with oral antiarrhythmic drugs that reduce AF is associated with a reduction of postoperative hospital stay. CONCLUSIONS: Despite baseline characteristics differed between patients with and without postoperative AF, most of the prolongation of hospital stay can be attributed to the rhythm disturbance itself.

Risk factors for coronary heart disease in rural Hungary.

This is a ten-year study of a cohort of 1088 Hungarian men aged 40-59 at entry, with a 99% baseline response rate and complete ascertainment of cases and follow-up. The methods were state of the art for the period the survey was performed, with quality control for standard procedure and training. Zero, five- and ten-year examinations were carried out and standard risk factors measured and analysed in relation to the ten-year experience, ie, age, blood cholesterol, blood pressure, smoking, body mass, vital capacity, and skinfolds. Risk factor levels were high relative to the Mediterranean and Oriental populations in the Seven Countries Study. The five-year coronary heart disease rates were intermediate between the low rates in Yugoslavia and Greece and high rates in Finland. Ten-year events were significantly and linearly related to quintile values of serum cholesterol and of 3, 4, 6, and 9 risk factors in the Walker-Duncan logistic model. Discrimination was not substantially improved beyond three factors apart from age. The maximal prediction concentrated 62% of events in the upper 20% of multifactor risk, and up to 80% in the upper 40% of risk. The authors conclude, from this separate but comparable study to the Seven Countries Study, that the results are not greatly different from that study or from the US Pooling Project. Unique features of the study, and its results, are the eastern European population, the absence of a strong CHD relationship with smoking, and the strong independent relationship with body mass.

Effective control of hypertension: a project of the Hungarian Society of Hypertension, baseline data.

The aim of the project is to assess the quality and improve the preventive and curative practices at the primary care level in Hungary. A total of 50 general practitionaires were selected on a voluntary basis in Budapest, Hungary, and from them, 30 were randomized to the intervention (I) group and 20 to the reference (R) group. The members in the I group have been trained for the official hypertension guideline and their everyday work is monitored. Those in the R group have only been monitored to measure the efficacy of the training. In all, 10% from the known hypertensive persons (N=10,799) and 5% of the remaining (nonhypertensive) patients (N=60,341) were selected randomly from the GP's computer files and invited for screening investigation performed by trained medical students. They measured the blood pressure of patients, assessed the cardiovascular risk status and the quality of education of patients by standardized questionnaires. In total, 4083 patients were invited, but only 39.2% attended the screening visit. The prevalence of undetected hypertension was 34.6%. This prevalence was significantly higher in the older (>60 years: 46.8%) than in the younger (<50 years: 20.8%, P<0.0001) age group and it was higher in men (41.5%) than in women (30.1%, P<0.001). The proportion of H patients on drug treatment was 85.3% and the frequency of patients under effective blood pressure control (eg<140/90 mmHg) was 27.8%. Counselling to patients for a healthier lifestyle (exercise, smoking, alcohol consumption, diet) was very rare. In conclusion, our data represent the primary care of Budapest and may not be relevant to the whole country. As a consequence of this study, education of primary care physicians and patients is a must for further improvement of hypertension care.

Antiarrhythmic therapy on prevention of postoperative atrial fibrillation in patients after heart surgery.

The incidence of supraventricular arrhythmias is high following open-heart surgery, occurring in 25% to about 50% of patients. The most common of these arrhythmias is atrial fibrillation (AF). Postoperative AF has been associated with increased incidence of other complications and increased hospital length of stay. Atrial arrhythmias are most frequent in the first two to three days after cardiothoracic surgery, but they can occur at any point in the recovery period. Age and concomitant valular heart disease are consistently the independent factors most strongly associated with postoperative atrial fibrillation. Prevention of AF seems to be a reasonable clinical goal, and, consequently, many randomized trials have evaluated the effectiveness of pharmacological and nonpharmacological interventions for prevention of AF. The main indication for AF prophylaxis remains the shorteningof length of hospital stay and possibly reduction in stroke. The optimal treatment strategies for reducing postoperative AF are not well established. Commonly used therapeutic approaches include the use of rate-controlling drugs such as beta-blockers, calcium antagonists, and digoxin. Some pharmacological strategies including beta-blockers, sotalol, and amiodarone have shown to reduce risk of postoperative AF and may reduce length of hospital stay. There is no convincing evidence that reducing postoperative AF reduces stroke. This review summarizes current evidence from randomized controlled trials to estimate the effect of pharmacological and non pharmacologic interventions on the occurrence of AF after open-heart surgery and its effects on postoperative outcome.

Differentiated nursing practice: assessing the state-of-the-science.

The authors present their findings following an exhaustive literature review of research on differentiated nursing practice (DNP) that used a number of tools to measure various aspects of DNP that are applicable across the health care delivery continuum. Issues related to DNP include: optimal nursing care, matching patient needs with nurse competencies, effective use of nursing resources, equitable compensation, career satisfaction, loyalty to employers, and enhanced prestige of the nursing profession. One 1992 Massachusetts study of a three-role oncology unit project (including patient care manager, clinical nurse, and patient care technician), showed positive change in five criteria including: standards of nursing care, actual care hours, average labor costs, job satisfaction and patient satisfaction. A 1990 Arizona study that included unit assistants concluded that DNP supported a decline in the use of supplemental staff and staff overtime which led to cost savings, and increases in the actual hours of care and nurse satisfaction.