The effects of biphasic waveform design on post-resuscitation myocardial function

OBJECTIVES: This study examined the effects of biphasic truncated exponential waveform design on survival and post-resuscitation myocardial function after prolonged ventricular fibrillation (VF). BACKGROUND: Biphasic waveforms are more effective than monophasic waveforms for successful defibrillation, but optimization of energy and current levels to minimize post-resuscitation myocardial dysfunction has been largely unexplored. We examined a low-capacitance waveform typical of low-energy application (low-energy biphasic truncated exponential [BTEL]; 100 microF, < or =200 J) and a high-capacitance waveform typical of high-energy application (high-energy biphasic truncated exponential [BTEH]; 200 microF, > or =200 J). METHODS: Four groups of anesthetized 40- to 45-kg pigs were investigated. After 7 min of electrically induced VF, a 15-min resuscitation attempt was made using sequences of up to three defibrillation shocks followed by 1 min of cardiopulmonary resuscitation. Animals were randomized to BTEL at 150 J or 200 J or to BTEH at 200 J or 360 J. RESULTS: Resuscitation was unsuccessful in three of the five animals treated with BTEH at 200 J. All other attempts were successful. Significant therapy effects were observed for survival (p = 0.035), left ventricular ejection fraction (p < 0.001), stroke volume (p < 0.001), fractional area change (p < 0.001), cardiac output (p = 0.044), and mean aortic pressure (p < 0.001). Hemodynamic outcomes were negatively associated with energy and average current but positively associated with peak current. Peak current was the only significant predictor of survival (p < 0.001). CONCLUSIONS: Maximum survival and minimum myocardial dysfunction were observed with the low-capacitance 150-J waveform, which delivered higher peak current while minimizing energy and average current.     

Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance

OBJECTIVE: Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity. METHODS: Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Student's t-test, P < 0.05). RESULTS: Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002). CONCLUSIONS: Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI.     

Staff attitudes towards institutionalised dementia residents

Aim. To explore the attitudes of staff caring for institutionalised dementia residents and the variables associated with these attitudes. Methods. Fourteen nursing homes and one hospital‐based geriatric ward in Bergen, Norway were surveyed, using the translation of an Approach to Dementia Questionnaire. The study population (n = 291) was a mixture of registered nurses, auxiliary nurses, nursing assistants and non‐trained aides. Design. Survey. Results. Significant differences in hope and person‐centred attitudes were identified in this study. Nursing assistants, compared with registered nurses (p = 0·02), had significantly lower hope attitudes· Staff over 50 years of age reported significantly lower hope attitudes (p = 0·01) than those under 40 years of age. Staff with 10 and fewer years of work experience reported significantly lower hope attitudes (p = 0·02) than those with more than 10 years of experience. Nurses with specialised training in geriatrics, psychiatry or dementia care had significantly higher hope attitudes, compared with nurses without any special training (p = 0·04). The person‐centred attitude was lower among participants who were over 50 years old, compared with their counterparts under the age of 40 (p ≤ 0·01). Discussion. Education, age, work experience, care unit size and specialised training are associated with differences in attitudes. We recommend that employers be proactive in encouraging and facilitating staff development by offering further training that aims to impart more positive attitudes. Relevance to clinical practice. Improvements in staff competency levels will be more important in the future, as a result of the forecasted increase in the percentage of the population who will suffer from dementia and reside in nursing homes.     

Absolute stereochemistry of gastric antisecretory compound P371A1 and its congener P371A2 from streptomyces species P371

Absolute configurations of the gastric antisecretory compound P371A1 (1) and its congener P371A2 (2) from Streptomyces sp. P371 were determined on the basis of identification of the methyl glycosides 9, 10, and 11 obtained by the acid degradation of 1 and 2, as well as application of the modified Mosher method to the P371A2 C-glycoside MTPA esters 7 and 8 and observation of the excitation chiralities in the P371A2 C-glycoside benzoate derivatives 5 and 6.     

Vascular access for dialysis in the intensive care unit

Management of the vascular access (VA) for renal replacement therapy (RRT) in acute renal failure (ARF) patients is faced with a twofold problem: first, the creation of an angio-access that is adequate for RRT in the acute setting; second, the preservation of the patient's vascular network in order not to preclude further use of the vessel in the event of evolution to chronic renal failure. Central venous catheters are the preferred VA for RRT in the intensive care setting. Semi-rigid double-lumen polyurethane catheters may be considered for short-time use (up to 2-3 weeks). Soft silicone double-lumen or twin-catheters, preferably with subcutaneous tunnelling, are highly desirable for prolonged RRT (over 3 weeks). The femoral route is the first option in the presence of associated risk factors (respiratory failure, pulmonary oedema, bleeding...). The internal jugular route should be considered for mid-term use in order to facilitate the patient's mobilization and to reduce the risk of infection. The subclavian route should be avoided because of the risk of stenosis and/or thrombosis of the outflow vein. Catheter insertion must be performed by a trained physician with ultrasound guidance using either skin mapping or continuous vein guidance. Catheter handling and care should comply with best practice guidelines and should be part of a continuous quality improvement programme in order to reduce catheter-related morbidity. Preservation of the upper limb vascular network of the patient consists of sparing the native vessels (artery and vein) of the patient and preserving the functionality of the permanent VA in chronic renal failure patient. This 'lifeline' of chronic renal failure patients may be maintained by preventing inflammation, infection and thrombosis of the superficial vessels of the arm and forearm of patient.     

Akt: a potential target for thyroid cancer therapy

Thyroid cancer is a heterogeneous disorder characterized by gene mutations that activate signaling pathways, and also by abnormalities in tumor suppressor genes and cell cycle proteins. Activation of the Akt/PKB signaling pathway appears to be an important event in thyroid tumorigenesis and, perhaps, in tumor progression too. Akt is activated in Cowden's syndrome through inactivation of PTEN, a negative regulator of Akt. Cowden's syndrome is an autosomal dominant multiorgan hamartoma syndrome characterized by benign and malignant thyroid tumors, breast cancers, and colon cancers. In addition, the Akt pathway appears to be activated in a significant proportion of sporadic thyroid cancers through activation of growth factor pathways by thyroid oncogenes and/or receptor overexpression. Disruption of PI3-kinase activity pharmacologically or disruption of Akt signaling using dominant negative cDNA expression have demonstrated salutary effects on several cancer models in vitro. Therefore, Akt represents an attractive target for pharmaceutical development for a variety of malignancies, including thyroid cancer.     

Stroke volumes generated by precordial compression during cardiac resuscitation

OBJECTIVES: To quantitate stroke volumes generated by precordial compression during cardiopulmonary resuscitation and to determine their relationship to coronary perfusion pressure and the success of resuscitation. DESIGN: Prospective, observational animal study. SETTING: Medical research laboratory in a university-affiliated research and educational foundation. SUBJECTS: Domestic pigs. INTERVENTIONS: Ventricular fibrillation was electrically induced in 25 anesthetized male domestic pigs. After an interval of 7 mins, electrical defibrillation was attempted. Failing to reverse ventricular fibrillation in each instance, precordial compression was begun coincident with mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Stroke volumes were computed from differences between diastolic and systolic areas of the left ventricle by utilizing transesophageal echocardiography. Both stroke volumes and coronary perfusion pressure were consistently greater in successfully resuscitated animals. Progressive decreases in stroke volumes during precordial compression were predictive of unsuccessful resuscitation. A linear correlation between stroke volume and coronary perfusion pressure (r =.70) was documented. CONCLUSION: These observations support the concept that stroke volumes generated by precordial compression are quantitatively related to the coronary perfusion pressure and to the success of cardiopulmonary resuscitation.