Urgent reoperative transapical valve-in-valve shortly after a transapical aortic valve implantation.

Urgent reoperative transapical aortic valve-in-valve has never been proposed as a treatment option in case of a failed transcatheter aortic valve implantation (TAVI) or in case of worsening of an existing paravalvular leak, if this complication occurs right after, or a few days after, the primary transapical aortic valve implantation. Experienced surgeons should argue that after a transapical TAVI, the apex is damaged and fragile, with a high risk of irreparable ventricular tears and life-threatening bleeding if a second transapical procedure is scheduled during the acute phase. Nevertheless, if the patient is inoperable and the vascular status, including the ascending aorta, limits alternative accesses, the urgent reoperative transapical valve-in-valve becomes an alternative. We illustrate, for the first time ever, our experience with an 81-year old female patient who underwent a transapical (TA) TAVI with a Sapien? XT 23 mm. The day after the procedure, the patient haemodynamically worsened in combination with a worsening of a known (grade 1-2) paravalvular leak. Thus, on postoperative day two, an urgent transapical valve-in-valve was performed, and a second Sapien? XT 23 mm was placed, with an excellent haemodynamic result and absence of leak. The redo apical access did not appear very complicated and the postoperative recovery was uneventful

Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion

Aims/hypothesis: The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect. Methods: Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-d-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects. Results: Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulin-stimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content. Conclusions/interpretation: Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administratio

Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats.

OBJECTIVE Blockade of the CB1 receptor is one of the promising strategies for the treatment of obesity. Although antagonists suppress food intake and reduce body weight, the role of central versus peripheral CB1 activation on weight loss and related metabolic parameters remains to be elucidated. We therefore specifically assessed and compared the respective potential relevance of central nervous system (CNS) versus peripheral CB1 receptors in the regulation of energy homeostasis and lipid and glucose metabolism in diet-induced obese (DIO) rats. RESEARCH DESIGN AND METHODS Both lean and DIO rats were used for our experiments. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR, and euglycemic-hyperinsulinemic clamps were used for insulin sensitivity and glucose metabolism studies. RESULTS Specific CNS-CB1 blockade decreased body weight and food intake but, independent of those effects, had no beneficial influence on peripheral lipid and glucose metabolism. Peripheral treatment with CB1 antagonist (Rimonabant) also reduced food intake and body weight but, in addition, independently triggered lipid mobilization pathways in white adipose tissue and cellular glucose uptake. Insulin sensitivity and skeletal muscle glucose uptake were enhanced, while hepatic glucose production was decreased during peripheral infusion of the CB1 antagonist. However, these effects depended on the antagonist-elicited reduction of food intake. CONCLUSIONS Several relevant metabolic processes appear to independently benefit from peripheral blockade of CB1, while CNS-CB1 blockade alone predominantly affects food intake and body weight

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

Pacing in hypertrophic obstructive cardiomyopathy: A randomized crossover study

Background Uncontrolled studies have shown that short atrioventricular delay dual chamber pacing reduces outflow tract obstruction in hypertrophic obstructive cardiomyopathy. Although the exact mechanism of this beneficial effect is unclear, this seems a promising potential new treatment for hypertrophic obstructive cardiomyopathy. Method In order to evaluate the impact of pacing therapy, we performed a randomized multicentre double-blind crossover (pacemaker activated vs non activated) study to investigate modification of echocardiography, exercise tolerance, angina, dyspnoea and quality of life in 83 patients with a mean age of 53 (range 22-87) years with symptoms refractory or intolerant to classical drug treatment. Results After 12 weeks of activated or inactivated pacing, independent of which phase was first, the pressure gradient fell from 59±36 mmHg to 30±25 mmHg (P<0·001) with active pacing. Exercise tolerance improved by 21% in those patients who at baseline tolerated less than 10 min of Bruce protocol; symptoms of dyspnoea and angina also improved significantly from NYHA class 2·4 to 1·4 and 1·0 to 0·4, respectively (P<0·007). Quality of life assessment with a validated questionnaire objectivated the subjective improvement. Conclusion Pacemaker therapy is of clinical and haemodynamic benefit for patients with hypertrophic obstructive cardiomyopathy, left ventricular outflow gradient at rest over 30 mmHg who are symptomatic despite drug treatmen

Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents

Aims/hypothesis: The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. Methods: We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. Results: We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn −/− animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn −/− animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. Conclusions/interpretation: The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistanc

Valuing families' preferences for drug treatment: a discrete choice experiment

The burden on family members of those who are dependent on illicit drugs is largely unidentified despite the presence of significant negative financial, health and social impacts. This makes it difficult to provide appropriate services and support. This study aimed to assess the preferences for treatment attributes for heroin dependence among family members affected by the drug use of a relative and to obtain a measure of the intangible economic benefit. Discrete choice experiment. Data were analysed using mixed logit which accounted for repeated responses. Australia PARTICIPANTS: Eligible participants were Australian residents of 18+ years of age with a relative with problematic drug use. Complete data on 237 respondents were analysed; 21 invalid responses were deleted. Participant preference for likelihood of staying in treatment, family conflict, own health status, contact with police and monetary contribution to a charitable organisation providing treatment. All attributes were significant, and the results suggest there was a preference for longer time in treatment, less family discord, better own health status, less likelihood of their relative encountering police, and while they were willing to contribute to a charity for treatment to be available, they prefer to pay less not more. In order of relative importance, participants were willing to pay an additional $4.46 (95$42.00 (95% CI 28.30-55.69) to avoid 5 days per week of family discord, $87.94 (95$129.66 (95% CI 53.50-205.87) for each 1% decline in the chance of police contact. Drug treatment in Australia appears to have intangible benefits for affected family members. Families are willing to pay for treatment which reduces family discord, improves their own health, increases time in treatment and reduces contact with police. BACKGROUND AND AIMS DESIGN SETTING MEASUREMENTS FINDINGS CONCLUSION

Pacing in hypertrophic obstructive cardiomyopathy. A randomized crossover study. PIC Study Group

BACKGROUND: Uncontrolled studies have shown that short atrioventricular delay dual chamber pacing reduces outflow tract obstruction in hypertrophic obstructive cardiomyopathy. Although the exact mechanism of this beneficial effect is unclear, this seems a promising potential new treatment for hypertrophic obstructive cardiomyopathy. METHOD: In order to evaluate the impact of pacing therapy, were performed a randomized multicentre double-blind cross-over (pacemaker activated vs non activated) study to investigate modification of echocardiography, exercise tolerance, angina, dyspnoea and quality of life in 83 patients with a mean age of 53 (range 22-87) years with symptoms refractory or intolerant to classical drug treatment. RESULTS: After 12 weeks of activated or inactivated pacing, independent of which phase was first, the pressure gradient fell from 59 +/- 36 mmHg to 30 +/- 25 mmHg (P &lt; 0.001) with active pacing. Exercise tolerance improved by 21% in those patients who at baseline tolerated less than 10 min of Bruce protocol; symptoms of dyspnoea and angina also improved significantly from NYHA class 2.4 to 1.4 and 1.0 to 0.4, respectively (P &lt; 0.007). Quality of life assessment with a validated questionnaire objectivated the subjective improvement. CONCLUSION: Pacemaker therapy is of clinical and haemodynamic benefit for patients with hypertrophic obstructive cardiomyopathy, left ventricular outflow gradient at rest over 30 mmHg who are symptomatic despite drug treatment