Abdominal adiposity assessed using CT angiography associates with acute kidney injury after trans-catheter aortic valve replacement.

AIM: To determine if there is an association between area-based visceral abdominal adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAT), and abdominal circumference measured on computed tomography (CT) angiography before trans-catheter aortic valve replacement (TAVR) and post-TAVR acute kidney injury (AKI). MATERIALS AND METHODS: In this retrospective cohort study of 106 TAVR patients, SAT and VAT areas and abdominal circumference was measured on a single CT section at L4 vertebral level. Univariate comparisons between patients who did and did not develop AKI were undertaken for radiological measurements. Multivariable logistic regression was used to assess association between CT measurements and the development of post-TAVR AKI. RESULTS: Post-TAVR AKI occurred in 20 of 106 patients (19%). In univariate comparisons, body mass index (BMI) did not differ significantly between patients who did and did not develop AKI (p=0.14); however, VAT+SAT (443.2±163.7 versus 351±168.7 cm2; p=0.03), VAT (213.9±110.6 versus 153.9±96.1 cm2; p=0.03), and outer abdominal circumference (100.2±14.4 cm versus 91.8±13.3 cm; p=0.02) were significantly higher in the patients who did not develop post-TAVR AKI. These three measures on pre-TAVR CT angiogram remained significantly associated with reduced post-TAVR AKI with a lower incidence of post-TAVR AKI after multivariable adjustment for pre-TAVR estimated glomerular filtration rate and patient height (p<0.05). CONCLUSION: This study found that increased abdominal obesity as assessed by measures on pre-TAVR CT angiogram is associated with a significantly lower incidence of AKI.

Restoration of the coagulation cascade on CPB: a case report.

Coagulopathy can sometimes be observed when CPB times are prolonged. Correction of coagulopathy post CPB can present the surgical team with a number of challenges, including right ventricular volume overload, hemodilution, anemia and excessive cell salvage with further loss of coagulation factors. Restoration of the coagulation cascade on CPB may help to avoid these issues. This case report is of a 64-year-old male with a delayed diagnosis of aortic dissection. The patient presented to the cardiac surgery operating room with hepatic and renal shock/failure, with the resulting coagulopathy. The described technique is representative of a technique that we sometimes employ to restore the clotting mechanism before separating from bypass.

Effects of diet and exercise on common cardiovascular disease risk factors in moderately obese older women.

Diet and exercise studies of premenopausal women have shown reductions in obesity and other cardiovascular disease (CVD) risk factors. Forty-one healthy, moderately obese (120-140% of ideal body weight, LBW), postmenopausal women (65.6 +/- 3.3 y) participating in 24-wk diet or diet + exercise programs were studied to determine whether similar CVD risk reduction would occur. Daily energy need (DEN) was estimated from basal energy expenditure and self-reported activity. The diet + exercise group (n = 16) reduced their daily energy intake (DEI) by 2092 kJ from their DEN and expended 837 kJ/d in walking and resistance exercise. The two diet-only groups (n = 13 and n = 12) reduced their DEI by 2092 and 2929 kJ from their DEN, respectively. Body weight, waist-to-hip and subscapula-to-triceps ratios, blood lipids (total, low-density-lipoprotein, and high-density-lipoprotein cholesterol, and triacylglycerols), glucose, and insulin concentrations were measured at baseline and after 12 and 24 wk of diet and diet + exercise. Data were analyzed by using analysis of variance with repeated measures (P < or = 0.05) and Tukey's post hoc test. Loss of body weight was significant for all groups between baseline and 12 and 24 wk (baseline: 79.3 +/- 7.6 kg; 12 wk; 75.1 +/- 7.7 kg; 24 wk; 72.8 +/- 8.0 kg) but did not differ among groups. No significant time or treatment effects were observed between baseline and 24 wk for changes in mean blood lipid, glucose, and fasting insulin concentrations or measures of body fat distribution. Although 24 wk of diet or diet+exercise significantly reduced body weight in this group, this loss in body weight was not accompanied by a reduction of other commonly accepted CVD risks.

Moexipril in the treatment of mild to moderate essential hypertension: comparison with sustained-release verapamil.

To compare and contrast the antihypertensive efficacy of an angiotensin-converting enzyme (ACE) inhibitor to a calcium antagonist, 88 and 90 patients with essential hypertension were randomly assigned to receive moexipril and verapamil, respectively. At the end of the first 6 weeks of active therapy, sitting diastolic blood pressure decreased by 11 mmHg in patients receiving moexipril and by 9 mmHg in patients receiving verapamil. The 24-week treatment period was completed by 72 patients who received moexipril and 71 patients who received verapamil. Mean decreases in sitting diastolic blood pressure of 10 mmHg and 11 mmHg were observed in the respective intent-to-treat moexipril and verapamil groups. At doses of 7.5 mg and 15 mg once daily, moexipril had an antihypertensive effect comparable to that of sustained-release verapamil at doses of 180 mg and 240 mg once daily.

Comparison of moexipril, a new ACE inhibitor, to verapamil-SR as add-on therapy to low dose hydrochlorothiazide in hypertensive patients.

The antihypertensive effects of moexipril, a new angiotensin converting enzyme inhibitor, and verapamil-SR as add-on therapy to hydrochlorothiazide (HCTZ) were investigated in patients with moderate to severe (stages II and III) essential hypertension. Of 147 patients treated for 4 weeks with 25 mg/day HCTZ, 108 whose sitting diastolic blood pressure (SDBP) was 100 to 114 mm Hg inclusive were randomized to 7.5 mg/day moexipril (56 patients) and 180 mg/day verapamil-SR (52 patients) in addition to 25 mg/day HCTZ. If after 4 weeks of treatment the SDBP was > or = 90 mm Hg, the dose of moexipril was increased to 15 mg/day and that of verapamil-SR increased to 240 mg/day; the patients were followed for an additional 8 weeks. Blood chemistries, plasma renin activity, and plasma aldosterone were done during the study. Both moexipril and verapamil-SR were safe and well tolerated and decreased the sitting and standing blood pressure similarly (P < .001). This study demonstrated that the addition of moexipril and verapamil-SR to low dose HCTZ is effective for the treatment of moderate to severe hypertension.

Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring.

To assess the efficacy and time-dependent effects of once-daily moexipril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-blind, placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure (BP) recordings. Patients were included in the trial based on a minimum of 40% of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase; and the primary endpoint was change in 24-hour ambulatory diastolic BP. Patients were randomized to receive placebo, 7.5 mg of moexipril, or 15 mg of moexipril once daily. Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy. After the 7.5-mg dose, there were no significant changes in the acute or prolonged clinic BPs compared with placebo. Compared with adjusted mean changes for placebo, the 15-mg moexipril dose lowered clinic systolic BP, but not diastolic BP. In contrast, acute (1 day) reductions in 24-hour diastolic BPs were -2/-3 mm Hg, -6/-4 mm Hg, and -14/-9 mm Hg on placebo, 7.5 mg of moexipril, and 15 mg of moexipril, respectively (P < .01 for the 15-mg dose). Similarly, after long-term dosing for 8 weeks, reductions in 24-hour diastolic BPs were 1/-2 mm Hg, -6/-4 mm Hg, and -12/-9 mm Hg for the respective treatment groups (P < .01 for the 15-mg dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term efficacy and safety of moexipril in the treatment of hypertension.

The purpose of this study was to assess the long-term efficacy and safety of moexipril, a new angiotensin-converting enzyme inhibitor, alone or in combination with hydrochlorothiazide in patients with hypertension. The patient population consisted of 281 hypertensive men and women, 30-84 years old, with seated diastolic BP between 95 and 114 mmHg. The study was a two year multicenter (22 centers), open-label protocol of moexipril monotherapy or combination therapy (with hydrochlorothiazide). Blood pressure, pulse rate, weight, adverse side-effects and laboratory studies were assessed following moexipril dosing at 7.5, 15 or 30 mg once daily or 15-30 mg daily in combination with 12.5 mg hydrochlorothiazide if the DBP was > or = 90 mmHg. The primary measure of efficacy was change from baseline in seated DBP. Secondary outcome measures included changes in seated SBP, heart rate, laboratory parameters and subjective complaints. Following one year of therapy in 183 patients, the BP fell 13/14 mmHg among patients receiving moexipril monotherapy and 18/15 mmHg those receiving combined therapy compared with baseline (P < 0.001 for both). After two years of treatment, reductions were similar in 161 patients. Forty-four (16%) patients were prematurely withdrawn from the study because of inadequate therapeutic response and 34 (12%) secondary to adverse experiences. There were no changes in pulse rate or postural BP reductions. Four adverse side-effects occurred at a frequency exceeding 2% that were possibly or probably attributable to moexipril: fatigue (3%), headache (2%), dizziness (3%) and increased cough (5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal drug exposure and its possible implications for learning in the preschool and school-age population.

For the past 5 years there has been an exponential increase in the use of cocaine, phenylcyclidine hydrochloride (PCP), and other central nervous system (CNS) active drugs. A significant amount of this accelerated usage is in sexually active females, resulting in some urban hospitals reporting positive drug screens in over 16% of the infants born on their busy obstetrical service. There is a growing body of data showing that fetal exposure to cocaine, phenylcyclidine hydrochloride (PCP), and other CNS-active drugs results in infants and children with abnormal brain wave patterns, short-term neurologic signs, depression of interactive behavior, and poor organizational responses to environmental stimuli. Whether such neurologic findings will translate into a significant number of children with learning and behavioral problems needs to be the focus of long-term longitudinal studies of children with fetal drug exposure to cocaine, PCP, and other CNS-active drugs.

Comparative studies of some semisynthetic K-strophanthins with natural cardiac glycosides.

In this study the pharmacological effects of seven semisynthetic cardenolides have been investigated and compared with those of 11 natural cardiac glycosides. These compounds are of different potency on electrically driven isolated guinea-pig atria. Their concentration response curves showed different slopes, which could be an indication of varying therapeutic range. The pharmacodynamics of these compounds on isolated guinea-pig atria are in good correlation with the data obtained from binding studies on guinea-pig ventricular homogenate as well as that obtained from comparative experiments on Na+,K+-ATPase activity inhibition.

Speech and language disorders in children.

Speech and language development is a sensitive and important diagnostic tool for the family physician. Speech defects and delayed speech and language development can be the presenting evidence for neurologic abnormalities, cognitive difficulties and abnormal hearing. They can also be signs of emotional, social, family and behavioral problems. Finally, they can signify the need for evaluation of abnormalities of tracheal and laryngeal function and oral-motor development.

Cardiac glycosides and sodium/potassium-ATPase.

The sodium/potassium-ATPase complex is, according to modern research, the binding site for cardiac glycosides on the outer surface of the cell membrane and their receptor. Inhibition of this enzyme by cardiac glycosides leads for instance in the heart to a decrease or a delay in membrane sodium/potassium-ion transport, and indirectly to an increase in the intracellular ionized calcium-concentration and an increase in cardiac contractile force. According to recent observations the activity of the sodium/potassium-ATPase or its concentration, and therefore the concentration of binding sites can increase in some tissues after long term treatment with cardiac glycosides. This might explain the occasionally observed tolerance to digitalis glycosides.

Effects of vanadate on isolated vascular tissue: biochemical and functional investigations.

Vanadate is a potent inhibitor of Na+,K+-ATPase derived from bovine aorta. The Ca2+, Mg2+-ATPase of the same preparation was inhibited at 10 times higher concentrations. Compared with [3H]ouabain, 48V bound quickly to bovine aortic microsomes. Equilibrium binding experiments revealed one high-affinity, low-capacity and one low-affinity binding site for 48V, whereas [3H]ouabain possessed only one binding site of high affinity. A high NADH-vanadate reductase activity was measured in the same preparation, suggesting that, in this tissue, vanadate may be converted to vanadyl, a form to which the Na+,K+-ATPase is relatively insensitive. An increase in the contractile force of isolated rabbit aorta was measured with the following potency: phenylephrine greater than ouabain greater than vanadate. The order in intrinsic activity was as follows: phenylephrine congruent to ouabain greater than vanadate. The action of vanadate was rapid in onset and stable over several hours, while that of ouabain was slow and transitory. Vanadate increased tension in isolated rabbit veins to an extent similar to phenylephrine, but at concentrations two orders of magnitude higher. Vanadate action decreased with decreasing (Ca2+)0, but remained constant at a constant ratio of (Ca2+)0/(Na+)2(0). Vanadate-induced increases in tension were decreased by verapamil by about 43% and persisted in a solution in which Na+ was replaced by Li+. Vanadate increased electrically stimulated contractions. It is concluded that most of the effect of vanadate is due to an increase in calcium influx into the smooth muscle cell and that the effect of vanadate on Na+,Ca2+ exchange is of minor importance.

Inotropic effects and Na+,K+-ATPase inhibition of ouabain in isolated guinea-pig atria and diaphragm.

Effects of ouabain on force of contraction were compared in electrically driven isolated tissue preparations of guinea-pig left atria and diaphragm. A distinct and steady positive inotropic effect of ouabain was observed in atrial preparations, whereas in diaphragm preparations, ouabain produced only a slight and transient positive inotropic effect, followed by the negative inotropic phase. The transient positive inotropic effect of ouabain was observed even in the absence of extracellular calcium, but was markedly dependent on the extracellular sodium concentration. In vitro [3H]ouabain binding studies revealed that the affinity of Na+,K+-ATPase for ouabain was about eight times higher and tissue concentration of the enzyme was significantly lower in diaphragm than in cardiac tissue. The Ki value for ouabain inhibition of the cardiac Na+,K+-ATPase was also approximately ten times higher than for the diaphragm enzyme. Ouabain-sensitive 86Rb uptake, an estimate of sodium pump activity, was inhibited by ouabain at a time when it produced its transient positive inotropic effect in diaphragm preparations. These results indicate that the lack of a distinct and steady positive inotropic effect of ouabain in diaphragm was due neither to the difference in the ouabain-Na+,K+-ATPase interaction between diaphragm and cardiac tissues nor the failure of sodium pump inhibition by ouabain in diaphragm.

Influence of vanadate on electrophysiological and contractile parameters of atrial myocardium.

Whereas vanadate increases isometric force of contraction in stimulated rat left atria (EC50: 36.6 mumol/1), it decreases force of contraction in guinea-pigs (EC50: 4.7 mumol/1). Action potential duration at 90 and 30% repolarisation is decreased in guinea-pig atria by 70 and 60%, but in rat atria by only 40 and 7% respectively. Whereas the time course of the negative inotropic action is rapid and correlates with that of the shortening of the action potential, there is no relationship between action potential changes and the slowly developing positive intropic effect. Negative and positive inotropic actions seem to be the result of two superimposed processes, whose kinetics suggest an extra- and intracellular site of action. Na+, K+-ATPase prepared from rat and guinea-pig atria and ventricle is inhibited by vanadate to a similar extent: IC50 (mumol/1) rat: atria 1.05, ventricle 0.49; guinea-pig: atria 0.75, ventricle 0.62. This indicates that the discrepancy in inotropy cannot be explained by the different sensitivity of the Na+, K+-ATPase to vanadate.