Acarbose has become an important adjuvant therapy for diabetic patients. Many of these patients are also treated with digoxin for congestive heart failure or chronic atrial fibrillation.To evaluate a possible drug interaction between acarbose and digoxin.An open-label, analyst-blind, randomized, crossover, two-period study was conducted in 11 healthy subjects. In period I, each subject received one single oral dose of 0.75 mg digoxin. In period II, they were given acarbose tablets, 50 mg 3 times a day for 12 days. On day 8, one hour after acarbose administration, a single oral dose of 0.75 mg digoxin was administered. The study periods were separated by a 3 week washout interval. Serum digoxin levels, over time, in the two periods were compared by standard techniques.There were no differences in the pharmacokinetic parameters of digoxin in the two periods, apart from a significant increase in the mean maximum serum concentration (Cmax) when digoxin was given with acarbose (5.97 compared to 4.67 g/L, P = 0.02). Simulated steady-state peak levels of digoxin (Cmax,ss) achieved with a daily dose of 0.25 mg digoxin, in the presence and absence of acarbose, were 2.89 and 2.40 g/L respectively (P = 0.05). Simulated steady-state trough (Cmin,ss) and average (Cave,ss) concentrations were similar and within the therapeutic window.There was no significant pharmacokinetic interaction between digoxin and acarbose at current therapeutic doses in the healthy volunteers. This interaction should be further studied with higher doses of acarbose and at steady-state conditions.
Na+,K+-ATPase (porcine alpha1/His10*beta1 or human alpha1/porcine His10*beta1) has been expressed in Pichia pastoris and purified by Co2+-chelate affinity resin chromatography, yielding about 80% pure, functional, and stable protein in a single step. The protein was eluted in nonionic detergents together with a phosphatidylserine. Size exclusion chromatography showed that the protein eluted in n-dodecyl beta-d-maltoside is an alpha1/beta1 protomer, whereas that in octaethylene glycol dodecyl monoether contains a mixture of alpha1/beta1 protomer and higher order oligomers. The Na+,K+-ATPase activity (8-16 (mumol/min)/mg of protein) is similar in both detergents. Thus, the minimal functional unit is the alpha1/beta1 protomer, and activity is unaffected by the presence of oligomeric forms. Screening of phospholipids for stabilization of the Na+,K+-ATPase activity shows that (a) acid phospholipids are required and phosphatidylserine is somewhat better than phosphatidylinositol and (b) optimal stabilization is achieved with asymmetric phosphatidylserines having saturated (18:0 >or= 16:0) and unsaturated (18:1 > 18:2) side chains at sn-1 an sn-2 positions, respectively. In the presence of phosphatidylserine, cholesterol stabilizes the protein at 37 degrees C, but not at 0 degrees C. Cholesterol also increases the "apparent affinity" of the phosphatidylserine and stabilizes optimally in the presence of phosphatidylserines with a saturated fatty acyl chain at the sn-1 position. Ergosterol is a poor stabilizer. We propose that phosphatidylserine and cholesterol interact specifically with each other near the alpha1/beta1 subunit interface, thus stabilizing the protein. These interactions do not seem to affect Na+,K+-ATPase activity.
Abstract The potent immunosuppressive drugs used by transplant recipients place them at risk of infections. Data on infective endocarditis ( IE ) in the setting of renal transplantation ( RT ) are sparse. We describe a 36‐year‐old woman referred to a tertiary medical center for evaluation of elevated creatinine levels 1 month after a second RT . Work‐up revealed the presence of all four of Duke's criteria: fever, persistent bacteremia, new‐onset tricuspid regurgitation, and masses suspected to be vegetation attached to the tricuspid annulus. Symptoms resolved with antibiotic treatment and fluids. Fluorodeoxyglucose‐positron emission tomography/computed tomography ( FDG ‐ PET / CT ) revealed hypermetabolic absorption in the femoral vascular graft that had been used for hemodialysis prior to transplantation. The graft was removed by open surgery, and the patient was discharged home in good condition with continued antibiotic treatment. Review of the literature yielded 73 previously reported cases of IE in renal transplant recipients. Several differences were noted from IE in the general population: lower male predominance, younger age (<60 years), absence in most cases of a preexisting structural cardiac anomaly, and more variable causative pathogens. Our case also highlights the importance of FDG ‐ PET / CT for detecting the source of IE and alerts clinicians to the sometimes unexpected course of the disease in renal transplant recipients.
In the emergency department the physician is often confronted with the decision of where to hospitalize a patient presenting with chest pain and a possible acute myocardial infarction--in the cardiac care unit or in the internal medicine ward.To characterize the clinical factors involved in the triage disposition of patients hospitalized with AMI in Israel to either CCUs or IMWs and to determine to what extent the perceived probability of ischemia influenced the disposition decision.During a 2 month nationwide prospective survey in the 26 CCUs and 82 of the 94 IMWs in Israel, we reviewed the charts of 1,648 patients with a discharge diagnosis of AMI. The probability of ischemia at admission was determined retrospectively by the Acute Coronary Ischemia Time-Insensitive Predictive Instrument. Co-morbidity was coded using the Index of Coexistent Diseases.The ACI-TIPI score for patients admitted to CCUs or to IMWs was 76.2% and 57.7% respectively (P < 0.001). Multivariate analysis showed that young patients with a high probability of ischemia and low co-morbidity or functional impairment were more likely to be hospitalized in CCUs than in IMWs.In Israel, the factors that strongly influence the initial triage disposition of AMI patients to CCUs or IMWs are age, perceived probability of ischemia, status of co-morbid conditions and functional impairment.
Current guidelines regarding the use of intravenous morphine (IM) in the management of patients with acute decompensated heart failure (ADHF) are discordant; whereas the American guidelines reserve IM for terminal patients, the European guidelines recommend its use in the early stage of treatment. Our aim was to determine the impact of IM on outcomes of ADHF patients.Stepwise logistic regression and propensity score analysis of ADHF patients with and without use of IM was performed in a national heart failure survey.Of the 4102 enrolled patients, we identified 2336 ADHF patients, of whom 218 (9.3%) received IM. IM patients were more likely to have acute coronary syndromes, acute rather than exacerbation of chronic heart failure, and diabetes mellitus and dyslipidemia. They had higher heart rate, were less likely to receive diuretics and more likely to receive aspirin and statins. Unadjusted in-hospital mortality rates were 11.5% versus 5.0% for patients who did or did not receive IM, and the adjusted odds ratio (OR) for in-hospital death was: 2.0 (1.1 – 3.5, P = 0.02). Using propensity analysis, we identified 218 matched pairs of patients who did or did not receive IM. In multivariable analysis accounting for the propensity score (c-statistic 0.82), IM was not associated with increased in-hospital death (OR: 1.2 (0.6 – 2.4), P = 0.55).IM was used sparingly in our ADHF cohort, and was independently associated with increased in-hospital death in multivariable analysis, but not in propensity score analysis. Thus, IM may be used in ADHF, but with caution. Further randomized trials are warranted.
The study sought to determine the duration of standing needed to detect most cases of orthostatic hypotension (OH) in the emergency room (ER) and to correlate OH with symptoms, hospitalization and survival. Patients attending a tertiary‐center ER within a 2‐month period underwent orthostatic tests after 1, 3 and 5 min of standing. OH was defined as a drop of ⩾20 mmHg in systolic pressure or ⩾10 mmHg in diastolic pressure on assuming an upright posture. Of the 814 patients tested (402 men, mean age 56.6±19.9 years), 206 (25.3%) had OH, detected in most cases (83.5%) after 3 min of standing. OH was associated with significantly higher supine systolic (p = 0.013) and diastolic (p = 0.004) blood pressure, symptoms of syncope (r = 0.11, p<0.001) or dizziness (r = 0.14, p<0.0001) and risk of hospitalization (50.9% vs 22.9%, p<0.0001). Crude mortality was similar between patients with and without OH (13.8% vs 8.7%, p = 0.06). However, on age‐adjusted analysis, patients older than 75 years with OH had significantly increased mortality (p = 0.04). In conclusion, 3 min of standing is apparently sufficient for the diagnosis of most cases of OH. Considering the high rate of OH and its predictive value for hospitalization, it should be routinely assessed in all ER patients.
'/%3e%3c/g%3e%3cuse xlink:href='%23d' x='45.714'/%3e%3cuse xlink:href='%23e' transform='matrix(-1 0 0 1 479.792 0)'/%3e%3cg id='f' fill='%23fff'%3e%3cpath fill='%23039' d='M232.636 202.406v.005c0 2.212.85 4.227 2.212 5.69 1.365 1.466 3.245 2.377 5.302 2.377 2.067 0 3.944-.905 5.303-2.365 1.358-1.459 2.202-3.472 2.202-5.693v-10.768l-14.992-.013-.028 10.766'/%3e%3ccircle cx='236.074' cy='195.735' r='1.486'/%3e%3ccircle cx='244.392' cy='195.742' r='1.486'/%3e%3ccircle cx='240.225' cy='199.735' r='1.486'/%3e%3ccircle cx='236.074' cy='203.916' r='1.486'/%3e%3ccircle cx='244.383' cy='203.905' r='1.486'/%3e%3c/g%3e%3cuse xlink:href='%23f' y='-26.016'/%3e%3cuse xlink:href='%23f' x='-20.799'/%3e%3cuse xlink:href='%23f' x='20.745'/%3e%3cuse xlink:href='%23f' y='25.784'/%3e%3c/svg%3e)
