Cushing syndrome and severe adrenal suppression caused by fluticasone and protease inhibitor combination in an HIV-infected adolescent

A 14-year-old female with perinatally acquired HIV on boosted protease inhibitor (PI) therapy with atazanavir and ritonavir rapidly developed cushingoid features with excessive weight gain and moon facies within 2 weeks of receiving inhaled fluticasone/salmeterol for asthma treatment. Soon after discontinuing PIs and inhaled steroid, she required hospitalization for dyspnea, headache, muscle weakness, and extreme fatigue requiring hydrocortisone replacement therapy for presumed adrenal insufficiency. Cushing syndrome and adrenal suppression were very likely caused by elevated steroid systemic concentrations resulting from the cytochrome p450 interaction between the protease inhibitors and fluticasone. The Naranjo probability scale score of 5 suggests that the event was probably drug related. This is the first case report of fluticasone and PI-induced Cushing syndrome and adrenal suppression in a pediatric patient without a history of recent or concomitant treatment with systemic steroid therapy. Additionally, this case is unique as it is the most rapid (<2 weeks) presentation documented, thus far. Health care professionals should be conscious of this important drug-drug interaction in HIV-infected children and adolescents and be aware that rapid onset of hypercortisolism and adrenal suppression are possible.     

Evaluation of fractal-coated temporary pacing leads in the early postoperative course

Background: The performance of temporary pacing wires is still limited by capture and sensing problems. Fractal coating can enhance electrical properties and reliability. We therefore investigated fractal-laminated wires in comparison with conventional wires.
Methods: In 21 patients two unipolar, fractal-coated pacing wires (fe) and one conventional bipolar electrode (se) were implanted in ventricular position. Afterward pacing threshold (V), R-wave sensing (mV), lead impedance (ohm), and slew-rate (mV/s) were measured. Loss of capture or sensing and dislocation was documented. fe wires were examined with energy dispersive x-ray diffraction (EDX)-analysis and scanning electrode microscopy (SEM).
Results: Failure in pacing was less frequent in fe wires. Also fe leads had lower pacing thresholds at implantation (0.76 ± 0.15 V vs 1.51 ± 0.95 V, P< 0.0001) and afterward. Furthermore fe wires showed lower increase of pacing threshold/time (0.25 V/day vs 0.42 V/day). R-wave sensing and slew-rate values in the fe group on day of operation (5.81 ± 4.80 mV; 0.63 ± 0.71 V/s) were lower than in the se group (10.37 ± 6.89 mV; 1.85 ± 1.71 V/s P< 0.0001) and afterward. Nevertheless, decrease of amplitude/time was lower in fe wires (0.17mV/day vs 0.46 mV/day). fe wires always had lower impedance values.
Conclusions: Lower pacing threshold and increase of threshold/time in fe wires indicate more reliable function. Initial lower sensitivity values are still not understandable and must be investigated. However, fe wires, constancy of sensing and impedance values was more stable, so fe epicardial wires can be recommended for safe and feasible use.     

A cross-sectional observational study to investigate daily symptom variability, effects of symptom on morning activities and therapeutic expectations of patients and physicians in COPD-SUNRISE study

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized with limitation of airflow that is not completely reversible, progressive deterioration of airways and systemic inflammation. This study has been planned to determine daily symptom variability of patients, expectations of patient and physicians from treatment and patient profiles. A total of 514 patients with COPD from 25 centers were included in this national, multicenter, cross-sectional observational study. Data regarding demographic features, concomitant diseases, history and treatment of COPD and expectations of patients and physicians were all obtained in a single visit. Mean [standard deviation (SD)] age of the patients was 64.1 (9.5) years; age range was 41-92 years, 50% of the patients were younger than 65 years and 91% were males. Educational level of the patients was at least primary school in 80.2%; and 54.3% (30.4%) of the patients had at least one concomitant disease, particularly a cardiovascular disease. Mean (SD) duration of having COPD was 5.4 (4.6) years. The majority of patients were at moderate (43.2%) and severe (35.0%) COPD stages and one or more exacerbations per year was determined in 71%. Inhaled beta-2 agonists (84.2%), inhaled steroids (76.3%) and inhaled long-acting anti-cholinergics (70.0%) were the most commonly used medications. Dyspnea (99.0%), sputum production (92.8%) and wheezing (90.5%) were the most common symptoms, and symptom variability for dyspnea (41.1%), sputum production (61.0%) and cough (53.5%) were seen the most in the morning hours (p< 0.001). Most commonly affected morning activity was climbing up/down the stairs (point of effect: 6.7), followed by wearing socks/shoes (point of effect: 4.3) and showering/bathing (point of effect: 4.2) by COPD. Major treatment expectations of patients were greater symptomatic relief (82.3%) and greater mobility (70.0%), faster symptomatic relief (61.1%) and improvement in morning activities (59.3%); while major treatment expectations of physicians included increased quality of life (100.0%) and decreased morbidity (96.0%). Quitting smoking was the most commonly recommended (88.3%) and implemented (67.9%) non-drug protective approach aimed at decreasing the frequency of exacerbations. Consequently, our results demonstrate that COPD is not a disease of only the elderly, is an important healthcare issue that often disrupt daily living of the patients due to inadequate disease awareness leading to overlooking of the symptoms by patient and physicians, and that a patient-centered approach based on the living standards, life expectancies and preferences of patients was crucial in patient management.     

Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function

OBJECTIVE: We investigated the effects of thyroxine (T4) therapy on the cardiac function in subclinical hypothyroidism (SHT) by using the index of myocardial performance (IMP) and the conventional echocardiographic parameters. METHODS: Forty-five SHT patients (F/M:38/7, age 39.9+/-7.9) and 29 healthy subjects (F/M:25/4, age 38.3+/-8.6) were studied. Patients were randomly assigned, in a double-blind manner to receive T4 therapy (group I) or a placebo (group II) and for a period of up to 12 months, were followed up using thyroid function tests and both conventional and Doppler echocardiographic measurements. RESULTS: At the baseline, the SHT patients has a significantly higher isovolumic relaxation time (IRT) (98.3+/-23.7 vs. 81.7+/-14.7<0.01), IMP (0.52+/-0.06 vs. 0.42+/-0.05; P<0.001), A max (late mitral peak velocity) (83.4+/-12.6 vs. 74.3+/-13.5; P<0.01) and significantly lower (early mitral peak velocity) Emax/Amax ratio (1.19+/-0.18 vs. 1.34+/-0.17; P<0.01) than the individuals in the control group. In group I, the thyroid hormone profile became normalized after 1 year of L-T4 therapy, but there was no significant change in the left ventricular (LV) morphology or systolic function. After 1 year of follow-up, group I showed a significant reduction of MPI (0.53+/-0.05 vs. 0.42+/-0.07; P<0.001), Amax (84.2+/-13.7 vs. 74.5+/-11; P<0.001) and IRT (98.6+/-23.7 vs. 82.9+/- 23.3; P<0.001) along with a normalization of the E/A ratio (1.17+/-0.16 vs. 1.33+/-0.19; P<0.001). Conversely, no change was observed in group II. CONCLUSIONS: An impairment of left ventricular diastolic function, which may be reversible with T4 therapy, was observed in the SHT patients, and IMP may be useful in the evaluation of LV myocardial dysfunction in these patients.     

Assessing the effect of low dose dobutamine on various diastolic function indexes.

OBJECTIVE: The aim of this study was to evaluate the effect of low dose dobutamine (LDD) on various diastolic function parameters in patients without wall motion abnormality. METHODS: Thirty-one volunteer patients who had no regional wall motion abnormality were included in the study. Echocardiographic measurements were taken both at pre-dobutamine and during LDD infusion. The peak E velocity, A velocity, the E/A ratio, deceleration time (DT), isovolumetric relaxation time (IVRT), myocardial performance index (MPI) and flow propagation velocity (FPV) were assessed as left ventricular diastolic function parameters. Tissue Doppler velocities were also obtained in order to calculate the E/Em and Em/Am ratios. RESULTS: No significant changes were observed in heart rate, E velocity, A velocity, E/A ratio, E/Em ratio, Em/Am ratio, systolic and diastolic blood pressure with LDD. With LDD, DT (239+/-40 ms vs. 201+/-31 ms, p<0.001), IVRT (109+/-12 ms vs. 94+/-11 ms, p<0.001) and MPI (0.57+/-0.15 vs. 0.44+/-0.22, p<0.001) were found to be decreased, while there was an increase in FPV (45+/-8 cm/s vs. 59+/-10 cm/s, p<0.001) and ejection fraction (64+/-6% vs. 66+/-7%, p<0.05). CONCLUSION: Low dose dobutamine (5 mcg/kg of body weight) improves left ventricular relaxation in patients with normal wall motion, while it has no effect on left ventricular filling pressure index.     

The report of male gender and retinopathy status improves the current consensus guidelines for the screening of myocardial ischemia in asymptomatic type 2 diabetic patients

Background and aimsAmerican Diabetes Association (ADA), French-speaking Societies for diabetes & cardiology (ALFEDIAM-SFC) and Cardiac Radionuclide Imaging (CRI) have proposed guidelines for the screening of silent myocardial ischemia (SMI). The aim of the study was to evaluate their diagnostic values and how to improve them.Methods and results731 consecutive type 2 diabetic patients with ≥1 additional risk factor were screened between 1992 and 2006 for SMI by stress myocardial scintigraphy and for silent coronary artery disease (CAD) by coronary angiography. A total of 215 (29.4%) patients had SMI, and 79 of them had CAD. ADA (Odds Ratio 1.7 [95% Confidence Interval: 1.2–2.5]; p < 0.05), ALFEDIAM-SFC (OR 1.5 [1.0–2.5], p < 0.05) and CRI criteria (OR 2.0 [1.4–2.8], p < 0.01) predicted SMI. Considering the presence of male gender and retinopathy added to the prediction of SMI allowed by ADA criteria (c statistic: area under the curve AROC 0.651 [0.605–0.697] versus 0.582 [0.534–0.630]), p < 0.01 and ALFEDIAM-SFC criteria (AROC 0.672 [0.620–0.719] versus 0.620 [0.571–0.670], p < 0.05). CRI prediction of SMI was improved by considering the presence of macroproteinuria and retinopathy (AROC 0.621 [0.575–0.667] versus 0.594 [0.548–0.641], p < 0.01). Severe retinopathy (OR 3.4 [1.2–9.4], p < 0.05), smoking habits (OR 2.1 [1.1–4.2], p < 0.05) and triglyceride levels (OR 1.3 [1.0–1.6], p < 0.05) were independent predictors of CAD in the patients with SMI.ConclusionCurrent guidelines criteria are able to predict SMI but prediction may be improved by considering male gender and the presence of retinopathy. CAD is more frequent in the patients with SMI who are current smokers, have severe retinopathy and higher triglyceride levels.