Reversible impairment of coronary flow reserve in takotsubo cardiomyopathy: A myocardial PET study

Background. The precise etiology of takotsubo cardiomyopathy remains unclear. The study of myocardial blood flow (MBF) and coronary flow reserve (CFR) by use of positron emission tomography might help in understanding this syndrome. Methods and Results. Three postmenopausal women underwent adenosine/rest perfusion with nitrogen 13 ammonia and metabolism with fluorine 18 fluorodeoxyglucose positron emission tomography, coronary angiography, cardiac magnetic resonance, and echocardiography in the acute phase of takotsubo cardiomyopathy and at 3 months’ follow-up, after normalization of left ventricular function. PET study was performed in 2 parts: the perfusion analysis with nitrogen ammonia and the metabolism of the heart using FDG. MBF and CFR were analyzed quantitatively in the acute phase and at follow-up. The images highlighted the impairment of tissue metabolism in the dysfunctioning left ventricular segments in the acute phase, mainly in the apical segments and progressively less in the medium segments. At the same time, a clear inverse metabolic/perfusion mismatch emerged, which normalized 3 months later. The quantitative analysis of MBF showed a reduction in the acute phase in apical segments in comparison to basal segments without differences between midventricular and basal segments. In the acute phase CFR proved to be reduced in apical versus basal segments. CFR impairment of apical segments recovered completely after 3 months. Conclusion. The acute phase of takotsubo cardiomyopathy is characterized by an inverse perfusion/metabolism mismatch with a reduction in CFR in the apical segments. However, the impairment of CFR and the reduction of metabolism in the apical segments recovered completely after 3 months.     

Objective measurement of optical aberrations in myopic eyes.

PURPOSE: To determine whether the degree of myopia affects the optical quality of the retinal image after appropriate correction, monochromatic aberrations of the human eye were measured as a function of the degree of myopia. METHODS: Using a modified Hartmann-Shack method, a population of 27 myopic (up to -9.25 D) and 7 emmetropic optometry students (18-32 years) were objectively evaluated before and after pupil dilation. We then identified for each subject the most influential aberration types, and we calculated the profile of wavefront aberration. To study the behavior of aberration as a function of the degree of myopia, we determined the maximum value of aberration as well as the root mean square (rms) value. RESULTS: It turned out that aberration increases with the refractive error in a quasi-linear relationship for pupil diameters of 5 and 9 mm. This result is valid for both rms and maximum values. CONCLUSIONS: We objectively showed that optical quality decreases as myopia increases and as the pupil gets larger. Coma is more frequent in high myopia, and spherical aberration occurs more frequently for dilated pupils.     

Societal and ethical considerations of artificial hearts

The present state of artificial heart research and development is analyzed in light of public perceptions affected by accounts of the experiences of those who received the Jarvik-7. On the assumption that research will continue, it is argued that the therapeutic goals of the artificial heart can be realized, and funding be obtained, only in an atmosphere of positive publicity. To this end, formation of an association of companies involved in artificial heart R & D is recommended. Such a group would articulate voluntary standards and produce reports of advances in the field. Artificial hearts, it is noted in conclusion, have been effective as temporary assist devices in patients destined to receive heart transplants.     

An efficient cryoprobe to inactivate cortical surfaces

This paper describes a cryoprobe constructed of glass capillary tubes commonly employed for cellular recordings. It is inexpensive, it is easily and rapidly constructed and most importantly it can easily be adjusted to cool larger areas and tightly fit brain curvatures and gyri.     

Complications of intravascular catheters in ICU: definitions,incidence and severity. A randomized controlled trial comparing usual transparent dressings versus new-generation dressings (the ADVANCED study)

Purpose

To describe all post-insertion complications involving most used intravascular access, and to determine whether the use of a new-generation transparent dressing (3M? IV Advanced) might reduce their number and impact on ICU patient outcomes.

Methods

Patients older than 18, with an expected length of stay ≥48 h and requiring at least one central venous catheter (CVC), arterial catheter (AC), haemodialysis catheter (HDC), pulmonary arterial catheters (PAC) or peripheral venous catheter (PVC) were randomized into two groups: a new-generation transparent dressing, or the hospital’s classical transparent dressing, and were followed daily for any infectious and non-infectious complications. Complications were graduated for severity by an independent international multicentre multidisciplinary panel of practitioners using a Delphi process.

Results

We included 628 patients, 2214 catheters (873 PVCs, 630 CVCs, 512 ACs and 199 HDCs and PACs) and 4836 dressings. Overall incidence rate was of 60.9/1000 catheter-days. The most common complication was dysfunction (34.6/1000 catheter-days), mainly for PVCs (16/1000 catheter-days) and ACs (12.9/1000 catheter-days). Infectious complications incidence rate in CVCs and ACs was of 14.5/1000, mostly due to colonization (14.2/1000 catheter-days). Thrombosis incidence was of 3.8/1000 catheter-days with severe and very severe complications in 16 cases (1.8/1000 catheter-days) and one thrombosis-related death. 3M? IV Advanced dressing did not decrease the rate of catheters with at least a minor complication [57.37/1000 vs. 57.52/1000 catheter-days, HR 1.03, CI (0.84–1.27), p = 0.81]. Incidence rates for each single complication remained equivalent: infectious [HR 0.93 (0.62–1.40), p = 0.72], deep thrombosis [HR 0.90 (0.39–2.06), p = 0.80], extravasation and phlebitis [HR 1.40 (0.69–2.82), p = 0.35], accidental removal [1.07 (0.56–2.04), p = 0.84] and dysfunction [HR 1.04 (0.80–1.35), p = 0.79].

Conclusion

The ADVANCED study showed the overall risk of complications to intravascular catheters in ICU patients being dysfunction, infection and thrombosis. The 3M? IV Advanced dressing did not decrease complication rates as compared to standard dressings.

     

Pharmacoscintigraphic comparison of HMR 1031, a VLA-4 antagonist, in healthy volunteers following delivery via a nebulizer and a dry powder inhaler

A pharmacoscintigraphic study was conducted to compare the dose deposition of HMR 1031 from the existing nebulizer formulation and the new Ultrahaler device to help determine the doses for future phase 2 trials. This was a single-dose, open-label, randomized, two-way crossover study in which HMR 1031 (3 mg) was delivered by the Ultrahaler and the Pari LC Star nebulizer to 12 healthy male subjects. For both treatments, the formulations were radiolabeled with technetium-99m pertechnetate such that a maximum of 10 MBq was delivered on each study day. Scintigraphic images were acquired immediately after dosing to estimate the percentage of the dose delivered to the lungs and oropharynx. Serial plasma samples were collected up to 12 hours post-dose on each occasion and analyzed for HMR 1031 by a LC/MS/MS method with a lower limit of quantitation of 10 pg/mL (0.01 ng/mL). Pharmacokinetic parameters were calculated for HMR 1031 using noncompartmental methods. No serious adverse events were reported. The systemic absorption of HMR 1031 following inhalation administration was relatively rapid, with median T(max) values of 0.5 hours and 1.0 hours post-dose after administration via Ultrahaler and nebulizer, respectively. The mean plasma AUC(0-12) (Ultrahaler, 15.8 ng*h/mL; nebulizer, 11.1 ng*h/mL) and C(max) (Ultrahaler, 4.96 ng/mL; nebulizer, 2.28 ng/mL) values were approximately 42% and 118% higher for the Ultrahaler compared with the nebulizer. The mean terminal half-life of HMR 1031 was similar after administration from both devices (2.91 and 3.18 hours). Based on the scintigraphic data, the lung deposition of HMR 1031 after administration by Ultrahaler (24.6% of the administered dose) was approximately 37% higher compared with the lung deposition from the nebulizer (18.0% of the administered dose). This observation was in agreement with the relative difference in the plasma AUC values achieved after administration of the two formulations. The in vivo results based on the scintigraphic data were also comparable with those from in vitro studies for the Ultrahaler. Based on the ratio of the dose delivered by both the formulations, the required doses for the future Ultrahaler formulation can be predicted.     

Functional MRI with active, fully implanted, deep brain stimulation systems: safety and experimental confounds

We investigated safety issues and potential experimental confounds when performing functional magnetic resonance imaging (fMRI) investigations in human subjects with fully implanted, active, deep brain stimulation (DBS) systems. Measurements of temperature and induced voltage were performed in an in vitro arrangement simulating bilateral DBS during magnetic resonance imaging (MRI) using head transmit coils in both 1.5 and 3.0 T MRI systems. For MRI sequences typical of an fMRI study with coil-averaged specific absorption rates (SARs) less than 0.4 W/kg, no MRI-induced temperature change greater than the measurement sensitivity (0.1 degrees C) was detected at 1.5 T, and at 3 T temperature elevations were less than 0.5 degrees C, i.e. within safe limits. For the purposes of demonstration, MRI pulse sequences with SARs of 1.45 W/kg and 2.34 W/kg (at 1.5 T and 3 T, respectively) were prescribed and elicited temperature increases (>1 degrees C) greater than those considered safe for human subjects. Temperature increases were independent of the presence or absence of active stimulator pulsing. At both field strengths during echo planar MRI, the perturbations of DBS equipment performance were sufficiently slight, and temperature increases sufficiently low to suggest that thermal or electromagnetically mediated experimental confounds to fMRI with DBS are unlikely. We conclude that fMRI studies performed in subjects with subcutaneously implanted DBS units can be both safe and free from DBS-specific experimental confounds. Furthermore, fMRI in subjects with fully implanted rather than externalized DBS stimulator units may offer a significant safety advantage. Further studies are required to determine the safety of MRI with DBS for other MRI systems, transmit coil configurations and DBS arrangements.