I.V. LABETALOL IN THE TREATMENT OF HYPERTENSION FOLLOWING CORONARY-ARTERY SURGERY

SUMMARY The cardiovascular effects of incremental fixed i.v. doses of labetalol were evaluated in 10 normovolaemic sedated patients presenting with hypertension and tachycardia in the early period after myocardial revas-cularizaoon. A first dose of 20 mg was sufficient to provoke a (P < 0.01) mean decrease in systolic (−9.3%), diastolic (−8.2%) and mean arterial (−7.9%) pressure (AP) and in the rate-pressure product (RPP) (−13.1%). The mean heart rate (HR) did not change significantly, but a linear correlation could be established between the change at 2 min and the value before injection (r = 0.73). A second dose of labetalol 40 mg given S min later did not decrease AP further, but a significant decrease in HR was noted. A marked difference in the individual response among patients was found as the range of effective total doses per kg body weight was 0.6-4.1 mg kg−1 (mean 2.2). Apart from one patient, no patient needed vagolytic or sympathomimetic drugs to oppose the alpha or beta actions of labetalol during the 24-h follow-up perio

PREDICTIVE VALUE OF FRC AND RESPIRATORY COMPLIANCE ON PULMONARY GAS EXCHANGE INDUCED BY HIGH FREQUENCY JET VENTILATION IN HUMANS

SUMMARY To determine if functional residual capacity (FRC), compliance of the respiratory system (C), or underlying pulmonary disease are predictive for the efficacy of high frequency jet ventilation (HFJV) on pulmonary gas exchange, we investigated six adult patients within 4 h of abdominal surgery and six patients with severe adult respiratory distress syndrome. Gas exchange during intermittent positive pressure ventilation (IPPV) was compared with that during HFJV at frequencies of 100 b.p.m. (HFJV100) and 200 b.p.m. (HFJV200), resulting in a minute ventilation of about 400 ml kg−1 with both ventilatory frequencies, and in both groups of patients. Baseline FRC and C were measured during IPPV with the multiple-breath nitrogen washout method and from expiratory pressure-volume curves, respectively. Changes in the alveolar-arterial oxygen difference (PAO2−PaO2): FlO2 ratio induced by HFJV correlated negatively with C (HFJV100: r = −0.78, P <0.005; HFJV200: r = −0.84, P < 0.005); that is, greater oxygenation was obtained in patients with a better compliance. Similarly, changes in arterial partial pressure of carbon dioxide (Paco2) induced by HFJV correlated negatively with C (HFJV100: r = −0.77, P < 0.001; HFJV200: r = —0.61, P < 0.05). In contrast, there was no significant correlation between FRC measured during IPPV and changes in (PAO2−PaO2): FlO2 ratio or Paco2 induced by HFJV, as these changes were influenced more by the patient's pulmonary disease than by baseline FRC. These results should be interpreted in the context of different underlying pathophysiological mechanisms reducing FRC in both groups of patient

Nonanalytic behavior of the spin susceptibility in clean Fermi systems

The wavevector and temperature dependent static spin susceptibility, \chi_s(Q,T), of clean interacting Fermi systems is considered in dimensions 1\leq d \leq 3. We show that at zero temperature \chi_s is a nonanalytic function of |Q|, with the leading nonanalyticity being |Q|^{d-1} for 1<d<3, and Q^2\ln|Q| for d=3. For the homogeneous spin susceptibility we find a nonanalytic temperature dependence T^{d-1} for 1<d<3. We give qualitative mode-mode coupling arguments to that effect, and corroborate these arguments by a perturbative calculation to second order in the electron-electron interaction amplitude. The implications of this, in particular for itinerant ferromagnetism, are discussed. We also point out the relation between our findings and established perturbative results for 1-d systems, as well as for the temperature dependence of \chi_s(Q=0) in d=3.Comment: 12pp., REVTeX, 5 eps figures, final version as publishe

A Closest Point Proposal for MCMC-based Probabilistic Surface Registration

We propose to view non-rigid surface registration as a probabilistic inference problem. Given a target surface, we estimate the posterior distribution of surface registrations. We demonstrate how the posterior distribution can be used to build shape models that generalize better and show how to visualize the uncertainty in the established correspondence. Furthermore, in a reconstruction task, we show how to estimate the posterior distribution of missing data without assuming a fixed point-to-point correspondence. We introduce the closest-point proposal for the Metropolis-Hastings algorithm. Our proposal overcomes the limitation of slow convergence compared to a random-walk strategy. As the algorithm decouples inference from modeling the posterior using a propose-and-verify scheme, we show how to choose different distance measures for the likelihood model. All presented results are fully reproducible using publicly available data and our open-source implementation of the registration framework

Holistic approach to dissolution kinetics : linking direction-specific microscopic fluxes, local mass transport effects and global macroscopic rates from gypsum etch pit analysis

Dissolution processes at single crystal surfaces often involve the initial formation and expansion of localized, characteristic (faceted) etch-pits at defects, in an otherwise comparatively unreactive surface. Using natural gypsum single crystal as an example, a simple but powerful morphological analysis of these characteristic etch pit features is proposed that allows important questions concerning dissolution kinetics to be addressed. Significantly, quantitative mass transport associated with reactive microscale interfaces in quiescent solution (well known in the field of electrochemistry at ultramicroelectrodes) allows the relative importance of diffusion compared to surface kinetics to be assessed. Furthermore, because such mass transport rates are high, much faster surface kinetics can be determined than with existing dissolution methods. For the case of gypsum, surface processes are found to dominate the kinetics at early stages of the dissolution process (small etch pits) on the cleaved (010) surface. However, the contribution from mass transport becomes more important with time due to the increased area of the reactive zones and associated decrease in mass transport rate. Significantly, spatial heterogeneities in both surface kinetics and mass transport effects are identified, and the morphology of the characteristic etch features reveal direction-dependent dissolution kinetics that can be quantified. Effective dissolution velocities normal to the main basal (010) face are determined, along with velocities for the movement of [001] and [100] oriented steps. Inert electrolyte enhances dissolution velocities in all directions (salting in), but a striking new observation is that the effect is direction-dependent. Studies of common ion effects reveal that Ca2+ has a much greater impact in reducing dissolution rates compared to SO42−. With this approach, the new microscopic observations can be further analysed to obtain macroscopic dissolution rates, which are found to be wholly consistent with previous bulk measurements. The studies are thus important in bridging the gap between microscopic phenomena and macroscopic measurements

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570