Local cooling does not prevent hyperalgesia following burn injury in humans

One of the oldest methods of pain relief following a burn injury is local application of ice or cold water. Experimental data indicate that cooling may also reduce the severity of tissue injury and promote wound healing, but there are no controlled studies in humans evaluating the anti-inflammatory or anti-hyperalgesic potential of early cooling after thermal injury. Twenty-four healthy volunteers participated in this randomized, single-blinded study. Following baseline measurements, which included inflammatory variables (skin temperature, erythema index) and sensory variables (thermal and mechanical detection thresholds, thermal and mechanical pain responses, area of secondary hyperalgesia), first degree burn injuries were induced on both calves by contact thermodes (12.5 cm(2), 47 degrees C for 7 min). Eight minutes after the burn injury, contact thermodes (12.5 cm(2)) were again applied on the burns. One of the thermodes cooled the burn (8 degrees C for 30 min) whereas the other thermode was a non-active dummy on the control burn. Inflammatory and sensory variables were followed for 160 min after end of the cooling procedure. The burn injury induced significant increases in skin temperature (P<0.0005), erythema index (P<0.0001), thermal pain responses (P<0.0005), mechanical pain responses (P<0.005) and secondary hyperalgesia, and significant decreases in heat pain threshold (P<0.0005) and mechanical pain threshold (P<0.0005). There were no post-cooling effects on skin temperature (P>0.5), erythema (P>0.9), heat pain threshold (P>0.5), thermal or mechanical pain responses (P>0.5) or the development of secondary hyperalgesia (P>0.4) compared with the control burn. However, a significant, albeit transient, increase in cold detection threshold was observed on the cooled burn side (P<0.0001). In conclusion, cooling with 8 degrees C for 30 min following a first degree burn injury in humans does not attenuate inflammatory or hyperalgesic responses compared with a placebo-treated control burn.     

Similar long-term overall and disease-free survival after conventional and extralevator abdominoperineal excision—a nationwide study

Purpose

The purpose of the present study was to assess, compare, and identify factors of importance for long-term overall (OS) and disease-free (DFS) survival after conventional (cAPE) and extralevator abdominoperineal excision (ELAPE) on a nationwide basis.

Methods

This was a database study based on data from a nationwide colorectal cancer database. Patients undergoing surgery for rectal cancer in the period January 1, 2009 to August 31, 2012 were examined. Factors of importance for disease-free and overall survival were identified by multivariate Cox regressions.

Results

Five hundred patients were included in the final population. Two hundred seventy-six were operated by ELAPE and 224 by APE. Disease-free and overall survival did not differ between groups (4-year DFS 67 and 66 % after cAPE and ELAPE, respectively, (log-rank p?=?0.82); 4-year OS 74 and 77 % after cAPE and ELAPE, respectively, (log-rank p?=?0.59)). In Cox regression, the type of procedure did not affect DFS or OS. Factors of importance for DFS included increasing age, ypN-positive disease and neoadjuvant chemoradiation therapy. Factors of importance for OS included increasing age, circumferential resection margin (CRM) positivity, fixation of the tumor, blood transfusion, and increasing American Society of Anesthesiologists (ASA) score.

Conclusions

In this nationwide study, we did not find any differences in DFS or OS after extralevator versus conventional abdominal perineal excision, and the type of procedure did not affect survival after adjusted analyses.

     

Dynamics of the echolocation beam during prey pursuit in aerial hawking bats

In the evolutionary arms race between prey and predator, measures and countermeasures continuously evolve to increase survival on both sides. Bats and moths are prime examples. When exposed to intense ultrasound, eared moths perform dramatic escape behaviors. Vespertilionid and rhinolophid bats broaden their echolocation beam in the final stage of pursuit, presumably as a countermeasure to keep evading moths within their “acoustic field of view.” In this study, we investigated if dynamic beam broadening is a general property of echolocation when catching moving prey. We recorded three species of emballonurid bats, Saccopteryx bilineata, Saccopteryx leptura, and Rhynchonycteris naso, catching airborne insects in the field. The study shows that S. bilineata and S. leptura maintain a constant beam shape during the entire prey pursuit, whereas R. naso broadens the beam by lowering the peak call frequency from 100 kHz during search and approach to 67 kHz in the buzz. Surprisingly, both Saccopteryx bats emit calls with very high energy throughout the pursuit, up to 60 times more than R. naso and Myotis daubentonii (a similar sized vespertilionid), providing them with as much, or more, peripheral “vision” than the vespertilionids, but ensonifying objects far ahead suggesting more clutter. Thus, beam broadening is not a fundamental property of the echolocation system. However, based on the results, we hypothesize that increased peripheral detection is crucial to all aerial hawking bats in the final stages of prey pursuit and speculate that beam broadening is a feature characterizing more advanced echolocation.The evolutionary arms race between echolocating bats and their insect prey provides a textbook example of continuous evolution of measures and countermeasures to either acquire prey or escape capture (1). Bats can navigate and forage in complete darkness using echolocation, emitting short ultrasonic sound pulses and locating objects and prey in their surroundings from the returning echoes (2). In response, moths and other nocturnal insects have evolved ultrasound-sensitive ears that enable them to avoid foraging echolocating bats (negative phonotaxis) and to initiate dramatic escape responses when in close proximity to them (3). As a possible countermeasure, some species of bats have evolved echolocation calls with low intensities [Barbastellus barbastella (4)] and/or frequencies [Euderma maculatum (5)] outside the moths’ hearing range, enabling them to sneak up undetected, or at least without eliciting escape maneuvers from the prey.Another potential countermeasure is the sudden broadening of the beam observed in the very last phases of prey pursuit in aerial hawking vespertilionid bats (6) and rhinolophid bats (7). When searching for, and approaching, prey, both vespertilionids and rhinolophids emit a fairly directional sound beam with higher sound pressure in the acoustic axis right in front of the bat and decreasing steeply as the off-axis angle increases (8, 9). Although the directional emissions provide the bats with a number of advantages over an omnidirectional emission (6), the downside is a decreased acoustic “field of view” that would enable prey to escape the bat’s sonar space, especially at close range. Presumably to counteract this effect, vespertilionids and rhinolophids broaden their echolocation beam when closing in on prey (6, 7). Vespertilionids do so by lowering the frequency of their calls by almost an octave. The width of a sound beam depends on the wavelength emitted relative to the size of the emitter. Hence, increasing the wavelength by lowering the frequency by an octave will substantially increase the width of the beam for a constant mouth opening (6). The mechanism is still unknown for rhinolophids, but manipulating the fine structure of their nose-leaf could account for the change in beam directionality (10). By broadening the beam during the final stage of prey pursuit (the buzz), the bats counteract the prey’s evasive maneuvers, keeping larger off-axis angles within their acoustic field of view compared with the approach phase. The ubiquitous nature of this aspect of predator–prey interaction in echolocators is emphasized by recent findings showing that harbor porpoises (Phocena phocena) also broaden their beam during the buzz phase when catching fish (11).Whereas the Vespertilionidae and Rhinolophidae are considered advanced echolocators, the Emballonuridae are thought to emit calls closely resembling those calls emitted by the first echolocating bats (12, 13). Like most vespertilionids, emballonurids hunt airborne insects. They emit sounds through their mouth. Their calls are short, multiharmonic, and of an almost constant frequency, with a suppressed first harmonic and most energy in the second harmonic (14) (Fig. 1). They go through the three standard hunting phases, search, approach, and buzz, when catching airborne prey (Fig. 1), but they do not change the call frequency during the buzz phase. Thus, emballonurids can only broaden their echolocation beam during the buzz by reducing their effective emitter size (e.g., by reducing their gape size). Investigating whether emballonurids broaden their beam during prey pursuit will throw light on whether the beam broadening is a fundamental property of the echolocation system in all aerial hawking bats, or possibly a more advanced trait that has only evolved in some families/species. Hence, the main purpose of this study is to investigate if emballonurids are broadening their beam during the terminal buzz. The only known exception to the general observation of constant frequency throughout the whole pursuit sequence is Rhynchonycteris naso, which is considered an outlier within the emballonurid family. It uses very high frequencies, around 100 kHz, and lowers the frequency to ca. 67 kHz in the terminal phase (15). Thus, a second purpose of our study is to investigate how the frequency shift affects the beam shape of this exception within the emballonurid family.Open in a separate windowFig. 1.Recorded call sequences. Exemplary call sequences for each recorded species and from M. daubentonii for comparison. (Top) Oscillograms of the hunting sequences for each species; the arrow indicates the beginning of the buzz. (Middle) Spectrograms of the hunting sequence showing the frequency drop in the buzz for R. naso and M. daubentonii and the lack of frequency change in S. bilineata and S. leptura. Frequency spectra (Bottom) corresponding to calls marked with colored asterisks (Top) comparing search/approach calls and buzz calls; two search/approach calls are shown for the two Saccopteryx bats as they alternate call frequency.     

15-O-water myocardial flow reserve PET and CT angiography by full hybrid PET/CT as a potential alternative to invasive angiography

Combined myocardial flow reserve (MFR) by PET and CT coronary angiography (CTA) is a promising tool for assessment of coronary artery disease. Prior analyses of MFR/CTA has been performed as side-by-side interpretation, not as volume rendered, full hybrid analysis, with fused MFR/CTA. We aimed to: (i) establish a method for full hybrid analysis of MFR/CTA, (ii) validate the inter- and intra-observer reproducibility of MFR values, and (iii) determine the diagnostic value of side-by-side versus full hybrid MFR/CTA with 15-O-water PET. Forty-four outpatients scheduled for invasive coronary angiography (ICA) were enrolled prospectively. All underwent rest/stress 15-O-water PET/CTA with ICA as reference. Within two observers of different experience, the Pearson r at global and territorial level exceeded 0.953 for rest, stress, and MFR values, as determined by Carimas software. Within and between observers, the mean differences between rest, stress, and MFR values were close to zero and the confidence intervals for 95% limits of agreement were narrow. The diagnostic performance of full hybrid PET/CTA did not outperform the side-by-side approach, but performed better than MFR without CTA at vessel level: specificity 93% (95% confidence limits: 89–97%) versus 76% (64–88%), p?=?0.0004; positive predictive value 71% (55–86%) versus 51% (37–65%), p?=?0.0001; accuracy 90% (84–95%) versus 77% (69–84%), p?=?0.0009. MFR showed high reproducibility within and between observers of different experience. The full hybrid model was not superior to side-by-side interpretation of MFR/CTA, but proved better than MFR alone at vessel level with regard to specificity, positive predictive value, and accuracy.     

Pseudomonas aeruginosa isolates: comparisons of isolates from campers and from sibling pairs with cystic fibrosis

Sputum or deep throat specimen cultures were obtained from 47 cystic fibrosis (CF) patients residing together at an eight-day summer camp. Pre-camp, initial day, final day and post-camp cultures were obtained and Pseudomonas aeruginosa isolates were characterized by morphology, serotype, pigment production, serum sensitivity, antibiotic susceptibility patterns, hemolysis on blood agar, and CO2 growth requirement. Of the 47 patients, four were not chronically colonized with Pseudomonas and did not become colonized at camp. Analysis of the isolates from the other 43 revealed no significant alteration in the Pseudomonas colonization pattern. Cultures obtained from four sibling pairs among the campers and from 20 additional pairs of siblings revealed that siblings in 20/24 pairs had at least one identical serotype in common. Of the criteria used for characterization, serotyping was the most definitive method for strain identification. Serotyping by both the Homma system and the International system did not detect any serotype at a frequency of more than 31%. In this study, the predominant P. aeruginosa strain of the colonized patients did not change, and non-colonized individuals did not become colonized with P. aeruginosa.     

Natriuretic peptide response to dynamic exercise in patients with atrial fibrillation

BACKGROUND: In patients with atrial fibrillation (AF) information regarding exercise release of atrial natriuretic peptide (ANP) is sparse and data on plasma brain natriuretic peptide (BNP) response to exercise is lacking. The aim of this study was to investigate plasma ANP and BNP response to exercise in patients with permanent AF and to assess if the response was different from the response in healthy age- and sex-matched control subjects. METHODS: Plasma venous concentrations of ANP and BNP were determined at rest, at peak exercise and 30 min from the end of exercise in 38 patients with permanent AF and in 43 age- and sex-matched healthy control subjects. RESULTS: Plasma concentrations of ANP and BNP were significantly higher in AF patients compared with the healthy control group at rest, peak exercise and after 30 min of recovery (p<0.0001). ANP and BNP increased significantly during exercise in both patients with AF and in the healthy control subjects (p<0.05). The increase in plasma concentration of ANP and BNP during exercise was significantly higher in AF patients compared with healthy controls (p=0.0002 for ANP; p<0.0001 for BNP). In the recovery period plasma BNP decreased significantly (p<0.0001) where as the decrease in plasma ANP was insignificant (p=0.4). CONCLUSIONS: Patients with permanent AF have elevated levels of ANP and BNP at rest and exhibit much higher exercise release compared to healthy control subjects. This enhanced secretion of potent vasodilating and natriuretic agents may represent an important compensatory mechanism to improve exercise capacity in patients with AF.     

Pathophysiological-based treatments of complications of cirrhosis

Abstract

Detailed knowledge and understanding of the pathophysiological mechanisms and changes in hepatic and splanchnic function leading to the development of haemodynamic changes and portal hypertension in patients with cirrhosis are essential since it guides the search for targets to ameliorate liver-related abnormalities. Recent research has focused on the gut-liver axis, changes in intestinal permeability, translocation of bacterial products, and inflammation as important drivers of haemodynamic alterations and thereby targets for treatment. Additionally, treatment strategies should focus on microbiotic modulation, antiangiogenics, anti-inflammatory strategies, and modulation of bile acid metabolism. This paper aims to review contemporary pathophysiological-based treatment principles of the major complications of cirrhosis and portal hypertension and future targets for treatment.