Factors at scene and in transfer related to the development of hypothermia in major burns.

There is a paucity of evidence regarding incidence and causes of hypothermia in patients with major burns and its impact on outcomes. This paper identifies contributing factors to hypothermia and its relationship with the severity of physiological scoring systems on admission to a tertiary centre. Patients with burns >20% TBSA admitted between March 2010 and July 2013 comprised this retrospective survey. Data relating to causative factors at time of burn, during transfer, physiological outcome scores (BOBI, SOFA, RTS and APACHE II), length of hospital stay and mortality were collected. SPSS statistical software was used for analysis. The study included 31 patients (medians: age 32 years, burn size 30% TBSA). 13% (n=4) of patients died during hospital admission. 42% (n=13) of patients had a temperature <36.0C on arrival. Temperature on arrival at the burns centre was related to the severity of all physiological scores (p=<0.001). There was no difference between groups in terms of mortality in hospital (p=0.151) or length of hospital stay (p=0.547). Our results show that hypothermia is related to burn severity and patient physiological status. They do not show a relationship between hypothermia and external factors at the time of the burn. This paper prompts further investigation into the prevention of hypothermia in patients with major burns.

Il n'existe que peu de données sur l'incidence et les causes de survenue d'une hypothermie chez les brûlés, ni de son incidence sur le devenir. Cette étude répertorie les facteurs contribuant à l'hypothermie à l'admission dans un centre de référence et sa relation avec les scores de gravité initiaux. Cette étude rétrospective a concerné les patients brûlés sur plus de 20% de SCT admis entre mars 2010 et juillet 2013. Les données concernant les causes d'hypothermie au moment de la brûlure et pendant le transfert, les scores de gravité (BOBI, SOFA, RTS et APACHE II), la durée de séjour et la mortalité ont été relevées. Trente et un dossiers ont été étudiés (âge médian 32 ans, surface brûlée 30%). Quatre (13%) d'ente eux décédés. Treize (42%) avait une température <36°C à l'admission et il existait une corrélation entre la température et les scores de gravité (p<0.001). Il n'y avait pas de différence en termes de mortalité ni de durée de séjour. Cette étude montre que l'hypothermie est corrélée à la gravité de la brûlure et à la gravité générale des patients. On ne retrouve pas de relation entre les facteurs environnementaux au moment de la brûlure et l'hypothermie. Des données supplémentaires sont nécessaires pour la prévention de l'hypothermie liée à la brûlure.

Low muscle mass in older men: the role of lifestyle, diet and cardiovascular risk factors.

OBJECTIVE: To explore associations between low muscle mass and a wide range of lifestyle, dietary and cardiovascular risk factors in older men including metabolic risk factors, markers of inflammation, endothelial dysfunction and coagulation. DESIGN: Cross-sectional study. SETTING: British Regional Heart Study. PARTICIPANTS: 4252 men aged 60-79 years. MEASUREMENTS: PARTICIPANTS attended a physical examination in 1998-2000, and completed a general questionnaire and a food frequency questionnaire. Low muscle mass was assessed by two measures: midarm muscle circumference (MAMC) and fat-free mass index (FFMI). Associations between risk factors and low muscle mass were analysed using logistic regression. RESULTS: Physical inactivity, insulin resistance, C-reactive protein, von Willebrand factor and fibrinogen were associated with significantly increased odds of low MAMC and FFMI after adjustment for body mass index, lifestyle characteristics and morbidity. Those with higher percent energy intake from carbohydrates showed decreased odds of low MAMC (OR: 0.73, 95% CI: 0.55-0.96) and FFMI (OR: 0.76, 95% CI: 0.58-0.99). Other dietary variables, smoking, alcohol intake, D-dimer, interleukin 6 and homocysteine showed no important associations with MAMC and FFMI. CONCLUSION: Increasing physical activity, consuming a diet with a high proportion of energy from carbohydrates, and taking steps to prevent insulin resistance and reduce inflammation and endothelial dysfunction may help to reduce the risk of low muscle mass in older men.

Pro-inflammatory alterations and status of blood plasma iron in a model of blast-induced lung trauma.

Impact of blast shock waves (SW) with the body wall produces blast lung injuries characterized by bilateral traumatic hemorrhages. Such injuries often have no external signs, are difficult to diagnose, and therefore, are frequently underestimated. Predictive assessment of acute respiratory distress syndrome outcome in SW-related accidents should be based on experimental data from appropriate animal models. Blood plasma transferrin is a major carrier of blood iron essential for proliferative "emergency" response of hematopoietic and immune systems as well as injured tissue in major trauma. Iron-transferrin complexes (Fe3+ TRF) can be quantitatively analyzed in blood and tissue samples with low-temperature EPR techniques. We hypothesized that use of EPR techniques in combination with assays for pro-inflammatory cytokines and granulocytes in the peripheral blood and BAL would reveal a pattern of systemic sequestration of (Fe3+)TRF that could be useful for development of biomarkers of the systemic inflammatory response to lung injury. With this goal we (i) analyzed time-dependent dynamics of (Fe3+)TRF in the peripheral blood of rats after impacts of SW generated in a laboratory shock-tube and (ii) assayed the fluctuation of granulocyte (PMN) counts and expression of CD11b adhesion molecules on the surface of PMNs during the first 24 h after SW induced injury. Sham-treated animals were used as control. Exposure to SW led to a significant decrease in the amount of blood (Fe3+)TRF that correlated with the extent of lung injury and developed gradually during the first 24 h. Thus, sequestration of (Fe3+)TRF occurred as early as 3 h post-exposure. At that time, the steady state concentration of (Fe3+)TRF in blood samples decreased from 19.7+/-0.6 microM in controls to 7.5+/-1.3 microM in exposed animals. The levels of (Fe3+)TRF remained decreased throughout the entire study period. PMN counts increased 5-fold and 3.5-fold over controls respectively, at 3 and 6 h postexposure. These effects were accompanied by an increase in expression of CD11b on the surface membrane of PMNs. Extensive release of cytokines IL-1, IL-6, MCP-1, and MIP-2 was observed in BAL fluid and blood plasma during 24 h postexposure. We conclude that EPR monitoring of blood (Fe3+)TRF can be a useful approach for assessment of systemic pro-inflammatory alterations due to SW-induced lung injury.

The use of linezolid in the treatment of vancomycin-resistant enterococcal septicaemia in two patients with burn injuries.

Vancomycin-resistant enterococci (VRE) are multi-resistant micro-organisms that have emerged as important nosocomial pathogens during the last decade. Emergence of this organism has been blamed mainly on the increased and inappropriate use of antibiotics, in particular, the cephalosporins and the glycopeptide, vancomycin. Burns patients are highly vulnerable to acquiring VRE infections, being both debilitated and immunocompromised, and often receiving antibiotics that further diminish their intrinsic microbial flora. We report on two patients with large burn injuries who acquired vancomycin-resistant enterococcal septicaemia during their in-patient stay. Both patients were successfully treated using the antibiotic, linezolid. Linezolid is the first in a new class of antibiotics known as the oxazolidinones whose mode of action inhibits early bacterial protein synthesis. Linezolid has a spectrum of activity against Gram-positive micro-organisms including methicillin-resistant Staphylococcus aureus (MRSA) and VRE, and can provide a useful treatment alternative to the glycopeptides.

Substance P decreases fluid absorption in the renal proximal tubule.

Substance P is a neuropeptide found principally in the central nervous system and peripheral afferent nerve fibers. It is widely distributed in the body, and its local release is thought to have important effects in the normal physiology and pathophysiology of several organ systems. Substance P releases histamine from mast cells and nitric oxide from endothelial cells. Systemic infusion of substance P causes a brisk natriuresis. Previously, proximal tubule transport in the kidney was measured in vivo during the infusion of substance P. Transport was inhibited. This could have been a direct action of substance P or secondary to the release of histamine or nitric oxide. Therefore, we have now studied the effect of substance P on isolated proximal tubules perfused in vitro. We found that 10(-10) M substance P caused a 50% reduction in the rate of fluid absorption in rabbit proximal straight tubule. This effect was reversible on removal of substance P from the bath. Inhibition of nitric oxide production with NG-monomethyl-L-arginine (10(-4) M) did not influence the action of substance P at 10(-10) M. The sensitivity of the proximal tubule to low concentrations of substance P, together with the recent findings of substance P-containing afferent fibers within the cortex of the kidney, suggest a role for substance P in the control of proximal tubule reabsorption, particularly in pathophysiological conditions associated with increased afferent nerve activity, such as ureteric occlusion.

The role of histamine in mediating the decompensatory phase of hemorrhagic shock in the rat.

Our laboratory has previously reported that plasma histamine levels rise significantly and coincidentally with the onset of the decompensatory phase of isobaric hemorrhagic shock in rats. The histamine levels seen in shock were comparable to those that induce profound vasodilatation in many vascular beds under normovolemic conditions. We, therefore, sought to determine whether the elevation in plasma histamine contributes to the cardiovascular collapse seen in the decompensatory phase of hemorrhagic shock. Sprague-Dawley rats were bled according to an isobaric bleeding protocol which maintained the mean arterial blood pressure (MAP) at 40 mmHg until death. Selected H1 (diphenhydramine) and/or H2 (cimetidine and famotidine) antagonists were administered at 75% of the estimated peak shed blood volume (PSBV), a point preceding the rise in plasma histamine. Plasma histamine levels in all groups were similar throughout the time course of hemorrhagic shock. None of the histamine receptor antagonists affected the time of onset or the rate of decompensation. Suspecting that hypotension may alter the animal's response to histamine, we investigated the effect of exogenous histamine administration on MAP before and after hemorrhage. In unbled animals, bolus histamine infusions (.6 mg/kg) dropped the MAP by 62.0 +/- 2.7 mmHg, however, in animals bled to 40 mmHg, histamine dropped the MAP by 7.2 +/- 2.7 mmHg (p = .002). On the basis of the results of these two interventions, we conclude that histamine is not an important mediator of the cardiovascular collapse seen in the decompensatory phase of hemorrhagic shock in the rat.

Renal lymphatic obstruction in diabetic rats induces systemic hypotension.

We obstructed renal lymph drainage from a single kidney in diabetic rats who had received 65 mg/kg streptozotocin 6 months prior to the study. Lymphatic obstruction led to a progressive fall in systematic blood pressure from a mean arterial pressure of 101 +/- 5 (SEM) mm Hg (n = 7) to 62 +/- 4 mm Hg (n = 5) (p < .02) after 1.5 h. No change was seen in a sham-operated animal. Despite the decline in systemic blood pressure there was no significant change in the GFR of either kidney. Sodium excretion increased significantly in the experimental kidney. There was no change in the urinary excretion of cyclic GMP from either kidney, and plasma levels of atrial natriuretic peptide (ANP) did not change (55 +/- 21 pg/mL pre- to 64 +/- 18 postobstruction). The results are consistent with a systemic vasodilatation after lymphatic obstruction. The mechanism of this response is still under investigation, but apparently it does not involve ANP.

Changes in cytochrome oxidation in outer and inner stripes of outer medulla.

To examine regional cytochrome oxidation in the outer medulla, we developed fiber optic probes that allowed us to obtain localized reflectance measurements from the outer and inner stripes of the outer medulla. We measured directional changes in cytochrome oxidation in these two regions. In the outer stripe furosemide surprisingly caused a significant decrease in cytochrome oxidation. The decrease occurred concomitantly with a fall in outer medullary blood flow as measured by laser-Doppler flowmetry. Saralasin, an antagonist of angiotensin II caused a significant increase in cytochrome oxidation in the outer stripe. In the inner stripe furosemide tended to increase cytochrome oxidation, and saralasin had no effect. These results indicate that the two regions of the outer medulla may be affected differently by the same agent. They suggest that cytochrome oxidation in the outer stripe is predominantly influenced by outer medullary blood flow, whereas the inner stripe is predominantly influenced by the rate of oxygen consumption. The advantages and limitations of this methodology are discussed.

Role of postglomerular microvessels in pathophysiology of diabetic nephropathy. Assessment and hypothesis.

Although glomerular damage plays a well-established and important role in the pathomechanism of diabetic nephropathy, it alone does not fully explain the progression of renal complications in long-term diabetes mellitus. We discuss experimental evidence showing involvement of the postglomerular microvessels (peritubular capillaries and venules) in diabetic microangiopathy. This involvement is manifest in increased permeability of these vessels to plasma proteins and in highly augmented lymphatic drainage of the extravasated proteins from the renal interstitium. We suggest that in the advanced phase of diabetic nephropathy, proteinuria (corresponding to excess leakage of proteins through the glomerular capillary wall) indicates the probability that postglomerular microvessels have also allowed leakage of plasma proteins. As long as lymphatic drainage is capable of removing the increased quantity of extravasated plasma proteins from the interstitium, renal function should not be deleteriously affected. However, if the excess amount of extravasated proteins exceeds the capacity of lymphatic drainage, increases in interstitial volume and pressure are unavoidable with detrimental consequences for glomerular filtration and tubular reabsorption. Under these conditions, a potential positive-feedback loop can be visualized that involves increased extravasation of plasma proteins leading to increased interstitial pressure that through dilation of the afferent and efferent arterioles results in a further increase in protein extravasation. These conditions combined with glomerular damage should lead to the eventual collapse of renal function.

Corticosterone is converted to 6 beta-hydroxycorticosterone in rat: effects of the metabolite on urinary electrolyte excretion.

This study was performed to determine whether corticosterone (B), the major glucocorticoid of rat, is metabolized to its 6 beta-OH derivative (6 beta-OH-B) and whether this derivatives has any effects on Na+ or K+ transport in rat kidney. Normal and adrenalectomized (adx) rats were injected with [3H]B and urine was collected for 5 h and examined for metabolites of B. Metabolites were collected by solid phase extraction on mu Bondapak C18 cartridges and fractionated by reversed phase high performance liquid chromatography. Fractions coeluting with 6 beta-OH-B were rechromatographed by normal phase thin layer chromatography. Approximately 5% of the radioactivity recovered from the urine of both intact and adx rats cochromatographed with 6 beta-OH-B on the two systems. Mass spectra of this fraction were virtually identical to those of authentic 6 beta-OH-B, demonstrating that rats do metabolize B to its 6 beta-OH derivative. To evaluate the biological activity of this metabolite, adx rats were injected with NaCl and KCl and with varying dosage of either 6 beta-OH-B or reference steroids (aldosterone, B, 6 beta-OH-F). 6 beta-OH-B produced a significant antinatriuresis at all doses. Kaliuresis occurred only at the highest dose and creatinine excretion increased, suggesting increased glomerular filtration from a glucocorticoid effect. Although 6 beta-OH-B may simply be exerting mineralo- and glucocorticoid actions there are two unexplained findings. First, 6 beta-OH-B (10 micrograms/100 g) significantly decreased urinary K excretion with associated antinatriuresis, an effect which has not been seen with Aldo administration. Second, neither a kaliuretic nor antinatriuretic effect of 6 beta-OH-B could be demonstrated in experiments using a method to enhance mineralocorticoid induced K+ excretion (K+ deprivation and NaCl loading only). Yet, the dose used was clearly antinatriuretic in the initial bioassay. It is concluded that the rat is capable of metabolizing B to its 6 beta-OH-B derivative which appears in substantial quantity in the urine. This metabolite produces antinatriuresis in the adrenalectomized rat.

Control of steady-state pH in rabbit proximal straight tubules.

Steady-state pH (defined as the limiting pH reached at slow flow rates) was measured in isolated perfused rabbit proximal straight tubules (S2). With normal bath conditions (pH 7.4, bicarbonate 25 mM) the luminal steady-state pH was 6.85. Steady-state pH was directly related to bath pH and bicarbonate, but not to bath PCO2. Lowering of bath pH or bicarbonate consistently decreased luminal steady-state pH, and raising either caused steady-state pH to increase. When bath PCO2 was increased, on the other hand, steady-state pH either increased or decreased, depending on the concomitant changes in bicarbonate and pH. The changes in steady-state pH observed in the present studies following alterations in bath pH and bicarbonate concentration should, when extrapolated to the in vivo kidney, result in decreased delivery of bicarbonate from the proximal tubule in acidosis and increased delivery in alkalosis. The effects of potassium and chloride were also determined. Removal of potassium from the bath increased the steady-state pH, but removal of chloride from both the perfusate and bath had no significant effect.

Effect of sodium bicarbonate preloading on ischemic renal failure.

Rats pretreated with sodium bicarbonate were functionally protected from the damage of bilateral renal artery occlusion. The rise in serum creatinine (day 1 minus day 0) during the first 24 h after ischemia was 2.88 +/- 0.28 mg% in the bicarbonate-loaded animals versus 3.90 +/- 0.26 mg% in their matched controls (p less than or equal to 0.01). Pretreatment with acetazolamide produced a similar alkaline urine as the bicarbonate loading (pH 8.3 vs. 7.0 in controls) and a similar degree of protection (delta creatinine 2.85 +/- 0.41 vs. 4.23 +/- 0.26 mg%; p less than or equal to 0.01). A direct effect of sodium loading was excluded by comparing NH4HCO3 with NaHCO3 loading and observing no difference in delta creatinine levels after ischemia (3.39 +/- 0.69 vs. 3.20 +/- 0.61 mg%). These data indicate that NaHCO3 protects in this model of acute renal failure and further suggest that the mechanism of protection is not related to either systemic alkalosis or sodium loading.

Bicarbonate transport by isolated perfused rat collecting ducts.

Previously, bicarbonate transport was measured in isolated perfused rabbit cortical collecting ducts (CCD) and outer medullary collecting ducts (OMCD). Rabbit CCD either absorbed or secreted bicarbonate in vitro, depending on whether the animals were treated with NH4Cl or NaHCO3, but the OMCD absorbed bicarbonate regardless of the treatment. The general significance of these findings (particularly the bicarbonate secretion) was questioned because rabbits are herbivores that normally excrete alkaline urine. Therefore, we have now studied rats, an omnivorous species, that normally excrete acid urine. The overall pattern of bicarbonate transport in rats was similar to that previously found in rabbits. CCD from rats given NaHCO3 initially secreted bicarbonate, but those from rats given NH4Cl absorbed bicarbonate. Rat OMCD all absorbed bicarbonate, regardless of the treatment. The significant differences between the results with rats and rabbits were 1) a marked shift in bicarbonate transport in control and bicarbonate-loaded rat (but not rabbit) CCD with time of perfusion in vitro from secretion toward absorption; this implies an additional regulatory mechanism in rats; and 2) rat OMCDs absorbing bicarbonate more than three times faster than rabbit OMCD. These results provide additional evidence that conditioned changes in cortical collecting duct bicarbonate transport, now observed in two different species, play a significant role in the control of net acid excretion.