Early respiratory manifestations of severe burn patient.

Respiratory dysfunction with hypoxemia is common in early phase of severe burn, with or without smoke inhalation injury. In this article, we discuss the mechanisms associated with the occurrence of pulmonary injury in burn intensive care patients, diagnostics approaches and therapeutics options to be implemented based on identified causes.

Une défaillance respiratoire avec hypoxémie est fréquemment observée dans les jours suivant la survenue d'une brûlure grave, qu'il y ait eu inhalation de fumée d'incendie ou non. Dans ce texte, nous discuterons les mécanismes associés à la survenue d'une atteinte pulmonaire chez les patients graves, les démarches diagnostiques et les options thérapeutiques à mettre en oeuvre en fonction des causes identifiées.

Brûlures Profondes Des Membres Inférieurs Chez Les Patients Diabétiques: À Propos De 30 Cas.

We checked the files of 30 inpatients with diabetes and deep burns to the lower limbs. We looked for a diabetes-related neuropathy (60% had one), the context of the accident, the topography of burns, any delays before the first and possible subsequent surgeries, the length of stay, and return to walking, if achieved. Burns mostly involved distal parts of the lower limbs, were thermal in 90% with an intentional action in 43%, and frequently occurred in a bathing room (48%) during a footbath (54%). Mean time to the first surgery was day 3,35 and, when needed, the second one was performed 6,54 days later. Mean LOS was 14,6 days, eleven patients were walking again by this time. We found a significant (p<0.001) association between the time to the 1st surgery and time elapsed between the burn and hospitalization. The existence of a diabetes-related neuropathy is a risk factor of lower limb burns, provided it suppresses the alarm of pain. Early surgery seems to reduce the LOS.

Repair Of Palm Burns Of The Hand: A Contralateral Inner Arm Bag-Shaped Flap.

Hands are one of the most often burnt parts of the body. Deep palmar burns are often the result of an electrical burn or a thermal burn from grasping a hot item. With a deep burn, joints, vasculo-nervous pedicles, tendons or bones can become exposed and lead to amputation. Different surgical repair methods are used depending on the area of the hand that is burnt. Most of the publications to date have described surgical techniques for dorsal hand burns. The abdominal bag-shaped flap is one of the main surgical techniques to cover dorsal deep tissue exposure. Bag-shaped flaps need time to achieve the vascular autonomy of the flap without any movement. Abdominal bagshaped flaps are particularly suitable for dorsal soft-tissue defects, while for palmar defects, it is an uncomfortable position to maintain for three weeks. A contralateral arm bag-shaped flap for palmar burns allows a comfortable position to be achieved as the upper burnt limb is positioned as if the patient has their arms crossed. Furthermore, as stated above, the contralateral arm bag-shaped flap has the advantage of allowing a flap to be used that is thinner than an abdominal bag-shaped flap. At the Saint Louis Burns Center, we recently treated two patients with deep palmar burns and deep tissue exposure. We performed a contralateral arm bag-shaped flap for both of these patients. In our experience, the use of the contralateral arm bag-shaped flap technique to cover palmar lesions resulted in favorable postoperative progression, with complete closure of the lesions, good functional outcomes, as well as other advantages such as a hidden scar at the donor site. This technique allows amputation of fingers to be avoided when pedicles, joints, or tendons are exposed and when the burnt area of the palm is extensive and no other flaps can be used.

Les brûlures surviennent fréquemment au niveau des mains. Les brûlures profondes de la face palmaire des mains sont souvent secondaires à des brûlures électriques ou à des contacts sur des solides chauds. À la suite d'une brûlure profonde, les articulations, les pédicules vasculonerveux, les tendons ou les os peuvent être exposés, conduisant à des indications d'amputation. Différentes techniques de chirurgie réparatrice peuvent être utilisées, en fonction de la zone anatomique brûlée. La plupart des publications décrivent des techniques de couverture des brûlures de la face dorsale de la main. Le lambeau d'empochement abdominal est l'une des principales techniques décrites pour la couverture des pertes de substance profondes de la face dorsale de la main. Ces lambeaux d'empochement nécessitent une immobilisation stricte pour permettre une revascularisation anatomique du lambeau. Si ces lambeaux d'empochement abdominaux sont une très bonne indication pour les pertes de substance de la face dorsale de la main, la position est particulièrement inconfortable à maintenir trois semaines pour les faces palmaires. Un lambeau d'empochement à la face interne du bras controlatéral pour les brûlures palmaires de la main permet de maintenir une position confortable, comme si le patient avait les bras croisés. De plus, le lambeau d'empochement sur la face interne du bras controlatéral a l'avantage de fournir un lambeau plus fin que le lambeau d'empochement abdominal. Au centre de brûlés de Saint-Louis, nous avons récemment traité deux patients présentant des brûlures profondes de la face palmaire de la main et avec exposition de tissus nobles. Nous avons réalisé un lambeau d'empochement du bras controlatéral pour chacun de ces patients. Dans notre expérience, cette technique d'empochement des lésions palmaires a permis une couverture complète, de bons résultats fonctionnels et, a l'avantage que la cicatrice du site donneur est peu visible. Cette technique permet d'éviter des amputations digitales en cas d'exposition articulaire, tendineuse ou pédiculaire lorsque la surface palmaire brûlée ne permet pas l'utilisation d'autres lambeaux.

Prise en charge du patient brûlé en préhospitalier. Première partie : cas général et inhalation de fumées.

Severe burn is a circumstantial pathology, most often accidental but more and more caused by voluntary acts. In the initial phase, the failures encountered are essentially hemodynamic, respiratory and metabolic, placing the emergency physician and the intensivist at the centre of medical care. The role of the pre-hospital physician is essential but often difficult due to the circumstances of intervention. First actions and treatments initiated as well as the evaluation of gravity can favorably modify the prognosis when they are well carried out. In view of this, we will unfold the different stages of pre-hospital care to implement in the event of severe burn.

Involvement of the cytoskeleton in the steroidogenic response of frog adrenal glands to angiotensin II, acetylcholine and serotonin.

In order to determine the role of the cytoskeleton in adrenal steroidogenesis, we have studied the effect of cytochalasin B (a microfilament-disrupting agent) and vinblastine (an antimicrotubular drug) on corticosteroid secretion by frog interrenal tissue in vitro. Perifusion of interrenal fragments with cytochalasin B (50 mumol/l) induced a marked inhibition of basal corticosteroid output. In addition, stimulation of corticosteroidogenesis by all corticotrophic factors was also inhibited by cytochalasin B. Using an immunohistochemical technique and specific anti-tubulin antiserum, we verified that vinblastine (10 mumol/l) was responsible for the disappearance of the microtubular network in adrenocortical cells. Administration of vinblastine (10 mumol/l) did not affect the spontaneous secretion of corticosterone and aldosterone and had no effect on the steroidogenic response of interrenal glands to angiotensin II and acetylcholine. In contrast, vinblastine was responsible for a marked decrease in serotonin-induced stimulation of corticosteroid production. On the other hand, data from high-performance liquid chromatography showed that infusion of cytochalasin B or vinblastine was not associated with the production of any new steroid which could interfere in the radioimmunoassays. Taken together, these data suggest that microfilaments are involved in a late and common step of corticosteroidogenesis while microtubules are only required for the coupling of the secretory response to certain corticotrophic factors such as ACTH and serotonin.

Acetylcholine stimulates steroidogenesis in isolated frog adrenal gland through muscarinic receptors: evidence for a desensitization mechanism.

The effect of cholinergic agonists on glucocorticoid and mineralocorticoid production by frog interrenal (adrenal) tissue was studied in vitro by means of continuous perifusion. Acetylcholine, at doses ranging from 1 to 100 mumol/l, stimulated both corticosterone and aldosterone output in a dose-dependent manner, with a half-maximal effective dose of 2.5 mumol/l. Corticosteroid production was also stimulated by muscarine (10 mumol/l). In contrast, neither nicotine nor nicotine bitartrate (1-100 mumol/l) enhanced corticosteroid biosynthesis. The kinetics of the response of adrenal cells to acetylcholine and muscarine were similar to those observed during angiotensin II stimulation. In particular, a significant reduction (20-40%) in the spontaneous level of corticosteroid production was recorded after the initial infusion of muscarinic agents, but no further decrease in the basal level occurred after a second cholinergic administration. The effect of acetylcholine was blocked by the muscarinic receptor antagonist atropine (10 mumol/l). These results indicate that acetylcholine can stimulate frog adrenocortical cells through muscarinic receptors. Repeated 20-min pulses of acetylcholine (50 mumol/l) or muscarine (10 mumol/l), given at one pulse per 130 min, resulted in a marked reduction in the secretory response to the second pulse. No reduction in the stimulatory effect of acetylcholine or muscarine was observed when a 6.5-h interval separated two 20-min infusions of the secretagogue. In contrast with these findings, iterative pulses of the muscarinic agonist pilocarpine (in the range 1-100 mumol/l) did not cause any desensitization. These data show that the neurotransmitter acetylcholine can modulate frog adrenocortical function and suggest that, in addition to more conventional regulators, i.e. ACTH and angiotensin II, the cholinergic endings of the splanchnic nerve might participate in the regulation of corticosteroid secretion, at least under some physiological conditions such as neurogenic stress.

Immunohistochemical and biochemical evidence for the presence of the pentapeptide met-enkephalin and the heptapeptide met-enkephalin-Arg(6)-Phe(7) but not the octapeptide met-enkephalin-Arg(6)-Gly(7)-Leu(8) in amphibian chromaffin cells.

Using specific antibodies to met-enkephalin, met-enkephalin-Arg(6)-Phe(7) and met-enkephalin-Arg(6)-Gly(7)-Leu(8), we have studied the distribution of these opioid peptides in the frog adrenal gland by means of the indirect immunofluorescence technique. Bright staining of all chromaffin cells was observed by application of met-enkephalin and met-enkephalin-Arg(6)-Phe(7) antisera. No nerve endings could be detected. A few chromaffin cells were weakly stained by met-enkephalin-Arg(6)-Gly(7)-Leu(8) antiserum. Using a specific radioimmunoassay for met-enkephalin, the dilution curve of frog adrenal extracts was parallel to that of synthetic met-enkephalin. The concentration of met-enkephalin-like material measured in crude acetic extracts of frog adrenals (2.31 +/- 0.16 pmol/mg w. wt) was high when compared to those reported for most mammalian species. No leu-enkephalin and virtually no met-enkephalin-Arg(6)-Gly(7)-Leu(8) were detected by the corresponding radioimmunoassays. Reverse phase HPLC analysis revealed that oxidized met-enkephalin was the main form of met-enkephalin detected in acetic extracts of frog adrenals. HPLC separation showed the presence of a peptide co-eluting with synthetic met-enkephalin-Arg(6)-Phe(7). Higher molecular weight forms were also separated by HPLC. These results show the presence of both met-enkephalin and the heptapeptide met-enkephalin-Arg(6)-Phe(7) and the lack of met-enkephalin-Arg(6)-Gly(7)-Leu(8) in frog chromaffin cells.

Localization and identification of neuropeptide Y (NPY)-like immunoreactivity in the frog brain.

The distribution of neuropeptide Y (NPY) in the central nervous system of the frog Rana ridibunda was determined by immunofluorescence using a highly specific antiserum. NPY-like containing perikarya were localized in the infundibulum, mainly in the ventral and dorsal nuclei of the infundibulum, in the preoptic nucleus, in the posterocentral nucleus of the thalamus, in the anteroventral nucleus of the mesencephalic tegmentum, in the part posterior to the torus semicircularis, and in the mesencephalic cerebellar nucleus. Numerous perikarya were also distributed in all cerebral cortex. Important tracts of immunoreactive fibers were found in the infundibulum, in the preoptic area, in the lateral amygdala, in the habenular region, and in the tectum. The cerebral cortex was also densely innervated by NPY-like immunoreactive fibers. A rich network of fibers was observed in the median eminence coursing towards the pituitary stalk. Scattered fibers were found in all other parts of the brain except in the cerebellum, the nucleus isthmi and the torus semicircularis, where no immunoreactivity could be detected. NPY-immunoreactive fibers were observed at all levels of the spinal cord, with particularly distinct plexus around the ependymal canal and in the distal region of the dorsal horn. At the electron microscope level, NPY containing perikarya and fibers were visualized in the ventral nuclei of the infundibulum, using the peroxidase-antiperoxidase and the immunogold techniques. NPY-like material was stored in dense core vesicles of 100 nm in diameter. A sensitive and specific radioimmunoassay was developed. The detection limit of the assay was 20 fmole/tube. The standard curves of synthetic NPY and the dilution curves for acetic acid extracts of cerebral cortex, infundibulum, preoptic region, and mesencephalon plus thalamus were strictly parallel. The NPY concentrations measured in these regions were (pmole/mg proteins) 163 +/- 8, 233 +/- 16, 151 +/- 12 and 60 +/- 13, respectively. NPY was not detectable in cerebellar extracts. After Sephadex G-50 gel filtration of acetic acid extracts from whole frog brain, NPY-like immunoreactivity eluted in a single peak. Reverse phase high performance liquid chromatography (HPLC) and radioimmunoassay were used to characterize NPY-like peptides in the frog brain. HPLC analysis revealed that infundibulum, preoptic area and telencephalon extracts contained a major peptide bearing NPY-like immunoreactivity. The retention times of frog NPY and synthetic porcine NPY were markedly different. HPLC analysis revealed also the existence, in brain extracts, of several other minor components cross-reacting with NPY antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuronal and paracrine regulation of adrenal steroidogenesis: interactions between acetylcholine, serotonin and vasoactive intestinal peptide (VIP) on corticosteroid production by frog interrenal tissue.

The adrenocortical cells of frog interrenal (adrenal) tissue are controlled by multiple factors. Recently, we have shown that corticosteroidogenesis is stimulated by acetylcholine released from splanchnic nerve terminals as well as by serotonin and vasoactive intestinal peptide (VIP) which are both contained in chromaffin cells. Since these 3 putative neuroregulators are known to interact with each other on various target organs, we have investigated possible coordinate actions of acetylcholine, serotonin and VIP on adrenal steroid production, using a perifusion system technique for frog interrenal tissue. Simultaneous infusion of submaximal doses of VIP (10(-5) M) and acetylcholine (5 X 10(-5) M) induced stimulations of corticosteroids (corticosterone and aldosterone) which were strictly additive. When VIP (10(-5) M) and serotonin (5 X 10(-6) M) were infused together, a potentiation of the individual responses was observed. In contrast, concomitant infusion of acetylcholine (5 X 10(-5) M) and serotonin (5 X 10(-6) M) caused a total blockage of the stimulatory effect of serotonin. Muscarine (10(-5) M) caused a similar blockade of the response of adrenocortical cells to serotonin while nicotine (5 X 10(-5) M) did not alter the stimulatory effect of serotonin. The inhibitory effect of acetylcholine on serotonin-induced steroidogenesis was antagonized by atropine (10(-5) M). Thus, acetylcholine appears to block the corticotropic action of serotonin by interacting with typical muscarinic receptors. Taken together our results indicate that 3 of the neuroregulators which participate in the control of adrenal steroidogenesis, namely acetylcholine, serotonin and VIP, may interact on their target cell to modulate the activity of their congeners.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization and identification of alpha-melanocyte-stimulating hormone (alpha-MSH) in the frog brain.

The distribution of alpha-melanocyte-stimulating hormone (alpha-MSH) in the central nervous system of the frog Rana ridibunda was determined by immunofluorescence using a highly specific antiserum. alpha-MSH-like containing perikarya were localized in the infundibular region, mainly in the ventral hypothalamic nucleus. A rich plexus of immunoreactive fibers directed towards the ventral telencephalic region was detected. Reverse-phase high-performance liquid chromatography and radioimmunoassay were used to characterize alpha-MSH-like peptides in the frog brain. Chromatographic separation revealed that immunoreactive alpha-MSH coeluted with synthetic des-N alpha-acetyl alpha-MSH, authentic alpha-MSH and their sulfoxide derivatives. The heterogeneity of alpha-MSH-like material in the frog brain was in marked contrast with the figure observed in the intermediate lobe of the pituitary gland where only des-N alpha-acetyl alpha-MSH is present. These findings support the existence of discrete alpha-MSH immunoreactive neurons in the frog brain containing both desacetyl and authentic alpha-MSH.

Neuropeptide Y in the intermediate lobe of the frog pituitary acts as an alpha-MSH-release inhibiting factor.

The presence of neuropeptide tyrosine (NPY) in the intermediate lobe of the frog pituitary was demonstrated using indirect immunofluorescence, the immunogold technique and a specific radioimmunoassay combined with high pressure liquid chromatography (HPLC). A high density of NPY-containing fibers, was found among the parenchymal cells of the intermediate lobe. These fibers originated from the ventral infundibular nucleus, travelled via the median eminence to the pars intermedia. At the electron microscopic level, NPY-like material was found exclusively in nerve fibers where the product of the immunoreaction was associated to dense-core vesicles. High concentrations of NPY-like peptide were found in neurointermediate lobe extracts. After Sephadex G-50 gel filtration the major peak of immunoreactive material appeared to co-elute with synthetic porcine NPY. Conversely, HPLC analysis revealed that the NPY-like peptide of the frog pituitary had a retention time shorter than the porcine NPY. The localization of NPY-like material in the pars intermedia suggested a possible role of NPY in the regulation of melanotropic cell secretion. In fact, graded concentrations of synthetic NPY induced a dose-dependent inhibition of alpha-melanotropin (alpha-MSH) release in vitro. The lack of effect of a dopaminergic antagonist on NPY-induced alpha-MSH release inhibition demonstrated that the local dopaminergic system could not account for the NPY action. These results indicate that NPY located in the hypothalamo-hypophyseal system of the frog may act as a melanotropin-release inhibiting factor.

[Localization and identification of neuropeptide Y (NPY) in the brain of an anuran amphibian]. / Localisation et identification du neuropeptide tyrosine (NPY) dans le cerveau d'un amphibien anoure.

A neuropeptide Y (NPY)-like peptide has been localized in the frog brain by the direct immunofluorescence method. Subcellular localization of NPY has been studied by PAP immunocytochemistry and the immunogold technique. Using a specific radioimmunoassay technique, NPY-like peptide has been quantified in various brain areas and the immunoreactive material was characterized by Sephadex G-50 gel filtration and high performance liquid chromatography. The results indicate that frog NPY is closely related to the porcine molecule and largely distributed in the frog brain. This peptide may play both neurotransmitter and neuroendocrine functions in amphibia.

Effects of candidaemia on outcome of burns.

AIM: To evaluate the diversity and antifungal susceptibilities of Candida isolates from wounds and blood of burn victims, and the associated mortality rates compared with those of controls without candidaemia. METHODS: We performed a nested case-control study within a database of clinical data for all patients admitted to our burn unit from January 2001 to December 2005. Each candidaemic patient was compared with two matched controls. Bloodstream cultures were performed if the core temperature was >39 degrees C, and three sites were cultured weekly for fungal identification (burn wound, pharynx, urinary tract). RESULTS: At least one episode of candidaemia was diagnosed among 20 of 851 persons admitted during the study period. Isolates in bloodstream infection were Candida albicans (65%), C. parapsilosis (25%) and C. tropicalis (10%). The median time between admission and onset of candidaemia was greater with C. albicans infection (42.6+/-31 days) than with infection by other yeasts (18+/-12 days). Candidaemia was associated with more extensive burn and longer duration of hospital stay but with similar mortality, compared with controls. CONCLUSION: Candidaemia in burn cases is mostly due to fluconazole-susceptible C. albicans and is not associated with increased mortality.

Case report: cytomegalovirus primoinfection may be associated with severe outcome in burns.

We report two cases of severe cytomegalovirus (CMV) primoinfection in seriously burned patients. The infection may have contributed to both patients' fatal outcome. This underlines the importance of research in viral aetiology, especially with regard to CMV, when immunodeficient patients - as burn patients are - develop unexplained fever. We propose a monitoring and a prevention strategy for CMV in the most severely burned patients. The prevention strategy involves the use of skin allografts and blood products in seronegative patients. CMV infection should not be underestimated in severely burned patients.

Effect of the intermediate filament inhibitor IDPN on steroid secretion by frog adrenal glands.

In order to determine the role of intermediate filaments in adrenal steroidogenesis, we have studied the effect of IDPN (beta-beta'iminodipropionitrile), an intermediate filaments perturbing agent, on corticosteroid secretion by frog interrenal glands in vitro. A 6-h administration of IDPN (10(-3) M) did not affect the spontaneous release of corticosterone and aldosterone. While IDPN did not alter the response of adrenal fragments to ACTH, the drug caused a marked decrease in angiotensin II-induced stimulation of corticosterone and aldosterone production. These results indicate that, in contrast to microfilaments, which play an important role in spontaneous steroidogenesis, intermediate filaments are not required for basal corticosteroid secretion but are involved in the mechanism of action of angiotensin in frog adrenocortical cells.

[Role of microtubules in adrenal gland steroidogenesis]. / Rôle des microtubules dans la stéroïdogénèse surrénalienne.

In order to determine the role of the microtubular network in adrenal steroidogenesis, we have studied the effect of vinblastine, a potent antimicrotubular agent on corticosteroid secretion by frog adrenocortical fragments in perifusion. Administration of vinblastine (10(-5) M) did not alter the spontaneous secretion of corticosteroids and had no effect on the steroidogenic response to angiotensin II and prostaglandin E1. In contrast, vinblastine induced a marked decrease in ACTH-induced stimulation of corticosteroidogenesis. To investigate further the site of action of the microtubular system in ACTH-induced steroidogenesis we have studied the effect of vinblastine on the different steps of the stimulation of the adenylate cyclase system. Our results show that vinblastine does not alter the stimulatory action of cAMP, the second messenger of ACTH. In addition, the corticosteroidogenic effect of forskolin and NaF (which respectively stimulate the adenylate-cyclase subunit and the guanyl nucleotide regularly protein) was not affected by vinblastine. These results indicate that the microtubular network interferes in the coupling of the secretory response of the adrenal glands to ACTH, either at the level of the binding of ACTH to its receptor or in the coupling of the receptor to the guanyl nucleotide regulatory protein.

[Alpha-melanotropin in the frog brain: regional distribution, quantification and subcellular distribution]. / L'alpha-mélanotropine dans l'encéphale de la grenouille: régionalisation, quantification et distribution subcellulaire.

The distribution of alpha-MSH containing neurons was studied by immunofluorescence in the brain of the frog Rana ridibunda. Most immunoreactive cell bodies were found in the ventral hypothalamic area. A rich network of fluorescent fibers was observed in the ventral infundibular region, coursing towards the preoptic area and the ventral telencephalon. Some fibers, directed backwards, project into median eminence. By means of a specific radioimmunoassay, the concentrations of alpha-MSH immunoreactive material has been determined in 10 different regions of the brain. The highest concentrations were observed in the infundibular and the preoptic regions. Using the immunogold technique, electron microscopy showed that immunostaining was restricted to 70-100 nm dense core vesicles in positive cell bodies and fibers. These results suggest that, in addition to well known hormonal (melanotropic) activity, alpha-MSH could play the role of a neurotransmitter in the frog brain.

Involvement of prostaglandins in the response of frog adrenocortical cells to muscarinic receptor activation.

The role of prostaglandins (PGs) in the mechanism of action of acetylcholine (ACh) on frog adrenocortical cells has been examined. Administration of a single dose of ACh (5 X 10(-5) M) to perifused frog interrenal fragments, for 20 min, stimulated the production of corticosterone, aldosterone, PGE2 and 6-keto-PGF1 alpha. In contrast ACh did not significantly alter TXB2 production. The effect of ACh could be mimicked by muscarine (10(-5) M). Conversely, nicotine (10(-6) to 10(-4) M) was totally inactive. The increase in PG biosynthesis preceded the peak of corticosteroid release. Repeated 20-min pulses of ACh (5 X 10(-5) M) or muscarine (10(-5) M) given at 130-min intervals induced a desensitization phenomenon. In presence of indomethacin (5 X 10(-6) M), the effect of ACh on PG and steroid secretion was totally abolished. In calcium-free medium, the effect of ACh on PG and corticosteroid production was completely blocked. These results indicate that, in the frog, ACh stimulates corticosteroid secretion through a PG-dependent mechanism.