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T. Peer. Georgia Institute of Technology.

Este consta de dos etapas: en la primera se realiza la corrección de la orientación y centrado de los cortes en los planos coronal y transversal a partir de la maximización de dos índices de simetría inter­ hemisférica purchase 400 mg viagra plus free shipping, y en la segunda se corrige la orientación en el plano sagital a partir de la deter­ minación automática del ángulo de inclinación de las imágenes en el plano sagital 400 mg viagra plus overnight delivery, calculado por el ajuste lineal de los puntos de una curva discount 400 mg viagra plus with amex, que es definida por el borde inferior del encéfalo en la imagen formada por la superposición de los cortes en el plano sagital order viagra plus 400 mg with mastercard. Con este valor, y conociendo la posición del plano órbito meatal (O-M) a partir de un estudio de calibra­ ción realizado previamente, se hace la corrección por rotación en el plano sagital. Para la valoración de este método se estudió a 20 pacientes, y se examinó un juego de imágenes simuladas con lesiones únicas y múltiples (software phantom). La reorientación y centrado de las imágenes en los tres planos arrojó resultados satisfactorios, presentando un error menor que 1,4° en la reorientación, y menor que 0,5 pixeles en el centrado. La orientación y centrado de estos estudios tienen una importancia preponderante ya que permiten obtener niveles de cortes predeterminados que son comparados con patrones conocidos de perfusión, los cuales son utilizados como referencia para evaluar los resultados. La exactitud en el cálculo de índices relativos de perfusión interhemisférica a través de regiones de interés, también requiere de un adecuado centrado y alineamiento de las imágenes. Existen varios métodos empleados para garantizar una adecuada orientación y centrado de estas imágenes. Algunos de estos procedimientos consisten en posicionar la cabeza del paciente de tal forma que el plano orbito-meatal sea perpendicular al plano del detector y, otros, en reorientar las imágenes después de procesadas por “ software” de forma interactiva. Estos métodos son muy inexactos y tienen una gran dependencia de las habilidades y experiencias del operador, aunque en la actualidad se emplean sistemas con posicionamiento por láser con los que se logra una gran exactitud. Se adquireron 128 proyecciones de 15 s cada una, en formato de 64 X 64 y zoom de 1,14. La reconstrucción de los cortes transversales se realizó empleando el método de la retroproyección filtrada (filtro Butterworth 4/16) y fueron recons­ truidos cortes sagitales y coronales en un volumen de 64 x 64 x 64. Confección de los program as Para la reorientación y centrado de las imágenes se utilizó un conjunto de programas que ejecutan el realineamiento total del volumen. Orientación y centrado en los planos transversal y coronal En primer lugar se realiza el centrado del volumen y la reorientación en los planos transversal y coronal. El centrado inicial se efectúa tomando como base el centro geométrico del volumen. Posteriormente, el algoritmo asume una simetría grosera entre ambos hemisferios para determinar los valores óptimos de corrección de traslación y rotación a partir de la maximización de dos índices de similitud interhemisférica obtenidos empleando dos criterios. Este consiste en maximizar la suma de los cambios de signo en la imagen creada por la substrac­ ción de las imágenes que son comparadas. Calculando el número de cambios de signos de la resta de estas imágenes, se obtiene un índice de similitud entre ambos hemis­ ferios cuyo valor máximo se obtendrá cuando el volumen esté adecuadamente centrado y orientado en los planos sagital y coronal. El índice de similitud calculado estará en correspondencia con el número de pares de puntos simétricos que presentan diferencias no significativas. Este será máximo cuando el plano sagital medio coincida con el plano sagital medio del cerebro. Para la busqueda de este plano, empleando los dos criterios anteriormente expuestos, se calculan los máximos de estos índices de similitud entre diversas com­ binaciones de traslación y rotación de las imágenes. Orientación de las imágenes en el plano sagital La reorientación de las imágenes en el plano sagital se basa en calcular el ángulo de inclinación del volumen en este plano. Esto se logra a partir de una curva que se ajusta al borde inferior del encéfalo en el plano sagital, calculada de la imagen formada por la superposición de los cortes en este plano (Fig. Para la obten­ ción de dicha curva, esta imagen es recentrada en su centro de gravedad y llevada a coordenadas polares, obteniéndose su contorno inferior con búsquedas radiales de isocontornos y empleando condiciones de contorno (Fig. Se utilizaron condiciones de extremo para obtener los límites del intervalo de la curva que es empleado. Los valores de ésta se ajustan a una recta empleando el método de regre­ sión por mínimos cuadrados y el valor de su pendiente se usa para calcular el ángulo que debe ser rotado el volumen en este plano para ser llevado a la posición final deseada. En nuestro caso, el volumen es rotado hasta una posición en que los cortes transversales son paralelos al plano órbito meatal (O-M). Adicionalmente, se cal­ cularon los coeficientes de correlación (r) con el objetivo de dicernir la bondad del ajuste lineal (Fig. Luego de la reconstrucción de los cortes tomográficos, los estudios fueron reorientados de forma manual e interactiva hasta lograr que los cortes transversales fuesen paralelos al plano O-M (definido por las cuatro fuentes puntuales). En esta posición se calculó el ángulo de inclinación del volumen empleando la metodología anteriormente expuesta y se determinó el valor medio obtenido entre los 10 sujetos estudiados. Este valor es empleado por el “ soft­ ware” como inclinación final del volumen que define la condición de paralelismo entre los cortes transversales y el plano O-M. La reorientación y centrado de estas imágenes en los planos transversal y coronal fueron evaluadas de forma visual por tres observadores independientes. Estas imágenes fueron rotadas en los tres planos y descentradas hasta alcanzar 50 combinaciones. Los ángulos y desplazamientos empleados fueron registrados para corroborar los resultados de las correcciones realizados por el algoritmo. Los cortes realineados tras la corrección fueron comparados con los originales y se calcularon los valores medios de los errores tanto del centrado como de la reorientación en estos dos planos. En la valoración de los resultados se emplearon análisis de correlación y tests de comparación de medias y varianzas muéstrales. Esto fue corroborado a través del cálculo de los valores medios de los errores obtenidos en el proceso de realineamiento. Estudio de calibración Se corroboró que existe una dependencia lineal entre los puntos que forman el contorno inferior del encéfalo, a través de su análisis en los 20 pacientes seleccionados para la validación del método. En todos se obtuvieron coeficientes de correlación r >0,85 y un número de puntos n > 20 en cada curva analizada. Esto confirma que estos puntos tienen una dependencia lineal con un nivel de significación a = 0,05. Se calculó que la inclinación que debe tener el volumen para lograr la condición de paralelismo entre el plano O-M y los cortes transversales es de -9 ,8 ° ± 0,9° (valor medio ± desviación estándar). Validación de la reorientación El valor medio de los ángulos obtenidos tras la rotación para cada uno de los 20 paciente estudiados fue de -9 ,9 ° ± 0,6°. No se encontraron diferencias significativas entre ambas magnitudes, lo que habla en favor de la exactitud del algoritmo propuesto. La comparación de las varianzas de los resultados finales de las rotaciones se realizó por el test de Cochran, sin que se detectaran diferencias significativas (a = 0,05) entre ellas. La corrección de rotación en el plano sagital reportó resultados satisfactorios, aunque consideramos que el estudio de calibración para determinar la posición del plano orbito meatal debe ser ampliado con el fin de obtener resultados más exactos. These radionuclides can be incorporated position specifically into a variety of tracer molecules. Upon ß + emission, two annihilation photons are emitted at 180° from each other, making it possible to measure quantitatively the radioactivity concen­ tration, for example by a positron camera. Since some of these are radionuclides of elements common in biomolecules, the potential is very great for developing many tracer molecules by synthetic labelling chemistry. They are all produced by nuclear reactions using charged particle accelerators with protons or deuterons. Despite the short half-life, synthetic methods and techniques are available to produce radiopharmaceuticals labelled with some of these radi­ onuclides in a controlled way, allowing routine production of a large number of radiotracers with application potential in many areas. The selection of the tracers has of course to be made in relation to the question addressed. Here, considerations regarding stereochemistry, the position of the label or the use of multiple labelling can give the most valuable information. The high specific radioactivity and the short half-lives allow the design of experimental pro­ tocols utilizing combinations of such short lived positron emitting tracer molecules in multitracer studies. The design aspects of the radiotracer with respect to which radionuclide to choose, what position to label, which stereochemical form to use or by combining multiple isotopic labelling are becoming more and more important. In this perspective, the selection of synthetic strategies useful for the routine production of radiotracers is important. Special emphasis has to be placed on the development of precursors and on which synthetic pathways to select. The determi­ nation of radionuclidic, optical and chemical purity, as well as specific radioactivity, are essential factors in combination with the technical procedures used. Using these labelled starting materials, a large number of other labelled precursors can be produced, allowing more or less sophisticated synthetic strategies to produce the appropriate labelled tracers. In designing selected labelled tracer molecules, factors such as: the appropriate stereochemistry and what position to label are two important considerations [1-3] (Table П), and some of these points will be discussed. So far, both enantiomers of a chiral tracer have been applied in studies to verify stereoselective interactions and, if used with caution, this approach might be of value also from the modelling point of view. However, the interpretation of such data has to be performed very carefully, since the so-called non-active enantiomer of the two antipodes might have different protein binding profiles and/or metabolism. One example is the binding of the two enantiomers of nomifensine, which have different profiles for the dopaminergic re-uptake sites and the adrenergic receptors. In Table in [4-10], some examples of n C labelled enan­ tiomers applied in multiple modality studies (multiple tracer protocols) are presented. When tracers are designed to visualize metabolism, it is important to know in which position to place the radiolabel. The label in the carboxy position in L-dopa yields as a product labelled carbon dioxide, while the label in the carbon skeleton, such as in the ß position, gives as a product labelled dopamine. The label in the carboxy position in L-dopa will yield as a product labelled carbon dioxide, while the label in the carbon skeleton, for example the ß position, will give as a product labelled dopamine, which is illustrated in Fig. Scheme illustrating the fate of the label with regard to the conversion ofpyruvic or lactic acid in the energy producing pyruvate dehydrogenase or lactate dehydrogenase steps to yield acetate for the citric acid cycle. In recent years, there have been significant advances in n C and 18F precursor synthesis. Some of these labelled precursors have already been established so that they are now considered routine tools when looking for synthetic pathways to label interesting molecules. For example, a large number of receptor ligands can be labelled by a synthetic procedure involving alkylation reactions on various substrates, such as the appropriate amine, amide, sulphide, alkoxide, carboxylate, carbanion and phosphonium nucleo­ philes [1-3]. Recently, a useful electrophilic one-carbon n C labelled precursor has been made available by the conversion of n C-cyanide to cyanogenbromide [20-22]. This is interesting because the reversal of polarity of cyanide has created a new type of cyanide molecule with different properties. With this precursor a new set of reactions and functional group transformations can be achieved and it has opened new possibil­ ities for the labelling of macromolecules, such as proteins and carbohydrates with n C, even if 18F with a longer half-life is more interesting with regard to the poten­ tial of matching the longer biological half-lives which are related to macromolecules. Illustration o f the multifunctional precursor approach through a scheme which produces the labelled pyruvic acid as a general synthon for the synthesis of 11С labelled lactic acid, L-tyrosine, L-dopa, tryptophane and S-hydroxytryptophane. M ultifu nction al precursors There have been developments in various directions and examples of multi­ functional precursors are shown, such as n C-halonitrile [23, 24]. This multifunc­ tional precursor has shown to be useful in the synthesis of various substituted phenylalanine and tryptophane compounds [12, 13, 15]. Optimization of the time parameter with respect to reaction times and purification procedures is thus essential. Furthermore, the search for techniques and methods supporting one-pot or flow-reactor systems in miniaturized versions is also very important. From the radiation safety point of view, the development of remote handling techniques using automation, e. The tomographic technique allows imaging of the radiotracer disposition in slices of the body of the object and measurements of the change of radioactivity in the tissue with time. The method gives accurate quantitative measurements of parameters relat­ ing to physiological processes in the tissue, such as blood flow, pH, energy metabolism, protein synthesis rate and cell proliferation. Furthermore, radiolabel­ ling of enzyme substrates will give information on the function of enzymes, such as neurotransmitter synthesis via decarboxylation of the appropriate amino acid to get information on the synthesis rate of neurotransmitters. The labelled drugs permit quantitation of the receptor number, as well as bind­ ing kinetics, together with information on selectivity for different receptor popula­ tions.

Wilkinson Department of Ophthalmology buy generic viagra plus 400 mg line, Pennsylvania State University purchase viagra plus 400 mg free shipping, College of Medicine buy discount viagra plus 400 mg on-line, Hershey generic viagra plus 400mg online, Pennsylvania, U. Quillen Department of Ophthalmology, George and Barbara Blankenship, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, U. Often an eye exam is deferred because of a lack of comfort or familiarity with funduscopic and, to a lesser degree, external ocular examination. However, clinicians should take time to carefully inspect the internal and external anatomy of the eye in search of a physical finding that may tip the scales toward one diagnosis over another. Nowhere is this more the case than in critically ill patients, who are often unable to provide historical clues as to the nature of their condition. We should, therefore, not relegate this exam solely to the purview of ophthalmologists, but rather add it to our armamentarium of diagnostic tools. This chapter, presented in tabular form, contains a collection of both internal and external eye findings in conditions that may be seen in an intensive care setting. This is designed to act as a guide to supplement the internists ocular exam of critically ill patients—to be used for initial evaluation of a patient or when an ophthalmologist is not readily available. These findings, in concert with the history, physical, and laboratory analyses, may help to identify the etiology of the patient’s illness (1–4). Disease External eye findings Fundoscopic findings Stevens–Johnson syndrome l Bilateral hemorrhagic conjunctivitis. Various imaging modalities are usually needed in the workup of infection in these patients to exclude or diagnose alternate disorders such as malignancy and autoimmune disease. In this chapter, the radiologic presentation of various abdominal, neurologic, and thoracic infections as well as the findings in other diseases that may mimic infection on imaging are discussed, as are potentially helpful differentiating factors. Infection occurs primarily via ascending spread of a urinary tract infection, although hematogenous spread can occur less frequently. However, complications such as emphysematous pyelonephritis in diabetics, abscess formation, or sepsis increase the morbidity and mortality substantially. Risk factors for the development of complications include age greater than 65, bedridden status, immunosuppression, and a long-term indwelling urinary tract catheter (1). The diagnosis of acute pyelonephritis is usually made via history and physical exam in conjunction with positive urinalysis, and imaging is not generally needed except for cases of atypical presentation or a suspected complication. There is also usually stranding of the perinephric fat and thickening of Gerota’s fascia. The kidney involved may also be enlarged or demonstrate areas of focal swelling in the acute setting and then may become scarred and contracted if the infection progresses to a chronic state. Findings include a normal or enlarged kidney with decreased echogenicity and wedge-shaped zones of hypoechogenicity (hyper- echogenic foci, which are less likely, usually indicate a hemorrhagic component). The disease results in destruction of the renal parenchyma and a nonfunctioning kidney. There is bright enhancement of the rims of the collections secondary to inflammation and formation of granulation tissue. As in conventional pyelonephritis, there is inflammatory change of the perinephric fat, but in contrast, there is much more frequent involvement of adjacent structures, particularly the ipsilateral psoas muscle, with rare involvement of other structures such as the colon. Unlike in conventional pyelonephritis, the previously mentioned staghorn calculus is usually present or rarely some other chronically obstructing lesion, such as tumor. Clinical and Radiologic Diagnosis of Renal Abscess Focal or multifocal bacterial infections can result in formation of renal abscess. Cortical abscesses result from hematogenous spread of infection, with Staphylococcus aureus being the most common pathogen. Much more commonly, in contrast, corticomedullary abscesses result from ascending spread of infection from organisms in the urine. The latter type of abscess is more likely to extend to the renal capsule and perforate, resulting in perinephric abscess formation (Fig. Corticomedullary abscesses are uncommon complications of urinary tract infections; risk factors for their development include recurrent infections, untreated or ineffectively treated infections, renal calculi, instrumentation, vesicoureteral reflux, and diabetes mellitus (4). Plain radiographs may show radiopaque stones or intraparenchymal gas in patients with emphysematous pyelonephritis, but are generally not helpful for the identification of abscess alone. The “comet sign,” consisting of internal echogenic foci, indicates the presence of gas within the lesion. Gas may or may not be present within the lesion, and there is no enhancement centrally within the lesion. Uptake of indium-111-labeled leukocytes within the abscess can be seen, although false-negative results may occur if the patient has already been on antibiotic therapy, if the abscess is walled off, or if there is a poor inflammatory response (3,4). Mimic of Renal Abscess Renal cell carcinoma may mimic renal abscess on imaging examinations. Both are mass-like lesions within the kidney; however, unlike renal abscess, which does not enhance centrally, renal cell carcinoma typically demonstrates heterogeneous enhancement. Clinical and Radiologic Diagnosis of Psoas Abscess Primary psoas abscess is rare and usually idiopathic. Immunocompromised patients are at risk Radiology of Infectious Diseases and Their Mimics in Critical Care 79 for infection by opportunistic agents. Secondary psoas abscess is more common and may result from spread of infection from adjacent structures, including colon, kidney, and bone (6). Other findings include obliteration of normal fat planes as well as bone destruction and gas formation. Gas within a psoas abscess may also be related to an underlying bowel fistula, such as in Crohn’s disease or diverticulitis. Abnormal uptake on a Ga-67 scan may also be used for diagnosis, although other entities, such as lymphoma, also show increased uptake; this finding is therefore not specific. An indium-111 white blood cell scan alternatively can be used to confirm infection if needed and should be more specific, although percutaneous aspiration (and drainage) can be performed for more definitive diagnosis and therapy (6–8). Mimic of Psoas Abscess Differentiation from tumor, such as lymphoma, can be difficult with imaging alone, as both can present as low-attenuation lesions, although the presence of gas makes the diagnosis of abscess far more likely. Adjacent structures should be examined to determine if there is a source of secondary infection. In the case of lymphoma originating from para-aortic lymph nodes, a potential helpful differentiating feature is that there may be medial or lateral displacement of the muscle by tumor, rather than extension into the muscle, as would be seen in an abscess (9,10). Clinical and Radiologic Diagnosis of Prostate Abscess Prostatic abscess occurs as a complication of acute bacterial prostatitis. Diabetic and immunocompromised patients are especially prone to this complication. The symptoms are similar to acute bacterial prostatitis, including fever, chills, and urinary frequency, with focal prostatic tenderness on physical exam (11). Abscesses can occur anywhere in the prostate, although they are usually centered away from the midline. Findings on ultrasound include focal hypoechoic or anechoic masses, with thickened or irregular walls, septations, and internal echoes. Mimic of Prostate Abscess A potential mimicker of prostate abscess is prostate carcinoma. Prostate cancer is the most common noncutaneous cancer in American men and the second most common cause of male cancer deaths after lung cancer. Unlike prostate abscess, which can occur anywhere in the gland, prostate cancer occurs mainly in the peripheral zones. Ultrasound findings are somewhat similar to abscess in that carcinoma appears as an anechoic to hypoechoic mass. The contour is classically asymmetric or triangular with the base close to the capsule and extending centrally into the gland based on the pattern of tumor growth. Clinical and Radiologic Diagnosis of Liver Abscess There are three main types of liver abscess: pyogenic, amebic, and fungal. Pyogenic abscesses occur most often in the United States and are usually polymicrobial. Pyogenic liver abscesses occur by direct extension from infected adjacent structures or by hematogenous spread via the portal vein or hepatic artery. Clinical presentation may be insidious, with fever and right upper quadrant pain being the most common presenting complaints. The right lobe of the liver is more often affected secondary to bacterial seeding via the blood supply from both the superior mesenteric and portal veins. Untreated, the disease is usually fatal, but with prompt abscess identification and then antibiotic administration and drainage, mortality is significantly decreased (15). A commonly seen finding is the “cluster sign” representing a conglomerate of small abscesses coalescing into a single large cavitating lesion. Secondary findings include right pleural effusion and right lower lobe atelectasis. On ultrasound, the lesion is usually spherical or ovoid with hypoechoic, irregular walls. Centrally, the abscess may be anechoic or less often hyperechoic or hypoechoic, depending on the presence of septa, debris, or necrosis (3,7). Like abscess, these also appear more often on the right side of the liver when solitary. On ultrasound, the mass appears mixed in echogenicity and demonstrates increased vascularity on color Doppler interrogation. There is then washout of contrast on the portal venous phase, as the tumor is supplied almost exclusively by the hepatic artery, and, if performed, on the delayed phase (3,16,17). With gadolinium administration, the enhancement pattern varies from central to peripheral and from homogeneous to rim enhancing. Clinical and Radiologic Diagnosis of Splenic Abscess Splenic abscess is a rare entity with a high mortality rate. The most common etiology is hematogenous spread of infection from elsewhere in the body. There are a diverse array of pathogens, including bacteria (aerobic and anaerobic) and fungi (18). As with abscesses elsewhere in the abdomen and pelvis, there may be gas or an air-fluid level. Ultrasound demonstrates a hypoechoic lesion that may contain internal septations and low-level internal echoes, representing either debris or hemorrhage. Mimic of Splenic Abscess Splenic infarct may have a similar clinical presentation, including fever, chills, and left upper quadrant pain. Differentiating the two entities is important, as an infarct can be managed conservatively, whereas abscess requires antibiotic therapy and possibly drainage. Lack of mass effect on the splenic capsule may be a helpful differentiating factor from abscess. Unlike abscess, on follow-up cross-sectional imaging, an infarct should become better demarcated and eventually resolve, leaving an area of fibrotic contraction and volume loss. A deviation from this expected course suggests a complication such as hemorrhage or superimposed infection (19). Clinical and Radiologic Diagnosis of Cholangitis/Calculous Cholecystis Acute infection of the biliary system is often associated with biliary obstruction from gallbladder calculi.

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Salves are generally applied directly to the wound and left exposed or covered with cotton dressings purchase viagra plus 400mg on line, and soaks are generally poured into cotton dressings on the wound purchase viagra plus 400 mg line. Salves may be applied once or twice a day viagra plus 400mg without a prescription, but may lose effectiveness between dressing changes purchase viagra plus 400 mg otc. More frequent dressing Infections in Burns in Critical Care 361 Table 1 Topical Antimicrobials Commonly Used in Burn Care Salves Advantages Disadvantages Silver sulfadiazine l Broad-spectrum l Transient leucopenia (Silvadene 1%) l Relatively painless on application l Does not penetrate eschar l May tattoo dermis with black flecks Mafenide acetate l Broad-spectrum l Transient pain upon application to (Sulfamylon 11%) l Penetration of eschar partial thickness burns l May cause an allergic rash l Carbonic anhydrase inhibition Polymyxin B/neomycin/ l Wide spectrum l Antimicrobial coverage less bacitracin l Painless on application than alternatives l Colorless allowing direct inspection of the wound Mupirocin (Bactroban) l Broad-spectrum (especially l Expensive Staphylococcus species) Nystatin l Broad antifungal coverage l May inactivate other antimicrobials (Sulfamylon) Soaks Silver nitrate (0. Soaks will remain effective because antibiotic solution can be added without removing the dressing, however, the underlying wound and skin can become macerated. No single agent is completely effective, and each has advantages and disadvantages. It has a broad spectrum of activity from its silver and sulfa moieties covering gram-positives, most gram-negatives, and some fungal forms. It is relatively painless upon application, has a high patient acceptance, and is easy to use. Occasionally, patients will complain of some burning sensation after it is applied, and a substantial number of patients will develop a transient leukopenia three to five days following its continued use. This leukopenia is generally harmless, and resolves with or without cessation of treatment. Control of the microbial density in the burn wound by topical therapy not only decreases the occurrence of burn wound infection per se but also permits burn wound excision to be carried out with marked reduction of intraoperative bacteremia and endotoxemia. These two conditions formerly compromised the effectiveness of burn wound excision performed on other than the day of injury. Disadvantages include transient pain following application to skin with sensation, 362 Wolf et al. It also can cause an allergic skin rash and has carbonic anhydrase inhibitory characteristics that can result in a metabolic acidosis when applied over large surfaces. For these reasons, mafenide acetate is typically reserved for small full-thickness injuries, wounds with obvious bacterial overgrowth, or in those full-thickness wounds that cannot be rapidly excised, such as in patients with concomitant devastating head injuries. Petroleum-based antimicrobial ointments with polymyxin B, neomycin, and bacitracin are clear on application, painless, and allow for easy wound observation. These agents are commonly used for treatment of facial burns, graft sites, healing donor sites, and small, partial- thickness burns. Mupirocin is another petroleum-based ointment that has improved activity against gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus and selected gram-negative bacteria. Nystatin, either in a salve or powder form, can be applied to wounds to control fungal growth. Nystatin-containing ointments can be combined with other topical agents to decrease colonization of both bacteria and fungus. The exception is the combination of nystatin and mafenide acetate because each will inactivate the other. Silver nitrate has the advantage of painless application, and almost complete antimicrobial coverage. The disadvantages include its staining of surfaces to a dull gray or black when the solution dries. This can become problematic in deciphering wound depth during burn excisions and in keeping the patient and surroundings clean of the black staining with exposure to light. The solution is hypotonic as well, and continuous use can cause electrolyte leaching, with rare methemoglobinemia as another complication. Dakin’s is a basic solution with effectiveness against most microbes; however, it also has cytotoxic effects on the patients wounds, thus inhibiting healing. Low concentrations of sodium hypochlorite have less cytotoxic effects while maintaining the antimicrobial effects in vitro. In addition, hypochlorite ion is inactivated by contact with protein, so the solution must be continually changed either with frequent application of new solution or continuous irrigation. The same is true for acetic acid solutions; however, this solution may be more effective against Pseudomonas, although this may only be a discoloration of pyocyanine released by this organism without effect on its viability. Mafenide acetate soaks have the same characteristics of the mafenide acetate salve but are not recommended for primary treatment of intact eschar. It must be stated that all topical agents inhibit epithelialization of the wound to some extent, presumably due to toxicity of the agents to keratinocytes and/or fibroblasts, polymorphonuclear cells, and macrophages. The alternative of wound infection occurring in an untreated wound, however, justifies the routine use of topical agents. The use of perioperative systemic antimicrobials also has a role in decreasing burn wound sepsis until the burn wound is closed. Common organisms that must be considered when choosing a perioperative regimen include Staphylococcus and Pseudomonas species, which are prevalent in wounds. After massive excisions, gut flora are often found in the wounds, mandating consideration of these species as well, particularly Klebsiella pneumoniae. The use of perioperative antibiotics has been linked to the development of multiple resistant strains of bacteria and the emergence of fungi in several types of critical care units. Considering this and other data, we recommend that systemic antibiotics should be used short term (24 hours) routinely as perioperative treatment during excision and grafting because the benefits outweigh the risks. We use a combination of vancomycin and amikacin for this purpose, covering the two most common pathogens on the burn wound, i. The preferred perioperative regimen includes 1 g of vancomycin given intravenously one hour prior to surgery, and another gram 12 hours after the surgical procedure, and a dose of amikacin (based on patient weight, age, and estimated creatinine clearance) given 30 minutes prior to surgery and again eight hours after surgery. Next, systemic antibiotics should be used for identified infections of the burn wound, pneumonia, etc. The antibiotics chosen should be directed presumptively at multiply resistant Staphylo- coccus and Pseudomonas and other gram-negatives. The antibiotic regimen is modified if necessary on the basis of culture and sensitivity results. Infections in Burns in Critical Care 363 The most common sources of sepsis are the wound and/or the tracheobronchial tree; efforts to identify causative agents should be concentrated there. Another potential source, however, is the gastrointestinal tract, which is a natural reservoir for bacteria. Starvation and hypovolemia shunt blood from the splanchnic bed and promote mucosal atrophy and failure of the gut barrier. Early enteral feeding has been shown to reduce morbidity and potentially prevent failure of the gut barrier (13). At our institution, patients are fed immediately during resuscitation through a nasogastric tube. Early enteral feedings are tolerated in burn patients, preserve the mucosal integrity, and may reduce the magnitude of the hypermetabolic response to injury. Enteral feedings can and should be continued throughout the perioperative and operative periods. Selective decontamination of the gut has been reported to be of use in preventing sepsis in the severely burned. This is refuted by another smaller study that showed no benefit to selective gut decontamination, but only an increase in the incidence of diarrhea (15). The denatured protein comprising the eschar presents a rich pabulum for microorganisms. Both of these conditions conspire to make the burn wound a locus minoris resistentiae in the setting of burn-induced immunosuppression. Effective antimicrobial chemotherapy, achieved by the use of topical agents such as mafenide acetate and silver sulfadiazine burn creams and silver nitrate soaks or silver-impregnated materials, impedes colonization and reduces proliferation of bacteria and fungus on the burn wound. The combined effect of topical therapy and early burn wound excision decreased the incidence of invasive burn wound sepsis as the cause of death in patients at burn centers from 60% in the 1960s to only 6% in the 1980s. An historical study of the use of mafenide acetate in burned combatants during the Vietnam War demonstrated a 10% reduction in mortality in those with severe burns treated with mafenide versus those without topical treatment (17). In the past 14 years, invasive burn wound infection, both bacterial and fungal, has occurred in only 2. Army Burn Center in San Antonio (18) who were treated with early excision and topical/systemic antibiotics as described above. Prior to the availability of penicillin, beta-hemolytic streptococcal infections were the most common infections in burn patients. Soon after penicillin became available, Staphylococci became the principal offenders. The subsequent development of anti- staphylococcal agents resulted in the emergence of gram-negative organisms, principally Pseudomonas aeruginosa, as the predominant bacteria causing invasive burn wound infections. Topical burn wound antimicrobial therapy, early excision, and the availability of antibiotics effective against gram-negative organisms was associated with a recrudescence of staph- ylococcal infections in the late 1970s and 1980s, which has been followed by the reemergence of infections caused by gram-negative organisms in the past 15 years. During this time period, it was also noted that hospital costs and mortality are increased in those patients from whom Pseudomonas organisms were isolated (19). Recent data in the literature indicate that coagulase-negative Staphylococcus and S. In the following weeks, these organisms were superseded by Pseudomonas, indicating that these organisms are the most common found on burn wounds later in the course, and are therefore the most likely organisms to cause infection (20). In another burn center, it was again found that late isolates are dominated by Pseudomonas, which was shown to be resistant to most antibiotics save amikacin and tetracycline (21). Of late, common isolates in the burn wound are those of the Acinetobacter species, which are often resistant to most known antibiotics. Army Burn Center (2003–2008), approximately 25% of the isolates from patients newly admitted are of this type. However, in no case were these organisms found to be invasive, and in those who died, infection with this organism was not found to be the most likely cause of death (22). This is in congruence with the findings of Wong et al in Singapore, who showed that acquisition of Acinetobacter was not associated with mortality. They did note, however, that acquisition of Acinetobacter was associated with the number of intravenous lines placed and length of hospital stay (23), which increased hospital costs (24). If treatment is deemed necessary, oftentimes this will require intravenous colistin, which has a high toxicity profile. It was recently shown to have a 79% response rate when used in the severely burned with Acinetobacter infection, however, 14% of these developed renal insufficiency (25). Of other historical note, the isolation of vancomycin- resistant Enterococcus species was common in burn centers in the 1990s, but again, these organisms were not found to cause invasive wound infection and were at best associative with burn death, which was much more likely to be due to other causes and other organisms. The entirety of the wound should be examined at the time of the daily wound cleansing to record any change in the appearance of the burn wound. The most frequent clinical sign of burn wound infection is the appearance of focal dark brown or black discoloration of the wound, but such change may occur as a consequence of focal hemorrhage into the wound due to minor local trauma. The most reliable sign of burn wound infection is the conversion of an area of partial thickness injury to full thickness necrosis. Other clinical signs that should alert one to the possibility of burn wound infection include unexpectedly rapid eschar separation, degeneration of a previously excised wound with neoeschar formation, hemorrhagic discoloration of the subeschar fat, and erythematous or violaceous discoloration of an edematous wound margin. Pathognomonic of invasive Pseudomonas infection are metastatic septic lesions in unburned tissue (ecthyma gangrenosum) (Fig. The dark staining viable organisms shown as a “cuff” around the vessel can readily enter the circulation and spread hematogenously to form nodular foci of infection in remote tissues and organs. Infections in Burns in Critical Care 365 Figure 3 Gross appearance of invasive Pseudomonas infection in the burn wound. Note the focal areas of dark green discoloration distributed unevenly in the burn eschar and exposed subcutaneous tissue in the base of the escharotomy incision.

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Both of these diseases may present with an acute abdomen secondary to severe abdominal pain from uncomplicated disease or as a result of complicated disease such as cyst rupture in 330 Wood-Morris et al buy 400 mg viagra plus with amex. Risk factors for intestinal perforation in typhoid fever were a short duration of symptoms (within 2 weeks of illness onset) viagra plus 400 mg without prescription, inadequate antibiotic therapy cheap viagra plus 400mg otc, male gender discount viagra plus 400mg otc, and leukopenia in a case-control study in Turkey (95). Enteric fever is most commonly due to Salmonella typhi, but also can be caused by S. A larger proportion (69%) has been imported during foreign travel especially from Mexico and India (98). Confirmatory diagnosis of typhoid fever requires blood culture isolation that is positive in approximately 80% of cases or approximately 90% with bone marrow culture (97,101). Stool and urine cultures are occasionally positive, 37% and 7%, respectively, but do not constitute definitive evidence of systemic infection. Adjunctive therapy with high-dose corticosteroids has been shown to decrease mortality in severely ill typhoid fever patients with delirium, obtundation, coma, or shock (104). The majority (95%) of amebic liver abscesses will present within the first two to five years after leaving the endemic region (93,105,106). The differential diagnosis must also include bacterial liver abscess, echinococcal cyst, and hepatoma. Therapy with parenteral metronidazole results in mortality rates of <1% in uncomplicated liver abscesses (93). However, complicated amebic liver abscesses with extension into the thoracic cavity, peritoneum, or pericardium have case-fatality rates of 6. Dysentery and Severe Gastrointestinal Fluid Losses Dysentery is characterized by a toxic appearance, fever, lower abdominal pain, tenesmus, and frequent small-volume loose stools containing blood and/or mucus with large numbers of fecal leukocytes on microscopic exam. Etiologies of dysentery can be divided into amebic (Entamoeba histolytica) versus bacillary [Shigella spp. Shigellosis is the most common etiology and is associated with fatality rates as high as 9% in indigenous populations in endemic regions and 20% during S. Predictive factors associated with increased risk of death in shigellosis (age older than one year, diminished serum total protein, thrombocytopenia, and altered consciousness) reflect the importance of sepsis in shigellosis-related deaths (108). Diarrhea-related mortality in noninflammatory diarrhea has been significantly reduced globally with the institution of oral rehydration therapy. Dysentery-related deaths have not been significantly reduced and require antimicrobial therapy and supportive intensive care in addition to appropriate rehydration (106,107,109,110). Noninflammatory diarrhea due to cholera may present in a returning traveler with life- threatening dehydrating illness with profound fluid and electrolyte deficits (111). Imported Vibrio cholerae is rare in the United States; however, an appreciation of regional risks of epidemic strains (El Tor in South/Central America and Africa, non-O1 V. Fulminant Hepatitis Fulminant hepatitis manifests as severe acute liver failure with jaundice and hepatic encephalopathy (112). Hepatitis B accounts for 30% to 60% with coinfection with delta virus in 30% to 40% that has been demonstrated to increase disease severity (116). Hepatitis C association with fulminant non-A, non-B hepatitis has been reported in Japan but is very uncommon in Western countries (117,118). Hepatitis E, a virus transmitted via an enteric route, has an increased fatality rate in pregnant women (119). Early indicators of a poor prognosis and the potential need for liver transplantation in viral hepatitis include age <11 years or >40 years, duration of jaundice before onset of encephalopathy less than seven days, serum bilirubin >300 mmol/L, and prothrombin time >50 seconds (120). Early diagnosis of acute hepatitis is important, given evidence of specific benefit from antiviral therapies including lamivudine in acute Hepatitis B and interferon therapy for Hepatitis C (121–125). Other less common causes of fulminant hepatitis include Yellow fever virus and leptospirosis. A resurgence in yellow fever in Africa and South America emphasize the continued threat from this agent for unvaccinated travelers (126). Severe yellow fever is fatal in >50% of cases and continues to be a cause of deaths in returning travelers (127–130). Leptospirosis has widespread distribution and is usually transmitted to humans through contact with surface water contaminated with urine from infected animals (131). Travelers returning with leptospirosis typically present with a mild or moderate illness. A recent randomized controlled trial demonstrated equal efficacy of seven-day intravenous therapy with ceftriaxone (1 g daily) and penicillin G (1. Fever with Eosinophilia Eosinophilia in the returning traveler is not uncommon and requires an initial assessment of 3 the absolute eosinophil count (eosinophilia >450/mm ), consideration if travel-related (i. Critically important is a determination of whether the eosinophilia is related to the patient’s current symptoms since most causes of eosinophilia in travelers result in either asymptomatic or mild disease; although the predictive value of peripheral eosinophilia has limitations (139). A tenet of tropical infectious diseases is that patients may present with multiple infections, an acutely ill traveler with moderate eosinophilia may have malaria as the cause of the symptoms and asymptomatic hookworm infection as the etiology of the eosinophilia. Infectious etiologies of fever and eosinophilia that may present with potentially life-threatening illnesses include acute schistosomiasis (acute serum sickness-like disease termed Katayama fever or acute neurologic sequelae of myelitis or encephalitis), visceral larva migrans, tropical pulmonary eosinophilia, acute fascioliasis, and acute trichinosis (138). Schistosomiasis is the most common of these infections with reported high infection rates (mean 77%) in groups of travelers exposed to fresh water in endemic regions occasionally resulting in severe acute infection approximately four to eight weeks postexposure (140–142). Definitive diagnosis of schistosomiasis requires identi- fication of the ova in stool, urine, or tissue specimens. Specific therapy with praziquantel is highly efficacious in the low worm density infections seen in travelers (143). The acute hypersensitivity syndromes often require adjunctive corticosteroid therapy. Toxic Appearance and Fever Patients with a toxic appearance with fever often present difficult diagnostic dilemmas. Other potential diagnoses already discussed such as typhoid fever, early shigellosis, leptospirosis, and anicteric hepatitis remain in the differential diagnosis. This group of conditions can be further subdivided into the presence or absence of a rash. The presence of a hemorrhagic rash is somewhat helpful in narrowing the differential to arboviral, rickettsial, and meningococcal etiologies but even this is not completely reliable. Rickettsial diseases are usually in the differential for critically ill patients with fever and rash. There has been increasing recognition of rickettsial infections as etiologies of serious travel-associated infections (144,145). Scrub typhus has reported case fatality rates in indigenous populations of 15% and rarely has caused life- threatening disease in returning travelers (150). These reports highlight the importance of including rickettsial agents in the differential diagnosis and consideration of empiric therapy with doxycycline. Rapid responses to doxycycline therapy within 24 hours support the diagnosis and the lack of response should prompt alternative diagnoses. Sexually transmitted diseases such as secondary syphilis, disseminated gonococcal infection, or acute retroviral syndrome may rarely present in this manner and need consideration. Measles has significant morbidity with the most common complication, pneumonitis, resulting in mortality rates of 2% to 15% in children and <1% in adults (151,152). A study of hospitalized adults with complications of typical measles revealed pneumonitis rates of approximately 50% with respiratory failure and mechanical ventilation in 18% (153). Dengue fever is, by far, the most common arboviral etiology of nonspecific febrile illness in returning travelers (126,154,155). In West Africa, Lassa fever is endemic, causing 100,000–300,000 human infections and approximately 5000 deaths each year (158). To date, approximately 20 cases of imported Lassa fever have been reported worldwide with one death in the United States in 2004 after travel to West Africa (158). These viruses have distinct geographic distributions, variable case fatality rates, and potential therapeutic options as detailed on Table 3. Nosocomial transmission has been documented for each of these agents and is primarily transmitted through direct contact or aerosolization of blood or body fluids from often terminally ill infected patients (157,162). Consideration should also be given to postexposure Tropical Infections in Critical Care 333 334 Wood-Morris et al. The practice of travel medicine: guidelines by the Infectious Disease Society of America. Spectrum of disease and relation to place of exposure among ill returned travelers. Mortality from Plasmodium falciparum malaria in travelers from the United States, 1959 to 1987. Conquering the intolerable burden of malaria: what’s new, what’s needed: a summary. Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange transfusion. Artesunate versus quinine for treatment of severe falciparum malaria: a randomized trial. New medication for severe malaria available under an investigational new drug protocol. Exchange transfusion as an adjunct to the treatment of severe falciparum malaria: case report and review. Exchange transfusion as an adjunct therapy in severe Plasmodium falciparum malaria: a meta-analysis. Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam. The clinical spectrum of severe imported falciparum malaria in the intensive care unit: report of 188 cases in adults. Respiratory tract infections in travelers: a review of the GeoSentinel Surveillance Network. Risk of infection with Mycobacterium tuberculosis in travelers to areas of high tuberculosis endemicity. Miliary tuberculosis: epidemiology, clinical manifestations, diagnosis, and outcome. Miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities. Retreatment tuberculosis cases* factors associated with drug resistance and adverse outcomes. Outbreak of Legionnaires’ disease among cruise ship passengers exposed to a contaminated whirlpool spa. Prevalence and diagnosis of Legionella pneumonia: a 3-year prospective study with emphasis on application of urinary antigen detection. Clinical features that differentiate hantavirus pulmonary syndrome from three other acute respiratory illnesses. Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome. Prospective, double-blind, concurrent, placebo- controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome.

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