Management of pressure ulcers.

PURPOSE: Wound healing, the epidemiology and staging of pressure ulcers, and pressure ulcer prevention and treatment are discussed. SUMMARY: The principal event leading to the formation of pressure ulcers appears to be a consistent interruption in blood supply to the skin. Several known risk factors exist and can be attributed to patient-specific variables and wound-specific conditions. Initial management should include removal of the source of pressure, a comprehensive assessment of the patient, and proper staging of the ulcer. Preparation of the wound for treatment is essential and can have a significant impact on healing. While the patient's nutritional status is thought to affect wound healing, only an increased protein content in the diet has been demonstrated to have a benefit. Specialized wound dressings are available for pressure ulcers of all stages and drainage characteristics. With wide variation in cost and in application regimens, a direct cost-effectiveness comparison of commercially available dressing products is difficult. Many of the growth factors commonly present in healing wounds have been synthesized and evaluated as treatments. Although topical platelet-derived growth factor has demonstrated benefit in some studies, its use remains controversial. To date, no topical growth factors carry FDA-approved labeling for use in the treatment of pressure ulcers. Human skin equivalents mark the latest advancement in therapy. Certain species of bacteria have been associated with poorly healing ulcers and may warrant intervention with either local or systemic antibiotic therapy. CONCLUSION: No pharmacologic intervention has been conclusively shown to be effective for pressure ulcers. The cornerstones of therapy remain elimination of the source of pressure or friction and appropriate wound care. usa.     

Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine

Reversal of opioid effects by naloxone (NX) can lead to significant cardiovascular problems. We have reported previously that hypercapnic dogs develop greater increases in blood pressure and plasma catecholamine (CA) levels than hypocapnic ones when reversed with naloxone. We have also demonstrated differences between NX and nalbuphine (NBPH) in producing excitatory adrenergic responses when administered during normocapnia. The present study was designed to investigate possible dissimilarities in cardiovascular and sympathetic events after administration of either NX or NBPH in dogs made hypercapnic following fentanyl administration. After induction of anaesthesia with thiopentone and intubation, two groups of dogs were maintained with controlled ventilation on enflurane in oxygen anaesthesia and given 50 micrograms.kg-1 fentanyl IV. This caused a significant decrease in heart rate (HR) (P less than 0.001), mean arterial blood pressure (MAP) (P less than 0.001), and plasma concentrations of norepinephrine (NE) (P less than 0.002). Then, ventilation was decreased to produce a PaCO2 of 60 mmHg; this was accompanied by a significant elevation in plasma level of both epinephrine (EPI) (P less than 0.02) and NE (P less than 0.001). Administration of 20 micrograms.kg-1 NX to six dogs resulted in immediate increases in HR (P less than 0.01) and MAP (P less than 0.01), and a further rise in CA levels to greater than pre-fentanyl baseline values. In six other dogs, NBPH (0.3 mg.kg-1) caused increases in HR (P less than 0.001) and MAP (P less than 0.001) only, and the MAP rise was significantly less than that seen in the NX group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidermal growth factor receptors and adenylate cyclase activity in human thyroid tissues

Thyroid stimulating hormone (TSH) and epidermal growth factor (EGF) are growth factors for some thyroid cells in cultures. We have previously found more EGF receptors in neoplastic human thyroid tissues than in normal thyroid tissues. We have also found a higher TSH-stimulated adenylate cyclase (AC) activity in neoplastic human thyroid tissues than in normal thyroid tissues. To clarify the relationship between the effect of EGF and TSH on thyroid tissue, we measured the binding of EGF and TSH and the basal, TSH-stimulated and forskolin-stimulated adenylate cyclase activity in 49 normal, hyperplastic and neoplastic human thyroid tissues (5 normal, 2 Hashimoto thyroiditis, 5 Graves' disease, 14 multinodular goiters, 9 follicular adenomas, S follicular carcinomas, 8 papillary carcinomas, and 1 undifferentiated carcinoma). Specific binding of EGF and TSH were measured by radioreceptor assays using competitive inhibition of radio-labeled ligand by unlabeled ligand. Basal, maximally (300 mU/ml) TSH-stimulated, and maximally (100 mM) forskolin-stimulated adenylate cyclase activities were also measured in the same membrane particulate fractions from the thyroid tissues. We found: neoplastic thyroid tissues bind more labeled EGF than nonneoplastic thyroid tissues; follicular adenomas and carcinomas have higher EGF binding than other thyroid tissues; a weak but significant correlation between specific EGF binding and specific TSH binding, and between specific EGF binding and TSH-stimulated adenylate cyclase activity of the thyroid membrane preparations. These findings are consistent with the hypothesis that TSH stimulates an increase in thyroid EGF receptors by increasing intracellular cAMP. The higher binding of EGF and the higher TSH-stimulated AC activity may explain why thyroid neoplasms grow to a larger size than normal thyroid tissues.

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Resumen La hormona estimuladora de tiroides (TSH) y el factor de crecimiento epidermal (EGF) son factores de crecimiento para algunas células tiroideas en cultivo tisular. Previamente hemos informado el hallazgo de más receptores de EGF en tejidos tiroideos neoplásicos humanos que en tejidos tiroideos normales. Con el objeto de clarificar la relación entre el efecto del EGF y de la TSH sobre el tejido tiroideo, realizamos la determinacion de la ligación del EGF y de la TSH y de la actividad basai y de la actividad estimulada por TSH y forskolina de la adenilato-ciclasa (AC) en 49 especímenes de tejido tiroideo humano (5 normales, 2 tiroiditis de Hashimoto, 5 enfermedad de Graves, 14 bocios multinodulares, 9 adenomas foliculares, 5 carcinomas foliculares, 8 carcinomas papilares, y 1 carcinoma indiferenciado). La ligadura especifica del EGF y de la TSH fue medida mediante determinaciones de receptores utilizando inhibición competitiva radiomarcada. También se determinó la actividad basai y la actividad estimulada por forskolina de la adenilato-ciclasa en las mismas fracciones de tejidos tiroideos. Se registraron los siguientes hallazgos: los tejidos neoplásicos ligan más EGF marcado que los tejidos tiroideos no neoplásicos; los adenomas foliculares y los carcinomas poseen una capacidad de ligación del EGF mayor que los otros tejidos tiroideos; hay una débil pero significativa correlación entre la ligación especifíca del TGF y la de la TSH, y entre la ligación específica del EGF y la actividad estimulada por TSH de la adenilato-ciclasa en las preparaciones de membrana tiroidea. Estos hallazgos aparecen consistentes con la hipótesis de que la TSH estimula un aumento en los receptores de EGF mediante el incremento de la cAMP intracelular. La aumentada ligación de EGF y la incrementada actividad estimulada de TSH pueden explicar el por qué los neoplasmas tiroideos crecen hasta un tamaño mayor que los tejidos tiroideos normales.

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Résumé La thyroid stimulating hormone (TSH) et l'epidermal growth factor (EGF) sont des facteurs de croissance agissant sur certaines cellules thyroïdes en culture. Nous avons trouvé qu'il y avait plus de récepteurs EGF dans le tissu thyroïde humain néoplasique que dans le tissu thyroïdien normal. Nous avons également montré qu'il y avait plus d'activité d'adenylate cyclase stimulée par la TSH dans le tissu thyroïden néoplasique par rapport au tissu normal. Pour clarifier le rapport entre les effets de l'E.GF et la TSH sur le tissu thyroïden, nous avons mesuré l'activité de liaison d'EGF, de TSH et l'activité adénulate cyclase de base, stimulée par la TSH, et par la forskoline chez 49 patients ayant du tissu normal, hyperplasique ou néoplasique (5 normaux, 2 thyroïdites de Hashimoto, 5 maladies de Basedow, 14 goîtres multinodulaires, 9 adénomes folliculaires, 5 cancers folliculaires, 8 cancers papillaires, et 1 cancer indifférencié). Les liaisons spécifiques d'EGF et de TSH ont été mesurées par le dosage des récepteurs nucléaires par la méthode de déplacement des ligands marqués par des ligands froids (non marquées). Les activités adénylate cyclase de base, maximale (300 mU/mL), stimulée par la TSH (300 mU/mL) et la forskoline (100 mM) ont été également mesurées dans les mêmes fractions de particules membranaires provenant des tissus thyroïdens. Nous avons trouvé que: les tissus néoplasiques se liaient davantage avec l'EGF que les tissus non néoplasiques; les adénomes folliculaires et les cancers avaient un index de liaison plus élevé que les autres tissus thyroïdens; et il y avait une corrélation faible mais significative entre la liaison spécifique EGF et TSH, et entre la liaison spécifique EGF et l'activité adénylate cyclase des préparations de membrane thyroïdienne. Ces résultats sont en faveur de l'hypothèse selon laquelle la TSH provoque une augmentation des récepteurs EGH de la thyroïde en augmentant la concentration intracellulaire d'AMP cyclique. Le degré de liaison d'EGF élevé, et l'augmentation de l'activité stimulée par la TSH peuvent expliquer la croissance accélérée des tissus néoplasiques par rapport à celle des tissus normaux.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.

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Supported in part by the Medical Research Service of the Veterans Administration Medical Center, San Francisco, California and the Affirmative Action Faculty Development Grant of the University of California, San Francisco, California.     

Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.

We tested the hypothesis that astrocytic matrix metalloproteinase-9 (MMP-9) mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP-9 co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model where blood was injected into striatum, MMP-9 was colocalized with astrocytes surrounding the hemorrhagic lesion. Because MMP-9 is present in blood as well as brain, we compared four groups of wild type (WT) and MMP-9 knockout (KO) mice: WT blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and KO blood into WT brain. Gel zymography showed that MMP-9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. However, edema was ameliorated when MMP-9 was absent in either blood or brain or both. To further assess the mechanisms involved in astrocytic induction of MMP-9, we next examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly upregulated MMP-9 in conditioned media within 1 to 24 h. Hemoglobin-induced MMP-9 was reduced by the free radical scavenger U83836E. Taken together, these data suggest that although there are large amounts of MMP-9 in blood, hemoglobin-induced oxidative stress can trigger MMP-9 in astrocytes and these parenchymal sources of matrix degradation may also be an important factor in the pathogenesis of hemorrhagic brain edema.     

Similarities in Skeletal Muscle Strength and Exercise Capacity Between Renal Transplant and Hemodialysis Patients

Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients. Aim of the study was to assess to what extent exercise capacity and skeletal muscle strength of RTx patients differ from HD patients and healthy controls and to elucidate potential determinants of exercise capacity in RTx patients. Exercise capacity, muscle strength, lean body mass (LBM) and physical activity level (PAL) were measured by cycle-ergometry, isokinetic dynamometry, DEXA and Baecke Questionnaire, respectively, in 35 RTx, 16 HD and 21 controls. VO2peak and muscle strength of the RTx patients were significantly lower compared to controls (p<0.01), but not different compared to HD patients. In RTx patients, strength (p<0.001), PAL (p=0.001) and age (p=0.045) were significant predictors of VO2peak. Muscle strength was related to LBM (p=0.001) and age (p=0.001), whereas gender (p<0.001) and renal function (p=0.01) turned out to be significant predictors of LBM. No effects of corticosteroids were observed. Exercise capacity and muscle strength seem equally reduced in RTx and HD patients compared to controls. In RTx patients, muscle strength and PAL are highly related to exercise capacity. Renal function appears to be a significant predictor of LBM, and through the LBM, of muscle strength and exercise capacity.     

Heat inactivation of avian influenza and Newcastle disease viruses in egg products.

Avian influenza (AI) and Newcastle disease (ND) viruses are heat labile viruses, but exact parameters for heat inactivation at egg pasteurization temperatures have not been established. In this study we artificially infected four egg products with two AI (one low [LP] and one high pathogenicity [HP]) and three ND (two low and one highly virulent) viruses, and determined inactivation curves at 55, 57, 59, 61 and 63 degrees C. Based on D(t) values, the time to inactivation of the viruses was dependent on virus strain and egg product, and was directly related to virus titre, but inversely related to temperature. For all temperatures, the five viruses had the most rapid and complete inactivation in 10% salt yolk, while the most resistant to inactivation was HPAI virus in dried egg white. This study demonstrated that the LPAI and all ND viruses were inactivated in all egg products when treated using industry standard pasteurization protocols. By contrast, the HPAI virus was inactivated in liquid egg products but not in dried egg whites when using the low-temperature industry pasteurization protocol.