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1.
Gen Comp Endocrinol ; 195: 21-7, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24161750

RESUMEN

Age-related changes in the concentration of factors like TGF-1ß, DHEA-S and IGF-1 may increase the risk of disease and illnesses in advanced life. A better understanding of these changes would aid in the development of more appropriate treatments and/or preventative care for many conditions associated with age. Due to their similar immune system and vulnerability to pathogens, baboons are an ideal model for humans. However, little research has been done examining the general effects of age in baboons. Therefore, we wanted to further examine the effects of aging in baboons by determining the age-dependent changes in serum TGF-1ß, DHEA-S and IGF-1 concentrations. Blood samples were collected during routine health checks in 113-118 captive baboons. In addition, longitudinal samples from 23 to 27 adult individuals were collected an average of 10.7years apart. Both age and gender influenced the concentrations of serum TGF-1ß and IGF-1. When both genders were analyzed together, TGF-1ß increased 16.1% as adults, compared to younger and older animals, but male and female baboons showed a slightly different temporal pattern of change. IGF-1 decreased with increasing age and males had a 30% greater concentration of IGF-1 than did females. While there was no effect of gender among our population, serum DHEA-S was negatively correlated with age, decreasing by 51.6% in the oldest animals. There were no effects of age or gender on serum IGFBP-3. In longitudinal samples collected from the same individuals, the concentrations of TGF-1ß, DHEA-S and IGF-1 were reduced with age. The results presented herein provide additional knowledge of the aging process in baboons and further validate the use of this species as an appropriate model for aging in humans.


Asunto(s)
Envejecimiento , Sulfato de Deshidroepiandrosterona/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor de Crecimiento Transformador beta1/sangre , Animales , Ensayo de Inmunoadsorción Enzimática , Femenino , Sistema Inmunológico/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Masculino , Papio hamadryas , Radioinmunoensayo , Factores Sexuales
2.
Updates Surg ; 73(2): 711-718, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32715438

RESUMEN

Trauma pancreaticoduodenectomy (TP) remains a challenging operation with morbidity and mortality rates as high as 80% and 50%. Many trauma surgeons consider it surgical dogma to avoid performing a TP during the index operation for patients with severe pancreatic or duodenal injuries. However, there is no modern analysis evaluating this belief. Therefore, we hypothesized no difference in risk of mortality between patients with severe pancreatic or duodenal injury undergoing a TP for penetrating trauma to propensity-matched controls undergoing laparotomy without TP. The Trauma Quality Improvement Program (2010-2016) was queried for adults with severe penetrating pancreatic or duodenal injuries undergoing laparotomy. A 1:2 propensity-matching including demographics/comorbidities, injury severity score, vitals on admission, Glasgow Coma Scale and concomitant injuries for laparotomy with or without TP was performed. Risk of mortality was reported using a univariable logistic regression model. Of 2182 patients with severe pancreatic or duodenal injuries undergoing laparotomy, 54 (2.5%) underwent TP and 2128 (97.5%) underwent laparotomy without TP. There were no differences in propensity-matching characteristics. Patients undergoing TP had a similar mortality rate (20.0% vs. 28.7%, p = 0.302) but a longer length of stay (LOS) (27.5 vs. 16.5 days, p = 0.017). The TP group had a similar associated risk of mortality (OR = 0.62, p = 0.302) but higher risk of major complications (OR 3.44, CI 1.35-17.47, p = 0.015). In appropriately selected penetrating trauma patients with severe pancreatic/duodenal injuries, TP is associated with a similar risk of mortality compared to laparotomy without TP. However, TP patients did have an increased associated risk of major complications and longer LOS.


Asunto(s)
Traumatismos Abdominales , Heridas Penetrantes , Traumatismos Abdominales/cirugía , Adulto , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Pancreatectomía , Pancreaticoduodenectomía , Estudios Retrospectivos , Heridas Penetrantes/cirugía
3.
Am J Transplant ; 10(2): 273-85, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20041862

RESUMEN

A lack of deceased human donor livers leads to a significant mortality in patients with acute-on-chronic or acute (fulminant) liver failure or with primary nonfunction of an allograft. Genetically engineered pigs could provide livers that might bridge the patient to allotransplantation. Orthotopic liver transplantation in baboons using livers from alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs (n = 2) or from GTKO pigs transgenic for CD46 (n = 8) were carried out with a clinically acceptable immunosuppressive regimen. Six of 10 baboons survived for 4-7 days. In all cases, liver function was adequate, as evidenced by tests of detoxification, protein synthesis, complement activity and coagulation parameters. The major problem that prevented more prolonged survival beyond 7 days was a profound thrombocytopenia that developed within 1 h after reperfusion, ultimately resulting in spontaneous hemorrhage at various sites. We postulate that this is associated with the expression of tissue factor on platelets after contact with pig endothelium, resulting in platelet and platelet-peripheral blood mononuclear cell(s) aggregation and deposition of aggregates in the liver graft, though we were unable to confirm this conclusively. If this problem can be resolved, we would anticipate that a pig liver could provide a period during which a patient in liver failure could be successfully bridged to allotransplantation.


Asunto(s)
Trasplante de Hígado/inmunología , Animales , Animales Modificados Genéticamente , Coagulación Sanguínea/inmunología , Femenino , Galactosiltransferasas/inmunología , Humanos , Inmunosupresores/inmunología , Hígado/inmunología , Fallo Hepático/inmunología , Masculino , Papio , Sus scrofa , Trombocitopenia/inmunología
4.
J Bone Joint Surg Br ; 88(11): 1519-20, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17075101

RESUMEN

Bilateral coracoclavicular joints were found in a 44-year-old male patient following a fall. He had an Indonesian mother and a Dutch father. Prior to the injury he was asymptomatic and had full range of movement in both shoulders but the trauma resulted in pain and limitation of movement in the left shoulder which required resection of the anomalous joint, after which full pain-free movement was restored.


Asunto(s)
Clavícula/cirugía , Escápula/cirugía , Lesiones del Hombro , Adulto , Clavícula/diagnóstico por imagen , Clavícula/patología , Humanos , Masculino , Procedimientos Ortopédicos/métodos , Radiografía , Rango del Movimiento Articular , Escápula/diagnóstico por imagen , Escápula/patología , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía , Resultado del Tratamiento
5.
Cancer Res ; 53(22): 5483-6, 1993 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-8221688

RESUMEN

Cachexia and malnutrition play a significant role in the morbidity associated with antineoplastic chemotherapy regimens. Conventional nutritional support during cancer therapy has shown little benefit in terms of reducing morbidity and mortality. We examined the anabolic properties of growth hormone (GH) that preserve normal body composition in sarcoma-bearing animals treated with doxorubicin. On day 0, 40 male Fischer 344 rats were inoculated with 10(6) methylcholanthrene-induced sarcoma cells s.c. in the left flank. On day 9, animals were randomized into 3 groups: control (CTL, n = 13); doxorubicin (DOX, n = 13); and doxorubicin plus GH (DOX-GH, n = 14). Two CTL animals were excluded due to tumor invasion into the peritoneal cavity. From day 9 to day 23, the DOX-GH group received daily s.c. recombinant rat GH injection (1 mg/kg). On day 13, DOX and DOX-GH groups received 7 mg/kg of DOX i.v. while the CTL group received sham i.v. sterile saline injection. Body weight and tumor dimensions were measured daily. On day 23, all animals were weighed and sacrificed. Tumors were resected and weighed. Body composition analysis was performed. Plasma GH levels were measured by radioimmunoassay and insulin growth factor 1 levels were measured by chondrocyte proliferation bioassay. The DOX-GH group had a significantly higher mean body weight, carcass weight, total fat free body mass, insulin growth factor 1, and GH plasma levels as compared to the DOX group. No difference in total food intake was observed between the DOX and DOX-GH groups. There was no difference in final tumor weight and tumor growth rate between DOX and DOX-GH groups. Exogenous growth hormone can attenuate weight loss and preserve host body composition in tumor-bearing rats treated with doxorubicin without stimulating tumor growth.


Asunto(s)
Composición Corporal/efectos de los fármacos , Doxorrubicina/farmacología , Hormona del Crecimiento/farmacología , Sarcoma/tratamiento farmacológico , Animales , Ingestión de Alimentos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Ratas , Ratas Endogámicas F344 , Sarcoma/sangre
6.
Cancer Res ; 52(14): 3845-50, 1992 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-1617658

RESUMEN

Data defining the isolated effect of insulin on whole body protein and glucose metabolism in cancer patients are limited. Ten normal volunteers (controls), age 55 +/- 3 years (mean +/- SEM); 8 cancer patients, age 61 +/- 3 years, weight loss 2 +/- 1% (CANWL); and 8 cancer patients, age 55 +/- 2 years, weight loss 18 +/- 2% (CAWL), were studied in the post-absorptive state. Whole body leucine kinetics were determined during a baseline and then a study period during which insulin was infused at 1.0 milliunits/kg/min to achieve a high physiological level of 71 +/- 6, 83 +/- 5, and 64 +/- 5 microunits/ml in controls, CANWL, and CAWL, respectively. Whole body net balance equals protein synthesis minus protein breakdown. Glucose disposal (mg/kg/min) is the rate of D30 infusion at steady state. Glucose disposal of CANWL and CAWL during the study period was significantly (P less than 0.05, analysis of variance) less than controls (3.91 +/- 0.6 in CANWL, 3.66 +/- 1.0 in CAWL, and 5.87 +/- 0.6 mg/kg/min in controls), suggesting resistance to insulin with respect to carbohydrate metabolism. Hyperinsulinemia, under euglycemic and near basal amino acid conditions, significantly reversed the negative postabsorptive leucine net balance (P less than 0.05, analysis of variance) by decreasing protein breakdown in controls as well as weight-stable and weight-losing cancer patients, suggesting that cancer patients are not resistant to the anti-catabolic effect of insulin with respect to whole body protein metabolism.


Asunto(s)
Peso Corporal , Neoplasias Gastrointestinales/metabolismo , Glucosa/metabolismo , Hiperinsulinismo/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas/metabolismo , Femenino , Humanos , Leucina/sangre , Masculino , Persona de Mediana Edad
7.
Exp Hematol ; 24(4): 518-23, 1996 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8608801

RESUMEN

Platelet life spans in dogs were measured pre- and post- splenectomy utilizing in vitro whole blood biotinylation. Four splenectomized dogs were found to have significantly lengthened platelet life spans, 193 +/- 7 hours (mean +/- 1 SD;n=4) postsurgery vs. control life spans of 131 +/- 15 hours (n=6; p< 0.01) when analyzed with the multiple-hit model. Additionally, platelets from normal dogs transfused into splenectomized dogs were found to have convex survival curves with extended life spans approximating that of the splenectomized dog. These data indicate that the spleen is a significant determinant of platelet life span in dogs, with survivals increasing approximately 47% upon splenectomy.


Asunto(s)
Plaquetas/citología , Animales , Supervivencia Celular , Perros , Esplenectomía
8.
Transplantation ; 64(1): 147-52, 1997 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-9233715

RESUMEN

BACKGROUND: The purpose of this study was to investigate whether phosphorus-31 magnetic resonance spectroscopy (31P-MRS) of the isolated donor liver can serve as a viability indicator with prognostic value for transplantation outcome. METHODS: Forty human donor livers preserved with University of Wisconsin solution were studied shortly before transplantation. The respective spectral peak areas of the isolated donor liver were correlated with the amount of hepatocellular graft damage and liver metabolic function shortly after implantation. RESULTS: The individual phosphomonoesters, inorganic phosphate, phosphodiesters, and nicotine adenine dinucleotide peaks were not prognostic for postoperative hepatocellular damage or liver metabolic capacity. The presence of adenosine triphosphate, however, predicts a significantly better metabolic capacity to eliminate bilirubin, to synthesize fibrinogen and antithrombin III, and to maintain a better prothrombin time after transplantation. Furthermore, this study is probably the first 31P-MRS demonstration in the human liver of phosphocreatine. CONCLUSIONS: In the clinical setting described, metabolic assessment using 31P-MRS did not result in a reliable noninvasive test to predict primary graft dysfunction. Study of the role of phosphocreatine in liver metabolism during cold storage is needed.


Asunto(s)
Hígado/metabolismo , Donantes de Tejidos , Nucleótidos de Adenina/fisiología , Supervivencia Celular , Estudios de Seguimiento , Humanos , Hígado/química , Hígado/citología , Trasplante de Hígado/fisiología , Espectroscopía de Resonancia Magnética , Fósforo , Pronóstico , Análisis de Regresión , Factores de Tiempo
9.
Transplantation ; 61(1): 66-70, 1996 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-8560576

RESUMEN

It is not known whether the tissue acidosis that accompanies cold storage is the beginning of irreversible cell injury, ultimately leading to cell death, or whether it is a natural "protective" mechanism for cells to survive hypoxic periods. To answer this question, the tissue pH of 45 cold-stored human donor livers preserved in University of Wisconsin solution (UW) was assessed shortly before implantation using noninvasive 31P magnetic resonance spectroscopy. We conclude that tissue pH during cold storage may be partly dependent upon hepatic glycogen stores and donor age. The wide range of tissue pH values that was observed at the time of implantation does not result in significant effects on cellular damage after transplantation. This indicates that tissue pH is not a major determinant for the viability of UW solution-preserved human donor livers, as indicated by postoperative hepatocellular damage and liver synthesis function. The membrane stabilizing and buffering capacity of UW solution appears to protect liver viability against tissue acidosis. Our results also indicate that liver tissue pH can be lower than has been previously assumed in the literature without significant adverse effects on liver viability.


Asunto(s)
Criopreservación , Hígado , Soluciones Preservantes de Órganos , Adenosina , Adolescente , Adulto , Alopurinol , Niño , Preescolar , Glutatión , Humanos , Concentración de Iones de Hidrógeno , Lactante , Insulina , Trasplante de Hígado , Espectroscopía de Resonancia Magnética , Persona de Mediana Edad , Rafinosa
10.
Transplantation ; 57(8): 1189-94, 1994 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-8178345

RESUMEN

To determine the relation between tissue hydration state--as indicated by tissue proton magnetic resonance relaxation times--in UW-preserved human donor livers and viability parameters of the donor and early graft function, "ex vivo" magnetic resonance relaxometry was performed with a clinical MR imaging system. Relaxometric data were obtained from MR images in which signal intensities were directly proportional to T1 and T2. Forty-three subsequently transplanted livers and five discarded livers were studied. The donor serum concentrations of direct and total bilirubin had a positive correlation with T1 (P < 0.05 and P < 0.01, respectively). Sequential measurements in 7 livers demonstrated a firm time relation between the cold storage time and the length of the relaxation times. As cold storage time lengthened, T1 and T2 shortened. T1 of the donor liver showed a significant negative correlation with recipient ASAT and ALAT values on days 1, 2, and 3 after transplantation. T1 in the discarded group was significantly higher than T1 in the accepted group. T2 was not different in the two groups. It is concluded that in UW-preserved human donor livers, the tissue hydration state, as indicated by the tissue MR relaxation times, is largely independent of the clinical condition of the organ donor and the preservation procedure. An optimum tissue hydration state, in UW-preserved donors liver might have protective properties against parenchymal damage, although the clinical consequences appear to be of minor importance. The capacity of relaxometry as a discriminative instrument to accept or to discard donor livers is poor.


Asunto(s)
Trasplante de Hígado/fisiología , Hígado , Soluciones Preservantes de Órganos , Preservación de Órganos , Agua , Adenosina , Adulto , Alopurinol , Glutatión , Humanos , Insulina , Hígado/química , Hígado/patología , Trasplante de Hígado/patología , Espectroscopía de Resonancia Magnética , Preservación de Órganos/métodos , Protones , Rafinosa , Análisis de Regresión , Agua/análisis
11.
Thromb Haemost ; 77(5): 1020-4, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9184421

RESUMEN

Erythropoietin (EPO) has been previously shown to affect platelet as well as red cell production. In addition, recent studies demonstrated that platelets from EPO-treated dogs are hyperreactive towards thrombin when compared to age-matched, control platelets. This report extends these observations by quantitating the thrombogenic potential of EPO in dogs. Dogs with arterio-venous (A-V) shunts received 100 U EPO/kg/day for 6 days, and thrombogenicity was serially monitored by insertion of a thrombotic surface into the A-V shunt. The resulting experimental thrombi were analyzed for platelet and erythrocyte content after formalin-fixation and chymotrypsin digestion, a technique which allows non-isotopic quantitation of cellular components. By day 5 of EPO-administration all animals demonstrated a significant increase in platelet and red cell content of the experimental thrombi; the average increase in platelet number was 2.94 +/- 0.12 fold (mean +/- 1 SE; n = 3; p = 0.006) above baseline while that for red cells was 2.46 +/- 0.18 fold above baseline (p = 0.023). After cessation of EPO, thrombogenicity returned to normal. During EPO-treatment, the percentage of thiazole orange-positive (TO+) platelets increased significantly to 17.2 +/- 1.6% (mean +/- 1 SE; n = 3) on day 5 compared to a pre-treatment level of 8.5 +/- 0.9% (p = 0.029). Although the percentage of TO+ erythrocytes also increased during the short course of EPO administration, the change was not significant. Despite the increases in TO+ cells, total platelet and erythrocyte counts did not change significantly within the time frame of these experiments. Fibrin/fibrinogen content of the experimental thrombi was unaltered with EPO-treatment. These data demonstrate that human EPO is pro-thrombotic in dogs and, in conjunction with earlier studies, suggest that hyperreactive platelets may be responsible for the potentiated thrombogenicity.


Asunto(s)
Plaquetas/fisiología , Eritropoyetina/farmacología , Trombosis/fisiopatología , Animales , Derivación Arteriovenosa Quirúrgica , Plaquetas/efectos de los fármacos , Perros , Recuento de Eritrocitos , Fibrina/análisis , Fibrinógeno/análisis , Humanos , Recuento de Plaquetas , Proteínas Recombinantes/farmacología , Factores de Tiempo
12.
Thromb Haemost ; 78(6): 1505-9, 1997 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9423803

RESUMEN

Administration of erythropoietin (EPO) to adult dogs resulted in a dramatic increase in the number of thiazole orange-positive (TO+) platelets, also referred to as reticulated platelets. Pre-treatment level of TO+ platelets was 6.2 +/- 0.5% (mean +/- 1 SE: n = 5); following day 5 of treatment with 500 U EPO/kg/day, the percentage of TO+ platelets peaked at 16.8 +/- 2.3% (n = 5; p <0.02). After cessation of the hormone, the number of TO+ platelets fell rapidly to below starting levels. Unexpectedly, there was a significant decline in total platelet count during EPO administration despite an increased level of TO+ platelets. To assess platelet reactivity, total platelets and TO+ platelets from EPO-treated dogs were analyzed for thrombin-responsiveness as quantitated by P-selectin expression on the cell surface; reactivity was expressed as a thrombin EC50, the thrombin concentration required to activate 50% of platelets. Both total and TO+ platelets were hyperreactive during EPO treatment when compared either to pre-treatment values or to control animals. Thrombin EC50 values for total and TO+ platelets on day 5 fell to 66.5 +/- 5.4% (mean +/- 1 SE; n = 5; p <0.02) and 62.2 +/- 8.7% (n = 5; p <0.025), respectively, of pre-treatment levels. These data indicate that EPO not only promotes the synthesis of increased numbers of TO+ platelets in the dog but that these newly produced platelets are hyperreactive when compared to TO+ platelets from control animals.


Asunto(s)
Plaquetas/citología , Eritropoyetina/farmacología , Activación Plaquetaria/efectos de los fármacos , Animales , Benzotiazoles , Perros , Relación Dosis-Respuesta a Droga , Recuento de Eritrocitos , Eritropoyetina/administración & dosificación , Citometría de Flujo , Colorantes Fluorescentes , Hematopoyesis/efectos de los fármacos , Selectina-P/efectos de los fármacos , Selectina-P/metabolismo , Quinolinas , Reticulocitos/citología , Coloración y Etiquetado , Tiazoles , Trombina/administración & dosificación , Trombina/farmacología , Factores de Tiempo
13.
Thromb Haemost ; 75(4): 668-73, 1996 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8743197

RESUMEN

Experimental animal models of thrombosis have been established in several species to examine factors responsible for thrombotic disorders in man. One technical facet of all thrombosis models is the need to quantitate cell deposition on thrombogenic surfaces, and this is routinely accomplished with radioisotopic labeling of specific components. Data reported here demonstrate that formalin-fixed thrombi can be hydrolyzed with chymotrypsin allowing recovery and quantitation of platelets and erythrocytes incorporated within the clot. Recovery of platelets from in vitro generated, model thrombi averaged 99 +/- 10% (mean +/- 1 SD; n = 7; range 88-116%) of calculated content; recovery of erythrocytes was 94.1 +/- 1.1% (n = 6) as measured by recovery of cellular hemoglobin after chymotrypsin hydrolysis of clots. Chymotrypsin was also shown to release platelets and erythrocytes from string-bound thrombi generated in vivo with an arterio-venous shunt model in beagle dogs. Platelet recovery from these string clots after chymotrypsin hydrolysis was independently verified with a quantitative Western blot assay of platelet antigens. These data demonstrate that experimental thrombi can be hydrolyzed with chymotrypsin, thereby not only eliminating the need for radioisotopes, but also permitting flow cytometric analysis of cells comprising the thrombus.


Asunto(s)
Recuento de Eritrocitos , Recuento de Plaquetas , Trombosis/patología , Animales , Western Blotting , Quimotripsina , Modelos Animales de Enfermedad , Perros , Citometría de Flujo , Hidrólisis , Técnicas In Vitro
14.
Biomaterials ; 15(8): 577-85, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7948576

RESUMEN

The in vitro degradation properties of glutaraldehyde cross-linked albumin and albumin-heparin conjugate microspheres (AMS and AHCMS respectively) were evaluated using light microscopy, turbidity measurements and heparin release determinations, showing that the microspheres are degraded by proteolytic enzymes such as trypsin, proteinase K and lysosomal enzymes. The degradation rate was inversely related to the cross-link density of the microspheres. After intrahepatic administration of AHCMS, cross-linked with 0.5% glutaraldehyde, to male Wag/Rij rats by injection into a mesenteric vein (intravenoportal: i.v.p.), the microspheres were entrapped in the hepatic vascular system. The AHCMS were entrapped within terminal portal veins predominantly at the periphery of the liver. The AHCMS were degraded by cellular enzymatic processes within 2 wk after injection, with a half life of approximately 1 d. Biocompatibility of AHCMS and adriamycin-loaded AHCMS was evaluated by histological assessment of the mitotic activity of liver parenchyma and inflammatory response, and by determination of liver damage marker enzymes during 4 wk after administration. Liver damage marker enzymes were not increased compared with controls, nor were adverse effects observed upon histological examination. There was no difference in response between empty and adriamycin-loaded AHCMS.


Asunto(s)
Albúminas/metabolismo , Materiales Biocompatibles/metabolismo , Heparina/metabolismo , Hígado/metabolismo , Microesferas , Albúminas/síntesis química , Animales , Reactivos de Enlaces Cruzados , Doxorrubicina/administración & dosificación , Glutaral , Heparina/síntesis química , Inyecciones Intravenosas , Hígado/enzimología , Hígado/patología , Masculino , Ratas
15.
Surgery ; 112(2): 284-91; discussion 291-2, 1992 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1641767

RESUMEN

BACKGROUND: A cooperative effect of exogenous insulin and recombinant human growth hormone (r-hGH) with respect to whole-body and skeletal muscle protein metabolism has not been demonstrated previously. This study examined the effect of r-hGH and insulin administration during euglycemic clamping and concurrent amino acid supplementation. METHODS: Twenty-three normal volunteers in the postabsorptive state were either treated with r-hGH for 3 consecutive days before a metabolic study (GH group; n = 10) or not treated (CTRL group; n = 13). The r-hGH dose was 0.2 mg/kg/day (n = 5) or 0.1 mg/kg/day (n = 5). All subjects then received an infusion of 14C-labeled leucine and tritiated phenylalanine, followed by measurement of baseline protein kinetics (GH and CTRL). Subsequently a euglycemic insulin infusion (1 mU/kg/min) with concurrent amino acid infusion was administered, and protein kinetic measurements were repeated at steady state. RESULTS: GH and insulin separately produced an increase in whole-body and skeletal muscle protein net balance. GH plus insulin was associated with a higher net balance of protein than was insulin alone. CONCLUSIONS: r-hGH and insulin in the presence of amino acids and glucose combine to improve whole-body and skeletal muscle protein kinetics.


Asunto(s)
Hormona del Crecimiento/farmacología , Insulina/farmacología , Proteínas Musculares/metabolismo , Proteínas/metabolismo , Aminoácidos/sangre , Glucemia/análisis , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Antebrazo/irrigación sanguínea , Glucagón/sangre , Humanos , Insulina/sangre , Cinética , Concentración Osmolar , Proteínas Recombinantes , Flujo Sanguíneo Regional/efectos de los fármacos
16.
Metabolism ; 43(1): 70-8, 1994 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8289678

RESUMEN

In vitro, insulin has been shown to increase skeletal muscle (SM) protein synthesis and decrease SM protein breakdown. Whether these same effects are found in vivo in man is less clear. The study of the effect of hyperinsulinemia (INS) on SM protein turnover (SMPT) is complicated by hypoaminoacidemia, which can obviate the true effect of insulin on SMPT. To prevent this, we studied the effect of INS on SMPT in the human forearm with amino acid (AA) infusion to ensure adequate substrate for full evaluation of insulin's effect. Twelve healthy volunteers (aged 53 +/- 3 years) were studied. Steady-state AA kinetics were measured across the forearm after a systemic 2-hour primed continuous infusion of 3H-phenylalanine (3H-Phe) and 14C-leucine (14C-Leu) in the postabsorptive (PA) state and in response to systemic INS (71 +/- 5 microU/mL). AAs were infused during INS as 10% Travasol (Travenol Laboratories, Deerfield, IL) at .011 mL/kg/min to maintain PA branched-chain AA (BCAA) levels, known regulators of SMPT, and to mildly elevate total AA levels. The negative PA net balance of both Phe and total Leu carbons (LeuC) became positive with INS + AA infusion (Phe from -16 +/- 2 to 12 +/- 3 nmol/min/100 g [P < .01]; LeuC from -26 +/- 6 to 24 +/- 7 nmol/min/100 g [P < .01]).(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Aminoácidos/metabolismo , Hiperinsulinismo/sangre , Hiperinsulinismo/metabolismo , Proteínas Musculares/metabolismo , Adulto , Anciano , Aminoácidos/análisis , Aminoácidos de Cadena Ramificada/análisis , Aminoácidos de Cadena Ramificada/metabolismo , Glucemia/análisis , Radioisótopos de Carbono , Cromatografía Líquida de Alta Presión , Femenino , Antebrazo , Glucagón/sangre , Humanos , Hiperinsulinismo/fisiopatología , Insulina/sangre , Insulina/farmacología , Leucina/análisis , Leucina/metabolismo , Masculino , Persona de Mediana Edad , Proteínas Musculares/análisis , Músculos/química , Músculos/metabolismo , Fenilalanina/análisis , Fenilalanina/metabolismo , Factores de Tiempo , Tritio
17.
J Am Coll Surg ; 185(1): 60-4, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9208962

RESUMEN

BACKGROUND: Serial carcinoembryonic antigen (CEA) levels have been recommended to detect asymptomatic recurrent colorectal cancer and to facilitate curative additional therapy. This study was designed to investigate the outcome of additional treatment for recurrent cancer in patients undergoing primary colorectal cancer treatment in a specialty center and subsequent relapsing with an elevation in serum CEA. STUDY DESIGN: Patients treated for their primary cancers at our institution whose followup included CEA monitoring and whose cancers subsequently recurred, were analyzed from a prospective database of almost 1,900 patients. CEA levels of > or = 5 ng/mL were considered elevated for purposes of treatment results. One hundred sixty-three patients were suitable for analysis. Median followup before and after recurrence was 14 months and 16 months, respectively. RESULTS: Fifty patients were able to undergo complete resection of their recurrence, and 26 of these patients are without evidence of recurrence at last followup. Two-thirds of recurrences were associated with an elevation of CEA; this elevation at recurrence was associated with decreased survival (p < 0.05, Kaplan Meier). Of the 109 patients with an elevation of CEA at recurrence, complete re-resection was accomplished in 26 patients. Of these, half remain cancer free. Of those with a normal CEA at recurrence, complete re-resection was feasible in 24 patients. CONCLUSIONS: Only 17% of patients with recurrent colorectal cancer undergoing potentially curative reresection have an elevated CEA. If we use the denominator of our patient population using an estimated relapse rate of 25-50%, the overall likelihood of CEA-directed curative re-resection confirms early estimates of less than a 5% survival advantage.


Asunto(s)
Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/inmunología , Análisis Actuarial , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Bases de Datos Factuales , Humanos , Metástasis Linfática , Invasividad Neoplásica , Estadificación de Neoplasias , Vigilancia de la Población , Valor Predictivo de las Pruebas , Recurrencia , Análisis de Supervivencia , Resultado del Tratamiento
18.
Surg Oncol ; 1(4): 257-67, 1992 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1341259

RESUMEN

This study was designed to study the effect of systemic hyperinsulinaemia (INS) on glucose and protein metabolism in cancer patients. Sixteen cancer patients (8 > 10% weight loss (WL); 8 < 10% weight loss (NWL)) were compared with 12 healthy controls. Glucose uptake (GU) and phenylalanine (PHE) exchange kinetics were measured across the forearm in the postabsorptive state (PA) and in response to INS (71 +/- 5 microU ml-1). At steady state in response to INS, the negative PA PHE net balance became significantly positive, and GU significantly increased, for cancer and control groups, with no significant differences between the two groups. Subset analysis of NWL cancer vs. WL cancer found no difference between WL and NWL for the change in PHE balance from PA and INS, however GU increased significantly only for the NWL group between PA and INS. These data indicate that cancer patients are not resistant to the anabolic effect of INS on protein metabolism, regardless of weight loss, but are resistant to the effect of INS on glucose metabolism when further along in the disease process as evident by more significant weight loss. This differential response to the effect of INS can be exploited in an attempt to promote protein accrual in weight-losing cancer patients.


Asunto(s)
Glucemia/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/sangre , Antebrazo/fisiología , Neoplasias Gastrointestinales/sangre , Insulina/administración & dosificación , Neoplasias Pulmonares/sangre , Proteínas Musculares/sangre , Anciano , Aminoácidos/sangre , Aminoácidos/efectos de los fármacos , Glucemia/análisis , Glucemia/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Evaluación de Medicamentos , Femenino , Neoplasias Gastrointestinales/tratamiento farmacológico , Humanos , Hiperinsulinismo/sangre , Resistencia a la Insulina , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Proteínas Musculares/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos
19.
Magn Reson Imaging ; 13(2): 227-31, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7739364

RESUMEN

To evaluate whether the hepatic veins can be visualized with a rapid noninvasive technique, and if so, whether the obtained images could be helpful in the preparation of split liver grafts for transplantation, six cold stored human donor livers were investigated with magnetic resonance imaging (MRI). The hepatic vein branches and their confluence were clearly visualized. Anatomic variations of the middle hepatic vein with consequences for the choice of the transection plane could be demonstrated. Furthermore, unexpected vascular abnormalities were detected. From these preliminary results it is concluded that visualization of the hepatic veins can be helpful in determining the feasibility of the bipartition procedure and the choice of the transection plane. A potential wide application of this fast and noninvasive technique is possible.


Asunto(s)
Medios de Contraste , Venas Hepáticas/anatomía & histología , Trasplante de Hígado , Hígado/irrigación sanguínea , Angiografía por Resonancia Magnética/métodos , Soluciones Preservantes de Órganos , Adenosina , Alopurinol , Glutatión , Humanos , Aumento de la Imagen/métodos , Insulina , Trasplante de Hígado/métodos , Preservación de Órganos , Rafinosa
20.
Magn Reson Imaging ; 11(2): 163-7, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8455427

RESUMEN

Magnetic resonance imaging (MRI) of the flexor pollicis longus-tendon (FPL-tendon) with the thumb in different positions allows the in vivo assessment of its abduction-adduction/flexion excursion. Measurements can also be performed in different positions of the wrist. In our study, the mean excursion amplitudes of the FPL-tendon in seven healthy volunteers were 2.6 (+/- 0.26), 2.6 (+/- 0.25), and 2.7 (+/- 0.63) cm for neutral position, ulnar, and radial deviation of the wrist, respectively. The contribution of the abduction-neutral position route and the neutral position-adduction/flexion route to the total excursion of the thumb varied for the different positions of the wrist, despite the equal excursion amplitudes. The possibility of visualization and the accurate determination of the FPL-tendon excursions is of use in the reconstruction and the transposition of the FPL-tendon. In addition, the shift of the FPL-tendon can be visualized for different positions of the thumb and the wrist.


Asunto(s)
Imagen por Resonancia Magnética , Tendones/anatomía & histología , Pulgar/anatomía & histología , Muñeca/anatomía & histología , Adulto , Mano/anatomía & histología , Mano/fisiología , Humanos , Masculino , Metacarpo , Movimiento , Postura , Radio (Anatomía) , Tendones/fisiología , Pulgar/fisiología , Cúbito , Muñeca/fisiología
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