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1.
J Arthroplasty ; 32(5): 1483-1487, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28089184

RESUMEN

BACKGROUND: Total knee arthroplasty (TKA) is associated with major blood loss and blood transfusion is often required. This study aimed to evaluate the efficacy of bone wax in reducing blood loss and transfusion rates after TKA. METHODS: A prospective randomized controlled study that included 100 patients undergoing primary unilateral TKA with cement was conducted in a tertiary center between March 2014 and June 2014. The bone wax group received 2.5 g of bone wax, applied onto the uncovered bone around the prostheses and the nail holes before the tourniquet was released, whereas the control group had hemostasis achieved using electrocautery only. Total blood loss was calculated using the hemoglobin balance method. RESULTS: There were no demographic differences between the 2 groups. The preoperative serum hemoglobin levels were comparable between the 2 groups. The drop in serum hemoglobin levels at 24 h post-TKA was 1.6 ± 0.9 and 2.1 ± 1.1 g/dL in the bone wax and control groups respectively (P = .021), while the drop in serum hemoglobin levels at 72 h post-TKA was 2.7 ± 1.1 and 3.6 ± 1.2 g/dL respectively (P = .013). Total blood loss at 72 h post-TKA was 987.9 and 1183.5 mL for the bone wax and control groups respectively (P = .017). There was no adverse event associated with the use of bone wax at the 3-month follow-up. CONCLUSION: The application of bone wax in TKA was safe and effective for reducing total blood loss and maintaining higher hemoglobin levels.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Pérdida de Sangre Quirúrgica/prevención & control , Palmitatos/uso terapéutico , Hemorragia Posoperatoria/etiología , Ceras/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Transfusión Sanguínea , Índice de Masa Corporal , Cementos para Huesos , Electrocoagulación , Femenino , Hemoglobinas/análisis , Hemostasis , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Torniquetes , Resultado del Tratamiento
2.
Haemophilia ; 22(5): e417-22, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27501477

RESUMEN

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.


Asunto(s)
Deficiencia del Factor VII/terapia , Factor VII/uso terapéutico , Hemorragias Intracraneales/prevención & control , Trasplante de Hígado , Proteínas Recombinantes/uso terapéutico , Preescolar , Deficiencia del Factor VII/complicaciones , Femenino , Humanos , Lactante , Recién Nacido , Hemorragias Intracraneales/etiología
3.
BMC Cardiovasc Disord ; 15: 20, 2015 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-25885579

RESUMEN

BACKGROUND: The use of intra-aortic balloon pump (IABP) via the trans-femoral approach has been established for hemodynamic support in patients undergoing high-risk percutaneous coronary intervention (PCI). However, there are various challenges associated with its use, especially in patients with aortoiliac occlusive arterial disease. CASE PRESENTATION: We describe a case of high-risk PCI with IABP support complicated by intra-procedural detection of severe abdominal aortic stenosis that was successfully overcome with angioplasty of the stenotic lesion. CONCLUSIONS: Our report highlights distal abdominal aortic stenosis as a potential barrier to successful PCI with IABP support, and angioplasty as an effective means to overcome it.


Asunto(s)
Contrapulsador Intraaórtico/métodos , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea/métodos , Anciano , Angioplastia , Aorta Abdominal/diagnóstico por imagen , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/terapia , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/terapia , Humanos , Masculino , Infarto del Miocardio/complicaciones , Radiografía , Factores de Riesgo , Stents
4.
Pulm Circ ; 12(3): e12082, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35864910

RESUMEN

Severe pulmonary hypertension (PH) is not common even in patients with severe chronic lung disease (CLD) but data on hemodynamic characteristics among patients with severe CLD is scarce. All adult patients who had right heart catheterization for lung transplant assessment for severe CLD in the only lung transplant service and for PAH management in the only tertiary pulmonary hypertension service in Hong Kong from 2010 to 2020 were included and classified into CLD group and PAH group. Patient characteristics and hemodynamic parameters were analyzed. There were 153 patients included with 106 patients in the CLD group and 47 in the PAH group. There were only 19.8% of the patients in the CLD group had severe pulmonary hypertension. Patients in the CLD group had significantly lower systolic pulmonary arterial pressure (PAPs), lower mean pulmonary arterial pressure (PAPm), higher cardiac index, and lower PVR when compared with the PAH group (p < 0.001). The area under curve (AUC) of PAPs, PAPm, and PVR were excellent, 0.973, 0.970, and 0.938, respectively for discrimination between CLD and PAH on receiver operator characteristics curve analysis. Optimal cutoff values were 55.5 mmHg, 35.5 mmHg, and 6.1 Wood Units for PAPs, PAPm, and PVR with Youden Index 0.85, 0.80, and 0.82, respectively. There were distinct hemodynamic characteristics between the CLD group and the PAH group. Systolic pulmonary arterial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance are useful to discriminate between the phenotype of severe CLD and PAH.

5.
J Pathol ; 217(3): 389-97, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18973191

RESUMEN

SmgGDS is a guanine nucleotide exchange factor with the unique ability to activate multiple small GTPases, implicating it in cancer development and progression. Here, we investigated the role of SmgGDS in prostate cancer by studying the expression of SmgGDS in benign and malignant prostatic tissues. We also probed SmgGDS function in three prostate carcinoma cell lines using small interfering RNA (siRNA). Immunohistochemical analysis revealed that SmgGDS levels were elevated in prostatic intraepithelial neoplasia (PIN), prostate carcinoma, and metastatic prostate carcinoma. In addition, expression of SmgGDS positively correlated with that of cyclooxygenase-2 (COX-2), a protein believed to promote the development of prostate carcinoma. Reduction of SmgGDS expression in prostate carcinoma cells inhibited proliferation and migration, irrespective of androgen receptor status. These effects were accompanied by a reduction in COX-2 expression and in activity of NF-kappaB, a known regulator of COX-2. Taken together, these findings suggest that SmgGDS promotes the development and progression of prostate cancer, possibly associated with NF-kappaB-dependent up-regulation of COX-2.


Asunto(s)
Carcinoma/metabolismo , Regulación Neoplásica de la Expresión Génica , Factores de Intercambio de Guanina Nucleótido/metabolismo , Neoplasias de la Próstata/metabolismo , Regulación hacia Arriba , Carcinoma/química , Carcinoma/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Ciclooxigenasa 2/análisis , Ciclooxigenasa 2/metabolismo , Factores de Intercambio de Guanina Nucleótido/análisis , Factores de Intercambio de Guanina Nucleótido/genética , Humanos , Inmunohistoquímica , Masculino , FN-kappa B/metabolismo , Próstata/química , Próstata/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , ARN Interferente Pequeño/farmacología , Análisis de Matrices Tisulares , Transcripción Genética , Transfección/métodos
6.
Stem Cells Int ; 2020: 5142797, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32104185

RESUMEN

OBJECTIVE: To evaluate the possible biological effect of allogenic mesenchymal stem cells (MSCs) combined with tissue fusion technology on the anastomosis. METHODS: Sixteen pigs were divided into a 7 d group and 14 d group, each of which was further subdivided into an MSC-treated group and a control group. Five anastomoses per animal were established using LigaSure ForceTriad (Covidien, MA, USA), a tissue sealing system. Cell migration and tissue-specific differentiation potency, in addition to potential cytokine and genetic changes, were investigated. RESULTS: There were no significant between-group differences in postoperative complications and anastomosis burst pressure. The number of proliferating cell nuclear antigen- (PCNA-) positive cells was significantly higher in the MSC-treated group as compared with that in the control group (P = 0.021). Labeled MSCs were found in the mucosal layer, villus, and lamina propria, as well as in the lamina muscularis mucosae, where they exhibited characteristics of smooth muscle cells. CONCLUSIONS: Grafted MSCs significantly promoted epithelial and connective cell proliferation and maintained their cell migration capacity and differentiation potential in the fused anastomotic tissues, without causing severe postoperative complications.

7.
Br J Neurosurg ; 22(6): 776-7, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18661310

RESUMEN

Silver-Russell syndrome is a rare genetically heterogeneous disorder in which patients demonstrate intrauterine and postnatal growth retardation, triangular facies, excessive sweating during early childhood, late closure of the anterior fontanelle and skeletal asymmetry. An association with malignancy exists and only one previous intracranial tumour has been reported, a craniopharyngioma. We report the first case of Silver-Russell syndrome associated with a supratentorial juvenile pilocytic astrocytoma.


Asunto(s)
Astrocitoma/complicaciones , Trastornos de los Cromosomas/complicaciones , Retardo del Crecimiento Fetal , Trastornos de Cefalalgia/etiología , Adulto , Astrocitoma/diagnóstico , Astrocitoma/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética Intervencional/métodos , Síndrome , Resultado del Tratamiento
8.
Pharm Pract (Granada) ; 16(2): 1166, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30023025

RESUMEN

OBJECTIVE: The current study was carried out to assess community pharmacists' perceptions towards online health information, to examine the type of information seek from Internet and to identify the barriers when they retrieved online health information. METHODS: The study was designed as a cross-sectional questionnaire-based survey whereby all (300) community pharmacists practicing in Federal Territory of Kuala Lumpur, Malaysia were targeted for data collection. A 35-itemed questionnaire was posted out along with a stamped addressed envelope, invitation letter and support letter. Responses were also accepted via online response. Both descriptive and inferential statistics were used for data analysis. All statistical analysis was performed using SPSS v. 20.0. RESULTS: A total of 67 responses were received with a response rate of 22.3%. The top three frequently health information searched by respondents were medicine information, general healthcare information and disease-related information. High number of respondents agreed that Internet had too much health information to scan through. Gender (p=0.018) showed significant association with visiting established health websites. Meanwhile, statistical significant was observed between age and searching medicine information (p=0.037), undertaking online continuing professional development (p=0.023), as well as searching clinical guidelines (p=0.047). Respondents' education level showed significant association with uncertainty about the reliability of online health information (p=0.023) and unsure about filtering the information (p=0.007). CONCLUSIONS: Majority of the respondents expressed positive perception with the use of Internet for health information. The findings of the current study showed the widely use of Internet for health information among community pharmacists. Hence, this study provides opportunity for future works to further examine community pharmacist's retrieval and appraisal skills for online health information, as well as application of this information into their daily pharmacy practice.

9.
J Natl Cancer Inst ; 84(7): 510-5, 1992 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-1545441

RESUMEN

BACKGROUND: One objective of regional chemotherapy is to achieve the therapeutic drug levels in local tissues and primary nodal drainage fields, while minimizing systemic drug toxicity. The composition of the drug-delivery vehicle may influence local drug absorption and thereby modulate both tissue drug levels and systemic toxicity. PURPOSE: We evaluated the effect of dimethyl sulfoxide (DMSO) as a drug-delivery vehicle on regional and systemic levels of doxorubicin (DOX) and on the cytotoxicity of DOX following continuous intravesical administration in an invasive rat transitional cell bladder carcinoma model. METHODS: F344 rats received continuous intravesical DOX infusion for a 7-day period using a regional drug administration system. A constant dose of DOX was administered in one of three DMSO concentrations (0%, 10%, or 50%) to groups of animals (N = 20 per group). These concentrations corresponded to target urinary concentrations of 0%, 0.1%, and 0.5%, respectively. DOX levels in urine, serum, muscle, liver, bladder wall, and retroperitoneal lymph nodes were measured using a fluorescence assay on experimental days 0, 2, 4, 6, and 8 (N = four animals/group per day). In vitro assays evaluated the effect of DMSO concentration on the cytotoxicity of DOX against six transitional cell carcinoma cell lines. A final experiment on rats with established bladder tumors compared the cytoreductive effect of continuous intravesical infusion of DOX in 50% DMSO with that of DOX alone and with that in a sham-treated control group; there were 20 rats in each group. RESULTS: Mean and peak tissue and serum levels of DOX increased as a direct function of DMSO concentration. Compared with the results in controls, mean concentrations of DOX in the bladder were increased 7.1-fold and 12.1-fold in the groups given 10% and 50% DMSO, respectively. Average drug concentrations in the lymph nodes were increased 9.6-fold and 9.3-fold in the groups given 10% and 50% DMSO, respectively. In vitro, DMSO synergistically enhanced the cytotoxicity of DOX in two of the six cell lines studied. Solubilizing the test agent in 5% DMSO reduced the IC50 (drug concentration required to reduce cell viability to 50% of control values) to an average of 56% +/- 41% (+/- SD) of control values; 10% DMSO further decreased the average IC50 to 20% +/- 18% (+/- SD) of control values. The mean bladder tumor weight of animals treated with the combination of DOX and DMSO was 0.52 g. This compared with a mean tumor-bearing bladder weight of 2.69 g in the control group (P = .012) and 0.80 g in the group treated with DOX alone (P = .0544). CONCLUSIONS: These results suggest that the use of DMSO as a solvent vehicle for DOX improves drug absorption while simultaneously potentiating DOX cytotoxicity. The use of DMSO as a drug carrier merits further evaluation as a way of enhancing the efficacy of regional chemotherapy regimens.


Asunto(s)
Carcinoma de Células Transicionales/tratamiento farmacológico , Dimetilsulfóxido/farmacología , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Intravesical , Animales , Carcinoma de Células Transicionales/metabolismo , Sinergismo Farmacológico , Femenino , Ratas , Ratas Endogámicas F344 , Neoplasias de la Vejiga Urinaria/metabolismo
10.
Cancer Res ; 51(5): 1378-83, 1991 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-1997176

RESUMEN

Previous studies demonstrated that single doses of systemic cyclophosphamide (CY) as low as 0.5 mg/kg are effective in preventing bladder tumor implantation in a rat model. In an effort to determine if the urinary bladder represents a unique site of CY activity, a series of experiments were performed to define the mechanism by which low-dose CY prevents bladder tumor implantation. Potential sites for CY antitumor activity include direct tumor cytotoxicity resulting from serum delivery of drug to the tumor; tumor cytotoxicity resulting from tissue drug levels at the site of implantation; altered tumor cell adherence to the urothelial injury site; nonspecific urothelial cytotoxicity resulting from urinary excretion of the CY metabolites; tumor cell-specific cytotoxicity resulting from urinary excretion of the CY metabolite acrolein; and second-pass cytotoxicity resulting from urinary excretion of the active form of CY. Experiments were performed to determine if a single predominant site of activity could be defined. Cyclophosphamide levels at the site of tumor implantation appeared to be the most important determinant of antiimplantation activity. Only tumor recipients pretreated with CY had a significant decrease in bladder tumor implantation. In vivo and in vitro assays measuring the effect of blood-borne drug delivery directly to the tumor failed to demonstrate cytotoxic activity. Tumor cell adherence assays measuring in vitro adherence of CY-treated tumor cells and in vivo adherence of tumor cells in CY-treated recipients showed no difference in comparison to control groups. Interval histological comparison of CY-treated and control bladders failed to demonstrate any difference. Urinary levels of acrolein did not contribute to antiimplantation activity. Preimplantation CY doses prevented tumor development in a s.c. implantation model, thereby excluding a second-pass effect resulting from urinary drug excretion. These data suggest that the bladder is not unique in its response to systemic low-dose CY administered for the prevention of implantation-mediated tumor recurrence. Low-dose, perioperative chemoprophylaxis may be applicable to other tumor systems in which intraoperative tumor dissemination is felt to contribute to recurrence risk.


Asunto(s)
Ciclofosfamida/uso terapéutico , Neoplasias de la Vejiga Urinaria/prevención & control , Animales , Ciclofosfamida/administración & dosificación , Femenino , Recurrencia Local de Neoplasia/prevención & control , Trasplante de Neoplasias , Ratas , Ratas Endogámicas F344 , Vejiga Urinaria/efectos de los fármacos
11.
Cancer Res ; 50(8): 2499-504, 1990 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-2317832

RESUMEN

Prior reports have described the mechanism initially responsible for transitional tumor cell adherence and implantation on injured urothelial surfaces. This study further quantifies variables that influence the size of tumor inoculum at the injury site and thereby affect bladder tumor recurrence risk. The surface area of urothelial injury, the concentration of tumor cells in the intravesical bathing medium, the viability of tumor cells, the time of urothelial exposure to tumor cells, and the intravesical pressure were the variables studied. Increasing the surface area of urothelial injury resulted in a linear increase in the size of the tumor inoculum (r2 = 0.805, P = 0.0001). Tumor inoculum increased as a direct function of the concentration of tumor cells in the bathing medium. This relationship was linear at low cell concentrations (r2 = 0.64, P = 0.0001). Higher concentrations of tumor cells appeared to result in saturation of the system, with a relationship best described by a log/log function (r2 = 0.975, P = 0.0001). Viable and nonviable tumor cells appeared to compete for available binding sites with equal efficacy. A simple logarithmic relationship was seen for the effect of exposure time on the size of the tumor inoculum (r2 = 0.513, P = 0.0198). Tumor inoculum increased as a linear function of the intravesical pressure (r2 = 0.314, P = 0.0125). These results demonstrate a significant positive correlation between each of the experimental variables and the size of tumor inoculum. Manipulation of these variables in clinical practice may alter the size of tumor inoculum and thereby have an impact on tumor recurrence secondary to implantation.


Asunto(s)
Carcinoma de Células Transicionales/fisiopatología , Neoplasias de la Vejiga Urinaria/fisiopatología , Vejiga Urinaria/fisiopatología , Animales , Carcinoma de Células Transicionales/patología , Adhesión Celular , Línea Celular , Supervivencia Celular , Epitelio/patología , Epitelio/fisiología , Femenino , Cinética , Ratas , Ratas Endogámicas F344 , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología
12.
Cancer Res ; 49(19): 5414-8, 1989 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-2766306

RESUMEN

The mechanism by which transitional tumor cells adhere to areas of urothelial injury and the means by which heparin prevents this phenomenon were studied. Scanning electron microscopy and a radiolabeled tumor cell adherence assay were used to assess the activity of heparin and a "nonglycosaminoglycan" thrombolytic agent, recombinant tissue plasminogen activator, in preventing tumor cell adherence to areas of urothelial injury. Systemically administered heparin and intravesical therapy with recombinant tissue plasminogen activator duplicated the activity of intravesical heparin. Scanning electron microscopy showed tumor cells entrapped at the injury surface in a RBC/fibrin clot, which was prevented by intravesical heparin. These data suggest that clotting cascade activation by urothelial injury is the mechanism by which particulate adherence to the urothelium occurs. Interruption of this process by local or systemic anticoagulation with heparin or shifting of the equilibrium of clot formation/lysis toward thrombolysis with recombinant tissue plasminogen activator prevents tumor cell adherence. Intravesical thrombolytic therapy may represent a new approach to recurrence prophylaxis for superficial bladder carcinoma.


Asunto(s)
Carcinoma de Células Transicionales/fisiopatología , Heparina/farmacología , Neoplasias de la Vejiga Urinaria/fisiopatología , Vejiga Urinaria/fisiopatología , Animales , Carcinoma de Células Transicionales/patología , Adhesión Celular/efectos de los fármacos , Femenino , Ratones , Microscopía Electrónica de Rastreo , Ratas , Ratas Endogámicas F344 , Trombosis/fisiopatología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/lesiones , Vejiga Urinaria/patología , Vejiga Urinaria/ultraestructura , Neoplasias de la Vejiga Urinaria/patología
13.
Cancer Res ; 51(5): 1373-7, 1991 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-1997175

RESUMEN

An implantable rat bladder tumor model using the rat transitional carcinoma cell line 4909 was used to evaluate the effect of single-dose, preoperative, systemic chemotherapy on the risk of intravesical tumor implantation. To simulate the clinical setting in which drug levels would be present in both the tumor and the site of implantation, both tumor donor animals and tumor recipients were given a single dose of cyclophosphamide (CY) 1 h prior to tumor harvest and implantation. This protocol resulted in a significant reduction in the incidence of tumor implantation, in tumor volume, and in the incidence of nodal metastases relative to control animals. Dose-response experiments demonstrated that 10 of 139 (7%) animals treated with single doses of CY ranging from 2.5-100 mg/kg developed tumors as compared to 46 of 66 (70%) animals with tumors in the control groups (P less than 0.001). CY doses below 2.5 mg/kg were associated with an increased incidence of tumor implantation (19 of 45, 42%). No lethal toxicity was seen at doses of 50 mg/kg or less. Peak antitumor activity occurred when the CY was administered 1 h prior to tumor implantation as compared to 48 or 24 h before or 1 or 24 h after tumor implantation. Preoperative "chemoprophylaxis" may be an effective strategy for preventing bladder tumor recurrences resulting from tumor implantation.


Asunto(s)
Carcinoma de Células Transicionales/prevención & control , Ciclofosfamida/uso terapéutico , Neoplasias de la Vejiga Urinaria/prevención & control , Animales , Ciclofosfamida/administración & dosificación , Ciclofosfamida/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Recurrencia Local de Neoplasia/prevención & control , Trasplante de Neoplasias , Ratas , Ratas Endogámicas F344
14.
Diabetes ; 50(2): 404-10, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11272154

RESUMEN

In diabetic patients, alpha-lipoic acid (LA) improves skeletal muscle glucose transport, resulting in increased glucose disposal; however, the molecular mechanism of action of LA is presently unknown. We studied the effects of LA on basal and insulin-stimulated glucose transport in cultured rat L6 muscle cells that overexpress GLUT4. When 2-deoxy-D-glucose uptake was measured in these cells, they were more sensitive and responsive to insulin than wild-type L6 cells. LA, at concentrations < or = 1 mmol/l, had only small effects on glucose transport in cells not exposed to oxidative stress. When cells were exposed to glucose oxidase and glucose to generate H2O2 and cause oxidative stress, there was a marked decrease in insulin-stimulated glucose transport. Pretreatment with LA over the concentration range of 10-1,000 pmol/l protected the insulin effect from inhibition by H2O2. Both the R and S isomers of LA were equally effective. In addition, oxidative stress caused a significant decrease (approximately 50%) in reduced glutathione concentration, along with the rapid activation of the stress-sensitive p38 mitogen-activated protein kinase. Pretreatment with LA prevented both of these events, coincident with protecting insulin action. These studies indicate that in muscle, the major site of insulin-stimulated glucose disposal, one important effect of LA on the insulin-signaling cascade is to protect cells from oxidative stress-induced insulin resistance.


Asunto(s)
Resistencia a la Insulina/fisiología , Proteínas Musculares , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Estrés Oxidativo/fisiología , Ácido Tióctico/farmacología , Animales , Muerte Celular/fisiología , Línea Celular , Activación Enzimática/efectos de los fármacos , Glucosa/farmacología , Glucosa Oxidasa/farmacología , Transportador de Glucosa de Tipo 4 , Glutatión/metabolismo , Peróxido de Hidrógeno/metabolismo , Insulina/farmacología , Membranas Intracelulares/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas de Transporte de Monosacáridos/efectos de los fármacos , Proteínas de Transporte de Monosacáridos/metabolismo , Músculo Esquelético/citología , Concentración Osmolar , Oxidantes/metabolismo , Ratas , Valores de Referencia , Proteínas Quinasas p38 Activadas por Mitógenos
15.
Phys Med Biol ; 60(2): 689-708, 2015 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-25554968

RESUMEN

Applying the thermoacoustic (TA) effect to diagnostic imaging was first proposed in the 1980s. The object under test is irradiated by high-power pulses of electromagnetic energy, which heat tissue and cause thermal expansion. Outgoing TA pressure pulses are detected by ultrasound transducers and reconstructed to provide images of the object. The TA contrast mechanism is strongly dependent upon the frequency of the irradiating electromagnetic pulse. When very high frequency (VHF) electromagnetic irradiation is utilized, TA signal production is driven by ionic content. Prostatic fluids contain high levels of ionic metabolites, including citrate, zinc, calcium, and magnesium. Healthy prostate glands produce more ionic metabolites than diseased glands. VHF pulses are therefore expected to generate stronger TA signal in healthy prostate glands than in diseased glands. A benchtop system for performing ex vivo TA computed tomography with VHF energy is described and images are presented. The system utilizes irradiation pulses of 700 ns duration exceeding 20 kW power. Reconstructions frequently visualize anatomic landmarks such as the urethra and verumontanum. TA reconstructions from three freshly excised human prostate glands with little, moderate, and severe cancerous involvement are compared with histology. TA signal strength is negatively correlated with percent cancerous involvement in this small sample size. For the 45 regions of interest analyzed, a reconstruction value of 0.4 mV provides 100% sensitivity but only 29% specificity. This sample size is far too small to draw sweeping conclusions, but the results warrant a larger volume study including comparison of TA images to the gold standard, histology.


Asunto(s)
Acústica , Medios de Contraste , Radiación Electromagnética , Calor , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias de la Próstata/radioterapia , Temperatura Corporal , Simulación por Computador , Humanos , Aumento de la Imagen , Masculino , Neoplasias de la Próstata/patología , Relación Señal-Ruido
16.
Clin Exp Metastasis ; 10(2): 99-109, 1992 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1537139

RESUMEN

The mechanism by which intravesical recombinant tissue plasminogen activator (rTPA) prevents tumor cell adherence to injured bladder surfaces, and the optimal parameters for the in vivo use of rTPA for adherence prevention, were evaluated. Intravesical rTPA decreased tumor cell adherence to sites of urothelial injury as a direct function of drug concentration in the intravesical fluid. Recombinant TPA concentrations of 1 mg/ml and 0.1 mg/ml significantly decreased tumor cell adherence relative to the control group. The efficacy of rTPA in removing adherent cells was time-dependent with maximal activity occurring at 15 min or later following intravesical administration. Intravesical rTPA effectively reduced the size of the tumor inoculum when administered either concomitant with, or subsequent to, tumor cell exposure. The relative efficacy of these two approaches was dependent upon the presence of serum in the intravesical fluid. Administration of rTPA concomitant with tumor cell exposure proved more effective in the absence of serum, while postadherence administration was more effective in the presence of 10% fetal calf serum. The addition of exogenous plasminogen to the rTPA solution did not increase anti-adherence activity relative to rTPA alone. However, blockade of endogenous plasminogen conversion with systemically administered epsilon-amino-caproic acid reversed the anti-adherence activity of exogenous rTPA. In vitro experiments evaluating cellular adherence to fibrin substrate confirmed that rTPA's anti-adherence activity was dependent on the presence of plasminogen. Exogenous rTPA administered immediately following tumor cell adherence decreased tumor cell implantation in animals receiving low to moderate tumor inoculums. These data suggest that rTPA prevents cellular adherence as a result of plasminogen activation and subsequent fibrinolysis. Intravesical rTPA administered in sufficient concentration for relatively short periods of time effectively reduces the adherent tumor inoculum and alters implantation as an inverse function of the tumor inoculum. This approach represents a novel strategy which may prove applicable for the prevention of implantation-mediated tumor recurrence at sites of surgical trauma.


Asunto(s)
Carcinoma de Células Transicionales/prevención & control , Recurrencia Local de Neoplasia/prevención & control , Siembra Neoplásica , Activador de Tejido Plasminógeno/administración & dosificación , Neoplasias de la Vejiga Urinaria/prevención & control , Administración Intravesical , Animales , Carcinoma de Células Transicionales/inducido químicamente , Adhesión Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Metilcolantreno , Ratas , Ratas Endogámicas F344 , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Activador de Tejido Plasminógeno/farmacología , Neoplasias de la Vejiga Urinaria/inducido químicamente
17.
Transplantation ; 52(4): 630-3, 1991 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1926341

RESUMEN

Urinary levels of trypsinogen and active trypsin were measured in 34 urine samples from 14 patients an average of 23 months following whole organ pancreas transplantation and duodenocystostomy. Timed urine specimens obtained 30 min and 90 min following a time zero void were collected from 5 patients in an effort to define the kinetics of trypsinogen secretion and activation. Total urinary protein and urinary pH were correlated with urinary levels of trypsin and trypsinogen. Twenty-one specimens from 8 normal volunteers and a single specimen from a pancreas transplant patient with a duodenoenterostomy served as controls. Activated trypsin was present in 33 of 34 specimens from 13 of the 14 transplant patients. The average total trypsin activity in all samples was 84.4 micrograms/ml urine (+/- SE 9.6). Trypsinogen was present in 13 of 34 samples, from 7 of 14 patients. The average trypsinogen concentration of all 34 samples was 9.6 +/- 6.2 micrograms/ml. No trypsin or trypsinogen activity was identified in any control sample. In the 5 patients undergoing timed urine collections total trypsin increased an average of 1.3-fold at 30 min and 1.1-fold at 90 min relative to time zero. Urinary trypsinogen increased an average of 7.1-fold at 30 min and 3.1-fold at 90 min following the initial void. Urinary pH and total urinary protein failed to show a significant correlation with urinary levels of total trypsin or trypsinogen. These data suggest that trypsinogen is rapidly converted to active trypsin following secretion into the bladder, resulting in the high urinary trypsin levels that were detected in the majority of patients.


Asunto(s)
Cistostomía , Duodenostomía , Trasplante de Páncreas/fisiología , Tripsina/orina , Humanos , Ovomucina/metabolismo , Proteinuria/orina , Factores de Tiempo , Tripsinógeno/orina
18.
Sleep ; 14(5): 439-47, 1991 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1836894

RESUMEN

Paroxetine is a novel antidepressant drug with selective serotonin (5-HT) reuptake inhibitory properties. In a double-blind placebo-controlled crossover sleep laboratory study the single-dose effects on objective and subjective sleep and awakening qualities were investigated after paroxetine 20, 30 and 40 mg morning doses (PX 20, 30, 40), paroxetine 30 mg evening dose, fluoxetine 40 mg morning dose (FX 40) and placebo in 18 healthy young volunteers. The drugs were orally administered in 2-wk intervals. In addition to each drug night, the adaptation night and washout night were recorded. Polysomnographic investigations (10:30 p.m. to 6:00 a.m.) showed a delayed sleep onset only after the morning intake of paroxetine, PX 40 being statistically different from placebo. Total sleep time and sleep efficiency deteriorated under morning PX 30, PX 40 and evening PX 30 as compared to placebo. The nocturnal wake time and sleep stage 1 increased under the paroxetine. Rapid eye movement (REM) reduction (min and %) occurred dose dependently after all paroxetine doses, but the REM latency was lengthened only after the morning intake. The suppressant effect on REM sleep is characteristic for antidepressants and was still significant in the washout nights following PX 40 and evening PX 30. The only statistically relevant finding under 40 mg fluoxetine referred to the increase of REM latency in both drug and washout nights. In contrast to objective results, subjective sleep quality remained generally unchanged. Attention, concentration and reaction performance improved under paroxetine as compared to baseline. The deterioration of well-being under PX 40 might be related to the appearance of drowsiness and nausea. Blood pressure and pulse rate were unaffected.


Asunto(s)
Electroencefalografía/efectos de los fármacos , Fluoxetina/farmacología , Monitoreo Fisiológico , Piperidinas/farmacología , Antagonistas de la Serotonina/farmacología , Fases del Sueño/efectos de los fármacos , Vigilia/efectos de los fármacos , Adulto , Nivel de Alerta/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paroxetina
19.
Am J Clin Pathol ; 99(3): 244-8, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8447285

RESUMEN

The authors retrospectively reviewed a series of bladder wash cytologic specimens and concurrently available bladder biopsy samples to evaluate granulomatous inflammation in patients receiving intravesical bacillus Calmette-Guerin (BCG) immunotherapy for transitional cell carcinoma of the bladder. Comparisons were made during the 2-month period following six weekly BCG instillations in 25 patients and during the 1-year period following the last dose of BCG in 23 patients. At some point during the 2-month follow-up period, cytologic specimens contained free histiocytes in 64%, histiocyte aggregates (resembling fragments of granulomas) in 76%, and multinucleated histiocytic giant cells in 56% of patients. Similarly, concurrent biopsy samples contained granulomas in 78% and multinucleated giant cells in 56% of patients. During the 1-year period following the last dose of BCG, inflammatory changes peaked within the first 3 months and gradually resolved at 9-12 months. In none of these instances were the cytologic features of granulomatous inflammation misinterpreted as malignant. It was concluded that the cytologic findings after intravesical BCG are more specific than previously realized and closely parallel the histologic changes seen in corresponding bladder biopsy specimens.


Asunto(s)
Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/patología , Granuloma/patología , Neoplasias de la Vejiga Urinaria/patología , Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/terapia , Femenino , Humanos , Inflamación/patología , Masculino , Persona de Mediana Edad , Manejo de Especímenes , Neoplasias de la Vejiga Urinaria/terapia
20.
Obstet Gynecol ; 78(3 Pt 2): 552-5, 1991 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1870821

RESUMEN

We report two cases in which urologic anomalies presented with vaginal discharge and fever in young women, aged 9 and 18 years. Both patients were ultimately diagnosed as having duplicated collecting systems with ectopic upper-pole ureters opening into the introitus. Although congenital urologic anomalies are a rare cause of vaginal discharge in young women, they should be included in the differential diagnosis of patients presenting with these symptoms.


Asunto(s)
Leucorrea/etiología , Uréter/anomalías , Vagina/anomalías , Adolescente , Niño , Diagnóstico Diferencial , Femenino , Humanos , Tomografía Computarizada por Rayos X , Uréter/diagnóstico por imagen , Vagina/diagnóstico por imagen
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