RESUMEN
BACKGROUND: Sphincter-preserving techniques like autologous compound platelet-rich fibrin foam have gained popularity, offering potential for better functional outcomes in anal fistula treatment. The present study aimed to evaluate the efficacy and safety of Obsidian RFT®. METHODS: The study conducted a retrospective analysis from January 2018 to December 2022 on patients who received anal fistula closure with Obsidian RTF® at the Department of General Surgery, Medical University of Vienna. Clinical diagnosis, complemented by radiographic imaging, was employed to confirm inconclusive cases. Demographic and fistula characteristics and postoperative data were collected from electronic records following STROCSS criteria. RESULTS: Fifteen patients received Obsidian RFT® treatment for anal fistulas. We found no intra- and postoperative complications. The median hospital stay was 3 days. After a median follow-up of 32 months, a closure rate of 53.3% was detected. Non-significant differences were observed in various variables, yet trends emerged, indicating associations between abscess presence and non-healing fistulas. A distinct age threshold (≥ 42.7 years) served as an indicator for an inability to achieve anal fistula cure. CONCLUSION: Obsidian RFT® represents a safe, minimally invasive operative procedure. Approximately half the patients experienced healing, with better outcome in a younger population. TRIAL REGISTRATION: Ethical Approval number Medical University of Vienna (#1258/2018). This study was registered retrospectively in ClinicalTrials.gov (NCT06136325).
Asunto(s)
Fibrina Rica en Plaquetas , Fístula Rectal , Humanos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Fístula Rectal/cirugía , Fístula Rectal/terapia , Persona de Mediana Edad , Resultado del Tratamiento , Canal Anal/cirugía , Cicatrización de Heridas/efectos de los fármacos , AncianoRESUMEN
Tumours express a variety of novel epitopes which represent potential immune targets, and thus clinically evident tumours are thought to have effectively avoided immune recognition and elimination. Transporters associated with antigen presentation (TAP) are thought to be responsible for conveying intracellular peptides into the endoplasmic reticulum for complex formation with class I MHC and subsequent recognition by cytotoxic T lymphocytes. In this study, we evaluated 79 human solid tumours and cell lines for genetic abnormalities in TAP1 that might have led to an acquired loss of antigen presenting ability. A novel sequence (R659Q) was discovered near the ATP binding site in a human small cell lung cancer (SCLC) cell line, H1436. This cell line is heterozygous for this allele, but only the R659Q allele is transcribed into RNA. Even though the R659Q protein is expressed, these cells act as if they were TAP deficient by peptide binding and antigen presentation studies, which are restored after transfection of a functional TAP1 allele. This is the first evidence for a naturally occuring protein structural defect resulting in defective peptide transport in a human solid tumour.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Antígenos de Histocompatibilidad Clase I/genética , Neoplasias Pulmonares/genética , Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2 , Transportadoras de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfato/metabolismo , Alelos , Secuencia de Bases , Sitios de Unión , Carcinoma de Células Pequeñas/genética , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/virología , Codón , Heterocigoto , Antígenos de Histocompatibilidad Clase I/biosíntesis , Antígenos de Histocompatibilidad Clase I/efectos de los fármacos , Humanos , Interferón gamma/farmacología , Neoplasias Pulmonares/patología , Datos de Secuencia Molecular , Orthomyxoviridae , Polimorfismo Conformacional Retorcido-Simple , Linfocitos T Citotóxicos/inmunología , Células Tumorales CultivadasRESUMEN
Inadequate presentation of tumor antigens by host professional antigen-presenting cells (APCs), including dendritic cells (DCs), is one potential mechanism for the escape of tumors from the host immune system. Here, we show that human cancer cell lines release a soluble factor or factors that dramatically affect DC maturation from precursors without affecting the function of relatively mature DCs. One factor responsible for these effects was identified as vascular endothelial growth factor (VEGF). Thus, VEGF may play a broader role in the pathogenesis of cancer than was previously thought, and therapeutic blockade of VEGF action may improve prospects for immunotherapy as well as inhibit tumor neovasculature.
Asunto(s)
Células Dendríticas/efectos de los fármacos , Factores de Crecimiento Endotelial/fisiología , Linfocinas/fisiología , Proteínas de Neoplasias/fisiología , Neoplasias/metabolismo , Presentación de Antígeno/efectos de los fármacos , Secuencia de Bases , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Células Dendríticas/inmunología , Factores de Crecimiento Endotelial/farmacología , Endotelio Vascular/metabolismo , Factores de Crecimiento de Célula Hematopoyética/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Linfocinas/farmacología , Datos de Secuencia Molecular , Proteínas de Neoplasias/farmacología , Proteínas Tirosina Quinasas Receptoras/análisis , Receptores de Factores de Crecimiento/análisis , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes/farmacología , Subgrupos de Linfocitos T/inmunología , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
We have described a case of cysticercosis in the vitreous chamber of the left eye of a 16-year-old female student. The patient had presented with marked loss of visual acuity of about two months duration, but there were no other clinical signs and no evidence of intestinal taeniasis. The initial response to chemotherapy with praziquantel was good, but the patient defaulted treatment and when seen again, there was an indication of increased inflammatory responses in the eye. A vitrectomy was carried out to remove the cysticercus and associated fibrous strands. When last seen, the patient was well with improvement of vision.
Asunto(s)
Cisticercosis/diagnóstico , Infecciones Parasitarias del Ojo/diagnóstico , Adolescente , Terapia Combinada , Cisticercosis/cirugía , Cisticercosis/transmisión , Infecciones Parasitarias del Ojo/cirugía , Infecciones Parasitarias del Ojo/transmisión , Femenino , Humanos , Praziquantel/administración & dosificación , Praziquantel/uso terapéutico , VitrectomíaRESUMEN
A prospective study of 204 patients undergoing operations requiring cardiopulmonary bypass was undertaken to determine the incidence and etiologic factors leading to postperfusion cerebral dysfunction and to determine whether pretreatment with thiopental, 15 mg/kg, would reduce the incidence. Patients were randomly assigned to a control (diazepam) or study (thiopental) group and were treated identically except for the drug administered. Patients were examined neurologically on the 1st and 4th postoperative day and a psychometric test was administered on the 4th day. Although fewer neuropsychiatric complications were present in patients given thiopental, the difference was not significant. The overall incidence of cerebral dysfunction attributable to cardiopulmonary bypass alone was 16.2% for transient and 6.4% for persistent dysfunction (present at the 10th postoperative day). The incidence of postoperative cerebral dysfunction was more than twice as high in patients undergoing intracardiac than in patients having extracardiac operations and more than 4 times as high in patients more than 60 years of age than in younger patients. Perfusion pressure less than 50 torr with hematocrit less than 30% was not related to development of postoperative cerebral dysfunction. The data suggest that air or particulate emboli originating within the heart or aorta are the major causes of postbypass cerebral dysfunction.
Asunto(s)
Encefalopatías/etiología , Puente Cardiopulmonar/efectos adversos , Diazepam/uso terapéutico , Trastornos Psicofisiológicos/etiología , Tiopental/uso terapéutico , Adulto , Encefalopatías/prevención & control , Puente Cardiopulmonar/psicología , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicofisiológicos/prevención & controlRESUMEN
An assay procedure for HMG-CoA reductase is described which allows rapid measurement of the activity of this enzyme in isolated rat hepatocytes. In a one step procedure digitonin permeabilizes the plasma membrane and at the same time HMG-CoA reductase activity is measured. Digitonin at a concentration of 64 micrograms per mg of cell protein was found to be optimal for exposing microsomal HMG-CoA reductase to the assay components. The enzyme assay is linear with time up til 5 min and with protein concentrations in the range of 0.06-0.6 mg of cell protein per assay. It is shown that cellular enzyme activity is affected by preincubation of intact hepatocytes with a variety of short-term modulators of hepatic cholesterogenesis.
Asunto(s)
Permeabilidad de la Membrana Celular , Digitonina/farmacología , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hígado/enzimología , Animales , Células Cultivadas , Éteres Cíclicos/farmacología , Glucagón/farmacología , Insulina/farmacología , Cinética , Hígado/efectos de los fármacos , Masculino , Ácido Ocadaico , Ratas , Ratas Endogámicas , Vasopresinas/farmacologíaRESUMEN
The escape of tumor cells from immune recognition is a central problem in tumor immunology. Here, we examined the functional role of somatic beta 2-microglobulin (beta2m) gene mutations in human lung and breast cancers. Using single-strand conformational polymorphism (SSCP) analysis and DNA sequencing, we found mutations in the beta2m gene in 2 of 110 tested lung, colon and breast tumors and tumor cell lines. No mutations were identified in 63 breast cancer tumors, in B-lymphoblastoid cell lines or normal tissues from these or other patients. In these cell lines, beta2m protein was undetectable by Western blot analysis and there was no MHC class I on their cell surface even after treatment with interferon-gamma. Transfection of these tumor cell lines with the beta2m gene, but not addition of purified beta2m protein restored MHC expression without addition of exogenous pepticles, indicating that endogenous beta2m expression is necessary for proper intracellular MHC assembly and stabilization by endogeneous pepticles. Mutation in beta2m caused cell line H2009 to be resistant to specific lysis by influenza virus-specific CTL from HLA matched donors, and transfection of the beta2m gene restored this killing. A small cell lung cancer cell line with low class I expression and with a normal beta2m genomic sequence nonetheless also demonstrated increased class I expression after transfection of the beta2m expression vector alone, indicating that the availability of beta2m may be rate limiting for MHC assembly in this line. Our results indicate that somatic mutations or selective loss of expression of the beta2m gene in human lung cancer is rare, but can cause defective MHC class I expression and function allowing these cells to escape recognition by cytotoxic T cells.