RESUMO
Blood transfusions are a common medical treatment. Risks arise when compatible blood is not available. This study assesses the correlation between antibody reaction strength at the antihuman globulin (AHG) phase of testing and the antibody clinical significance as predicted using the monocyte monolayer assay (MMA). Multiple examples of anti-K donor plasma samples were selected to sensitize K+k+ red blood cells (RBCs). Reactivity was confirmed by testing the sensitized K+k+ RBCs at saline-AHG. Antibody titers were determined by serial dilution using neat plasma. Sixteen samples were selected for the study based on comparable graded reactions with neat plasma (1+, 2+, 3+, and 4+) and similar titration endpoints. Each sample was used to sensitize the same Kk donor and then tested by monocytes to evaluate the clinical significance using the MMA, an in vitro procedure that mimics in vivo extravascular hemolysis to predict the survivability of incompatible transfused RBCs. The monocyte index (MI), i.e., the percentage of RBCs adhered, ingested, or both versus free monocytes, was calculated for each sample. Regardless of the reaction strength, all examples of anti-K were predicted to be clinically significant. While anti-K is known to be clinically significant, the immunogenicity rate of K ensures ample supply of antibody samples for inclusion in this project. This study demonstrates that in vitro antibody strength is highly subjective and variable. These results show no correlation between graded reaction strength at AHG and the predicted clinical significance of an antibody as assessed using the MMA.
Assuntos
Antígenos de Grupos Sanguíneos , Monócitos , Humanos , Transfusão de Sangue , Anticorpos , Eritrócitos , IsoanticorposRESUMO
Over the last two decades, we have witnessed a revolution in the field of Parkinson's disease (PD) genetics. Great advances have been made in identifying many loci that confer a risk for PD, which has subsequently led to an improved understanding of the molecular pathways involved in disease pathogenesis. Despite this success, it is predicted that only a relatively small proportion of the phenotypic variability has been explained by genetics. Therefore, it is clear that common heritable components of disease are still to be identified. Dissecting the genetic architecture of PD constitutes a critical effort in identifying therapeutic targets and although such substantial progress has helped us to better understand disease mechanism, the route to PD disease-modifying drugs is a lengthy one. In this review, we give an overview of the known genetic risk factors in PD, focusing not on individual variants but the larger networks that have been implicated following comprehensive pathway analysis. We outline the challenges faced in the translation of risk loci to pathobiological relevance and illustrate the need for integrating big-data by noting success in recent work which adopts a broad-scale screening approach. Lastly, with PD genetics now progressing from identifying risk to predicting disease, we review how these models will likely have a significant impact in the future.
Assuntos
Predisposição Genética para Doença , Doença de Parkinson/genética , Redes Reguladoras de Genes , Estudos de Associação Genética , Heterogeneidade Genética , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Providing adequate transfusion support for alloimmunised patients for whom antigen negative blood is not readily available is hampered by the risk of a haemolytic reaction. The monocyte monolayer assay (MMA) has shown good correlation between the antibody clinical significance and the fate of antigen positive blood. MATERIALS AND METHODS: From 2006 to 2013, the clinical significance of red cell alloantibodies produced by 61 patients was evaluated using a MMA; and antigen positive blood offering the best survival advantage was selected for transfusion following a secondary MMA crossmatch. Post-transfusion, patients were evaluated for clinical signs of haemolysis. RESULTS: Overall, 19 of 61 (31·1%) of our antibodies were potentially clinically significant, with a monocyte index (MI) > 5%. There was no correlation between the clinical significance as showed by the MMA, and the specificity of the antibody or the strength of reactivity at antihuman globulin (AHG) phase. Using the MMA as a secondary crossmatch method, 31 alloimmunised patients (including: eight anti-hr(B), four anti-Yt(a), one each anti-Rg1, -Co(a), Er(a), Le(b), -LW, -Sl1) received 103 antigen positive blood units with no clinical sign of a post-transfusion reaction. For three patients (one each anti-Jo(a), -AnWj, unidentified 'HTLA'), initial MMA was performed as part of an investigation of a suspected haemolytic reaction. In each case, the MMA accurately identified the unit responsible for the reaction. CONCLUSION: Used as a crossmatch surrogate, the MMA provided valuable information in the decision of transfusing antigen positive blood to alloimmunised patients, avoiding delay because of the search of rare antigen negative units.
Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Tipagem e Reações Cruzadas Sanguíneas/métodos , Isoanticorpos/sangue , Reação Transfusional , Adulto , Idoso de 80 Anos ou mais , Anemia Falciforme/sangue , Anemia Falciforme/terapia , Proteínas do Sistema Complemento/análise , Feminino , Hemorragia Gastrointestinal/sangue , Hemorragia Gastrointestinal/terapia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Isoanticorpos/classificação , Isoanticorpos/imunologia , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Monócitos , Reação Transfusional/etiologia , Reação Transfusional/prevenção & controleRESUMO
INTRODUCTION: For patients with potentially resectable pancreatic cancer, diagnostic laparoscopy may identify liver and peritoneal metastases that are difficult to detect with other staging modalities. The aim of this study was to utilize a population-based pancreatic cancer database to assess the cost effectiveness of preoperative laparoscopy. MATERIAL AND METHODS: Data from a state cancer registry were linked with primary medical record data for years 1996-2003. De-identified patient records were reviewed to determine the role and findings of laparoscopic exploration. Average hospital and physician charges for laparotomy, biliary bypass, pancreaticoduodenectomy, and laparoscopy were determined by review of billing data from our institution and Medicare data for fiscal years 2005-2006. Cost-effectiveness was determined by comparing three methods of utilization of laparoscopy: (1) routine (all patients), (2) case-specific, and (3) no utilization. RESULTS AND DISCUSSION: Of 298 potentially resectable patients, 86 underwent laparoscopy. The prevalence of unresectable disease was 14.1% diagnosed at either laparotomy or laparoscopy. The mean charge per patient for routine, case-specific, and no utilization of laparoscopy was $91,805, $90,888, and $93,134, respectively. CONCLUSION: Cost analysis indicates that the case-specific or routine use of laparoscopy in pancreatic cancer does not add significantly to the overall expense of treatment and supports the use of laparoscopy in patients with known or suspected pancreatic adenocarcinoma.
Assuntos
Adenocarcinoma/diagnóstico , Laparoscopia/economia , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/economia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Feminino , Seguimentos , Humanos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/economia , Estadiamento de Neoplasias/métodos , Oregon , Pancreatectomia , Neoplasias Pancreáticas/economia , Neoplasias Pancreáticas/cirurgia , Cuidados Pré-Operatórios/economia , Cuidados Pré-Operatórios/métodos , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: To better define the efficacy and safety of argon plasma coagulation (APC), specifically for brachytherapy-related proctitis, we reviewed the clinical course of 7 patients treated for persistent rectal bleeding. Approximately 2-10% of prostate cancer patients treated with 125I or 103Pd brachytherapy will develop radiation proctitis. The optimum treatment for patients with persistent bleeding is unclear from the paucity of available data. Prior reports lack specific dosimetric information, and patients with widely divergent forms of radiation were grouped together in the analyses. METHODS AND MATERIALS: Seven patients were treated with APC at the Veterans Affairs Puget Sound Health Care System and the University of Washington from 1997 to 1999 for persistent rectal bleeding due to prostate brachytherapy-related proctitis. Four patients received supplemental external beam radiation, delivered by a four-field technique. A single gastroenterologist at the Veterans Affairs Puget Sound Health Care System treated 6 of the 7 patients. If the degree of proctitis was limited, all sites of active bleeding were coagulated in symptomatic patients. An argon plasma coagulator electrosurgical system was used to administer treatments every 4-8 weeks as needed. The argon gas flow was set at 1.6 L/min, with an electrical power setting of 40-45 W. RESULTS: The rectal V100 (the total rectal volume, including the lumen, receiving the prescription dose or greater) for the 7 patients ranged from 0.13 to 4.61 cc. Rectal bleeding was first noticed 3-18 months after implantation. APC (range 1-3 sessions) was performed 9-22 months after implantation. Five patients had complete resolution of their bleeding, usually within days of completing APC. Two patients had only partial relief from bleeding, but declined additional APC therapy. No patient developed clinically evident progressive rectal wall abnormalities after APC, (post-APC follow-up range 4-13 months). CONCLUSIONS: Most patients benefited from APC, and no cases of clinically evident progressive tissue destruction were noted. Although APC appears to be efficacious and safe in the setting of the rectal doses described here, caution is in order when contemplating APC for brachytherapy patients.
Assuntos
Braquiterapia/efeitos adversos , Hemorragia Gastrointestinal/cirurgia , Fotocoagulação a Laser/métodos , Proctite/complicações , Neoplasias da Próstata/radioterapia , Lesões por Radiação/complicações , Doenças Retais/cirurgia , Argônio/uso terapêutico , Hemorragia Gastrointestinal/etiologia , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Masculino , Paládio/efeitos adversos , Paládio/uso terapêutico , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Doenças Retais/etiologiaRESUMO
BACKGROUND: In an effort to improve the cure rates associated with surgical therapy, neoadjuvant chemoradiotherapy is being used with increasing frequency before resection (trimodality therapy). A variety of clinical trials have reviewed this approach, but only one study to the authors' knowledge has shown a survival benefit for trimodality therapy. The extent to which trimodality therapy has gained acceptance in general practice is not clear. The objective of the current study was to determine the extent to which both surgery and trimodality therapy are used for the management of esophageal carcinoma within a large, national health care system and to determine the outcome of patients treated with these treatment approaches. METHODS: The current study was a retrospective cohort study. The study population was comprised of all veterans who underwent either surgery alone or trimodality therapy for operable esophageal carcinoma between the fiscal years of 1993 and 1997. Data were obtained from the Veterans Administration Patient Treatment File, Outpatient Clinic File, and the Beneficiary Identification Record Locator System. The main outcome measures were perioperative mortality and patient survival. RESULTS: During the study period, 695 patients underwent either surgery alone or trimodality therapy for esophageal carcinoma. Five hundred thirty-four (77%) patients were treated with surgery only. One hundred sixty-one (23%) patients underwent surgery after induction chemoradiotherapy (trimodality therapy). Patients selected for trimodality therapy were younger (mean age, 60.8 years vs. 65.6 years), had fewer comorbidities, and were more likely to have a midesophageal tumor. The median survival for all patients was 15.2 months. The type of treatment had no apparent effect on survival. Favorable prognostic factors included younger age, a distal esophageal tumor, and the absence of metastases. The overall perioperative mortality was 13.7 %. The use of trimodality therapy did not increase perioperative mortality. CONCLUSIONS: Trimodality therapy is commonly used within the VA system. The nonrandomized nature of this study does not allow comparison of trimodality therapy to surgery alone, but the overall survival was limited for all patients. The predictors of survival are related to the biology of the disease, and they include patient age, tumor location, and stage at diagnosis.
Assuntos
Neoplasias Esofágicas/terapia , Idoso , Terapia Combinada , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Hospitais de Veteranos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Posttreatment follow-up is a staple of oncologic practice. Clinicians have traditionally presumed that close surveillance improves clinical outcome. However, new evidence reveals that frequent, procedure-intensive follow-up may provide no more significant benefit to patients than simpler approaches. Several recent consensus recommendations from major oncology organizations support this theory. Published surveys of clinician and institutional follow-up policies reveal significant variations in practice, with many providers continuing to use costly, unproven regimens. This review highlights current data on follow-up care for three common cancers--breast, colorectal, and prostate. These data suggest an acute need for changes leading to more rational, consistent, and efficient follow-up practices.
Assuntos
Assistência ao Convalescente/economia , Neoplasias/terapia , Neoplasias da Mama/terapia , Neoplasias Colorretais/terapia , Feminino , Seguimentos , Humanos , Masculino , Neoplasias/economia , Neoplasias da Próstata/terapia , Qualidade de VidaRESUMO
We describe a case of a patient who had a percutaneous endoscopic gastrostomy (PEG) tube placed for enteral access. The patient's medical history was remarkable for chronic malnutrition, coronary artery disease, coronary bypass surgery, and severe esophageal dysmotility. We discuss the patient&'s course through treatment and we review the management options for patients that sustain colonic injury related to PEG placement. We conclude that colonic injury can be difficult to diagnose in the acute setting and that diagnosis may be facilitated by abdominal computerized tomographic (CT) scanning.
Assuntos
Colo/lesões , Gastroscopia/efeitos adversos , Perfuração Intestinal/etiologia , Intubação Gastrointestinal/efeitos adversos , Doença Aguda , Idoso , Anastomose Cirúrgica , Colo/diagnóstico por imagem , Colo/cirurgia , Endoscopia do Sistema Digestório , Nutrição Enteral , Fluoroscopia , Gastrostomia , Humanos , Perfuração Intestinal/diagnóstico por imagem , Perfuração Intestinal/cirurgia , Masculino , Tomografia Computadorizada por Raios XRESUMO
A variety of commercial surfactants were tested to determine their effect on polychlorinated biphenyl (PCB) transformation by Pseudomonas LB400. Initial tests determined that most surfactants were fully or partially able to solubilize the PCB congeners 2,5,2'-chlorobiphenyl (CBP), 2,4,2',4'-CBP, 2,3,5,2',5'-CBP and 2,4,5,2',4',5'-CBP, at concentrations above the surfactants' critical micelle concentration (CMC). Surfactants were also found to have no negative effect on bacterial survival, as cell numbers were the same or higher after incubation in the presence of surfactants than after incubation without surfactants. A comparison of the extent of biotransformation of single PCB congeners by the bacterium revealed that, at surfactant concentrations above the CMC, the presence of an anionic surfactant promoted while nonionic surfactants inhibited PCB transformation, compared to a control with no surfactant. The rates of transformation of PCB congeners were also higher in the presence of the anionic surfactant compared to the control. The inhibitory effects of a nonionic surfactant, Igepal CO-630 at a concentration above its CMC, on transformation of 2,4,5,2',5'-CBP could be eliminated by diluting the surfactant/PCB solution to a concentration close to the surfactant CMC.
Assuntos
Bifenilos Policlorados/metabolismo , Pseudomonas/metabolismo , Poluentes do Solo/metabolismo , Tensoativos/farmacologia , Ânions/farmacologia , Biodegradação Ambiental/efeitos dos fármacos , Micelas , Polietilenoglicóis/farmacologia , Solubilidade/efeitos dos fármacosRESUMO
OBJECTIVE: To report the patterns of disease and postmetastasis survival for patients with pulmonary metastases from soft tissue sarcoma in a large group of patients treated at a single institution. Clinical factors that influence postmetastasis survival are analyzed. SUMMARY BACKGROUND DATA: For patients with soft tissue sarcoma, the lungs are the most common site of metastatic disease. Although pulmonary metastases most commonly arise from primary tumors in the extremities, they may arise from almost any primary site or histology. To date, resection of disease has been the only effective therapy for metastatic sarcoma. METHODS: From July 1982 to February 1997, 3149 adult patients with soft tissue sarcoma were admitted and treated at Memorial Sloan-Kettering Cancer Center. During this interval, 719 patients either developed or presented with lung metastases. Patients were treated with resection of metastatic disease whenever possible. Disease-specific survival was the endpoint of the study. Time to death was modeled using the method of Kaplan and Meier. The association of factors to time-to-event endpoints was analyzed using the log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. RESULTS: The overall median survival from diagnosis of pulmonary metastasis for all patients was 15 months. The 3-year actuarial survival rate was 25%. The ability to resect all metastatic disease completely was the most important prognostic factor for survival. Patients treated with complete resection had a median survival of 33 months and a 3-year actuarial survival rate of 46%. For patients treated with nonoperative therapy, the median survival was 11 months. A disease-free interval of more than 12 months before the development of metastases was also a favorable prognostic factor. Unfavorable factors included the histologic variants of liposarcoma and malignant peripheral nerve tumors and patient age older than 50 years at the time of treatment of metastasis. CONCLUSIONS: Resection of metastatic disease is the single most important factor that determines outcome in these patients. Long-term survival is possible in selected patients, particularly when recurrent pulmonary disease is resected. Surgical excision should remain the treatment of choice for metastases of soft tissue sarcoma to the lung.
Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Sarcoma/mortalidade , Sarcoma/secundário , Neoplasias de Tecidos Moles/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Despite optimal multimodality limb-sparing therapy for extremity soft tissue sarcoma (STS), a significant number of patients develop distant metastasis. The objective of this study was to analyze patterns of metastatic disease and define prognostic factors for survival in a large group of patients followed prospectively at a single institution. METHODS: Between July 1, 1982, and June 30, 1996, all adult patients admitted to the Memorial Sloan-Kettering Cancer Center with primary extremity sarcoma were treated and prospectively followed. Patients who developed distant metastases constituted the study group. Prognostic factors were analyzed for postmetastasis survival. These included both factors related to the primary tumor and factors related to the pattern of metastasis. Postmetastasis survival was modeled using the Kaplan-Meier method. Statistical significance was evaluated using the log rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. RESULTS: During the study period, the authors admitted and treated 994 patients with primary extremity STS. The median follow-up was 33 months. Distant metastasis developed in 230 patients (23%). Median survival after distant metastasis was 11.6 months. The lungs were the first metastatic site in 169 patients (73%). Other first sites of metastasis included the skin and soft tissues of the head and neck, trunk, and extremities. There was no statistically significant difference in survival between patients with pulmonary and those with nonpulmonary metastatic disease. In multivariate analysis, resection of metastatic disease, the length of the disease free interval, the presence of a preceding local recurrence, and patient age > 50 years all were significant predictors of postmetastasis survival. Other factors that defined the primary tumor, including histologic grade, depth, and microscopic margins, were not associated with postmetastasis survival. CONCLUSIONS: Despite optimal multimodality therapy, 23% of the patients in this series with primary extremity sarcoma developed distant metastasis. Median survival after metastasis was approximately 1 year. After metastasis, the independent favorable factors that are associated with patient survival include resection of the metastases, a long disease free interval, the absence of preceding local recurrence, and patient age < 50 years. Although a definitive conclusion regarding the benefit of resection can be made only with a randomized clinical trial, these data suggest that resection of metastatic STS may contribute to patient survival, which in some cases may be long term.
Assuntos
Doenças do Pé/mortalidade , Sarcoma/mortalidade , Sarcoma/secundário , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Doenças do Pé/diagnóstico , Doenças do Pé/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Prospectivos , Sarcoma/diagnóstico , Análise de Sobrevida , SobreviventesRESUMO
BACKGROUND: Improvements in the understanding of intrahepatic anatomy and radiographic technology have facilitated a segment-oriented approach to liver resection. This approach involves the resection of isolated anatomic segments or sectors of the liver as dictated by the extent of the intrahepatic pathology. Segment-oriented resection allows maximal conservation of normal liver parenchyma while clearing tumor. This report describes the technical features and the results of a prospective evaluation of segmental and sectoral resections in the treatment of malignant hepatic neoplasms. STUDY DESIGN: Patients with malignant hepatic neoplasms that were treated with a segment-oriented hepatic resection were identified from a prospective clinical data base. After undergoing segment-oriented liver resection, the patients were followed at regular intervals. Recurrent disease was the end point of the study. Followup is reported at a median of 12 months. This review outlines the technique of resection, intraoperative events, operating time, blood loss, and the ability to obtain negative resection margins. RESULTS: During the 5-year period between July 1992 and July 1997, 400 patients underwent liver resection for metastatic neoplasms and hepatocellular carcinoma (HCC). During this period, 79 patients (20%) were treated with a segment-oriented resection. These patients represent the study group for this report. The overall mortality rate was 2.5%; all postoperative deaths occurred in patients with HCC and cirrhosis. Overall morbidity was 26%. The median hospital stay was 8 days. Mean transfusion requirements were 1.0 +/- 0.3 U of packed red blood cells. Patients with HCC showed a greater transfusion requirement than did patients without HCC: 2.7 +/- 1.2 U versus 0.6 +/- 0.2 U (p < 0.05). Of the patients without HCC, 17% required transfusion. During the 12-month median followup period, the overall disease recurrence rate was 23%. Disease recurred at the hepatic-resection margin in 2.5% of the patients. CONCLUSIONS: Segmental resection is a safe technique that allows complete resection of liver tumors with preservation of normal liver parenchyma. Segmental resection is particularly useful for patients with HCC and patients undergoing repeat liver resections or bilobar resections.
Assuntos
Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Transfusão de Eritrócitos , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Hepatectomia/classificação , Humanos , Cuidados Intraoperatórios , Tempo de Internação , Fígado/irrigação sanguínea , Fígado/patologia , Fígado/cirurgia , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Reoperação , Segurança , Taxa de Sobrevida , Fatores de Tempo , Ultrassonografia de IntervençãoRESUMO
Resting cells of Pseudomonas strain LB400, grown on biphenyl, transformed 80, 50 and 17% of Aroclor 1242, 1254, and 1260, respectively. Resting cells grown on glucose or glycerol also transformed these polychlorinated biphenyl (PCB) mixtures to the extent of 60, 35, and 9% for Aroclors 1242, 1254, and 1260, respectively. Time courses of the transformation of the separated individual congeners in the Aroclors were plotted and used to determine the transformation rate constants (k). By analysis of the rate constants, it was concluded that the order of degradation of the different congeners in an Aroclor were similar regardless of the growth substrate. In general, k values for the conversion of a particular congener were lower for cells grown on glucose or glycerol compared with cells grown on biphenyl. Generally, k values for the transformation of the same congener in different Aroclors were not the same: rate constants had highest values for the congener in Aroclor 1242 and lowest values in Aroclor 1260. The data allowed congeners to be grouped according to their relative rates of degradation. The ratio of k values for transformation of individual congeners in Aroclors by cells grown on biphenyl and glucose were not constant.
Assuntos
Arocloros/metabolismo , Bifenilos Policlorados/metabolismo , Pseudomonas/metabolismo , Biodegradação Ambiental , Compostos de Bifenilo/metabolismo , Carcinógenos/metabolismo , Poluentes Ambientais/metabolismo , Glucose/metabolismo , Glicerol/metabolismo , Pseudomonas/crescimento & desenvolvimentoRESUMO
BACKGROUND: The cellular basis for augmented cytokine production in the tumor-bearing host is not known. Recently leukemia inhibitory factor (LIF) and interleukin (IL)-6, produced by a variety of tumors, have been implicated as mediators of cachexia. METHODS: Five murine tumor cell lines were tested for the production of these cytokines. 4JK tumor was further tested to determine if IL-1, tumor necrosis factor (TNF), or cocultivation with RAW 264 cells augmented IL-6 or LIF production. RESULTS: 4JK from in vivo tumors produced significantly more IL-6 than did 4JK from culture, indicating that tumor production of IL-6 and LIF is potentially augmented by infiltrating macrophages. When 4JK was cocultured with RAW 264 cells, TNF, or IL-1 in vitro, a three- to 15-fold increase in tumor production of LIF and IL-6 was noted (p2 < or = 0.03). Conversely, in coculture experiments performed with a neutralizing TNF antibody, a 50% reduction in tumor production of LIF ad IL-6 was noted (p2 < 0.04). Resting RAW cells produced only minimal quantities of TNF; however, when RAW cells were exposed to tumor-conditioned supernatant from 4JK, their TNF production was markedly increased. CONCLUSIONS: In the tumor microenvironment, host macrophages may be activated and produce inflammatory cytokines such as TNF. Local TNF then appears to act on tumor cells to stimulate production of IL-6 and LIF. Enhanced tumor production of cytokine mediators may contribute to deleterious effects of neoplastic growth on the host.
Assuntos
Caquexia/metabolismo , Inibidores do Crescimento/metabolismo , Interleucina-6/metabolismo , Linfocinas/metabolismo , Neoplasias Experimentais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anticorpos/imunologia , Caquexia/etiologia , Caquexia/patologia , Técnicas de Cocultura , Fator Inibidor de Leucemia , Camundongos , Neoplasias Experimentais/complicações , Neoplasias Experimentais/patologia , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/imunologia , Regulação para CimaRESUMO
We have earlier shown that passive immunization against differentiation-inducing factor/leukemia-inhibitory factor (D factor) activity improves the survival of endotoxemic mice, suggesting that D factor may contribute to the systemic toxicity associated with tumor necrosis factor (TNF). In the current experiments, TNF induced D-factor gene expression in various tissues of non-tumor-bearing female C57BI/6 mice. Passive immunization against D-factor significantly improved survival after a lethal TNF challenge in both non-tumor-bearing (p2 < 0.02) and tumor-bearing mice (p2 < 0.01). In mice bearing 10-day s.c. MCA 105 sarcomas, D-factor antibody alone had no effect on tumor growth as compared with control IgG. Tumor regression and regrowth in mice treated i.v. with TNF was not affected by pre-treatment with D-factor antibody, as compared with pre-treatment with IgG. However, TNF-treatment-related mortality was abrogated by pre-treatment with D-factor antibody (0% vs. 36% for IgG-pre-treated controls). These results indicate that endogenous D-factor activity contributes to the toxicity but not to the anti-tumor effects of TNF therapy. With renewed interest in the use of TNF for the treatment of patients with cancer, improved understanding of the role of D factor in mediating the effects of TNF may have important clinical benefits.
Assuntos
Inibidores do Crescimento/fisiologia , Interleucina-6 , Linfocinas/fisiologia , Fator de Necrose Tumoral alfa/toxicidade , Animais , Sequência de Bases , Primers do DNA/química , Feminino , Expressão Gênica/efeitos dos fármacos , Inibidores do Crescimento/toxicidade , Imunização Passiva , Fator Inibidor de Leucemia , Linfocinas/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , RNA Mensageiro/genéticaRESUMO
BACKGROUND: Between 5% and 10% of patients who undergo cervical exploration for primary hyperparathyroidism will have persistent or recurrent hyperparathyroidism. Many of these patients have parathyroid tumors in unusual locations. One such site of ectopic parathyroid tissue is an undescended parathyroid adenoma at or superior to the carotid bifurcation. We describe our experience with the preoperative localization and surgical management of undescended parathyroid adenomas. METHODS: From 1982 to 1993 a consecutive series of 255 patients have undergone localization studies and surgical exploration for persistent or recurrent hyperparathyroidism at the Clinical Center of the National Institutes of Health. Operative strategy was determined by review of the patient's surgical history, disease reports, and data from localizing studies. Patients with an undescended parathyroid adenoma identified before the operation were examined with a direct approach high in the neck. Patients who did not have definitive preoperative localization were explored with the previous transverse cervical incision. RESULTS: Seventeen undescended parathyroid adenomas were identified in 255 patients. Thirteen (76%) of 17 patients had an undescended parathyroid adenoma precisely localized before the operation and were examined via a limited, oblique incision high in the neck anterior to the sternocleidomastoid muscle. In the 13 patients who had undergone accurate localization before the operation, the median operative time was 75 minutes compared with 235 minutes for four patients who did not have an undescended parathyroid adenoma identified before the operation and were examined via a previous transverse cervical incision. All patients were cured of their hyperparathyroidism. CONCLUSIONS: Undescended parathyroid adenomas were the cause of failed cervical exploration in 17 (7%) of 255 patients. Accurate preoperative localization of these lesions is possible in most cases with a combination of noninvasive and invasive modalities. Successful preoperative localization can convert a prolonged exploration of the neck and mediastinum into a brief, curative procedure with minimal morbidity.
Assuntos
Adenoma/cirurgia , Hiperparatireoidismo/cirurgia , Neoplasias das Paratireoides/cirurgia , Adenoma/diagnóstico , Adulto , Idoso , Cálcio/sangue , Feminino , Seguimentos , Humanos , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/diagnósticoAssuntos
Doença , Inibidores do Crescimento/farmacologia , Inibidores do Crescimento/fisiologia , Inflamação/fisiopatologia , Interleucina-6 , Linfocinas/farmacologia , Linfocinas/fisiologia , Doença Aguda , Animais , Caquexia/fisiopatologia , Doença Crônica , Expressão Gênica/efeitos dos fármacos , Inibidores do Crescimento/uso terapêutico , Humanos , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Lipase Lipoproteica/biossíntese , Linfocinas/uso terapêutico , Modelos Biológicos , Receptores de Citocinas/fisiologia , Receptores de OSM-LIFRESUMO
The mating of CBA/j female mice (H2k) by DBA/2j male mice (H2d) typically results in an elevated incidence of spontaneous embryo loss thus providing an ideal genetically controlled laboratory model for the study of the factors causing early embryo loss during pregnancy. There is now considerable data on the cells and factors involved in fetal resorption but little is known about the events which activate this process. While the activation of the maternal response to the fetal implant could have endogenous or genetic origins, a role for exogenous factors including microbial pathogens could also be involved. In order to investigate these possibilities, the reproductive success of CBA/j female x DBA/2j male matings in a conventional animal care facility were compared with matings in a specific pathogen free (SPF) animal facility. All animals housed under these conditions were routinely screened by immunoassay and culture, for the presence of a number of viral and bacterial pathogens of mice. The incidence of spontaneous embryo loss in specific pathogen free CBA female mice mated by DBA and other male strains was found to be virtually identical to that of CBA female mice infected with multiple viral pathogens and housed under otherwise identical conditions (non-SPF). However, the numbers of implantation per pregnancy was significantly greater in an SPF facility. Therefore, exposure of mating mice to exogenous viral and bacterial pathogens did not appear to alter the overall incidence of spontaneous embryo resorption. It was concluded that the immunomodulatory effects of infection by common murine pathogens neither augmented nor reduced post-implantation embryo losses.
Assuntos
Aborto Animal/etiologia , Criação de Animais Domésticos , Animais , Infecções por Coronavirus/complicações , Perda do Embrião/etiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Vírus da Hepatite Murina , Gravidez , Viroses/complicaçõesRESUMO
Dispositional optimism and choice of coping strategies were measured twice to test the hypothesis that optimists and pessimists routinely use different methods of coping with stressful events and that these choices are stable over time. 82 participants completed a measure of optimism (LOT) and of coping strategy choice (COPE) at each of two sessions, four weeks apart. Repeated-measures t tests showed that overall the self-reports of dispositional optimism and all 15 coping strategy factors were stable over the four-week period. In addition, all 16 scales were significantly related to the first administration at follow-up. Regarding the relation between the 15 coping factors and optimism, five remained significantly correlated with optimism at both testings, five remained uncorrelated with optimism at both testings, and five showed minor changes in magnitude of their correlation (and statistical significance) at both testings.