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1.
Surg Endosc ; 35(11): 6358-6365, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34114069

RESUMEN

BACKGROUND: Optimized drug delivery systems are needed for intraperitoneal chemotherapy. The aim of this study was to develop a technology for applying pressurized intraperitoneal aerosol chemotherapy (PIPAC) under hyperthermic conditions (hPIPAC). METHODS: This is an ex-vivo study in an inverted bovine urinary bladder (IBUB). Hyperthermia was established using a modified industry-standard device (Humigard). Two entry and one exit ports were placed. Warm-humid CO2 was insufflated in the IBUB placed in a normothermic bath to simulate body thermal inertia. The temperature of the aerosol, tissue, and water bath was measured in real-time. RESULTS: Therapeutic hyperthermia (target tissue temperature 41-43 °C) could be established and maintained over 30 min. In the first phase (insufflation phase), tissue hyperthermia was created by insufflating continuously warm-humid CO2. In the second phase (aerosolization phase), chemotherapeutic drugs were heated up and aerosolized into the IBUB. In a third phase (application phase), hyperthermia was maintained within the therapeutic range using an endoscopic infrared heating device. In a fourth phase, the toxic aerosol was discarded using a closed aerosol waste system (CAWS). DISCUSSION: We introduce a simple and effective technology for hPIPAC. hPIPAC is feasible in an ex-vivo model by using a combination of industry-standard medical devices after modification. Potential pharmacological and biological advantages of hPIPAC over PIPAC should now be evaluated.


Asunto(s)
Hipertermia Inducida , Desarrollo Industrial , Aerosoles , Animales , Bovinos , Humanos
2.
Colorectal Dis ; 22(6): 635-640, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32359223

RESUMEN

AIM: The rapid spread of the COVID-19 pandemic has created unprecedented challenges for the medical and surgical healthcare systems. With the ongoing need for urgent and emergency colorectal surgery, including surgery for colorectal cancer, several questions pertaining to operating room (OR) utilization and techniques needed to be rapidly addressed. METHOD: This manuscript discusses knowledge related to the critical considerations of patient and caregiver safety relating to personal protective equipment (PPE) and the operating room environment. RESULTS: During the COVID-19 pandemic, additional personal protective equipment (PPE) may be required contingent upon local availability of COVID-19 testing and the incidence of known COVID-19 infection in the respective community. In addition to standard COVID-19 PPE precautions, a negative-pressure environment, including an OR, has been recommended, especially for the performance of aerosol-generating procedures (AGPs). Hospital spaces ranging from patient wards to ORs to endoscopy rooms have been successfully converted from standard positive-pressure to negative-pressure spaces. Another important consideration is the method of surgical access; specifically, minimally invasive surgery with pneumoperitoneum is an AGP and thus must be carefully considered. Current debate centres around whether it should be avoided in patients known to be infected with SARS-CoV-2 or whether it can be performed under precautions with safety measures in place to minimize exposure to aerosolized virus particles. Several important lessons learned from pressurized intraperitoneal aerosolized chemotherapy procedures are demonstrated to help improve our understanding and management. CONCLUSION: This paper evaluates the issues surrounding these challenges including the OR environment and AGPs which are germane to surgical practices around the world. Although there is no single universally agreed upon set of answers, we have presented what we think is a balanced cogent description of logical safe approaches to colorectal surgery during the COVID-19 pandemic.


Asunto(s)
Infecciones por Coronavirus/prevención & control , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Laparoscopía/métodos , Quirófanos , Pandemias/prevención & control , Equipo de Protección Personal , Neumonía Viral/prevención & control , Neumoperitoneo Artificial/métodos , Filtros de Aire , Betacoronavirus , COVID-19 , Cirugía Colorrectal , Infecciones por Coronavirus/transmisión , Procedimientos Quirúrgicos del Sistema Digestivo/instrumentación , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Humanos , Control de Infecciones/instrumentación , Laparoscopía/instrumentación , Neumonía Viral/transmisión , SARS-CoV-2 , Paños Quirúrgicos
3.
Colorectal Dis ; 18(4): 364-71, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26400556

RESUMEN

AIM: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an experimental drug delivery method that applies chemotherapy into the abdominal cavity as an aerosol under pressure. We present the first results obtained with PIPAC in colorectal peritoneal metastasis (CPM). METHOD: This is a retrospective analysis. PIPAC was applied in 17 consecutive patients with pretreated CPM. All patients had previously undergone surgery, and 16 had undergone previous lines of systemic chemotherapy (median, two lines). The mean peritoneal metastasis index (peritoneal cancer index) was 16 ± 10. Forty-eight applications of PIPAC with oxaliplatin (92 mg/m2 ) were given every 6 weeks at 37 °C and 12 mmHg for 30 min. The outcome criteria were microscopic pathological response, survival and adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. RESULTS: Forty-eight PIPAC administrations were performed with no intra-operative complications. The mean number of PIPAC administrations per patient was 2.8 (minimum one, maximum six). Postoperative adverse events (CTCAE level 3) were observed in four patients (23%), no CTCAE level-4 adverse events were reported. The hospital mortality was zero. Objective tumour responses were observed in 12/17 patients (71%), and the overall responses were as follows: complete pathological response (seven patients), major response (four patients), partial response (one patient), no response (two patients) and not eligible (three patients). The mean survival after first PIPAC was 15.7 months. CONCLUSION: Repeated PIPAC with oxaliplatin can induce the regression of pretreated CPM. The toxicity appears to be low. These preliminary results are encouraging and justify prospective clinical studies.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Neoplasias Peritoneales/tratamiento farmacológico , Aerosoles , Anciano , Neoplasias Colorrectales/patología , Aire Comprimido , Femenino , Humanos , Infusiones Parenterales/métodos , Masculino , Persona de Mediana Edad , Oxaliplatino , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Resultado del Tratamiento
4.
Rev Sci Instrum ; 94(10)2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37823768

RESUMEN

Annealing tests are of utmost importance in nuclear fuel research, particularly to study the thermophysical properties of the material, microstructure evolution, or the released gas as a function of temperature. As an alternative to conventional furnace or induction annealing, we report on a laser-heating experiment allowing one to heat a nuclear fuel pellet made of uranium dioxide, UO2, or potentially other nuclear fuel pellets in an isothermal and controlled manner. For that purpose, we propose to use an indirect heating method based on a two compartment tungsten crucible, one containing the sample and the other acting as a laser susceptor for efficient and homogeneous heating of the assembly. With this concept, we demonstrate the heating of UO2 samples up to 1500 °C at a maximum heating rate of 30 °C/s with the use of two 500 W lasers. The system is, however, scalable to higher heating rates or higher temperatures by increasing the laser power up to few kW. The experiment has been designed to heat a pressurized water reactor fuel pellet, but the concept could be easily applied to other sample geometries or materials.

5.
Plant Methods ; 18(1): 125, 2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36424625

RESUMEN

BACKGROUND: Grasses internodes are made of distinct tissues such as vascular bundles, epidermis, rind and pith. The histology of grasses stem was largely revisited recently taking advantage of the development of microscopy combined with the development of computer-automated image analysis workflows. However, the diversity and complexity of the histological profile complicates quantification. Accurate and automated analysis of histological images thus remains challenging. RESULTS: Herein, we present a workflow that automatically segments maize internode cross section images into 40 distinct tissues: two tissues in the epidermis, 19 tissues in the rind, 14 tissues in the pith and 5 tissues in the bundles. This level of segmentation is achieved by combining the Hue, Saturation and Value properties of each pixel and the location of each pixel in FASGA stained cross sectiona. This workflow is likewise able to highlight significant and subtle histological genotypic variations between maize internodes. The grain of precision provided by the workflow also makes it possible to demonstrate different levels of sensitivity to digestion by enzymatic cocktails of the tissues in the pith. The precision and strength of the workflow is all the more impressive because it is preserved on cross section images of other grasses such as miscanthus or sorghum. CONCLUSIONS: The fidelity of this tool and its capacity to automatically identify variations of a large number of histological profiles among different genotypes pave the way for its use to identify genotypes of interest and to study the underlying genetic bases of variations in histological profiles in maize or other species.

7.
Plant Methods ; 17(1): 89, 2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34380508

RESUMEN

BACKGROUND: Since the introduction of studies on maize silage digestibility at the end of the nineteenth century, protocols to estimate dry matter digestibility have not stopped evolving. Since the early 1980s, the protocol developed by Aufrère became a benchmark in many laboratories to estimate in vitro dry matter digestibility. In order to increase its throughput, to facilitate its execution and to decipher the impact of the different parameters of the protocol we decided to test the combination of 7 parameters in 21 different protocols. RESULTS: We thus tested the impact of (1) the presence or absence of pepsin in HCl solution, (2) the temperature of incubation during enzymatic hydrolysis, (3) the presence or absence of a gelatinization step, (4) washing/rinsing versus neutralization step, (5) the presence or absence of α-amyloglucosidase in enzymatic solution, (6) the duration of cellulase incubation, and (7) the concentration of the cellulase solution. The major result of our work highlighted that it was essential to carry out a gelatinization step to correctly estimate the in vitro dry matter digestibility of maize silage. CONCLUSIONS: The proposed protocol in this paper is innovative, reliable, highthroughput and easy to implement in many laboratories to accurately quantity in vitro dry matter digestibility.

8.
Pathobiology ; 77(2): 53-63, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20332665

RESUMEN

In lung cancer, integrating translational data from various histologies obtained in different patients under different conditions can increase their robustness. This is a meta-analysis of cDNA array data obtained in 688 tumor patients (541 non-small cell lung cancer, 33 small cell lung cancer and 114 others) and 205 controls. 1,206 genes were found to be dysregulated in one of the 12 transcriptomics studies available. 748 results (62%) were obtained only once and might be questioned. 38% of observations could be reproduced twice or more. 346 genes were reported twice, 80 three times, 27 four and 5 five times. A common set of genes dysregulated in lung cancer was obtained, including BPA1, DUSP6, ASCL1, RNAS1 and S100P. p63 and CK 5/6 p63 are useful for differentiating adenocarcinoma and small cell lung cancer from squamous cell carcinoma. TFF-3 and MUC1 are over-expressed in adenocarcinoma. INSM1, SGNE1 and H2AFZ are typical for small cell lung cancer. Using a meta-analysis approach, it was possible to detect a robust set of genes differentially expressed in lung cancer and to determine a limited number of key genes linked to subtypes in lung cancer molecular pathology.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Investigación Biomédica Traslacional/tendencias , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , ADN de Neoplasias/análisis , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Análisis de Secuencia por Matrices de Oligonucleótidos
9.
Zentralbl Chir ; 135(6): 523-7, 2010 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-21154209

RESUMEN

The treatment of advanced rectal cancer is a complicated task that can only poorly be reduced to the simple question "to operate or not to operate?" Instead the following factors must be taken into consideration: symptomatic versus non-symptomatic patients, emergency surgery versus elective surgery, proximal versus distal rectal cancer, local advanced versus metastatic disease, primary tumour versus recurrence, unresectable versus potentially resectable metastases, resection versus diversionary surgical procedures, etc. Also within the conservative group one must decide between interventional therapy (combined chemotherapy, stent placement, radiotherapy, etc.) and purely palliative therapy. Results from studies are not sufficient for the formulation of general recommendations. However, there are only few arguments against a surgical procedure in a symptomatic situation when the primary tumour dominates. In cases of metastasizing colorectal cancer modern chemotherapeutic procedures and new antibody therapies can markedly prolong survival. These results cannot be achieved by surgery alone. In this situation, it should be considered whether the longer life expectancy will be accompanied by the later occurrence of symptoms, which again justifies a surgical indication within the framework of multimodality therapy. The widely differing starting situations lead to different therapeutic approaches so that an individual indication can be made in the course of a tumour board discussion.


Asunto(s)
Cuidados Paliativos/métodos , Neoplasias del Recto/cirugía , Terapia Combinada , Procedimientos Quirúrgicos Electivos , Urgencias Médicas , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Estadificación de Neoplasias , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Stents
10.
J Crohns Colitis ; 14(11): 1524-1534, 2020 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-32533769

RESUMEN

BACKGROUND: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. AIMS: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. METHODS: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. RESULTS: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). CONCLUSION: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.


Asunto(s)
Adalimumab , Enfermedad de Crohn , Infliximab , Mucosa Intestinal , Imagen por Resonancia Magnética/métodos , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Adulto , Biomarcadores Farmacológicos/análisis , Proteína C-Reactiva/análisis , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/fisiopatología , Estudios de Factibilidad , Femenino , Francia/epidemiología , Humanos , Infliximab/administración & dosificación , Infliximab/efectos adversos , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patología , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Inducción de Remisión/métodos , Índice de Severidad de la Enfermedad , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Inhibidores del Factor de Necrosis Tumoral/efectos adversos
12.
J Agric Food Chem ; 66(19): 4800-4808, 2018 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-29690760

RESUMEN

Water supply and valorization are two urgent issues in the utilization of maize biomass in the context of climate change and replacement of fossil resources. Maximizing maize biomass valorization is of interest to make biofuel conversion competitive, and to increase forage energetic value for animal fodder. One way to estimate biomass valorization is to quantify cell wall degradability. In this study, we evaluated the impact of water supply on cell wall degradability, cell wall contents and structure, and distribution of lignified cell types in maize internodes using dedicated high-throughput tools to effectively phenotype maize internodes from 11 inbred lines under two contrasting irrigation scenarios in field trials over three years. Overall, our results clearly showed that water deficit induced significant changes in lignin content and distribution along with a reduction in lignin p-coumaroylation, thereby impacting cell wall degradability. Additionally, we also observed that responses to a water deficit varied between the lines examined, underscoring biochemical and histological target traits for plant breeding.


Asunto(s)
Pared Celular/metabolismo , Lignina/metabolismo , Agua/metabolismo , Zea mays/metabolismo , Riego Agrícola , Pared Celular/genética , Endogamia , Tallos de la Planta/genética , Tallos de la Planta/metabolismo , Zea mays/genética
13.
Cancer Res ; 60(20): 5870-8, 2000 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-11059785

RESUMEN

Caveolin-1 expression and function were investigated in human colon cancer. Low levels of caveolin-1 mRNA and protein were detected in several colon carcinoma cell lines. Moreover, caveolin-1 protein levels were significantly reduced in human tumor epithelial mucosa (3.6 +/- 1.4-fold) when compared with normal colon mucosa for a majority (10 of 15) of the patients characterized. To directly assess the role of caveolin-1 in tumor development, caveolin-1 was reexpressed in the HT29 and DLD1 colon carcinoma cells, and the resulting HT29-cav-1 or DLD1-cav-1 cells were tested for tumorigenicity in nude mice. In most experiments, tumor formation was either blocked or retarded for HT29-cav-1 cells (10 of 13 mice) and DLD1-cav-1 cells (5 of 7 mice), as compared with both mock-transfected and parental HT29 or DLD1 cells. Interestingly, basal caveolin-1 levels were significantly reduced in HT29-cav-1 and DLD1-cav-1 cells isolated from tumors. Likewise, endogenous caveolin-1 mRNA and protein levels were found to be reduced in NIH-3T3 cells recovered from tumors after injection into nude mice. Thus, reexpression of caveolin-1 in colon carcinoma lines reduced the probability of tumor formation in vivo, and when tumors did develop from either HT29-cav-1, DLD1-cav-1, or NIH-3T3 cells, lower basal levels of caveolin-1 were detected. Finally, evidence was obtained indicating that initial caveolin-1 down-regulation in colon cancer cells need not be an entirely irreversible process because cell survival on selection for either drug resistance or increased metastatic potential correlated with increased caveolin-1 expression levels.


Asunto(s)
Carcinoma/metabolismo , Caveolinas/biosíntesis , Neoplasias del Colon/metabolismo , Células 3T3/metabolismo , Animales , Antimetabolitos Antineoplásicos/farmacología , Carcinoma/genética , Carcinoma/patología , Caveolina 1 , Caveolinas/genética , Colon/metabolismo , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Perros , Regulación hacia Abajo , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Células HT29/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Metotrexato/farmacología , Ratones , Ratones Desnudos , Metástasis de la Neoplasia , Transfección , Células Tumorales Cultivadas
14.
Circulation ; 100(7): 700-5, 1999 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-10449690

RESUMEN

BACKGROUND: Administration of protease inhibitors (PIs) to HIV-infected individuals has been associated with hyperlipidemia. In this study, we characterized the lipoprotein profile in subjects receiving ritonavir, indinavir, or nelfinavir, alone or in combination with saquinavir. METHODS AND RESULTS: Plasma lipoprotein levels were quantified in 93 HIV-infected adults receiving PIs. Comparison was done with pretreatment values and with 28 nonPI-treated HIV-infected subjects. An elevation in plasma cholesterol levels was observed in all PI-treated groups but was more pronounced for ritonavir (2.0+/-0.3 mmol/L [mean+/-SEM], n=46, versus 0.1+/-0.2 mmol/L in nonPI treated group, P<0.001) than for indinavir (0.8+/-0.2 mmol/L, n=26, P=0.03) or nelfinavir (1.2+/-0.2 mmol/L, n=21, P=0.01). Administration of ritonavir, but not indinavir or nelfinavir, was associated with a marked elevation in plasma triglyceride levels (1.83+/-0.46 mmol/L, P=0.002). Plasma HDL-cholesterol levels remained unchanged. Combination of ritonavir or nelfinavir with saquinavir did not further elevate plasma lipid levels. A 48% increase in plasma levels of lipoprotein(a) was detected in PI-treated subjects with pretreatment Lp(a) values >20 mg/dL. Similar changes in plasma lipid levels were observed in 6 children receiving ritonavir. CONCLUSIONS: Administration of PIs to HIV-infected individuals is associated with a marked, compound-specific dyslipidemia. The risk of pancreatitis and premature atherosclerosis due to PI-associated dyslipidemia remains to be established.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Arteriosclerosis/etiología , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Hiperlipidemias/inducido químicamente , Lipoproteínas/sangre , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Niño , Quimioterapia Combinada , Femenino , Infecciones por VIH/sangre , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Hipercolesterolemia/inducido químicamente , Hipercolesterolemia/epidemiología , Hiperlipidemias/sangre , Hiperlipidemias/complicaciones , Hiperlipidemias/epidemiología , Hipertrigliceridemia/inducido químicamente , Hipertrigliceridemia/epidemiología , Indinavir/administración & dosificación , Indinavir/efectos adversos , Indinavir/uso terapéutico , Lípidos/sangre , Lipoproteína(a)/sangre , Modelos Logísticos , Masculino , Nelfinavir/administración & dosificación , Nelfinavir/efectos adversos , Nelfinavir/uso terapéutico , Factores de Riesgo , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Saquinavir/administración & dosificación , Saquinavir/efectos adversos , Saquinavir/uso terapéutico , Tirotropina/sangre
15.
J Clin Oncol ; 16(1): 324-9, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9440760

RESUMEN

PURPOSE: Total mesorectal excision (TME) and other technical surgical factors reduce local recurrence rate in rectal cancer. Scientific evidence of the positive effect of optimal surgery on survival is locking. Whether a reduction in the incidence of distant metastases can be achieved with optimal surgery is uncertain. We examine the effects of the quality of surgery, as reflected by local recurrence rate, on survival and the incidence of initial distant metastases. PATIENTS AND METHODS: Between 1974 and 1991, 1,581 consecutive patients who underwent curative resection (RO) for rectal carcinoma were monitored for recurrence and survival. TME was introduced in 1985. No patient received adjuvant radiotherapy or chemotherapy. The median follow-up time was greater than 13 years. RESULTS: The local recurrence rate decreased from 39.4% to 9.8% during the study period (P < .0001). The observed 5-year survival rate improved from 50% to 71% (P < .0001). Three hundred six patients with local recurrence had a significantly lower observed 5-year survival rate (P < .0001). A total of 1,285 patients had no local recurrence, but 275 of them developed distant metastases (International Union Against Cancer [UICC] stage I, 8%; stage II, 16%; stage III, 40%). Better-quality surgery had no effect on the incidence of initial distant metastases, which remained constant (P = .44). CONCLUSION: Quality of surgery is an independent prognostic factor for survival in rectal cancer, but has no influence on initial occurrence of distant metastases. Local recurrence cannot be considered an outcome criterion of adjuvant treatment without consideration of the surgeon as a risk factor.


Asunto(s)
Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Cirugía General/normas , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Neoplasias del Recto/epidemiología , Neoplasias del Recto/patología , Tasa de Supervivencia
16.
J Clin Oncol ; 19(11): 2837-43, 2001 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-11387355

RESUMEN

PURPOSE: To study bone marrow micrometastases from colorectal cancer patients for the presence of K-ras mutations and to compare their genotype with that of the corresponding primary tumor. PATIENTS AND METHODS: Bilateral iliac crest aspiration was performed in 51 patients undergoing surgery for colorectal cancer, and bone marrow micrometastases were detected by immunohistochemistry. The presence of K-ras mutations was determined by single-strand conformation polymorphism analysis on both primary tumors and paired bone marrow samples and was confirmed by sequencing. RESULTS: In six patients with primary tumor mutations, it was possible to amplify a mutated K-ras gene also from the bone marrow sample. In three of those patients the pattern of K-ras mutations differed between both samples, in two patients the mutation was identical between the bone marrow and its primary tumor, and in one patient the same mutation plus a different one were found. Fifteen of 17 K-ras mutations found in primary tumors were located in codon 12, whereas in bone marrow, five of seven mutations were found in codon 13 (P =.003). CONCLUSION: Our results demonstrate that, at least for K-ras mutations, disseminated epithelial cells are not always clonal with the primary tumor and they question the malignant genotype of bone marrow micrometastases. They also indicate that different tumoral clones may be circulating simultaneously or sequentially in the same patient. Analysis of the type of mutations suggests that cell dissemination might be an early event in colorectal carcinogenesis.


Asunto(s)
Neoplasias de la Médula Ósea/genética , Neoplasias de la Médula Ósea/secundario , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , ADN de Neoplasias/genética , Genes ras/genética , Anciano , Transformación Celular Neoplásica , Células Clonales , Codón , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Células Neoplásicas Circulantes , Reacción en Cadena de la Polimerasa , Estudios Prospectivos
17.
Diabetes ; 38(4): 471-6, 1989 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2647554

RESUMEN

To investigate the role of the mediobasal hypothalamus (MBH) in diabetic gonadal axis disorders, the MBHs of adult male streptozocin-induced diabetic (STZ-D) rats were examined after incubation in basal conditions or in K+-enriched medium and compared with those of controls. Diabetes lasted 1 mo. Both luteinizing-hormone-releasing hormone (LHRH) release and MBH morphology were studied. After incubation in basal conditions, the LHRH release was unchanged. By light microscopy, the dilated-axon cross sections were more numerous (P less than .01) in the basal arcuate nucleus and in the median eminence. By electron microscopy, the ratio of exocytoses to neurosecretory granules observed in the median eminence axon cross sections was smaller (P less than .05). The total LHRH immunoreactivity, the number of labeled axons, and the amount of positive material in the axons were reduced (P less than .05). After incubation in K+-enriched medium, the LHRH release was markedly reduced (P less than .01). The number and area of dilated-axon cross sections, possibly because of the relation between exocytosis and physiological dilation, were less augmented (P less than .01). Whereas the number of exocytoses and the ratio of exocytoses to neurosecretory granules were not decreased, the total LHRH immunoreactivity and the number of labeled axons were reduced (P less than .05). The releasable LHRH pool therefore seems to be exhausted in control MBH because of long-term stimulation and reduced in the MBH of STZ-D rats because of diabetes. In conclusion, STZ-D causes functional and anatomical MBH lesions that should be pathogenetically relevant for the disorders of the gonadal axis documented in this animal model.


Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo Medio/metabolismo , Animales , Femenino , Hipotálamo Medio/efectos de los fármacos , Hipotálamo Medio/fisiopatología , Técnicas In Vitro , Eminencia Media/patología , Eminencia Media/ultraestructura , Microscopía Electrónica , Potasio/farmacología , Ratas , Ratas Endogámicas , Valores de Referencia
18.
Diabetes ; 38(11): 1351-6, 1989 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-2515982

RESUMEN

Streptozocin-induced diabetes (STZ-D) in rats is associated with marked hypothyroidism characterized by functional impairment and structural lesions of the pituitary-thyroid axis. Degenerative axonal lesions, which can be prevented by insulin administration, have been reported in the mediobasal hypothalamus (MBH) of STZ-D rats. However, direct evidence connecting anatomic MBH lesions with functional impairment is still missing. We therefore performed a combined functional and morphological investigation in 4-mo-old STZ-D male rats (diabetes lasted 1 mo), applying an in vitro model to study in the same isolated MBH 1) the basal and depolarization-induced thyrotropin-releasing hormone (TRH) release during two successive incubations of 20 min each and 2) morphological and morphometric aspects, including distribution and amount (densitometric evaluation) of immunoreactive TRH in the incubated tissue. In basal conditions, TRH release was much lower in diabetic than control MBH during both incubations (P less than .01 vs. P less than .05). In depolarizing conditions, TRH release was increased during the second incubation in control (P less than .05) and during both incubations in diabetic (P less than .01) rats, the percentage increase of the TRH release due to ionic stimulation being much higher in diabetic than control animals (P less than .01). As determined by light-microscope morphometry, the total area of dilated-axon cross sections was larger in diabetic than control MBH under basal conditions (P less than .01), thus confirming degenerative axonopathy in diabetic rats. By densitometry determination, the amount of immunoreactive TRH was higher in stimulated diabetic MBH compared with both stimulated control and basal diabetic MBH (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Hipotálamo Medio/metabolismo , Hormona Liberadora de Tirotropina/metabolismo , Animales , Axones/patología , Glucemia/metabolismo , Peso Corporal , Diabetes Mellitus Experimental/patología , Hipotálamo Medio/patología , Hipotiroidismo/etiología , Hipotiroidismo/metabolismo , Inmunohistoquímica , Técnicas In Vitro , Masculino , Eminencia Media/metabolismo , Ratas , Ratas Endogámicas
19.
J Mol Biol ; 243(4): 736-53, 1994 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-7966293

RESUMEN

The sources of the stability of a type VI turn formed with high population in the cis isomeric form of an unblocked six residue peptide, Ser1-Tyr2-Pro3-Tyr4-Asp5-Val6 (SYPYDV), were investigated by making extensive amino acid substitutions at residues 2, 4 and 5. Several NMR parameters indicate the presence of the turn, including significant upfield shifts of the proton resonances of the cis proline, a small 3JHN alpha coupling constant for residue 2, a cross-turn d alpha N(i,i+2) from residue 2 to residue 4 and in increased mole fraction of the cis form in the conformational ensemble. By these criteria, a number of peptides were found to contain significant populations of type VI turn conformers in the cis form of the peptide. The NMR parameters are highly dependent on the sequence of the peptide, and are strongly correlated with each other and with the population of type VI turn. The greatest populations of turn conformations were observed for peptides of the general form AA-Ar-Pro-Ar-Hp, where AA represents any amino acid, Ar an aromatic residue and Hp a small hydrophilic residue. There is no evidence in the form of lowered amide proton temperature coefficients for direct hydrogen bonding as a primary source of turn stability. Instead, the major stabilizing factor, indicated by the strong dependence of the turn population on the presence of aromatic (not hydrophobic) residues at positions 2 and 4, is the stacking of the aromatic and proline rings. A measurable preference for deprotonated aspartate at position 5, which is not part of the turn itself, and the destabilization of the turn at high and low pH, indicate that electrostatic interactions between the unblocked N terminus and the aspartate carboxyl group also act to stabilize the turn conformation when the Ar-Pro-Ar sequence is present. Implications for stabilization of local elements of secondary structure during the earliest events in protein folding are discussed.


Asunto(s)
Péptidos/química , Conformación Proteica , Estructura Secundaria de Proteína , Secuencia de Aminoácidos , Ácido Aspártico/química , Derivados del Benceno/química , Simulación por Computador , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Datos de Secuencia Molecular , Prolina/química , Pliegue de Proteína , Estándares de Referencia , Estereoisomerismo , Agua/química
20.
Eur J Surg Oncol ; 41(10): 1379-85, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26138283

RESUMEN

BACKGROUND: Quality of Life (QoL) plays an important role in patients with peritoneal metastasis and is deteriorating continuously until death. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative palliative treatment of peritoneal metastasis. We present the first QoL results under PIPAC therapy. METHODS: Retrospective analysis of QLQ30 questionnaire results during repeated courses of PIPAC applications in palliative patients with pretreated peritoneal metastasis. RESULTS: 91 patients (M:F = 40:51, median age 64 (34-77) years) with 158 PIPAC applications were analyzed. 86% patients had previously received systemic chemotherapy. Peritoneal metastasis was advanced (Peritoneal Carcinomatosis Index I = 16 ± 10). At admission, only moderate impairment of functioning (62-83%) and symptom scores (17-47%) was observed. 48 patients received at least 2 PIPAC every 6 weeks. After PIPAC # 1, the global physical score deteriorated slightly (from 82% to 75%), but improved after PIPAC # 2 (up to 89%). Gastrointestinal symptoms (nausea/vomiting, constipation, diarrhoea, anorexia) remained stable under PIPAC therapy. CONCLUSIONS: Quality of life was relatively high in this group of patients with advanced, pretreated peritoneal metastasis, explaining their wish for further therapy. Functioning scores and disease-related symptoms were not altered for at least 3 months in the patients able to receive repeated PIPAC. Except for a transient moderate increase of pain scores, PIPAC did not cause therapy-related QoL deterioration, especially no gastrointestinal symptoms.


Asunto(s)
Aerosoles/uso terapéutico , Antineoplásicos/administración & dosificación , Carcinoma/tratamiento farmacológico , Neoplasias Gastrointestinales/patología , Mesotelioma/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Peritoneales/tratamiento farmacológico , Calidad de Vida , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carcinoma/secundario , Estudios de Cohortes , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Femenino , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Cuidados Paliativos , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Resultado del Tratamiento
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