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BACKGROUND AND AIMS: The present standard of care in treating lower extremity soft tissue sarcomas is function-sparing, limb-preserving resection and reconstruction with or without oncological therapy. The aim of this pilot study was to test the suitability and adequacy of the Finnish translations of two functional outcome questionnaires (Toronto Extremity Salvage Score and Musculoskeletal Tumor Society score) and to perform a preliminary investigation of functional outcomes of Finnish lower-limb soft tissue sarcoma patients after operative treatment. MATERIALS AND METHODS: Between June 2015 and December 2015, consecutive surgically treated outpatients were asked to participate in the study. Demographic, clinical, surgical, and oncological outcome data were collected. Two functional outcome questionnaires were used (Toronto Extremity Salvage Score and Musculoskeletal Tumor Society scores). A comparative analysis is presented. RESULTS: A total of 19 lower-limb soft tissue sarcoma patients with a mean follow-up time of 2 years and 10 months were included. All (n = 19) invited patients participated in the study. Mean age was 62.3 years. In total, 13 had high-grade sarcomas. Eight wounds were closed directly, four used skin grafts, and five required flap reconstructions. One patient required a tumor prosthesis, and one required a rotationplasty. A total of 14 patients received oncological therapy. No problems or difficulties were reported in using and completing the Finnish versions of the Toronto Extremity Salvage Score or Musculoskeletal Tumor Society questionnaires. The overall Toronto Extremity Salvage Score and Musculoskeletal Tumor Society scores were 88 and 76, respectively. CONCLUSION: This pilot study suggests that the Finnish versions of the Toronto Extremity Salvage Score and Musculoskeletal Tumor Society questionnaires are suitable for measuring functional outcome after lower extremity soft tissue sarcomas treatment. Functional outcomes vary from moderate to excellent.
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Recuperación del Miembro , Extremidad Inferior , Recuperación de la Función , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Finlandia , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Encuestas y Cuestionarios , Traducciones , Resultado del TratamientoRESUMEN
It has been reported that foetal death follows a seasonal pattern. Influenza virus infection has been postulated as one possible contributor to this seasonal variation. This ecological study explored the temporal association between the influenza activity and the frequency of foetal death. Time series analysis was conducted using weekly influenza-like illness consultation proportions from the Danish sentinel surveillance system and weekly proportions of spontaneous abortions and stillbirths from hospital registers from 1994 to 2009. The association was examined in an autoregressive (AR) integrated (I) moving average (MA) model and subsequently analysed with cross-correlation functions. Our findings confirmed the well-known seasonality in influenza, but also seasonality in spontaneous abortion. No clear pattern of seasonality was found for stillbirths, although the analysis exposed dependency between observations. One final AR integrated MA model was identified for the influenza-like illness (ILI) series. We found no statistically significant relationship between weekly influenza-like illness consultation proportions and weekly spontaneous abortion proportions (five lags: P = 0.52; 11 lags: P = 0.91) or weekly stillbirths (five lags: P = 0.93; 11 lags: P = 0.40). Exposure to circulating influenza during pregnancy was not associated with rates of spontaneous abortions or stillbirths. Seasonal variations in spontaneous abortion were confirmed and this phenomenon needs further investigation.
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BACKGROUND: Extensive compound tibial fractures present reconstructive challenges. The present study aimed to assess the outcomes of microvascular latissimus dorsi (LD) flap combined with the Ilizarov technique for extensive compound tibial fractures with bone loss and bone healing complications. METHODS: Patient records were reviewed retrospectively. The Lower Extremity Functional Scale (LEFS), the Disabilities of the Arm, Hand and Shoulder (DASH), and the 15D health-related quality of life (HRQoL) instrument were applied. RESULTS: Between 1989 and 2014, 16 patients underwent reconstruction with a microvascular LD flap and bone transport (11/16) or late bone lengthening (5/16). The mean clinical follow-up time was 6.6 (standard deviation (SD): 6.5) years. Three patients had minor complications requiring reoperation. Partial necrosis of one flap required late flap reconstruction in one case. Late bone grafting was used to enhance union in eight of 16 cases. The mean new bone gain was 3.8 cm (SD: 2.5). Overall, 11 patients completed the questionnaires in a mean of 22.3 years (SD: 2.4) after surgery. The main findings revealed a relatively good function of the reconstructed limb and good shoulder function. The mean HRQoL was comparable to that of an age-standardized sample of the general population. CONCLUSION: Segmental tibia transport and lengthening to correct limb length discrepancy do not compromise the microvascular muscle flap. Combined microvascular LD flap reconstruction and the Ilizarov technique can be used in treating acute compound tibial defects, pseudoarthrosis, and osteitis, all associated with significant amputation risk. Fair long-term functional outcomes and HRQoL are achieved when these combined techniques are used.
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Técnica de Ilizarov , Músculo Esquelético/trasplante , Colgajos Quirúrgicos/irrigación sanguínea , Fracturas de la Tibia/cirugía , Adolescente , Adulto , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/irrigación sanguínea , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
In a non-dysmorphic 5-year-old boy with developmental delay, well-controlled epilepsy, and microcephaly, a 234-kb deletion of Xp22.12 was detected by copy number analysis. The maternally inherited deletion removed the initial 15 of the 21 exons of the connector enhancer of KSR-2 gene called CNKSR2 or CNK2. Our finding suggests that loss of CNKSR2 is a novel cause of non-syndromic X-linked mental retardation, an assumption supported by high gene expression in the brain, localization to the post-synaptic density, and a role in RAS/MAPK-dependent signal transduction.
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This study evaluated whether anti-Müllerian hormone (AMH) was differentially expressed in cumulus (CC) and granulosa (GC) cells from large antral and pre-ovulatory follicles collected from individual follicles in women undergoing in-vitro maturation (IVM) or IVF treatment. Expression studies of AMH, AMH receptor 2, FSH receptor, aromatase and androgen receptor were performed in CC in IVM patients where cumulus-oocyte-complex had expanded, CC in IVM patients where cumulus-oocyte-complex remained compacted, GC from immature follicles and CC and GC from IVF patients. Microarray data on corresponding GC and CC from follicles from IVF patients was included. AMH expression was significantly higher in CC than in GC from both mature and immature follicles and in CC from immature follicles than in CC from pre-ovulatory follicles from IVF patients (P < 0.05). AMH expression was significantly higher in CC that remained compacted compared with those that had expanded (P < 0.008). AMH was correlated to the expression of FSH receptor, androgen receptor and AMH receptor 2 but not to aromatase expression. The expression pattern of AMH receptor 2 reflected that of AMH. AMH may exert intrafollicular functions even in human large antral and pre-ovulatory follicles and may be related to follicular health.
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Hormona Antimülleriana/metabolismo , Células del Cúmulo/metabolismo , Folículo Ovárico/crecimiento & desarrollo , Técnicas Reproductivas Asistidas , Aromatasa/metabolismo , Western Blotting , ADN Complementario/genética , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Modelos Lineales , Análisis por Micromatrices , Folículo Ovárico/metabolismo , Reacción en Cadena de la Polimerasa , Receptores Androgénicos/metabolismo , Receptores de HFE/metabolismo , Receptores de Péptidos/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismoRESUMEN
Human small antral follicles (diameter 3-9 mm) were obtained from ovaries surgically removed for fertility preservation. From the individual aspirated follicles, granulosa cells and the corresponding follicular fluid were isolated in 64 follicles, of which 55 were available for mRNA analysis (24 women). Expressions of androgen receptor (AR) mRNA levels in granulosa cells, and of androstenedione and testosterone in follicular fluid, were correlated to the expression of the FSH receptor (FSHR), LH receptor (LHR), CYP19 and anti-Müllerian Hormone-receptor II (AMHRII) mRNA in the granulosa cells and to the follicular fluid concentrations of AMH, inhibin-B, progesterone and estradiol. AR mRNA expression in granulosa cells and the follicular fluid content of androgens both showed a highly significant positive association with the expression of FSHR mRNA in granulosa cells. AR mRNA expression also correlated significantly with the expression of AMHRII, but did not correlate with any of the hormones in the follicular fluid. These data demonstrate an intimate association between AR expression in immature granulosa cells, and the expression of FSHR in normal small human antral follicles and between the follicular fluid levels of androgen and FSHR expression. This suggests that follicular sensitivity towards FSH stimulation may be augmented by stimulation of androgens via the AR.
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Andrógenos/metabolismo , Líquido Folicular/metabolismo , Células de la Granulosa/metabolismo , Folículo Ovárico/metabolismo , Receptores Androgénicos/genética , Receptores de HFE/genética , Adolescente , Adulto , Western Blotting , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Inmunohistoquímica , Técnicas In Vitro , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Ovaries surgically removed for fertility preservation from a total of 24 women served as a source of human small antral follicles, including the follicular fluid (FF) and the corresponding granulosa cells (GC). The FF was used to evaluate the intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-B, estradiol, progesterone, androstenedione and testosterone. In GC mRNA expression of the AMH type II receptor (AMH-r2) was determined and correlated to the mRNA expression of CYP19 (aromatase), FSH-receptor (FSH-r) and LH-receptor (LH-r) and to the hormonal profiles of the corresponding FF. GC and FF from a total of 64 follicles (diameter of 3-9 mm) were evaluated. Concentrations of AMH in FF showed a highly significant inverse correlation with CYP19 mRNA expression in the corresponding GC and with concentrations of estradiol, progesterone and inhibin-B in the FF. However, a small subgroup of follicles exhibited high levels of AMH simultaneously with relative high levels of CYP19 mRNA. In contrast to AMH, mRNA expression of AMH-r2 was significantly positively correlated to the mRNA expression of FSH-r and CYP 19, but failed to correlate to any other measured parameters. These data confirms an intimate correlation between follicular AMH levels, AMH-r2, FSH-r expression and estradiol secretion in the developing human follicle.
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Hormona Antimülleriana/análisis , Aromatasa/genética , Líquido Folicular/química , Células de la Granulosa/enzimología , ARN Mensajero/aislamiento & purificación , Adolescente , Adulto , Androstenodiona/análisis , Estradiol/análisis , Femenino , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Humanos , Inhibinas/análisis , Progesterona/análisis , Receptores de HFE/genética , Receptores de HL/genética , Receptores de Péptidos/genética , Receptores de Factores de Crecimiento Transformadores beta/genética , Testosterona/análisis , Adulto JovenRESUMEN
AIMS: Limb-sparing surgery combined with radiotherapy (RT) is the basis of extremity soft tissue sarcoma (STS) treatment. The aim of this study was to evaluate the results of microvascular reconstruction after extensive tumour resections in the upper extremity. METHODS: Twenty patients with STS of the upper extremity were treated with excision and microvascular reconstruction. RT was administered if surgical margins were less than 25 mm. Results were evaluated retrospectively. RESULTS: Twenty free flaps were performed and no flaps were lost. There was no operative mortality, and wound complication rate was 15%. Median follow-up length was 74 months. Five-year local recurrence-free survival was 57%, metastasis-free survival 67%, disease-free survival 45% and disease-specific overall survival 80%. Ten patients had no or only mild impairment of upper extremity function, seven had impaired function affecting daily life, and three patients underwent amputation. For patients treated with curative intent, limb salvage rate was 94%. CONCLUSIONS: Free flaps are useful and reliable in the treatment of patients with STS of the upper extremity. Without microvascular reconstruction limb salvage would have been impossible in these patients. Oncological outcome is comparable to other extremity STS patients and upper extremity function is acceptable.
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Recuperación del Miembro , Microcirugia , Microvasos/cirugía , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Colgajos Quirúrgicos/irrigación sanguínea , Extremidad Superior , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Procedimientos de Cirugía Plástica , Sarcoma/radioterapia , Sarcoma/secundario , Neoplasias de los Tejidos Blandos/radioterapiaRESUMEN
BACKGROUND: Self-expanding metallic stents are widely used for relieving biliary duct obstruction in patients with unresectable periampullary malignancies. However, only a few studies have assessed the occurrence of fractures in these stents. PURPOSE: To determine the prevalence and significance of stent fracture after placement of self-expanding metallic stents for periampullary malignant biliary obstruction. MATERIAL AND METHODS: Over a 5-year period, 48 patients underwent placement of self-expanding metallic stents for periampullary malignant biliary obstructions. Stents were introduced 2-6 weeks after a percutaneous transhepatic biliary decompression. The medical records and relevant images were reviewed for stent patency, stent fracture, type of stent, and stent-related complications. RESULTS: Stent fracture was detected in four of the 48 patients (8%): in one patient at 1 month and in three patients between 10 and 21 months after stenting. All four fractures involved one type of nitinol stent used in 38 patients. In one of the patients, fracture was complicated by life-threatening gastrointestinal bleeding. The mean survival time for all patients was 251 days (standard deviation [SD]+/-275 days) and the mean overall patency time for all stents was 187 days (SD+/-205 days). CONCLUSION: Stent fracture occurs after placement of self-expanding nitinol stents for periampullary malignant biliary obstruction. The low reported incidence of this complication may be due to a lack of awareness of and difficulty in detecting stent fracture. Fracture should be considered as a possible contributing factor in recurrent biliary obstruction after self-expanding metallic stent insertion.
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Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/secundario , Colestasis/terapia , Neoplasias Pancreáticas/patología , Stents/efectos adversos , Anciano , Anciano de 80 o más Años , Aleaciones , Colangiografía , Colestasis/etiología , Colestasis/patología , Resultado Fatal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Falla de PrótesisRESUMEN
BACKGROUND: Limb-sparing surgery and satisfactory functional outcome is the goal of extremity soft tissue sarcoma (STS) surgery. Tissue defects after tumour excision are often extensive, and microvascular reconstruction is frequently required. METHODS: Seventy-three patients with STS of the leg requiring microvascular reconstruction were treated between 1985 and 2006. Radiotherapy was delivered if the microscopic surgical margin was less than 2.5 cm. RESULTS: Mean follow-up was 65.9 months. Seventy-five free flaps were performed, with a success rate of 95 per cent. One patient died within a month of surgery. Five-year local recurrence-free survival was 82 per cent, metastasis-free survival 59 per cent, disease-free survival 56 per cent and disease-specific overall survival 70 per cent. Fifty-five (75 per cent) of the 73 patients were able to walk normally or had only minor walking impairment. CONCLUSION: Without microvascular reconstruction, amputation would have been necessary in most patients. Microvascular reconstruction is safe and reliable in lower extremity STS reconstruction.
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Complicaciones Posoperatorias/etiología , Sarcoma/cirugía , Neoplasias Cutáneas/cirugía , Colgajos Quirúrgicos/irrigación sanguínea , Procedimientos Quirúrgicos Vasculares/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/mortalidad , Amputación Quirúrgica/estadística & datos numéricos , Supervivencia sin Enfermedad , Femenino , Humanos , Pierna , Tiempo de Internación , Masculino , Microcirculación , Persona de Mediana Edad , Metástasis de la Neoplasia , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Sarcoma/mortalidad , Neoplasias Cutáneas/mortalidad , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/mortalidad , Adulto JovenRESUMEN
BACKGROUND: The optimal treatment for recurrent inguinal hernia is of concern due to the high frequency of recurrence. METHODS: This randomized multicenter study compared the short- and long-term results for recurrent inguinal hernia repair by either the laparoscopic transabdominal preperitoneal patch (TAPP) procedure or the Lichtenstein technique. RESULTS: A total of 147 patients underwent surgery (73 TAPP and 74 Lichtenstein). The operating time was 65 min (range, 23-165 min) for the TAPP group and 64 min (range, 25-135 min) for the Lichtenstein group. Patients who underwent TAPP reported significantly less postoperative pain and shorter sick leave (8 vs 16 days). The recurrence rate 5 years after surgery was 19% for the TAPP group and 18% for the Lichtenstein group. CONCLUSION: The short-term advantage for patients who undergo the laparoscopic technique is less postoperative pain and shorter sick leave. In the long term, no differences were observed in the chronic pain or recurrence rate.
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Hernia Inguinal/cirugía , Laparoscopía/métodos , Laparotomía/métodos , Mallas Quirúrgicas , Adulto , Anciano , Distribución de Chi-Cuadrado , Estudios de Seguimiento , Hernia Inguinal/diagnóstico , Humanos , Laparoscopía/efectos adversos , Laparotomía/efectos adversos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/epidemiología , Satisfacción del Paciente , Complicaciones Posoperatorias/epidemiología , Probabilidad , Recurrencia , Medición de Riesgo , Estadísticas no Paramétricas , Suecia , Resultado del TratamientoRESUMEN
OBJECTIVE: The aims of this study were: 1) To develop protocols for, integration and assessment of the usefulness of high quality fMRI (functional magnetic resonance imaging) and DTI (diffusion tensor imaging) data in an ultrasound-based neuronavigation system. 2) To develop and demonstrate a co-registration method for automatic brain-shift correction of pre-operative MR data using intra-operative 3D ultrasound. METHODS: Twelve patients undergoing brain surgery were scanned to obtain structural and fMRI data before the operation. In six of these patients, DTI data was also obtained. The preoperative data was imported into a commercial ultrasound-based navigation system and used for surgical planning and guidance. Intra-operative ultrasound volumes were acquired when needed during surgery and the multimodal data was used for guidance and resection control. The use of the available image information during planning and surgery was recorded. An automatic voxel-based registration method between preoperative MRA and intra-operative 3D ultrasound angiography (Power Doppler) was developed and tested postoperatively. RESULTS: The study showed that it is possible to implement robust, high-quality protocols for fMRI and DTI and that the acquired data could be seamlessly integrated in an ultrasound-based neuronavigation system. Navigation based on fMRI data was found to be important for pre-operative planning in all twelve procedures. In five out of eleven cases the data was also found useful during the resection. DTI data was found to be useful for planning in all five cases where these data were imported into the navigation system. In two out of four cases DTI data was also considered important during the resection (in one case DTI data were acquired but not imported and in another case fMRI and DTI data could only be used for planning). Information regarding the location of important functional areas (fMRI) was more beneficial during the planning phase while DTI data was more helpful during the resection. Furthermore, the surgeon found it more user-friendly and efficient to interpret fMRI and DTI information when shown in a navigation system as compared to the traditional display on a light board or monitor. Updating MRI data for brain-shift using automatic co-registration of preoperative MRI with intra-operative ultrasound was feasible. CONCLUSION: In the present study we have demonstrated how both fMRI and DTI data can be acquired and integrated into a neuronavigation system for improved surgical planning and guidance. The surgeons reported that the integration of fMRI and DTI data in the navigation system represented valuable additional information presented in a user-friendly way and functional neuronavigation is now in routine use at our hospital. Furthermore, the present study showed that automatic ultrasound-based updates of important pre-operative MRI data are feasible and hence can be used to compensate for brain shift.
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Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Monitoreo Intraoperatorio/métodos , Neuronavegación/métodos , Procedimientos Neuroquirúrgicos/métodos , Ultrasonografía Doppler Transcraneal/métodos , Adulto , Anciano , Encéfalo/anatomía & histología , Encéfalo/patología , Encéfalo/cirugía , Mapeo Encefálico/métodos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Femenino , Humanos , Imagenología Tridimensional , Aneurisma Intracraneal/patología , Aneurisma Intracraneal/cirugía , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/instrumentación , Neuronavegación/instrumentación , Neuronavegación/tendencias , Procedimientos Neuroquirúrgicos/instrumentación , Procedimientos Neuroquirúrgicos/tendencias , Cuidados Preoperatorios/métodos , Factores de Tiempo , Interfaz Usuario-ComputadorRESUMEN
OBJECTIVE: This case report suggests that screening of patients with psychiatric symptoms using modern neuroimaging can help identify organic causes of mental illness. METHOD: A single case study was reported. RESULTS: We report the case of a 25-year-old woman with a recent diagnosis of bipolar II disorder having an magnetic resonance imaging (MRI) scan as part of a research project that reveals an intraventricular brain tumour. The latter is most likely the cause of her irritability and 'hypomanic' symptoms and is defined anatomically using diffusion tensor imaging and structural and functional imaging using MRI and positron emission tomography. CONCLUSION: The lesion in this individual case most probably produces mood symptoms by impinging upon the fornix, a component of the limbic system. However, more generally, the increase in diagnosis of bipolar disorder has to be tempered against alternate causes of similar symptoms and necessitates vigilance of potential organic mechanisms.
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Trastorno Bipolar/complicaciones , Neoplasias del Ventrículo Cerebral/complicaciones , Adulto , Encéfalo/diagnóstico por imagen , Neoplasias del Ventrículo Cerebral/diagnóstico , Neoplasias del Ventrículo Cerebral/patología , Electroencefalografía , Femenino , Humanos , Imagen por Resonancia Magnética , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: The need for thromboembolism (TE) prophylaxis during laparoscopic surgery is not well established. The aim of this study was to investigate current TE prophylaxis in patients undergoing laparoscopic cholecystectomy (LC) in Sweden. METHODS: Mail questionnaire to all Surgical Departments in Sweden about the current use of thromboembolism prophylaxis in patients undergoing laparoscopic cholecystectomy. RESULTS: The response rate was 78 of 80 departments of surgery (98%). Seventy reported performing LC. Thirty-six percent used thromboembolism prophylaxis in all patients, 17% in most, 9% in half their patients and 39% only rarely. The current use of thromboembolism prophylaxis ranged from low-molecular-weight heparin for 7 days + stockings in all patients to no prophylaxis at all in the majority of patients. CONCLUSIONS: The use of thromboembolism prophylaxis in LC patients is highly variable, even in the small and homogenous country of Sweden. Further studies concerning the risk of TE complications after laparoscopic surgery are warranted.
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Colecistectomía Laparoscópica , Complicaciones Posoperatorias/prevención & control , Tromboembolia/prevención & control , Terapia Trombolítica , Humanos , Encuestas y Cuestionarios , SueciaRESUMEN
BACKGROUND: It can be impossible to differentiate a mass forming chronic pancreatitis from adenocarcinoma of the pancreas using standard anatomical imaging. Positron emission tomography using 2-[18F] fluoro-2deoxy-D-glucose (18FDG-PET) and 1-[11C]-acetate (11C-acetate-PET) are methods taking advantage of the metabolic differences between benign and malignant tissues. AIMS: To determine the diagnostic accuracy of 18FDG-PET and 11C-acetate-PET in indeterminate pancreatic masses. METHODS: Twenty patients with an indeterminate mass of the head of the pancreas were prospectively studied. All patients underwent 18FDG-PET and eighteen of them 11C-acetate-PET. Scans were evaluated qualitatively and quantitatively; the later by using regional standardised uptake value (SUV). Final diagnosis was established using histopathologic evaluation of resected specimen or biopsy. RESULTS: Adenocarcinoma was diagnosed in twelve patients and chronic pancreatitis in eight. Qualitative evaluation of 18FDG-PET imaging revealed three false negative and one false-positive results. The sensitivity, specificity, and diagnostic accuracy were 75 %, 88 %, and 80 %, respectively. The cut-off SUV to differentiate malignant from benign disease was 3,5 demonstrating a sensitivity of 91.7 % and a specificity of 75 %. CONCLUSION: 18FDG-PET imaging could not confirm or exclude malignancy in indeterminate masses of the head of the pancreas with high sensitivity and diagnostic accuracy. 11C-acetate-PET provided no additional diagnostic benefits.
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Adenocarcinoma/diagnóstico por imagen , Radioisótopos de Carbono , Fluorodesoxiglucosa F18 , Neoplasias Pancreáticas/diagnóstico por imagen , Pancreatitis/diagnóstico por imagen , Tomografía de Emisión de Positrones , Enfermedad Crónica , Diagnóstico Diferencial , Reacciones Falso Positivas , Humanos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Laparoscopic living donor nephrectomy is increasingly being performed, although the effects of carbon dioxide pneumoperitoneum (CO2 PP) on renal function and hemodynamics and the levels of vasopressin are not well studied. METHODS: Renal blood flow, renal venous pressure, urine output, and vasopressin concentrations in renal venous blood were measured in pigs subjected to 12 mmHg of CO2 PP for 150 min. RESULTS: Renal blood flow was decreased at induction of PP and increased during the first 30 min after exsufflation. Renal venous pressure was increased during PP. There was indirect evidence of a decrease in urine output during PP. No changes in renal venous vasopressin concentrations were seen. CONCLUSION: A CO2 PP of 12 mmHg causes changes in renal hemodynamics and urine output. No changes in vasopressin levels were seen in this pig model, suggesting that other explanations for the observed changes must be sought.
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Dióxido de Carbono/efectos adversos , Riñón/fisiología , Neumoperitoneo Artificial/efectos adversos , Circulación Renal , Vasopresinas/sangre , Animales , Femenino , Hemodinámica , Riñón/irrigación sanguínea , Masculino , Porcinos , Orina , Presión VenosaRESUMEN
All antibodies (Abs) with effector function are produced in mammalian cells, whereas bacterial production is restricted to smaller targeting fragments (scFv and Fab) without effector functions. In this project, we isolated different peptides that bind one of several Ab effector molecules. We have developed bacterial expression vectors for direct cloning of these peptides as fusions to scFv and Fab, and have obtained targeting fragments that also have the ability to bind Ab effector molecules. Some of these fusions (pepbodies) may also initiate Ab effector functions. We have also genetically inserted T-cell epitopes into Abs with specificity for antigen-presenting cell (APC) surface molecules to target the Ab-T-cell epitope fusions (Troybodies) to APCs. The approach is to exchange loops in Ig constant domains with single copies of well-defined T-cell epitopes. We have shown that a number of such T-cell epitopes are loaded on to MHC class II on APCs and are presented to specific T-cells. An increase in T-cell activation of up to four orders of magnitude is achieved compared with synthetic peptide. Our current goal is to identify all the loops in all Ig constant domains that may be loaded with T-cell epitopes to produce a multi-vaccine.
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Anticuerpos/inmunología , Células Presentadoras de Antígenos/inmunología , Linfocitos T/inmunología , Secuencia de Aminoácidos , Secuencia de Bases , Epítopos/inmunología , Antígenos HLA-D/inmunología , Humanos , Inmunoglobulina D/inmunología , Fragmentos de Inmunoglobulinas/química , Fragmentos de Inmunoglobulinas/inmunología , Datos de Secuencia Molecular , Péptidos/inmunología , Proteínas Recombinantes/inmunologíaRESUMEN
A major objective in vaccine development is the design of reagents that give a strong, specific T cell response. Targeting of antigens to antigen presenting cells (APC) results in enhanced antigen presentation and T cell activation. In this paper, we describe a novel targeting reagent denoted 'Troy-bodies', namely recombinant antibodies with APC-specificity and with T cell epitopes integrated in their C regions. We have made such antibodies with V regions specific for either IgD or MHC class II, and five different T cell epitopes have been tested. All epitopes could be introduced into loops of C domains without disrupting immunoglobulin (Ig) folding. Four have been tested in T cell activation studies, and all could be released and presented by APC. Furthermore, whether IgD- or MHC-specific, the molecules tested enhanced T cell stimulation compared to non-specific control antibodies in vitro as well as in vivo. Using this technology, specific reagents can be designed that target selected antigenic peptides to an APC of choice. Troy-bodies may therefore be useful for manipulation of immune responses, and in particular for vaccination purposes.
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Anticuerpos/inmunología , Células Presentadoras de Antígenos/inmunología , Epítopos/inmunología , Ingeniería de Proteínas , Linfocitos T/inmunología , Animales , Anticuerpos/genética , Especificidad de Anticuerpos , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Inmunoglobulina D/inmunología , Región Variable de Inmunoglobulina/química , Técnicas In Vitro , Ratones , Ratones Endogámicos BALB C , Modelos Estructurales , Mutagénesis Insercional , Nitrohidroxiyodofenilacetato , Pliegue de Proteína , Estructura Terciaria de Proteína , Proteínas Recombinantes/inmunologíaRESUMEN
Targeting of antigens to antigen-presenting cells (APCs) increases CD4(+) T cell activation, and this observation can be exploited in the development of new vaccines. We have chosen an antigen-targeting approach in which we make recombinant antibodies (Abs) with T cell epitopes in their constant region and APC-specific variable regions. Three commonly used model epitopes, amino acids 110-120 of hemagglutinin, 323-339 of ovalbumin, and 46-61 of hen egg lysozyme, were introduced as loops in the C(H)1 domain of human IgG3. For all three epitopes, we show that the recombinant molecules are secreted from transfected cells. The epitopes are presented to specific T cells, and targeting to IgD on B cells in vitro enhances the presentation efficiency by 10(4) to 10(5) compared with the free peptide. After i.v. injection, the epitopes targeted to IgD are presented by splenic APCs to activate specific T cells, whereas little or no activation could be detected without targeting, even after the amount of antigen injected was increased 100-fold or more. Because a wide variety of T cell epitopes, in terms of both length and secondary structure, can be tolerated in loops in constant domains of Abs, the Ab constant region seems to have the intrinsic stability that is needed for this fusion molecule strategy. It might thus be possible to load the Ab with several different epitopes in loops in different domains and thereby make a targeted multisubunit vaccine.
Asunto(s)
Células Presentadoras de Antígenos/inmunología , Epítopos/administración & dosificación , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos/administración & dosificación , Anticuerpos/química , Anticuerpos/genética , Secuencia de Bases , Pollos , Cartilla de ADN/genética , Epítopos/genética , Femenino , Glicoproteínas Hemaglutininas del Virus de la Influenza/administración & dosificación , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/química , Inmunoglobulina G/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Transgénicos , Datos de Secuencia Molecular , Muramidasa/administración & dosificación , Muramidasa/genética , Ovalbúmina/administración & dosificación , Ovalbúmina/genética , Péptidos/administración & dosificación , Péptidos/genética , VacunaciónRESUMEN
Type-B T cells raised against the immunodominant peptide in hen egg lysozyme (HEL(48-62)) do not respond to whole lysozyme, and this has been thought to indicate that peptide can bind to l-A(k) in different conformations. Here we demonstrate that such T cells recognize a deamidated form of the HEL peptide and not the native peptide. The sequence of the HEL epitope facilitates rapid and spontaneous deamidation when present as a free peptide or within a flexible domain. However, this deamidated epitope is not created within intact lysozyme, most likely because it resides in a highly structured part of the protein. These findings argue against the existence of multiple conformations of the same peptide-MHC complex and have important implications for the design of peptide-based vaccines. Furthermore, as the type-B T cells are known to selectively evade induction of tolerance when HEL is expressed as a transgene, these results suggest that recognition of posttranslationally modified self-antigen may play a role in autoimmunity.