RESUMO
The Achilles tendon is the strongest tendon in the human body but its mechanical behaviour during failure has been little studied and the basis of its high tensile strength has not been elucidated in detail. In the present study, healthy, human, Achilles tendons were loaded to failure in an anatomically authentic fashion while the local deformation and strains were studied in real time, with very high precision, using digital image correlation (DIC). The values determined for the strength of the Achilles tendon were at the high end of those reported in the literature, consistent with the absence of a pre-existing tendinopathy in the samples, as determined by careful gross inspection and histology. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. However, immediately before rupture, the mid-substance of the Achilles tendon, its weakest part, started to show high longitudinal strains. These new insights advance the understanding of the mechanical behaviour of tendons as they are stretched to failure.
Assuntos
Tendão do Calcâneo , Tendinopatia , Fenômenos Biomecânicos , Humanos , Técnicas In Vitro , RupturaRESUMO
The interphase between tendon and bone consists of a highly specialised tissue called enthesis. Typically, the enthesis is described as a succession of four different zones: tendon, non-mineralised fibrocartilage, mineralised fibrocartilage and bone. However, the microstructure of the entheses, cellular composition and mechanical properties vary depending on their anatomical location. The present study aimed to characterise three of the most relevant sites of enthesis injury in a rat model: the patellar tendon, the Achilles tendon and the supraspinatus enthesis, in terms of biomechanics, histology and genetic expression. The patellar enthesis presented the highest ultimate load and lowest stiffness of the three, while the supraspinatus was the weakest and stiffest. The histological characterisation revealed key differences at the insertion site for each enthesis. The patellar enthesis showed a large cartilaginous area at the tendon-to-bone interphase whilst this interphase was smaller in the supraspinatus entheses samples. Furthermore, the Achilles tendon enthesis displayed a more abrupt transition from tendon to bone. Additionally, each enthesis exhibited a particular and distinct pattern of expression of tenogenic, chondrogenic and osteogenic markers. This study provided valuable insights for a better understanding of the three entheses at relevant anatomical sites. Moreover, the larger cross-sectional area of the patellar enthesis, the strong mechanical properties and the easier surgical access to this location led to the conclusion that the patellar tendon enthesis site could be most suitable for the development of a preclinical model for general enthesis regeneration studies in rats.
Assuntos
Tendão do Calcâneo , Fibrocartilagem , Tendão do Calcâneo/patologia , Animais , Osso e Ossos , Osteogênese , Ratos , Manguito RotadorRESUMO
BACKGROUND: Immunocompromised patients are at high risk of complicated severe acute respiratory coronavirus 2 infection. The aim of this retrospective study was to describe the characteristics and outcomes of heart transplantation (HTx) recipients with coronavirus disease 2019 (COVID-19) in the Netherlands. METHODS: HTx patients from one of the three HTx centres in the Netherlands with COVID-19 (proven by positive reverse-transcription polymerase chain reaction or serology test result) between February 2020 and June 2021 were included. The primary endpoint was all-cause mortality and the secondary endpoint was disease severity. RESULTS: COVID-19 was diagnosed in 54/665 HTx patients (8%), with a mean (±â¯standard deviation (SD)) time after HTx of 11⯱ 8 years. Mean (±â¯SD) age was 53⯱ 14 years and 39% were female. Immunosuppressive therapy dosage was reduced in 37% patients (20/54). Hospitalisation was required in 39% patients (21/54), and 13% patients (7/54) had severe COVID-19 (leading to intensive care unit (ICU) admission or death). In-hospital mortality was 14% (3/21), and all-cause mortality was 6%. Compared with patients with moderate COVID-19 (hospitalised without ICU indication), severe COVID-19 patients tended to be transplanted earlier and had a significantly higher mean (±â¯SD) body mass index (26⯱ 3 vs 30⯱ 3â¯kg/m2, pâ¯= 0.01). Myocardial infarction, cellular rejection and pulmonary embolism were observed once in three different HTx patients. CONCLUSION: HTx patients were at increased risk of complicated COVID-19 with frequent hospitalisation, but the all-cause mortality was substantially lower than previously described (7-33%).
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There is much interest in understanding the influence of the immune system on bone healing, including a number of reports suggesting a beneficial effect of FK506 (tacrolimus) in this regard. The influence of FK506 in a rat, femoral, critical size defect was examined using locally implanted, recombinant, human (rh) BMP-2 and adenovirally-transduced, autologous, adipose-derived mesenchymal stromal cells (AD-MSCs) expressing BMP-2. FK506 was delivered systemically using an implanted osmotic pump. Empty defects and those implanted with unmodified AD-MSCs did not heal in the presence or absence of FK506. Defects treated with rhBMP-2 healed with a large callus containing thin cortices and wispy trabeculae; this, too, was unaffected by FK506. A third of defects implanted with adenovirally-transduced AD-MSCs healed, but this improved to 100 % in the presence of FK506. New bone formed in response to BMP-2 synthesised endogenously by the genetically modified cells had a slimmer callus than those healed by rhBMP-2, with improved cortication and advanced reconstitution of marrow. These results suggest that FK506 may have had little effect on the intrinsic biology of bone healing, but improved healing in response to adenovirally-transduced cells by inhibiting immune responses to the first-generation adenovirus used here. Because the genetically modified cells produced bone of higher quality at far lower doses of BMP-2, this approach should be explored in subsequent research.
Assuntos
Diáfises/patologia , Fêmur/patologia , Tacrolimo/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/metabolismo , Diáfises/diagnóstico por imagem , Diáfises/efeitos dos fármacos , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fibrina/metabolismo , Masculino , Ratos Endogâmicos F344 , Torção MecânicaRESUMO
Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFß1) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery. After 1, 2, 4 and 8 weeks, healing was assessed based on tendon length and thickness, mechanical strength, stiffness and histology. Best results were achieved when GFs were loaded onto a collagen sponge - with a rapid increase in mechanical strength (load to failure, 71.2 N vs. 7.7 N in controls), consistent tendon length over time (9.9 mm vs. 16.2 mm in controls) and faster tendon remodelling, as measured by histology - followed by tiered injection therapy over 96 h. In conclusion, implantation of a GF-loaded collagen sponge could provide a promising treatment, especially in high-performance athletes and revision cases prone to re-rupture. For conservative treatment, tiered percutaneous GF application could be an option for improving clinical outcome.
Assuntos
Proteínas Morfogenéticas Ósseas/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Tendões/patologia , Fator de Crescimento Transformador beta1/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Fenômenos Biomecânicos , Colágeno/metabolismo , Cavalos , Masculino , Ratos Sprague-Dawley , Tendões/cirurgia , Suporte de CargaRESUMO
BACKGROUND: The objective of this investigation was to assess whether preoperative carcinoembryonic antigen (CEA) level is an independent predictor of overall survival in rectal cancer patients. METHODS: All patients (n=504) undergoing a resection for stage I-III rectal cancer at the Kantonsspital St Gallen were included into a database between 1991 and 2008. The impact of preoperative CEA level on overall survival was assessed using risk-adjusted Cox proportional hazard regression models and propensity score methods. RESULTS: In risk-adjusted Cox proportional hazard regression analyses, preoperative CEA level (hazard ratio (HR): 1.98, 95% confidence interval (CI): 1.36-2.90, P<0.001), distance from anal verge (<5 cm: HR: 1.93, 95% CI: 1.11-3.37; P=0.039), older age (HR: 1.07, 95% CI: 1.05-1.09; P<0.001), lower body mass index (HR: 0.94, 95% CI: 0.89-0.98; P=0.006), advanced tumour stage (stage II HR: 1.41, 95% CI: 0.85-2.32; stage III HR: 2.08, 95% CI: 1.31-3.31; P=0.004), R 1 resection (HR: 5.65, 95% CI: 1.59-20.1; P=0.005) and chronic kidney disease (HR: 2.28, 95% CI: 1.03-5.04; P=0.049) were all predictors for poor overall survival. CONCLUSION: This is one of the first investigations based on a large cohort of exclusively rectal cancer patients demonstrating that preoperative CEA level is a strong predictor of decreased overall survival. Preoperative CEA should be used as a prognostic factor in the preoperative assessment of rectal cancer patients.
Assuntos
Adenocarcinoma/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Retais/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Estudos de Coortes , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Análise de Regressão , Taxa de Sobrevida , Suíça/epidemiologiaRESUMO
BACKGROUND: Postoperative ileus is a common problem after abdominal surgery. It was postulated that coffee intake would decrease postoperative ileus after colectomy. METHODS: This was a multicentre parallel open-label randomized trial. Patients with malignant or benign disease undergoing elective open or laparoscopic colectomy were assigned randomly before surgery to receive either coffee or water after the procedure (100 ml three times daily). The primary endpoint was time to first bowel movement; secondary endpoints were time to first flatus, time to tolerance of solid food, length of hospital stay and perioperative morbidity. RESULTS: A total of 80 patients were randomized, 40 to each group. One patient in the water arm was excluded owing to a change in surgical procedure. Patient characteristics were similar in both groups. In intention-to-treat analysis, the time to the first bowel movement was significantly shorter in the coffee arm than in the water arm (mean(s.d.) 60·4(21·3) versus 74·0(21·6) h; P = 0·006). The time to tolerance of solid food (49·2(21·3) versus 55·8(30·0) h; P = 0·276) and time to first flatus (40·6(16·1) versus 46·4(20·1) h; P = 0·214) showed a similar trend, but the differences were not significant. Length of hospital stay (10·8(4·4) versus 11·3(4·5) days; P = 0·497) and morbidity (8 of 40 versus 10 of 39 patients; P = 0·550) were comparable in the two groups. CONCLUSION: Coffee consumption after colectomy was safe and was associated with a reduced time to first bowel action.
Assuntos
Café , Colectomia/efeitos adversos , Doenças do Colo/prevenção & controle , Íleus/prevenção & controle , Análise de Variância , Colectomia/métodos , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Íleus/etiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVES: Earlier studies indicated that hamster pancreatic ductal adenocarcinoma not only derives from ductal/ductular structures but also from cells within the islet. So far unidentified cells within the islet are responsive to the carcinogenic effect of N-nitrosobis (2-oxopropyl) amine (BOP) forming poorly differentiated ductal adenocarcinoma. However, studies indicated a major role of ß-cells during carcinogenesis. To find out, if ß-cells are the primary target cells of BOP and if they are capable to form ductal adenocarcinoma after malignant transformation, we established a long-term culture of undifferentiated cells deriving from isolated ß-cells and treated them with BOP. METHODS: Langerhans' islets from pancreata of Syrian golden hamsters were isolated and dispersed into single cells by dispase digestion. Cells were labeled with a highly specific ß-cell surface antibody (K14D10) and these K14D10+ cells were extracted from the suspension by paramagnetic Dynabeads. Cells were cultured in vitro and treated with BOP. Untreated cells served as control. RESULTS: K14D10+ cells formed a monolayer and produced insulin over a period of 28 days in culture. However, with time in culture they became undifferentiated with a higher proliferation rate and after about 60 days in culture BOP treated cells showed anchorage independent growth. These cells autotransplanted s.c. formed a well-differentiated ductal adenocarcinoma. CONCLUSIONS: Pancreatic ß-cells are the primary target of BOP without necessarily being embedded in the compound of the Langerhans' islet. With time in culture, they give rise to undifferentiated cells and after malignant transformation they are able to form ductal adenocarcinoma.
Assuntos
Adenocarcinoma/induzido quimicamente , Carcinógenos , Carcinoma Ductal Pancreático/induzido quimicamente , Células Secretoras de Insulina/efeitos dos fármacos , Nitrosaminas/toxicidade , Neoplasias Pancreáticas/induzido quimicamente , Adenocarcinoma/patologia , Animais , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células , Separação Celular , Transformação Celular Neoplásica/induzido quimicamente , Células Cultivadas , Cricetinae , Feminino , Células Secretoras de Insulina/patologia , Mesocricetus , Invasividade Neoplásica/patologia , Transplante de Neoplasias , Neoplasias Pancreáticas/patologiaRESUMO
BACKGROUND: Healthcare-associated infections are the most frequent adverse events in healthcare worldwide, with limited available evidence suggesting highest burden in resource-limited settings. Recent Ebola epidemics emphasize the disastrous impact that spread of infectious agents within healthcare facilities can have, accentuating the need for improvement of infection control practices. Hand hygiene (HH) measures are considered to be the most effective tool to prevent healthcare-associated infections. However, HH knowledge and compliance are low, especially in vulnerable settings such as Guinea. The aim of PASQUALE (Partnership to Improve Patient Safety and Quality of Care) was to assess knowledge and compliance with HH and improve HH by incorporating the WHO HH Strategy within the Faranah Regional Hospital (FRH), Guinea. METHODS: In a participatory approach, a team of FRH staff and leadership was invited to identify priorities of the hospital prior to the start of PASQUALE. The local hygiene committee was empowered to increase its activities and take ownership of the HH improvement strategy. A baseline assessment of knowledge, perception and compliance was performed months before the intervention. The main intervention consisted of local alcohol-based-hand-rub (ABHR) production, with final product efficacy testing, in conjunction with a training adapted to the needs identified in the baseline assessment. A follow-up assessment was conducted directly after the training. Effectiveness of the intervention was assessed via uncontrolled before-and-after comparison. RESULTS: Baseline knowledge score (13.0/25) showed a significant increase to 19.0/25 in follow-up. Baseline-Compliance was 23.7% and increased significantly to 71.5% in follow-up. Compliance rose significantly across all professional groups except for midwifes and in all indications for HH, with the largest in the indication "Before aseptic tasks". The increase in compliance was associated with the intervention and remained significant after adjusting for confounders. The local pharmacy successfully supplies the entire hospital. The local supply resulted in a ten-fold increase of monthly hospital disinfectant consumption. CONCLUSION: The WHO HH strategy is an adaptable and effective method to improve HH knowledge and compliance in a resource-limited setting. Local production is a feasible method for providing self-sufficient supply of ABHR to regional hospitals like the FRH. Participatory approaches like hygiene committee ownership builds confidence of sustainability.
Assuntos
Infecção Hospitalar/prevenção & controle , Higiene das Mãos/organização & administração , Recursos Humanos em Hospital/educação , Fidelidade a Diretrizes/estatística & dados numéricos , Guiné , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Guias de Prática Clínica como Assunto , Organização Mundial da SaúdeRESUMO
OBJECTIVE: The adamalysin metalloproteinase 15 (ADAM15) has been shown to protect against development of osteoarthritis in mice. Here, we have investigated factors that control ADAM15 levels in cartilage. DESIGN: Secretomes from wild-type and Adam15 -/- chondrocytes were compared by label-free quantitative mass spectrometry. mRNA was isolated from murine knee joints, either with or without surgical induction of osteoarthritis on male C57BL/6 mice, and the expression of Adam15 and other related genes quantified by RT-qPCR. ADAM15 in human normal and osteoarthritic cartilage was investigated similarly and by fluorescent immunohistochemistry. Cultured HTB94 chondrosarcoma cells were treated with various anabolic and catabolic stimuli, and ADAM15 mRNA and protein levels evaluated. RESULTS: There were no significant differences in the secretomes of chondrocytes from WT and Adam15 -/- cartilage. Expression of ADAM15 was not altered in either human or murine osteoarthritic cartilage relative to disease-free controls. However, expression of ADAM15 was markedly reduced upon aging in both species, to the extent that expression in joints of 18-month-old mice was 45-fold lower than in that 4.5-month-old animals. IL-13 increased expression of ADAM15 in HTB94 âcells by 2.5-fold, while modulators of senescence and autophagy pathways had no effect. Expression of Il13 in the joint was reduced with aging, suggesting this cytokine may control ADAM15 levels in the joint. CONCLUSION: Expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging human and murine joints, possibly due to a concomitant reduction in IL-13 expression. We thus propose IL-13 as a novel factor contributing to increased osteoarthritis risk upon aging.
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Drosophila melanogaster embryos are a source for homogeneous and stable 26S proteasomes suitable for structural studies. For biochemical characterization, purified 26S proteasomes were resolved by two-dimensional (2D) gel electrophoresis and subunits composing the regulatory complex (RC) were identified by amino acid sequencing and immunoblotting, before corresponding cDNAs were sequenced. 17 subunits from Drosophila RCs were found to have homologues in the yeast and human RCs. An additional subunit, p37A, not yet described in RCs of other organisms, is a member of the ubiquitin COOH-terminal hydrolase family (UCH). Analysis of EM images of 26S proteasomes-UCH-inhibitor complexes allowed for the first time to localize one of the RC's specific functions, deubiquitylating activity. The masses of 26S proteasomes with either one or two attached RCs were determined by scanning transmission EM (STEM), yielding a mass of 894 kD for a single RC. This value is in good agreement with the summed masses of the 18 identified RC subunits (932 kD), indicating that the number of subunits is complete.
Assuntos
Drosophila melanogaster/enzimologia , Peptídeo Hidrolases/química , Complexo de Endopeptidases do Proteassoma , Ubiquitinas/metabolismo , Animais , Eletroforese em Gel Bidimensional , Eletroforese em Gel de Poliacrilamida , Embrião não Mamífero/enzimologia , Substâncias Macromoleculares , Microscopia Eletrônica de Transmissão e Varredura , Modelos Moleculares , Dados de Sequência Molecular , Peso Molecular , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/isolamento & purificação , Peptídeo Hidrolases/ultraestrutura , Estrutura Terciária de Proteína , Análise de Sequência de DNA , Análise de Sequência de Proteína , Homologia de Sequência de Aminoácidos , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismo , Ubiquitina TiolesteraseRESUMO
With advancements in the operative techniques, patient survival following liver transplantation (LTx) has increased substantially. This has led to the acceleration of pre-existing kidney disease because of immunosuppressive nephrotoxicity making additional kidney transplantation (KTx) inevitable. On the other hand, in a growing number of patients on the waiting list to receive liver, long waiting time has resulted in adverse effect of decompensated liver on the kidney function. During the last two decades, the transplant community has considered combined liver kidney transplantation (CLKTx) to overcome this problem. The aim of our study is to present an overview of our experience as well as a review of the literature in CLKTx and to discuss the controversy in this regard. All performed CLKTx (n = 22) at our institution as well as all available reported case series focusing on CLKTx are extracted. The references of the manuscripts were cross-checked to implement further articles into the review. The analyzed parameters include demographic data, indication for LTx and KTx, duration on the waiting list, Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, immunosuppressive regimen, post-transplant complications, graft and patient survival, and cause of death. From 1988 to 2009, a total of 22 CLKTx were performed at our institution. The median age of the patients at the time of CLKTx was 44.8 (range: 4.5-58.3 yr). The indications for LTx were liver cirrhosis, hyperoxaluria type 1, polycystic liver disease, primary or secondary sclerosing cholangitis, malignant hepatic epithelioid hemangioendothelioma, cystinosis, and congenital biliary fibrosis. The KTx indications were end-stage renal disease of various causes, hyperoxaluria type 1, polycystic kidney disease, and cystinosis. The mean follow-up duration for CLKTx patients were 4.6 +/- 3.5 yr (range: 0.5-12 yr). Overall, the most important encountered complications were sepsis (n = 8), liver failure leading to retransplantation (n = 4), liver rejection (n = 3), and kidney rejection (n = 1). The overall patient survival rate was 80%. Review of the literature showed that from 1984 to 2008, 3536 CLKTx cases were reported. The main indications for CLKTx were oxalosis of both organs, liver cirrhosis and chronic renal failure, polycystic liver and kidney disease, and liver cirrhosis along with hepatorenal syndrome (HRS). The most common encountered complications following CLKTx were infection, bleeding, biliary complications, retransplantation of the liver, acute hepatic artery thrombosis, and retransplantation of the kidney. From the available data regarding the need for post-operative dialysis (n = 673), a total of 175 recipients (26%) required hemodialysis. During the follow-up period, 154 episodes of liver rejection (4.3%) and 113 episodes of kidney rejection (3.2%) occurred. The cumulative 1, 2, 3, and 5 yr survival of both organs were 78.2%, 74.4%, 62.4%, and 60.9%, respectively. Additionally, the cumulative 1, 2, 3, and 5 yr patient survival were 84.9%, 52.8%, 45.4%, and 42.6%, respectively. The total number of reported deaths was 181 of 2808 cases (6.4%), from them the cause of death in 99 (55%) cases was sepsis. It can be concluded that there is still no definitive evidence of better graft and patient survival in CLKTx recipients when compared with LTx alone because of the complexity of the exact definition of irreversible kidney function in LTx candidates. Additionally, CLKTx is better to be performed earlier than isolated LTx and KTx leading to the avoidance of deterioration of clinical status, high rate of graft loss, and mortality. Shorter graft ischemia time and more effective immunosuppressive regimens can reduce the incidence of graft malfunctioning in CLKTx patients. Providing a model to reliably determine the need for CLKTx seems necessary. Such a model can be shaped based upon new and precise markers of renal function, and modification of MELD system.
Assuntos
Transplante de Rim/métodos , Transplante de Fígado/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: To determine the long-term effects of obstetric anal sphincter rupture on the frequency of faecal incontinence and sexual complaints. DESIGN: Retrospective case-control study. SETTING: Department of Gynaecology and Obstetrics, Ikazia Hospital, The Netherlands. POPULATION: All 171 women operated for anal sphincter rupture between 1971 and 1990 and 171 controls matched for parity and date of delivery. METHODS: Postal questionnaires regarding faecal incontinence were sent in 1996 and 2005 to all cases and controls with questions regarding sexual complaints added to the questionnaire in 2005. MAIN OUTCOME MEASURES: Anorectal complaints defined as any form of faecal incontinence including faecal urgency and faecal soiling. Sexual complaints defined as dyspareunia or faecal incontinence during intercourse. RESULTS: Sixty-one percent of the women responded to both questionnaires. Anorectal complaints were reported by 38% of case versus 16% of controls in 1996 (risk difference: 0.22, 95% CI 0.10-0.34) and by 61% of cases versus 22% of controls in 2005 (risk difference: 0.41, 95% CI 0.29-0.53). In contrast to the control group, the increase of anorectal complaints in the case group between 1996 and 2005 was highly significant (P < 0.0001). Postmenopausal state was not associated with an increased risk for faecal incontinence. Dyspareunia was reported by 29% of cases versus 13% of controls (P = 0.01). Faecal incontinence during intercourse was reported by 13% of cases versus 1% of controls (P = 0.005). CONCLUSIONS: Obstetric anal sphincter rupture is an important risk factor for sexual complaints and for faecal incontinence increasing with age irrespective of menopausal state.
Assuntos
Canal Anal/lesões , Incontinência Fecal/etiologia , Complicações do Trabalho de Parto , Disfunções Sexuais Fisiológicas/etiologia , Adulto , Fatores Etários , Estudos de Casos e Controles , Episiotomia/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Gravidez , Estudos Retrospectivos , Ruptura , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: The discipline of liver transplantation (LTx) has been developed over the past decades, and LTx is now considered the gold standard for the treatment of patients with end-stage liver diseases and early liver tumors in cirrhotic livers. This procedure is now performed routinely in many transplant centers, and it has provided an enormous technical innovation to the field of hepatobiliary surgery. Allocation decision of liver organs is based on medical need and timing. MATERIALS AND METHODS: The Mayo Model for End Stage Liver Disease based on patient-specific criteria was developed and applied to prioritize patients on the waiting list. From the donor aspects of LTx, sources of organ, excluding xenotransplantation, can be brain-dead donors, living donors, and non-heart-beating donors. Today, the majority of livers are procured from cadaveric donors. In addition to the conventional LTx, other types are living-donor LTx, reuse of grafts as domino transplantation, ex situ as well as in situ split LTx, and reduced-size LTx. The transplantation procedure consists of several steps including donor selection and management, liver procurement and preservation, back-table preparation, recipient operation with liver implantation, postoperative care, immunosuppression, and follow-up. RESULTS: The postoperative complications are divided into surgical, non-surgical, and multifactorial complications. Surgical complications account about 34% of morbidities after LTx and are mainly categorized to vascular and biliary complications. The main medical ones are non-surgical bleeding and infections. The multifactorial complications include primary non- or poor function and small-for-size syndrome. The pretransplant outcome predictors of LTx can be divided into donor, recipient, operative, and postoperative factors. CONCLUSION: LTx is now considered a safe and standardized procedure with a substantially improved graft and patient survival and acceptable morbidity rates. However, the new problems, including recurrence of hepatitis C or hepatocellular carcinoma, chronic biliary complications, opportunistic infections, and development of de-novo malignancies are the major problems affecting the long-term outcome of transplanted patients.
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Cirrose Hepática/cirurgia , Falência Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/tendências , Idoso , Cadáver , Europa (Continente) , Previsões , Alemanha , Hepatectomia , Humanos , Unidades de Terapia Intensiva , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Falência Hepática/epidemiologia , Testes de Função Hepática , Neoplasias Hepáticas/epidemiologia , Doadores Vivos/provisão & distribuição , Equipe de Assistência ao Paciente/tendências , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Coleta de Tecidos e Órgãos , Obtenção de Tecidos e Órgãos/tendências , Listas de EsperaRESUMO
Since 1963, orthotopic liver transplantation (OLT) has developed into an established interdisciplinary therapy concept for patients with end-stage liver disease, acute irreversible liver failure, and hepatic malignancies in selected cases. In 26 centers in Germany, around 900 full-size OLTs are performed annually. The classic technique has been replaced by the "piggyback" method, which has become the standard in many centres. Improvements in surgical techniques, anaesthetic protocols, and medical management along with the introduction of new immunosuppressive regimens and early adequate therapy against infections and transplant rejection have increased patient survival. These factors have resulted in 1-year survival rates of 80-90% and led to an increase in indications for OLT. Despite decades of experience, approximately 10% of the mortality in the first 3 months still can be traced to technical complications.
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Falência Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Anastomose Cirúrgica/métodos , Ductos Biliares/cirurgia , Hepatectomia/métodos , Artéria Hepática/cirurgia , Humanos , Fígado/irrigação sanguínea , Veia Porta/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Taxa de Sobrevida , Doadores de Tecidos , Coleta de Tecidos e Órgãos/métodos , Veia Cava Superior/cirurgiaRESUMO
Rodent models are commonly used to investigate tendon healing, with the biomechanical and structural properties of the healed tendons being important outcome measures. Tendon storage for later testing becomes necessary when performing large experiments with multiple time-points. However, it is unclear whether freezing rodent tendons affects their material properties. Thus the aim of this study was to determine whether freezing rat Achilles tendons affects their biomechanical or structural properties. Tendons were frozen at either -20⯰C or -80⯰C directly after harvesting, or tested when freshly harvested. Groups of tendons were subjected to several freeze-thaw cycles (1, 2, and 5) within 3â¯months, or frozen for 9â¯months, after which the tendons were subjected to biomechanical testing. Additionally, fresh and thawed tendons were compared morphologically, histologically and by transmission electron microscopy. No major differences in biomechanical properties were found between fresh tendons and those frozen once or twice at -20⯰C or -80⯰C. However, deterioration of tendon properties was found for 5-cycle groups and both long-term freezing groups; after 9â¯months of freezing at -80⯰C the tear resistance of the tendon was reduced from 125.4⯱â¯16.4N to 74.3⯱â¯18.4N (pâ¯=â¯0.0132). Moreover, tendons stored under these conditions showed major disruption of collagen fibrils when examined by transmission electron microscopy. When examined histologically, fresh samples exhibited the best cellularity and proteoglycan content of the enthesis. These properties were preserved better after freezing at -80⯰C than after freezing at -20⯰C, which resulted in markedly smaller chondrocytes and less proteoglycan content. Overall, the best preservation of histological integrity was seen with tendons frozen once at -80⯰C. In conclusion, rat Achilles tendons can be frozen once or twice for short periods of time (up to 3â¯months) at -20⯰C or -80⯰C for later testing. However, freezing for 9â¯months at either -20⯰C or -80⯰C leads to deterioration of certain parameters.
Assuntos
Tendão do Calcâneo/fisiologia , Congelamento , Tendão do Calcâneo/ultraestrutura , Animais , Fenômenos Biomecânicos , Masculino , Microscopia Eletrônica de Transmissão , Ratos Sprague-Dawley , Preservação de TecidoRESUMO
Image-guided surgery and navigation have resulted from convergent developments in radiology, teletransmission, and computer science and are well-established procedures in the surgical routine in orthopedic, neurosurgery, and head-and-neck surgery. In abdominal surgery, however, these tools have gained little attraction so far. The inability to transfer the methodology from orthopedic or neurosurgery is mainly a result of intraoperative organ movement and shifting. To practice and establish navigated interventions in the liver, a custom-designed respiratory liver motion simulator was built which models the human torso and is easy to recreate. To simulate breathing motion, an explanted porcine or human liver is mounted to the diaphragm model of the simulator, and a lung ventilator causes a periodic movement of the liver along the craniocaudal axis. Additionally, the liver can be connected to a circulating pump device which simulates hepatic perfusion and provides real surgical options to establish navigated interventions and simulate management of possible complications. Respiratory motion caused by the simulator was evaluated with an optical tracking system and it was shown that in vitro movement and deformation of a liver mounted to the device are similar to the liver movements in human or porcine bodies. Based on the tests, it is concluded that the novel respiratory liver motion simulator is suitable for in vitro evaluation of navigated systems and interventional and surgical procedures.
Assuntos
Fígado/fisiologia , Fígado/cirurgia , Modelos Biológicos , Movimento , Respiração , Animais , Elasticidade , Expiração , Humanos , Inalação , Cirurgia Assistida por Computador , Suínos/fisiologiaRESUMO
In the thick filaments of body muscle in Caenorhabditis elegans, myosin A and myosin B isoforms and a subpopulation of paramyosin, a homologue of myosin heavy chain rods, are organized about a tubular core. As determined by scanning transmission electron microscopy, the thick filaments show a continuous decrease in mass-per-length (MPL) from their central zones to their polar regions. This is consistent with previously reported morphological studies and suggests that both their content and structural organization are microdifferentiated as a function of position. The cores are composed of a second distinct subpopulation of paramyosin in association with the alpha, beta, and gamma-filagenins. MPL measurements suggest that cores are formed from seven subfilaments containing four strands of paramyosin molecules, rather than the two originally proposed. The periodic locations of the filagenins within different regions and the presence of a central zone where myosin A is located, implies that the cores are also microdifferentiated with respect to molecular content and structure. This differentiation may result from a novel "induced strain" assembly mechanism based upon the interaction of the filagenins, paramyosin and myosin A. The cores may then serve as "differentiated templates" for the assembly of myosin B and paramyosin in the tapering, microdifferentiated polar regions of the thick filaments.
Assuntos
Caenorhabditis elegans , Músculos/ultraestrutura , Miosinas/ultraestrutura , Animais , Caenorhabditis elegans/química , Caenorhabditis elegans/citologia , Caenorhabditis elegans/ultraestrutura , Microscopia Eletrônica de Transmissão e Varredura , Músculos/química , Músculos/citologia , Cadeias Pesadas de Miosina/química , Cadeias Pesadas de Miosina/ultraestrutura , Miosinas/química , Miosina não Muscular Tipo IIB , Isoformas de Proteínas/química , Isoformas de Proteínas/ultraestrutura , Tropomiosina/química , Tropomiosina/ultraestruturaRESUMO
The multidomain Mac-2 binding protein (M2BP) is present in serum and in the extracellular matrix in the form of linear and ring-shaped oligomers, which interact with galectin-3, fibronectin, collagens, integrins and other large glycoproteins. Domain 1 of M2BP (M2BP-1) shows homology with the cysteine-rich SRCR domain of scavanger receptor. Domains 2 and 3 are related to the dimerization domains BTB/POZ and IVR of the Drosophila kelch protein. Recombinant M2BP, its N-terminal domain M2BP-1 and a fragment consisting of putative domains 2, 3 and 4 (M2BP-2,3,4) were investigated by scanning transmission electron microscopy, transmission electron microscopy, analytical ultracentrifugation and binding assays. The ring oligomers formed by the intact protein are comprised of approximately 14 nm long segments composed of two 92 kDa M2BP monomers. Although the rings vary in size, decamers predominate. The various linear oligomers also observed are probably ring precursors, dimers predominate. M2BP-1 exhibits a native fold, does not oligomerize and is inactive in cell attachment. M2BP-2,3,4 aggregates to heterogeneous, protein filled ring-like structures as shown by metal shadowed preparations. These aggregates retain the cell-adhesive potential indicating native folding. It is hypothesized that the rings provide an interaction pattern for multivalent interactions of M2BP with target molecules or complexes of ligands.