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1.
Hernia ; 24(4): 747-757, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31786700

RESUMO

INTRODUCTION: Inguinal hernias are repaired using either open or minimally invasive surgical techniques. For both types of surgery it has been demonstrated that a higher annual surgeon volume is associated with a lower risk of recurrence. This present study investigated the volume-outcome implications for recurrence operations, surgical complications, rate of chronic pain requiring treatment, and 30-day mortality based on the hospital volume. MATERIALS AND METHODS: The data basis used was the routine data collected throughout the Federal Republic of Germany for persons insured by the Local General Sickness Fund "AOK" who had undergone inpatient inguinal hernia repair between 2013 and 2015. Complications were recorded by means of indicators. Hospitals were divided into five groups on the basis of the annual caseload volume: 1-50, 51-75, 76-100, 101-125, and ≥ 126 inguinal hernia repairs per year. The effect of the hospital volume on the indicators was assessed using multiple logistic regression. RESULTS: 133,449 inguinal hernia repairs were included. The incidence for recurrence operations was 0.95%, for surgical complications 4.22%, for chronic pain requiring treatment 2.87%, and for the 30-day mortality 0.28%. Low volume hospitals (1-50 and 51-75 inguinal hernia repairs per year) showed a significantly increased recurrence risk compared to high volume hospitals with ≥ 126 inguinal hernia repairs per year (odds ratio: 1.53 and 1.24). No significant correlations were found for the other results. CONCLUSIONS: The study gives a detailed picture of hospital care for inguinal hernia repair in Germany. Furthermore, it was noted that the risk of hernia recurrence decreases in line with a rising caseload of the treating hospital.


Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/estatística & dados numéricos , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Idoso , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Cirurgiões , Resultado do Tratamento
2.
Hernia ; 24(3): 661-668, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31745653

RESUMO

BACKGROUND: Three-dimensional (3D) laparoscopy improves the surgical skills of novice surgeons and positively affects the learning curve in experimental settings. This study aimed to investigate the effect of a 3D passive polarizing display (3DPPD) and a novel 3D head-mounted display (3DHMD; HMS-3000MT) on the performance of the first laparoscopic inguinal hernia repair by novices and compare both systems with standard high-definition 2D (HD2D) laparoscopy. METHODS: Patients with symptomatic inguinal hernia underwent transabdominal preperitoneal (TAPP) approach hernia repair using 3DHMD, 3DPPD, or a conventional HD2D laparoscopic system. All surgeries were performed for the first time by three laparoscopically novice surgeons. Operative performance was compared in terms of the time taken for mesh placement and peritoneal suturing under standardized conditions. Additionally, visual perception parameters and adverse effects were assessed. RESULTS: The use of both 3D techniques shortened the time required for mesh placement and peritoneal suturing compared with the conventional HD2D approach. Generally, 3D laparoscopy was superior to HD2D laparoscopy in terms of visual perception parameters such as depth perception, sharpness, ghosting, and contrast. However, compared with the use of HD2D laparoscopy, the use of 3DHMD significantly impaired a surgeon's comfort, with the greatest impairment caused by ear discomfort, headaches, and facial and physical discomforts. CONCLUSIONS: The 3DHMD and 3DPPD systems showed clear improvement in first hernia repair laparoscopy by novice surgeons in terms of surgical performance, as well as visual perception; however, the 3DHMD system was not superior to the 3DPPD system. The reduction in training time for new surgeons is obviously advantageous. In this respect, the 3D equipment may be a worthwhile investment.


Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/educação , Herniorrafia/instrumentação , Laparoscopia/educação , Laparoscopia/instrumentação , Competência Clínica , Feminino , Herniorrafia/métodos , Humanos , Imageamento Tridimensional , Laparoscopia/métodos , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade
3.
Langenbecks Arch Surg ; 404(6): 711-716, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31446471

RESUMO

PURPOSE: The aim of this long-term study was the comparison of appendiceal stump closure with polymeric clips or staplers with respect to perioperative costs and surgical outcome under routine conditions in a university centre. METHODS: For this retrospective chart review, a total of 618 patients undergoing laparoscopic appendectomy for suspected acute appendicitis between 2010 and 2017 were reviewed: 410 patients in the stapler group and 208 patients in the clip group. The database contained demographic data, operation time, inflammation parameters, closure method of the stump, surgeon status, length of hospital stay, and complications as well as histology reports. The costs were also compared. RESULTS: Clip application was more likely among younger patients (mean age 33.6 years vs. 41.7 years). Histopathological evidence for appendiceal pathology was found in 96.6% of patients in the clip group and 99.5% of patients in the stapler group. Laparoscopic appendectomy in the clip group was more frequently performed by resident physicians (69.2%) than in the stapler group (57.8%). The mean postoperative stay was 2.9 days in the clip group and 3.7 days in the stapler group. The use of the polymeric clip resulted in considerable cost savings (19.94€ vs. 348.70€). CONCLUSIONS: The use of polymeric clips for appendiceal stump closure during appendectomy is safe and effective. The base of the appendix is amenable to clipping in 32% of appendectomies in adult patients. This study supports the use of polymeric clips over staplers to decrease cost and environmental impact.


Assuntos
Apendicectomia/métodos , Apendicite/cirurgia , Laparoscopia/métodos , Instrumentos Cirúrgicos , Suturas , Técnicas de Fechamento de Ferimentos/instrumentação , Adulto , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos
4.
Surg Endosc ; 32(11): 4624-4631, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29777354

RESUMO

BACKGROUND: 3D laparoscopy has proven to be superior to the 2D approach in experimental settings. The aim of the present study was to investigate the influence of 3D laparoscopy using a novel head-mounted display on the performance of defined steps within a laparoscopic inguinal hernia repair. This effect was investigated both in laparoscopically advanced surgeons and in beginners. METHODS: Patients suffering from symptomatic inguinal hernia were randomly assigned to laparoscopic hernia repair using either a head-mounted 3D display or a conventional 2D laparoscopic approach. Operative performance of both groups was compared in terms of the time taken for mesh placement and for peritoneal suturing. Additionally, quality of imaging and physical discomfort were assessed. RESULTS: The use of a head-mounted 3D display was able to shorten the time required for placement of the mesh as well as that for peritoneal suturing, both for experienced and novice surgeons when compared to the conventional 2D approach. 3D laparoscopy was significantly superior to 2D laparoscopy in terms of depth perception, image sharpness and image contrast. Additionally, increased impairment caused by ghosting effects could not be detected in 3D laparoscopy. Evaluation of image quality was independent of experience in laparoscopic surgery. However, use of a head-mounted 3D display resulted in a significant impairment of surgeon's comfort when compared to 2D laparoscopy. Thereby, the greatest impairment was caused by ear discomfort. CONCLUSIONS: This is the first study examining the effect of a head-mounted 3D system on the performance of laparoscopy in a randomized controlled trial (RCT) showing a clear advantage of this system in surgical performance as well as in depth perception and image quality.


Assuntos
Hérnia Inguinal , Herniorrafia , Imageamento Tridimensional , Laparoscopia , Percepção de Profundidade , Feminino , Hérnia Inguinal/diagnóstico por imagem , Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Herniorrafia/instrumentação , Herniorrafia/métodos , Humanos , Aumento da Imagem/instrumentação , Aumento da Imagem/métodos , Imageamento Tridimensional/instrumentação , Imageamento Tridimensional/métodos , Laparoscopia/efeitos adversos , Laparoscopia/instrumentação , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Ultrassonografia de Intervenção/métodos
5.
J Wound Care ; 26(8): 470-475, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28795892

RESUMO

OBJECTIVE: The use of cold atmospheric pressure plasma (CAPP) as a new therapeutic option to aid the healing of chronic wounds appears promising. Currently, uncertainty exists regarding their classification as medical device or medical drug. Because the classification of CAPP has medical, legal, and economic consequences as well as implications for the level of preclinical and clinical testing, the correct classification is not an academic exercise, but an ethical need. METHOD: A multidisciplinary team of physicians, surgeons, pharmacists, physicists and lawyers has analysed the physical and technical characteristics as well as legal conditions of the biological action of CAPP. RESULTS: It was concluded that the mode of action of the locally generated CAPP, with its main active components being different radicals, is pharmacological and not physical in nature. CONCLUSION: Depending on the intended use, CAPP should be classified as a drug, which is generated by use of a medical device directly at the point of therapeutic application.


Assuntos
Pressão Atmosférica , Temperatura Baixa , Equipamentos e Provisões/classificação , Preparações Farmacêuticas/classificação , Gases em Plasma/uso terapêutico , Infecção dos Ferimentos/terapia , Humanos
6.
Zentralbl Chir ; 142(1): 39-45, 2017 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-25393734

RESUMO

Background: History taking and systematic clinical examination are central techniques of physicians. Medicine in general and surgery in particular frequently require immediate decisions and start of therapies. So far, a standardised surgical system for history taking and clinical examination in teaching has been lacking at our faculty. A consensus of all medical faculties on a standardised system could be a tool to improve the medical teaching and education at our teaching institutions. Methods: The established Anglo-Saxonian system of history taking and clinical examination was adapted to our own clinical needs. Thereafter, this system was sent out to all chairmen of general and visceral surgery departments in German University Hospitals asking for evaluation and improvements. We adapted the system according to the chairmen's comments and suggestions. Since winter semester 2011 this system has been integrated into the clinical course of history taking and examination. It is compulsory for all 5th semester students (first clinical year/graduate course) at the Universitätsmedizin Greifswald. In addition, a video was produced demonstrating all major techniques of clinical examination. This video is available for all students on a password blocked site of the World Wide Web. Results: Altogether, 89 % of all contacted chairmen returned their comments and suggestions for improvements. After implementation of the new system, positive evaluations of students increased significantly from 63.5 to 77.0 % in general and abdominal surgery (p < 0.0001) and from 76.4 to 83.5 % in vascular and thoracic surgery (p < 0.0001). Conclusions: The presented system is a standardised tool of history taking and clinical examination applicable for students as well as qualified surgeons in daily routine work. It has been approved by the majority of the departments of surgery of all German university hospitals. Furthermore, it can be applied by other medical specialties, in particular, internal medicine. Furthermore, the standardisation of history taking and clinical examination can contribute to improve patients' safety as well as medical documentation. Also, the standardisation will be a sound basis for expert medical opinions in legal actions. Finally, it has improved the value of medical education at our medical faculty and could form the basis for the development of national medical standards.


Assuntos
Educação Médica/normas , Cirurgia Geral/educação , Anamnese/normas , Exame Físico/normas , Universidades , Atitude do Pessoal de Saúde , Currículo/normas , Alemanha , Hospitais Universitários/normas , Humanos , Melhoria de Qualidade/normas
7.
Chirurg ; 87(1): 5-12, 2016 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-26661744

RESUMO

Despite intensive research efforts peritonitis leading to subsequent sepsis remains associated with a high mortality. The initial effector cells are the locally residing cells of the peritoneum, such as mesothelial cells, mast cells, macrophages and lymphocytes. Through the secretion of chemokines, an influx of neutrophils initially takes place followed by monocytes. The latter can differentiate into inflammatory macrophages. The non-directed activity of neutrophilic granulocytes is limited by the induction of apoptotic programs. Through the breaching of cytokines, bacteria and microbial products into the circulation, a systemic reaction in the sense of systemic inflammatory response syndrome (SIRS) or sepsis arises. This is viewed as a concomitant derailing of inflammatory as well as anti-inflammatory responses, which leads to extensive apoptosis of lymphocytes. The presentation of apoptotic cells leads to a strong immunosuppression. Due to the coexistence of hyperinflammation and immunosuppression, exact knowledge of the current immune status of the patient is a prerequisite in the development of immunotherapies for the treatment of sepsis.


Assuntos
Peritonite/fisiopatologia , Animais , Citocinas/fisiologia , Modelos Animais de Doenças , Fidelidade a Diretrizes , Humanos , Tolerância Imunológica/fisiologia , Imunidade Celular/imunologia , Inflamação/fisiopatologia , Linfócitos/imunologia , Camundongos , Peritonite/complicações , Peritonite/mortalidade , Peritonite/terapia , Sepse/complicações , Sepse/fisiopatologia , Sepse/terapia , Análise de Sobrevida
8.
Zentralbl Chir ; 141(1): 62-7, 2016 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-24771217

RESUMO

OBJECTIVE: Undergloves are a way to reduce moisture-related skin damage. The aim of this feasibility study was to gain experience with logistics, applicability, acceptability and cost of the routine use of reusable textile undergloves in a hospital setting. METHODS: Undergloves were tested with 18 health-care workers on an intensive care unit over three months. Data on usage as well as logistics were recorded. At baseline, personal data and knowledge and use of cotton undergloves, existing skin problems and the nursing behaviour of the hands by the subjects were determined by means of an input questionnaire. After each wearing, data on usage were collected by a questionnaire. Participants were interviewed by means of a questionnaire with respect to their experience with the use of the undergloves. RESULTS: Acceptance and compliance with the use of undergloves was remarkably good. This was partly due to the properties of the gloves, and partly to the reduction of sweating and very positive effect on the skin of the hands. In the study period 2165 underglove uses were documented, resulting in an average daily consumption of four pairs per person per day. The average wearing time was 28.6 min. The undergloves were suitable for application as well as reprocessing. Reprocessment-related fatigue was relatively low and did not lead to the loss of the properties, only few gloves had to be sorted out. Even if one assumes a complete write-off of the gloves with end of the study, costs for reprocessing were about 0.46 € or 64 % less than the single use. CONCLUSION: The routine use of textile, reprocessable undergloves is feasible. Major challenges for broad usage are within logistics and acceptance by the user.


Assuntos
Reutilização de Equipamento/estatística & dados numéricos , Luvas Cirúrgicas/estatística & dados numéricos , Têxteis/estatística & dados numéricos , Custos e Análise de Custo , Dermatite Ocupacional/economia , Dermatite Ocupacional/prevenção & controle , Reutilização de Equipamento/economia , Estudos de Viabilidade , Alemanha , Luvas Cirúrgicas/economia , Humanos , Inquéritos e Questionários , Têxteis/economia
9.
Zentralbl Chir ; 141(3): 277-84, 2016 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-23918726

RESUMO

Ten to 15 years ago the number of applications for a surgical residency position was very much larger than the positions available. Today, this situation has clearly reversed itself as indicated through a noticeable deficit in recruits. The decision to become a surgeon has become more uncommon. This can be blamed upon not only the demotivatingly viewed "work-life imbalance" associated with being a surgeon, but also on the basically non-inspiring training process during medical school. Due to the fact that university educators/instructors are not fundamentally trained teachers, they often fail in their capacity to convey their extensive knowledge to medical students and potentially future surgical residents. The quality of primary as well as postgraduate training is an important central factor in the effort to once again restore the attractive image of surgery within the realm of the medical disciplines. This paper presents an overview of the basic modern training concepts by which every surgeon should be able to effectively convey knowledge and practical skills. Furthermore, this work should inspire a more intensive interest in clinical graduate and postgraduate education. Due to the hand in hand relationship, this manuscript does not differentiate between student teaching and postgraduate training.


Assuntos
Competência Clínica , Currículo , Educação Médica Continuada , Educação de Pós-Graduação em Medicina , Cirurgia Geral/educação , Alemanha , Humanos
10.
Zentralbl Chir ; 141(1): 68-74, 2016 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-23824614

RESUMO

BACKGROUND: Surgical interventions induce changes in postoperative immune competence due to the surgical trauma. Consequently, the immune system cannot react sufficiently in case of septic complications. The dimension of postoperative immune suppression can be determined by HLA-DR surface expression on circulating monocytes. MATERIAL AND METHODS: In the present study relevant literature was researched and patients with visceral and thoracic surgery were included. 17 patients underwent minor surgery, i.e., cholecystectomy, thyroidectomy or hernia repair. 101 patients underwent major surgery, i.e., visceral or thoracic resections. Expression of HLA-DR on circulating monocytes (HLA-DR) was analysed by FACS, whereas gene expression of T-cells was determined by gene-array methods. RESULTS: Postoperative complications or postoperative acquired sepsis were predominantly seen in patients with significantly reduced HLA-DR. The postoperative immune suppression was influenced by the type of operation itself: following colon surgery there was a longer-lasting immune suppression compared to that after surgery on the thorax or rectum. In addition, postoperative immune suppression depends on preoperative existing risk factors: adipositas and further risk factors cause a decrease of HLA-DR. Gene expression analysis revealed a distinct down-regulation of transcriptional activity of T-cells following surgical intervention. This effect is much more pronounced in patients with septic complications. CONCLUSION: The expression of HLA-DR is a useful parameter to describe postoperative immune suppression. Furthermore, regulation of transcriptional T-cell activity can provide additional information on the postoperative immune status.


Assuntos
Tolerância Imunológica/imunologia , Complicações Pós-Operatórias/imunologia , Procedimentos Cirúrgicos Torácicos , Vísceras/cirurgia , Adulto , Idoso , Feminino , Antígenos HLA-DR/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Fatores de Risco , Linfócitos T/imunologia
11.
Pathologe ; 36 Suppl 2: 210-5, 2015 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-26483250

RESUMO

Activation of the AKT/mTOR and Ras/MAPK pathways and the lipogenic phenotype are evident both in human hepatocellular carcinoma and in the rat model of insulin-induced hepatocarcinogenesis in the earliest preneoplastic lesions, i.e. clear cell foci (CCF) of altered hepatocytes. These CCFs have also been described in the human liver but characterization of molecular and metabolic changes are still pending. In this study, human sporadic CCFs were investigated in a collection of human non-cirrhotic liver specimens using histology, histochemistry, immunohistochemistry, electron microscopy and molecular pathological analysis. Human CCFs occurred in approximately 33 % of non-cirrhotic livers and stored masses of glycogen in the cytoplasm, largely due to reduced activity of glucose-6-phosphatase. Hepatocytes revealed an upregulation of the AKT/mTOR and the Ras/MAPK pathways, the insulin receptor, glucose transporters and enzymes of glycolysis and de novo lipogenesis. Proliferative activity was 2-fold higher than in extrafocal tissue. The CCFs of altered hepatocytes are metabolically and proliferatively active lesions even in humans. They resemble the well-known preneoplastic lesions from experimental models in terms of morphology, glycogen storage, overexpression of protooncogenic signaling pathways and activation of the lipogenic phenotype, which are also known in human hepatocellular carcinoma. This suggests that hepatic CCFs also represent very early lesions of hepatocarcinogenesis in humans.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Hepatócitos/patologia , Lipogênese/genética , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Animais , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Humanos , Fígado/patologia , Glicogênio Hepático/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Proteína Quinase 1 Ativada por Mitógeno , Proteína Oncogênica p21(ras)/genética , Proteína Oncogênica v-akt/genética , Fenótipo , Lesões Pré-Cancerosas/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Regulação para Cima/genética
12.
Chirurg ; 86(6): 540-6, 2015 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-25986675

RESUMO

Although the mortality associated with major hepatopancreaticobiliary surgery has continuously decreased during the last decades, the morbidity of these procedures remains high. Functional disturbances of normal gastrointestinal motility as well as inflammation and infections of surgically treated organs are frequent complications resulting in considerably prolonged lengths of stay in hospital and increased healthcare costs. This review article highlights the therapeutic approaches and recent developments in the treatment of delayed gastric emptying, prolonged postoperative ileus, postoperative cholangitis and pancreatitis after hepatopancreaticobiliary surgery. Current practice is discussed on the basis of recent results in basic and clinical research, review articles, meta-analyses and guidelines.


Assuntos
Doenças Biliares/cirurgia , Colangite/etiologia , Colangite/terapia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Gastroparesia/etiologia , Gastroparesia/terapia , Íleus/etiologia , Íleus/terapia , Hepatopatias/cirurgia , Pancreatopatias/cirurgia , Pancreatite/etiologia , Pancreatite/terapia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Estenose Pilórica/etiologia , Estenose Pilórica/terapia , Colangite/diagnóstico , Gastroparesia/diagnóstico , Humanos , Íleus/diagnóstico , Pancreatite/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Estenose Pilórica/diagnóstico , Fatores de Risco
13.
Chirurg ; 85(12): 1103-8, 2014 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-25488115

RESUMO

BACKGROUND: The Patient Rights Act has converted court rulings into legal paragraphs. Two new aspects have been introduced: the duty to hand over a copy of the signed written consent form to the patient (in which detailed recommendations are offered) and the obligation of a thorough documentation of findings and treatments within patient files. In addition the legislators, through the Joint Federal Committee (Gemeinsamer Bundesausschuss, GBA) have made the introduction of clinical risk management mandatory. The Infection Protection Act and its regulations have elevated the prerequisites of hygiene within hospitals and private practices with a parallel increase in liability. RESULTS AND DISCUSSION: Both laws and regulations offer no reference as to who (and to what extent) is financially responsible for the excessive increase in personnel costs, which are as yet not included in the German diagnosis-related groups (G-DRG) system. Despite all additional measures within the area of risk management, mistakes (avoidable or unavoidable) will nevertheless occur. In order to avoid longstanding legal battles the authors recommend an open and rapid communication with the patient and family. The wall of silence should be a thing of the past.


Assuntos
Infecção Hospitalar/prevenção & controle , Programas Nacionais de Saúde/legislação & jurisprudência , Direitos do Paciente/legislação & jurisprudência , Infecção da Ferida Cirúrgica/prevenção & controle , Alemanha , Humanos , Consentimento Livre e Esclarecido/legislação & jurisprudência , Imperícia/legislação & jurisprudência , Gestão de Riscos/legislação & jurisprudência , Gestão da Qualidade Total/legislação & jurisprudência
14.
J Pharm Biomed Anal ; 100: 393-401, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25218440

RESUMO

Cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGT) are major determinants in the pharmacokinetics of most drugs on the market. To investigate their impact on intestinal and hepatic drug metabolism, we developed and validated quantification methods for nine CYP (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) and four UGT enzymes (UGT1A1, UGT1A3, UGT2B7 and UGT2B15) that have been shown to be of clinical relevance in human drug metabolism. Protein quantification was performed by targeted proteomics using liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based determination of enzyme specific peptides after tryptic digestion using in each case stable isotope labelled peptides as internal standard. The chromatography of the respective peptides was performed with gradient elution using a reversed phase (C18) column (Ascentis(®) Express Peptide ES-C18, 100mm×2.1mm, 2.7µm) and 0.1% formic acid (FA) as well as acetonitrile with 0.1% FA as mobile phases at a flow rate of 300µl/min. The MS/MS detection of all peptides was done simultaneously with a scheduled multiple reaction monitoring (MRM) method in the positive mode by monitoring in each case three mass transitions per proteospecific peptide and the internal standard. The assays were validated according to current bioanalytical guidelines with respect to specificity, linearity (0.25-50nM), within-day and between-day accuracy and precision, digestion efficiency as well as stability. Finally, the developed method was successfully applied to determine the CYP and UGT protein amount in human liver and intestinal microsomes. The method was shown to possess sufficient specificity, sensitivity, accuracy, precision and stability to quantify clinically relevant human CYP and UGT enzymes.


Assuntos
Cromatografia de Fase Reversa , Sistema Enzimático do Citocromo P-450/isolamento & purificação , Glucuronosiltransferase/isolamento & purificação , Jejuno/enzimologia , Fígado/enzimologia , Proteômica/métodos , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Adulto , Idoso , Calibragem , Cromatografia de Fase Reversa/normas , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Glucuronosiltransferase/metabolismo , Humanos , Isoenzimas , Masculino , Microssomos Hepáticos/enzimologia , Pessoa de Meia-Idade , Mapeamento de Peptídeos , Proteômica/normas , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/normas , Especificidade por Substrato , Espectrometria de Massas em Tandem/normas , Adulto Jovem
15.
Chirurg ; 85(7): 622-7, 2014 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-24449081

RESUMO

BACKGROUND: The recommendations for the treatment of an appendiceal mass are still controversial. The need for staged appendectomy is still under discussion. PATIENTS AND METHODS: In a retrospective study all patients with the diagnosis appendiceal mass (ICD 10 K35.32) treated in the surgical clinic of the University Clinic in Greifswald between June 1999 and June 2011 were analyzed. RESULTS: A total of 38 patients were included in the study whereby 17 patients (9 male and 8 female) were treated with drainage and antibiotics (group A) and 21 (14 male and 7 female) were treated by immediate surgery (group B). Nonsurgical therapy with drainage of the abscess was found to be efficient. Immediate surgical treatment was also effective and should be performed when signs of peritonitis exist. Interval appendectomy is not indicated.


Assuntos
Abscesso Abdominal/cirurgia , Apendicectomia/métodos , Apendicite/cirurgia , Abscesso Abdominal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Apendicite/diagnóstico , Estudos de Coortes , Terapia Combinada , Drenagem , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Peritonite/diagnóstico , Peritonite/cirurgia , Estudos Retrospectivos , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X
16.
Pancreatology ; 13(5): 508-16, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24075516

RESUMO

INTRODUCTION: More effective therapies are required to improve survival of pancreatic cancer. Possible immunologic targets include tumour associated macrophages (TAMs), generally consisting of M1- and M2-macrophages. We have analysed the impact of TAMS on pancreatic cancer in a syngeneic orthotopic murine model. METHODS: 6606PDA murine pancreatic cancer cells were orthotopically injected into C57BL6 mice. Tumour growth was monitored using MRI. Macrophages were depleted by clodronate liposomes. Tumours including microvessel density were evaluated using immunohistochemistry, immunofluorescence and/or cytometric beads assays. Naïve macrophages were generated employing peritoneal macrophages. In vitro experiments included culturing of macrophages in tumour supernatants as well as tumour cells cultured in macrophage supernatants using arginase as well as Griess assays. RESULTS: Clodronate treatment depleted macrophages by 80% in livers (p = 0.0051) and by 60% in pancreatic tumours (p = 0.0169). MRI revealed tumour growth inhibition from 221.8 mm(3) to 92.3 mm(3) (p = 0.0216). Micro vessel densities were decreased by 44% (p = 0.0315). Yet, MCP-1-, IL-4- and IL-10-levels within pancreatic tumours were unchanged. 6606PDA culture supernatants led to a shift from naïve macrophages towards an M2-phenotype after a 36 h treatment (p < 0.0001), reducing M1-macrophages at the same time (p < 0.037). In vivo, M2-macrophages represented 85% of all TAMs (p < 0.0001). Finally, culture supernatants of M2-macrophages induced tumour growth in vitro by 63.2% (p = 0.0034). CONCLUSIONS: This quid pro quo of tumour cells and M2-macrophages could serve as a new target for future immunotherapies that interrupt tumour promoting activities of TAMs and change the iNOS-arginase balance towards their tumoricidal capacities.


Assuntos
Macrófagos/imunologia , Neoplasias Pancreáticas/imunologia , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Ácido Clodrônico/administração & dosagem , Meios de Cultura/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Pancreáticas/patologia
17.
J Pharm Biomed Anal ; 85: 253-61, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23973632

RESUMO

Multidrug transporter proteins are crucial determinants in the pharmacokinetics of many drugs. To evaluate their impact on intestinal drug absorption, we developed and validated quantification methods for 10 uptake transporters (OATP1A2, OATP2B1, PEPT1, ASBT, OCT1, OCT3) and efflux transporters (ABCB1, ABCC2, ABCC3, ABCG2) that have been reported to be expressed and to be of clinical relevance in the human intestine. Quantification was performed by targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based quantification of proteospecific peptides after tryptic digestion using stable isotope labeled internal standard peptides. The chromatography of the respective peptides was performed by gradient elution using a reversed phase (C18) column (Kinetex(®), 100 × 3.0 mm, 2.6 µm) and 0.1% formic acid (FA) and acetonitrile with 0.1% FA as mobile phases at a flow rate of 0.5 ml/min. The MS/MS detection was done in the positive multiple reaction monitoring (MRM) mode by monitoring in each case three mass transitions for the transporter-derived peptides and the internal standard peptides. The assays were validated with respect to specificity, linearity (0.1-25 nM), within-day and between-day accuracy and precision as well as stability according to current bioanalytical guidelines. Finally, the developed methods were used to determine the transporter protein content in human intestinal tissue (jejunum and ileum). The methods were shown to possess sufficient specificity, sensitivity, accuracy, precision and stability to measure transporter proteins in the human intestine.


Assuntos
Cromatografia Líquida/métodos , Absorção Intestinal , Proteínas de Membrana Transportadoras/análise , Espectrometria de Massas em Tandem/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla
18.
Int J Colorectal Dis ; 28(10): 1337-49, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23657400

RESUMO

PURPOSE: Tumour-associated macrophages have been shown to promote proliferation, angiogenesis and metastasis in several carcinomas. The effect on colon cancer has not yet been clarified. Furthermore, Kupffer cells in the liver might initiate the formation of metastases by directly binding tumour cells. METHODS: An orthotopic syngeneic mouse model of colon cancer as well as a liver metastases model has been studied, using murine CT-26 colon cancer cells in Balb/c-mice. Macrophages were depleted in both models by clodronate liposomes. Tumour sizes and metastases were determined using 7-Tesla MRI. The macrophage and vascular density in the orthotopic tumours as well as the Kupffer cell density in the livers were evaluated using immunohistochemistry. RESULTS: Animals in the macrophage-depleted group displayed significantly smaller primary tumours (37 ± 20 mm(3)) compared to the control group (683 ± 389 mm(3), p = 0.0072). None of the mice in the depleted group showed liver or peritoneal metastases, whereas four of six control mice displayed liver and five out of six mice peritoneal metastases. The vascular density was significantly lower in the macrophage-depleted group (p = 0.0043). In the liver metastases model, animals of the Kupffer cell-depleted group (14.3 ± 7.7) showed significantly less liver metastases than mice of the two control groups (PBS liposomes, 118.5 ± 28.2, p = 0.0117; NaCl, 81.7 ± 23.2, p = 0.0266). The number of liver metastases correlated directly with the Kupffer cell density (p = 0.0221). CONCLUSION: Macrophages promote tumour growth, angiogenesis and metastases in this orthotopic syngeneic mouse model. Kupffer cells enhance the formation of metastases in the liver.


Assuntos
Neoplasias do Colo/patologia , Neoplasias Hepáticas/secundário , Macrófagos/patologia , Transplante de Neoplasias , Animais , Contagem de Células , Morte Celular , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/irrigação sanguínea , Modelos Animais de Doenças , Células de Kupffer/patologia , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos BALB C
19.
Chirurg ; 84(2): 117-24, 2013 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-23371027

RESUMO

Pancreatic pseudocysts are frequent complications following acute and chronic pancreatitis as well as abdominal trauma. They originate from enzymatic and/or necrotizing processes within the organ involving the surrounding tissues through inflammatory processes following pancreatic ductal lesion(s). Pseudocysts require definitive treatment if they become symptomatic, progressive, larger than 5 cm after a period of more than 6 weeks and/or have complications. Cystic neoplasms must be excluded before treatment. Endoscopic interventions are commonly accepted first line approaches. Should these fail or not be feasible surgical procedures have been well established and show comparable results. In summary, pancreatic pseudocysts require a reliable diagnostic approach with a multidisciplinary professional management involving gastroenterologists and surgeons.


Assuntos
Pseudocisto Pancreático/cirurgia , Algoritmos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Comportamento Cooperativo , Diagnóstico Diferencial , Drenagem/métodos , Endossonografia/métodos , Gastrostomia/métodos , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Comunicação Interdisciplinar , Jejunostomia/métodos , Laparoscopia/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/diagnóstico , Pseudocisto Pancreático/diagnóstico , Pseudocisto Pancreático/etiologia , Recidiva , Stents , Ultrassonografia/métodos , Ultrassonografia de Intervenção
20.
Zentralbl Chir ; 138(6): 657-62, 2013 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-23325521

RESUMO

BACKGROUND: Risk reducing measures like the surgical checklist have been proven to reduce effectively adverse events and improve patient safety and teamwork among surgical staff members. Nevertheless, many physicians still refuse to use even simple safety tools like the WHO checklist. A progress in patient safety can only be achieved by changing the operating proceedings and mentality of medical students. This is best performed by teaching patient safety already very early in the medical education. METHOD: The present study demonstrates the implementation and evaluation of the curriculum "patient safety" for undergraduate medical students in the 4th year of medical school at the Department of Surgery, University of Greifswald. 141 students evaluated a total of six lectures from April to October 2011. RESULTS: The results indicate that young medical students show great enthusiasm in safety matters and are willing to adopt the principles. Especially the importance of the issue and the didactic design were evaluated as being very high. CONCLUSION: The curriculum "patient safety" as part of the training program in medical school is a powerful and effective educational tool that is able to raise the student's awareness of patient safety affairs. Thereby it is crucial to start early within medical education during the phase of socialisation. We recommend the general implementation of a patient safety curriculum in medical school.


Assuntos
Currículo/normas , Educação de Graduação em Medicina/normas , Cirurgia Geral/educação , Segurança do Paciente/normas , Atitude do Pessoal de Saúde , Lista de Checagem , Competência Clínica/normas , Alemanha , Humanos , Imperícia/legislação & jurisprudência , Erros Médicos/prevenção & controle , Centro Cirúrgico Hospitalar
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