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Biomedical subjects

R Kopp

Publications and source records attributed to R Kopp.

At least 19 recordsLinked to original sources

Imaging of aortic abnormalities with contrast-enhanced ultrasound. A pictorial comparison with CT.

Aortic abnormalities are commonly encountered and may represent a diagnostic challenge in patients with acute or chronic clinical symptoms. Contrast-enhanced ultrasound (CEUS) with low mechanical index (low MI) is a new promising method in the diagnosis and follow-up of pathological aortic lesions. CEUS with SonoVue allows a more rapid and noninvasive diagnosis, especially in critical patients because of its bedside availability. This review compares CEUS findings with those documented on computed tomography angiography (CTA), allowing the reader to appreciate the usefulness of CEUS in this clinical situation.

Aortic Dissection↗

Outcome following lung resections for pT1 non-small cell lung cancer.

AIMS: To analyse the outcome of patients with pT1 NSCLC treated at our institution by antero-lateral thoracotomy, anatomical lung resections and mediastinal lymph node dissection between 1980 and 2001. METHODS: Follow-up data were obtained retrospectively from 1980 to 1990 and prospectively after 1990. Survival was analysed using the Kaplan-Meier method. RESULTS: Histopathological examinations revealed mediastinal lymph node infiltration in 27.6% (pN1 17.8% and pN2 9.8%). pN2 was classified in 14.1% of adenocarcinomas compared to 6.2% of squamous cell carcinomas. Median overall survival of patients with pT1 carcinomas was 89+16 months (median+standard error). Histopathological N-classification indicates differential prognostic and therapeutic implications in pT1 adeno- and squamous cell carcinomas. CONCLUSIONS: Complete lymph node dissection is required for all patients with T1 NSCLC treated by either open surgery or VATS resection. Histopathological N-classification indicates differential prognostic and therapeutic implications in pT1 adeno- and squamous cell carcinomas.

Carcinoma, Non-Small-Cell Lung↗

Results of different operative procedures for patients with popliteal artery aneurysms.

BACKGROUND: Long term results of four different operative procedures for the treatment of popliteal artery aneurysms were investigated either performed by short venous or segmental alloplastic interpositions or long femoro-popliteal below the knee bypass using alloplastic grafts or autologous vein. PATIENTS AND METHODS: 47 patients treated for 50 popliteal aneurysms (mean diameter +/- SD: 3.5 +/- 1.1 cm) were analyzed (follow-up: 40.2 +/- 4.9 months). RESULTS: Primary patency rate was 78% and secondary patency rate was 86% at 5 years. Frequency of operative reinterventions was higher in patients treated for acute ischemia and in patients treated with alloplastic interpositions or alloplastic bypass (p = 0.026). Secondary patency rates were higher in patients treated with autologous venous interpositions or venous femoro-popliteal bypass (p = 0.022). Times of secondary vascular patency were significantly shorter for patients treated with short alloplastic interpositions in comparison to long alloplastic femoro-popliteal bypass procedures, short venous interpositions or long venous bypass operations (p = 0.018). CONCLUSIONS: For the treatment of patients with popliteal aneurysms autologous venous interposition is therefore recommended or as an alternative venous or alloplastic femoro-popliteal below the knee bypass.

Amputation, Surgical↗

[Role of vacuum therapy in the management of the septic abdomen].

Progress in intensive care medicine contributed substantially in lowering the mortality rate of patients suffering from diffuse secondary peritonitis. In the medical care of patients presenting a septic abdomen the persisting septic focus is one of the greatest problems. This is associated with other problems like temporary closure of the abdomen, complications due to re-laparotomies, healing of the abdominal wall after soft tissue infection, loss of abdominal wall musculature, or persisting enteral fistulas. The vacuum therapy is used with increasing frequency for the treatment of septic complications in different areas of the body. The excellent drainage characteristics of the vacuum therapy appear to be a therapeutic option for the control of surgically untreatable septic processes in the abdominal cavity. More and more experience is gathered with the successful treatment of enterocutaneous fistulas, small intestine and pancreatic fistulas as well as anastomotic leakage after rectal surgery. There exist hardly any evidence-based recommendations for the application of vacuum therapy for treatment of the septic abdomen. But the good results of temporary closure of open abdomen of trauma patients by the vacuum therapy arises hope that the results can be transferred to the treatment modalities of persisting peritonitis. Additionally, these patients could profit from the drainage characteristics of the vacuum therapy.

Abdominal Wall↗

Role of extracorporeal lung assist in the treatment of acute respiratory failure.

For patients with most severe acute respiratory distress syndrome (ARDS) conservative treatment with lung protective ventilation is often not sufficient to prevent life-threatening hypoxemia and additional strategies are necessary. Extracorporeal lung assist (ECLA) or extracorporeal membrane oxygenation (ECMO) using capillary membrane oxygenators can provide sufficient gas exchange and lung rest. In 2 randomized trials mortality was unchanged for ECMO. Today an technically enhanced ECMO is used for most severe ARDS using clinical algorithm and different case studies demonstrated a survival rate about 56%. Today miniaturized ECMO with optimized blood pumps and oxygenators are available and could enhance safety and clinical management. Another approach is an arterio-venous pumpless interventional lung assist (ILA) with a low resistance oxygenator. Advantages seem a simplified clinical management and less blood trauma. At present new devices are developed for chronic respiratory failure or bridge to lung transplant. Oxygenators with even less flow resistance could be implanted paracorporeal using the right ventricle as driving force. An intravascular oxygenator has been developed using the combination of a miniaturized blood pump and an oxygenator for implantation in the vena cava. Well designed clinical trials are necessary to demonstrate a clinical benefit for these experimental devices.

Acute Disease↗

Prognostic relevance of p53 and bcl-2 immunoreactivity for early invasive pT1/pT2 gastric carcinomas: indicators for limited gastric resections?

BACKGROUND: Laparoscopic or endoscopic limited resection is intended to be an additional therapeutic option for the treatment of early gastric cancer. However, tumorbiologic markers to predict the outcome for patients after limited resections are missing. This study therefore investigated the prognostic relevance of p53 and bcl-2 immunoreactivity as well as the percentage of apoptotic tumor cells in early invasive pT1/pT2 tumors managed with standard operations for gastric adenocarcinoma. METHODS: Histologic slides of 65 pT1/pT2 gastric carcinomas were investigated for bcl-2 and p53 immunoreactivity. For 35 patients, DNA fragmentation of tumor cell nuclei was determined by the terminal uridine 5'-triphosphate (UTP) nick end-labeling (TUNEL) method. Follow-up evaluation of the patients was prospectively documented for 53.4 +/- 4.1 months. RESULTS: Findings showed that bcl-2 immunoreactivity was associated with tumors of the intestinal type according to Lauren s classification (p = 0.042), and that p53 immunoreactivity was increased in more invasive tumors (pT1 vs pT2 tumors; p = 0.047). Mean survival time was significantly longer for patients with bcl-2-negative tumors (74.3 +/- 6.8 months) than for patients with bcl-2-positive tumors (50.8 +/- 7.6 months; p = 0.024). The percentage of apoptotic tumor cell nuclei did not have prognostic relevance in the population studied and was not associated with several histopathologic parameters or bcl-2 and p53 immunoreactivity. Subgroup analysis indicated that the survival of patients with differentiated G2 and bcl-2-negative/p53-negative tumors was significantly longer (82 +/- 6 months) than the survival of patients with G2 bcl-2- and/or p53-positive tumors (41.8 +/- 12.5 months; p = 0.005), with independent prognostic relevance determined by multivariate analysis (p = 0.024). CONCLUSION: The data reported indicate that the analysis of bcl-2 and p53 immunoreactivity seems to have prognostic implications for early invasive (pT1/pT2) gastric adenocarcinomas and may subclassify patients for minimally invasive laparoscopic or endoscopic gastric resections.

Adenocarcinoma↗

Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically defined by familial clustering of colorectal cancer and other associated tumours. METHODS: By thorough molecular and clinical evaluation of 41 families, two different groups were characterised: group 1, 25 families with truncating mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam positive families without mutations in these genes and without microsatellite instability in their corresponding tumours. RESULTS: Significant clinical differences between these two groups were found. Firstly, earlier age of onset for all colorectal cancers (median 41 v 55 years; p < 0.001) and all tumours (median 43 v 56 years; p = 0.022) was observed, comparing groups 1 and 2. Secondly, 68% of the index colorectal cancers were localised proximally of the splenic flexure in group 1 compared with 14% in group 2 (p < 0.010). Thirdly, more synchronous and metachronous colorectal (p = 0.017) and extracolorectal tumours (p < 0.001) were found in group 1. Fourthly, a higher colorectal adenoma/carcinoma ratio (p = 0.030) and a tendency towards more synchronous or metachronous adenomas in group 2 (p = 0.084) was observed, indicating a slower progression of adenomas to carcinomas. As three mutation negative tumours revealed chromosomal instability after comparative genomic hybridisation, these tumours may be caused by one or more highly penetrant disease alleles from the chromosomal instability pathway. CONCLUSION: These data show that HNPCC includes at least two entities with clinical and molecular differences. This will have implications for surveillance programmes and for cancer research.

Adaptor Proteins, Signal Transducing↗

Effect of hirudin versus heparin on hemocompatibility of blood contacting biomaterials: an in vitro study.

Hirudin serves as an alternative anticoagulant for extracorporeal blood circulation. Comparing anticoagulation with hirudin (2.5 or 5.0 microg/mL) and heparin (2.0 or 4.0 IU/mL) human blood was circulated in a modified 'Chandler System' using PVC-tubes for 2 hours at 37 degrees C. Activation of coagulation (thrombin-antithrombin III-complex, prothrombin fragment 1+2 and D-Dimer), platelet (platelet factor 4 - PF4) and complement systems was analyzed. Both heparin concentrations and 5.0 microg/dL hirudin led to as significantly less activated plasmatic coagulation as 2.5 microg/dL hirudin. Decreased levels of PF4 and anaphylatoxin C5a (p<0.05) as well as terminal complement complex demonstrated improved hemocompatibility after anticoagulation with heparin in contrast to hirudin. Because initial coagulation cascade, platelet activation and complement activation is less influenced by hirudin than by heparin, hemocompatibility is more dependent on the characteristics of the biomaterials used. This predestines hirudin as anticoagulant for in vitro studies analyzing hemocompatibility of biomaterials or surface modifications.

Analysis of Variance↗

Artificial lung and extracorporeal gas exchange.

Over the last years, several observational studies have suggested that extracorporeal lung assist (ECLA) may be an important contribution to clinical algorithms for the treatment of most severe acute respiratory distress syndrome (ARDS). Today ECLA is used only as a rescue therapy in life threatening gas exchange disorders if maximal conventional therapy fails to prevent from hypoxemia. With subsequent reduction of complications and improvement of biocompability, extracorporeal membrane oxygentation (ECMO) indications may be extendend to treat patients earlier and not only in rescue situations along the original idea to buy the lung some time to heal by avoiding further ventilator associated lung injury. Veno-venous ECMO therapy at present is an important therapeutic option in severe ARDS with persisiting life threatening gas exchange disorder as a rescue therapy. The development of smaller, less complex and more secure ECMO or pumpless veno-arterial ECLA systems has the potential to perform controlled studies of its use in ARDS and potentially expand indications.

Animals↗

Extended microsatellite analysis in microsatellite stable, MSH2 and MLH1 mutation-negative HNPCC patients: genetic reclassification and correlation with clinical features.

BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder predisposing to predominantly colorectal cancer (CRC) and endometrial cancer frequently due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2 and also MSH6 in families seen to demonstrate an excess of endometrial cancer. As a consequence, tumors in HNPCC reveal alterations in the length of simple repetitive genomic sequences like poly-A, poly-T, CA or GT repeats (microsatellites) in at least 90% of the cases. AIM OF THE STUDY: The study cohort consisted of 25 HNPCC index patients (19 Amsterdam positive, 6 Bethesda positive) who revealed a microsatellite stable (MSS)--or low instable (MSI-L)--tumor phenotype with negative mutation analysis for the MMR genes MLH1 and MSH2. An extended marker panel (BAT40, D10S197, D13S153, D18S58, MYCL1) was analyzed for the tumors of these patients with regard to three aspects. First, to reconfirm the MSI-L phenotype found by the standard panel; second, to find minor MSIs which might point towards an MSH6 mutation, and third, to reconfirm the MSS status of hereditary tumors. The reconfirmation of the MSS status of tumors not caused by mutations in the MMR genes should allow one to define another entity of hereditary CRC. Their clinical features were compared with those of 150 patients with sporadic CRCs. RESULTS: In this way, 17 MSS and 8 MSI-L tumors were reclassified as 5 MSS, 18 MSI-L and even 2 MSI-H (high instability) tumors, the last being seen to demonstrate at least 4 instable markers out of 10. Among all family members, 87 malignancies were documented. The mean age of onset for CRCs was the lowest in the MSI-H-phenotyped patients with 40.5 +/- 4.9 years (vs. 47.0 +/- 14.6 and 49.8 +/- 11.9 years in MSI-L- and MSS-phenotyped patients, respectively). The percentage of CRC was the highest in families with MSS-phenotyped tumors (88%), followed by MSI-L-phenotyped (78%) and then by MSI-H-phenotyped (67%) tumors. MSS tumors were preferentially localized in the distal colon supposing a similar biologic behavior like sporadic CRC. MSH6 mutation analysis for the MSI-L and MSI-H patients revealed one truncating mutation for a patient initially with an MSS tumor, which was reclassified as MSI-L by analyzing the extended marker panel. CONCLUSION: Extended microsatellite analysis serves to evaluate the sensitivity of the reference panel for HNPCC detection and permits phenotype confirmation or upgrading. Additionally, it confirms the MSS status of hereditary CRCs not caused by the common mutations in the MMR genes and provides hints to another entity of hereditary CRC.

Adaptor Proteins, Signal Transducing↗

[Extracorporeal membrane oxygenation by acute respiratory distress syndrome].

After various observational studies demonstrated a benefit of extracorporeal membrane oxygenation (ECMO) in the therapy of severe acute respiratory distress syndrome (ARDS), ECMO now represents an important contribution for ARDS therapy using clinical algorithms despite a lack of positive controlled studies. In specialized centers patients with severe ARDS and imminent hypoxia despite intensive conventional therapy, are treated with ECMO using blood pumps and artificial membrane lungs (oxygenators) for extracorporeal lung assist. The development of new surface modifications, optimized oxygenators and miniaturized blood pumps should increase hemocompatibility and lead to simplified treatment as well as less complications. New oxygenators with significantly decreased blood resistance allow the clinical application of pumpless arteriovenous extracorporeal lung assist (ECLA). After these new developments indications for ECMO could be extended from use not only as ultimate ratio but to less severe ARDS to enable lung protective, less invasive mechanical ventilation.

Anticoagulants↗

[Treatment of acute respiratory distress syndrome in a treatment center. Success is dependent on risk factors].

SUBJECT: Mortality rates remain high for the acute respiratory distress syndrome (ARDS) despite standardised treatment algorithms. Little is known about prognostic factors and exclusion criteria for advanced treatment including extracorporeal membrane oxygenation (ECMO). METHODS: In an observational study design a cohort of 93 patients with severe ARDS admitted to a referral centre were analysed according to ventilatory and vital parameters. RESULTS: Overall survival rate was 70% and in patients who received ECMO treatment it was 67%. In patients exhibiting relevant co-morbidity the odds ratio for fatal outcome increased to 4.7 (95% CI: 3.3-24.9), and patients with multiple organ failure had a 7.5-fold increase (95% CI: 2.3-25.2) for risk of death. Survivors demonstrated a more pronounced improvement in oxygenation ( p<0.05) and CO(2) removal ( p<0.05) than non-survivors. CONCLUSIONS: Advanced treatment of ARDS including ECMO represents a therapeutic option if none of the currently considered contraindications are present. An improvement in gas exchange parameters, but not a defined value per se may be useful as a prognostic factor for favourable outcome.

Adult↗

[Evidence-based medicine of the acute respiratory distress syndrome].

Different therapeutic approaches have recently been developed for treatment of acute respiratory distress syndrome (ARDS) with the aim of improving the outcome. The clinical significance and success of these therapies is variable with respect to evidence based medicine. Lung protective ventilation is accepted as a proven therapy and the use of positive end-expiratory pressure as well as spontaneous breathing during controlled ventilation are common therapies. High frequency ventilation, partial liquid ventilation and pulmonary surfactant application are still in the experimental stage. The prone position is recommended for severe cases of ARDS and the application of inhaled nitric oxide and of extracorporeal membrane oxygenation is established in specialized centers for patients with imminent hypoxia. But for the routine use of these three therapies a clear improvement in outcome could not demonstrated. Recommended drug therapy is limited to the administration of stress doses of corticosteroids and a special anti-inflammatory enteral diet.

Evidence-Based Medicine↗

[Acute limb ischemia from the general surgeon's point of view. How much knowledge of vascular surgery is necessary?].

The diagnosis of acute peripheral ischemia can be obtained based on clinical presentation, inspection, and palpation of the affected extremity. Unfractionated heparin as a single shot is immediately given followed by continuous infusion when diagnosis is clinically evident and contraindications are excluded. Thromboembolectomy using a Fogarty catheter is immediately performed in patients with evidence of arterial embolization and signs of advanced ischemia (TASC IIb/III) followed by intraoperative angiography. Patients with evidence of arterial thrombosis require urgent angiography followed by thrombectomy and probably subsequent endovascular or surgical interventions and vascular reconstruction. For patients with moderate ischemia (TASC IIa), initial diagnostic angiography is recommended followed by primary thrombectomy with subsequent intraoperative angiography and immediate endovascular or operative treatment of remaining vascular problems. As an alternative therapeutic option initial catheter-guided local thrombolysis can be performed in selected patients with the intention of subsequent limb revascularization or unmasking relevant vessel alterations leading to specific endovascular or surgically performed vascular reconstruction. Possible development of muscle ischemia because of increased compartment pressure should be considered and fasciotomy performed when indicated. Primary amputation of the severely ischemic limb after initial thrombectomy might be recommended in patients with life-threatening organ failure related to muscle necrosis.

Acute Disease↗

Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms?

5-8% of all colorectal cancer cases are assumed to be due to germline mutations in DNA mismatch repair genes. Mutation analysis of these genes in affected families enables one to identify subjects with an inborn susceptibility to colorectal tumorogenesis and to offer presymptomatic testing to family members at risk, provided that the mutation detected is a truncating one or a missense mutation that has either been judged as disease causing in other families or segregates with the disease and results in a microsatellite instability of the corresponding tumor. Segregation analysis within the family or microsatellite analysis of the tumor is, however, not always possible. In these cases, assessment of the relevance of the sequence variation identified is very difficult. On the other hand, discrimination between inactivating mutations and innocuous sequence polymorphisms is of extreme importance for clinical and genetic counseling of affected families. Here we report 16 rare sequence variants of the hMLH1 and hMSH2 genes including 11 different missense variations found in a cohort of 254 suspected HNPCC patients. We provide evidence, that missense variations in hMLH1 do not necessarily result in microsatellite instability of the corresponding tumor DNA. These patients would have been missed had one followed the recommendations of using only microsatellite analysis for the selection of patients at high risk of hereditary non-polyposis colorectal cancer for mutation analysis.

Adaptor Proteins, Signal Transducing↗

MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis.

MICA and MICB belong to a multicopy gene family located in the major histocompatibility complex (MHC) class I region near the HLA-B gene. They encode for MHC class I molecules, which are induced by stress factors like infection, heat shock or neoplastic transformation and which are mainly expressed on gastrointestinal epithelium. They are recognized by gammadelta T lymphocytes and natural killer (NK) cells. Additionally they are located within a linkage region on chromosome 6p around HLA-B and TNFalpha. Thus the polymorphic MICA and MICB genes are excellent candidate genes for providing the genetic background of inflammatory bowel disease. A strong association of allele A6 of the MICA exon 5 trinucleotide microsatellite polymorphism with ulcerative colitis has been found in Japanese patients. Therefore, we have analysed the MICA exon 5 polymorphism, the MICB intron 1 dinucleotide polymorphism and in addition the tetranucleotide polymorphism C1_4_1, which is located between the MICA gene and the HLA-B gene, in patients of Caucasoid origin with Crohn's disease (n=94) and ulcerative colitis (n=94). In this study we could not find any associations of particular alleles of the MICA, MICB and C1_4_1 polymorphisms with Crohn's disease or ulcerative colitis. We could also not discover any associations of specific two-point or three-point haplotypes with these diseases. Thus it is unlikely that the MICA and MICB genes are involved in causing susceptibility for inflammatory bowel disease, although it cannot be excluded that a weak association could be identified in a larger patient sample.

Colitis, Ulcerative↗