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Biomedical subjects

D Jäger

Publications and source records attributed to D Jäger.

At least 19 recordsLinked to original sources
PubMed2007

[Paraneoplastic syndrome in renal cell carcinoma].

Renal cell carcinoma associated paraneoplastic symptoms include constitutional symptoms as well as specific metabolic and biochemical abnormalities. These are present in up to 40% of patients with renal cell carcinoma during the course of the disease. This report provides information on the most common manifestations and their therapy; some rare variants are also mentioned. The importance of paraneoplasia lies partly in the fact that paraneoplastic symptoms may be the precursor of either primary or recurrent disease. The presence of paraneoplastic manifestations does not necessarily imply a poor prognosis or metastatic disease.

Carcinoma, Renal Cell↗
PubMed2006

Clinical significance of cyclooxygenase-2 (COX-2) in multiple myeloma.

Several biological and clinical considerations suggest the involvement of cyclooxygenase-2 (COX-2), the key enzyme of prostaglandin (PG) synthesis, in the pathogenesis and progression of haematological malignancies. Despite the wealth of data concerning COX-2 expression, only limited information is available on multiple myeloma (MM). Using standard immunohistochemistry we therefore evaluated COX-2 protein expression in samples from 57 patients with a primary diagnosis of MM. Time to progression and a variety of clinicopathological features were evaluated by the Kaplan-Meier method and the Cox regression model. In addition, COX-2 expression was evaluated by staining bone marrow from healthy donors and 11 patients with MGUS. Overall, 31 MM samples (54%) expressed COX-2. Positivity for COX-2 was unrelated to stage or clinical or molecular features of the disease. However, patients with COX-2 positive tumours experienced a significantly shorter time to progression (17 vs 30 months, p = 0.037). In summary, COX-2 is frequently expressed in MM and correlates with shorter progression-free survival.

Adult↗
PubMed2006

Protein-Z-deficiency as a rare case of unexpected perioperative bleeding in a patient with spinal cord injury.

STUDY DESIGN: Case report describing the management of repeated perioperative bleeding probably due to Protein-Z-deficiency in a post-traumatic paraplegic patient. OBJECTIVES: To describe the difficulty in diagnosing this rare form of hypocoagulability and the monitoring and substitution concept during three elective surgical interventions. SETTING: Spinal Cord Injury Center, Bergmannstrost, Halle, Germany. CASE REPORT: A 19-year-old male suffering from a post-traumatic paraplegia sub Th8 (ASIA-A) since childhood had experienced two life-threatening intraoperative bleeding incidents before finally Protein-Z-deficiency as the underlying coagulation disorder was diagnosed. After substitution of 2000 IE PPSB (Beriplex P/N) a repeatedly postponed implantation of a sphincter-externus (Brindley-) stimulator could be performed without bleeding complications, and this was also true for two additional urological interventions 1 year later. Protein-Z levels were monitored before, during and after the operations. The preoperative application of between 1000 and 2000 IE PPSB was safe and sufficient to raise the patients' plasma Protein-Z level to almost normal and so prevent excessive intraoperative blood loss. CONCLUSION: In case of repeated bleeding tendency of unknown origin it is mandatory to look for rare causes of hypocoagulability such as Protein-Z-deficiency. We developed a substitution concept using a plasma concentrate with guaranteed Protein-Z amount (PPSB) allowing the safe performance of elective surgical interventions.

Adult↗
PubMed2006

[Importance of anesthesia in multimodal oncologic therapeutical concepts].

Patients with malignant diseases are increasingly being treated with multimodal therapeutical concepts based on the three major modalities surgery, radiotherapy and chemotherapy. The perioperative period is crucial within this multimodal concept as the prognosis of patients may be directly influenced by perioperative measures. In addition, it is of major importance to avoid complications in the perioperative phase, as these might worsen the prognosis of the patient and in order to prevent a delay in the beginning of planned adjuvant therapies. These aspects demonstrate the important role of anesthesia in the treatment of patients with cancer. Further studies defining the relevance of anesthesiologic measures in oncologic patients are needed.

Aged↗
PubMed2006

[Targeted therapy in the treatment of solid tumors and in hematology-oncology. Advances and disappointments].

The development and clinical introduction of targeted therapies has resulted in significant progress for the treatment of malignant diseases. These forms of therapy supplement traditional methods of chemotherapy, radiation, and surgery. As new therapies increase the complexity of therapeutic options in oncology, the treatment costs steadily climb as well. Parameters need to be identified which will predict a response to new substances, and this effort is the subject of ongoing studies.

Antineoplastic Agents↗
PubMed2006

Do intensive care patients need an individualized dosing regimen for levofloxacin?

OBJECTIVE: In general, the pharmacokinetics (PK) of antibiotics in intensive care unit (ICU) patients are known to differ from healthy subjects. These differences can pose challenges in developing appropriate dosing guidelines. The primary objective of this report was to characterize the disposition of levofloxacin in critically ill patients and to assess any relationships between patient covariates and the PK parameters. METHODS: 20 patients in the ICU were given levofloxacin, 500 mg, as an i.v. infusion for a half hour. Plasma samples were taken until 24 hours and assayed using HPLC. The concentration-time data were analyzed using population analysis with NONMEM. RESULTS: The data were described using a 2-compartment model. Creatinine clearance was determined to be a statistically significant predictor of variability in total levofloxacin clearance. For patients with higher levofloxacin clearance, the resulting efficacy for different strains of bacteria (expressed as free AUC/MIC ratios) suggested that for less sensitive pathogens, a dosage adjustment may be needed. CONCLUSION: A model describing the pharmacokinetics of levofloxacin in critically ill patients was developed. It was determined that creatinine clearance has a significant role in the disposition of levofloxacin. This may have significant implications in the clinical setting for identifying optimal dosage regimens for ICU patients.

Anti-Bacterial Agents↗
PubMed2005

Normal angiogram in acute coronary syndrome-preangiographic risk stratification, angiographic findings and follow-up.

BACKGROUND: Coronary angiographies performed during acute coronary syndrome show different coronary morphologies-vessel occlusions, thrombi and various types of stenoses. In a few cases of acute coronary syndrome, angiography reveals normal coronary arteries. It is the purpose of this study to analyze this specific subset of patients who presented with an acute coronary syndrome but had a normal coronary angiogram with respect to the preangiographic diagnostics, risk stratification and clinical follow-up. METHODS AND RESULTS: A total of 897 coronary angiographies were performed as an emergency procedure in our institution. The majority of patients (n = 821) presented with coronary artery disease and the majority was treated by mechanical revascularization (86.3%). In 76 patients (8.5%), no coronary artery stenosis was documented. However, according to the preangiographic risk stratification, coronary artery disease was expected in these patients. Observations documented angiographically included coronary spasms (6.6%) and muscle bridges (5.3%). During a mean follow-up of 11.2 +/- 6.4 months, one patient developed an acute myocardial infarction requiring coronary intervention. All other patients were free of any cardiac event. CONCLUSIONS: In summary, we have to consider that coronary angiography may not always detect the cause of myocardial ischemia in every patient. There is a small group of patients with normal coronary angiograms during acute coronary syndrome. Additional diagnostic procedures like intravascular ultrasound (IVUS) or the assessment of intracoronary physiological parameters may increase the diagnostic value of angiography.

Acute Disease↗
PubMed2005

[Systemic therapy for colorectal cancer].

Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to the traditional 5-fluorouracil, newer anticancer drugs are available including irinotecan and oxaliplatin. Monoclonal antibodies like bevacizumab and cetuximab have been integrated into modern treatment regimens. Based on randomized clinical trials we can formulate rational treatment strategies as outlined in this article.

Antibodies, Monoclonal↗
PubMed2004

[Identification of tumor antigens: strategies and perspectives].

The identification of tumor antigens is crucial for the development of antigen-specific immunotherapies in cancer. Ideal target antigens for immunotherapies have a tumor specific expresssion pattern. Antigen expresssion in solid tumors is typically heterogenous. Therefore an effective immunotherapy should target several antigens simultaneously (polyvalent vaccine). Here we discuss strategies how tumor antigens can be identified and further analyzed as potential target antigens for active immunotherapy (cancer vaccine).

Antigens, Neoplasm↗
PubMed2004

[New drugs for colorectal cancer].

Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to fluorouracil new anticancer drugs like irinotecan and oxaliplatin have become available. The activity of fluorouracil was optimized by using schedules of prolonged infusion. Capecitabine is an oral pro-drug of fluorouracil. When colorectal metastases are limited to the liver they should be resected if possible. Sometimes they can be reduced in size by primary chemotherapy (downstaging) and resected later. Very new and exciting are reports with the monoclonal antibody bevacizumab in combination with chemotherapy. Bevacizumab blocks angiogenesis. So far it is available only in the USA.

Antibodies, Monoclonal↗
PubMed2004

Dose escalation study for defining the maximum tolerated dose of continuous oral trofosfamide in pretreated patients with metastatic lung cancer.

BACKGROUND: Trofosfamide is increasingly used in the treatment of patients with several types of malignancies. However, the optimal dose of trofosfamide for patients with advanced cancer has not been systematically investigated yet. The aim of this study was to define the maximum tolerated dose (MTD) of continuous oral trofosfamide. PATIENTS AND METHODS: 16 patients with advanced lung cancer (14 nonsmall cell lung cancer, 2 small cell lung cancer; 10 male, 6 female; median age 64 years (range 46-82); median Karnofsky status 70%; median number of organs involved 3 (range 1-6)) were enrolled. All patients were previously treated with chemotherapy (median 2x, range 1-6) and 8/16 (50%) with radiotherapy. Patients received trofosfamide p.o. administered in 3 doses per day for 3 weeks (1 cycle) using a 3-patient-cohort dose-escalation strategy. Toxicities were graded according to the WHO Criteria. RESULTS: Patients received a median of 2 cycles of trofosfamide (range 1-4) at 3 dose levels (90, 125, and 175 mg/m2). Grade 3 and 4 neutropenia, anemia, and thrombocytopenia were observed in 20, 13.3, and 6.6%, respectively. Dose-limiting toxicities during the first cycle were grade 3 muscle weakness and anorexia observed in 1/6 patients in cohort 1 (trofosfamide 90 mg/m2), grade 3 neutropenia in 1/6, and encephalopathy in 1/6 patients in cohort 3 (trofosfamide 175 mg/m2). Therefore, the dose level of 125 mg/m2 was defined as the MTD. CONCLUSION: Trofosfamide at 125 mg/m2 administered in 3 doses per day was well tolerated. This dose level is recommended for further clinical studies.

Administration, Oral↗
PubMed2003

[Electronic distribution of patient records and images through PACS: implementation of data protection at the University Hospital in Freiburg].

In large installations of a Picture Archiving and Communication System (PACS), data protection becomes an issue. Above all, not every employee should have access to all data stored in the system. At the Freiburg University Hospital, we developed a concept of dynamic assignment of authorization, assuring that every physician is authorized to the data of all patients under his care. We describe the technical implementation of data protection developed for the integration of PACS and electronic patient records in Freiburg. The system was installed in January 2001 and the experience of its two years in operation is reported.

Computer Security↗
PubMed2003

[Protein-z-deficiency as a rare case of perioperative bleeding].

Protein Z is a vitamin-K-dependent plasma glycoprotein synthesized by the liver, showing great structural similarity to other vitamin-K-dependent coagulation factors such as factors II, IX, X and protein C and S. Protein Z seems to assist haemostasis by binding thrombin and promoting its association with phospholipid surfaces, and it downregulates coagulation by forming a complex with the plasma protein-Z-dependent protease inhibitor, which inhibits activated factor Xa. Studies in patients with a bleeding tendency of unknown origin during and after surgery displayed diminished protein-Z-concentrations in about 50 % of the patients with recurrent bleeding. We report about a 19 year old patient, who suffers from a posttraumatic paraplegia subTh 8 since childhood. In 1998 a correction operation in order to reduce scoliosis with restrictive ventilatory defects had to be stopped before successful spondylodesis because of massive bleeding. After a second intraoperative bleeding incident and exclusion of other more frequent thrombocytic or plasmatic causes of hypocoagulability protein-Z-deficiency finally was diagnosed. Under substitution of protein-Z using PPSB (Beriplex P/N) a repeatedly postponed implantation of a sphincter-externus (Brindley-) stimulator could be performed without bleeding complications in 2001, and this was also true for two other urological interventions in 2002. This report about repeated life-threatening intraoperative bleeding in a patient with protein-Z-deficiency, which could be successfully counteracted using selected plasma concentrates with guaranteed protein-Z-amounts, underlines the importance of protein-Z-assessment in some rare cases of bleeding tendency of "unknown origin" and documents the preventive plasma Protein-Z-levels achieved with the substitution of PPSB.

Adult↗
PubMed2003

Stromal antigen targeting by a humanised monoclonal antibody: an early phase II trial of sibrotuzumab in patients with metastatic colorectal cancer.

BACKGROUND: A novel immunological approach to colon cancer therapy is the antibody targeting of the fibroblast activation protein (FAP), which is highly expressed by stroma cells of this tumour. Unconjugated sibrotuzumab (BIBH 1), which is a humanised version of the murine anti-FAP mAb F19, was investigated for its anti-tumour activity, safety and pharmacokinetics. PATIENTS AND METHODS: Patients with metastatic colorectal cancer received weekly intravenous infusions of unconjugated sibrotuzumab at a dose of 100 mg over 12 scheduled weeks. The study was implemented as an open-label, uncontrolled, multicentre trial. RESULTS: 25 patients were enrolled. Patients had one or more measurable lesions, predominantly liver lesions, at baseline. At least 8 repeated weekly infusions of sibrotuzumab in 17 evaluable patients did not result in complete or partial remission. Rather, ongoing tumour progression was noted in all patients except for 2 patients with stable disease. However, progressive disease was also observed post-study in these 2 patients who received 1 and 6 additional infusions, respectively, of sibrotuzumab. Sibrotuzumab exhibited 2-compartment pharmacokinetics with a dominant terminal phase and t1/2 beta = 5.3 +/- 2.3 days. Adverse drug reactions (rigors/chills, nausea, flushing and one incidence of bronchospasm) were observed in 5 patients. Of the 24 patients given 2 or more infusions of sibrotuzumab, antibodies against sibrotuzumab were found in 3 patients (12.5%) after 4-12 infusions. CONCLUSIONS: Sibrotuzumab was well tolerated and safe. The minimal requirement for the continuation of this exploratory trial, of at least one complete or partial remission, or equivalently, of 4 patients with stable disease, was not met.

Aged↗
PubMed2002

Separation and identification of human heart proteins.

Heart failure is not a uniform disease entity, but a syndrome with various causes, including hypertension, ischemia and congenital heart disease, cardiomyopathy, myocarditis and intoxication. During the recent years a number of molecular and cellular alterations have been identified in the diseased heart, but a direct causative link between these changes and functional impairment, medical responsiveness, progression of the disease and the patients' outcome remains to be established. After an accumulation of large amounts of DNA sequence data in genomic projects, scientists have now turned their attention to the central executors of all programs of life, the proteins. In complementation of the genomic initiatives, proteomics based approaches have lined up not only for large-scale identification of proteins and their post-translational modifications, but also to study the function of protein complexes, protein-protein interactions and regulatory and signalling cascades in the cellular network. In concert with genomic data functional proteomics will hold the key for a better understanding and therapeutical management of cardiovascular diseases in the future.

Humans↗
PubMed2002

A CMOS clock and data recovery circuit for intraocular microsystems.

This paper presents the implementation of a clock and data recovery circuit (CDR) for intraocular microsystems. The CDR was designed to minimize chip area and power consumption and to recover the clock and data signals from the incoming data stream. Since the CDR has been designed without any external components it is well suited for being integrated in an intraocular microsystem. Simulation results show that this CDR works with power dissipation of less than 2.4 mW with a single 3.3 V power supply. The simulations are based on a 0.6 micron n-well CMOS single-polysilicon, three-metal technology.

Blindness↗