Biomedical subjects

T Schroeder

Publications and source records attributed to T Schroeder.

At least 55 records · Page 3Linked to original sources

PubMed2005

Branching fraction and CP asymmetries of B0-->K0(S)K0(S)K0(S).

We present measurements of the branching fraction and time-dependent CP-violating asymmetries in B0-->K0(S)K0(S)K0(S) decays based on 227 x 10(6) Upsilon4S-->BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We obtain a branching fraction of (6.9(+0.9)(-0.8)+/-0.6) x 10(-6), and CP asymmetries C=-0.34(+0.28)(-0.25)+/-0.05 and S=-0.71(+0.38)(-0.32)+/-0.04, where the first uncertainties are statistical and the second systematic.

Journal Article↗

PubMed2005

Anatomical and physiological classification of hepatic vein dominance applied to liver transplantation.

BACKGROUND: Proper outflow reconstruction is essential in LDLT. Preoperative planning requires meticulous attention to hepatic vein dominance patterns. The purpose of our study was to provide a combined anatomical-physiological classification of hepatic vein dominance useful for surgical decision-making in both donors and recipients. METHODOLOGY: We analyzed 3-dimensional CT-imaging reconstructions of 55 potential live liver donors evaluated at our Institution between January 2003 and May 2004. RESULTS: Our data revealed that: 1) The middle hepatic vein (MHV) and left hepatic vein (LHV) show a relative lack of anatomical diversity, whereas the right hepatic vein (RHV) exhibits multiple variants, 2) 45% donors had inferior hepatic veins (IHV) with anatomically and physiologically relevant venous drainage territories, 3) The RHV is usually dominant when present as a single vein without anatomical IHV (type 1A), or when considered as a complex with IHV (type 1Bx) (80% vs. 88%), 4) Only 55% of dominant type 1Bx RHV/IHV-complex automatically included a dominant type 1By RHV by itself, 5) A single RHV out of anatomical complex with IHV (type 1By) was dominant in only 48% of our donor candidates, 6) The MHV types 2A and 2By are strongly dominant accounting for up to 57% of total liver volume (TLV). CONCLUSIONS: We propose a new classification based on both anatomical and physiological hepatic venous configurations. Our model also provides a new nomenclature that can be universally applied to preoperative planning in LDLT.

Adolescent↗

PubMed2005

Measurements of branching fractions and time-dependent CP-violating asymmetries in B --> eta'K decays.

We present measurements of the B --> eta(')K branching fractions; for B(+) --> eta(')K(+) we measure also the time-integrated charge asymmetry Alpha(ch), and for B(0) --> eta(')K(0)(S) the time-dependent CP-violation parameters S and C. The data sample corresponds to 232 x 10(6) BB pairs produced by e(+)e(-) annihilation at the Upsilon (4S). The results are Beta(B --> eta(')K(+)) = (68.9 +/- 2.0 +/- 3.2) x 10(-6), Beta(B(0) --> eta(')K(0)) = (67.4 +/- 3.2) x 10(-6), Alpha(ch) = 0.033 +/- 0.028 +/- 0.005, S = 0.30 +/- 0.140 +/- 0.02, and C = -0.21 +/- 0.10 +/- 0.02, where the first error quoted is statistical and the second is systematic.

Journal Article↗

PubMed2005

Branching fractions and CP asymmetries in B0-->pi0pi0, B+-->pi+pi0, and B+-->K+pi0 decays and isospin analysis of the B-->pipi system.

Based on a sample of 227 x 10(6) BB pairs collected by the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC, we measure the branching fraction B(B0-->pi(0)pi(0))=(1.17+/-0.32+/-0.10)x10(-6), and the asymmetry Cpi(0)(pi(0))=-0.12+/-0.56+/-0.06. The B0-->pi(0)pi(0) signal has a significance of 5.0 sigma. We also measure B(B+-->pi(+)pi(0))=(5.8+/-0.6+/-0.4)x10(-6), B(B+-->K+pi(0))=(12.0+/-0.7+/-0.6)x10(-6), and the charge asymmetries Api(+)(pi(0))=-0.01+/-0.10+/-0.02 and AK+(pi(0))=0.06+/-0.06+/-0.01. Using isospin relations, we find an upper bound on the angle difference |alpha-alpha(eff)| of 35 degrees at the 90% C.L.

Journal Article↗

PubMed2005

Search for factorization-suppressed B-->chi(c)K(*) decays.

We search for the factorization-suppressed decays B-->chi(c0)K(*) and B-->chi(c2)K(*), with chi(c0) and chi(c2) decaying into J/psi gamma, using a sample of 124 x 10(6) BB events collected with the BABAR detector at the PEP-II storage ring of the Stanford Linear Accelerator Center. We find no significant signal and set upper bounds for the branching fractions.

Journal Article↗

PubMed2005

Measurement of branching fractions and charge asymmetries for exclusive B decays to charmonium.

We report measurements of branching fractions and charge asymmetries of exclusive decays of neutral and charged B mesons into two-body final states containing a charmonium state and a light strange meson. The charmonium mesons considered are J/psi, psi(2S) and chi(c1), and the light meson is either K or K(*). We use a sample of about 124x10(6) BB pairs collected with the BABAR detector at the PEP-II storage ring at the Stanford Linear Accelerator Center.

Journal Article↗

PubMed2005

Limit on the B0-->rho0rho0 branching fraction and implications for the Cabibbo-Kobayashi-Maskawa angle alpha.

We search for the decay B0-->rho(0)rho(0) in a data sample of about 227x10(6) Upsilon(4S)-->BB decays collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) collider at SLAC. We find no significant signal and set an upper limit of 1.1x10(-6) at 90% C.L. on the branching fraction. As a result, the uncertainty due to penguin contributions on the Cabibbo-Kobayashi-Maskawa unitarity angle alpha measured in B-->rhorho decays is decreased to 11 degrees at 68% C.L.

Journal Article↗

PubMed2005

[Diagnostic imaging in liver transplantation. Preoperative evaluation and postoperative complications].

Complimentary to orthotopic liver transplantation (OLT), living donor liver transplantation (LDLT) is increasingly considered a therapeutic option in the therapy of end-stage liver disease. Accurate pre- and postoperative imaging is crucial for the transplantation success and represents an established part of the current evaluation algorithms. This article summarizes the most important requirements and the current imaging standards. Preoperative imaging is important for exclusion of transplantation contraindications in the recipient and for reliable assessment of anatomical variants in the donor. The main purpose of postoperative imaging is the early detection and characterization of complications. In both instances, multislice CT currently represents the most versatile and reliable imaging modality, still superior to MRI. For postoperative follow-up, the imaging modality of first choice is still bedside ultrasound; however, unclear findings usually need to be further assessed by CT.

Angiography, Digital Subtraction↗

PubMed2004

Splanchnic oxygen transport, hepatic function and gastrointestinal barrier after normothermic cardiopulmonary bypass.

BACKGROUND: The effect of non-pulsatile, normothermic cardiopulmonary-bypass (CPB) on the splanchnic blood-flow and oxygen-transport, the hepatic function and the gastrointestinal barrier were observed in a prospective observational study in 31 adults undergoing cardiac valve replacement surgery. METHODS: The splanchnic (i.e. hepatic) blood-flow (HBF) was measured by the constant infusion of indocyanine-green (ICG) using a hepatic-venous catheter. Liver function was examined by calculation of lactate uptake, ICG extraction and the monoethylglycinexylidide (MEGX) test. A day before and after surgery the gastrioduodenal and intestinal permeability was measured by determination of sucrose and lactulose/mannitol excretion. RESULTS: Splanchnic blood flow and oxygen delivery did not decrease during and after surgery while splanchnic oxygen consumption (P < 0.0125) and arterial lactate concentrations increased. The splanchnic lactate uptake paralleled the lactate concentration. After but not during CPB an increase of systemic oxygen consumption was observed. The MEGX test values decreased on the first day after surgery. The ICG extraction was attenuated during the operation. The gastroduodenal and the intestinal permeability increased significantly postoperatively (P < 0.002, respectively, P < 0.001). There was no correlation between these findings and the duration of CPB. There was a significant correlation of the intestinal permeability but not of the gastroduodenal permeability between the prior and after surgery values (P < 0.001). CONCLUSION: Increased oxygen consumption during CPB may indicate an inflammatory reaction due to the pump beginning in the splanchnic area or a redistribution of the splanchinc blood flow during the CPB. Normothermic CPB does not lead to a significant or prolonged reduction of liver function. Normothermic CPB causes an increase of gastrointestinal permeability. The intestinal barrier function prior to surgery was accountable for the degree of loss of intestinal barrier function following surgery.

Adult↗

PubMed2004

Lactate in solid malignant tumors: potential basis of a metabolic classification in clinical oncology.

A number of studies have demonstrated that malignant transformation is associated with an increase in glycolytic flux and in anaerobic and aerobic cellular lactate excretion. Using quantitative bioluminescence imaging in various primary carcinomas in patients (uterine cervix, head and neck, colorectal region) at first diagnosis of the disease, we showed that lactate concentrations in tumors in vivo could be relatively low or extremely high (up to 40 micromol/g) in different individual tumors or within the same lesion. In all tumor entities investigated, high molar concentrations of lactate were correlated with a high incidence of distant metastasis already in an early stage of the disease. Low lactate tumors (< median of approx. 8 micromol/g) were associated with both a longer overall and disease free survival compared to high lactate lesions (lactate > approx. 8 micromol/g). Lactate dehydrogenase was found to be upregulated in most of these tumors compared to surrounding normal tissue. Numerous recent reports support these data by demonstrating various biological activities of lactate that can enhance the malignant behavior of cancer cells. These mechanisms include the activation of hyaluronan synthesis by tumor-associated fibroblasts, upregulation of VEGF and of HIF-1 alpha, and direct enhancement of cellular motility which generates favorable conditions for metastatic spread. Thus, lactate accumulation not only mirrors but also actively enhances the degree of tumor malignancy. We propose that determination of lactate in primary tumors may serve as a basis for a novel metabolic classification which can lead to an improvement of prognosis and therapy in clinical oncology.

Animals↗

PubMed2003

[Rhabdomyolysis, hyponatremia and fever in a patient with Schmidt's syndrome].

HISTORY: A 38-year-old man had fever (40 degrees C) and a swollen right leg. Two weeks before admission he had received non-steroid anti-inflammatory drugs (paracetamol and ibuprofen) after a tooth extraction. Some weeks before he had noticed a rough voice and a dry skin. INVESTIGATIONS: The patient had a sinus tachycardia of 145/min (blood pressure of 130/80 mm Hg). Laboratory data revealed a CK of 16,650 U/l (< 80 U/l), myoglobin of 2420 U/l (< 90 microg/l) and LDH of 1250 U/l (<240 U/l), leukocyte count of 12,000 / microl and C-reactive protein of 3.0 mg/dl (<0.5 mg/dl). Sodium was markedly decreased (110 mmol/l (135 - 145 mmol/l)). Determination of thyroid hormone showed primary hypothyroidism with an elevated TSH of 62.6 mU/l (0.3 - 4.0 mU/l); T4 of 38 nmol/l (58 - 154 nmol/l), T3 1.17 of nmol/l (1.23 - 3.08 nmol/l) and fT4 of 6 pmol/l (10 - 25 pmol/l). The thyroid autoantibodies were increased (thyroxine peroxidase antibodies of 684 U/l (<35 U/l) and thyroglobulin antibodies of 173 U/l (<40 U/l)). Ultrasound of the thyroid revealed an nonhomogeneous structure. Cortisol at 8.00 a. m. was reduced by 63 mmol/l (180 - 640 mmol/l) and did not increase after administration of ACTH (60 min. cortisol at 90 mmol/l (>550 mmol/l)). ACTH was increased (141 pg/ml; normal range 17 - 52 pg/ml). TREATMENT AND COURSE: The initial therapy consisted of hydrocortisone (100 mg i.v as bolus and 100 mg during the next 24 hours) and levothyroxine replacement (200 micro g) was initiated. During the following 8 days clinical symptoms regressed. Values of sodium, myoglobin and LDH decreased. After therapy with cephalosporin (Ceftriaxon) and penicillin (Flucloxacillin) fever and inflammation parameters decreased. CONCLUSION: This is a rare case of a rhabdomyolysis and hyponatriaemia due to hypothyroidism and Addison's disease (Schmidt's syndrome).

Addison Disease↗

PubMed2002

Expression pattern of the urokinase-plasminogen activator system in rat DS-sarcoma: role of oxygenation status and tumour size.

The urokinase plasminogen activator system plays a central role in malignant tumour progression. Both tumour hypoxia and enhancement of urokinase plasminogen activator, urokinase plasminogen activator-receptor and plasminogen activator inhibitor type 1 have been identified as adverse prognostic factors. Upregulation of urokinase plasminogen activator or plasminogen activator inhibitor type 1 could present means by which hypoxia influences malignant progression. Therefore, the impact of hypoxia on the expression pattern of the urokinase plasminogen activator system in rat DS-sarcoma in vivo and in vitro was examined. In the in vivo setting, tumour cells were implanted subcutaneously into rats, which were housed under either hypoxia, atmospheric air or hyperoxia. For in vitro studies, DS-sarcoma cells were incubated for 24 h under hypoxia. Urokinase plasminogen activator and urokinase plasminogen activator-receptor expression were analysed by flow cytometry. Urokinase plasminogen activator activity was measured using zymography. Plasminogen activator inhibitor type 1 protein levels in vitro and in vivo were examined with ELISA. PAI-1 mRNA levels were determined by RT-PCR. DS-sarcoma cells express urokinase plasminogen activator, urokinase plasminogen activator-receptor, and plasminogen activator inhibitor type 1 in vitro and in vivo. The urokinase plasminogen activator activity is enhanced in DS-sarcomas compared to normal tissues and rises with increasing tumour volume. The oxygenation level has no impact on the urokinase plasminogen activator activity in cultured DS-sarcoma cells or in solid tumours, although in vitro an increase in plasminogen activator inhibitor type 1 protein and mRNA expression after hypoxic challenge is detectable. The latter plasminogen activator inhibitor type 1 changes were not detectable in vivo. Hypoxia has been demonstrated to contribute to the upregulation of some components of the system in vitro, although this effect was not reproducible in vivo. This may indicate that the serum level of plasminogen activator inhibitor type 1 is not a reliable surrogate marker of tumour hypoxia.

Animals↗

PubMed2002

[The value of computed tomography in the early treatment of seriously injured patients].

BACKGROUND: The availability of newer, faster computed tomography (CT) technology has engendered discussion about whole-body CT-scanning for primary radiological diagnostics of seriously injured patients. METHOD: Within a quality management system, the scaled, priority-oriented scheme of conventional radiological and CT-diagnostics used in each institution was analysed and compared with the possible benefit of whole-body CT-scanning. Every patient with severe trauma admitted directly from the scene of an accident, underwent basic radiological and sonographic diagnostics in the emergency room (ER). According to the findings, patients in a stable vital condition had CT-scans when indicated by the guidelines of the particular institution. RESULTS: From 5/1998 until 12/2000, a total of 832 patients were treated in the ER. Of those, 480 patients (average ISS 20) were admitted directly from the scene of the accident. Basic radiological - sonographic diagnostics (radiographs of cervical spine, chest, and abdomen, as well as abdominal sonography) took 15+/-8 min. Twenty-two (5%) of the patients in hemorrhagic shock needed emergency operations after 57+/-43 min. The remaining patients underwent further radiological diagnostics (spine, extremities etc.) after 44+/-27 min. In 79% (379) of patients, CT was indicated. Cranial CT for traumatic brain injury prevailed clearly with 74% of cases. Spine (24%), chest (18%), abdomen (5%) and pelvis (5%) were indicated comparatively less frequently. The incidence of delayed diagnoses (after ICU-admission) was 4% (22). In 2% (nine) of patients the lesions possibly could have been detected by a primary CT-scan. In the three cases with thoracic lesions, there was a deviation from the indication guidelines for thoracic CT as normally used in the institution. There were three cases of delayed diagnoses in both the cerebral (small contusion haematomas) region and the abdominal region. The abdominal lesions were detected by sonographic control examinations. No patient died because of a delayed diagnosis. The average X-ray dose was five times lower with the scaled diagnostic management comprising indicated CT when compared to the doses calculated for routine whole-body CT. CONCLUSION: While 74% of patients had cranial CT, only 25% needed CT for the trunk regions. Delayed diagnoses were rare and without severe consequences for the patient. Considering the five times higher X-ray doses combined with the possible time loss in patients with unstable conditions, primary whole-body CT-scanning should not be performed routinely when serious injury is suspected.

Adult↗

PubMed2001

Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer.

PURPOSE: Hypoxia shifts the balance of cellular energy production toward glycolysis with lactate generation as a by-product. Quantitative bioluminescence imaging allows for the quantitation of lactate concentrations in individual tumors. We assessed the relationship between pretreatment tumor lactate concentrations and subsequent development of metastatic disease in patients with newly diagnosed head-and-neck cancer. METHODS AND MATERIALS: At the time of biopsy of the primary site, a separate specimen was taken and flash-frozen for subsequent quantitation of lactate concentration using a luciferase bioluminescence technique. The two-dimensional spatial distribution of the bioluminescence intensity within the tissue section was registered directly using a microscope and an imaging photon counting system. Photon intensity was converted to distributions of volume-related tissue concentrations (micromol per gram wet weight). Treatment consisted of either surgery and postoperative radiotherapy or primary radiotherapy, based on presenting disease stage and institutional treatment policies. The subsequent development of metastatic disease constituted the primary clinical endpoint. RESULTS: Biopsies obtained from 40 patients were evaluable in 34. The larynx was the most frequent primary site (n = 25). Other sites included oropharynx (n = 5), hypopharynx (n = 3), and oral cavity (n = 1). Most patients (74%) presented with an advanced stage T3 or T4 primary tumor. Nodal involvement was present in 19 (54%) patients. The median tumor lactate concentration was 7.1 micromol/g. Tumors were classified as having either low or high lactate concentrations according to whether these values were below or above the median. The median follow-up time for surviving patients is 27 months. Two-year actuarial survival was 90% for patients with low-lactate-concentration tumor vs. 35% for patients with high-lactate-concentration primaries (<0.0001). Two-year metastasis-free survival was adversely influenced by high tumor lactate concentrations (90% vs. 25%, p < 0.0001). The median lactate concentration for tumors that subsequently metastasized was 12.9 micromol/g vs. 4.8 micromol/g for patients who remained continuously free of disease (p < 0.005). Lactate concentration was not correlated with presenting T stage or N stage. DISCUSSION: Elevated tumor lactate concentrations are associated with the subsequent development of nodal or distant metastases in head-and-neck cancer patients. This more aggressive malignant phenotype is probably associated with hypoxia-mediated radioresistance and the upregulation of metastasis-associated genes.

Biomarkers, Tumor↗

PubMed2001

DNA damage-activated kinase Chk2 is independent of proliferation or differentiation yet correlates with tissue biology.

The Chk2 kinase is a tumor suppressor and key transducer of DNA-damage checkpoints. We show that the human Chk2 protein is relatively stable, nuclear, and responding to gamma-radiation throughout the cell cycle. Contrary to the retinoblastoma protein-regulated, labile Chk1 kinase restricted to S-G(2) phases, Chk2 remains activatable even in quiescent and differentiating cells. In human tissues, Chk2 is homogeneously expressed in renewing cell populations such as epidermis or intestine, heterogeneous in conditionally renewing tissues, and absent or cytoplasmic in static tissues such as muscle or brain. These data highlight striking differences between Chk2 and Chk1 and show unexpected correlation of Chk2 expression with tissue biology.

Antibodies, Monoclonal↗

PubMed2001

Interstitial MR lymphography with gadoterate meglumine: initial experience in humans.

Magnetic resonance (MR) lymphography was performed in five healthy volunteers and three patients (two adults and one infant). Subcutaneous administration of gadoterate meglumine in the foot allowed visualization of draining lymph vessels and nodes. In one patient, an inguinal fluid collection could be characterized as a lymphocele. In the infant, a chylothorax was diagnosed. The authors conclude that interstitial MR lymphography with commercially available compounds is feasible.

Adult↗

PubMed2000

Notch signalling via RBP-J promotes myeloid differentiation.

The expression of Notch receptors on hematopoietic cells and of cognate ligands on bone marrow stromal cells suggests a possible role for Notch signalling in the regulation of hematopoiesis. In order to assess the involvement of Notch1 signalling in myelopoiesis, 32D myeloid progenitor cell lines were engineered to permit the conditional induction of the constitutively active intracellular domain of murine Notch1 (mN1(IC)) by the 4-hydroxytamoxifen-inducible system. The induction of mN1(IC) resulted in accelerated and increased granulocytic differentiation. These effects were observed under growth conditions that support differentiation and, to a lesser degree, under conditions that normally promote self-renewal. Transient transfection of mN1(IC) deletion mutants showed that the differentiation promoting activity correlated with RBP-J transactivation. Furthermore, expression of a transcriptionally active derivative of RBP-J (RBP-J-VP16) increased myeloid differentiation. To test further the role of Notch signalling in a physiological context, 32D cells expressing mNotch1 were cultured on fibroblast layers that either expressed or did not express the Notch ligand Jagged1. Similar to the induction of mN1(IC), Jagged1 accelerated granulocytic differentiation of 32D cells. Taken together, our data suggest that activation of mNotch1 promotes myeloid differentiation via RBP-J transactivation.

Animals↗

PubMed2000

mNotch1 signaling reduces proliferation of myeloid progenitor cells by altering cell-cycle kinetics.

Notch receptors are involved in the regulation of cell-fate decisions, differentiation, and proliferation in many tissues. The expression of Notch receptors on hemopoietic cells and of cognate ligands on bone marrow stromal cells suggests a possible role for Notch signaling in the regulation of hemopoiesis. We were interested to assess the involvement of Notch1 signaling on cell proliferation of myeloid progenitor cells. Proliferation, cell-cycle status, and apoptosis of myeloid progenitor 32D cell lines engineered to permit the conditional induction of the constitutively active intracellular domain of mNotch1 (mN1(IC)) by the 4-hydroxytamoxifen(OHT)-inducible system were analyzed in the presence or absence of OHT. The induction of mN1(IC) by OHT resulted in reduction of proliferation (p<0.01) and accumulation of cells in the G(1)/G(0) phase of the cell cycle (p<0.001) without substantially affecting apoptosis of 32D cells. These effects were observed under culture conditions that allow differentiation and, to a lesser degree, under conditions that normally promote self-renewal in the absence of differentiated cells. Our data suggest that mNotch1 signaling suppresses proliferation of myeloid progenitor cells by altering cell-cycle kinetics.

Cell Cycle↗