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S Ziegler

Publications and source records attributed to S Ziegler.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Metabolic characterization of ovarian tumors with positron-emission tomography and F-18 fluorodeoxyglucose].

PURPOSE: This study describes diagnostic accuracy of PET imaging in patients with ovarian tumours using histological diagnosis as gold standard. METHODS AND RESULTS: Pet studies were performed in 19 patients who were scheduled to undergo exploratory surgery for a suspicious ovarian mass and in 5 patients with suspected recurrence. The PET data were analyzed visually and quantitatively and compared to the histologic findings. 6 patients had ovarian cancer, while in 13 patients a benign tumour was found including inflammatory processes in 4 cases. All malignant tumours showed an enhanced FDG uptake with the exception of one false-negative borderline carcinoma. 4 cases with inflammatory processes as well as endometrial and follicular cysts revealed a high FDG uptake. A successful localisation of a recurrent tumour was possible in 4 out of 5 cases. Disseminated peritoneal carcinomatosis in two patients could not be detected by PET. CONCLUSIONS: Enhanced glucose metabolism of ovarian cancer enables PET diagnosis with a sensitivity of 83%. An intensive FDG uptake in inflammatory processes resulted in a specificity of only 54% in this study. The high sensitivity of PET for malignant tumours may be useful in the detection of recurrent ovarian cancer.

Adult↗
PubMed1997

The repertoire of T cell antigen receptor beta-chain variable regions associated with psoriasis vulgaris.

We investigated whether the pattern of T-cell receptors expressed by T cells in inflamed psoriatic skin differed substantially from the pattern seen in T cells from the peripheral blood. A bias or restriction in the repertoire of T-cell receptors found in the lesional skin of different patients might imply that specific subsets of T cells were causally associated with initiating or maintaining the lesions. By using a polymerase chain reaction-based assay of T-cell receptor beta-chain variable region mRNA, we found that the patterns of beta-chain mRNAs displayed in 14 samples of lesional skin or six samples of noninvolved skin were not significantly less diverse than the patterns found in matched peripheral blood samples. There was no evidence that the active lesions of multiple patients showed overexpression of T cells expressing one or a few T-cell receptor forms. The pattern of T-cell receptors displayed in clinically normal skin from normal control individuals showed about the same diversity as normal blood. While these results may not exclude either classical antigen or superantigen-based T-cell activation mechanisms in active plaques, the absence of a simple pattern of Vbeta usage in different patients suggests than other aspects of T-cell biology including trafficking, proliferation, co-stimulation, or responses to cytokines must also be considered.

DNA Primers↗
PubMed1997

Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical intervention: update of previous meta-analyses.

BACKGROUND: Previous meta-analyses comparing low molecular weight heparin (LMWH) and unfractionated heparin for thrombosis prophylaxis after surgical interventions need updating. METHODS: This is a publication-based meta-analysis of 36 double-blind studies including 16583 patients. Main outcome measures are incidence of deep vein thrombosis (efficacy) and wound haematoma (safety). RESULTS: In general surgery there is no increased efficacy in favour of LMWH (odds ratio (OR) 0.88, 95 per cent confidence interval (c.i.) 0.60-1.30) but there exists a higher incidence of bleeding complications (OR 1.47, 95 per cent c.i. 1.07-2.01). Low-dose LMWH is equally efficacious (OR 1.03, 95 per cent c.i. 0.85-1.26) but safer than unfractionated heparin (OR 0.68, 95 per cent c.i. 0.56-0.82). In orthopaedic surgery there is a trend towards an increased efficacy for LMWH (OR 0.83, 95 per cent c.i. 0.68-1.02) with equivalent safety (OR 0.96, 95 per cent c.i. 0.68-1.36). CONCLUSION: A superiority of LMWH is suggested but heterogeneity might make generalizability to future patients questionable. A meta-analysis on individual patient data should be the next step before randomizing additional patients in future trials.

Double-Blind Method↗
PubMed1997

Assessment of local brain activation. A simultaneous PET and near-infrared spectroscopy study.

In five healthy human subjects, near-infrared spectroscopy (NIRS) and positron emission tomography (PET) examinations were performed simultaneously. Changes in [oxy-Hb], [deoxy-Hb] and [total-Hb] as measured by NIRS over the left forehead were compared to measurements of cerebral blood flow by PET during rest and during performance of a calculation task and a Stroop task. When a penetration depth of near-infrared light 0.9 cm into the brain cortex was assumed, a statistically significant correlation between changes in CBF and changes in [total-Hb] was found. These data confirm the validity of NIRS measurements in human adults.

Aged↗
PubMed1996

Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose.

BACKGROUND: The presence of metastatic tumor cells in the axillary lymph nodes is an important factor when deciding whether or not to treat breast cancer patients with adjuvant therapy. Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases. PURPOSE: This study was undertaken to evaluate before surgery the diagnostic accuracy of PET for detection of axillary lymph node metastases in patients suspected of having breast cancer. METHODS: Women who were scheduled to undergo surgery for newly discovered, suspected breast cancers were referred for PET imaging of the axilla region. The women were first clinically examined to determine the status of their axillary lymph nodes (i.e., presence or absence of metastases). Fifty-one women were intravenously administered F-18 FDG and were studied by PET imaging. Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region. All patients underwent surgery for their suspected breast cancers. Axillary lymph node dissection was also performed on all patients with breast cancer, with the exception of four patients who received primary chemotherapy for locally advanced breast cancer. A single pathologist analyzed breast tumor and lymph node tissue specimens. RESULTS: The overall sensitivity (i.e., the ability of the test to detect disease in patients who actually have disease) and specificity (i.e., the ability of the test to rule out disease in patients who do not have disease) of this method for detection of axillary lymph node metastases in these patients were 79% and 96%, respectively. When only patients with primary breast tumors larger than 2 cm in diameter (more advanced than stage pT1; n = 23) were considered, the sensitivity of axillary PET imaging increased to 94%, and the corresponding specificity was 100%. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33%. Axillary PET imaging provided additional diagnostic information in 12 (29%) of 41 breast cancer patients with regard to the extension of disease to other sites (i.e., other lymph nodes, skin, bone, and lung). CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1. Detection of micrometastases and small tumor-infiltrated lymph nodes is limited by the currently achievable spatial resolution of PET imaging. IMPLICATIONS: In clinical practice, PET imaging cannot substitute for histopathologic analysis in detecting axillary lymph node metastases in breast cancer patients. PET imaging, however, improves the preoperative staging of the disease in breast cancer patients and, therefore, might alter therapeutic regimen options.

Adult↗
PubMed1996

Defective STAT signaling by the leptin receptor in diabetic mice.

Leptin and its receptor, obese receptor (OB-R), comprise an important signaling system for the regulation of body weight. Splice variants of OB-R mRNA encode proteins that differ in the length of their cytoplasmic domains. We cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6. A point mutation within the OB-R gene of diabetic (db) mice generates a new splice donor site that dramatically reduces expression of this long isoform in homozygous db/db mice. In contrast, an OB-R protein with a shorter cytoplasmic domain is present in both db/db and wild-type mice. We show that this short isoform is unable to activate the STAT pathway. These data provide further evidence that the mutation in OB-R causes the db/db phenotype and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin.

Alternative Splicing↗
PubMed1996

Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene.

Primary mediastinal (thymic) B-cell lymphoma is a high-grade non-Hodgkin's lymphoma with unique features. By using comparative genomic hybridization and interphase cytogenetics, 26 tumors were analyzed to identify genomic imbalances. Gains of chromosomal material were much more frequent than losses (110 v 10) and involved chromosomes 9p, 12q, and Xq (31% to 50%). Interestingly, gain of Xq coincided with gain of 9p. Distinct high-level amplifications were found in four subregions. In 2 cases, amplifications of proto-oncogene REL were shown by filter hybridization, indicating a possible pathogenic role of this gene. The characteristic pattern of chromosomal imbalances distinct from other B-cell lymphomas suggests a specific pathway of genetic changes associated with this lymphoma.

Aneuploidy↗
PubMed1996

Quantitative evaluation of manganese-52m as a myocardial perfusion tracer in pigs using positron emission tomography.

There is a need for a quantitative myocardial perfusion agent that does not require an on-site cyclotron. Early studies with manganese demonstrated that this trace metal is of potential use for myocardial imaging. 52mMn can be produced in a 52Fe-52mMn generator and is suitable for positron emission tomographic (PET) imaging. The purpose of this study was to evaluate 52mMn with regard to its potential to quantitatively assess myocardial perfusion. Dynamic PET imaging was performed in six pigs with various doses of dipyridamole to increase blood flow. Retention (R) and model-based K1 values were correlated with microsphere blood flow. The models consisted of one (K1, k2) and two (K1, k2, k3) tissue compartments. Anterior, lateral and septal regions showed a good myocardium-to-background ratio; the evaluation of the inferior wall was impaired by high liver uptake. Linear regression yielded the following equations: K1=1.152 flow+0.059 (r=0.92), R=0.069 flow+0.034 (r=0.84). Based on these regressions, K1 increased 2.7-fold and R 2.6-fold in the examined flow range of 0.5-2 ml/min/g (fourfold increase), demonstrating an underestimation of higher flow rates by both measures. It is concluded that 52mMn allows the qualitative assessment of myocardial perfusion but does not meet the requirements of a quantitative myocardial perfusion agent.

Animals↗
PubMed1996

Clinical relevance of heart rate variability changes after heart transplantation.

Heart rate variability (HRV) of the healthy innervated heart is controlled and regulated by the autonomous nervous system and is influenced by respiratory frequency. Physiologically, there are slow and fast variations of heart rate which are of sympathetic or parasympathetic origin respectively. Spectral analysis of heart rate variability permits a selective quantification of these periodic influences of autonomous neural control. In the absence of neural influence on the pacemaker of the donor heart, we do not expect a high periodic heart rate variability (HRV). Due to the almost rigid heart rhythm we only anticipate a slight deviation of the R-R intervals from their mean value. Interventions such as valsalva maneuvers, controlled respiration and tilt table result in a very small but significant change of heart rate variability. These changes are most likely due to local influences at the donor sinus node. Neural influences from reinnervation may also play an important role in patients long after transplantation.

Acute Disease↗
PubMed1996

Deactivation of human visual cortex during involuntary ocular oscillations. A PET activation study.

Prompted by the observation of decreased glucose metabolism in the striate and extrastriate visual cortex in a patient with opsoclonus, we studied the influence of involuntary eye movements on visual cortex activity. Repeated measurements of cerebral blood flow (CBF) by PET were performed in 12 healthy volunteers using H2(15)O-bolus technique after ear canal irrigation with ice cold or warm (44 degrees C) water with the subjects eyes closed. In addition to blood flow increases in areas involved in central vestibular processing, statistical subtraction analysis revealed a nearly symmetrical, bilateral, highly significant decrease in the occipital cortex covering Brodmann areas 17, 18, and 19 after ice water stimulation of either ears. Region of interest analysis revealed in all subjects a mean decrease in regional CBF (rCBF) of 12.8% (range 4.6-21.0%) in these areas. A similar but less pronounced effect (mean rCBF decrease in visual cortex 4.8%, range 1.1-11.5%) was observed after warm water irrigation. The observations suggest that deactivation of the visual cortex is induced by involuntary ocular oscillations. This deactivation is not dependent on changes of the retinal input (eyes closed). The physiological significance of this hitherto unknown phenomenon may be the protection from inadequate visual input (oscillopsia) during involuntary ocular oscillations.

Adult↗
PubMed1996

Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema.

Bronchoalveolar lavage fluids (BALF) were analyzed for surfactant abnormalities in 153 patients with acute respiratory failure necessitating mechanical ventilation. Diagnoses were acute respiratory distress syndrome (ARDS) in the absence of lung infection (n = 16), severe pneumonia (PNEU; n = 88), ARDS and PNEU (n = 36), and cardiogenic lung edema (CLE; n = 13). The PNEU group was subdivided into groups with alveolar PNEU (n = 35), bronchial PNEU (n = 16), interstitial PNEU (n = 18) and nonclassified PNEU (n = 19). Comparison with healthy controls (n = 20) was undertaken. Total phospholipids (PL), proteins, PL classes (HPTLC) and surfactant apoproteins SP-A and SP-B (ELISA) were quantified in the original BALF. The 48,000 x g pellet from centrifugation of the BAL was used to assess the percentage of large surfactant aggregates (LSA) and the biophysical properties of the surfactant (pulsating bubble surfactometer). All groups with inflammatory lung injury (PNEU and/or ARDS) showed some decrease in the lavageable PL pool, a reduced LSA content in BALF, and a manifold increase in alveolar protein load. Marked changes in the PL profile were noted throughout the groups (a decrease in phosphatidylcholine (PC) and phosphatidylglycerol (PG) and an increase in phosphatidylinositol [PI] and sphingomyelin [SPH]). Concentrations of SP-A but not of SP-B in BALF were reduced. Minimum surface-tension values approached 0 mN/m in controls, and ranged from 10 to 25 mN/m in the absence of supernatant protein and from 20 to 35 mN/m in recombination with leaked protein in the groups with ARDS and/or PNEU. Abnormalities in alveolar PNEU surpassed those in bronchial PNEU, and interstitial PNEU presented a distinct pattern with extensive metabolic changes. All surfactant changes were absent in CLE except for a slight inhibition of surface activity by proteins. We conclude that pronounced surfactant abnormalities, comparable to those in ARDS in the absence of lung infection, occur in different entities of severe PNEU, but not in CLE.

Acute Disease↗
PubMed1996

Bronchoalveolar and systemic cytokine profiles in patients with ARDS, severe pneumonia and cardiogenic pulmonary oedema.

The aim of this study was to investigate whether bronchoalveolar lavage (BAL) and serum levels of proinflammatory cytokines discriminate between different entities of patients with acute respiratory failure. BAL and circulating concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were measured in 74 mechanically-ventilated patients and 17 healthy controls. Patients were classified as cardiogenic pulmonary oedema (CPO), acute respiratory distress syndrome (ARDS), primary severe pneumonia (PN) and a combined group (PN+ARDS). In all patients with ARDS and/or PN, markedly elevated BAL levels of IL-6 and IL-8 were detected, which were significantly greater than levels in CPO and healthy controls. Absolute quantities and time-course of these cytokines did not differentiate between the absence and presence of lung infection, or different categories of PN. Similarly, circulating IL-6 levels were comparably elevated in patients with ARDS and/or PN, whereas circulating IL-8 concentrations were inconsistently increased. TNF-alpha was rarely detected in BAL samples, but increased serum concentrations were measured in ARDS and/or PN patients. Bronchoalveolar lavage levels of interleukin-6 and interleukin-8, but not tumour necrosis factor-alpha, and serum concentrations of interleukin-6 are consistently elevated in acute respiratory distress syndrome and/or severe pneumonia, discriminating these entities from cardiogenic pulmonary oedema. Alveolar and systemic cytokine profiles do not differentiate between acute respiratory distress syndrome in the absence of lung infection and states of severe primary or secondary pneumonia, which evidently present with comparable local and systemic inflammatory sequelae.

Acute Disease↗
PubMed1996

Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose.

PURPOSE: To evaluate the diagnostic value of position emission tomographic (PET) imaging with F-18 fluorodeoxyglucose (FDG) in differentiating between benign and malignant breast tumors. PATIENTS AND METHODS: Fifty-one patients, with suspicious breast lesions newly discovered either by physical examination or by mammography, underwent PET imaging before exploratory surgery. FDG-PET images of the breast were analyzed visually and quantitatively for objective assessment of regional tracer uptake. RESULTS: Primary breast cancer was identified visually with a sensitivity of 68% to 94% and a specificity of 84% to 97% depending on criteria used for image interpretation. Quantitative analysis of FDG uptake in tumors using standardized uptake values (SUV) showed a significant difference between benign (1.4 +/- 0.5) and malignant (3.3 +/- 1.8) breast tumors (P < .01). Receiver operating characteristic (ROC) curve analysis exhibited a sensitivity of 75% and a specificity of 100% at a threshold SUV value of 2.5. Sensitivity increased to 92% with a corresponding specificity of 97% when partial volume correction of FDG uptake was performed based on independent anatomic information. CONCLUSION: PET imaging allowed accurate differentiation between benign and malignant breast tumors providing a high specificity. Sensitivity for detection of small breast cancer ( < 1 cm) was limited due to partial volume effects. Quantitative image analysis combined with partial volume correction may be necessary to exploit fully the diagnostic accuracy. PET imaging may be helpful as a complimentary method in a subgroup of patients with indeterminate results of conventional breast imaging.

Breast Neoplasms↗
PubMed1996

Quantitative assessment of myocardial perfusion: is it of clinical relevance?

Positron emission tomography provides unique qualitative and quantitative information on myocardial perfusion, metabolism and membrane function which potentially has an important impact on diagnostic workup and treatment in patients with known or suspected coronary artery disease (CAD). CAD contributes up to one third of all deaths among persons between the ages of 35 to 60 in western countries. Risk factors and symptoms turned out to have low specificity to identify persons with the disease and thus, will not help to establish objective diagnostic workup. Assessing severity of CAD by coronary angiography and means of binary classification (disease yes/no) of morphological abnormalities, i.e. stenosis > 50%, has shown to poorly correlate with coronary blood flow and, thus, might not serve as an optimal reference standard for the disease. Cardiac PET using N-13 ammonia and Rb-82 represents a well validated and clinically usable technique for both quantitative and qualitative (semiquantitative) assessment of myocardial blood flow. However, the clinical benefit of absolute flow values for diagnosis and localisation of CAD remains controversial. Most centers rely on qualitative image interpretation due to the technical requirements for image processing needed for determination of absolute flow values. However, quantitative assessment of myocardial blood flow might offer advantages when measurement of coronary flow reserve in response to medical or interventional therapy is necessary and in addition may provide early detection of CAD in asymptomatic patients who have risk factors.

Coronary Circulation↗
PubMed1995

Comparison of fluorine-18-fluorodeoxyglucose PET, MRI and endoscopy for staging head and neck squamous-cell carcinomas.

UNLABELLED: Accurate, preoperative assessment of tumor extent and lymph node involvement is mandatory for individualized therapy in patients with squamous-cell carcinomas (SCCs) of the head and neck region. Metabolic imaging, [18F]fluorodeoxyglucose (FDG) PET and MRI were compared with postoperative, histologic tissue characterization. METHODS: Dynamic and static PET with 370 MBq [18F]FDG up to 60 min postinjection and MRI were compared prospectively in 22 patients with head and neck SCCs. PET results with and without attenuation correction were compared with postoperative T and N stages based on pathologic findings. RESULTS: Kinetic characteristics and tracer uptake intensity were similar in primary tumors and lymph node metastases. In both, FDG uptake did not reach a plateau phase 60 min postinjection. There was no statistically significant correlation of FDG uptake with plasma glucose level or histologic grading. All primary tumors were clearly demonstrated by PET, which tended to overestimate tumor size. The sensitivity and specificity for detecting individual lymph node involvement were 90% and 96%, respectively, for PET and, thus, significantly higher for MRI (78% and 71%, respectively; p < 0.05). N stages were correctly identified by MRI in only 4 patients; PET correctly staged lymph nodes in 15 of 17 patients. Based on "neck sides", the sensitivity and specificity were higher for PET, 89% and 100%, respectively, compared with MRI values of 72% and 56%, respectively. CONCLUSION: FDG-PET may be helpful in detecting occult primary tumors with positive lymph nodes.

Adult↗
PubMed1995

Noninvasive assessment of hepatobiliary and renal elimination of cysteinyl leukotrienes by positron emission tomography.

N-Acetyl-leukotriene E4 has been identified as an endogenous, biologically less active cysteinyl leukotriene metabolite in rodents and humans. To evaluate the ratio of hepatobiliary to renal elimination of leukotrienes noninvasively by positron emission tomography (PET), we synthesized N-[11C]acetyl-leukotriene E4 by chemical N-acetylation of leukotriene E4. After the intravenous injection of N-[11C]acetyl-leukotriene E4 in normal rats and monkey, uptake by the liver and subsequent excretion into bile were largely responsible for its rapid elimination from blood. In the Cynomolgus monkey, renal excretion of the leukotriene into urine was of additional quantitative importance. Kinetic modeling indicated a mean transit time through the liver of 17 minutes and 34 minutes in rat and monkey, respectively; the corresponding hepatic excretion half-times amounted to 8.5 minutes and 16 minutes. In a mutant rat strain deficient in the hepatobiliary excretion of cysteinyl leukotrienes across the canalicular membrane, the apparent mean liver transit time was 54 minutes, and the hepatic excretion half-time was 29 minutes, indicating prolonged organ storage and metabolism. After transport from the liver back into the circulating blood of omega-oxidized and beta-oxidized metabolites of N-[11C]acetyl-leukotriene E4, renal excretion compensated for the impairment of hepatobiliary elimination in the transport mutant. Metabolite analyses in urine after intravenous injection of N-[3H]acetyl-leukotriene E4 indicated the extensive inactivation of N-acetyl-leukotriene E4 by beta-oxidation from the omega-end in the mutants. A similar shift from hepatobiliary to renal cysteinyl leukotriene elimination was monitored in rats with cholestasis due to bile duct obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Increased resistance against shortening in myocardium from recipient hearts of 7 patients transplanted for dilated cardiomyopathy.

UNLABELLED: The contractile behaviour of demembranized atrial and ventricular myocardium of 7 patients transplanted for end-stage heart failure (ESHF) was analyzed. Atrial muscle specimens of patients undergoing coronary artery bypass surgery (n = 9) and pig papillary muscle were used as reference preparations (n = 9). Extreme care was taken for dissection and mounting the muscle fibres (0.3 x 6 mm) in order to keep the passive series compliance small. Calcium sensitivity, cross-bridge cycling rate (estimated by the force-clamping technique and calculation of the shortening velocity at zero load [Vmax]) and isometric force development were measured. Analysis on light- and electronmicroscopic level was carried out. RESULTS: 1) Calcium sensitivity was not altered in ESHF patients; 2) the velocity of the force generating process (cross-bridge cycling rate) was normal in ventricular and reduced in atrial ESHF myocardium, 3) maximum isometric force development was reduced in ventricular, but not in atrial myocardium of ESHF patients, and 4) Vmax was significantly reduced in ventricular and atrial ESHF myocardium (p < 0.0001). Perimysial and endomysial fibrosis was present in ventricular, not in atrial myocardium of ESHF patients. CONCLUSION: A normal cross-bridge cycling rate in left-ventricular ESHF myocardium combined with a decreased capability of muscle shortening indicates the presence of a resistance against shortening localized either on the cross-bridge level or/and due to intra- and pericellular fibrosis. Left-ventricular contractile dysfunction in patients with end-stage heart failure may be related to a normal contractile apparatus contracting within an abnormal intracellular or interstitial environment.

Animals↗