Biomedical subjects

S Ziegler

Publications and source records attributed to S Ziegler.

At least 19 recordsLinked to original sources

PubMed2006

Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.

AIMS: The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. METHODS: Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of (153)Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. RESULTS: (153)Sm-labelled tablets reached the ascending colon after a mean +/- SD 9.8 +/- 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C(max) values from 1429 +/- 1014 to 1040 +/- 601 pg mL(-1) (P = 0.028) and AUC values from 14 814 +/- 11 254 to 13 486 +/- 9369 pg h(-1) mL(-1) (P = 0.008). Mean residence time and t(max) increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. CONCLUSIONS: MMX-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

Absorption↗

PubMed2004

The size of pancreatic pseudocyst does not influence the outcome of invasive treatments.

BACKGROUND: Authors generally agree that Giant Pancreatic Pseudocysts (> 10 cm) have a lower spontaneous resolution and are more difficult to treat than smaller pancreatic pseudocysts. This study was carried out on two groups of patients with larger and smaller pancreatic pseudocysts (pancreatic pseudocysts > 10 cm versus pancreatic pseudocysts < 10 cm), and aims to establish whether the size of pancreatic pseudocysts is a factor influencing treatment outcomes. PATIENTS AND METHODS: In a retrospective study, we examined 71 patients with pancreatic pseudocysts following an episode of acute pancreatitis, which were treated in our hospital from 1980 to 2000. Forty-one (57.5%) patients had a large pancreatic pseudocyst. Most patients underwent invasive treatments: 9 (12.6%) had percutaneous drainage, 37 (52.1%) open surgery and 13 (18.3%) endoscopic cyst gastrostomy. 12 patients (16.9%) of the 71 were cured with medical therapy alone. RESULTS: As far as the aetiology of the pancreatitis, location and number of the cysts were concerned, no major differences emerged between the two groups, although large pancreatic pseudocysts followed more severe pancreatitis (P = 0.0005). All giant pancreatic pseudocysts required invasive treatments; 40% of the pancreatic pseudocysts < 10 cm were successfully treated with medical therapy alone. No statistical differences were found regarding hospital mortality, morbidity, recurrence rate and hospital stay among the patients treated invasively. CONCLUSIONS: Giant pancreatic pseudocysts more often require invasive therapy due to persistent symptoms or complications. Treatment outcomes do not seem to be influenced by the size of the pancreatic pseudocysts.

Adult↗

PubMed2003

Influence of systemic inflammation on efficiency of antiplatelet therapy in PAOD patients.

Recently it was shown that inflammation adversely influences results obtained from the platelet function analyzer system, PFA-100, hypothesizing that inflammation could confound interpretation of platelet function results. We investigated the clinical relevance of these results in patients with peripheral arterial occlusive disease (PAOD), with and without signs of systemic inflammation. In 98 PAOD patients, all treated with acetyl-salicylic acid (ASA), we obtained PFA-100 values upon stimulation with epinephrine. C-reactive protein (CRP) values were investigated as indicator for systemic inflammation. Mean CRP levels were elevated in 23 patients (23%). There was no difference of mean PFA-100 results between patients with elevated CRP levels and those without. Our results indicate that the effect of ASA on platelet aggregation, as measured by the PFA-100, is not relevantly influenced in PAOD patients with elevated CRP.

Arterial Occlusive Diseases↗

PubMed2003

Long-term outcome of primary Raynaud's phenomenon and its conversion to connective tissue disease: a 12-year retrospective patient analysis.

OBJECTIVES: To determine the frequency of development of connective tissue disease (CTD) in patients considered to have idiopathic Raynaud's phenomenon (RP) > 10 years. PATIENTS AND METHODS: Based on initial evaluation, 113 women and 29 men were divided into either 'primary RP' (n=109) or 'possible secondary RP' (n=33) groups and were re-evaluated after a median follow-up period of 12.4 years. RESULTS: Overall 20 patients (14.1%) progressed to a definite CTD; 10 from 'primary RP' (9.2%) and 10 from possible secondary RP' (30.3%). Initial presence of antinuclear antibodies, thickening of fingers, higher age at onset of RP, and female sex seemed to be important determinants for a possible transition to a CTD. CONCLUSION: In RP-patients, who are at risk of development of a CTD, serial clinical and laboratory controls are warranted for the decision to initiate therapy early.

Adolescent↗

PubMed2003

Late improvement of regional wall motion after the subacute phase of myocardial infarction treated by acute PTCA in a 6-month follow-up.

BACKGROUND: The aim of this follow-up study was to investigate the late effects of acute coronary angioplasty (PTCA) on regional wall motion after the subacute phase of myocardial infarction (MI). METHODS AND RESULTS: Seventeen patients were investigated initially at a median of 11 days and again at 6 months after acute PTCA for myocardial infarction (< 8 hours after onset of symptoms) by cardiac magnetic resonance imaging. Corresponding short-axis slices encompassing the left ventricle (LV) were acquired using a standard cine MR for regional wall motion analysis and using delayed contrast enhanced magnetic resonance imaging (ceMRI) for infarct size quantification. The infarct size was similar in the subacute phase and the 6 month follow-up (20.8 and 21.9%, respectively; n.s.). Regional wall motion improved significantly in the area of hyperenhancement [percentage wall thickening (PWT) 21.9% and 37.9%, p < 0.05] in contrast to remote normal myocardium (46.4% and 38.4%; n.s.). Regional wall motion was significantly poorer in transmural compared with nontransmural MI in the subacute stage, and a late improvement could only be observed in transmural MI. CONCLUSION: Transmural areas of hyperenhancement displayed significant late long-term improvement of regional wall motion after acute PTCA, possibly related to prolonged stunning compared with nontransmural areas.

Adult↗

PubMed2002

[Evaluation of myocardial perfusion reserve in patients with CAD using contrast-enhanced MRI: a comparison between semiquantitative and quantitative methods].

OBJECTIVE: Comparison between two semiquantitative methods and a quantitative evaluation of myocardial blood flow (MBF) for assessment of myocardial perfusion reserve (MPR) in patients with CAD. MATERIAL AND METHODS: 9 patients with coronary stenoses > 50 % were examined with an ECG-gated Saturation Recovery Turbo FLASH sequence by using Gd-DTPA as contrast agent (CA). The entive measurements were performed both during rest and hyperemia induced by adenosine. The up-slopes of the signal-time S(t) curves in the myocardium and left ventricular (LV) cavity were evaluated by a linear fit. MPR was calculated from the original up-slopes of the myocardial S(t) curves and from the up-slopes, which were normalized to the up-slopes of the LV S(t) curves, respectively. For quantification of MBF values, the mathematical model MMID 4 was used and MPR was evaluated from the MBF values. RESULTS: With all tested methods, MPR was reduced in myocardial regions subtended by arteries with stenoses >/= 70 % compared with remote regions. With MMID 4 and the normalized up-slope method, differences between severe ischemic and remote regions were statistically significant. CONCLUSION: The up-slope method with normalization and quantification with MMID 4 are more sensitive methods to differentiate between remote and ischemic myocardium than the up-slope method without normalization.

Adult↗

PubMed2002

Monitoring of antiplatelet therapy with the PFA-100 in peripheral angioplasty patients.

BACKGROUND: In patients suffering from peripheral arterial occlusive disease (PAOD) the risk of restenosis after percutaneous transluminal angioplasty (PTA) might be influenced by platelet mediated factors. OBJECTIVE: To look for a correlation between the effect of antiplatelet therapy and recurrence of disease after PTA by monitoring platelet function in 3-month intervals by the platelet function analyzer system, PFA-100, over a period of 1 year. PATIENTS AND METHODS: A group of 98 patients (43 females, 55 males) with PAOD, treated with aspirin (n = 52), thienopyridine (n = 34) or combination therapy of both (n = 12) were followed over a period of 12 months after elective PTA of the lower extremities with regard to occurrence of restenosis or reocclusion at the site of angioplasty, to demonstrate inhibitory effects on platelets, induced by antiplatelet therapy. RESULTS: PFA-100 proved suitable to identify 'non-responders' to antiplatelet therapy, in a 12-month follow-up period. In 'non-responders' to clopidogrel therapy, a higher incidence of restenosis or reocclusion after PTA of the lower limbs was detected compared with 'responders'. CONCLUSION: PFA-100, upon stimulation with ADP, might predict patients under clopidogrel therapy with elevated risk for the development of complications following PTA of the lower limbs. This could offer the chance to switch to an alternative therapy or adapt the dose.

Angioplasty, Balloon↗

PubMed2001

Characterization of rat LANCL1, a novel member of the lanthionine synthetase C-like protein family, highly expressed in testis and brain.

We isolated and characterized the cDNA coding for rat LANCL1, a new member of the eukaryotic LanC-like protein family which is related to the bacterial lanthionine synthetase components C (LanC). LanC is involved in the synthesis of antimicrobial peptides. Rat LANCL1 showed 91.5% and 96% identity when compared with the previously characterized human and mouse orthologs, respectively. Northern blot analysis revealed the presence of two major transcripts, at 1.5 kb and 5 kb, probably arising from the usage of two different polyadenylation signals. The 1.5 kb mRNA is massively expressed in testis, whereas the 5 kb transcript is most abundant in brain. The high level of expression of rat LANCL1 in these tissues was confirmed by Western blotting. In situ hybridization analyses of various rat tissues revealed a strong signal in the germinal cells of the seminiferous tubules in testis, in the neurons of the cerebellum, in liver hepatocytes, and in cardiac myocytes. The clear relationship between LANCL1 and bacterial LanC proteins suggests similar functions as peptide-modifying enzymes synthesizing antimicrobial peptides. In particular, the high expression of LANCL1 in testis and brain, organs separated by blood-tissue barriers, may hint at a role in the immune surveillance of these organs.

Amino Acid Sequence↗

PubMed2001

Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis: meta-analysis based on original patient data.

A meta-analysis (MA) based on original patient data has been performed comparing low molecular weight heparins (LMWH) with unfractionated heparin (UFH) in thrombosis prophylaxis after major surgical interventions. The analyses have been done for the following prespecified groups of studies: all studies, studies in orthopaedic surgery (OS) and studies in general surgery (GS, with further separation into low-dose studies [GS-LD] and high-dose studies [GS-HD]). Deep vein thrombosis (DVT, all locations) and wound haematoma were used as primary endpoints for efficacy and safety, respectively. The analysis confirms the results of previous publication-based meta-analyses. In GS there is no relevant difference between LMWH and UFH regarding efficacy; the safety results strongly depend on the dosage: under low-dose LMWH the risk of wound haematoma is significantly lower, under high-dose LMWH it is significantly higher than under UFH. However, most of the studies in the last group used regimens of LMWH that are not considered appropriate any more. In OS there is a trend towards a better efficacy and safety of LMWH. In addition, LMWHs are superior to UFH, in OS, with respect to the secondary endpoints proximal DVT and pulmonary embolism. The rates of proximal DVT and pulmonary embolism, respectively, are consistently lower under LMWH than under UFH, whereas slightly smaller rates of distal DVT are observed under UFH.

Double-Blind Method↗

PubMed2001

Post-thrombotic syndrome after primary event of deep venous thrombosis 10 to 20 years ago.

AIMS: We investigated the impact of the extent of primary deep venous thrombosis (DVT) and recurrent thrombotic events in accordance to other presumed prognostic factors for long-term clinical outcome after first DVT. PATIENTS AND METHODS: All consecutive in-patients, who were treated following first acute DVT between January 1, 1978 and December 31, 1988 at the Department of Angiology were identified by admission lists. Localisation, extent of primary DVT, etiology and concomitant pulmonary embolism (PE) at the time of initial presentation and occurrence of post-thrombotic syndrome (PTS) at follow-up visits were assessed by chart review. The duration and quality of the compression therapy, as well as the accuracy of the oral anticoagulant (OAC) treatment were documented. Recurrence of thrombosis embolism and/or PE with respect to the intensity of OAC was analyzed. Patients were invited to participate in clinical reinvestigation. Patients' history and clinical stage of PTS were re-evaluated and patients were asked for compliance in wearing compression stockings. A survey concerning restriction in quality of life was conducted. Hemodynamic measurements by strain-gauge plethysmography (SGP) were performed. RESULTS: One hundred and sixty-one patients were eligible for the study. Out of these 132 patients, 82% suffered from the PTS, defined as signs of chronic venous insufficiency (CVI) secondary to DVT of the lower limbs: 74 patients (46%) presented with clinical stage I after Widmer, 47 patients (29%) with clinical stage II and 11 patients (7%) with clinical stage III. No sign of PTS was seen in 29 patients (18%). The mean follow-up period of 6.6 years was statistically not different between the three severity groups of PTS. The severity of clinical symptoms was significantly associated with the recurrence of ipsilateral thrombosis (n = 26/16%). Highest risk for developing severe PTS was seen after four-level DVT and deep vein thrombosis of the lower leg. Patients having had a non-sufficient OAC (Hepatoquick > 25% in more than 50% of measurements) exhibited worse progradient clinical stages. Besides the high rate of bleeding complications after thrombolytic therapy, this strategy did not show more efficiency in prevention of development of severe PTS than heparin therapy alone. CONCLUSION: Our results show that primary four-level DVT, calf vein thrombosis, recurrence of ipsilateral DVT and a non-sufficient oral anticoagulation are of prognostic significance for developing clinically relevant PTS within 10 to 20 years after first DVT.

Adolescent↗

PubMed2001

Identification of a novel exon in apolipoprotein E receptor 2 leading to alternatively spliced mRNAs found in cells of the vascular wall but not in neuronal tissue.

Novel members of the low density lipoprotein receptor family were identified in human endothelial and vascular smooth muscle cells utilizing a homology-cloning strategy. Four novel mRNA transcripts could be identified as isoforms of the apolipoprotein E receptor 2 (apoEr2): one form lacking three ligand binding repeats (nucleotides 497-883) but containing a novel ligand binding repeat adjacent to a unique cysteine-rich domain preceding the epidermal growth factor precursor domain of apoEr2, forms lacking the O-linked sugar domain, and forms containing a 59-amino acid deletion within the cytoplasmic tail. By fluorescence in situ hybridization for chromosome mapping, we could confirm that the novel alternative forms of apoEr2 are splice variants of transcripts from a single copy gene on chromosome 1p34. To analyze whether the different splice variants of apoEr2 mRNA are expressed in a splice variant-specific pattern, we concentrated on the central nervous system, where high expression of apoEr2 has been described originally. By means of splice variant-specific in situ hybridization, we could confirm that apoEr2 mRNA is abundantly expressed in brain tissue and, with exception of the newly identified ligand binding domain, all mRNA splice variants exhibited a similar expression pattern. The mRNA of the newly identified ligand binding domain, however, was expressed in brain only in cells of the vascular wall, confirming data from Northern blotting, where the mRNA of the newly identified ligand binding domain was found in several tissues but was absent in brain tissue.

Alternative Splicing↗

PubMed2001

K562 erythroleukemic cells are equipped with multiple mechanisms of resistance to lysis by complement.

Resistance of tumor cells to lysis by complement is generally attributed to several protective mechanisms. The relative impact of these mechanisms in the same tumor cell, however, has not been assessed yet. We have analyzed the interaction of the human erythroleukemia tumor cell line K562 with human complement. K562 cells express the membrane complement regulatory proteins CD59, CD55 and CD46. As shown here for the first time, K562 also spontaneously release the soluble regulators C1 inhibitor, factor H, and soluble CD59. Complement resistance of K562 cells is augmented upon treatment with PMA, TNF or even with sublytic complement. Unlike TNF and sublytic complement, PMA enhanced the expression of membrane-bound CD55 and CD59 and led to increased secretion of soluble CD59. In addition, we show that complement-resistant K562 cells express a membrane-associated proteolytic activity, higher than the complement-sensitive K562/S cells. Treatment of complement-resistant K562 cells with serine protease inhibitors enhance their sensitivity to complement-mediated lysis. Inhibitors of protein kinase C (PKC) also sensitize K562 cells to complement lysis, implicating PKC-mediated signaling in cell resistance to complement. Neutralization of the CD55 and CD59 but not of CD46 regulatory activity with specific antibodies significantly increases complement-mediated K562 cell lysis. Treatment of K562 cells with a mixture of inhibitory reagents results in a significant additive enhancing effect on complement-mediated lysis of K562. In conclusion, K562 cells resist a complement attack by concomitantly using multiple molecular evasion strategies. Future attempts in antibody-based tumor therapy should include strategies to interfere with those resistance mechanisms.

Antigens, CD↗

PubMed2001

[Rapid reviews for evidence-based decision support. (Restricting) requirements].

Since evidence-based decision making is increasingly gaining acceptance among German health care authorities the need for evidence-based support for time-critical decisions becomes obvious. The best method to identify and summarize the available evidence is the conduct of systematic reviews of the literature. However, generally systematic reviews are not applicable in matters of urgency, because of their time consuming preparation. Concepts for "rapid reviews" are urgently required which ensure that these reviews still produce reliable results. The article proposes strategies to accelerate the preparation of a systematic review and discusses their possible influences on the conclusions of the review. Research efforts are needed to clarify which of the accelerations actually yield valid results.

Delivery of Health Care↗

PubMed2001

Deficits and remedy of the standard random effects methods in meta-analysis.

The random effects model is often used in meta-analyses. A corresponding significance test based on a normal approximation has been established. Its type I error is derived in this article by theoretical considerations and computer simulations. The test can be conservative as well as unacceptably anti-conservative. The anti-conservatism increases with the increasing number of patients and the decreasing number of studies. A modification is proposed, which keeps the nominal level asymptotically as the number of patients approaches infinity. Simulations show that the modified test is often conservative, but its conservatism is small in those situations where the standard test is highly anti-conservative.

Bias↗

PubMed2001

A randomized evaluation of a computer-based nursing documentation system.

A two-month randomized, controlled trial based on 60 patients has been performed on a ward of the Department of Psychiatry at Heidelberg University Medical Center, Germany, to investigate the influence of computer-based nursing documentation on time investment for documentation, quality of documentation and user acceptance. Time measurements, questionnaires, documentation analysis and interviews were used to compare patients documented with the computer-based system (PIK group) with the control group (patients documented with the paper-based system). The results showed the advantages and disadvantages of computer-based nursing documentation. Time needed for nursing care planning was lower in the PIK group. Some formal aspects of quality were considerably better in the PIK group. On the other hand, time required for documentation of tasks and for report writing was greater in the PIK group. User acceptance increased significantly during the study. The interviews indicated a positive influence of PIK on the cooperation between nurses and physicians.

Attitude to Computers↗

PubMed2000

Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations.

PURPOSE: To evaluate the diagnostic value of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) for the diagnosis of primary breast cancer. PATIENTS AND METHODS: Preoperatively, 144 patients with masses suggestive of breast cancer underwent PET imaging of the breast. To identify breast cancer by increased metabolic activity, parametric FDG-PET images were analyzed for increased tracer uptake applying conventional image reading (CIR) and sensitive image reading (SIR). One hundred eighty-five breast tumors were evaluated by histology, revealing 132 breast carcinomas and 53 benign masses. RESULTS: Breast carcinomas were identified with an overall sensitivity of 64.4% (CIR) and 80.3% (SIR). The increase in sensitivity (SIR) resulted in a noticeable decrease in specificity, from 94.3% (CIR) to 75.5% (SIR). At stage pT1, only 30 (68.2%) of 44 breast carcinomas were detected, compared with 57 (91.9%) of 62 at stage pT2. A higher percentage of invasive lobular carcinomas were false-negative (65.2%) compared with invasive ductal carcinomas (23.7%). Nevertheless, positive PET scans provided a high positive-predictive value (96.6%) for breast cancer. CONCLUSION: Partial volume effects and varying metabolic activity (dependent on tumor type) seem to represent the most significant limitations for the routine diagnostic application of PET. The number of invasive procedures is therefore unlikely to be significantly reduced by PET imaging in patients presenting with abnormal mammography. However, the high positive-predictive value, resulting from the increased metabolic activity of malignant tissue, may be used with carefully selected subsets of patients as well as to determine the extent of disease or to assess therapy response.

Breast Neoplasms↗

PubMed2000

[Meta-analysis as a tool for evaluation of evidence].

In these days, more than one clinical trial is mostly performed to evaluate a new treatment or therapeutic intervention. This necessitates a combined evaluation of their results. An integration of evidence from several trials is also helpful to determine the actual knowledge. These are the main goals of meta-analyses. Since the end of the 80s meta-analyses are widely used in clinical research. At the beginning of a meta-analysis, a protocol has to be developed. Similar to a protocol of a clinical trial, the inclusion and exclusion criteria for trials, the hypotheses and the planned analyses have to be fixed. After a careful localization of trials, a combined statistical analysis is performed. An investigation of heterogeneity, i.e., differences between study results, is indispensable. During the last years, the tool meta-analysis has been criticized. The criticism mainly results from poorly conducted meta-analyses which generated results without prespecifying hypotheses or which merely combined study results. Well-planned meta-analyses, on the contrary, have an increasing influence in clinical research.

Clinical Protocols↗

PubMed2000

Evaluation of sympathetic nerve terminals with [(11)C]epinephrine and [(11)C]hydroxyephedrine and positron emission tomography.

BACKGROUND: The goal of the present study was to directly compare the new radiopharmaceutical agent [(11)C]epinephrine (EPI) with [(11)C]hydroxyephedrine (HED) through the use of PET. METHODS AND RESULTS: Seven healthy volunteers and 10 patients were investigated after heart transplantation. PET images of both tracers were of excellent quality in the volunteers. Values for radiolabeled metabolites (measured in percent of blood activity) at 5, 20, and 60 minutes after injection were approximately 35%, approximately 82%, and approximately 86% for EPI and approximately 13%, approximately 47%, and approximately 78% for HED, respectively. At 35 minutes, metabolite-corrected mean myocardial retention fraction of EPI (0. 235+/-0.022 min(-1)) was significantly greater (P<0.01) than that of HED (0.142+/-0.012 min(-1)). Corrected tracer retention fractions of both EPI and HED were significantly reduced in transplant recipients (0.055+/-0.004 min(-1), P<0.0001; and 0.050+/-0.006 min(-1), P<0. 0001, respectively) compared with volunteers. Normalization of retention fractions of patients with transplantation within 1 year to volunteers resulted in a value (ratio expressed in percent) of 20. 6+/-1.8% for EPI, significantly (P<0.03) smaller than 27.8+/-0.8% for HED. In patients with transplantation later than 1 year, the values were 26.0+/-2.9% for EPI compared with 44.2+/-5.6% for HED (P<0.014). CONCLUSIONS: Both tracers showed high selectivity for neuronal uptake in the heart, with a significant reduction in tracer retention in transplant recipients compared with volunteers. Compared with HED, EPI showed greater retention in volunteers and a lower retention ratio in transplant recipients, suggesting that EPI may be the superior tracer with higher sensitivity to neuronal abnormalities. Because EPI reflects neuronal uptake, metabolism, and storage, it may be more suitable for the study of neuronal integrity than HED, which primarily traces uptake-1 capacity.

Adult↗