Search PubMed⌕ Search

Biomedical subjects

S Witte

Publications and source records attributed to S Witte.

At least 19 recordsLinked to original sources
PubMed2006

Protocol design and current status of CLIVIT: a randomized controlled multicenter relevance trial comparing clips versus ligatures in thyroid surgery.

BACKGROUND: Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT. METHODS/DESIGN: CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers. DISCUSSION: As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice.

Journal Article↗
PubMed2006

[Project selection and protocol design in the Study Centre of the German Surgical Society].

BACKGROUND: The Study Centre of the German Surgical Society (SDGC) designs, conducts, and analyses multicentre randomised controlled surgical trials. The aim of this paper is to present the decision-making process and responsibilities of the SDGC from submission of a study idea to full protocol development in order to achieve transparency in trial selection. METHODS: The process is divided into four steps. Study ideas can be submitted electronically by members of the German Surgical Society using a form via the homepage of the institution. Firstly, ideas are screened by staff members within 4 weeks for methodological and clinical relevance. Feasible and novel ideas are then converted to trial outlines in cooperation with the submitting surgeon. As a third step, the Steering Committee of the SDGC decides whether to accept the project using a list of defined criteria. Finally, the SDGC draws up a full protocol together with the submitting surgeon. All ideas and decisions are accessible via the SDGC homepage. CONCLUSIONS: The process described should help in the selection of relevant projects, acquisition of grants, and maintenance of transparency in trial selection and the protocol development process.

Decision Making↗
PubMed2005

Acupuncture treatment in irritable bowel syndrome.

BACKGROUND AND AIMS: Despite occasional positive reports on the efficacy of acupuncture (AC) on functions of the gastrointestinal tract, there is no conclusive evidence that AC is effective in the treatment of irritable bowel syndrome (IBS). PATIENTS AND METHODS: Forty three patients with IBS according to the Rome II criteria were randomly assigned to receive either AC (n = 22) or sham acupuncture (SAC) (n = 21) using the so-called "Streitberger needle". Treatment duration was 10 sessions with an average of two AC sessions per week. The primary end point was improvement in quality of life (QOL) using the functional digestive diseases quality of life questionnaire (FDDQL) and a general quality of life questionnaire (SF-36), compared with baseline assessments. QOL measurements were repeated three months after treatment. RESULTS: Both the AC and SAC groups improved significantly in global QOL, as assessed by the FDDQL, at the end of treatment (p = 0.022), with no differences between the groups. SF-36 was insensitive to these changes (except for pain). This effect was partially reversed three months later. Post hoc comparison of responders and non-responders in both groups combined revealed a significant prediction of the placebo response by two subscales of the FDDQL (sleep, coping) (F = 6.746, p = 0.003) in a stepwise regression model. CONCLUSIONS: Acupuncture in IBS is primarily a placebo response. Based on the small differences found between the AC and SAC groups, a study including 566 patients would be necessary to prove the efficacy of AC over SAC. The placebo response may be predicted by high coping capacity and low sleep quality in individual patients.

Acupuncture Therapy↗
PubMed2005

High-power parametric amplification of 11.8-fs laser pulses with carrier-envelope phase control.

Phase-stable parametric chirped-pulse amplification of ultrashort pulses from a carrier-envelope phase-stabilized mode-locked Ti:sapphire oscillator (11.0 fs) to 0.25 mJ/pulse at 1 kHz is demonstrated. Compression with a grating compressor and a LCD shaper yields near-Fourier-limited 11.8-fs pulses with an energy of 0.12 mJ. The amplifier is pumped by 532-nm pulses from a synchronized mode-locked laser, Nd:YAG amplifier system. This approach is shown to be promising for the next generation of ultrafast amplifiers aimed at producing terawatt-level phase-controlled few-cycle laser pulses.

Journal Article↗
PubMed2004

A 63bp deletion in the promoter of rage correlates with a decreased risk for nephropathy in patients with type 2 diabetes.

Several polymorphisms have been identified in the RAGE-promoter region that might modulate the outcome of disease. Here we analyse the association of a 63bp deletion (delta63) spanning from bp - 407 to bp - 345 with diabetic nephropathy. The deletion was determined using the polymerase chain reaction (PCR) in a cross-sectional study with 1087 patients with type 1 diabetes (n = 559) and type 2 diabetes (n = 528). 475 patients with osteoporosis served as disease independent control. The prevalence of the heterozygous genotype did not significantly differ between the three groups (type 1: 2.15 %, type 2: 2.27 %, controls: 1.47 %), indicating that heterozygous delta63 is not related to the manifestation of diabetes. Homozygous carriers were not identified in this study. The heterozygous delta63 genotype, was associated with a reduced prevalence of diabetic nephropathy in patients with type 2 diabetes (OR = 0.06; 95 % CI: [0.05, 0.07]), but not in patients with type 1 (OR = 1.49; 95 % CI: [1.14, 1.94]). We conclude, that patients with type 2 diabetes and the 63bp deletion in the promoter of RAGE seem to be protected from diabetic nephropathy. The observed difference between type 1 and type 2 diabetes might point to diverse pathomechanisms of nephropathy in both types of diabetes.

Diabetes Mellitus, Type 1↗
PubMed2004

Some problems with the investigation of noninferiority in meta-analysis.

OBJECTIVES: Noninferiority trials have become commonplace in recent years. Like individual clinical trials, meta-analyses can also investigate noninferiority. However, certain important topics have to be considered. METHODS: The proposed methods in this paper have their origin in the framework of noninferiority trials and meta-analyses. This paper can therefore be seen as a combination of both fields. Two issues are highlighted in the paper; difficulties in the choice of delta for a noninferiority meta-analysis leading to different deltas and methods for meta-analyses with different analysis sets, based on the full-analysis set with the intention-to-treat principle or the per-protocol population. Analytical methods, sensitivity analyses, meta-regression, and a bivariate method are introduced. The proposed graphical presentations support the analytical results. CONCLUSION: The confidence interval approach using meta-regression or bivariate methods is appropriate using both analysis sets for meta-analyses investigating noninferiority.

Clinical Trials as Topic↗
PubMed2002

[Meta-analysis of the efficacy of adenosylmethionine and oxaceprol in the treatment of osteoarthritis].

The aim of this meta-analysis based on the literature was to gather all evidence of randomized clinical trials to assess the efficacy of adenosylmethionine (SAM) and oxaceprol in the treatment of osteoarthritis. Findings in MEDLINE and EMBASE were added to publications catalogued by the AkdA and a reference search. The meta-analysis was based mostly on pain scores but also on pain and function scores. We used the fixed effects and the random effects model.A superiority of SAM vs placebo ( n=468) could not be shown; the 95% CI of standardized difference of pain scores was (-0.89, 0.12). The comparison of SAM vs NSAIDs with seven studies ( n=850) did not show a difference: (-0.59, 0.19). This cannot be seen as proof for equivalence. A post-hoc analysis of SAM vs ibuprofen gave nearly a positive result for SAM: (-0.43, 0.02). No adequate placebo-controlled RCT was found. There was no significance for a difference between oxaceprol and NSAIDs using the four trials found (two diclofenac and two ibuprofen); the 95% CI of standardized difference of pain and function scores was (-0.19, 0.27). Since only a few trials with heterogeneous results were found which mostly have a low quality of the studies and/or publications, the results must be interpreted very carefully. The meta-analysis does not give enough evidence for the efficacy of SAM and oxaceprol for treating the symptoms of osteoarthritis, but it might be that there is a comparable effect to other NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

The role of community consultants in designing an HIV prevention intervention.

This article describes the significant role of community members during the intervention development phase of a randomized clinical trial of an HIV prevention intervention for African American and Latina women and their main sexual partners. Sixteen women and 13 male partners were engaged as "consultants" in a series of focus group discussions aimed at exploring their reactions and ideas about potential topics and approaches for the intervention. Each individual participated in three focus groups-two single-sex groups and a third that brought women and their male partners together. Focus group data extended our knowledge about the impact of relationship dynamics on safer sex negotiation and allowed us to design an intervention that is contextually specific and pragmatic. Target community members can provide critical input during the intervention development process and should be recognized as viable and meaningful collaborators in all phases of intervention research.

Adult↗
PubMed2000

Regulation of protein kinase Ctheta function during T cell activation by Lck-mediated tyrosine phosphorylation.

Protein kinase C theta (PKCtheta) is a novel Ca(2+)-independent PKC isoform, which is selectively expressed in skeletal muscle and hematopoietic cells, especially T cells. In T cells, it colocalizes with the T cell antigen receptor (TCR).CD3 complex in antigen-stimulated T cells and is involved in the transcriptional activation of the interleukin-2 gene. In the present study, we report that PKCtheta is tyrosine phosphorylated in Jurkat T cells upon TCR.CD3 activation. The Src family protein-tyrosine kinase, Lck, was critical in TCR-induced tyrosine phosphorylation of PKCtheta. Lck phosphorylated and was associated with the regulatory domain of PKCtheta both in vitro and in intact cells. This association was constitutive, but it was enhanced by T cell activation, with both Src-homology 2 and Src-homology 3 domains of Lck contributing to it. Tyrosine 90 (Tyr-90) in the regulatory domain of PKCtheta was identified as the major phosphorylation site by Lck. A constitutively active mutant of PKCtheta (A148E) could enhance proliferation of Jurkat T cells and synergized with ionomycin to induce nuclear factor of T cells activity. However, mutation of Tyr-90 into phenylalanine markedly reduced (or abolished) these activities. These results suggest that Lck plays an important role in tyrosine phosphorylation of PKCtheta, which may in turn modulate the physiological functions of PKCtheta during TCR-induced T cell activation.

Humans↗
PubMed2000

Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain.

Protein kinase C-theta (PKCtheta) is a Ca(2+)-independent PKC isoform that is selectively expressed in T lymphocytes (and muscle), and is thought to play an important role in T cell receptor-induced activation. To gain a better understanding of the function and regulation of PKCtheta, we have employed the yeast two-hybrid system to identify PKCtheta-interacting proteins. We report the isolation and characterization of a cDNA encoding a novel 335-amino acid (37. 5-kDa) PKCtheta-interacting protein termed PICOT (for PKC-interacting cousin of thioredoxin). PICOT is expressed in various tissues, including in T cells, where it colocalizes with PKCtheta. PICOT displays an N-terminal thioredoxin homology domain, which is required for the interaction with PKC. Comparison of the unique C-terminal region of PICOT with expressed sequence tag data bases revealed two tandem repeats of a novel domain that is highly conserved from plants to mammals. Transient overexpression of full-length PICOT (but not its N- or C-terminal fragments) in T cells inhibited the activation of c-Jun N-terminal kinase (but not extracellular signal-regulated kinase), and the transcription factors AP-1 or NF-kappaB. These findings suggest that PICOT and its evolutionary conserved homologues may interact with PKC-related kinases in multiple organisms and, second, that it plays a role in regulating the function of the thioredoxin system.

Amino Acid Sequence↗
PubMed1999

NMDA receptor activity stabilizes presynaptic retinotectal axons and postsynaptic optic tectal cell dendrites in vivo.

To investigate the role of N-methyl-D-aspartate (NMDA) receptor activity in the stability of the presynaptic axon arbor and postsynaptic dendritic arbors in vivo, we took time-lapse confocal images of single DiI-labeled Xenopus retinotectal axons and optic tectal neurons in the presence and absence of the NMDA receptor antagonist, APV. Retinotectal axons or tectal neurons were imaged at 30-min intervals over 2 h, or twice over a 24-h period. Retinal axons in animals exposed to DL-APV (100 microM) showed an increase in rates of branch additions and a decrease in branch lifetimes over 2 h compared to untreated axons. Under the same experimental conditions, tectal neurons showed a decreased rate of branch tip additions and retractions. APV treatment over 24 h had no apparent effect on axon arbor morphology, but did decrease tectal cell dendritic arbor elaboration. These observations demonstrate that NMDA receptor activity in postsynaptic neurons stabilizes pre- and postsynaptic neuronal morphology in vivo.. However, when NMDA receptor activity is blocked, presynaptic retinal axons respond with increased arbor dynamics while postsynaptic tectal cell dendrites decrease arbor dynamics. Such differential responses of pre- and postsynaptic partners might increase the probability of coactive afferents converging onto a common target under conditions of lower NMDA receptor activity.

Animals↗
PubMed1999

Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation.

Cbl-b, a mammalian homolog of Cbl, consists of an N-terminal region (Cbl-b-N) highly homologous to oncogenic v-Cbl, a Ring finger, and a C-terminal region containing multiple proline-rich stretches and potential tyrosine phosphorylation sites. In the present study, we demonstrate that upon engagement of the T cell receptor (TCR), endogenous Cbl-b becomes rapidly tyrosine-phosphorylated. In heterogeneous COS-1 cells, Cbl-b was phosphorylated on tyrosine residues by both Syk- (Syk/Zap-70) and Src- (Fyn/Lck) family kinases, with Syk kinase inducing the most prominent effect. Syk associates and phosphorylates Cbl-b in Jurkat T cells. A Tyr-316 Cbl-binding site in Syk was required for the association with and for the maximal tyrosine phosphorylation of Cbl-b. Mutation at a loss-of-function site (Gly-298) in Cbl-b-N disrupts its interaction with Syk. Cbl-b constitutively binds Grb2 and becomes associated with Crk-L upon TCR stimulation. The Grb2- and the Crk-L-binding regions were mapped to the C-terminus of Cbl-b. The Crk-L-binding sites were further determined to be Y655DVP and Y709KIP, with the latter being the primary binding site. Taken together, these results implicate that Cbl-b is involved in TCR-mediated intracellular signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1998

MS-325: albumin-targeted contrast agent for MR angiography.

PURPOSE: To evaluate the protein-binding and signal enhancement characteristics of MS-325, a gadolinium-based magnetic resonance (MR) imaging blood pool agent that binds to albumin, and compare results with those obtained with existing gadolinium- and iron oxide-based agents. MATERIALS AND METHODS: Protein binding in human plasma was measured by means of ultrafiltration. T1 relaxation times (20 MHz) were measured in human plasma or ex vivo samples from rabbits and monkeys injected with 0.1 mmol of MS-325 per kilogram of body weight. Imaging (three-dimensional fast imaging with steady-state precession, or FISP) was performed at 1.0 T in phantoms, which contained varying concentrations of different agents, or rabbits after injection of 0.015-0.100 mmol/kg MS-325. RESULTS: MS-325 is 80%-96% bound in human plasma and exhibits a relaxivity approximately six to 10 times that of gadolinium diethylenetriaminepentaacetic acid (DTPA). Images of phantoms containing MS-325 were significantly brighter than those containing existing gadolinium chelates or iron particles (monocrystalline iron oxide nanoparticle, or MION) at equivalent concentrations. Findings of in vivo studies indicated strong, persistent plasma T1 reduction with MS-325 for 1 hour (T1 of MS-325, 50-100 msec; T1 of Gd-DTPA, 200-400 msec) and strong vascular enhancement on MR images. CONCLUSION: MS-325 is highly protein bound after injection and provides vascular signal enhancement superior to that provided with other agents. As the first gadolinium-based blood pool agent in human trials, MS-325 has the potential to enhance both dynamic and steady-state MR angiograms.

Animals↗
PubMed1998

Steady-state and dynamic MR angiography with MS-325: initial experience in humans.

PURPOSE: To evaluate the imaging performance and patient tolerance of a blood-pool contrast agent (MS-325) for magnetic resonance (MR) angiography. MATERIALS AND METHODS: Imaging of peripheral and carotid vessels was performed in seven healthy volunteers in a phase I clinical trial of the gadolinium chelate MS-325. Each volunteer received an intravenous injection of 0.05 mmol/kg MS-325 over 30 seconds. Dynamic (arterial phase) and steady-state (arterial-venous phase) three-dimensional gradient-echo MR angiograms were acquired during, immediately after, and approximately 50 minutes after injection. Images were ranked (1 [poor] to 5 [excellent]) for overall image quality, and signal-to-noise ratio (S/N) and contrast-to-noise ratio (C/N) were measured by using standard techniques. RESULTS: All volunteers tolerated the procedure well. The MS-325-enhanced studies demonstrated intense vascular signal. Mean peripheral arterial C/N was 12.9 +/- 4.8 (standard deviation), 78.8 +/- 29.4, 46.1 +/- 10.9, and 41.9 +/- 14.1 for the two-dimensional (2D) time-of-flight (TOF) and the contrast material-enhanced dynamic, early steady-state, and late steady-state images, respectively. Image quality of steady-state postcontrast images was statistically significantly (P < .02) higher than that of 2D TOF images. Image quality of early and late postcontrast images was similar, but a small (10%) decrease in C/N was noted from early to late images. CONCLUSION: MS-325 provides excellent vascular and selective arterial enhancement during dynamic MR angiography. The long blood residence time also allows acquisition of steady-state images of the arteries and veins with excellent spatial resolution.

Abdomen↗
PubMed1998

Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density.

We recently demonstrated that insulin growth factor-I (IGF-I) cosegregates with bone mineral density (BMD) in progenitor crosses of two inbred strains of mice. Additionally, we reported that men with idiopathic osteoporosis (IOM) have low serum IGF-I levels, which can be related to BMD and bone turnover. In this study, we considered the possibility that serum IGF-I levels are influenced by molecular genetic variation in the IGF-I structural gene, and that a polymorphic microsatellite (CA repeat) in this locus can be used as a genetic marker for such comparisons. We studied 171 men and women, classified according to the trial in which they were participating. First, in 25 Caucasian men with IOM we noted a very high frequency (64%) of homozygosity for the most common allele (192 bp) in a dinucleotide repeat 1 kb upstream from the transcription start site of the IGF-I gene. This compared with a frequency of only 32% in healthy populations (both men and women) (P < 0.004). Next, we determined that for 116 healthy Caucasian men and women the 192/192 genotype was associated with lower serum IGF-I levels than all other genotypes (192/192: 129 +/- 7 ng/mL vs. others: 154 +/- 7 ng/mL, P = 0.03). We also noted that subjects possessing one 194-bp allele exhibited serum IGF-I levels 25% higher than those homozygous for 192 bp (192/192), (P < 0.005) even after correction for age and sex. Similarly, for men with the 192/192 genotype, serum IGF-I concentrations were lower than any other genotype (145 +/- 10 ng/mL vs. 183 +/- 9 ng/ml P < 0.02). In conclusion, low serum IGF-I levels found in men with IOM are associated with homozygosity for a specific allele of the IGF-I microsatellite (192/192), and individual variation in serum IGF-I levels is influenced by genetic factors and may be specifically influenced by variation at the IGF-I structural locus. Further family and pedigree studies are needed to characterize the relationship of bone mass acquisition to the IGF-I genotype.

Aged↗
PubMed1998

Acceptability of the female condom among STD clinic patients.

This study examines the acceptability of the female condom among African American and Latino patients from two inner-city sexually transmitted disease (STD) clinics through focus group discussions. Prior to the initial focus group sessions, 90% (n = 90) had heard about the female condom, 8% (n = 8) had seen it, and 2% (n = 2) had used it. Among the 41 participants (22 males and 19 females) attending a second focus group session, 85.4% (n = 35) had used the female condom at least once. Female study participants who had previous experience inserting a barrier contraceptive device, such as a diaphragm, indicated that they felt more comfortable inserting the female condom than those who had never used such a device. Male participants indicated that they were more comfortable using the female condom with their steady partners than with casual partners, whereas female participants indicated no such distinctions. These and other study findings suggest that need to promote and expand the use of the female condom as a device that protects women from STD transmissions including HIV and AIDS.

Acquired Immunodeficiency Syndrome↗