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Biomedical subjects

A Schäffler

Publications and source records attributed to A Schäffler.

At least 19 recordsLinked to original sources
PubMed2006

Role of adipose tissue as an inflammatory organ in human diseases.

Reviews on the inflammatory role of adipose tissue outside the field of metabolism are rare. There is increasing evidence provided by numerous basic research studies from nearly all internal medicine subspecializations that adipocytes and adipocytokines are involved in primary inflammatory processes and diseases. Therefore, it is the aim of the present review to discuss and to summarize the current knowledge on the inflammatory role of adipocytokines and special types of regional adipocytes such as retroorbital, synovial, visceral, subdermal, peritoneal, and bone marrow adipocytes in internal medicine diseases. Future clinical and therapeutic implications are discussed.

Adipocytes↗
PubMed2006

[Treatment of pituitary gland hyperfunction: from acromegaly to prolactinoma].

Evidence based drug therapy is currently available for the treatment of prolactinomas and growth hormone secreting adenomas (acromegaly). Dopamine agonists such as bromocriptine, quinagolide or cabergoline represent the standard therapy for the treatment of micro- and macro-prolaktinomas. In pregnancy, more differentiated, individual and patient-adapted therapeutic procedures have to be considered. Transsphenoidal adenomectomy is the treatment of choice for patients suffering from acromegaly. If biochemical cure (defined by normalized IGF-1 serum levels or by a GH nadir <1 microg/l during a 3-h oral glucose tolerance test) cannot be achieved, somatostatin analogues such as octreotide and lanreotide are effective. In some cases, dopamine agonists can be added. In therapy-resistant cases, growth hormone receptor antagonists can be used.

Acromegaly↗
PubMed2006

[Clinical experience with the Siremobil Iso-C(3D) imaging system in pelvic surgery].

In pelvic and acetabular surgery intraoperative control of reduction and implant position is sometimes hard to achieve with conventional C-arm technology. The Siemens C-arm Iso-C(3D) imaging system enables axial cuts and two- or three-dimensional reconstructions to be generated. Following the good experience in surgery of the spine and extremities, its clinical applicability in pelvic surgery was evaluated in 30 patients in a prospective clinical trial. In all 20 patients with acetabular fractures reduction quality and implant position could be well assessed. In one postoperative examination an intraarticular screw placement was evident, which intraoperatively was not as clear and was revised. In one procedure an intraarticular fragment was visualized, and was extracted in the same procedure. In one procedure the use of the Iso-C(3D) system enabled the approach to be limited. In all ten pelvic ring injuries the osseous structures in the posterior pelvic ring could be visualized with an adequate image quality. Reduction quality and implant position could be assessed in all open and closed procedures. On two occasions the SI screws were navigated based upon the Iso-C(3D) dataset. Overall the use of the Iso-C(3D) system was successful in all cases. Image quality, which is clearly inferior to that of CT, was sufficient for the assessment of reduction quality and implant position. One revision was indicated, and one avoided. However, in spite of its advantages in pelvic surgery, handling, sterile covering and data transfer need to be improved. For bilateral pelvic injuries the image size is too small.

Acetabulum↗
PubMed2006

[Percutaneous reduction and stabilization of a dislocated acetabular fracture. Case report].

In the treatment of acetabular fractures, anatomic reconstruction of the joint is the primary aim. To achieve this, rather large approaches with approach-related morbidity are needed. Percutaneous stabilizations are still limited to nondisplaced or minimally displaced fractures. For displaced acetabular fractures there are percutaneous procedures described with intraoperative CT control, requiring that CT be available in the OR and posing a logistic challenge. The fluoroscope Siremobil Iso-C3D offers the possibility of displaying osseous structures with CT-like quality using a fluoroscopy technique. The case of a minimally displaced acetabular T-type fracture with a clear articular step in the weight-bearing area is presented. The percutaneous reduction and stabilization after intraoperative control of the reduction quality with the Siremobil Iso-C3D is demonstrated. Using the enhanced fluoroscopy technology with the ability to generate axial cuts and reconstructions comparable to CT clearly improves the reduction control also in acetabular surgery. Thus even displaced acetabular fractures can be reduced and stabilized percutaneously. Anatomic reconstruction of the joint remains the primary aim.

Acetabulum↗
PubMed2006

[Integrated navigation. Preclinical evaluation and initial clinical experience].

BACKGROUND: Computer navigation systems have increasingly become part of the surgical routine due to the improvements of intraoperative visualization procedures. Because of limited space in the operating room and insufficient workflow, the project of integrated navigation had been started. METHODS: As the first step, the navigation system VectorVision2 and the second-generation fluoroscopic C-arm system Orbic 3D were integrated into one common trolley. In an experimental study the integrated navigation system was used to drill 160 pedicle screws. Afterwards the system was clinically evaluated in 11 surgical procedures. RESULTS: During the whole experimental study the system could be used for all 160 drilling procedures without any technical faults, causing a failure rate of 4.2%. For clinical evaluation the integrated navigation system was used in seven patients with navigated dorsal spine instrumentation, in three cases sacroiliac screws were placed, and in one case supra-acetabular screw osteosynthesis was performed for an acetabular fracture. In all cases the positioning of the screws was correct and no system failure occurred. CONCLUSIONS: The combination of the navigation system and the C-arm system in one common trolley is a major improvement of the surgical workflow. In the experimental study and the clinical trials the system worked extremely reliably and with high precision.

Acetabulum↗
PubMed2006

Lack of correlation between the vitamin D receptor Fokl start codon polymorphism and bone mineral density in patients with Crohn's disease.

INTRODUCTION: We have examined the association of bone mineral density of patients with inflammatory bowel disease with a polymorphism in the gene encoding the vitamin D receptor. The thymine/cytosine (T/C) polymorphism in the first of two start codons can be defined by a restriction fragment length polymorphism using the restriction endonuclease FokI. Vitamin D receptor alleles containing the polymorphism have been denoted by f and alleles lacking the site by F. METHODS: We report on an association analysis of a basic population of 244 caucasian patients with Crohn's disease. We have genotyped the FokI polymorphism of the VDR in these patients and associated the genotype with the bone mineral density of the lumbar spine and the femoral neck. RESULTS: In the cohort 42% of the patients were scored FF homozygous, 43.7% Ff heterozygous, and 14.3% ff homozygous. 14.4% of the FF patients, 18.8% of the Ff patients, and 9.7% of the ff patients had osteoporosis of the lumbar spine and 21.25% of the FF patients, 25.3% of the Ff patients, and 18.5% of the ff patients had osteoporosis of the femoral neck. In this cohort no association between the genotype and the bone mineral density in the group as a whole nor when separated according to sex or age was found. CONCLUSIONS: In summary in our cohort no association of the FokI polymorphism and the BMD of the lumbar spine and femoral neck in patients with inflammatory bowel disease was found.

Bone Density↗
PubMed2006

Use of anticoagulation during wireless capsule endoscopy for the investigation of recurrent obscure gastrointestinal bleeding.

Detecting the source of obscure gastrointestinal bleeding can be difficult. Capsule endoscopy is a promising diagnostic tool for investigating patients with this condition, although identifying the source of intermittent or low-grade bleeding remains a diagnostic challenge. We present case reports of two patients with obscure gastrointestinal bleeding, in whom the source of recurrent bleeding episodes was diagnosed by capsule endoscopy while they were on anticoagulation therapy. The first patient, an 81-year-old white woman, was on long-term oral anticoagulation because she had chronic atrial fibrillation. Capsule endoscopy demonstrated a bleeding tumor in the region of the terminal ileum. The second patient, a 59-year-old white man, underwent an initial capsule endoscopy, which was negative. After initiation of anticoagulation with heparin, a second capsule endoscopy procedure in this patient revealed several small bleeding lesions in the proximal small bowel. In both cases a gastrointestinal stromal tumor was identified as the bleeding source and was resected. These two cases demonstrate that provocation of bleeding during capsule endoscopy may increase its sensitivity.

Aged, 80 and over↗
PubMed2005

Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue.

Genomic structure, promoter region, amino acid sequence and exon-specific primer combinations of the human omentin gene are presented. Omentin mRNA expression differs between omental adipose tissue probes from patients with chronic inflammatory bowel diseases such as Crohn's disease. Sequence comparisons revealed a 100% identity of omentin with human intelectin. Based on this, omentin might be a new adipocytokine playing a role in the defense against intestinal bacterial translocation in the context of Crohn's disease.

Adipose Tissue↗
PubMed2005

Hypothesis paper Brain talks with fat--evidence for a hypothalamic-pituitary-adipose axis?

The adipose tissue signals to the brain via its secretory products. However, it is unknown whether the brain itself can directly contact the fat tissue. In order to test this hypothesis, the adipocytic expression of receptors for pituitary hormones and hypothalamic peptides was investigated. Besides FSH- and LH-receptors, adipocytes do express the specific receptors for ACTH, TSH, GH, prolactin, oxytocin and the three receptor subtypes for vasopressin. Thus, the adipose tissue might no longer be regarded as an inert and steady tissue but as a fast acting player downstream of and under the control of the brain. Based on this, the potential existence and clinical impact of a hypothalamic-pituitary-adipose axis should further be investigated.

Adipose Tissue↗
PubMed2005

Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the -2518 A-->G promoter polymorphism.

AIM: To investigate the association of serum levels and the -2518 A-->G promoter polymorphism of the gene for chemokine monocyte chemoattractant protein-1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, with metabolic parameters as well as insulin, leptin and the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in 534 Caucasian patients with type 2 diabetes mellitus. METHODS: MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. MCP-1 genotyping was performed by RFLP analysis in a subset of 426 patients. RESULTS: Two hundred and thirty-one (54.2%) patients were homozygous for the wildtype allele (AA), 156 (36.6%) were heterozygous (AG) and 39 (9.2%) were homozygous for the mutated allele (GG). Allelic frequency was similar to non-diabetic populations (wildtype allele A: 0.73; mutated allele G: 0.27). MCP-1 mean concentrations and percentiles were substantially higher in non-diabetic populations but were not influenced by the genotype (AA: 662.0 +/- 323.0 pg/ml; AG: 730.6 +/- 491.4 pg/ml; GG: 641.2 +/- 323.8 pg/ml). MCP-1 serum levels and genotypes were only marginally related to hormones (insulin and leptin) and cytokines (TNF-alpha and IL-6). CONCLUSIONS: This is the first study providing MCP-1 levels, percentiles and genotype frequency in a large and representative cohort of patients with type 2 diabetes mellitus. Compared to the literature, MCP-1 levels were found to be substantially higher in patients with type 2 diabetes mellitus. In contrast, genotype frequencies were similar compared to those in non-diabetic patients and were not related to MCP-1 levels. The mechanisms behind these elevated MCP-1 serum levels in type 2 diabetes are not to be explained by simple associations with hormones, cytokines or genotypes.

Aged↗
PubMed2004

Role of specificity protein-1, PPARgamma, and pituitary protein transcription factor-1 in transcriptional regulation of the murine CORS-26 promoter.

The collagenous repeat-containing sequence of 26-kDa protein (CORS-26) was recently described as a new gene that is induced during adipocyte differentiation. Since the transcription factors specificity protein-1 (SP-1) and PPARgamma have been demonstrated to modulate transcriptional activation of adipocytic genes, we investigated the putative role of SP-1 and PPARgamma in the regulation of the murine CORS-26 promoter. Computer-based sequence analysis revealed two putative SP-1 binding sites and binding sites for PPARgamma and Pit-1 within the TATA-box containing promoter. Electrophoretic mobility shift assays (EMSA) with nuclear extracts from 3T3-L1 adipocytes and appropriate promoter fragments demonstrated that SP-1 binds specifically to both SP-1 binding sites. Specificity was demonstrated by (i) the appearance of supershift bands, (ii) competition experiments and, (iii) by using oligonucleotides carrying mutated SP-1 binding sites. Functional promoter activity was analyzed by Luciferase reporter gene assays and SP-1 was shown to exert inhibitory effects on the transcriptional activation of the murine CORS-26 gene. Additionally, specific binding activity of PPARgamma and Pit-1 to the CORS-26 promoter was demonstrated. Taken together, the present data demonstrate the functionality of the proximal murine CORS-26 promoter, which is regulated specifically by two SP-1 binding sites via SP-3-independent repressive effects of SP-1 on transcriptional activation. Pit-1 and PPARgamma can bind specifically to the promoter and might play an additive functional role in gene regulation of murine CORS-26.

3T3-L1 Cells↗
PubMed2004

["Tingling feet," forgetfulness, and progressive personality changes in a 63-year-old patient].

A 63-year-old female was admitted to the hospital with leg and forearm paresthesias. We found progressive ataxia, dementia, and psychosocial deterioration. The clinical symptoms, the neurologic and psychiatric abnormalities together with the inflammatory cerebrospinal fluid alteration and the cerebral magnetic resonance imaging changes suggested a paraneoplastic etiology. It was confirmed by paraneoplastic antineuronal antibodies in the patient's serum and the histological diagnosis of a small cell bronchial carcinoma. The prognosis of patients with paraneoplastic symptoms is the better the earlier a diagnosis is established and antitumor therapy is initiated.

Adenomatous Polyps↗
PubMed2004

[33-year old patient with thoraco-abdominal pain and differences of blood pressure].

We report on a 33-year-old women with ulcerative colitis, who presented with inspiratory thoracic pain due to perimyocarditis. Furthermore, postprandial abdominal pain associated with diarrhea and different blood pressure values on both arms were recorded. Computed tomography revealed embolism of the pulmonal arteries and angiography demonstrated stenoses of the subclavian and renal arteries and the celiac trunc suggesting the diagnosis of Takayasu's arteritis. A coronary or infectious etiology could be excluded. Since a coincidence of Takayasu's arteritis and ulcerative colitis has been reported in the literature, abdominal pain and diarrhea can either be explained by the inflammatory bowel disease or by chronic ischemia due to intestinal vasculitis. Differential diagnosis will be facilitated by the future course of the disease.

Abdominal Pain↗
PubMed2004

Identification of influencing variables on adiponectin serum levels in diabetes mellitus type 1 and type 2.

BACKGROUND: Adiponectin represents an adipocyte-specific secretory protein that has been discussed recently as candidate gene and promising new drug target to restore insulin sensitivity in diabetes mellitus type 2. AIM: The aim of the present study was to define influencing variables on adiponectin serum levels in a large cohort of caucasian patients with type 1/type 2 diabetes and healthy controls. Additionally, adiponectin gene polymorphisms (Tyr111His and Gly15Gly) were investigated for possible associations with adiponectin serum levels. METHODS: Adiponectin serum concentrations were measured in a metabolically well characterized cohort of 892 caucasian patients (556 with type 2 diabetes, 118 with type 1 diabetes, 218 controls) by ELISA. Gene polymorphisms were determined by PCR-based RFLP. RESULTS: 1) Adiponectin values are dependent on gender with higher levels in diabetic females than in diabetic males. This gender-specific effect was only restricted to patients with diabetes and cannot be observed in controls. 2) In contrast to previous studies, the presence of diabetes does not influence adiponectin serum levels after correction for BMI. In addition, age has no influence on adiponectin levels. 3) Adiponectin levels are dependent on renal function at a creatinine clearance < 45 ml/min. 4) Regression analysis showed a significant, but only weak correlation between BMI and adiponectin in patients with diabetes mellitus type 2 (r = 0.47) and type 1 (r = 0.57). 5) Adiponectin gene polymorphisms (Tyr111His and Gly15Gly) do not influence adiponectin levels. CONCLUSIONS: Adiponectin serum concentrations can only be interpreted after careful correction for gender and renal function, whereas the genetic variants Tyr11His and Gly15Gly do not seem to play a role. The correlation between BMI and adiponectin was weaker than expected in diabetic patients.

Adiponectin↗
PubMed2004

Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Resistin, a peptide hormone, has been discussed controversially as a missing link between obesity and insulin resistance. In contrast to resistin mRNA expression in adipose tissue, data on human serum levels in obesity and diabetes mellitus is scarce. The physiological range of serum resistin levels, reference values or adjusted percentiles have not yet been determined, making the interpretation of serum resistin concentrations quite difficult. METHODS: Resistin serum concentrations were measured systematically by ELISA in 216 healthy controls, 555 patients with type 2 diabetes and 114 patients with type 1 diabetes. Mean values, median, and range were determined, and BMI-, gender-, and disease-adapted percentiles were calculated for all subgroups. RESULTS: Age and gender did not have any influence on resistin levels. BMI and resistin levels were positively correlated in healthy controls (p = 0.02), albeit with a weak correlation coefficient. This correlation was absent in patients with type 1 and type 2 diabetes. In both genders, healthy controls had significantly higher resistin levels than patients with type 1 and type 2 diabetes (7.9 +/- 0.2 ng/ml vs. 5.7 +/- 0.2 ng/ml and 5.5 +/- 0.1 ng/ml, respectively; p < 0.0001). There was no correlation between resistin levels and occurrence of diabetic retinopathy or nephropathy. CONCLUSIONS: Serum resistin levels can be measured by ELISA over a broad range from 0.6 ng/ml up to 27.7 ng/ml, suggesting that percentiles might be helpful in the interpretation of an individuals resistin value. While age and gender do not influence resistin levels, BMI and occurrence of diabetes have to be considered.

Adolescent↗
PubMed2004

Allelic frequency of the PAI-1 4G/5G promoter polymorphism in patients with type 2 diabetes mellitus and lack of association with PAI-1 plasma levels.

Plasminogen activator inhibitor-1 (PAI-1) levels were found to be associated with obesity, indicating that adipocytes might influence PAI-1 plasma levels. In addition, the 4G/5G promoter polymorphism of the PAI-1 gene possibly modulates PAI-1 gene transcription and, as a consequence, PAI-1 plasma levels. Metabolic parameters, diabetes complications, PAI-1 plasma levels, and PAI-1 promoter genotypes were determined and were tested for correlation in 547 Caucasian patients with type 2 diabetes. Genotyping was performed by using allele-specific PCR, and PAI-1 plasma levels were measured in 547 well-characterized subjects with type 2 diabetes. The allelic frequencies of the polymorphism (0.56 for the 4G-genotype, 0.44 for the 5G-genotype) were not different from those observed in nondiabetic controls. The PAI-1 concentration was positively associated with MI, but not with the 4G/5G polymorphism. Statistical analysis of metabolic parameters, diabetic complications, and the 4G/5G polymorphism revealed that serum fibrinogen levels were significantly higher in the 4G/4G subgroup compared with the 4G/5G and 5G/5G subgroups. The correlation between serum fibrinogen and 4G allele remained significant, even when additional variables, such as gender, age, BMI, duration of diabetes, and HbA1c, were controlled. In patients with type 2 diabetes mellitus, the PAI-1 4G/5G promoter polymorphism does not predict PAI-1 plasma levels and is not associated with common metabolic parameters besides fibrinogen levels.

Aged↗
PubMed2004

Plasminogen activator inhibitor-1 promoter activity in adipocytes is not influenced by the 4 G/5 G promoter polymorphism and is regulated by a USF-1/2 binding site immediately preceding the polymorphic region.

Plasminogen activator inhibitor-1 (PAI-1) levels were found to be associated with obesity indicating that adipocytes influence PAI-1 plasma levels. In addition, the 4 G/5 G promoter polymorphism of the PAI-1 gene may modulate PAI-1 transcription. We investigated the transcriptional regulation of the human PAI-1 gene in adipocytes and analyzed the genetic contribution of the 4 G/5 G polymorphism. The PAI-1 promoter was analyzed using electrophoretic mobility shift assays (EMSAs) and luciferase reporter gene assays. A putative binding site for the upstream stimulatory factor-1/2 (USF-1/2) at the polymorphic region of the PAI-1 promoter was identified. The binding of USF-1/2 was studied using nuclear extracts prepared from adipocytes and was similar in all the promoter variants as analyzed by EMSA. A 257 bp PAI-1 promoter fragment including the 4 G/5 G site was transcriptionally active in adipocytes and was not influenced by the polymorphism. The present data indicate for the first time that USF-1/2 is transcriptionally active in differentiated adipocytes. However, USF-1/2 binding activity and PAI-1 transcription are not influenced by the 4 G/5 G-allele. These data possibly explain the observation that PAI-1 secretion from adipose tissue is not influenced by the PAI-1 promoter polymorphism.

3T3-L1 Cells↗