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Biomedical subjects

P Decker

Publications and source records attributed to P Decker.

At least 19 recordsLinked to original sources

[Guideline for therapy of malignant thyroid tumours: pleading for an actualization].

Total (or near total) thyroidectomy (TE) followed by radioiodine ((131)I) ablation (RIA) of residual thyroid tissue is considered to be the ideal treatment for differentiated thyroid carcinoma. However, the actual guideline of the DGN (German Society of Nuclear Medicine) recommends for the so-called papillary micro-carcinoma of the thyroid (PMC) no further therapeutic strategy (no complete TE, no (131)I-ablation of the remaining lobe). PMC has been defined as papillary carcinoma measuring 1 cm (T1) in maximal diameter according to the World Health Organization classification system for thyroid tumours (1988). The new WHO-classification (starting in 2003) defines the T1-tumour measuring 2 cm in maximal diameter. The authors demand a new, modern guideline, following the new WHO classification. This includes, that despite the overall excellent prognosis for patients with PMC, the treatment of patients with T1-tumours of the new WHO-classification (including the "old" PMC) should be no different from the treatment of patients with conventional papillary thyroid carcinoma, i.e. complete surgery (TE and central lymph node dissection) followed by RIA of residual thyroid tissue. The authors argue that it is not appropriate to consider the tumour size as the single most important key factor for therapy and prognosis. Even small tumours may have poor prognostic factors, such as lymph node metastasis, multifocality or molecular characteristics (expression of oncogenes).

Contraindications↗

Changes in TH1/TH2 immunity after endovascular and conventional infrarenal aortic aneurysm repair: its relevance for clinical practice.

OBJECTIVE: to evaluate local surgical trauma induced by endovascular (TPEG) and conventional infrarenal aortic aneurysm repair (AAA-C), the inflammatory response and changes in cell-mediated and antibody-mediated immunity as illustrated by the type-1/type-2 T-helper (TH1/TH2) cell balance were investigated. DESIGN: prospective study. PATIENTS AND METHODS: sixteen patients were included, eight patients underwent AAA-C and eight TPEG. Venous peripheral blood samples were collected 24h preoperatively and 24, 48, 72h, 5 and 7 days postoperatively. Besides the WBC, intracellular TH1/TH2 cytokines (IFN-gamma/IL-4) and the cell surface markers HLA-DR on monocytes and CD23 on B cells were measured by four colour flow cytometry. RESULTS: statistically significant higher values in the AAA-C group were demonstrated for neutrophiles. The TH1/TH2 immunobalance (expressed by forming the ratio of IFN-(gamma/IL-4 producing T cells as well as by the ratio of HLA-DR(pos) monocytes/CD23(pos) B-cells) showed a significant shift towards TH2 immunity in the AAA-C group whereas TPEG led to a significant lesser shift 24-72h after surgery (p < 0.05). CONCLUSIONS: TPEG leads to a minor distortion of the TH1/TH2 immunobalance. This implies that TPEG is a less stressing procedure, that is especially beneficial in patients whose conditions are considered less suitable for AAA-C due to age and serious comorbidity.

Aged↗

[Massive localized lymphedema - a rare entity].

Massive localized lymphedema is a rare disease. Only a few cases have been described in the literature. These monstrous pseudotumors of the subcutis are mostly localized in the inguinal region or at the lower extremity. These tumors often show a slow growth for many years. Besides hernias, lipomatous tumors must be distinguished. The therapy of choice is the excision of the tumor. Relapse is not uncommon in the few cases described in the literature so far. The diagnostic procedure and therapy of an 48-year-old women with a massive localized lymphedema weighing about 22 kg are demonstrated and discussed.

Diagnosis, Differential↗

The congenital duplication cyst: a rare differential diagnosis of retrosternal pain and dysphagia in a young patient.

Congenital cysts are malformations developing from the endoderm and mesoderm of the digestive and respiratory system in the early weeks of gestation. Unilocular or multilocular dysontogenic cysts are most commonly thoracically located adjacent to the trachea and bronchus and the development of an oesophageal duplication cyst in the oesophageal wall is extremely rare. The duplication cyst in the adult is usually asymptomatic and an incidental diagnosis. Potential symptoms include dysphagia and retrosternal pain. Next to endoscopy and computer tomography, endoscopic ultrasonography is mandatory for a distinguished and accurate preoperative evaluation. Transthoracic excision is crucial for definitive diagnosis and inhibition of complications.

Adult↗

[Thoracoscopic video-assisted talcum pleurodesis (TTP)--effective treatment of malignant pleural effusion].

INTRODUCTION: Aim of the palliative therapeutic procedure should be a fast, efficient and pain free treatment of the malignant pleural effusions. PATIENTS AND METHOD: Since 1995 the results of malignant pleural effusions treatment were analyzed retrospectively in 46 patients who underwent 51 video-assisted TTP. The most frequent origin of malignant pleural effusion was breast cancer, followed by bronchial carcinoma. Precondition for video-assisted TTP was the verification of a malignant pleural effusion by cytology. RESULTS: Following TTP one patient suffered from pneumonia, two recurrent diseases occurred. Four patients died due to their severe primary malignancy. Average hospitalization was 8 days (3-55). CONCLUSION: Video-assisted TTP is the standard procedure in palliative treatment of malignant pleural effusion; the recurrence rate is low and the technique minimal invasive.

Adult↗

[Aortic rupture in Behçet's disease].

Behçet's disease is a vasculitis of unknown aetiology, which becomes apparent by ocular and mucocutaneous symptoms. In rare cases, owing to vasculitis of the vasa vasorum of large arteries, necrosis of the vascular wall and thus spurious aneurysms occur. The case of a 41-year-old patient is described who presented with a rupture of an infrarenal aortic aneurysm due to Behçet's disease. Therapy consisted of placement of an aortic-aortic Dacron prosthesis. On the basis of the case report, the diagnostic approach, the therapy and the value of secondary prophylaxis of Behçet's disease are discussed.

Adult↗

Use of the Polyflex stent in the palliative therapy of esophageal carcinoma: results in 14 cases and review of the literature.

BACKGROUND: Several prospective randomized trials have shown that self-expanding stents have advantages over conventional plastic tubes. Nevertheless, the optimal stent has not yet been developed. The Polyflex stent is a completely new model that represents an improvement over the old metal stents. We have used this stent in a prospective study and herein our present preliminary results. METHODS: In 14 patients with nonresectable esophageal carcinoma, the Polyflex stent was implanted to reduce dysphagia. The grade of dysphagia, the complications following intervention, and the patients' total survival time were documented prospectively every 4 weeks. RESULTS: The implantation of the stent was successful in all cases. The grade of the dysphagia was reduced from 3.0 to 0.5 after stent implantation. One patient died during the hospital stay from a non-stent-induced complication. Stent dislocation occurred once, and tumor overgrowth at the stent margins was observed twice. The mean survival time was 6.2 months, and the reintervention rate was 21.3%. CONCLUSION: The new Polyflex stent, which is based on a completely new design, can be implanted without any difficulty and has had very good short- and long-term results. Therefore, it is a worthy alternative to the metal stents in current use.

Adenocarcinoma↗

[Experiences in stage-adapted therapy of pleural empyema].

INTRODUCTION: Up till now the phases adapted treatment of a pleural empyema unfortunately is still not obvious, but recently the operative spectrum has been widened in the field of video-assisted thoracoscopic surgery (VATS) of the pleural empyema. PATIENTS AND METHODS: In the present study we examined all our patients with a pleural empyema and we followed them for a postoperative period of 4 years analysing our therapy-efficacy and our treatment concept of pleural empyema. RESULTS: 52 out of 102 patients--who suffered from a pleural empyema in the last 10 years--were reexamined postoperatively. In 96% of the 102 cases we found a phase II-III empyema. Initially all patients were treated with a closed-chest-tube drainage, followed by an operation in 78%. In 6 cases a video-assisted-thoracoscopic evacuation of the cavity with an early decortication was performed. All the 52 patients who were treated in an early phase showed the best functional results 4 years later. CONCLUSION: Especially in phase III the open operative revision of a pleural empyema is the method of choice. In the fibrinopurulent phase the drainage therapy may be sufficient. If the empyema cavity is divided we recommend the early video-assisted-thoracoscopic revision of the thoracic empyema.

Adolescent↗

Detection of nucleosome particles in serum and plasma from patients with systemic lupus erythematosus using monoclonal antibody 4H7.

OBJECTIVE: To develop a monoclonal antibody reagent that would react with nucleosomes but not directly with constituent double stranded DNA (dsDNA) or with histones. METHODS: Mice were immunized with highly purified chicken mononucleosomes and hybridomas employed to produce Mab that did not react with dsDNA or histones but still showed reactivity with nucleosomes. RESULTS: Murine monoclonal IgG antibody 4H7, generated from a mouse immunized with highly purified chicken erythrocyte nucleosomes, showed no direct ELISA reactivity with either dsDNA or isolated histones or with Sm and RNP antigens or combinations of any of these components. Mab 4H7 did show strong ELISA reactivity for chicken erythrocyte and calf thymus nucleosomes as well as for human leukocyte nucleosomes. The Mab did show strong ELISA reactions with peptides 1-25 of histone H2B and 1-21 of H3, which correspond to sequences known to be located at the surface of nucleosomes. We then measured relative serum levels of 4H7 reactive nucleosome antigen in 140 patients with systemic lupus erythematosus (SLE) in parallel with 50 non-SLE patients with other types of connective tissue disease and 92 healthy subjects. Occasional low levels of serum nucleosomal antigen were seen in 4 of 92 controls, but many patients with SLE (66/140) showed marked elevations of serum nucleosomal antigen. No difference was observed when serum or plasma samples were studied. A marked correlation (R = 0.401, p < 0.0001) was noted when disease activity score (SLEDAI) was plotted against optical density value measured with 4H7 in ELISA. Further, the levels of circulating nucleosomes were raised in SLE patients with very active central nervous system and renal involvement. CONCLUSION: Presence of nucleosome related antigen in sera from patients with SLE may provide insight into the sequence of disease related antigenic stimuli in active SLE.

Adult↗

Identification of a minimal T cell epitope recognized by antinucleosome Th cells in the C-terminal region of histone H4.

Autoreactive T cells responding to systemic autoantigens have been characterized in patients and mice with autoimmune diseases and in healthy individuals. Using peptides covering the whole sequence of histone H4, we characterized several epitopes recognized by lymph node Th cells from nonsystemic lupus erythematosus-prone mice immunized with the same peptides, the H4 protein, or nucleosomes. Multiple T epitopes were identified after immunizing H-2d BALB/c mice with H4 peptides. They spanned residues 28-42, 30-47, 66-83, 72-89, and 85-102. Within the region 85-102, a minimal CD4+ T epitope containing residues 88-99 was characterized. Although Abs to peptide 88-99 recognized H4, this peptide does not contain a dominant B cell epitope recognized by anti-H4 Abs raised in BALB/c mice or Abs from NZB/NZW H-2d/z lupus mice. Th cells primed in vivo with H4 responded to H4, but not to peptide 88-99. However, this peptide was able to stimulate the proliferation and IL-2 secretion of Th cells generated after immunization with nucleosomes. H488-99 thus represents a cryptic epitope with regard to H4 and a supradominant epitope presented by nucleosome, a supramolecular complex that plays a key role in lupus. This study shows that in the normal repertoire of naive BALB/c mice, autoreactive Th cells specific for histones are not deleted. The reactivity of these Th cells seems to be relatively restricted and resembles that of Th clones generated from SNF1 ((SWR x NZB)F1; I-Ad/q) lupus mice described earlier.

Amino Acid Sequence↗

Molecular and structural properties of three autoimmune IgG monoclonal antibodies to histone H2B.

In systemic autoimmune diseases such as lupus the immune system produces autoantibodies to nuclear antigens including DNA and histone molecules. In the present study, we describe three monoclonal IgG antibodies that have been obtained from lupus-prone MRL/lpr mice. These three antibodies react with the amino terminus of histone H2B, a region of the molecule that is accessible in chromatin. Using a series of overlapping H2B synthetic peptides and structural analogues, we have mapped the different epitopes recognized by these antibodies. We have also sequenced the combining sites (variable regions) of the antibodies and modeled their interactions with the corresponding epitopes. Overall, the data suggest that the mechanisms of interaction with antigen are different for each of the three antibodies, even though they all react with the amino-terminal domain of the histone H2B molecule. The results also suggest that the binding between these antibodies and histone H2B is different from that between most antibodies and conventional protein antigens since the heavy chain complementarity-determining region 3 appears to play only a limited role in the three antibodies tested. The study of the interaction between self-antigens and spontaneously occurring autoantibodies may help us elucidate the mechanisms driving the expansion of self-reactive lymphocytes.

Amino Acid Sequence↗

Inhibition of caspase-3-mediated poly(ADP-ribose) polymerase (PARP) apoptotic cleavage by human PARP autoantibodies and effect on cells undergoing apoptosis.

Autoantibodies directed to nuclear antigens are serological hallmarks of autoimmune rheumatic diseases such as systemic lupus erythematosus. Although much more is known about the molecular identity and functions of targeted self-antigens, with few exceptions, evidence that autoantibodies to these targets have a particular function and contribute directly to the pathological process is lacking. Here we show that human autoantibodies reacting with the zinc fingers of poly(ADP-ribose) polymerase involved in the recognition of damaged DNA totally prevent the cleavage of poly(ADP-ribose) polymerase by caspase-3, a process that normally occurs during early apoptosis. Furthermore, these antibodies, which are frequent in certain autoimmune rheumatic and bowel diseases, affect the characteristic features of apoptosis and increase cell survival ex vivo. This new observation is important, because failure to remove autoimmune or abnormal cells can give rise to prolonged autoimmune stimulation and tumor formation.

Antibody Specificity↗

The Kluyver effect for trehalose in Saccharomyces cerevisiae.

Saccharomyces cerevisiae cells are able to grow using trehalose as a sole source of carbon and energy. However, the biomass yield obtained with trehalose was higher, and the specific growth rate lower, than that obtained with glucose or maltose. The respiratory inhibitor antimycin A prevented cell growth on trehalose, and no ethanol or glycerol was formed during batch growth on this carbon source. Thus, S. cerevisiae exhibits the KLUYVER effect for trehalose: this disaccharide is assimilated and respired, but, in contrast to glucose or maltose, it cannot be fermented. The high-affinity trehalose-H+ symporter encoded by the AGT1 gene is required for growth on trehalose. Analysis of the differences in the metabolism of maltose and trehalose (both disaccharides of glucose transported by active transport systems) indicated that the absence of trehalose fermentation is a consequence of low sugar influx into the cells during growth on this carbon source.

Antifungal Agents↗

FDG PET and immunoscintigraphy with 99mTc-labeled antibody fragments for detection of the recurrence of colorectal carcinoma.

UNLABELLED: The aim of this study was to compare FDG PET with a new monoclonal antibody-based imaging agent that comprises an anti-carcinoembryonic antigen (CEA) monoclonal antibody Fab' fragment directly labeled with 99mTc. METHODS: Twenty-eight patients who were previously treated for colorectal carcinoma and in whom recurrence was suspected were examined with FDG PET and immunoscintigraphy. The most common indications were an elevation of serum CEA (13 patients), suggestive lesions documented by CT (9 patients), sonography (4 patients), and severe constipation (2 patients). Planar imaging and SPECT were performed 4-6 h after intravenous injection of the new imaging agent. Whole-body PET was performed 45-60 min after intravenous injection of FDG. The findings were confirmed by conventional diagnostic modalities, surgery, and histology. RESULTS: Histology confirmed local tumor recurrence in 9 of 28 patients. Clinical follow-up or CT confirmed the presence of liver metastases in 9 patients and lymph node involvement, lung metastases, and bone metastases in 2 patients each. The new agent correctly detected 8 of 9 local recurrences, whereas FDG PET was able to detect all 9 cases and in 1 case was false-positive. Liver metastases were confirmed in 9 patients by FDG PET but in only 1 patient by the new agent. Two cases with lymph node metastases and 2 cases with lung metastases were correctly identified by FDG PET, but none were detected by the new agent. Finally, bone metastases were identified in 1 patient by FDG PET but not with the new agent, whereas bone marrow infiltration (n = 1) was diagnosed by both imaging modalities. CONCLUSION: These results indicate that FDG PET and 99mTc-labeled anti-CEA Fab' are suitable for the diagnosis of local recurrence of colorectal carcinoma but that FDG PET is clearly superior in the detection of distant metastases (liver, bone, and lung) and lymph node involvement.

Antibodies, Monoclonal↗

Resistance to endotoxic shock as a consequence of defective NF-kappaB activation in poly (ADP-ribose) polymerase-1 deficient mice.

Poly (ADP-ribose) polymerase-1 is a nuclear DNA-binding protein that participates in the DNA base excision repair pathway in response to genotoxic stress in mammalian cells. Here we show that PARP-1-deficient cells are defective in NF-kappaB-dependent transcription activation, but not in its nuclear translocation, in response to TNF-alpha. Treating mice with lipopolysaccharide (LPS) resulted in the rapid activation of NF-kappaB in macrophages from PARP-1(+/+) but not from PARP-1(-/-) mice. PARP-1-deficient mice were extremely resistant to LPS-induced endotoxic shock. The molecular basis for this resistance relies on an almost complete abrogation of NF-kappaB-dependent accumulation of TNF-alpha in the serum and a down-regulation of inducible nitric oxide synthase (iNOS), leading to decreased NO synthesis, which is the main source of free radical generation during inflammation. These results demonstrate a functional association in vivo between PARP-1 and NF-kappaB, with consequences for the transcriptional activation of NF-kappaB and a systemic inflammatory process.

3T3 Cells↗

PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase.

Poly(ADP-ribosylation) is a post-translational modification of nuclear proteins in response to DNA damage that activates the base excision repair machinery. Poly(ADP-ribose) polymerase which we will now call PARP-1, has been the only known enzyme of this type for over 30 years. Here, we describe a cDNA encoding a 62-kDa protein that shares considerable homology with the catalytic domain of PARP-1 and also contains a basic DNA-binding domain. We propose to call this enzyme poly(ADP-ribose) polymerase 2 (PARP-2). The PARP-2 gene maps to chromosome 14C1 and 14q11.2 in mouse and human, respectively. Purified recombinant mouse PARP-2 is a damaged DNA-binding protein in vitro and catalyzes the formation of poly(ADP-ribose) polymers in a DNA-dependent manner. PARP-2 displays automodification properties similar to PARP-1. The protein is localized in the nucleus in vivo and may account for the residual poly(ADP-ribose) synthesis observed in PARP-1-deficient cells, treated with alkylating agents or hydrogen peroxide.

3T3 Cells↗

Hydronephrosis after aorto bifemoral graft surgery: a marker for late graft complications.

Ureteral obstructions are serious late complications after aortoiliac reconstructive vascular surgery, which lead to loss of kidney function if they remain untreated. One case report serves to describe the incidence, aetiology, clinical presentation and treatment options of an obstructive uropathy following graft surgery. Hydronephrosis due to a ureteral obstruction is considered as a "marker" of graft complication. Therefore, ultrasound examination and close follow-up beyond 1 year are recommended in all patients who undergo aortoiliac surgery.

Aorta, Abdominal↗