20 results on '"Raphaela Verheggen"'
Search Results
2. Tran's Arterial Embolization of an Unusual Pleomorphic Rhabdomyosarcoma in Adulthood for Better Preoperative Conditioning
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Sheila Fatehpur, Johann Philipp Addicks, Van Khiem Tran, Raphaela Verheggen, and Masoud Mirzaie
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Rhabdomyosarcomas, being the most common sarcomas of childhood, have an extremely poor prognosis, and pleomorphic rhabdomyosarcomas occur very rarely in adults. Despite advanced diagnostics, it is not uncommon for such tumours to be misinterpreted. The 73-year-old patient was diagnosed with a swelling on the inner side of the left thigh 3 years previously after a minor trauma, which was interpreted as a small well-revascularised haemangioma in original CT angiography. While this mass showed little change over the last 2.5 years, a sudden progression of growth occurred 6 months ago. With the working diagnosis of a haemangioma, differential diagnosis of a schwanoma, the vessels supplying the tumour from profunda femoral artery were visualised preoperatively in a selective angiography and embolised. Shortly before the operation, dupex sonography revealed a renewed hypervasculariasis of the tumour. The supplied vessels from the superficial femoral artery and from the main left profunda trunc were embolised with Embosphere Microspheres 500-700 (Merit). Complete devascularisation of the tumour was achieved, so that the tumour could be resected very effectively in accordance with the compartment. The histological work-up of the tumour resulted in the diagnosis of a pleomorphic rhabdomyosarcoma grade II with tumor-free margins. Preoperative embolisation could be an effective method for preoperative conditioning of such rhabdomyosarcoma. Using this example, this study discusses the current diagnostic and therapeutic options for adult rhabdomyosarcomas.
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- 2021
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3. BIBN4096BS and CGRP8-37 antagonize the relaxant effects of α-CGRP more than those of β-CGRP in human extracranial arteries
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Alberto J. Kaumann, Steffi Hoffmann, Raphaela Verheggen, Martin Webel, and Kordian Wojtas
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Adult ,Male ,medicine.medical_specialty ,Calcitonin Gene-Related Peptide ,Vasodilator Agents ,Pharmacology toxicology ,Peptide ,Calcitonin gene-related peptide ,Muscle, Smooth, Vascular ,Piperazines ,Internal medicine ,medicine ,Humans ,Binding site ,Receptor ,CGRP receptor ,Aged ,Pharmacology ,chemistry.chemical_classification ,integumentary system ,Chemistry ,General Medicine ,Anatomy ,Middle Aged ,Peptide Fragments ,Temporal Arteries ,Vasodilation ,Endocrinology ,nervous system ,Vasoconstriction ,Quinazolines ,Female ,Temporal artery ,Antagonism ,Miotics - Abstract
We hypothesize that dilatation of extracranial arteries during migraine could be caused by CGRP. We compared the relaxant effects of alpha-calcitonin gene-related peptide (alpha-CGRP) and beta-calcitonin gene-related peptide (beta-CGRP) and the antagonism by BIBN4096BS and CGRP(8-37) on rings of human temporal and occipital arteries precontracted with KCl. beta-CGRP relaxed temporal (-logEC50M = 8.1) and occipital arteries (-logEC50M = 7.6) with 19-fold and 29-fold lower potencies respectively than alpha-CGRP. Nearly maximal effective concentrations of alpha-CGRP (4 nM) and beta-CGRP (50 nM) caused stable relaxations of the temporal artery for 4 h without fading. BIBN4094BS antagonized the effects of alpha-CGRP (pK(B) = 10.1 and 9.9, respectively) more than beta-CGRP (pK(B) = 9.3 and 9.2 respectively) on both temporal and occipital arteries. CGRP(8-37) antagonized the effects of alpha-CGRP (pK(B) = 6.6 and 6.4 respectively) more than beta-CGRP (pK(B) = 5.7 and 5.5 respectively) on both temporal and occipital arteries. Antagonism of the relaxant effects of alpha-CGRP (4 nM) and beta-CGRP (50 nM) by BIBN4096BS (10 and 100 nM) was reversible for beta-CGRP, but irreversible for alpha-CGRP, 1 h after BIBN4096BS washout. We conclude that alpha-CGRP and beta-CGRP interact either at different binding sites of the same CGRP receptor system or all together with different receptor systems in human extracranial arteries. BIBN4096BS binds more firmly to the receptor activated by alpha-CGRP than to the receptor activated by beta-CGRP.
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- 2005
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4. BIBN4096BS is a potent competitive antagonist of the relaxant effects of α-CGRP on human temporal artery: comparison with CGRP(8-37)
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Katja Bumann, Raphaela Verheggen, and Alberto J. Kaumann
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Pharmacology ,0303 health sciences ,medicine.medical_specialty ,Papaverine ,integumentary system ,business.industry ,Calcitonin gene-related peptide ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Muscle relaxation ,Endocrinology ,Migraine ,Competitive antagonist ,Internal medicine ,medicine ,Sodium nitroprusside ,Antagonism ,Receptor ,business ,030217 neurology & neurosurgery ,030304 developmental biology ,medicine.drug - Abstract
Release of CGRP during migraine may produce harmful dilatation of cranial arteries, thereby possibly causing pain. We have compared the antagonism by BIBN4096BS and CGRP(8-37) of the relaxant effects of α-CGRP on rings of human temporal artery. α-CGRP relaxed the arteries precontracted with 9 – 24 mM KCl (−logEC50=9.4) nearly as efficaciously as sodium nitroprusside (10 μM). BIBN4096BS (0.1 – 100 nM) antagonized the effects of α-CGRP in surmountable manner with slopes of Schild-plots not different from unity. −LogKB values of 10.1 and 10.4 were estimated for BIBN4096BS when administered before or during the KCl-contracture respectively. BIBN4096BS (1 μM) did not modify the relaxant effects of papaverine and sodium nitroprusside. CGRP(8-37) (1 – 10 μM) antagonized the effects of α-CGRP in a surmountable manner with slopes of Schild-plots not different from unity. −LogKB values of 6.6 and 6.7 were estimated for CGRP(8-37) administered before or during the KCl-contracture respectively. The high affinity of BIBN4096BS for CGRP receptors of human temporal artery makes it an excellent tool to explore the hypothesis of CGRP-evoked cerebral vasodilation in migraine. British Journal of Pharmacology (2002) 136, 120–126; doi:10.1038/sj.bjp.0704682
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- 2002
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5. Myopericytoma: A Series of 5 Cases Affecting the Nervous System
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Uwe Wildförster, Walter Stummer, Klaus Müller, Astrid Jeibmann, Raphaela Verheggen, and Markus Holling
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Nervous system ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Spinal Cord Neoplasm ,Myopericytoma ,Vascular Neoplasm ,Diplopia ,Medicine ,Humans ,Spinal Cord Neoplasms ,Aged ,Hemangiopericytoma ,Muscle Weakness ,Ophthalmoplegia ,medicine.diagnostic_test ,business.industry ,Brain Neoplasms ,Soft tissue ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,Vascular Neoplasms ,medicine.anatomical_structure ,Neuralgia ,Surgery ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Follow-Up Studies - Abstract
Background Myopericytomas are benign vascular tumors composed of perivascular myoid cells that usually arise in superficial soft tissues of the extremities. Methods We here report on 5 cases of myopericytoma, malignant myopericytoma, and glomangiopericytoma arising from subcutaneous, paraspinal, orbital, and sellar regions that secondarily involved the nervous system. Patients experienced orbital swelling, progressing neuropathic pain, dermatoma specific pain, and oculomotor paresis. Results Mean age at diagnosis was 56.8 years (range, 38–74 years). After a mean follow-up of 38 months, no recurrence was detected. All tumors were unencapsulated but relatively well-circumscribed lesions, showing typical histologic and immunohistochemical features of soft-tissue myopericytoma, including one malignant case. Conclusion We conclude that myopericytoma may affect the nervous system and for prognostic and therapeutic reasons, needs to be differentiated from other vascular tumors.
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- 2014
6. Spontaneous adrenal hemorrhage: a little-known complication of intracranial tumor surgery
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Wolfgang Brück, Bastian Gunawan, Raphaela Verheggen, Bettina Lange, Angelika Gutenberg, Joerg Larsen, and Veit Rohde
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Male ,medicine.medical_specialty ,Intracranial tumor ,Adrenal Gland Diseases ,Hemorrhage ,Context (language use) ,Neurosurgical Procedures ,Meningioma ,Central nervous system disease ,03 medical and health sciences ,0302 clinical medicine ,Adrenal Cortex Hormones ,Seizures ,medicine ,Humans ,030212 general & internal medicine ,Intraoperative Complications ,Aged ,Falcine Meningioma ,business.industry ,Adrenalectomy ,medicine.disease ,3. Good health ,Surgery ,030220 oncology & carcinogenesis ,Intracranial surgery ,Adrenal Cortex Function Tests ,Complication ,Adrenal Hemorrhage ,business - Abstract
✓ Nontraumatic adrenal hemorrhage in adults is uncommon and unexpected in the context of intracranial surgery. The authors report on a patient in whom hemodynamically relevant retroperitoneal bleeding developed within hours after an otherwise uneventful operation for a falcine meningioma. In this brief report they seek to draw attention to this rare but life-threatening complication, because rapid diagnosis can be life-saving.
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- 2007
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7. 5-HT1Breceptor-mediated contractions in human temporal artery: evidence from selective antagonists and 5-HT receptor mRNA expression
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Marcus Schindler, A. G. Hundeshagen, Raphaela Verheggen, A. M. Brown, and Alberto J. Kaumann
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Pharmacology ,0303 health sciences ,medicine.medical_specialty ,Ketanserin ,Antagonist ,Biology ,3. Good health ,Biphenyl compound ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Serotonin Antagonists ,medicine.symptom ,Receptor ,Antagonism ,030217 neurology & neurosurgery ,5-HT receptor ,030304 developmental biology ,Muscle contraction ,medicine.drug - Abstract
1 In the human temporal artery both 5-HT1-like and 5-HT2A receptors mediate the contractile effects of 5-hydroxytryptamine (5-HT) and we have suggested that the 5-HT1-like receptors resemble more closely recombinant 5-HT1B than 5-HT1D receptors. To investigate further which subtype is involved, we investigated the blockade of 5-HT-induced contractions by the 5-HT1B-selective antagonist SB-224289 (2,3,6,7-tetrahydro-1′-methyl-5-{2-methyl-4′[(5-methyl-1,2,4-oxadiazole-3-yl) biphenyl-4-yl] carbonyl} furo[2,3-f]indole-3-spiro-4′-piperidine oxalate) and the 5-HT1D-selective antagonist BRL-15572 (1-phenyl-3[4-3-chlorophenyl piperazin-1-yl] phenylpropan-2-ol). We also used RT-PCR to search for the mRNA of 5-HT1B, 5-HT1D and other 5-HT receptors. 2 The contractile effects of 5-HT in temporal artery rings were partially antagonized by SB-224289 (20, 200 nm) (apparent KB = 1 nm) and ketanserin (1 μm) but not by BRL-15572 (500 nm). 3 Sumatriptan evoked contractions (EC50, 170 nm) that were resistant to blockade by BRL-15572 (500 nm) but antagonized by SB-224289 (20, 200 nm). 4 The potency of 5-HT (EC50) was estimated to be 94 nm for the ketanserin-sensitive receptor and 34 nm for the SB-224289-sensitive receptor. The fraction of maximal 5-HT response mediated through SB-224289-sensitive receptors was 0.20–0.67, the remainder being mediated through ketanserin-sensitive receptors. 5 We detected arterial receptor mRNA for the following receptors (incidence): 5-HT1B (8/8), 5-HT1D (2/8), 5-HT1F (0/4), 5-HT2A (0/8), 5-HT2B (0/8), 5-HT2C (0/8), 5-HT4 (4/8) and 5-HT7 (4/8). 6 We conclude that the ketanserin-resistant fraction of the 5-HT effects and the effects of sumatriptan are mediated by 5-HT1B receptors. The lack of antagonism by BRL-15572 rules out 5-HT1D receptors as mediators of the contractile effects of 5-HT and sumatriptan. British Journal of Pharmacology (1998) 124, 1345–1354; doi:10.1038/sj.bjp.0701929
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- 1998
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8. The potential value of ultrasonography in the evaluation of carpal tunnel syndrome
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Raphaela Verheggen, Carl D. Reimers, Hans-Joachim Bittermann, and Henrich Kele
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Adult ,Male ,medicine.medical_specialty ,Electrodiagnosis ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Reference Values ,medicine ,Humans ,Carpal tunnel ,Carpal tunnel syndrome ,Aged ,Ultrasonography ,Therapeutic strategy ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Ultrasound ,Middle Aged ,Wrist ,medicine.disease ,Carpal Tunnel Syndrome ,Median Nerve ,nervous system diseases ,Surgery ,Electrophysiology ,medicine.anatomical_structure ,Predictive value of tests ,Reference values ,Female ,Neurology (clinical) ,Radiology ,business ,030217 neurology & neurosurgery - Abstract
The authors compared ultrasonography with electrophysiology for the diagnosis of carpal tunnel syndrome (CTS) on 110 clinically affected wrists. An increased cross sectional area in the proximal carpal tunnel larger than 0.11 cm(2) in combination with compression signs on longitudinal scans proved to be highly predictive for CTS (sensitivity, 89.1%; specificity, 98.0%). Ultrasound was comparable to electrophysiology in the diagnosis of CTS, and in 35% of cases changes in morphology suggested a specific therapeutic strategy.
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- 2003
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9. [Reconstruction of the anterior wall of frontal sinus with biopolymers]
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Axel, Nitsch, Raphaela, Verheggen, Jörg, Holste, and Hans-Albert, Merten
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Biopolymers ,Bone Regeneration ,Bone Transplantation ,Guided Tissue Regeneration ,Swine ,Polyesters ,Absorbable Implants ,Bone Substitutes ,Animals ,Frontal Sinus ,Swine, Miniature ,Membranes, Artificial ,Polyglycolic Acid - Abstract
The two biopolymers Ethisorb and its modification Ethisorb Rapid were implanted in 80 defects of the anterior wall of frontal sinus in 20 Goettingen minipigs to analyze density of trabecula (Mann-Whtiney-Rank-Sum-Test), degradation of biopolymers and histomorphology. To optimate bone regeneration, particular resorbable membranes and autogenic spongiosa chips were used. The animals were killed after six, 12, 26 and 52 weeks and then postoperative undecalcified bone cuts were obtained. All in all, with Ethisorb contrary to Ethisorb Rapid a faster biopolymer resorption in the 12th and 26th week with a statistically significant greater density of trabecula could be observed. The use of resorbable membranes and autogenic spongiosa chips led, in comparison to simple implantation of biopolymers, to significantly greater densities of trabecula. The use of Ethisorb contrary to Ethisorb Rapid with membranes led to a Guided Bone Regeneration (GBR) with persistence of membrane particles to week 12 and 26. By mixing biopolymers with autogenic spongiosa chips a multiloculated bone regeneration could be generated. For Ethisorb with resorbable membranes and autogenic spongiosa chips the best bone regeneration with highest densities of trabecula could be recognized.
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- 2008
10. [Histological comparison of different biopolymers in osseous defects]
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Axel, Nitsch, Hans-Albert, Merten, and Raphaela, Verheggen
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Bone Regeneration ,Bone Transplantation ,Tibia ,Swine ,Polyesters ,Absorbable Implants ,Bone Substitutes ,Animals ,Swine, Miniature ,Bone and Bones ,Polyglycolic Acid - Abstract
The goal of this animal study in Goettingen minipigs was to compare Ethisorb with its modification Ethisorb Rapid where the hydrolytic degradation process has started, with respect to degradation and bony substitution qualitites. For comparison, both biopolymers were implanted with and without addition of autogenic spongiosa chips in comparison with blank defects in metaphysis of the tibia. The animals were killed after six, 12, 26 and 52 weeks. Undecalcified bone cuts were obtained and subjected to a histomorphometric and histomorphological analysis. All in all, with increasing time after implantation a continuous decrease of the density of trabecula could be observed. In comparison to Ethisorb Rapid and blank defects, the implantation of the slowly degrading but quickly resorbing Ethisorb led to statistically significantly higher densities of trabecula (Tuckey Test, por = 0.05) and to best bone regeneration. In contrast to this, Ethisorb Rapid could be degraded more quickly but resorbed more slowly. In the polarizing microscope, Ethisorb could still be detected after 12 weeks of implantation. Ethisorb Rapid could still be detected after 26 weeks of implantation. To conclude, Ethisorb proved to be a suitable scaffold for autogenic spongiosa-chips in critical-size defects of the tibia so that a multiloculated bone regeneration could be obtained.
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- 2007
11. 5-Hydroxytryptamine-induced contraction of human temporal arteries coexpressing 5-HT2A receptors and wild-type or variant (Phe124Cys) 5-HT1B receptors: increased contribution of 5-HT1B receptors to the total contractile amplitude in arteries from Phe124Cys heterozygous individuals
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Raphaela Verheggen, Manfred Göthert, Michael Brüss, Alberto J. Kaumann, Anne Lücker, and Inga Werner
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Agonist ,Adult ,Male ,medicine.medical_specialty ,Heterozygote ,Serotonin ,Contraction (grammar) ,Adolescent ,Genotype ,medicine.drug_class ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Genetics ,medicine ,Humans ,Receptor, Serotonin, 5-HT2A ,General Pharmacology, Toxicology and Pharmaceutics ,Receptor ,Molecular Biology ,Genetics (clinical) ,030304 developmental biology ,Aged ,Aged, 80 and over ,0303 health sciences ,Sumatriptan ,Wild type ,Antagonist ,Genetic Variation ,Middle Aged ,Temporal Arteries ,Endocrinology ,Receptor, Serotonin, 5-HT1B ,Molecular Medicine ,Female ,medicine.symptom ,030217 neurology & neurosurgery ,Vasoconstriction ,Muscle contraction ,Muscle Contraction - Abstract
Objectives Expression studies of the rare Phe124Cys sequence variant of the human 5-HT 1B receptor in HEK293 cells demonstrated that 5-hydroxytryptamine (5-HT) and sumatriptan had both three times higher binding affinity and agonist potency at the variant receptor than wild-type receptor. We examined whether in-vivo expression of the variant compared to the wild-type Phe/Phe genotype at codon 124 of the 5-HT 1B receptor in human temporal arteries modifies their agonist-induced contraction. Methods Rings of arteries, coexpressing 5-HT 1B and 5-HT 2A receptors, from 98 patients undergoing neurosurgery were set up to measure contraction. Blood sample genotyping was performed by PCR using a mutagenic primer which induces a NheI restriction site in the Cys but not in the Phe allele. Results Three patients exhibited the Cys/Phe genotype, probably yielding coexpression of both the 124Phe and the 124Cys 5-HT 1B receptors. In 95 Phe/Phe patients, exclusively the 124Phe receptor was expressed. The contractile potencies of 5-HT and sumatriptan were not significantly different in arteries from Cys/Phe or Phe/Phe individuals. The 5-HT 1B receptor-selective antagonist SB224289 was five-fold more potent in blocking the effects of 5-HT in arteries from three Cys/Phe than from 30 Phe/ Phe individuals (P
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- 2006
12. Cellular, histomorphologic, and clinical characteristics of a new octyl-2-cyanoacrylate skin adhesive
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Johannes Franz Hönig, Alfred Pabyk, Axel Nitsch, Hans-Albert Merten, and Raphaela Verheggen
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Pathology ,medicine.medical_specialty ,Swine ,Administration, Topical ,Biocompatible Materials ,In Vitro Techniques ,law.invention ,Suture (anatomy) ,Dermis ,law ,Ultimate tensile strength ,Surgical Wound Dehiscence ,medicine ,Animals ,Cyanoacrylates ,Submandibular lymph nodes ,Wound Healing ,business.industry ,Enbucrilate ,Plastic surgery ,Disease Models, Animal ,medicine.anatomical_structure ,Treatment Outcome ,Cyanoacrylate ,Swine, Miniature ,Surgery ,Tissue Adhesives ,Adhesive ,business ,Neck ,Biomedical engineering - Abstract
Short-chained cyanoacrylates have been used for many years for topical skin closure. Toxic effects in cell culture of a new long-chained octyl-2-cyanoacrylate tissue adhesive are compared with those of short-chained ethyl-2- and butyl-2-cyanoacrylates. Two cellular tests were used: the agar overlay test and the MTT test. An in vitro test using copper plates coated with the three types of cyanoacrylates serves for evaluating the stability of polymerized skin adhesives. Bilateral neck skin incisions in Goettingen miniature pigs were glued on one side with Dermabond. On the other side, conventional sutures were applied. After the pigs were killed, the resulting skin samples were tested for the tensile strength of their wound stability. Samples of pig dermis were exemplarily and histomorphologically characterized. A clinical examination after submandibular lymph node dissection should examine the application in humans. Cell culture tests were used to show the toxic effects of the three cyanoacrylates. In a copper test, octyl-2-cyanoacrylate was more stabile than ethyl- and butyl-cyanoacrylates. Breaking strength was 30% lower 28 days after operation with the new product than with sutures. In electron microscopy, octyl-2-cyanoacrylate showed no disadvantages with regard to tissue regeneration and no histotoxicity. For plastic surgery, this new topical skin adhesive is a real alternative with attractive results, as compared with conventional suture.
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- 2004
13. Altered expression and new mutations in DNA mismatch repair genes MLH1 and MSH2 in melanoma brain metastases
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Monika, Korabiowska, Fatima, König, Raphaela, Verheggen, Thilo, Schlott, Carlos, Cordon-Cardo, Bernd, Romeike, and Ulrich, Brinck
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Adult ,Male ,DNA Repair ,Base Pair Mismatch ,Brain Neoplasms ,Gene Expression ,Nuclear Proteins ,Middle Aged ,Immunohistochemistry ,Genomic Instability ,Neoplasm Proteins ,DNA-Binding Proteins ,MutS Homolog 2 Protein ,Proto-Oncogene Proteins ,Mutation ,Humans ,Female ,Carrier Proteins ,MutL Protein Homolog 1 ,Melanoma ,Adaptor Proteins, Signal Transducing ,Aged - Abstract
Brain metastases, including those of malignant melanoma (known for its high genomic instability), are the most common intracranial tumors. The main objective of this study was to investigate expression and mutation in the DNA mismatch repair system in melanoma brain metastases. Expression of MLH1, MSH2, PMS1 and PMS2 was investigated immunohistochemically in 31 melanoma metastatic tumors. Mutational analysis of MLH1 and MSH2 was performed in 17 melanoma brain metastases. Loss of MLH1 and MSH2 expression was found in 10/31 and 12/31 tumors. PMS1 (27/31) and PMS2 (28/31) expression was preserved in the majority of lesions. Potential missense mutation was found in MSH2 (exon 13) in 2/17 melanomas. Mutation in the intron sequence between exon 14 and 15 of MLH1 (exon 15) was observed in 4/17 cases. Our results indicate that the two major DNA mismatch repair genes, MLH1 and MSH2, are more frequently affected by alterations in the DNA mismatch repair system than the helper genes PMS1 and PMS2. The presence of mutations of MSH2 and MLH1 in melanoma brain metastases, which has not been found in primary melanomas, indicates the high genomic instability of melanoma brain metastases.
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- 2004
14. Functional 5-HT receptors in human occipital artery
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Finn Olav Levy, Inga Werner, Raphaela Verheggen, Thomas Kruschat, Alberto J. Kaumann, Andreas Meier, Andreas Wienekamp, and Trond Brattelid
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Adult ,Male ,medicine.medical_specialty ,Ketanserin ,Contraction (grammar) ,Intrinsic activity ,Adolescent ,Muscle Relaxation ,Prostaglandin ,In Vitro Techniques ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Prazosin ,Humans ,RNA, Messenger ,Receptor ,5-HT receptor ,030304 developmental biology ,Aged ,Pharmacology ,Aged, 80 and over ,0303 health sciences ,Reverse Transcriptase Polymerase Chain Reaction ,General Medicine ,Cerebral Arteries ,Middle Aged ,Serotonin Receptor Agonists ,Endocrinology ,chemistry ,Receptors, Serotonin ,Female ,Endothelium, Vascular ,Occipital Lobe ,Serotonin Antagonists ,030217 neurology & neurosurgery ,medicine.drug ,Muscle Contraction - Abstract
5-HT receptors were studied in human occipital arteries, obtained from patients during neurosurgery. We detected mRNA for the following receptors (incidence): 5-HT(1B) (14/18), 5-HT(1D) (15/18), 5-HT(2A) (16/18), 5-HT(2B) (8/8), 5-HT(4(a)) (13/18), 5-HT(4(b)) (5/18), 5-HT(4(g)) (7/18), 5-HT(4(i)) (1/18), 5-HT(7(a/b)) (10/18) and 5-HT(7(d)) (12/18). 5-HT contracted and relaxed arterial rings at low (-logEC(50) M=7.0) and high (-logEC(50) M=4.2) concentrations, respectively. 5-HT-evoked contractions were antagonized partially by both 5-HT(1B)-selective SB224289 (200 nM) and 5-HT(2A)-selective ketanserin (1 microM) but not by 5-HT(1D)-selective BRL15572 (500 nM) or prazosin (1 microM). Sumatriptan caused contractions (-logEC(50) M=6.8, intrinsic activity with respect to 5-HT=0.3). Sumatriptan-evoked contractions were antagonized by SB224289 with high potency (pK(B)=9.4) but not by BRL15572. 5-HT-induced relaxations were resistant to blockade by 5-HT(1B)-selective SB224289 (1 microM), 5-HT(1D)-selective BRL15572, 5-HT(2B)-selective SB204741 (1 microM), 5-HT(4)-selective GR113808 (100 nM) and 5-HT(7)-selective SB269970 (1 microM), and a combination of SB204741 and SB269970, inconsistent with an involvement of 5-HT(1B), 5-HT(1D), 5-HT(2B), 5-HT(4) and 5-HT(7) receptors. Triton X-100 treatment of the arteries abolished acetylcholine-induced relaxations of rings precontracted by prostaglandin F(2alpha), but a reduction of the relaxant effects of 5-HT did not reach significance. Nitro-L-arginine (1 mM) reduced 5-HT-induced relaxations, suggesting a contribution of nitric oxide released from endothelial cells. Ketanserin (1 microM) prevented the relaxant effects of 5-HT. We conclude that 5-HT contracts human occipital artery through 5-HT(1B) receptors at low concentrations and through 5-HT(2A) receptors at high concentrations. Sumatriptan contracts mostly through 5-HT(1B) receptors. These results are consistent with the 5-HT(1B) and 5-HT(2A) mRNA data. 5-HT-induced relaxation is mediated, in part, through ketanserin-sensitive receptors, but 5-HT(1B), 5-HT(1D), 5-HT(2B), 5-HT(4) and 5-HT(7) receptors appear not to be involved.
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- 2003
15. Participation of 5-HT1-like and 5-HT2A receptors in the contraction of human temporal artery by 5-hydroxytryptamine and related drugs
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Raphaela Verheggen, Alberto J. Kaumann, Frauke Meyer-Dulheuer, and S. Freudenthaler
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Agonist ,Adult ,Male ,medicine.medical_specialty ,Serotonin ,Ketanserin ,Intrinsic activity ,medicine.drug_class ,In Vitro Techniques ,Partial agonist ,Muscle, Smooth, Vascular ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,heterocyclic compounds ,Collagenases ,Receptor ,030304 developmental biology ,Aged ,Pharmacology ,0303 health sciences ,Chemistry ,Sumatriptan ,musculoskeletal, neural, and ocular physiology ,Headache ,Benzazepines ,Middle Aged ,musculoskeletal system ,Serotonin Receptor Agonists ,Temporal Arteries ,Endocrinology ,Receptors, Serotonin ,cardiovascular system ,5-HT1 receptor ,Female ,Endothelium, Vascular ,Serotonin Antagonists ,medicine.symptom ,030217 neurology & neurosurgery ,Muscle contraction ,medicine.drug ,Muscle Contraction ,Research Article - Abstract
1. We investigated the hypothesis that, as in some other large human arteries, 5-HT-induced contraction of the temporal artery is mediated through two co-existing receptor populations, 5-HT1-like- and 5-HT2A. Temporal arterial segments were obtained from patients undergoing brain surgery and rings prepared set up to contract with 5-HT and related agents. Fractions of maximal 5-HT responses mediated through 5-HT1-like and 5-HT2A receptors, f1 and f2 = 1-f1, were estimated by use of the 5-HT2A-selective antagonist ketanserin. 2. In rings with intact endothelium 5-HT evoked contractions with a -log EC50, M of 7.0. Ketanserin (10-1000 nM) antagonized part of the 5-HT-induced contractions. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M of 6.9 and f1 of 0.17 (100 nM ketanserin) and -log EC50, M of 6.4 and f1 of 0.20 (1000 nM ketanserin). 3. In rings with endothelial function attenuated by enzymatic treatment, 5-HT caused contractions with a -log EC50, M of 7.2 that were partially blocked by ketanserin. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M 7.4 and f1 of 0.16 (100 nM ketanserin) and -log EC50, M of 7.5 and f1 of 0.14 (1000 nM ketanserin). 4. The ketanserin-resistant component of 5-HT-evoked contraction was blocked by methiothepin (100-1000 nM) consistent with mediation through 5-HT1-like receptors. 5. In rings with intact endothelium the 5-HT1-like-selective agonist, sumatriptan, caused small contractions with a -log EC50, M of 6.5 and intrinsic activity of 0.21 with respect to 5-HT that were resistant to blockade by 1000 nM ketanserin but antagonized by 100 nM methiothepin. 6. In rings with intact endothelium the 5-HT2A receptor partial agonist SK&F 103829 (2,3,4,5-tetrahydro-8[methyl sulphonyl]-1H3-benzazepin-7-ol methensulphonate) contracted rings with a -log EC50, M of 5.0 and an intrinsic activity of 0.49 with respect to 5-HT; the effects were antagonized by ketanserin 1000 nM. 7. We conclude that 80-86% of the maximum 5-HT-evoked contraction of human temporal artery is mediated through 5-HT2A receptors, the remainder through 5-HT1-like-receptors, regardless of whether or not endothelium is functional. The 5-HT1-like-receptors are more likely to be 5-HT1D beta receptors than 5-HT1D alpha receptors and sumatriptan is a full agonist for these receptors. As found in arteries of other species, SK&F 103829 is a partial agonist for 5-HT2A receptors of human temporal artery.
- Published
- 1996
16. Evaluation of Shunt Failures by Compliance Analysis and Inspection of Shunt Valves and Shunt Materials, Using Microscopic or Scanning Electron Microscopic Techniques
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Raphaela Verheggen, Christian Reparon, Evangelos Markakis, and Wolfgang F. Schoener
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Tissue migration ,medicine.disease ,Surgery ,Hydrocephalus ,Cerebrospinal fluid ,Valve replacement ,Occlusion ,medicine ,Foreign body ,business ,Shunt (electrical) ,Calcification - Abstract
Shunt dysfunction or malfunction in the treatment of hydrocephalus still causes multiple difficulties in the clinical management of this condition. In this study the results of micro-inspection of explanted shunt valves and tubes by light and scanning electron microscopy are presented. From our findings in 36 patients aged from 1 month to 79 years (mean age 49.03 years) we discovered that 61.1% of the patients had shunt related defects which led to tissue migration into the shunt lumens or to tissue adherence to the tube surface. Calcification and destruction of the silicone-elastomer tubing was found in all cases of shunt tube occlusion (25%). There were shunt fractures in 11.1% of the tubes. Histological analysis verified foreign body tissue reactions on all explanted alloplasts. In five cases (13.8%) migration of chorioid plexus or glial cells to the inner lumen of the ventricular catheter was found. Of 36 patients who underwent compliance (Co), reabsorption resistance (R), and cerebrospinal fluid (CSF) formation rate (F) analysis, one patient required a valve replacement due to significant intracranial content compliance changes after craniostenosis surgery. Furthermore, four of 36 patients had shunt infections, three cases with bacteria Staphylococcus aureus (8.3%), and one case with Candida albicans (2.8%) hyphae inside the valve lumen. Work-bench valve tests, following the ISO/DIS 7197 protocol (1989), clarified that of seven valves tested, six did not match the CSF-drainage requirements for an individual patient.
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- 1991
- Full Text
- View/download PDF
17. Contouring of Cranial Vault Irregularities With Hydroxyapatite Cement: A Clinical and Experimental Investigation.
- Author
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Johannes F Hnig, Hans A Merten, Axel Nitsch, and Raphaela Verheggen
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- 2005
- Full Text
- View/download PDF
18. The Modification of Platelet-Induced Coronary Vasoconstriction by a Thromboxane Receptor Antagonist
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Karsten Schrör and Raphaela Verheggen
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Blood Platelets ,Serotonin ,medicine.medical_specialty ,Thromboxane ,Arachidonic Acids ,In Vitro Techniques ,Pharmacology ,Muscle, Smooth, Vascular ,Thromboxane A2 ,Internal medicine ,Cyclic AMP ,medicine ,Animals ,Platelet ,Sulfonamides ,Arachidonic Acid ,biology ,Chemistry ,medicine.disease ,Coronary Vessels ,Coronary arteries ,medicine.anatomical_structure ,Vasoconstriction ,Coronary vasospasm ,Coronary vessel ,Circulatory system ,cardiovascular system ,biology.protein ,Cardiology ,Cattle ,Thromboxane-A synthase ,medicine.symptom ,Cardiology and Cardiovascular Medicine - Abstract
The role of platelet-derived vasoconstrictors in coronary vasospasm was studied using arachidonic acid-stimulated washed human platelets (WPS). Transfer of this system into an organ bath, containing bovine coronary arteries (BCA) and a mixture of blocking agents resulted in a biphasic contraction, consisting of a first phase, mediated by release of thromboxane (TX) A2 and a second phase, mediated by release of 5-hydroxytryptamine (5-HT) from the WPS (1,2). Treatment of the WPS with 4-[2-(benzenesulfonamido)-ethyl]-phenoxyacetic acid (BM 13.177) (0.03-3 mumol/L) prior to stimulation revealed a concentration-dependent inhibition of the 5-HT component of the contractile response with a minor reduction of the TXA2 component of contraction and enhanced amounts of immunoreactive TXB2 in the bath fluid. Treatment of the BCA with BM 13.177 prior to addition of stimulated WPS resulted in a significant reduction of the TXA2 component of contraction, by 56% at 30 mumol/L whereas 3 mumol/L were ineffective. The 5-HT component of contraction was enhanced. For comparison, the IC50 for BM 13.177 to inhibit PGF2 alpha-induced contractions was 6 mumol/L and that to inhibit U-46,619 was 0.5 mumol/L. BM 13.177 was at least 1 order of magnitude more potent as an inhibitor of U-46,619 than of PGF2 alpha- or TXA2-induced contractions. It is concluded that BM 13.177 is a weak inhibitor of TXA2-mediated contractions of coronary vessels, suggesting different thromboxane receptors in coronary vessels and platelets.
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- 1986
- Full Text
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19. Use of human post-mortem cerebral blood vessels to study vasospasm
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Karsten Schrör and Raphaela Verheggen
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Pharmacology ,business.industry ,Model system ,Vasospasm ,Toxicology ,medicine.disease ,Postmortem Changes ,Cerebral vasospasm ,Ischemic Attack, Transient ,Anesthesia ,Vasoactive ,medicine ,Animals ,Humans ,In patient ,Subarachnoid haemorrhage ,business ,Cause of death - Abstract
Although it is a major cause of death in patients with subarachnoid haemorrhage, little is known about the mechanisms involved in cerebral vasospasm. This is due to the difficulty in obtaining human tissue, and to wide differences between species in the response to vasoactive compounds. In this review, Karsten Schror and Raphaela Verheggen discuss the evidence that the response of human cerebral blood vessels changes little during the first 24 h after death, and argue that samples obtained post-mortem provide a suitable model system to study vasospasm in vitro.
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- 1988
20. Prostacyclins are only weak antagonists of coronary vasospasm induced by authentic thromboxane A2 and serotonin
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Raphaela Verheggen and Karsten Schrör
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Blood Platelets ,Serotonin ,Thromboxane ,Indomethacin ,Methysergide ,Prostacyclin ,Arachidonic Acids ,Pharmacology ,In Vitro Techniques ,Thromboxane A2 ,chemistry.chemical_compound ,medicine ,Animals ,Humans ,Platelet ,Iloprost ,Arachidonic Acid ,Coronary Vessels ,Epoprostenol ,chemistry ,Vasoconstriction ,Anesthesia ,Coronary vessel ,cardiovascular system ,lipids (amino acids, peptides, and proteins) ,Arachidonic acid ,Cattle ,Serotonin Antagonists ,Cardiology and Cardiovascular Medicine ,circulatory and respiratory physiology ,medicine.drug - Abstract
The actions of prostacyclin and its synthetic analog iloprost on the release and action of platelet-derived serotonin (5-HT) and thromboxane (TX) A2 were studied in vitro. Washed human platelet suspensions (WPS) (4 X 10(8) platelets/ml) were stimulated with arachidonic acid (AA) (30 mumol/L) and the incubate transferred into an organ bath containing bovine coronary arteries (BCA) in Krebs-Henseleit buffer supplemented with a mixture of blocking agents, including indomethacin. This resulted in a biphasic contraction of the coronary arteries, consisting of first, a TXA2-mediated response and second, a 5-HT-mediated response. The 5-HT-mediated reaction was dose-dependently inhibited by methysergide (IC50: 80 nmol/L). Treatment of the WPS with prostacyclin (PGI2) or iloprost prior to stimulation by AA resulted in a dose-dependent inhibition of the 5-HT-mediated contraction, due to inhibition of 5-HT release. The TXA2-mediated component, as well as the concentration of immunoreactive TXB2 in the bath medium, remained unchanged. Addition of PGI2 or iloprost to the BCA prior to transfer of stimulated WPS to the bath medium was followed by a dose-dependent inhibition of both phases. This, however, required concentrations of 100 nmol/L 5-HT and greater than 300 nmol/L TXA2 (IC50), which already produced a nearly complete direct relaxation of the vessel preparations (EC50: 30 nmol/L). It is concluded that a significant spasmolytic action of prostacyclins against platelet-derived vasoconstrictors in vivo might only be obtained at concentrations that already produce considerable direct effects on vessel tone.
- Published
- 1986
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