Central Tapia's syndrome ("matador's disease") caused by metastatic hemangiosarcoma.
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Aged↗
Biomedical subjects
U Krause
Publications and source records attributed to U Krause.
[Malignant schwannoma of the trachea].
Malignant schwannoma of the trachea is a rarity among the infrequent neurogenic tumours of the cervical region. Only individual cases have been described in the literature to date. A 30-year-old patient came to us with acute dyspnoea. A bronchoscopy showed a polypoid-stemmed tumour, which was removed using a loop. Histologically, it was a malignant neurogenic tumour of a low-grade schwannoma nature. A tracheal segment resection was carried out to remove the tumour completely. Six years after the operation, the patient was still recurrence-free. The prognosis depends on whether a high or low grade malignant schwannoma is present. The histological grading of the neurogenic peripheral neurilemmoma is made depending on a number of histological parameters and is often rather difficult. Specialists agree that only the radical surgical removal of the tumour might lead to patient's recovery. Adjuvant measures like chemo- or radiotherapy do not significantly prolong the life expectancy.
Adult↗
New targets of AMP-activated protein kinase.
The discovery of the AMP-activated protein kinase (AMPK) more than a decade ago has shed much light on the cellular response to stresses characterized by a fall in the concentration of ATP and an increase in the AMP/ATP ratio. All conditions known to increase this ratio activate AMPK, whose major role is to act as an emergency signal to conserve ATP. It does so by inhibiting anabolic processes and by activating pathways producing ATP. In recent years, our laboratory has discovered new targets of AMPK. The purpose of this short review is to summarize our contribution to this field.
AMP-Activated Protein Kinases↗
HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours.
BACKGROUND: Hyperparathyroidism is a common endocrinopathy characterised by the formation of parathyroid tumours. In this study, we determine the role of the recently identified gene, HRPT2, in parathyroid tumorigenesis. METHODS: Mutation analysis of HRPT2 was undertaken in 60 parathyroid tumours: five HPT-JT, three FIHP, three MEN 1, one MEN 2A, 25 sporadic adenomas, 17 hyperplastic glands, two lithium associated tumours, and four sporadic carcinomas. Loss of heterozygosity at 1q24-32 was performed on a subset of these tumours. RESULTS: HRPT2 somatic mutations were detected in four of four sporadic parathyroid carcinoma samples, and germline mutations were found in five of five HPT-JT parathyroid tumours (two families) and two parathyroid tumours from one FIHP family. One HPT-JT tumour with germline mutation also harboured a somatic mutation. In total, seven novel and one previously reported mutation were identified. "Two-hits" (double mutations or one mutation and loss of heterozygosity at 1q24-32) affecting HRPT2 were found in two sporadic carcinomas, two HPT-JT-related and two FIHP related tumours. CONCLUSIONS: The results in this study support the role of HRPT2 as a tumour suppressor gene in sporadic parathyroid carcinoma, and provide further evidence for HRPT2 as the causative gene in HPT-JT, and a subset of FIHP. In light of the strong association between mutations of HRPT2 and sporadic parathyroid carcinoma demonstrated in this study, it is hypothesised that HRPT2 mutation is an early event that may lead to parathyroid malignancy and suggest intragenic mutation of HRPT2 as a marker of malignant potential in both familial and sporadic parathyroid tumours.
Adult↗
[Cardiac resynchronization therapy by biventricular pacing. How many patients with left ventricular dysfunction are eligible?].
BACKGROUND AND OBJECTIVE: Cardiac resynchronization therapy by multisite biventricular pacing presents an additive therapeutic option in the treatment of severe congestive heart failure. The objective of the study was to evaluate how many patients with left ventricular dysfunction may potentially benefit from this therapy. METHODS: A total of 975 patients were screened for the prevalence of left ventricular dysfunction. Patients with a left ventricular ejection fraction (LVEF) <45 % were included into the investigation. Potential benefit of biventricular pacing was presumed in the presence of: LVEF < 35 %, severe heart failure (NHYA class III or IV), intrinsic left bundle branch block pattern with QRS interval > 150 ms and the absence of atrial fibrillation in the last 3 months before study inclusion. RESULTS: In 203 patients (168 male, 35 female, mean age: 64 +/- 11) an LVEF <45 % was found. A total of 12 of these patients (6 %) or 12 of 113 patients (11 %) with an LVEF <35 % were identified as appropiate candidates for biventricular resynchronization therapy. CONCLUSIONS: Cardiac biventricular pacing currently serves as a therapeutic option for a relatively small subgroup of patients with left ventricular dysfunction. Focusing on estimations that the incidence of heart failure in Germany amounts to more than 100.000 cases per year our results suggest that after all more than 6.000 patients per year may potentially benefit from electric resynchronization therapy. This number may increase substantially if prospective studies can prove that patients with heart failure and atrial fibrillation or left ventricular conduction delay due to univentricular pacing also benefit from cardiac resynchronization therapy.
Aged↗
High resolution contrast enhanced MR-angiography of the hand arteries: preliminary experiences.
BACKGROUND: In contrast to magnetic-resonance-angiography (MRA) of the peripheral vessels of the lower extremity, which gains more and more clinical application, MRA of the hand arteries is still exceptional. Our objective was to introduce an appropriate protocol for high resolution contrast-enhanced MR-angiography of the hand arteries. PATIENTS AND METHODS: 7 healthy volunteers and 13 patients with suspected hand artery obstructions underwent MRA. The examinations were performed on a 1.5 T system equipped with a flexible surface coil. A modified 3D-gradient-echo sequence was used. Criteria for image analysis were the overall image quality, vessel visibility and the timing of the contrast material bolus. RESULTS: In the volunteer group delineation of the superficial or deep palmar arch, common palmar digital arteries and of the proximal and middle segments of the digital arteries was possible. No pathologic findings were seen in the volunteer group. In 10 patients MRA revealed pathologic findings. In 9 examinations bolus-timing was correct, 7 examinations showed incomplete arterial enhancement, 4 examinations showed venous overlay. CONCLUSIONS: Contrast enhanced MR-angiography of the hand arteries in the described technique is a promising method. Compared to intraarterial digital subtraction angiography (IA-DSA) MRA still has limitations concerning spatial and temporal resolution. For clinical evaluation comparative studies with IA-DSA are necessary.
Adult↗
Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.
Amino Acid Sequence↗
[First clinical experience with a full-size, flat-panel detector for imaging the peripheral skeleton - Part II: Post-processing with a newly developed adaptive autowindow algorithm].
PURPOSE: of the second part of the investigation was the evaluation of a newly developed adaptive autowindow algorithm in comparison to the system processing radiographs of the wrist and ankle to further optimize the image quality with softcopy reading. MATERIAL AND METHODS: All 120 radiographs of the wrist and all 100 radiographs of the ankle used in the 1st part of this paper were processed with the adaptive autowindow algorithm. The evaluation was again performed by 5 radiologists with softcopy reading. For the data analysis a variation of the Visual Grading Analysis (VGA) was used. RESULTS: Up to 19 % of the wrist radiographs and 2 % of the ankle radiographs processed with the system software had to be processed manually afterwards to get acceptable results. By the application of the adaptive autowindow algorithm a manual post-processing was no longer necessary. Highly significant (p less-than-or-equal 0.001) differences for all criteria to be evaluated were found for the wrist radiographs and in the case of the ankle radiographs for the bone contrast, the contrast in soft-tissue regions, the fine details in the bone and the artifacts, the adaptive autowindow algorithm performed always better than the system software. CONCLUSION: Using half of the exposition dose on a flat-panel detector, an optimized post-processing leads to comparable or better results compared to the conventional film-screen-system concerning the image quality.
Algorithms↗
Clubbing due to peripheral hypervascularization: recognition by contrast-enhanced, three-dimensional magnetic resonance angiography.
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Adult↗
Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides.
AMP-activated protein kinase (AMPK) is known to be activated by phosphorylation on Thr172 in response to an increased AMP/ATP ratio. We report here that such an activation indeed occurred in anaerobic rat hearts and that it was antagonized (40-50%) when the hearts were pre-treated with 100 nM insulin. The effect of insulin (1) was blocked by wortmannin, an inhibitor of phosphatidylinositol-3-kinase; (2) only occurred when insulin was added before anoxia, suggesting a hierarchical control; (3) resulted in a decreased phosphorylation state of Thr172 in AMPK and (4) was unrelated to changes in the AMP/ATP ratio. This is the first demonstration that AMPK activity could be changed without a detectable change in the AMP/ATP ratio of the cardiac cell.
AMP-Activated Protein Kinases↗
Tumor hypoxia, p53, and prognosis in cervical cancers.
BACKGROUND: The p53 protein is involved in the regulation of initiation of apoptosis. In vitro, p53-deficient cells do not respond to hypoxia with apoptosis as do p53-normal cells, and this may lead to a relative growth advantage of cells without a functioning p53 under hypoxia. On the basis of this hypothesis, a selection of cells with a functionally inactive p53 may occur in hypoxic tumors. The development of uterine cervical carcinomas is closely associated with infections of human papilloma viruses, which may cause a degradation of the tumor suppressor gene p53, resulting in a restriction of apoptosis. Thus, cervical cancers have often a functionally inactive p53. The purpose of our clinical study was therefore to investigate the association between p53, hypoxia, and prognosis in cervical cancers in which the oxygenation status can be determined by clinical methods. MATERIAL AND METHODS: Seventy patients with locally advanced squamous cell cervical cancer Stages IIB (n = 14), IIIB (n = 49), and IVA (n = 7) were investigated in the period from 1996 through 1999. All were treated with definitive radiotherapy with curative intent by a combination of external radiotherapy plus high-dose-rate afterloading. Before therapy, tumor oxygenation was measured with a needle probe polarographically using the Eppendorf histograph. Hypoxic tumors were defined as those with pO(2) measurements below 5 mm Hg (HF5). Pretreatment biopsies were taken and analyzed immunohistologically for p53 protein expression with the DO-7 antibody. The DNA index was measured by flow cytometry. The statistical data analysis was done with SPSS 9.0 for Windows. RESULTS: The 3-year overall survival was 55% for the whole group of patients. Clinical prognostic factors in a multivariate analysis were pretreatment hemoglobin level (3-year survival 62% for patients with a pretreatment hemoglobin > or =11 g/dl vs. 27% for hemoglobin <11 g/dl, p = 0.006) and FIGO stage (Stage IIB: 65%; Stage IIIB: 60%; Stage IVA: 29%, p = 0.01). Sixty of the 70 tumors showed positive immunohistologic staining for p53 protein (transformed p53 = tp53), and 10/70 were negative (wild-type p53 = wtp53); p53 expression had no significant impact on survival (50% for tp53 vs. 79% for wtp53, p = 0.11). FIGO stage and anemia had no impact on p53 expression. Forty-nine of 70 tumors were hypoxic (HF5+), and 21 showed no hypoxia (HF5-). Hypoxic carcinomas were more frequently positive for p53 as compared to nonhypoxic tumors (27% vs. 13%, p = 0.011) and showed a trend toward a lower survival (48% vs. 70%, p = 0.07). In a further multivariate analysis, the impact of a combination of p53 expression and hypoxia on survival was examined. After adjusting for FIGO stage and pretreatment anemia, patients with wtp53 tumors had the best prognosis (3-year survival 79%) followed by tp53-HF5(-) patients (57%), and the most unfavorable prognosis was observed for tp53-HF5(+) patients (47%). The DNA index was higher in tp53 carcinomas compared to wtp53 tumors, 1.97 +/- 0.4 vs. 1.67 +/- 0.1, p = 0.05. The highest DNA index was found in hypoxic tumors with transformed p53 (2.2 +/- 3.1). CONCLUSIONS: Advanced stage and pretreatment hemoglobin level are independent prognostic factors in cervical carcinomas. The immunohistologic detection of (a functionally inactive) p53 and the presence of hypoxia had no prognostic impact, if analyzed as single parameters. However, the combination of both parameters was able to discriminate different prognostic subgroups. Moreover, hypoxic cancers were more often immunohistologically positive for tp53 protein and had a higher DNA index with the highest DNA index in tumors with both hypoxia and tp53 protein expression. These findings in summary support the theory that the tumor's microenvironment may influence the biologic behavior via hypoxia.
Adult↗
No-flow ischemia inhibits insulin signaling in heart by decreasing intracellular pH.
Glucose-insulin-potassium solutions exert beneficial effects on the ischemic heart by reducing infarct size and mortality and improving postischemic left ventricular function. Insulin could be the critical protective component of this mixture, although the insulin response of the ischemic and postischemic myocardium has not been systematically investigated. The aim of this work was to study the insulin response during ischemia by analyzing insulin signaling. This was evaluated by measuring changes in activity and/or phosphorylation state of insulin signaling elements in isolated perfused rat hearts submitted to no-flow ischemia. Intracellular pH (pH(i)) was measured by NMR. No-flow ischemia antagonized insulin signaling including insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, protein kinase B, p70 ribosomal S6 kinase, and glycogen synthase kinase-3. These changes were concomitant with intracellular acidosis. Perfusing hearts with ouabain and amiloride in normoxic conditions decreased pH(i) and insulin signaling, whereas perfusing at pH 8.2 counteracted the drop in pH(i) and the inhibition of insulin signaling by ischemia. Incubation of cardiomyocytes in normoxic conditions, but at pH values below 6.75, mimicked the effect of ischemia and also inhibited insulin-stimulated glucose uptake. Finally, the in vitro insulin receptor tyrosine kinase activity was progressively inhibited at pH values below physiological pH(i), being abolished at pH 6.0. Therefore, ischemic acidosis decreases kinase activity and tyrosine phosphorylation of the insulin receptor thereby preventing activation of the downstream components of the signaling pathway. We conclude that severe ischemia inhibits insulin signaling by decreasing pH(i).
Animals↗
The lipid phosphatase SHIP2 controls insulin sensitivity.
Insulin is the primary hormone involved in glucose homeostasis, and impairment of insulin action and/or secretion has a critical role in the pathogenesis of diabetes mellitus. Type-II SH2-domain-containing inositol 5-phosphatase, or 'SHIP2', is a member of the inositol polyphosphate 5-phosphatase family. In vitro studies have shown that SHIP2, in response to stimulation by numerous growth factors and insulin, is closely linked to signalling events mediated by both phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase. Here we report the generation of mice lacking the SHIP2 gene. Loss of SHIP2 leads to increased sensitivity to insulin, which is characterized by severe neonatal hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death. Adult mice that are heterozygous for the SHIP2 mutation have increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in skeletal muscles. Our results show that SHIP2 is a potent negative regulator of insulin signalling and insulin sensitivity in vivo.
Animals↗
[Multi-modality therapy concept in metastatic follicular thyroid carcinoma with hyperthyroidism].
The coincidence of hyperthyroidism and thyroid carcinoma seldom occurs. Only few reports on functionally metastases of thyroid carcinoma have been published. We report a 59-year-old man who underwent subtotal thyroidectomy for toxic nodular goiter. Histological examination revealed a follicular thyroid carcinoma. After thyroidectomy and cervical lymphadenectomy the patient developed a strong hyperthyreosis. Scintigraphy showed strong radioiodine uptake in the sacrum. De-bulking resection of the metastasis followed by high-dose radioiodine treatment was performed. After radioiodine therapy the patient became euthyroid. Treatment of hyperthyreosis in metastatic thyroid cancer requires a multimodal therapeutic concept.
Adenocarcinoma, Follicular↗
[Early operation as a treatment measure in thyrotoxic crisis].
INTRODUCTION: Thyroid storm is a rare disease, occurring in less than 1% of all thyrotoxicoses. Diagnosis and therapy still have serious problems. METHODS: We review 14 patients who were operated on between 1992 and 1999 because of thyroid storm. RESULTS: All of the ten women and four men, aged 27 to 77 years, had an underlying thyroid disease. Autonomies were found in seven, Grave's disease in four, and a nodular goiter in three patients. The precipitating events were in five patients an antiarrhythmic therapy with amiodarone, on three occasions application of contrast medium, two times omission of antithyroid drugs and in one patient severe hyperglycemia with acidosis. In three patients no triggering factor was discovered. All patients were treated with high-dose antithyroid therapy. On admission, four patients were graded as stage-one thyroid crisis, three patients had stage-two and seven patients stage-three disease. All patients were operated on within 18 h of admission. Surgical procedure was in seven cases a bilateral subtotal resection, four times thyroidectomy, and in three patients a Dunhill procedure. After the operation, 12 patients improved rapidly. Two 77 and 74-year-old women died 1 or 2 days after the operation, respectively, one from heart failure and the other from multiple organ failure. Both had been diagnosed as thyrotoxic crisis stage three. CONCLUSION: Early operation should be adopted as a standard option in thyroid storm that cannot be controlled medically. Best results are achieved if the operation is done at stage one or two of the disease.
Adult↗
["If I were the department head in this case..."--interventional interview with patients and co-workers of a psychiatric department].
OBJECTIVE: How can patients and staff participate in redesigning psychiatric procedures through survey research? METHODS: Using interviews with circular-hypothetical questioning, 58 patients and 30 staff members of a psychiatric department of a general hospital were interviewed about their preferences for change and continuity in clinical practices, and results were feedbacked. RESULTS: Suggestions for change concerning doctors' rounds, the integration of music therapy, the number of individual sessions and the postdischarge care initiated real change. CONCLUSIONS: Surveys planned cooperatively with staff and without competitive benchmarking can be effective tools in psychiatric organization development.
Attitude of Health Personnel↗
[First clinical experience with a full-size, flat-panel detector for imaging the peripheral skeletal system].
PURPOSE: This investigation was intended to show that exposures of the peripheral skeleton system can be done with half of the dose used for conventional screen-film systems with a full-size CsI/a-Si flat panel detector. MATERIAL AN METHODS: 120 exposures of the wrist and 100 exposures of the ankle have been made on a full-size flat panel detector system (43 x 43 cm). The patient dose has been reduced by a factor of two compared to conventional images. Five radiologists evaluated every image as a softcopy and a hardcopy image. For the evaluation, a variation of the Visual Grading Analysis (VGA) without reference images was used. For the determination of the patient entrance dose, measurement of a phantom were performed. RESULTS: A dose reduction of about 50 % is possible with the same or even better image quality in routine diagnostics. Only 3 % of the ankle and approx. 21 % of the wrist exposures required a postprocessing. Exposures with implants did not show any artifacts and some of the those achieved better evaluation results compared with exposures without implants. CONCLUSION: A halving of the patient dose is possible with acceptable results for the image quality. The effect of an improved image processing remains to be evaluated. The patient entrance dose is suitable for an evaluation of a radiographic detector and especially for a dose-referred comparison of digital X-ray units.
Ankle Joint↗
MR angiography of the hand arteries.
The aim of this study was to optimize different magnetic resonance angiography (MRA) techniques and to evaluate MRA of the hand arteries compared to intraarterial digital subtraction angiography (IA-DSA). The MRA examinations were performed on a 1.5-T system equipped with a flexible surface coil. The protocol contained time-of-flight (TOF), rephased/dephased (Re/De), and contrast enhanced (CE) techniques. Maximum intensity projection (MIP) was used for postprocessing. The IA-DSA procedure was performed as pharmaco-angiography (after intraarterial injection of a vasodilatator) via a transbrachial approach. Nine patients suffering from peripheral vascular disease were examined with IA-DSA, TOF-MRA, and Re/De-MRA; six patients were examined with CE-MRA and IA-DSA. Best overall image quality was attained with IA-DSA, followed by TOF-MRA, Re/De-MRA, and CE-MRA. Selective arterial visualization of digital arteries was possible with IA-DSA and TOF-MRA. Rephased/dephased MRA showed venous overlay. Contrast-enhanced MRA was limited by inconstant quality of bolus timing. Appropriate arterial bolus timing was achieved in four of six patients; one examination showed venous overlay, one examination incomplete arterial enhancement. Time-of-flight MRA detected 96% of the digital artery segments that were identified with IA-DSA and revealed 34 segments that were failed on IA-DSA. Rephased/dephased MRA and CE-MRA were inferior to IA-DSA and TOF-MRA regarding detection of digital arteries. Magnetic resonance angiography with optimized protocols is a noninvasive procedure to visualize hand arteries in patients with ischemic disease. With TOF-MRA it is possible to detect angiographically occluded arterial segments of digital arteries.
Adolescent↗