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Biomedical subjects

A Thalhammer

Publications and source records attributed to A Thalhammer.

At least 19 recordsLinked to original sources

Subunit dependencies of N-methyl-D-aspartate (NMDA) receptor-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization.

N-Methyl-D-aspartate (NMDA) receptor (NMDAR) activity regulates the net number of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR) at the cell surface by modulating the balance between AMPAR membrane insertion and endocytosis. In this study, we addressed the role of NMDAR subtypes and of NMDAR-mediated Ca2+ influx in the NMDAR-induced endocytosis of GluR2-containing AMPARs in primary murine hippocampal neurons. We found that NMDAR activation enhanced the endocytosis of AMPARs containing the GluR2 splice variants with short, but not long, cytoplasmic tails. NMDA-induced GluR2 endocytosis was completely inhibited by pharmacological block of NR2B-containing NMDARs. In turn, preferential block of NR2A-containing NMDARs did not affect NMDA-induced AMPAR endocytosis, indicating that AMPAR internalization is controlled by a restricted set of NMDARs. The NMDA-induced GluR2 internalization was also observed in the absence of extracellular Na+ ions, suggesting that membrane depolarization is not a prerequisite for this effect. Furthermore, the activation of Ca2+-impermeable NMDARs containing the mutant NR1(N598R) subunit failed to enhance AMPAR endocytosis, indicating a requirement of Ca2+ influx directly through the NMDAR channels. In summary, our findings suggest that the NMDAR-induced selective internalization of short C-terminal GluR2-containing AMPARs requires a Ca2+ signal that originates from NMDAR channels and is processed in an NMDAR subtype-restricted manner.

Animals↗

The Protease Inhibitor Transfer Study (PROTRA 1): abacavir and efavirenz in combination as a substitute for a protease inhibitor in heavily pretreated HIV-1-infected patients with undetectable plasma viral load.

OBJECTIVES: The aim of the study was to evaluate the safety and efficacy of abacavir (ABC) and efavirenz (EFV) instead of a protease inhibitor (PI) in HIV-1-infected subjects treated with two nucleoside reverse transcriptase inhibitors (NRTIs) and one PI with undetectable viral loads (< 50 HIV -1 RNA copies/mL). To be eligible for inclusion, patients had to have a history of viral load < 400 copies/mL for at least 3 months and had to be naive to treatment with nonnucleoside reverse transcriptase inhibitors (NNRTIs) and ABC, but multiple pretreatment and treatment failure were allowed. DESIGN: An open-label, single-centre pilot study of duration 48 weeks was conducted. ABC was added to the original treatment with two NRTIs and one PI at baseline, and at week 6 the PI was replaced by EFV. At each study visit, CD4 cell count, viral load [measured by polymerase chain reaction (PCR)] and clinical chemistry were measured. Fasting blood samples were taken at baseline and at weeks 12, 24, 36 and 48 to measure levels of cholesterol [high-density lipoprotein (HDL)/low-density lipoprotein (LDL)], triglycerides, insulin and C-peptide. Additionally, an oral glucose tolerance test (OGTT) was performed. A bioelectric impedance analysis (BIA) and a single slice abdominal and mid-thigh computed tomography (CT) scan were carried out to assess changes in body composition. RESULTS: Thirty patients were included in the study. Three patients experienced ABC-hypersensitivity and one patient demonstrated virological failure caused by nonadherence. At week 48, all remaining patients had viral loads < 50 copies/mL with stable CD4 counts. The fasting metabolic parameters and abdominal fat distribution remained unchanged. CONCLUSIONS: In heavily pretreated patients, ABC and EFV in combination provide an effective, simplified and well-tolerated alternative to PI treatment.

Adult↗

Phosphorylation state of postsynaptic density proteins.

The postsynaptic density (PSD) is an electron-dense structure located at the synaptic contacts between neurons. Its considerable complexity includes cytoskeletal and scaffold proteins, receptors, ion channels and signaling molecules, in line with the role of PSDs in signal transduction and processing. The phosphorylation state of components of the PSD is central to synaptic transmission and is known to play a role in synaptic plasticity, learning and memory. The presence of a range of kinases and phosphatases in the PSD defines potential key players in this context. However, the substrates that these enzymes target have not been fully identified to date. We analyzed the protein composition of purified PSD samples from adult mouse brains by strong cation exchange chromatography fractionation of a tryptic digest followed by nano-reverse phase liquid chromatography coupled with electrospray ionization-quadrupole time of flight tandem mass spectrometry. This led to the identification of 244 proteins. To gain an insight into the phosphoproteome of the PSD we then purified phosphorylated tryptic peptides by immobilized metal ion affinity chromatography. This approach for the specific enrichment of phosphopeptides resulted in the identification of 42 phosphoproteins in the PSD preparation, 39 of which are known PSD components. Here we present a total of 83 in vivo phosphorylation sites.

Animals↗

Traumatic injuries of the pelvis and thoracic and lumbar spine: does thin-slice multidetector-row CT increase diagnostic accuracy?

The objective is to evaluate different multidetector-row CT (MDCT) strategies for adequate classification of spinal and pelvic injuries. Seventy intubated patients after multiple trauma underwent conventional radiography (CR) and MDCT. Examinations included the pelvis (P), the lumbar spine (LS) and the thoracic spine (TS). Conventional radiographs, 3-mm (CT5) and 5-mm scans (CT3) and 3-mm and 5-mm scans combined with MPR (CT3R/CT5R) were compared to surgery, autopsy and clinical course. MDCT led to significantly better results than CR (P<0.01). Correlation coefficients were r=1.0 (CT3R), r=0.96 [TS] to r=1.0 [P/LS] (CT5R), r=0.8 [P] to r=1.0 [TS] (CT3), r=0.80 [P] to r=0.86 [TS] (CT5) and r=0.3 [TS] to r=0.69 [P] (CR). Fractures were identified by CT3R in 100% of cases, by CT5R in 95%, by CT3 in 90% [P]-100% [TS], by CT5 in 83.3% [LS]-90% [P] and by CR in 57.1% [TS]-87.2% [P]. Unstable fractures were identified in 100% by CT3R, CT5R and CT3, 85.7% [TS]-100% [P/LS] by CT5 and 57.1% [TS]-80% [P] by CR. Only overlapping thin-slice multiplanar reformation allows for an adequate classification of spinal and pelvic injuries and thus is highly emphasized in patients after severe blunt trauma.

Adult↗

[Splenic trauma--a rare complication during colonoscopy].

The less frequent complications of colonoscopy include pneumothorax, pneumoperitoneum, emphysema of the retroperitoneum or of the subcutis, septicemia and injuries of visceral organs (mainly the spleen). Since the mid 1970 s more than 30 splenic injuries during colonoscopy have been described. Any cause of increased splenocolic adhesions (inflammatory bowel disease, pancreatitis or prior abdominal surgery) might be a predisposing factor for splenic injury during colonoscopy. Other contributing factors are techniques that result in a strong torsion of the spleno-colic ligament. Patients with left shoulder and abdominal pain, hypotension, and a drop in hemoglobin without rectal bleeding after colonoscopy should be suspected to have splenic injury. Many physicians are not aware of splenic injuries as a potential complication of colonoscopy. Therefore the diagnosis of splenic injury during colonoscopy is often described in the literature as delayed (hours until 10 days). Since a colonoscopic splenic injury can be fatal, this exceedindly rare event must be considered when a patient shows the above-mentioned symptoms and no signs of colon perforation.

Colonoscopy↗

Ovarian function and morphology after deletion of the DARPP-32 gene in mice.

A plethora of systemic and local signaling molecules regulate ovarian function, but how different signaling molecules interact within an ovarian target cell is not known. Here we report that endocrine cells of the ovary express a phosphoprotein, DARPP-32 (dopamine and cyclic AMP-regulated phosphoprotein of Mr 32,000), which integrates signaling molecules in neurons. We thus hypothesized that DARPP-32 might act in a similar way in ovarian endocrine cells and therefore studied whether DARPP-32 gene deletion has consequences for ovarian functions in mice. Reproductive performance of adult mutants did not differ from wild-type females, as judged from numbers of litters and pups delivered. Similar steroid levels in mutant and wild-type mice ruled out gross abnormalities in the hypothalamic-pituitary-ovarian axis. However, an analysis of ovarian morphology, using serially sectioned ovaries, revealed several differences. Ovaries of young adult mutant mice at 2 - 3 months contained luteinized follicles, but fewer corpora lutea. At 5 - 6 months, large cysts were found in mutant mice, as well as reduced numbers of preantral follicles and antral follicles. Interstitial cell hypertrophy and degeneration was marked in all mutant ovaries at this age. Thus, while the lack of DARPP-32 does not overtly alter reproductive performance in adult mice, it is associated with progressive alterations and derangements of growth and development of ovarian follicles, suggesting premature ovarian ageing. This implies that ovarian DARPP-32 is involved in follicular development, presumably by integrating effects of signaling molecules, which act together to ensure efficient follicular development.

Animals↗

[Thoracic aortic stenting: indications and results].

AIM: Determination of the conditions for good acute and long term results of interventional therapy of lesions of the thoracic aorta using stent-grafts. PATIENTS, MATERIAL AND METHODS: 51 patients with aneurysm of the thoracic aorta (type B dissections) covered rupture and aortobronchial fistula were evaluated. All cases were discussed in an interdisciplinary conference consisting of thoracic surgeon and interventional radiologist. Primarily, 20 patients were operated and 31 were treated by intervention. For all a multidetector row CT angiography was ordered prior to the discussion. All procedures were performed in a DSA suite under general anaesthesia. In 29 patients Talent LPS trade mark tube grafts and in four patients an Excluder trade mark graft was implanted. RESULTS: 29 patients had an aneurysm of the thoracic aorta, 21 a type B dissection, 19 a perforation and one patient had an aortobronchial fistula. The follow up was 13.4 months. In 29 patients the stent-graft implantation was successful, in 2 patients stent-graft delivery failed due to severe calcification and kincking of both common iliac arteries. One patient had an iliacal dissection after stent-graft delivery which was treated successfully by surgery. In two patients CT angiographic control detected endoleaks, which were treated with a second stent-graft placement. One patient with an acute perforation of the descending aorta died due to cardiac failure prior to stent-graft implantation. Any neurological complication did not occur. CONCLUSION: Percutaneous treatment of lesions of the descending thoracic aorta using stent-grafts is a safe and feasible alternative treatment to surgical repair. Prior to the a multidetector row CT angiography is necessary for exact planning of the endo-luminal treatment.

Aged↗

[Importance of coloncontrast enema].

Screening for colorectal cancer starts with digital exploration of the rectum and was extended in 1977 using the haemoccult test. It was referred to detect 24% of malignancies, but with a high number of false positive findings. Combination of regular follow up examinations and coloscopy reached a sensitivity of 80%. International studies demonstrated the need of a complete colon examination, so that the coloscopy is actually an important screening method in Germany. The coloncontrast examination is a safe, cost-effective method with a low complication rate. It is suitable especially for patients, in which the colonoscopic evaluation of the colon was not complete and provides additional morphological informations in many cases.

Adenomatous Polyps↗

[Stents in the iliac arteries: a minimally invasive method].

AIM: We demonstrate patients to reveal the conditions for good results with respect to acute and long term out-come of interventional therapy of iliac artery occlusion. MATERIAL AND METHODS: 225 Patients with aortoiliacal occlusion who underwent surgery or intervention were evaluated. All patients were discussed in an interdisciplinary angiologic conference. 63 patients primary had an operation, 161 patients primary were treated by intervention. The two cohorts were compared concerning their structure, the primary success and the primary and secondary patency over one year. RESULTS: Both cohorts showed significant differences, the surgical treated patient had a higher clinical stage as well as more complex iliacal occlusion. The interventional treated patients had higher comorbidity. Primary technical success and patency rates did not show any difference. The complication rate was equally low in both cohorts. In percutaneous treated patients after predilatation, embolization into the periphery occurred. With primary stent PTA, there was no embolization. CONCLUSION: The percutaneous recanalization also of long iliac occlusion is a save, successful alternative to surgery. Nevertheless, there are limits. For optimal therapy management an interdisciplinary consultation is necessary. To avoid embolization, after recanalization primary stent PTA should be performed.

Arterial Occlusive Diseases↗

Notched ureter sign.

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Diagnosis, Differential↗

Role of ultrasonography in the detection of small adrenal masses.

AIM: Computed tomography (CT) scanning is commonly used for evaluation of adrenal masses in adults. In this prospective study we evaluated whether adrenal gland masses of less or equal than 20 mm in diameter could be detected by modern abdominal ultrasonography (US). METHOD: Between July 1999 and June 2000, 44 consecutive patients with 50 adrenal masses documented by contrast-enhanced CT (left adrenal gland, n = 31; right adrenal gland, n = 19; bilateral, n = 6; median size, 15 [5 +/- 80] mm) and, additionally, 50 patients without CT findings of an adrenal mass were prospectively evaluated by high-resolution US performed by physicians. Based upon CT measurement, 34 adrenal masses were </= 20 mm and 16 were > 20 mm in diameter. RESULTS: The overall sensitivity of US for the detection of adrenal masses was 96 % (48/50) (94 % [29/31] for left and 100 % [19/19] for right adrenal masses, respectively). The overall specificity of US for the detection of adrenal masses was 92 % (92/100) (90 % [45/50] for left and 94 % [47/50] for right adrenal masses, respectively). Thus, the diagnostic accuracy of US for the detection of adrenal masses is 93 % (140/150). Sensitivity and specificity of US for the detection of adrenal masses </= 20 mm (n = 34) did not differ significantly from those > 20 mm (n = 16). CONCLUSION: US is effective for detecting small adrenal masses. In rare cases small masses of the left adrenal gland might be missed and nodular adrenal hyperplasia or retroperitoneal lymph nodes might be misinterpreted as adrenal masses.

Adrenal Gland Neoplasms↗

Vessel wall MRI of the thoracic aorta: correlation to histology and transesophageal ultrasound. Preliminary results.

PURPOSE: To visualise the vessel wall of the descending thoracic aorta using magnetic resonance imaging. To evaluate the diagnostic potential of tailored T1-weighted sequences with contrast enhancement to assess systemic atherosclerotic disease. METHODS: This study was performed on a clinical 1.5 Tesla scanner using a gradient strength of 30 mT/m and the phased array spine coil. A cadaver was examined to optimise a magnetic resonance imaging (MRI) protocol to evaluate atherosclerotic aortic wall disease. The acquired MR images were compared to gross specimens and histology. Subsequently seven patients who had undergone transesophageal ultrasound (TEU) with detailed assessment of the descending thoracic aorta were examined with MRI. The optimised protocol included untriggered and fat suppressed T2-weighted turbo spin echo sequences and ECG-triggered and fat suppressed T1-weighted spin echo sequences before and after iv administration of Gd-DTPA. Findings of the MR images were compared to the results of TEU. Contrast enhancement measurements were performed in normal and thickened vessel wall segments. RESULTS: For the cadaver study a good correlation of the degree of vessel wall thickening and the extent of plaque imaged with the applied MR protocol was found. Tissue characterisation was limited due to post mortem changes. In vivo ECG-triggered T1-weighted images showed good correlation to TEU in terms of vessel wall thickness and plaque extension as verified by means of consensus reading. Differentiation of the plaque components fat, calcium and fibrous tissue was possible. In thickened aortic wall segments and fibrous caps a mean contrast enhancement of 50.4 % +/- 23.5 % was measurable while normal wall segments showed an enhancement of 6.7 % +/- 3.1 %. The difference of contrast enhancement was highly significant (p < 0.0001). CONCLUSION: Using fat suppressed T1-weighted sequences with contrast enhancement the extent of atherosclerotic vessel wall changes can be demonstrated. The suggested MR protocol contains a high potential for diagnosis and follow-up of therapy of atherosclerotic disease of the descending thoracic aorta.

Aorta, Thoracic↗

[Bronchial artery embolization for therapy of pulmonary bleeding in patients with cystic fibrosis].

INTRODUCTION: Acute pulmonary emergencies in patient with cystic fibrosis (CF) can be found in cases of pneumothorax as well as hemoptysis. If the bleeding cannot be stopped by conservative methods, an embolization of the bronchial arteries should be done. MATERIALS AND METHOD: 11 patients were embolized using a combination of PVA particles and microcoils. RESULTS: From January 1996 to June 2001 17 bronchial arteries in 11 patients were embolized. 7 patients suffered from chronical hemoptysis, 4 patients had an acute hemoptysis. In 4 patients both sides were embolized, in 3 patients only one side. The remaining 4 patients needed a second intervention, embolizing the other side. The primary embolizated bronchial artery was still closed in all 4 patients. In 1 patient the selective catheterization of a bronchial artery was not successful, thus the embolization could not be carried out. 1 patient died 5 days after the intervention due to a fulminant pneumonia (Pseudomonas aeruginosa) without recurrent bleeding. In two patients atypical branches from intercostal arteries feeding the bronchial arteries were detected and successfully embolized. All patients profited from the therapy, as bleeding could be stopped or at least be reduced. 3 patients suffered from back pain during or after intervention. There were no severe complications like neurological deficiencies or necroses. CONCLUSION: The embolization of bronchial arteries using particles and microcoils is an effective intervention with a low complication rate in pulmonary bleeding of CF patients.

Bronchial Arteries↗

[Transarterial chemoembolization of liver metastases: Indication, technique, results].

We have analyzed the effectiveness of repetitive transarterial chemoembolization (TACE) of liver metastases as a neoadjuvant or palliative treatment modality in comparison with published data. Chemoembolization of liver metastases is performed with different cytotoxic drugs. In a 4-week interval, 357 patients were treated with repetitive 1,158 TACE courses performed with lipiodol, mitomycin C and spherex. 254 patients were treated palliatively, 18 patients symptomatically and 79 patients via the neoadjuvant protocol, 71 patients of whom received additional MR-guided laser-induced thermoablation (LITT) of the metastases after TACE. Our results were compared with the literature. Most of the patients with a low rate of local complications like vascular occlusion or liver abscess could be treated successfully using TACE. In 81 % of the treated lesions a primary high lipiodol retention was observed. In the palliative group a reduction of the tumor size was noted in 36 % of the lesions, a growth stop in 24 % and a reduction of the tumor growth rate in 40 %. In 70 % of the patients treated neodadjuvantly a reduction of the tumor size was found. The median survival rate of our collective of patients with liver metastases averages 8.6 months. In the literature median survival rates in patients with liver metastases were between 8.5 and 23 months after TACE. TACE is judged as a minimal invasive and outpatient treatment protocol for liver metastases. A combination of TACE and different local treatment modalities presents a neoadjuvant treatment strategy to control the diseased liver.

Adult↗

Repositioning of malpositioned or flipped central venous catheters.

Primary misplaced or secondary flipped implanted catheters are located mostly in the right jugular vein. We demonstrate an effective method to replace fix implanted catheters such as Ports, Grochomg or Hickman catheters. Using a femoral venous approach, replacement into the superior vena cava can easily be done with a Sidewinder 1 catheter which is hooked over the misplaced central venous approach. In all our patients the method was successful. The repositioning technique described is simple, fast and has low costs. We can keep sterile conditions and do not need to solve the catheters' fixation.

Catheterization, Central Venous↗

Identification of domains and amino acids involved in GLuR7 ion channel function.

The kainate receptors GluR6 and GluR7 differ considerably in their ion channel properties, despite sharing 86% amino acid sequence identity. When expressed in Xenopus oocytes GluR6 conducts large agonist-evoked currents, whereas GluR7 lacks measurable currents. In the present study, we localized the determinants that are responsible for the functional differences between GluR6 and GluR7 to the extracellular loop domain L3. In addition, we generated several GluR7 point mutants that are able to conduct currents that can be readily measured in Xenopus oocytes. In GluR6, glutamate- and kainate-evoked maximal currents are of the same magnitude when desensitization is inhibited with the lectin concanavalin A. By contrast, all functional GluR7 mutants were found to have glutamate current amplitudes significantly larger than those evoked by kainate. We localized the domain that determines the relative agonist efficacies to the C-terminal half of the L3 domain of GluR7. Our data show that EC(50) values for glutamate (but not for kainate) in GluR7 mutants or chimeras tend to be increased in comparison to the EC(50) values in GluR6. The high EC(50) for wild-type GluR7 reported in the literature appears to be linked to the S1 portion of the agonist-binding domain. Finally, we determined the C-terminal half of the L3 domain plus the far C-terminal domain of GluR7 to be responsible for the recently reported reduction of current amplitude seen when GluR7 is coexpressed with GluR6. We conclude that coexpression of GluR6 and GluR7 leads to nonstochastical assembly of heteromeric receptor complexes.

Amino Acids↗

[Transjugular portosystemic stent shunt (TIPSS) as intervention in clinical complications of portal hypertension].

Most frequent complications in patients with liver cirrhosis are due to portal hypertension. Beside ascites circumvent vessels formate with vasodilatation. Due to counterregulation a secondary hyperaldosteronism develops with release of vasocontrictive agents. If conservative and endoscopic methods fail, indication for building a portosystemic shunt is given. The TIPSS procedure is less invasive than the surgical method of Warren-Shunt, so the radiological intervention has replaced surgery. Reducing the portal pressure by the shunt, the clinical complications change for the better. Still problems are defined as hepatic encephalopathy and right ventricular heart failure. Regular follow up investigations have to be performed to detect complications in the shunt. Using regular clinical and radiological check up TIPSS is of clinical benefit with good long term results.

Diagnostic Imaging↗