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Biomedical subjects

Thomas Weber

Publications and source records attributed to Thomas Weber.

At least 19 recordsLinked to original sources
PubMed2005

Solution NMR structure of the SH3 domain of human nephrocystin and analysis of a mutation-causing juvenile nephronophthisis.

Human nephrocystin is a protein associated with juvenile NPH, an autosomal recessive, inherited kidney disease responsible for chronic renal failure in children. It contains an SH3 domain involved in signaling pathways controlling cell adhesion and cytoskeleton organization. The solution structure of this domain was solved by triple resonance NMR spectroscopy. Within the core, the structure is similar to those previously reported for other SH3 domains but exhibits a number of specific noncanonical features within the polyproline ligand binding site. Some of the key conserved residues are missing, and the N-Src loop exhibits an unusual twisted geometry, which results in a narrowing of the binding groove. This is induced by the replacement of a conserved Asp, Asn, or Glu residue by a Pro at one side of the N-Src loop. A systematic survey of other SH3 domains also containing a Pro at this position reveals that most of them belong to proteins involved in cell adhesion or motility. A variant of this domain, which carries a point mutation causing NPH, was also analyzed. This change, L180P, although it corresponds to a nonconserved and solvent-exposed position, causes a complete loss of the tertiary structure. Similar effects are also observed with the L180A variant. This could be a context-dependent effect resulting from an interaction between neighboring charged side-chains.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Rapamycin rescue therapy in patients after kidney transplantation: first clinical experience.

This study was aimed at analysing rapamycin (RAPA) rescue therapy with calcineurin inhibitor (CNI) withdrawal in renal transplant patients primarily presenting with CNI-nephrotoxicity (CNI-Neph), chronic allograft nephropathy (CAN) without [CAN(a)] and with histological changes suggestive of chronic rejection [CAN(b)]. In 36 patient with CNI-Neph (n = 6), CAN(b) (n = 21), CAN(a) (n = 7), and others (n = 2) RAPA therapy was started 4.4-115 months (median 30.6 months) after renal transplantation. During a follow up of 3-33 months (median 19 months) parameters of kidney function were recorded. Three patients on haemodialysis did not show any recovery of graft function. Of the remaining 33 patients renal function improved in 22 (66.7%), was stable in three (9%) but deteriorated in eight (24%) patients, of whom seven (21%) required haemodialysis thereafter. Success rate of RAPA therapy differed with respect to the histological diagnosis: 70% in CAN(b), 80% in CNI-Neph and 33% in CAN(a). Furthermore, in patients with creatinine levels above 400 mum (n = 6) graft function rarely improved (n = 2, 33%). The RAPA rescue therapy with CNI withdrawal appears promising in a special cohort of patients with chronic renal allograft dysfunction even late after transplantation.

Adult↗
PubMed2005

The diagnostic and prognostic value of brain natriuretic peptide and aminoterminal (nt)-pro brain natriuretic peptide.

The discovery of B-type natriuretic peptide (BNP) and n-terminal pro BNP (nt-proBNP) as markers for the diagnosis, severity and prognosis of patients with congestive heart failure has been called a true breakthrough for patients and physicians faced with this disorder. Moreover, the literature on their prognostic value in other clinical conditions like acute coronary syndromes, right-sided heart failure and even in the general population is rapidly growing. This review aims to sort out the current evidence on the clinical utility of the natriuretic peptides with a focus on their diagnostic and prognostic values. With respect to their diagnostic properties, the test is best used to rule out heart failure in patients with acute dyspnoe, because low levels of these neurohormones in this clinical context make the presence of heart failure very unlikely. In patients with elevated values of BNP or nt-proBNP, further cardiological assessment is necessary, as their plasma levels are affected not only by left ventricular function.

Biomarkers↗
PubMed2005

Experimental autoimmune encephalomyelitis in the rat spinal cord: lesion detection with high-resolution MR microscopy at 17.6 T.

BACKGROUND AND PURPOSE: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disorder of the CNS and an animal model of multiple sclerosis. We used high-field MR microscopy at 17.6 T to image spinal cord inflammatory lesions in the acute stage of chronic relapsing rat EAE. We sought to compare lesions detected on MR imaging with histopathologic findings and to quantify the inflammatory lesion load. METHODS: Imaging of fixed spinal cord specimens was performed by using a 3D gradient-echo sequence with a spatial resolution of 35 x 35 x 58 microm3 and a total imaging time of 5.5 hours. Histopathologic analysis was performed by staining axial sections with hematoxylin-eosin or Luxol fast blue to identify cellular infiltration and demyelination. RESULTS: Clinical signs of EAE occurred on days 10-14 after immunization. On day 22, healthy white matter and gray matter were differentiated by high contrast on T2*-weighted images, with white matter lesions appearing as hyperintense areas in the normal-appearing white matter. Inflammatory lesions identified on histopathologic evaluation were readily detected with MR imaging and vice versa. MR imaging and histopathologic analysis had excellent correlation regarding the extent of white matter lesions. Inflammatory infiltrates of gray matter were not detectable with MR imaging. Using a semiautomatic segmentation of the acquired MR data, we could quantify white matter lesion load. CONCLUSION: Ex vivo high-resolution MR microscopy of the spinal cord at 17.6 T allows rapid and highly accurate determination of CNS inflammation by demonstrating virtually all histologically detectable white matter inflammatory lesions.

Animals↗
PubMed2004

Reconstitution of Ca2+-regulated membrane fusion by synaptotagmin and SNAREs.

We investigated the effect of synaptotagmin I on membrane fusion mediated by neuronal SNARE proteins, SNAP-25, syntaxin, and synaptobrevin, which were reconstituted into vesicles. In the presence of Ca2+, the cytoplasmic domain of synaptotagmin I (syt) strongly stimulated membrane fusion when synaptobrevin densities were similar to those found in native synaptic vesicles. The Ca2+ dependence of syt-stimulated fusion was modulated by changes in lipid composition of the vesicles and by a truncation that mimics cleavage of SNAP-25 by botulinum neurotoxin A. Stimulation of fusion was abolished by disrupting the Ca2+-binding activity, or by severing the tandem C2 domains, of syt. Thus, syt and SNAREs are likely to represent the minimal protein complement for Ca2+-triggered exocytosis.

Animals↗
PubMed2004

[Infection sources in HNO- and jawbone regions in patients before valve replacement surgery].

BACKGROUND: Prosthetic valve endocarditis is a life-threatening complication after valve replacement surgery. Therefore, it is common to perform a screening for potential sources of infection before surgery in order to be able to do a prophylactic treatment. PATIENTS AND METHOD: The incidence of potential infectious sources of bacteremia in the dental, jaw and nasopharyngeal area was evaluated in 92 patients going to have valve replacement surgery. Screening examinations were an X-ray of the paranasal sinuses and a panoramic radiograph of the dental arch. Chronic apical periodontitis, cysts and remaining radices were counted as dental sources. Each shadow in the paranasal sinuses X-ray was seen as pathological and was further investigated by an otorhinolaryngologist. RESULTS: A potential infectious source was found in 49 patients. 42 patients had a dental infectious source with need for treatment. 19 patients showed a pathologic sinus X-ray (three aspergillomas, three sinusitis, the others had a chronic polyposis with no need for treatment). Twelve patients had dental as well as sinusoidal sources. Erythrocyte sedimentation rate did not refer to the appearance of infectious sources. Patients going to have a mitral valve replacement had most dental sources (61%), 47% of the patients with planned aortic valve replacement, 50% of the patients planned to get more than one heart valve replaced, 50% of the patients getting mitral valve replacement and CABG and 40% of the patients waiting for aortic valve replacement and CABG had dental foci. CONCLUSION: Screening for infectious foci before valve replacement surgery diagnosed foci in a high percentage of the patients. Nevertheless current data concerning whether a prophylactic treatment may reduce the incidence of prosthetic valve endocarditis are conflicting.

Adult↗
PubMed2004

Bilateral intermittent claudication and the aorta.

With the increasing utilization of imaging strategies such as transesophageal echocardiography and magnetic resonance imaging, thrombi of the aorta are becoming increasingly recognized as sources of peripheral emboli. This report describes a 70-year-old man with bilateral intermittent claudication. Arteriography revealed occlusion of the distal part of the right tibialis posterior artery and the left tibialis anterior artery, but no occlusive atherosclerotic disease of the iliac, femoral, or popliteal artery. Additionally, no calcification of the vessels could be demonstrated. In contrast, a giant thrombus of the descending aorta was identified as the source of systemic thromboembolism. The patient was treated successfully with long-term anticoagulation.

Aged↗
PubMed2004

A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial.

BACKGROUND: Atrial fibrillation (AF) frequently occurs after cardiac surgical procedures, and beta-blockers, sotalol, and amiodarone may reduce the frequency of AF after open heart surgery. This pilot trial was designed to test whether each of the active oral drug regimens is superior to placebo for prevention of postoperative AF and whether there are differences in favor of 1 of the preventive strategies. METHODS AND RESULTS: We conducted a randomized, double-blinded, placebo-controlled trial in which patients undergoing cardiac surgery in the absence of heart failure and without significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) received oral amiodarone plus metoprolol (n = 63), metoprolol alone (n = 62), sotalol (n = 63), or placebo (n = 65). Patients receiving combination therapy (amiodarone plus metoprolol) and those receiving sotalol had a significantly lower frequency of AF (30.2% and 31.7%; absolute difference, 23.6% and 22.1%; odds ratios [OR], 0.37 [95% CI, 0.18 to 0.77, P <.01 vs placebo] and 0.40 [0.19 to 0.82, P =.01 vs placebo]) compared with patients receiving placebo (53.8%). Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]. Treatment effects did not differ significantly between active drug groups. Adverse events including cerebrovascular accident, postoperative ventricular tachycardia, nausea, and dyspepsia, in hospital death, postoperative infections, and hypotension, were similar among the groups. Bradycardia necessitating dose reduction or drug withdrawal occurred in 3.1% (placebo), 3.2% (combined amiodarone and metoprolol; P =.65 vs placebo), 12.7% (sotalol; P <.05 vs placebo), and 16.1% (metoprolol; P <.05 vs placebo). Patients in the placebo group had a nonsignificantly longer length of hospital stay as compared with the active treatment groups (13.1 +/- 8.9 days vs 11.3 +/- 7; P =.10), with no significant difference between the active treatment groups. CONCLUSIONS: Oral active prophylaxis with either sotalol or amiodarone plus metoprolol may reduce the rate of AF after cardiac surgery in a population at high risk for postoperative AF. Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF.

Administration, Oral↗
PubMed2004

Video-assisted thoracoscopic surgery of mediastinal bronchogenic cysts in adults: a single-center experience.

BACKGROUND: Mediastinal bronchogenic cysts are rarely diagnosed in adults, hence surgical experience is limited particularly with regard to video-assisted thoracoscopic surgery. In support of the thoracoscopic approach we report our single-center experience in this rare entity. METHODS: Between June 1995 and December 2002, a nonselected series of 12 consecutive patients presenting with mediastinal bronchogenic cysts underwent video-assisted thoracoscopic surgery. Six cysts (50%) had been diagnosed 2 to 22 years prior, only three of which became symptomatic. In asymptomatic patients (n = 7) surgery was performed because of increasing cyst size (n = 3), patient's request (n = 3), or suspected metastasis (n = 1). RESULTS: Mediastinal bronchogenic cysts were correctly diagnosed by computed tomography in 83% (10/12) and by magnetic resonance imaging in 100% (9/9). Using a three-trocar technique thoracoscopic surgery was successfully performed in 11 of 12 cases (92%). We noted no signs of acute cyst infection. No serious postoperative complications were observed. In 1 patient conversion to open thoracotomy was necessary due to extensive pleural adhesions. In another case thoracoscopic excision of the cyst wall was incomplete. Patients with thoracoscopic excision were discharged after a median of 5.5 days (range 4 to 14 days). No recurrences or complications were observed during a mean follow-up of 40.5 months. CONCLUSIONS: Considering the low conversion and complication rate in our series, video-assisted thoracoscopic surgery should be the primary therapeutic choice among adults with symptomatic mediastinal bronchogenic cysts. Surgical intervention in patients with asymptomatic and uncomplicated cysts appears optional.

Adult↗
PubMed2004

Laparoscopic unroofing of nonparasitic liver cysts within segments VII and VIII: technical considerations.

BACKGROUND: The laparoscopic accessibility of congenital liver cysts located in the anterosuperior (VIII) and posterosuperior (VII) segments has been questioned for some time. In support of the laparoscopic approach, we here describe our minimally invasive technique in two patients with solitary congenital cysts located in the apex of liver segments VIII and VII, respectively. METHOD: Both patients were placed in the inverted Y position. Four trocars were used, their position depending on the location of the cyst. RESULTS: The segment VIII cyst was easily reached via this anterior approach, while the segment VII cyst required significant mobilization of the right liver lobe. In both cases a complete excision of the cystic roof was achieved using the harmonic scalpel. Without performing an omentoplasty no recurrences were observed after 20 and 28 months, respectively. CONCLUSION: Solitary cysts located in segments VII and VIII of the liver can be safely treated by laparoscopic unroofing. Cyst recurrences may best be prevented by a complete excision of the cystic roof with an adjacent rim of hepatic parenchyma.

Adult↗