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Matthias Meier

Publications and source records attributed to Matthias Meier.

13 recordsLinked to original sources
PubMed2006

The fate of the distal aorta after repair of acute type A aortic dissection.

OBJECTIVES: The residual aorta's behavior after repair of acute type A dissection is incompletely understood. We analyzed segmental growth rates, distal reoperation, and factors influencing long-term survival. METHODS: One hundred seventy-nine consecutive patients (70% male; mean age, 60 years) with acute type A dissection underwent aggressive resection of the intimal tear and open distal anastomosis (1986-2003). Hospital mortality was 13.4%. Survivors had serial computed tomographic scans: digitization yielded distal segmental dimensions. Segment-specific average rates of enlargement and factors influencing faster growth were analyzed. Distal reoperations and patient survival were examined. RESULTS: Eighty-nine (57%) patients had imaging data sufficient for growth rate calculations. The median diameters after repair were as follows: aortic arch, 3.6 cm; descending aorta, 3.7 cm; and abdominal aorta, 3.2 cm. Subsequent growth rates were 0.8, 1.0, and 0.8 mm/y, respectively. Initial size of greater than 4 cm (P = .005) and initial diameter of less than 4 cm with a patent false lumen (P = .004) predicted greater growth in the descending aorta, and male sex (P = .05) significantly affected growth in the abdominal aorta. No significant factors were found for the aortic arch. There were 25 distal aortic reoperations (16 patients), and risk of reoperation was 16% at 10 years. Risk factors reducing long-term survival after repair of acute type A dissection included age (P < .0001), new neurological deficit at presentation (P = .04), absence of preoperative thrombus in the false lumen of the ascending aorta (P = .03), and a patent distal false lumen postoperatively (P = .06) but not distal reoperation. CONCLUSIONS: Growth of the distal aorta after repair of acute type A dissection is typically slow and linear. Distal reoperation is uncommon, and late risk of death is approximately twice that of a healthy population.

Acute Disease↗
PubMed2006

Cellular and molecular mechanisms of tissue protection by lipophilic calcium channel blockers.

Long-acting third-generation dihydropyridine calcium channel blockers (CCBs) improve endothelial dysfunction and prevent cardiovascular events in humans, but their cellular and molecular mechanisms of tissue protection are not elucidated in detail. We assessed organ (renal) protection by the highly lipophilic CCB lercanidipine in a double-transgenic rat (dTGR) model with overexpression of human renin and angiotensinogen genes. We randomly treated dTGR with lercanidipine (2.5 mg/kg/day; n=20) or vehicle (n=20) for 3 wk. Furthermore, we explored the influence of lercanidipine on protein kinase C (PKC) signaling in vivo and in vitro using endothelial and vascular smooth muscle cell cultures. Cumulative mortality was 60% in untreated dTGR, whereas none of the lercanidipine-treated animals died (P<0.001). We found significantly less albuminuria and improved renal function in lercanidipine-treated dTGR (both P<0.05). Lercanidipine treatment also significantly (P<0.05) reduced blood levels of the endogenous NOS inhibitor asymmetric dimethylarginine. On histological examination, we observed significantly less tissue inflammation and fibrosis in lercanidipine-treated animals (both P<0.05). Lercanidipine significantly inhibited angiotensin (ANG) I-mediated PKC-alpha and -delta activation in vivo and in vitro, partly due to reduced intracellular calcium flux. As a result, lercanidipine improved endothelial cell permeability in vitro. Lercanidipine prevents tissue injury and improves survival in a model of progressive organ damage. These effects may result, at least in part, from inhibition of tissue inflammation as well as improved NO bioavailability. Modulation of PKC activity may be an important underlying intracellular mechanism.

Albumins↗
PubMed2005

Reverse micelles dissolved in supercritical xenon: an NMR spectroscopic study.

Reverse micelles currently gain increasing interest in chemical technology. They also become important in biomolecular NMR due to their ability to host biomolecules such as proteins. In the present paper, a procedure for the preparation of high-pressure NMR samples containing reverse micelles dissolved in supercritical xenon is presented. These reverse micelles are formed by sodium bis(2-ethylhexyl) sulfosuccinate (AOT). For the first time, NMR spectroscopy could be applied to reverse micelles in supercritical xenon. The AOT/H(2)O/Xe system was studied as a function of experimental parameters such as xenon pressure, water content, and salt concentration. Optimum conditions for reverse micelle formation in supercritical xenon could be determined. It is, furthermore, demonstrated that biomolecules such as amino acids and proteins can be incorporated into the reverse micelles dissolved in supercritical xenon.

Chemistry, Physical↗
PubMed2005

Aortic arch replacement using a trifurcated graft: simple, versatile, and safe.

BACKGROUND: Hypothermic selective antegrade cerebral perfusion during aortic arch replacement may prevent adverse neurologic sequelae. It can be provided via balloon-tipped catheters or a branched graft sewn to the brachiocephalic vessels. We report a consecutive series of total arch replacement using a trifurcated graft. METHODS: From September 1999 through October 2004, 109 patients underwent nonemergent total arch replacement using this technique. The graft, placed during a period of hypothermic circulatory arrest, was used for selective cerebral perfusion during the arch reconstruction. RESULTS: Adverse outcomes were seen in 9 (8.3%) patients: hospital death in 5 (4.6%), and stroke in 5 (4.6%). Transient neurologic dysfunction was noted in 6 (5.5%) patients. Mean duration of hypothermic circulatory arrest was 31.2 +/- 6.6 minutes and selective cerebral perfusion was 65.3 +/- 20.9 minutes. Reoperation for bleeding was required in 3 (2.8%) patients and prolonged intubation in 15 (13.8%). Median intensive care unit stay was 3 days (interquartile range 2-4; range, 1 to 108) and hospital stay was 9 (interquartile range 8-15; range, 5 to 108). CONCLUSIONS: The trifurcated graft technique results in low rates of perioperative mortality, temporary neurologic dysfunction, and stroke. It may reduce cerebral embolization as it requires no instrumentation of the aortic arch to establish selective cerebral perfusion and, although it mandates hypothermic circulatory arrest to place the graft, this interval is reliably brief enough to fall within accepted safe limits. This strategy leaves no residual arch tissue behind, and allows placement of an elephant trunk proximal to one or more arch vessels if anatomically indicated.

Adult↗
PubMed2005

Prokinetic therapy: what can be measured by gastric scintigraphy?

OBJECTIVE: To evaluate whether gastric scintigraphy with quantitative analysis of gastric peristalsis may be a useful tool for documenting the effects of prokinetic therapy. METHODS: Gastric emptying was determined in eight patients with insulin dependent diabetes mellitus (IDDM) and nine patients with progressive systemic sclerosis (PSS) after ingestion of a semi-solid test meal. Fourier analysis of condensed images was used to evaluate contraction amplitudes of the entire stomach, as well as frequency and velocity of gastric contractions. Patients were studied twice, first under baseline conditions and then after 4 weeks of continuous oral prokinetic therapy with cisapride (10 mg t.i.d.). Findings were compared with data derived from 15 healthy controls. RESULTS: At baseline conditions IDDM and PSS patients exhibited reduced gastric peristalsis and delayed emptying compared to controls. After 4 weeks of prokinetic treatment, gastric contraction amplitudes increased significantly, especially in the gastric corpus and the proximal stomach, associated with a slight improvement of gastric emptying. Changes in frequency and velocity of gastric contractions during prokinetic treatment correlated with the improvement of gastric motility and emptying. CONCLUSIONS: Prokinetic therapy with cisapride stimulates gastric motility, and could be non-invasively monitored by scintigraphy. This radionuclide technique provides a number of relevant parameters of gastric function, such as gastric emptying, contraction amplitudes, frequency and velocity of gastric contractions, which give crucial insights into the mechanisms of action of prokinetic drugs.

Adult↗
PubMed2004

[Diabetic nephropathy - current concepts in early diagnosis and treatment of diabetic microvascular complications].

Diabetic nephropathy represents the most important microvascular complication in long-term diabetes mellitus because chronic renal insufficiency is further aggravated by increased cardiovascular morbidity and mortality in diabetic patients. Although early intensive insulin therapy has led to a significant reduction of incidence and prevalence of end-stage renal failure over the last decades in juvenile type 1 diabetes mellitus, the total number of type 2 diabetic patients with chronic renal insufficiency is dramatically increasing due to the improved life expectancy of the general population and the more effective medical treatment of macrovascular complications such as arterial hypertension, coronary artery disease, and peripheral arterial occlusive disease. Apart from the personal burden for each individual the frightening epidemiologic dimension of diabetic nephropathy represents an outstanding challenge for our social systems.

Comorbidity↗
PubMed2004

Attenuation of extracellular matrix accumulation in diabetic nephropathy by the advanced glycation end product cross-link breaker ALT-711 via a protein kinase C-alpha-dependent pathway.

This study investigated the role of advanced glycation end products (AGEs) in mediating protein kinase C (PKC) isoform expression in diabetic nephropathy. In vitro, vascular smooth muscle cells incubated in a high-glucose (25-mmol/l) medium demonstrated translocation and increased expression of PKC-alpha as compared with those from a low-glucose (5-mmol/l) environment. Coincubation with the cross-link breaker ALT-711 and, to a lesser extent, with aminoguanidine, an inhibitor of AGE formation, attenuated the increased expression and translocation of PKC-alpha. Streptozotocin-induced diabetic rats were randomized to no treatment, treatment with ALT-711, or treatment with aminoguanidine. Diabetes induced increases in PKC-alpha as well as in the -betaI, -betaII, and -epsilon isoforms. Treatment with ALT-711 and aminoguanidine, which both attenuate renal AGE accumulation, abrogated these increases in PKC expression. However, translocation of phosphorylated PKC-alpha from the cytoplasm to the membrane was reduced only by ALT-711. ALT-711 treatment attenuated expression of vascular endothelial growth factor and the extracellular matrix proteins, fibronectin and laminin, in association with reduced albuminuria. Aminoguanidine had no effect on VEGF expression, although some reduction of fibronectin and laminin was observed. These findings implicate AGEs as important stimuli for the activation of PKC, particularly PKC-alpha, in the diabetic kidney, which can be directly inhibited by ALT-711.

Animals↗
PubMed2004

Diminished loss of proteoglycans and lack of albuminuria in protein kinase C-alpha-deficient diabetic mice.

Activation of protein kinase C (PKC) isoforms has been implicated in the pathogenesis of diabetic nephropathy. We showed earlier that PKC-alpha is activated in the kidneys of hyperglycemic animals. We now used PKC-alpha(-/-) mice to test the hypothesis that this PKC isoform mediates streptozotocin-induced diabetic nephropathy. We observed that renal and glomerular hypertrophy was similar in diabetic wild-type and PKC-alpha(-/-) mice. However, the development of albuminuria was almost absent in the diabetic PKC-alpha(-/-) mice. The hyperglycemia-induced downregulation of the negatively charged basement membrane heparan sulfate proteoglycan perlecan was completely prevented in the PKC-alpha(-/-) mice, compared with controls. We then asked whether transforming growth factor-beta1 (TGF-beta1) and/or vascular endothelial growth factor (VEGF) is implicated in the PKC-alpha-mediated changes in the basement membrane. The hyperglycemia-induced expression of VEGF165 and its receptor VEGF receptor II (flk-1) was ameliorated in PKC-alpha(-/-) mice, whereas expression of TGF-beta1 was not affected by the lack of PKC-alpha. Our findings indicate that two important features of diabetic nephropathy-glomerular hypertrophy and albuminuria-are differentially regulated. The glucose-induced albuminuria seems to be mediated by PKC-alpha via downregulation of proteoglycans in the basement membrane and regulation of VEGF expression. Therefore, PKC-alpha is a possible therapeutic target for the prevention of diabetic albuminuria.

Albuminuria↗
PubMed2003

Optical sectioning in wide-field microscopy obtained by dynamic structured light illumination and detection based on a smart pixel detector array.

Optical sectioning in wide-field microscopy is achieved by illumination of the object with a continuously moving single-spatial-frequency pattern and detecting the image with a smart pixel detector array. This detector performs an on-chip electronic signal processing that extracts the optically sectioned image. The optically sectioned image is directly observed in real time without any additional postprocessing.

Journal Article↗
PubMed2002

An advanced approach for the assessment of gastric motor function in long-term type 1 diabetes mellitus with and without autonomic neuropathy.

Gastric motor dysfunction is a frequent and deleterious long-term complication in diabetes mellitus (DM) but the exact contribution of diabetic autonomic dysfunction remains unclear. The aim of this study was to assess indices of gastric motor function in long-term Type 1 DM in the light of the presence and absence of autonomic neuropathy by means of an advanced dynamic scintigraphic technique. Gastric scintigraphy with condensed images of a short dynamic sequence was applied to 27 long-term Type 1 diabetic patients (duration > 10 years) and 15 control subjects. Two indices of gastric peristalsis, the frequency of contractions (FC) and amplitude of contractions (AC), were assessed scintigraphically together with half-time of gastric emptying (t 1/2). Five cardiac reflex tests were performed to study electrocardiogram (ECG)-based cardiac autonomic neuropathy (CAN). Mean AC was significantly decreased in diabetic patients compared to control subjects (13 +/- 9% vs. 28 +/- 8%, p < 0.005). Mean FC was comparable between diabetic patients and control subjects min(-1). (3.1 +/- 0.4 min(-1) vs. 3.1 +/- 0.2 Compared to control subjects, half-time of gastric emptying was significantly prolonged in diabetic patients (31 +/- 17 min vs. 20 +/- 3 min, p < 0.001). Mean AC, FC and t 1/2 did not differ significantly between diabetic patients with (n = 10) and without (n = 17) ECG-based CAN. Our study demonstrates that in both long-term Type 1 DM with and without autonomic neuropathy, the amplitude but not the frequency of gastric contractions, is frequently reduced. A delay of gastric emptying in Type 1 DM is confirmed although it was independent from the presence of cardiac autonomic neuropathy (CAN). Analyzing gastric motor function with dynamic scintigraphic techniques using condensed images is a promising clinical approach to further elucidate the mechanisms of impaired gastric motility in DM.

Adult↗
PubMedDate not supplied

Identification of urinary protein pattern in type 1 diabetic adolescents with early diabetic nephropathy by a novel combined proteome analysis.

Diabetic nephropathy is the main cause of morbidity and mortality in patients with Type 1 diabetes mellitus. Microalbuminuria has been established as a risk factor for the development and the progression of diabetic renal disease. A strong demand exists for better technologies to provide accurate diabetic nephropathy risk estimates before renal functional or structural disturbances already become established. Here, we present the application of a novel proteomics technology identifying urinary polypeptides and proteins. In this pilot study, we investigated 44 Type 1 diabetic patients with more than 5 years of diabetes duration compared with an age-matched control group. Random spot urine samples were examined utilizing high-resolution capillary electrophoresis (CE), coupled to mass spectrometry (MS). More than 1000 different polypeptides, characterized by their separation time and mass, were found between 800 Da and 66.5 kDa. Mathematical analysis revealed specific clusters of 54 polypeptides only found in Type 1 diabetic patients and an additional 88 polypeptides present or absent in patients with beginning nephropathy defined by the albumin-to-creatinine ratio (ACR; >35 mg/mmol). We observed polypeptide patterns characteristic for healthy controls and diabetic patients and subdivision of patients according to the excretion of polypeptides typical for diabetic nephropathy. Our study revealed that the urinary proteome contains a much greater variety of polypeptides than previously recognized and demonstrated the successful application of a novel high-throughput technology towards the human urinary proteome. Future prospective studies with the application of this technique may enable the earlier and more accurate detection of individuals at high risk to develop diabetic nephropathy.

Adolescent↗