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Biomedical subjects

R Wiest

Publications and source records attributed to R Wiest.

At least 19 recordsLinked to original sources
PubMed2006

Role of NPY for vasoregulation in the splanchnic circulation during portal hypertension.

Vascular dysfunction in the splanchnic circulation during portal hypertension is characterized by enhanced NO-mediated vasorelaxation and vascular hyporeactivity to norepinephrine that lead to arterial vasodilation. NPY most likely counteracts both of these key features. Firstly, NPY appears to inhibit Ach- and PNS-induced vasorelaxation in mesenteric arteries. This effect is more pronounced in portal hypertensive rats as compared to control, and most likely reflects the inhibition of increased e- and nNOS-derived NO-synthesis during portal hypertensive conditions. Secondly, NPY sensitizes the mesenteric vasculature to alpha(1)-adrenergic vasoconstriction. Most importantly, in portal hypertensive rats but not in sham rats NPY markedly augments vascular contractility and thereby corrects vascular hyporeactivity. Both actions of NPY increase vascular tone and may well act synergistically in the splanchnic circulation during portal hypertension. Moreover, the vasoconstrictive effects of NPY are most pronounced at particularly high levels of alpha(1)-adrenergic activity. Therefore, it appears that NPY becomes increasingly important for optimizing adrenergic vasoconstriction at particularly high adrenergic drive and also for playing a predominant role for vascular homeostasis. Cirrhotic patients present with elevated circulating plasma levels of NPY, which appears to be independent from the severity of liver dysfunction and to correlate with portal pressure. This finding indicates enhanced NPY release during portal hypertension that may represent a compensatory mechanism aimed at counterbalancing arterial vasodilation by restoring the efficacy of endogenous catecholamines and inhibiting vasodilative drive in the splanchnic circulation.

Humans↗
PubMed2006

The role of the sympathetic nervous system in intestinal inflammation.

The nervous system in the intestine controls motility, secretion, sensory perception, and immune function. Peptidergic neurones with neurotransmitters such as substance P and nerve growth factors have been the main focus of neuroimmunomodulation research in the gut. This review summarises the present knowledge concerning the role of the sympathetic nervous system (SNS) in modulating intestinal inflammation. The role of the SNS for gut inflammation is compared with its role in rheumatoid arthritis which demonstrates notable similarities. Nerve fibres of the SNS not only enter the enteric plexuses but also innervate the mucosa and gut associated lymphoid tissue (GALT). The SNS has pro- and anti-inflammatory functions. Neurotransmitters such as norepinephrine, adenosine, and others can evoke remarkably different opposing effects depending on concentration (presence of sympathetic nerve fibres and extent of neurotransmitter release), receptor affinity at different receptor subtypes, expression of adrenoceptors, availability of cotransmitters, and timing of SNS activity in relation to the inflammatory course. This review attempts to integrate the different perspectives of the pro- and anti-inflammatory effects of the SNS on inflammatory disease of the gut.

Gastroenteritis↗
PubMed2005

Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems.

OBJECTIVE: To study in parallel the outflow of the sympathetic nervous system (SNS) and the hypothalamic-pituitary adrenal (HPA) axis tone in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: 32 patients with SLE, 62 with RA, and 65 healthy subjects (HS) were included. To measure the tone of the HPA axis, plasma ACTH and serum cortisol were determined. Serum neuropeptide Y (NPY) was used to evaluate the sympathetic outflow. RESULTS: Patients with SLE had increased NPY levels in comparison with HS, irrespective of prior prednisolone treatment (p<0.001). For patients with RA, only those with prednisolone treatment had increased NPY levels in comparison with HS (p = 0.016). Daily prednisolone dose correlated positively with serum NPY in RA (R(Rank) = 0.356, p = 0.039). In contrast, plasma ACTH levels were generally decreased significantly in comparison with HS in SLE with prednisolone, and in RA with/without prednisolone. Similarly, serum cortisol levels were also decreased in SLE with/without prednisolone, and in RA with prednisolone. The NPY/ACTH ratio was increased in SLE and RA, irrespective of prior prednisolone treatment. The NPY/cortisol ratio was increased in SLE with/without prednisolone, and in RA with prednisolone. Twelve weeks' anti-TNF antibody treatment with adalimumab did not decrease NPY levels in RA, irrespective of prednisolone treatment. CONCLUSIONS: An increased outflow of the SNS was shown and a decreased tone of the HPA axis in patients with SLE and RA. Low levels of cortisol in relation to SNS neurotransmitters may be proinflammatory because cooperative anti-inflammatory coupling of the two endogenous response axes is missing.

Adalimumab↗
PubMed2004

A patient with myelofibrosis complicated by refractory ascites and portal hypertension: to tips or not to tips? A case report with discussion of the mechanism of ascites formation.

In patients with myelofibrosis, clinically significant portal hypertension is known to be predominantly presinusoidal; however, the exact mechanisms are still controversial. The pathophysiology is particularly enigmatic in those patients without histological and angiographic evidence of significant intra- or extrahepatic obstruction to portal blood flow, respectively. Moreover, ascites formation has been reported in such cases, but in general is rare in presinusoidal portal hypertension. Here we present such a patient in which ascites developed even in the presence of unchanged serum protein levels (oncotic pressure) and was refractory to sodium restricted diet and high-dose diuretic treatment. A discussion on the parameters influencing fluid exchange and ascites formation particularly emphasizing the potential importance of the hyperdynamic circulation in this case is given. Finally, the patient was treated by implanting a transjugular intrahepatic shunt (TIPS), exerting a diuretic effect sufficient enough to avoid re-formation of ascites for several months. However, ascites re-accumulated potentially due to the appearance of ectopic peritoneal myeloid metaplasia and the patient died soon afterwards. In conclusion, TIPS may be considered as rescue management for refractory ascites secondary to portal hypertension, but caution in respect to the presence and/or development of peritoneal or other ectopic haematopoesis has to be taken.

Aged↗
PubMed2003

Effect of Lactobacillus-fermented diets on bacterial translocation and intestinal flora in experimental prehepatic portal hypertension.

Spontaneous bacterial infections in cirrhosis and portal hypertension have been attributed to translocation of gut-derived bacteria, a process promoted by intestinal bacterial overgrowth and disruption of the gut mucosal barrier. Bacteriotherapy with Lactobacillus has been reported to correct bacterial overgrowth, stabilize mucosal barrier function, and decrease bacterial translocation in rat models of acute liver injury and failure. In this study we investigated the effect of Lactobacillus-supplemented diets on intestinal flora and on bacterial translocation rate in portal vein ligated rats. Lactobacillus-fermented milk (yogurt) containing at least 2 x 10(9) colony forming units/ml or placebo (water) was adminstrated by gavage twice daily (2 ml) for 9 days. Portal vein ligation was performed on day 7 of treatment. Bacterial translocation to mesenteric lymph nodes and quantification of intestinal flora was assessed by standard bacteriological cultures. Bacterial translocation was not significantly different between animals that received yogurt (82%) and those that received placebo (75%). Yogurt did not induce any significant changes in intestinal flora, whether it was produced with Lactobacillus acidophilus or Lactobacillus GG. In conclusion, in acute prehepatic portal hypertension, bacteriotherapy with Lactobacillus was unable to induce changes in bacterial translocation probably because it was unable to induce changes in bacterial flora.

Animals↗
PubMed2003

[Therapeutic interventional neuroradiology in acute stroke].

Interventional neuroradiological techniques are described, which are used for revascularisation of the intra-extracranial vessels in acute stroke. The results are based on our experience gained during the endovascular treatment of more than 300 patients suffering from acute stroke during the last years. Indication, procedures and results of intraarterial thrombolysis, thrombo-aspiration, percutaneous transluminal angioplasty, and implantation of stents in cases of occlusion or pseudoocclusion of brain supplying vessels are discussed. Furthermore first experiences with new techniques from other centers are presented, e.g., thrombolysis by ultrasound (sonothrombolysis), by angiojet aspiration, and laser evaporation of the thromboembolic occlusion of intra- and extracranial blood vessels.

Acute Disease↗
PubMed2002

EEG analysis with simulated neuronal cell models helps to detect pre-seizure changes.

OBJECTIVES: To test if a method for real-time detection of epileptic seizures based on electroencephalographic (EEG) analysis with simulated neuronal cell models can be modified to identify pre-seizure changes. METHODS: Our EEG analysis method consists of two simulated leaky integrate and fire units (LIFU) connected to a signal preprocessing stage that marks parts of the EEG signals with slopes larger than a preset threshold Hth with unit pulses. The LIFUs change their spiking frequency depending on the rate and the synchrony of the impinging pulse trains. Here, we use our method in a high-sensitivity mode by setting Hth to low values, which causes the LIFUs to continuously spike during the interictal state. We test if the LIFUs spiking rates change before seizure onset. RESULTS: We used 9 long-term EEGs (16+/-7 h) of 7 patients with drug resistant epilepsy. Fifteen seizures were analyzed and all were preceded by an increase of the time-averaged spiking rates SR(av) of the LIFUs. We defined a function F(Sz), which quantifies the changes of SR(av). F(Sz) increased and stayed above an individually set and fixed threshold 83+/-91 min (range: 4-330 min) before EEG seizure onset. Only two false alarms occurred. CONCLUSIONS: We conclude that EEG analysis with simulated neuronal cell models may be used to detect pre-seizure changes with high sensitivity and specificity.

Adolescent↗
PubMed2001

Hyperperfusion of anterior cingulate gyrus in a case of paroxysmal nocturnal dystonia.

The authors report the clinical, EEG, and SPECT findings of a patient with nocturnal paroxysmal dystonia. Ictal and interictal scalp EEG showed epileptiform activity over both frontal lobes. Subtraction ictal SPECT co-registered to MRI indicated a bilateral significant hyperperfusion in the anterior part of the cingulate gyrus. These results support earlier electrophysiologic investigations by others suggesting that anterior cingulate epilepsy may manifest as nocturnal paroxysmal dystonia, and illustrate the usefulness of computer-assisted SPECT analysis.

Adult↗
PubMed2001

Using simulated neuronal cell models for detection of epileptic seizures in foramen ovale and scalp EEG.

OBJECTIVE: To demonstrate a novel approach for real-time and automatic detection of epileptic seizures in EEG recorded with foramen ovale (Fov) or scalp electrodes. METHODS: Our seizure detection method is based on simulated leaky integrate and fire units (LIFU), which are classical simple neuronal cell models. The LIFUs are connected to a signal preprocessing stage and increase their spiking rates in response to rhythmic and synchronous EEG signals as typically occur at the onset and during seizures. RESULTS: We analyzed 22 short-term (10+/-3 min) and 4 long-term (18+/-7 h) Fov or scalp EEGs of 10 patients with drug resistant partial epilepsy. Seizures (n=36) were marked by increases of the LIFUs spiking rates above a preset threshold. The durations of increased spiking rates due to seizures were always longer than 10 s (36+/-21 s) and allowed separation from artifacts, which caused only short durations (1.2+/-0.6 s) of high spiking rates. The LIFUs correctly detected all the seizures and produced no false alarms. In the long term Fov EEGs seizure detection occurred before the onset of clinical signs (41+/-22 s). CONCLUSIONS: By using simulated neuronal cell models it is possible to automatically detect epileptic seizures in scalp and Fov EEG with high sensitivity and specificity.

Action Potentials↗
PubMed2001

Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive and control rats.

BACKGROUND & AIMS: The effect of octreotide on vascular tone in the superior mesenteric artery (SMA) was studied in portal-hypertensive (portal vein-ligated) and sham-operated rats. METHODS: In vitro-perfused SMA vascular beds were tested for the cumulative dose-response to octreotide at baseline conditions and after preconstriction with different vasoconstrictors (alpha1-agonist methoxamine, endothelin [ET-1], phorbol ester [PdBu], and potassium chloride [KCl]). RESULTS: Octreotide did not affect baseline perfusion pressures (without preconstriction). alpha1-Adrenergic-, ET-1-, and PdBu-, but not KCl-, induced vasoconstriction was significantly potentiated by octreotide. This effect was dose-dependent and not different in portal vein-ligated and sham rats. Amplification of alpha1-adrenergic vasoconstriction by octreotide was significantly enhanced by nitric oxide inhibition (N(W)-nitro-L-arginine, 10(-4) mol/L) as well as by removal of the endothelium, and was completely suppressed by inhibition of protein kinase C (calphostin C, 1 micromol/L), phospholipase A2 (quinacrine, 5 micromol/L), and cyclooxygenase (indomethacin, 20 micromol/L). CONCLUSIONS: Not directly, but in the presence of vasoconstrictors involving activation of protein kinase C, octreotide exerts a local vasoconstrictive effect on vascular smooth muscle of SMA. This potentiation is equipotent in portal vein-ligated and sham rats, immediate in onset, and mediated via phospholipase A2 and cyclooxygenase-derived prostanoids. This indicates that in preprandial conditions octreotide enhances the vasoconstrictive effect of dependent vasoconstrictors.

Adrenergic alpha-Agonists↗
PubMed2001

Hepatocellular carcinoma in southern Germany: epidemiological and clinicopathological characteristics and risk factors.

UNLABELLED: The aetiology of chronic liver disease leading to hepatocellular carcinoma (HCC) and the clinical characteristics of patients with HCC vary considerably internationally and intranationally. This study analyses the characteristics of HCC patients in southern Germany, a low endemic area of HCC. METHODS: The files of 118 consecutive patients with HCC observed in a single tertiary care hospital between 1994 and 2000 have been reviewed. Epidemiological and clinicopathological characteristics such as age at presentation, ethanol consumption, serological hepatitis virus markers, and fibrosis were studied. Additionally, serum levels of alpha-fetoprotein (AFP) were analysed at the time of diagnosis in 77 patients. RESULTS: The male:female ratio was 4:1 and the mean age at presentation was 61.8 years. Alcohol abuse (49.2%) and chronic hepatitis C infection (17.8%) were the most frequent risk factors. Histologically proven liver cirrhosis in the surrounding non-tumorous tissue was present in only 59.0% of cases. AFP levels were elevated in 78% of cases, but only 34% reached >500 ng/ml, a value considered to be significant for the diagnosis of HCC. AFP levels correlated with the stage of fibrosis. SUMMARY AND CONCLUSIONS: The sensitivity of AFP serum levels as a tumour marker is poor but might help to detect at least a minority of cases. As in other populations within Europe, chronic alcohol abuse is frequently associated with HCC in southern Germany, confirming that alcohol is still the most important risk factor for hepatocarcinogenesis in areas with low hepatitis virus prevalence. Considering the poor prognosis of HCC, prevention is of pivotal importance, particularly for patients with chronic liver disease and other risk factors for the development of HCC.

Adult↗
PubMed1999

Nitric oxide and portal hypertension: its role in the regulation of intrahepatic and splanchnic vascular resistance.

In recent years it has become well established that nitric oxide (NO) plays a crucial role in the hemodynamic abnormalities that develop in chronic portal hypertension. The purpose of this review is to summarize the available data and current concepts regarding the involvement of NO in the pathophysiologic changes in the micro-circulation of the liver and the splanchnic and systemic circulation that associate portal hypertension.

Animals↗
PubMed1999

NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats.

Chronic high blood flow and the hyperdynamic circulatory syndrome in portal hypertension are associated with endothelial constitutive nitric oxide (NO) synthase (eNOS) upregulation and increased NO release. In portal vein-ligated (PVL) rats the splanchnic circulation is not yet hyperdynamic on day 3 postoperatively. In vitro perfused superior mesenteric arteries (SMAs) of day 3 PVL and sham rats were challenged with increasing flow rates or the alpha-adrenoreceptor agonist methoxamine (30 and 100 microM) before and after incubation with the NO inhibitor, Nomega-nitro-L-arginine (L-NNA, 10(-4) M). Perfusate NO metabolite (NOx) concentrations were measured by chemiluminescence. PVL rats expressed a significant hyporesponsiveness to increases in flow rate or methoxamine that was overcome by incubation with L-NNA. The PVL vasculature showed significantly higher slopes of NOx production vs. flow-induced shear stress, higher increases in perfusate NOx concentration in response to methoxamine, and higher eNOS protein levels (Western blot) compared with sham rats. In conclusion, eNOS-upregulation and increased NO release by the SMA endothelium occur before the development of the hyperdynamic splanchnic circulation, suggesting a primary role of NO in the pathogenesis of arterial vasodilatation.

Animals↗
PubMed1999

Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension.

The molecular chaperone, heat shock protein 90 (Hsp90), acts as an intermediate in the signaling cascades leading to activation of endothelial nitric oxide synthase (eNOS). In this study, we examine the participation of this pathway in nitric oxide (NO)-dependent vasodilation in the rat mesentery in vitro. In normal animals, immunoprecipitation of eNOS from intact mesentery coimmunoprecipitates Hsp90 and, additionally, both eNOS and Hsp90 colocalize to the endothelial lining of mesenteric vessels. In the perfused mesenteric vasculature of normal animals, geldanamycin (GA), a specific inhibitor of Hsp90 signaling, attenuates ACh-dependent vasodilation but does not affect vasodilation in response to sodium nitroprusside. Next, studies were performed in animals with experimental portal hypertension induced by portal vein ligation (PVL). In PVL animals, NOS catalytic activity is markedly enhanced in mesenteric tissue and the perfused mesentery is hyporesponsive to the vasoconstrictor methoxamine (MTX). GA significantly potentiates MTX-induced vasoconstriction after PVL, thereby partially reversing the hyporeactivity to this agent exhibited in the mesenteric vasculature after PVL. These studies suggest that Hsp90 can act as a signaling mediator of NO-dependent responses in the mesenteric circulation and indicate that the excessive NO production observed in portal hypertension is mediated in part through Hsp90 signaling.

Acetylcholine↗