The significance of resection margins on R0 results in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma with an increasing incidence worldwide. Surgical resection is still the only potential cure, and survival rates are dismal due to disease relapse after resection and/or metastatic disease. Positive resection margins are associated with recurrence, with conflicting studies regarding the benefits of wide resection margins to reduce recurrence rates. METHODS: 126 patients with an R0 resection treated with hepatic surgery for intrahepatic cholangiocarcinoma at the Surgical Department at the Medical University Centre Essen, Germany were identified in a database and retrospectively analysed. Patients were grouped into three groups according to margin width, <1 mm (very narrow margin width) 1-5 mm (narrow margin width) and >5 mm (wide margin width). Epidemiological as well as perioperative data was analysed, and a univariate analysis as well as Kaplan-Meier plots carried out to investigate recurrence-free and overall survival. RESULTS: Wider resection margins did not lead to better recurrence-free survival. A wider resection margin >5 mm was not significantly associated with improved overall survival. Positive lymph nodes (HR 2.50, 95% CI 1.11-5.61, p=0.027) and non-anatomic resections (HR 2.06, 95% CI 1.13-3.75, p=0.019) are significantly associated with poorer overall survival. Regarding recurrence-free survival, V2 vascular invasion was the only risk factor statistically significantly associated with poorer recurrence-free survival (HR 8.83, 95% CI 0.85-2.83, p=0.005). CONCLUSION: Resection margins did not have a significant impact on disease free survival or overall survival following hepatic resection for intrahepatic cholangiocarcinoma. Non-anatomical resections, lymph node and vascular invasion all significantly impacted oncological outcomes.

Idiosyncratic Drug-Induced Liver Injury in a Healthy Patient following PCSK9-Inhibitor Injection.

Background: Acute liver injury is a life-threatening condition with disparate aetiology. Swift and adequate interdisciplinary treatment is essential to assure the best possible outcomes in these patients. Investigations to identify the cause of the condition and the implementation of quick and appropriate treatment can be lifesaving. Case Presentation. In October 2022, an otherwise healthy 66-year-old male presented at the University Hospital Essen with acute liver injury following an inclisiran injection for hypercholesterinaemia. Four weeks following admission, the patient fully recovered after initially receiving short-term cortisol therapy and open albumin (OPAL) dialysis, and the indices of liver, kidney, and coagulation function were normal at discharge. Conclusion: This is to our knowledge the first reported acute liver injury due to an inclisiran injection. Cortisol in combination with OPAL dialysis is an effective method for the treatment of acute liver injury caused by inclisiran injury, and in this case, it led to a near-complete reversal of the acute liver injury at the time of discharge.

Prognostic factors of poor postoperative outcomes in gastrectomies.

Background: Gastric cancer is one of the most common cancers worldwide and is the third most common cause of cancer related death. Improving postoperative results by understanding risk factors which impact outcomes is important. The current study aimed to compare immediate perioperative outcomes following gastrectomy. Methods: 302 patients following gastric resections over a 10-year period (January 2009-January 2020) were identified in a database and retrospectively analysed. Epidemiological as well as perioperative data was analysed, and a univariate and multivariate analysis performed to identify risk factors for in-hospital mortality. Results: In general, gastrectomies were mainly performed electively (total vs. subtotal 95% vs. 85%, p = 0.004). Patients having subtotal gastrectomy needed significantly more PRBC transfusions compared to total gastrectomy (p = 0.039). Most emergency surgeries were performed for benign diseases, such as ulcer perforations or bleeding and gastric ischaemia. Only emergency surgery was significantly associated with poorer overall survival (HR 2.68, 95% CI 1.32-5.05, p = 0.003). Conclusion: In-hospital mortality was comparable between total and subtotal gastrectomies. Only emergency interventions increased postoperative fatality risk.

Afferent vagal stimulation via gastric electrical stimulation alters sympathetic-vagal balance in domestic pigs - a pilot trial.

The disturbance of the sympathetic-vagal balance with increasing sympathetic activity and consecutive increase in cytokine release is a major threat in numerous hyperinflammatory syndromes. Therapeutic interventions that modulate the activity in the sympathetic-vagal system are suggested as an effective treatment in these incidences. The purpose of this pilot study was to investigate the effect of electrical stimulation of the gastric wall on sympathetic-vagal balance. German domestic pigs (n=5) were prepared with a modified gastric tube (mGT) for repetitive gastric electrical stimulation (GES). Electrocardiogram was recorded continuously and heart rate variability (HRV) as measure of sympathetic-vagal activity was calculated for three-minute epochs at baseline condition before GES and during GES condition. In comparison to baseline, activity of the autonomic nervous system (ANS) shifted significantly toward increased dominance of vagal activity during GES with a decrease of normalized low frequency (nLF from 58.00 to 25.52) as marker of sympathetic dominance and parallel increase of normalized high frequency (nHF from 41.48 to 74.16) as marker of vagal dominance. During GES, compared to baseline, no difference in heart rate was found. These results indicate that electrical stimulation of the gastric wall may result in shifting the sympathetic-vagal balance toward a parasympathetic predominance.

In vivo biomarkers of structural and functional brain development and aging in humans.

Brain aging is a major determinant of aging. Along with the aging population, prevalence of neurodegenerative diseases is increasing, therewith placing economic and social burden on individuals and society. Individual rates of brain aging are shaped by genetics, epigenetics, and prenatal environmental. Biomarkers of biological brain aging are needed to predict individual trajectories of aging and the risk for age-associated neurological impairments for developing early preventive and interventional measures. We review current advances of in vivo biomarkers predicting individual brain age. Telomere length and epigenetic clock, two important biomarkers that are closely related to the mechanistic aging process, have only poor deterministic and predictive accuracy regarding individual brain aging due to their high intra- and interindividual variability. Phenotype-related biomarkers of global cognitive function and brain structure provide a much closer correlation to age at the individual level. During fetal and perinatal life, autonomic activity is a unique functional marker of brain development. The cognitive and structural biomarkers also boast high diagnostic specificity for determining individual risks for neurodegenerative diseases.

Association Between Systemic Inflammation, Carotid Arteriosclerosis, and Autonomic Dysfunction.

Systemic inflammation is associated with arteriosclerotic disease progression and worse stroke outcome in patients with carotid arteriosclerotic disease. We hypothesize that systemic inflammation is mediated by impaired carotid baroreceptor and chemoreceptor function induced by carotid arteriosclerosis rather than by the generalized inflammatory arteriosclerotic process.Heart rate variability (HRV), serum levels of inflammatory markers, demographic and life style factors, and concomitant diseases with potential impact on systemic inflammation were determined in 105 patients with asymptomatic carotid stenosis of varying degree. Multivariate linear regression analyses were performed to ascertain independent determinants of carotid stenosis severity, autonomic function, and inflammation.Systemic inflammation (C-reactive protein, beta = .255; P = .014), age (beta = .232; P < .008), and arterial hypertension (beta = .206; P = .032) were associated with carotid stenosis severity. Only carotid stenosis severity and not generalized arteriosclerotic disease, concomitant diseases (arterial hypertension, diabetes mellitus, dyslipidemia, hypothyroidism), life style factors (smoking, obesity), or age was associated with a reduction in vagal tone (HRV HF band power beta = - .193; P < 0.049). Systemic inflammation was related to a reduction in vagal tone (HRV HF band power, beta = - .214; P = .031), and not to generalized arteriosclerotic disease, concomitant diseases (arterial hypertension, diabetes mellitus, dyslipidemia), life style factors (smoking, obesity), and age.In conclusion, systemic inflammation is associated with carotid rather than with generalized arteriosclerotic disease. The association between systemic inflammation and carotid arteriosclerosis is mediated by a reduction in vagal tone which indicates a major role of carotid arteriosclerosis-mediated autonomic dysfunction in the pathogenesis of systemic inflammation in arteriosclerotic disease.

Advanced automatic detection of fetal body movements from multichannel magnetocardiographic signals.

OBJECTIVE: Both heart rate (HR) monitoring and detection and description of fetal movements provide essential information of the integrity of in utero development and fetal wellbeing. Our previously described method to identify movements from multichannel magnetocardiographic (MCG) recordings lacks of reliability in some cases. This work is aimed at the improvement of fetal movement detection by means of an advanced signal processing and validation strategy. APPROACH: The previously proposed methodology of fetal body movement detection from MCG recordings using single space angle (SSA), min-max amplitude (MMA) and a measure of the overall signal strength across (RSS) was extended by moving correlation coefficient (MCC). The methodology was developed with respect to the discrimination between active and quiet sleep, validated by testing its coupling with HR accelerations in a total of 137 recordings lasting 30 min from 98 fetuses aged 34-38 weeks of gestation (WGA) of normal pregnancy. MAIN RESULTS: The developed algorithm improves the reliable automatic detection of fetal body movements independent of the fetal sleep states and their changes in the individual MCG recordings. In the fetuses aged 34-38 WGA 94% of 15 × 15 HR accelerations were coupled with detected movements. The visual inspection of the movement graphs of 30 fetuses aged 20-32 WGA supports the transferability of the movement detector to this age. In four subjects MCG-based movement detection and maternal report on percepted fetal movements were consistent. SIGNIFICANCE: The presented methodology allows the parallel automatic acquisition of precise fetal heart rate variability (HRV) indices based on subsequent beat intervals and of fetal body movements from MCG recordings during late 2nd and 3rd trimester. Potential advantages of parallel monitoring of fetal HRV and movements using MCG compared to established ultrasound technology should be investigated in subsequent studies with respect to the identification of fetuses at risk.

One-year Allograft and Patient Survival in Renal Transplant Recipients Receiving Antiplatelet Therapy at the Time of Transplantation.

BACKGROUND: Antiplatelet therapy is common in patients on the waiting list for kidney transplantation. OBJECTIVE: To evaluate the incidence of post-operative bleeding in patients with antiplatelet therapy undergoing kidney transplantation and analyze the impact on the outcome. METHODS: We studied all patients with concomitant antiplatelet therapy undergoing kidney transplantation in our center from January 2007 to June 2012. Data were collected by chart review. Univariate and multivariate logistic regression and Cox proportional hazard model were used to identify risk factors for the long-term outcome. RESULTS: Of 744 kidney transplant recipients during the study period, 161 received oral antiplatelet therapy and were included in the study. One-third of the patients demonstrated signs of bleeding, half of which requiring surgical treatment. Coronary artery disease, deceased donor kidney transplantation, and dual antiplatelet medication were independent risk factors for post-operative bleeding. One-year allograft survival was significantly better in the non-bleeding group (91.4% vs 75.9%, p=0.023). Multivariable analysis found that post-operative bleeding, recipient age, and biopsy-proven rejection were independent risk factors for graft survival. Recipient age and biopsy-proven rejection were also identified as independent risk factors for patient survival. CONCLUSION: This analysis indicated a high risk for post-operative bleeding in renal transplant patients under antiplatelet therapy. The associated negative effect on allograft survival underscored the need to reduce any risk factors for post-operative bleeding.

Diurnal variations of short-term variation and the impact of multiple recordings on measurement accuracy.

OBJECTIVE: Short-term variation (STV) from computerized cardiotocogram heart rate analysis is a parameter that complements decision making, regarding the delivery of fetuses in several high-risk situations. Although studies on the effects of gestational age and fetal pathology are convincing, there is a lack of data exploring diurnal variation and the adequacy of a single measurement. STUDY DESIGN: In this prospective observational study, fetal STV was monitored with the AN24 fetal ECG monitor (Monica Healthcare) each hour for at least 10 h in total, beginning at different times. This resulted in data covering all 24 h of the day. Seventy fetuses, low risk with respect to conditions accessible to heart rate monitoring (median 37th week of gestation) were monitored for an average of 12 h. Results of STV per hour were categorized as 'compromised' (STV<4 ms) or 'healthy', (STV⩾4 ms) to calculate the model of predictability. RESULTS: The model proposed (STV of 'healthy' fetuses: 9.6±2.6 ms, 'compromised' fetuses 3.0±0.5 ms, prevalence 1%) leads to a positive predictive value of 39%, which increased to 68 or 80% given two or three pathological (STV<4 ms) measurements, respectively. Diurnal variation was not observed. CONCLUSIONS: Single pathological STV values should be corroborated by further measurements in a 24-h interval in otherwise low-risk fetuses before inducing delivery. This may help to avoid unnecessary early births and give the fetus valuable days for intrauterine maturity.

Dysautonomia in prodromal α-synucleinopathy: peripheral versus central autonomic degeneration.

BACKGROUND AND PURPOSE: There is an urgent need for early predictive markers for the course of disease in prodromal α-synucleinopathies such as idiopathic rapid eye movement (REM) sleep behaviour disorder. Autonomic cardiac/vascular dysfunction is a prominent feature in advanced α-synucleinopathies, but its diagnostic value as an early neurodegenerative marker remains unclear. The latter may be complicated since synuclein-mediated neurodegeneration may involve central and peripheral components of the autonomic nervous system. METHODS: The diagnostic value of autonomic symptoms and central and peripheral autonomic markers of blood pressure and heart rate regulation were prospectively evaluated in 20 subjects with idiopathic REM sleep behaviour disorder and 20 age-matched healthy controls. RESULTS: Although subjects with REM sleep behaviour disorder showed no clinical autonomic symptoms, blood pressure (P ≤ 0.035) and heart rate response (P ≤ 0.065) were slightly diminished during orthostatic challenge. Autonomic dysregulation was distinctively reflected in lower resting heart rate (all components, P ≤ 0.05) and blood pressure variability (low frequency component, P ≤ 0.024) indicating peripheral cardiac/vascular denervation. In contrast, baroreflex sensitivity and central cardiac autonomic outflow (sympathovagal balance) were well preserved indicating intact central autonomic regulation. Heart rate variability [very low frequency component, receiver operating characteristic (ROC) area under the curve (AUC) 0.80, P ≤ 0.001] and blood pressure variability (low frequency component ROC AUC 0.73, P ≤ 0.01) but not baroreflex sensitivity and sympathovagal balance showed an excellent diagnostic accuracy in identifying subjects with REM sleep behaviour disorder and healthy controls. CONCLUSIONS: Cardiac/vascular dysfunction in prodromal α-synucleinopathy arises from peripheral rather than from central autonomic degeneration. Autonomic indices encoded in heart rate and blood pressure variability are precise functional markers of early synuclein-mediated neurodegeneration.

Assessment of fetal maturation age by heart rate variability measures using random forest methodology.

Fetal maturation age assessment based on heart rate variability (HRV) is a predestinated tool in prenatal diagnosis. To date, almost linear maturation characteristic curves are used in univariate and multivariate models. Models using complex multivariate maturation characteristic curves are pending. To address this problem, we use Random Forest (RF) to assess fetal maturation age and compare RF with linear, multivariate age regression. We include previously developed HRV indices such as traditional time and frequency domain indices and complexity indices of multiple scales. We found that fetal maturation was best assessed by complexity indices of short scales and skewness in state-dependent datasets (quiet sleep, active sleep) as well as in state-independent recordings. Additionally, increasing fluctuation amplitude contributed to the model in the active sleep state. None of the traditional linear HRV parameters contributed to the RF models. Compared to linear, multivariate regression, the mean prediction of gestational age (GA) is more accurate with RF than in linear, multivariate regression (quiet state: R(2)=0,617 vs. R(2)=0,461, active state: R(2)=0,521 vs. R(2)=0,436, state independent: R(2)=0,583 vs. R(2)=0,548). We conclude that classification and regression tree models such as RF methodology are appropriate for the evaluation of fetal maturation age. The decisive role of adjustments between different time scales of complexity may essentially extend previous analysis concepts mainly based on rhythms and univariate complexity indices. Those system characteristics may have implication for better understanding and accessibility of the maturating complex autonomic control and its disturbance.

[Left-Lateral Living Related Liver Donation - The Essen Experience]. / Linkslaterale Leberlebendspende ­ Erfahrungen aus Essen.

Background: The international organ shortage for liver transplantation exists particularly in paediatric transplantation. Therefore left-lateral living related liver donation (LLRLD) plays a major role in this field. The aim of the present study was to analyse all procedures of LLRLD in terms of donor safety from December 2008 to October 2012 at the University Hospital of Essen, Germany. Methods: All procedures of LLRLD from December 2008 to October 2012 at the University Hospital of Essen were included in the present study. All operations were carried out via an open narrowed median longitudinal laparotomy. General donor data were analysed. Complications were recorded and classified in accordance to their relevance. Results: 35 LLRLD were performed between December 2008 and October 2012 at the University Hospital of Essen, Germany. Mean age of the donors was 31.9 (23.4-61.7) years and 60 % were female. Past medical histories of the donors showed no relevant diagnoses. Mean length of the surgical procedure was 180 (± 89) minutes. Survival rate was 100 %. Minor complications were seen in 1 of 35 patients. Laboratory data showed a peak of the transaminases on the first postoperative day which resolved during the further course. Median postoperative hospital stay was 7 (5-11) days. Conclusion: LLRLD can be performed safely for the donors after adequate donor selection. The organ pool for paediatric recipients can be expanded by this procedure at suitable transplant centres.

[Relevance of Ablation Therapies for HCC: "A Real Bridging" for Liver Transplantation?]. / Stellenwert der ablativen Tumortherapie beim HCC: "eine reale Brücke" zur Lebertransplantation?

BACKGROUND: The utilisation of interventional ablation procedures in the context of bridging and downstaging plans for hepatocellular carcinomas before liver transplantation is increasing. The aim of the present study was to summarise current data for the application of bridging and downstaging procedures before liver transplantation. METHODS: The present study is based on an extensive investigation of the literature in PubMed. RESULTS of controlled trials, cohort studies, meta-analyses and reviews were included. RESULTS: Recommendations for the usage of bridging procedures for hepatocellular carcinomas within the Milan criteria and an expected waiting time of more than 6 months until transplantation depend on the size of the lesions and have a low level of evidence. After successful downstaging of hepatocellular carcinomas beyond the Milan criteria into the range of the Milan criteria liver transplantation is recommended with a low level of evidence, as well. CONCLUSION: Randomised controlled trials, clearly proving the success of bridging and downstaging procedures, are not available at the time and are not awaited for ethical reasons. Due to the uncomplicated application and low risk for therapy-associated complications, interventional procedures for bridging and downstaging are accepted and recommended.

Formation of functional associations across time scales in the fetal autonomic control system--a multifractal analysis.

During fetal development, different control systems mediated by the autonomic nervous system form functional connections over a wide range of time scales. Using multiscale multifractal analysis (MMA) of fetal heart rate variability (HRV), we describe fundamental relationships in the developing scale-wide adjustments within fetal behavior states as well as across state changes. MMA yields the local Hurst exponent surface h(q,s) with q as the multifractal parameter and s as the scale. In 30-minute recordings of healthy fetuses between 24 and 36weeks of gestation (n=25 in quiet sleep, n=29 in active sleep, n=30 changing sleep state) we investigated the dependency of h(q,s) on gestation age. In univariate models, we found a decreasing persistence for short scales and small amplitudes in the quiet (s1=39, q1=-0.7, R(2)=0.52) and in the active (s1=69, q1=-1.4, R(2)=0.23) sleep in contrast to an increasing persistency for long scales and large amplitudes (s1=147, q1=2.4, R(2)=0.29) in the mixed state. Bivariate models (additional scales considered) presented increased coefficients of determination R(2)=0.56, 0.4, and 0.43, respectively. Persistency increasing with age in connection with the sleep state changes (independent of the age related short range dependencies within the separate homogeneous sleep states) is reported here for the first time. The MMA indices obtained for the fetal HRV represent characteristics of the maturating scale-wide cardiovascular control in the context of the evolving sleep state dynamics, which have so far not been considered. They should be incorporated in the search for HRV indices for prenatal diagnosis of developmental disorders and risk assessment.

Developing fetal motor-cardiovascular coordination analyzed from multi-channel magnetocardiography.

Fetal movements (FM) related heart rate accelerations (AC) are an important maturation criterion. Since Doppler-based time resolution is not sufficient for accompanying heart rate variability analysis, the work is aimed at a comprehensive FM-AC analysis using magnetocardiographic recordings from fetuses during sleep.We identify FM and AC by independent component analysis and automatic recognition algorithms. We investigate associations between FM and AC of different magnitude by means of event coincidence and time series cross-correlation over the maturation period of 21-40 weeks of gestation (WGA).FM related AC appear with increasing AC magnitude and WGA. Vice versa, AC related FM appear independent of WGA, but more frequently with increasing AC amplitude. The FM-AC correlation exists already at 21 WGA and further increases with WGA while the variability of its time delay decreases. Hence, FM and AC are clearly associated over the whole investigated maturation period. The increase of FM related AC runs parallel to the increasing AC magnitude.The MCG methodology was confirmed and results from previous Doppler-based analyses reproduced. Hence, MCG recordings allow the collective analysis of heart rate variability based maturation indices and FM related AC. This synergism may improve the diagnosis of fetal developmental disorders.

Heart rate variability - a potential early marker of sub-acute post-stroke infections.

OBJECTIVE: Infection is the most relevant complication after acute ischemic stroke. Activity of the autonomic nervous system seems to control post-stroke immunodepression. We investigated heart rate variability (HRV) indices that reflect autonomic readjustments as predictors of post-stroke infection. MATERIALS AND METHODS: Forty-three patients with acute ischemic stroke were enrolled in a prospective study. The predictability of sub-acute infections (day 4 ± 1 after admission) was investigated in 34 patients without acute infection by means of HRV indices obtained in the acute period (48 h after admission). RESULTS: Sub-acute infection could be predicted in patients without clinical or paraclinical (white blood cell count and C-reactive protein) signs of infection in the acute period at (i) day: increased HFnorm, reduced LFnorm and LF/HF; (ii) night: reduced LF and VLF (P < 0.05). CONCLUSIONS: HRV indices are candidates for early markers of developing post-stroke infections, preceding routine blood samples. Thus, HRV-based early diagnosis of post-stroke infection should be investigated in more detail as it may have implications as a novel tool for timely and appropriate treatment. A corresponding continuous HRV-based risk assessment using the ECG provided by the routine stroke monitoring system would be possible without any additional burden for patients and staff.

Subcutaneous thigh fat area is unrelated to risk of type 2 diabetes in a prospective study of Japanese Americans.

AIMS/HYPOTHESIS: Cross-sectional research has reported a negative association between subcutaneous thigh fat (STF) and type 2 diabetes prevalence but no prospective research on this association exists using direct measurements of STF obtained from imaging studies while adjusting for other fat depots. We studied the independent associations of intra-abdominal fat (IAF), subcutaneous abdominal fat (SAF) and STF with future risk of diabetes. METHODS: We prospectively followed 489 non-diabetic Japanese Americans (BMI 25.0-29.9 kg/m(2) 32.7%, ≥30.0 kg/m(2) 5.4%) over 10 years for the development of diabetes defined by use of hypoglycaemic medication or a fasting plasma glucose ≥7.0 mmol/l or 2 h ≥11.1 mmol/l during an OGTT. STF, SAF and IAF area were measured by computed tomography scan and mid-thigh circumference (TC) by tape measure at baseline. RESULTS: Over 10 years, 103 people developed diabetes. STF area was not independently associated with the odds of developing diabetes in a univariate or multiple logistic regression model (OR for a 1 SD increase 0.8 [95% CI 0.5, 1.2]) adjusted for age, sex, BMI, IAF and SAF. The only fat depot associated with diabetes odds in this model was IAF. TC was borderline significantly associated with a lower odds of developing diabetes (0.7 [95% CI 0.5, 1.0], p = 0.052). CONCLUSIONS/INTERPRETATION: Similar to other research, TC was negatively associated with diabetes risk, whereas STF was not, arguing that the negative association between TC and diabetes observed in other research is not due to STF mass. IAF area emerged as the only measured fat depot that was independently associated with type 2 diabetes risk.

Changes of AMPA receptors in MPTP monkeys with levodopa-induced dyskinesias.

Overactivity of glutamate neurotransmission is suspected to be implicated in Parkinson's disease and levodopa-induced dyskinesia. The fast glutamatergic transmission in the striatum from the cortex is mediated mainly by non-n-methyl-d-aspartate (non-NMDA) receptors. Animal models of Parkinson's disease reveal conflicting data concerning striatal glutamate AMPA receptors. The present study thus sought to shed light on the relationship of striatal AMPA receptors to the development of levodopa-induced dyskinesia. [(3)H]Ro 48-8587, a highly potent and selective-specific antagonist ligand for AMPA receptors, was used to investigate, by autoradiography, striatal AMPA receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated for 1 month with levodopa alone, levodopa+CI-1041 (NMDA receptor antagonist) or levodopa+cabergoline (D2 receptor agonist). Levodopa-treated MPTP monkeys developed dyskinesias while those that received levodopa+CI-1041 or levodopa+cabergoline did not. In the anterior caudate nucleus and putamen, specific binding of [(3)H]Ro 48-8587 was reduced in all MPTP-treated monkeys compared to control monkeys, but no significant effect of MPTP was measured in the posterior striatum. In dyskinetic monkeys, specific binding of [(3)H]Ro 48-8587 was elevated in subregions of the posterior caudate nucleus and putamen as compared to saline-treated MPTP monkeys. Levodopa+CI-1041 treatment left unchanged specific binding of [(3)H]Ro 48-8587 whereas levodopa+cabergoline treatment reduced it in subregions of the posterior caudate nucleus and putamen compared to control and levodopa-treated MPTP monkeys. Specific binding of [(3)H]Ro 48-8587 was low in the globus pallidus and remained unchanged following both lesion and treatments. In conclusion, the elevated values of AMPA receptors in dyskinetic monkeys (and their prevention through treatments) were only observed in subregions of the striatum.

Autonomic dysfunction and risk stratification assessed from heart rate pattern.

The modulation of the autonomic nervous system (ANS) under physiological and pathophysiological conditions is in focus of recent research. Many patients with cardio- and cerebrovascular diseases display features of sympathovagal dysregulation. Measuring specific ANS parameters could improve risk stratification. Thus, the early diagnosis of ANS dysfunction in these patients poses a great challenge with high prognostic relevance.The most relevant methods and measures of Heart Rate Variability (HRV) analysis and HRV monitoring will be described in detail in this chapter. The grown importance of these easily obtainable heart rate patterns in stratifying the risk of patients with myocardial infarction and heart failure as well as ischemic stroke will be demonstrated based on recent clinical studies. In order to perspectively improve clinical management of these patients further large scale clinical investigations on the role of ANS dysfunction will be useful.