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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 19 recordsLinked to original sources

Patients' ability to react before complex partial seizures.

OBJECTIVE: The purpose of the study described here was to investigate the pathophysiology of patients' ability to react during the conscious (aura) phase of complex partial seizures (CPS) originating from the temporal lobe. METHODS: We reviewed video recordings of CPS experienced by 130 adult patients who had undergone epilepsy surgery for intractable medial temporal lobe epilepsy. All patients were instructed to push the alarm button when they felt an aura. We defined the preictal reactivity as the ability to push the alarm button before the complex partial (unconscious) phase of seizures. RESULTS: Seventy-seven patients (59%) pushed the alarm button before seizures. Patients with preictal reactivity were significantly younger, more often had lateralized EEG seizure patterns, and had a better postoperative outcome. Patients who did not push the alarm button had secondarily generalized seizures more often. CONCLUSIONS: Ability to react before CPS is associated with a circumscribed region involved at seizure onset and spread, and with a seizure-free postoperative outcome.

Adolescent↗

[Ischemic pre- and postconditioning].

One or several short cycles of ischemia/reperfusion before (preconditioning) or after (postconditioning) a sustained coronary occlusion with subsequent reperfusion reduce the ultimate infarct size. The protection is potent, but limited to a narrow time frame. In animal experiments a complex signal transduction cascade was identified which results specifically in a reduction of reperfusion injury. There is evidence for both ischemic pre-and postconditioning in patients with coronary artery disease.

Animals↗

Matrix metalloproteinases contribute to endotoxin and interleukin-1beta induced vascular dysfunction.

BACKGROUND AND PURPOSE: The acute vascular inflammatory dysfunction associated with endotoxaemia may reflect an imbalance between matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs), induced by the endotoxin. This possibility was tested in rat aortic tissue. EXPERIMENTAL APPROACHES: Tone induced by phenylephrine in aortic rings was measured after exposure in vitro to ambient lipopolysaccharide (LPS) or the proinflammatory cytokine interleukin-1beta (IL-1beta) for 6h, with or without MMP inhibitors (doxycycline or GM6001). Gelatinase and MMP activities, TIMP proteins and contractility were measured in aortae taken from rats 6h after receiving LPS in vivo. KEY RESULTS: Inhibition of MMP prevented the loss of phenylephrine-induced tone in aortic rings after LPS or IL-1beta. IL-1beta also increased release of MMP-2 activity from aortic tissue. In aortae exposed in vivo to LPS, net gelatinase, MMP-9 activities and TIMP-1 protein levels were increased, whereas TIMP-4 was reduced. These aortae were hypocontractile to both phenylephrine and KCl. Hypocontractility was partially reversed by doxycycline ex vivo. CONCLUSIONS AND IMPLICATIONS: MMP inhibitors ameliorate vascular hyporeactivity induced by either LPS or IL-1beta in vitro. LPS in vivo alters the balance between MMPs and TIMPs, contributing to vascular dysfunction which is partially reversed by MMP inhibitors. Vascular MMPs are activated as a result of LPS or IL-1beta-induced stress and contribute to the hyporeactivity of blood vessels to vasoconstrictors.

Animals↗

Unilateral hand automatisms in temporal lobe epilepsy.

OBJECTIVES: To analyse the lateralising value of unilateral manual automatism (UMA), its relation to contralateral dystonia and the hand by which the UMA was performed. METHODS: In this retrospective study, we reviewed video recordings of 141 patients (mean age 34.1+/-10) who had consecutively undergone presurgical evaluations with ictal video-EEG recordings and high-resolution MRI, had had epilepsy surgery due to intractable medial temporal lobe epilepsy with complex partial seizures due to unilateral medial temporal lobe lesions. The video recordings were prospectively reviewed by one of the authors blinded to patient's clinical data except the diagnosis of medial temporal lobe epilepsy. Altogether 310 archived seizures were analysed. RESULTS: Hand automatisms occurred in 86.5% of patients. UMA occurred in 53% of patients. If UMA was accompanied by contralateral hand dystonia, it had a high lateralising value to the ipsilateral epileptic focus (EF), it was ipsilateral in 85% of patients. Conversely, if UMA occurred without contralateral dystonia, it had only a limited lateralising value because it was ipsilateral to the EF in only 63% of patients. However, we found that left-sided UMA without dystonia had a high lateralising value to the left hemisphere (ipsilateral to the EF in 82%), while right-sided UMA without dystonia has practically no lateralising value. CONCLUSIONS: UMA with contralateral dystonia has a high lateralising value to the ipsilateral hemisphere. Left-sided UMA without contralateral dystonia has a lateralising value to the left hemisphere. Right-sided UMA without contralateral dystonia has no lateralising value.

Adolescent↗

[Pathophysiology of the renin-angiotensin-system in atrial fibrillation].

Cardiovascular diseases which are associated with an activation of the renin-angiotensin-system -- myocardial infarction, heart failure, hypertension -- often induce atrial fibrillation. The initiation and maintenance of atrial fibrillation is not only initiated by mechanical distension of the atria, but also by increased atrial expression of components of the renin-angiotensin-system, which initiate an inflammatory signal cascade and oxidative stress and in consequence myolysis and interstitial fibrosis. Ultimately, locally decreased conduction velocity and abbreviated refractory period facilitate reentry circuit(s) as an underlying pathomechanism of atrial fibrillation. In a meta-analysis, ACE inhibitors and AT (1) blockers, both reduce the relative risk of atrial fibrillation by about 30 %. Further prospective randomized clinical studies are required to establish final evidence.

Angiotensin Receptor Antagonists↗

Angiotensin II in the failing heart. Short communication.

In the failing heart, the local angiotensin II concentration is increased, and the extent of cardiac angiotensin II release is related to the clinical signs of heart failure. The enzymes involved in myocardial generation of angiotensin II are the angiotensin-converting enzyme (ACE) and chymases. While myocardial angiotensin II is mainly generated by chymases in the human heart, ACE inhibitors nevertheless improve left ventricular (LV) function, attenuate LV remodelling and reduce mortality in heart failure patients. These beneficial actions of ACE inhibitors, however, relate to their beneficial effect on kinin metabolism. Angiotensin II type 1 receptor (AT1) antagonists also mediate part of their beneficial effects through increased bradykinin formation. However, in contrast to ACE inhibitors, AT1 receptor antagonists attenuate downstream signalling of angiotensin II-induced AT1 receptor activation, which increases the activity of existing proteins (e.g. NADPH oxidase) and the de novo synthesis of proteins (e.g. inducible nitric oxide synthase, tumor necrosis factor-alpha ) in cardiomyocytes. Given the multiple actions of AT1 receptor activation on cardiomyocyte and non-cardiomyocyte function in the presence of an increased myocardial AngII concentration, the reduction of cardiovascular mortality and rate of hospitalization following AT1 receptor blockade in heart failure patients not receiving ACE inhibitors is not surprising. Most importantly, the beneficial effects of AT1 receptor blockade are not only achieved when used as an alternative to ACE inhibition, but also when used on top of ACE inhibitors.

Angiotensin II↗

Prognostic factors for surgery of neocortical temporal lobe epilepsy.

OBJECTIVES: In the current classification of epilepsies two forms of temporal lobe epilepsy (TLE) were included: mesial and lateral (neocortical) TLE. We aimed at identifying prognostic factors for the surgical outcome of lesional neocortical TLE. METHODS: We included consecutive patients who had undergone presurgical evaluation including ictal video-EEG and high-resolution MRI, who had TLE due to neocortical lateral epileptogenic lesions, who had a lesionectomy and who had >2-year follow-up. RESULTS: There were 29 patients who met the inclusion criteria. Twenty of them became postoperatively seizure-free. Patients' mean age was 34.8+/-9 years (range 18-52). The age at epilepsy onset was 20.1+/-8 years. We found that left-sided surgery (p=0.048) and focal cortical dysplasia (FCD) on MRI (p=0.005) were associated with non-seizure-free outcome, while lateralized/localized EEG seizure pattern (p=0.032), tumors on the MRI (p=0.013), and a favorable seizure situation at the 6-month postoperative evaluation were associated with 2-year postoperative seizure-freedom (p<0.001). Multivariate analysis indicated that the side of surgery was not an independent predictor. CONCLUSION: More than two-thirds of the patients with neocortical TLE became seizure-free postoperatively. Lateralized/localized EEG seizure pattern and tumors on the MRI were associated with postoperative seizure-freedom, while FCD were associated with a poor outcome. The 6-month postoperative outcome is a reliable predictor for the long-term outcome.

Adolescent↗

Caregiver cognitive status and potentially harmful caregiver behavior.

The association between caregiver cognitive status and potentially harmful caregiver behavior was assessed in a sample of 180 caregiver-care recipient dyads. Compromised cognitive status was identified in 39% of these informal caregivers. Beyond variance explained by demographic factors, amount of care provided, care recipient cognitive status, and caregiver depressed affect, care recipients reported more frequently being subjected to potentially harmful caregiver behavior when their caregivers evidenced compromised cognitive status. While preliminary, critical areas of caregiver cognition appeared to be deficits in language comprehension and memory. Results indicate that compromised cognitive status is common among informal caregivers of impaired elders and that this may adversely influence the quality of care they provide.

Adult↗

Religion, spirituality and the well-being of informal caregivers: a review, critique, and research prospectus.

The purpose of this article is to review and critique the published literature examining the relationships between religion/spirituality and caregiver well-being and to provide directions for future research. A systematic search was conducted using bibliographic databases, reference sections of articles, and by contacting experts in the field. Articles were reviewed for measurement, theoretical, and design limitations. Eighty-three studies were retrieved. Research on religion/spirituality and caregiver well-being is a burgeoning area of investigation; 37% of the articles were published in the last five years. Evidence for the effects of religion/spirituality were unclear; the preponderance (n = 71, 86%) of studies found no or a mixed association (i.e., a combination of positive, negative, or non-significant results) between religion/spirituality and well-being. These ambiguous results are a reflection of the multidimensionality of religion/spirituality and the diversity of well-being outcomes examined. They also partially reflect the frequent use of unrefined measures of religion/spirituality and of atheoretical approaches to studying this topic. Investigators have a fairly large number of studies on religion/spirituality and caregiver well-being on which to build. Future studies should be theory driven and utilize psychometrically sound measures of religion/spirituality. Suggestions are provided to help guide future work.

Caregivers↗

Impact of low copy repeats on the generation of balanced and unbalanced chromosomal aberrations in mental retardation.

Low copy repeats (LCRs) are stretches of duplicated DNA that are more than 1 kb in size and share a sequence similarity that exceeds 90%. Non-allelic homologous recombination (NAHR) between highly similar LCRs has been implicated in numerous genomic disorders. This study aimed at defining the impact of LCRs on the generation of balanced and unbalanced chromosomal rearrangements in mentally retarded patients. A cohort of 22 patients, preselected for the presence of submicroscopic imbalances, was analysed using submegabase resolution tiling path array CGH and the results were compared with a set of 41 patients with balanced translocations and breakpoints that were mapped to the BAC level by FISH. Our data indicate an accumulation of LCRs at breakpoints of both balanced and unbalanced rearrangements. LCRs with high sequence similarity in both breakpoint regions, suggesting NAHR as the most likely cause of rearrangement, were observed in 6/22 patients with chromosomal imbalances, but not in any of the balanced translocation cases studied. In case of chromosomal imbalances, the likelihood of NAHR seems to be inversely related to the size of the aberration. Our data also suggest the presence of additional mechanisms coinciding with or dependent on the presence of LCRs that may induce an increased instability at these chromosomal sites.

Chromosome Aberrations↗

The role of matrix metalloproteinase inhibitors in ischemia-reperfusion injury in the liver.

Liver ischemia-reperfusion injury is characterized by cell necrosis and apoptosis and by profound modifications in the extracellular matrix (ECM). During the complex series of events that take place both during ischemia and when normal blood flow is restored (reperfusion), a concerted regulation of release and activation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) mainly by stellate cells, Kupffer cells and inflammatory cells leads first to endothelial cell injury and subsequent infiltration of neutrophils into the wounded area. Later, MMP activation causes degradation of extracellular matrix components of the liver, mainly collagen and fibronectin, altering tissue architecture. The fibrosis that can result after liver injury is also dependent on the imbalance between MMPs and TIMPs and to new collagen deposition. Several experimental models of liver ischemia-reperfusion injury have demonstrated protective effects of MMP inhibitors in terms of cell necrosis, apoptosis and rearrangement of the extracellular matrix. This review summarizes current knowledge of MMP biology, with particular attention to the most recent evidence of novel, non-extracellular matrix MMP substrates involved in inflammation and cell cycle regulation. An overview of MMP and TIMP expression and activation in hepatic ischemia-reperfusion injury is provided. The analysis of such provides a rational basis for MMP inhibition as a viable strategy to prevent liver injury.

Animals↗

Connexin 43 signalling and cardioprotection.

Connexin (Cx) 43 is the predominant protein forming gap junctions and non-junctional hemichannels in ventricular myocardium. The Cx43 proteins are central to the cardioprotection afforded by ischaemic preconditioning (IP). The specific role of mitochondrial Cx43 in protection by IP is reviewed.

Cell Communication↗

Influence of vegetation in mitigation of methyl parathion runoff.

A pesticide runoff event was simulated on two 10 m x 50 m constructed wetlands (one non-vegetated, one vegetated) to evaluate the fate of methyl parathion (MeP) (Penncap-M). Water, sediment, and plant samples were collected at five sites downstream of the inflow for 120 d. Semi-permeable membrane devices (SPMDs) were deployed at each wetland outflow to determine exiting pesticide load. MeP was detected in water at all locations of the non-vegetated wetland (50 m), 30 min post-exposure. MeP was detected 20 m from the vegetated wetland inflow 30 min post-exposure, while after 10d it was detected only at 10 m. MeP was measured only in SPMDs deployed in non-vegetated wetland cells, suggesting detectable levels were not present near the vegetated wetland outflow. Furthermore, mass balance calculations indicated vegetated wetlands were more effective in reducing aqueous loadings of MeP introduced into the wetland systems. This demonstrates the importance of vegetation as sorption sites for pesticides in constructed wetlands.

Biomass↗

Mitigation of azinphos-methyl in a vegetated stream: comparison of runoff- and spray-drift.

The effectiveness of aquatic macrophytes in reducing runoff- and spray-drift-induced azinphos-methyl (AZP) input was compared in a vegetated stream. Water, sediment and plant samples were taken at increasing distances from a point of input during a spray-drift event and two runoff (10 and 22 mm/day) events. Peak concentrations of AZP decreased significantly (R2=0.99; p<0.0001; n=5) from 0.24 microg/l to 0.11 microg/l during the 10mm runoff event. No reduction took place during the 22 mm event. AZP concentrations were reduced by 90% following spray-drift input, with peak concentrations decreasing significantly (R2=0.93; p=0.0084; n=5) from 4.3 microg/l to 1.7 microg/l with increasing distance from the point of input. Plant samples taken after the spray-drift event showed increased AZP concentrations in comparison to before the event indicating sorption of the pesticide to the macrophytes. Although peak concentrations of AZP were as effectively mitigated during the 10mm runoff event as during the spray-drift event, predictive modelling revealed that maximum concentrations expected during a worst-case scenario 10mm runoff event (0 days after application) are an order of magnitude lower than what can be expected for a worst-case spray-drift and 22 mm runoff event, suggesting that spray-drift-derived pesticide concentrations are more effectively mitigated than those of runoff.

Azinphosmethyl↗

Assessment of insecticide contamination in runoff and stream water of small agricultural streams in the main soybean area of Argentina.

The first- and second-order streams, Brown and Horqueta, respectively, which are located in the main area of soybean production in Argentina were examined for insecticide contamination caused by runoff from nearby soybean fields. The insecticides most widely used in Argentina (chlorpyrifos, cypermethrin and endosulfan) were detected in sediments, suspended particles and water. Highest concentrations in suspended particles were 318 microg/kg for endosulfan in the stream Horqueta, while 226 microg/kg chlorpyrifos and 13.2 microg/kg cypermethrin were measured in the stream Brown. In the Horqueta stream 150 and 53 microg/kg chlorpyrifos and cypermethrin were detected in runoff sediments, respectively. Whereas cypermethrin concentrations in the suspended particles were relatively low, levels in the floodwater of Brown reached 0.7 microg/l. The highest chlorpyrifos concentration in floodwater was 0.45 microg/l in Brown. However, endosulfan was not detected in the water phase. In runoff water the highest concentrations measured were 0.3 microg/l for chlorpyrifos in Horqueta and 0.49 microg/l for cypermethrin in the Brown stream. On five sampling dates during the pesticide application period in Brown stream (2002/2003) the concentration of chlorpyrifos and cypermethrin in runoff and/or floodwater exceeded the water quality criteria for freshwater mentioned in this study. In three cases this insecticide concentration was measured in stream water, indicating an acute risk to aquatic life. The acute toxicity-exposure-ratio (TER) for chlorpyrifos and cypermethrin also shows an acute risk for aquatic invertebrates in the Brown stream. In the Horqueta chlorpyrifos concentrations in the runoff exceeded the safety levels three times during the application period (2001/2002), potentially endangering the aquatic fauna. Effects on aquatic macroinvertebrates after insecticide contamination were reported in earlier studies in Horqueta stream.

Agriculture↗

Recent advances in the understanding of the role of nitric oxide in cardiovascular homeostasis.

Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. To date, 3 distinct NOS isoforms have been identified: neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3). Biochemically, NOS consists of a flavin-containing reductase domain, a heme-containing oxygenase domain, and regulatory sites. NOS catalyse an overall 5-electron oxidation of one Nomega-atom of the guanidino group of L-arginine to form NO and L-citrulline. NO exerts a plethora of biological effects in the cardiovascular system. The basal formation of NO in mitochondria by a mitochondrial NOS seems to be one of the main regulators of cellular respiration, mitochondrial transmembrane potential, and transmembrane proton gradient. This review focuses on recent advances in the understanding of the role of enzyme and enzyme-independent NO formation, regulation of NO bioactivity, new aspects of NO on cardiac function and morphology, and the clinical impact and perspectives of these recent advances in our knowledge on NO-related pathways.

Animals↗