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Biomedical subjects

M Schulz

Publications and source records attributed to M Schulz.

At least 73 records · Page 4Linked to original sources

A combined functional in vivo measure for primary and secondary auditory cortices.

Auditory evoked magnetic fields are reliable physiological in vivo markers of activity generated in auditory cortices. In recent years, several components of auditory evoked fields have been demonstrated with specific topographies within the auditory cortex in man. Their differential elicitation and analyses has rendered the discrimination of neural activities in primary vs. secondary auditory cortical fields possible. This in vivo measure may be of interest in a number of (neuro)psychiatric and neuropsychological disorders with central auditory deficits, in which in vivo anatomical measures do not allow a clear distinction of primary vs. secondary auditory cortex involvement. To help better understand the pathophysiology of such disorders, we developed and introduce a combined measure of steady-state field (SSR) and the N1 component of the transient evoked field. The acoustic stimulus for this paradigm consists of a 500-ms tone burst with 39-Hz amplitude modulation of the carrier frequency. This combined stimulation allows assessment of both auditory cortex components in one brief examination to be well tolerated by patients. We examined the source locations of SSR and N1 component with separate classical stimulation and combined stimulation within-session in healthy volunteer subjects. We demonstrate here that the distinct sources of steady-state (primary auditory cortex) and N1 (secondary auditory cortex) responses can be reliably measured without significant spatial distortion with this combined stimulation paradigm.

Acoustic Stimulation↗

Demographic, symptom, and medication profiles of cancer patients seen by a palliative care consult team in a tertiary referral hospital.

In this retrospective study, the charts of 100 consecutive cancer patients who had been referred to a palliative care consult team within a tertiary acute care hospital were reviewed. Demographic characteristics, including reason for admission and disease status upon admission, length of stay, and discharge and admission location, were recorded. Symptom acuity, cognitive status, and risk for substance abuse were evaluated. Medications before and after the consult were tabulated and compared to recommended medications; compliance with the recommendations was assessed. Five patients were not palliative at the time of the consult. Only 46/95 (48%) were known to have untreatable cancer at the time of their admission. The CAGE questionnaire for alcoholism and the Mini-Mental State Questionnaire (MMSQ) were abnormal in 19/78 (24%) and 40/91 (44%), respectively. The most intense symptoms, as measured by the 100-mm scales of the Edmonton Symptom Assessment Scale (ESAS) were fatigue (72 +/- 24), appetite (60 +/- 32), and well-being (50 +/- 29). Eighty-nine of the 95 patients were living at home prior to admission and 34/95 were able to return home. Twenty died during hospitalization, 23 were transferred to a palliative care unit, and the remaining 18 were discharged to another hospital or long-term care. The patient's physician complied with the palliative care consult team's recommendation in 122/137 cases (89%).

Adult↗

CCKB/gastrin receptors mediate changes in sodium and potassium absorption in the isolated perfused rat kidney.

BACKGROUND: To evaluate the function of cholecystokinin B (CCKB)/gastrin receptors in the rat kidney, we identified the receptors by Northern blot and localized the receptors by immunohistochemistry. The functional effects of gastrin were studied under standardized in vitro conditions using the isolated perfused kidney. METHODS: Rat kidneys were mounted in an organ bath by attaching the renal artery to a perfusion system. A catheter was inserted into the renal vein and the ureter to collect samples that were analyzed for the concentrations of electrolytes. After a preperfusion period, gastrin-17-I was given via the renal artery (10-8 to 10-6 mol/L). Subsequently, hemodynamic parameters (for example, perfusate flow) and changes in sodium and potassium absorption were determined. All data were subjected to a nonparametric analysis of variance and, in case of significant results, to subsequent paired comparisons by the a posteriori Wilcoxon test. RESULTS: Northern blot analysis detected CCKB receptor transcripts in total RNA isolated from kidneys. Immunohistochemistry localized CCKB receptors on tubules and collecting duct cells. Compared with controls, gastrin (10-6 mol/L) caused a decrease in the fractional sodium reabsorption (basal 80%, 10 minutes after application of gastrin 71%, after 20 minutes 62%, P < 0.05). This effect was inhibited by the CCKB receptor antagonist L-365,260. Gastrin decreased urinary potassium excretion at 10-8 and 10-6 mol/L [maximal decrease at 10-6 mol/L from baseline values (100%) to 49% after 10 minutes and to 69% after 20 minutes, P < 0.05, N = 6]. This effect was also abolished by the CCKB receptor antagonist L-365,260. Gastrin (10-6 mol/L) reduced perfusate flow by 31% (P < 0.05). CONCLUSIONS: CCKB receptors are expressed in the rat kidney on tubules and collecting ducts. These receptors mediate changes in renal potassium and sodium absorption. In addition, gastrin causes a decrease in perfusate flow, indicating that CCKB receptors might also modulate vascular resistance in the kidney.

Animals↗

Liver support by extracorporeal blood purification: a clinical observation.

Liver failure associated with excretory insufficiency and jaundice results in an endogenous accumulation of toxins involved in the impairment of cardiovascular, kidney, and cerebral function. Moreover, these toxins have been shown to damage the liver itself by inducing hepatocellular apoptosis and necrosis, thus creating a vicious cycle of the disease. We report a retrospective cohort study of 26 patients with acute or chronic liver failure with intrahepatic cholestasis (bilirubin level > 20 mg/dL) who underwent a new extracorporeal blood purification treatment. A synthetic hydrophilic/hydrophobic domain-presenting semipermeable membrane (pore size < albumin size, 100-nm thick) was used for extracorporeal blood detoxification using dialysis equipment. The opposite side was rinsed with ligandin-like proteins as molecular adsorbents that were regenerated online using a chromatography-like recycling system (molecular adsorbent recirculating system [MARS]). Bile acid and bilirubin levels, representing the previously described toxins, were reduced by 16% to 53% and 10% to 90% of the initial concentration by a single treatment of 6 to 8 hours, respectively. Toxicity testing of patient plasma onto primary rat hepatocytes by live/dead fluorescence microscopy showed cell-damaging effects of jaundiced plasma that were not observed after treatment. Patients with a worsening of Child-Turcotte-Pugh (CTP) index before the treatments showed a significant improvement of this index during a period of 2 to 14 single treatments with an average of 14 days. After withdrawal of MARS treatment, this improvement was sustained in all long-term survivors. Ten patients represented a clinical status equivalent to the United Network for Organ Sharing (UNOS) status 2b (group A1), and all survived. Sixteen patients represented a clinical status equivalent to UNOS status 2a, and 7 of these patients survived (group A2), whereas 9 patients (group B) died. We conclude that in acute excretory failure caused by a chronic liver disease, this treatment provides a therapy option to remove toxins involved in multiorgan dysfunction secondary to liver failure.

Adult↗

[Opinions and attitudes on the topic of vaccination of established physicians, pharmacists and their personnel and current vaccination status of these groups].

Object of this investigation was to evaluate attitudes and opinions of general practitioners, internal specialists and pharmacists with regard to vaccination. At the same time we investigated the actual vaccination state of these groups and of the medical staff and pharmacy staff. Physicians and pharmacists answered by using a four-page written questionnaire. The vaccination state was evaluated by a single-page questionnaire. Analyses were made by using the statistical program SPSS. The 161 physicians and 188 pharmacists participating in this study generally agree that the risk of infection in practice and pharmacy is not significant. The best vaccine protection in these groups was observed for tetanus. An effective inoculation against this pathogen was documented by 79.4% of physicians and 63.3% of pharmacists. 73.4% of physicians had also a protection against hepatitis B. All other vaccinations were documented as actually protective only in 6-55% of the cases. Physicians and pharmacists agree that their staff should have a vaccination against tetanus, diphtheria and poliomyelitis, followed by hepatitis B and influenza. The vaccination state of medical staff and pharmacy-staff does not attain the demanded standard. It shows levels of 3-70%. Further education in vaccination is more often practised by pharmacists and their staff than by physicians and medical staff. Physicians are more active in advising patients about vaccination than pharmacists and patients rather consult their doctor than a pharmacist to give them vaccination advice. There is still a need for motivation of physicians and pharmacists to be an example for their patients and clients respectively. In addition, more of public information could be helpful.

Adult↗

Collective diffusion and a random energy landscape

Starting from a master equation in a quantum Hamiltonian form and a coupling to a heat bath, we derive an evolution equation for a collective hopping process under the influence of a stochastic energy landscape. Different equations result for an arbitrary occupation number per lattice site or in a system under exclusion. Based on scaling arguments it will be demonstrated that both systems belong below the critical dimension d(c) to the same universality class, leading to anomalous diffusion in the long time limit. The dynamical exponent z can be calculated by an epsilon=d(c)-d expansion. Above the critical dimension we discuss the differences in the diffusion constant for sufficient high temperatures. For a random potential we find a higher mobility for systems with exclusion.

Journal Article↗

The long-term reinfection rate and the course of duodenal ulcer disease after eradication of Helicobacter pylori in a developing country.

OBJECTIVE: The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. METHODS: A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. RESULTS: The radication rate was 76% (95% CI: 67-83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8%+/-3% in yr 1, 11%+/-4% in yr 2, and 13%+/-4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. CONCLUSIONS: In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries.

Adolescent↗

Mast cell granule composition and tissue location--a close correlation.

This review provides a survey on mast cell heterogeneity, with aspects differing in humans and rodents or which are subject of conflicting evidence being discussed in greater detail. Mast cell subsets have been first defined in rats by their fixation and dye-binding properties, and detailed studies in humans and pigs reveal very similar observations. The dye-binding properties of rat mast cell subsets are causally related to the absence or presence of heparin in their granules. In humans, this relation has not been shown. Rodent mast cell subsets store different chymase-isoforms. In contrast, just a single chymase has been defined in humans, and mast cells are classified by the presence or relative absence of this chymase. Different investigators find quite different proportions of chymase-positive to chymase-negative mast cells. Tryptase(s) are found in most or every human mast cell, but in rodents, they have hitherto been essentially localised to mast cells in connective tissues. Human mast cell subsets may also be defined by their expression of receptors such as C5aR and possibly the beta-chemokine receptor CCR3; the CCR3 expression seems to be related to the human mast cell chymase expression. Ultrastructural studies are helpful to distinguish human mast cell subsets, and allow to distinguish between chronic and acute activation. The phenotypical characteristics may change in association with inflammation or other disease processes. Studies in humans and pigs show changed dye-binding and fixation properties of the granules. Experimental rodent infection models reveal similar changes of chymase isoform expression. Human lung mast cells have been reported to strongly upregulate their chymase content in pulmonary vascular disease. This line of evidence can explain some inconsistent information on mast cell heterogeneity and may help to understand the physiological role of mast cells.

Animals↗

Optimized activation of the primary sensorimotor cortex for clinical functional MR imaging.

BACKGROUND AND PURPOSE: One application of functional MR imaging is to identify the primary sensorimotor cortex (M1 and S1) around the central sulcus before brain surgery. However, it has been shown that undesirable coactivation of nonprimary motor areas, such as the supplementary motor area and the premotor area, can interfere with the identification of the primary motor cortex, especially in patients with distorted anatomic landmarks. We therefore sought to design a simple functional MR imaging paradigm for selective activation of the primary sensorimotor cortex. METHODS: Different paradigms using finger tapping for motor activation were examined and compared with respect to the distribution of activated voxels in primary and nonprimary cortical areas. Studies were conducted in 14 healthy volunteers using a blood oxygen level-dependent multislice echo-planar imaging sequence. RESULTS: The most selective activation of the primary sensorimotor cortex was obtained with a paradigm combining right-sided finger tapping as the activation condition with left-sided finger tapping as the control condition. Analysis of the signal time course of primary and nonprimary areas revealed that the highly selective primary motor activation was due to it being restricted to contralateral finger movements, as opposed to the nonprimary motor areas, which were activated by ipsilateral, contralateral, and bilateral finger movements alike. CONCLUSION: When performing functional MR imaging to determine the location of the primary sensorimotor cortex, one should compare unilateral voluntary movements as the activation condition with contralateral movements as the control condition to accentuate activation of the primary motor area and to suppress undesirable coactivation of nonprimary motor areas.

Adult↗

Ultrastructural localization of adhesion molecules in the healthy and inflamed choroid plexus of the mouse.

The functional expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and MAdCAM-1 in the choroid plexus is indicative of a role of this structure in the communication of the immune system with the central nervous system (CNS). In order to gain further insight into the possible functions of adhesion molecules expressed in the choroid plexus, we investigated the exact ultrastructural localization of VCAM-1, ICAM-1 and MAdCAM-1 on semithin and ultrathin cryosections of the choroid plexus of healthy mice and of mice suffering from experimental autoimmune encephalomyelitis (EAE). In the healthy choroid plexus VCAM-1 and ICAM-1, but not MAdCAM-1, could be detected on the apical surface of the choroid plexus epithelial cells. During EAE, immunoreactivity for VCAM-1 and ICAM-1 was dramatically increased. Additionally, apical expression of MAdCAM-1 was observed on individual choroid plexus epithelial cells during EAE. At the same time, VCAM-1, ICAM-1 or MAdCAM-1 were never present on the endothelial cells of the fenestrated capillaries within the choroid plexus. The polar expression of VCAM-1, ICAM-1 and MAdCAM-1 on the apical surface of choroid plexus epithelial cells, which form the blood-cerebrospinal fluid barrier, implies a previously unappreciated function of this barrier in the immunosurveillance of the CNS.

Animals↗

A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology.

SDZ ASM 981, a novel ascomycin macrolactam derivative, has high anti-inflammatory activity in animal models of allergic contact dermatitis and shows clinical efficacy in atopic dermatitis, allergic contact dermatitis and psoriasis, after topical application. Here we report on the in vitro activities of this promising new drug. SDZ ASM 981 inhibits the proliferation of human T cells after antigen-specific or non-specific stimulation. It downregulates the production of Th1 [interleukin (IL)-2, interferon-gamma] and Th2 (IL-4, IL-10) type cytokines after antigen-specific stimulation of a human T-helper cell clone isolated from the skin of an atopic dermatitis patient. SDZ ASM 981 inhibits the phorbol myristate acetate/phytohaemagglutinin-stimulated transcription of a reporter gene coupled to the human IL-2 promoter in the human T-cell line Jurkat and the IgE/antigen-mediated transcription of a reporter gene coupled to the human tumour necrosis factor (TNF)-alpha promoter in the murine mast-cell line CPII. It does not, however, affect the human TNF-alpha promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the FcgammaRIII receptor. SDZ ASM 981 also prevents the release of preformed pro-inflammatory mediators from mast cells, as shown in the murine cell line CPII after stimulation with IgE/antigen. In summary, these results demonstrate that SDZ ASM 981 is a specific inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro.

Animals↗

[Ventilatory failure in COPD: follow-up under intermittent positive pressure ventilation (IPPV)].

Effectiveness of IPPV in COPD is controversial. We examine the course of 29 patients with longterm IPPV (19 male, 10 female, age 60.3 years, BMI 23.7, FEV1 mean 22% predicted, PaCO2 mean 67 mmHg). PaCO2 is significantly by IPPV reduced. Patients are followed for 2 to 48 months (mean 16.5). Five stop IPPV (1 bilateral lung transplantation, 1 lung volume reduction surgery, 3 non-compliance), 8 die of respiratory failure, 5 of non-respiratory causes (non-RI) (3 tumor, 2 cardiovascular), and 10 survive (SV, 20.5 months). No difference in survival is observed between non-RI and SV. Weight increase by +5% is seen in SV more frequently, lung function is worse in RI, especially in weaning pts., hospital days are less frequent in SV and non-RI. Probability of survival is 70% at 1 year, 57% at 2 years, and 23% at 3 years, and is seriously influenced by non-RI. Our results are influenced by the high number of non-RI, the quitting of IPPV, and the primary inclusion of tumour pts. Still a high number of deaths by RI leads us to the conclusion that IPPV may be helpful for palliation, bridging before surgery and in subgroups who still have to be defined.

Female↗

Induction of inducible nitric oxide synthase is an essential part of tumor necrosis factor-alpha-induced apoptosis in MCF-7 and other epithelial tumor cells.

TNF-alpha-induced cytotoxicity is mediated by the intracellular "death domain" of the 55-kDa TNF-alpha receptor and has been demonstrated to be coupled with induction of inducible nitric oxide synthase (iNOS), leading to generation of nitric oxide radicals (NO*). Because it is still widely unknown, to what extent NO* participates in the execution of TNF-alpha-induced apoptosis, NO* production, iNOS expression, and enzyme activity in relation to TNF-alpha-induced apoptotic cell death were investigated in the human breast cancer cell line MCF-7 and various other malignant cell lines. Incubation with TNF-alpha led to induction of iNOS mRNA and protein as well as enhancement of NOS activity. Augmented synthesis of NO2, the stable end product of NO* generation, was significantly correlated with augmented rates of cell death. Measurement of TNF-alpha-triggered production of reactive oxygen species (ROS) suggested a major role for NO* within the generated oxygen radicals. Dying cells showed characteristic features of apoptosis. Addition of cycloheximide (CX) enhanced apoptotic cell death by increasing iNOS activity. L-Nitro-arginine-methylester (L-NAME), a competitive NOS-inhibitor, and iNOS antisense oligonucleotides effectively prevented NO2 generation and apoptosis. Evaluation of iNOS expression during TNF-alpha-induced cell death in various malignant cell lines demonstrated iNOS positivity for all TNF-alpha-sensitive cells. The only primarily resistant line was iNOS negative. In a resistant variant of MCF-7, iNOS mRNA was still detectable; however, treatment with TNF-alpha did not enhance NOS activity. TNF-alpha sensitivity and NO2 production were completely restored by the addition of CX. Taken together, iNOS induction plays an essential role in TNF-alpha-induced apoptosis of the investigated cell lines. Further studies are necessary to define the impact of NO* in relation to other specific effectors of apoptosis such as the caspases.

Apoptosis↗

[Doppler ultrasound findings in therapy with urapidil].

OBJECTIVE: In a prospective study we investigated, whether changes in fetal or maternal circulation can be found by Doppler sonography under therapy with urapidil. PATIENTS AND METHODS: We investigated in 11 patients with severe pregnancy-induced hypertension (PIH) or superimposed preeclampsia in the third trimester. Doppler flow results of maternal and fetal vessels before and during therapy with urapidil. Hemodynamic parameters, like maternal blood pressure, and heart rate as well as other clinical parameters were assessed. RESULTS: Whereas the antihypertensive effects in the systolic and diastolic blood pressure were significant, we couldn't find changes in the resistance indices of fetal circulation. In contrast we found a decrease in the resistance indices in maternal vessels after an average of six days of urapidil therapy. These changes were significant in the uterine artery on the side of placental insertion. CONCLUSIONS: Because of only few side effects and a safe lowering of blood pressure, therapy with urapidil seems preferable to other well known drugs. Although Doppler flow velocimetry of uteroplacental vessels has no diagnostic benefit in monitoring PIH, the findings with this method under prolonged antihypertensive therapy are a chance for a better understanding of hemodynamic changes. The decrease in the resistance indices is another argument for the use of urapidil.

Adult↗

[Current aspects of antihypertensive therapy in pregnant patients with pre-eclampsia].

Preeclampsia is a disease which occurs in Europe in about 6-8%, in the USA in about 7-10% and in Africa in about 18% of all pregnancies. A causal treatment of preeclampsia is, with the exception of delivery, not possible up to now. Since a prematurely delivery of the newborn has to be avoided because of the risks caused by immaturity of lungs, treatment and care of pregnant women having preeclampsia or any other kind of hypertensive diseases is restricted to the following approaches: antihypertensive treatment, volume expansion, and eclampsia prophylaxis with magnesium sulfate. Object of this treatment is to avoid complications on the mother's side caused by the disease and to postpone delivery, as far as possible from the child's side, in order to reduce the consequences of premature birth. During antihypertensive treatment of patients with serious hypertension, i.e. with diastolic blood pressure of 110 x mm Hg and higher, dihydralazine is in clinical use since 40 years, although many patients suffer from side-effects of dihydralazine such as distinctive tachycardia, headaches, fluid retention and nausea. With urapidil a well controllable antihypertensive is available, which prevents the effect of catecholamines at the vascular wall by a postsynaptic alpha-1 receptor blockade. Previous studies related to the application of urapidil in the treatment of hypertension during pregnancy certify the good controllability of urapidil following intravenous application as well as minor side-effects after start of treatment.

Antihypertensive Agents↗

The development of experimental autoimmune encephalomyelitis in the mouse requires alpha4-integrin but not alpha4beta7-integrin.

Because monoclonal antibodies (mAbs) directed against alpha4-integrin and VCAM-1 inhibit the development of experimental autoimmune encephalomyelitis (EAE) in vivo, it has been concluded that the successful therapeutic effect is due to interference with alpha4beta1/VCAM-1-mediated interaction of autoaggressive T cells with the blood-brain barrier. A possible role for alpha4beta7-integrin, or interference with other T cell mediated events during the pathogenesis of EAE, has not been considered. We have compared the effects of mAb therapy on the development of EAE in the SJL/N mouse, using a large panel of mAbs directed against alpha4, beta7, the alpha4beta7-heterodimer, and against VCAM-1. Although encephalitogenic T cells express both alpha4-integrins, mAbs directed against the alpha4beta7-heterodimer or against the beta7-subunit did not interfere with the development of EAE. In contrast, mAbs directed against alpha4 and VCAM-1 inhibited or diminished clinical or histopathological signs of EAE. Our data demonstrate for the first time that alpha4beta7 is not essential for the development of EAE. Furthermore, our in vitro studies suggest that the therapeutic effect of anti-alpha4-treatment of EAE might also be caused by inhibition of antigen-specific T cell proliferation.

Animals↗

Cost-effectiveness of vitamin E therapy in the treatment of patients with angiographically proven coronary narrowing (CHAOS trial). Cambridge Heart Antioxidant Study.

Epidemiologic studies have suggested that vitamin E (alpha-tocopherol) may play a preventive role in reducing the incidence of atherosclerosis. The aim of this paper was to conduct a cost-effectiveness analysis of vitamin E supplementation in patients with coronary artery disease using data from the Cambridge Heart Antioxidant Study (CHAOS). The study compared cost-effectiveness in the context of Australian and United States (US) health care utilization. The main clinical outcome used in the economic evaluation was the incidence of acute myocardial infarction (AMI) which was nonfatal. Utilization of health care resources was estimated by conducting a survey of Australian clinicians and published Australian and US cost data. Cost savings of $127 (A$181) and $578/patient randomized to vitamin E therapy compared with patients receiving placebo were found for Australian and US settings, respectively. Savings in the vitamin E group were due primarily to reduction in hospital admissions for AMI. This occurred because the vitamin E group had a 4.4% lower absolute risk of AMI than did the placebo group. Less than 10% of health care costs in the Australian evaluation was due to vitamin E ($150 [A$214/patient]). Our economic evaluation indicates that vitamin E therapy in patients with angiographically proven atherosclerosis is cost-effective in the Australian and US settings.

Australia↗