Search PubMed⌕ Search

Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 37 records · Page 2Linked to original sources
PubMed2004

Association between inflammation and nigral neuronal damage following striatal excitotoxic lesion.

We examined the expression of TNF-alpha within the substantia nigra pars reticulata (SNR) following intrastriatal injection of quinolinic acid (QA) and studied the effect of rolipram, a TNF-alpha-inhibitor, on the secondary neuronal damage. QA (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. After survival of 1, 3 or 10 days, the animals were sacrificed and immunohistochemical staining with an antibody against TNF-alpha was performed. From day 1 to day 10 after striatal QA injection TNF-alpha positive cells were observed within ipsilateral substantia nigra which were neither present on the contralateral side nor in sham-operated controls. Double labeling with antibodies against TNF-alpha and NeuN, keratan sulfate proteoglycan or GFAP displayed a good overlap between TNF-alpha and NeuN, which suggests that TNF-alpha positive cells are neurons. For the pharmacological approach, three groups of QA rats were treated intraperitoneally with either solvent (n=5), the NMDA receptor antagonist MK 801 (4 mg/kg, n=6) or the TNF-alpha inhibitor rolipram (0.3 mg/kg, n=6), which was started 24 h after QA-injection and continued with daily applications for 14 days. The amount of striatal damage did not differ between the three groups. The number of intact neurons within the ipsilateral substantia nigra of the solvent treated group was reduced by approximately 30% compared to the contralateral side. Both MK 801 and rolipram ameliorated this secondary damage and reduced the number of TNF-alpha positive cells. The observed association between expression of TNF-alpha and secondary neuronal damage within the substantia nigra induced by intrastriatal QA application might hint towards an involvement of this cytokine in transneuronal degeneration.

Animals↗
PubMed2004

Validation of the 'Vienna List' as a proxy measure of quality of life for geriatric rehabilitation patients.

The reason for the study was to investigate the discriminative, content- and criterion-related validity of the 'Vienna List', a newly developed proxy-rating measurement for quality of life in very old and severely demented persons. The total population of patients of a geriatric rehabilitation clinic of one year (from November 2001 to October 2002; n = 687) was evaluated at admission and discharge by means of this proxy rating method together with the mini mental state examination, the timed up and go test, the Tinetti measure, the Barthel Index, and the Katz activities of daily living list. Differences, mainly on factors communication, mobility, aggression, and negative affect, appeared between seven diagnostic groups as well between several care-related categories and destination after discharge. The five factors of the measurement explained a significant amount of variance with a high specificity and more than 50% of the Barthel Index scores. The 'Vienna List', originally developed for the assessment of quality of life in severely demented patients, proved to be a useful, differentiating, less time-consuming and practical tool for the documentation of the outcome of geriatric inpatient rehabilitation, as well.

Activities of Daily Living↗
PubMed2004

Flow-cytometric DNA analysis of intracranial tumors in children.

The objective of this study was to investigate flow-cytometric DNA values of pediatric intracranial tumors, and to establish DNA analysis as a potential prognostic parameter. Twenty-nine brain tumor specimens from 26 pediatric patients were cryo-preserved within a 3-year period. The DNA content was measured by flow cytometry. Six of the tumor specimens had aneuploid DNA patterns. The median of the proliferation index was lower in the survivor group compared with the non-survivor group (36.4% and 47.5%, respectively). Ten of the 26 patients are still alive, eight were lost to follow up, and eight died. Flow-cytometric DNA analysis may be a helpful tool for examining brain tumors in children. The small size of this study could not establish flow cytometry as a definite prognostic factor, but further prospective multicenter studies will evaluate the prognostic significance of flow-cytometric DNA analysis.

Adolescent↗
PubMed2004

Improving the rate of organ donation.

BACKGROUND: Organ shortage is a major problem in transplantation. Many potential donors are still lost due to a lack of information and communication. Many transplantation centers report a major donor increase after introducing new donor policies. The aim of this study was to evaluate in retrospective fashion a new donor policy in our region. METHODS: For the past 10 years all reported donors from intensive care units (ICUs) in our region were evaluated. Our new policy had 2 main steps: accepting more marginal grafts and using a transplantation representative. The goal was the improved communication with ICUs to support physicians involved in donor care. A public information program was also implemented. RESULTS: In the first year, numbers of donors obviously improved (+60.5%) and remained stable the following year. The mean donor age increased to 41.56 years. The donor pool showed mainly an improved kidney-donation rate (+53%) with also an increase in multiorgan donation (+37%). One year posttransplantation survival was not negatively influenced by this donor pool. As expected, transplantation activities increased notably, particularly liver transplantation (+31.11%) but also kidney transplantation (+26.73%). DISCUSSION: Many donors are lost because physicians in charge of brain dead patients are not fully informed about modified donation criteria. The reason for this is a lack of information and communication by transplantation units. Improved surgical techniques and better preoperative, intraoperative, and postoperative treatment have yielded better results with marginal grafts. Immediate graft function in recipients of suboptimal grafts may be delayed, but without a significantly negative impact on patient and graft survival. Because the age of organ recipients is steadily increasing with fewer contraindications for transplants, more organs will be needed.

Brain Death↗
PubMed2004

Dysmyelination in the brain of adolescents and young adults with maple syrup urine disease.

Maple syrup urine disease (MSUD) is associated with increased branched-chain amino acids (BCAA), their keto acids (BCKA), and acute or chronic encephalopathy. Aim of treatment is to reduce BCAA and BCKA to prevent or minimize brain dysfunction. We investigated 14 juvenile and adult patients with MSUD by means of cerebral magnetic resonance imaging (MRI) and correlated MRI changes to biochemical control measured as median plasma BCAA concentrations over 6-36 months prior to investigation. Abnormalities consisted of an increased signal in the white matter on T2-weighted images which is compatible with a disturbed water content of the white matter and dysmyelination. Areas affected most commonly were mesencephalon, brain stem, thalamus and globus pallidus; supratentorial lesions seem to be restricted to severe cases. No patient with white matter changes had acute neurological/encephalopathic symptoms indicating that the severity of dysmyelination does not correlate to acute neurotoxicity.

Adolescent↗
PubMed2004

Effective long-term control of cardiac events with beta-blockers in a family with a common LQT1 mutation.

The congenital long QT syndrome (LQTS) is characterized by a prolonged QT interval on the surface electrocardiogram and an increased risk of recurrent syncope and sudden cardiac death. Mutations in seven genes have been identified as the molecular basis of LQTS. beta-blockers are the treatment of choice to reduce cardiac symptoms. However, long-term follow-up of genotyped families with LQTS has been rarely reported. We have clinically followed a four-generation family with LQTS being treated with beta-blocker therapy over a period of 23 years. Seven family members were carriers of two amino acid alterations in cis (V254M-V417M) in the cardiac potassium channel gene KCNQ1. Voltage-clamp recordings of mutant KCNQ1 protein in Xenopus oocytes showed that only the V254M mutation reduced the IKs current and that the effect of the V417M variant was negligible. The family exhibited the complete clinical spectrum of the disease, from asymptomatic patients to victims of sudden death before beta-blocker therapy. There was no significant reduction in QTc (556 +/- 40 ms(1/2) before therapy, 494 +/- 20 ms(1/2) during 17 years of treatment; n = 5 individuals). Of nine family members, one female died suddenly before treatment, three females of the second generation were asymptomatic, and four individuals of the third and fourth generation were symptomatic. All mutation carriers were treated with beta-blockers and remained asymptomatic for a follow-up up to 23 years. Long-term follow-up of a LQT1 family with a common mutation (V254M) being on beta-blocker therapy was effective and safe. This study underscores the importance of long-term follow-up in families with specific LQT mutations to provide valuable information for clinicians for an appropriate antiarrhythmic treatment.

Adrenergic beta-Antagonists↗
PubMed2004

Difficulties in making the diagnosis of Hirschsprung disease in early infancy.

This study highlights the less common presentations of Hirschsprung disease (HD) and HD-associated enterocolitis (HAE) in neonates and infants. We present three infants whose diagnosis was delayed because of atypical presenting features, especially with failure to gain weight, decreased appetite, episodes of diarrhoea and vomiting and hypoalbuminaemia. The reported incidence of HAE ranges from 0 to 16.2%. To avoid complications of life-threatening HAE, primary care physicians require a high index of suspicion of the more unusual presentations of HD in neonates and infants.

Colostomy↗
PubMed2004

[A gearing mechanism with 4 degrees of freedom for robotic applications in medicine].

Applications in robot-aided surgery are currently based on modifications of manipulators used in industrial manufacturing processes. In this paper we describe novel rotatory kinematics for a manipulator, specially developed for deployment in robot-aided surgery. The construction of the gearing mechanism used for the positioning and orientation of a linkage point is described. Forward and inverse kinematics were calculated, and a constructive solution proposed. The gearing mechanism is based on two disk systems, each of which consists of two opposing rotatable discs. The construction was designed in such a way that the linkage point can be positioned freely anywhere within the mechanism's range of motion. The kinematics thus permits an x-y-positioning via rotating movements only. The spatial arrangement of two of such disc systems permits movements in four degrees of freedom (DOF). The construction is compact, but can be further miniaturized, is flexible and manufacturing costs are low. On the basis of this mechanical concept a new, small automated manipulator for surgical application will be developed.

Computer-Aided Design↗
PubMed2004

Medical care for individual patients: concepts beyond evidence-based medicine.

Todays evidence-based medicine has brought the practicing physician a vast amount of statistical evidence from which various stakeholders in the healthcare system obtain their arguments for and against the use of new therapies. Physicians assume an obligation to prescribe these new treatment options for their patients, firstly because of their eagerness to provide the best medicine, and secondly because of their fear of litigations. On looking at the published data, however, we have observed that the arguments for saving lives with a new treatment are not always supported by the underlying data. Sometimes the data show that the effect of treatment, in real terms, is only a relatively small gain in life-time prolongation. It is concluded that EBM-based concepts such as NNT (number needed to treat), absolute risk and relative risk fall short in ensuring real benefit for the patient. We have, therefore, put forward a mathematic model which takes into account the benefit of a treatment for the individual patient in terms of expected gain in lifetime duration. This model is readily applicable to published results on the clinical effects of a medical therapy and gives the practicing physician a useful tool for deciding whether to administer a medical therapy or not. By looking at the duration of treatment and the individual gain in lifetime expected, we have derived an effectiveness coefficient which can be used to categorize medical treatments into highly effective (close to 100%) and not effective (< 5%), and at the same time arrive at a cost-benefit analysis of the treatment in question. These simple concepts will help physicians and individual patients to make informed decisions based only on those medical therapies which are proven and appropriate. The model we have developed provides a new perspective in therapy for the individual patient using medicines that constitute a rational therapy i.e. a therapy that makes "sense" (sense-orientated medicine = SOM).

Age Factors↗
PubMed2003

Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases.

The objective of the present study was to validate the use of intralesional injection of interleukin-2 (IL-2) in patients with skin and soft-tissue melanoma metastases. A total of 24 patients with AJCC stage III or IV melanoma and single or multiple skin and soft-tissue metastases were included. Interleukin-2 injections were administered intralesionally into the total number of cutaneous and soft-tissue metastases accessible from the skin, 2-3 times weekly, over 1-57 weeks. Single doses varied from 0.6 to 6 x 10(6) IU, depending on lesion size. The clinical response was monitored by sonography and confirmed by histopathology; response evaluation was confined to the intralesionally treated tumours. Complete response (CR) of the treated metastases was achieved in 15 patients (62.5%), the longest remission lasting 38 months to date. In five patients, partial response (PR) was achieved (21%) and in another three patients, progressive disease was observed (one patient not assessable). A total of 245 metastases were treated with CR in 209 (85%), and PR in 21 (6%). The therapy was generally well tolerated; the observed adverse events were mainly of grade 1-2 severity. Immunohistochemical studies showed the tumour cells undergoing apoptosis and revealed a mixed character of the inflammatory infiltrate. The unusual high CR rate in metastatic melanoma of 62.5% and the limited toxicity suggest that treatment of skin and soft-tissue melanoma metastases with intralesional injection of IL-2 may be a safe and effective alternative to conventional therapies. The optimal dosage and duration of this therapy still remain to be defined in larger prospective multicentre trials.

Adult↗
PubMed2003

Preexistence and evolution of imatinib mesylate-resistant clones in chronic myelogenous leukemia detected by a PNA-based PCR clamping technique.

Recently, various mutations within the Abl sequence have been described that negatively affect imatinib binding to Bcr/Abl resulting in cellular resistance of chronic myeloid leukemia (CML) cells. So far, little is known as to whether these mutations are preexisting or develop under imatinib therapy as current mutation analyses are limited by a low sensitivity of approximately 1:2 (50%) to 1:5 (20%). By combining peptide nucleic acid (PNA)-based DNA clamping with a fluorescence hybridization probe assay, we developed a new and highly sensitive technique for the detection of known mutations within the Bcr/Abl kinase domain. With this approach we investigated 19 cases of CML refractory to imatinib treatment before and during therapy. By clamping of wild-type Abl through PNA we could effectively enhance the detection sensitivity for the Bcr/Abl mutations Thr315Ile, Glu255Lys, and Tyr253His such that 1 mutant cDNA molecule could be detected in 500 negatives (0.2%). We observed in one case that a Gly255Lys mutation was detectable before treatment. By DNA analysis of buccal swaps, a genetic polymorphism could be excluded. In two cases clonal evolution of known mutations developed gradually under treatment. In another case an initially detectable Tyr253His mutation disappeared after therapy onset but was again observed after 6 weeks of imatinib treatment. Preexisting and evolving Bcr/Abl mutations associated with an unfavorable prognosis could be safely detected by the presented technique. This may facilitate risk stratification in CML and may serve as a model for individualized molecular monitoring and therapeutic strategies in other malignant diseases.

Adult↗
PubMed2003

[Pancreatic cancer. The relative importance of neoadjuvant therapy].

Neoadjuvant radiochemotherapy in patients suffering from pancreatic cancer is presently not well established. Neoadjuvant radiochemotherapy is recommended to be applied in 5-8 weeks. The full dose of radiotherapy is between 50 and 54 Gy with 5FU used as radiosensitator. In patients with resectable pancreatic cancer, particularly in UICC-stage II neoadjuvant radiochemotherapy, this results in an improvement in survival: the median survival is between 15 and 30 months. In about 15% of the patients with resectable pancreatic cancer (UICC I-III), neoadjuvant radiochemotherapy results in downstaging. In combination with a R0-resection,neoadjuvant radiochemotherapy effects a reduction of local recurrence. Results from controlled clinical trials are necessary to objectify the benefits of neoadjuvant radiochemotherapy.

Adult↗
PubMed2003

Plasma catecholamines and N-terminal proBNP in patients with acute myocardial infarction undergoing primary angioplasty. Relation to left ventricular function and clinical outcome.

BACKGROUND: Neither profiles nor prognostic values of neurohormonal markers have been prospectively evaluated in patients with acute myocardial infarction (AMI) undergoing primary angioplasty. METHODS AND RESULTS: In 118 consecutive patients with AMI undergoing successful reperfusion (TIMI 2 and 3) by primary angioplasty, plasma concentrations of norepinephrine, epinephrine and N-terminal proBNP (NT-proBNP) were measured before, 60 min and 10 days after angioplasty. Catecholamine concentrations (mean+/-SEM) rose to a maximum in the first hour after angioplasty (norepinephrine: 602+/-44 ng/L, epinephrine: 213+/-24 ng/L) and returned to normal at day 10. Conversely, NT-proBNP levels maintained a further increase from 799+/-44 pmol/L at baseline to 924+/-54 pmol/L at day 10. A NT-proBNP concentration above median at 60 min post-angioplasty predicted major adverse cardiac events (n=27) during the 18-36 month follow-up with an odds ratio of 5.9 (1.7-20.3) and was superior to catecholamines, to left ventricular ejection fraction and to other established postinfarction risk markers. CONCLUSIONS: In a low-risk cohort of patients with AMI undergoing successful reperfusion therapy, plasma NT-proBNP concentrations are elevated for at least ten days. The prognostic value of early plasma NT-proBNP should be further evaluated concerning its ability to facilitate risk stratification of infarct patients.

Aged↗
PubMed2003

Decreased sTNF-RI in migraine patients?

Tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have recently been found to have a pain-mediating function in addition to their immunological, proinflammatory function. According to the hypothesis of neurovascular inflammation in migraine, these two cytokines could contribute to migraine pain generation. We analysed IL-6 and its soluble receptors sIL-6R and sgp130 as well as TNF-alpha and its soluble receptor sTNF-RI in 27 migraine patients and eight headache-free controls. Migraine patients tended to have less sTNF-RI (794 +/- 158 pg/ml) than controls (945 +/- 137 pg/ml). No differences in cytokine concentrations were observed. If TNF-alpha plays a role in migraine physiopathology, migraine patients may lack sufficient antagonistic sTNF-RI to neutralize hyperalgesic TNF-alpha during a migraine attack.

Adult↗
PubMed2003

Soluble interleukin-2 receptors increase during the active periods in cluster headache.

OBJECTIVE: To investigate whether cytokines are altered during the active period of cluster headache. BACKGROUND: Patients with cluster headache show activation of the hypothalamus in PET studies and via endocrinologic parameters. Data also suggest an inflammatory process occurs in cluster headache. A connection between the presumed inflammatory cause, an immunological activation, and the hypothalamus could be generated by certain cytokines. DESIGN AND METHODS: ELISA was used to determine the serum levels of soluble interleukin-2 receptors, interleukin-1, interleukin-6, and 2 soluble interleukin-6 receptors (sIL-6R and soluble gp130) in 18 patients with cluster headache (6 women and 12 men) during the cluster period and in 17 healthy controls who were headache-free (3 women and 14 men). RESULTS: Patients with cluster headache had significantly increased soluble interleukin-2 receptors (413.6+/-223 U/mL vs. 290.0+/-112 U/mL; P <.05) compared with controls. Serum levels of interleukin-1 (0.29+/-0.30 pg/mL vs. 0.13+/-0.13 pg/mL, n.s.), interleukin-6 (0.87+/-0.6 pg/mL vs. 0.91+/-0.7 pg/ml; n.s.), soluble interleukin-6 receptors (33,131+/-8,349 pg/mL vs. 35,063+/-7,606 pg/mL; n.s.), or soluble gp130 (289+/-59 pg/mL vs. 283+/-20 pg/mL; n.s.) did not differ between the 2 groups, although patients with cluster tended to have higher interleukin-1 values. CONCLUSIONS: Because elevated soluble interleukin-2 receptors indicate T cell activation, our findings suggest immune activation during cluster headache. Because interleukin-2 can activate the hypothalamus and stimulate the release of Corticotropin-releasing Factor (CRF), interleukin-2 could link a putative immunological cause of cluster headache with the observed hypothalamic activation. Systemic changes of interleukin-1 or the interleukin-6 system do not seem to play a role in cluster headache, as no alterations of serum levels were observed. Even so, unchanged serum levels do not exclude limited local production.

Adult↗
PubMed2002

Interaction of fibronectin and aggregation substance promotes adherence of Enterococcus faecalis to human colon.

This in vitro study investigates the interaction between aggregation substance (AS), a virulence factor of Enterococcus faecalis, and colonic mucosal fibronectin in normal colon and colon from patients with Crohn's disease. Fibronectin was found to be overexpressed in Crohn's disease compared to normal colon. Compared to E. faecalis OG1X:pAM944 (AS-negative), E. faecalis OG1X:pAM721 (expressing AS) showed a significantly enhanced adhesion to human colonic mucosa in normal colon and in colon from patients with Crohn's disease. Double-staining of fibronectin and AS-positive enterococci showed that colocalization of bacteria and fibronectin was significantly more frequent in Crohn's disease than in normal colon. Preincubation of bacteria with soluble fibronectin caused a significant reduction in the adherence to fibronectin. In conclusion, the interaction between AS and fibronectin plays is an important factor that mediates adhesion of Enterococcus faecalis to colonic mucosa. This might be one of the mechanisms responsible for bacterial translocation of Enterococcus faecalis.

Bacterial Adhesion↗