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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 55 records · Page 3Linked to original sources

Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004.

AIM: (131)I-meta-iodobenzylguanidine ((131)I-MIBG) therapy has been used in neuroblastoma treatment for many years but its value in high intensive first line treatment protocols is not exactly known. PATIENTS, METHODS: Stage 4 neuroblastoma patients >1 year with (123)I-MIBG positive residual disease (primary tumour and/or metastasis) after complete induction chemotherapy according to the German neuroblastoma trial NB97 were retrospectively analyzed. RESULTS: One-hundred-eleven patients had (123)I-MIBG positive residual disease after complete induction chemotherapy. Forty patients received (131)I-MIBG therapy using a median activity of 0.44 GBq/kg body weight. By univariate analysis, patients who underwent (131)I-MIBG therapy had a better 3-year event free survival (3-y-EFS 46 +/- 8%) and 3-year overall survival (3-y-OS 58 +/- 9%) than 71 patients without (131)I-MIBG therapy (3-y-EFS 19 +/- 5%, p = 0.003; 3-y-OS 43 +/- 6%, p = 0.037). However, subgroup analysis of 66 patients who underwent high dose chemotherapy with autologous stem cell transplantation (ASCT) during treatment found a very similar outcome with (131)I-MIBG therapy (3-y-EFS 49 +/- 9%, 3-y-OS 59 +/- 10%) and without (131)I-MIBG therapy (3-y-EFS 33 +/- 9%, p = 0.171; 3-y-OS 59 +/- 9%, p = 0.285) due to the dominating effect of ASCT. By multivariate analysis, (131)I-MIBG therapy had no impact on EFS (p = 0.494) and OS (p = 0.891). Only ASCT, external beam radiation therapy and MYCN amplification were important for EFS and OS. CONCLUSIONS: An independent advantage of I-131-MIBG therapy could not be proven in this retrospective analysis. The ongoing German Neuroblastoma Trial NB2004 will address the influence of (131)I-MIBG therapy with emphasis on tumour dosimetry.

3-Iodobenzylguanidine↗

Molecular epidemiology of West Nile Virus in humans.

After the introduction of West Nile Virus into the United States of America in 1999 followed by annual WNV epidemics during the mosquito seasons and spreading of the virus from the East (New York; 1999) to the West of the U.S. (California; 2003/2004) there appeared the question of whether a similar scenario could happen in Europe, too. To be able to answer this question the German Ministry of Health decided to investigate the prevalence and incidence of WNV infections in German blood donors. First a test algorithm was established taking into account the high level of cross-reactivity between different flavivirus infections in serological test systems. AntiWNV-suspicious specimens were further investigated for their neutralisation capacity and by an antiWNV confirmation assay developed in-house. As a preliminary result of our studies a very low prevalence of WNV infections in healthy German blood donors was measured. Development of highly specific test systems is necessary for accurate and reliable differential diagnosis of flavivirus infections.

Antibodies, Viral↗

Influence of diabetes mellitus and nodal distribution in endometrial cancer and correlation to clinico-pathological prognostic factors.

OBJECTIVE: The aim of this study was to describe the relationships between the distribution of nodal disease, clinico-pathological patterns and recurrence and survival in surgically staged cases of endometrial cancer. METHODS: Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence and survival were collected. The chi square test was used to test associations between variables. The Kaplan-Meier method was used for survival analysis and Cox's proportional hazards model for multiple regression analysis. RESULTS: Sixty-nine out of 181 patients underwent lymph node dissection. Twenty-three had pelvic lymph node dissection, 23 underwent pelvic and paraaortic lymph node dissection and 20 patients had lymph node sampling. The median count of removed lymph nodes was 22.4. Fifty-four lymph node dissections showed negative lymph nodes and in 15 cases there was a minimum of one positive lymph node. Overall survival was in correlation to nodal involvement with a p value of 0.0017. Patients with lymph node involvement showed significantly more recurrence than patients with negative lymph nodes (p = 0.003). The depth of myometrial invasion correlated with lymph node metastasis (p = 0.01) and patients with additional diabetes mellitus showed significantly more nodal involvement (p = 0.02). CONCLUSION: Endometrial cancer showed pelvic lymph node (PLN) and paraaortic lymph node (PALN) involvement. Under-diagnosis of the disease might result if there was only a PLN, but with or without PALN involvement there was no significant difference in overall survival or recurrence. There was an univariate correlation between lymph node involvement and diabetes.

Acanthoma↗

[Dosimetry for therapeutic treatment of neuroblastoma by 131I-mIBG].

AIM: Targeted radiotherapies using iodine-131 meta-iodobenzylguanidin have long been in use for treatment of stage IV neuroblastoma but reliable dosimetric data are scarce. METHOD: This work presents an approach to determine the whole body exposure and tumour doses delivered during therapy. Dosimetric data are reported and discussed for six treatments carried out according to the trial protocol NB2004 as it is in use in our study in the last two years. RESULTS: Whole body exposures are found to be in the range of 1.75 to 2.5 Gy whereas tumour doses vary between 15 and 55 Gy. CONCLUSION: The course of action prescribed by the trial protocol allows whole body exposure as well as tumour doses to be determined routinely.

3-Iodobenzylguanidine↗

Diagnosis and metaphylaxis of stone disease. Consensus concept of the National Working Committee on Stone Disease for the upcoming German Urolithiasis Guideline.

This review draws the recent state of the art in metabolic diagnosis and metaphylaxis of stone disease. It is the basis for the consensus approval with the other medical societies and institutions in Germany involved in the guideline process of the new "Urolithiasis Guideline". The German Working Committee on Stone Disease reviewed critically the current literature in the field of urolithiasis-including the existing German and EAU-Guidelines as well as the Conference Book of the First International Consultation on Stone Disease. As far as possible the references were rated according to the EBM criteria. On this basis the expert group discussed all pathways and statements regarding the management of stone disease. The present review coincides with the consented guideline draft of the German Working Committee on Stone Disease. Occurrence of stone disease in the western world increases seriously. Modern lifestyle, dietary habits and overweight-problems of the affluent societies-emerge to be the important promoters of the "stone-boom" in the new millennium. This even affects children, whose stone prevalence is otherwise significantly less than that of adults. Criteria for the high risk group of stone formers were clearly defined. A diagnostic standard is formulated for the basic and the elaborate metabolic evaluation of a stone patient. Approximately 75% of all stone patients could anticipate stone recurrence with elementary reorientation of their lifestyle and dietary habits, summarized as general metaphylaxis. About 25% of the stone formers require additional pharmacological intervention to normalize their individual biochemical risk, precisely compiled for each stone type as specific metaphylaxis.

Consensus↗

Androgens regulate the immune/inflammatory response and cell survival pathways in rat ventral prostate epithelial cells.

A major hurdle in understanding the role of androgens is the heterogeneity of androgen receptor (AR) expression in the prostate. Because the majority of prostate cancer arises from the AR-positive secretory luminal epithelial cells, identifying the androgen-mediated pathways in the prostate epithelium is of great significance to understanding their role in prostate pathogenesis. To meet this objective, the current study was designed to identify immediate-early genes expressed in response to the synthetic androgen R1881 in cultured rat ventral prostate epithelial cells. Rat ventral prostate epithelial cells, purified from 20-d-old rats, were cultured, and the presence of AR and the response to androgen were established. The cells were then treated with R1881 for 2 and 12 h to capture immediate-early genes in an Affymetrix-based gene chip platform. A total of 66 nonredundant genes were identified that were responsive to R1881. The functional androgen response elements were identified in the proximal promoter to determine possible molecular mechanism. Cluster analysis identified five distinct signatures of R1881-induced genes. Pathway analysis suggested that R1881 primarily influences cell proliferation/differentiation and inflammatory/immune response pathways. Androgens appear to regulate cell renewal by regulating differentiation, cell proliferation, and apoptosis. Two mutually exclusive inflammatory response pathways were observed. The interferon pathway was up-regulated, and the ILs were down-regulated. The data identified novel androgen-regulated genes (e.g. Id1, Id3, IL-6, IGF-binding protein-2 and -3, and JunB). The loss of androgen regulation of these genes can have important consequences for cellular transformation and transition to androgen-independent growth and survival.

Androgens↗

[Cardiac resynchronization therapy].

Severe cardiac insufficiency with a clearly diminished contraction of the left ventricle is often accompanied by a pronounced left bundle branch block in the EKG. The early and late activated sides of the ventricular walls contract asynchronously, further decreasing the cardiac output. Resynchronization can be achieved through a biventricular pacemaker, which simultaneously stimulates the early and late sides of the ventricular walls. In addition to the electrode usually placed in the tip of the right ventricle, a second electrode is placed on the lateral wall of the left ventricle. This normally leads to an immediate small increase in the blood pressure and to an increased functional capacity. For patients with asynchrony of the left ventricle, an improvement of the cardiac insufficiency by approximately a half of an NYHA class and a decrease in the yearly mortality by 4% has been documented.

Algorithms↗

[Typical angina pectoris complaints without coronary macroangiopathy].

HISTORY AND CLINICAL FINDINGS: A 46-year-old patient with repetitive chest pain on exercise and exclusion of coronary heart disease was transferred for further diagnostic evaluation and therapy because of the suspicion of cardiac syndrome X. INVESTIGATIONS: Coronary angiography showed no evidence for a stenotic coronary heart disease. However, a decreased coronary blood flow reserve was detected upon adenosin treatment (RCA), and myocardial scintigraphy (single-photon emission tomography-investigation [SPECT]) revealed a perfusion defects in the inferior wall. TREATMENT AND COURSE: Endothelial dysfunction (syndrom X) was diagnosed and an optimised therapy regime was initiated in order to improve endothelial function. CONCLUSION: In patients with typical angina pectoris and positive treadmill exercise stress test in the absence of stenotic coronary heart disease, cardiac syndrome X should be considered, and further invasive- and non-invasive tests should be performed. Therapeutic goals should be to improve endothelial function and to control chest pain and improve quality of life.

Chest Pain↗

Symptom control in children and adolescents with attention-deficit/hyperactivity disorder on switching from immediate-release MPH to OROS MPH Results of a 3-week open-label study.

AIM: The aim of this study was to assess the impact of switching from immediate-release (IR) methylphenidate (MPH) to OROS MPH (CONCERTA, a once-daily long-acting MPH formulation, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects with ADHD aged 6-16 (n=105),who were stably maintained on their current IR MPH regimen (10-60 mg/day), were switched to 18, 36 or 54 mg OROS MPH once daily for 21 days, depending on pre-study daily MPH dose. ADHD symptoms were assessed by parents, teachers and investigators. RESULTS: By Day 21, parent/caregiver IOWA Conners ratings had decreased from baseline by 2.7 points to 5.2 (I/O), and by 1.8 points to 5.0 (O/D). Teacher IOWA Conners ratings were maintained. Decreases in IOWA Conners ratings are indicative of ADHD symptom improvement. Approximately 75% of parents and investigators rated therapy as good or excellent. OROS MPH therapy was well tolerated. CONCLUSIONS: Switching from IR MPH to OROS MPH maintained and may have improved symptom control in children and adolescents with ADHD, during the course of this study. The changes in parent/caregiver IOWA Conners ratings suggest that OROS MPH improves symptom control in the after-school period. This is consistent with the 12-h duration of action previously demonstrated for OROS MPH.

Adolescent↗

Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture.

Recent reports on sporadic cases of liver disorders (acute hepatitis, icterus, hepatocellular necrosis) after ingestion of dietary supplements based on hydro-alcoholic extracts from green tea leaves led to restrictions of the marketing of such products in certain countries of the EU. Since green tea is considered to exert a number of beneficial health effects, and, therefore, green tea products are widely used as dietary supplements, we were interested in the possible mechanism of hepatotoxicity of green tea extracts and in the components involved in such effects. Seven hours after seeding on collagen, rat hepatocytes in primary culture were treated with various hydro-alcoholic green tea extracts (two different native 80% ethanolic dry extracts and an 80% ethanolic dry extract cleared from lipophilic compounds). Cells were washed, and reduction of resazurin, used as a viability parameter monitoring intact mitochondrial function, was determined. It was found that all seven green tea extracts examined enhanced resazurin reduction significantly at a concentration range of 100-500 microg/ml medium, while a significant decrease was observed at 1-3mg/ml medium. Decreased levels were concomitant with abundant necrosis as observed by microscopic inspection of the cultures and with increased leakage of lactate dehydrogenase activity from the cells. In a separate series of experiments, the green tea constituents (-)-epicatechin, (-)-epigallocatechin-3-gallate, caffeine and theanine were tested at concentrations reflecting their levels in a typical green tea extract. Synthetic (+)-epigallocatechin (200 microM) was used for comparison. Cytotoxicity was found with (-)-epigallocatechin-3-gallate only. The concomitant addition of 0.25 mM ascorbate/0.05 mM alpha-tocopherol had no influence on cytotoxicity. In conclusion, our results suggest that high concentrations of green tea extract can exert acute toxicity in rat liver cells. (-)-Epigallocatechin-3-gallate seems to be a key constituent responsible for this effect. The relatively low bioavailability of catechins reported after oral exposure to green tea argues, however, against a causal role of these constituents in the reported liver disorders.

Animals↗

[Magnetic resonance imaging (MRI) of the pelvis in diagnosing endometriosis].

Widely accepted as an established method in the diagnostic imaging of diseases of the female pelvis, magnetic resonance imaging (MRI) holds promising potential for the diagnosis of endometriosis. This review describes the general prerequisites for performing MRI scans of the pelvis and presents, based on recent studies, an imaging protocol suited to the diagnosis of endometriosis. Typical manifestations and sites of endometriosis are discussed and illustrated with sample images. For endometriotic cysts and implants, axial T (1)-weighted, fat-saturated turbo spin echo sequences (TSE) have the highest diagnostic value. In diagnosing adenomyosis, sagittal T (2)-weighted TSE sequences visualise changes in the uterine zonal anatomy. In essence, MRI is capable of detecting many manifestations of endometriosis in a non-invasive, yet reliable manner, and its value in relation to laparoscopy must be considered as complementary.

Endometriosis↗

[Specific effects of boxing on functional parameters of the locomotor system].

PROBLEMS: Boxer that take part on contests regularly are characterized by high strains on the locomotor system. Especially the area of shoulder girdle and neck can be overused by the fighting posture and standard techniques, that are often associated with non-physiological patterns. METHODS: Of 11 young boxers (age 14.6 +/- 0.6 years; 7.3 +/- 0.6 training units per week) and a control group (CG) of 52 male pupils (age 15.4 +/- 0.4 years) the static of head, shoulder girdle, and pelvis was detected by somatoscopy. Additionally, cyclical rotations of the cervical spine were measured using the 3-d-motion recording system CMS70 (Zebris, Germany) and the active range of motion was analysed. RESULTS: In comparison to the CG, head and shoulder of the boxers were ventralised more often (p < 0.01). Furthermore, highly significant group differences in the bilateral position of the shoulder heights and the iliac crests were detected in the frontal plane. On average, the active maximal rotation of the boxers was decreased by 17.8 degrees (p = 0.006; d = 0.800). DISCUSSION: Our study was able to detect significant differences in the analysed functional parameters of the locomotor system that may be explained by boxing specific strains and which are prerequisites of optimal performance. As long-term pathologic effects can not be excluded, adequate compensational exercises should be integrated in the training.

Adaptation, Physiological↗

[A sample of the health status quo of the (German) population].

Germany and other western countries are more and more affected by chronic degenerative diseases. Initially in many cases they are combined with overweight and a sedentary lifestyle. The Innungskrankenkasse Bayern initiated health-information-days with common health-tests. The results of these tests are confirming this trend. Strategies of prevention could possibly stop that development. According to the Salutogenese the possibilities of each individual are most important. Advice, assistance and interventions on the setting are necessary to provide the adequate information about a healthy lifestyle.

Body Composition↗

Case-control study of lifetime occupational and recreational physical activity and risks of colon and rectal cancer.

Important aspects of the inverse relation between physical activity and colon cancer risk are still under discussion. In 2000-2003, 239 incident cases of colorectal cancer confirmed by histopathology and 239 hospital-based controls, matched by age and gender, were enrolled. In standardized interviews, data on occupational and recreational physical activity for ages 20, 30, 40, 50 and 60 years were collected from 98 colon cancer cases, 141 rectal cancer cases, and from 193 controls. Besides lifestyle and sociodemographic characteristics, a detailed food frequency questionnaire was assessed. In multivariate logistic regression for colon cancer, significant risk reductions for the highest quartile of total physical activity were found for almost all ages. For lifetime mean physical activity, the multivariate odds ratio for the highest quartile was 0.37 [95% confidence interval (CI) 0.17, 0.83]. For lifelong constantly high-exercisers compared with lifelong non-exercisers an odds ratio of 0.26 (95% CI 0.08, 0.84) was estimated. For rectal cancer, no consistent association with physical activity was found. No confounding effects were observed but the authors found effect modification with total energy intake. These data support an inverse association of colon cancer risk and physical activity which is most expressed if activity is kept up throughout life.

Adult↗

Effect of Xenon on elevated intracranial pressure as compared with nitrous oxide and total intravenous anesthesia in pigs.

BACKGROUND: Xenon in low concentrations has been investigated in neuroradiology to measure cerebral blood flow (CBF). Several reports have suggested that inhalation of Xenon might increase intracranial pressure (ICP) by increasing the cerebral blood flow and blood volume, raising concerns about using Xenon as an anesthetic in higher concentrations for head-injured patients. A porcine study is presented in which the effects of inhaled 75% Xenon on elevated ICP, cerebral perfusion pressure and the efficacy of hyperventilation for ICP treatment were compared with nitrous oxide anesthesia and total intravenous anesthesia (TIVA). METHODS: Twenty-one pentobarbital-anesthetized pigs (age: 12-16 weeks) were randomly assigned to three groups to receive either 4 h of Xenon-oxygen ventilation, nitrous oxide-oxygen ventilation or air-oxygen (75%/25%) ventilation, respectively. After instrumentation for parenchymal ICP measurement and ICP manipulation, an epidurally placed 6-F balloon catheter was inflated until a target ICP of 20 mmHg was achieved. After 4 h of anesthesia hyper- and hypoventilation maneuvers were performed and consecutive ICP and CBF changes were investigated. RESULTS: Intracranial pressure and CBF increased significantly in the nitrous oxide group as compared with the controls. There was no increase of ICP or CBF in the Xenon or control group. Intracranial pressure changed in all three groups corresponding to hyper- and hypoventilation. CONCLUSIONS: During Xenon anesthesia, elevated ICP is not increased further and is partially reversible by hyperventilation. Our study suggests that inhalation of 75% Xenon seems not to be contraindicated in patients with elevated ICP.

Anesthesia, Intravenous↗

Evaluation of an automated high-volume extraction method for viral nucleic acids in comparison to a manual procedure with preceding enrichment.

BACKGROUND AND OBJECTIVES: Nucleic acid extraction still harbours the potential for improvements in automation and sensitivity of nucleic acid amplification technology (NAT) testing. This study evaluates the feasibility of a novel automated high-volume extraction protocol for NAT minipool testing in a blood bank setting. MATERIALS AND METHODS: The chemagic Viral DNA/RNA Kit special for automated purification of viral nucleic acids from 9.6 ml of plasma by using the chemagic Magnetic Separation Module I was investigated. Analytical sensitivity for hepatitis C virus (HCV), human immunodeficiency virus-1 (HIV-1), hepatitis B virus (HBV), hepatitis A virus (HAV) and parvovirus B19 (B19) was compared to our present manual procedure that involves virus enrichment by centrifugation. RESULTS: Chemagic technology allows automation of the viral DNA/RNA extraction process. Viral nucleic acids were bound directly to magnetic beads from 9.6-ml minipools. By combining the automated magnetic beads-based extraction technology with our in-house TaqMan polymerase chain reaction (PCR) assays, 95% detection limits were 280 IU/ml for HCV, 4955 IU/ml for HIV-1, 249 IU/ml for HBV, 462 IU/ml for HAV and 460 IU/ml for B19, calculated for an individual donation in a pool of 96 donors. The detection limits of our present method were 460 IU/ml for HCV, 879 IU/ml for HIV-1, 90 IU/ml for HBV, 203 IU/ml for HAV and 314 IU/ml for B19. CONCLUSIONS: The 95% detection limits obtained by using the chemagic method were within the regulatory requirements for blood donor screening. The sensitivities detected for HCV, HBV, HAV and B19 were found to be in a range similar to that of the manual purification method. Sensitivity for HIV-1, however, was found to be inferior for the chemagic method in this study.

Automation↗