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M Schaefer

Publications and source records attributed to M Schaefer.

At least 19 recordsLinked to original sources
PubMed2006

Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study.

BACKGROUND: Wilson's disease is a rare inborn disease related to copper storage, leading to liver cirrhosis and neuropsychological deterioration. Clinical data on larger cohorts are limited owing to low disease frequency. OBJECTIVE AND METHODS: We performed a retrospective analysis of 163 patients with Wilson's disease, examined at the University of Heidelberg, Heidelberg, Germany, to determine clinical presentation, diagnostic course and long-term outcome. RESULTS: Diagnostic criteria for non-caeruloplasmin-bound serum copper, serum caeruloplasmin, 24-h urinary copper excretion, liver copper content, presence of Kayser-Fleischer rings and histological signs of chronic liver damage were reached in 86.6%, 88.2%, 87.1%, 92.7%, 66.3% and 73% of patients, respectively. By analysis of the coding region of ATP7B (except exons 2, 3 and 21), disease-causing mutations were detected in 57% and 29% of patients with Wilson's disease on both chromosomes and on one chromosome, respectively. No mutations were detected in 15% of patients with Wilson's disease. No significant differences were found in clinical parameters or initial presentation between patients grouped according to their mutations. The patients with neurological symptoms were significantly older at the onset of symptoms than patients with hepatitic symptoms (20.2 v 15.5 years of age, p<0.05), and the neurological symptoms were associated with a significantly longer time from onset to diagnosis than hepatic symptoms (44.4 v 14.4 months, p<0.05). After initiating treatment, 76.1% of the patients had a stable or improved course of the disease. Disease progression under treatment was more likely for neuropsychiatric than for hepatic symptoms. Side effects of treatment occurred in 74.4% of patients. CONCLUSIONS: Patients with Wilson's disease having predominantly neuropsychiatric symptoms manifest symptoms later, have a longer time delay from onset of symptoms until definitive diagnosis and have a poorer outcome than patients with hepatic symptoms.

Adenosine Triphosphatases↗
PubMed2006

[Nutrition and immunonutrition in septic patients].

Nutrition in septic patients is more than just caloric support. Not all nutritional concepts in general intensive care may be applied to septic patients. A tight glycemic control successfully used in post-operative intensive care patients has to be modified for the septic patient. Enteral immunonutrition leading to reduced length of stay in post-operative patients may be associated with increased mortality in patients suffering from severe sepsis. Newly developed lipid emulsions for parenteral nutrition became available. Application of these emulsions may prove to be beneficial in septic patients. An intravenous supplementation with glutamine of long-term exclusively parenterally fed intensive care patients may reduce their mortality. A nutrition individually optimized and adapted to the severity of the disease is considered to be an adjunct therapeutic measure in the treatment concept in sepsis.

Administration, Oral↗
PubMed2006

Analysis of German package inserts.

OBJECTIVE: Package inserts have an important impact on patients compliance and thus on the effectiveness of drug use. Despite efforts of the European or national regulatory authorities and manufacturers to improve the readability and comprehensiveness of package inserts, they are still the subject of critical discussion. MATERIAL AND METHODS: 68 German package inserts were chosen for a detailed analysis of their quality and suitability based on a set of 104 quality criteria developed prior to the survey. RESULTS: In many cases package inserts available on the German drug market did not include important information or were difficult to read or understand. In 73.5% of cases, the daily maximum dose was missing and 63.2% gave no information on the measures to take for each of the interactions. 66.2% of package inserts provided no instructions about the correct storage and 58.8% gave no instructions on the appropriate storage temperature. In 13 cases, dosage instructions were provided only in milligrams of active substance instead of a number of tablets or volume of liquid. 98.5% of the 68 package inserts included non-quantifiable statements such as "high dosage" or "take 2 - 4 tablets, 1 - 3 times daily". 97.1% contained repetitious information, 83.8% included advertising elements and 8.8% contained contradictory information. CONCLUSION: Package inserts must be optimized and tested by selected groups of patients prior to approval of the drug. This will avoid misunderstandings and lack of information and ensure that use of the drug will give the best possible outcome and avoid safety risks.

Comprehension↗
PubMed2005

Surface contact measurement of electrical cell uncoupling in the mouse heart during ischemia.

Electrical cell uncoupling via gap junction closure is assumed to cause characteristic changes of the passive dielectric spectrum of ischemic heart tissue. In order to find an independent evidence for this assumption, we analysed heart tissue during ischemia, measured the open state of gap junctions by means of dye transfer and correlated this parameter with the time course of the dielectric permittivity. The hearts were pre-ischemically arrested by perfusion with Ringer solution containing 20 mmol/L of potassium (group KCL, n=10). This solution was also used with the addition of two gap junction blockers, either 3 mmol/L heptanol (group HEP, n=4) or 20 micromol/L palmitoleic acid (group PA, n=7). During subsequent ischemia at 21.0+/-0.5 degrees C, we monitored the passive dielectric permittivity spectrum and the spread of dye. After a sigmoidal increase the dielectric permittivity reached an upper plateau at 61+/-22 min of ischemia in KCL, at 45+/-7 min in PA, and already during perfusion at 2+/-1 min in group HEP. At the beginning of ischemia, dye migrated to neighbouring cells in groups KCL and PA but not in HEP. In KCL and PA, the intercellular diffusion of dye stopped after 64+/-26 and 40+/-11 min of ischemia, respectively. Our results suggest that the sigmoidal increase in dielectric permittivity and the reduction of dye diffusion depend on a common mechanism, namely gap junction closure.

Animals↗
PubMed2005

[Systematic drug documentation].

Medication histories as the most common way to document individual drug use provide a valuable database. Their main purpose is to check the patient's medication for so-called drug-related problems such as interactions, compliance problems, adverse drug reactions, and others. A second concern is to gain epidemiological evidence which increases the knowledge about benefits and risks of drugs including economic consequences. By referring to well-accepted principles of data protection, the documentation of drug use data has to be an essential part of complex care programmes which allows improvement of the individual drug therapy by reducing possible risks and increasing the therapeutic outcome of drug use more effectively. In addition, systematic drug documentation can be used to build structured databases which usually make use of prescription data. Given that principles of data protection, especially with regard to anonymity, are considered such databases provide an opportunity of data linkage with other health-related information such as health care services or number of sick leave days. Regardless of certain methodological limitations, these databases can also be used for health economics research and evaluation.

Computer Security↗
PubMed2005

Literature review of instruments to assess health-related quality of life during and after menopause.

BACKGROUND AND OBJECTIVES: Menopause is a physiological event occurring in women at about the age of 50. It signals the end of the reproductive years and is associated with signs of estrogen deficiency having a considerable impact on women's health-related quality of life (HRQoL). The most common form of treatment is hormone replacement therapy (HRT). Studies have shown negative events can arise from long-term use of HRT. The aim of this review is to determine if there are any HRQoL instruments that address the impact of menopausal symptoms including positive and negative effects of HRT. METHODS: The following eight instruments were identified: Greene Climacteric Scale, Women's Health Questionnaire (WHQ), Qualifemme, Menopause-Specific QOL Questionnaire (MENQOL), Menopausal Symptoms List (MSL), Menopause Rating Scale (MRS), Menopausal Quality of Life Scale (MQOL), and the Utian Quality of Life Scale (UQOL). RESULTS: All instruments reviewed proved to be reasonably structured and have their place in applied research. None were found that addressed all aspects of the impact of HRT on HRQoL. CONCLUSION: In order to capture the possible short-term side effects of HRT on HRQoL, it is necessary to modify one or more of the existing instruments or develop a new instrument applicable in many different countries and languages.

Estrogen Replacement Therapy↗
PubMed2004

Influence of intra-fractional breathing movement in step-and-shoot IMRT.

Efforts have been made to extend the application of intensity-modulated radiotherapy to a variety of organs. One of the unanswered questions is whether breathing-induced organ motion may lead to a relevant over- or underdosage, e.g., in treatment plans for the irradiation of lung cancer. Theoretical considerations have been made concerning the different kinds of IMRT but there is still a lack of experimental data. We examined 18 points in a fraction of a clinical treatment plan of a NSCLC delivered in static IMRT with a new phantom and nine ionization chambers. Measurements were performed at a speed of 12 and 16 breathing cycles per minute. The dose differences between static points and moving target points ranged between -2.4% and +5.5% (mean: +0.2%, median: -0.1%) when moving with 12 cycles min(-1) and between -3.6% and +5.0% (mean: -0.4%, median: -0.6%) when moving with 16 cycles min(-1). All differences of measurements with and without movements were below 5%, with one exception. In conclusion, our results underline that at least in static IMRT breathing effects (concerning target dose coverage) due to interplay effects between collimator leaf movement and target movement are of secondary importance and will not reduce the clinical value of IMRT in the step-and-shoot technique for irradiation of thoracic targets.

Body Burden↗
PubMed2004

Monitoring water content of rat lung tissue in vivo using microwave reflectometry.

Measurement of lung water is an important diagnostic means of assessing pulmonary oedema. Water content affects the dielectric spectrum at microwave frequencies, but quantification is still a problem. A new lung tissue model is presented that allows the calculation of water content from dielectric permittivity. The dielectric permittivity of lung tissue was measured by microwave reflectometry using a non-invasive surface probe. During perfusion of rat lungs (n = 22) with blood, injury was induced by interruption of the blood supply for a duration between 0 (control) and 2 h. Water content was assessed from dielectric permittivity using a new mixture formula and was also determined by drying and weighing. The mixture formula allows for the dielectric polarisation of water, dry matter and air in the tissue. A linear correlation was found between total water content determined from dielectric permittivity and that from drying and weighing (y= 1.001x, R2 = 0.8). Lung injury showed an increase in total water content from 80.9 +/- 1.2% (control) to 84.1 +/- 0.9% (p < 0.01). The analysis of dielectric permittivity data at microwave frequencies with the new tissue model is sensitive enough to detect water accumulation produced by lung injury and it can be used to monitor total water content without tissue destruction.

Animals↗
PubMed2004

[Ventricular septal defect and aortic regurgitation-pathophysiological aspects and therapeutic consequences].

The development of aortic regurgitation (AI) is a rare but serious complication of subaortic ventricular septal defects (VSD). Over a period of 5 years we observed VSD-related AI in 24 patients, a frequency of 4.5% of all isolated VSD's encountered during that time frame. The location of the defects was in the infundibular septum in 59%, it was perimembranous in 25% and in the trabecular septum in 16%. Hemodynamically the defects were small except for 2 where the Q(p)/Q(s) ratio was > 2. Of the 24 pts, 16 had surgical closure of their VSD accompanied in 9 by aortic valvuloplasty. AI was caused by elongation or defect of the right coronary leaflet in 42%, of the noncoronary leaflet in 25% and a combination of both, in 8%. In 6 pts with infundibular VSD absence of part of the aortic valve ring above the defect was the underlying mechanism for AI. Postoperatively AI was improved to moderate in one pt and to none to trivial in 15. LV end-diastolic diameter decreased significantly in all pts operated. Pathogenetic mechanisms for the development of AI are a deficiency in the aorto-infundibular junction with prolaps of the right-or non-coronary leaflet, deficiency of the valve supporting structures including the valve ring as well as suction of the already elongated leaflet into the VSD with further damage to the antiregurgitant mechanism of the semilunar valve at risk. In perimembranous VSD's, late AI is probably related to turbulent flow through the adjacent LVOT. Surgical closure of isolated VSD's with a location immediately beneath the aortic valve is indicated regardless of their size to prevent the development of AI. If AI has occurred, VSD closure including aortic valvuloplasty improves the amount of regurgitation and normalizes LV enddiastolic dimension.

Adolescent↗
PubMed2004

Assessing 2,4,6-trinitrotoluene (TNT)-contaminated soil using three different earthworm test methods.

Within the scope of a phytoremediation project, the toxicity of 2,4,6-trinitrotoluene (TNT) contaminated soil (and its toxic metabolites) on earthworms was assessed. In addition to the standard acute and reproduction tests (ISO 11268), an avoidance response test was applied. The test methods covered all important ecological relevant endpoints (acute, chronic, behavioral). At a concentration of 1142 mg/kg, TNT caused significant toxic effects in all test methods, but at lower test concentrations no significant acute or reproduction toxic effects could be observed. The avoidance response test, however, showed significant repellent effects at a concentration of 29 mg/kg TNT and therefore proved to be more sensitive than the other tests in this case. Results of the earthworm tests compared well with results of an ecotoxicological biotest battery. Thus, earthworm toxicity tests are useful tools for terrestrial risk assessment but require a hierarchy of test designs that differ in effect levels (behavior, sublethal, lethal). Whereas higher concentrations of a pollutant can easily be assessed with the acute test (which requires lethal concentrations to show an effect), contaminated soils with lower (sublethal) pollutant concentrations require more sensitive test methods such as reproduction or behavioral tests in their risk assessment.

Animals↗
PubMed2003

Remote activation of referred phantom sensation and cortical reorganization in human upper extremity amputees.

Phantom limb sensation, whether painful or not, frequently occurs after peripheral nerve lesions. It can be elicited by stimulating body parts adjacent to the amputation site (referred to as phantom sensation) and it is often similar in quality to the stimulation at the remote site. The present study induced referred phantom sensations in two upper limb amputees. Neuroelectric source imaging (ESI) as well as functional magnetic resonance imaging (fMRI) was used to assess reorganization in primary somatosensory cortex (SI). Whereas recent studies found mislocalization of sensation related to stimulation mainly in regions adjacent and ipsilateral to the amputation site, we report here the elicitation of phantom sensation in the arm by stimulation in the lower body part both ipsi- and contralateral to the amputation in two arm amputees. The fMRI evaluation of one patient showed no shift in the location of the foot whereas ESI revealed major reorganization of the mouth region in primary somatosensory cortex in both patients. These data suggest that cortical structures other than SI might be contributing to the phenomenon of referred sensation. Candidate structures are the thalamus, secondary somatosensory cortex, posterior parietal cortex and prefrontal cortex.

Adult↗
PubMed2003

Response to combination therapy with interferon alfa-2a and ribavirin in chronic hepatitis C according to a TNF-alpha promoter polymorphism.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of chronic active hepatitis C. Polymorphisms in the promoter region of the TNF-alpha gene can alter the TNF-alpha expression and modify the host immune response. The present study aimed at the correlation of the G308A TNF-alpha polymorphism with the response to antiviral combination therapy in chronic hepatitis C. PATIENTS AND METHODS: 62 patients with HCV and 119 healthy unrelated controls were genotyped for the G308A TNF-alpha promoter polymorphism. The patients received 3 x 3 million units of interferon alfa-2a and 1,000-1,200 mg ribavirin daily according to their body weight. A response was defined as absence of HCV-RNA and normalization of S-ALT after 6 months of combination therapy. RESULTS: With respect to the allele and genotype frequency, a significant difference was not observed between controls and patients with chronic hepatitis C. Furthermore, such a difference was also not observed if responders and non-responders to antiviral therapy were compared. CONCLUSIONS: The promoter polymorphism of the TNF-alpha gene investigated herein is equally distributed in healthy individuals and patients with hepatitis C and does not seem to predict the response to therapy with interferon alfa-2a and ribavirin.

Adult↗
PubMed2003

Monitoring of water content and water distribution in ischemic hearts.

We determined water content and water distribution by fitting dielectric spectra of ischemic canine hearts between 5 MHz and 3 GHz with a newly developed model which describes heart cells and subcellular organelles as rotational ellipsoids filled with electrolyte enclosed by an isolating membrane. The fraction of dry material is modelled by spherical particles with a small dielectric permittivity. Free model parameters were water content, cell volume fraction, and the conductivity of the electrolytes. Resulting model parameters were compared to data from tissue desiccation and to conductivity changes produced by protons and lactate ions. We investigated hearts in two states: during ischemia after interruption of blood flow (pure ischemia, PI, n=5) and during ischemia after resuscitation with Tyrode's solution (IAR, n=14). The difference between water content determined by tissue desiccation and by dielectric spectroscopy was less than 0.5%. During 360 min of ischemia, water content in IAR decreased from 85+/-1.6% to 83+/-2.2% and in PI from 80+/-0.8% to 78+/-1.5%. Cellular volume fraction in IAR increased from 0.47+/-0.045 to 0.63+/-0.031 and in PI from 0.62+/-0.014 to 0.73+/-0.013, which is consistent with published morphometric data. After 180 min of ischemia, the increase of the cytosolic conductivity was 0.14+/-0.02 S/m as calculated from the dielectric spectrum and was similar to the conductivity increase which was roughly estimated on the basis of tissue lactate concentration. In conclusion, dielectric spectroscopy combined with our model analysis facilitates the monitoring of water content and distribution by means of nondestructive surface probes.

Animals↗
PubMed2003

The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon-alpha and ribavirin.

Unlike in HIV, homozygosity for a 32-bp deletion (Delta 32) of the chemokine receptor 5 (CCR5) gene was recently described in increased frequency in patients with chronic hepatitis C (HCV). Thus, it was speculated that this mutation might be relevant for disease susceptibility and influence the response to antiviral therapy. The present study sought to confirm the association between HCV and the Delta 32 mutation of the CCR5 gene and to correlate it with the response to therapy with interferon-alpha-2a and ribavirin. Sixty-two patients with HCV and 119 healthy unrelated controls were genotyped for the Delta 32 mutation. For the correlation between the Delta 32 mutation and response to therapy, only patients (n = 59) who completed 6 months of combination therapy as part of a prospective study were evaluated. The Delta 32 mutation was not observed in increased frequency in HCV. Furthermore, a significant difference of the HCV load or aminotransferase concentrations was not observed in carriers versus noncarriers of the Delta 32 mutation. After stratification for potentially confounding factors such as gender or HCV genotype, a significant difference was also not detected with respect to treatment outcome. These observations argue strongly against a role of CCR5 for susceptibility to HCV infection or response to combination therapy.

Antiviral Agents↗
PubMed2003

Neurotransmitter changes by interferon-alpha and therapeutic implications.

Interferon alpha (IFN-alpha) is a cytokine that is widely used for the treatment of chronic viral infection or malignant disorders. During treatment with IFN-alpha, severe neuropsychiatric syndromes may occur such as depression with suicidal ideation, paranoid psychoses or confusional states. The neurobiological correlates of these side effects are widely unknown. Besides induction of other cytokines and hormonal changes, IFN-alpha has been shown to modulate the opioid, serotonin, dopamine and glutamate neurotransmitter system. Positive therapeutic effects of antidepressants such as selective serotonin-reuptake-inhibitors (SSRI) or of opioid receptor antagonists support the hypothesis that neurotransmitter changes play an important role in the development of IFN-alpha associated neuropsychiatric side effects. We review recent research about IFN-associated neurotransmitter changes in the central nervous system and discuss treatment strategies.

Animals↗
PubMed2002

The complex dielectric spectrum of heart tissue during ischemia.

INTRODUCTION: Because of the variety of tissue structures, the interpretation of the passive complex dielectric permittivity spectrum epsilon (omega) of the heart is still a problem. The aim of this work was to correlate epsilon (omega) of heart tissue with physical processes on cellular level. METHODS: epsilon (omega) of canine hearts was continuously measured in the range from 10 Hz to 400 MHz during cardioplegic perfusion and during following ischemia. Cardioplegic perfusion was performed with HTK (Custodiol) without or with heptanol, in order to produce electrical cell uncoupling via the closure of gap junctions. To analyse epsilon (omega), we present two heart models which consider cell shape, electrical cell coupling, and dielectric polarisation of cell membranes and membranes of intracellular structures. RESULTS: epsilon (omega) of heart tissue shows an alpha-, beta-, and gamma-dispersion. epsilon (omega) remains unchanged during cardioplegic perfusion with HTK, but if heptanol is added, there is an immediate decrease in the region of alpha-dispersion and an increase in the low frequency part of beta-dispersion. Similar changes are observed during ischemia following HTK perfusion without heptanol; additionally, the beta-dispersion shifts to higher frequencies. Using our models, we obtain analogue changes of epsilon (omega) by fitting model parameters which describe water content, water distribution, extra- and intracellular conductivity, and gap junction resistance. DISCUSSION: Changes of these tissue properties as calculated by our models based on the measurement of epsilon (omega) are consistent with intraischemic changes of heart tissue known from immunohistochemical, biochemical, and histological investigations. The next step will be to use our models for the prognosis of irreversible tissue damage.

Animals↗