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Biomedical subjects

A Schneider

Publications and source records attributed to A Schneider.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Unanswered questions in the management of cervical cancer].

The Task Force Group "Uterus of the Association of Gynecologic Oncology" has recently published the interdisciplinary S2 guidelines on diagnostics and therapy of cervical cancer. In view of quality development strategies of the German Cancer Society and the German Society for Obstetrics and Gynecology, a practicable concept with clear algorithms for gynecologists has been presented. Nevertheless, both development of oncologic sciences and daily practice, lead to new questions which should be answered by prospective studies. In this respect, women with cervical cancer should be treated on the same level of quality as patients with breast cancer. As discussed both nationally and internationally, laparoscopic staging, the development of laparoscopic surgical techniques (i. e., laparoscopic-assisted radical vaginal hysterectomy), the safety and efficacy of the sentinel concept, and TMMR, and finally, the indication for trachelectomy are main scientific questions. Also, innovative vaccination studies that might increase hope of a breakthrough even in cervical cancer prevention, the implementation of nerve-sparing surgical techniques, the radical parametrectomy or current strategies on exenteration are main focuses of clinical gynecologic oncology.

Cervix Uteri↗
PubMed2006

Patients' satisfaction with laparoscopic myomectomy.

BACKGROUND: Laparoscopic myomectomy offers a uterus-conserving alternative to hysterectomy for patients suffering from symptomatic myomas. The following study aimed to examine clinically relevant aspects of perceived satisfaction following laparoscopic myomectomy. METHOD: 191 women completed a 17-item questionnaire on retrospective satisfaction with their choice for the operation and with the surgical outcome (e.g., "all myomas were removed", "termination of discomfort"). A comparison was performed using questionnaire data, patients' demographical data and surgical records (e.g., duration of surgery). RESULTS: Women who trusted in their decision for the surgical procedure revealed better surgical outcome and greater satisfaction with the treatment process than those who were insecure with their choice. Age did not influence the patients' perceived satisfaction. In anticipation of the surgical outcome, patients placed stronger emphasis on tissue preservation than on their wish for a child or on the termination of discomfort. CONCLUSIONS: The high overall level of satisfaction and positive outcome in various age groups contradicts current recommendations against laparoscopic myomectomy for women over 40 years of age.

Adult↗
PubMed2006

A family of new instruments for laparoscopic radiofrequency ablation of malignant liver lesions.

Primary and secondary liver tumors may be treated with radiofrequency ablation (RFA) to improve tumor control and to increase patient survival. Lesions are punctured percutaneously or during open surgery. However, not all of the lesions are accessible percutaneously due to their localization: Adjacent structures could be endangered and/or the treatment would cause severe pain. Open surgery is an option in these cases but significantly more invasive. Laparoscopic RFA (LRFA) is an additional possibility in those cases: It offers a better access to difficult lesions than via the percutaneous route and is also less invasive than open surgery. The precision of targeting, however, in LRFA still has to be improved. In an in-vivo feasibility study we used a tumor mimic model in pigs to examine the applicability of laparoscopic RFA in combination with laparoscopic ultrasound using a set of dedicated new instruments to handle the RFA probe. To increase the ablation volume, the liver blood flow was reduced performing a Pringle maneuver. It is demonstrated that this set of specially designed instruments is indeed applicable and facilitates the targeting of liver lesions of any localization. Accordingly, it could significantly enlarge the applicability of LRFA.

Animals↗
PubMed2006

Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience.

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.

Adult↗
PubMed2006

Strain-dependent regulation of neurotransmission and actin-remodelling proteins in the mouse hippocampus.

Individual mouse strains differ significantly in terms of behaviour, cognitive function and long-term potentiation. Hippocampal gene expression profiling of eight different mouse strains points towards strain-specific regulation of genes involved in neuronal information storage. Protein expression with regard to strain- dependent expression of structures related to neuronal information storage has not been investigated yet. Herein, a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry (MALDI-TOF/TOF) has been chosen to address this question by determining strain-dependent expression of proteins involved in neurotransmission and activity-induced actin remodelling in hippocampal tissue of five mouse strains. Of 31 spots representing 16 different gene products analysed and quantified, N-ethylmaleimide-sensitive fusion protein, N-ethylmaleimide-sensitive factor attachment protein-alpha, actin-like protein 3, profilin and cofilin were expressed in a strain-dependent manner. By treating protein expression as a phenotype, we have shown significant genetic variation in brain protein expression. Further experiments in this direction may provide an indication of the genetic elements that contribute to the phenotypic differences between the selected strains through the expressional level of the translated protein. In view of this, we propose that proteomic analysis enabling to concomitantly survey the expression of a large number of proteins could serve as a valuable tool for genetic and physiological studies of central nervous system function.

Actin-Related Protein 3↗
PubMed2006

Hypoxic ventilatory response in successful extreme altitude climbers.

A very high ventilatory response to hypoxia is believed necessary to reach extreme altitude without oxygen. Alternatively, the excessive ventilation could be counterproductive by exhausting the ventilatory reserve early on. To test these alternatives, 11 elite climbers (2004 Everest-K2 Italian Expedition) were evaluated as follows: 1) at sea level, and 2) at 5,200 m, after 15 days of acclimatisation at altitude. Resting oxygen saturation, minute ventilation, breathing rate, hypoxic ventilatory response, maximal voluntary ventilation, ventilatory reserve (at oxygen saturation = 70%) and two indices of ventilatory efficiency were measured. Everest and K2 summits were reached 29 and 61 days, respectively, after the last measurement. Five climbers summited without oxygen, the other six did not, or succeeded with oxygen (two climbers). At sea level, all data were similar. At 5,200 m, the five summiters without oxygen showed lower resting minute ventilation, breathing rate and ventilatory response to hypoxia, and higher ventilatory reserve and ventilatory efficiency, compared to the other climbers. Thus, the more successful climbers had smaller responses to hypoxia during acclimatisation to 5,200 m, but, as a result, had greater available reserve for the summit. A less sensitive hypoxic response and a greater ventilatory efficiency might increase ventilatory reserve and allow sustainable ventilation in the extreme hypoxia at the summit.

Acclimatization↗
PubMed2005

Strain-dependent expression of signaling proteins in the mouse hippocampus.

Individual mouse strains may differ significantly in terms of behavior and cognitive function. Hippocampal gene expression profiling on several mouse strains has been carried out and points toward substantial strain-specific variation of more than 200 genes including components of major signaling pathways involved in neuronal information storage. Strain-specific hippocampal protein expression, however, has not been investigated yet. A proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry has been chosen to address this question by determining strain-dependent expression of signaling proteins in hippocampi of four inbred and one outbred mouse strain. Forty-six spots corresponding to 37 different signaling proteins have been analyzed and quantified. Statistical analysis revealed strain-dependent expression of serine/threonine protein phosphatase 1, serine/threonine protein phosphatase 2A, large GTP binding protein OPA1, guanine nucleotide-binding protein beta, putative GTP-binding protein Ran, receptor of activated protein kinase C1, WASP-family protein member 1, voltage-dependent anion channel 2 and 14-3-3 protein gamma. Differential expression of signaling proteins in the hippocampus may contribute to the molecular understanding of strain-dependent behavioral and cognitive performance. Moreover, these data highlight the importance of the genetic background for the analysis of signaling pathways in the hippocampus in wild-type mice as well as in gene-targeting experiments.

Animals↗
PubMed2005

Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing.

Stromal derived factor-1 (SDF-1 or CXCL12) controls many aspects of stem cell function including trafficking and proliferation. Previously, it was demonstrated that DNA-damaging agents such as irradiation, cyclophosphamide or 5-fluorouracil increase the expression of SDF-1 by osteoblasts in murine marrow. Here, the production of SDF-1 by osteoblasts in vitro in response to cytokines known to be particularly important in bone physiology was examined using primary human osteoblasts (HOBs), mixed marrow stromal cells (BMSCs), and by, mouse, rat and human osteoblast-like cell lines. From these studies, it was determined that the expression of SDF-1 is an early feature of osteoblastic induction that may be modulated by IL-1beta, PDGF-BB, VEGF, TNF-alpha and PTH. Each of these factors increased SDF-1 synthesis, while TGF-beta1 decreased SDF-1 secretion. Of note, the biodistribution of SDF-1 in culture was equally distributed between the medium and detergent-soluble and -insoluble fractions of the cultures. Immunohistochemistry of developing bones demonstrated that SDF-1 was also a feature of early bone development first beginning in the perichondrium and moving into the marrow cavity of the developing bone analogue. As SDF-1 expression increases in response to PTH in vitro, animals were treated with an anabolic regime of PTH for 21 days. Under these conditions, significant increases in SDF-1 mRNA expression were observed near the growth plate and epiphysis regions of the long bones. Yet, in serum, immunodetectable SDF-1 levels were significantly reduced (24%) in the PTH-treated animals (Vehicle: 408 +/- 25 vs. PTH 308 +/- 20 SDF-1 pg/ml). Together, these data suggest a possible mechanism for localizing stem cells into a developing marrow where increased expression of SDF-1 in the local marrow environment along with decreased SDF-1 in the serum may create a homing gradient.

Cell Proliferation↗
PubMed2005

Acupuncture treatment in irritable bowel syndrome.

BACKGROUND AND AIMS: Despite occasional positive reports on the efficacy of acupuncture (AC) on functions of the gastrointestinal tract, there is no conclusive evidence that AC is effective in the treatment of irritable bowel syndrome (IBS). PATIENTS AND METHODS: Forty three patients with IBS according to the Rome II criteria were randomly assigned to receive either AC (n = 22) or sham acupuncture (SAC) (n = 21) using the so-called "Streitberger needle". Treatment duration was 10 sessions with an average of two AC sessions per week. The primary end point was improvement in quality of life (QOL) using the functional digestive diseases quality of life questionnaire (FDDQL) and a general quality of life questionnaire (SF-36), compared with baseline assessments. QOL measurements were repeated three months after treatment. RESULTS: Both the AC and SAC groups improved significantly in global QOL, as assessed by the FDDQL, at the end of treatment (p = 0.022), with no differences between the groups. SF-36 was insensitive to these changes (except for pain). This effect was partially reversed three months later. Post hoc comparison of responders and non-responders in both groups combined revealed a significant prediction of the placebo response by two subscales of the FDDQL (sleep, coping) (F = 6.746, p = 0.003) in a stepwise regression model. CONCLUSIONS: Acupuncture in IBS is primarily a placebo response. Based on the small differences found between the AC and SAC groups, a study including 566 patients would be necessary to prove the efficacy of AC over SAC. The placebo response may be predicted by high coping capacity and low sleep quality in individual patients.

Acupuncture Therapy↗
PubMed2005

Evaluation and cultural adaptation of a German version of the AIMS2-SF questionnaire (German AIMS2-SF).

OBJECTIVES: The aim of the study was to examine the validity of a translated and culturally adapted version of the Arthritis Impact Measurement Scales 2, Short Form (AIMS2-SF) in patients suffering from osteoarthritis (OA) in primary care. METHODS: A structured procedure was used for the translation and cultural adaptation of the AIMS2-SF into German. The questionnaire was administered to 220 primary care patients with OA of the knee or hip. Test-retest reliability was tested in 35 randomly selected patients, who received the questionnaire a second time after 1 week. The physical scale of the original AIMS2-SF was divided into an 'upper body limitations' scale and a 'lower body limitations' scale. RESULTS: With values ranging from 0.52 to 0.97 for Pearson's r, item-scale correlations were reasonably good. The discriminative power of separate scales was also good, reflected in low values for correlation between different scales, indicating little redundancy. Only two items (13 and 15) referring to the symptom scale showed item-scale correlation of r = 0.72 and r = 0.67, respectively with the lower body limitation scale. The assessment of internal consistency reliability also revealed satisfactory values: Cronbach's alpha was > or =0.83 for all scales, except for the social interaction scale (0.66). The test-retest reliability, estimated as the intraclass correlation coefficient (ICC), exceeded 0.85 except for the affect scale (0.72). Substantial floor effects occurred in the upper limb scale (33.8%). Principal factor analysis confirmed the postulated three-factor structure with physical, physiological and social dimensions, explaining 49.8, 14.1 and 6.4% of the variation, respectively. The assessment of external validity revealed satisfactory correlations with the corresponding WOMAC (Western Ontario and McMaster Universities Arthrosis Index) scales. As expected, correlations with radiological grading were moderate to low. The correlation with the physician's assessment was high in the scales that were dominated by physical factors, but rather low in the areas of health, which were found to be dominated by psychological or social factors. CONCLUSION: The German AIMS2-SF is a reliable and valid instrument to assess the quality of life in primary care patients suffering from OA. When addressing the different impacts of OA, the physical scale should be divided into an upper body scale and a lower body scale. The floor and ceiling effects revealed are in accordance with the disease characteristics of the study sample and do not limit the significance of the questionnaire.

Adult↗
PubMed2005

[Conservative treatment of chronic pancreatitis].

Chronic pancreatitis represents an inflammatory disease of the pancreas with progressive fibrotic destruction of the gland. The disease is characterized by abdominal pain, exocrine and endocrine insufficiency. Morphological alterations of the pancreas and signs of exocrine and endocrine insufficiency are difficult to detect early in the course of the disease. The conservative treatment of chronic pancreatitis aims at (1) control of abdominal pain, (2) replacing lost exocrine function, (3) treatment of endocrine insufficiency, (4) prevention of weight loss or achievement of weight gain, (5) limiting progression and complications of the disease, and finally (6) psychiatric and social advice with special emphasis on the treatment of chronic alcohol abuse. The patient must be counselled about the importance of abstinence from alcohol. Abdominal pain is controlled with strict analgetic medication using a step-by-step approach in increasing the dosage. Exocrine insufficiency is treated with a diet of several small meals per day and supplementation of pancreatic enzymes. Endocrine insufficiency is treated with insulin.

Chronic Disease↗
PubMed2005

Hammerhead ribozymes targeted against cyclin E and E2F1 cooperate to down-regulate coronary smooth muscle cell proliferation.

BACKGROUND: Anti-proliferative drugs released from endo-vascular stents have substantially contributed to reduce in-stent restenosis rates in coronary arteries bearing single primary lesions by down-regulating coronary smooth muscle cell (CSMC) growth. However, the considerably lower drug efficacy shown in treatment of more complex coronary lesions suggests that alternative anti-proliferative approaches can be beneficial. Thus, we explored the use of hammerhead ribozymes as tools to knock down cyclin E and E2F1, two potent activators of cell proliferation which cooperate to promote the G1 to S phase transition. METHODS: Two ribozymes, one directed against cyclin E and the other against E2F1 mRNAs, were delivered by liposomes to cultured human CSMCs. The influences on cell proliferation were measured evaluating BrdU incorporation into newly synthesised DNA. The effects on cell cycle phase distribution were determined by BrdU and 7-aminoactinomycin D incorporation into DNA. RESULTS: Both ribozymes exhibited a sequence-specific and dose-dependent reduction in BrdU incorporation, which, at a concentration of 280 nM, persisted up to 4 days after transfection of CSMCs. A combined administration of the two ribozymes (210+210 nM) resulted in a more pronounced decrease in BrdU incorporation compared to the administration of an equimolar amount (420 nM) of each of them. Finally, both ribozymes induced a significant (P<0.05) reduction in S phase cells with a concomitant increase of G1/G0 and G2-M phase cells, compared to controls. CONCLUSIONS: The ribozymes selected represent potent tools to prevent CSMC proliferation, especially when administered together, and thus are ideal candidates for in vivo application.

Cell Cycle↗
PubMed2005

Resistance to cytarabine and gemcitabine and in vitro selection of transduced cells after retroviral expression of cytidine deaminase in human hematopoietic progenitor cells.

Overexpression of the detoxifying enzyme cytidine deaminase (CDD) renders normal and leukemic hematopoietic cells resistant to cytarabine (1-beta-D-arabinofuranosylcytosine), and studies on murine cells have suggested transgenic CDD overexpression as a way to reduce the substantial myelotoxicity induced by the deoxycytidine analogs cytarabine and gemcitabine (2',2'-difluorodeoxycytidine). We now have investigated CDD (over-)expression in the human hematopoietic system. Retroviral gene transfer significantly increased the resistance of CDD-transduced cord blood and peripheral blood-derived progenitor cells for doses ranging from 20-100 nM cytarabine and 8-10 nM gemcitabine. Protection was observed for progenitors of erythroid as well as myeloid differentiation, though the degree of protection varied for individual drugs. In addition, significant selection of CDD-transduced cells was obtained after a 4-day culture in 30-100 nM cytarabine. Thus, our data demonstrate that overexpression of CDD cDNA results in significant protection of human progenitors from cytarabine- as well as gemcitabine-induced toxicity, and allows in vitro selection of transduced cells. This strongly argues for a potential therapeutic role of CDD gene transfer in conjunction with dose-intensive cytarabine- or gemcitabine-containing chemotherapy regimen.

Cells, Cultured↗
PubMed2005

The MONICA Augsburg surveys--basis for prospective cohort studies.

As part of the WHO MONICA project three population-representative surveys were conducted in the study region of Augsburg since 1984/85 to describe time trends of classical cardiovascular risk factors. These surveys provide relevant baseline-information for prospective health outcome studies. Three independent study populations were recruited in 1984/85 (S1: age 25 - 64 years), 1989/90 (S2: age 25 - 74 years), and 1994/95 (S3: age 25 - 74 years) by a two-stage cluster sampling, with random sampling for the city of Augsburg, and a random selection of 16 communities by community size in the two adjacent counties. In the three surveys, 13,427 persons have had 13,818 study participations, since some subjects were by chance sampled for more than one survey. From 1984 to 1995, no trends in hypertension could be observed, but an increase of 15 % (men) resp. 30 % (women) in dyslipidaemia (total/HDL cholesterol ratio > or = five). Cigarette smoking decreased in 55 to 64 year old men und increased in 35 to 64-year old women. The predictive impact for incident Acute Myocardial Infarction (AMI) per 100,000 person years is highest for cigarette smoking (men 880, women 360), followed by dyslipidemia (men 739, women 318) and systolic blood pressure > or = 160 mm Hg (men 658, women 276). By 31st December 2002 1,551 persons (1,031 men, 520 women) had died. The surveys will be used for further gender-specific cross-sectional and longitudinal analyses with special focus on classical, new laboratory and genetic risk factors as determinants of mortality, incident AMI and incident type 2 diabetes, to improve preventive strategies.

Adult↗
PubMed2005

[Case-cohort studies: an effective design for the investigation of biomarkers as risk factors for chronic diseases--demonstrated by the example of the MONICA/KORA Augsburg Case-Cohort Study 1984-2002].

As it is often not possible to determine specific measures of exposure in all participants of a prospective cohort study due to financial or other restrictions, new study designs have been developed. The aim of these designs is to obtain valid results even though expensive measurements are restricted to a limited number of participants of the original cohort study. The case-cohort study is a design that has recently become interesting as an alternative to the well known nested case-control study. The following article describes the case-cohort design considering as an example data from the MONICA/KORA Augsburg cohort study 1984-2002 and the outcomes of type 2 diabetes mellitus and acute myocardial infarction. Furthermore, results obtained in the full cohort for selected exposures are compared with results obtained in the case-cohort study.

Adult↗
PubMed2005

Serum gamma-glutamyltransferase and risk of type 2 diabetes mellitus in men and women from the general population.

OBJECTIVES: To examine gender-specific associations between gamma-glutamyltransferase (GGT) and incident type 2 diabetes mellitus in a representative population-based sample in Germany. DESIGN: Prospective population-based study. METHODS: The study was based on 1851 men and 1836 women (aged 25-64 years) who participated in the first Monitoring Trends and Determinants on Cardiovascular Diseases (MONICA) Augsburg Survey 1984/1985, and who were free of diabetes at baseline. Incident cases of type 2 diabetes were assessed using follow-up questionnaires in 1987/1988, 1997/1998 and 2002/2003 and were validated with medical records. Gender-specific hazard ratios (HRs) were estimated from Cox proportional hazard models. RESULTS: A total of 172 cases of incident type 2 diabetes amongst men and 109 amongst women were registered during a mean follow-up period of 14.7 years. In both sexes the risk of type 2 diabetes increased with increasing levels of serum GGT. After multivariable adjustment HRs for incident type 2 diabetes across GGT categories (<25th, <50th, <75th, <87.5th and > or =87.5th percentiles) were 1.0, 1.81, 2.37, 3.41 and 4.24 (P-value for trend <0.0001) in men and 1.0, 1.42, 1.48, 1.95 and 2.41 (P-value for trend 0.0179) in women. Obesity appeared to be more strongly associated with type 2 diabetes in women with GGT equal or greater than the median compared to women with GGT below the median. However, in men the association between obesity and type 2 diabetes was almost identical in the two groups. CONCLUSIONS: The GGT is an important predictor for incident type 2 diabetes in men and women from the general population.

Adult↗