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T Schmidt

Publications and source records attributed to T Schmidt.

At least 37 records · Page 2Linked to original sources

Tumour suppression induced by the macrophage activating lipopeptide MALP-2 in an ultrasound guided pancreatic carcinoma mouse model.

BACKGROUND AND AIM: Carcinoma of the exocrine pancreas has a particularly poor prognosis. Therefore, novel therapeutic strategies such as immunotherapy are required. Here we investigated the immunomodulatory capacity of macrophage activating lipopeptide 2 (MALP-2), which binds to toll-like receptors 2 and 6 and induces activation of nuclear factor kappaB in monocytes. This causes the release of early stage leucocyte attracting chemokines and proinflammatory cytokines. METHODS: MALP-2 was tested in a new orthotopic ultrasound guided pancreatic cancer mouse model. This model is close to the biological situation and avoids the stress and immunostimulation caused by laparotomy. Cells from the syngeneic, highly aggressive, and metastatic cell line Panc 02 were administered orthotopically, by ultrasound guidance, to C57bl/6 mice. MALP-2 was administered intratumorally or intraperitoneally and tumour growth, immune status, and leucocyte infiltration at the tumour site were determined. RESULTS: We showed a tumour suppressive effect induced by a single injection of MALP-2. Median survival increased from 21 to 30 days (p<0.002). Combining chemotherapy (gemcitabine) with MALP-2 treatment caused further prolonged survival (median survival 27 days with chemotherapy alone v 37 days for combined treatment; p<0.0002). The life prolonging effect was paralleled by a significant increase in cytotoxic T cells, restoration of beta2 integrin expression on lymphocytes, and high expression of CD45RB on T helper cells. Immunohistochemical stains showed strong cytotoxic T lymphocyte and natural killer cell infiltration. CONCLUSIONS: In conclusion, in a model of orthotopic pancreatic cancer in mice, we induced a tumour suppressive effect by treatment with a synthetic lipopeptide. Treatment with MALP-2 could be an option for immunotherapy in pancreatic cancer.

Adenocarcinoma↗

Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector.

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon neutrinos. This search yielded no excess events above those expected from background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux measured at the earth. For an assumed E-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E2Phi(E)=8.4 x 10(-7) cm(-2) s(-1) sr(-1) GeV (for a predominant neutrino energy range 6-1000 TeV), which is the most restrictive bound placed by any neutrino detector. Some specific predicted model spectra are excluded. Interpreting these limits in terms of the flux from a cosmological distributions of sources requires the incorporation of neutrino oscillations, typically weakening the limits by a factor of 2.

Journal Article↗

[Acrocyanosis: crucial symptom in a case of chronic diarrhea and weight loss].

The patient reported here was admitted because of severe dehydration caused by watery diarrhea. As underlying disease we found bacterial overgrowth of the small bowel due to myopathic dysmotility of the small bowel as a manifestation of CREST syndrome. An important clue to the diagnosis was the result of a ward round: the patient showed Raynaud's phenomenon when exposed to the cold at an open window airing the room. A leading tool for diagnosis and therapy proved to be small bowel manometry which is further discussed in this case report.

Aged↗

Do alterations of endogenous angiotensin II levels regulate erythropoietin production in humans?

AIMS: Recent evidence suggests a potential role of angiotensin II in the physiological regulation of erythropoietin (Epo) production. While the administration of exogenous angiotensin II (AII) has been used so far to study its effects, the role of endogenous AII has remained unclear. METHODS: To alter endogenous AII in humans experimentally we used furosemide bolus injection as a short-term (study 1) and dietary salt as a long-term modulator (study 2). In an open crossover design, 12 healthy male volunteers received furosemide (F) 0.5 mg kg(-1) intravenously or placebo (P) in random order (study 1). With the same design, 12 volunteers received high-salt (HS), normal-salt (NS) and low-salt (LS) diet (study 2). Plasma renin activity (PRA) was analysed along with AII. Inulin and paraaminohippurate (PAH) clearances were used to indicate glomerular filtration rate (GFR) and renal plasma flow (RPF), respectively. RESULTS: While F stimulated AII and PRA and decreased GFR and RPF significantly, no concomitant alteration of Epo was observed [AUCEpo: placebo 5709 +/- 243 (% of baseline x h), furosemide: 5833 +/- 255 (% of baseline x h); 95% confidence interval (CI) -608.4, 856.0; P = 0.73]. F decreased GFR (from 103.6 +/- 4.0 to 90.6 +/- 4.8 ml min(-1) 1(-1) 73 m-2; 95% CI 1.1, 24.9; P < 0.05), but not RPF (study 1). Correspondingly, LS stimulated and HS decreased AII and PRA significantly. HS increased GFR and RPF. Again, Epo concentrations were not affected (AUCEpo: normal sodium 44 +/- 6.7 mIU x day ml(-1), low sodium 39 +/- 2.4 mIU x day ml(-1), high sodium 48.5 +/- 6.1 mIU x day ml(-1); normal salt/low salt 95% CI -11.9, 21.9, P = 0.54; normal salt/high salt 95% CI -14.4, 23.3, P = 0.63; study 2). CONCLUSIONS: We conclude that, at least in the physiological setting in healthy volunteers, increased concentrations of endogenous AII may not be a major factor of Epo regulation.

Adult↗

[Comparison of conventional enteroclysis, intestinal ultrasound and MRI-enteroclysis for determining changes in the small intestine and complications in patients with Crohn's disease].

BACKGROUND: Enteroclysis, intestinal wall ultrasound (IWU) and abdominal magnetic resonance imaging (MRI) are three established methods in the diagnosis of Crohn's disease (CD). To date, however, the three methods have not been compared in one patient collective. AIMS: The present prospective study compared the relative performance of IWU, MRI and enteroclysis in determining the extent of disease involvement and intestinal complications in patients with CD both at initial diagnosis and during follow-up. PATIENTS AND METHODS: Included in the present study were 48 patients with confirmed CD (age: 19-66 years) examined with all three methods between August 1999 and December 2000. IWU was performed in B-mode with a 4-7 MHz convex transducer head and a 5-12 MHz linear transducer head by an experienced examiner. At MRI, T1 and T2 weighted sequenced (Flash 2D before and after intravenous application of gadolinium DTPA or TSE) were acquired in coronal and transverse planes. Enteroclysis was performed using conventional biphasic technique. Interpretation was conducted on the basis of a standardized catalogue of findings. RESULTS: Changes in bowel segments consistent with inflammation were identified in 41 of 48 patients. All three methods returned equivalent findings with regard to the length of inflamed bowel segments (IWU, range: 3-25 cm, mean: 12 cm; MRI, range: 3-25 cm, mean: 10 cm; enteroclysis, range: 3-30 cm, mean: 11 cm) and wall thickness (IWU, range: 4-10 mm, mean: 7 mm; MRI, range: 5-10 mm, mean: 7 mm; of nine patients with stenotic change, five were correctly diagnosed with IWU (sensitivity, 55.6%; specificity, 97.4%), four with MRI (sensitivity, 44.4%; specificity, 100%) and six with enteroclysis (sensitivity, 66.7%; specificity, 100%). Fistulae were correctly identified in five patients with IWU (sensitivity, 55.6%; specificity, 97.4%), in four with MRI (sensitivity, 44.4%; specificity, 100%) and in six with enteroclysis (sensitivity, 66.7%; specificity, 100 %) of a total of nine patients with confirmed fistula formation. Abscesses were correctly identified in five patients with IWU (specificity, 66.7%; specificity, 100%), in five with MRI (sensitivity, 83.3%; specificity, 100%) and in no patients with enteroclysis (sensitivity, 0%; specificity, 100%) in six patients with abscesses. CONCLUSION: Both IWU and MRI identify extent, severity and intestinal complications with adequate diagnostic accuracy in patients with CD. Both techniques possess the potential for replacing enteroclysis in the work-up of CD. Enteroclysis should be reserved for the work-up of complex fistula systems.

Adult↗

Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT.

Patients in persistent vegetative state (PVS) after severe head trauma were investigated with 99mTc-ECD SPECT and 18F-FDG PET to further characterize the degree of brain damage and to obtain insight into changes of brain perfusion and glucose metabolism. 18F-FDG PET and 99mTc-ECD SPECT were performed in 16 patients in PVS. Quantitative PET data were compared with that obtained from seven normal controls. After spatial normalization into Talairach space, global grey matter values and regional data using predefined ROI sets were derived. For comparison of PET and SPECT, regional data were normalized to their individual mean grey matter values. Patients in PVS showed significantly lower values of cerebral glucose metabolism than did the controls. The mean reduction of grey matter values in cortical and subcortical structures was 58%, except in the vermis cerebelli, where only a reduction of 16% was found compared to the controls. Comparing the glucose metabolism and perfusion within the patient group, the pattern of both modalities was similar in the neocortex and internal ganglia. In the cerebellar hemispheres a relatively higher perfusion than glucose metabolism was found. The overall reduction of 58% of glucose metabolism in grey matter structures is in accordance with other PET studies investigating PVS patients with different disease histories. The relative preserved activity of vermis cerebelli seems to be an uncommon finding not described by other authors up to now.

Adolescent↗

Handling of slaughter cattle in pre and post transport situations including loading and unloading on journeys up to 8 hours in Germany.

In a field study 63 commercial cattle transports to German slaughter plants including 580 bulls, cows and heifers were investigated to estimate the impact of pre and post transport aspects on animal welfare. Study 1 evaluated these aspects as part of a large model covering all possible influences at transport and slaughter on biochemical stress response and carcass and meat quality. Included were keeping system, behavioural and clinical observations at loading, unloading and lairage, transport time, loading density, mounting prevention, regrouping and lairage time. In study 2 more detailed questions about loading and unloading were answered by investigating the impact of facility design and handling criteria on cattle behaviour and heart rate. Cattle from tied housing show an increased stress response to all transport procedures. Many aspects of facility design and handling contribute to quality of loading. Cattle show calmer behaviour, turn, balk or fall less if they are not mixed and driven in small groups on driveways without impediments but with regular sideblock, not wider than the vehicle ramp. Vehicle ramps should have high and closed side gates, be inclined less than 20 degrees, and the step towards ramp should be less than 15 cm. Unloading is improved if performed level and to the back of the vehicle (behaviour, heart rate, cortisol, CK). Direct reloading should be avoided and mounting should be prevented during transport and lairage (CK, lactate, bruising). But mounting prevention devices may increase bruising if set too low (< 20 cm above withers). Longer lairage time is disadvantageous (CK, energy metabolism).

Animal Husbandry↗

Weekly carboplatin and docetaxel for locally advanced primary and recurrent cervical cancer: a phase I study.

OBJECTIVE: The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated doses (MTDs) of a docetaxel-carboplatin regimen in patients with locally advanced cervical cancer (LACC) or recurrent cervical cancer. The regimen was administered weekly, with a maximum of 12 courses. PATIENTS AND METHODS: Twenty patients were treated with with a total of 145 cycles of weekly carboplatin and docetaxel. The starting dose of docetaxel was 25 mg/m(2) with increments of 5 mg/m(2) until a final dose of 35 mg/m(2) was reached. Dose-escalation of docetaxel was followed by carboplatin at AUC 2, AUC 2.5, and AUC 3, respectively. Defined dose-limiting toxicities were WHO grade (G) 3 hematotoxicity, G4 mucositis, and G2 neurotoxicity. The response status of the patients was assessed using the common ECOG response criteria. RESULTS: Two of four patients developed a DLT at dose level 4. Nonhematological toxicity was generally mild, except for ubiquitous complete alopecia. The MTD was reached at docetaxel 35 mg/m(2) and carboplatin AUC 2 mg/mL.min. The overall response rate was 65% in the entire group of evaluable patients and 77% in patients with primary LACC, with two cases of pathological complete response. CONCLUSION: This dose-dense regimen was well-tolerated and could be administered on an outpatient basis.

Adult↗

[Keratosis lichenoides chronica. Bath PUVA therapy].

We describe the case of a 51-year-old male patient with characteristic lesions of keratosis lichenoides chronica confined to the back of his hands and feet. The lichenoid papules, linear hyperkeratotic ridges and erythematosquamous plaques appeared first in early childhood and recurred after a short episode of spontaneous remission. They didn't respond to various topical treatment modalities over the years. After a local PUVA therapy all lesions disappeared with no recurrence for over two years now. Our case report indicates a new promising indication for bath-PUVA-therapy.

Balneology↗

[Acute peripheral vestibular lesions. Monocular subjective visual vertical and cyclodeviation].

BACKGROUND: A deviation of the subjective visual vertical (svv) is often found in patients with unilateral peripheral vestibular lesions and in most cases the deviation is transitory and easy to compensate. The purpose of the study was to find out if there is a correlation between deviation of the svv and objective cyclodeviation of the retina. PATIENTS AND METHODS: A total of 20 patients (10 females and 10 males aged between 16 and 78 years) with acute vestibular disease were enrolled. Only patients with a binocular deviation of the svv of more than 2 degrees and/or a difference between the monocular deviation of more than 1.5 degrees were included. The svv was examined monocular in a darkened room and after pupil dilatation, fundus photography was performed on each eye. The angle between papilla and macula was measured manually. RESULTS: We found a good qualitative correlation between svv (mean 7.9 degrees) and objective cyclodeviation (mean 10.6 degrees). CONCLUSION: In contrast to the binocular measurement of the svv, we found good correlation between the monocular svv and the objective cyclorotation measured with fundus photography. It is not yet clear which part of the vestibular system is responsible for cyclodeviation. Because of our results we recommend monocular measurement of the svv in clinical examinations.

Adolescent↗

Is visual field constriction in epilepsy patients treated with vigabatrin reversible?

OBJECTIVE: To evaluate the reversibility of vigabatrin associated visual field constriction. BACKGROUND: Visual field constriction (VFC) occurs in approximately 40 % of epilepsy patients under treatment with vigabatrin (VGB). There is still controversy about whether VGB-associated VFC is reversible. From a cross-sectional study there is evidence that VFC does not reverse three to six months after stopping VGB treatment. So far, there are no long term studies on this subject. METHODS: We performed a follow-up study on 15 epilepsy patients (eight women, seven men, median age 45 (21-58) years) with VGB-associated VFC but otherwise normal ophthalmological examination. Kinetic and static perimetry was performed one and two years after VFC was diagnosed (baseline examination). Visual field size at first and at second year-follow-up was compared with the baseline examination. Because discontinuation of VGB-treatment was dependant on clinical needs, patients either stopped VGB treatment before or after VFC was diagnosed. In a small group of patients VGB treatment was continued despite of VFC. RESULTS: There was no statistically significant difference in visual field size comparing baseline values with first year and second year follow-up examinations either in patients who stopped VGB treatment (n = 11) or in patients who continued VGB treatment on a reduced dosage (n = 4). CONCLUSION: Although our data are based on a relatively small group of patients there is evidence that VFC resulting from VGB treatment is not reversible in epilepsy patients after stopping the drug.

Adult↗

Visual field constriction in epilepsy patients treated with vigabatrin and other antiepileptic drugs: a prospective study.

BACKGROUND: Visual field constriction (VFC) has been described in about 30 % to 50 % of patients treated with the antiepileptic drug (AED) Vigabatrin (GVG). The exact incidence of VFC related to GVG exposure is unknown. Risk factors other than medication have not been identified as yet, and it is unclear whether the occurrence of VFC is restricted to the use of GVG. METHODS: In a longitudinal study, we investigated 60 epilepsy patients who received GVG and other AEDs. Patients underwent full ophthalmological examination including perimetry. RESULTS: 16 of 60 patients exposed to different AEDs developed VFC, which was judged as clinically relevant by an experienced neuroophthalmologist. VFC was observed significantly more often in patients treated with GVG as add-on- or monotherapy as compared with patients who had never been exposed to GVG (13/29 versus 3/31). Within the subgroup of 23 patients who received GVG as add-on therapy, those who developed VFC had been exposed to GVG for significantly longer than patients without VFC. The only non-treatment related feature associated with VFC was older age. Type and severity of epilepsy or type and number of concomitant AED were not related to the occurrence of VFC. CONCLUSIONS: The findings of an overrepresentation of VFC in patients receiving GVG and of a correlation between duration of GVG treatment and occurrence of VFC support the causal role of GVG treatment in the development of VFC. Old age is a possible risk factor for the development of VFC associated with GVG in epilepsy patients.

Adult↗

[Results of early mobilisation of acute whiplash injuries].

BACKGROUND: Diagnostic evaluation and therapeutic management of acute neck pain after whiplash is a frequent but unsolved clinical problem. Long-lasting symptoms and disability are common. Former studies proposed beneficial effects of physiotherapy in the early management of whiplash injury. The purpose of this study was to assess the effects of early active mobilization versus standard treatment with a soft cervical collar. METHODS: Between August 1997 and February 2000 a prospective randomized clinical trial with a total of 168 patients was performed. Of these patients 81 (31 male, 50 female; average age 28,78 years) were randomly assigned to the standard therapy group, which received a soft cervical collar, and 87 (31 male, 56 female; average age 29,62 years) to the early mobilization group, treated by physiotherapy. Study participants documented pain and disability twice (baseline and six week follow-up) during a one week period by diary, using numeric rating scales ranging from 0 to 10. RESULTS: The initial mean pain intensity (4,75) reported by the standard therapy group was similar to disability (4,76). There were no significant differences to initial pain (4,50) and disability (4,39) reported by the early mobilization group. The mean pain intensity reported by the standard therapy group after 6 weeks was 2,66 and disability was 2,40. The mean pain intensity indicated by physiotherapy group was 1,44 and mean disability was 1,29. The differences between the groups were both significant. CONCLUSIONS: Early mobilization is superior to the standard therapy regarding pain intensity and disability. We conclude that mobilization should be recommended as the new adequate standard-therapy in the acute management of whiplash injury.

Adult↗

[Sonography and hysteroscopy for endometrial carcinoma and its precursors].

The transvaginal sonography is a non invasive diagnostic method to evaluate the endometrium. It has a high reliability in the diagnosis of endometrial carcinoma, in the assessment of the depth of myometrial invasion as well as in preoperative staging. Patients with an episode of postmenopausal vaginal bleeding and an endometrial thickness (double layer) less-than-or-equal 4 mm should be controlled by transvaginal ultrasound examination after 3 month. In case of a endometrial thickness > 4 mm or in case of a persistent bleeding a histologic assessment should be obtained. Because of the highest sensitivity and specificity a hysteroscopic biopsy or a diagnostic hysteroscopy with subsequent D & C should be performed. Vaginal bleeding under hormonal replacement therapy should not be regarded to have more importance than vaginal bleeding in patients without HRT. After the current consensus hysteroscopy causes only a slightly increase in the rate of positive peritoneal cytology. This phenomenon seems to be of no influence on the disease free survival rate.

Biopsy↗

[Multi-value regulatory systems for extracorporeal circulation].

Extracorporeal perfusion is the standard technique in cardiac surgery. It is controlled by perfusionists on the basis of their clinical experience and on the available data collected pre- and intra-operatively. But in spite of intensive monitoring postoperative complications occur. An appropriate control of the heart-lung machine (HLM) using an "autopilot" might improve the quality of heart-surgery and decrease postoperative complications. Hence, a mathematical model of a human circulatory system has been developed which provides much more information about haemodynamics, blood gases and acid-base status than standard monitoring. It has been implemented on a system which is capable of integrating measured data as input parameters in real-time in the simulation. Now, soft- and hardware control concepts based on the human circulatory system have to be developed which are able to control the HLM.

Coronary Disease↗