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Biomedical subjects

A Mohr

Publications and source records attributed to A Mohr.

At least 19 recordsLinked to original sources
PubMed2006

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

Adult↗
PubMed2006

Effects of mycophenolic acid on inosine monophosphate dehydrogenase I and II mRNA expression in white blood cells and various tissues in sheep.

Mycophenolic acid (MPA) is a mycotoxin commonly found as Penicillium genus secondary metabolite in feedstuffs and silages. Feeding with MPA contaminated silages may modulate the immune system in the farm animals and can cause appetite lost, ketosis, paralysis and abortion. The aim of the present study was to characterize the long-term MPA effect on both the inosine monophosphate dehydrogenase (IMPDH) isoforms I and II mRNA expression in white blood cells (WBC) and various tissue of healthy sheep. In treated animals 300 mg MPA/day/sheep was applied. In all investigated tissues the IMPDH I and II mRNA was abundant: WBC, spleen, thymus, ileum, jejunum, kidney, liver, pharyngeal and mesenterial lymph node. An efficiency-corrected relative quantification of the IMPDH types I and II isoforms mRNA were performed by normalizing with the constant reference gene expression of beta-actin. High IMPDH I mRNA expression levels were seen in kidney > mesenterial lymph node > jejunum > spleen > pharyngeal lymph node. Medium and low abundance was found in ileum > WBC > liver > thymus. Type II mRNA was highly expressed in liver > thymus > jejunum. In pharyngeal lymph node > spleen > ileum > mesenterial lymph node > kidney > WBC medium to low IMPDH II mRNA concentrations were detected. Under MPA treatment the IMPDH I mRNA expression was not significantly regulated in WBC, only trends of down- and upregulation were observed. Surprisingly in jejunum an upregulation could be observed (P < 0.05). In pharyngeal lymph node a tendency to downregulation was shown. This may be due to frequent ruminant activities and frequent exposition of MPA to the pharyngeal lymph nodes. In contrast to type I mRNA expression, IMPDH II mRNA was significantly downregulated in ileum (3.4-fold, P < 0.01) and tendencies in downregulation could be seen in jejunum (5.1-fold, P = 0.14). In addition, significant downregulation of IMPDH II gene expression over the entire feeding experiment could be shown in WBC of MPA-treated animals compared with untreated animals (P < 0.05). In conclusion, the recent study demonstrates that feeding sheep with MPA-contaminated silage did not induce IMPDH I mRNA expression in various tissues and blood, except in jejunum, but has suppressive effects on IMPDH II mRNA expression in WBC and ileum.

Animals↗
PubMed2006

Core hypothermia in multiple sclerosis: case report with magnetic resonance imaging localization of a thalamic lesion.

Hypothermia is a rare condition in multiple sclerosis (MS). We report on a patient with a long-standing secondary progressive MS and six episodes of recurring hypothermia down to 29.9 degrees C with associated hypotension, bradycardia, coagulopathy and electrolyte dysequilibrium. Magnetic resonance imaging (MRI) demonstrated severe involvement of the corpus callosum with an associated lesion in the right posterior thalamus. These findings may link hypothermia in MS with callosal and associated thalamic pathology to Shapiro's syndrome, where agenesis of the corpus callosum and associated abnormalities are related to episodic spontaneous hypothermia. In MS, hypothermic episodes may be triggered by preceding infections, as shown in the present case.

Corpus Callosum↗
PubMed2005

Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. RESULTS: An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. CONCLUSION: Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

Adult↗
PubMed2005

[Heat stroke with alpha coma. A case report].

We report the case of a near-fatal heat stroke in a 41-year-old patient. The comatose patient had a body core temperature of 41.5 degrees C. The clinical course was complicated by systemic inflammatory response syndrome and multiorgan failure. The EEG showed an alpha coma that did not react to external stimuli and, in general, has a poor prognosis. The patient regained consciousness and was discharged from our intensive care unit after 16 days. In the further course cerebral toxoplasmosis developed which was treated with a combination therapy of sulfadiazine and pyrimethamine. The patient was transferred to a neurorehabilitation clinic with a moderate neurological deficit 65 days after heat stroke onset.

Adult↗
PubMed2005

Morphological findings in lymphatic tissues of sheep following oral application of the immunosuppressive mycotoxin mycophenolic acid.

Mycophenolic acid (MPA) is applied in immunosuppressive therapy after organ transplantation. As a common contaminant in silage, this substance is also frequently fed to sheep unintentionally. In this study, the effect of MPA on the immune system of sheep was examined. Four groups of 9 sheep each were fed 0, 0.5, 1.2, or 5 mg of MPA per kg body weight per day for 6 weeks. Then, the animals were slaughtered and various organs were examined macroscopically, histologically, and immunohistochemically. No effect of MPA on general health was detected. With increasing dose of MPA, germinal centres in the retropharyngeal lymph nodes displayed an activated morphology with numerous centroblasts. In the highest dose group, the sheep showed shrinkage of thymic lobules. The numbers of IgG or IgM positive plasma cells decreased in the ileum with increasing MPA-doses. These results suggest, that MPA in a high concentration may affect the morphology of immune organs of sheep.

Administration, Oral↗
PubMed2005

[Micro-CT analysis of cancellous bone fragments from the distal radius fracture zone in osteoporosis].

The incidence and prevalence of osteoporosis must be considered to continue to increase significantly due to the expected demographic development and environmental changes. In the diagnosis and staging of osteoporosis the three-dimensional bone structure should be as important as the bone mass or the mineral content of the bone. In this study, microfragments were taken from distal radius fracture zones and investigated in Micro-CT scans. Patients in which osteodensitometry of the lumbal spine had revealed osteoporosis in were found to have significantly reduced bone mass, bone density and trabecular thickness. Trabecular fractures which were found in non-osteoporotic patients even in robust trabeculae were detected by the two-dimensional analysis in thin locations and arborizations. Despite some trabeculae turned out to be very small the differences in the histomorphometry and the quality of trabecular fractures in osteoporotic as well as non-osteoporotic patients could be visualized very good in the Micro-CT analysis.

Absorptiometry, Photon↗
PubMed2004

Identification of deficient mitochondrial signaling in apoptosis resistant leukemia cells by flow cytometric analysis of intracellular cytochrome c, caspase-3 and apoptosis.

Deficient activation of apoptosis signaling pathways may be responsible for treatment failure of malignant diseases. In primary leukemia samples the detection of deficient mitochondrial apoptosis signaling would enable identification of chemo-resistant cells. To investigate the key events of apoptosis at the mitochondrial level, we developed a flow cytometric method for simultaneous detection of mitochondrial cytochrome c release and caspase-3 processing using conformation sensitive monoclonal antibodies. This method proved to identify deficient mitochondrial apoptosis signaling in leukemia cells overexpressing Bcl-2 by a pattern of apoptosis resistance, deficient cytochrome c reduction and partial processing of caspase-3. In primary leukemia cells, reduction of cytochrome c and caspase-3 activation was induced by treatment with anticancer drugs in vitro. In leukemia cells of a patient with resistant disease, a pattern of deficient apoptosis signaling as in Bcl-2 transfected cells was observed, suggesting that deficient mitochondrial signaling contributed to the clinical phenotype of drug resistance in this patient. Flow cytometric analysis of mitochondrial apoptosis signaling may provide a useful tool for the prediction of drug resistance and treatment failure in primary leukemia.

Antibodies, Monoclonal↗
PubMed2004

AAV-encoded expression of TRAIL in experimental human colorectal cancer leads to tumor regression.

Gene transfer vectors based on the adeno-associated virus (AAV) are used for various experimental and clinical therapeutic approaches. In the present study, we demonstrate the utility of rAAV as a tumoricidal agent in human colorectal cancer. We constructed an rAAV vector that expresses tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) and used it to transduce human colorectal cancer cells. TRAIL belongs to the TNF superfamily of cytokines that are involved in various immune responses and apoptotic processes. It has been shown to induce cell death specifically in cancer cells. Transduction with AAV.TRAIL gave rise to rapid expression of TRAIL, followed by induction of apoptosis, which could be inhibited by the caspase inhibitor z-VAD.fmk, in several human colon cancer cell lines. The apoptotic mechanism included activation of caspase-3, as well as cytochrome c release from mitochondria. The outgrowth of human colorectal tumors grown in mice was completely blocked by transduction with AAV.TRAIL in vitro, while in vivo transduction significantly inhibited the growth of established tumors. AAV vectors could provide a safe method of gene delivery and offer a novel method of using TRAIL as a therapeutic protein.

Animals↗
PubMed2004

[Quantitative ultrasound for the diagnosis of osteoporosis].

Quantitative ultrasound (QUS) methods are promising tools for the assessment of the bone status in osteoporosis. The techniques are based on changes in speed and amplitude of a broadband ultrasound signal propagating through the bone. However, ultrasound propagation through the anisotropic bone is complex and cannot be described in a simple way. The devices are easy to use, inexpensive, portable, do not use ionizing radiation, and therefore have advantages compared to conventional densitometry. This review discusses the technical basics, current research, clinical applications, points of weakness, and future prospects of QUS. For better understanding ultrasound propagation through bone is visualized with a simulation software.

Bone and Bones↗
PubMed2004

[Biochemical bone marrow markers and their significance in postmenopausal osteoporosis--a new method in the diagnosis of osteoporosis?].

This study analyzes the qualification of biochemical markers in the diagnosis of osteoporosis and evaluates the potential of a multiparametric classification of premenopausal and non-osteoporotic as well as osteoporotic postmenopausal women, which is based on biochemical marker profiles. For this evaluation data of 29 women in the age between 28-74 years were used. The classification of osteoporosis was done by the trabecular density of the lumbar spine using qCT-measurements. The biochemical markers of formation and resorption AP, bAP, OC, ucOC, PICP, PYD, DPD, NTX, BSP and vitamin K were analyzed on day 1 and 42 in all patients. For vitamin K we found significant distribution differences between non-osteoporotic and osteoporotic women (p<0.005). The crosslinks PYD and DPD showed weakly significant differences. All other parameters exhibited non-significant results. Vitamin K acted with a sensitivity of 64% and a specificity of 82%. The used multiparameter classification process improved sensitivity and specificity considerably. The parameter profiles of OC/PYD, vitamin K/PYD and vitamin K/bAP revealed the highest sensitivities with specificities of more than 82%.

Adult↗
PubMed2003

Apoptosis induction in peripheral leukemia cells by remission induction treatment in vivo: selective depletion and apoptosis in a CD34+ subpopulation of leukemia cells.

In vitro studies demonstrating the induction of programmed cell death by cytotoxic drugs used in anticancer chemotherapy suggested that antileukemic treatment eliminates leukemia cells by apoptosis. We therefore analyzed apoptosis induction and activation of apoptosis signaling molecules in patients receiving remission induction treatment for AML and ALL during the initial phase of leukemia cell reduction. A coexistence of distinct populations of CD34(+) and CD34(-) leukemia cells could be identified. During chemotherapy, CD34(+) leukemia cells were more rapidly depleted than CD34(-) cells. Furthermore, a significant increase in leukemia cell apoptosis ex vivo was detected in CD34(+) cells, while no such increase was observed in the CD34(-) subpopulation, suggesting that CD34(+) leukemia cells are the main targets for apoptosis induction through antileukemic treatment. No alterations in Bax and Bcl-2 expression were found during in vivo chemotherapy, and CD95 expression and sensitivity remained low, indicating the induction of apoptosis independent of the CD95 system or regulation of protein levels of Bax and Bcl-2. The data suggest that analysis of leukemia cell subpopulations is required for further identification of apoptosis signaling molecules relevant for response to treatment and assessment of drug efficacy in vivo and in vitro.

Adult↗
PubMed2003

[Radiology in managed care environment: opportunities for cost savings in an HMO].

PURPOSE: A large regional health plan in the Northeastern United States noted that its radiology costs were increasing more than it anticipated in its pricing, and noted further that other similar health plans in markets with high managed care penetration had significantly lower expenses for radiology services. This study describes the potential areas of improvement and managed care techniques that were implemented to reduce costs and reform processes. MATERIALS AND METHODS: We performed an in-depth analysis of financial data, claims logic, contracting with provider units and conducted interviews with employees, to identify potential areas of improvement and cost reduction. A detailed market analysis of the environment, competitors and vendors was accompanied by extensive literature, Internet and Medline search for comparable projects. All data were docu-mented in Microsoft Excel(R) and analyzed by non-parametric tests using SPSS(R) 8.0 (Statistical Package for the Social Sciences) for Windows(R). RESULTS: The main factors driving the cost increases in radiology were divided into those internal or external to the HMO. Among the internal factors, the claims logic was allowing overpayment due to limitations of the IT system. Risk arrangements between insurer and provider units (PU) as well as the extent of provider unit management and administration showed a significant correlation with financial performance in terms of variance from budget. Among the external factors, shared risk arrangements between HMO and provider unit were associated with more efficient radiology utilization and overall improvement in financial performance. PU with full-time management had significantly less variance from their budget than those without. Finally, physicians with imaging equipment in their offices ordered up to 4 to 5 times more imaging procedures than physicians who did not perform imaging studies themselves. CONCLUSION: We identified initiatives with estimated potential savings of approximately $ 5.5 million. Some of these initiatives are similar to the reforms to reduce cost and improve quality that are already implemented or proposed within the German healthcare system.

Budgets↗