Search PubMed⌕ Search

Biomedical subjects

P Weber

Publications and source records attributed to P Weber.

At least 37 records · Page 2Linked to original sources
PubMed2004

Somatostatin: beneficial effects on remission in young adult patients with newly diagnosed diabetes mellitus type 1.

To assess a possible influence of short-term administration of somatostatin on remission development in adult patients with newly diagnosed diabetes mellitus type 1, the somatostatin analog octreotide was given for two weeks after the establishment of the diagnosis at the daily dose of 150 microg subcutaneously in addition to the regular insulin and metabolic therapy. When compared to the control group, the remission was achieved earlier in the octreotide group (6+/-4 weeks vs. 11+/-12 weeks in the control group, p 0.05) and its duration was longer (99+/-49 weeks vs. 49+/-31 weeks in the control group, p 0.05). Moreover, remission also appeared in patients from the octreotide group with lower endogenous residual secretion of insulin (basal C peptide at the time of diagnosis in patients who later entered remission was 0.23+/-0.16 nmol/l vs. 0.34+/-.18 nmol/l in the control group, p<0.05). The increase of 24-h urine excretion of C-peptide after the therapy with octreotide was predictive for remission development. It can thus be concluded that octreotide administration in adults with newly diagnosed diabetes mellitus type 1 positively influences both the onset and duration of remission.

Adult↗
PubMed2004

[Polypharmacotherapy in clinical gerontology].

Multimorbidity frequently develops in old age and it is usually accompanied with pharmacotherapy of elderly patients. The growing number of seniors and comparatively low attention given to this reality among the medical community makes the problem highly significant for the practical medicine. Solution requires in the broad medical community a deeper knowledge of gerontopharmacotherapy and of its specific features, including the pharmacodynamics and pharmacokinetics in elderly organism. Non-geriatric physicians will face in their daily clinical praxis the questions of drug interactions and undesirable general and local side effects. Moreover, some foods, beverages or preservatives can influence the pharmacological effect. Due to multimorbidity in the senescence, such problems can be linked to large geriatric syndromes (instability with downfalls, immobility, decubitus, incontinency, intellectual and sensory defects of vision and hearing).

Aged↗
PubMed2003

The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells.

In the present study, we investigated the role of the phytoestrogen genistein and 17beta-estradiol in human bone marrow stromal cells, undergoing induced osteogenic or adipogenic differentiation. Profiling of estrogen receptors (ERs)-alpha, -beta1, -beta2, -beta3, -beta4, -beta5, and aromatase mRNAs revealed lineage-dependent expression patterns. During osteogenic differentiation, the osteoblast-determining core binding factor-alpha1 showed a progressive increase, whereas the adipogenic regulator peroxisome proliferator-activated receptor gamma (PPARgamma) was sequentially decreased. This temporal regulation of lineage-determining marker genes was strongly enhanced by genistein during the early osteogenic phase. Moreover, genistein increased alkaline phosphatase mRNA levels and activity, the osteoprotegerin:receptor activator of nuclear factor-kappaB ligand gene expression ratio, and the expression of TGFbeta1. During adipogenic differentiation, down-regulation in the mRNA levels of PPARgamma and CCAAT/enhancer-binding protein-alpha at d 3 and decreased lipoprotein lipase and adipsin mRNA levels at d 21 were observed after genistein treatment. This led to a lower number of adipocytes and a reduction in the size of their lipid droplets. At d 3 of adipogenesis, TGFbeta1 was strongly up-regulated by genistein in an ER-dependent manner. Blocking the TGFbeta1 pathway abolished the effects of genistein on PPARgamma protein levels and led to a reduction in the proliferation rate of precursor cells. Overall, genistein enhanced the commitment and differentiation of bone marrow stromal cells to the osteoblast lineage but did not influence the late osteogenic maturation markers. Adipogenic differentiation and maturation, on the other hand, were reduced by genistein (and 17beta-estradiol) via an ER-dependent mechanism involving autocrine or paracrine TGFbeta1 signaling.

Adipocytes↗
PubMed2003

[Comparative study of spatial imaging techniques in stereo-endoscopy].

PURPOSE: This study compares the two-dimensional presentation of stereo-endoscopic video data with three-dimensional presentation using polarization glasses and three-dimensional presentation with an autostereoscopic display. The aim of this study was to evaluate possible advantages of the three display technologies. MATERIAL AND METHODS: Fifty-nine test persons untrained in endoscopy had to complete three endoscopic tasks with different levels of difficulty. Each test involved a new presentation method. Different measurements were noted such as speed of task completion, accuracy of task performance, and quantity of solved tasks. The data collected were statistically evaluated. RESULTS: Neither sex, handedness, nor level of stereopsis had any statistically significant impact on the test results. The differences between the three presentation methods of stereo-endoscopic pictures were not statistically significant. CONCLUSION: Similar results were achieved with all three presentation methods. None of the presentation methods was significantly superior in the values measured. A final assessment of the possibilities of spatial endoscopy should await future technological developments in endoscopic devices (e.g., picture acquisition).

Adult↗
PubMed2002

Laparoscopic Roux-en-Y gastric bypass: defining the learning curve.

BACKGROUND: Increasing numbers of laparoscopic surgeons are performing laparoscopic Roux-en-Y gastric bypass (LGB). Our aim was to determine the length of the learning curve for a skilled laparoscopic surgeon. METHODS: The study population consisted of the first 225 consecutive LGB procedures attempted by one laparoscopic surgeon (HJS). Outcome parameters included mortality, morbidity, operative time, and conversion to an open procedure. RESULTS: Average operative time decreased from 189 min (first 75 patients) to 125 minutes (last 75 patients). Most of the improvement in operative time occurred over the first 75 patients. The perioperative complication rate decreased from 32% (first 75 patients) to 15% (second and third groups of 75 patients). Complication rates did not significantly decrease after the first 75 patients. Low mortality and conversion rates were achieved early in the series. CONCLUSION: Low mortality rates and low conversion rates can be achieved early in the learning curve for LGB. Complication rates plateau after approximately 75 LGBs, and operative times decrease substantially over the initial 75 cases. Operative times continue to decrease at a slower rate beyond 75 cases.

Adult↗
PubMed2002

Comparison between three-dimensional presentation of endoscopic procedures with polarization glasses and an autostereoscopic display.

BACKGROUND: Most endoscopic procedures are done with a two-dimensional (2D) view or a spatial presentation with polarization glasses. A new method of presenting three-dimensional (3D) spatial views is the autostereocopic display. We compared the performances of untrained test persons using these methods. METHODS: We designed three tests that had to be performed with one of the presentations. We used a Karl Storz 3D set with a 0 degrees stereooptic and a grasper. The autostereoscopic display was the Dresden 3D display. The 59 test persons were students who had never before worked with endoscopic devices. RESULTS: There were few differences between the tests, and none were statistically significant. The results with 2D were slightly better than those with polarization glasses, and the results with polarization glasses were slightly better than those with the autostereoscopic display. CONCLUSIONS: There are few differences between the procedures. A true spatial view is limited by the similarity of the two half-pictures.

Depth Perception↗
PubMed2002

Switch recombination in fetal porcine thymus is uncoupled from somatic mutation.

Since fetal serum Ig isotype profiles suggested that IgG and IgA could be of de novo origin, we studied their transcription and secretion. IgM transcripts were present at 50 days of gestation in major fetal lymphoid tissues, IgG and IgA transcription was pronounced at 60 days in fetal thymus and both transcription and secretion in this organ increased in late fetal life. The CDR3 spectratype of thymic IgG and IgA transcripts was as polyclonal as that of IgM already at 70 days in utero indicating a broad repertoire of switched B-cells. However, VDJs transcribed with the switched isotypes were not hypermutated as were those from immunized fetuses, indicating that switch recombination and somatic mutation are not coupled in utero in piglets. This finding and the fact that the oligoclonal IgA and IgM repertoires in a non-inductive site of the mucosal immune system (parotid gland) becomes polyclonal in piglets reared germ-free, suggest that initial expansion of switched B-cells in fetal and neonatal piglets is not driven by environmental antigen. Our findings collectively suggest that all IgA and IgM may result from de novo synthesis while some IgG probably results from selective transport. The latter is consistent with the gradual decline in serum IgG concentration in germ-free isolator piglets and the expression of FcRn in the porcine placenta.

Animals↗
PubMed2002

Isotope effects and intermediates in the reduction of NO by P450(NOR).

The mechanism of the heme-thiolate-dependent NADH-NO reductase (P450(NOR)) from Fusarium oxysporum was investigated by kinetic isotope effects including protio, [4S-2H]-, [4R-2H]-, [4,4(2)H(2)]-NADH and stopped-flow measurements. The respective kinetic isotope effects were measured at high NO concentrations and were found to be 1.7, 2.3 and 3.8 indicating a rate-limitation at the reduction step and a moderate stereoselectivity in binding of the cofactor NADH. In a different approach the kinetic isotope effects were determined directly for the reaction of the Fe(III)-NO complex with [4R-2H]- and [4S-2H]-NADH by stopped-flow spectroscopy. The resulting isotope effects were 2.7+/-0.4 for the R-form and 1.1+/-0.1 for the S-form. In addition the 444 nm intermediate could be chemically generated by addition of an ethanolic borohydride solution to the ferric-NO complex at -10 degrees C. In pulse radiolysis experiments a similar absorbing species could be observed when hydroxylamine radicals were generated in the presence of Fe (III) P450(NOR). Based on these results we postulate hydride transfer from NADH to the ferric P450-NO complex resulting in a ferric hydroxylamine-radical or ferryl hydroxylamine-complex and this step, as indicated by the kinetic isotope effects, to be rate-limiting at high concentrations of NO. However, at low concentrations of NO the decay of the 444 nm species becomes the rate-limiting step as envisaged by stopped-flow and optical kinetic measurements in a system in which NO was continuously generated. The last step in the catalytic cycle may proceed by a direct addition of the NO radical to the Fe-hydroxylamine complex or by electron transfer from the NO radical to the ferric-thiyl moiety in analogy to the postulated mechanisms of prostacyclin and thromboxane biosynthesis by the corresponding P450 enzymes. The latter process of electron transfer could then constitute a common step in all heme-thiolate catalyzed reactions.

Cytochrome P-450 Enzyme System↗
PubMed2002

Effect of either gamma-tocotrienol or a tocotrienol mixture on the plasma lipid profile in hamsters.

BACKGROUND/AIMS: Tocotrienols has been shown to inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity; however, the published animal and human studies yield conflicting results. We investigated the effects of a 4-week dietary supplement of either gamma-tocotrienol (86% gamma-T3) or a mixture of tocotrienols (29.5% alpha-T3, 3.3% beta-T3, 41.4% gamma-T3, 0.1% delta-T3: mix-T3) on the plasma lipid profile in hamsters receiving a high fat diet. METHODS: The hamsters were randomized into 7 groups: no treatment, 16 mg/day/kg BW simvastatin, 23, 58, 263 mg/day/kg BW gamma-tocotrienol, and 39 or 263 mg/day/kg BW for the mixture of tocotrienols. Plasma lipid levels were measured after 2 and 4 weeks of treatment. RESULTS: In all groups treated with tocotrienol total cholesterol levels were decreased, ranging from 7 to 23% after 2 weeks of treatment and from 7 to 15% after 4 weeks. Low-density lipoprotein plasma levels changed accordingly: a decline of 6-37% after 2 weeks and of 12-32% at the end of the study was observed. After 4 weeks of treatment, total cholesterol and low-density lipoprotein plasma levels were significantly reduced in the 263 mg/day/kg BW mixed tocotrienols and the 58 mg/day/kg BW and 263 mg/day/kg BW gamma-tocotrienol groups when compared to the no treatment group. Plasma triglycerides and high-density lipoprotein levels did not change significantly. CONCLUSION: This study provides further evidence that tocotrienols lower total cholesterol and low density lipoprotein plasma levels in hamsters and that gamma-tocotrienol is a more potent agent than a mixture of tocotrienols.

Acyl Coenzyme A↗
PubMed2001

Antibody repertoire development in fetal and neonatal piglets. IV. Switch recombination, primarily in fetal thymus, occurs independent of environmental antigen and is only weakly associated with repertoire diversification.

The epitheliochorial placenta of swine is considered a barrier to Ag and selective transport of IgG, so this species should be an excellent model with which to determine whether switch recombination is Ag dependent. Analysis of Ig levels and Ig isotype profiles in >150 normal and virus-infected fetuses from 38-110 days of gestation (DG) suggested that IgG, IgA, and IgM were most likely the result of de novo fetal synthesis. Although transcripts for IgM could be recovered at DG 50 (114 DG is full gestation) in all major fetal lymphoid tissues, those for IgG and IgA first became prominent at 60 DG in thymus, and transcription and spontaneous secretion became especially pronounced in this organ in older fetuses. Data on transcription, secretion, and serum isotype profiles suggest that although all fetal IgA and IgM may result from de novo synthesis, some IgG may result from low-level selective transport. The complementarity-determining region 3 spectratypes of thymic IgA and IgG transcripts at 70 and 90 days, respectively, were as polyclonal as that of IgM, indicating a broad repertoire of switched B cells although the VDJs transcribed with these switched isotypes in normal fetuses were not diversified in comparison to those from animals exposed to environmental Ags such as age-matched, virus-infected fetuses, colonized isolator piglets, and conventional adults. However, VDJs expressed with switched isotypes were more diversified than those expressed with IgM. Thus, switch recombination in fetal life does not appear to be driven by environmental Ag and is only weakly coupled to VDJ diversification. These findings, and the fact that the oligoclonal IgA and IgM repertoires in a noninductive site of the mucosal immune system (parotid gland) become polyclonal in piglets reared germfree, suggest that initial expansion of the switched cells in the B cell compartment of fetal and neonatal piglets is not driven by environmental Ag.

Animals↗
PubMed2001

[Glaucoma and pitfalls in therapy in the elderly with multiple morbidity from the viewpoint of the geriatrician].

Glaucoma in multi-morbid patients is frequently treated by specialists non-ophthalmologists. The growing number of elderly patients with glaucoma and comparatively small knowledge on this disease among the medical workers brought us to review recent findings on the aetiology, pathogenesis, risks of development and namely the problems of glaucoma treatment, possible drug interactions and their side effects. Considering the growing incidence of glaucoma with age, general practitioners, internists, geriatrists and other specialists will face the problems of drug interactions and global or ophthalmological side effects during the polypharmacological treatment of their multi-morbid seniors. The article gives basic information on the problems of using antiglaucoma drugs and their effects on the organism and eyes. Effects of some foodstuff and medicaments used in therapy of other diseases on the intraocular pressure and glaucoma are also summarise.

Aged↗
PubMed2001

[Streptococcus pneumoniae: lack of emergence of pristinamycin resistance].

Since 1997, a few studies have been published suggesting the emergence of clinical isolates of Streptococcus pneumoniae resistant to pristinamycin. Such results were not confirmed by recent studies from different investigators using reference techniques for the determination of susceptibilities, which is in accordance with the low probability of emergence of resistance to this antibiotic in vitro. Discrepancies are encountered with macrolide-resistant strains and may be due to the type of method used for susceptibility testing (agar-diffusion test), the final inoculum used in this technique, or the recent lowering of breakpoint for susceptibility. On the contrary, correlation between reference techniques and commercial galleries using liquid medium is excellent. Despite 35 years of exerting selective pressure, the in vitro activity of pristinamycin remains constant against clinical isolates of S. pneumoniae.

Drug Resistance, Microbial↗
PubMed2001

Vitamin K and bone health.

In the past decade it has become evident that vitamin K has a significant role to play in human health that is beyond its well-established function in blood clotting. There is a consistent line of evidence in human epidemiologic and intervention studies that clearly demonstrates that vitamin K can improve bone health. The human intervention studies have demonstrated that vitamin K can not only increase bone mineral density in osteoporotic people but also actually reduce fracture rates. Further, there is evidence in human intervention studies that vitamins K and D, a classic in bone metabolism, works synergistically on bone density. Most of these studies employed vitamin K(2) at rather high doses, a fact that has been criticized as a shortcoming of these studies. However, there is emerging evidence in human intervention studies that vitamin K(1) at a much lower dose may also benefit bone health, in particular when coadministered with vitamin D. Several mechanisms are suggested by which vitamin K can modulate bone metabolism. Besides the gamma-carboxylation of osteocalcin, a protein believed to be involved in bone mineralization, there is increasing evidence that vitamin K also positively affects calcium balance, a key mineral in bone metabolism. The Institute of Medicine recently has increased the dietary reference intakes of vitamin K to 90 microg/d for females and 120 microg/d for males, which is an increase of approximately 50% from previous recommendations.

Bone Density↗
PubMed2001

Coronary artery bypass grafting surgery without the routine application of blood products: Is it feasible?

OBJECTIVE: Fresh frozen plasma (FFP) substitution is currently standard practise in cardiac surgery. In this study we investigate whether elective coronary artery bypass grafting (CABG) surgery is feasible without the administration of blood products compared to the substitution of fresh frozen plasma. PATIENTS AND METHODS: From September 1997 to April 1998, 120 consecutive patients underwent CABG surgery at our institution. In the FFP group patients (n=60; men, n=43; women, n=17; mean age: 64+/-8.5 years) received 4 units of fresh frozen plasma (FFP) intraoperatively. In comparison, patients in the control group (n=60; men, n=44; women, n=16; mean age: 65+/-7.5 years) did not receive FFP. Main endpoints included perioperative hematologic parameters, blood loss, and the amount of blood products that were administered. RESULTS: Intraoperatively, the substitution of packed red blood cells (pRBC) in the FFP group was significantly higher compared with the control group (0.63+/-0.94 units/patient vs. 0.12+/-0.38 units/patient, P=0.001). Postoperatively, patients in the FFP group required significantly more pRBC products than patients in the control group (0.78+/-1.09 vs. 0.42+/-0.77, P=0.024). There were no significant differences in hemoglobin (FFP group: 99+/-11.1 g/dl; control group: 105+/-13.5 g/dl) and hematocrit levels (FFP group: 30+/-3.39%; control group: 32+/-4%). Also, no significant differences regarding the postoperative blood loss was observed between groups (FFP group: 588+/-224 vs. control group: 576+/-272 ml/24 h). CONCLUSIONS: This study clearly demonstrates that the avoidance of routine intraoperative FFP administration does not lead to an increase in blood loss postoperatively compared to patients that received FFPs. Furthermore, we did not observe increased requirements for postoperative FFP infusion in patients that did not receive FFPs intraoperatively.

Aged↗
PubMed2001

Temporally controlled targeted somatic mutagenesis in the mouse brain.

To develop spatio-temporally controlled somatic mutagenesis in the adult mouse nervous system, we established transgenic mice expressing the tamoxifen-inducible Cre-ERT recombinase under the control of the mouse prion protein (PrP) promoter. Cre-ERT was expressed in most regions of the brain and in the retina of one transgenic line, whereas its expression was mostly restricted to the hippocampus and the cerebellum in another line. As tamoxifen efficiently induced Cre-mediated recombination in the various neuronal cell types expressing Cre-ERT in the brain of adult mice, the PrP-Cre-ERT lines should be valuable tools to study the functions of genes involved in neurodegenerative diseases or regeneration, and in complex processes such as behaviour, learning and memory. Some limitations of presently available reporter lines for Cre-mediated recombination in adult mouse CNS are discussed.

Animals↗
PubMed2001

Role of biomarkers in nutritional science and industry - a comment.

We are encountering a significant progress in nutritional knowledge, relevant to the practice of all aspects of human nutrition, medicine and public health. So, it is conceivable that we may view the role of nutrition differently in the future. The diet may not only provide an adequate amount of nutrients to meet the metabolic requirements, but could also contribute to improving human health status. As a consequence, extracts of plants or single compounds thereof which are believed to benefit human health need to be identified and developed for the food market to complement a balanced diet. The assessment of risk and benefit of constituents of a diet or plants will be a challenge for scientists working in this area. The number of compounds to be tested is enormous. Their impact on human health is supposed to be through prevention. Their effect on the human system may be modest, yet still significant when consumed over an entire lifespan. Trials employing traditional clinical endpoints, for many reasons, appear not to be feasible to investigate the relevance of these compounds on human health. Rather biomarkers, which are 'surrogate endpoints' for clinical events, may be used in the field of nutritional science. These biomarkers have to be highly sensitive and specific, non- or minimally invasive and inexpensive and they need to be validated and standardized. The biomarker concept may prove essential in nutritional science to demonstrate the effect of diet constituents on human health.

Biomarkers↗