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Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

At least 127 records · Page 7Linked to original sources
PubMed1998

Research note: effect of duodenal--infused unsaturated fatty acids on dairy milk composition.

Investigations were conducted to assess the effect of duodenal infusions of oleic and linoleic acids both on milk composition and fatty acid patterns of milk fat. The investigations were carried out in two trials, I and II, each with 3 cows, fitted with a ruminal and a duodenal cannula. 56 g of oleic acid (Trial I) and 46 g linoleic acid (Trial II) were infused daily into the duodenum over a period of 7 days, while no application of fatty acids acted as a control in each case. An increase in milk fat content was observed in both trials whereas the content of protein and lactose in milk remained unaffected. In both trials the milk oleic acid and linoleic acid concentrations increased. In trial I C18:1 increased from 14.8 to 18.7%. In trial II C18:2 increased from 2.5 to 5.8% of total lipids. It was estimated that 84.8% of the infused C18:1 and 86.5% of C18:2 were transferred into milk fat.

Animals↗
PubMed1998

Sequential changes of biochemical bone parameters after kidney transplantation.

BACKGROUND: Persistent hyperparathyroidism after renal transplantation (Rtx) has been reported in several studies. However these studies evaluated biochemical bone parameters either only during a short time period (up to 6 months) or for a longer time period, but with long intervals in between. Therefore, we prospectively evaluated biochemical bone parameters of kidney-transplant recipients at short intervals for 2 years after surgery. METHODS: Biochemical bone parameters were prospectively investigated in 129 patients 2, 3, 5, 8, 12, 18 and 24 months after Rtx. All patients received prednisone and cyclosporin A as immunosuppressive therapy, and 75 patients also received azathioprine. None of the patients was treated with calcium, phosphorus, or vitamin D preparations. RESULTS: Serum creatinine levels decreased from 166.8 +/- 5.4 mumol/l to 140.0 +/- 4.9 two years after Rtx; (data are expressed as mean +/- s.e.m.). Serum phosphorus levels increased slightly from 0.9 +/- 0.022 mmol/l to 0.98 +/- 0.025 (12 m), but remained within the lower normal range. We observed a rise in total and albumin adjusted calcium concentrations 3 months after Rtx. 52% of all patients had serum calcium levels above 2.62 mmol/l (upper normal limit in our laboratory) 3 months after renal transplantation with a gradual decrease thereafter. There was no correlation of calcium and PTH levels. We observed a significant rise in biochemical bone parameters from 2 to 5 months after renal transplantation (P < 0.001): alkaline phosphatase (AP) increased from 164.3 +/- 9.4 to 236 +/- 12.7 U/l (normal 50-180), bone specific alkaline phosphatase (BAP) rose from 17.7 +/- 1.36 to 23.2 +/- 1.7 ng/ml (normal:4-20) and osteocalcin (OC) increased from 20.2 +/- 1.5 to 26.7 +/- 1.9 ng/ml (normal 4-12). AP and BAP levels values normalized 12 months after renal transplantation, whereas OC was still above normal throughout the study period. Patients were subdivided into two groups: those with good and those with impaired graft functions. Patients with good graft function had stable serum creatinine levels (< or = 132 mumol/l or < or = 1.5 mg/dl) well below the mean serum creatinine concentration during the study period. The significant changes in AP, BAP, and OC occurred irrespective of renal function. However, patients with impaired graft function (n = 65) had significantly higher PTH-levels (70 pg/ml higher) than patients with good graft function (n = 64), P < 0.01. PTH was positively correlated with serum creatinine (r = 0.81, P < 0.001). Moreover, patients with low 25 (OH) vitamin D levels (n = 63) had significantly higher PTH concentrations (between 40 and 80 pg/ml, P < 0.01) throughout the study period compared to patients (n = 66) with a sufficient 25(OH)D supply irrespective of graft function. There was a negative correlation of 25 (OH)D levels and PTH; (r = -0.49, P < 0.001). 1,25(OH)2D3 (evaluated in 24 patients) levels increased from 46.5 +/- 6.6 to 76.9 +/- 7.6 pg/ml (normal:35-90) at 12 months. CONCLUSION: Hypercalcaemia is a common phenomenon in the early period after kidney transplantation and occurs in the presence of low normal phosphorus levels. It is most probably related to improved PTH action and 1-hydroxylation of vitamin D. The rise in biochemical bone parameters between 3 and 5 months occurs irrespective of graft function and normalization is only achieved 1 year after transplantation. PTH is constantly elevated for up to 2 years after kidney transplantation and is most probably related (a) to impaired graft function and (b) to suboptimal 25 OH vitamin D supply.

Adult↗
PubMed1998

Isolation of a 370 kb YAC fragment spanning a translocation breakpoint at 3p14.1 associated with holoprosencephaly.

Holoprosencephaly (HPE) is a common developmental defect involving the brain and face. HPE is extremely heterogeneous, some cases being associated with structural anomalies of the short arm of chromosome 3. For a detailed characterization of a t(3;19)(p14.1;p13.1) breakpoint associated with HPE, we performed fluorescence in situ hybridization (FISH) analysis using yeast artificial chromosomes (YACs) mapped to the short arm of chromosome 3 from the Le Centre d'Etude du Polymorphisme Humain (CEPH) library. Three YACs mapped proximal, and one was located distal to the described breakpoint on chromosome 3. One of the chromosome 3 'Mega-YACs' spanned the translocation breakpoint. From this chimeric YAC we generated a site specific probe of about 370 kb by digestion of the YAC-DNA, which will be assessed for gene alterations that could underlie HPE in this patient.

Chromosomes, Artificial, Yeast↗
PubMed1998

Molecular recognition of cobalt(III)-ligated peptides by serine proteases: the role of electrostatic effects.

A series of peptides with a positively charged cobalt(III)-complex group attached to the carboxylate terminal was synthesized. The behavior of these metallopeptides as acceptor nucleophiles in acyl transfer reactions catalyzed by the three serine proteases bovine pancreatic alpha-chymotrypsin, porcine pancreatic trypsin, and proteinase K from Tritirachium album was examined. The efficiency of the substrates was assessed by kinetic measurement of the partition between aminolysis and hydrolysis. The results are discussed with special reference to coulombic interactions between the metal-ligated substrates and charged residues on the enzyme surfaces. The idea of using the metallopeptides in practical enzymatic peptide synthesis is put forward.

Animals↗
PubMed1998

Inhibition of human airway sensitization by a novel monoclonal anti-IgE antibody, 17-9.

We investigated the effect of a novel mouse IgG2b nonanaphylactogenic anti-human IgE antibody, 17-9, on allergen and histamine responses in passively sensitized human airways in vitro to determine the specific contribution of IgE to the sensitization process. Bronchial rings were sensitized with serum containing high levels of allergen-specific IgE (Dermatophagoides farinae), or with a hapten-specific chimeric humanized IgE (JW8). There was a concentration-dependent contraction of serum-sensitized bronchial rings to D. farinae (517 +/- 188 mg tension at 10 U/ml, n = 8) that was not observed in nonsensitized controls. This response was practically abolished when tissues were sensitized in the presence of 100 microg/ml anti-IgE antibody 17-9 (54 +/- 20 mg). In tissues sensitized with the anti-NIP IgE, JW8, there was a concentration-dependent contraction to the specific antigen NIP-BSA (560 +/- 154 mg at 0.3 microg/ml, n = 5) that was not observed in nonsensitized control subjects and that was substantially inhibited when 17-9 was present in the sensitization buffer (124 +/- 109 mg). The inhibition with 17-9 was specific, as pretreatment with a non-IgE-specific IgG2b antibody did not affect allergen responses. Potency and maximal contractions to histamine in serum-sensitized tissues were significantly elevated compared with nonsensitized controls; this was not affected by the presence of 17-9 during sensitization (pEC50 = 5.1 +/- 0.2 versus 5.0 +/- 0.3 in tissues sensitized in the absence of 17-9). In tissues sensitized with JW8 there was no significant increase in responsiveness to histamine. We conclude that allergen responses in sensitized human airways are dependent on IgE levels in the sensitizing serum while nonspecific (hyper)responsiveness depends on serum factors other than IgE. Nonanaphylactogenic anti-human IgE antibodies effectively inhibit allergen responses of human airways in vitro but may not affect other factors inducing hyperresponsiveness.

Aged↗
PubMed1998

Frequencies of T cells expressing interleukin-4 and interleukin-5 in atopic asthmatic children. Comparison with atopic asthmatic adults.

T-cell-derived cytokines have been implicated in the pathogenesis of asthma and it has been suggested that Th2-type cytokines (interleukin-4 [IL-4], interleukin-5 [IL-5]) are pivotal in the allergic inflammation. However, there are little data on human cytokine production by individual T cells at the protein level, in particular in asthmatic children. In this study we analyzed the cytokine production at the single cell level in peripheral blood from mild atopic asthmatic (AA) children and adults and age-matched atopic nonasthmatic (AN) and nonatopic nonasthmatic (NN) control subjects (n = 9 in each group) using the technique of intracellular cytokine detection by flow cytometry. Comparing asthmatic children with atopic and nonatopic control subjects, an increased percentage of IL-5-producing T cells (AA: median 4.9% [range 1.1 to 8.9%]; AN: 0.3% [0.2 to 0.9%], p = 0.003; NN: 0.4% [0.1 to 3.8%], p = 0.001) was detectable, with a positive correlation to the number of peripheral eosinophils and to bronchial hyperresponsiveness. The frequency of IL-4-producing T cells was increased in both atopic groups compared with nonatopic controls (AA: 1.2% [0.2 to 2.6%], p = 0.011; AN: 0.8% [0.4 to 3.7%], p = 0.007; NN: 0.4% [0.2 to 0.9%]) with a positive correlation to total IgE concentration. In adults there were no differences in IL-5- or IL-4-producing T cells between all three groups. A substantial proportion of T cells coproducing IL-4 and IL-5 was not detectable in children and adults. These findings indicate that in asthmatic children the frequencies of Th2-type-producing T cells are increased and that expression of IL-4 and IL-5 is regulated independently.

Adult↗
PubMed1998

Acceptance and feasibility of peripheral stem cell mobilisation compared to bone marrow collection from healthy unrelated donors.

Allogeneic peripheral blood stem cell transplantation leads to an earlier engraftment compared to BMT. The feasibility, acceptance and long-term side-effects of G-CSF mobilisation of PBSC in unrelated healthy donors needs to be evaluated. Forty unrelated healthy donors received G-CSF in a dose of 10 microg/kg bodyweight for 5 days and two aphereses were performed. The donors were monitored prospectively. The data were compared to bone marrow harvests from unrelated donors. Almost all stem cell donors reported some side-effects due to Filgrastim application. Bone pain (32), headache (20), chest pain (two) and night sweats (one) were complained of. By taking analgesics, the pain was relieved in most cases. No donor discontinued the filgrastim application. Bone pain and headache resolved within 2-4 days after termination of Filgrastim application. There was, as expected, a seven-fold increase in the number of total WBCs. There were no significant changes of platelet counts during G-CSF application. After 4 weeks haemoglobin concentration and platelet counts showed no significant differences compared to baseline values. The aphereses were mostly tolerated very well. Eighteen donors reported paraesthesia, one donor developed dizziness, two complained of nausea and vomiting. There was a significant decrease in platelet count (242 before, 98 x 10(9)/l after aphereses). Autologous platelets were transfused after the second aphereses in four donors. These data were compared to data from 245 unrelated bone marrow donors, who had on average, 14 days bone pain and tiredness after donation. The G-CSF mobilisation and apheresis of peripheral blood stem cells is an alternative to traditional bone marrow harvesting in unrelated healthy donors. It is well tolerated and the duration of side-effects on average is shorter than after the surgical procedure. So far no long-term effects have been observed in the follow-up.

Adult↗
PubMed1997

The market made them do it. Participants in the Medicare Choices project say they're nudging out the insurance middleman--and insuring their own survival. Panel discussion.

Medicare is experimenting again. This time HCFA wants to figure out ways to expand managed care options for the elderly. Under the Medicare Choices Demonstration Project, hospitals and health systems are developing and testing alternatives to standard Medicare HMOs. Dick Davidson, president of the American Hospital Association, sees these pilot programs as the precursors to provider-sponsored organizations building up a base of knowledge about what it means to manage risk. The AHA recently convened a meeting of organizations involved in the demonstration project and asked Hospitals & Health Networks executive editor Alden Solovy to lead a panel discussion on the lessons being learned.

Aged↗
PubMed1997

Rescue therapy with tacrolimus in simultaneous pancreas/kidney transplantation.

Tacrolimus has been effective both in primary and rescue therapy following steroid and OKT3-resistant acute rejection in liver and kidney transplantation. Due to the effects of tacrolimus on glucose metabolism, there has been concern about its use in simultaneous pancreas/kidney transplantation. We report on the results of six patients (three female, three male, age 35.2 +/- 7.3 years) converted from cyclosporin A to tacrolimus following simultaneous pancreas/kidney transplantation in steroid-resistant acute rejection. Tacrolimus was induced 2.8 +/- 1.7 months (range 1-4.8 months) after transplantation; follow-up was 3-18 months. Following conversion, creatinine levels declined in all patients [3.5 +/- 1.2 mg/dl before conversion, 3.0 +/- 1.9 mg/dl (n = 6) at three months, 1.4 +/- 0.1 mg/ dl at 1 year (n = 3)]. Before conversion, fasting blood glucose levels averaged 154 +/- 33 mg/dl, with three patients receiving insulin. Three months later no patient required insulin, the mean glucose level being 107 +/- 23 mg/dl (n = 6); at 1 year it was 92 +/- 9 mg/dl (n = 3). One patient lost his pancreatic graft after 4 months due to a mycotic aneurysm. We conclude that conversion to tacrolimus is a safe and effective treatment in cases of steroid-resistant rejections following pancreas/ kidney transplantation.

Administration, Oral↗
PubMed1997

Analytical Debye-Huckel model for electrostatic potentials around dissolved DNA.

We present an analytical, Green-function-based model for the electric potential of DNA in solution, treating the surrounding solvent with the Debye-Huckel approximation. The partial charge of each atom is accounted for by modeling DNA as linear distributions of atoms on concentric cylindrical surfaces. The condensed ions of the solvent are treated with the Debye-Huckel approximation. The resultant leading term of the potential is that of a continuous shielded line charge, and the higher order terms account for the helical structure. Within several angstroms of the surface there is sufficient information in the electric potential to distinguish features and symmetries of DNA. Plots of the potential and equipotential surfaces, dominated by the phosphate charges, reflect the structural differences between the A, B, and Z conformations and, to a smaller extent, the difference between base sequences. As the distances from the helices increase, the magnitudes of the potentials decrease. However, the bases and sugars account for a larger fraction of the double helix potential with increasing distance. We have found that when the solvent is treated with the Debye-Huckel approximation, the potential decays more rapidly in every direction from the surface than it did in the concentric dielectric cylinder approximation.

DNA↗
PubMed1997

Influence of duodenal infusion of nicotinic acid on the milk fat composition of dairy cows.

Two experiments I and II, with 2 and 4 lactating dairy cows respectively, each fistulated with ruminal and duodenal cannulae, were carried out. The effects on milk composition and milk fat fatty acids' pattern through a continuous daily infusion into the duodenum with 6 g nicotinic acid were investigated. Treatments were nicotinic acid (NA) infusion in experiment I, and nicotinic acid infusion plus feeding 270 g of stearic acid in experiment II. No application of NA and stearic acid in experiments I and II respectively, acted as controls. Nicotinic acid infusion did not significantly influence protein, fat and lactose contents of milk. In both experiments, infusion of nicotinic acid decreased the proportion of short and middle chain fatty acids in milk fat and increased significantly the percentage of oleic acid from 19.0 to 25.4%. The addition of stearic acid alone had no effect on milk composition and fatty acids' pattern. Additional infusion of nicotinic acid infusion significantly increased nicotinamid concentration in the milk from 49.7 to 87.2 micrograms/100 ml.

Administration, Oral↗
PubMed1997

Differentiation of hypoglycaemia induced cognitive impairments. An electrophysiological approach.

Effects of hypoglycaemia on distinct cognitive processes were assessed with event-related brain-potential (ERP) measures and reaction times in a hybrid selective-attention/response-choice task. One group of subjects received a euglycaemia-hypoglycaemia-euglycaemia treatment order and a second group a euglycaemia-placebo(euglycaemia)-euglycaemia sequence of treatments. During hypoglycaemia, ERP measures of selective attention (selection negativity), response choice (lateralized readiness potential) and reaction time were delayed compared with baseline performance. After restoration of euglycaemia, the onset of the selection negativity returned to baseline, whereas the lateralized readiness potential was still delayed, and error frequencies remained elevated. These results suggest that hypoglycaemia delays both the stimulus selection and the motor-response selection. They further suggest that the stimulus-selection process recovers quickly after restoration of euglycaemia, but that the response-selection process does not. Slow shifts in cortical potentials with a broad frontal distribution that occurred during hypoglycaemia, are discussed in relation to frontal lobe mechanisms involved in the control of subordinate, modality-specific selection mechanisms.

Adult↗
PubMed1997

New-onset diabetes mellitus in pediatric thoracic organ recipients receiving tacrolimus-based immunosuppression.

BACKGROUND: Tacrolimus has a negative effect on the pancreatic beta islet cell, and both glucose intolerance and diabetes mellitus are well-recognized complications of tacrolimus-based immunosuppression among adult solid organ transplant recipients. METHODS: To determine the association between tacrolimus and new-onset diabetes mellitus in childhood, we reviewed data on 78 pediatric heart and heart-lung/lung recipients receiving tacrolimus-based immunosuppression. Trough tacrolimus levels, fasting and random blood glucose levels, and corticosteroid requirements were reviewed. Diabetes was defined as glucose intolerance requiring long-term insulin treatment more than 30 days after transplantation. RESULTS: No patient had diabetes before introduction of tacrolimus. In heart-lung/lung recipients, 12 of 28 (43%) had development of diabetes at a median follow-up of 7 months (range 1 to 39). In this group diabetes developed in three of eight (38%) patients with cystic fibrosis and nine of 20 (45%) without (p = NS). In contrast, only two of 50 (4%) heart transplant recipients had development of diabetes. Of the 14 patients with diabetes, 10 had development of diabetes during augmentation of immunosuppression with pulsed corticosteroids. Tacrolimus trough levels were significantly lower in heart compared with heart-lung/lung transplant recipients (9.4 +/- 3.3 versus 15.3 +/- 0.9 ng/ml) (p < 0.01), and at latest follow-up significantly fewer heart transplant recipients were treated with maintenance corticosteroids (28% versus 75%; p < 0.01). In the heart-lung/lung group, no significant difference in tacrolimus levels was found between patients with and without diabetes, nor was there a significant difference in the average corticosteroid dose or number of pulses of corticosteroids per patient. CONCLUSIONS: New-onset diabetes mellitus is rare in pediatric heart transplant recipients receiving tacrolimus-based immunosuppression, but it occurs with a high incidence after pediatric heart-lung/lung transplantation and usually develops during pulsed corticosteroid therapy. However, it is currently not possible to predict which heart-lung/ lung transplant recipients will have development of this serious complication.

Adolescent↗