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Biomedical subjects

C Baldauf

Publications and source records attributed to C Baldauf.

16 recordsLinked to original sources
PubMed2003

Resorption of the element zinc from spermatozoa by the epididymal epithelium.

In this study, elimination of the element zinc from spermatozoa during epididymal maturation was investigated. Testes and epididymides from 40 bulls were collected; epididymal fluid was flushed, pooled, labelled with 0.5 MBq 65Zn2+ per sample and proteins were separated on a Sephacryl S-200 HR and zinc chelate column chromatography. To follow the resorption of zinc in the epididymal epithelial lining, an autometallographic technique (AMG) was performed in tissue from caput, corpus, cauda and vas deferens. The results showed a zinc-binding protein fraction with an apparent molecular weight of 150-160 kDa, which was enriched after chelate column chromatography. Specific labelling of 65Zn was about five times higher in the caput than in the cauda epididymidis. AMG revealed no detectable zinc in the caput, but a significant increase of zinc resorption from the corpus to the cauda and vas deferens. Controls showed that the detectable zinc was located within the principal cells. In conclusion, our study proves that zinc present in the sperm flagellum starts to be mobilized in the caput epididymidis and is resorbed by the epididymal epithelium as from the corpus. This zinc elimination is a mandatory step in sperm maturation to obtain motility.

Animals↗
PubMed2001

Results of surgery in patients with refractory extratemporal epilepsy with normal or nonlocalizing magnetic resonance findings investigated with subdural grids.

PURPOSE: To study the efficacy of extensive coverage of the brain surface with subdural grids in defining extratemporal cortical areas amenable for resection in patients with refractory extratemporal epilepy (R-ExTE) and normal or nonlocalizing magnetic resonance imaging (MRI) scans. METHODS: Sixteen patients with R-ExTE were studied. Eleven patients had simple partial, eight had complex partial, and three had supplementary motor area seizures. Seizure frequency ranged from three per month to daily episodes. Interictal EEG showed large focal spiking areas in 11 patients, secondary bilateral synchrony in four, and was normal in one patient. Surface ictal recordings were nonlocalizing in six patients, and in 10, they disclosed large ictal focal spiking areas. MRI was normal in 10 patients, and in six patients, focal nonlocalizing potentially epileptogenic lesions were found. All patients were given an extensive coverage of the cortical convexity with subdural electrodes through large unilateral (n = 13) or bilateral (n = 3) craniotomies. Bipolar cortical stimulation was carried out through the implanted electrodes. RESULTS: Interictal invasive recording findings showed widespread spiking areas in 13 patients and secondary bilateral synchrony in three. Ictal invasive recordings showed focal seizure onset in all patients. There were six frontal, two parietal, one temporooccipital, four rolandic, and three posterior quadrant resections. Thirteen patients had been rendered seizure free after surgery, and three had > or =90% of seizure-frequency reduction. Pathologic findings included gliosis (n = 10), cortical dysplasia (n = 5), or no abnormalities (n = 1). Six patients had transient postoperative neurologic morbidity. CONCLUSIONS: Extensive subdural electrodes coverage seems to be an effective way to investigate patients with R-ExTE and normal or nonlocalizing MRI findings.

Adolescent↗
PubMed2001

Seizure's outcome after cortical resections including the face and tongue rolandic areas in patients with refractory epilepsy and normal MRI submitted to subdural grids' implantation.

PURPOSE: To study the seizure's outcome in patients with refractory epilepsy and normal MRI submitted to resections including the rolandic cortex. METHODS: Four adult patients were studied. All patients had motor or somatosensory simple partial seizures and normal MRI and were submitted to subdural grids' implantation with extensive coverage of the cortical convexity (1 in the non-dominant and 3 in the dominant hemisphere). RESULTS: ECoG was able to define focal areas of seizures' onset in every patient. All patients were submitted to resection of the face and tongue motor and sensitive cortex; two patients had resections including the perirolandic cortex and 2 had additional cortical removals. Three patients are seizures' free and one had a greater then 90% reduction in seizure frequency. CONCLUSION: Resections including the face and tongue rolandic cortex can be safely performed even within the dominant hemisphere.

Adult↗
PubMed2000

Influence of fluconazole on phagocytosis, oxidative burst and killing activity of human phagocytes. Using a flow cytometric method with whole blood.

OBJECTIVES: The aim of this study was to investigate the influence of fluconazole, an antimycotic on phagocytosis, oxidative burst and killing activity of phagocytes in human whole blood with Candida albicans as a test strain using a flow cytometric method. METHODS: Candida albicans was stained with Calcein AM, a greenfluorescent dye from Bioprobes (Molecular Probes, Inc., P.O. Box 22010, Eugene, OR 97402-0469, USA). To measure phagocytosis and burst activity diluted monoclonal antibody (CD-13-R-PE, Molecular Probes, Inc., P.O. Box 22010, Eugene, OR 97402-0469, USA) attaching at the surface of granulocytes and monocytes was added as well as Dihydroethidium solution (Molecular Probes, Inc., P.O. Box 22010, Eugene, OR 97402-0469, USA) which changes into red fluorescent Ethidium by oxidation when killing activity takes place. With Ethidium-Homodimer-1-solution (Molecular Probes, Inc., P.O. Box 22010, Eugene, OR 97402-0469, USA) killing activity can be observed. Three different tests, one incubating the Candida for 1- 4 hrs in advance, another incubating whole blood for 1 h, and the third incubating neither yeast nor blood, and a combined main test were carried out. Measurement of phagocytosis, burst- and killing activtiy was performed with a flow cytometric method (Coulter Company, type: Epics-Profile II). RESULTS: Three different concentrations of fluconazole (5, 20 and 100 microg/ml) show neither decreasing nor increasing influence on phagocytosis and burst activity, irrespective of whether yeasts or phagocytes had been incubated with fluconazole in advance or not. Also after incubating the drug with phagocytes for 1 h, neither an increase nor a decrease of killing activity was observed. A significant increase was, however, found with increasing incubation time of yeasts and fluconazole. - The minimum concentration of fluconazole, just enough to show a significant increase of the killing rate was 1 microg/ml after 3hrs of incubation. No further significant increase was detected when the concentration exceeded 5 microg/ml. CONCLUSION: 1 h incubation of human phagocytes with fluconazole does not have any significant influence on cellular activities. After advanced incubation of Candida a corresponding increase of the intracellular killing rate in phagocytes occurs, probably due to changes of the cytomorphology of yeasts.

Antifungal Agents↗
PubMed2000

The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1 ,5-a]-pyrimidine: a corticotropin-releasing factor (hCRF1) antagonist.

Structure activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazo lo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki = 1.0+/-0.2 nM (n = 8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50= 10.0+/-0.01 nM versus 10 nM r/hCRF, n = 8); alpha-helical CRF(9-41) had weaker potency (IC50 = 286+/-63 nM, n = 3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4+/-7.6 h. 0.49+/-0.08 L/kg/h and 23.0+/-4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax t1/2 and bioavailability values were equal to 1260+/-290 nM, 0.75+/-0.25 h. 45.1+/-10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.

Animals↗
PubMed1996

Incremental dosage of the new antipsychotic mazapertine induces tolerance to cardiovascular and cognitive effects in healthy men.

OBJECTIVES: Mazapertine is a structurally novel antipsychotic compound with high affinity for D2, D3, 5-HT1a, and alpha 1 receptors. The objectives were to determine whether tolerance to orthostatic hypotension caused by this compound could be induced by slowly increasing the dose administered and to investigate its effect on cognitive and motor functions. METHODS: Thirteen healthy male subjects received incremental oral doses of mazapertine (from 5 to 50 mg over 7 days; n = 10) or placebo (n = 3) in part I and single doses in parts II (20 or 30 mg or placebo) and III (40 mg or placebo) in a double-blind fashion. Blood pressure, heart rate, cardiac hemodynamics, cognitive functions, and occurrence of acute extrapyramidal symptoms were investigated. RESULTS: Mazapertine appears to be safe and well tolerated when administered orally for 7 days to normal healthy men. No accumulation of serum prolactin occurred after multiple dosing, suggesting limited potential for inducing galactorrhea. The drug was rapidly absorbed, and kinetics appeared to be dose dependent, without accumulation. The elimination half-life was about 5 to 10 hours. No evidence of any positive or negative cognitive effects could be detected. Mild motor symptoms were observed only at high doses (not statistically significant). Mazapertine had a minimal effect on cardiac output and stroke volume. Tolerance to hypotension could be induced by slowly increasing the dose administered. CONCLUSIONS: Mazapertine is well tolerated when administered orally for seven days, and tolerance to hypotension can be induced by slowly increasing the dose administered. Therefore, nothing precludes further clinical testing on patients with schizophrenia.

Administration, Oral↗
PubMed1996

Biochemical activity, pharmacokinetics and tolerability of tepoxalin, a cyclooxygenase/5-lipoxygenase inhibitor, in man.

Tepoxalin, a novel inhibitor of cyclooxygenase (CO) and 5-lipoxygenase (5-LO), was investigated for biochemical activity and pharmacokinetics in two studies. Study I was a 4-period, double-blind, randomized, single rising dose using 2 alternating panels (A, B) with interspersed placebo design (A: 25, 100, 400 mg, B: 50, 200, 800 mg p.o.). Study II was a 3-panel, randomized, placebo-controlled, double-blind, multiple dose study (A: 100 mg, B: 200 mg, C: 400 mg). In both studies, CO inhibition was assessed by generation of serum thromboxane (TxB2), 5-LO activity by LTB4 production ex vivo in Caionophore-stimulated blood. Plasma drug concentrations were assayed by HPLC for tepoxalin and its identified acid metabolite. It was found in both studies that at all dose levels the TxB2 generation was markedly suppressed (> 95% 2 h postdose). In study I, at 2 h postdose, % inhibition of LTB4 biosynthesis was marginal for the 3 lower doses but significant at 200 (14%), 400 (25%) and 800 mg (43%). In study II, the only significant inhibition occurred at the 400 mg dose at 6 h postdose on day 1 (17%) and on day 8 at 4, 6 and 8 h postdose (32, 42 and 32% respectively). In both studies and at all doses, plasma concentrations of tepoxalin varied widely between subjects. Linearity between plasma concentrations and dose could not be ascertained, and correlation between drug plasma levels and effect on LTB4 synthesis was poor. Single doses up to 800 mg and multiple doses up to 400 mg of tepoxalin were generally well tolerated.

Adult↗
PubMed1994

A randomized trial of OKT3-based versus cyclosporine-based immunoprophylaxis after liver transplantation. Long-term results of a European and Australian multicenter study.

A multicenter randomized trial was performed to compare two immunosuppressive protocols after first ABO-compatible liver transplantation. Forty six patients were randomized to a 14-day treatment with Orthoclone (OKT3) in association with steroids and azathioprine, cyclosporine being progressively introduced on day 11 posttransplant. Fifty patients were randomized to a standard protocol of cyclosporine with steroids and azathioprine. Minimum follow-up was 1 year and graft and patient survivals were updated for the purpose of the study. The cumulative 1-year incidence of acute rejection tended to be greater in the cyclosporine group (75%) than in the OKT3 group (67%), especially when patients who did not receive full-course treatment with OKT3 were excluded (59%). Renal function was better preserved during the first two postoperative weeks in the OKT3 group than in the control group but plasma creatinine levels were comparable in both groups thereafter. The incidence of severe infections was lower in the OKT3 group (13.6%) than in the cyclosporine group (32%). The 4-year incidences of patient and graft survival in the OKT3 group (69% and 61%, respectively) were not different from those in the cyclosporine group (62% versus 54%, respectively). Thus this prospective trial shows that OKT3 immunoprophylaxis is a safe alternative to cyclosporine immunoprophylaxis in unselected recipients of a first liver graft.

Adolescent↗
PubMed1994

A study of recombinant human erythropoietin in the treatment of anaemia of chronic renal failure in children on haemodialysis.

This was an open-label multicentre study of recombinant human erythropoietin (r-HuEPO) in 116 children aged 6 months to 20 years with anaemia of chronic renal failure undergoing haemodialysis. Haemoglobin concentration at entry ranged from 3.4 to 9.5 g/dl. r-HuEPO was given intravenously two or three times per week, the starting dose being 75 U/kg per week. This was subsequently titrated in steps of 75 U/kg per week with the goal of increasing haemoglobin concentration at the rate of 1 g/dl per 4 weeks into the range 9.6-11.2 g/dl (6-7 mmol/l), with treatment then continued for up to 1 year with the aim of maintaining the haemoglobin concentration within the target range. Of the 115 children in whom efficacy could be evaluated, 93 (81%) achieved the target haemoglobin and a further 6 had a rise in haemoglobin concentration of at least 2 g/dl. At 52 weeks, the median maintenance dose for children < 30 kg was 225 U/kg per week, compared with 107 U/kg per week for children > or = 30 kg. Analysis suggested that 150 U/kg per week would have been a more appropriate starting dose. The mean transfusion requirement fell from 8.9 to 0.7 units/patient per year. Of the 22 patients who failed to reach the target, 15 went on to transplantation and left the study prematurely. Sub-group analysis showed that similar doses lead to similar rates of rise in haemoglobin regardless of the severity of the original anaemia. Assessment of quality of life suggested that this may have improved with r-HuEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

HLA in bullous pemphigoid. The probable role of HLA-B7 as a marker for poor responders to immunosuppressive therapy.

The frequency of HLA-class I and DR antigen frequencies were studied in 38 (class I) and 19 (DR) patients with bullous pemphigoid, respectively, and compared with controls. There was no important difference in the frequency of HLA-A,B,C, and DR antigens between patients and controls. An increase in the HLA-B7 frequency in poor responders to immunosuppressants (50% vs. 27% in the control group and vs. 13% in the group of all patients) was noticed, and the possible role of this antigen as a marker for poor responders to therapy was suggested.

Aged↗
PubMed1989

[HLA and leukemia].

HLA-A, -B, -C characteristics were determined in 85 AML patients and in 47 ALL patients as well as in 95 pairs of parents of leukemic patients. The detected antigen frequencies of patients were compared with those of 2,947 donors from Leipzig. A significant increase of frequency was found for Cw4 and in the group of ALL patients (p = 0.05), an increase of frequency could be observed for B22 and in the group of PR/NR patients for pcor = 0.05. A correlation between A9 and longer survival time in leukemic patients could not be found. Parents of leukemic patients (but not the patients themselves) showed a limited genetic heterogeneity with respect to the HLA system.

Acute Disease↗
PubMed1989

[HLA-A, B, C phenotype frequencies in progressive systemic scleroderma].

In 41 patients suffering from progressive systemic sclerosis (PSS) the phenotype frequencies of 28 HLA-A, B, C antigens were determined. Compared to 2947 blood donors the PSS patients exhibited an increase in the HLA-B8 frequency (37% versus 19%). This difference revealed to be not significant after the correction according to the number of antigens tested. The same was with the increase in the frequency of HLA-B5, B13, B27, Cw2 and the decrease in the frequency of HLA-A2, B12, B14, B15, B4 and Cw3. The results were compared with the data reported in the literature. Additionally, there were no differences when compared the diffuse PSS with the acral form and CREST, respectively.

Adolescent↗
PubMed1988

Lymphocytotoxic autoantibodies in progressive systemic sclerosis.

In 53 patients with progressive systemic sclerosis (PSS) the lymphocytotoxic activity of their serum was measured in a microlymphocytotoxicity assay. In 21 of the 53 patients the test reacted distinctly positively in the heterologous system, and in 9 of these 21 also in the autologous system. After preparation of the immunoglobulins from these positive sera, whole cytotoxic activity was detected only in the IgM fraction but not in the IgG fraction. When using prepared T lymphocytes as target cells in the microlymphocytotoxicity test, the cytotoxic activity of the positive PSS sera showed itself to be directed against this lymphocyte population. Further analysis using the Western-blot technique showed that the IgM autoantibody in PSS sera reacted with the cell surface of CD4+ lymphocytes. The cross reactivity with extractable nuclear antigens was rather improbable. These results suggest that lymphocytotoxic autoantibodies may play a role in immunological disturbances in PSS.

Adolescent↗