Search PubMed⌕ Search

Biomedical subjects

K Walter

Publications and source records attributed to K Walter.

At least 55 records · Page 3Linked to original sources
PubMed1998

Distribution of HLA class II alleles among Spanish patients with pemphigus vulgaris.

Twenty-six unrelated Spanish Caucasian individuals affected by pemphigus vulgaris (PV) were HLA typed and frequencies compared with those of 200 ethnically matched healthy controls. Twenty-three out of 26 patients were HLA-DR4. The frequency of HLA-DR14 was also increased (31%; controls: 4%). Of the 23 patients positive for HLA-DR4, 21 carried the DRB1*0402 allele. Therefore, the frequency of HLA-DRB1*0402 among patients was 81% (4% in controls; P=4.7x10(-27), OR=100.8). Interestingly, HLA-DR13, a frequent HLA-DR specificity in the Spanish general population (27%), was absent among the PV patients (P=0.009; Pc=0.1; OR=0.05). Taking together these data, we can conclude that, in the Spanish population, PV is preferentially and strongly associated with HLA-DRB1*0402, whereas DRB1*13 seems to confer a protective effect in our population.

Alleles↗
PubMed1998

Relationship between hepatic cytochrome P450 3A content and activity and the disposition of midazolam administered orally.

It was recently shown by others that the clearance of midazolam/kg body weight after iv administration correlates with hepatic cytochrome P450 (CYP or P450) 3A content in liver transplant patients. However, after po administration midazolam undergoes significant first-pass metabolism, with significant intestinal extraction. The relationship between hepatic CYP3A and midazolam disposition after po administration had not previously been investigated. The aim of this study was to compare intraindividually hepatic CYP3A content and activity with the in vivo pharmacokinetics of midazolam (7.5 mg) administered po. For 15 patients scheduled for partial liver resection, the AUC values for the observed time period (AUC0-5hr) and to infinity (AUCinf) and the clearance were determined. In a macroscopically normal area of resected liver tissue, the microsomal CYP3A4 content (nanomoles per nanomole of total P450) was measured by immunoblot analysis and parameters (apparent Vmax, apparent KM, and intrinsic clearance) for the microsomal alpha-hydroxylation of midazolam were determined. Clearance/kg in vivo correlated with the apparent Vmax (r2 = 0.45, p < 0.01) and the CYP3A4 content (r2 = 0.29, p < 0.05). We conclude that interindividual variability in the pharmacokinetics of po administered midazolam is in part determined by interindividual variability in the hepatic microsomal Vmax for the alpha-hydroxylation of midazolam. However, the relationship between the disposition of midazolam administered po and hepatic CYP3A content is weaker than that reported after iv administration, indicating the importance of the contribution of intestinal CYP3A to the in vivo disposition of midazolam administered po.

Adult↗
PubMed1998

[Quality circles in expert assessment as an instrument in quality management].

An intercomparison programme was carried out as part of the quality management of medical assessments in the public health service in Baden-Württemberg. All physicians who performed medical assessments in January 1997 were invited to participate. They received a case description adopted from medical records of a precedent case (56-year-old head of a department in an administrative authority, severely disabled after left-sided stroke with residual right-sided partial hemiparesis, reduced work performance), and were asked to assess whether the patient was permanently unable to work. Access to medical expert opinions was requested. Participation was voluntary. Assessments were reviewed twice as to whether five prospectively defined evaluation criteria were fully met, or only partially or not at all. Participants and reviewers remained unknown to each other. Among 246 eligible physicians, 103 returned an assessment (43%). Forty-five respondents had requested additional expert opinions. Anticipations for five criteria were met to their full extent with regard to: formal construction, all submissions; case description, 84%; sociomedical diagnosis, 65%; description of ability to work, 53%; and response to the question posed, 75% of submissions. The programme required considerable work time in its preparatory, field, and evaluation phases. The procedure was however found to be practicable, and a suitable element within a quality management programme can contribute towards motivation, quality assurance and the identification of possible deficits, and thus indicate possible topics and issues for continuing education and quality control programmes.

Cerebrovascular Disorders↗
PubMed1997

Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance.

The Erm family of methyltransferases is responsible for the development of resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics. These enzymes methylate an adenine of 23S ribosomal RNA that prevents the MLS antibiotics from binding to the ribosome and exhibiting their antibacterial activity. Here we describe the three-dimensional structure of an Erm family member, ErmAM, as determined by NMR spectroscopy. The catalytic domain of ErmAM is structurally similar to that found in other methyltransferases and consists of a seven-stranded beta-sheet flanked by alpha-helices and a small two-stranded beta-sheet. In contrast to the catalytic domain, the substrate binding domain is different from other methyltransferases and adopts a novel fold that consists of four alpha-helices.

Amino Acid Sequence↗
PubMed1996

Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases.

PURPOSE: In a prospective randomized trial we examined whether radiotherapy of painful bone metastases can be shortened using larger single doses without impairing effectivity. METHODS AND MATERIALS: One hundred patients with painful bone metastases having no prior surgical intervention or treatment with x-ray therapy and had a median follow-up of 12 months were analyzed. The primary tumor was located in the breast in 43%, in the lung in 24%, and in the prostate in 14%. The most frequent sites of metastases were the pelvis (31%), the vertebral column (30%), and the ribs (20%). Further percentages of sites were: lower extremity 11%, upper extremity 6%, and skull 2%. Fifty-one patients received a short course radiotherapy with a total dose of 20 Gy in 1 week (daily dose 4 Gy), and 49 patients received 30 Gy in 3 weeks (daily dose 2 Gy). RESULTS: There were no significant differences in frequency, duration of pain relief, improvement of mobility, recalcification, frequency of pathologic fractures nor survival. There was a light trend favoring 30 Gy in frequency of pain relief and recalcification. Survival was mostly influenced by primary tumor site, Karnofsky performance status, and possibly by the response to radiotherapy (pain relief). CONCLUSIONS: Because of the very short life expectancy of patients with metastatic bone disease, we now use 20 Gy in 1 week as our standard to reduce hospital stay.

Adult↗
PubMed1996

Purification and partial characterisation of a reversible artificial mediator accepting NADH oxidoreductase from Clostridium thermoaceticum.

An NAD(H)-dependent artificial mediator accepting pyridine nucleotide oxidoreductase present in Clostridium thermoaceticum has been purified 50-fold by three chromatographic steps to apparent electrophoretical homogeneity with a yield of 25%. By PAGE and gel filtration the molecular mass of the native enzyme was estimated to be 200 kDa and 210 kDa, respectively. By SDS/gel electrophoresis, a single band was found at 17000 Da, suggesting a homododecamer. Reducing carbamoylmethylviologen or hexacyanoferrate(III) with NADH, the enzyme was most active at pH 10 and the specific activities were 100 mumol min-1 mg-1 protein and 800 mumol min-1 mg-1 protein, respectively. The K(m) values for hexacyanoferrate(III), carbamoylmethylviologen and NADH at pH 8.5 were determined to be 0.40, 0.55 and 1.1 mM, respectively. Other electron acceptors for the dehydrogenation of NADH were 2,6-dichlorophenolindophenol, anthraquinone-2,6-disulphonate, ubiquinone 0 and FAD. In the reduction of NAD+ with reduced methyl viologen (MV+), the specific activity was about 225 mumol min-1 mg-1 protein at the pH maximum of 5.0. The K(m) values for reduced methylviologen, NADH and NAD+ were 1.0, 1.1 and 0.25 mM, respectively. The enzyme had 10.6 atoms iron and 12.7 atoms sulphur per dodecamer. A significant content of flavin or molybdopterin cofactor could not be detected. The first 45 amino acids of the oxidoreductase show a surprisingly high degree of identity or similarity with the ribosomal L12 protein of various eubacteria, the acyl carrier proteins of microorganisms, but also with bovine heart mitochondria and a 3-phosphoglycerate dehydrogenase as well as a gyceraldehyde-3-phosphate dehydrogenase from bacteria and pea chloroplasts, respectively.

2,6-Dichloroindophenol↗
PubMed1996

Solution structure of the DNA-binding domain of a human papillomavirus E2 protein: evidence for flexible DNA-binding regions.

The three-dimensional structure of the DNA-binding domain of the E2 protein from human papillomavirus-31 was determined by using multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy. A total of 1429 NMR-derived distance and dihedral angle restraints were obtained for each of the 83-residue subunits of this symmetric dimer. The average root mean square deviations of 20 structures calculated using a distance geometry-simulated annealing protocol are 0.59 and 0.90 angstroms for the backbone and all heavy atoms, respectively, for residues 2-83. The structure of the human virus protein free in solution consists of an eight-stranded beta-barrel and two pairs of alpha-helices. Although the overall fold of the protein is similar to the crystal structure of the bovine papillomavirus-1 E2 protein when complexed to DNA, several small but interesting differences were observed between these two structures at the subunit interface. In addition, a beta-hairpin that contacts DNA in the crystal structure of the protein-DNA complex is disordered in the NMR structures, and steady-state 1H-15N heteronuclear NOE measurements indicate that this region is highly mobile in the absence of DNA. The recognition helix also appears to be flexible, as evidenced by fast amide exchange rates. This phenomenon has also been observed for a number of other DNA-binding proteins and may constitute a common theme in protein/DNA recognition.

Amino Acid Sequence↗
PubMed1996

Ten years disease-free survival after solitary brain metastasis from breast cancer.

The unique case of a 51-year-old woman who developed a solitary brain metastasis as the first site of systemic disease 11 months after a total mastectomy for an undifferentiated infiltrating ductal carcinoma of her right breast is described. After surgery for the pT2pN0 carcinoma, the patient received radiotherapy of the internal mammary and supraclavicular lymph nodes. The brain metastasis was treated with surgery and adjuvant whole-brain radiotherapy to a total dose of 30 Gy in December 1984 and January 1985. Afterwards a hormonal treatment with tamoxifen was initiated, which still continues. Since then no further distant or lymph node metastases have developed. The patient is under regular after-care and undergoes various apparative examinations every 6 months. She is generally well and suffers only from a postoperatively persistent hemianopsia. This is the first case in which a disease-free survival for more than 10 years after brain metastases from breast cancer has been reported. It illustrates the specific biological behaviour of this tumour type and the chance of achieving long-term survival in very selected cases.

Antineoplastic Agents, Hormonal↗
PubMed1996

[Physostigmine in treatment of cerebellar ataxia].

Cerebellar ataxias are still a challenging problem for neurologists, and to this day there exists no medical, physiotherapeutic, psychot-erapeutic or surgical therapy which constantly leads to a reduction of ataxic symptoms. In the pathophysiology of cerebellar ataxia a cholinergic defect has often been described. In a double-blind, cross-over study with 14 patients with cerebellar ataxia and an open follow-up, long-term study with 21 patients, the clinical effects of physostigmine capsules in doses up to 10 mg per day were studied. Moreover, a transdermal application (physostigmine patch) was developed, achieving constant physostigmine plasma levels for 24 h. Of 14 patients treated with physostigmine during the double-blind, cross-over study, nine could correctly distinguish between verum and placebo. They all showed small but constant improvements, clearly experienced by the patients. With the physostigmine patch, 12 of 14 patients improved. Thirteen of 14 patients decided to take part in open follow-up studies with physostigmine, and most of them preferred the physostigmine patch as long-term medication. To date, 21 patients with cerebellar ataxia have been treated with physostigmine. As far as we can judge at the end of a treatment period of at least 2 years, the progression of the disease could be stopped in 17 of 21 patients. These patients reported small but constant effects, and none wants to live without the physostigmine patch.

Administration, Cutaneous↗
PubMed1996

[Work with relatives from the viewpoint of the relatives].

The concept of "self-management", which developed within the association of family members of psychiatric patients, the so called "family movement", stands for two main objects: first, providing mutual help and support among and, secondly, participating in the shaping of psychiatric care, also in consideration of the standpoints of the "former patient group". In future, they will also focus on psycho-informative family-work and quality management in psychiatric and community care.

Adaptation, Psychological↗
PubMed1995

Relation between local result and total dose of radiotherapy for brain metastases.

PURPOSE: Some studies published recently focused on the improvement of the treatment results of patients with brain metastases who underwent radiation therapy. They evaluated survival as a measure for the expected improvement, but failed to demonstrate a significant benefit from an increased total dose of radiotherapy. This study was targeted to investigate the effect of dose escalation with a different endpoint, the local response. METHODS AND MATERIALS: As a first step, a retrospective analysis of 164 patients treated with a standard regimen of 10 x 3 Gy was performed to find factors correlating with the local result. All patients were systematically followed and underwent regular computed tomography (CT) examinations of the brain after irradiation. The second step was to compare, with respect to local control and survival, 39 patients treated with a total dose of 40-60 Gy with 39 patients treated with the standard regimen selected by means of a matched cohort pairs method. RESULTS: The retrospective analysis showed a dependence of the local result after irradiation on three parameters: diameter of brain metastases, primary tumor, and tumor histology. Small-cell and adenocarcinoma were found to be more radiosensitive than squamous-cell carcinoma. The highest radiosensitivity was found in breast cancer metastases. The matching procedure was performed with respect to those parameters and also the number of brain metastases and total cerebral tumor volume. The resulting groups were absolutely equivalent and differed only with regard to the total dose applied. The local response (complete or partial remission) was 48-52% after 30 Gy vs. 77% after 40-60 Gy (p < or = 0.05). Survival was not significantly different. A further analysis of the dose-response relationships showed the tendency of control probability to increase with total dose. CONCLUSION: This study suggests that there is a rationale for dose escalation in the treatment of brain metastases with radiotherapy, when local control is the aim. However, it seems questionable whether an improvement in survival results.

Brain Neoplasms↗
PubMed1995

Low-dose radiotherapy for stage I seminoma: early results.

One hundred and one patients with stage I seminoma were irradiated with total doses of 30, 25.5 and 20 Gy to gradually reduced target volumes (paraaortic, pelvic, and inguinal regions to paraaortic only). Low doses and small target volumes resulted in excellent survival and freedom of recurrence but in more frequent nausea.

Adult↗
PubMed1995

[The outcome of surgery and radiotherapy in treatment of brain metastases of breast carcinoma].

In a group of 45 patients who had been conventionally irradiated, a multivariate analysis of prognostic factors was performed to find criteria for patient selection for surgery and radiotherapy or radiotherapy only. Nine patients underwent resection of metastases before irradiation. In most cases 10 x 3 Gy over 2 weeks were administered. 28 patients received concomitant hormonal treatment. Complete remission was seen in 30% of the non-operated cases (partial remission 25%). Symptomatic relief was seen in 67% of all cases. Median survival was 4 months (9.5 months after surgery) (p = 0.02). Survival of patients having had simultaneous extracerebral metastases and low Karnofsky performance status was disappointing. All long-time survivors received either hormonal treatment or chemotherapy. Karnofsky performance status and interval between the diagnosis of the primary tumour and the development of brain metastases were the most important prognostic factors. The influence of age and extracerebral metastases was less pronounced. In case of favourable prognostic factors and solitary metastases surgical treatment should be considered. Primary irradiation seems to be appropriate for the majority of patients. In any case an additional hormonal or chemotherapy must be considered. It seems to be questionable if patients with poor Karnofsky performance status and extracerebral metastases should be irradiated.

Adult↗
PubMed1995

Pharmacokinetics of physostigmine in man following a single application of a transdermal system.

1. The pharmacokinetics of physostigmine were investigated in a three-way cross-over design in six healthy, male volunteers comparing a physostigmine transdermal system (PTS), an oral solution and an i.v. infusion. 2. A single application of the patch over 24 h produced detectable plasma drug concentrations after a mean lag-time of 4 h. Thereafter, the drug was absorbed continuously from the PTS and putative therapeutic plasma concentrations were measured over approximately 18 h. 3. A mean absolute bioavailability of 36% was determined for the transdermal system and 3% for the oral solution. In comparison with the oral solution, interindividual variability of pharmacokinetics was less with the PTS. 4. The mean amount of physostigmine released from the transdermal system after 24 h was 5.7 mg. Because of extensive metabolism, only 2.2 mg of physostigmine were detected systemically. 5. After removing the PTS, the mean apparent half-life of elimination was 4.9 h, compared with 0.5 h for the i.v. infusion. This indicates continued drug absorption from a skin depot. 6. Physostigmine was well tolerated by the volunteers. With the PTS, a mild erythema was observed at the area of application, disappearing within a few hours.

Administration, Cutaneous↗
PubMed1995

Pharmacokinetics of ibuprofen following a single administration of a suspension containing enteric-coated microcapsules.

The relative bioavailability of ibuprofen (CAS 15687-27-1) was investigated following a single administration of a suspension containing enteric-coated microcapsules (A) in comparison to a rapid-release film-coated tablet (B) and a sustained-release tablet (C). The study was carried out in a three-way crossover design in 9 healthy male volunteers. Each formulation contained 800 mg ibuprofen. Plasma concentrations of ibuprofen were determined with a specific HPLC method. A mean relative bioavailability of 0.96 (B) and 1.01 (C) was determined for the test formulation. Since the corresponding 90% confidence intervals were within the recommended limits, bioequivalence for the extent of bioavailability of the test formulation can be concluded. Differences in pharmacokinetics were observed for the rate-dependent parameters. For the test formulation, the highest mean maximum plasma concentration (54.3 micrograms/ml) was measured with a corresponding tmax of 1.9 h. For the reference formulations, mean peak plasma concentrations of 45.2 micrograms/ml after 2.6 h (B) and 25.7 micrograms/ml after 5.6 h (C) were observed. Despite the enteric coating of the microcapsules, a very short lagtime of 0.03 h was determined for the suspension. For the other rapid release formulation (B), the lagtime was in a similar magnitude (0.11 h), while the absorption from the sustained-release tablet was clearly decelerated (tlag = 0.97 h). In comparison to the other rapid-release formulation (B), significant higher amounts of the drug were absorbed from the test formulation (A) within the first hour.

Adult↗