Biomedical subjects
M Wilhelm
Publications and source records attributed to M Wilhelm.
[Phase-contrast MR angiography of the lower extremity. Comparison of methods and clinical application].
PURPOSE: To investigate whether phase-contrast MRA is a clinically suited approach to examine arteries of the pelvis and lower extremities. METHODS: The study was divided into two parts, a volunteer study and patient study. Three MRA techniques-2D TOF with venous saturation, 3D magnitude contrast and 2D phase contrast with ECG triggering-were intraindividually compared in 15 volunteers and evaluated by three blinded readers. Subsequently, a total of 230 vessel segments of 45 MRA studies using ECG-triggered phase contrast were compared with intraarterial DSA. All vessel segments were scored by three blinded readers using a five-point scale with DSA serving as the gold standard. RESULTS: ECG-triggered phase contrast provided better image quality than the other MRA techniques as assessed by the Friedman test. Clinical studies demonstrated a significant correlation of DSA and MRA as assessed by the Spearman correlation and kappa statistics for individual readers. CONCLUSION: MRA of the pelvis and lower extremities may be performed with 2D ECG-triggered phase-contrast MRA within a reasonable time frame (< 30 min). MRA slabs provide orientation similar to that with DSA projections and good to very good correlation of vessel pathology as shown by kappa statistics.
A phase-II study with idarubicin, ifosfamide and VP-16 (IIVP-16) in patients with refractory or relapsed aggressive and high grade non-Hodgkin's lymphoma.
We report a phase-II study of idarubicin, ifosphamide and etoposide (IIVP-16) in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. The IIVP-16 regimen consisted of idarubicin (10 mg/m2 i.v. days 1 + 2 or days 1 + 8), ifosfamide (1000 mg/m2 i.v. days 1-5) and VP-16 (150 mg/m2 i.v. days 103). 40 patients were enrolled. Of 38 evaluable patients, 26 had centroblastic subtype, followed by lymphoblastic (6), immunoblastic (2), and other entities (4). 18 patients were primary resistant; 14 patients had early relapse (CR less than 12 months) and 8 patients late relapse (CR longer than 12 months). The median number of different prior chemotherapy regimens was 2 (range 1 to 6). 20 patients had received additional radiotherapy. The response-rate was 47.4% including 8 CR (21.1%) and 10 PR (26.3%). IIVP-16 was more effective in patients with relapsed disease when compared with patients with primary resistant disease (response rate 65% vs. 27.8%, p < 0.025). Leukopenia and thrombocytopenia were the major toxicities occurring in 73/107 (68.2%) and 57/107 (53.3%) of cycles (WHO grade IV). IIVP-16 is an effective regimen particularly in patients with unfavorable relapsed NHL.
First-line therapy of advanced chronic lymphocytic leukemia.
There is general agreement that patients with advanced chronic lymphocytic leukemia (CLL) should be treated if they develop anemia or thrombocytopenia. The combination of chlorambucil (CLB) and prednisone is often used for first-line therapy of these patients, but compared to monotherapy with CLB, no difference in survival could be demonstrated. Steroids should be generally reserved, therefore, for the management of complications such as hemolytic anemia and thrombocytopenia or other autoimmune manifestations. CLB can still be considered standard therapy for advanced CLL, since polychemotherapy protocols as well as newer agents such as fludarabine have failed to show an improvement in survival compared to CLB. However, the results regarding response and survival of the CLB-treated patients seem to depend on dosage intensity and treatment duration. Biological response modifiers such as interferons, interleukins, and monoclonal antibodies have not improved responses or remission duration. Because experiences with CLL patients are limited, the indications and procedure of bone marrow transplantation are not yet clear. However, since results of current treatment protocols are unsatisfactory, regardless of age, patients should be involved in clinical studies that address the question whether high-dose CLB, fludarabine or the combination of fludarabine with other active agents can improve patients' outcome. In addition, autologous and allogeneic bone marrow transplantation as a consolidation therapy is under study and might be a step towards a potential cure of this disease.
[The nursing process guidelines at the Frankfurt University Hospital. The guidelines do not contain measurable criteria for quality assurance].
Explore the source record for details and available documents.
Long-term left ventricular assist device support: a novel pump rate challenge exercise protocol to monitor native left ventricular function.
A novel, hemodynamically guided exercise protocol with two different left ventricular assist device settings in two long-term recipients is presented. This protocol allows for quantitation of the contribution of the native left ventricle to total cardiac output. It facilitates estimation of the risk associated with device dysfunction, as well as prediction of left ventricular recovery and the potential for weaning.
FHIT gene and the FRA3B region are not involved in the genetics of renal cell carcinomas.
The FHIT gene locus at 3p14.2 covers about 500 kb, including the fragile site FRA3B and the constitutional t(3;8) breakpoint associated with the development of multiple renal cell carcinomas (RCC). A terminal deletion of the short arm of chromosome 3 with the most distal breakpoint in the FRA3B region is the characteristic genetic event in nonpapillary RCC. Since aberrant FHIT transcripts have been observed in gastrointestinal and other tumors, this gene has been suggested to function as a tumor suppressor. To evaluate the role of FHIT and the FRA3B region in the genetics of RCC, we analyzed FHIT expression by RT-PCR and performed microsatellite deletion mapping in the FHIT region. In addition to two cases from a t(3;8) family, only three out of 100 sporadic nonpapillary RCC showed a breakpoint within the FHIT region, whereas 94 tumors showed a deletion breakpoint proximal to the FHIT gene. FHIT transcripts of normal size were observed in 33 out of 34 tumors. Direct sequencing of eight PCR products revealed a normal FHIT sequence without mutations in the coding region. An established cell line from a renal cancer xenograft showed a smaller FHIT transcript. Sequence analysis revealed a mixture of several splicing variants of the FHIT gene. Since only three out of 100 sporadic nonpapillary RCC had a deletion breakpoint within the FRA3B/FHIT region, and since all but one renal cell tumor showed a normal FHIT transcript, we can exclude the involvement of the FHIT gene and the FRA3B region in the genetics of renal cell cancer.
NADPH-diaphorase positive myenteric neurons in the ileum of guinea-pig, rat, rabbit and cat.
Explore the source record for details and available documents.
Hepatic clearance and retention of aluminium: studies in the isolated perfused rat liver.
Aluminium (Al) exposure can result in Al accumulation in the liver and this metal can be toxic to the hepatic tissue at high concentrations. In the present study the model of the isolated perfused rat liver was used to investigate the hepatic handling of Al. Livers from male Wistar rats were perfused in a recirculating system for 240 min. The liver function remained unchanged at perfusate concentrations of Al ranging from 4.9 to 1530.0 micrograms/l. At higher Al levels of 6535.3-16694.9 micrograms/l signs of toxicity towards isolated perfused livers were observed as indicated by an increased release of the enzymes AST and ALT into the perfusate, a pronounced reduction of bile flow rate and a 50% suppression of oxygen consumption. The hepatic Al clearance was low and decreased with increasing concentrations of Al in the perfusate from 4.3 +/- 0.6 microliters/min per g liver at a nominal Al concentration of 9.1 micrograms/l in control perfusate to 0.04 +/- 0.02 microliter/min per g liver at the highest concentration group. There was almost a linear dose dependent retention of Al in the liver with 4.9-635.7 micrograms Al/l perfusate while at higher concentrations Al levels in this organ increased disproportionally. It is concluded that by using the isolated perfused rat changes of liver functions occur only at very high Al concentrations in the perfusate and that only negligible amounts of Al are eliminated by the liver.
Refining a proximal breakpoint cluster at chromosome 3p11.2 in non-papillary renal cell carcinomas.
Our previous cytogenetic and microsatellite analyses showed a terminal deletion of chromosome 3p segments with a breakpoint region between 3p11.2 and 3p14.1 bands in 98% of non-papillary renal cell carcinomas (RCC). This breakpoint region covers approx. 20-25 cM genetic distance. Earlier, we found a higher frequency of rearrangements at chromosome 3p11.2 and have therefore now analyzed 74 sporadic and 26 VHL-associated RCCs with 6 polymorphic microsatellite markers mapped to this region. Thirty-three per cent of the breakpoints were mapped to a genetic distance of less than one-twentieth of the large breakpoint region 3p11.2-14.1. We suggest that unstable DNA sequences at chromosome 3p11.2 serve as a genetic basis for deletions and homologous and non-homologous recombinations to remove distal 3p sequences with one copy of RCC gene(s) in different types of tumors. We have identified a YAC clone 909d5 that spans the most frequently occurring breaks between loci D3S1251, D3S1101, and D3S1552 and allows this region to be cloned.
The effect of free radicals on the conductance induced by alamethicin in planar lipid membranes: activation and inactivation.
Exposure to ionizing radiation of planar lipid membranes doped with alamethicin gives rise to an increase and to a subsequent decrease of the membrane conductance. Both effects are due to the presence of radiation-induced free radicals of water radiolysis as was shown by addition of various radical scavengers. The increase of the conductance was found to be a consequence of free radical-initiated lipid peroxidation favouring the formation of active ion channels. The decrease of the conductance observed at larger radiation doses is due to an inactivation of alamethicin monomers. The characteristic D37 dose of inactivation was found to be about two orders of magnitude larger than in the case of gramicidin A. The comparatively high sensitivity of the latter is due to the presence of its four tryptophan residues. Inactivation of trichorzianine AIIIc, an analogue of alamethicin with a C-terminal tryptophanol residue, occurs at radiation doses two orders of magnitude lower than observed with alamethicin.
Correlation of Pneumocystis carinii PCR with clinical diagnosis in immunocompromised patients.
Explore the source record for details and available documents.
Mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinomas.
To define the possible role of the VHL gene in the development of sporadic renal cell carcinomas, 91 different parenchymal tumours of the kidney have been investigated for mutation of the VHL gene by single strand conformation polymorphism (SSCP) and/or heteroduplex (HD) techniques. Chromosome 3p deletion was detected in 98 per cent of non-papillary renal cell carcinomas and in 25 per cent of chromophobe renal cell carcinomas. In 22 of the 43 non-papillary renal cell carcinomas, abnormally migrating DNA bands were detected by SSCP and/or HD analysis. No mobility shift was seen in any of the 23 chromophobe renal cell carcinomas. In addition, 15 papillary renal cell tumours and ten renal oncocytomas, which are characterized by genetic changes other than loss of chromosome 3p sequences, were analysed for mutation of the VHL gene. None of these tumours showed abnormal migration patterns. The results indicate that mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinoma.
Biological monitoring of mercury vapour exposure by scalp hair analysis in comparison to blood and urine.
The reliability of human scalp hair as an indicator of mercury vapour exposure is contentious. In this study mercury concentrations in hair were compared with those in blood and urine of 20 dental students during their first "occupational" exposure to mercury vapour. Samples were collected before, at the end of the technical course of operating dentistry which lasted 6 weeks, and 3 months later. Mercury was measured by cold vapour atomic absorption spectrometry. In all biological media studied, mercury levels significantly (P < 0.05) reflected exposure to mercury vapour. After the time period without exposure mercury content decreased. Hair mercury levels were correlated to those in erythrocytes at sampling times 1 and 3 (r = 0.686 and r = 0.492) and to the frequency of fish consumption at sampling time 1. It is concluded that hair may be used as an indicator of internal uptake of mercury provided that it was not externally exposed to mercury vapour. In cases of occupational exposure to mercury vapour, hair is an useful tool for monitoring external exposure.
Role of RNA primers in initiation of minus-strand and plus-strand DNA synthesis of the yeast retrotransposon Ty1.
The Ty1 retrotransposon of the yeast Saccharomyces cerevisiae is a long terminal repeat mobile genetic element that transposes through an RNA intermediate. Initiation of minus-strand and plus-strand DNA synthesis are two critical steps during reverse transcription of the retrotransposon genome. Initiation of minus-strand DNA synthesis of the Ty1 element is primed by the cytoplasmic initiator methionine tRNA base paired to the primer binding site near the 5' end of the genomic RNA. A structural probing study of the primer tRNA-Ty1 RNA binary complex reveals that besides interactions between the primer binding site and the last 10 nucleotides at the 3' end of the primer tRNA, three short regions of Ty1 RNA named box 0, box 1 and box 2.1 interact with the T and D stems and loops of the primer tRNA. Some in vivo results underline the functional importance of the nucleotide sequence of the boxes and suggest that extended interactions between genomic Ty1 RNA and the primer tRNA play a role in the reverse transcription pathway. Plus-strand DNA synthesis is initiated from an RNase H resistant oligoribonucleotide spanning a purine-rich sequence, the polypurine tract (PPT). Two sites of initiation located at the 5' boundary of the 3' long terminal repeat (PPT1) and near the middle of the TyB (pol) gene in the integrase coding sequence (PPT2) have been identified in the genome of Ty1. The two PPTs have an identical sequence, TGGGTGGTA. Mutations replacing purines by pyrimidines in this sequence significantly diminish or abolish initiation of plus-strand DNA synthesis. Ty1 elements bearing a mutated PPT2 sequence are not defective for transposition whereas mutations in PPT1 abolish transposition.
Platelet PGI2 receptor affinity is reduced in pre-eclampsia.
Prostacyclin (PGI2) receptors were studied in platelet membrane preparations from women with normal pregnancy, pregnancy-induced hypertension (PIH) or pre-eclampsia. Patient groups showed no differences in gestational week at delivery. A markedly lower birth weight, however, was found in pre-eclampsia. No differences between groups could be detected in platelet PGI2 receptor number. In contrast, the binding affinity to the PGI2 mimetic iloprost was considerably reduced in pre-eclampsia, whereas receptor affinity between PIH and normal pregnancy did not differ significantly.
Direct proof of the two-phonon character of the dipole excitations in 142Nd and 144Sm around 3.5 MeV.
Explore the source record for details and available documents.
[32 years of Senning's correction for transposition of the great vessels].
Between 1962 and 1994 342 patients with transposition of the great arteries (TGA) were treated by atrial correction. Since 1992 the atrial switch operation is the treatment of choice for TGA. We reviewed our 32 year experience. Average age of the patients at operation was 69 months (7 days--8.5 years). 177/342 (52%) patients had a complex TGA: 74 patients with ventricular septal defect (VSD), 49 patients with pulmonary stenosis (PS) and 54 with both (VSD and PS). The 30 day mortality was for the whole series 15.7%. In the last 4 years 7.5%. The actuarial survival rate for all patients was 88% after 10 years and 82% after 20 years. For simple TGA 91% after 10 years and 83% after 20 years, for complex TGA 84% and 81%. The most important cause of death during our longterm observation were heart failure (19 patients) and sudden death (7 patients). Average follow-up for the whole group was 13.4 years. Most of the survivors are functionally symptom free (66% NYHA I) or they have slight symptoms (29% NYHA II). Only 5% were NYHA III or IV. Arterial switch operation has replaced the atrial correction for TGA. Nevertheless the longterm results after atrial correction remains encouraging. The main threat to the patients is the failure of the systemic ventricle.