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Biomedical subjects

M Wilhelm

Publications and source records attributed to M Wilhelm.

At least 37 records · Page 2Linked to original sources
PubMed2003

Methicillin-resistant Staphylococcus aureus whole-body decolonization among hospitalized patients with variable site colonization by using mupirocin in combination with octenidine dihydrochloride.

The object of this study was to investigate the efficacy of a methicillin-resistant Staphylococcus aureus (MRSA) multisite carriage decolonization in 32 hospitalized carriers--25 from surgical and seven from medical wards. Twenty-four of the patients had wounds (e.g. chronic ulcers, surgical sites) and 17 were spinal cord injury patients. Decolonization was performed by intranasal application of mupirocin, combined with an octenidine dihydrochloride bodywash over a period of five days. Samples from the nose, forehead, neck, axilla and groin were taken 24-48 h before beginning decolonization (sample point I, N=32) and 24-48 h afterwards (sample point II, N=32). Further samples, were taken seven to nine days after the procedure (sample point III, N=25). Contact sheep blood agar plates (24 cm2) were used to quantify MRSA colonies on forehead and neck. MRSA from other sample sites was determined semi-quantitatively. All patients were proven to be MRSA positive at one or more extranasal site(s); 18.8% did not have nasal carriage. The overall decolonization rate for all sites was 53.1% (sample point II) and 64% (sample point III), respectively. The reduction was significant for every site, showing a rate of 88.5% for nose (II, III) and of 56.3% (II) and 68% (III) for all extranasal sites together. Of 32 patients, a median of 6.5 cfu MRSA/24 cm2 was obtained for the forehead before decolonization and 0.5 cfu MRSA/24 cm2 for the neck. A significant reduction (0 cfu MRSA/24 cm2) from both sites was shown after treatment. Before decolonization procedures, median MRSA levels for the nose, groin and axilla were 55, 6 and 0 cfu/swab. After treatment, MRSA from each of these sites was significantly reduced. We conclude that nasal mupirocin combined with octenidine dihydrochloride whole-body wash is effective in eradicating MRSA from patients with variable site colonization.

Administration, Cutaneous↗
PubMed2003

What is CD4+CD56+ malignancy and how should it be treated?

CD4+CD56+ malignancy is a rare neoplasm with a typical clinical pattern, an aggressive course and high early relapse rate despite good initial response to chemotherapy. In this review, the impact of different therapeutic approaches on clinical outcome has been studied. We evaluated 91 published cases and our own six patients in terms of clinical features, immunophenotype/cytogenetics and treatment outcome. Treatment was divided into four groups: (A) chemotherapy less intensive than CHOP; (B) CHOP and CHOP-like regimens; (C) therapy for acute leukemia; (D) allogeneic/autologous stem cell transplantation. The median overall survival was only 13 months for all patients. Patients with skin-restricted disease showed no difference in the overall survival from patients with advanced disease (17 and 12 months, respectively). Age >/=60 years was a negative prognostic factor. Age-adjusted analysis revealed improved survival after high-dose chemo/radiotherapy followed by allogeneic stem cell transplantation when performed in first complete remission. This therapeutic approach should be recommended for eligible patients with CD4+CD56+ malignancy. For older patients the best treatment option is still unknown.

Antigens, Neoplasm↗
PubMed2003

Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea.

The optimum treatment conditions of interferon (IFN) alpha therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.

Adolescent↗
PubMed2003

Female patient with a history of Hashimoto's thyroiditis, diagnosed with MALT lymphoma of both breasts.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphomas are a distinct subgroup of non-Hodgkin's lymphomas with preferable localization in the gastrointestinal tract. PATIENTS AND METHODS We describe the unusual case of a 48-year-old female patient, who was diagnosed with simultaneous MALT lymphoma of both breasts. Cervical, axillary and retroperitoneal lymph nodes were slightly enlarged, indicating an infiltration by the lymphoma. In her medical history the patient suffered from Hashimoto's thyroiditis. After 6 cycles of chemotherapy with CHOP regimen, the patient achieved complete remission. CONCLUSION: To our knowledge, this is the first case describing a patient with MALT lymphoma of the breast and a history of Hashimoto's thyroiditis. As patients suffering from autoimmune disorders, especially Sjögren's syndrome and Hashimoto's thyroiditis, are at a higher risk to develop B-cell lymphoma, we assume that Hashimoto's thyroiditis favored development of MALT lymphoma in our patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Aseptic necrosis of both femoral heads as first symptom of chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a disease of the elderly; in rare cases it occurs in childhood or adolescence. One complication at primary diagnosis is leukostasis, which usually causes respiratory, retinal, or central nervous symptoms. In this report we describe the case of a 24-year-old woman who developed aseptic necrosis of both femoral heads, which was successfully treated by bore holes in the femoral heads. This is a very rare complication of severe leukostasis, leading to the diagnosis of CML in this case. To our knowledge, this is the first case of an adult patient showing aseptic necrosis of femoral heads caused by leukostasis.

Adult↗
PubMed2002

Concentrations of lead in blood, hair and saliva of German children living in three different areas of traffic density.

Lead contents in hair, whole blood and saliva were determined for 245 healthy children (121 male, 124 female, age: 8-10 years) from three residential areas of Düsseldorf (North-Rhine-Westphalia, Germany) with different traffic densities. The geometric mean for the lead content in hair was found to be 0.87 microg/g (range: 0.2-9.9 microg/g) for the entire test group. While the levels of lead in hair in the suburban population were significantly lower than in the two city centre populations, no significant difference concerning the lead content in hair could be detected in the latter. The geometric mean for lead concentration in whole blood amounted to 25.0 microg/l (range: 8.0-154 microg/l). There was no significant difference between the sub-groups. The lead concentrations found in saliva were rather low (range: < 1.5-47.0 microg/l). Of the values, 89% were below the detection limit of 1.5 microg/l. Due to reduced levels of lead in fuel, the present study exposes that the amount of lead in the children examined has further decreased compared to preceding surveys. The correlation between the lead content in hair and the road traffic density was not corroborated by the findings with regard to amounts of lead found in blood, indicating that residual lead from fuel does not result in a substantial burden of lead found in the whole body. In contrast to levels of lead found in blood, levels of lead found in hair may be influenced more by environmental conditions. Saliva is not a suitable material for biological monitoring with respect to lead exposure in children.

Air Pollutants↗
PubMed2002

Splenectomy in patients with mixed myelodysplastic/myeloproliferative disease.

According to the classification of the World Health Organization, the designation myelodysplastic/myeloproliferative disorder, unclassifiable may be applied to cases that have clinical, laboratory, and morphologic features that support a diagnosis of a myelodysplastic syndrome (MDS) as well as a myeloproliferative disorder (MPD), but that do not meet the criteria for any of the other entities included in the MDS/MPD category [3]. In this paper we report on two Caucasian patients with unclassifiable myelodysplastic syndromes with proliferative characteristics. Both patients were suffering from thrombocytopenia and splenomegaly and underwent splenectomy. The weight of the spleen specimens was more than 2000 g. Histopathology findings revealed a marked infiltration of the spleen with extramedullary hematopoiesis. After surgery, one patient showed a rapid increase of platelets in peripheral blood and developed severe thrombocytosis. In the other case, the patient was suffering from a decrease of platelets and died in hypovolemic shock caused by gastrointestinal bleeding. In summary, these two cases demonstrate the difficulties of prognosis and treatment in patients with mixed myelodysplastic/myeloproliferative disorders. Additionally, we indicate the potential positive outcome of splenectomy as ultima ratio in patients with these hematological features and severe thrombopenia.

Blood Cell Count↗
PubMed2002

Susceptibility of recombinant porcine endogenous retrovirus reverse transcriptase to nucleoside and non-nucleoside inhibitors.

Transplantation of organs, tissues or cells from pigs to humans could be a potential solution to the shortage of human organs for transplantation. Porcine endogenous retroviruses (PERVs) remain a major safety concern for porcine xenotransplantation. Thus, finding drugs that could be used as virological prophylaxis (or therapy) against PERV replication would be desirable. One of the most effective ways to block retroviral multiplication is to inhibit the enzyme reverse transcriptase (RT) which catalyzes the reverse transcription of viral RNA to proviral double-stranded DNA. We report here the cloning and expression of PERV RT and its susceptibility to several inhibitors. Our data demonstrate PERV susceptibility in vitro to the triphosphorylated nucleoside analog of zidovudine (AZT) and to ddGTP and to a lesser extent to ddTTP but almost no susceptibility to the non-nucleoside RT inhibitors tested.

Amino Acid Sequence↗
PubMed2002

Tracheal stenosis caused by false aneurysm of the right subclavian artery.

The development of tracheal stenosis following insertion of a central venous catheter is a rare complication of this procedure. We present the case of an 81-year-old woman, who suffered acute onset of dyspnea, stridor and dysphagia 4 weeks after coronary artery bypass surgery. Investigations revealed a false aneurysm of the right subclavian artery, compressing the trachea and the oesophagus. The iatrogenic lesion was caused by the insertion of a central venous catheter via the right subclavian route. By the time symptoms developed the catheter had already been removed.

Aged↗
PubMed2002

Mercury concentrations in urine, scalp hair, and saliva in children from Germany.

Mercury levels measured in urine, hair, and saliva of 245 German children (8-10 years old) are reported. Mercury concentrations in urine ranged between <0.1 and 5.3 microg/l [geometric mean (GM) 0.26 microg/l or 0.25 microg/g creatinine; median for both, 0.22 in microg/l and microg/g, respectively]. Using multiple linear regression analysis, two predictors have been found accounting for 25.3% of the variance of mercury levels in urine: the number of teeth with amalgam fillings (23.2%) and the number of defective amalgam fillings (2.1%). The mercury content in hair ranged from <0.06 to 1.7 microg/g (GM 0.18 microg/g; median 0.18 microg/g). The frequency of fish consumption, the smoking habits of the parents, and the age of the children accounted for 20.4% of the variance of mercury levels in hair. The correlation between the hair mercury content and urine mercury concentration was low (r=0.297). Mercury levels in saliva ranged between <0.32 and 4.5 microg/l (median 0.16 microg/l). The mercury concentration in saliva was below the limit of quantification of 0.32 microg/l in more than 70% of the samples. Mercury analysis in urine is suitable to estimate mercury exposure due to amalgam fillings, whereas hair mercury better reflects mercury intake by fish consumption. Up to now, saliva does not seem to be a suitable tool to monitor the mercury burden, at least not at low exposure levels.

Animals↗
PubMed2002

Analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms.

The relationship between biomarkers of effect (8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo, HPLC system) and tail extent moment (comet assay)), markers of external and internal exposure, and biomarkers of susceptibility was evaluated for coke-oven and graphite-electrode-producing plant workers exposed to polycyclic aromatic hydrocarbons (PAHs). Mean 8-oxodGuo levels in white blood cells (WBC) of exposed workers were between 1.38 times (coke-oven, n = 20; P < 0.01) and 2.15 times (graphite-electrode-producing plant, n = 30; P < 0.01) higher than levels found in control samples (mean +/- SD 0.52 +/- 0.16 8-oxodGuo/10(5) dGuo, n = 47). The mean tail extent moment in lymphocytes was 1.38 times higher for coke-oven workers (n = 19; P = 0.09) and 3.13 times higher for graphite-electrode-producing plant workers (n = 29; P < 0.01) when compared with controls (mean plus minus SD 2.54 +/- 0.68, n = 32). Elevated tail extent moments (>3.73) were found in the majority (84%) of PAH-exposed workers showing increased DNA adduct levels (>0.78 8-oxodGuo/10(5) dGuo). However, no association (P > 0.05) was found between DNA damage (8-oxodGuo/10(5) dGuo or tail extent moment) in WBC of all PAH-exposed workers and either benzo[a]pyrene levels or the sum of 16 PAH levels in the air at work place. Furthermore, no relation (P > 0.05) could be established between DNA damage in WBC and biomarkers of internal exposure (1-hydroxypyrene (1-OHP) and sum of five hydroxyphenanthrenes (OHPHs)). Higher exposure to airborne pyrene and phenanthrene led to increasing concentrations of the metabolites 1-OHP (P < 0.01) and the sum of five OHPHs (P < 0.01) in the urine of PAH-exposed workers. The polymorphisms of genes CYP1A1, GSTM1, GSTT1 and GSTP1 (biomarkers of susceptibility) showed no association with biomarkers of effect. In conclusion, both biomarkers of effect may be appropriate for further surveillance studies of workers under PAH exposure.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

[Induction of apoptosis by preoperative passive immunotherapy in resectable stomach carcinoma].

The antibody SC-1 is a human IGM molecule, which binds to a tumor specific receptor. This SC-1 receptor is detectable on biopsies, it is present in about 50% of gastric cancers. After binding of the antibody to the receptor the tumor cells go into apoptosis. 50 patients expressing the SC-1 receptor on their tumors have been treated with SC-1 prior to gastrectomy. In 80% of cases apoptosis induction could be demonstrated in the tumors. The only side effect of the SC-1 therapy was a reversible episode of fever during antibody infusion in 8% of our patients.

Antibodies, Monoclonal↗
PubMed2001

Polypurine tract formation by Ty1 RNase H.

To better understand the mechanism by which Ty1 RNase H creates the polypurine tract (PPT) primer, we have demonstrated the polymerase-dependent hydrolytic activity of Ty1 reverse transcriptase (RT) during minus-strand synthesis. Using RNase H and polymerase mutants of the recombinant Ty1 RT protein, we show that the two domains of Ty1 RT can act independently of one another. Our results indicate that RNA/DNA substrates containing a short RNA PPT, which serve as primers for plus-strand DNA synthesis, are relatively resistant to RNase H cleavage. RNA substrates with a correct 5' end but with 3' end extending beyond the plus-strand initiation site were cleaved specifically to generate the correct 3' end of the PPT. Using long RNA/DNA duplexes containing the PPT, we show that Ty1 RT is able to make specific internal cleavages that could generate the plus-strand primer with correct 5' and 3' ends. Long RNA/DNA duplexes with mutations in the PPT or in a U-rich region upstream of the PPT, which abolish plus-strand initiation in vivo, were not cleaved specifically at the 5' end of the PPT. Our work demonstrates that the in vitro enzyme can recapitulate key processes that control proper replication in vivo.

Base Sequence↗
PubMed2001

Human wig-1, a p53 target gene that encodes a growth inhibitory zinc finger protein.

We previously identified a novel p53-induced mouse gene, wig-1, that encodes a 290 amino acid zinc finger protein (Varmeh-Ziaie et al., 1997). Here we have identified and characterized the human homolog of mouse wig-1. The human wig-1 protein is 87% identical to the mouse protein and contains three zinc finger domains and a putative nuclear localization signal. Human wig-1 mRNA and protein is induced following activation of wild type p53 expression in our BL41-ts p53 Burkitt lymphoma cells. Wig-1 is also induced in MCF7 cells following treatment with the DNA-damaging agent mitomycin C. Northern blotting detected low levels of wig-1 mRNA in normal human tissues. Fluorescence in situ hybridization mapped wig-1 to human chromosome 3q26.3-27. FLAG-tagged human wig-1 localizes to the nucleus. Ectopic overexpression of human wig-1 inhibits tumor cell growth in a colony formation assay. These results suggest that human wig-1 has a role in the p53-dependent growth regulatory pathway.

Amino Acid Sequence↗
PubMed2001

Rituximab therapy of patients with B-cell chronic lymphocytic leukemia.

Rituximab (IDEC-C2B8) is a chimeric antibody that binds to the B-cell surface antigen CD20. Rituximab has significant activity in follicular non-Hodgkin lymphomas. Much less is known about the effects in chronic lymphocytic leukemia (CLL). We have initiated a phase II trial to evaluate the efficacy and safety of rituximab in patients with CD20+ pretreated CLL. To avoid the rituximab-associated toxicity, we restricted the tumor cell load, as measured by the number of circulating lymphocytes and the spleen size, in the first 2 cohorts of patients included in the study. Patients received 4 intravenous infusions of 375 mg/m2 once a week over a period of 1 month. Of the 28 patients evaluable for response, 7 patients showed a partial remission (National Cancer Institute criteria) lasting for a median of 20 weeks, with 1 patient still in remission after 71 weeks. Based on lymphocyte counts only, we found at least a 50% reduction of lymphocyte counts lasting for at least 4 weeks in 13 (45%) of 29 patients. Fifteen patients from 3 institutions were monitored for the immunophenotype profile of lymphocyte subsets. The number of CD5+CD20+ cells decreased significantly and remained low until day 28 after therapy. T-cell counts were not affected. With the exception of one rituximab-related death, adverse events in the remaining patients were mild. The results suggest that rituximab has clinical activity in pretreated patients with B-CLL. Toxicity is tolerable. Response duration after withdrawal of rituximab is rather short. Therefore, other modes of application and the combination with other agents need to be tested.

Adolescent↗
PubMed2001

DNA synthesis fidelity by the reverse transcriptase of the yeast retrotransposon Ty1.

The fidelity of the yeast retrotransposon Ty1 reverse transcriptase (RT) was determined by an assay based on gel electrophoresis. Steady-state kinetics analyses of deoxyribonucleotide (dNTP) incorporation at a defined primer-template site indicate that Ty1 RT misincorporates dNTP at a frequency of 0.45 x 10(-5) for the A(t):A mispair in which dATP is misincorporated opposite a template A to 6.27 x 10(-5) for the C(t):A mispair. The G(t):G and T(t):T mispairs are formed with very low efficiency. The fidelity parameters of Ty1 RT do not depend on whether RNA or DNA are copied. Relative to lentiviral RTs (HIV-1, HIV-2 or EIAV) Ty1 RT is approximately 10-fold less error prone. Our data also show that the Ty1 RT is able to recapitulate two error-generating mechanisms: extension of mismatches and non-templated addition of nucleotides at the end of a blunt-end primer-template.

DNA, Fungal↗