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Biomedical subjects

M Nolte

Publications and source records attributed to M Nolte.

At least 19 recordsLinked to original sources
PubMed2003

Outcome analysis of 189 consecutive cancer patients referred to the intensive care unit as emergencies during a 2-year period.

The referral of critically ill cancer patients to an intensive care unit (ICU) is a matter of controversial debate. This study was conducted by an interdisciplinary clinical group to evaluate the outcome of ICU treatment in cancer patients according to their characteristics at the time of referral. A retrospective analysis was used to identify relevant subgroups among 189 consecutive cancer patients referred as emergencies to one of four ICUs during a 2-year period. Reasons for ICU referral were pneumonia (29.6%), sepsis (27.0%), fungal infection (11.1%), another infection (9.5%), gastrointestinal emergency (16.9%), treatment-related organ toxicity (6.9%), or other, non-infectious complications (43.9%). Vasopressor support was required in 50.3%, mechanical ventilation in 49.7%, and haemodialysis/-filtration in 26.5% of the patients. Overall, 41.3% died during ICU treatment, 12.2% died after transfer from ICU to a non-ICU ward, and 35.4% were discharged alive. Sepsis, mechanical ventilation, vasopressor support, renal replacement therapy and neutropenia were independent risk factors for fatal outcome, but no single risk factor unequivocally predicted death. All patients with fungal infection who required vasopressor support and either had sepsis (n=13) or needed mechanical ventilation (n=14) died during ICU treatment, while all non-septic patients. who did not require mechanical ventilation, were younger than 74 years of age and had a non-infectious underlying complication (n=29), survived. This analysis may help to early identify relevant subgroups of cancer patients with different prognoses under ICU treatment. A prospective study to confirm the predictive usefulness of this approach is needed. Cancer patients should not be excluded from referral to the intensive care unit in an emergency solely due to their underlying malignant disease or a single unfavourable prognostic factor.

Adult↗
PubMed2002

[Incidence and differential diagnosis of chronic eosinophilic leukemia].

The diagnosis of chronic eosinophilic leukemia (CEL) is based on the evidence of an autonomous, clonal proliferation of eosinophilic precursors and the exclusion of other myeloid neoplasms with eosinophilia. Histopathological evaluations of bone marrow are rare, and reliable data on the frequency of CEL do not yet exist. A total of 100 cases characterized by eosinophilia >/=1.5x10(9)/l blood for more than 6 months were evaluated. In 87 cases, the eosinophilia turned out to be secondary and a reactive genesis was likely, but not proven in 3 further cases. Idiopathic hypereosinophilic syndrome was diagnosed in three cases. The diagnosis CEL was considered in four out of a total of seven cases with a myeloid neoplasia and all four disorders showed an abnormal karyotype. However, only one of them could be classified as CEL. We conclude that CEL is a rare disease concerning only a minority of cases with chronic eosinophilia.

Diagnosis, Differential↗
PubMed2002

[Endovascular gamma-irradiation for prevention or restenosis after angioplasty of femoropopliteal de-novo-stenoses-long-term results of a feasibility study].

OBJECTIVES: To evaluate the performance and efficacy of endovascular irradiation after percutaneous transluminal angioplasty (PTA) of de-novo femoropopliteal stenoses in a pilot study. METHODS: 6 patients received non-centered endovascular irradiation (12 Gray at surface of the vessel wall) immediately after angioplasty of de-novo femoropopliteal stenosis, 1 patient was given centered endovascular irradiation using 192-iridium (12 Gray at surface of the vessel wall) Centered irradiation was considered for two other patients. Duplex sonographies and interviews were performed the day before and after PTA and after 1, 3, 6, 9, 12, 18, 24 months up to 4 years. Intraarterial angiography was performed in symptomatic patients. RESULTS: Non-centered endovascular irradiation was possible in all patients without problems or complications. Centered irradiation was not possible in two patients with the cross-over approach. One thromboembolic complication occurred during centered irradiation. Both restenosis and new stenosis at the edge of irradiated distance occurred in 1/7 patients. No other side effects were observed during follow-up. CONCLUSIONS: In our pilot study endovascular irradiation after angioplasty of de-novo femoropopliteal stenosis was possible with low rates of complications and restenosis and taking vessel anatomy into account.

Adult↗
PubMed2001

[Anesthesia in extreme obesity].

BACKGROUND: Approximately 1-2% of all anesthetized patients are morbidly obese (body mass index > 35 kg/m2). The perioperative mortality is significantly elevated (up to 20%) compared with lean patients. Morbidly obese patients are at high risk for cardiopulmonary dysfunction. Difficult airway management is reported in 13-20% of obese patients. Hypoxia is often observed due to faster desaturation during induction of anesthesia. After surgery, patients are endangered by a high incidence of obstructive sleep apnea syndrome (50%), pulmonary atelectasis (5%) and acute pulmonary embolism (5-12%). ANESTHESIA: Individualized perioperative management is required based on preoperative history and physical examination. Modern anesthetic drugs (desfluran, sevoflurane or propofol, and remifentanil, respectively) allow rapid recovery and early postoperative mobilization. Adequate monitoring, e.g. by an intraarterial blood pressure monitoring and repetitive blood gas analyses, improves patient safety prior the onset of complications. POSTOPERATIVE MANAGEMENT: Postoperative admission on an intensive care unit of morbidly obese patients is based upon concomitant diseases and surgical requirements. The main reason for admission is an inadequate pulmonary gas exchange. This interdisciplinary approach will reduce the risk of anesthesia and avoid complications in morbidly obese patients.

Anesthesia, General↗
PubMed1999

Crystal structure of the alpha1beta1 integrin I-domain: insights into integrin I-domain function.

The alpha1beta1 integrin is a major cell surface receptor for collagen. Ligand binding is mediated, in part, through a 200 amino acid inserted 'I'-domain contained in the extracellular part of the integrin alpha chain. Integrin I-domains contain a divalent cation binding (MIDAS) site and require cations to interact with integrin ligands. We have determined the crystal structure of recombinant I-domain from the rat alpha1beta1 integrin at 2.2 A resolution in the absence of divalent cations. The alpha1 I-domain adopts the dinucleotide binding fold that is characteristic of all I-domain structures that have been solved to date and has a structure very similar to that of the closely related alpha2beta1 I-domain which also mediates collagen binding. A unique feature of the alpha1 I-domain crystal structure is that the MIDAS site is occupied by an arginine side chain from another I-domain molecule in the crystal, in place of a metal ion. This interaction supports a proposed model for ligand-induced displacement of metal ions. Circular dichroism spectra determined in the presence of Ca2+, Mg2+ and Mn2+ indicate that no changes in the structure of the I-domain occur upon metal ion binding in solution. Metal ion binding induces small changes in UV absorption spectra, indicating a change in the polarity of the MIDAS site environment.

Animals↗
PubMed1999

Cytogenetic aberrations in myelodysplastic syndrome detected by comparative genomic hybridization and fluorescence in situ hybridization.

Conventional cytogenetics (CC) is proven as a diagnostic and prognostic factor in myelodysplastic syndrome (MDS). However, CC may be hampered by insufficient metaphase preparation and cannot analyze interphase nuclei. These problems are solved by using comparative genomic hybridization (CGH). The CGH was applied to samples from 45 patients with MDS, and the results were compared with CC and fluorescence in situ hybridization (FISH). The CC detected aberrations in 12 of 45 samples, including chromosomes 3 (n = 1), 5 (n = 9), 7 (n = 2),8(n = 1), 18(n = 1),21 (n = 1), X (n = 1), and Y(n = 2). In one patient, loss of B and C group chromosomes and a marker chromosome were seen. The CGH revealed chromosomal imbalances in 18 of 45 samples, including chromosomes 5 (n = 11), 7 (n = 2), 8 (n = 1), 18(n = 1), 20(n = 1), 21 (n = 1), X (n = 1), and Y (n = 2). All unbalanced aberrations found by CC were detected by CGH, too. In two patients, the CGH found additional aberrations and redefined the aberrations of the chromosomes of the B and C group in one sample. The FISH confirmed these aberrations. Additionally performed FISH for chromosomes 5, 7, and 8 gave normal findings in all patients found to be normal in CC and CGH. The CGH and FISH confirmed the results obtained by CC. All three techniques showed changes of chromosomes 5 and 7 as the most frequent aberrations, emphasizing the importance of these chromosomes in the development of MDS. Furthermore, the CC is proven as the basic technique for cytogenetic evaluation of MDS.

Adolescent↗
PubMed1998

Kinetic and X-ray structural studies of three mutant E. coli alkaline phosphatases: insights into the catalytic mechanism without the nucleophile Ser102.

Escherichia coli alkaline phosphatase (EC 3.1.3.1) is a non-specific phosphomonoesterase that catalyzes the hydrolysis reaction via a phosphoseryl intermediate to produce inorganic phosphate and the corresponding alcohol. We investigated the nature of the primary nucleophile, fulfilled by the deprotonated Ser102, in the catalytic mechanism by mutating this residue to glycine, alanine and cysteine. The efficiencies of the S102G, S102A and S102C enzymes were 6 x 10(5)-fold, 10(5)-fold and 10(4)-fold lower than the wild-type enzyme, respectively, as measured by the kcat/Km ratio, still substantially higher than the non-catalyzed reaction. In order to investigate the structural details of the altered active site, the enzymes were crystallized and their structures determined. The enzymes crystallized in a new crystal form corresponding to the space group P6322. Each structure has phosphate at each active site and shows little departure from the wild-type model. For the S102G and S102A enzymes, the phosphate occupies the same position as in the wild-type enzyme, while in the S102C enzyme it is displaced by 2.5 A. This kinetic and structural study suggests an explanation for differences in catalytic efficiency of the mutant enzymes and provides a means to study the nature and strength of different nucleophiles in the same environment. The analysis of these results provides insight into the mechanisms of other classes of phosphatases that do not utilize a serine nucleophile.

Alanine↗
PubMed1998

Analysis of hematologic diseases using conventional karyotyping, fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH).

Comparative genomic hybridization (CGH) has been proven to be an important tool in interphase cytogenetics of solid tumors. Although, because of methodological implications, balanced aberrations are not detected by CGH, the technique has uncovered a variety of new and interesting imbalanced karyotype changes. However, only a few studies deal with its application to hematologic disorders, although this is a main topic of cytogenetics. The aim of our study was, therefore, to evaluate the usefulness of CGH in the examination of hematologic neoplasms. For this purpose, bone marrow aspirates of 33 patients with different hematologic disorders were examined with CGH and the results compared with conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH). CGH showed chromosome changes in 8 of 33 cases. CC found balanced aberrations in 4 of 33 and unbalanced changes in 9 of 33 samples. Differences between CGH and CC in unbalanced aberrations were seen in four cases. In these samples, either the number of aberrant cells found by CC was low and, therefore, difficult to detect by CGH, or complex aberrations in different cell clones as seen in CC were lumped together as one karyotype by CGH. In one sample, CC was not capable of giving any results at all, whereas CGH showed trisomy 8. CGH was also helpful in defining the bands involved in the structural aberrations, which was difficult by CC in some cases because of the low quality of metaphase spreads. All results obtained by CGH were confirmed by FISH, whereas CC and FISH were discordant in one case. Although CGH was not able to detect all aberrations, it gave important additional information for the correct localization of the aberrations found in CC, and it was most helpful in samples not processed successfully in CC. These advantages would open up a new field of application for CGH not only for research, but also for diagnostic purposes.

Adult↗
PubMed1998

Expression of proliferation associated antigens and detection of numerical chromosome aberrations in primary human liver tumours: relevance to tumour characteristics and prognosis.

AIMS: To assess cell proliferation and the presence of numerical chromosome aberrations involving chromosomes 1 and 8 in benign and malignant liver tumours. METHODS: Cell proliferation was studied immunohistochemically in paraffin wax embedded material from 62 primary liver tumours (20 hepatocellular carcinomas, 16 cholangiocellular carcinomas, 15 liver cell adenomas, 11 focal nodular hyperplasias), and the results were compared with histological characteristics and clinical data. Copy numbers of chromosomes 1 and 8 were assessed by interphase fluorescence in situ hybridisation (FISH) with satellite probes in fresh tumour material. RESULTS: The expression of proliferation associated antigen Ki67, using the monoclonal antibody MIB-1, and proliferating cell nuclear antigen (PCNA), using the antibody PC10, was found to be significantly higher in malignant versus benign liver tumours. Neither Ki67 nor PCNA expression were independent prognostic parameters. However, there was a tendency for a worse outcome (survival < 12 months) for patients with a high MIB-1 labelling index (> 20%) compared with patients having the same tumour stage and a low MIB-1 index. Aneusomy for chromosomes 1 and 8 was demonstrated by FISH in malignant tumours (six of seven hepatocellular carcinomas, four of five cholangiocellular carcinomas) but not in benign tumours (none of nine) or non-neoplastic liver (none of nine). CONCLUSION: Both the determination of the proliferating cell fraction and FISH analysis are useful for distinguishing hepatocellular carcinoma from liver cell adenoma or focal nodular hyperplasia; high fractions of proliferating cells are predictive of an early relapse.

Antigens, Neoplasm↗
PubMed1997

The crystal structure of human interferon beta at 2.2-A resolution.

Type I interferons (IFNs) are helical cytokines that have diverse biological activities despite the fact that they appear to interact with the same receptor system. To achieve a better understanding of the structural basis for the different activities of alpha and beta IFNs, we have determined the crystal structure of glycosylated human IFN-beta at 2.2-A resolution by molecular replacement. The molecule adopts a fold similar to that of the previously determined structures of murine IFN-beta and human IFN-alpha2b but displays several distinct structural features. Like human IFN-alpha2b, human IFN-beta contains a zinc-binding site at the interface of the two molecules in the asymmetric unit, raising the question of functional relevance for IFN-beta dimers. However, unlike the human IFN-alpha2b dimer, in which homologous surfaces form the interface, human IFN-beta dimerizes with contact surfaces from opposite sides of the molecule. The relevance of the structure to the effects of point mutations in IFN-beta at specific exposed residues is discussed. A potential role of ligand-ligand interactions in the conformational assembly of IFN receptor components is discussed.

Computer Simulation↗
PubMed1997

Value of fluorescence in situ hybridization for detecting the bcr/abl gene fusion in interphase cells of routine bone marrow specimens.

Fluorescence in situ hybridization (FISH) is a new technique that allows demonstrating of the bcr/abl gene fusion in bone marrow cells of patients with Philadelphia translocation (Ph)-positive chronic myeloid leukemia (CML). In this study, bone marrow samples of 150 patients were investigated routinely by interphase FISH, cytogenetics, and bone marrow histopathology. In 20 patients with reactive hyperplasia of the granulopoiesis and normal karyotypes, FISH revealed nonspecific bcr/abl fusion signals at a mean frequency of 2.7% of the cells examined. The cutoff level for specific fusion signals was set at three times the standard deviation (9.0%). None of the 29 cytogenetically Ph-negative patients with myeloproliferative disease other than CML had fusion signals exceeding 9%. The mean frequency of specific fusion signals in nontreated patients with CML (n = 59) was 92.7%, and 49.3% in patients with CML who received therapy (n = 42). For diagnosing Ph-positive CML, interphase FISH has been faster, more reliable, and more sensitive than cytogenetics, which was successful in 54 of 59 patients investigated at first diagnosis but only in 27 of 42 patients receiving therapy, and it failed to detect Ph-positive cells in three patients with CML. However, small percentages of less than 9.0% of cells with bcr/abl fusion signals were below the threshold of interphase FISH, thereby limiting its use for detecting minimal residual disease.

Aged↗
PubMed1997

[Importance of cytogenetic investigations in canine leukemias].

Like in man, in neoplastic haematopoietic diseases of the dog genetical changes can be detected cytogenetically. In this study, some cytogenetically characterized cases are presented and discussed against the background of comparable cases reported in the literature. In two out of three patients investigated, one or two extra copies of chromosome 1 were detected. Corresponding changes have also been described in two other cases in the literature.

Animals↗
PubMed1996

Megakaryocytes carry the fused bcr-abl gene in chronic myeloid leukaemia: a fluorescence in situ hybridization analysis from bone marrow biopsies.

Histological examination of bone marrow biopsies shows that about one-third of chronic myeloid leukaemia (CML) patients exhibit an increase of megakaryocytes. The megakaryocytic predominance may be so striking that differentiation from other chronic myeloproliferative disorders (CMPD) may be difficult in some CML patients. Megakaryocytes in CML are clonal as demonstrated by loss of glucose-6-phosphate dehydrogenase isoenzymes. The Ph translocation, fusing the abl and bcr genes on chromosomes 9 and 22, however, obviously occurs as a second step in tumour development. So far, the Ph translocation has not been assigned explicitly to megakaryocytes. The question is whether the megakaryocytic cell lineage could harbour the bcr/abl fusion in those CML cases with striking proliferation of megakaryocytes but lack this genetic defect in cases with normal or decreased megakaryocyte counts. We therefore performed triple-colour fluorescence in situ hybridization (FISH) for portions of the bcr and abl genes flanking the breakpoint in CML in paraffin sections of CML cases with normal and with increased numbers of megakaryocytes. This method allows identification of the bcr/abl fusion in single, morphologically intact cells, whereas conventional cytogenetics requires lysis and thus destruction of the cell. Among the 21 CML patients examined by FISH, 10 were informative for bcr and abl genes and displayed distinct hybridization signals within nuclei of bone marrow cells. Besides the granulopoietic cells, megakaryocytes of all those patients (4 without and 6 with varying grades of megakaryocytic increase) displayed bcr/abl fusion signals indicative of a Ph translocation. The lack of hybridization signals in the remaining 11 cases indicates that this technique is not of value diagnostically and should be reserved for scientific questions. Positive controls consisted of conventional chromosome preparations from bone marrow aspirates demonstrating the Ph chromosome in all patients examined, and negative controls of paraffin sections of bone marrow biopsies from non-CML patients. These showed no fusion signals in bone marrow cells, including megakaryocytes, using FISH. Our results demonstrate clearly that not only the transforming event but also the Ph translocation leading to the bcr/abl fusion happens prior to the differentiation of the pluripotent stem cell into different myeloid lineages. The megakaryocytic proliferation evident in some CML cases is probably a consequence of the disease progress.

Biopsy↗
PubMed1996

Detection of numerical karyotype changes in the giant cells of Hodgkin's lymphomas by a combination of FISH and immunohistochemistry applied to paraffin sections.

Conventional karyotyping of Hodgkin's disease (HD) has until now yielded only limited insight into karyotypic characteristics of this disease. For this reason, fluorescence in situ hybridization (FISH) using alpha-satellite chromosome-specific probes was applied to paraffin sections of HD tumors in order to verify numerical aberrations suggested to be specific for HD in the literature. The FISH technique was combined with immunohistochemical detection of the CD30 antigen to allow easier identification of the Reed-Sternberg and Hodgkin (RS&H) cells. The number of specific FISH signals per nucleus was determined both in CD30-positive RS&H cells as well as in non-malignant "bystander" cells in order to assess differences in the signal distribution. Contrasted with normal lymphoid cells, the tumor cells in HD were found to be polysomic for at least one of the chromosomes analyzed (1,2,4, and 8). The technique described is a reliable method for confirmation of results obtained from conventional cytogenetics, which is especially suited for archival material or samples not containing dividing cells.

Antigens↗
PubMed1996

Microwave pretreatment improves RNA-ISH in various formalin-fixed tissues using a uniform protocol.

RNA is situ hybridization technique (RNA-ISH) is hampered by formalin fixation of tissues. This necessitates a pretreatment step of enzymatic digestion. However, to achieve the best results, digestion times and concentrations of enzymes have to be adapted for every specimen in a cumbersome procedure. Microwave pretreatment (MP) of formalin-fixed tissues has developed to become a powerful tool in immunohistochemistry (IHC) in recent years. To evaluate whether MP could also be helpful for RNA-ISH, we compared MP and conventional enzymatic pretreatment systematically using different tissues and various fixation times. As a model for RNA-ISH we chose the detection of kappa/lambda light chain mRNA in tonsils and lymph nodes with follicular hyperplasia and lymph nodes of patients with lymphocyte predominant Hodgkin's Disease (LPHD). Signal intensity obtained after MP was at least as good or dramatically enhanced as that obtained with optimized, single case adapted conventional pretreatment, the morphology being much better preserved after MP. These results confirm MP as a suitable method to unify the staining protocols in RNA-ISH, regardless of the duration of formalin fixation. Based on our results we recommend MP as a reliable and inexpensive method to enhance, standardized and simplify RNA-ISH.

Formaldehyde↗
PubMed1996

Fluorescence in situ hybridization (FISH) is a reliable diagnostic tool for detection of the 9;22 translocation.

The fluorescence in situ hybridization (FISH) technique for detection of the 9;22 translocation was compared with the "gold standard" of conventional cytogenetics. For this purpose, both methods were applied to 81 bone marrow aspirates and/or peripheral blood specimens comprising 50 CML cases and controls from 31 patients without CML. Independently, core biopsies of these 81 patients were investigated by three histopathologists. Conventional karyotype analysis from unstimulated bone marrow cells was successful in 71/81 cases and demonstrated the Ph-chromosome in 42/46 CML patients. With FISH, results were obtained in all 81 cases investigated, confirming fusion of the ber and abl genes in all cytogenetically Ph-positive patients. Among the five Ph-chromosome-negative specimens bcr/abl fusions were detected in only one patient. The percentage of cells found to be Ph-positive by both methods was correlated, but in individual cases considerable differences in the numbers of Ph-positive cells were observed. Different results may be due to selection of cells after in vitro cultivation predominantly. FISH proved to be a very reliable technique for specimens that do not contain dividing cells. With FISH, large numbers of cells can easily be scored which is an advantage compared to conventional cytogenetics. Therefore, this method is particularly suitable for those whose therapy is being monitored or a relapse is suspected. However, the FISH results should be evaluated critically with respect to the practical limit of sensitivity since non-specific fusion signals can also be observed in a small percentage of cells in non-CML cases. It is suggested that each laboratory define its own threshold of bcr/abl fusion signals for diagnosing Ph-positive CML by FISH.

Adolescent↗