[Compression therapy of venous varicose ulcer. New bandage saves time and money].
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Aged↗
Biomedical subjects
M König
Publications and source records attributed to M König.
Characterization of sealpox virus, a separate member of the parapoxviruses.
A disease outbreak characterized by lesions of the skin and mucosa of the oral cavity was recognized in harbor seals ( Phoca vitulina) from the German North Sea. Using electron microscopy typical parapoxvirus particles were observed. The presence of parapoxvirus was confirmed by PCR and nucleotide sequencing of part of the putative major envelope protein coding gene. Comparative sequence analysis revealed that the virus from seal is significantly different from the established parapoxvirus species Orf virus, Bovine papular stomatitis virus, Pseudocowpox virus, and Parapoxvirus of red deer in New Zealand. The results of our analysis provide evidence for inclusion of the seal parapoxvirus as member of a separate species within the genus Parapoxvirus.
Amino Acid Sequence↗
Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.
BACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status. RESULTS: After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment. CONCLUSIONS: No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.
Adult↗
Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia.
To determine the incidence of leukemia-specific rearrangements, 60 cases of childhood acute myeloblastic leukemia and transient myeloproliferative disorder were screened with a novel multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and the results were correlated with the cytogenetic findings. The RT-PCR assay detects 28 different fusion genes and more than 80 different fusion transcript variants. RNA was isolated from methanol/acetic acid-fixed cells that had been routinely prepared for cytogenetic analysis. Nine different fusion transcripts were found in 40% of the cases, whereas 78.3% of the cases had abnormal karyotypes. Two cases with a t(6;11) and an MLL/AF6 gene fusion were missed cytogenetically. Conversely, cytogenetic analysis revealed 10 other well-defined chromosome rearrangements. Although cytogenetic analysis reveals a much broader range of abnormalities, multiplex RT-PCR serves as quality control and provides the essential information for minimal residual disease studies. Moreover, discrepant findings lead to the detection of new rearrangements on the molecular genetic level.
Adolescent↗
An ins(X;11)(q24;q23) fuses the MLL and the Septin 6/KIAA0128 gene in an infant with AML-M2.
The MLL (HRX, ALL-1 HTRX) gene at chromosome band 11q23 frequently is rearranged in acute lymphoblastic and myeloblastic leukemia. To date, more than 40 different 11q23 abnormalities have been described on the cytogenetic level, and at least 25 of the respective fusion partner genes are cloned. The vast majority of the respective reciprocal translocations generate a chimeric 5'-MLL/partner-3' gene on the derivative 11q23. In this work, we report a unique ins(X;11)(q24;q23) in an infant with acute myeloid leukemia (AML-M2) that fuses the human KIAA0128 gene at Xq24 with MLL. In contrast to the typical reciprocal MLL translocations, however, we provide evidence that the 5'-MLL/KIAA0128-3' fusion resides on Xq24 rather than on 11q23. The KIAA0128 gene encodes the human Septin 6 protein, which contains an ATP-GTP binding motif and three nuclear targeting sequences in its carboxy terminus. The maintenance of the reading frame of the 5'-MLL/KIAA0128-3' mRNA fusion allows for the formation of a novel chimeric protein. Septin 6 is the third member of the Septins that is fused to the MLL protein; the other two are hCDCrel at 22q11 and MSF at 17q25.
Chromosomes, Human, Pair 11↗
Modification of slow cortical potentials in patients with refractory epilepsy: a controlled outcome study.
PURPOSE: To compare self-regulation of low-frequency EEG components (slow cortical potentials, SCPs) with other methods of seizure control for patients with drug-refractory partial epilepsy and to separate the real anticonvulsive effect from placebo effects. METHODS: Results of a treatment program of SCP self-regulation (experimental group) are compared with two groups of patients, one of which learned self-control of respiratory parameters (end-tidal CO2 and respiration rate: RES group); the other received medication with new anticonvulsive drugs (AEDs) in combination with psychosocial counseling (MED group). Clinical, cognitive, behavioral, and personality measures were assessed before and after treatment. In addition, to control for placebo responses, patients repeatedly estimated their beliefs in the efficiency of the respective treatment, their satisfaction and expectations, and the quality of the relationship with their therapists. RESULTS: SCP and MED groups showed a significant decrease of seizure frequency, but the RES group did not. Clear positive changes in the sociopsychological adjustment were obtained in all three groups, with the maximal improvement being attained in the RES group. CONCLUSIONS: All kinds of therapy result in considerable improvement of patients' emotional state, which may in part be due to potential placebo effects: however, this improvement is not related to the quality of the therapeutic effect proper (i.e., seizure reduction). Traditional double-blind control group designs are inappropriate for behavioral interventions or treatments with psychoactive pharmacologic drugs. Rather, specific tests can be developed to control the placebo effect and to separate it from the genuine therapeutic effects.
Adolescent↗
CBFB/MYH11 fusion in a patient with AML-M4Eo and cytogenetically normal chromosomes 16.
We present a unique case of acute myeloid leukemia M4Eo (AML-M4Eo) with a CBFB/MYH11 fusion transcript and a trisomy 22, but in whom cytogenetic analyses did not disclose an inv(16). Fluorescence in situ hybridization (FISH) analysis with chromosome arm-specific painting probes as well as with the c40 and c36 cosmids also revealed no evidence for an inv(16), whereas the application of locus-specific probes confirmed the presence of a masked inv(16). The results of our comprehensive FISH investigations indicate that the events leading to this masked inv(16) were complex and concurred with deletions on both the long and short arms. The most likely explanation for the formation of the relevant CBFB/MYH11 fusion is an insertion of parts of the MYH11 into the CBFB gene, although it is also possible that it was formed by a double inversion.
Adolescent↗
Culture requirements for induction of dendritic cell differentiation in acute myeloid leukemia.
Peripheral blood mononuclear cells (PBMCs) from 15 newly diagnosed acute myeloid leukemia (AML) patients were cultured in fetal calf serum-free media supplemented with either granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor alpha (TNFalpha), or GM-CSF, stem cell factor (SCF), TNFalpha and transforming growth factor beta (TGFbeta) in order to generate leukemia-derived dendritic cells (DCs). Cultured cells were analyzed by flow cytometry with respect to DC-associated surface molecules (CD1a, CD83, CD40, CD80, CD86, HLA-DR) when they showed significant DC morphology in culture (14 cases). After cultivation, neo-expression or upregulation of CD1a antigen was found in 8 samples, CD83 in 2, CD40 in 14, CD80 in 7, and CD86 in 9. Twelve of 14 AMLs, in which DC morphology could be induced upon cultivation, showed upregulation of at least 2 DC-associated molecules. For induction of DC differentiation. GM-CSF, IL-4 plus TNFalpha was superior in 11 cases, and better results were obtained with GM-CSF, SCF, TNFalpha plus TGFbeta in 3 cases. In 7 of 14 samples tested, a marked increase of the T-cell stimulatory capacity could be demonstrated in the allogeneic mixed lymphocyte reaction. The leukemic origin of in vitro-generated DCs was demonstrated by fluorescence in situ hybridization in a patient with translocation t(15;17). Our results suggest that the use of different culture conditions may extend the number of AML patients in which a differentiation towards the DC lineage can be induced in vitro.
Acute Disease↗
Functional reconstitution of ICln in lipid bilayers.
Reconstitution of purified ICln in lipid bilayer leads to functional ion channels showing varying rectification. The reconstituted single channels have a conductance of approximately equal to 3 pS and their open probability is sensitive to nucleoside analogues. Mutation of a putative nucleotide binding site identified at the predicted extracellular mouth of the ICln channel protein leads to the reduction of the nucleoside-analogue sensitivity. Reconstituted ICln channels can be permeated both by cations and anions. The relative permeability of cations over anions depends on the presence of calcium. In the presence of calcium reconstituted ICln channels are more permeable to bromide than chloride, and more permeable to potassium than sodium. Similarly in NIH3T3 fibroblasts, the relative permeability of cations over anions of swelling-dependent chloride channels depends on extracellular calcium. Site-directed mutagenesis revealed the calcium-binding site responsible for the shift of the selectivity from cations towards anions of reconstituted ICln channels. Additional indirect structural information has been obtained by mutating a histidine in the predicted pore region of ICln. This histidine seems to have access to the ion-conducting tunnel of the pore. Our experiments show that ICln can act as an ionic channel, which does not exclude additional functions of the protein in regulatory mechanisms of the cell. Since knocking down the ICln protein in fibroblasts and epithelial cells leads to an impaired regulatory volume decrease (RVD) after cytoplasmic swelling and reconstituted ICln channels show several biophysical features of ion channels activated after swelling, ICln is a molecular candidate for these channels.
3T3 Cells↗
[Mandibular involvement in chronic recurrent multifocal osteomyelitis (CRMO) in adulthood].
A 42-year-old patient was admitted to our clinic with the diagnosis of primary chronic osteomyelitis of the mandible. Since the initial manifestation, approximately 9 months earlier, the patient had undergone numerous antibiotic treatment trials. Various tissue specimens exhibited no microbial growth. Computer tomography demonstrated severe sclerotic changes with partly osteolytic areas in the complete right horizontal ramus of the mandible. Decortication was carried out and both soft and hard tissue specimens were taken. Histological assessment revealed slightly sclerotic bone with reactive periosteal bone production, as in chronic non-specific osteomyelitis. Because of progressive pain and paresthesia, a 3-phase skeletal scanning was performed before the planned resection. In addition to an intensive labeling in the right mandible, further intensive lesions were found at the first right rib, the sternum, and the vertebral column. The subsequent magnetic resonance tomography confirmed the infiltration, as seen in osteomyelitis, in all these areas. Under the assumption of chronic recurrent multifocal osteomyelitis (CRMO), an immunosuppressive therapy with diclofenac and prednisolone was started, which at first brought about complete remission. As CRMO is very rare in our specialty, it might be suspected that it is the cause of some cases of primary therapy-resistant osteomyelitis. The importance of early diagnosis must be underlined, because therapy differs fundamentally from that of the more common bacterial osteomyelitis. A bone scan is therefore of great value in the diagnostic scheme of therapy-resistant osteomyelitis.
Adult↗
MRD levels during the first months of treatment indicate relapses in children with t(12;21)-positive ALL.
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Biomarkers, Tumor↗
[Cerebral perfusion CT: theoretical aspects, methodical implementation and clinical experience in the diagnosis of ischemic cerebral infarction].
Cerebral perfusion CT using dynamic CT after bolus injection of contrast has recently been introduced in the clinical management of stroke patients. Based on the indicator dilution principle various theoretical models can be formulated which all aim at the quantitative determination of cerebral blood flow (CBF). Our Perfusion CT approach is based on the "maximum slope" model and allows in addition to the calculation of CBF parameter images the display of cerebral blood volume (CBV) and "time to peak" as diagnostically meaningful parameters. This approach allows the detection of acute ischemia of the supratentorial brain with a sensitivity of 91% and has proven its value as a routine diagnostic tool for acute stroke. The combination of various functional maps provides excellent information regarding the type of ischemia. Although the direct assessment of ischemia using absolute CBF values is severely restricted by patient dependent systematic errors, the severity of ischemia may reliably be assessed by using relative CBF perfusion indices.
Acute Disease↗
[CT perfusion imaging in acute ischemic cerebral infarct: comparison of cerebral perfusion maps and conventional CT findings].
PURPOSE: To evaluate the findings of acute brain ischemia on different functional maps of cerebral perfusion CT in stroke patients and to compare the results with early ischemic changes on conventional CT. METHODS: The baseline CT scans of 45 acute stroke patients were retrospectively evaluated with respect to early CT findings. For each patient the extent of cerebral ischemia as shown on the maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and "time to peak" (TP) was compared and the severity of ischemia was assigned to one of three levels based on the findings of the CBF image. RESULTS: In 75% of all patients conventional CT was performed within 2 hours from symptom onset. 29 of 45 patients showed early signs of ischemia on conventional CT, whereas perfusion CT revealed cerebral ischemia in all patients. Severe ischemia was found in approximately the same rate of incidence in patients with early CT changes (55.2%) and in those with normal findings (43.8%). If the perfusion impairment was judged as mild or moderate the extent of the hypoperfused area was significantly larger on the CBF and TP images than on the CBV map. This was significantly different in patients with severe hypoperfusion where a complete correspondence of the affected area between the three functional maps was found. DISCUSSION: The use of conventional CT for the assessment of stroke in the hyperacute phase is limited. Perfusion CT yields excellent information regarding the severity and extent of ischemia. The use of various perfusion maps helps to differentiate the core of infarction from the ischemic penumbra zone.
Acute Disease↗
[Perfusion parameters in MRI diagnosis of pancreas transplants].
PURPOSE: Evaluation of the role of perfusion parameters in the detection of circulatory disturbance and chronic rejection in patients after pancreas transplantation. MATERIALS AND METHODS: 70 examinations of 39 patients after pancreas transplantation were performed. Using a dynamic gadolinium-enhanced Turbo-FLASH-sequence, we evaluated the perfusion parameters in a group of patients with chronic rejection, with circulatory disturbance, and in a control group with normal organ function. RESULTS: There were statistically significant differences of the perfusion parameters in patients with chronic rejection and circulatory disturbance compared to the control group. CONCLUSION: Dynamic MRI can help detect patients with chronic rejection and circulatory disturbance and should therefore be part of the routine follow-up in patients after pancreas transplantation.
Adult↗
Structure and function of the ion channel ICln.
Normal function of organs and cells is tightly linked to the cytoarchitecture. Control of the cell volume is therefore vital for the organism. A widely established strategy of cells to counteract swelling is the activation of chloride and potassium channels, which leads to a net efflux of salt followed by water - a process termed regulatory volume decrease. Since there is evidence for swelling-dependent chloride channels (IClswell) being activated also during pathological processes, the identification of the molecular entity underlying IClswell is of utmost importance. Several proteins are discussed as the channel forming IClswell, i.e. phospholemman, p-glycoprotein, CLC-3 and ICln. In this review we would like to focus on the properties of ICln, a protein cloned from a Madin Darby canine kidney (MDCK) cell library whose expression in Xenopus laevis oocytes resulted in a nucleotide sensitive outwardly rectifying chloride current closely resembling the biophysical properties of IClswell.
Amino Acid Sequence↗
Hysteroscopic surgery--complications and their prevention.
During the last few years, diagnostic hysteroscopy has become a standard procedure in the diagnosis of abnormal uterine bleeding, sonographically suspicious endometrial reflex and fertility disorders. At the same time the hysteroscopic treatment of intrauterine pathology is becoming more common. Today, hysteroscopic resection of uterine myomas, dissection of uterine septa, and endometrial ablation are standard procedures. Using monopolar cutting devices and saline-free distension media, hysteroscopic surgery bears specific risks. The knowledge of these risks is important to avoid typical complications of operative hysteroscopy. This article gives an overview about the most common procedures of operative hysteroscopy and the combined risks. Criteria for a safe procedure are defined in order to increase the quality management of operative hysteroscopy.
Endometrium↗
The 'HysteroTrainer'--an in vitro simulator for hysteroscopy and falloposcopy. Experimental and clinical background and technical realisation including the development of organ modules for electrothermal treatment.
Hysteroscopy and falloposcopy are routine procedures in gynecological endoscopy. Injuries to the cervix or uterine perforations due to blind manipulation or wrong use of instruments are the most common complications associated with these procedures. In vitro simulators have been shown to be valuable tools in the laparoscopic training of physicians. Therefore we developed a simulator for hysteroscopy offering realistic anatomical and physiological training conditions. Additionally, we examined different polymer substances as basic materials for organ modules that allow the realistic application of electric instruments, e.g. resector blades and rollerball.
Equipment and Supplies↗
Generation of dendritic cells from human chronic myelomonocytic leukemia cells in fetal calf serum-free medium.
It is generally believed that the immune system plays a role not only in the acquisition of malignant diseases but also in the rejection of microscopic as well as established tumor cells. Failure of the immune system to eliminate tumor cells may be, among other factors, due to an insufficient presentation of tumor antigens. Dendritic cells (DCs), as professional antigen-presenting cells, therefore, may be therapeutically used to initiate or enhance immune responses in patients with malignancies. In this study we demonstrate that peripheral blood cells of patients with chronic myelomonocytic leukemia (CMML) can be induced to acquire DC characteristics. Upon culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4) plus tumor necrosis factor alpha (TNFalpha), CMML cells develop DC morphology and acquire the phenotypic characteristics of DCs. When a CD14+ cell population is used for DC generation, a homogeneous differentiation towards the DC lineage occurs similar to that, observed in normal peripheral blood monocytes. CMML-derived DCs are potent stimulators of the allogeneic mixed lymphocyte reaction (MLR) when compared with uncultivated cells. The demonstration of a deletion of the long arm of chromosome 7, del(7)(q22), in 86% of highly enriched CD1a+ cells by fluorescence in situ hybridization (FISH) indicates the leukemic origin of generated DCs. In addition, we present data that generation of CMML-derived DCs is also possible under fetal calf serum-free conditions for a potential clinical use. These DCs may be used as a cellular vaccine to induce anti-tumor immunity in patients with CMML.
Cell Differentiation↗