[Fetal pain--a systematic multidisciplinary survey].
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Female↗
Biomedical subjects
A Schwarzer
Publications and source records attributed to A Schwarzer.
Management of fulminating ulcerative colitis in childhood with chimeric anti-CD25 antibody.
Fulminating acute ulcerative colitis (UC) is a potentially life threatening medical emergency. Up to 30% of individuals respond poorly to corticosteroids alone and second line medical or surgical therapies are indicated. We describe the successful use of chimeric anti-CD25 therapy in 4 such children poorly responsive to combined therapy with intravenous steroids and calcineurin inhibitors with a pretreatment predictive risk of colectomy of 85-100%. Clinical disease activity scores normalized within 72 hours of anti-CD25 administration and colonic histology provided evidence of mucosal healing within 10-14 days. None required emergency colectomy. Anti-CD25 is efficacious in fulminating UC and randomized placebo controlled trials appear indicated.
Acute Disease↗
[Pain treatment of patients with incurable malignant tumors].
BACKGROUND AND OBJECTIVE: Efficacious pain therapy is one of the main challenges in the management of patients with advanced cancer. It was the aim of this study to ascertain whether adequate pain treatment was achieved in a palliative care unit and what changes in medical treatment were undertaken during the patients stay in this unit. SUBJECTS AND METHODS: Medication against pain and pain intensity were documented during hospital care of 94 patients with cancer (mean age: 66.8 years; female/male 52.2/47.8%; discharged/deceased 58.5/41.5%) at admission and discharge. 32 patients were interviewed by phone after discharge about their current perception and intensity of pain, as well as their health. RESULTS: Highly significant reduction of pain intensity was achieved in all patients while receiving palliative care. Only those patients who were on oral morphine at admission to hospital required significantly raised morphine dosages while receiving palliative treatment. The other patients did not need significant changes of opioid medication. Pain reduction persisted even after discharge. CONCLUSION: In patients with advanced cancer the effects of psychological, social and spiritual factors on their perception of pain is probably of greater importance in achieving efficacious pain reduction than a change of medication. Further studies will be needed to confirm these findings.
Aged↗
Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).
PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.
Adult↗
[Strong opioids and constipation].
In cancer pain therapy treatment with strong opioids is essential. However, it may be accompanied by the occurrence of various adverse effects. The most frequent and persistent side effect in the course of opioid treatment is constipation. It is mainly caused by linkage of the opioid to the peripheral mu-receptors in the bowel and may increase as a result of certain concomitant circumstances, such as poor intake of fluids or electrolyte disorder. Present research indicates that there is a relation between type of opioid and degree of constipation, i.e. treatment with transdermal fentanyl or methadone tends to cause less constipation compared to morphine or hydromorphone. The route of administration of morphine--oral vs. subcutaneous--does not seem to affect the incidence of opioid-induced constipation. Furthermore, prophylaxis and efficient control of opioid-induced constipation still fail to be part of the routine in pain treatment.
Analgesics, Opioid↗
Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.
Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.
Adolescent↗
Binding of the cGMP-gated channel to the Na/Ca-K exchanger in rod photoreceptors.
The intracellular Ca(2+) concentration in rod outer segments of vertebrate photoreceptors is controlled by Ca(2+) influx through cGMP-gated channels and by Ca(2+) efflux driven by Na/Ca-K exchangers. Previously, we suggested that channel and exchanger are associated (Bauer, P. J., and Drechsler, M. (1992) J. Physiol. (Lond. ) 451, 109-131). This suggestion has been thoroughly examined using a variety of biochemical approaches. First, we took advantage of the fact that cGMP-gated channels bind calmodulin (CaM). Using CaM affinity chromatographic purification of the channel in 10 mm CHAPS, a significant fraction of exchanger was co-eluted with the channel indicating a binding affinity between channel and exchanger. Binding of channel and exchanger was examined more directly by cross-linking of proteins in the rod outer segment membranes. Activation of the channel with cyclic 8-bromo-GMP lead to exposure of a cysteine, which allowed cross-linking of the channel to the exchanger with the thiol-specific reagent dl-1,4-bismaleimido-2,3-butanediol. Cleavage of the cross-links and electrophoretic analysis indicated that a cross-link between the alpha-subunit of the channel and the exchanger formed. Furthermore, a cross-link between two adjacent alpha-subunits of the channel was found, suggesting that the alpha-subunits of the native channel are dimerized. Further support for an interaction between alpha-subunit and exchanger was obtained by in vitro experiments. Specific binding of the exchanger to the alpha-subunit but not to the beta-subunit of the channel was observed in Western blots of purified channel incubated with purified exchanger. This study suggests that two exchanger molecules bind to one cGMP-gated channel and, more specifically, that binding of exchanger molecules occurs at the alpha-subunits, which in the native channel are dimerized. The implications of these findings regarding the possibility of local Ca(2+) signaling in vertebrate photoreceptors will be discussed.
Animals↗
Direct evidence of Na+/Ca2+ exchange in squid rhabdomeric membranes.
Na+/Ca2+ exchange has been investigated in squid (Loligo pealei) rhabdomeric membranes. Ca2+-containing vesicles have been prepared from purified rhabdomeric membranes by extrusion through polycarbonate filters of 1-micrometer pore size. After removal of external Ca2+, up to 90% of the entrapped Ca2+ could be specifically released by the addition of Na+; this finding indicates that most of the vesicles contained Na+/Ca2+ exchanger. The Na+-induced Ca2+ efflux had a half-maximum value (K1/2) of approximately 44 mM and a Hill coefficient of approximately 1.7. The maximal Na+-induced Ca2+ efflux was approximately 0.6 nmol Ca2+. s-1. mg protein-1. Similar Na+-induced Ca2+ effluxes were measured if K+ was replaced with Li+ or Cs+. Vesicles loaded with Ca2+ by Na+/Ca2+ exchange also released this Ca2+ by Na+/Ca2+ exchange, suggesting that Na+/Ca2+ exchange operated in both forward and reverse modes. Limited proteolysis by trypsin resulted in a rate of Ca2+ efflux enhanced by approximately fivefold when efflux was activated with 95 mM NaCl. For vesicles subjected to limited proteolysis by trypsin, Na+/Ca2+ exchange was characterized by a K1/2 of approximately 25 mM and a Hill coefficient of 1.6. For these vesicles, the maximal Na+-induced Ca2+ efflux was about twice as great as in control vesicles. We conclude that Na+/Ca2+ exchange proteins localized in rhabdomeric membranes mediate Ca2+ extrusion in squid photoreceptors.
Animals↗
Recombinant human megakaryocyte growth and development factor (MGDF) increases the numbers of megakaryocyte progenitor cells to normal values in long-term bone marrow cultures of patients with AML in first remission.
The megakaryopoietic potential in the bone marrow (BM) of patients in first remission after treatment for acute myelogenous leukaemia (AML) was investigated using long-term bone marrow cultures (LTC) stimulated with megakaryocyte growth and development factor (MGDF). The baseline number of megakaryocyte colony-forming cells (Meg-CFC) was very low. However, there was a 10 to 100-fold increase of Meg-CFC in cultures treated with 10 ng/ml MGDF with mean numbers within the normal range for the first 4 weeks of culture with a 24-fold increase in their cumulative numbers. Similarly, a 12-fold increase in the numbers of megakaryocytes (MKs) was found by CD61 immunostaining. These effects were lost at the dose of 100 ng/ml. In contrast, the cumulative mean numbers of Meg-CFC in the control cultures from normal bone marrow (NBM) were not significantly different from those in cultures treated with 10 or 100 ng/ml MGDF. These results demonstrate that MGDF stimulates megakaryocytopoiesis in patients with AML in first remission, restoring the Meg-CFC compartment to normal values, a result with potential clinical implications for their treatment with autologous transplantation.
Adult↗
The Na/Ca-K exchanger of rod photoreceptor exists as dimer in the plasma membrane.
The oligomeric state of the Na/Ca-K exchanger in the plasma membrane of bovine photoreceptors was investigated using chemical cross-linking techniques. In the natural membrane, virtually all Na/Ca-K exchanger could be cross-linked mainly to a complex having an apparent molecular mass of 490 kDa by cupric phenanthroline catalyzed disulfide bonding as evidenced by Western blotting. Stable cross-links of the exchanger were also obtained with the thiol-specific reagent N,N'-p-phenylidenedimaleimide. Neuraminidase treatment reduced the apparent molecular mass of the highly glycosylated Na/Ca-K exchanger and of the 490 kDa cross-link product by 50 and 85 kDa, respectively. DL-1,4-Bismaleimido-2,3-butanediol (BMBD), a novel cleavable dimaleimide, was synthesized in order to produce cross-links that were stable to reductive conditions. Purification of the BMBD cross-linked exchanger followed by two-dimensional SDS polyacrylamide electrophoresis identified the cross-linked homodimers of the exchanger. There was no indication of higher oligomers, suggesting that the exchanger exists as a dimer in the plasma membrane. Hydrodynamic properties of the detergent-solubilized exchanger were determined by velocity sedimentation and gel filtration chromatography. The Triton X-100-solubilized exchanger ran as a single species having a Stokes radius of 10.0 nm, a sedimentation coefficient of 5.4 S, and a partial specific volume of 0.74 mL/g in Triton X-100. Similar results were obtained for the CHAPS-solubilized exchanger. A molecular mass of 236 and 205 kDa was calculated for the exchanger-detergent complex and the detergent-free protein, respectively. Neuraminidase treatment further reduced the molecular mass of the exchanger indicating that glycosylation contributes significantly to the mass of the exchanger. Cross-links of the exchanger were not detected if cross-linking was attempted after solubilization in 10 mM CHAPS. However, after reconstitution of the purified exchanger into soybean phosphatidylcholine vesicles, chemical cross-linking yielded again dimers. On the basis of these cross-linking and hydrodynamic studies, we conclude that the exchanger exists as a homodimer in the rod outer segment plasma membrane but dissociates into a monomer when solubilized in detergent.
Animals↗
Fictional women physicians in the nineteenth century: the struggle for self-identity.
By the late nineteenth century, there were large numbers of women physicians in the United States. Three Realist novels of the time, Dr. Breen's Practice, by William Dean Howells, Dr. Zay, by Elizabeth Stuart Phelps and A Country Doctor, by Sarah Orne Jewett, feature women doctors as protagonists. The issues in these novels mirrored current issues in medicine and society. By contrasting the lives of these fictional women doctors to their historical counterparts, it is seen that, while the novels are good attempts to be truthful treatments of women physicians' struggles, in certain areas they do not accurately address the concerns of women physicians.
History, 19th Century↗
Construction of L-lysine-overproducing strains of Brevibacterium lactofermentum by targeted disruption of the hom and thrB genes.
The mobilization of plasmids from gram-negative Escherichia coli to gram-positive Brevibacterium lactofermentum, mediated by P-type transfer functions, was used to construct disrupted mutants blocked specifically in the homoserine branch of the aspartate pathway. The mutant strain B. lactofermentum R31 showed an efficiency of conjugal transfer two to three orders of magnitude higher than that of the wild-type strain B. lactofermentum ATCC 13869. The hom- and thrB-disrupted mutants of B. lactofermentum ATCC 13869 were lysine overproducers. B. lactofermentum R31 mutants do not overproduce lysine because R31 is an alanine-overproducing strain and channels the pyruvate needed for lysine biosynthesis to the production of alanine.
Alanine↗
[Chronic myeloid leukemia--a rare cause of labyrinth apoplexy].
BACKGROUND: Cochleovestibular lesions in patients with acute myeloid leukemia or the blastic phase of chronic myeloid leukemia are usually due to leukemic infiltration, infection or hemorrhage. In contrast, the most likely cause of cochleovestibular lesions in the chronic phase of the chronic myeloid leukemia seems to be disturbed microvascular perfusion and vascular occlusion. CASE REPORT: A 45-year old patient with a chronic myeloid leukemia presented with the sudden onset of profound deafness in his right ear combined with a total loss of vestibular function on the same side. The hemoglobin count was 10.5 g/dl; the white blood cell count 448 x 10(9)/I; the platelet count 71 x 10(9)/I. All of the plasmatic coagulation factors were in the normal range. The patient was treated with cytostatic drugs and responded well (rapid cytoreduction), but the deafness persisted. DISCUSSION: Cochleovestibular lesions in the chronic phase of the chronic myeloid leukemia are very rare. The most likely cause in the case described above seems to be increased blood viscosity due to the high white cell count and alterations in the leukocyte rheology (leukostasis syndrome). CONCLUSION: In patients with leukemia and acute cochleovestibular lesions in contrast to other patients with sudden deafness and/or sudden loss of peripheral vestibular function, a combination of chemotherapy and leukopheresis capable of rapid cytoreduction is necessary, whereas a conventional hemorrheologic therapy seems to be insufficient.
Cerebrovascular Disorders↗
Guillain Barré syndrome, a possible side effect of buffy coat transfusion and IFN alpha therapy in relapsed CML after bone marrow transplantation.
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Adult↗
Facet joint pain.
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Adrenal Cortex Hormones↗
Cloning and characterization of a DNA region encoding a stress-sensitive restriction system from Corynebacterium glutamicum ATCC 13032 and analysis of its role in intergeneric conjugation with Escherichia coli.
RP4-mediated transfer of mobilizable plasmids in intergeneric conjugation of Escherichia coli donors with Corynebacterium glutamicum ATCC 13032 is severely affected by a restriction system in the recipient that can be inactivated by a variety of exogenous stress factors. In this study a rapid test procedure based on intergeneric conjugal plasmid transfer that permitted the distinction between restriction-negative and restriction-positive C. glutamicum clones was developed. By using this procedure, clones of the restriction-deficient mutant strain C. glutamicum RM3 harboring a plasmid library of the wild-type chromosome were checked for their restriction properties. A complemented clone with a restriction-positive phenotype was isolated and found to contain a plasmid with a 7-kb insertion originating from the wild-type chromosome. This plasmid, termed pRES806, is able to complement the restriction-deficient phenotype of different C. glutamicum mutants. Sequence analysis revealed the presence of two open reading frames (orf1 and orf2) on the complementing DNA fragment. The region comprising orf1 and orf2 displayed a strikingly low G+C content and was present exclusively in C. glutamicum strains. Gene disruption experiments with the wild type proved that orf1 is essential for complementation, but inactivation of orf2 also resulted in a small but significant increase in fertility. These results were confirmed by infection assays with the bacteriophage CL31 from Corynebacterium lilium ATCC 15990.
Adaptation, Biological↗
Comparison of keratan sulphate concentrations and the size distribution of proteoglycans in the synovial fluid of patients with osteoarthritis and pyrophosphate arthropathy.
In order to evaluate the effect of calcium pyrophosphate dihydrate (CPPD) deposition on articular cartilage catabolism, the proteoglycans released into normal synovial fluid were compared with those in synovial fluid obtained from patients with osteoarthritis (OA), chronic pyrophosphate arthropathy (CPA) and acute pyrophosphate arthropathy (APA). Keratan sulphate (KS) was measured by the modified 1,9-dimethylmethylene blue (DMB) assay in synovial fluids treated with chondroitin ABC lyase. This enzyme was found to eliminate all of the sulphated glycosaminoglycans in synovial fluid except KS. In OA, CPA and APA the concentrations of KS were found to be significantly higher than in normal synovial fluid (NSF) (P less than 0.01). Similar KS concentrations were observed in CPA and APA. In CPA they were significantly higher than in OA (P less than 0.02). The size distribution of proteoglycan fragments varied between different patients with the same disease, but only minor differences were observed in patients with OA and CPA who were matched for age, sex and disease severity. Furthermore, the size distribution of proteoglycan fragments in the acute and chronic phases of pyrophosphate arthritis was similar. Thus although in pyrophosphate arthritis the rate at which proteoglycans are released from the cartilage may be greater than in OA or normal joints, the fundamental processes governing the release of these macromolecules may be the same.
Adult↗
Manipulation of Corynebacterium glutamicum by gene disruption and replacement.
We have developed a system for the genetic manipulation of the amino acid-producing Corynebacterium glutamicum. Gene disruption and replacement were achieved by introducing, via conjugation, Escherichia coli vector plasmids carrying manipulated C. glutamicum DNA fragments. We obtained stable mutants in which the chromosomal lysA gene, encoding meso-diaminopimelate decarboxylase, was interrupted by a chloramphenicol resistance cartridge, or in which an essential internal part of the lysA gene was deleted. The deletion mutants retain neither antibiotic resistance markers nor vector sequences. This strategy is generally applicable to the construction of industrial strains to be used in fermentation processes.
Chromosome Deletion↗