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Biomedical subjects

S Becker

Publications and source records attributed to S Becker.

At least 37 records · Page 2Linked to original sources

Evaluation of red blood cell deformability and uterine blood flow in pregnant women with preeclampsia or iugr and reduced uterine blood flow following the intravenous application of magnesium.

OBJECTIVE: Red blood cells (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), RBC deformability and, consequently, microcirculation appear to be impaired. Magnesium sulfate is administered to reduce the risk of seizures in PE. The aim of our study was to detect the effect of 24-hour intravenous (IV) magnesium on RBC deformability and on uterine artery blood flow in pregnant patients with preeclampsia or IUGR and pathologic uterine blood flow. METHODS: Magnesium IV (1 g/h) was administered to 25 pregnant women with reduced uterine blood flow for a period of at least 24 hours. The RBC deformability was measured by uterine artery Doppler. Measurements were taken before the start of magnesium therapy and 24 h later. Magnesium plasma levels were measured at the same time. RESULTS: High plasma levels of magnesium improve RBC deformability from E = 0.109 (SD +/- 0.023) to E = 0.115 (SD +/- 0.021) after 24 h IV magnesium (p = 0.043). There is no correlation of E to the plasma magnesium level either before or after 24 h magnesium treatment. Blood volume flow in the uterine arteries increased significantly from 5.09 mL/s (SD +/- 3.03) to 10.02 mL/s (SD +/- 5.86) after 24 h magnesium (p = 0.0002). The differences in the resistance index do not significantly differ from 0 (p = 0.46). CONCLUSION: A high IV dosage of magnesium over a period of 24 hours dilates the uterine arteries of pregnant women with PE and/or IUGR, reduces uterine blood flow and improves the deformability of RBC. Both parameters enhance the oxygen supply to the fetus, a clinical parameter in these pregnancies. Thus magnesium might not only be effective as phrophylaxis against seizures but also in cases of IUGR with a reduced uterine blood flow. The clinically observed beneficial effect of magnesium in PE could be due to the improved blood supply for the fetus.

Adult↗

Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients.

OBJECTIVES: To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts <500 cells/microL following 48 weeks of highly active antiretroviral therapy (HAART). METHODS: Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus. RESULTS: HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/microL to a week-48 median of 617 cells/microL. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and 36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/microL at week 48. Both soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6400 copies/microg at baseline to a week-48 median value of 26 697 copies/microg. CONCLUSION: Immune functional reconstitution was not achieved in these HAART naive patients.

Adult↗

Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer.

INTRODUCTION: To minimize the surgical morbidity after lymphadenectomy, sentinel node biopsy (SLNB) has become fundamental in the management of different malignancies. We decided to evaluate sentinel lymph node (SNL) biopsies also in patients with endometrial cancer undergoing hysterectomy with lymphadenectomy. METHODS: In the setting of a prospective study we developed a technique for sentinel node biopsy of ten patients with histologically confirmed endometrial cancer. Prior to surgery 99m Tc Nanocol was injected in the peritumoral region by hysteroscopy. Six hours later lymphoscintigraphy was performed to identify the draining lymph nodes. During surgery we first detected the sentinel lymph node by a hand-held gamma tracer and then removed it. Surgery was completed by the standard therapy of total hysterectomy, bilateral salpingo-oophorectomy and pelvic and/or para-aortic lymphadenectomy. RESULTS: Scintigraphic identification was possible in eight out of ten patients. Intraoperative identification of sentinel lymph nodes was possible in seven out of eight patients. In five patients we found the sentinel lymph nodes in the pelvic region while the other two patients had bilateral sentinel nodes in the pelvic and para-aortic region. Histologically confirmed microscopic tumor metastases of the SLNs and para-aortic lymph nodes were only found in one case. The sentinel lymph nodes from the other six patients were free of tumor and accurately reflected the pathological status. CONCLUSION: The identification of sentinel lymph nodes in endometrial cancer is a practical and safe method. In order to improve this technique as a standard procedure for staging of endometrial cancer further studies with a larger number of patients have to be done.

Adenocarcinoma, Clear Cell↗

Integration of study material in the problem-based learning method.

Throughout the world educators are starting to realise that integrated curricula reflect the "real world". Students learn how to integrate theory appropriately with practice and it stimulates higher order thinking skills. Problem-based learning (PBL) was used as a learning strategy in an integrated undergraduate programme. A quantitative non-experimental design, a survey, was used to determine how problem-based learning influences integration of learning by the students. Using a purposive sampling method all the first-year nursing students (43) at the University of the Free State participating in the programme were included in the study. Data was collected by means of a student perception questionnaire (SPQ). PBL does contribute to an integration of learning. All the students agreed that community problems were brought to the classroom and that theory and practice were complementary. Students also indicated that PBL enhanced gathering of information from various sources and a holistic view of a situation. Problem-based learning also increased the ability to consider problems from various viewpoints and taught students clinical reasoning. Certain aspects of integration still seem to be a problem as 42% of the students indicated that subjects were not related, 21% that subjects were not integrated and 37% that scenarios were not realistic. This might be attributed to the fact that only the nursing subjects were taught by means of PBL. It is recommended that scenarios be revised to make them more realistic and that traditional subjects such as Anatomy, Microbiology and Chemical Science be integrated with nursing subjects by means of problem-solving themes, to form a meaningful core curriculum.

Adult↗

[Haemorrhagic cellulitis: three cases].

BACKGROUND: Haemorrhagic erysipelas (cellulitis) is a recently described clinical condition. We report 3 new cases of this rare bacterial dermatosis requiring both antibiotics and systemic corticosteroids for complete resolution. CASE REPORTS: Case 1 was a 75 year-old male patient, with a past history of hypertension and diabetes mellitus. Case 2 was a 69 year-old female patient with a past history of hepatic cirrhosis. Case 3 was a 56 year-old female patient without medical past history, except for obesity. All patients presented with a haemorrhagic and bullous erysipelas of the leg without clinical improvement under parenteral antibiotics. In all cases, adjuvant systemic corticosteroids (prednisone: 0.5 mg/kg/d) for 5-8 days in addition to antibiotics provided dramatic and complete resolution of skin lesions and disappearance of pain and fever. DISCUSSION: Haemorrhagic cellulitis may be misdiagnosed as necrotizing fasciitis because of ecchymotic areas with frequent bullae resulting in haemorrhagic crusts and partial inefficacy of antibiotics given alone. Adjuvant anticoagulant therapy or coagulation abnormalities may have facilitated the clinical condition in 2 of our 3 cases. The efficacy of adjuvant systemic corticosteroids during 5-8 days, in addition to antibiotics is the hallmark of this syndrome.

Aged↗

Low frequency of enteric infections by Salmonella, Shigella, Yersinia and Campylobacter in patients with acute leukemia.

BACKGROUND: Several authors found that isolation of Salmonella, Shigella, Yersinia and Campylobacter spp. (SSYC) from stool cultures after the 3rd day of hospitalization is a rare event. The significance of enteric infections caused by these pathogens has not been systematically investigated in severely immunosuppressed patients with acute leukemia. PATIENTS AND METHODS: We screened all patients treated on the leukemia ward of a university medical center. A total of 1,185 stool cultures from 371 episodes of diarrhea, mostly following myelosuppressive chemotherapy, were examined for the complete range of classic bacterial enteric pathogens (i.e. SSYC). RESULTS: Only three (0.25%) cultures from one patient were positive for Salmonella enteritidis. This patient suffered from cholangitis. S. enteritidis could also be detected by liver biopsy. Other infections by classic enteric pathogens were not observed. CONCLUSION: Symptomatic infections by classic bacterial enteric pathogens in hospitalized patients with acute leukemia are very rare. Stool cultures for these pathogens cannot be recommended as a routine test in uncomplicated diarrhea occurring after the 3rd hospital day.

Acute Disease↗

Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages.

It has been proposed that oxidant stress of cells in the lung is one of the underlying mechanisms of particulate pollution-induced exacerbation of lung disease. Individuals who are considered most sensitive to particulate pollution are those with pre-existing airways inflammation, such as chronic obstructive pulmonary disease (COPD), lung infection or asthma. These diseases are characterized by a presence of inflammatory cells in the airways including neutrophils (PMN), eosinophils and monocytes (Mo), and increased numbers of alveolar macrophages (AM). These cells have a high capacity for production of oxygen radicals, as compared to other cell types of the lung. To assess the oxidative response of these various cell types to pollution particles of various sources, luminol-dependent chemiluminescence was employed. Particles including transition metal-rich residual oil fly ashes (ROFAs), coal fly ashes, diesel, SiO2, TiO2 and fugitive dusts were co-cultured with AM, Mo and PMN in a dose range of 10-100 microg/2 x 10(5) cells and chemiluminescence determined following a 20-min interaction. A strong oxidant response of AM was restricted to oil fly ashes, while the PMN were most reactive to the dusts containing aluminium silicate. In general, the Mo response was less vigorous, but overlapped both AM- and PMN-stimulating dusts. However, in response to SiO2 and volcanic ash the Mo chemiluminescence exceeded that of the other cell types. Oxygen radicals generated in response to ROFA by the AM were likely to be dependent on mitochondrial processes, while the response in PMN involved the membrane NADPH oxidase complex, as determined by targeting inhibitors. The response of AM to SiO2 of various sizes and TiO2 in the fine size range obtained from different commercial sources, was highly variable, implying that composition rather than size was responsible for the oxidant response. A strong chemiluminescence response was not consistently associated with cytotoxicity in the responsive cell. Taken together, these results suggest that oxidant activation by various sources of particulate matter is cell specific. Therefore, the inflamed lung is likely to be more susceptible to harm of ambient air particulates because of the oxidant stress posed by a broader range of particles.

Adult↗

A marine bioassay test set to assess marine water and sediment quality-its need, the approach and first results.

There is a need for establishing a marine bioassay test set to assess marine water and sediment samples in Germany. The selected marine bioassay test set, two tests for the water phase (with the luminescence bacteria Vibrio fischeri and the algae Phaeodactylum tricornutum Bohlin) and a whole sediment test with the marine amphipod Corophium volutator (Pallas) is described and first results are shown.

Amphipoda↗

Modified magnetic resonance imaging score compared with orthopaedic and radiological scores for the evaluation of haemophilic arthropathy.

Twenty-four joints (10 knees and 14 ankles), with at least one manifestation of bleeding (proven by sonographic assessment), of 15 patients with haemophilia were investigated prospectively. For magnetic resonance imaging (MRI) evaluation, the MRI scale of Nuss et al. was modified to a MRI score (max. 13 points/joint) to allow a comparison with the physical examination score (max. 12 points) and the radiological score (Pettersson score; max. 13 points). The number of joint bleeds correlated well with the degree of arthropathy P < 0.01). In all 16 joints with a maximum of two bleeds, no alterations were found by physical examination, or radiological and MRI assessment. Joints with three bleeds had physical examination scores between 0 and 2, Pettersson scores from 0 to 3 and MRI scores of 2. Joints with four or more bleeds had physical examination scores ranging between 3 and 7, radiological scores between 7 and 12 and MRI scores between 3 and 8. The MRI score describes initial joint alterations more precisely and earlier than other assessments, allowing a discerning estimation of the degree of arthropathy, as well as a follow-up of haemophilic arthropathy and an improvement after change of treatment. In addition, the modified MRI score seems to differentiate better between early and advanced signs of arthropathy than the MRI scale of Nuss et al.

Adolescent↗

Clinically significant persistence and enlargement of an antenatally diagnosed isolated choroid plexus cyst.

Isolated choroid plexus cysts are usually diagnosed at the time of screening ultrasonography during the second trimester. While they raise the question of underlying chromosomal abnormalities, their clinical course is almost invariably benign with complete resolution often by the third trimester. We report the highly unusual case of a choroid plexus cyst diagnosed at 14 weeks of gestational age with subsequent further enlargement of the cyst, necessitating postpartum neurosurgical intervention.

Adult↗

[Driving capacity of diabetics against the background of legal principles].

Within the conversion of the 2nd Council Directive on Driving Licences of the Council of the European Communities (91/439/EEC) into national law, changes became necessary to the Road Traffic Act (StVG) and a new Driving Licence Ordinance (FeV) was created which has been in force since 01.01.1999 (Federal Law Gazette, 1998, Part I No. 55, 26. August 1998). Both in Annex III of the EC Directive and in Annex 4 of the Driving Licence Ordinance, statements are made with regard to the driving capability of diabetics. Besides this legal basis for evaluating capacity to drive a motor vehicle, the appraisal guidelines (Begutachtungs-Leitlinien zur Kraftfahrereignung) established in commission of the German Federal Ministry of Transport, Building and Housing are to be understood as a set of rules which are outside the framework of actual legal statute as such and which are intended to support assessors in making decisions in individual cases. When considering whether an appraisal of driving capacity has to take place, in particular a difference is made between the different classes of vehicle. For motor cycles and passenger cars (Classes A and B), it will also be the case in future that a medical examination will only be ordered if there is a specific reason. Apart from this, only a sight test is necessary, as has been the practice up to now. In the case of lorries and buses (Classes C and D) and the licence for transportation of passengers (on a commercial basis) there will be an initial appraisal, as has also been the case up to now, and there will also be repeat appraisals. This is new for Class C, where up to the present there has only been an initial appraisal. The basic principle which applies is that the driving licence authority has the duty to instigate appraisal of the driving capacity of an applicant for a driving licence or of the holder of a driving licence if there is justified doubt about the driving capacity of the person concerned.

Automobile Driver Examination↗

Generation and characterization of human hematopoietic cell lines expressing factor VIII.

Considering the plasticity of hematopoietic stem cells (HSC), they would be ideal targets for gene therapy of hemophilia A by virtue of their progeny providing immediate access to the bloodstream. However, several attempts to show expression of recombinant factor VIII (rFVIII) by primary hematopoietic cells and cell lines have failed; this failure was attributed to the inability of HSC to secrete rFVIII. Here we describe the generation of stable, FVIII-secreting hematopoietic cell lines representing different blood-cell types using a bicistronic lentiviral vector encoding for a B-domain-deleted FVIII (FVIII Delta B) and enhanced green fluorescence protein (EGFP). Transduced cell lines with erythroid and/or megakaryocytic background, (K562-F8 and TF-1-F8) secrete high levels of FVIII in the order of 76.4 and 41.6 ng FVIII:C/ml, whereas moderate and low levels are observed in B lymphoblastoid Raji-F8 cells and the T leukemia line Jurkat-F8 which secrete 6.73 and 1.83 ng FVIII:C/ml, respectively. The capacity to secrete rFVIII appeared to depend on factors related to the cell lineage rather than on the transduction efficacy. Stimulation of transduced cells with the protein kinase C (PKC)-activator phorbol myristate acetate (PMA) resulted in a marked augmentation of rFVIII secretion and enhanced green fluorescent protein (EGFP). Incubation with 0.1 and 1 ng/ml PMA resulted in up to 2.7-fold (K562-F8, Raji-F8) and 1.8-fold (293T-F8) increased rFVIII secretion. The established cell lines should be helpful in further elucidating mechanisms that are able to improve FVIII secretion in hematopoietic cells on a post-translational level and suggest reanalysis of hematopoietic cells as target for gene therapy of hemophilia.

Base Sequence↗

[Submicroscopic characteristics of Marburg virus and its mini genome analog replication in cell cultures].

Marburg virus (Filoviridae) causes severe hemorrhagic fevers in humans and some lower primates with high mortality. The virus genome is formed by a single strand RNA of negative polarity, coding for seven structural proteins. We studied the ultrastructure of Marburg virus replicative cycle and replication of its minigenome RNA (coding for the terminal areas of the genome) in the presence of helper virus in VERO fibroblastoid cell culture and epithelioid MDCK cell culture. Ultrastructural parameters of Marburg virus multiplication in these cell cultures are virtually the same. The virus nucleocapsid assembly is performed on the outer side of EPR membrane and is not associated with preliminary accumulation of the precursor material. Virions form by budding on plasmalemma and are located on the entire surface in Vero cells and only on the basolateral surface of MDCK cells. Replication of minigenome analog of marburg virus is associated with impairment of the helper virus morphogenesis and formation of spherical pseudoviral particles.

Animals↗

Memory for events and their spatial context: models and experiments.

The computational role of the hippocampus in memory has been characterized as: (i) an index to disparate neocortical storage sites; (ii) a time-limited store supporting neocortical long-term memory; and (iii) a content-addressable associative memory. These ideas are reviewed and related to several general aspects of episodic memory, including the differences between episodic, recognition and semantic memory, and whether hippocampal lesions differentially affect recent or remote memories. Some outstanding questions remain, such as: what characterizes episodic retrieval as opposed to other forms of read-out from memory; what triggers the storage of an event memory; and what are the neural mechanisms involved? To address these questions a neural-level model of the medial temporal and parietal roles in retrieval of the spatial context of an event is presented. This model combines the idea that retrieval of the rich context of real-life events is a central characteristic of episodic memory, and the idea that medial temporal allocentric representations are used in long-term storage while parietal egocentric representations are used to imagine, manipulate and re-experience the products of retrieval. The model is consistent with the known neural representation of spatial information in the brain, and provides an explanation for the involvement of Papez's circuit in both the representation of heading direction and in the recollection of episodic information. Two experiments relating to the model are briefly described. A functional neuroimaging study of memory for the spatial context of life-like events in virtual reality provides support for the model's functional localization. A neuropsychological experiment suggests that the hippocampus does store an allocentric representation of spatial locations.

Animals↗

Phosphorylation of Marburg virus VP30 at serines 40 and 42 is critical for its interaction with NP inclusions.

The Marburg virus (MBGV) nucleocapsid complex is composed of four viral proteins (NP, L, VP35, and VP30) and the negative-strand nonsegmented genomic RNA. NP, L, and VP35 are functionally conserved among the order Mononegavirales, whereas VP30, a phosphoprotein, represents a filovirus-specific nucleocapsid protein. In the present paper, we have characterized the localization and function of VP30 phosphorylation. The main phosphorylation sites are represented by seven serine residues in the region of amino acid 40 to 51 of VP30. Additionally, trace amounts of phosphothreonine were detected. Substitution of serine residues 40 and 42 by alanine abolished the interaction of VP30 with NP-induced inclusion bodies, which contain nucleocapsid-like structures formed by NP. Substitution of the other phosphoserine residues had little effect on this interaction. Replacement of the introduced alanine residues 40 and 42 by aspartate restored the interaction between VP30 and the NP inclusions pointing to the importance of negative charges at these particular positions.

Alkaline Phosphatase↗

Thymidine analog and multinucleoside resistance mutations are associated with decreased phenotypic susceptibility to stavudine in HIV type 1 isolated from zidovudine-naive patients experiencing viremia on stavudine-containing regimens.

Studies have demonstrated that HIV-1 isolated from subjects experiencing virologic failure on stavudine (d4T)-containing regimens often contains thymidine analog mutations (TAMs), consisting of reverse transcriptase (RT) mutations M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E, previously associated only with zidovudine (ZDV) resistance. In clinical study NZT40012, HIV-1 was isolated from 86 ZDV-naive subjects experiencing viremia on d4T-based therapies (plasma HIV-1 RNA > or =1000 copies/ml) and analyzed to examine the association between RT mutations and phenotypic resistance to d4T. Resistance-associated mutations were analyzed from HIV-1 isolated from 85 subjects. Of these, 24 samples (28%) had TAMs, and 30 samples (35%) had either TAMs and/or the Q151M multinucleoside resistance (MNR) mutation. Phenotypic susceptibility to d4T was determined by two commercially available methods. Statistically significant increases (p < 0.001) in phenotypic fold resistance to d4T were observed in virus with at least one TAM or MNR mutation. However, the mean increases in phenotypic resistance were 4-fold for the Antivirogram assay and 3-fold for the Phenosense HIV assay, only slightly above the levels used to designate decreased susceptibility to d4T. Subjects can experience viremia on d4T-containing regimens with virus exhibiting only small increases in IC(50), suggesting that relatively small changes in viral susceptibility to d4T may influence drug efficacy.

Anti-HIV Agents↗