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Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 91 records · Page 5Linked to original sources
PubMed2001

Homeopathy and conventional medicine: an outcomes study comparing effectiveness in a primary care setting.

BACKGROUND: Recent meta-analyses of randomized controlled trials in homeopathy have suggested that homeopathy is more than a placebo response. OBJECTIVE: Comparison of the effectiveness of homeopathy in primary care with conventional medicine in primary care for three commonly encountered clinical conditions. DESIGN: An international multicenter, prospective, observational study in a real world medical setting comparing the effectiveness of homeopathy with conventional medicine. PARTICIPANTS: Thirty (30) investigators with conventional medical licenses at six clinical sites in four countries enrolled 500 consecutive patients with at least one of the following three complaints: (1) upper respiratory tract complaints including allergies; (2) lower respiratory tract complaints including allergies; or (3) ear complaints. MAIN OUTCOME MEASURES: The primary outcomes criterion was the response to treatment, defined as cured or major improvement after 14 days of treatment. Secondary outcomes criteria were: (1) rate of recovery; (2) occurrence of adverse events; (3) patient satisfaction; and (4) length of consultation. RESULTS: Four hundred and fifty-six (456) patient visits were compared: 281 received homeopathy, 175 received conventional medicine. The response to treatment as measured by the primary outcomes criterion for patients receiving homeopathy was 82.6%, for conventional medicine it was 68%. Improvement in less than 1 day and in 1 to 3 days was noted in 67.3% of the group receiving homeopathy and in 56.6% of those receiving conventional medicine. The adverse events for those treated with conventional medicine was 22.3% versus 7.8% for those treated with homeopathy. Seventy-nine percent (79.0%) of patients treated with homeopathy were very satisfied and 65.1% of patients treated with conventional, medicine were very satisfied. In both treatment groups 60% of cases had consultations lasting between 5 and 15 minutes. CONCLUSIONS: Homeopathy appeared to be at least as effective as conventional medical care in the treatment of patients with the three conditions studied.

Adolescent↗
PubMed2001

The wheat cDNA LCT1 generates hypersensitivity to sodium in a salt-sensitive yeast strain.

Salinity affects large areas of agricultural land, and all major crop species are intolerant to high levels of sodium ions. The principal route for Na(+) uptake into plant cells remains to be identified. Non-selective ion channels and high-affinity potassium transporters have emerged as potential pathways for Na(+) entry. A third candidate for Na(+) transport into plant cells is a low-affinity cation transporter represented by the wheat protein LCT1, which is known to be permeable for a wide range of cations when expressed in yeast (Saccharomyces cerevisiae). To investigate the role of LCT1 in salt tolerance we have used the yeast strain G19, which is disrupted in the genes encoding Na(+) export pumps and as a result displays salt sensitivity comparable with wheat. After transformation with LCT1, G19 cells became hypersensitive to NaCl. We show that LCT1 expression results in a strong decrease of intracellular K(+)/Na(+) ratio in G19 cells due to the combined effect of enhanced Na(+) accumulation and loss of intracellular K(+). Na(+) uptake through LCT1 was inhibited by K(+) and Ca(2+) at high concentrations and the addition of these ions rescued growth of LCT1-transformed G19 on saline medium. LCT1 was also shown to mediate the uptake of Li(+) and Cs(+). Expression of two mutant LCT1 cDNAs with N-terminal truncations resulted in decreased Ca(2+) uptake and increased Na(+) tolerance compared with expression of the full-length LCT1. Our findings strongly suggest that LCT1 represents a molecular link between Ca(2+) and Na(+) uptake into plant cells.

Adaptation, Physiological↗
PubMed2001

Haemophilus influenzae Type b disease among Amish children in Pennsylvania: reasons for persistent disease.

OBJECTIVE: To identify reservoirs of Haemophilus influenzae type b (Hib) pharyngeal carriage and assess barriers to vaccination among 2 Amish communities in Pennsylvania. METHODS: We investigated recent cases, performed community surveys for Hib vaccination coverage and pharyngeal carriage, and administered a questionnaire assessing vaccination knowledge and attitudes to 298 members of 2 Amish communities (A and B) in Pennsylvania and, as a comparison group, 136 non-Amish family members who participated in state immunization clinics. From December 1999 to February 2000, 8 cases of invasive Hib disease occurred among children who were 5 years of age or younger in Pennsylvania. Six of the case-patients were from Amish communities. None of the children had been vaccinated. RESULTS: Among children who were 5 years of age or younger, Hib vaccine coverage was low in the 2 Amish communities: A (9 [28%] of 32) and B (3 [7%] of 41) compared with the non-Amish group (19 [95%] of 20). Hib carriage prevalence was higher in both Amish communities than in the non-Amish group (A: 3%; B: 8%; non-Amish: 0%). More households in community B had 1 or more Hib carriers than in community A (8 [28%] of 29 vs 3 [9%] of 32). Among Amish parents who did not vaccinate their children, only 25% (13 of 51) identified either religious or philosophical objections as a factor; 51% (26 of 51) reported that vaccinating was not a priority compared with other activities of daily life. Seventy-three percent (36 of 49) would vaccinate their children if vaccination were offered locally. CONCLUSIONS: Undervaccinated communities in the United States still exist and allow circulation of Hib strains, resulting in disease among susceptible children. Identification of undervaccinated populations, such as the Amish, and targeted education and vaccination campaigns are essential to achieving elimination of Hib disease.

Adolescent↗
PubMed2001

Student nurses' needs for developing basic study skills.

One of the key responsibilities of the nurse educator is to develop student nurses' abilities regarding self-directed study. Self-directed study requires inter alia, the ability to find information, synthesis and consequent application and integration of the information in practice. The development of the abovementioned skills does not only imply a multidimensional approach to the student in totality, but also requires the meticulous involvement of the student in her/his own learning. The latter also assumes that students possess certain essential skills relevant to learning and studying. From the literature it is evident that secondary schooling in general, does not prepare students adequately for tertiary education. This research intended to find answers to the questions whether student nurses require guidance regarding the development of specifically identified study skills, the guidance provided and whether the guidance provided was sufficient. A descriptive survey was done in order to address the above questions. The research instruments (questionnaires) were completed (during 1997) by nurse educators and student nurses in the Western Cape. On completion of the analysis and interpretation of the data, the researcher concluded that student nurses expressed a need for more guidance regarding the development of basic study skills ant that existing student support programs did not address all these needs adequately. Furthermore, it was concluded that the language medium of the prescribed study material had a profound effect on the learning and study processes of student nurses. Based on the conclusion, various recommendations were made concerning different facets of the teaching/learning event., in order to enhance students' learning and studying skills. Mastery of these skills can be regarded as being important prerequisites for effective, responsible, independent professional practice.

Adult↗
PubMed2001

Vulvodynia: an indicator or even an early symptom of vulvar cancer.

Vulvodynia is a symptom of chronic, painful vulvar discomfort of multicausal origin. Vulvar cancer is an underestimated cause of vulvodynia. Even early stages of vulvar neoplasia can lead to aching lesions. Three cases of vulvar carcinoma eliciting persistent pain have been diagnosed within a 2-year period. In 2 of our case studies, women had antecedent periods of vulvar pruritus of long duration (5 and 20 years, respectively). We conclude that early histologic examination of all visible vulvar lesions is necessary to exclude the presence of malignant vulvar neoplasia.

Aged↗
PubMed2000

Zinc plays a key role in human and bacterial GTP cyclohydrolase I.

The crystal structure of recombinant human GTP cyclohydrolase I was solved by Patterson search methods by using the coordinates of the Escherichia coli enzyme as a model. The human as well as bacterial enzyme were shown to contain an essential zinc ion coordinated to a His side chain and two thiol groups in each active site of the homodecameric enzymes that had escaped detection during earlier studies of the E. coli enzyme. The zinc ion is proposed to generate a hydroxyl nucleophile for attack of imidazole ring carbon atom eight of the substrate, GTP. It may also be involved in the hydrolytic release of formate from the intermediate, 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate, and in the consecutive Amadori rearrangement of the ribosyl moiety.

Amino Acid Sequence↗
PubMed2000

Piracetam versus acetylsalicylic acid in secondary stroke prophylaxis. A double-blind, randomized, parallel group, 2 year follow-up study.

Piracetam has been shown to inhibit platelet aggregation. Therefore, we performed a double-blind, randomized, parallel group study to compare the efficacy of daily 1600 mg piracetam t.i.d. vs. 200 mg acetylsalicylic acid (ASA) t.i.d. in secondary stroke prophylaxis. 563 patients after stroke as confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) were enrolled and received either piracetam or ASA during a 2 year follow-up period. The primary endpoint was the rate of stroke, transient ischaemic attack (TIA), or death from vascular cause. The secondary endpoint was the rate of adverse events leading to a premature discontinuation of the study medication. Patients were visited at home every 3 months and were examined in hospital after 1 and 2 years. At every visit, the platelet function was evaluated. No significant difference and no significant equivalence could be shown for the primary endpoint between the piracetam and the ASA group both in the intention-to-treat and in the per-protocol analysis. However, there was a not significant trend in favor of ASA (11.7 vs. 15.2%). After excluding those patients who did not respond to antiplatelet medication in vitro, however, piracetam and ASA were equivalent in secondary stroke prophylaxis (stroke, TIA, or vascular death 10.1% in the piracetam group vs. 9.7% in the ASA group). Piracetam was significantly superior to ASA in the secondary endpoint (P=0.0039). The data suggest that the overall efficacy of piracetam in secondary stroke prophylaxis is not as good as that of ASA but that piracetam is better tolerated. However, our data furthermore show that nonresponders to pharmacological inhibition of platelet function are more frequent under piracetam therapy and that they may influence the results of large studies on secondary prophylaxis in vascular diseases.

Aspirin↗
PubMed2000

Platelet glycoprotein expression in patients with myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are characterized by a haematopoetic insufficiency that can lead to acute leukemia. A multistep pathogenesis caused by a clonal stem cell defect affecting several differentiation pathways has been proposed for MDS. Contrary to the better characterized alteration of lymphoid and myeloid differentiation, defects in thrombocytopoesis in MDS remain less clear. In the present study, we analyzed the expression of platelet glycoprotein (GP) Ia/IIa, IIb/IIIa, Ib/IX, and IV in 21 MDS patients (12 RA, 2 RARS, 4 RAEB, 1 RAEB-T, 2 CMML) and healthy controls by flowcytometric analysis and quantitation of platelet GP RNA using fluorescence-based PCR. We observed a reduced cell surface expression of GPIb (p<0.01) and GPIIb/IIIa (p<0.01), while GPIa/IIa and GPIV expression was only marginally different between patients and controls. In contrast, there was a two-fold increase of platelet GPIb and GPIIb RNA and a three-fold increase of GPIV RNA among MDS patients. Increased levels of platelet GPIb and GPIIb RNA were significantly more prominent among patients with RAEB(-T)/CMML (p<0. 05) in comparison to patients with RA/RARS. In conclusion, we demonstrate alterations in the cell surface expression and RNA content of platelet GPs in MDS patients. These data are consistent with dysmegakaryocytopoiesis and a defect in thrombocytopoiesis among MDS patients resulting from the clonal stem cell defect in MDS.

Adult↗
PubMed2000

Collective singlet excitations and evolution of raman spectral weights in the 2D spin dimer compound SrCu2(BO3)(2)

Raman light scattering of the two-dimensional quantum spin system SrCu2(BO3)(2) shows a rich structure in the magnetic excitation spectrum, including several well-defined bound state modes at low temperature, and a scattering continuum and quasielastic light scattering contributions at high temperature. The key to the understanding of the unique features of SrCu2(BO3)(2) is the presence of strong interactions between well-localized triplet excitations in the network of orthogonal spin dimers realized in this compound.

Journal Article↗
PubMed2000

Effects of calcium on the discharge pattern of primary and secondary endings of isolated cat muscle spindles recorded under a ramp-and-hold stretch.

The impulse activity of muscle spindles isolated from the cat tenuissimus muscle was investigated under varying concentrations of external calcium (Ca(2+)). The outer capsule of the muscle spindle represents an effective diffusion barrier for Ca(2+) ions since activity changes were strong and rapid only if the capsule was partly removed from the sensory region of the receptor. The impulse activity of both primary and secondary muscle spindle endings was lowered by an increase in the external Ca(2+) concentration from 1.8 mM (normal Ringer's solution) to 2.7 mM and raised by a decrease in the Ca(2+) concentration from 1.8 to 0.9 mM. Primary endings were generally more strongly affected than secondary endings. With primary endings the firing rate changed by 23-52% when the external Ca(2+) concentration was altered by 0.9 mM. With secondary endings the discharge frequency changed by 15-24%. The afferent discharge patterns were obtained under repetitive ramp-and-hold stretches and were analyzed with regard to influences of external Ca(2+) ions on the static and dynamic components of the endings' responses. The stretch sensitivity and the adaptive response of both types of ending increased in the low Ca(2+) solution and decreased in the high Ca(2+) solution, but a specific effect on a single component of the responses to stretch was not observed. These findings indicate an overall change in excitability when the external Ca(2+) concentration was varied. The mechanical properties of the receptor were probably not affected since changes in the Ca(2+) concentration did not elicit a contraction or relaxation of the intrafusal muscle fibers. On the one hand, the observed effects can be explained according to the surface potential theory by an indirect influence of extracellular Ca(2+) ions on ion channels of the sensory nerve terminals, with Ca(2+) ions binding to negative charged sites at the endings' outer membrane. On the other hand, the results are consistent with the supposition that Ca(2+) ions act directly on ion channels of the sensory membrane of muscle spindle endings.

Adaptation, Physiological↗
PubMed2000

Residual HIV-RNA levels persist for up to 2.5 years in peripheral blood mononuclear cells of patients on potent antiretroviral therapy.

The long-term response of 10 asymptomatic, antiretroviral therapy-naive HIV-1-infected patients to potent combination antiretroviral therapy was characterized by monitoring levels of HIV-1 RNA in plasma, peripheral blood mononuclear cells (PBMC), and lymphoid tissue using highly sensitive HIV-1 RNA assays. Although plasma viral loads were continuously suppressed to levels below 50 HIV-1 RNA copies/ml for up to 2.5 years (60-128 weeks), HIV-1 RNA was still detectable at very low levels (1 to 49 HIV-1 RNA copies/ml) in 25% of the samples. In corresponding PBMC specimens, residual HIV-RNA was detectable in as much as 91% of samples tested (1 to 420 HIV-1 RNA copies/microg total RNA). Similarly, HIV-1 RNA levels in lymphoid tissue also remained detectable at a high frequency (86%). A highly significant correlation was demonstrated between therapy-induced change in PBMC HIV-1 RNA levels and change in plasma HIV-1 RNA levels (r2 = 0.69; p = 0.003). These findings support the concept that measurement of HIV-1 RNA in the easily accessible PBMC compartment is relevant for evaluating the potency of current and future antiretroviral therapies.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Biosynthesis of terpenoids: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase from tomato.

The putative catalytic domain (residues 81-401) of a predicted tomato protein with similarity to 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase of Escherichia coli was expressed in a recombinant E. coli strain. The protein was purified to homogeneity and was shown to catalyze the phosphorylation of the position 2 hydroxy group of 4-diphosphocytidyl-2-C-methyl-d-erythritol at a rate of 33 micromol small middle dotmg(-1) small middle dotmin(-1). The structure of the reaction product, 4-diphosphocytidyl-2-C-methyl-d-erythritol 2-phosphate, was established by NMR spectroscopy. Divalent metal ions, preferably Mg(2+), are required for activity. Neither the tomato enzyme nor the E. coli ortholog catalyzes the phosphorylation of isopentenyl monophosphate.

Amino Acid Sequence↗
PubMed2000

The atomic structure of pentameric lumazine synthase from Saccharomyces cerevisiae at 1.85 A resolution reveals the binding mode of a phosphonate intermediate analogue.

Lumazine synthase of Saccharomyces cerevisiae is a homopentamer with a molecular weight of 90 kDa. Crystals of the recombinant enzyme with a size of up to 1.6 mm were obtained. The space group is P4(1)2(1)2 with lattice dimensions 82.9 A x 82.9 A x 300.2 A. X-ray diffraction data collected under cryogenic conditions were complete to 1.85 A resolution. The structure of the enzyme in complex with the intermediate analogue, 5-(6-D-ribitylamino-2,4-dihydroxypyrimidine-5-yl)-1-pentyl-p hosphonic acid was solved via molecular replacement using the structure of the Bacillus subtilis enzyme as search model and was refined to a final R-factor of 19.8% (Rfree: 22.5%). The conformation of the active site ligand of the enzyme mimicks that of the Schiff base intermediate of the enzyme-catalyzed reaction. The data enable the reconstruction of the reactant topology during the early steps of the catalytic reaction. Structural determinants, which are likely to be responsible for the inability of the S. cerevisiae enzyme to form icosahedral capsids, will be discussed.

Amino Acid Sequence↗
PubMed2000

Localization of a short-term memory in Drosophila.

Memories are thought to be due to lasting synaptic modifications in the brain. The search for memory traces has relied predominantly on determining regions that are necessary for the process. However, a more informative approach is to define the smallest sufficient set of brain structures. The rutabaga adenylyl cyclase, an enzyme that is ubiquitously expressed in the Drosophila brain and that mediates synaptic plasticity, is needed exclusively in the Kenyon cells of the mushroom bodies for a component of olfactory short-term memory. This demonstrates that synaptic plasticity in a small brain region can be sufficient for memory formation.

Adenylyl Cyclases↗
PubMed2000

Stripe conductivity in La1.775Sr0.225NiO4

We report Raman light-scattering and optical conductivity measurements on a single crystal of La1.775Sr0.225NiO4 which exhibits incommensurate charge-stripe order. The extra phonon peaks induced by stripe order can be understood in terms of the energies of phonons that occur at the charge-order wave vector Q(c). A strong Fano antiresonance for a Ni-O bond-stretching mode provides clear evidence for finite dynamical conductivity within the charge stripes.

Journal Article↗
PubMed2000

Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides.

By analyzing the human antibody repertoire in terms of structure, amino acid sequence diversity and germline usage, we found that seven V(H) and seven V(L) (four Vkappa and three Vlambda) germline families cover more than 95 % of the human antibody diversity used. A consensus sequence was derived for each family and optimized for expression in Escherichia coli. In order to make all six complementarity determining regions (CDRs) accessible for diversification, the synthetic genes were designed to be modular and mutually compatible by introducing unique restriction endonuclease sites flanking the CDRs. Molecular modeling verified that all canonical classes were present. We could show that all master genes are expressed as soluble proteins in the periplasm of E. coli. A first set of antibody phage display libraries totalling 2x10(9) members was created after cloning the genes in all 49 combinations into a phagemid vector, itself devoid of the restriction sites in question. Diversity was created by replacing the V(H) and V(L) CDR3 regions of the master genes by CDR3 library cassettes, generated from mixed trinucleotides and biased towards natural human antibody CDR3 sequences. The sequencing of 257 members of the unselected libraries indicated that the frequency of correct and thus potentially functional sequences was 61 %. Selection experiments against many antigens yielded a diverse set of binders with high affinities. Due to the modular design of all master genes, either single binders or even pools of binders can now be rapidly optimized without knowledge of the particular sequence, using pre-built CDR cassette libraries. The small number of 49 master genes will allow future improvements to be incorporated quickly, and the separation of the frameworks may help in analyzing why nature has evolved these distinct subfamilies of antibody germline genes.

Amino Acid Sequence↗