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Biomedical subjects

R Weiss

Publications and source records attributed to R Weiss.

At least 91 records · Page 5Linked to original sources

Managing benign prostatic hyperplasia in primary care. Patient-centred approach.

PROBLEM ADDRESSED: Management of benign prostatic hyperplasia (BPH) is changing from a surgical approach to a medical approach, and the role of primary care physicians is expanding. OBJECTIVE OF PROGRAM: To introduce a patient-centred approach to managing BPH in primary care through a continuing medical education (CME) program. MAIN COMPONENTS OF PROGRAM: A practice-based, small group, peer-led CME program focused on application of the International Prostate Symptom Score and Quality of Life Assessment in four case studies on prostatism, including BPH. At 86 workshops held across Canada, 658 physicians participated in discussions with case materials that included videos and a handbook. A before-after practice behaviour questionnaire was administered at each workshop to evaluate "intent to change." CONCLUSIONS: Participating physicians showed willingness to learn new skills for patient-centred management of BPH. These results suggest that peer-led, small group CME can successfully encourage use of new practice guidelines in primary are and teach physicians practical steps for developing therapeutic alliances with their patients.

Aged↗

Retinoic acid receptor status in mouse spleen during a primary immune response against beta-galactosidase.

OBJECTIVE: Evaluation of the dynamics of all-trans retinoic acid receptor binding properties in mouse spleen nuclear extracts during a primary immune response against beta-galactosidase. METHODS: Female BALB/c mice, aged between 5 and 6 weeks were immunized intradermally into the shaved back (4 spots each) with 100 microg beta-galactosidase in 100 microl sterile phosphate buffered saline (pH 7.2) and blood was taken by tail bleeding on days 0 (preimmune serum), 4 and 6. Production of antibody in serum and the detection of cytokines (IL-4, IFN-gamma) from proliferation supernatants were determined by ELISA. Antigen-specific proliferation assay of isolated spleen cells was based on [3H]-thymidine incorporation measured in a liquid scintillation counter. Both, the maximal binding capacity (Bmax) and the affinity (Ka) of all-trans retinoic acid nuclear receptors (RAR) were evaluated according to Brtko (1994). RESULTS AND CONCLUSIONS: Injection of beta-galactosidase induced the first detectable antibody responses on day 4 (IgM) and on day 6 (IgG). These points of time, reflecting the early and the mature immune response served to measure the antigen-specific proliferation and production of IL-4 and IFN-gamma in the supernatants of the proliferation cultures as well as all-trans retinoic acid receptor (RAR) binding characteristics in spleen nuclear proteins. The RAR Bmax was significantly (P<0.05) decreased only at the time of the first specific IgG antibody production. CONCLUSIONS: The data obtained indicate the involvement of RAR in the late phase of an in vivo immune response.

Animals↗

[Yeasts of the genus Malassezia: taxonomic classification and significance in (veterinary and) clinical medicine].

The historical development of the taxonomic classification of Malassezia yeasts until today yielded the description of seven different species based upon molecularbiological, morphological and biochemical parameters (M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, M. slooffiae). Tests like Cremophor EL assimilation, esculin degradation, catalase test, pigment production and determination of polidocanol sensitivity appear to be suitable procedures for routine identification of the different species. Their colonization of clinically healthy humans (in particular M. sympodialis, M. globosa, M. obtusa) and animals (M. pachydermatis) skin renders interpretation difficulties, when isolating Malassezia spp. from clinical specimens. Out of the seven species, in man the clinical significance of M. furfur for pityriasis versicolor and systemic infections appears to be accepted largely. In dogs and cats M. pachydermatis has been regarded as cause of otitis externa and seborrhoeic dermatitis. But, due to geno- and phenotypic variabilities described for M. pachydermatis field isolates further investigations concerning the taxonomic uniformity of the species are necessary.

Animals↗

Hirudin therapy during thrombolysis for venous thrombosis in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is the most common drug-related thrombocytopenia. Thromboembolic complications occur in approximately 50% of patients with HIT and result in limb amputation and death in up to 20% and 30% respectively. Because patients with a history of HIT may require future intravenous anticoagulation but have a high-risk of thromboembolism if re-challenged with heparin, alternative therapies are necessary when further anticoagulation is indicated. The use of direct thrombin inhibitors in HIT patients who also require thrombolytic therapy offers unique challenges to anticoagulant monitoring and safety. We present a case of progressive ileofemoral deep venous thrombosis in a patient with a history of HIT in order to review the combined use of hirudin and thrombolysis in this setting.

Anticoagulants↗

Improvement of the immune response against plasmid DNA encoding OspC of Borrelia by an ER-targeting leader sequence.

The present study outlines the characterization of a DNA-based immune response against the OspC antigen, one of the most promising candidates for a Borrelia vaccine. Balb/c mice were injected intradermally with plasmid DNA encoding the OspC gene (lacking the natural leader sequence) under transcriptional control of the cytomegalovirus (CMV) promotor. Immunization with this construct elicited only a marginal response, which was drastically improved by a fusion construct containing the human tissue plasminogen activator (hTPA) signal sequence. The results indicate that for DNA-based immunization against OspC an ER-targeting signal may be necessary for both antibody production as well as cellular immune responses.

Amino Acid Sequence↗

The 5/2,3/2 Spin Admixture in the Chloroiron(III) Derivative of the Sterically Crowded 2,3,7,8,12,13,17,18-Octaethyl-5,10,15,20-tetraphenylporphyrin.

Despite similar ring deformations in solution and in the solid state, the chloroiron(III) derivative of 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetraphenylporphyrin ([FeCl(oetpp)], shown schematically) prepared in this study exhibits only a very weak quantum-mechanical admixture of spin S=3/2 (only 4-10 %) with spin S=5/2. In contrast, for the variety of [FeCl(oetpp)] studied earlier by other researchers a 40 % contribution of the S=3/2 state was found.

Journal Article↗

Antibodies against human herpesvirus 8 in black South African patients with cancer.

BACKGROUND: Infection with human herpesvirus 8 (HHV-8) has been consistently linked to Kaposi's sarcoma, but its mode of transmission, association with other cancers, and interaction with the human immunodeficiency virus type 1 (HIV-1) are largely unknown. METHODS: Between January 1992 and December 1997, we interviewed 3591 black patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 in 3344 of the patients. Antibodies against HHV-8 were detected with an indirect immunofluorescence assay. The intensity of the fluorescent signal correlated well with the titers of antibodies (P<0.001). The relations among the presence of anti-HHV-8 antibodies, sociodemographic and behavioral factors, type of cancer, and the presence or absence of coexistent HIV infection were examined with the use of unconditional logistic-regression models. RESULTS: Among the 3293 subjects with cancers other than Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 32 percent, which did not differ significantly from the standardized seroprevalence among black blood donors. Among these 3293 patients, the prevalence of antibodies against HHV-8 increased with increasing age (P<0.001) and an increasing number of sexual partners (P=0.05) and decreased with increasing years of education (P=0.007); it was not strongly associated with HIV-1 infection. Anti-HHV-8 antibodies were more frequent among black than white blood donors (P<0.001). Among the 51 patients with Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 83 percent, significantly higher than the prevalence among those without Kaposi's sarcoma (P<0.001). For 16 other specific types of cancer, including multiple myeloma (108 cases) and prostate cancer (202 cases), the variation in the standardized seroprevalence of antibodies against HHV-8 was not remarkable. At a given intensity of fluorescence of anti-HHV-8 antibodies, Kaposi's sarcoma was more frequent among HIV-1-positive patients than among those who were HIV-1-negative (P<0.001). CONCLUSIONS: Among black patients with cancer in South Africa, the seroprevalence of anti-HHV-8 antibodies is high and is specifically associated with Kaposi's sarcoma, particularly at high titers.

Adolescent↗

Stability of [123I]IBZM SPECT measurement of amphetamine-induced striatal dopamine release in humans.

Binding competition between endogenous dopamine (DA) and the D2 receptor radiotracer [123I]IBZM allows measurement of the change in synaptic DA following amphetamine challenge with SPECT in the living human brain. Previous investigations using this technique in healthy subjects have shown that the magnitude of amphetamine effect on [123I]IBZM binding potential (BP) is small (range between 5 to 15% decrease), and that a large between-subject variability in this effect is observed. Therefore, it was unclear how much of the apparent between-subject variability was due to a low signal-to-noise ratio in the measurement, vs. true between-subject differences in the magnitude of the response. The goals of this investigation were to test the within-subject reproducibility and reliability of amphetamine-induced decrease in [123I]IBZM BP with a test/retest paradigm, and to establish the presence or absence of tolerance or sensitization to single administration ofi.v. amphetamine. Six healthy male subjects, never previously exposed to psychostimulants, twice underwent measurement of striatal amphetamine-induced DA release (between-measurement interval 16 +/- 10 days) using SPECT and the [123I]IBZM constant infusion technique. Results demonstrated an excellent within-subject reproducibility of amphetamine-induced DA release: amphetamine-induced decreases in [123I]IBZM BP were significant on each day, and had an intraclass correlation coefficient (ICC) of 0.89. Moreover, values from the second experiment were not significantly different from first experiment, suggesting the absence of either sensitization or tolerance to the effect of amphetamine on DA release in these experimental conditions. The subjective activation, as rated by the subjects on analog scales, was also highly reproducible. In conclusion, this scanning technique provides a reliable measurement of amphetamine-induced reduction of [123I]IBZM BP and enables detection of between-subject differences that appear stable over time.

Adult↗

Different functions for the thyroid hormone receptors TRalpha and TRbeta in the control of thyroid hormone production and post-natal development.

The biological activities of thyroid hormones are thought to be mediated by receptors generated by the TRalpha and TRbeta loci. The existence of several receptor isoforms suggests that different functions are mediated by specific isoforms and raises the possibility of functional redundancies. We have inactivated both TRalpha and TRbeta genes by homologous recombination in the mouse and compared the phenotypes of wild-type, and single and double mutant mice. We show by this method that the TRbeta receptors are the most potent regulators of the production of thyroid stimulating hormone (TSH). However, in the absence of TRbeta, the products of the TRalpha gene can fulfill this function as, in the absence of any receptors, TSH and thyroid hormone concentrations reach very high levels. We also show that TRbeta, in contrast to TRalpha, is dispensable for the normal development of bone and intestine. In bone, the disruption of both TRalpha and TRbeta genes does not modify the maturation delay observed in TRalpha -/- mice. In the ileum, the absence of any receptor results in a much more severe impairment than that observed in TRalpha -/- animals. We conclude that each of the two families of proteins mediate specific functions of triiodothyronin (T3), and that redundancy is only partial and concerns a limited number of functions.

Animals↗

[When patients and doctors don't speak the same language-- concepts of interpretation practice].

In the Swiss Health Care System, working with an interpreter while medically treating migrants speaking a foreign language has become a common practice. However, the theoretical and conceptional framework of this practice has not yet been sufficiently elaborated. Specifically, the presence of an interpreter leads to a triadic interviewing situation that has implications for the medical treatment. Though an interpreter can improve and deepen the understanding between patient and physician, the communication can also become more complex and difficult with his or her presence. The article sheds light on the perspectives that arise from this situation by defining different role models for medical interpreters and discussing their advantages and disadvantages. The discussion focuses on the four following ideal types: word-for-word translation, cultural mediation, patient advocacy and co-therapy. The choice of interpreter's role in influenced by the institutional setting, the kind of treatment chosen as well as by the concrete interaction. To illustrate the different roles as they manifest in the therapeutic situation, examples from taped and retranslated interviews are presented. Doctor-patient interviews will illustrate the different roles interpreters take over while interpreting medical interviews with migrant patients speaking a foreign language.

Female↗

The effect of iron to manganese substitution on microperoxidase 8 catalysed peroxidase and cytochrome P450 type of catalysis.

This study describes the catalytic properties of manganese microperoxidase 8 [Mn(III)MP8] compared to iron microperoxidase 8 [Fe(III)MP8]. The mini-enzymes were tested for pH-dependent activity and operational stability in peroxidase-type conversions, using 2-methoxyphenol and 3,3'-dimethoxybenzidine, and in a cytochrome P450-like oxygen transfer reaction converting aniline to para-aminophenol. For the peroxidase type of conversions the Fe to Mn replacement resulted in a less than 10-fold decrease in the activity at optimal pH, whereas the aniline para-hydroxylation is reduced at least 30-fold. In addition it was observed that the peroxidase type of conversions are all fully blocked by ascorbate and that aniline para-hydroxylation by Fe(III)MP8 is increased by ascorbate whereas aniline para-hydroxylation by Mn(III)MP8 is inhibited by ascorbate. Altogether these results indicate that different types of reactive metal oxygen intermediates are involved in the various conversions. Compound I/II, scavenged by ascorbate, may be the reactive species responsible for the peroxidase reactions, the polymerization of aniline and (part of) the oxygen transfer to aniline in the absence of ascorbate. The para-hydroxylation of aniline by Fe(III)MP8, in the presence of ascorbate, must be mediated by another reactive iron-oxo species which could be the electrophilic metal(III) hydroperoxide anion of microperoxidase 8 [M(III)OOH MP8]. The lower oxidative potential of Mn, compared to Fe, may affect the reactivity of both compound I/II and the metal(III) hydroperoxide anion intermediate, explaining the differential effect of the Fe to Mn substitution on the pH-dependent behavior, the rate of catalysis and the operational stability of MP8.

Catalysis↗

Changes in autonomic activity and ventricular repolarization.

An increase in sympathetic activity, manifested by shortening of RR intervals (RRi) and changes in RRi variability, precedes and possibly triggers ventricular tachyarrhythmias (VTAs) by altering repolarization. We examined the effects of autonomic activity on the projection of repolarization as detected by body surface potential maps (BSPMs). We recorded 32 lead/192-point BSPMs during passive head-up tilt, tilt + infusion of isoproterenol, rapid atrial pacing, and atrial pacing + infusion of isoproterenol. Changes in QT; recovery time; activation-recovery interval (ARi); T-wave amplitude; and QT, QRST, and ST integrals and their dispersion were analyzed. Autonomic effects on sinus node were inferred from the Fourier transform-derived low and high frequency powers of RRi variability. Patients were divided into those with (SHD) and without structural heart disease (NSHD). Heart rate increased, whereas QT interval and ARi declined with tilt in both groups. RRi variability indices of sympathetic activity increased in NSHD but did not change in SHD. T-wave amplitudes declined in NSHD but did not change in SHD, suggesting altered responsiveness of ventricular repolarization to autonomic stimulation. Tilt and rapid atrial pacing during infusion of isoproterenol resulted in a paradoxical increase in T-wave amplitudes in some patients, similar to that observed before the onset of spontaneous arrhythmias. We conclude that altering autonomic activity by head-up tilt and/or infusion of sympathomimetic agents results in significant changes in the body surface projection of cardiac repolarization, which differ in patients with SHD from those without SHD. Similar paradoxical changes in the T-wave amplitude have been observed before the onset of spontaneous VTA, suggesting that abnormal response of repolarization to autonomic stimulation predisposes to arrhythmogenesis.

Adult↗

Immune responses after immunization with plasmid DNA encoding Bet v 1, the major allergen of birch pollen.

BACKGROUND: Immunization with plasmid DNA encoding various antigens is a promising method in vaccine research. Recent studies also indicate that DNA-based immunization might represent a potential approach in allergen-specific immunotherapy. OBJECTIVE: In this study we have characterized the immune responses induced by recombinant Bet v 1a and plasmid DNA encoding for Bet v 1a, the major allergen of birch pollen in a mouse system. METHODS: Balb/c mice were injected intraperitoneally with recombinant Bet v 1a and intradermally with plasmid DNA encoding for the gene of Bet v 1a (pCMV-Bet). In addition, the effect of immunostimulatory DNA sequences was investigated by appending CpG motifs to the gene of Bet v 1a, coinjecting CpG-oligodeoxynucleotides together with the pCMV-Bet construct, or both. IgE and IgG antibody responses, as well as IgG subclasses, were measured by ELISA in sera after each immunization. IFN-gamma and IL-4 levels were also measured by ELISA in sera and supernatants of allergen-stimulated spleen cells. RESULTS: The primary humoral response to a single treatment with pCMV-Bet was very weak, but the reaction could be boosted to higher levels by 2 additional injections. On the other hand, proliferation assays of spleen cells and measurements of cytokine levels already indicated a cellular response after the first injection of plasmid DNA. After 2 immunizations with pCMV-Bet, the ratio of IgG1 to IgG2a pointed to a TH1 subclass profile. IgE was not detectable in any group at any time during the immune reaction. Accordingly, IL-4 levels were markedly reduced in the serum, as well as in the supernatants, of stimulated spleen cells. Animals immunized with pCMV-Bet containing appended CpG motifs at the 3' end of the Bet v 1a gene and/or with the CpG-ODN GCTAGACGTTAGCGT plus pCMV-Bet displayed reduced humoral responses against Bet v 1a when compared with animals injected with pCMV-Bet alone. The levels of IFN-gamma measured after allergen stimulation of isolated spleen cells were significantly higher in animals immunized with pCMV-Bet plus CpG motifs than with pCMV-Bet alone. Immunization with recombinant Bet v 1a protein elicited a strong TH2 -type response, including IgE production, a high titer of IgG1, and IL-4 production in both serum and supernatants of proliferation cultures. CONCLUSION: In contrast to immunization with protein, DNA immunization induces a strong TH1 -type response against a relevant inhalant allergen. Our data support the concept of developing a novel type of allergen immunotherapy based on plasmid DNA immunization.

Allergens↗