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Biomedical subjects

C Beck

Publications and source records attributed to C Beck.

At least 55 records · Page 3Linked to original sources

Concentration-effect relationship of hydroxychloroquine in patients with rheumatoid arthritis--a prospective, dose ranging study.

OBJECTIVE: A 6 month prospective randomized double blind study was conducted to investigate hydroxychloroquine dose concentration-effect relationships in people with rheumatoid arthritis. METHODS: Patients were randomized in 2 groups: one group received 200 mg hydroxychloroquine sulfate daily (A) and one group received 400 mg daily (B). Each month, 8 disease variables were assessed, adverse events recorded, and hydroxychloroquine blood concentrations determined. RESULTS: Twenty-three patients were included: 10 in group A and 13 in group B. After 6 months of therapy, a significant improvement in disease activity was noted for 6 criteria with no statistical differences between groups: pain (assessed by a visual analog scale), joint scores (swelling and tenderness), impairment in daily living activity (18 activities graded 0 to 8), patient assessment of disease state, and erythrocyte sedimentation rate. Hydroxychloroquine steady-state blood concentrations (Month 6) were significantly different between groups (mean +/- SD): 450.6 +/- 285.3 ng/ml (A) vs 870.3 +/- 329.3 ng/ml (B) (p = 0.0001). Steady-state concentrations were correlated with the daily dose (r = 0.63, p = 0.005), the improvement in activity of daily living (r = 0.49, p = 0.03), and the improvement in joint tenderness score (r = 0.47, p = 0.038). CONCLUSION: The data indicate that hydroxychloroquine is an effective therapy, but there were no further improvements observed in the group receiving 400 mg daily compared to those receiving 200 mg. There were some correlations between hydroxychloroquine steady-state blood concentrations and effects.

Adult↗

Enabling and empowering certified nursing assistants for quality dementia care.

Currently, 1.2 million full-time equivalent employees (FTEs) care for more than 1.5 million residents in nursing homes where 75% of residents have dementia. By the year 2010, the number of residents in these institutions may double. Registered nurses (RNs) make up less than 7% of a home's total FTEs. In contrast, certified nursing assistants (CNAs) account for more than 40% of total FTEs. Thus, CNAs serve as the primary caregivers in nursing homes. Typically, CNAs have a high school education or less, and receive little more than minimum wage. Their extensive contact with residents has a tremendous impact on quality of life, but significant barriers limit their caregiving effectiveness. These barriers include poor pay, minimal long-term benefits, and insufficient training, recognition and support for their physically and emotionally labor-intensive care. This paper addresses the issues of training CNAs for dementia care by suggesting an organizational framework within which to view dementia training; providing an overview of barriers to empowering CNAs to provide quality care to dementia residents; reviewing research that has addressed a specific barrier; making recommendations for future research; and suggesting research approaches to address these recommendations.

Aged↗

NMDAR channel segments forming the extracellular vestibule inferred from the accessibility of substituted cysteines.

In NMDA receptor channels, the M2 loop forms the narrow constriction and the cytoplasmic vestibule. The identity of an extracellular vestibule leading toward the constriction remained unresolved. Using the substituted cysteine accessibility method (SCAM), we identified channel-lining residues of the NR1 subunit in the region preceding M1 (preM1), the C-terminal part of M3 (M3C), and the N-terminal part of M4 (M4N). These residues are located on the extracellular side of the constriction and, with one exception, are exposed to the pore independently of channel activation, suggesting that the gate is at the constriction or further cytoplasmic to it. Permeation of Ca2+ ions was decreased by mutations in M3C and M4N, but not by mutations in preM1, suggesting a functionally distinct contribution of the segments to the extracellular vestibule of the NMDA receptor channel.

Amino Acid Sequence↗

An encyclopedia of mouse genes.

The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

Animals↗

Approach to Gaussian stochastic behavior for systems driven by deterministic chaotic forces.

We consider skew-product dynamical systems that describe the stroboscopic dynamics of a damped particle subjected to a chaotic kick force. In a suitable scaling limit the dynamics converges to the Ornstein-Uhlenbeck process. We investigate the deterministic chaotic corrections in the vicinity of this Gaussian limit case for various examples of chaotic forces. We present numerical evidence that, for certain classes of chaotic forces, the deterministic chaotic corrections of the invariant density are universal. We provide analytical results for forces generated by Tchebyscheff maps and sketch a renormalization group theory in the space of probability densities.

Journal Article↗

Identifying patterns of disruptive behavior in long-term care residents.

OBJECTIVES: To determine the frequency, timing, and pattern of 45 operationalized disruptive behaviors (DB) in older people in long-term care units. DESIGN: Nursing staff collected prospective descriptive data over 21 consecutive shifts for each patient to document prevalence, frequency, and co-occurrences of DBs. SETTING: All of the eight long-term care units and one acute/admission unit of a large Veterans Administration Medical Center (VAMC). Each 40-bed unit had patients with varying levels of cognitive impairment and skilled nursing needs. PARTICIPANTS: The sample consisted of 240 hospitalized VA patients with a mean age of 72.8 (SD = 8.6) years and mean length of stay of 4.02 (SD = 8.6) years. Residents had dementia, a psychiatric diagnosis, or mixed dementia and psychiatric diagnoses. MEASUREMENTS: The Disruptive Behavior Scale (DBS), an instrument designed for collecting patient-level data on 45 separate DBs. RESULTS: In a 24-hour period, the average frequency was 3.6 DBs per subject. We found that 41.2% of DB occurred during the day shift, 39.2% during the evening shift, and 19.6% during the night shift. In 32% of observed occurrences, only one DB occurred within the hour. In the remaining 68% of observations, two or more DBs occurred within the same hour. We found two behaviors, Does Not Follow Directions and Excessive Motor Activity, to occur with multiple behaviors in multiple categories. Several characteristic patterns were noted; e.g., physically aggressive behaviors rarely co-occurred with verbal DBs. Physically nonaggressive behaviors seemed to occur most frequently with other physically nonaggressive behaviors and, to a lesser extent, with verbal DBs. CONCLUSIONS: These findings lend support to the existence of patterns of DBs in long-term care patients, a useful step toward targeting interventions early in the behavioral sequence.

Aged↗

HCP<=>CPH isomerization: caught in the act.

In this overview we discuss the vibrational spectrum of phosphaethyne, HCP, in its electronic ground state, as revealed by complementary experimental and theoretical examinations. The main focus is the evolution of specific spectral patterns from the bottom of the potential well up to excitation energies of approximately 25,000 cm(-1), where large-amplitude, isomerization-type motion from H-CP to CP-H is prominent. Distinct structural and dynamical changes, caused by an abrupt transformation from essentially HC bonding to mainly PH bonding, set in around 13,000 cm(-1). They reflect saddle-node bifurcations in the classical phase space--a phenomenon well known in the nonlinear dynamics literature--and result in characteristic patterns in the spectrum and the quantum-number dependence of the vibrational fine-structure constants. Two polar opposites are employed to elucidate the spectral patterns: the exact solution of the Schrödinger equation, using an accurate potential energy surface and an effective or resonance Hamiltonian (expressed in a harmonic oscillator basis set and block diagonalized into polyads), which is defined by parameters adjusted to fit either the measured or the calculated vibrational energies. The combination of both approaches--together with classical mechanics and semiclassical analyses--provides a detailed spectroscopic picture of the breaking of one bond and the formation of a new one.

Journal Article↗

Psychostimulant prescriptions by psychiatrists higher than expected: a self-report survey.

OBJECTIVE: To survey Alberta psychiatrists on their prescribing of psychostimulants to adults. METHOD: A questionnaire was mailed to all 245 registered psychiatrists in Alberta. The respondents were requested to anonymously report, for the previous year, the number of adult patients to whom they prescribed pemoline, methylphenidate, amphetamines, or other psychostimulants for the treatment of adult attention-deficit hyperactivity disorder (ADHD), narcolepsy, unipolar depression, bipolar disorder, dementia, and other disorders. RESULTS: The response rate was 93.9%; 88.7% treated adults. Of these, 46.6% prescribed psychostimulants to 1238 patients. The greatest proportion of prescriptions of psychostimulants was for adult ADHD, depression, and narcolepsy. CONCLUSIONS: Psychostimulants are more widely prescribed by psychiatrists than indicated in earlier studies and in recommendations for treatment.

Adult↗

Incidence and risk factors of catheter-related deep vein thrombosis in a pediatric intensive care unit: a prospective study.

OBJECTIVE: To estimate the incidence and to characterize risk factors for central venous catheter (CVC)-related deep vein thrombosis (DVT) in a pediatric intensive care unit. STUDY DESIGN: Consecutive children admitted to a pediatric intensive care unit who required a CVC for more than 48 hours were examined by Doppler ultrasonography of the catheterized vein at days 2, 4, 6, or 7 after insertion and weekly thereafter until CVC removal. RESULTS: The incidence of CVC-related DVT was 18.3% (17 of 93) (95% confidence interval = 10.2% to 25.8%). Thromboses were diagnosed within the first 4 days of catheter placement for 15 of 17 CVC-related thromboses. Multivariate analysis showed that risk factors most predictive of CVC-related DVT were presence of a cancer (odds ratio = 17.23, 95% confidence interval = 1.5 to 194) and young age (odds ratio for age = 0.72, 95% confidence interval = 0.54 to 0.96). CONCLUSION: The frequency of CVC-related DVT is substantial in pediatric intensive care units. Risk is highest during the 4 days after insertion and decreases thereafter. The clinical impact, optimal prevention, and therapy of these thromboses remain to be determined.

Catheterization, Central Venous↗

Correlates of disruptive behavior in severely cognitively impaired nursing home residents.

This article provides information about correlates of "disruptive behaviors" among nursing home residents with dementia. We used averages of multiple observations for a wide range of behaviors (n = 45) across 11 months to gather this information. We placed behaviors into four separate categories: physically aggressive, physically non-aggressive, vocally agitated, and vocally aggressive. Then, we tested associations between these categories and demographic, cognitive, and health variables. Cognitive status and selected demographic variables were associated with the behavior categories; adding health variables did not improve prediction. Lower cognitive status was associated with more disruptive behaviors. Our findings suggest that cognitive status, but not health variables, predicts disruptive behavior among nursing home residents with dementia.

Aged↗

Promoter selectivity of the Bradyrhizobium japonicum RpoH transcription factors in vivo and in vitro.

Expression of the dnaKJ and groESL1 heat shock operons of Bradyrhizobium japonicum depends on a sigma32-like transcription factor. Three such factors (RpoH1, RpoH2, and RpoH3) have previously been identified in this organism. We report here that they direct transcription from some but not all sigma32-type promoters when the respective rpoH genes are expressed in Escherichia coli. All three RpoH factors were purified as soluble C-terminally histidine-tagged proteins, although the bulk of overproduced RpoH3 was insoluble. The purified proteins were recognized by an anti-E. coli sigma32 serum. While RpoH1 and RpoH2 productively interacted with E. coli core RNA polymerase and produced E. coli groE transcript in vitro, RpoH3 was unable to do so. B. japonicum core RNA polymerase was prepared and reconstituted with the RpoH proteins. Again, RpoH1 and RpoH2 were active, and they initiated transcription at the B. japonicum groESL1 and dnaKJ promoters. In all cases, the in vitro start site was shown to be identical to the start site determined in vivo. Promoter competition experiments revealed that the B. japonicum dnaKJ and groESL1 promoters were suboptimal for transcription by RpoH1- or RpoH2-containing RNA polymerase from B. japonicum. In a mixture of different templates, the E. coli groESL promoter was preferred over any other promoter. Differences were observed in the specificities of both sigma factors toward B. japonicum rpoH-dependent promoters. We conclude that the primary function of RpoH2 is to supply the cell with DnaKJ under normal growth conditions whereas RpoH1 is responsible mainly for increasing the level of GroESL1 after a heat shock.

Bacterial Proteins↗

Allelic heterogeneity of Mediterranean myoclonus and the cystatin B gene.

Mediterranean myoclonus is a progressive myoclonus epilepsy with autosomal recessive inheritance. Another form has been described in Finland, the so-called Baltic myoclonus. Mediterranean myoclonus and Baltic myoclonus are also known as Unverricht-Lundborg disease. Linkage analyses have shown that the genes for both these forms of myoclonus are closely linked to 21q22.3 DNA markers, suggesting that they are caused by mutations at the same locus (EPM1). Recently, two heterozygous mutations were found in the cystatin B gene in patients with Unverricht-Lundborg disease. We report recombinational and linkage disequilibrium mapping of EPM1, and cystatin B gene sequencing, in 14 consanguineous pedigrees with Mediterranean myoclonus. Linkage to 21q22.3 DNA markers was observed in all these families. Haplotype analysis suggests that a common mutation segregates within these pedigrees, and that this mutation is different from the common one responsible for the Finnish form of Unverricht-Lundborg disease. No mutation was found in the exons or splice junctions of the cystatin B gene in the 14 pedigrees.

Base Sequence↗

Lack of correlation between rejection of tumor cells co-expressing interleukin-2 and B7.1 and vaccine efficiency.

Genetically modifying tumor cells to express a variety of cytokines such as interleukin-2 (IL-2) or the co-stimulatory molecule B7.1 leads to increased immunogenicity and reduced tumorigenicity of tumors in several models with T cells involved in the process. We have previously reported decreased tumorigenicity of the murine plasmacytoma J558L [major histocompatibility complex (MHC) class I+ and class II-] expressing IL-2 or B7.1. When systemic immunity was analyzed, immunization with either J558-IL2 or J558-B7.1 cells generated moderate protection against unmodified J558L tumor cells, comparable to immunization with a tumor cells/adjuvant Corynebacterium parvum mixture. In this study, we asked whether the co-expression of IL-2 and B7.1 in tumor cells would augment vaccine potency, cytotoxic T lymphocyte (CTL) activity and protective immunity. Rejection of single IL-2 or B7.1 or co-transfected IL-2/B7.1 cells occurred in most syngeneic animals but not in T cell-deficient nude mice, thus confirming that T cells were required for tumor rejection. We knew from previous experiments that CD8+ T cells were responsible for rejection. Surprisingly, immunization with J558-IL2/B7.1 cells followed by challenge with parental J558L caused a reduction in systemic protection as compared to J558-B7.1 or J558-IL2 alone. We examined the mechanism underlying this unexpected result: 6 days after injection of J558-IL2/B7.1 cells, tumor were nearly completely destroyed and were almost devoid of CD8+ cells, while CD8+ cells were increased in both IL-2- and B7.1-transfected tumors. In addition, immunization with J558-IL2/B7.1 tumors had an adverse effect on the generation of CTL. Mice immunized with J558-B7.1 and to a lesser extent J558-IL2 cells mounted a CTL response against J558L cells while, in contrast, no CTL activity could be detected in mice immunized with J558-IL2/B7.1, thus showing a correlation between the absence of CTL activity and the lack of in vivo protection. We demonstrate that "hyperstimulation" of the immune response by genetically modified cancer vaccines can have adverse effects on tumor immunity, even though the mechanism is not yet completely understood.

Animals↗

Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q.

Benign familial infantile convulsions (BFIC) are an autosomal-dominant epileptic syndrome characterized by an age of onset within the first year of life. Although they were first reported in families of Italian descent, BFIC have also been described in non-Italian families. We have mapped the BFIC gene to chromosome 19 by linkage analysis in five Italian families with a maximum two-point lod score of 6.36 at D19S114; maximum multipoint lod scores > 8 were obtained for the interval D19S250-D19S245. BFIC are therefore the third idiopathic partial epileptic syndrome to be mapped on the human genome.

Chromosome Mapping↗

Dissection of the transcription machinery for housekeeping genes of Bradyrhizobium japonicum.

By using a PCR approach, the Bradyrhizobium japonicum sigA gene, which encodes the primary RNA polymerase sigma factor, sigma80, was cloned and its nucleotide sequence was established. The deduced protein is highly homologous to the SigA protein of Rhizobium meliloti (72% amino acid sequence identity) but less so to RpoD of Escherichia coli (51% identity). Well conserved is the C-terminal end of the protein, which is probably involved in promoter recognition and binding of the RNA polymerase core enzyme. A remarkable feature of the primary sequence is an alanine- and proline-rich segment of 24 amino acids between conserved regions 1 and 2, which might function as an interdomain linker. We purified the B. japonicum RNA polymerase holoenzyme. One of the subunits had an apparent molecular mass of 90 kDa and corresponded to the sigA gene product, as judged by N-terminal amino acid sequencing. The purified RNA polymerase was used in an in vitro transcription system to determine the transcription start sites of the rrn and groESL4 operons. They were identical to those previously identified in vivo. The rrn promoter was cloned upstream of a rho-independent terminator, yielding a transcript of about 240 bases. This served as a suitable template to analyze promoter activity. Then mutant derivatives of the rrn promoter were constructed and tested in in vitro transcription experiments. Several base pairs essential for promoter activity were thus identified. The results suggest that the well-characterized -35/-10 promoter class is predominantly used in B. japonicum for the expression of "housekeeping" genes.

Amino Acid Sequence↗

Planning for the future of long-term care: consumers, providers, and purchasers.

The number of consumers needing long-term care services, including nursing home care, will more than triple during the next 30 years, and their characteristics will change dramatically. Providers will be in short supply, and an increasing variety of professionals will participate in meeting the long-term care needs of the older population. Purchasers will make decisions about providing services based on the health-related outcomes and value of these services. While an integrated delivery system that incorporates a range of alternatives to the nursing home is the ideal, the demands and preferences of consumers, the availability of providers, and purchasers' mostly financially driven decisions will influence the achievement of such a system. The challenge to the nursing profession will be to continue to serve as an advocate for the patient as the system evolves and to provide data for wise policy decision-making.

Aged↗