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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 145 records · Page 8Linked to original sources

Greater Cincinnati/Northern Kentucky Stroke Study: volume of first-ever ischemic stroke among blacks in a population-based study.

BACKGROUND AND PURPOSE: The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. METHODS: The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. RESULTS: There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm(3) (interquartile range, 0.5 to 8.8 cm(3)). There was a significant relation between location of lesion and infarct size (P<0.001) and between volume and mechanism of stroke (P=0.001). CONCLUSIONS: The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

Acute Disease↗

Varicella zoster virus-associated neurological disease in HIV-infected patients.

Varicella zoster virus (VZV) is an uncommon but well recognized cause of neurological disease in HIV-infected patients. Analysis of cerebrospinal fluid (CSF) using the polymerase chain reaction (PCR) in HIV-infected patients presenting with neurological disease has increasingly allowed diagnosis of VZV-associated pathology. We report clinical, radiological and virological data from 15 consecutive patients with VZV-associated neurological disease. Clinical presentation was varied, including meningo-encephalitis in 9 and isolated cranial nerve palsies in 6. VZV deoxyribonucleic acid (DNA) was detected by PCR in CSF of 11/15; pleocytosis was present in only 6/15, raised protein in 11/15. Magnetic resonance imaging (MRI) appearances were focal signal abnormalities in 8, meningeal enhancement in 2 and normal in 2. With specific anti-VZV therapy 10 patients recovered fully. The predictive value of PCR on CSF for diagnosis of VZV-associated neurological disease should take into account the patient's clinical presentation, concurrent infections and response to anti-VZV therapy.

Adult↗

Safe sex and first-episode schizophrenia.

The need for educating patients about the dangers of unprotected sexual activity is well documented in the literature. Using clinical examples, the authors describe safe-sex strategies for patients experiencing their first episode of schizophrenia. Interventions are based on a 2-year experience of working in a hospital-based treatment and research project with 68 patients. Strategies that begin in the healing phase of schizophrenia take place in both individual and group sessions. First-episode patients are encouraged to speak explicitly about their sex-related behaviors, and HIV testing is suggested when needed. The goal of this approach is to emphasize safe-sex/HIV prevention strategies within a framework of good clinical practice.

Acquired Immunodeficiency Syndrome↗

Software scripts for quality checking of high-throughput nucleic acid sequencers.

We have developed a graphical interface to allow the researcher to view and assess the quality of sequencing results using a series of program scripts developed to process data generated by automated sequencers. The scripts are written in Perl programming language and are executable under the cgibin directory of a Web server environment. The scripts direct nucleic acid sequencing trace file data output from automated sequencers to be analyzed by the phred molecular biology program and are displayed as graphical hypertext mark-up language (HTML) pages. The scripts are mainly designed to handle 96-well microtiter dish samples, but the scripts are also able to read data from 384-well microtiter dishes 96 samples at a time. The scripts may be customized for different laboratory environments and computer configurations. Web links to the sources and discussion page are provided.

Base Sequence↗

Population pharmacokinetics of clinafloxacin in healthy volunteers and patients with infections: experience with heterogeneous pharmacokinetic data.

OBJECTIVE: Clinafloxacin is a new fluoroquinolone antibacterial with inhibitory activity against aerobic, anaerobic and atypical bacterial pathogens. The objectives of this study are to evaluate the pharmacokinetics of clinafloxacin in healthy volunteers and patients with infections and to describe our experience with mixed-effects modelling using heterogeneous pharmacokinetic data. DESIGN AND SETTING: Retrospective analysis of data from phase I to III trials. PATIENTS AND PARTICIPANTS: 204 healthy volunteers and 221 patients with infections. METHODS: Nonlinear mixed-effects modelling (MEM) was used to evaluate 3437 clinafloxacin plasma concentrations collected in 15 phase I to III trials. Models were developed separately for the healthy volunteers and patients, and then for the combined study population. RESULTS: The phase I data were best described with a 2-compartment linear model with first-order absorption. The absorption lag-time and absorption rate constant were 0.24h and 1.17h(-1), respectively. The volumes of distribution were found to be nonlinear functions of body surface area. Estimated creatinine clearance was the most important covariate for systemic clearance (CL). Interoccasion variability (IOV) in CL was observed in the patients in the phase II trial. In the combined study population, the variability in CL was best described by a model including IOV and distinct variabilities for healthy volunteers and patients. CONCLUSION: MEM was useful for evaluating data collected during different phases of drug development for this new fluoroquinolone agent.

Administration, Oral↗

Dysphagia training programmes: 'fixes that fail' or effective inter-disciplinary working?

A number of factors influencing the development of dysphagia training programmes are identified, some of which relate to cultural issues and to the way systems operate. Lessons can be learned from current theories of relevance to effecting change in professionals' working practice. These lessons can be applied beyond dysphagia to other areas in which speech and language therapists are involved.

Deglutition Disorders↗

Factors associated with frequent admission to hospital for patients with chronic airflow limitation.

BACKGROUND: Chronic airflow limitation (CAL) is a common cause of admission and readmission to hospital. This study has explored associated factors with repeat hospital admission in patients with CAL. METHOD: A retrospective file review of patients admitted more than once to hospital during the 1999 calendar year, with a diagnosis of CAL. RESULTS: Two hundred and two patients admitted with CAL accounted for 284 admissions and 1815 bed days. Of these, 46 patients were admitted more than once accounting for 115 (40.5%) admissions and 730 (39.8%) bed days. The study found evidence of general practice involvement in 35 (30.5%) admissions immediately before presentation at the hospital emergency department (ED). The discharge summary following that admission revealed only 67 (54%) were referred back to their general practitioners for follow up. The number of admissions attending the ED between the hours of 9.00 am and 5.00 pm were 62 (53.9%) and 96 (83.5%) between the hours of 7.00 am and 10.00 pm. CONCLUSION: Treatments given in hospital were similar, in most cases, to what could be provided at home with appropriate community based support. General practitioners were involved in approximately one-third of those patients requiring admission or re-admission to hospital.

Female↗

Phase Transition Processes in Surfactant Adsorption Layers.

Adsorption data in the form of surface tension vs bulk concentration isotherms having strong changes in the slope have often been discussed in the literature in terms of phase transitions in the adsorption layer. It will be shown thermodynamically that these apparent kink points in the isotherms are unreal. A phase transition would cause a completely opposite change in the isotherm. Experimental surface tension data for sodium octanoate and dodecyl ammonium chloride obtained from the literature are reinterpreted on the basis of the Frumkin and reorientation isotherms. Copyright 2000 Academic Press.

Journal Article↗

Effect of the Nonstationary Viscous Flow in the Capillary on Oscillating Bubble and Oscillating Drop Measurements.

The dynamic behavior of a bubble or drop oscillating at the tip of a capillary immersed in a surfactant solution is considered. The pressure variation in the cell and the nonstationary flow in the capillary are taken into account. The amplitude- and phase-frequency characteristics of the system are obtained, which contain information about the relaxation processes at the interface and in the bulk phases. Their dependency on the system geometry, the bulk properties of contacting media, and the viscoelastic properties of the interface is analyzed. Copyright 2000 Academic Press.

Journal Article↗

Salvage radiotherapy for prostate cancer recurrence after cryosurgical ablation.

OBJECTIVES: To retrospectively determine the outcome of patients treated with salvage three-dimensional conformal radiotherapy (RT) for prostate cancer recurrence after cryosurgical ablation of the prostate (CSAP). Biochemical control rates and morbidity were analyzed. METHODS: Between January 1990 and November 1999, a total of 49 patients initially treated with CSAP were later irradiated because of a rising prostate-specific antigen (PSA) level and/or a positive biopsy at Allegheny General Hospital. The clinical stage before cryosurgery was T1c in 7 patients; T2a in 7 patients; T2b in 10 patients; T3 in 17 patients; and T4 and/or N1 in 8 patients. The Gleason score was 6 or lower in 29 patients, 7 in 11 patients, and 8 or higher in 9 patients. The mean pre-CSAP PSA level was 15.7 ng/mL (range 2.4 to 45). One patient had a PSA level less than 4 ng/mL, 16 had a PSA level of 4 to 10 ng/mL, 21 had a PSA level of 10 to 20 ng/mL, and 11 had a PSA level greater than 20 ng/mL. Before the start of RT, a complete restaging workup was performed and was negative for distant metastatic disease in all 49 patients. The mean interval to recurrence after CSAP was 19 months (range 3 to 78). The mean RT dose to the planning target volume was 62.9 Gy (range 50.4 to 68.4). RESULTS: The mean pre-RT PSA level was 2.4 ng/mL (range 0.1 to 7.4). After RT, the mean nadir PSA level was 0.4 ng/mL (range 0 to 4.2). The mean time to PSA nadir was 5.8 months (range 1 to 15). In 42 patients, the PSA nadir was less than 1.0 ng/mL, in 5 patients the PSA nadir was greater than 1 ng/mL, and in 2 patients the PSA level remained stable. With a median follow-up time of 32 months (range 12 to 85), the overall biochemical control rate was 61%. The mean time to biochemical failure was 14.5 months (range 1 to 47). Of 30 patients with a pre-RT PSA level of 2.5 ng/mL or less, the disease of 22 (73%) was controlled compared with only 8 (42%) of 19 with a pre-RT PSA level greater than 2.5 ng/mL (P = 0.040). Biochemical control occurred in 18 (69%) of 26 patients with a dose of 64 Gy or greater compared with only 12 (52%) of 23 patients with a dose of less than 64 Gy (P = 0.024). The disease of 20 (70%) of 29 patients with a Gleason score of 6 or lower was controlled versus 10 (50%) of 20 patients with a Gleason score of 7 or greater (P = 0.064). Only 2 patients developed subacute morbidity (proctitis and a urethral stricture). All complications resolved with conservative measures. CONCLUSIONS: Salvage RT for prostate cancer recurrence after CSAP appears feasible. Our preliminary experience revealed that post-CSAP RT in patients with prostate cancer appears to effectively diminish the post-RT PSA level to a nadir of 1.0 ng/mL or less in most patients. The pre-RT PSA level and radiation dose may be important predictors of biochemical control in the salvage setting. RT as described was associated with minimal toxicity to the gastrointestinal/genitourinary systems. Additional prospective randomized studies are necessary to better assess the role of RT in the treatment of these patients.

Aged↗

Geographic information systems. A new tool in environmental epidemiology.

PURPOSE: Geographic Information Systems (GIS) are useful tools for identifying populations with potential exposure to environmental contaminants. Using a GIS, features of the local environment around an individual's home, work, or school can be described. We present two examples illustrating methods and issues in identifying populations potentially exposed to agricultural pesticides and to toxic releases from the Toxic Release Inventory (TRI).METHODS: We used USDA Farm Service Agency records as ground reference data to classify a late summer 1984 satellite image into crop species in 3 counties in Nebraska. We located residences from a case-control study of non-Hodgkin's lymphoma (NHL) on the crop maps and calculated the distance to crop fields. Residences from a 4-center study of NHL were mapped and the distance to TRI sites was determined.RESULTS: Twenty-two percent of residences had crop fields within 500 meters of the home, an intermediate distance for the range of drift effects from pesticide applications. After accounting for the extent of primary drift from ground applications of pesticides, we estimated that 30 percent of residences were potentially exposed to crop pesticides. In the 4-center study, residence locations determined by address-matching methods and by a global positioning system were compared; the population 1 mile from specific TRI sites is described.CONCLUSIONS: These examples demonstrate the utility of a GIS in environmental epidemiology studies. A GIS can be a useful addition to questionnaire and other methods of exposure assessment in health studies.

Journal Article↗

Topological restriction of SNARE-dependent membrane fusion.

To fuse transport vesicles with target membranes, proteins of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) complex must be located on both the vesicle (v-SNARE) and the target membrane (t-SNARE). In yeast, four integral membrane proteins, Sed5, Bos1, Sec22 and Bet1 (refs 2-6), each probably contribute a single helix to form the SNARE complex that is needed for transport from endoplasmic reticulum to Golgi. This generates a four-helix bundle, which ultimately mediates the actual fusion event. Here we explore how the anchoring arrangement of the four helices affects their ability to mediate fusion. We reconstituted two populations of phospholipid bilayer vesicles, with the individual SNARE proteins distributed in all possible combinations between them. Of the eight non-redundant permutations of four subunits distributed over two vesicle populations, only one results in membrane fusion. Fusion only occurs when the v-SNARE Bet1 is on one membrane and the syntaxin heavy chain Sed5 and its two light chains, Bos1 and Sec22, are on the other membrane where they form a functional t-SNARE. Thus, each SNARE protein is topologically restricted by design to function either as a v-SNARE or as part of a t-SNARE complex.

Carrier Proteins↗

The genomic structure and promoter analysis of the human ABF-1 gene.

The human ABF-1 gene is expressed in activated B-cells and Epstein-Barr virus-immortalized lymphoblastoid cell lines. ABF-1 represents the only member belonging to the basic helix-loop-helix (bHLH) family of transcription factors whose expression pattern is restricted to B-cells. ABF-1 forms heterodimeric complexes with E2A to modulate gene transcription. We report the cloning and characterization of the human ABF-1 gene and the promoter region. The gene spans more than 3 kb and contains two exons. Exon 1 contains 274 bp of a 5'-untranslated sequence (UTR) while exon 2 contains 1097 bp of 3'-UTR. Promoter analysis of the 5'-flanking region revealed no apparent B-cell-restricted control elements within approximately 700 bp, but clearly demonstrated the presence of a functional minimal promoter residing immediately upstream of the transcription start site. Analysis of the region containing the minimal promoter activity identified no CCAAT or TATA sequence. Lastly, we have assigned the ABF-1 gene to human chromosome 8q21.1 using fluorescence in situ hybridization (FISH). The cloning of the human ABF-1 gene will facilitate further biochemical and genetic studies of its function in the regulation of B-cell differentiation.

Base Sequence↗

Dynamics of protein and mixed protein/surfactant adsorption layers at the water/fluid interface.

The adsorption behaviour of proteins and systems mixed with surfactants of different nature is described. In the absence of surfactants the proteins mainly adsorb in a diffusion controlled manner. Due to lack of quantitative models the experimental results are discussed partly qualitatively. There are different types of interaction between proteins and surfactant molecules. These interactions lead to protein/surfactant complexes the surface activity and conformation of which are different from those of the pure protein. Complexes formed with ionic surfactants via electrostatic interaction have usually a higher surface activity, which becomes evident from the more than additive surface pressure increase. The presence of only small amounts of ionic surfactants can significantly modify the structure of adsorbed proteins. With increasing amounts of ionic surfactants, however, an opposite effect is reached as due to hydrophobic interaction and the complexes become less surface active and can be displaced from the interface due to competitive adsorption. In the presence of non-ionic surfactants the adsorption layer is mainly formed by competitive adsorption between the compounds and the only interaction is of hydrophobic nature. Such complexes are typically less surface active than the pure protein. From a certain surfactant concentration of the interface is covered almost exclusively by the non-ionic surfactant. Mixed layers of proteins and lipids formed by penetration at the water/air or by competitive adsorption at the water/chloroform interface are formed such that at a certain pressure the components start to separate. Using Brewster angle microscopy in penetration experiments of proteins into lipid monolayers this interfacial separation can be visualised. A brief comparison of the protein adsorption at the water/air and water/n-tetradecane shows that the adsorbed amount at the water/oil interface is much stronger and the change in interfacial tension much larger than at the water/air interface. Also some experimental data on the dilational elasticity of proteins at both interfaces measured by a transient relaxation technique are discussed on the basis of the derived thermodynamic model. As a fast developing field of application the use of surface tensiometry and rheometry of mixed protein/surfactant mixed layers is demonstrated as a new tool in the diagnostics of various diseases and for monitoring the progress of therapies.

Adsorption↗

Effect of surfactant interfacial orientation/aggregation on adsorption dynamics.

The application of new thermodynamic adsorption isotherms allow to improve the description of surfactant adsorption kinetics based on a diffusional transport. While the consideration of interfacial reorientation corrects apparently too high diffusion coefficients, interfacial aggregation avoids too small diffusion coefficients or the assumption of adsorption barriers. The adsorption kinetics of alkyl dimethyl phosphine oxides is influenced by interfacial reorientation. While the lower homologues (C8-C12) follow the classical diffusion model, the higher homologues (C13-C15) yield diffusion coefficients several times larger than the physically reasonable values. Assuming two different adsorption states, the resulting diffusion coefficients agree with those expected from the geometric size of the molecules. The model also works well for oxyethylated non-ionics, such as C10EO8. As a second example, a good theoretical description is obtained for experiments of 1-decanol solutions when a mean surface aggregation number of n = 2.5 is assumed. The same n was obtained from the description of the equilibrium adsorption isotherm of 1-decanol. Assuming that the transition from one into the other state is controlled by a rate constant (change in orientation, formation or disintegration of two-dimensional aggregates) significant changes in the kinetics curves can result. The use of additional rate constants yields an improved fitting to experimental data.

Adsorption↗