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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 73 records · Page 4Linked to original sources

Oral contraceptives increase the plasma concentrations of chlorpromazine.

A 21-year-old female inpatient who was enrolled in a population pharmacokinetic study of chlorpromazine was given an oral chlorpromazine dose of 100 mg three times daily, and plasma concentrations of chlorpromazine were measured weekly. This dose was well tolerated during the first week of therapy. In the second week the patient took a combined oral contraceptive; this was followed by severe dyskinesias and tremor. Plasma chlorpromazine levels were found to be about sixfold higher than those in the first week, although the dose of chlorpromazine had not changed. This observation suggests that the oral contraceptive increased the plasma concentration of chlorpromazine.

Adult↗

Partnership synergy: a practical framework for studying and strengthening the collaborative advantage.

The substantial interest and investment in health partnerships in the United States is based on the assumption that collaboration is more effective in achieving health and health system goals than efforts carried out by single agents. A clear conceptualization of the mechanism that accounts for the collaborative advantage, and a way to measure it are needed to test this assumption and to strengthen the capacity of partnerships to realize the full potential of collaboration. The mechanism that gives collaboration its unique advantage is synergy. A framework for operationalizing and assessing partnership synergy, and for identifying its likely determinants, can be used to address critical policy, evaluation, and management issues related to collaboration.

Cooperative Behavior↗

Neuronal COX-2 expression in human myenteric plexus in active inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with changes in colonic motility which may contribute to the pain and diarrhoea associated with exacerbations of this disease. These changes may be mediated by prostaglandins which are increased in this condition. Increased expression of the inducible isoform of cyclo-oxygenase (COX-2) has been found in active IBD although its cellular distribution remains uncertain. AIMS: To evaluate the cellular distribution of COX-2 in active IBD. PATIENTS AND METHODS: Using reverse transcription-polymerase chain reaction, in situ hybridisation, and immunohistochemistry, COX-2 expression was evaluated in 12 colectomy specimens from patients with active ulcerative colitis (UC), and six specimens from patients with Crohn's colitis that had failed medical therapy. Histologically normal colon was obtained from 12 patients having resection for colorectal neoplasia and evaluated as above, acting as control specimens. RESULTS: All specimens expressed COX-2 mRNA, with some 6-8-fold increase in inflamed tissues on densitometric analysis (both UC and Crohn's) compared with controls. In situ hybridisation localised this mRNA to myenteric neural cells, surrounding smooth muscle cells, and inflammatory cells of the lamina propria in the IBD specimens, with some weaker labelling seen in the epithelium. No COX-2 labelling was seen in normal tissues. Immunohistochemistry confirmed these sites of COX-2 expression in all inflamed specimens, with absence of immunoreactivity in control tissues. CONCLUSIONS: These findings provide the first evidence of COX-2 expression in neural cells of the myenteric plexus in active IBD which, via increased prostaglandin synthesis at this site, may contribute to the dysmotilty seen in this condition.

Adult↗

The physiological expression of inducible nitric oxide synthase (iNOS) in the human colon.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed in the colonic epithelium in both inflammatory bowel disease and colorectal cancer. Nitric oxide (NO), the product of this enzyme, has been implicated in the pathogenesis of both conditions. However, there are conflicting data on whether iNOS is expressed in the normal, uninflamed human colon. AIMS: To evaluate the expression of iNOS in histologically normal, non-inflamed human colonic mucosa. PATIENTS/METHODS: Reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemistry were used to investigate the expression of iNOS in 17 histologically normal specimens obtained at colectomy performed for colorectal neoplasia. In addition, 16 endoscopic mucosal biopsies, taken from normal individuals, were also evaluated. Eleven surgical specimens and 16 endoscopic biopsies from patients with refractory ulcerative colitis were used as inflammatory controls. RESULTS: All types of specimens expressed iNOS mRNA. Immunoblotting revealed a protein of approximately 130 kDa consistent with iNOS in mucosal extracts of 77% of normal individuals, and 85% of diseased controls. Immunolabelling localised this protein to the surface epithelium in most of the normal specimens and also to the crypt epithelium and inflammatory cells in the diseased controls. CONCLUSIONS: These findings provide evidence that iNOS is often expressed in the surface epithelium of non-inflamed human colon, suggesting that it is induced by local luminal factors, such as bacterial lipopolysaccharide (endotoxin). The resultant NO produced at this site might act as an oxidative barrier, reducing bacterial translocation and providing a means of defence against pathogenic microorganisms.

Adult↗

Photofragment translational spectroscopy of weakly bound complexes: probing the interfragment correlated final state distributions.

The vibrational predissociation dynamics of weakly bound complexes is well known to be highly nonstatistical. In particular, the associated photofragment final state distributions are often far from statistical, consequently reflecting the nature of the dissociation process. For binary complexes consisting of two molecules, a complete description of the final state of the system must include the associated interfragment correlations, specifically between their internal states. Information of this type is imprinted in the translational energies of the fragments, which can be measured using a number of recently developed translational spectroscopy methods. These data can provide detailed insights into the nature of the bond rupture process, as well as accurate values for the dissociation energy of the complexes. The focus of the present review is on experiments that provide correlated final state distributions for weakly bound binary complexes. Where possible, comparisons with theoretical calculations are made.

Journal Article↗

Colon carcinoma: MR imaging with CO2 enema--pilot study.

Prior to surgery, seven patients with known colonic tumors underwent breath-hold single-shot fast spin-echo magnetic resonance imaging during a CO2 enema. The images were evaluated for depiction of tumor, adjacent structures, and the remaining colon, and findings were compared with findings at surgery. In all seven patients, the tumor was demonstrated, and in four (57%), breach of the muscularis propria was correctly predicted.

Adult↗

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↗