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Biomedical subjects

R A Miller

Publications and source records attributed to R A Miller.

At least 19 recordsLinked to original sources

The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures.

BACKGROUND: Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT). METHODS: We investigated by Western blotting and immunohistochemistry the expression of CYP1A1, CYP1A2, and NAT1 in human prostate and in prostate epithelial cells (PECs) derived from primary cultures and tested their ability to activate the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and its N-hydroxy metabolite (N-OH-IQ) to DNA-damaging moieties. RESULTS: Western blotting identified CYP1A1, CYP1A2, and NAT1. Immunohistochemistry localized NAT1 to the cytoplasm of PECs. Inter-individual variation was observed in the expression levels of CYP1A1, 1A2, and NAT1 (11, 75, and 35-fold, respectively). PECs expressed CYP1A1 and NAT1 but not CYP1A2. When incubated with IQ or N-OH-IQ, PECs formed DNA adducts indicating their ability to metabolically activate these compounds. CONCLUSIONS: Prostate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.

Arylamine N-Acetyltransferase↗

The Gurnham equation in characterizing the compressibility of pharmaceutical materials.

Limitations of the Heckel equation in characterizing material compression behavior have been well reported. In this work, the Gurnham equation, which was first introduced in chemical engineering, is proposed as an alternate method of evaluating the compressibility of pharmaceutical powders. The Gurnham equation was adapted for tablet compression and the estimated slope parameter c was proposed to represent material compressibility. Data from the compression of four commonly used excipients (microcrystalline cellulose, corn starch, lactose monohydrate, and dibasic calcium phosphate dihydrate) and one drug (acetaminophen) were evaluated using the Gurnham equation. Using compression data at different peak pressures, linear relationships between porosity and lnPressure of the five materials were obtained. The determined parameter c expresses the compressibility of materials. The analysis of previous experimental data, including granulations, mixtures and co-processed materials also indicates that c might be a representative parameter for material compressibility.

Acetaminophen↗

On exemplary scientific conduct regarding submission of manuscripts to biomedical informatics journals.

As the Editors of leading international biomedical informatics journals, the authors report on a recent pattern of improper manuscript submissions to journals in our field. As a guide for future authors, we describe ethical and pragmatic issues related to submitting work for peer-reviewed journal publication. We propose a coordinated approach to the problem that our respective journals will follow. This Editorial is being jointly published in the following journals represented by the authors: Computer Methods and Programs in Biomedicine, International Journal of Medical Informatics, Journal of Biomedical Informatics, Journal of the American Medical Informatics Association, and Methods of Information in Medicine.

Biomedical Research↗

The cost of chronic stress: impacts of a nonhabituating stress response on metabolic variables and swimming performance in sturgeon.

Metabolic scope for activity (MSA) and critical swimming velocity (U(crit)) were measured in green sturgeon exposed to two stressors daily for 28 consecutive days. The results were compared with unstressed fish in an effort to measure the "cost" of chronic stress. Chronic stress was simulated by exposing fish to a randomized order of acute stressors: a 5-min chasing stressor, a 10-min water depth reduction stressor, or a 5-min confinement stressor. The acute cortisol response to each stressor was initially determined, and the maintenance of that response was verified in 7-d intervals during the chronic stress regime. Exposure to the chronic stress regime resulted in a 25% reduction of MSA caused by significantly increased maintenance metabolic rate (0.27+/-0.01 vs. 0.19+/-0.02 mg O(2) h(-1) g(-1), chronic and control fish, respectively) but did not affect the U(crit) of sturgeon. In addition, a 50% reduction in liver glycogen levels and a twofold increase of resting plasma glucose levels were measured in chronically stressed fish. We conclude that our chronic stress regime resulted in a significant maintenance cost to green sturgeon, possibly because of their inability to habituate to the stressors, but did not decrease their swimming performance.

Analysis of Variance↗

Standardization of a broth microdilution susceptibility testing method to determine minimum inhibitory concentrations of aquatic bacteria.

A multiple laboratory study was conducted in accordance with the standards established by the Clinical and Laboratory Standards Institute (CLSI), formerly the National Committee for Clinical Laboratory Standards (NCCLS), for the development of quality control (QC) ranges using dilution antimicrobial susceptibility testing methods for bacterial isolates from aquatic animal species. QC ranges were established for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 when testing at 22, 28 and 35 degrees C (E. coli only) for 10 different antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, flumequine, gentamicin, ormetoprim/sulfadimethoxine, oxolinic acid, oxytetracycline and trimethoprim/sulfamethoxazole). Minimum inhibitory concentration (MIC) QC ranges were determined using dry- and frozen-form 96-well plates and cation-adjusted Mueller-Hinton broth. These QC ranges were accepted by the CLSI/NCCLS Subcommittee on Veterinary Antimicrobial Susceptibility Testing in January 2004. This broth microdilution testing method represents the first standardized method for determining MICs of bacterial isolates whose preferred growth temperatures are below 35 degrees C. Methods and QC ranges defined in this study will enable aquatic animal disease researchers to reliably compare quantitative susceptibility testing data between laboratories, and will be used to ensure both precision and inter-laboratory harmonization.

Aeromonas salmonicida↗

Case report: angioleiomyoma of the spermatic cord: a rare scrotal mass.

We report a case of angioleiomyoma of the spermatic cord. Tumours arising from the spermatic cord are rare and most of them are benign. The commonest are lipomas with sarcomas being the predominant malignant variety. This is the first reported case of angioleiomyoma of the spermatic cord.

Angiomyoma↗

Impact of tumour depth, tumour location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumours.

The goal of this study was to determine the significance of tumour depth, tumour location and multiple synchronous tumour masses for the prognostic evaluation of canine cutaneous mast cell tumours (MCTs). The study population consisted of 100 formalin-fixed, paraffin-embedded cutaneous MCTs that had been surgically removed from 100 dogs and submitted to the Diagnostic Center of Population and Animal Health at Michigan State University between 1998 and 2001. None of the dogs had received chemotherapy or radiation therapy. For each case the following data were obtained from the referring veterinarians: sex, breed, weight, age at diagnosis, diagnostics performed, adjunct medications given at the time of surgery, tumour location, number of tumour masses, tumour recurrence (development of MCTs at the surgical site), development of additional MCTs at distant sites (outside the surgical margins), tumour duration before removal, survival time and cause of death, if applicable. Tumour depth was determined through microscopic evaluation of 5 microm sections stained with haematoxylin and eosin. Based on univariable and multivariable survival analysis, dogs with multiple synchronous cutaneous MCTs at the time of diagnosis have a worse prognosis compared with dogs with single tumours. Additional treatment beyond surgical excision alone should be considered for these animals. Older dogs and Boxers with cutaneous MCTs were at higher risk to develop additional MCTs at distant sites (outside the surgical margins), and older and male dogs with cutaneous MCTs had significantly shorter survival times. Univariable analysis also determined that dogs with cutaneous MCTs located on the head and neck had an increased risk of additional MCT development at distant sites and that sterilized dogs with cutaneous MCTs had shorter survival times. However, these findings were not confirmed by multivariable analysis. Tumour depth was of no prognostic significance for dogs with cutaneous MCTs.

Animals↗

Separation of ions from explosives in differential mobility spectrometry by vapor-modified drift gas.

Differential mobility spectrometry (DMS) of nitro-organic explosives and related compounds exhibited the expected product ions of M- or M x NO2- from atmospheric pressure chemical ionization reactions in purified air at 100 degrees C. Peaks in the differential mobility spectra for these ions were confined to a narrow range of compensation voltages between -1 to +3 V which arose through a low dependence of mobility for the ions in electric fields at E/N values between 0 and 120 Td (1 Td = 10(-17) V cm2). The field dependence of ions, described as an alpha parameter, ranged from -0.005 to 0.02 at a separation field of 100 Td. The alpha parameter could be controlled through the addition of organic vapors into the drift gas and was increased to 0.08-0.24 with 1000 ppm of methylene chloride in the drift gas. This modification of the drift gas resulted in compensation voltages of +3 to +21 V for peaks. The improved separation of peaks was consistent with a model of ion characterization by DeltaK or Kl - Kh, where Kl is the mobility coefficient of ions clustered with vapor neutrals during the low-field portion of the separation field waveform and Kh is for the same core ion when heated and declustered during the high-field portion of waveform.

Journal Article↗

Differential mobility spectrometry of chlorocarbons with a micro-fabricated drift tube.

Chlorocarbons were ionized through gas phase chemistry at ambient pressure in air and resultant ions were characterized using a micro-fabricated drift tube with differential mobility spectrometry (DMS). Positive and negative product ions were characterized simultaneously in a single drift tube equipped with a 3 mCi (63)Ni ion source at 50 degrees C and drift gas of air with 1 ppm moisture. Scans of compensation voltage for most chlorocarbons produced differential mobility spectra with Cl(-) as the sole product ion and a few chlorocarbons produced adduct ions, M (.-) Cl(-). Detection limits were approximately 20-80 pg for gas chromatography-DMS measurements. Chlorocarbons also yielded positive ions through chemical ionization in air and differential mobility spectra showed peaks with characteristic compensation voltages for each substance. Field dependence of mobility was determined for positive and negative ions of each substance and confirmed characteristic behavior for each ion. A DMS analyzer with a membrane inlet was used to continuously monitor effluent from columns of bentonite or synthetic silica beads to determine breakthrough volumes of individual chlorocarbons. These findings suggest a potential of DMS for monitoring subsurface environments either on site or perhaps in situ.

Environmental Monitoring↗

Antibiotics on urethral catheter withdrawal: a hit and miss affair.

Globally, millions of patients undergo urethral catheterization every year. Our objective was to study the current use of prophylactic antibiotics on urinary catheter withdrawal. A questionnaire (N = 300) was sent to healthcare professionals involved in the management of patients with urinary catheters (consultant microbiologists, infection control nurses, consultant urologists, specialist nurses in urology, continence advisers and consultants in the care of older people). The questionnaire asked about their use of prophylactic antibiotics on the withdrawal of a urethral catheter. Sixty percent of healthcare professionals advocated the use of antibiotics for either all or selected groups of patients. The remainder did not. The use of prophylactic antibiotics varied among different groups. Of the healthcare professionals who used antibiotics, the majority cited more than one reason for their use (prevent bacteraemia, avoid an infection in a prosthesis or urinary tract infection). The course and type of antibiotic used varied. Our study has shown diversity in practice that is of concern. At present, just over one-half of patients with urinary catheters are being given antibiotics, although there is no evidence to suggest that such an intervention confers any benefit. If benefits do not exist, these patients are being exposed to the harm of antibiotics and providers are incurring costs unnecessarily. A formal trial to address this issue is urgently needed.

Aged↗

Oral quinolones in hospitalized patients: an evaluation of a computerized decision support intervention.

OBJECTIVE: To determine whether a computerized decision support system could increase the proportion of oral quinolone antibiotic orders placed for hospitalized patients. DESIGN: Prospective, interrupted time-series analysis. SETTING: University hospital in the south-eastern United States. SUBJECTS: Inpatient quinolone orders placed from 1 February 2001 to 31 January 2003. INTERVENTION: A web-based intervention was deployed as part of an existing order entry system at a university hospital on 5 February 2002. Based on an automated query of active medication and diet orders, some users ordering intravenous quinolones were presented with a suggestion to consider choosing an oral formulation. MAIN OUTCOME MEASURE: The proportion of inpatient quinolone orders placed for oral formulations before and after deployment of the intervention. RESULTS: There were a total of 15 194 quinolone orders during the study period, of which 8962 (59%) were for oral forms. Orders for oral quinolones increased from 4202 (56%) before the intervention to 4760 (62%) after, without a change in total orders. In the time-series analysis, there was an overall 5.6% increase (95% CI 2.8-8.4%; P < 0.001) in weekly oral quinolone orders due to the intervention, with the greatest effect on nonintensive care medical units. CONCLUSIONS: A web-based intervention was able to increase oral quinolone orders in hospitalized patients. This is one of the first studies to demonstrate a significant effect of a computerized intervention on dosing route within an antibiotic class. This model could be applied to other antibiotics or other drug classes with good oral bioavailability.

Administration, Oral↗

Do we need to perform cystoscopy on all adults attending urology centres as outpatients?

INTRODUCTION: There has been considerable expansion in the use of flexible cystoscopy (FC) and people who can perform the procedure. Hence, there is a criticism that this procedure is being overused with no management benefit. MATERIALS AND METHODS: We audited the use of FC in a district hospital for a period of 1 year. The results of FC for non-standard indications (other than haematuria and check cystoscopy) were analysed for their diagnostic yield. RESULTS: Of the 1,390 FCs performed, 295 were done for non-standard indications. 46.14% of these cystoscopies had positive findings. Cancer detection rate was 6.10%. Cystoscopy altered the management in 14.08% of patients and was supportive to diagnosis and management in 32.06%. CONCLUSION: This procedure is certainly not overused and the ever-increasing requirement of this simple procedure has serious resource implications for the National Health Service.

Adult↗

Carcinogenicity of inhaled vanadium pentoxide in F344/N rats and B6C3F1 mice.

Vanadium pentoxide (V2O5) is a slightly soluble compound found in airborne particle emissions from metallurgical works and oil and coal burning. Because the carcinogenic potential of V2O5 was not known, F344/N rats and B6C3F1 mice (N=50/sex/species) were exposed to V2O5 at concentrations of 0, 0.5 (rats only), 1, 2, or 4 (mice only) mg/m3, by whole-body inhalation for 2 years. The survival and body weights of rats were minimally affected by exposure to V2O5. The survival and body weights of male mice exposed to 4 mg/m3 and body weights of all exposed groups of female mice were lower than the controls. Alveolar/bronchiolar (A/B) neoplasms occurred in male rats exposed to 0.5 and 2 mg/m3 at incidences exceeding the National Toxicology Program (NTP) historical control ranges. A marginal increase in A/B neoplasms was also observed in female rats exposed to 0.5 mg/m3. Increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar hyperplasia/metaplasia and squamous metaplasia were observed in exposed male and female rats. A/B neoplasms were significantly increased in all groups of exposed mice. As with rats, increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar epithelial hyperplasia were observed in mice exposed to V2O5. Thus, V2O5 exposure was a pulmonary carcinogen in male rats and male and female mice. The marginal tumor response in the lungs of female rats could not be attributed conclusively to exposure to V2O5. These responses were noted at and slightly above the OSHA permissible occupational exposure limit of 0.5 mg/m3 (dust) (National Institute for Occupational Safety and Health, NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Washington, DC, 1997, p. 328).

Adenoma↗

Long-term surveillance of bladder tumours: current practice in the United Kingdom and Ireland.

INTRODUCTION: Surveillance of transitional cell carcinoma of the bladder forms a major part of the workload of many urology units. Unfortunately, the policy for long-term surveillance of these cancers is neither clear nor agreed upon in the absence of evidence base. Our study was performed to provide current national practice data, and begin the debate on consensus guidelines. MATERIALS AND METHODS: A questionnaire was sent to Consultant Urologists (CUs) in the UK and Ireland (n=501) asking about their policy on the long-term surveillance of different bladder tumours once patients are free of recurrence. RESULTS: A 73% response rate was observed (365/501). Views varied considerably. They ranged from life long cystoscopic surveillance for low-stage low-grade tumours (pTaG1) to discharge after 5 years (or less) of a recurrence-free period for pT1G3 tumour. Once long-term surveillance with cystoscopy had been discontinued, 55% of CUs felt no role was indicated for urine cytology in further follow up, whereas 17% would use it for all tumour types and 28% are selective. CONCLUSION: Our study has shown the complete lack of consensus regarding the long-term surveillance of bladder cancer in the UK and Ireland. This has major implications for policy making, resources allocation and cancer survival. We highlight the need for national guidelines in this area for optimal surveillance of bladder cancer, as a good prospective evidence-based data will not be available for many years. We believe our study might form the basis for discussion on such guidelines.

Carcinoma, Transitional Cell↗

Genetic polymorphisms in mouse genes regulating age-sensitive and age-stable T cell subsets.

To see whether genetic polymorphisms regulate inter-individual differences in T cell subset levels, we have conducted a genome scan in two populations of mice, bred as the progeny of a cross between CB6F1 females and C3D2F1 males. The data document quantitative trait loci (QTL) with statistically significant effects on CD4, CD8, and CD8 memory T cells, and on subsets of CD4 and CD8 T cells that express P-glycoprotein. Some of the loci detected were robust, in the sense that they produced effects of similar size both in mated female mice, and in a population that included male and female virgin animals. Some of the effects were stable, in that they were apparent at both 8 and 18 months of age, but others were age-specific, showing effects either at 8 or at 18 months but not at both ages. Genes that had an effect on the same T cell subset were in almost all cases additive rather than epistatic, and their combined effects could produce large overall effects, leading in the most dramatic case to a two-fold difference in CD8 memory cells. The analysis also documented two QTL, on chromosomes 4 and 13, that regulate an age-sensitive composite index of T cell subset pattern which has been shown previously to be a predictor of life expectancy in these mice. The analysis thus reveals both subset-specific genes and others which modulate the overall pattern of age-sensitive changes in T cell subset distributions.

Aging↗

Catheter-associated urinary tract infections: prevalence of uropathogens and pattern of antimicrobial resistance in a UK hospital (1996-2001).

OBJECTIVE: To assess the change in the bacterial profile and pattern of antibiotic resistance of catheter-associated urinary tract infections (CAUTIs, the most prevalent form of nosocomial infections) between 1996 and 2001. MATERIALS AND METHODS: Catheter samples of urine (CSUs) submitted in 1996, 1998 and 2001 (2451, 2460 and 3349 specimens, respectively) were analysed. The distribution of different uropathogens in bacterial CAUTIs and their in vitro antimicrobial resistance was evaluated over the study interval. The likelihood ratio test was used to assess whether there was a linear trend according to calendar year. RESULTS: Escherichia coli was the most frequently isolated pathogen in all years, but its frequency declined over time (35.6%, 32.5% and 26.6%, respectively). Enterococcus was the second most frequent overall, with a significant increase in frequency with time (11.8%, 15.3% and 22.0%, respectively). There was also a considerable change in resistance patterns to antibiotics. As a result, in 1996, CAUTIs were least often resistant to ciprofloxacin (8.0%) followed by co-amoxiclav (18.5%) and cephalexin (25.4%). In 2001, CAUTIs were least often resistant to co-amoxiclav (22.5%), followed by ciprofloxacin (27.2%) and nitrofurantoin (28.8%). CONCLUSION: The types of organisms associated with CAUTI have changed over the last 5 years in a UK institution, as have the patterns of antibiotic resistance. Currently, the most appropriate agents for the empirical management of CAUTIs seem to be co-amoxiclav, ciprofloxacin and nitrofurantoin.

Anti-Bacterial Agents↗

Antimicrobial susceptibility testing of aquatic bacteria: quality control disk diffusion ranges for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 at 22 and 28 degrees C.

Quality control (QC) ranges for disk diffusion susceptibility testing of aquatic bacterial isolates were proposed as a result of a multilaboratory study conducted according to procedures established by the National Committee for Clinical Laboratory Standards (NCCLS). Ranges were proposed for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 at 22 and 28 degrees C for nine different antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, gentamicin, oxolinic acid, oxytetracycline, ormetoprim-sulfadimethoxine, and trimethoprim-sulfamethoxazole). All tests were conducted on standard Mueller-Hinton agar. With >/=95% of all data points fitting within the proposed QC ranges, the results from this study comply with NCCLS guidelines and have been accepted by the NCCLS Subcommittee for Veterinary Antimicrobial Susceptibility Testing. These QC guidelines will permit greater accuracy in interpreting results and, for the first time, the ability to reliably compare susceptibility test data between aquatic animal disease diagnostic laboratories.

Aeromonas↗