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Biomedical subjects

R Snyder

Publications and source records attributed to R Snyder.

At least 19 recordsLinked to original sources
PubMed2002

Frequency of isolation of Staphylococcus lugdunensis in consecutive urine cultures and relationship to urinary tract infection.

Recent reports associate Staphylococcus lugdunensis with severe infection in humans. The frequency of this microorganism in urine cultures is unknown. Five hundred isolates of coagulase-negative staphylococci (CoNS) were recovered from 4,652 consecutive urine specimens submitted for culture to the Mayo Clinic Microbiology Laboratory. Thirty-one (6%) of 500 isolates of CoNS were identified as S. lugdunensis. In no case was S. lugdunensis isolated in pure culture; 29 (94%) of 31 S. lugdunensis isolates were part of mixed nonpathogenic flora. Medical records were reviewed for 30 of the 31 patients from whom these 31 isolates were isolated. Twenty-one (70%) of the 30 evaluable patients were not treated with antibiotics; the remaining 9 (30%) of 30 patients were treated with antibiotics that may be effective against S. lugdunensis. S. lugdunensis may be an unrecognized yet infrequent cause of urinary tract infection.

Aged↗
PubMed2001

Automated medication distribution systems and compliance with Joint Commission standards.

One health care institution's experience with an automated medication distribution (AMD) system is described, along with how the system met standards of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). AMD units were implemented in nearly 50 patient care locations in a medical center with the goal of providing cartless distribution for over 90% of all medications. Planning for the system began in the fall of 1998; the system was fully implemented by mid-2000. In compliance with JCAHO requirements, the system provided medications in unit dose or single unit-of-use packaging, supplied drugs in a ready-to-administer form, ensured that drugs were available only near the time of administration, created a patient-specific medication profile, allowed for pharmacist review of medication orders before dispensing, provided proper storage conditions, prevented unauthorized use, allowed for access in emergencies, and met federal and state regulations. Implementation of the system improved drug distribution at the medical center and saved nursing and pharmacy time. Challenges included waits by nurses trying to access the AMD units and the extensive, ongoing education and training required for users of the system. An AMD system should be fully integrated with the health care institution's medication-use process and comply with applicable JCAHO standards.

Drug Utilization↗
PubMed2001

Pharmacokinetic studies in Tg.AC and FVB mice administered [14C] benzene either by oral gavage or intradermal injection.

Chronic benzene toxicity has been demonstrated to result in either aplastic anemia or acute myelogenous leukemia, a form of granulocytic leukemia, in exposed people (Snyder and Kalf, Crit. Rev. Toxicol. 24, 177-209, 1994). Aplastic anemia has been demonstrated in animal models following benzene exposure but, heretofore, it has not been possible to replicate benzene-induced granulocytic leukemia in animals. The Tg.AC mouse appears to be the first animal model in which a granulocytic leukemia was produced by treatment with benzene (Tennant et al., The Use of Short- and Medium-Term Tests for Carcinogenic Hazard Evaluation, 1999; French and Saulnier, J. Toxicol. Environ. Health 61, 377-379, 2000). Leukemia was observed in Tg.AC mice to which benzene was administered dermally. Neither orally dosed Tg.AC mice or mice of the parental FVB strain treated by either route of exposure developed leukemia. It is well established that benzene metabolism is required to produce benzene toxicity. To determine whether metabolic differences arising from differences in route of exposure or strain of mouse directed the development of leukemia, the pharmacokinetics of benzene were compared between the two strains and between the two routes of administration. Regardless of the route of exposure or the strain of mouse, seven major metabolites plus unmetabolized benzene were detected in most samples at most time points. Few differences were observed between the two strains following either route of administration. These results suggest that the genetic modification in the Tg.AC mouse, i.e., insertion of the v-Ha-ras construct into the genome, did not disrupt any major pathways involved in determining the pharmacokinetics of benzene. Two significant differences were observed between the two routes of exposure: first, benzene was absorbed more slowly after intradermal injection than after oral gavage, and second, the intradermally dosed mice produced more conjugates of hydroquinone than did the orally dosed mice. These differences in metabolism may be involved in the previously observed differences in hematotoxicity between the two routes of exposure.

Administration, Oral↗
PubMed2001

Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group.

PURPOSE: To compare the efficacy and tolerability of tamoxifen with that of letrozole, an oral aromatase inhibitor, with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: Nine hundred seven patients were randomly assigned letrozole 2.5 mg once daily (453 patients) or tamoxifen 20 mg once daily (454 patients). Patients had estrogen receptor- and/or progesterone receptor-positive tumors, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression (TTP). Secondary end points included overall objective response rate (ORR), its duration, rate and duration of clinical benefit, time to treatment failure (TTF), overall survival, and tolerability. RESULTS: TTP was significantly longer for letrozole than for tamoxifen (median, 41 v 26 weeks). Treatment with letrozole reduced the risk of progression by 30% (hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P =.0001). TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole (median, 40 v 25 weeks). ORR was higher for letrozole (30% v 20%; P =.0006), as was the rate of clinical benefit (49% v 38%; P =.001). Survival data are currently immature and not reported here. Both treatments were well tolerated. CONCLUSION: Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer.

Adult↗
PubMed2001

The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER.

OBJECTIVE: To determine the prevalence of glaucoma in a population-based sample of Hispanic adults older than 40 years. METHODS: Using 1990 census data for Arizona, groups of persons living in sections of the city in Nogales and Tucson were randomly selected with a probability proportional to the Hispanic population older than 40 years. We tried to recruit all eligible adults in homes with 1 self-described Hispanic adult. Detailed ocular examinations at a local clinic included visual acuity testing, applanation tonometry, gonioscopy, an optic disc evaluation, and a threshold visual field test. Open-angle glaucoma (OAG) was defined using a proposed international system for prevalence surveys, including threshold visual field defect and optic disc damage. Angle-closure glaucoma was defined as bilateral appositional angle closure, combined with optic nerve damage (judged by field and disc as for OAG). RESULTS: Examinations were conducted in 72% (4774/6658) of eligible persons, with a 1.97% prevalence (95% confidence interval, 1.58%-2.36%) of OAG (94 persons). The age-specific OAG prevalence increased nonlinearly from 0.50% in those aged 41 to 49 years to 12.63% in those 80 years and older. Angle-closure glaucoma was detected in 5 persons (0.10%). Sex, blood pressure, and cigarette smoking were not significant OAG risk factors. Only 36 (38%) of the 94 persons with OAG were aware of their OAG before the study. Screening results with an intraocular pressure higher than 22 mm Hg (in the eye with a higher pressure) would miss 80% of the OAG cases. CONCLUSIONS: The prevalence of OAG in Hispanic persons was intermediate between reported values for white and black persons. The prevalence increased more quickly with increasing age than in other ethnic groups. Glaucoma was the leading cause of bilateral blindness.

Adult↗
PubMed2001

Comparative metabolism of [14C]benzene to excretable products and bioactivation to DNA-binding derivatives in maternal and neonatal mice.

Lactating adult female mice treated with a single dose of 880 mg/kg i.p. [14C]benzene, and their 2-day-old sucklings similarly treated or nursed by their treated dams were compared in terms of their ability to metabolize benzene to urinary products or reactive intermediates as assessed by covalently-bound benzene derivatives in whole blood or liver DNA. Six metabolite fractions were identified in the urine of sucklings by high performance liquid chromatographic (HPLC) analysis at 5 h following intraperitoneal (direct) treatment with benzene. Three of the metabolite fractions co-chromatographed with authentic phenol, phenyl glucuronide, and muconic acid, and contributed 11, 6.9 and 0.6%, respectively, to the total urinary benzene metabolites. Two of the fractions were unidentified. The sixth and most polar fraction consisted of multiple metabolites, 21% of which were conjugates, and accounted for 72% of the total urinary metabolites. A similar metabolite profile was observed in 24-h urine samples from treated dams with the exception that one of the unidentified fractions in the sucklings was absent and levels of the metabolites were quantitatively higher than those observed in sucklings 5 h following their treatment with benzene. Furthermore, 78% of the most polar fraction from the dams consisted of conjugates compared with 21% of that from the sucklings. The metabolite pattern in urine of sucklings nursed by treated dams was qualitatively similar to, but quantitatively different from the pattern in treated dams. Five hours following intraperitoneal treatment with benzene, covalent binding of the compound to DNA (expressed as pmol benzene equivalents/mg DNA) in sucklings was slightly higher in whole blood (1.15+/-0.07) than in liver (0.77+/-0.07), whereas in the dam, it was slightly lower in whole blood (0.88+/-0.48) than in liver (1.63+/-0.61). Twenty four hours following benzene exposure in sucklings of benzene-treated dams, DNA binding by the compound in whole blood (3.85+/-1.05) and liver (0.11+/-0.03) was higher and lower, respectively than the binding observed in benzene-injected sucklings 5 h following the injection. Our results show that excretable as well as reactive metabolites of benzene are formed substantially by the neonatal mouse, and that the extent of bioactivation of the compound is comparable in the adult and the suckling mouse. The results show also that sucklings of benzene-exposed mothers are exposed to substantial levels of the compound and are potentially susceptible to its toxic effects.

Animals↗
PubMed2001

Diabetes and diabetic retinopathy in a Mexican-American population: Proyecto VER.

OBJECTIVES: The prevalence rate of diabetes is probably higher in Hispanics than in Caucasians, although there is controversy about differences in the risk of diabetic retinopathy. The purpose of the study is to determine the prevalence rates of diabetes and diabetic retinopathy in a population-based study of Hispanics aged > or = 40 years. RESEARCH DESIGN AND METHODS: Proyecto VER is a random sample of Hispanic populations aged > or = 40 years in Arizona. A total of 4,774 individuals (71.6% of the eligible sample) completed the examinations. Diabetes was defined as self-report of a physician diagnosis or HbA(1c) value of > or = 7.0%. Diabetic retinopathy was assessed on stereo fundus photographs of fields 1, 2, and 4. RESULTS: The prevalence rate of diabetes in the Hispanic community (individuals > or = 40 years of age) was 22%. The prevalence rate of diabetic retinopathy (DR) was 48%; 32% had moderate to severe nonproliferative and proliferative retinopathy. DR increased with increasing duration of diabetes and increasing level of HbA(1c). The prevalence rate of DR-like changes in the sample of individuals without diabetic retinopathy was 15% and was not associated with hypertension, systolic blood pressure, or diastolic blood pressure. CONCLUSIONS: The prevalence rate of diabetes in this population of Hispanics is high, almost twice that of Caucasians. The prevalence rate of DR is high but similar to reports in a Caucasian population. The prevalence rate of 9% moderate to severe retinopathy in the newly diagnosed group suggests that efforts to improve detection and treatment of diabetes in Hispanics may be warranted.

Adult↗
PubMed2001

Psychometric properties of the 25-item NEI-VFQ in a Hispanic population: Proyecto VER.

PURPOSE: To assess the psychometric properties of the NEI-VFQ-25 in a population-based study of older Hispanic persons living in the United States, explore other demographic factors that affect participant response, and observe the comparability of the Spanish and English versions of the instrument. METHODS: A sample of randomly selected block groups in Tucson and Nogales, Arizona, were selected for study. Participants were interviewed at home; a majority of the interviews were conducted in Spanish. The home interview included questions from the NEI-VFQ-25 and HHANES: Presenting acuity was done using ETDRS methodology, followed by a standardized eye examination by an ophthalmologist. The authors analyzed the internal consistency of the NEI-VFQ-25 responses using Cronbach's alpha coefficient and the construct validity by assessing the relationship between presenting acuity and scale scores, adjusting for age and gender. A second model was also explored to determine whether other demographic variables affected scale scores; differences in reporting between the Spanish and English versions was observed in this model, used in a subset of the population that minimized interviewer effect. RESULTS: Of the 4774 participants in the study, 99.7% had completed questionnaires, not completed by proxy. The highest nonresponse rate occurred in the Driving scale, with 25% of participants not driving for reasons other than problems with vision. Internal consistency was high, with Cronbach alpha ranging between 0.65 and 0.86 for scales with multiple items. Adjusting for age and gender, those with presenting acuity worse than 20/40 scored significantly lower than those with presenting acuity 20/40 or better, for all scales. The demographic variables with the most consistent association across the NEI-VFQ-25 scales were presenting acuity, income, and gender. No significant differences in reporting were found between the Spanish and English versions of the questionnaire in the subset of the population. CONCLUSIONS: In this study of Hispanic people age 40 years or older, the NEI-VFQ-25 was sensitive to presenting acuity and other demographic variables, such as age, gender, and income. The findings from this psychometric analysis provide evidence of the reliability and validity of some of the scales in the 25-item NEI-VFQ when used among people with a range of visual acuity level, providing other explanatory variables are also considered.

Activities of Daily Living↗
PubMed1999

Metabolism of [14C]phenol in the isolated perfused mouse liver.

A previous report from this laboratory focused on the metabolism of [14C]benzene (BZ) in the isolated, perfused, mouse liver (C. C. Hedli, et al., 1997, Toxicol. Appl. Pharmacol. 146, 60-68). Whereas administration of BZ to mice results in bone marrow depression (R. Snyder et al., 1993, Res. Commun. Chem. Pathol. Pharmacol. 20, 191-194), administration of phenol (P), the major metabolite of BZ, does not. It was, therefore, of interest to determine whether the metabolic fate of P produced during BZ metabolism differed from that of P metabolized in the absence of BZ. Mouse livers were perfused with a solution of [14C]P in both the orthograde (portal vein to central vein) and retrograde (central vein to portal vein) direction to investigate the metabolic zonation of enzymes involved in P hydroxylation and conjugation. Perfusate samples were collected, separated by HPLC, and tested for radioactivity. Unconjugated metabolites were identified by comparing their retention times with nonradiolabeled standards, which were detected by UV absorption. Conjugated metabolites were identified and collected on the basis of radiochromatogram results, hydrolyzed enzymatically, and identified by co-chromatography with unlabeled BZ metabolites. The objective was to compare and quantify the metabolites formed during the perfusion of P in the orthograde and retrograde directions and to compare the orthograde P-perfusion results with the orthograde BZ results reported previously. Regardless of the direction of P perfusion, the major compounds released from the liver were P. phenylgucuronide, phenylsulfate, hydroquinone (HQ), and HQ glucuronide. A comparison of the results of perfusing P in the orthograde versus the retrograde direction showed that more P was recovered unchanged and more HQ was formed during retrograde perfusion. The results suggest that enzymes involved in P hydroxylation are generally closer to the central vein than those involved in conjugation, and that during retrograde perfusion, P metabolism may be limited by the sub-optimal conditions of perfusion. Comparison of the orthograde perfusion studies of P and BZ revealed that a larger percentage of the radioactivity released from the liver was identified as unconjugated HQ after BZ perfusion than after P perfusion. In addition, the amount of radioactivity covalently bound to liver macromolecules was measured after each perfusion and determined to be proportional to the amount of HQ and HQG detected in the perfusate samples.

Animals↗
PubMed1998

Genetic influences on electrical seizure threshold.

C57BL/6J (B6) and DBA/2J (D2) mice have been characterized previously as seizure-resistant and seizure-sensitive, respectively, a distinction based primarily upon a differential response to the convulsant effects of various drugs. In the present study, electroconvulsive shock (ECS) was used to assess maximal electroshock threshold (MET) in B6, D2 and hybrid mice. Results revealed that D2 mice have a significantly lower MET compared to B6 mice. There was also a significant gender effect for B6 and F2 mice with females exhibiting a lower MET compared to males. METs for F1 and F2 intercross mice were intermediate between the two parental strains. The difference in variance between F2 and F1 generation mice indicated that about three-quarters of the total variance is due to genetic influence. Taken together, results of this study suggest that the large difference in MET between B6 and D2 mice is a highly heritable trait which may yield to genetic dissection through use of quantitative trait locus mapping.

Animals↗