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Biomedical subjects

Robert Snyder

Publications and source records attributed to Robert Snyder.

12 recordsLinked to original sources
PubMed2006

Lobular intraepithelial neoplasia [lobular carcinoma in situ] with comedo-type necrosis: A clinicopathologic study of 18 cases.

The recent finding that lobular, and not ductal intraepithelial neoplasia (DIN) displays loss of E-cadherin expression has greatly facilitated the categorization of a large proportion of morphologically ambiguous intraepithelial neoplasias into ductal or lobular types. One reason for such morphologic ambiguity is the presence of comedo-type necrosis within an intraepithelial lesion that otherwise shows archetypal cytologic and architectural features of lobular intraepithelial neoplasia (LIN). The clinicopathologic features of 18 such cases are described in this report. These 18 cases of classic LIN were accumulated from the recent databases of 6 institutions. All cases, by definition, showed no expression of E-cadherin. The 18 patients, all women, were 41 to 85 years of age (mean 61.3). The lesions were initially identified in an excisional biopsy or mastectomy in 12 cases and in an incisional/core biopsy in the remaining 6 cases. An associated invasive carcinoma was present in 12 (67%) of 18 cases (7 classic lobular, 1 pleomorphic lobular, 1 ductal, 1 mixed lobular and ductal, 1 tubular, and 1 case with ductal and lobular carcinomas as separate foci). The average age of the 6 patients with pure LIN (ie, LIN without an invasive component (62.5 y) was not significantly different from the 12 patients in which there was an invasive component (60.7 y) (P = 0.78). The lesions had associated calcifications, typically within the necrotic foci, in 10 (55%) of 18 cases. Immunoreactivity for estrogen receptor, progesterone receptor (in >10% of lesional cells), and high-molecular weight keratin was present in 17/18 (94%), 15/18 (83%) and 17/18 (94%) of cases, respectively. Overexpression of HER2/neu, as assessed immunohistochemically, was absent in all 15 cases available for such evaluation. Foci of DIN, separate from the lobular lesions, were present in 6 (33%) of 18 cases. LIN with necrosis seems to occur at an older age than classic LIN, is commonly associated with invasive carcinoma and is significantly more frequently associated with lobular than ductal invasive carcinoma. When present without an invasive component, it may be mistaken for DIN 2 (grade 2 ductal carcinoma in situ). Although the necrosis suggests a ductal phenotype for these intraepithelial proliferations, architectural and cytologic features, high-molecular weight keratin[+], estrogen receptor[+], progesterone receptor[+], and human epidermal growth factor receptor 2 /neu[-] immunoprofile, frequent association with invasive lobular carcinoma, and lack of immunoreactivity for E-cadherin, strongly suggests that these lesions are within the morphologic spectrum of lobular neoplasia. Long-term follow-up studies are required to define the true natural history of these lesions. However, because classic LIN with necrosis is apparently rare in its pure form, reexcision is recommended when this lesion is detected in isolation in a core biopsy.

Adult↗
PubMed2005

International symposium: Recent advances in benzene toxicity.

The symposium overview describes the recent succession of scientific meetings to further understand the adverse effects of benzene. It reviews the epidemiological evidence for hematological changes including leukemias and non-Hodgkins lymphoma, the progress in molecular biology and mechanism of action as well as ongoing studies in these fields. Various national occupational and community exposure monitoring data show that there has been significant progress in reducing benzene exposures globally. Biomarkers and biomonitoring have been used to provide information on biological plausibility, mode of action and susceptibility, and in the discrimination of co-exposures. Current research should help to further clarify cell type specificity, relationship to exposure, and the molecular elements involved in mechanism.

Air Pollutants, Occupational↗
PubMed2005

Prevalence of age-related macular degeneration in a population-based sample of Hispanic people in Arizona: Proyecto VER.

OBJECTIVE: To report the prevalence of age-related macular degeneration (AMD) in a population-based sample of Hispanic individuals aged 50 years and older. METHODS: Proyecto VER (Vision and Eye Research) is a population-based study of blindness and visual impairment of Hispanic people in Arizona. Participants underwent complete ophthalmic evaluation, including stereoscopic fundus photography of fields 1, 2, and 4. All photographs for participants aged 50 years and older were graded using the Wisconsin Age-Related Maculopathy Grading system. The following signs were graded: drusen size, drusen type, and the area covered by drusen; pigmentary abnormalities; geographic atrophy; and exudative AMD. RESULTS: Sixty-seven percent (3178) of the original 4774 participants were 50 years of age or older. Of those, 92% (2928) had fundus photographs in at least 1 eye, and 95% (2780) of the photographs were of sufficient quality to grade early and late AMD. OUTCOME MEASURES: The overall prevalence of late AMD was 0.5%. The prevalence increased from 0.1% in the 50- to 59-year age group to 4.3% in the group aged 80 years and older. Likewise, early AMD was strongly associated with age with a prevalence of 20% in the 50- to 59-year age group, increasing to 54% in the group aged 80 years and older. The prevalence of early AMD in Hispanic people was significantly higher than the reported prevalence in the white population. However, the prevalence of late AMD was lower than the estimates for the white population of the United States. CONCLUSIONS: Although early macular changes were very common among Hispanic people, the prevalence of late AMD was infrequent. Further work is necessary to understand the underlying reasons for the different patterns of presentation of early and late signs of AMD among racial/ethnic groups and to characterize early AMD based on predictive value for severe disease in different populations.

Age Distribution↗
PubMed2005

Cataract and barriers to cataract surgery in a US Hispanic population: Proyecto VER.

OBJECTIVES: To report the prevalence of visually significant cataract and cataract surgery and to determine demographic and socioeconomic factors that influence use of cataract surgery in a US Hispanic population. METHODS: Proyecto VER is a population-based study of Hispanic individuals, 40 years or older, living in southern Arizona. Visual acuity was measured monocularly, and a dilated ophthalmic examination was performed to determine lens opacities. Visually significant cataract was defined as severe levels of opacity and acuity worse than 20/40. Risk factors were compared between those who obtained cataract surgery in the past and those having visually significant cataract. RESULTS: A majority of the 4774 participants in this study were of Mexican descent; 2.8% had visually significant cataract and 5.1% had undergone bilateral cataract surgery. Among those currently or previously needing surgery, having medical insurance (odds ratio, 2.88; P<.001) and speaking English (odds ratio, 1.80; P = .04) were significantly associated with having obtained surgery in the past. CONCLUSIONS: Visually significant cataract appears to be high among US Hispanic individuals of Mexican descent, as evidenced by rates of cataract and cataract surgery. Language and financial barriers in this population impede access to surgery. Further work to remove these barriers and provide sight restoration is warranted among Hispanic individuals of Mexican descent living in the United States.

Adult↗
PubMed2004

Xenobiotic metabolism and the mechanism(s) of benzene toxicity.

The investigation of the mechanism(s) of benzene toxicity/leukemogenesis over the past 50 years has been contemporaneous with developments in the study of xenobiotic metabolism. Research on the cytochrome P450 (CYP) enzyme system, and related systems in vivo and in vitro, which culminated in the isolation and reconstitution of the many CYPs, established pathways for the study of xenobiotic metabolism and its relationship to the biological activity of many chemicals. The essential role for metabolism of benzene as a precursor to the demonstration of benzene toxicity led to extensive studies of benzene metabolism, many of which will be reviewed here. Benzene toxicity/leukemogenesis, however, is a function of the bone marrow, a site remote from the liver where most benzene metabolism occurs. Studies of benzene metabolism have delineated the array of metabolites which appear to play a role in bone marrow damage, but further studies, both in vivo and in vitro, using appropriate animal models, will be needed to fully understand the impact of benzene and its metabolites on bone marrow function.

Animals↗
PubMed2004

Metabolic and biochemical issues in the molecular epidemiology of cancer.

In this chapter, we highlight the significance of some metabolic and biochemical issues in molecular epidemiology. We discuss biomarkers and biologically reactive intermediates and describe the significance of polymorphisms in xenobiotic metabolizing enzymes, with emphasis on the role of some of these enzymes in the generation of reactive metabolites and on the related issue of susceptibility biomarkers. In the final section, we have selected an example of a specific compound, benzene, for which a variety of different biomarkers have been studied.

Benzene↗
PubMed2002

Frequency and causes of vaccine wastage.

UNLABELLED: Assessing the frequency of vaccine wastage and the relative magnitude of its various causes may help to target efforts to reduce these losses and to husband funds for increasingly expensive vaccines. METHODS: As a preliminary overview of wastage in the United States, 64 public-sector state and local health department immunization programs were polled in 1998 and 1999 for wastage recording practices. Actual wastage data were collected from a non-random subset of five states. Data on returns of wasted vaccine to manufacturers were analyzed from routine national biologics surveillance and from an ad-hoc survey. Excise tax credit requests for such returns between 1994 and 1999 were reviewed. RESULTS: Rates of wastage among the five states ranged from about 1 to 5% in 1998, with an overall rate of 2.6% among 57 immunization programs in 1999. Categories of wastage used by the health departments varied widely, with overlapping classifications. The major causes appeared to be refrigeration (cold chain) lapses, followed by expiration. Overall rates of vaccine returns varied up to 8% by manufacturer, and from 1 to 50% by vaccine type, with higher return rates generally found for lesser-used vaccines. CONCLUSIONS: If these wastage estimates of 1-5% applied nationally, in 1998 there would have been approximately US dollars 6-31 million worth of unused vaccine in the public sector alone. The two most common forms of wastage reveal the potential value of developing vaccines with improved heat stability and longer shelf lives. We propose six main classifications of vaccine wastage for use in routine monitoring and reporting.

Humans↗
PubMed2002

Risk factors for Type II diabetes and diabetic retinopathy in a mexican-american population: Proyecto VER.

PURPOSE: Risk factors for type II diabetes and diabetic retinopathy were determined in a population-based study of Mexican-Americans. DESIGN: Proyecto VER (Vision, Evaluation, and Research) is a cross-sectional study in a random sample of the self-described Hispanic populations in Tucson and Nogales, Arizona, age 40 and older. METHODS: Of 6,659 eligible subjects, 4,774 (72%) participated in the home questionnaire and clinic visit. Diabetes was defined as self-report of a physician diagnosis or hemoglobin A(1c) value of > or = 7.0%. Only type II diabetes was included. Diabetic retinopathy was assessed on stereo fundus photographs of all persons with diabetes. Questions were asked about demographic, personal, socioeconomic, and diabetes related variables. RESULTS: 1023 (21.4%) of the sample had type II diabetes, and 68% were in the low-income group (annual income less than $20,000). Diabetes was associated with Native-American ancestry, higher acculturation, low income, less education, and increasing body mass index after age and gender adjustment. Persons with previously undiscovered diabetes were more likely to have no regular source of care, no insurance, and currently smoke compared with persons with known diabetes. Only low income was related to proliferative retinopathy, once adjusted for other factors (odds ratio [OR] = 3.93, 95%, confidence limitations [CL] = 1.31-11.80). CONCLUSIONS: Several socioeconomic and other factors were associated with diabetes, but few were related to diabetic retinopathy. Persons in the low-income group appeared to be at greater risk of diabetes and the ocular complications of diabetes compared with those with more income. Further longitudinal studies in this population are needed to confirm the associations.

Adult↗
PubMed2002

Blindness, visual impairment and the problem of uncorrected refractive error in a Mexican-American population: Proyecto VER.

PURPOSE: To report the prevalence of blindness and visual impairment and the contribution of uncorrected refractive error to visual loss, in a population-based sample of Mexican Americans aged 40 and older. METHODS: Proyecto VER is a population-based study of blindness and visual impairment in Mexican Americans in Arizona. Block groups in Tucson and Nogales were randomly selected with probability proportional to the size of the Mexican-American population aged 40 and older. Participants had a complete ophthalmic evaluation, including assessment of presenting and best corrected visual acuity using standardized procedures. Those with presenting visual acuity worse than 20/30 had refraction to determine best corrected vision. A home questionnaire and a clinic examination provided data on education, perception of visual impairment, income, and acculturation. RESULTS: The prevalence of presenting visual acuity worse than 20/40 was 8.2%, with uncorrected refractive error accounting for 73% of the impaired acuity. In multivariate models comparing those who improved two or more lines on the acuity chart with proper refraction with those who had adequate optical correction, uncorrected refractive error showed a strong association with age, less than 13 years of education (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.5-2.0), low acculturation index (OR 1.3, CI 1.1-1.3), lack of insurance coverage (OR 1.4, CI 1.1-1.7), and not having seen an eye-care provider in the past 2 years (OR 2.5, CI 2.1-3.0). Prevalence of best corrected acuity worse than 20/40 increased from 0.3% in those aged 40 to 49 years to 18% in those aged 80 years or more. CONCLUSIONS: Visual loss in this Mexican-American population is higher than has been reported in whites and is comparable to that in African Americans. Almost three quarters of those with visual acuity impairment would improve with optical correction. Socioeconomic factors that are probable markers of limited access to health care services were associated with uncorrected refractive error. These data suggest that education programs and interventions to improve access to eye care could significantly decrease the burden of visual loss among Mexican Americans.

Adult↗
PubMed2002

The impact of visual impairment and eye disease on vision-related quality of life in a Mexican-American population: proyecto VER.

PURPOSE: To describe the relationship of visual acuity impairment and eye disease on vision-related quality of life, as measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), in a cross-sectional, population-based study of older Hispanic persons living in Arizona. METHODS: A random sample of block groups with Hispanic residents in Nogales and Tucson, Arizona, were selected for study. Participants were interviewed at home with a questionnaire that included the NEI-VFQ-25, an instrument measuring vision-related quality of life. Acuity was obtained with Early Treatment Diabetic Retinopathy Study (ETDRS) charts and standard protocol. Cataract was determined by clinical examination, diabetic retinopathy was diagnosed on stereo fundus photographs, and glaucoma was diagnosed on the basis of clinical examination and visual field results. Analyses were done to determine the degree of association between subscale scores and acuity in the better-seeing eye, monocular visual impairment, and specific eye diseases, with adjustment for acuity. RESULTS: Of the 4774 participants in the study, 99.7% had completed questionnaires that were not completed by proxy. Participants with visual impairment had associated decrements in scores on all subscales, with a decrease in presenting acuity associated with a worse score (P < 0.05), after adjustment for demographic variables. Monocular impairment was also associated with lower scores in several subscales. In those with cataract, low acuity explained most of the low scores, but those with glaucoma or diabetic retinopathy had low scores independent of acuity. CONCLUSIONS: In this study of Mexican-American persons aged 40 or more, monocular impairment and better-eye acuity was associated with a decrease in most domains representing quality of life. Subjects with uncorrected refractive error, cataract, diabetic retinopathy, and glaucoma had associated decrements in quality of life, many not explained by loss of acuity. Further work on the specific measures of vision associated with reported decreases in quality of life, such as visual field or contrast sensitivity, is warranted.

Adult↗
PubMedDate not supplied

Inhibition of topoisomerase II in 32D.3(G) cells by hydroquinone is associated with cell death.

Studies showing the inhibition of isolated human topoisomerase II (topo II) by benzene metabolites such as hydroquinone, coupled with the recognition that benzene-induced acute myelogenous leukemia bears a resemblance to second cancers caused by topo II inhibitors such as etoposide, suggested that topo II inhibition by hydroquinone might induce leukemogenic mutations. In these studies the inhibition of topo II by hydroquinone or etoposide was studied in parallel with the effects of these agents on differentiation, maturation and viability in murine bone marrow 32D.3(G) cells. Topoisomerase II of 32D.3(G) cells was inhibited by hydroquinone at concentrations of 5 micro M or higher and by etoposide at concentrations of 50 micro M or higher. At concentrations of either agent below those that inhibited topo II the cells responded normally to interleukin-3, which promoted proliferation, and to granulocyte colony-stimulating factor, which promoted differentiation and maturation. In dose ranges in which topo II was inhibited by either hydroquinone or etoposide, the cells became progressively less viable and cell counts decreased during the incubation period. Progressive inability to detect topo II protein by Western blot analysis as hydroquinone concentrations were increased suggested that either association of the probe with the enzyme was inhibited by hydroquinone or there was degradation of the protein as a function of hydroquinone-induced apoptosis.

Animals↗