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Biomedical subjects

A Eaton

Publications and source records attributed to A Eaton.

At least 19 recordsLinked to original sources

Comparison of quality and cost-effectiveness in the evaluation of symptomatic cholelithiasis with different approaches to ultrasound availability in the ED.

Ultrasound is the imaging study of choice for the detection of gallstones, but ultrasound through medical imaging departments (MI Sono) is not readily available on an immediate basis in many emergency departments (EDs). Several studies have shown that emergency physicians can perform ultrasound themselves (ED Sono) to rule out gallstones with acceptable accuracy after relatively brief training periods, but there have been no studies to date specifically addressing the effect of ED Sono of the gallbladder on quality and cost-effectiveness in the ED. In this study, we investigated measures of quality and cost-effectiveness in evaluating patients with suspected symptomatic cholelithiasis during three different years with distinctly different approaches to ultrasound availability. The study retrospectively identified a total of 418 patients who were admitted for cholecystectomy or for a complication of cholelithiasis within 6 months of an ED visit for possible biliary colic. The percentage of patients who had gallstones documented at the first ED visit improved from 28% in 1993, when there was limited availability of ultrasound through the Medical Imaging Department (MI Sono), to 56% in 1995, when MI Sono was readily available, to 70% in 1997, when both MI Sono and ED Sono were readily available (P <.001). There were also significant differences over the 3 years in the mean number of days from the first ED visit to documentation of gallstones (19.7 in 1993, 10.7 in 1995, 7.4 in 1997, P <.001); the mean number of return visits for possible biliary colic before documentation of gallstones (1.67 in 1993, 1.24 in 1995, and 1.25 in 1997, P <.001); and the incidence of complications of cholelithiasis in the interval between the first ED visit for possible biliary colic and the date of documentation of cholelithiasis (6.8% in 1993, 5.9% in 1995, 1.5% in 1997, P =.049). The number of MI Sonos ordered by emergency physicians per case of symptomatic cholelithiasis identified increased from 1.7 in 1993 to 2.5 in 1995 and dropped back to 1.7 in 1997, when 4.2 ED Sonos per study case were also done. The cost of ED Sonos was more than offset by savings in avoiding calling in ultrasound technicians after regular Medical Imaging Department hours. The indeterminate rate for ED Sonos was 18%. Excluding indeterminates, the sensitivity of ED Sono for detection of gallstones was 88.6% (95% CI 83.1-92.8%), the specificity 98.2% (95% CI 96.0-99.3%), and the accuracy 94.8% (95% CI 92.5-96.5%). We conclude that greater availability of MI Sono in the ED was associated with improved quality in the evaluation of patients with suspected symptomatic cholelithiasis but also with increased ultrasound costs. The availability of ED Sono in addition to readily available MI Sono was associated with further improved quality and decreased costs. The indeterminate rate for ED Sono was relatively high, but excluding indeterminates, the accuracy of ED Sono was comparable with published reports of MI Sono.

Adolescent↗

Polymorphisms in the DNA repair gene XRCC1 and breast cancer.

X-ray repair cross complementing group 1 (XRCC1) encodes a protein involved in base excision repair. We examined the association of polymorphisms in XRCC1 (codon 194 Arg-->Trp and codon 399 Arg-->Gln) and breast cancer in the Carolina Breast Cancer Study, a population-based case-control study in North Carolina. No association was observed between XRCC1 codon 194 genotype and breast cancer, and odds ratios (ORs) were not modified by smoking or radiation exposure. A positive association for XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes compared with Arg/Arg was found among African Americans (253 cases, 266 controls; OR = 1.7, 95% confidence interval, 1.1-2.4) but not whites (386 cases, 381 controls; OR =1.0, 95% confidence interval, 0.8-1.4). Among African-American women, ORs for the duration of smoking were elevated among women with XRCC1 codon 399 Arg/Arg genotype (trend test; P < 0.001) but not Arg/Gln or Gln/Gln (P = 0.23). There was no difference in OR for smoking according to XRCC1 codon 399 genotype in white women. ORs for occupational exposure to ionizing radiation were stronger for African-American and white women with codon 399 Arg/Arg genotype. High-dose radiation to the chest was more strongly associated with breast cancer among white women with XRCC1 codon 399 Arg/Arg genotype. Our results suggest that XRRC1 codon 399 genotype may influence breast cancer risk, perhaps by modifying the effects of environmental exposures. However, interpretation of our results is limited by incomplete knowledge regarding the biological function of XRCC1 alleles.

Adult↗

High-performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for the analysis of xenobiotic metabolites in rat urine: application to the metabolites of 4-bromoaniline.

The use of HPLC-ICP-MS for the profiling and quantification of the metabolites of 4-bromoaniline following reversed-phase gradient chromatography is demonstrated. In the 0-8 h post dose sample, which contained the highest concentrations of compound-related material, it was possible to detect at least 16 metabolites of the compound. The methodology described offers the possibility of obtaining metabolite profiles and quantification for drugs and other xenobiotics in biological fluids and excreta without the requirement for radiolabelled tracers.

Aniline Compounds↗

Ultrasound availability in the evaluation of ectopic pregnancy in the ED: comparison of quality and cost-effectiveness with different approaches.

The liberal use of ultrasonography has been advocated in patients with first trimester cramping or bleeding to avoid misdiagnosis of ectopic pregnancy in the emergency department (ED). The cost-effectiveness of different approaches to ultrasound availability has not been previously reported. In this study, we investigated measures of quality and cost-effectiveness in detecting ectopic pregnancy in the ED over a 6-year period, divided into three approximately equal epochs with three distinct approaches to ultrasound availability. The study retrospectively identified 120 cases of ectopic pregnancy seen in the ED over 6 years. There was significant improvement in the percentage of patients with ectopic pregnancy who were documented to have absence of intrauterine pregnancy (IUP) at the first visit from 76% during Epoch 1, when there was limited availability of ultrasound through medical imaging (MI Sono), to 88% in Epoch 2, when MI Sono was readily available, to 96% in Epoch 3, when both MI Sono and ultrasound by emergency physicians (ED Sono) were readily available (P = .02). The estimated number of MI Sonos ordered by emergency physicians in patients at risk for ectopic pregnancy increased from 5.2 per ectopic pregnancy in Epoch 1 to 11.8 per ectopic pregnancy in Epoch 2, and declined to 5.5 per ectopic pregnancy in Epoch 3, when 19.9 ED Sonos per ectopic pregnancy were also done. The cost of ED Sono in Epoch 3 was more than offset by savings from avoiding calling in ultrasound technicians after regular medical imaging department hours. The specificity of ED Sono in ruling in an IUP was 100% (95% CI 98.3 to 100%), but analysis of secondary quality indicators reflecting times from first ED visit to treatment in Epoch 3 raised the possibility that an adnexal mass or signs of tubal rupture may have been missed on some ED Sonos. We conclude that increased availability of ultrasonography leads to improved quality in the detection of ectopic pregnancy in the ED, but at the expense of a disproportionate increase in the number of ultrasound studies done per ectopic pregnancy detected. Our study suggests that the most cost-effective strategy is for emergency physicians to screen all patients with first trimester cramping and bleeding with ED Sonos, and to obtain MI Sonos at the time of the initial ED visit in all cases in which the ED Sono is indeterminate or shows no IUP.

Adult↗

Quantification of osseous facial dysmorphology in untreated unilateral coronal synostosis.

Unilateral coronal synostosis results in dysmorphology of the midface in addition to well-characterized cranial and orbital deformities. Because most American infants with this problem have undergone cranio-orbital surgery within their first year of life for the past 25 years, a paucity of data exist regarding the natural history of untreated unilateral coronal synostosis. In an attempt to remedy this void, an international search was conducted to identify computed tomography data sets of living individuals with untreated unilateral coronal synostosis; data were obtained from two European centers and one center in the United States. Results limited to the study of the midface are presented here. Digital data from high-resolution head computed tomography scans of 11 living, white individuals with untreated unilateral coronal synostosis were obtained from three craniofacial centers (in Denmark, The Netherlands, and the United States). Image volumes were constructed from each scan using ANALYZE biomedical imaging software. Fourteen pairs of three-dimensional distances were calculated on the ipsilateral (the side of the synostosis) and the contralateral (the side opposite to the synostosis) hemifaces using 11 osseous landmarks. The resulting measurements were expressed as a ratio of the ipsilateral: contralateral sides. Descriptive statistics were derived for the untreated unilateral coronal synostosis population and compared with analogous measurements performed on dried skulls. Age at computed tomography ranged from 1.1 to 21.1 years (mean, 6.6 years; median, 4.1 years). Twelve of the 14 measured distances differed by greater than 5 percent on the ipsilateral side, and all but one of these measurements were decreased on the ipsilateral side when compared with contralateral values. The results of this study support the following conclusions: (1) There are discrete and measurable differences in the facial morphology between patients with untreated unilateral coronal synostosis and normal skulls. (2) Intercenter and international collaboration can provide a sufficient number of individuals with rare craniofacial anomalies to quantitatively determine group characteristics. (3) Quantitative documentation of rare anomaly natural history is necessary for quantitative outcome assessment of treated patients.

Adolescent↗

Evidence for an association between environmental tobacco smoke exposure and birthweight: a meta-analysis and new data.

Because of the strong association of active smoking with fetal growth retardation, increasing interest has focused on whether there is also an association with exposure to environmental tobacco smoke (ETS). We examined this issue in a retrospective study and by conducting a review of the literature and data pooling. In our study, nonsmoking women with singleton livebirths born in 1986-87 (n = 992) provided information on exposure to ETS for 1 h or more per day and paternal smoking. The risk of low birthweight (LBW, < 2500 g) was not increased in infants of ETS-exposed women, but there was a somewhat increased risk for LBW at term (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 0.6, 4.8) and small-for-gestational-age (< 10th percentile of weight; OR = 1.4, 95% CI = 0.8, 2.5). These results were in the range of 16 other studies in the literature that had odds ratios from 1.0 to 2.2. A weighted average of the results of all studies on LBW at term or small-for-gestational-age yielded a pooled estimate of 1.2 [95% CI = 1.1, 1.3] in nonsmoking women. The pooled estimate of mean birthweight indicated a decrement of 28 g with ETS exposure of nonsmoking women [95% CI = -41, -16], with a greater decrement (about 40 g) seen among more homogeneous studies.

Adult↗

Reliability of placental histology using archived specimens.

Archived placental materials provide a resource for retrospective studies of perinatal outcomes. Using archived specimens, we evaluated inter-rater reliability in the assessment of placental histological features possibly associated with neonatal illness and long-term neurological outcome. Five expert placental pathologists independently reviewed archived placental specimens on 30 subjects born during 1983-85 in six different hospitals. Moderate to substantial agreement among the raters was observed for a variety of indicators of inflammation, presence of macrophages with pigment and indicators of villous maturity, increased syncytial knots and maternal vasculopathy. Existing pathology reports for these specimens from routine histology examinations conducted at the time of delivery were in substantial agreement with expert review for the presence of any subchorionitis/chorionitis/chorioamnionitis. In conclusion, considerable inter-rater agreement was observed for several relatively common and potentially important placental findings. Archived placental materials and pathology reports may be useful in retrospective studies.

Cerebral Palsy↗

Characterization of anergic anti-DNA B cells: B cell anergy is a T cell-independent and potentially reversible process.

Anti-single stranded DNA (ssDNA) and anti-double stranded DNA (dsDNA) B cells are regulated in non-autoimmune mice. In this report we show that while both anti-ssDNA and anti-dsDNA B cells are blocked in their ability to differentiate into antibody-secreting cells, other phenotypic and functional characteristics distinguish them from one another. Splenic anti-ssDNA B cells are found distributed throughout the B cell follicle, and are phenotypically mature and long-lived. On the other hand, splenic anti-dsDNA B cells are short-lived, exhibit an immature and antigen-experienced phenotype, and localize to the T-B interface of the splenic follicle. Functionally, anti-ssDNA B cells proliferate, albeit suboptimally, in response to anti-IgM, lipopolysaccharide (LPS) and CD40L/IL-4 + anti-IgM stimulation, and tyrosine phosphorylate intracellular proteins upon mIgM cross-linking. Anti-dsDNA B cells, on the other hand, are functionally unresponsive to anti-IgM and LPS stimulation, and do not phosphorylate intracellular proteins, including Syk, upon mIg stimulation. Importantly, anti-DNA B cell anergy is maintained in the absence of T cells since both anti-ssDNA and anti-dsDNA B cells are as efficiently regulated in RAG2(-/-) mice as in their RAG2(+/+) counterparts. Interestingly, the severely anergic state of anti-dsDNA B cells is partially reversible upon stimulation with CD40 ligand and IL-4. In response to these signals, anti-dsDNA B cells remain viable, up-regulate cell surface expression of B7-2 and IgM, and restore their ability to proliferate and phosphorylate Syk upon mIg cross-linking. Collectively, these data suggest that anti-DNA B cell anergy encompasses distinct phenotypes which, even in its most severe form, may be reversible upon stimulation with T cell-derived factors.

Animals↗

Self-reactive B cells in nonautoimmune and autoimmune mice.

The defining feature of autoimmune disease is the presence of specific autoreactive lymphocytes. Systemic lupus erythematosus (SLE), for example, is characterized by a discrete set of antibodies directed to nuclear antigens; these include autoantibodies to DNA and snRNPs that are diagnostic for SLE. The murine model of SLE, the MRL-lpr/lpr mouse, likewise, has a similar autoantibody profile. To understand how SLE-associated autoantibodies are regulated in healthy individuals and to identify mechanisms underlying their expression in autoimmunity, we have developed a transgenic (tg) model system using multiple sets of tgs. The development of B cells bearing these tgs has been studied in BALB/c and MRL-lpr/lpr autoimmune backgrounds, and the relative fates of anti-ssDNA and anti-dsDNA tg B cells when they are a part of a diverse as well as monoclonal B cell repertoire have been evaluated.

Animals↗

Regulation of anti-double-stranded DNA B cells in nonautoimmune mice: localization to the T-B interface of the splenic follicle.

Systemic lupus erythematosus (SLE) and the MRL-lpr/lpr murine model for SLE are characterized by the presence of serum anti-double-stranded (ds)DNA antibodies (Abs), whereas nonautoimmune individuals have negligible levels of these Abs. To increase the frequency of anti-DNA B cells and identify the mechanisms involved in their regulation in nonautoimmune mice, we have used Ig transgenes (tgs). In the present study, we used the VH3H9 heavy (H) chain tg which expresses an H chain that was repeatedly isolated from anti-dsDNA Abs from MRL-lpr/lpr mice. Because the VH3H9 H chain can pair with endogenous L chains to generate anti-single-stranded DNA, anti-dsDNA, and non-DNA B cells, this allowed us to study the regulation of anti-dsDNA B cells in the context of a diverse B cell repertoire. We have identified anti-dsDNA B cells that are located at the T-B interface in the splenic follicle where they have an increased in vivo turnover rate. These anti-dsDNA B cells exhibit a unique surface phenotype suggesting developmental arrest due to antigen exposure.

Animals↗

Assessment of gestational age using birth certificate data compared with medical record data.

We assessed the extent to which use of medical record data might improve gestational age estimates compared with reliance on the birth certificate alone. Using population-based data from four northern Californian counties, we constructed an algorithm to select the best gestational age estimate from antenatal assessments recorded in medical records. A total of 172 singletons with moderate or severe congenital cerebral palsy from the California Cerebral Palsy Project were compared with 472 randomly selected controls with regard to discrepancies between the algorithm-derived estimated gestational age (bestgest) and an estimate based solely on the last menstrual period as recorded on birth certificates. Agreement between bestgest and birth certificate estimated gestational age was exact or within one week for at least 60% of both cases and controls in each of the three birthweight strata. In general, the greater the birthweight of the babies, the better the agreement. The mean number of weeks of overestimation by the birth certificate was 0.7 weeks for cases and 1.1 weeks for controls in the lowest birthweight group (< 1500 g). When compared with bestgest, clinical examination of the infant also tended to overestimate gestational age. In the < 1500 g birthweight group, cases were twice as likely as controls to have a bestgest of 'low certainty,' but antenatal estimates of 'high certainty' were obtained for at least a third of very low birthweight babies born during the mid-1980s. More widespread use of early ultrasound in more recent birth cohorts may result in a greater proportion of accurate antenatal estimates. When a distinction between immaturity and intrauterine growth retardation is important to the understanding of the aetiology of the outcome under investigation, the use of antenatal estimates from medical records may substantially improve the certainty of the data.

Algorithms↗

Early IL-4 production does not predict susceptibility to Leishmania major.

Leishmania major in mice can be self-limiting or fatal, depending upon the inbred mouse strain. It is well established that the outcome of infection is dependent upon the Th cell subset that dominates after infection. This has led to intense study of the early events associated with infection, in order to better understand the factors that determine Th1/2 cell development. In the present report, we have analyzed the kinetics of IL-4 and IL-4 mRNA production in three mouse strains: BALB/c, C3H, and C57BL/6. We found that in the first week IL-4 is absent in the C3H mice, but present in the susceptible BALB/c and relatively resistant C57BL/6 mouse. These data indicate that the presence of IL-4 by itself does not determine whether the immune response will be dominated by Th2 cells, since C57BL/6 mice will eventually develop a Th1 response and heal. We suggest that the critical cytokine that determines susceptibility in experimental leishmaniasis is IL-12, rather than IL-4. Thus, in C3H mice IL-12 is evident soon after infection, and IL-4 responses are not observed. In C57BL/6 mice, IL-12 production is delayed, but once evident, the IL-4 response is ablated. Further, we show that addition of IL-12 can block early IL-4 production in BALB/c mice, and neutralization of IL-12 in C3H mice uncovers IL-4 production in response to L. major infection. Taken together, these data indicate that susceptibility to L. major, while possibly requiring IL-4, is not determined by the presence or absence of IL-4.

Animals↗

Positive predictive value of screening mammography by age and family history of breast cancer.

OBJECTIVE: To determine the positive predictive value (PPV) of low-cost screening mammography according to age and family history of breast cancer. DESIGN: Cross-sectional. SETTING: Six counties in northern California. PARTICIPANTS: A total of 31,814 women aged 30 years and older referred for mammography to the University of California, San Francisco, Mobile Mammography Screening Program from April 18, 1985, through November 20, 1992. MEASUREMENTS: Breast cancer risk profile, two standard mammographic views per breast, and follow-up of abnormal screening examinations. RESULTS: Although women aged 50 years or older constituted only 38.3% of all women who received first-screening mammography, 74% of breast cancers were detected in this group. Ten cancers were diagnosed per 1000 first-screening examinations in women aged 50 years or older, with 14.8 diagnostic procedures per cancer diagnosed compared with two cancers per 1000 screening examinations and 48.3 diagnostic tests per cancer diagnosed in women younger than 50 years. The PPV of first-screening mammography (number of breast cancers detected per abnormal examination) increased with age: .03 for those aged 30 to 39 years; .04 for those aged 40 to 49; .09 for those aged 50 to 59; .17 for those aged 60 to 69; and .19 for those aged 70 years or older (chi 2 for trend, P < .001). Women aged 50 to 59 years had a higher PPV for first-screening mammography than women aged 40 to 49 years (.09 vs. .04; P = .004), and women with a family history of breast cancer had higher PPVs compared with women without history (40 to 49 years of age, .13 vs .04, P = .01; and 50 to 59 years of age, .22 vs .09, P = .01). CONCLUSION: Five times as many cancers per 1000 first-screening mammographic examinations were diagnosed in women aged 50 years or older compared with women aged less than 50 years. The highest PPVs for mammography were in women aged 50 years or older and in women aged 40 years or older with a family history of breast cancer. Efforts to promote screening mammography should focus on women in these groups, in whom the majority of breast cancers occur and for whom mammography has the highest PPVs.

Adult↗

The high-risk infant environment. Part 2. The role of caregiving and the social environment.

Neonatal intensive care units are essential for the successful care of very immature and sick infants. The technology of NICUs has contributed significantly to the reduction of neonatal mortality and improvement of neonatal outcome. While the outcome for high-risk neonates has vastly improved over the past three decades, a number of infants sustain injuries and complications that result in long-term disabilities. It is now clear that some of the long-term problems of high-risk infants are a result of the environment and care practices and are not attributable to the original disease or condition that necessitated intensive care. There is accumulating evidence that environmental factors and care practices can interact with disease processes in ways that can increase morbidity, and possibly mortality. In addition to developmental and behavioral problems, there is growing evidence of effects on visual function and perhaps other sensory systems. Many of the environmental and care factors may cause delay in recovery and increase NICU time or unnecessary discomfort, yet not produce long-term disabilities or problems, as currently assessed. Many of the potential behavioral and developmental problems, as well as many of the potential problems with visual, auditory, and other modes of sensory discrimination, are not included in the usual follow-up assessments. The absence of data or the limitations of existing studies are not a cause for comfort or the assumption that the environment and care practices are safe or not harmful.(ABSTRACT TRUNCATED AT 250 WORDS)

Environment↗