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A Silvers

Publications and source records attributed to A Silvers.

At least 19 recordsLinked to original sources
PubMed1999

Control of spatial orientation of the angular vestibulo-ocular reflex by the nodulus and uvula of the vestibulocerebellum.

Eye velocity produced by the angular vestibulo-ocular reflex (aVOR) tends to align with the summed vector of gravity and other linear accelerations [gravito-inertial acceleration (GIA)]. Defined as "spatial orientation of the aVOR," we propose that it is controlled by the nodulus and uvula of the vestibulocerebellum. Here, electrical stimulation, injections of the GABAA agonist, muscimol, and single-cell recordings were utilized to investigate this spatial orientation. Stimulation, injection, and recording sites in the nodulus were determined in vivo by MRI and verified in histological sections. MRI proved to be a sensitive, reliable way to localize electrode placements. Electrical stimulation at sites in the nodulus and sublobule d of the uvula produced nystagmus whose slow-phase eye-velocity vectors were either head centric or spatially invariant. When head centric, the eye velocity vector remained within +/- 45 degrees of the vector obtained with the animal upright, regardless of head position with respect to gravity. When spatially oriented, the vector remained relatively constant in space in one on-side position, with respect to the vector determined with the animal upright. A majority of induced movements from the nodulus were spatially oriented. Spatially oriented movements were generally followed by after-nystagmus, which had the characteristics of optokinetic after-nystagmus (OKAN), including orientation to the GIA. After muscimol injections, horizontal-to-vertical cross-coupling was lost or reduced during OKAN in tilted positions. This supports the hypothesis that the nodulus mediates yaw-to-vertical or roll cross-coupling. The injections also shortened the yaw-axis time constant and produced contralateral horizontal spontaneous nystagmus, whose velocity varied as a function of head position with regard to gravity. Nodulus units were tested with static head tilt, sinusoidal oscillation around a spatial horizontal axis with the head in different orientations relative to the pitching plane, and off-vertical axis rotation (OVAR). The direction of the response vectors of the otolith-recipient units in the nodulus, determined from static and/or dynamic head tilts, were confirmed by OVAR. These vector directions lay close to the planes of the vertical canals in 7/10 units; many units also had convergent input from the vertical canals. It is postulated that the orientation properties of the aVOR result from a transfer of otolith input regarding head tilt along canal planes to canal-related zones of the nodulus. In turn, Purkinje cells in these zones project to vestibular nuclei neurons to control eye velocity around axes normal to these same canal planes.

Animals↗
PubMed1999

Nonlinearity in the lung cancer dose-response for airborne arsenic: apparent confounding by year of hire in evaluating lung cancer risks from arsenic exposure in Tacoma smelter workers.

Most analytic studies of human epidemiologic data have affirmed the linear association between excess lung cancer risk and airborne arsenic exposure. Recent Canadian analyses, however, based on the mortality follow-up of Tacoma smelter workers from 1940-1976, provided strong evidence of a nonlinear dose-response when lung cancer risk was expressed in terms of the standardized mortality ratio. Using recently updated data covering ten additional years of mortality experience among Tacoma workers (1940-1986), new analyses were undertaken to further explore nonlinearity in the lung cancer dose-response in this worker cohort. Lung cancer risk was expressed in terms of both the standardized mortality ratio (SMR) and the excess mortality rate (EMR). As in Canadian analyses, nonlinearity was assessed through a three parameter model containing both linear and negative exponential terms for dose. Dropping the negative-exponential dose-term lead to the standard suite of linear dose-response models, with and without intercept, used for comparative purposes. Analyses were undertaken by subcohort as there was strong evidence of confounding by year of initial hire, which largely explained the nonlinearity in the dose-response observed in Canadian analyses. Subcohort analyses based on initial employment, prior to 1940 or thereafter, showed that the nonlinearity in the dose-response was strongly influenced by date of initial hire. whether the cohort risk was measured by either the SMR or EMR, a nonlinear dose-response was evident only among workers hired prior to 1940. This, however, was strongly related to the artifactually low lung cancer mortality seen among workers hired between 1930 and 1939. Among workers hired after 1940, analyses showed that a linear dose-response provided a clearly superior fit. While analyses showed comparable goodness of fit when models were fitted to the SMR and EMR. Only those based on the EMR provided strong evidence of a dose-response. Overall, nonlinearity as observed in Canadian analyses was likely the result of several sources of bias not taken into account by Canadian investigators.

Adult↗
PubMed1999

Clinical use of the optical digitizer for intracranial neuronavigation.

OBJECTIVE: Computer-assisted frameless navigation techniques are used in many centers for intracranial neurosurgical procedures. In this study, we assessed the accuracy and the clinical usefulness of a frameless system based on the optical digitizer in a variety of intracranial procedures. METHODS: The optical digitizer (StealthStation, Sofamor Danek, Memphis, TN) was used to perform 170 neurosurgical operations. Its accuracy was judged before and after each operation by comparing the computer-estimated error with the real estimated error measured on the patient's anatomy. Several objective factors were evaluated to assess the clinical usefulness of the optical digitizer. For craniotomies, the intraoperative extent of resection based on computer-generated images was compared with that on postoperative images, and the length of hospital stay of patients undergoing frameless procedures was compared with that of patients undergoing conventional procedures. For needle biopsies, clinical usefulness was based on the rate of success in establishing a histological diagnosis. RESULTS: The optical digitizer was accurate to within 2 mm for all procedures. The computer-estimated error was not significantly different from the real estimated error. The intraoperative extent of resection was accurate in 58 of 60 tumor resection patients, as confirmed on postoperative images. Patients undergoing frameless procedures had a significantly shorter hospital stay than those undergoing conventional procedures (7.5 +/- 1 versus 10.8 +/- 1.3 d, P < 0.05). All biopsies were diagnostic. CONCLUSION: The optical digitizer is an accurate frameless device that offers clinical benefits. These include precise surgical resection, decreased hospitalization time, and accurate tissue diagnosis.

Adolescent↗
PubMed1999

Anaesthesia and postoperative pain management for bilateral lung volume reduction surgery.

Bilateral lung volume reduction surgery was introduced into Australia in 1995 for treatment of selected patients with emphysema. We present our experience of the anaesthetic management of our first 55 cases and describe factors associated with outcome. There were four postoperative deaths (7%). Mean (SD) total operation time was 231 (72) minutes. Median intensive care unit (ICU) stay was 26 hours. There was a significant improvement in postoperative lung function (FEV1, VC, 6-minute walk test, all P < 0.001). Eight patients (15%) required reintubation for respiratory failure; three of these patients subsequently died. With multivariate analysis, total operation time was the only significant predictor of length of ICU stay R2 = 0.25, P = 0.001), which itself was the only significant predictor of hospital stay duration (R2 = 0.36, P < 0.001).

Adult↗
PubMed1998

Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort.

This paper presents benchmark (BMD) calculations and additional regression analyses of data from a study in which scores from 26 scholastic and psychological tests administered to 237 6- and 7-year-old New Zealand children were correlated with the mercury concentration in their mothers' hair during pregnancy. The original analyses of five test scores found an association between high prenatal mercury exposure and decreased test performance, using category variables for mercury exposure. Our regression analyses, which utilized the actual hair mercury level, did not find significant associations between mercury and children's test scores. However, this finding was highly influenced by a single child whose mother's mercury hair level (86 mg/kg) was more than four times that of any other mother. When that child was omitted, results were more indicative of a mercury effect and scores on six tests were significantly associated with the mothers' hair mercury level. BMDs calculated from five tests ranged from 32 to 73 mg/kg hair mercury, and corresponding BMDLs (95% lower limits on BMDs) ranged from 17 to 24 mg/kg. When the child with the highest mercury level was omitted, BMDs ranged from 13 to 21 mg/kg, and corresponding BMDLs ranged from 7.4 to 10 mg/kg.

Achievement↗
PubMed1998

Diffusion-weighted MR of acute cerebral infarction: comparison of data processing methods.

BACKGROUND AND PURPOSE: Some investigators have proposed that either calculated diffusion trace images or apparent diffusion coefficient (ADC) maps, which require imaging with multiple diffusion sensitivities and/or postacquisition image processing, are essential for the accurate interpretation of diffusion-weighted images in acute stroke because of the possible pitfalls of regional diffusion anisotropy, magnetic susceptibility artifacts, and confounding T2 effects, all of which alter signal on diffusion-weighted MR images. The purpose of our study was to compare the sensitivity, specificity, and accuracy of simple, orthogonal-axis diffusion-weighted imaging for the diagnosis of early cerebral infarction with three other sets of postacquisition-processed images: isotropic diffusion-weighted, diffusion trace-weighted, and diffusion trace images. METHODS: Twenty-six consecutive adult patients with signs and symptoms consistent with a clinical diagnosis of early cortical and/or subcortical cerebral infarction and 17 control subjects were studied with multisection, single-shot, spin-echo echo-planar diffusion-weighted imaging at 1.5 T to generate a set of three orthogonal-axis diffusion-weighted images. Isotropic diffusion-weighted, diffusion trace-weighted, and diffusion trace (mean ADC) images were then generated off-line and all four sets of images were interpreted blindly by two neuroradiologists. RESULTS: The average sensitivity, specificity, and accuracy for the orthogonal-axis diffusion-weighted images were 98.1%, 97.1%, and 97.7%, respectively. The average sensitivity, specificity, and accuracy for isotropic diffusion-weighted images were 88.5%, 100%, and 93% respectively. The average sensitivity, specificity, and accuracy for diffusion trace-weighted images were 82.7%, 73.6%, and 79.1%, respectively. The average sensitivity, specificity, and accuracy for diffusion trace images were 50.0%, 85.3%, and 64.0%, respectively. CONCLUSION: Orthogonal-axis diffusion-weighted images have the highest sensitivity and accuracy and very high specificity for early cerebral infarction. Our data contradict the contention that quantitative diffusion maps, requiring imaging with multiple diffusion sensitivities and/or subsequent image processing, are necessary for clinical stroke imaging.

Acute Disease↗
PubMed1997

Anesthesia for bilateral sequential lung transplantation: experience of 64 cases.

OBJECTIVES: To review the experience of anesthesia for bilateral sequential lung transplantation (BSLTx) and describe factors associated with outcome. DESIGN: Case series. SETTING: University hospital. PARTICIPANTS: Sixty-four adult patients undergoing BSLTx. INTERVENTIONS: Descriptive and inferential statistical analysis. MEASUREMENTS AND MAIN RESULTS: Details of anesthetic technique, patient, and perioperative characteristics are presented. Mean (SD) lung allograft ischemic times were 320 (81) minutes for the first lung and 446 (93) minutes for the second lung. Mean (SD) duration of surgery was 8.5(2) hours, and median time to extubation was 28 hours. There was a reduction in the use of cardiopulmonary bypass, from 10 of 19 (53%) in 1992 to 1993 to 10 of 45 (22%) in 1994 to 1996, p = 0.016. There was an association between time to extubation and duration of surgery (Spearman rank correlation, p = 0.33, p = 0.008), but no association with intraoperative fluid administration (p = 0.18, p = 0.16), or inotrope requirements (p = 0.06, p = 0.65). Predictors of in-hospital mortality were preoperative renal impairment (p = 0.034), early reoperation (p = 0.005), and delay in extubation (p = 0.013); and for 12-month mortality was patient age (p = 0.01). The actuarial survival rates were 90%, 73%, and 58% at 30 days, 1 year, and 2 years, respectively. CONCLUSIONS: Anesthesia for BSLTx is a most challenging procedure, for which maintenance of tissue oxygenation and right ventricular perfusion are essential. Recent advances include use of inhaled nitric oxide, ventilator management that reduces dynamic hyperinflation, and permissive hypercapnia. Analysis of outcome from a large case series such as this enables the anesthesiologist to be more aware of the important features of anesthesia for BSLTx, as well as identify potential areas of improvement.

Adult↗
PubMed1997

Projecting corporate health plan utilization and charges from annual ICD-9-CM diagnostic rates: a value-added opportunity for pathologists.

OBJECTIVE: To develop an allocation method for corporate health plan resources and expenditures based on annual International Classification of Disease, 9th revision, Clinical Modification (ICD-9-CM) diagnostic rate stratification as a surrogate for disease incidence. DESIGN: A data-mining process was applied to a self-insured corporate health plan database. Annual membership rates of Current Procedural Terminology (CPT) procedure utilization and charges between 1990 and 1994 for a cohort of 7216 continuously employed plan members were stratified according to the annual rates of the 19 major ICD-9-CM diagnostic classifications. The stratified annual CPT utilization and charge rates were analyzed by correlation analysis and one-tailed t test. RESULTS: Laboratory and pathology procedure utilization and charge rates were highly correlated with specific rankings of ICD-9-CM diagnostic classifications. The health plan diagnostic rate, laboratory utilization rate, and all charge rates increased significantly during the 5 study years. CONCLUSION: Although all procedure utilization and charge rates in this health plan increased each year, their proportionality consistently was maintained among diagnostically related groups of patients. By restraining global expenditures, managed health plans conflict with historical utilization and charge patterns. Treating ICD-9-CM diagnostic groups as disease management services within a managed care plan allows procedures and expenses to be allocated according to medical necessity in the context of total membership benefits. For pathologists, who recently were mandated by the Health Care Financing Administration and the Office of Inspector General of the Department of Health and Human Services to become stewards of ICD-9-CM coding, this is a unique opportunity to lead an initiative to perfect managed care. The process will require permanent patient numbers, computerized longitudinal patient records, and standardized coded medical terminology.

Adult↗
PubMed1996

(In) equality, (ab) normality, and the Americans With Disabilities Act.

The 1990 Americans with Disabilities Act enacted a conceptual shift in the meaning of 'disability.' Rather than defining 'disability' as a disadvantageous physical or mental deficit of persons, it codifies the understanding of 'disability' as a defective state of society which disadvantages these persons. In contrast, the standard medical model incorrectly conceptualizes disabled persons as biologically inferior, and thus confines them to the role of recipients of benevolence or care. Turning to an ethic of caring yields counter-intuitive results that conflict with the conceptual apparatus of the ADA. It is argued that in order to liberate social marginalized to being socially enabled, one must re-conceptualize current practice by adopting the ADA's conceptual framework.

Beneficence↗
PubMed1995

Reanalysis of dose-response data from the Iraqi methylmercury poisoning episode.

Applying a hockey stick parametric dose-response model to data on late or retarded development in Iraqi children exposed in utero to methylmercury, with mercury (Hg) exposure characterized by the peak Hg concentration in mothers' hair during pregnancy, Cox et al. calculated the "best statistical estimate" of the threshold for health effects as 10 ppm Hg in hair with a 95% range of uncertainty of between 0 and 13.6 ppm. A new application of the hockey stick model to the Iraqi data shows, however, that the statistical upper limit of the threshold based on the hockey stick model could be as high as 255 ppm. Furthermore, the maximum likelihood estimate of the threshold using a different parametric model is virtually zero. These and other analyses demonstrate that threshold estimates based on parametric models exhibit high statistical variability and model dependency, and are highly sensitive to the precise definition of an abnormal response. Consequently, they are not a reliable basis for setting a reference dose (RfD) for methylmercury. Benchmark analyses and statistical analyses useful for deriving NOAELs are also presented. We believe these latter analyses--particularly the benchmark analyses--generally form a sounder basis for determining RfDs than the type of hockey stick analysis presented by Cox et al. However, the acute nature of the exposures, as well as other limitations in the Iraqi data suggest that other data may be more appropriate for determining acceptable human exposures to methylmercury.

Child↗
PubMed1995

Nodal inclusion cysts of the parotid gland and parapharyngeal space: a discussion of lymphoepithelial, AIDS-related parotid, and branchial cysts, cystic Warthin's tumors, and cysts in Sjögren's syndrome.

The purpose of this report is to examine the computed tomography scans, magnetic resonance images, and pathologic findings in 44 patients, 42 of whom had inclusion-type cysts of the parotid and parapharyngeal space of varying etiologies. Two additional cases of cystic changes in the benign lymphoepithelial lesion (BLEL) of Sjögren's syndrome are highlighted here, since they had unusually large cystic components mimicking acquired immunodeficiency syndrome-related parotid cysts (ARPCs). A retrospective examination identified 18 ARPCs, 3 lymphoepithelial cysts (LECs), 13 cystic Warthin's tumors, 8 branchial cysts, and 2 cases of cysts in patients with Sjögren's syndrome (BLEL), all of whom had imaging studies and pathologic confirmation. There were 30 men and 14 women with an age range of 25 to 72 years (median, 46.82 years). Any similarities in the imaging appearances were noted, as were any differences in pathologic detail. On imaging, only the cystic Warthin's tumors had any focal wall nodularity; the other cysts had smooth walls. When multiple parotid cysts were present, the distinguishing feature between ARPCs and cysts in BLEL (and some cystic Warthin's tumors) was the presence of diffuse cervical adenopathy in patients with ARPCs. Imaging usually could not differentiate between a solitary parotid LEC, a branchial cyst, and some cystic Warthin's tumors. Extraparotid lesions were either branchial cysts or cystic Warthin's tumors. Physicians should be aware of the variety of different inclusion-type cysts that may occur in the parotid gland and parapharyngeal space, all of which may have similar imaging appearances. Although imaging clearly identifies these cysts and may suggest a specific diagnosis, it must always be remembered that the precise diagnosis remains in the province of the pathologist.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Unit risk estimates for airborne arsenic exposure: an updated view based on recent data from two copper smelter cohorts.

The current unit risk for airborne arsenic, 4.29 x 10(-3), was established by the EPA in 1984. Using updated results from a cohort mortality study on Tacoma smelter workers and recent findings from a cohort study of 3619 Swedish smelter workers, new unit risk estimates were developed for the respective cohorts. Methods were analogous to those used by the EPA in 1984, and all estimates were derived under an absolute risk model. A new unit risk 1.28 x 10(-3), was estimated for the Tacoma smelter cohort which was a factor of 5 less than the EPA's earlier estimate, and a direct result of radically revised exposure estimates. A unit risk of 0.89 x 10(-3) was estimated from the Swedish study. Pooling these new unit risk estimates with the EPA's earlier estimates from the Montana smelter cohort yielded a composite unit risk of 1.43 x 10(-3). Based on this estimate, the present unit risk may overestimate the effects of airborne arsenic by a factor of 3. A need to update the unit risk for airborne arsenic and the collateral IRIS database is evident from the results.

Air Pollutants, Occupational↗
PubMed1994

Plasma lipid effects of three common vegetable oils in reduced-fat diets of free-living adults.

We compared plasma lipid changes due to the polyunsaturated fatty acids (PUFAs) in partially hydrogenated soybean oil, corn oil, and sunflower oil fed in reduced-fat diets (22-26% of total energy). Each oil was the dominant fat in isoenergetic diets of centrally prepared foods consumed by 26 male and 35 female normolipidemic, free-living individuals. Test diets were consumed double-blind, alternating with self-selected diets for 5 wk each. The ranges of proportions of total fat were: 4.7-9.7% polyunsaturated fat, 8.9-14.2% monounsaturated fat and 5.4-7.4% saturated fat. All three diets lowered (P < 0.0001) total cholesterol (11%), LDL cholesterol (13%), and HDL cholesterol (10%), without triglyceride changes. We conclude that PUFAs at approximately 6% of total energy result in clinically relevant plasma cholesterol-lowering and that the proportion of polyunsaturated fat must be an important consideration when planning reduced-fat, reduced-saturated-fat diets.

Adult↗
PubMed1994

How children spend their time: a sample survey for use in exposure and risk assessments.

Children are becoming an increasingly important focus for exposure and risk assessments because they are more sensitive than adults to environmental contaminants. A necessary step in measuring the extent of children's exposure and in calculating risk assessments is to document how and where children spend their time. This 1990-1991 survey of 1000 households was designed for this purpose, targeting children between 5 and 12 years of age, in six states in varied geographic regions. The behavior of children was sampled on both weekdays and weekends over all four seasons of the year using a retrospective time diary to allocate time to activities during the previous 24 h. Information was obtained on the kinds and locations of activities, the nature of the microenvironments of the locations, and the time spent in the different environments. Measures of variability in addition to mean hours per day are reported. Results of this study closely match those of earlier research on California children's activities done by the California Air Resources Board. One important finding of the survey was that 5- to 12-year-old children in all geographic regions spend most of their time indoors at home, indicating that risk assessments should focus on indoor, onsite hazards.

Child↗
PubMed1994

Use of biological markers in risk assessment.

Measurements of intermediate end points in the carcinogenic process may reduce uncertainty in human risk assessment from bioassay data, by identifying sources of interspecies variation and dose nonlinearity. This paper describes desirable properties of such markers: persistence, predictive power, temporal relevance, and consistency across dose rate and species. We illustrate these properties by evaluating markers for squamous cell nasal carcinoma in rodents exposed to formaldehyde. We also discuss design issues for bioassays that evaluate markers and tumors simultaneously at necropsy.

Animals↗
PubMed1986

Pharmacokinetics in low dose extrapolation using animal cancer data.

Data on rodents exposed to carcinogens indicate that their tumor probabilities are proportional to effective concentrations of parent compound or metabolites at the target tissues. This proportionality suggests that observed nonlinear dose-response curves reflect dose-dependent kinetics between applied dose rate and effective concentrations. Therefore low dose extrapolation procedures that include pharmacokinetic data could improve extrapolation accuracy. To test such procedures, we simulated bioassay and pharmacokinetic "data." Then, ignoring the mechanisms generating the data, we used four extrapolation procedures to estimate tumor probability at a low applied dose rate. Two of the procedures use a pharmacokinetic model and simulated pharmacokinetic data, and two do not. The pharmacokinetic model used for extrapolation was only an approximation to the one used to generate the pharmacokinetic data. The procedures that include pharmacokinetics often performed better and never did much worse than those that ignore them, regardless of the relations used to generate the data, the amount of experimental error in the pharmacokinetic data, and the appropriateness of the pharmacokinetic and extrapolation models used. Moreover they performed substantially better when effective concentration and tumor probability were concave-up functions of applied dose rate.

Animals↗