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Biomedical subjects

M E Miller

Publications and source records attributed to M E Miller.

At least 73 records · Page 4Linked to original sources

Benefits of linkage to the National Death Index in the Longitudinal Study of Aging.

To reduce the potential bias resulting from differential loss to follow-up in the Longitudinal Study of Aging (LSOA), information obtained from household contact methods was supplemented with information from the National Death Index (NDI). This article examines the degree of agreement in the vital status data from two sources (reinterview contacts and the NDI system) and evaluates the potential gains of using the NDI data as a supplement to define participants' vital status. Results reveal that NDI information, used to supplement reinterview information, can substantially reduce bias due to the differential loss of participants to follow-up. Reliance on reinterview information alone was less likely to capture those deaths occurring in study participants who at the initial contact lived alone, were below the poverty index, were interviewed without use of a proxy, did not supply a phone number, and did not own a home.

Aging↗

Assessment of the discriminative stimulus effects of the D3 dopamine antagonist PNU-99194A in rats: comparison with psychomotor stimulants.

The present study examined the discriminative stimulus effects of the D3 dopamine receptor antagonist PNU-99194A [5,6-di-methoxy-2-(dipropylamino)indan-hydrochloride] in male Sprague-Dawley rats. Eight rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline in a two-choice, water-reinforced drug discrimination procedure. In tests of stimulus generalization, PNU-99194A (1.25-40.0 mg/kg, s.c. and i.p.) did not substitute for cocaine. PNU-99194A (5.0-20 mg/kg) also did not significantly block the discrimination of cocaine (10 mg/kg), nor did it potentiate a low dose (1.25 mg/kg) of cocaine. A separate group of eight rats were trained to discriminate PNU-99194A from saline. These subjects met the discrimination criterion within an average of 68 (S.E.M. = 6.5) training sessions; the ED50 for PNU-99194A was 2.6 mg/kg. In stimulus generalization tests, cocaine (1.25-10 mg/kg) did not substitute for PNU-99194A, when administered by either i.p. or by s.c. injection. In addition, neither amphetamine (0.25-1.0 mg/kg) nor caffeine (8.0-64 mg/kg) produced stimulus generalization in these rats. These results indicate that D3 receptors do not play a critical role in the discriminative stimulus effects of cocaine. Furthermore, although PNU-99194A is capable of establishing and maintaining discriminative stimulus control in rats, the effects of this D3-preferring antagonist are dissimilar from those of psychomotor stimulants. Given the unique behavioral profile of D3 receptor antagonists, the potential utility of these agents as adjunctive treatments for psychostimulant abuse is discussed.

Amphetamine↗

Some techniques for the analysis of work sampling data.

Work sampling is an observational technique that produces counts representing the number of times that an individual has been observed performing each of several tasks. These data are collected using either systematic or random times of observation, and typically exhibit correlation between repeated observations on the same individual, with the degree of correlation being a function of the amount of time elapsed between measurements. Using several recently developed statistical techniques, we illustrate how it is possible to carry out analyses of these nominal outcomes that account for the correlation between repeated outcomes. We use description of a work sampling study to motivate the techniques and we compare empirically results from analyses based on several different underlying assumptions.

Adult↗

Screening for social and environmental problems in a VA primary care setting.

Social workers are in an ideal position to identify and treat social and environmental problems early in the continuum of care. Information on these problems will facilitate informed decision making on the development and reallocation of resources to better meet patients needs. This study assessed the social and environmental problems of 132 patients seen in a primary care clinic at a university-affiliated Veterans Affairs (VA) medical center. The most prevalent social problems were financial difficulties, personal stress, family problems, legal concerns, and employment concerns. When asked, nearly one-third of all respondents requested social work services or information about services related to their problems. The findings suggest a clear need for social work interventions in VA primary care clinics that focus on both psychosocial problems.

Adult↗

The impact of practicing in multiple hospitals on physician profiles.

Although physicians are all too familiar with the psychologic impact of having multiple responsibilities, the associated impact on practice styles has not been examined systematically. To provide some data on the effects of "work dispersion," we examined the hypothesis that the inpatient resource use of physicians would rise with the number of hospitals in which they work. Data for 1991 from Medicare's National Claims History File were used to profile a sample of attending physicians (n = 33,756) in seven states. The attending physician "profile" was the case mix-adjusted relative value of all physician services (regardless of who delivered them) that were delivered during each patient's hospital stay. Relative value was measured in relative value units, used by Medicare in determining physician payments. The authors then categorized physicians in terms of the number of hospitals to which they admitted patients. Physician profiles were adjusted further to control for geography, physician specialty, and characteristics of the physician's primary (ie, most used) hospital. One third of the physicians in the sample had admissions to more than one hospital. Physicians working in one hospital had inpatient practice profiles 2.1% below the sample mean. Additional hospital affiliations were associated with progressively higher profiles: two hospitals, 2.3% above the mean; three hospitals, 4.5% above; four hospitals, 8.2% above; and five or more hospitals, 11.5% above (all P < 0.01). The practice of medicine in more than one hospital is associated with higher inpatient profiles and shows a dose-response relationship. Physicians and policy makers will need to consider carefully whether there are any associated benefits to justify the increased cost.

Adult↗

Adenovirus E1A specifically blocks SWI/SNF-dependent transcriptional activation.

Expression of the adenovirus E1A243 oncoprotein in Saccharomyces cerevisiae produces a slow-growth phenotype with accumulation of cells in the G1 phase of the cell cycle. This effect is due to the N-terminal and CR1 domains of E1A243, which in rodent cells are involved in triggering cellular transformation and also in binding to the cellular transcriptional coactivator p300. A genetic screen was undertaken to identify genes required for the function of E1A243 in S. cerevisiae. This screen identified SNF12, a gene encoding the 73-kDa subunit of the SWI/SNF transcriptional regulatory complex. Mutation of genes encoding known members of the SWI/SNF complex also led to loss of E1A function, suggesting that the SWI/SNF complex is a target of E1A243. Moreover, expression of E1A in wild-type cells specifically blocked transcriptional activation of the INO1 and SUC2 genes, whose activation pathways are distinct but have a common requirement for the SWI/SNF complex. These data demonstrate a specific functional interaction between E1A and the SWI/SNF complex and suggest that a similar interaction takes place in rodent and human cells.

Adenovirus E1A Proteins↗

Cyclic AMP signaling is required for function of the N-terminal and CR1 domains of adenovirus E1A in Saccharomyces cerevisiae.

We have constructed yeast vectors in which derivatives of the adenovirus E1A gene are expressed from the GAL1 promoter. Cells expressing E1A289 grow poorly and accumulate cells with a 1C DNA content. Using a series of E1A deletion mutants, we have identified three regions within the E1A protein that are necessary for the G1 growth phenotype; each deletion partially relieves the growth defect. These deletions span residues 4-25, 38-60 and 140-186, which fall within the N-terminal, CR1 and CR3 domains of E1A respectively. Expression of the first 82 residues of E1A, spanning just the N-terminal and CR1 domains, strongly inhibits yeast cell growth in G1 showing that these domains can function independently of other domains of E1A. Using this strong growth inhibition, we isolated a yeast mutant in the net1 gene that conferred resistance to the expression of E1A1-82. The mutant was insensitive to expression of both E1A1-82 and full length E1A, but remained sensitive to the toxicity caused by over-expression of a Gal4p-VP16 fusion. Finally, we found that the function of E1A in yeast depends on the cyclic AMP signaling pathway, providing a striking parallel with the action of E1A at the c-fos promoter in mammalian cells. These results suggest that a genetic analysis of the yeast model system will provide relevant new insights into mechanisms of gene regulation by E1A proteins.

Adenovirus E2 Proteins↗

Clinical and cytogenetic findings in seven cases of inverted duplication of 8p with evidence of a telomeric deletion using fluorescence in situ hybridization.

We report on the clinical and cytogenetic findings in 7 cases of inverted duplication of region 8p11.2p23. The phenotype of inv dup (8p) compiled from this series and the literature (N = 29) consists of severe mental retardation (100%), minor facial alterations (97%), agenesis of the corpus callosum (80%), hypotonia (66%), orthopedic abnormalities (58%), scoliosis/kyphosis (40%), and congenital heart defect (26%). A telomeric deletion of region 8p23.3-pter was confirmed in 3 of our cases studied using fluorescent in situ hybridization with a telomeric probe for 8p. Thus, these karyotypes are inv dup del(8) (qter-->p23.1::p23.1-->p11.2:). Our findings suggest that most cases of inv dup(8p) probably have a telomeric deletion.

Abnormalities, Multiple↗

Influence of hormones on platelet intracellular calcium.

The pathophysiology of thromboembolic disease associated with estrogen therapy is poorly understood. There are innumerable calcium-dependent activities involved in platelet function. To determine whether platelet calcium levels are affected by exogenous hormones, intracellular calcium and release were studied in platelets in various hormonal environments and findings were correlated with platelet adhesion and aggregation. Platelet intracellular calcium concentration and release was significantly decreased in women ingesting tamoxifen compared to controls and significantly increased, as was platelet adhesion, in oral contraceptive users. Platelets incubated ex vivo with estradiol had increased intracellular calcium and release but there was decreased adhesion to fibronectin. Intracellular calcium concentration and release were not affected when platelets were incubated with tamoxifen. Adhesion to collagen III was increased in tamoxifen-incubated platelets. Only oral contraceptive users had increased sensitivity to aggregating agents. This data suggests that 17 beta estradiol, progesterone, and tamoxifen likely have a nongenomic effect on platelet intracellular calcium and calcium release and that platelet calcium levels are closely related to the degree of platelet adhesion and aggregation in vivo.

Adult↗

Reassembly of the 66 kD neurofilament protein in vitro following isolation and purification from bovine spinal cord.

NF-66, also known as alpha-internexin, has been characterized as a 66 kD mammalian neurofilament (NF) protein whose expression in developing rat brain precedes that of the low molecular weight NF protein (NF-L). NF-66 is thought to assemble into 10 nm diameter intermediate filaments in vitro, although the precise nature of the assembly process remains obscure. Likewise, the ability of NF-66 to polymerize with the low (NF-L), middle (NF-M), and high (NF-H) M(r)NF proteins has not been defined. This investigation describes the reassembly of bovine NF-66 regarding its formation into 10 nm diameter filaments as well as its potential for polymerization with other type IV intermediate filaments. NF-66 and the NF triplet proteins were isolated from bovine spinal cord using established biochemical extraction and isolation procedures (Balin et al., Brain Res 556:181-195, 1991), and purified by a combination of high performance liquid chromatography (HPLC) (DEAE anion exchange and hydroxylapatite column chromatography) and gel elution strategies. In vitro reassembly experiments revealed that NF-66 formed approximately 10 nm diameter filaments of varying length; immunoelectron microscopy demonstrated labeling of these filaments by a monoclonal antibody to intermediate filament antigen (IFA), a polyclonal antibody against rat NF-66 and by a monoclonal antibody generated against the core region of NF-M but cross-reactive with NF-66. This report is the first investigation to look at the in vitro interaction between NF-66 and other type IV intermediate filament proteins (NF-H, -M, and -L) and establishes that NF-66 forms heteropolymeric filaments with these other neurofilament proteins, as confirmed by double immunolabeling. These studies suggest that NF-66 could provide a nucleation site for the polymerization of later-expressed proteins during neuronal development.

Animals↗

Primary care physician productivity: the physician factor.

OBJECTIVES: To model physician productivity as a function of clinic (support system) characteristics and physician characteristics and to model the time a physician spends with the patient as a function of patient characteristics. DESIGN: Observational study. SETTING: A general medicine clinic of a university-affiliated Veterans Affairs medical center. PATIENTS: A cohort of 2,520 patients having 2,721 consecutive outpatient visits to 56 physicians. MAIN OUTCOME MEASURES: Physician productivity defined as patients seen/physician/hour and time (minutes) spent with the patient. RESULTS: Physicians saw a mean (+/- SD) of 1.62 +/- 0.68 patients/hour. Clinic characteristics explained 8.2% of the variability of session-specific physician productivity. Controlling for clinic characteristics, a factor representing the physician explained an additional 55.4%. A model for overall physician productivity, using physician characteristics, explained 84.9% of the variance, and time spent with the patient was an important predictor. Modeling physician time with patients, patient characteristics accounted for only 7% of the variability. Controlling for patient characteristics, the individual physician again provided the greatest explanatory power, an additional 22.8% of the variability. CONCLUSIONS: Physicians' practice patterns, rather than clinic or patient characteristics, may account for most of the variation in physician productivity. Given the magnitude of the influence of individual practice patterns, interventions to increase productivity need to consider methods to affect physician behavior.

Appointments and Schedules↗

Improving compliance among women with abnormal Papanicolaou smears.

OBJECTIVE: To determine whether a clinic-based intervention, consisting of motivational brochures and a tracking system, increases adherence to recommendations for treatment in women with abnormal Papanicolaou smears. METHODS: Three pairs of clinics--two family planning clinics, two family practice clinics, and two dysplasia clinics--were randomized within pairs either to provide the intervention or to maintain usual contact procedures with women having abnormal Papanicolaou smears. Baseline adherence rates were assessed through chart review during 3 randomly selected months of the previous year. Intervention clinics received the tracking system and motivational brochures, which were sent to women on notification of their cervical abnormalities. Comparison clinics also used the tracking system but did not include the brochures when notifying women of their abnormalities. Adherence rates were assessed prospectively for approximately 100 consecutive nonpregnant women with abnormal Papanicolaou smears (inflammatory benign atypia, or cervical intraepithelial neoplasia I, II, or III) at each clinic. RESULTS: Within clinics, baseline adherence rates ranged from 34-69% for atypia and 33-88% for dysplasia. For dysplasia patients, the overall analysis indicated a significant increase in adherence for the intervention clinics (P = .03); however, for atypia patients, the observed difference was not statistically significant (P = .23). Extensive analyses of the data from family planning clinics indicated that women receiving the intervention were more likely to obtain follow-up treatment (odds ratio [OR] 2.6, 95% confidence interval 1.15-5.85). There was a suggestion that the intervention could have a greater effect among African-American women (OR 15.7) compared with white women (OR 1.8) (P = .09). White women, those with dysplasia, nonsmokers, and nulliparas were most likely to adhere to treatment recommendations. CONCLUSION: A motivational brochure can enhance adherence to treatment recommendations among women with abnormal Papanicolaou smears. Future studies should focus on techniques for enhancing adherence among more resistant participants.

Adult↗

Monoaminergic influences on temporal patterning of sexual behavior in male rats.

We evaluated the effects of the serotonin (5-HT) presynaptic uptake blocker fluoxetine (FLX) and the dopamine (DA)/noradrenaline (NE) releaser amantadine (AMA), separately and in combination, on the temporal patterning of male rat sexual behavior. FLX alone increased intermount-bout intervals, time-outs, grooming time, ejaculation latency, number of mounts per mount bout, and number of mount bouts per ejaculation. AMA alone had the opposite effect on these measures. Additionally, AMA, when given in combination with FLX, completely reversed the FLX-induced deficits in copulatory behavior. We interpret our results as suggesting an interaction between 5-HT and catecholamines in the temporal patterning of male rat copulatory behavior.

Amantadine↗

HIV risk exposure of injecting drug users in Sydney.

One thousand two hundred and forty-five Sydney injecting drug users (IDUs) were interviewed by questionnaire in 1989 to determine demographic and behavioural characteristics. One-sixth (16.7%) were considered to be at low risk of HIV from either needle sharing or sexual transmission as they had either never shared injecting equipment, or had not shared for years, or cleaned their injecting equipment effectively on 100% of the occasions when they did share; and were either celibate or monogamous or, if they had multiple partners, had not had unsafe sex in the previous 6 months. Over half (50.7%) had either unsafe injecting or sexual behaviour with the remaining third (32.6%) engaging in both unsafe injecting and sexual practises. Women were more at risk from sharing injection equipment than men but men were more at risk from sexual transmission than women. Increasing age was associated with greater likelihood of safer sex but age had no effect on injecting practises. There was no relationship between unsafe injecting and sexual practises. Amphetamine use was associated with low risk injecting practises while heroin use was associated with low risk sexual transmission. These findings indicate appreciable residual risk behaviour sufficient to allow for at least a slow diffusion of HIV among injecting drug users.

Journal Article↗

Predicting inpatient costs with admitting clinical data.

Hospital cost-containment programs should themselves be cost-effective, targeting high-cost physicians (which requires adjusting for case mix) and patients (which requires early identification). In this study, clinical data available within 24 hours of admission from an electronic medical record system were used to develop statistical models to predict hospital costs. In this retrospective analysis of clinical data and diagnosis-related groups (DRGs), study subjects were 2,355 patients admitted for at least 1 day to the medicine service at an urban teaching hospital with sophisticated electronic medical records. Of these 2,355 patients, 1,663 (71%) had one of the 41 most common DRGs. Predictive models were derived on a random subset of two thirds of the patients and were validated on the remaining third. The following patient data were obtained: admission and prior diagnostic test results, diagnoses, vital signs; demographic data; prior inpatient and outpatient visits; tests and treatments ordered within 24 hours of admission (discretionary data); DRGs; and total inpatient costs (estimated from charges). Diagnosis-related groups explained 24% of the variance in total costs in the derivation patient set and 16% in the validation set. When only nondiscretionary data were used, the models retained only clinical laboratory results and prior diagnoses, explaining 20% of the derivation set variance in total costs and 16% in the validation set. Adding DRGs increased the variance explained in the derivation set to 34%, but decreased to 24% in the validation set. Adding discretionary data substantially increased the explained variance in the derivation and validation patient sets. The models' median predicted costs underestimated true costs by 10% to 13%, with the lowest error in the models using all types of variables. Clinical data gathered during routine clinical care can be used to adjust for case mix and identify high-cost patients early in their hospital stays, when they could be targeted by cost-containment interventions.

Cost Control↗