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Biomedical subjects

C Whitney

Publications and source records attributed to C Whitney.

At least 19 recordsLinked to original sources
PubMed2004

Hemisphere-specific effects in word recognition do not require hemisphere-specific modes of access.

Consistent with converging experimental evidence, we assume that foveal information is initially split across the two cerebral hemispheres. We have previously presented the SERIOL model of letter-position coding, which specifies how the resulting two halves of a letter string are integrated into an abstract representation of letter order. This representation is based on ordered pairs of two letters (bigrams); such a representation is created for input occurring at any location in the visual field. Various studies have shown hemisphere-specific effects in lexical access by using unilateral presentation of stimuli. While the hemisphere-independent means of lexical access in the SERIOL model (via bigrams) may seem inconsistent with these findings, we propose that such effects arise from the hemisphere-specific transformations necessary to create the bigram representation. We provide a theoretical account of the finding that high N (lexical neighborhood size) evokes facilitation in the RH, but not the LH (Lavidor & Ellis, 2002a, 2002b); an experiment discussed elsewhere (Whitney & Lavidor, 2003) has verified key predictions of this account. We also discuss the differing effects of word length across visual fields.

Brain↗
PubMed2002

Chronic lymphocytic leukemia presenting with symptomatic central nervous system involvement.

Leukemic infiltration of the central nervous system (CNS) resulting in neurological manifestations is a rare complication of chronic lymphocytic leukemia (CLL). Furthermore, symptomatic CNS involvement as the initial presentation of previously undiagnosed CLL is extremely rare. In the present report, the authors describe a case of an 89-year-old female previously diagnosed with Alzheimer's disease who suddenly developed rapidly worsening mental changes. Cytological and immunocytological examinations of the lymphoid cells present on the cerebrospinal fluid (CSF) revealed CNS involvement by a clonal B-cell lymphoproliferative disorder, most consistent with de novo B-CLL expressing kappa light chain restriction. Subsequently, flow cytometric analysis done on the peripheral blood lymphocytes confirmed the diagnosis of B-CLL in this patient. Thus, this study shows the potential usefulness of immunocytological evaluation in detecting monoclonal lymphoid populations on CSF samples in adult patients presenting with altered mental status and CSF pleocytosis of lymphocytes.

Aged↗
PubMed2002

Pulmonary eosinophilia in a murine model of allergic inflammation is attenuated by small molecule alpha4beta1 antagonists.

Inhibition of alpha4beta1/vascular cell adhesion molecule-1 (VCAM-1) interactions have therapeutic potential in treating allergic airway disease because of the importance of these adhesion molecules in the trafficking of eosinophils, lymphocytes, and monocytes. We examined several small molecule inhibitors of alpha4beta1/VCAM-1 interactions with in vitro potencies (IC(50) values) ranging from 0.52 nM (CP-664511; 3-[3-(1-[2-[3-methoxy-4-(3-O-tolyl-ureido)phenyl]-acetylamino]-3-methyl-butyl)isoxazol-5-yl]-propionic acid) to 38.5 nM (CP-609643; 3-[3-methyl-1-[2-[4-(3-O-tolyl-ureido)-phenyl]-acetylamino]-butyl)-isoxazol-5-yl]-propionic acid). The same compounds were evaluated in vivo using a murine model of ovalbumin-induced pulmonary eosinophilia. In this model, systemic administration of antibodies against alpha4 reduced bronchoalveolar lavage (BAL) eosinophilia approximately 60%. Small molecule alpha4beta1 antagonists were administered by intratracheal instillation and demonstrated dose-dependent inhibition of BAL eosinophil numbers and achieved a maximum inhibition of approximately 60%. In general, the rank order of potency for these compounds in vitro was consistent with that observed in vivo, which confirms that their efficacy is likely via blockade of alpha4beta1/VCAM-1 interactions. The most potent compound, CP-664511, also inhibited BAL eosinophilia following s.c. administration (1-10 mg/kg, s.c.). These data support the utility of small molecule alpha4beta1 antagonists in the treatment of relevant diseases, such as asthma.

Animals↗
PubMed2001

Simultaneously detected endometrial and ovarian carcinomas--a prospective clinicopathologic study of 74 cases: a gynecologic oncology group study.

OBJECTIVES: The coexistence of carcinomas of the endometrium and ovary occurs in about 10% of women with ovarian carcinoma. It is often unclear whether this represents synchronous primary tumors or metastasis from endometrium to ovary, or from ovary to endometrium; consequently, staging, therapy, and expected outcome are uncertain. The Gynecologic Oncology Group sought to study patients with simultaneously detected adenocarcinomas in the endometrium and ovary with disease grossly confined to the pelvis to explore the possible correlation among discrete tumor subsets, natural history, and survival. METHODS: Between 1985 and 1991, 85 patients were prospectively enrolled, of whom 74 were eligible. All were initially treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging laparotomy, with radiation and chemotherapy left to the discretion of the treating physician and patient. Fifteen pathologic variables were examined to identify differences in tumor behavior. RESULTS: Of the 74 patients, 23 (31%) had microscopic spread of tumor in the pelvis or abdomen. Sixty-four (86%) patients had endometrioid carcinomas in both the endometrium and the ovary, and endometriosis was found in the ovary of 23 (31%) patients. There was concordance between the histologic grade of the tumor in the ovary and the uterus in 51 (69%) patients. The estimated probability of recurrence 5 years following staging surgery is 15.1% (95% confidence interval (CI): 8.7-25.2%). The presence of metastasis discriminated two groups of patients that experienced different probabilities of recurrence within 5 years: 10.0% (95% CI: 4.32-21.3%) for those with tumors confined to the uterus and ovary and 27.1% (95% CI: 13.0-48.5%) for those with metastasis (hazard ratio = 4.6, P = 0.006). The histologic grades of ovarian and uterine tumors also distinguished groups of patients with different probabilities of recurrence at 5 years: 8.0% (95% CI: 2.8-21.3%) for those patients with no more than grade 1 disease at either site and 22.4% (95% CI: 11.8-38.4%) for those with a higher grade in either the ovary or the endometrium (hazard ratio = 3.1, P = 0.047). The estimated overall probability of surviving 5 years is 85.9% and that of surviving 10 years is 80.3%. CONCLUSION: The prognosis for women with simultaneously detected carcinomas in the uterus and ovary with gross disease confined to the pelvis is surprisingly good, particularly for those with disease microscopically limited to the uterus and ovary or of low histologic grade.

Adenocarcinoma↗
PubMed2001

How the brain encodes the order of letters in a printed word: the SERIOL model and selective literature review.

This paper describes a novel theoretical framework of how the position of a letter within a string is encoded, the SERIOL model (sequential encoding regulated by inputs to oscillations within letter units). Letter order is represented by a temporal activation pattern across letter units, as is consistent with current theories of information coding based on the precise timing of neural spikes. The framework specifies how this pattern is invoked via an activation gradient that interacts with subthreshold oscillations and how it is decoded via contextual units that activate word units. Using mathematical modeling, this theoretical framework is shown to account for the experimental data from a wide variety of string-processing studies, including hemispheric asymmetries, the optimal viewing position, and positional priming effects.

Attention↗
PubMed2000

Impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia.

The impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia was evaluated in a retrospective cohort study conducted during population-based surveillance for invasive pneumococcal disease in the greater Atlanta region during 1994. Of the 192 study patients, 44 (23%) were infected with pneumococcal strains that demonstrated some degree of penicillin nonsusceptibility. Compared with patients infected with penicillin-susceptible pneumococcal strains, patients whose isolates were nonsusceptible had a significantly greater risk of in-hospital death due to pneumonia (relative risk [RR], 2.1; 95% confidence interval [CI], 1-4.3) and suppurative complications of infection (RR, 4.5; 95% CI, 1-19.3), although only risk of suppurative complications remained statistically significant after adjustment for baseline differences in severity of illness. Among adults with bacteremic pneumococcal pneumonia, infection with penicillin-nonsusceptible pneumococci is associated with an increased risk of adverse outcome.

Adult↗
PubMed1998

Dexamethasone but not indomethacin inhibits human phagocyte nicotinamide adenine dinucleotide phosphate oxidase activity by down-regulating expression of genes encoding oxidase components.

We investigated the effects of dexamethasone or indomethacin on the NADPH oxidase activity, cytochrome b558 content, and expression of genes encoding the components gp91-phox and p47-phox of the NADPH oxidase system in the human monocytic THP-1 cell line, differentiated with IFN-gamma and TNF-alpha, alone or in combination, for up to 7 days. IFN-gamma and TNF-alpha, alone or in combination, caused a significant up-regulation of the NADPH oxidase system as reflected by an enhancement of the PMA-stimulated superoxide release, cytochrome b558 content, and expression of gp91-phox and p47-phox genes on both days 2 and 7 of cell culture. Noteworthy was the tremendous synergism between IFN-gamma and TNF-alpha for all studied parameters. Dexamethasone down-regulated the NADPH oxidase system of cytokine-differentiated THP-1 cells as assessed by an inhibition on the PMA-stimulated superoxide release, cytochrome b558 content, and expression of the gp91-phox and p47-phox genes. The nuclear run-on assays indicated that dexamethasone down-regulated the NADPH oxidase system at least in part by inhibiting the transcription of gp91-phox and p47-phox genes. Indomethacin inhibited only the PMA-stimulated superoxide release of THP-1 cells differentiated with IFN-gamma and TNF-alpha during 7 days. None of the other parameters was affected by indomethacin. We conclude that dexamethasone down-regulates the NADPH oxidase system at least in part by inhibiting the expression of genes encoding the gp91-phox and p47-phox components of the NADPH oxidase system.

Anti-Inflammatory Agents↗
PubMed1998

The incentive effects of malpractice liability rules on dental practice behavior.

OBJECTIVES: The impact of malpractice liability rules on dental practice behavior was estimated using data from a 1992 nationwide survey of US general dentists. The study examined the premise that malpractice liability rules can affect quality of care and related resource allocation decisions by dentists, but that market features, such as relatively complete and "non-experience rated" malpractice insurance, are likely to weaken the incentive effects of malpractice liability. METHODS: General practice dentists in the United States were selected randomly, and 3,048 dentists were studied by mail survey. Secondary data on county-level characteristics were used to measure market area factors. Quality-of-care measures were derived from the survey about self-reported practice policies and behavior and participation in continuing education. Legal measures were assembled from state statutes and appellate court decisions. Ordinary least squares was used to assess the relation between legal variables and dependent variables of quality of care, continuing education, and the rate of dental output. RESULTS: Hypotheses about the effects of malpractice law on practice quality and participation in continuing education were not supported. The relation between pro-dentist law and output was supported. A number of legal provisions related to differences in practice behavior, but often in ways opposite to the expected direction. CONCLUSIONS: The direct effects of specific malpractice liability rules on dentist practice behavior often failed to point in the direction predicted by theory and were economically insignificant. It is possible that relatively complete malpractice liability insurance, coupled with "noisy" liability rules, substantially dulls the deterrent effect of malpractice liability. Other forces, such as the dentist's past malpractice claims experience, were more significant in shaping dentist behavior.

Education, Dental, Continuing↗
PubMed1997

A computational model of acute focal cortical lesions.

BACKGROUND AND PURPOSE: Determining how cerebral cortex adapts to sudden focal damage is important for gaining a better understanding of stroke. In this study we used a computational model to examine the hypothesis that cortical map reorganization after a simulated infarct is critically dependent on perilesion excitability and to identify factors that influence the extent of poststroke reorganization. METHODS: A previously reported artificial neural network model of primary sensorimotor cortex, controlling a simulated arm, was subjected to acute focal damage. The perilesion excitability and cortical map reorganization were measured over time and compared. RESULTS: Simulated lesions to cortical regions with increased perilesion excitability were associated with a remapping of the lesioned area into the immediate perilesion cortex, where responsiveness increased with time. In contrast, when lesions caused a perilesion zone of decreased activity to appear, this zone enlarged and intensified with time, with loss of the perilesion map. Increasing the assumed extent of intracortical connections produced a wider perilesion zone of inactivity. These effects were independent of lesion size. CONCLUSIONS: These simulation results suggest that functional cortical reorganization after an ischemic stroke is a two-phase process in which perilesion excitability plays a critical role.

Animals↗
PubMed1996

Refusal of food and water by a man with end stage Parkinson's disease.

In the future, we need to consider the social and financial implications of allowing someone to remain in an acute care hospital for comfort care until death. Other acceptable options for the non-terminal but, severely disabled patients must be identified so that we are able to respect and honor our patients' autonomous decisions without using the increasingly scarce health care resources. While not all ethical dilemmas of this nature will be resolved in such a relatively uncomplicated manner, this situation does provide us with a foundation from which to approach future cases. We have learned to listen closely to our patients; we have learned the importance of understanding who our patients were and who they are now; we have learned from Mr. K's strength to express his convictions.

Attitude of Health Personnel↗
PubMed1996

Frustrating patient visits.

OBJECTIVES: This study, part of a national mail survey of dentist malpractice liability claims, reports the reliability and validity of a new 22-item instrument measuring frustrating patient visits. METHODS: The items were subjected to factor analysis and subscales constructed. Reliability was assessed using Cronbach's alpha. Validity was assessed by comparing subscale scores to self-reports of satisfaction and liability claims. RESULTS: Factor analysis revealed four subscales representing unpleasant feelings, lack of communication, compliance, and practice organization (alpha = 0.60-0.86). Compliance was the most important factor. Subscale scores were related to satisfaction with practice and the proportion of patient visits in the practice that were frustrating to the dentist. Dentists who reported frustrating patient visits as quite typical of their practices were more likely to have had a malpractice liability claim within the last five years. CONCLUSION: This instrument may be of value in detecting patient-dentist communication difficulties that are the precursor to liability claims.

Communication↗
PubMed1995

Survival after retinoblastoma: long-term consequences and family history of cancer.

Retinoblastoma (Rb) is a rare childhood tumor of the eye. In the heritable form, tumors are often bilateral and survivors have a greatly increased risk both for a second malignancy and for having children with Rb. Familial patterns of both cancer and birth defects are poorly understood in families with a heritable cancer, and little is known of the ways that a heritable cancer affects the lives of long-term survivors. To find out more about these and other issues in the lives of long-term survivors of childhood and adolescent cancer, we interviewed 56 adult survivors of retinoblastoma (15 with the heritable form) and 84 brothers and sisters as controls, who formed part of a large retrospective cohort study. Rb survivors were interviewed between 1980 and 1983, when they were 30 years old on average. Types of employment and health problems did not differ between survivors and controls, regardless of sight, but the income of blind survivors was considerably less than that of partially sighted survivors. Despite similar marriage rates, fewer survivors than controls reported a pregnancy (RR = 0.45; 95% CI; 0.24-0.83 for both sexes combined). Parents of children with heritable Rb seemed more likely to have had cancer than parents in families with nonheritable Rb (P = 0.06), and mothers were more likely than fathers to be affected (P = 0.01). This small series suggests that having retinoblastoma may have many long-term consequences, reaching beyond genetic and physical effects to touch family life and income attainment and the health of other family members. Follow-up of more modern cohorts and the use of molecular tools will clarify the long-term consequences of more recent therapies, and patterns of familiar cancer.

Achievement↗
PubMed1995

Do changes in patient beliefs and coping strategies predict temporomandibular disorder treatment outcomes?

OBJECTIVE: This study examined the applicability of the cognitive-behavioral model for temporomandibular disorders (TMD) by determining whether changes in TMD patient pain-related beliefs and coping over the course of treatment related to improvement in symptoms and disability and whether patients' posttreatment beliefs and coping predicted future pain and functioning. PATIENTS/SETTING: We studied 139 TMD patients at a health maintenance organization or a university dental school who completed a clinical trial comparing usual treatment with or without a brief cognitive-behavioral intervention. OUTCOME MEASURES/DESIGN: Pain, disability, depression, objective physical impairment, and pain beliefs and coping strategies were assessed pretreatment and at 3- and 12-month follow-ups. RESULTS: Increased ability to control pain and decreased Disease Conviction and Passive Coping scores were associated with improved pain, jaw opening, and depression from pretreatment to 3-month follow-up. Patient beliefs and coping at 3-month follow-up did not contribute much to the prediction of pain or physical and psychological functioning at 12-month follow-up after controlling for 3-month pain and functioning scores. However, passive coping and low ability to control pain at 3 months predicted greater activity interference at 12 months. CONCLUSIONS: Pretreatment to 3-month follow-up changes in beliefs and coping are associated modestly with TMD patient improvement after conservative dental treatment with and without a brief cognitive-behavioral intervention. Research is needed to develop interventions that produce greater decreases in disease conviction, passive coping, and perceived inability to control pain and to determine whether these changes mediate symptom and disability improvement.

Adaptation, Psychological↗
PubMed1995

Tort reform and malpractice liability insurance.

Legal factors related to the malpractice liability insurance purchased by general dentists in the United States were investigated using a comprehensive multivariate model that assessed the contribution of legal provisions affecting the probability of a malpractice claim, the probability of a payment, and the average size of the payment. General practice dentists in the United States were selected randomly, and 3,048 dentists were studied by mail survey. A number of legal statutes (periodic payment allowed, percentage fault liability informed consent limits, limits on res ipsa loquitor, attorney fee control, some statute of limitations provisions) had the intended effect of reducing the malpractice insurance sought by dentists. Other provisions, such as binding arbitration, may have unintended cost-raising effects. Previous malpractice claims were associated with purchasing greater amounts of insurance. These findings have implications for future changes in the legal system as part of health care reform.

Dentistry↗
PubMed1995

Malpractice premiums in 1992: results of a national survey of dentists.

According to a 1992 national survey, more than 95 percent of general dentists in the United States purchased malpractice insurance. The authors evaluated the survey findings to identify factors that had the greatest effect on dentists' insurance premium costs. Premiums were higher for dentists who had been the subject of previous complaints or claims, as well as for those who owned their practices. States with fewer lawyers had lower premiums. Finally, state limits on use of dental hygienists, number of offices and the extent of water fluoridation also affected premium levels.

Fees and Charges↗
PubMed1994

Regulation of the human cellular glutathione peroxidase gene during in vitro myeloid and monocytic differentiation.

We have used the HL-60 and PLB-985 myeloid leukemia cell lines to examine the regulation of expression of the important intracellular antioxidant enzyme, glutathione peroxidase (GSH-Px), during phagocytic cell differentiation in vitro. Induction of differentiation along the monocytic pathway by phorbol ester results in an approximately twofold rise in enzyme activity and a parallel increase in the rate of 75Se incorporation into immunoprecipitable GSH-Px protein. Induction along the granulocytic pathway by dimethyl formamide (DMF) results in similar changes in steady-state enzyme levels and rates of GSH-Px protein synthesis. Steady-state levels of GSH-Px gene transcripts also increase more than twofold, approximately in parallel with the enzyme levels. Nuclear run-on transcription assays of GSH-Px mRNA synthesis show ratios of induced to uninduced transcript levels of 2.24 and 1.59 with phorbol myristate acetate (PMA) induction and DMF, respectively, in HL-60 cells, and ratios of 1.34 and 3.46 with PMA and DMF, respectively, in PLB-985 cells. Half lives of GSH-Px mRNA are unchanged or slightly shorter after differentiation of HL-60 cells, and slightly longer after induction of PLB-985. Overall, the present studies show that GSH-Px activity rises during in vitro-induced monocytic or granulocytic differentiation of myeloid cell lines and that the increased expression of the cellular GSH-Px gene occurs through complex mechanisms that include transcriptional up-regulation. This pattern contrasts with the nearly complete cotranslational regulation of GSH-Px expression by exogenous selenium.

Cell Differentiation↗