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Biomedical subjects

L M Sullivan

Publications and source records attributed to L M Sullivan.

At least 19 recordsLinked to original sources

Leptomeningeal carcinomatosis from perineural invasion of a lip squamous cell carcinoma.

Perineural invasion resulting in leptomeningeal carcinomatosis is a rare, but well-recognized phenomenon in head and neck carcinomas. We report the rare case of a patient with a squamous cell carcinoma of the lip resulting in leptomeningeal carcinomatosis and review the relevant published work. A 51-year-old man presented with progressive facial paraesthesia after treatment for a recurrent squamous cell carcinoma of the lower lip. Cavernous sinus involvement was confirmed on MRI and he received stereotactic radiotherapy. He subsequently developed progressive lower limb neurological signs. An MRI showed multiple enhancing leptomeningeal nodules in the cervical and lumbar spine consistent with leptomeningeal carcinomatosis. Whole spine radiotherapy and dexamethasone resulted in short-term stabilization of symptoms only and he rapidly succumbed to progressive neurological disease. To our knowledge, this is the first published report of a squamous cell carcinoma of the lip resulting in leptomeningeal disease of the cauda equina. It illustrates the potential aggressive natural history of squamous cell carcinomas with perineural invasion.

Carcinoma, Squamous Cell↗

Coronary heart disease risk in men and the epidemic of overweight and obesity.

OBJECTIVE: To evaluate the contributions of socioeconomic, lifestyle, and body weight factors to predicted risk of coronary heart disease (CHD) in the population and thus provide a focus for policies on prevention. DESIGN: Prospective study and cross-sectional population health survey. SUBJECTS: In all, 3090 men in the Framingham study and 2571 men in the 1998 Health Survey for England (HSE) aged 35-74 y with no history of cardiovascular disease participated in the study. MEASUREMENTS: Data on sex, age, systolic blood pressure and antihypertensive medication, total and high-density lipoprotein cholesterol levels, diabetes, and their association with the incidence of myocardial infarction and fatal CHD in the Framingham study population were used to derive functions for predicting individual 10-y risk of CHD. These functions were applied to the same data on participants in the HSE. High risk was defined as 10-y CHD risk > or = 15%. The proportion of high risk in the English population attributable to each of the risk factors examined was assessed. RESULTS: In all, 32% of men in England had predicted 10-y CHD risk > or =15%. Such high risk was significantly associated with body mass index (BMI, kg/m2), waist:hip ratio (WHR), smoking, and levels of physical activity, educational attainment, and income (all P < or = 0.007). In this population, 47% of high CHD risk was attributable to excess body weight--BMI > or = 25 kg/m2 and/or WHR > or = 0.95--and 31% to the sum of the four other significant factors: lack of educational qualifications, low income, smoking, and physical inactivity. CONCLUSION: Overweight and obesity now dominate the standard risk factors of CHD in men and should be the focus of national policies for prevention.

Adult↗

The effect of the elapsed time between blood draw and processing on the recovery of fetal cells from maternal blood.

OBJECTIVE: To test the hypothesis that a delay in initial fetal cell enrichment processing of maternal blood samples (defined as the time between blood draw and the initial density gradient centrifugation step) compromises the ability to recover fetal cells, we performed a randomized comparison of immediate (within 4 hours of draw) versus delayed (between 18-24 hours of draw) processing. METHODS: Four centers participated: two centers utilized flow cytometry (FLOW), and two centers utilized magnetic-activated cell sorting (MACS) techniques. Each center collected 34 samples. The outcome was the percentage of gamma positive (gamma(+)) cells for FLOW or the number of nucleated red blood cells (NRBCs) for MACS, found in the final enriched cell population. Both outcomes reflect cell properties that are potentially fetal in origin, thus making them representative of the ability to recover fetal cells. RESULTS: Our results did not support our hypothesis that delay in processing compromises fetal cell recovery. Instead, in MACS processing, we observed an increase in recovered NRBCs when blood sample processing was delayed compared with immediate processing. There was no significant difference in gamma(+) cells with FLOW. CONCLUSION: Time-related changes in the density of target cells, perhaps associated with their progress towards apoptosis during the delay period, may result in increased intact fetal cells with the study methods utilized.

Apoptosis↗

Robustness and power of analysis of covariance applied to ordinal scaled data as arising in randomized controlled trials.

In clinical trials comparing two treatments, ordinal scales of three, four or five points are often used to assess severity, both prior to and after treatment. Analysis of covariance is an attractive technique, however, the data clearly violate the normality assumption and in the presence of small samples, and large sample theory may not apply. The robustness and power of various versions of parametric analysis of covariance applied to small samples of ordinal scaled data are investigated through computer simulation. Subjects are randomized to one of two competing treatments and the pre-treatment, or baseline, assessment is used as the covariate. We compare two parametric analysis of covariance tests that vary according to the treatment of the homogeneity of regressions slopes and the two independent samples t-test on difference scores. Under the null hypothesis of no difference in adjusted treatment means, we estimated actual significance levels by comparing observed test statistics to appropriate critical values from the F- and t-distributions for nominal significance levels of 0.10, 0.05, 0.02 and 0.01. We estimated power by similar comparisons under various alternative hypotheses. The model which assumes homogeneous slopes and the t-test on difference scores were robust in the presence of three, four and five point ordinal scales. The hierarchical approach which first tests for homogeneity of regression slopes and then fits separate slopes if there is significant non-homogeneity produced significance levels that exceeded the nominal levels especially when the sample sizes were small. The model which assumes homogeneous regression slopes produced the highest power among competing tests for all of the configurations investigated. The t-test on difference scores also produced good power in the presence of small samples.

Analysis of Variance↗

Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study.

OBJECTIVE: To determine the independent effects of obesity and hypertension on cognitive functioning. METHODS: Using a prospective design, male (n=551) and female (n=872) participants of the Framingham Heart Study were classified by presence or absence of obesity and hypertension based on data collected over an 18-y surveillance period. All subjects were free from dementia, stroke, and clinically diagnosed cardiovascular disease up to the time of cognitive testing. Statistical models were adjusted for age, education, occupation, cigarette smoking, alcohol consumption, total cholesterol, and a diagnosis of type II diabetes. Body mass index status (nonobese or obese) and blood pressure status (normotensive or hypertensive) were then related to cognitive performance (learning, memory, executive functioning, and abstract reasoning) on tests administered 4-6 y later. RESULTS: Adverse effects of obesity and hypertension on cognitive performance were observed for men only. Obese and hypertensive men performed more poorly than men classified as either obese or hypertensive, and the best performance was observed in nonobese, normotensive men. CONCLUSIONS: The adverse effects of obesity and hypertension in men are independent and cumulative with respect to cognitive deficit.

Aged↗

Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study.

OBJECTIVES: The National Institute of Child Health and Human Development Fetal Cell Isolation Study (NIFTY) is a prospective, multicenter clinical project to develop non-invasive methods of prenatal diagnosis. The initial objective was to assess the utility of fetal cells in the peripheral blood of pregnant women to diagnose or screen for fetal chromosome abnormalities. METHODS: Results of fluorescence in situ hybridization (FISH) analysis on interphase nuclei of fetal cells recovered from maternal blood were compared to metaphase karyotypes of fetal cells obtained by amniocentesis or chorionic villus sampling (CVS). After the first 5 years of the study we performed a planned analysis of the data. We report here the data from 2744 fully processed pre-procedural blood samples; 1292 samples were from women carrying singleton male fetuses. RESULTS: Target cell recovery and fetal cell detection were better using magnetic-based separation systems (MACS) than with flow-sorting (FACS). Blinded FISH assessment of samples from women carrying singleton male fetuses found at least one cell with an X and Y signal in 41.4% of cases (95% CI: 37.4%, 45.5%). The false-positive rate of gender detection was 11.1% (95% CI: 6.1,16.1%). This was higher than expected due to the use of indirectly labeled FISH probes in one center. The detection rate of finding at least one aneuploid cell in cases of fetal aneuploidy was 74.4% (95% CI: 76.0%, 99.0%), with a false-positive rate estimated to be between 0.6% and 4.1%. CONCLUSIONS: The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study.

Adult↗

Patterns of proton pump inhibitor use in clinical practice.

BACKGROUND: Little is known about differences between gastroenterologists and primary care physicians in their patterns of prescribing proton pump inhibitors. SUBJECTS AND METHODS: A survey of practicing primary care physicians from the American Board of Medical Specialties and practicing gastroenterologists from the American Gastroenterological Association was conducted by facsimile. The survey instrument consisted of 13 questions about pharmacokinetics and administration of proton pump inhibitors. RESULTS: The overall response rate was 15% (491 of 3273), and 80% (395 of 491) of respondents were nontrainee gastroenterologists or primary care physicians. Approximately 90% (n = 355) of eligible respondents correctly identified proton pump inhibitors as inhibitors of H+,K+-adenosinetriphosphatase. Proton pump inhibitors were prescribed by 80% (n = 314) of each group for reflux esophagitis. They were prescribed by 67% (122 of 182) of gastroenterologists and 27% (58 of 213) of primary care physicians to prevent ulcers induced by nonsteroidal anti-inflammatory drugs (P <0.001). And they were prescribed by 40% (n = 73) of gastroenterologists and 16% (n = 34) of primary care physicians for uncomplicated heartburn (P <0.001). Proton pump inhibitors were prescribed before a meal by 95% (n = 173) of gastroenterologists and 33% (n = 70) of primary care physicians (P <0.001). Nearly 99% (n = 391) of respondents agreed that proton pump inhibitors were safe, but only 15% (n = 59) thought they should be available without prescription. CONCLUSION: Our survey suggests that the use of proton pump inhibitors differs between gastroenterologists and primary care physicians. Furthermore, although most physicians believe that proton pump inhibitors are safe, few believe that they should be available without a prescription.

Adult↗

Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation.

CONTEXT: The Framingham Heart Study produced sex-specific coronary heart disease (CHD) prediction functions for assessing risk of developing incident CHD in a white middle-class population. Concern exists regarding whether these functions can be generalized to other populations. OBJECTIVE: To test the validity and transportability of the Framingham CHD prediction functions per a National Heart, Lung, and Blood Institute workshop organized for this purpose. DESIGN, SETTING, AND SUBJECTS: Sex-specific CHD functions were derived from Framingham data for prediction of coronary death and myocardial infarction. These functions were applied to 6 prospectively studied, ethnically diverse cohorts (n = 23 424), including whites, blacks, Native Americans, Japanese American men, and Hispanic men: the Atherosclerosis Risk in Communities Study (1987-1988), Physicians' Health Study (1982), Honolulu Heart Program (1980-1982), Puerto Rico Heart Health Program (1965-1968), Strong Heart Study (1989-1991), and Cardiovascular Health Study (1989-1990). MAIN OUTCOME MEASURES: The performance, or ability to accurately predict CHD risk, of the Framingham functions compared with the performance of risk functions developed specifically from the individual cohorts' data. Comparisons included evaluation of the equality of relative risks for standard CHD risk factors, discrimination, and calibration. RESULTS: For white men and women and for black men and women the Framingham functions performed reasonably well for prediction of CHD events within 5 years of follow-up. Among Japanese American and Hispanic men and Native American women, the Framingham functions systematically overestimated the risk of 5-year CHD events. After recalibration, taking into account different prevalences of risk factors and underlying rates of developing CHD, the Framingham functions worked well in these populations. CONCLUSIONS: The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different settings and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events.

Black or African American↗

Understanding delay to medical care for HIV infection: the long-term non-presenter.

OBJECTIVE: To examine delayed presentation for HIV testing and primary care in the second decade of the AIDS epidemic. DESIGN: Cohort study in two urban hospitals in the USA between February 1994 and April 1996. METHODS: A total of 203 consecutive outpatients on initial HIV primary care presentation were interviewed about sociodemographic characteristics, alcohol and drug use, social support, sexual practices, HIV testing, awareness of possible HIV infection, and CD4 cell count. MAIN OUTCOME MEASURE: Duration of delay to medical presentation in years based on CD4 cell count, factors independently associated with low CD4 cell counts, frequency of awareness of HIV risk before testing. RESULTS: The estimated mean duration between acquiring HIV infection and initial presentation to primary care was 8.1 years (95% CI 7.5, 8.6) based on our cohort's median initial CD4 cell count of 280/microl. Male sex, older age, and no jail time were associated with lower CD4 cell counts; 34% reported not being aware that they were at risk of HIV before testing. Heterosexual intercourse as a risk behavior for HIV was the most statistically significant factor for personal unawareness of HIV risk. Of those who acknowledged awareness, the mean time between awareness of HIV risk and testing was 2.5 years (median 1.0 year). CONCLUSION: In the pre-highly active antiretroviral therapy era, HIV-infected patients frequently initiated primary medical care years after initial infection, at a time of advanced immunosuppression. Over one-third of HIV-infected patients were not cognisant of their HIV risk before testing, a condition significantly associated with heterosexual intercourse as the only HIV risk behavior.

Adult↗

Evolution of depressive symptoms in human immunodeficiency virus-infected patients entering primary care.

Our purpose was to examine among HIV-infected patients a) characteristics associated with depressive symptoms at initial primary care presentation and b) factors associated with improvement in depressive symptoms. We interviewed HIV-infected patients at initial presentation and reassessed them 6 months later. At baseline and follow-up, we collected data on depressive symptoms (CES-D) and other characteristics. Using multiple linear regression, we examined associations between CES-D score and baseline variables. We used multiple logistic regression to examine factors associated with improvement in depressive symptoms. Seventy-one percent of the baseline sample (N = 203) scored above the threshold considered indicative of depression. At 6 months, 36% of the subjects who were followed improved in depressive symptoms. Higher baseline CES-D scores, improvements in HIV-related symptoms, and joining a support group were associated with improvement. Depressive symptoms in this urban HIV-infected population were highly prevalent. It is essential to screen, identify, and treat depression among patients entering care for HIV disease. Encouragement in joining support groups is a reasonable component of a strategy for addressing this common condition.

Adult↗

Generation and analysis of mice lacking the chemokine fractalkine.

Fractalkine (CX(3)CL1) is the first described chemokine that can exist either as a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can mediate adhesion of cells expressing its receptor, CX(3)CR1. This activity, together with its expression on endothelial cells, suggests that fractalkine might mediate adhesion of leukocytes to the endothelium during inflammation. Fractalkine is also highly expressed in neurons, and its receptor, CX(3)CR1, is expressed on glial cells. To determine the biologic role of fractalkine, we used targeted gene disruption to generate fractalkine-deficient mice. These mice did not exhibit overt behavioral abnormalities, and histologic analysis of their brains did not reveal any gross changes compared to wild-type mice. In addition, these mice had normal hematologic profiles except for a decrease in the number of blood leukocytes expressing the cell surface marker F4/80. The cellular composition of their lymph nodes did not differ significantly from that of wild-type mice. Similarly, the responses of fractalkine(-/-) mice to a variety of inflammatory stimuli were indistinguishable from those of wild-type mice.

Animals↗

Correlates of violent assault among young male primary care patients.

Correlates of violent assault (defined here as having been shot, stabbed, shot at, or beaten) were identified among young male primary care patients. Data were analyzed from a cohort of young men ages 17 to 29 during their initial visits to an urban primary care facility. Each underwent a clinical assessment, including a self-report health inventory and provider history. In multivariable analysis, history of incarceration (odds ratio [OR] = 6.29, 95 percent confidence interval [CI], 2.34-16.89), having children (OR = 3.06, 95 percent CI, 1.30-7.17), and a high school education or less (OR = 0.69, 95 percent CI, 0.50-0.96) were significantly associated with increased likelihood of violent assault. Patients reporting more serious traumatic experiences, such as incarceration, witnessing violence, or carrying a weapon, had the highest risk (OR = 9.91, 95 percent CI, 4.0-24.57). These findings may help primary care physicians identify young men at risk for violence and foster better interventions.

Adolescent↗

Improving alcoholism treatment across the spectrum of services.

This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The chair was Michael E. Hilton. The presentations were (1) The effects of brief advice and motivational enhancement on alcohol use and related variables in primary care, by Stephen A. Maisto, Joseph Conigliaro, Melissa McNiel, Kevin Kraemer, Mary E. Kelley, and Rosemarie Conigliaro; (2) Enhanced linkage of alcohol dependent persons to primary medical care: A randomized controlled trial of a multidisciplinary health evaluation in a detoxification unit, by Jeffrey H. Samet, Mary Jo Larson, Jacqueline Savetsky, Michael Winter, Lisa M. Sullivan, and Richard Saitz; (3) Cost-effectiveness of day hospital versus traditional alcohol and drug outpatient treatment in a health maintenance organization: Randomized and self-selected samples, by Constance Weisner, Jennifer Mertens, Sujaya Parthasarathy, Charles Moore, Enid Hunkeler, Teh-Wei Hu, and Joe Selby; and (4) Case monitoring for alcoholics: One year clinical and health cost effects, by Robert L. Stout, William Zywiak, Amy Rubin, William Zwick, Mary Jo Larson, and Don Shepard.

Alcoholism↗

CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue.

Chemokine-directed migration of leukocyte subsets may contribute to the qualitative differences between systemic and mucosal immunity. Here, we demonstrate that in mice lacking the chemokine receptor CCR6, dendritic cells expressing CD11c and CD11b are absent from the subepithelial dome of Peyer's patches. These mice also have an impaired humoral immune response to orally administered antigen and to the enteropathic virus rotavirus. In addition, CCR6(-/-) mice have a 2-fold to 15-fold increase in cells of select T lymphocyte populations within the mucosa, including CD4+ and CD8+ alphabeta-TCR T cells. By contrast, systemic immune responses to subcutaneous antigens in CCR6(-/-) mice are normal. These findings demonstrate that CCR6 is a mucosa-specific regulator of humoral immunity and lymphocyte homeostasis in the intestinal mucosa.

Animals↗

The doctor-patient relationship and HIV-infected patients' satisfaction with primary care physicians.

OBJECTIVE: To assess the extent to which perceptions of specific aspects of the doctor-patient relationship are related to overall satisfaction with primary care physicians among HIV-infected patients. DESIGN: Longitudinal, observational study of HIV-infected persons new to primary HIV care. Data were collected at enrollment and approximately 6 months later by in-person interview. SETTING: Two urban medical centers in the northeastern United States. PARTICIPANTS: Patients seeking primary HIV care for the first time. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was patient-reported satisfaction with a primary care physician measured 6 months after initiating primary HIV care. Patients who were more comfortable discussing personal issues with their physicians (P =. 021), who perceived their primary care physicians as more empathetic (P =.001), and who perceived their primary care physicians as more knowledgeable with respect to HIV (P =.002) were significantly more satisfied with their primary care physicians, adjusted for characteristics of the patient and characteristics of primary care. Collectively, specific aspects of the doctor-patient relationship explained 56% of the variation in overall satisfaction with the primary care physician. CONCLUSIONS: Patients' perceptions of their primary care physician's HIV knowledge and empathy were highly related to their satisfaction with this physician. Satisfaction among HIV-infected patients was not associated with patients' sociodemographic characteristics, HIV risk characteristics, alcohol and drug use, health status, quality of life, or concordant patient-physician gender and racial matching.

Adult↗

Small-dose droperidol effectively reduces nausea in a general surgical adult patient population.

UNLABELLED: In this prospective, randomized, placebo-controlled study, we (1) determined whether 0.625 mg of IV droperidol given 30 min before emergence from general anesthesia reduces the incidence of immediate and delayed postoperative nausea and vomiting (PONV) in a general surgical adult patient population, and (2) compared the efficacy of droperidol, ondansetron, and promethazine for the rescue treatment of PONV. One hundred fifty adult patients receiving general anesthesia for >2 h received either droperidol (0.625 mg IV) or a placebo before emergence. Patients requiring treatment for PONV in the postanesthesia care unit were randomized to receive either droperidol (0.625 mg IV), ondansetron (4 mg IV), or promethazine (12. 5 mg IV). Droperidol effectively prevented PONV (6.8% in droperidol-treated patients versus 40.8% in placebo-treated patients, P: < 0.001). Droperidol, ondansetron, and promethazine were equally effective in treating established PONV, without significant differences in side effects or time to postanesthesia care unit discharge. IMPLICATIONS: Droperidol 0.625 mg IV before emergence from general anesthesia effectively reduces postoperative nausea and vomiting (PONV) in the general surgical population. Our randomized, double-blinded, placebo-controlled study demonstrated a reduction in PONV from 41% to 7%. Droperidol is a safe and inexpensive alternative to ondansetron. Droperidol, ondansetron, and promethazine are also equally effective in treating PONV in the postanesthesia care unit.

Anesthesia, General↗

Women in academic emergency medicine.

OBJECTIVE: To evaluate the achievement of women in academic emergency medicine (EM) relative to men. METHODS: This study was a cross-sectional mail survey of all emergency physicians who were employed at three-fourths full-time equivalent or greater at the 105 EM residency programs in the United States from August 1997 to December 1997. The following information was obtained: demographics, training and practice issues, roles and responsibilities in academic EM, percentage of time spent per week in clinical practice, teaching, administrative and research activities, academic productivity, and funding. RESULTS: Of the 1,575 self-administered questionnaires distributed by the office of the chairs, 1,197 (76%) were returned. Two hundred seventy-four (23%) of the respondents were women, and 923 (77%) were men. There was a significant difference noted between men and women in all demographic categories. The numbers of respondents who were nonwhite were extremely small in the sample and, therefore, the authors are hesitant to draw any conclusions based on race/ethnicity. There was no difference in training in EM between men and women (82% vs 82%, p = 0.288), but a significantly higher proportion of male respondents were board-certified in EM (84% vs 76%, p < 0.002). Women in academic EM were less likely to hold major leadership positions, spent a greater percentage of time in clinical and teaching activities, published less in peer-reviewed journals, and were less likely to achieve senior academic rank in their medical schools. CONCLUSIONS: These findings mirror those of most medical specialties: academic achievement of women in academic EM lags behind that of men. The paucity of minority physicians in academic EM didn't permit analysis of their academic achievements.

Academic Medical Centers↗

Social support among women veterans.

The beneficial effects of social support on well-being have been shown in various studies. Less is known about factors which constrain or enhance the availability of social support. The present study profiles social support among women veterans and attempts to identify factors which enhance or constrain perceptions of support and social integration for women of different military eras. Data are derived from a national sample of women veterans who had at least one VA out-patient visit during a one year time period. Twenty percent of women veterans report having no one to depend on. Social support is lowest among Vietnam and Post-Vietnam era women. Chronic strains (such as having problems with relatives, housing, and paying bills) are important factors which are associated with levels of perceived support. Factors related to loneliness/alone status appear to be associated with constraints in group activities and perceived support. This research illustrates the importance of examining factors which constrain and enhance supportive activities and relationships.

Adult↗