Digital Commons Network^™

Subsets More Likely To Benefit From Surgery Or Prophylactic Cranial Irradiation After Chemoradiation For Localized Non-Small-Cell Lung Cancer, Bruce Keith, Mark Vincent, Larry Stitt, Anna Tomiak, Richard Malthaner, Edward Yu, Pauline Truong, Richard Inculet, Michael Lefcoe, A. Dar, Walter Kocha, Ian Craig

Edward Yu

After chemoradiation for localized non-small-cell lung cancer, surgery and prophylactic cranial irradiation (PCI) have been used as additional therapies. Less than a third of patients develop brain recurrences, or have local recurrence as their sole initial site of recurrence; these are groups that would benefit from PCI or surgery, respectively. Pretreatment identification of patients more likely to benefit from surgery or PCI would be useful. A retrospective analysis of 80 patients was performed to determine prognostic factors for such patterns of failure. Twenty-nine patients were subsequently selected for surgery in a nonrandomized manner. Seventeen patients had isolated local initial recurrence …

Plasma Pge-2 Levels And Altered Cytokine Profiles In Adherent Peripheral Blood Mononuclear Cells In Non-Small Cell Lung Cancer (Nsclc), Giovanna E. Hidalgo, Li Zhong, Dennis E. Doherty, Edward A. Hirschowitz

Internal Medicine Faculty Publications

INTRODUCTION: PGE-2 is constitutively produced by many non-small cell lung cancers (NSCLC) and its immunosuppressive effects have been linked to altered immune responses in lung cancer. We asked whether elevated levels of plasma PGE-2 correlated with monocyte IL10 production in the NSCLC environment. Looking for correlation in NSCLC patient blood we assayed plasma from NSCLC patients for PGE2 and IL10; we further evaluated production of IL10 by adherent mononuclear cells from a subset of these patients looking for an altered cytokine profile.

RESULTS: Our initial in vitro experiments show that monocyte IL10 induction correlates with tumor cell PGE-2 production, confirming …

Consumer Health Information For Asians (Chia): A Collaborative Project., Deborah D. Halsted, Beatriz Varman, Marsha Sullivan, Lynne Nguyen

Library Staff Publications

According to the 2000 United States Census, the Asian population in Houston, Texas, has increased more than 67% in the last ten years. To supplement an already active consumer health information program, the staff of the Houston Academy of Medicine-Texas Medical Center Library worked with community partners to bring health information to predominantly Asian neighborhoods. Brochures on health topics of concern to the Asian community were translated and placed in eight informational kiosks in Asian centers such as temples and an Asian grocery store. A press conference and a ribbon cutting ceremony were held to debut the kiosks and to …

Brain Uptake, Retention, And Efflux Of Aluminum And Manganese, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

My colleagues and I investigated the sites and mechanisms of aluminum (Al) and manganese (Mn) distribution through the blood-brain barrier (BBB). Microdialysis was used to sample non-protein-bound Al in the extracellular fluid (ECF) of blood (plasma) and brain. Brain ECF Al appearance after intravenous Al citrate injection was too rapid to attribute to diffusion or to transferrin-receptor-mediated endocytosis, suggesting another carrier-mediated process. The brain:blood ECF Al concentration ratio was 0.15 at constant blood and brain ECF Al concentrations, suggesting carrier-mediated brain Al efflux. Pharmacological manipulations suggested the efflux carrier might be a monocarboxylate transporter (MCT). However, the lack of Al …

Functional Mri And The Study Of Human Consciousness., Dan Lloyd

Faculty Scholarship

Functional brain imaging offers new opportunities for the study of that most pervasive of cognitive conditions, human consciousness. Since consciousness is attendant to so much of human cognitive life, its study requires secondary analysis of multiple experimental datasets. Here, four preprocessed datasets from the National fMRI Data Center are considered: Hazeltine et al., Neural activation during response competition; Ishai et al., The representation of objects in the human occipital and temporal cortex; Mechelli et al., The effects of presentation rate during word and pseudoword reading; and Postle et al., Activity in human frontal cortex associated with spatial working memory and …

Current Practice Regarding The Use Of Fatty Livers: A Trans-Atlantic Survey., Charles J. Imber, Shawn D. St Peter, Inigo Lopez, Lynden Guiver, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

A strong association exists between the presence of steatosis in a donor liver for transplantation and the development of primary nonfunction in the recipient. Despite this, appraisal of the donor remains one of the least scientific aspects of the transplantation process, and many centers base their practice on subjective opinion, rather than objective data. We conducted this survey to illuminate controversial issues and highlight the variation of opinion and practice policies both between and within the United Kingdom and the United States. A simple, anonymous, one-page, 10-question survey with tick-box answers was sent to every practicing liver transplant surgeon in …

Characterization Of Subcellular Localization And Stability Of A Splice Variant Of G Alpha I2., Philip B Wedegaertner

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Alternative mRNA splicing of alpha(i2), a heterotrimeric G protein alpha subunit, has been shown to produce an additional protein, termed salpha(i2). In the salpha(i2) splice variant, 35 novel amino acids replace the normal C-terminal 24 amino acids of alpha(i2). Whereas alpha(i2) is found predominantly at cellular plasma membranes, salpha(i2) has been localized to intracellular Golgi membranes, and the unique 35 amino acids of salpha(i2) have been suggested to constitute a specific targeting signal. RESULTS: This paper proposes and examines an alternative hypothesis: disruption of the normal C-terminus of alpha(i2) produces an unstable protein that fails to localize to plasma …

Fibroblast Growth Factor–Specific Modulation Of Cellular Response By Syndecan-4, Arie Horowitz, Eugene Tkachenko, Michael Simons

Dartmouth Scholarship

Proteoglycans participate in growth factor interaction with the cell surface through their heparan sulfate chains (HS), but it is not known if they are otherwise involved in growth factor signaling. It appears now that the syndecan-4 core protein, a transmembrane proteoglycan shown previously to bind phosphatidylinositol 4,5-bisphosphate (PIP(2)) and activate PKC alpha, participates in mediating the effects of fibroblast growth factor (FGF)2 on cell function. Mutations in the cytoplasmic tail of syndecan-4 that either reduced its affinity to PIP(2) (PIP(2)(-)) or disrupted its postsynaptic density 95, disk large, zona occludens-1 (PDZ)-dependent binding (PDZ(-)) produced a FGF2-specific dominant negative phenotype in …

Hepatic Steatosis And Its Relationship To Transplantation., Charles J. Imber, Shawn D. St Peter, Ashok Handa, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Fatty infiltration of the liver is common in the brain-dead donor population and has a strong correlation with primary nonfunction after cold preservation, a condition that is catastrophic to liver transplant recipients. This literature review examines factors associated with the development, diagnosis, quantification, and clinical management of this difficult condition.

Improved Continuation Rate Of Depot-Medroxyprogesterone Acetate In Adolescent Mothers, Hatim A. Omar, Amy Fowler, Sandy D'Angelo

Pediatrics Faculty Publications

Poor compliance and high discontinuation rates of Depot-Medroxyprogesterone Acetate (DMPA) and other contraceptive methods are major factors in the continuing problem of adolescent pregnancy. In this study we attempted to determine if providing comprehensive health care for teen mothers and their babies would improve continuation rates of DMPA. Patients who started DMPA between 1/1/96 and 1/1/99 were included. Teen mothers and their babies received all their health care in this clinic, supported by State funding. Key elements regarding DMPA in this clinic were continuity of care, phone and mail reminders of appointments, free DMPA for patients without insurance, counseling at …

Effectiveness Of Current Therapy Of Bacterial Vaginosis, Petya M Andreeva, Hatim A. Omar

Pediatrics Faculty Publications

The study was conducted in order to evaluate effectiveness of the treatment of bacterial vaginosis (BV) with different therapeutic regimes according to recommendations of the World Health Organization (WHO). During a one-year period (February 2000-February 2001) the Sexually Transmitted Diseases (STD) Center was visited by 482 women aged 14-51. The diagnosis of BV was established by standard methods: Amsel's clinical criteria and Gram stain of vaginal discharge. The first-line treatment was oral Metronidazole 2 g single dose. Second line was Metronidazole 500 mg twice daily orally for 7 days or oral Clindamycin 300 mg twice daily for seven days. BV …

Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky

Dartmouth Scholarship

All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …

Breast Cancer On The World Wide Web: Cross Sectional Survey Of Quality Of Information And Popularity Of Websites., Funda Meric, Elmer V Bernstam, Nadeem Q Mirza, Kelly K Hunt, Frederick C Ames, Merrick I Ross, Henry M Kuerer, Raphael E Pollock, Mark A Musen, S Eva Singletary

Journal Articles

OBJECTIVES: To determine the characteristics of popular breast cancer related websites and whether more popular sites are of higher quality.

DESIGN: The search engine Google was used to generate a list of websites about breast cancer. Google ranks search results by measures of link popularity---the number of links to a site from other sites. The top 200 sites returned in response to the query "breast cancer" were divided into "more popular" and "less popular" subgroups by three different measures of link popularity: Google rank and number of links reported independently by Google and by AltaVista (another search engine).

MAIN OUTCOME …

Short-Circuiting Long-Lived Humoral Immunity By The Heightened Engagement Of Cd40, Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle

Dartmouth Scholarship

Agonistic αCD40 Ab’s have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can …

A Preliminary Study On The Reliability Of Physical Performance Measures In Older Day-Care Center Clients With Dementia., Vince Salazar Thomas, Patricia A. Hageman

Journal Articles: Physical Therapy

BACKGROUND: Decline in physical functional ability is an intrinsic component of the dementia syndrome. Reductions in muscle mass and strength represent a major factor in the loss of functional ability Although resistance exercise has been studied as a method for maintaining/recovering function in populations of frail older adults, people with dementia have been systematically excluded because of uncertainty about the reliability of outcome measurements.

OBJECTIVE: The purpose of this study was to determine the test-retest reliability of a battery of established performance-based measures of strength and function among subjects with dementia.

SETTING: A hospital-affiliated adult day-care facility.

SUBJECTS: Twelve of …

Circulating Testosterone And Prostate-Specific Antigen In Nipple Aspirate Fluid And Tissue Are Associated With Breast Cancer., Edward R Sauter, David S Tichansky, Inna Chervoneva, Eleftherios P Diamandis

Department of Surgery Faculty Papers

Preliminary evidence has associated testosterone and prostate-specific antigen (PSA) with breast cancer. Our objective was to determine whether a) testosterone levels in nipple aspirate fluid (NAF), serum, or breast tissue are associated with breast cancer; b) testosterone levels in serum are associated with levels in NAF; c) PSA in NAF, serum, or breast tissue is associated with breast cancer; and d) serum PSA is associated with NAF PSA levels. We obtained 342 NAF specimens from 171 women by means of a modified breast pump. Additionally, we collected 201 blood samples from 99 women and 51 tissue samples from 41 subjects …

Reduction In The Incidence Of Type 2 Diabetes With Lifestyle Intervention Or Metformin., William C. Knowler, Elizabeth Barrett-Connor, Sarah E. Fowler, Richard F. Hamman, John M. Lachin, Elizabeth A. Walker, David M. Nathan, P. G. Watson, J. T. Mendoza, K. A. Smith, J. Caro, B. Goldstein, C. Lark, L. Menefee, L. Murphy, C. Pepe, J. M. Spandorfer

Department of Medicine Faculty Papers

BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.

METHODS: We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least …

Triplet Repeat Dna Structures And Human Genetic Disease: Dynamic Mutations From Dynamic Dna., Richard R. Sinden, Vladimir N. Potaman, Elena A. Oussatcheva, Christopher E. Pearson, Yuri L. Lyubchenko, Luda S. Shlyakhtenko

Journal Articles: Pharmaceutical Sciences

Fourteen genetic neurodegenerative diseases and three fragile sites have been associated with the expansion of (CTG)n (CAG)n, (CGG)n (CCG)n, or (GAA)n (TTC)n repeat tracts. Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, slipped strand DNA, may stably and reproducibly form within triplet repeat sequences. The propensity to form slipped strand DNA is proportional to the length and homogeneity of the repeat tract. The remarkable stability of slipped strand DNA may, in part, be due to loop-loop interactions facilitated …

Retrospective Analysis Of Youth Evaluated For Suicide Attempt Or Suicidal Ideation In An Emergency Room Setting, Julie Hagedorn, Hatim A. Omar

Pediatrics Faculty Publications

Suicide is the third leading cause of death in adolescents and a major contributor to morbidity in this age group. The objective of this study was to look at the demographics, major stressors and factors leading to attempting suicide as well as the methods of attempted suicide in adolescents admitted to two hospitals in a medium size city. Medical records were reviewed of adolescents admitted to two area hospitals for attempted suicide between 7/1/97-12/31/99. Coroner's data on completed suicide were also reviewed. In the study period a total of 287 persons aged 21 years or under were admitted for attempted …

Assessment Of Validity Of The National Public Health Performance Standards: The Local Public Health Performance Assessment Instrument., Joyce Beaulieu, F. Douglas Scutchfield

Preventive Medicine and Environmental Health Faculty Publications

The National Public Health Performance Standards Program (NPHPSP) has developed performance standards measurement instruments, based on the 10 "Essential Services of Public Health" that are being tested in several states. This article is a report on the face and content validity of the instrument designed for local public health systems. Judgments about the face validity of the standards were obtained in a survey of local public health systems that had used the instrument in a test state. The validity of each standard was addressed along the following dimensions: the importance of the standard as a measure of the Essential Service; …

Surveillance For Waterborne-Disease Outbreaks--United States, 1999-2000, Sherline H. Lee, Deborah A. Levy, Gunther F. Craun, Michael J. Beach, Rebecca L. Calderon

Journal Articles: Epidemiology

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency (EPA), and the Council of State and Territorial Epidemiologists (CSTE) have maintained a collaborative surveillance system for the occurrences and causes of waterborne-disease outbreaks (WBDOs).This surveillance system is the primary source of data concerning the scope and effects of waterborne diseases on persons in the United States.

REPORTING PERIOD COVERED: This summary includes data regarding outbreaks occurring during January 1999-December 2000 and previously unreported outbreaks occurring in 1995 and 1997.

DESCRIPTION OF THE SYSTEM: The surveillance system includes data for outbreaks associated with drinking water and recreational water. State, territorial, and …

Associations Between Water-Treatment Methods And Diarrhoea In Hiv-Positive Individuals, J. N. S. Eisenberg, T. J. Wade, A. Hubbard, D. I. Abrams, R. J. Leiser, S. Charles, M. Vu, S. Saha, C. C. Wright, Deborah A. Levy, P. Jensen, J. M. Colford

Journal Articles: Epidemiology

This manuscript extends our previously published work (based on data from one clinic) on the association between three drinking water-treatment modalities (boiling, filtering, and bottling) and diarrhoeal disease in HIV-positive persons by incorporating data from two additional clinics collected in the following year. We conducted a cross-sectional survey of drinking water patterns, medication usage, and episodes of diarrhoea among HIV-positive persons attending clinics associated with the San Francisco Community Consortium. We present combined results from our previously published work in one clinic (n = 226) with data from these two additional clinics (n = 458). In this combined analysis we …

Risk Factors In Hiv-Associated Diarrhoeal Disease: The Role Of Drinking Water, Medication And Immune Status, J. N. S. Eisenberg, T. J. Wade, S. Charles, M. Vu, A. Hubbard, C. C. Wright, Deborah A. Levy, P. Jensen, J. M. Colford

Journal Articles: Epidemiology

In a cross-sectional survey of 226 HIV-infected men, we examined the occurrence of diarrhoea and its relationship to drinking water consumption patterns, risk behaviours, immune status and medication use. Diarrhoea was reported by 47% of the respondents. Neither drinking boiled nor filtered water was significantly associated with diarrhoea (OR = 0.5 [0.2, 1.6], 1.2 [0.6, 2.5] respectively), whereas those that drank bottled water were at risk for diarrhoea (OR = 3.0 [1.1, 7.8]). Overall, 47% always or often used at least one water treatment. Of the 37% who were very concerned about drinking water, 62% had diarrhoea, 70% always or …

Participant Blinding And Gastrointestinal Illness In A Randomized, Controlled Trial Of An In-Home Drinking Water Intervention, John M. Colford, Judy R. Rees, Timothy J. Wade, Asheena Khalakdina, Joan F. Hilton, Isaac J. Ergas, Susan Burns, Anne Benker, Catherine Ma, Cliff Bowen, Daniel C. Mills, Duc J. Vugia, Dennis D. Juranek, Deborah A. Levy

Journal Articles: Epidemiology

We conducted a randomized, triple-blinded home drinking water intervention trial to determine if a large study could be undertaken while successfully blinding participants. Households were randomized 50:50 to use externally identical active or sham treatment devices. We measured the effectiveness of blinding of participants by using a published blinding index in which values >0.5 indicate successful blinding. The principal health outcome measured was "highly credible gastrointestinal illness" (HCGI). Participants (n=236) from 77 households were successfully blinded to their treatment assignment. At the end of the study, the blinding index was 0.64 (95% confidence interval 0.51-0.78). There were 103 episodes of …

Toward A Cognitive Taxonomy Of Medical Errors., Jiajie Zhang, Vimla L Patel, Todd R Johnson, Edward H Shortliffe

Journal Articles

One critical step in addressing and resolving the problems associated with human errors is the development of a cognitive taxonomy of such errors. In the case of errors, such a taxonomy may be developed (1) to categorize all types of errors along cognitive dimensions, (2) to associate each type of error with a specific underlying cognitive mechanism, (3) to explain why, and even predict when and where, a specific error will occur, and (4) to generate intervention strategies for each type of error. Based on Reason's (1992) definition of human errors and Norman's (1986) cognitive theory of human action, we …

Comparing Communication Technology On Chinese, English, And Spanish Diabetes Web Sites., Yanko F Michea, Karen Pancheri, Yang Gong, Elmer Bernstam

Journal Articles

Technological and cultural factors influence access to health information on the web in multifarious ways. We evaluated structural differences and availability of communication services on the web in three diverse language and cultural groups: Chinese, English, and Spanish. A total of 382 web sites were analyzed: 144 were English language sites (38%), 129 were Chinese language sites (34%), and 108 were Spanish language sites (28%). We did not find technical differences in the number of outgoing links per domain or the total availability of communication services between the three groups. There were differences in the distribution of available services between …

Prophylactic Cranial Irradiation Revisited: Cost-Effectiveness And Quality Of Life In Small-Cell Lung Cancer, T. Tai, Edward Yu, Peter Dickof, Glen Beck, Jon Tonita, Tete Ago, David Skarsgard, Marlene Schmidt, Matthew Schmid, John Liem

Edward Yu

PURPOSE: To investigate the therapeutic usefulness and cost-effectiveness of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC) who had achieved a complete remission. METHODS: A retrospective chart review was undertaken of all patients diagnosed in Saskatchewan with SCLC between 1987 and 1998 inclusive. Patients who achieved a complete remission were divided into two groups, depending on whether they underwent PCI (PCI+ and PCI-, respectively). The quality-of-life-adjusted survival was estimated by the Q-TWiST method (quality time without symptoms and toxicity). The mean incremental costs per month of incremental OS were calculated in a cost-effectiveness analysis. RESULTS: Among …