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Biomedical subjects

D A Wheeler

Publications and source records attributed to D A Wheeler.

At least 19 recordsLinked to original sources
PubMed2001

Availability of HIV care in Central America.

Central America is an area with a growing human immunodeficiency virus (HIV) epidemic, but with marked limitations in its health care infrastructure. Estimated adult HIV infection rates range from 0.20% in Nicaragua to 2.01% in Belize. Hospitals and clinicians with experience in HIV care exist mainly, if not only, in capital cities and principal economic centers. Nationally sponsored social security systems in each country consistently offer a wider range of services than do ministry of health systems. Estimated access to the social security system ranges from 0% in Belize and 10% of the population in Honduras to 95% in Costa Rica. Combination antiretroviral therapy is not available through the ministries of health and zidovudine is only sporadically available for prevention of perinatal transmission. Combination therapy is available through the social security system in the countries of Guatemala, Panama, and Costa Rica only. A wide variety of antiretroviral agents are available through private pharmacies in all countries except Belize. With the exception of Costa Ricans, most people with HIV infection in Central America have limited access to HIV-specific health services and limited or no access to antiretroviral agents.

Central America↗
PubMed2001

Apical root resorption in patients treated with comprehensive orthodontics.

External apical root resorption (EARR) is a common--but seldom extreme--consequence of orthodontic treatment. Incisors are most at risk, perhaps because of their single roots and because they typically are moved farther than other teeth. We followed a cohort of patients (n = 153) treated with comprehensive orthodontics. EARR was scored on the upper incisors with a qualitative five-grade ordinal scale. There was no EARR at the start of treatment, but most (> 80%) exhibited slight-to-moderate EARR by the end of treatment (i.e., a loss of 1-2 mm). Cases treated with premolar extractions experienced more EARR because their incisors were retracted farther; however, the sum of the effects of patients' sex and age, and severity of the malocclusion, and the kind of mechanics used accounts for little of the overall variation in EARR. Instead, it appears that genetically-based inter-individual variation in susceptibility to EARR is the most influential factor. Research should be directed at understanding the biochemical nature of susceptibility so prospective patients can be screened to identify those at particular risk.

Adolescent↗
PubMed2000

Digital reviews in molecular biology: approaches to structured digital publication.

MOTIVATION: It is widely appreciated that it is no longer possible for biomedical research scientists to keep up with as much of what is published in their field as they ought. One solution to this problem is to increase the efficiency of information use by moving away from the classical browsing model for scientific information dissemination towards an information on demand model which would allow researchers to access information quickly and efficiently only as they need it. The most common approach to this goal has been to use information retrieval technology to improve access to text databases of biomedical information. We are interested in exploring an alternative; encoding this information for storage in structured databases for efficient retrieval. RESULTS: Two small databases described here are test beds for development of structured digital publication software; the Tumor Gene Database, containing information about genes which are the sites for cancer-causing mutations, and the Mammary Transgene Database, containing information about expression of transgenes in agriculturally important animals. Both have been successfully searched by users and edited by curators via the World Wide Web.

Algorithms↗
PubMed1999

The breast cancer gene database: a collaborative information resource.

The Breast Cancer Gene Database (BCGD) is a compendium of molecular genetic data relating to genes involved in breast cancer, and which is freely available via the World Wide Web. The data in BCGD is extracted from the published biomedical research literature and stored as a collection of 'Facts', which in turn are collected into topical categories organized by gene. This organization facilitates quick searches and rapid retrievals of specific data such as gene characteristics, functions and role in oncogenesis, and is an important factor allowing for continuous updates. BCGD can be searched either by gene name or keyword. Data is deposited and retrieved from the database through a set of interactive Web forms, making it both platform-independent and universally accessible in facilitating worldwide collaborative authoring of the database. Data in BCGD is linked to other on-line resources such as Entrez, GeneCards and On-Line Mendelian Inheritance in Man. BCGD is located at http://mbcr.bcm.tmc.edu/ermb/bcgd/bcgd.html.

Breast Neoplasms↗
PubMed1999

Randomized, controlled trial of caloric supplements in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To compare the efficacy of three nutritional regimens in the prevention of weight loss. DESIGN: A three-arm randomized controlled trial with primary outcome measure percent change in weight over four months. PATIENTS: A total of 536 patients with CD4 count <200 cells/mm3 and stable weight, defined as <5% weight loss as determined by a weight measurement 3 to 6 months before randomization were recruited at fourteen administrative units in the United States, each unit consisting of multiple primary care sites. INTERVENTION: The three arms were 500 kcal daily of caloric supplement with peptides and medium-chain triglycerides plus a multivitamin and mineral supplement, 500 kcal of a caloric supplement with whole protein and long-chain triglycerides plus a multivitamin and mineral supplement, and a multivitamin and mineral supplement only. RESULTS: There were no significant differences among the three regimens in the percent change in weight (p = .74) and body cell mass (p = .63). On average, 65% of the recommended 500 kcal/day of caloric supplements containing peptides with medium-chain triglycerides and 82% of the 500 kcal/day of the caloric supplement containing whole protein and long-chain triglycerides were consumed. CONCLUSIONS: Caloric supplements do not promote increases in average weight or body cell mass in weight-stable, HIV-infected adults beyond that offered by a multivitamin and mineral supplement.

Adult↗
PubMed1999

Using statistical process control charts for the continual improvement of asthma care.

BACKGROUND: Home monitoring of lung function using simple, inexpensive tools to measure peak expiratory flow rate (PEFR) has been possible since the 1970s. Yet although current national and international guidelines recommend monitoring of PEFRs via traditional run charts, their use by both patients and physicians remains low. The role of statistical process control (SPC) theory and charts in the serial monitoring of lung function at home were explored and applied to the direct care of patients with asthma. The method represents an integration of collective professional and improvement knowledge with the related disciplines of continual improvement, SPC, system thinking/system dynamics, paradigms, and the learning community/organization. CASE STUDIES: Use of PEFR control charts for four patients cared for at the Asthma-Allergy Clinic and Research Center (Shreveport, La) is described. The key to good asthma control is the ability to optimize lung function by reducing the variation between serial lung function measurements and thereby generate a safe range of function. Knowledge of the type of variation (special cause or common cause) in the system helps in focusing clinical decision making. Case 4, an 11-year-old boy, for example, shows how control charts were used to learn the effects of a new inhaled corticosteroid. Comparison of the last 14 days of baseline and the last 14 days of open label use of the inhaled corticosteroid showed an obvious improvement in actual PEFR values--which a run chart or comparison of means would have easily demonstrated. The control chart showed that this child's care process at baseline was functionally at risk for severe asthma (46% personal best) and that the effect of the new medication not only elevated the mean function but shifted the range of function from 46%-72% personal best to 78%-102% personal best. At this new range of function the patient's system of care was not capable of delivering values that are at risk for severe asthma. Unless the range of function the change in care is capable of producing is specifically quantitated, misinterpretation of improvement data can occur. DISCUSSION: Developing the concept of the PEFR control chart involved examining and challenging traditional mental models for monitoring PEFR at home in the care of asthma, acquiring a better understanding of the workings of dynamic systems and with system thinking, and sharing what was learned with patients and seeking their input. CONCLUSIONS: The PEFR control chart employs an interesting statistical platform that enables the integration of knowledge of serial measurements and knowledge of the variation between those measurements into a tool with which to better assess the asthma care process being followed. This tool provides clinical insights, practical knowledge, and opportunities unavailable to patients and physicians via traditional PEFR charting.

Adolescent↗
PubMed1999

A managed care organization's attempt to increase influenza and pneumococcal immunizations for older adults in an acute care setting.

OBJECTIVE: Among the high risk groups for complications from influenza and pneumococcal disease, individuals aged 65 and older hospitalized within the previous year represent the group at highest risk. Studies have demonstrated that targeting hospitalized patients aged 65 and older for immunization before hospital discharge can be successful. This study addressed the efficacy of such a program within a managed care organization to immunize this highest risk group. DESIGN: A cross-sectional study. SETTING: Oxford Health Plans, a major managed care organization in New York serving a large Medicare population. PARTICIPANTS: A total of 106 Primary Care Physicians caring for 153 patients aged 65 and older, who were hospitalized in one of 10 high volume hospitals during October and November of 1996. Nine of these facilities were located in New York and one was in New Jersey. INTERVENTION: Patients aged 65 and older admitted to any of the 10 hospitals were identified daily. A fax was sent to each patient's primary care physician explaining the program and requesting that he/she administer influenza and/or pneumococcal vaccine to his/her patient before hospital discharge. Literature references citing past successful programs were included in the fax. MEASUREMENTS: Measurements included medical record documentation of influenza and pneumococcal immunization, both ordered and given, for the individual member before discharge; patient age; sex; and primary and secondary diagnoses. Physicians were sent follow-up questionnaires to determine reasons for not vaccinating. RESULTS: A total of 206 patients were admitted during the eligible time period. One hundred fifty-three hospitalized patients (average age = 74 years) participated. The median length of stay among this study population was 5 days (range, 1-63 days). The distribution of the median length of stay for the 25th and 75th percentiles was 3 and 9 days. The rate for influenza and pneumococcal immunization, both ordered and given, before hospital discharge was 1.96% for the influenza vaccine (n = 3) and .65% for the pneumococcal vaccine (n = 1), respectively. Results of a follow-up survey mailed to all physicians (n = 106) with eligible members in the study indicated that the most frequent reasons for not vaccinating included: patients were vaccinated before admission, patients were not stable enough to be vaccinated before discharge, and the acute care setting is not appropriate for vaccination. Response rate of 58% (n = 61) was achieved with an initial mailing and one follow-up telephone call to all previous nonresponders. Some physician survey responses do not correlate with data obtained from retrospective patients' claims analysis. CONCLUSION: Well-coordinated and timely attempts to encourage primary care physicians to immunize patients 65 years and older before hospital discharge were unsuccessful in our study. Rather than working with physicians, it may be that managed care organizations should work directly with hospitals to implement influenza and pneumococcal immunization programs.

Aged↗
PubMed1998

Weight loss as a predictor of survival and disease progression in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS.

Severe weight loss in HIV is associated with decreased length of survival. It is unclear whether mild weight loss is associated with an increased risk of death or opportunistic complications of HIV. Participants in four interventional studies (n = 2382) conducted by a community-based clinical trials network were evaluated for percentage change in weight during their first 4 months in the study. Proportional hazards models were performed for the occurrence of opportunistic complications and death subsequent to the 4-month visit. The relative risk of death and opportunistic complications for those with 5% to 10% weight loss over 4 months was 2.22 (p < .001) and 1.89 (p < .001), respectively, and 1.26 (p < .01) and 1.19 (p < .01) among those who lost 0% to 5% of their body weight, respectively, when compared with those with no weight loss. Among those who lost 5% to 10% of their body weight, the relative risk of individual opportunistic complications increased significantly, including Pneumocystis carinii pneumonia (PCP) (1.61; p < .01), cytomegalovirus (CMV) (2.33; p < .001), and Mycobacterium avium complex (MAC) (1.81; p < .01). As little as 5%t weight loss over a 4-month period is associated with increased risk of death and opportunistic complications in HIV. A weight loss of 5% to 10% is also associated with an increased risk of individual opportunistic complications.

AIDS-Related Opportunistic Infections↗
PubMed1998

QS-21 and QS-7: purified saponin adjuvants.

QS-21 and QS-7 are two adjuvant-active saponins that can be obtained in high purity from Quillaja saponaria Molina extracts. QS-21 is a highly characterized compound and is known to be a potent adjuvant for antibody and CD8+ CTL response to subunit antigens. Less is known about the activity and structure of the hydrophilic saponin QS-7. Hence, we have carried out a detailed structural and immunological characterization. As with QS-21, QS-7 was shown to be a 3,28-O-bisglycoside quillaic acid, with some differences being a higher degree of glycosylation and a considerably shorter fatty acyl unit in QS-7. These differences were correlated to a lower lytic activity against sheep red blood cells. Different doses of QS-7 were evaluated for stimulation of immune response to the antigen ovalbumin, given three times by subcutaneous route to C57BL/6 mice. QS-7 doses of 40 micrograms or higher were shown to induce a strong CD8+ CTL response reproducibly against E. G7-OVA targets (similar to that induced by a 5-10 micrograms dose of QS-21). QS-7 (at doses above 5 micrograms) was also shown to stimulate CTL against peptide 18 of HIV-1IIIB gp120 after three immunizations of Balb/c mice with recombinant gp120 and different doses of QS-7. These data suggest that a hydrophilic saponin with low lytic activity can stimulate MHC Class I CTL responses although a higher minimum dose may be required for some antigens.

Adjuvants, Immunologic↗
PubMed1997

Structure and expression of the mouse casein gene locus.

The analysis of yeast artificial chromosomes (YACs) containing the complete mouse casein gene locus revealed the presence of five casein genes, alpha-, beta-, gamma-, delta-, and kappa-casein, in this order, in the locus. The alpha- and beta-casein genes are only 10 kb apart and have convergent transcriptional orientations. The distance between the beta-casein gene and the alpha s2-like gamma-casein gene is about 70 kb, and these genes have divergent transcriptional orientations. The gamma- and delta-casein genes, both encoding a alpha s2-like casein, are linked within 60 kb and convergently transcribed. The kappa-casein gene is located about 100 kb from the delta-gene. Except for the presence of the delta-casein gene, the organization of the mouse casein locus resembles that of the bovine locus, including the transcriptional orientation of the genes. In contrast to the other casein genes, which are strongly induced at mid-lactation, expression of the delta-casein gene is abruptly induced upon parturition. Comparative analysis of alpha s2-like sequences from various species suggests that the ancestral alpha s2-like gene duplicated around the time of radiation of the rodent and artiodactylid ancestors.

Amino Acid Sequence↗
PubMed1996

Defects in courtship and vision caused by amino acid substitutions in a putative RNA-binding protein encoded by the no-on-transient A (nonA) gene of Drosophila.

The Drosophila no-on-transient A (nonA) gene is involved in the visual behaviors and courtship song of the fly. The NONA polypeptide contains two copies of the RNA-recognition motif (RRM), a hallmark of proteins involved in RNA binding, and an adjacent conserved charged region. This 311-amino-acid region is found in four other proteins and largely overlaps the Drosophila-Behavior/Human Splicing (or DBHS) domain. The newest family member, Drosophila nAhomo, was discovered in a database search, and encodes a protein with 80% identity to NONA. In this study, three nonA mutations generated by chemical mutagenesis were sequenced and found to fall within the conserved region. Site-directed mutagenesis of the two RRMs, and within a (conserved) charged region located C-terminal to them, was performed to determine the significance of these domains with respect to whole-organismal phenotypes. Behavior and viability were assessed in transformed flies, the genetic background of which lacks the nonA locus. Point mutations of amino acid 548 in the charged region confirmed the etiology of the nonAdiss courtship-song mutation and showed that a milder substitution at this site produced intermediate singing behavior, although it failed to rescue visual defects. Mutagenesis of the RRM1 domain resulted in effects on viability, vision, and courtship song. However, amino acid substitutions in RNP-II of RRM2 led to near-normal phenotypes, and the in vivo nonA mutations located in or near RRM2 caused visual defects only. Thus, we suggest that the first RRM could be important for all functions influenced by nonA, whereas the second RRM may be required primarily for normal vision.

Amino Acid Sequence↗
PubMed1996

Structure of the saponin adjuvant QS-21 and its base-catalyzed isomerization product by 1H and natural abundance 13C NMR spectroscopy.

The saponin QS-21, derived from the bark of the Quillaja saponaria Molina tree, has shown great potential as an adjuvant with a number of vaccines. Kinetic studies carried out to establish the stability of vaccine formulations show that commercially supplied QS-21 (primarily QS-21A) is converted slowly at pH 5.5, and rapidly at higher pH, to an equilibrium mixture of two regioisomers, QS-21A and QS-21B, in a ratio of 20:1. NMR studies show that QS-21A and QS-21B differ only in the point of attachment of the fatty acyl moiety to the fucose sugar ring. The major isomer, QS-21A, has the fatty acyl portion attached at the 4-hydroxyl group whereas the minor isomer, QS-21B, has the fatty acyl portion attached at the 3-hydroxyl group. The isomerization most likely involves ionization of the 3-hydroxy group and intramolecular acyl transfer from the 4-hydroxy group. The relative stereochemistry of the triterpene and the sugar anomeric centers is also established by NMR methods.

Adjuvants, Immunologic↗
PubMed1996

Isomerization and formulation stability of the vaccine adjuvant QS-21.

The stability of the immunologic adjuvant QS-21 (Cambridge Biotech Corp.) was optimized for use in the MN rgp120 HIV-1 subunit vaccine. QS-21, a saponin purified by reversed phase HPLC from an extract of the bark of the Quillaja saponaria Molina tree, consisted initially of one species (QS-21A), but converted to two species, QS-21A and QS-21B, in aqueous solution. NMR studies indicated that the two species are structural isomers and that isomerization occurs by intramolecular trans-esterification of the fatty acid moiety between the 3- and 4-hydroxyl groups of the fucose ring (Jacobsen et al. Carbohydr. Res., in press). Both isomers were adjuvant active. Storage of QS-21 in aqueous solution resulted in the interconversion between these isomer forms, as well as the slow formation of degradation products due to ester hydrolysis. The critical micellar concentration of QS-21 in succinate buffer was measured by a fluorescent probe method to be 51 +/- 9 micrograms/mL. Studies were performed at different concentrations of QS-21 to assess the influence of micelle formation on stability. These experiments indicated that QS-21 is more stable in the micellar form, presumably because the most labile ester bond linking the fatty acid moiety to fucose is constrained or buried in the hydrophobic micellar environment. The pH of maximum stability was pH 5.5, the pH for minimum degradation of most esters. The final formulation, 500 micrograms/mL QS-21 in 20 mM sodium succinate, 150 mM NaCl, pH 5.5, provided a shelf-life of greater than 2 years.

Adjuvants, Immunologic↗
PubMed1996

Development of a faculty research interest resource.

We have developed a faculty research interests resource by "mining" MEDLINE for relationships that are not directly queryable through the normal MEDLINE schema. Faculty citations are retrieved and World-Wide Web pages built to interconnect authors, their citations, and the MeSH terms that have been assigned to these citations. The design and development of the resource are discussed and examples of the results illustrated.

Databases, Factual↗
PubMed1995

Comparison of human VDAC1 with streptococcal streptokinase and bovine bactericidal permeability increasing protein: role of structural information in identifying functionally significant domains.

Comparison of the primary amino acid sequence of the human X-linked voltage-dependent anion channel, with other sequences in data base searches, identified regions of similarity in streptococcal streptokinase and bovine bactericidal permeability increasing protein. These regions of similarity were in different areas of the protein and were relatively short. However, examination of an empirically derived structural model of the channel showed that each region of similarity in streptokinase and bovine bactericidal permeability increasing protein corresponded to contiguous transmembrane domains within the channel protein. We speculate that these transmembrane domains may be functionally significant for streptokinase and bovine bactericidal permeability increasing protein. These investigations demonstrate the need for incorporation of information regarding secondary, tertiary, and quaternary structures, as well as function, in algorithms used for database searches.

Amino Acid Sequence↗