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Biomedical subjects

C Davis

Publications and source records attributed to C Davis.

At least 91 records · Page 5Linked to original sources

A survey of leading chronic disease management programs: are they consistent with the literature?

Caring for patients with chronic illness in an era of cost constraints and performance monitoring has led to a sharp growth in "disease management" efforts by health systems utilizing internal innovators or outside firms. This paper describes surveys and site visits of the chronic disease management activities of 72 programs nominated by experts in the field of chronic illness care as being particularly innovative and effective. The survey and analysis were guided by a Model for Effective Chronic Illness Care derived from a process of literature synthesis and expert review. The model proved to be useful in describing the characteristics consistently shared by successful programs, and the surveys indicated common barriers to further expansion of innovative pilot programs. The survey indicated that most of the nominated programs were limited in their effectiveness and reach by their reliance on traditional patient education, rather than modern self-management support, poor linkages to primary care, and reliance on referrals rather than population-based approaches.

Case Management↗

Efficient transition to growth on fermentable carbon sources in Saccharomyces cerevisiae requires signaling through the Ras pathway.

Strains carrying ras2(318S) as their sole RAS gene fail to elicit a transient increase in cAMP levels following addition of glucose to starved cells but maintain normal steady-state levels of cAMP under a variety of growth conditions. Such strains show extended delays in resuming growth following transition from a quiescent state to glucose-containing growth media, either in emerging from stationary phase or following inoculation as spores onto fresh media. Otherwise, growth of such strains is indistinguishable from that of RAS2(+) strains. ras2(318S) strains also exhibit a delay in glucose-stimulated phosphorylation and turnover of fructose-1,6-bisphosphatase, a substrate of the cAMP-dependent protein kinase A (PKA) and a key component of the gluconeogenic branch of the glycolytic pathway. Finally Tpk(w) strains, which fail to modulate PKA in response to fluctuations in cAMP levels, show the same growth delay phenotypes, as do ras2(318S) strains. These observations indicate that the glucose-induced cAMP spike results in a transient activation of PKA, which is required for efficient transition of yeast cells from a quiescent state to resumption of rapid growth. This represents the first demonstration that yeast cells use the Ras pathway to transmit a signal to effect a biological change in response to an upstream stimulus.

Carbon↗

Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action.

BACKGROUND: Intravenous gammaglobulin (i.v.IG) contains anti-idiotypic antibodies that are potent inhibitors of HLA-specific alloantibodies in vitro and in vivo. In addition, highly HLA-allosensitized patients awaiting transplantation can have HLA alloantibody levels reduced dramatically by i.v.IG infusions, and subsequent transplantation can be accomplished successfully with a crossmatch-negative, histoincompatible organ. METHODS: In this study, we investigated the possible use of i.v.IG to reduce donor-specific anti-HLA alloantibodies arising after transplantation and its efficacy in treating antibody-mediated allograft rejection (AR) episodes. We present data on 10 patients with severe allograft rejection, four of whom developed AR episodes associated with high levels of donor-specific anti-HLA alloantibodies. RESULTS: Most patients showed rapid improvements in AR episodes, with resolution noted within 2-5 days after i.v.IG infusions in all patients. i.v.IG treatment also rapidly reduced donor-specific anti-HLA alloantibody levels after i.v.IG infusion. All AR episodes were reversed. Freedom from recurrent rejection episodes was seen in 9 of 10 patients, some with up to 5 years of follow-up. Results of protein G column fractionation studies from two patients suggest that the potential mechanism by which i.v.IG induces in vivo suppression is a sequence of events leading from initial inhibition due to passive transfer of IgG to eventual active induction of an IgM or IgG blocking antibody in the recipient. CONCLUSION: I.v.IG appears to be an effective therapy to control posttransplant AR episodes in heart and kidney transplant recipients, including patients who have had no success with conventional therapies. Vascular rejection episodes associated with development of donor-specific cytotoxic antibodies appears to be particularly responsive to i.v.IG therapy.

Adult↗

An immunoassay for the detection and quantitative determination of mycothiol.

Mycothiol (MSH) is a glycosylated derivative of N-acetylcysteine that may have antioxidant functions in mycobacteria and other actinomycetes. To develop a highly specific assay for MSH, we capitalized on the selective binding of thiols to a maleimide residue linked to bovine serum albumin and employed affinity-purified polyclonal antibody and an enzyme-linked secondary antibody for detection. The assay was shown to be specific and to detect MSH at levels as low as 0.1 pmol when conducted in the form of a microtiter plate-based ELISA. A similar, nitrocellulose membrane-based immunoassay was shown to be useful for qualitative detection of MSH-producing bacterial colonies.

Animals↗

Differentially expressed genes in the Trypanosoma brucei life cycle identified by RNA fingerprinting.

RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR) was used to identify genes that were differentially expressed during the life cycle of Trypanosoma brucei, as well as in response to heat shock. The standard RAP-PCR protocol was varied in two ways. First, the PCR reactions sometimes included a primer derived from the 5' mini-exon sequence, to ensure that most of the products contained the 5' end of mRNAs. Second, differentially amplified products were reamplified, isolated on single strand conformation polymorphism (SSCP) gels, cloned, and sequenced. Clones representing 32 different expressed sequence tags (ESTs) were obtained. Twenty-four ESTs were confirmed as differentially expressed by RT-PCR between different stages of the parasite cycle, or in response to temperature elevation. Nine clones had significant similarities to sequences already in the database. These transcripts included genes encoding cell surface proteins, metabolic enzymes, and heat shock proteins, either from trypanosomes or other organisms. Of particular interest, ESAG1 was shown to be heat-inducible in the procyclic stage. Most of the transcripts were unrelated to any other sequences in the database, and were deposited as new ESTs. The identification of stage-specific and heat shock-regulated transcripts will complement the growing T. brucei database. In addition, this experimental approach allows previous entries in the sequence database to be annotated with regulatory information.

Animals↗

Chinese men and women in the United States and Hong Kong: body and self-esteem ratings as a prelude to dieting and exercise.

OBJECTIVE: The present study compared the body and weight satisfaction, self-esteem, and depression of Chinese male and female university students in Hong Kong and the United States and assessed the impact of these ratings on compensatory behavior such as dieting and exercise. METHOD: Self-report measures were administered to 501 Chinese participants in the language of their university's locale. RESULTS: Females reported significantly more body dissatisfaction and depression, and males reported greater weight dissatisfaction (the majority of men wishing to be larger). Overall, Chinese subjects in Hong Kong reported significantly more body and weight dissatisfaction, lower self-esteem, higher depression, more dieting, and less exercise as compared to their counterparts in the United States. DISCUSSION: Asian students in this study mirrored gendered patterns previously reported in Caucasian samples with respect to the relation of body image, self-esteem, and mood. For both sexes, there appeared to be a caricatured mimicking of the bodies perceived to be associated with the dominant culture--men wanted to be larger while the women wanted to be even more petite.

Adult↗

Knowledge, attitudes and behaviours related to HIV and AIDS among chinese adolescents in hong kong.

The purpose of this study was to assess HIV and AIDS knowledge and attitudes, source of HIV and AIDS information, and behaviours related to HIV and AIDS among Chinese adolescents in Hong Kong. Participants included 1259 (826 females and 433 males) Chinese adolescents in Hong Kong between 12-18 years of age. Findings revealed that over 80% of the adolescents had rarely or never discussed HIV and AIDS with their family or teacher, and the primary source of HIV and AIDS information was media sources such as television and newspapers. Findings revealed HIV and AIDS misinformation among both male and female adolescents in the areas of transmission, facts, personal vulnerability and attitudes. However, participants reported engaging in little at-risk behaviour associated with HIV and AIDS. Implications for HIV and AIDS education and prevention are discussed.

Acquired Immunodeficiency Syndrome↗

Severe insulin resistance in a patient with type 1 diabetes and stiff-man syndrome treated with insulin lispro.

We describe a patient with type 1 diabetes with recurrent diabetic ketoacidosis and severe insulin resistance. Extensive evaluation of the etiology of the insulin resistance did not reveal an etiology, and well over 1000 U of daily insulin did not prevent the ketoacidosis. Her blood glucose and insulin requirements were improved with glucocorticoids and octreotide, but the effects of both of these agents were short-lived. She was given a trial of insulin lispro with immediate and dramatic effects, lowering her HbA1c from 14.6 to 5.1% in 7 months with a decrease in insulin requirements of 1600-100 U per day. Besides her diabetes, she had a history of pain and stiffness affecting numerous muscle groups, and hospitalization was required for pain control. The diagnosis of stiff-man syndrome (SMS) was confirmed with high titers of glutamic acid decarboxylase 65 antibodies in both serum and cerebral spinal fluid. In summary, we describe the first patient with type 1 diabetes, SMS, and severe insulin resistance. Although the etiology of the insulin resistance is unknown, due to the efficacious response to insulin lispro, hydrocortisone, and perhaps octreotide, we propose an immune-mediated etiology. Although rare, this syndrome needs to be considered as an etiology of insulin resistance.

Adult↗

Recommendations for training in performance and interpretation of stress echocardiography. Committee on Physician Training and Education of the American Society of Echocardiography.

Stress echocardiography has emerged as a clinically useful procedure in the management of patients with ischemic heart disease and other conditions. However, the accuracy of this test relies on the ability of those who carry out the technical aspects of the test and depends critically on proper interpretation of the images. Appreciation of wall motion abnormalities is generally acknowledged as one of the most difficult skills to master in echocardiography. There is consensus that this is also one of the most difficult skills to teach. Appreciating stress-induced changes in wall motion, which sometimes are subtle, requires a significant commitment to initial training in this skill and its maintenance. This document provides recommendations for physician training in stress echocardiography.

Cardiology↗

Intravenous immunoglobulin and the risk of hepatic veno-occlusive disease after bone marrow transplantation.

Recent reports using historical controls or registry cohorts suggest, respectively, either an increase in the mortality or a decrease in the incidence of hepatic veno-occlusive disease (VOD) with the administration of intravenous immunoglobulin (i.v.Ig) after bone marrow transplantation. These divergent results prompted us to conduct a retrospective analysis of two randomized clinical trials conducted at our center to determine the effect of i.v.Ig infusions on the development and severity of VOD. Patients were randomized to receive (n=318) or not to receive (n=315) i.v.Ig prophylaxis after human leukocyte antigen-identical sibling (n=414), mismatched or unrelated (n=178), or autologous or syngeneic (n=41) marrow transplantation. To determine the relationship of i.v.Ig to the development and severity of VOD, a single observer reviewed data displays created for each patient for grading VOD without knowledge of patient i.v.Ig use. In this analysis, VOD was defined as hyperbilirubinemia > or =2.0 mg/dL before day 20 and abrupt weight gain > or =2% before day 14 posttransplant in the absence of other causes of liver disease. Hepatic VOD developed in 235 (37%) of the 633 randomized patients. No evidence for VOD was found in 230 (36%) patients. The remaining 168 (27%) patients were classified as having liver disease of uncertain etiology. Hepatic VOD was judged to be severe in 63 (10%) and mild or moderate in 172 (27%) patients. The number of patients developing any VOD or severe VOD was similar between those randomized to i.v.Ig prophylaxis and untreated controls (115 vs. 120 and 32 vs. 31, respectively). Logistic regression models identified several covariates as significant (p < 0.01) factors associated with the development of severe VOD. Increased risk occurred with elevated pretransplant serum aspartate aminotransferase (odds ratio [OR] = 2.64) and earlier year of transplant (OR = 3.73); decreased risk occurred with autologous or twin donors (OR = 0.09) and acute myeloid leukemia (OR = 0.39). The development of any VOD was associated with an elevated pretransplant alkaline phosphatase (OR = 4.1), pretransplant use of vancomycin (OR = 1.6) or amphotericin (OR = 3.0), posttransplant use of cyclosporine (OR = 2.5), older patient age (OR = 1.03), and obesity (OR = 0.78). We concluded from the controlled trials of 633 patients that the administration of i.v.Ig did not influence the development or severity of VOD after bone marrow transplantation.

Bone Marrow Transplantation↗

Metabolic activation of racemic and enantiomeric trans-8, 9-dihydroxy-8,9-dihydrodibenzo[a,l]pyrene (dibenzo[def,p]chrysene) to dibenzo[a,l]pyrene-bis-dihydrodiols by induced rat liver microsomes and a recombinant human P450 1A1 system: the role of the K-region-derived metabolic intermediates in the formation of dibenzo[a,l]pyrene-DNA adducts.

Metabolic activation studies of dibenzo[a,l]pyrene (DB[a,l]P) (dibenzo[def,p]chrysene), an extremely potent environmental carcinogen, have been focused on metabolism at the fjord region, a region associated with high mutagenic and carcinogenic activities of the corresponding fjord-region DB[a,l]P-11,12-diol-13,14-epoxides. DB[a,l]P is metabolized by beta-naphthoflavone (BNF)- and 3-methylcholanthrene-induced rat liver microsomes and a recombinant human P450 1A1 system to two major dihydrodiols, the K-region dihydrodiol, DB[a,l]P-8,9-dihydrodiol (DB[a,l]P-8,9-diol), and the fjord-region dihydrodiol, DB[a,l]P-11,12-dihydrodiol. We have investigated the further metabolic activation of DB[a,l]P-8,9-diol by BNF-induced rat liver microsomes and a recombinant human P450 1A1 system with epoxide hydrolase to DB[a,l]P-bis-diols and to DNA adducts. (+/-)-trans-DB[a,l]P-8,9-diol was synthesized and resolved into its enantiomers. Racemic trans-DB[a,l]P-8,9-diol was metabolized by BNF-induced rat liver microsomes to six metabolites: two diastereomers of trans,trans-DB[a,l]P-8,9:11,12-bis-diol, two diastereomers of trans,cis-DB[a,l]P-8,9:11,12-bis-diol, and two diastereomers of trans-DB[a,l]P-8,9:13,14-bis-diol as characterized by NMR, MS, and UV spectroscopy. Metabolic studies using both enantiomeric (-)- and (+)-trans-DB[a,l]P-8,9-diol further demonstrated that each diastereomer of trans,trans-DB[a,l]P-8,9:11, 12-bis-diol and trans-DB[a,l]P-8,9:13,14-bis-diol was comprised of two enantiomers. Similarly, incubations of enantiomeric or racemic trans-DB[a,l]P-8,9-diol with a recombinant human P450 1A1 system and epoxide hydrolase also gave the same two enantiomeric mixtures of diastereomers of trans,trans-DB[a,l]P-8,9:11,12-bis-diol and the same two enantiomeric mixtures of diastereomers of trans-DB[a,l]P-8, 9:13,14-bis-diol. This suggested that the microsomal oxidations of (-)- and (+)-trans-DB[a,l]P-8,9-diol were stereospecific. The stereospecific formation of enantiomers of trans-DB[a,l]P-8,9-diol from DB[a,l]P was examined using both BNF-induced rat liver microsomes and a recombinant human P450 1A1 system with epoxide hydrolase. Stereospecificity was observed as both metabolic systems favored the formation of (-)-trans-DB[a,l]P-8,9-diol by 8-9-fold. DNA adduct studies were undertaken using TLC/HPLC 32P-postlabeling techniques. In the presence of a recombinant human P450 1A1 system with epoxide hydrolase, DB[a,l]P gave two groups of calf thymus DNA adducts. The group of later-eluting adducts were identified as arising from syn- and anti-DB[a,l]P-11,12-diol-13,14-epoxides, while the more polar early-eluting adducts were derived, in part, from the further activation of trans-DB[a,l]P-8,9-diol. Our data indicate that, in P450 1A1-mediated microsomal incubations, DB[a,l]P is metabolized to trans-DB[a,l]P-8,9-diol which is further metabolized to DB[a,l]P-bis-diols. trans-DB[a,l]P-8,9-diol is metabolically activated to intermediates that can bind to DNA and give DNA adducts similar to those observed with DB[a,l]P. These results indicate that DB[a,l]P can be metabolically activated by both fjord-region and K-region pathways.

Animals↗

Distribution of afferent axons in the bladder of rats.

The distribution of afferent axons in the bladder of rats was studied by means of immunohistochemistry for calcitonin gene-related peptide (CGRP), in frozen sections and in wholemount preparations of mucosa and muscle coat. Synaptophysin-immunofluorescence was used for the general detection of all intramural axons. The afferent axons were distributed over four distinct targets: at the base of the epithelium, inside the epithelium, on blood vessels (both arteries and veins) and along muscle bundles. In the mucosa, all the afferent axons, except the perivascular ones, lay either inside the epithelium or in a subepithelial plexus very close to the basal surface of the epithelium. The plexus was thickest in the neck of the bladder and in the initial portion of the urethra, and it became progressively less dense in the adjacent regions; it did not extend beyond the equatorial region, and therefore the mucosa of the cranial region of the bladder had no afferent axons. Most of the axons in the subepithelial plexus were terminal axons and included conspicuous varicosities arranged in very long chains; branching points were numerous, usually at right angles and located at the level of a varicosity; some axons split and then rejoined, forming closed axonal loops. The afferent innervation of the musculature was more diffuse, and appeared uniform throughout the bladder. After unilateral surgical denervation (by excision of the pelvic ganglion 5-7 days earlier) areas of complete denervation were observed, but there were large areas where the innervation was only reduced. The results showed that there is a bilateral innervation of many regions of the mucosa and the musculature, including individual muscle bundles. A substantial number of fibres crossed the midline into the contralateral side of the bladder. CGRP-immunofluorescence in mucosal afferent axons is enhanced in the surviving axons 5 days after contralateral denervation, a change which is interpreted as an early sign of regeneration.

Afferent Pathways↗

Activated T-lymphocytes express occludin, a component of tight junctions.

T-lymphocytes routinely traffic from the lymphoid and vascular compartments to the tissues during immune surveillance and inflammatory responses. This egress occurs without compromising endothelial barrier, which is maintained by tight junctions (zonula occludens). We report that T-lymphocytes up-regulate the expression of occludin, a major component of the tight junction in response to stimulation with phorbol ester (PMA) + calcium ionophore, CD3 antibody or T-cell receptor (TCR) antibody. Only activated T-lymphocytes express occludin; this adhesion molecule is nearly absent in resting T-lymphocytes. By immunofluorescence, occludin is seen in lymphocyte aggregates, but does not appear to mediate aggregation since only 50% of the cells in these clusters express occludin. Occludin is expressed between 8 and 24 h following stimulation, and persists for at least 48 h. These data indicate that activated T cells produce occludin which may regulate lymphocyte adhesion and trafficking.

Animals↗

Human submandibular saliva inhibits human immunodeficiency virus type 1 infection by displacing envelope glycoprotein gp120 from the virus.

Human submandibular saliva reduces human immunodeficiency virus type 1 (HIV-1) infection in vitro. To define the mechanism of inhibition, virus was incubated with saliva or medium, velocity sucrose gradient centrifugation was performed, and fractions were analyzed for p24 and gp120. The results show that after incubation with saliva, the envelope glycoprotein was displaced from both a laboratory-adapted and a low-passage clinical HIV-1 isolate. To identify the salivary protein(s) responsible, submandibular saliva was fractionated by anion- exchange chromatography. Protein fractions containing anti-HIV activity were assayed for their ability to strip gp120 from virus. The partially purified active fractions contained two high-molecular-weight sialyated glycoproteins identified as salivary agglutinin and mucin, as well as several lower-molecular-weight proteins. It thus appears that specific salivary proteins interact with HIV-1 to strip gp120 from the virus with a resultant decrease in infectivity.

Antiviral Agents↗

Major histocompatibility complex genotype is associated with disease progression and virus load levels in a cohort of human immunodeficiency virus type 1-infected Caucasians and African Americans.

To assess the influence of HLA on AIDS-free survival, human immunodeficiency virus load, and CD4 cell counts, 91 Caucasian and 48 African-American seroprevalent men were typed for HLA classes I and II and TAP alleles. HLA associations with these markers were assessed by assigning sum integer scores based on 7 class I allele-TAP variants (+1) and 13 class I-class II-TAP combinations (-1) with different AIDS-free survival times found in a prior study. Subjects in both racial groups and combined with positive sum scores were less likely to have CD4 cell decline (P=.0004), to have increased virus burden (P=.014), and to develop AIDS (P=.034) in the follow-up period than were Caucasians and African Americans with scores of 0 or -1. These results confirm the reported associations of specific major histocompatibility complex genes with AIDS-free survival time in Caucasians and specifically extend them to African Americans and to two established markers of disease progression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗