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Biomedical subjects

C Davis

Publications and source records attributed to C Davis.

At least 73 records · Page 4Linked to original sources

The use of automated data to identify complications and comorbidities of diabetes: a validation study.

We evaluated the accuracy of administrative data for identifying complications and comorbidities of diabetes using International Classification of Diseases, 9th edition, Clinical Modification and Current Procedural Terminology codes. The records of 471 randomly selected diabetic patients were reviewed for complications from January 1, 1993 to December 31, 1995; chart data served to validate automated data. The complications with the highest sensitivity determined by a diagnosis in the medical records identified within +/-60 days of the database date were myocardial infarction (95.2%); amputation (94.4%); ischemic heart disease (90.3%); stroke (91.2%); osteomyelitis (79.2%); and retinal detachment, vitreous hemorrhage, and vitrectomy (73.5%). With the exception of amputation (82.9%), positive predictive value was low when based on a diagnosis identified within +/-60 days of the database date but increased with relaxation of the time constraints to include confirmation of the condition at any time during 1993-1995: ulcers (88.5%); amputation (85.4%); and retinal detachment, vitreous hemorrhage and vitrectomy (79.8%). Automated data are useful for ascertaining potential cases of some diabetic complications but require confirmatory evidence when they are to be used for research purposes.

Adolescent↗

A new sensor for monitoring chest wall motion during high-frequency oscillatory ventilation.

The recently developed technique of fibre optic respiratory plethysmography (FORP) has been modified to monitor the rapid, small amplitude movements of the chest wall during high-frequency oscillatory ventilation (HFOV). The FORP sensor is an expandable belt encircling the chest, in which is housed a fibre optic loop that alters its radius of curvature as a function of chest perimeter. These curvature changes cause variations in macrobending losses of light transmitted through the fibre, which are proportional to the chest perimeter. Dynamic measurement of transmitted light intensity can hence be used to monitor chest wall motion (CWM). For application to HFOV, the design of the FORP belt was altered to increase sensitivity and the materials were chosen to maximise macrobending effects induced by the CWM. FORP was tested in four piglets ventilated with HFOV, both in the normal and surfactant-deficient lung. Measurement of CWM was possible over the full range of tidal volumes and ventilation frequencies used during HFOV. In all cases, the measured frequency of the CWM fell within 3% of the applied ventilation frequency. In addition, the technique was sufficiently sensitive to detect changes in the amplitude of CWM in response to changes in applied tidal volume. It is anticipated that application of this new non-invasive measurement device will lead to an increased understanding of the dynamics of chest and abdominal wall motion during HFOV.

Animals↗

Epitope-specific glutamic acid decarboxylase-65 autoantibodies in intravenous immunoglobulin preparations.

Intravenous immunoglobulin (IVIG) has been used to treat many autoimmune disorders including Stiff-Man Syndrome (SMS). SMS is a neurological disorder associated with an immune-mediated deficiency of gamma-aminobutyric acid (GABA) due to autoantibodies against the GABA synthesizing enzyme glutamic acid decarboxylase-65 (GAD65). GAD65 autoantibodies are present among 1-2% of healthy individuals. It can therefore not be excluded that GAD65 autoantibodies may be present in IVIG, which is prepared from multiple blood donors. We report here that GAD65 but not IA-2 autoantibodies were present in commercial IVIG preparations. The presence of autoantibodies may affect the outcome of IVIG treatment and screening commercial preparations of IVIG for GAD65 autoantibodies is therefore recommended before treating patients.

Antibody Affinity↗

Repeated immunization with recombinant gp160 human immunodeficiency virus (HIV) envelope protein in early HIV-1 infection: evaluation of the T cell proliferative response.

This longitudinal study was designed to evaluate cellular immunity in early-stage, asymptomatic human immunodeficiency virus (HIV)-1-infected persons (CD4 cell count,>400/mm3; median, 625/mm3) who were immunized with either recombinant (r) gp160 or placebo every 2 months for 5 years. Proliferative responses were assessed against rgp160, rp24, and a panel of recall antigens and mitogens. Despite good reactivity to recall antigens, at baseline approximately 33% had proliferative responses to gp160, and approximately 42% showed p24 gag responses. There was no statistical difference between vaccine and placebo groups for antigens or mitogens. After 1 year, approximately 73% of the subjects in the vaccine arm had new or boosted responses to gp160, versus approximately 18% in the placebo arm. Statistical significance was maintained throughout the study. Recurrent vaccination with recombinant gp160 was proven to be persistently immunogenic, increasing significantly the ability of HIV-1-infected persons to mount new proliferative responses to the vaccine.

AIDS Vaccines↗

The identification of [2-(14)C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine metabolites in humans.

[2-(14)C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ([14C]PhIP), a putative human carcinogenic heterocyclic amine found in well-done cooked meat, was administered orally to three colon cancer patients undergoing a partial colonectomy. Forty-eight to seventy-two hours prior to surgery, subjects received a 70-84 microg dose of 14C. Urine and blood were analyzed by HPLC for PhIP and PhIP metabolites. Metabolites were identified based on HPLC co-elution with authentic PhIP metabolite standards, mass spectral analysis and susceptibility to enzymatic cleavage. In two subjects, approximately 90% of the administered [14C]PhIP dose was eliminated in the urine, whereas in the other, only 50% of the dose was found in the urine. One subject excreted three times more radioactivity in the first 4 h than did the others. Twelve radioactive peaks associated with PhIP were detected in the urine samples. The relative amount of each metabolite varied by subject, and the amounts of each metabolite within subjects changed over time. In all three subjects the most abundant urinary metabolite was identified as 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine-N2-glucuron ide (N-hydroxy-PhIP-N2-glucuronide), accounting for 47-60% of the recovered counts in 24 h. PhIP accounted for <1% of the excreted radiolabel in all three patients. Other metabolites detected in the urine at significant amounts were 4-(2-amino-1-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulfate, N-hydroxy-PhIP-N3-glucuronide and PhIP-N2-glucuronide. In the plasma, N-hydroxy-PhIP-N2-glucuronide accounted for 60, 18 and 20% of the recovered plasma radioactivity at 1 h post PhIP dose in subjects 1, 2 and 3 respectively. Plasma PhIP was 56-17% of the recovered dose at 1 h post exposure. The relatively high concentration of N-hydroxy-PhIP-N2-glucuronide and the fact that it is an indicator of bioactivation make this metabolite a potential biomarker for PhIP exposure and activation. Determining the relative differences in PhIP metabolites among individuals will indicate metabolic differences that may predict individual susceptibility to carcinogenic risk from this suspected dietary carcinogen.

Administration, Oral↗

Targeted inactivation of Dp71, the major non-muscle product of the DMD gene: differential activity of the Dp71 promoter during development.

The dystrophin gene, which is defective in Duchenne muscular dystrophy (DMD), also encodes a number of smaller products controlled by internal promoters. Dp71, which consists of the two C-terminal domains of dystrophin, is the most abundant product of the gene in non-muscle tissues and is the major product in adult brain. To study the possible function of Dp71 and its expression during development, we specifically inactivated the expression of Dp71 by replacing its first and unique exon and a part of the concomitant intron with a beta-galactosidase reporter gene. X-Gal staining of Dp71-null mouse embryos and tissues revealed a very stage- and cell type-specific activity of the Dp71 promoter during development and during differentiation of various tissues, including the nervous system, eyes, limb buds, lungs, blood vessels, vibrissae and hair follicles. High activity of the Dp71 promoter often seemed to be associated with morphogenic events and terminal differentiation. In some tissues the activity greatly increased towards birth.

Animals↗

Compulsive physical activity in adolescents with anorexia nervosa: a psychobehavioral spiral of pathology.

The excessive exercising that is frequently observed in anorexia nervosa (AN) has been viewed both as an addictive behavior and as a type of obsessive compulsive disorder. The present study tested a nonrecursive structural equation model that specified associations among personality factors, cognitions, and behavior in the development and progression of excessive exercise in adolescent patients with AN. As proposed, findings indicated that both addictive personality and obsessive-compulsive personality contributed to excessive exercising by means of their influence on obligatory/pathological cognitions about exercising. Childhood physical activity also predicted excessive exercising. The implications of these results are discussed from a psychobiological perspective.

Adolescent↗

Coenzyme Q10 can in some circumstances block apoptosis, and this effect is mediated through mitochondria.

The mitochondrial component coenzyme Q10 (CoQ10) has been used for many years as a dietary supplement intended to promote good health by trapping free radicals, thus preventing lipid peroxidation and DNA damage. We have tested its use as a generic anti-apoptotic compound and have found that its ability to protect against apoptosis varies depending on both cell type and mode of cell death induction. We have further established that this protection may be mediated by its effect on mitochondrial function and viability. We provide additional evidence that CoQ10's protective effect on mitochondrial membrane potential does not always result in altered mitochondrial enzyme activity and neither does it guarantee survival. These observations open the way for further investigations into the mechanisms involved in mitochondrial control of apoptosis.

Animals↗

The Doors and People Memory Test: validation of norms and some new correction formulae.

OBJECTIVES: To validate the normative data on the Doors and People Memory Test (D&P) using a new sample of normal participants, and to investigate the relationship between D&P performance and general intellectual level. DESIGN: 281 normal participants (16-75 years), subdivided into 10-year age bands, were tested on the D&P and the National Adult Reading Test (NART). METHOD: Each participant's raw scores on the D&P were converted into scaled scores, and scaled memory 'indices' were derived using the test manual. Stepwise multi-linear regression was used to predict the indices using age and NART error score as predictor variables. For each participant the discrepancy between the predicted and obtained values of each index was converted into a [symbol: see text] score using the SD of the discrepancies from the whole sample. RESULTS: The distributions of raw and scaled scores on the D&P were similar to those of the original standardization sample. The Visual-Verbal and Recall-Recognition Discrepancy indices had smaller dispersions in the present sample than in the original sample. None of the indices was significantly related to age. The Total Memory, Combined Visual Memory, Combined Verbal Memory, and Overall Forgetting indices were significantly correlated with NART error score. CONCLUSIONS: The present data constitute a cross-validation of the normative data presented in the D&P test manual. Two points of dissimilarity are noted: (i) cutting scores derived for the Visual-Verbal and Recall-Recognition indices based on the test manual norms may be unduly conservative; and (ii) the relationship between some of the D&P indices and NART error score may lead to systematic errors in interpreting the scaled scores derived from the manual. 'Correction formulae' based on the regression equations derived from the present sample are provided.

Adolescent↗

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↗