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Biomedical subjects

M Young

Publications and source records attributed to M Young.

At least 37 records · Page 2Linked to original sources

Determinants of HIV-1 shedding in the genital tract of women.

BACKGROUND: Plasma HIV-1 RNA concentration has been the best predictor for risk of heterosexual and perinatal transmission. However, direct contact with HIV-1 present locally in the genital tract might be necessary for transmission. We aimed to assess the relation between HIV-1 shedding (RNA or culturable virus) in female genital secretions and other factors that might affect HIV-1 shedding. METHODS: This was a cross-sectional study within the Women's Interagency HIV Study (WIHS), a prospective longitudinal cohort study of HIV-infected women. We enrolled 311 HIV positive women from Jan 30, 1997 to July 1, 1998. We did clinical assessments, cultured HIV-1, and measured RNA in peripheral blood mononuclear cells (PBMC) and genital secretions. We compared the results with univariate and multivariate analyses. Presence of HIV-1 RNA or culturable virus in genital secretions was defined as HIV-1 shedding. FINDINGS: HIV-1 RNA was present in genital secretions of 57% (152/268) of women whereas infectious virus was detected only in 6% (17/271). Genital tract HIV-1 shedding was found in 80% (130/163) of women with detectable plasma RNA and 78% (116/148) of women with positive PBMC cultures. 33% (27/83) of women with less than 500 copies/mL plasma RNA and 39% (35/90) of those with negative PBMC cultures also had genital tract shedding. INTERPRETATION: Plasma RNA concentration, both qualitatively and quantitatively, was the most important factor in predicting genital HIV-1 shedding, even among women receiving potent antiretroviral therapy. However, HIV-1 shedding did occur in women with less than 500 copies/mL plasma HIV-1 RNA. This finding suggests that a separate reservoir of HIV-1 replication may exist in some women.

Adult↗

Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity.

Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC(50) = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of 1a led to 1c, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of 1c with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC(50) of 1.2 nM in the Src enzymatic assay, an IC(50) of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

Animals↗

Sleep in the laboratory and sleep at home II: comparisons of middle-aged insomnia sufferers and normal sleepers.

STUDY OBJECTIVES: The study compared adaptation responses and sleep pattern differences shown by normal sleepers and insomnia sufferers during lab (LPSG) and home (HPSG) polysomnography. DESIGN: A counter-balanced, matched-group design was used. Participants underwent 3 consecutive nocturnal LPSG's and 3 consecutive nocturnal PSG's in their homes (HPSG's). SETTING: The sleep disorders laboratories at affiliated VA and university medical centers. PARTICIPANTS: Thirty-five (18 women) middle-aged (40 to 59 years) noncomplaining normal sleepers and an age-matched sample of 33 (17 women) individuals who met structured interview criteria for persistent primary insomnia were the study participants. MEASUREMENTS AND RESULTS: A series of multivariate and univariate analyses were conducted with 9 common sleep parameters to address study objectives. Bed partner influences were controlled by conducting separate sets of analyses for those with and without routine home bed partners. The interaction of participant type (normal vs. insomnia), sleep setting, and PSG sequence (HPSG 1st vs. LPSG 1st) affected first night values of sleep efficiency and stage 2 sleep among those without routine bed partners, and REM latency and sleep efficiency among those with routine bed partners. Analyses which controlled for first night and sequencing effects showed a significant participant type x sleep setting interaction among those with bed partners. These latter analyses suggested that LPSG's may underestimate the home sleep time of insomnia sufferers and overestimate the sleep continuity of normal sleepers, at least among those who routinely sleep with a bed partner. CONCLUSIONS: The nocturnal recording site may influence adaptation effects and sleep pattern differences noted between insomnia sufferers and normal sleepers.

Adaptation, Physiological↗

Mechanism of processivity clamp opening by the delta subunit wrench of the clamp loader complex of E. coli DNA polymerase III.

The dimeric ring-shaped sliding clamp of E. coli DNA polymerase III (beta subunit, homolog of eukaryotic PCNA) is loaded onto DNA by the clamp loader gamma complex (homolog of eukaryotic Replication Factor C, RFC). The delta subunit of the gamma complex binds to the beta ring and opens it. The crystal structure of a beta:delta complex shows that delta, which is structurally related to the delta' and gamma subunits of the gamma complex, is a molecular wrench that induces or traps a conformational change in beta such that one of its dimer interfaces is destabilized. Structural comparisons and molecular dynamics simulations suggest a spring-loaded mechanism in which the beta ring opens spontaneously once a dimer interface is perturbed by the delta wrench.

Amino Acid Sequence↗

Functional genomic studies of aldo-keto reductases.

Aldose reductase (AR) is considered a potential mediator of diabetic complications and is a drug target for inhibitors of diabetic retinopathy and neuropathy in clinical trials. However, the physiological role of this enzyme still has not been established. Since effective inhibition of diabetic complications will require early intervention, it is important to delineate whether AR fulfills a physiological role that cannot be compensated by an alternate aldo-keto reductase. Functional genomics provides a variety of powerful new tools to probe the physiological roles of individual genes, especially those comprising gene families. Several eucaryotic genomes have been sequenced and annotated, including yeast, nematode and fly. To probe the function of AR, we have chosen to utilize the budding yeast Saccharomyces cerevisiae as a potential model system. Unlike Caenorhabditis elegans and D. melanogaster, yeast provides a more desirable system for our studies because its genome is manipulated more readily and is able to sustain multiple gene deletions in the presence of either drug or auxotrophic selectable markers. Using BLAST searches against the human AR gene sequence, we identified six genes in the complete S. cerevisiae genome with strong homology to AR. In all cases, amino acids thought to play important catalytic roles in human AR are conserved in the yeast AR-like genes. All six yeast AR-like open reading frames (ORFs) have been cloned into plasmid expression vectors. Substrate and AR inhibitor specificities have been surveyed on four of the enzyme forms to identify, which are the most functionally similar to human AR. Our data reveal that two of the enzymes (YDR368Wp and YHR104Wp) are notable for their similarity to human AR in terms of activity with aldoses and substituted aromatic aldehydes. Ongoing studies are aimed at characterizing the phenotypes of yeast strains containing single and multiple knockouts of the AR-like genes.

Alcohol Oxidoreductases↗

Prevalence and correlates of anemia in a large cohort of HIV-infected women: Women's Interagency HIV Study.

Anemia is a common manifestation of HIV infection, occurring in approximately 30% of patients with asymptomatic infection and in as many as 75% to 80% of those with AIDS. Anemia has been associated with decreased quality of life and decreased survival. We performed a cross-sectional study nested within a multicenter prospective cohort study to describe the prevalence of anemia in 2056 HIV-infected and 569 HIV-negative women as well as to define the demographic, clinical, immunologic, and virologic correlates of anemia among HIV-infected women. A total of 37% of HIV-positive women and 17% of HIV-negative women had hemoglobin levels < 12 g/dl (p < .001). Factors associated with anemia in HIV-positive and HIV-negative women included mean corpuscular volume (MCV) < 80 fl (p < .001) and black race (p < .001). Among HIV-infected women, multivariate logistic analyses revealed that African American race (p < .0001), MCV < 80 fl (p < .0001), CD4 count < 200 per microliter (p <.0001), higher HIV RNA in plasma (p = .02), current use of ZDV (p = .01), and history of clinical AIDS (p = .004) were all independent predictors of anemia. These data indicate that worsening parameters of HIV disease are associated with anemia among HIV-infected women. Black women and women with low MCV values are at increased risk for anemia independent of HIV status.

Adolescent↗

Immunoexpression of interleukin-1beta in pancreatic islets of NOD mice during cyclophosphamide-accelerated diabetes: co-localization in macrophages and endocrine cells and its attenuation with oral nicotinamide.

During insulin-dependent diabetes mellitus, islet invading immune cells destroy beta cells over a prolonged asymptomatic pre-diabetic period. Cytokines synthesised and secreted by specific immune cells within the islet infiltrate may be crucial effectors of beta cell destruction or protection during the disease. Interleukin-1beta may be a key cytokine which may act in concert with other cytokines in initiating and/or promoting beta cell destruction. We have examined this hypothesis in NOD mice by assessing the intra-islet expression and co-localization of interleukin-1beta at different time-points following cyclophosphamide administration. We have also tested the effects of long-term oral nicotinamide given to NOD mice in suppressing intra-islet expression of the cytokine in this accelerated model. Cyclophosphamide was administered to day 95 female NOD mice. Pancreatic tissues were examined by dual-label confocal immunofluorescence microscopy for the expression and co-localization of interleukin-1beta at days 0, 4, 7, 11 and at onset of diabetes (day 14). Diabetes developed in 7/11 mice 14 days after administration of cyclophosphamide while nicotinamide completely prevented the disease. At day 0, interleukin-1beta immunolabelling was observed in selective intra-islet macrophages, several somatostatin cells and in a few beta cells. However, at day 4, it was seen mostly in somatostatin and some beta cells. At day 7, an increasing number of interleukin-1beta cells were observed within the islets and co-localized to several somatostatin cells, beta cells and macrophages. The mean number of intra-islet interleukin-1beta cells reached a peak at day 11 and was significantly higher than at day 7 (p = 0.05) and at day 14 (onset of diabetes; p = 0.03). At day 11, interleukin-1beta immunolabelling was also present in selective macrophages which co-expressed inducible nitric oxide synthase. At onset of diabetes, some macrophages, residual beta cells and somatostatin cells showed immunolabelling for the cytokine. Exposure of NOD mice to oral nicotinamide was associated with a considerably reduced expression of interleukin-1beta cells within the islet at day 11 (p = 0.002). We conclude that cylophosphamide treatment enhances the expression of interleukin-1beta in selective macrophages, somatostatin and beta cells during the course of the disease. Its expression reaches a maximum immediately prior to onset of diabetes. Interleukin-1beta present in intra-islet macrophages, somatostatin and beta cells may influence its expression by autocrine and paracrine means. Interleukin-1beta expression within islet macrophages may also up-regulate inducible nitric oxide synthase within the same macrophage or adjacent macrophage populations. These intra-islet molecular events may corroborate with other local cytotoxic processes leading to beta cell destruction. Oral nicotinamide may attenuate intra-islet expression of interleukin-1beta and thus inducible nitric oxide synthase during prevention of Type 1 diabetes in this animal model. The expression of interleukin-1beta in specific islet endocrine cell-types shown in this study requires further investigation.

Adjuvants, Immunologic↗

Degeneration of solventogenic Clostridium strains monitored by Fourier transform infrared spectroscopy of bacterial cells.

Strain degeneration in solventogenic clostridia is a known problem in the technical acetone-butanol fermentation bioprocess, especially in the continuous process mode. Clostridial strain degeneration was studied by Fourier transform infrared (FT-IR) spectroscopy of the bacterial cells. Degenerative variant formation in two strains, Clostridium beijerinckii NCIMB 8052 and Clostridium species AA332, was detected spectroscopically. Colonies on solid media were sampled, or assayed directly in situ by IR microscopy. It has previously been shown that the distinctive acidogenic and solventogenic physiological phases of Clostridium acetobutylicum in liquid medium can be discriminated by FT-IR spectroscopy. This was confirmed here for C. beijerinckii NCIMB 8052. The proportion of degenerate cells in a mixed population in liquid medium could be quantified, as the spectral features change in different ways during the normal growth cycle of wild type organisms and degenerate variants in batch culture. This opens a new perspective for physiology-based process monitoring and control, especially of the continuous acetone-butanol fermentation.

Acetone↗

Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls.

Corticotropin-releasing hormone (CRH) is a key neuroendocrine factor implementing endocrine, immune and behavioral responses to stress. CRH exerts its action through two major receptors, CRH-R1 and CRH-R2. Recently novel non-peptidic antagonists directed against CRH-R1 or CRH-R2 have been proposed as promising agents in the treatment of depression, anxiety and eating disorder. However, so far the CRH-receptor system has not been widely studied in humans. Therefore, we employed quantitative TaqMan PCR to analyze the expression and distribution of both CRH-R1 and CRH-R2 in human brain tissue and peripheral organs. Furthermore the expression of CRH receptors was analyzed for the first time in pituitaries of suicide victims by in situ hybridization and quantitative PCR. Our data demonstrated a different expression pattern in humans as compared to rodents. Both CRH-R1 and CRH-R2 were expressed in high amounts in the brain with the strongest expression in the pituitary. As described in rodents, however the CRH-R1 in human was the predominant receptor in the brain (82.7 +/- 11.0%), whilst CRH-R2 was the predominant receptor in peripheral organs (77.0 +/- 15.8%). There was a shift in the ratio of CRH-R1/R2 in the pituitaries of suicide victims. In conclusion, both CRH-R1 and CRH-R2 are widely expressed in human tissues with a distribution substantially different from rodents. Strong expression of both CRH-R1 and CRH-R2 in human pituitaries suggests that particularly under stress, activation of the HPA axis can be maintained through both receptors.

Adolescent↗

Perceptions of human immunodeficiency virus and sexually transmitted disease risk among low-income adults: a pilot study.

Sexual risk-taking research and subsequent intervention programs have focused almost exclusively on adolescents and men who have sex with men. In comparison, less research has been conducted into adult heterosexual risk-taking behavior. The purposes of this pilot study were to test a survey instrument, assess how low-income adults perceive their risk of human immunodeficiency virus (HIV) and sexually transmitted disease (STD) infection, and determine the degree to which condom use is a function of age. The Health Belief Model was used to guide the development of the survey instrument. In the Health Belief Model, age is a mediating factor that influences a person's likelihood to take action to change his or her lifestyle. Respondents perceived that their vulnerability to infection declined because of increased age and decreased frequency of coitus. Condom use was found to significantly decline as the age of the respondents increased. Although this is only a pilot study, the findings highlight the need for HIV and STD education for all age groups and genders.

Adult↗

Prevalence and predictors of skin disease in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: We attempted to determine the prevalence and predictors of skin disease in a cohort of women with and at risk for HIV infection. METHODS: We analyzed baseline data from a multicenter longitudinal study of HIV infection in women. RESULTS: A total of 2018 HIV-infected women and 557 HIV-uninfected women were included in this analysis. Skin abnormalities were reported more frequently among HIV-infected than uninfected women (63% vs 44%, respectively; odds ratio [OR] 2.10; 95% confidence interval [95% CI], 1.74-2.54). Infected women were also more likely to have more than 2 skin diagnoses (OR, 3.27; 95% CI, 1.31-8.16). Folliculitis, seborrheic dermatitis, herpes zoster, and onychomycosis were more common among HIV-infected women (P < .05). Independent predictors of abnormal findings on skin examination in the infected women were African American race (OR, 1.38; 95% CI, 1.07-1.77), injection drug use (OR, 2.74; 95% CI, 2.11-3.57), CD4(+) count less than 50 (OR, 1.68; 95% CI, 1.17-2.42), and high viral loads (100,000-499,999 = OR, 1.77; 95% CI, 1.32-2.37; > 499,999 = OR, 2.15; 95% CI, 1.42-3.27). CONCLUSION: HIV infection was associated with a greater number of skin abnormalities and with specific dermatologic diagnoses. Skin abnormalities were also more common among women with CD4(+) cell depletion or higher viral load.

Adolescent↗

Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis.

Although adjunctive treatment with retinoids in concert with either psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment option for chronic, moderate to severe plaque psoriasis for nearly two decades, acitretin-UV therapy is an underutilized therapeutic modality. According to a recent member survey by the National Psoriasis Foundation, many psoriasis patients are frustrated with available treatment options, which they perceive as ineffective, inconvenient, and/or excessively conservative. Treatment of psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable clinical strategy. Compared with either acitretin or UV light monotherapy alone, the combination regimen enhances efficacy and limits treatment frequency, duration, and cumulative doses. These effects translate into care that is more effective, better tolerated, more convenient, less costly, and, perhaps, safer during long-term treatment than phototherapy alone. Drawing from an extensive literature search and the expertise of its participants, this consensus conference advances clinical recommendations as well as "clinical pearls" for health providers who treat patients with chronic, moderate to severe plaque psoriasis and suggests avenues for future research.

Acitretin↗

Complexities of androgen action.

Androgens mediate a wide range of processes during embryogenesis and in the adult. In mammals, the principal androgens are testosterone and its 5alpha-reduced metabolite, 5alpha-dihydrotestosterone (DHT). Although these androgenic hormones are diverse in character, it is believed that their effects are mediated via the protein products of a single androgen receptor gene encoded on the X-chromosome. A great deal of information has now accumulated pertaining to the mechanisms by which nuclear receptors, such as the androgen receptor, modulate the activity of responsive genes. The studies have demonstrated the participation of a number of ancillary proteins in modulating activation or repression by nuclear receptors. In addition to studies focused on the mechanisms of nuclear receptor function, additional work has illuminated the mechanism by which androgens are metabolized in selected tissues. This information provides a perspective on the number of levels of complexity by which differential gene regulation by androgens may occur in different tissues and in different cell types.

Alopecia↗

Ischemia-reperfusion injury after relief of ureteral obstruction: an animal study.

BACKGROUND AND PURPOSE: The complex series of pathophysiologic alterations associated with obstruction nephropathy includes renal ischemia. Free-radical production follows relief of obstruction. We sought to determine whether free radicals caused additional reduction in blood flow after relief of obstruction. MATERIALS AND METHODS: In White-Landrace pigs, the left ureter was divided 6 cm distal to the ureteropelvic junction, and a nephrostomy tube was passed into the renal pelvis and exteriorized. A catheter was placed in the renal vein and exteriorized. Mean renal blood flow was measured before manipulation and during and after 6 hours of obstruction in animals receiving (N = 7) or not receiving (N = 7) allopurinol. The control groups were not subjected to ureteral obstruction and received (N = 7) or did not receive (N = 7) allopurinol. Free radicals in venous blood were measured by the Fox-1 assay for lipid peroxidation. RESULTS: After obstruction, renal blood flow declined significantly by the sixth hour (-28.73% +/- 1.81). The increase after relief of obstruction was only temporary, and by the third hour, the blood flow was again reduced (-20.14% +/- 2.67). Free radical production was significantly increased, with a peak of +24.63% being found 60 minutes after relief of obstruction. Allopurinol prevented free radical production after relief of obstruction and was associated with a return of blood flow to baseline values. CONCLUSION: Free radicals contribute to renal blood flow reduction after relief of ureteral obstruction. Functional impairment may be preventable by free radical blockade, but further studies are required to confirm this hypothesis.

Allopurinol↗

Clostridium beijerinckii and Clostridium difficile detoxify methylglyoxal by a novel mechanism involving glycerol dehydrogenase.

In contrast to gram-negative bacteria, little is known about the mechanisms by which gram-positive bacteria degrade the toxic metabolic intermediate methylglyoxal (MG). Clostridium beijerinckii BR54, a Tn1545 insertion mutant of the NCIMB 8052 strain, formed cultures that contained significantly more (free) MG than wild-type cultures. Moreover, BR54 was more sensitive to growth inhibition by added MG than the wild type, suggesting that it has a reduced ability to degrade MG. The single copy of Tn1545 in this strain lies just downstream from gldA, encoding glycerol dehydrogenase. As a result of antisense RNA production, cell extracts of BR54 possess significantly less glycerol dehydrogenase activity than wild-type cell extracts (H. Liyanage, M. Young, and E. R. Kashket, J. Mol. Microbiol. Biotechnol. 2:87-93, 2000). Inactivation of gldA in both C. beijerinckii and Clostridium difficile gave rise to pinpoint colonies that could not be subcultured, indicating that glycerol dehydrogenase performs an essential function in both organisms. We propose that this role is detoxification of MG. To our knowledge, this is the first report of targeted gene disruption in the C. difficile chromosome.

Biodegradation, Environmental↗

Abnormal localisation and hyperclustering of (alpha)(V)(beta)(3) integrins and associated proteins in Src-deficient or tyrphostin A9-treated osteoclasts.

The non-receptor tyrosine kinase Src was shown to be essential for osteoclast function in vivo. We have previously reported that engagement of (alpha)(v)(beta)(3) integrin in osteoclasts induces tyrosine phosphorylation and activation of the adhesion kinase PYK2 and the adaptor protein p130(Cas) in a Src-dependent manner. The objective of this study was to analyse the role of c-Src in the (alpha)(v)(beta)(3) integrin-dependent recruitment of signalling and cytoskeletal molecules in osteoclasts during bone resorption. Using prefusion osteoclasts (pOCs) obtained from cocultures of osteoblasts and spleen cells isolated from Src(-/-) mice or their normal littermates, we found: (1) similar expression levels and ligand binding affinities of (alpha)(v)(beta)(3) integrins in Src(-/-) and Src(+/?) pOCs, (2) reduced adhesion and spreading of Src(-/-) pOCs, (3) defective organisation of the microfilament proteins, F-actin, vinculin and paxillin, and of PYK2 and p130(Cas) in the sealing zone of Src(-/-)OCLs, and (4) hyperclustering of (alpha)(v)(beta)(3) integrins together with microfilament and signalling proteins in the basal membrane of Src-deficient OCLs. In normal OCLs, the tyrosine kinase inhibitor tyrphostin A9 inhibits actin ring formation, bone resorption and tyrosine phosphorylation of several proteins, including c-Src. Furthermore, tyrphostin A9 induced similar hyperclustering of (alpha)(v)(beta)(3) integrins in osteoclasts as observed in Src(-/-) OCLs. Taken together, these findings suggest that normal localisation of (alpha)(v)(beta)(3) and recruitment of its downstream effectors to the appropriate compartments of the osteoclast during resorption depend on Src kinase activity.

Animals↗

Experience and covariates of depressive symptoms among a cohort of HIV infected women.

OBJECTIVES: The objectives of this study are to assess (a) the level of depressive symptoms among a cohort of HIV infected women and comparable controls and (b) the relationship with covariates including socioeconomic status, substance use, social relations, disease status. METHODS: Participants were enrolled in the Women's Interagency HIV Study (WIHS). Depressive symptoms were measured using the Center for Epidemiological Studies Depression Scale (CESD). Data from 1993 HIV seropositive and 551 seronegative women are presented. RESULTS: Of HIV positive women 57.7% of HIV positive women scored 16 or higher on the CESD (ns) as compared to 55.0% of HIV negative women; at a cutoff of 23, the percents were 40.4% and 35.9% respectively (p = .06). The mean score was high 19.8 but not significantly different between groups. Scores were higher among women who had less education, lower income, were of Hispanic ethnicity, used alcohol or drugs, experienced domestic abuse, had more than one partner, or had less supportive relationships. Among infected women, higher CESD scores were not significantly associated with CD4 cell count but were elevated for self-reported Class C AIDS defining clinical conditions. CONCLUSIONS: The scores on the CESD were elevated for both HIV positive and HIV negative women and the differences between the groups were small. Lower socioeconomic status and social support and higher substance use and domestic abuse were associated with depressive symptoms similarly for both groups.

Analysis of Variance↗

A telephone-linked computer system for COPD care.

The current revolution in communications technology provides an opportunity for novel approaches to management of medical illness. As economic imperatives lead to a progressive reduction in the time that health-care providers spend with their patients, computerized, telephone-linked communication systems offer an inexpensive, widely available alternative with which patients and providers can maintain contact. Such systems may be particularly useful for providing ongoing monitoring and education of patients with chronic illnesses such as COPD. In this article, we describe the general application of telephone-linked communication systems in the health-care setting. We then present in detail one such system, which provides telephone-linked care for COPD (TLC-COPD). The operation of the system is described, as are its theoretical underpinnings in social learning theory. A randomized clinical trial currently is being performed to study the effects of the TLC-COPD system. The rationale for expected improvements in disease control and quality of life, and for a reduction in acute health-care utilization, is discussed.

Algorithms↗