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Biomedical subjects

C Pomeroy

Publications and source records attributed to C Pomeroy.

At least 19 recordsLinked to original sources
PubMed2000

Cytokine production in patients with anorexia nervosa, bulimia nervosa, and obesity.

OBJECTIVE: We previously reported elevated serum levels of the cytokines interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) in patients with anorexia nervosa (AN). We investigated the cellular production of these two cytokines and of interferon-gamma (IFN-gamma), interleukin-1alpha (IL-1alpha), and tumor necrosis factor-alpha (TNF-alpha) in subjects with AN, bulimia nervosa (BN), and obesity as well as in normal-weight control subjects. METHODS: Supernatant fluids from isolated peripheral blood mononuclear cells (PBMC) incubated with and without concanavalin A (ConA) were assayed for cytokine concentrations by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant differences across the four groups were found in the stimulated cellular production of IFN-gamma and IL-6. Stimulated IFN-gamma production was elevated in the AN group compared to controls. IL-6 production was significantly elevated in obese subjects relative to the two normal-weight groups, BN and controls, and tended to be higher in the AN group than in the controls, but not significantly so. IL-1alpha production was greater in obese subjects. CONCLUSION: The findings of increased IFN-gamma production and a tendency toward increased IL-6 production (both of which suppress food intake in animals) in individuals who severely restrict food intake suggest a potential role for these cytokines in the pathogenesis of AN. Elevated IL-6 and IL-1alpha production by PBMC in obese individuals requires further investigation to determine if these cytokines contribute to the development or perpetuation of obesity.

Adolescent↗
PubMed2000

Revising appointment, promotion, and tenure procedures to incorporate an expanded definition of scholarship: the University of Kentucky College of Medicine experience.

Scholarly activity and scholarly productivity are key features of the academic health center (AHC) and the work of college of medicine faculty. Recent changes in the academic environment of the University of Kentucky (UK) College of Medicine led to an examination of its appointment, promotion, and tenure procedures. This, in turn, led to a re-examination of the college's definition of scholarship. This article describes three of UK's scholarship-related challenges, particularly those related to clinical departments. The authors describe some of the new procedures being implemented to address these challenges; these include new faculty designations, clearer articulation of promotion procedures, explicit recognition of multiple forms of scholarship, expectations for investment in junior faculty, and mandatory discussion of faculty success in chairs' annual reviews. Faculty reactions, positive and negative, to these changes in procedures are also presented.

Career Mobility↗
PubMed2000

Human immunodeficiency virus drug resistance testing: state of the art in genotypic and phenotypic testing of antiretrovirals.

Antiretroviral drugs have significantly reduced death rates from the acquired immunodeficiency syndrome in the United States. They are highly effective in reducing viral replication, but their utility is threatened by rapid development of drug resistance. Although antiretroviral drug resistance testing is available by either genotyping or phenotyping, no consensus guidelines have been published regarding the appropriate use or interpretation of these new tests. Even though their role in clinical practice is not defined, it is important for clinicians to become familiar with relative advantages and disadvantages of genotypic and phenotypic testing and various mechanisms of antiretroviral resistance.

Anti-HIV Agents↗
PubMed2000

Prenatal HIV prevention practices in a low seroprevalence state.

The purpose of this study was to build understanding of prenatal HIV counseling and testing practices in low seroprevalence states. Responses from a 1998 population-based survey of Kentucky prenatal care providers (67% response; 312 analyzed) were compared with findings from patient focus groups. Sixty-two percent of clinicians said they routinely counsel prenatal patients with risk factors, but only 46% routinely counsel patients without risk factors. The proportions routinely offering HIV testing to patients with and without risk factors were 94% and 84%, respectively. Prenatal patients identified "fear of a positive test result" as the major barrier to test acceptance. This fear was fueled by lack of knowledge regarding the benefits of early detection. The study concludes that achieving universal prenatal HIV testing will require new strategies, such as the distribution of a standardized protocol, that address clinicians' concerns about "time burdens" without depriving patients of the opportunity to receive individualized counseling.

Adult↗
PubMed1999

Immunogenicity of three Haemophilus influenzae type b protein conjugate vaccines in HIV seropositive adults and analysis of predictors of vaccine response.

HIV-seropositive adults may be at increased risk of infection due to Haemophilus influenzae type b (Hib) as compared with HIV-seronegative adults. Protein conjugate vaccines have been demonstrated to induce protective levels of antibodies against Hib in immunocompetent infants and also in HIV-seropositive infants. In this study we determined the immunogenicity of three protein conjugate Hib vaccines (PRP-D, HbOC, HbNOMP) in 135 HIV-seropositive adults who received one dose of Hib vaccine. Anti-polyribosylribitol phosphate (PRP) antibodies were measured at 0, 1, 3 and 12 months postimmunization by the Farr method. We demonstrate that all three vaccines are highly immunogenic and result in protective (> 1.0 microg/ml) levels of antibody. Overall the anti-PRP antibody level was > 1.0 microg/ml in 26% of patients preimmunization, 91% at both 1 and 3 months, and 79% at 12 months postvaccination. Comparison of responses to the three vaccines over time demonstrated differences in the mean geometric anti-PRP antibody level at 1 month (p=0.03) and the 12 month time points (p=0.03) with lower geometric mean levels in the HbNOMP group, though baseline differences in groups limit the interpretation of these findings. In a univariate analysis of baseline characteristics which predicted poor vaccine response, low total IgG2 levels preimmunization predicted a poor antibody response at 1 month (p < 0.01) and at 12 months (p=0.05), while low CD4 T-cell count predicted poor response at 12 months (p < 0.01). We conclude that all three US licensed protein conjugate Hib vaccines are immunogenic in HIV-seropositive adults, and that baseline CD4 T-cell count and IgG2 levels predict the likelihood of antibody response to vaccine.

Adult↗
PubMed1999

Renal manifestations of hepatitis C infection.

Hepatitis C is an important cause of renal disease, and renal complications may be the presenting manifestation of hepatitis C infection. About half of patients present with evidence of renal insufficiency, and up to one quarter present with nephrotic syndrome. Others present with proteinuria or evidence of diminished renal function. The pathogenesis of hepatitis C-associated renal disease remains incompletely defined, but most evidence suggests that glomerular injury results from deposition of circulating immune complexes in the subendothelium and mesangium. Membranoproliferative glomerulonephritis, with or without cryoglobulinemia, is the most common renal lesion. Interferon alpha-2b is currently the treatment of choice. However, success is limited, with many patients failing to respond or suffering relapse upon discontinuation of therapy. Studies of newer treatment modalities, such as longer courses of interferon or the use of ribavirin or immunosuppressive agents, are underway. Hepatitis C-associated renal disease may progress to end-stage renal failure requiring dialysis in about 10% of patients.

Antiviral Agents↗
PubMed1999

Adenovirus infections in hematopoietic stem cell transplant recipients.

We report a 12% incidence of adenovirus infections among 532 recipients of hematopoietic stem cell transplant (HSCT) from January 1986 through March 1997. The median time from day of stem cell infusion to first positive culture was 41 days. Recipients of allogeneic stem cells, as opposed to autologous stem cell recipients, were more likely to have a culture positive for adenovirus (16% vs. 3%; P<.0001). Pediatric patients were also more likely than adults to have a positive culture (23% vs. 9%; P<.0001). Among stem cell recipients with partially matched related donors, pediatric recipients appear to be at significantly greater risk for infection than adult recipients (P<.001). Positive cultures were associated with evidence of invasion in 64% of cases (41 of 64). A multiple logistic regression analysis showed that isolating adenovirus from more than 1 site correlated with greater risk for invasive infections (P=.002). Invasive infections were associated with poorer chance of survival.

Adenovirus Infections, Human↗
PubMed1999

Changes in cytokine levels during reactivation of Toxoplasma gondii infection in lungs.

We studied cytokine proteins and mRNAs in mice with two forms of Toxoplasma gondii pneumonia resulting from reactivation of infection. In the first form, mice were infected with T. gondii, developed and recovered from systemic disease, and then developed pneumonia 3 weeks later. As pulmonary inflammation developed, levels of cytokine mRNAs for gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-10 increased in bronchoalveolar lavage (BAL) cells or lung tissue, and the level of IFN-gamma protein increased in BAL fluid. The second form of pneumonia occurred as a complication of primary cytomegalovirus (CMV) disease in mice with dormant T. gondii infection. During CMV disease, IL-2 mRNA levels decreased in lung tissue, IL-10 protein levels increased in lung tissue, and IL-10 protein levels increased in BAL fluid. As the mice recovered from CMV disease, T. gondii infection was reactivated in the lungs and was manifested as T. gondii pneumonia. During CMV-induced T. gondii pneumonia, IFN-gamma, IL-2, IL-4, and IL-10 mRNA levels increased in BAL cells or lung tissue, and both IFN-gamma and IL-2 protein levels increased in BAL fluid. We concluded that both forms of T. gondii pneumonia are accompanied by increases in both type 1 T-helper and type 2 T-helper cytokine levels in lungs. The mechanism of CMV-induced reactivation of T. gondii infection in lungs may involve local decreases in IL-2 levels and/or increases in IL-10 levels.

Animals↗
PubMed1999

Hydroxyurea to inhibit human immunodeficiency virus-1 replication.

Treatment of human immunodeficiency virus (HIV) infection continues to be a challenge. Drug regimens that include two nucleoside reverse transcriptase inhibitors and a protease inhibitor are now the standard of care. These regimens require strict patient adherence and have numerous adverse effects at a high cost, so clinicians must continue to explore other therapeutic options. Hydroxyurea is a ribonucleotide reductase inhibitor that may have efficacy against HIV. We conducted a critical review of the literature to examine the utility of hydroxyurea-based drug combinations.

Anti-HIV Agents↗
PubMed1998

Role of interferon-gamma in murine cytomegalovirus infection.

Interferon-gamma has well-documented antiviral and immunomodulatory activity, but its role in the control of cytomegalovirus (CMV) infection is not well studied. In a mouse model of murine CMV (MCMV) disease, interferon-gamma concentrations in serum but not in bronchoalveolar lavage fluid increased in response to viral infection. Serum interferon-gamma levels peaked at day 2 in the relatively resistant C57BL/6 mice, and, in contrast, did not peak until day 6 in susceptible BALB/c mice. Mice genetically lacking interferon-gamma (GKO) were more susceptible to MCMV, although strain differences persisted, with C57BL/6 GKO mice experiencing less severe MCMV disease than BALB/c GKO mice. Treatment of MCMV-infected BALB/c mice with exogenous interferon-gamma starting 2 days after viral infection had a modest protective effect at lower interferon-gamma doses (10(4) units), but interferon-gamma therapy markedly increased morbidity and mortality when higher doses (10(5) units) were used. We conclude that interferon-gamma plays a significant role in host response to MCMV and that the cytokine has dose- and time-dependent beneficial and adverse effects.

Animals↗
PubMed1998

Leptin in anorexia nervosa.

Serum leptin levels are low in untreated anorexia nervosa, but studies of the exact relationship between leptin and body weight and the impact of refeeding in anorectics are limited. Therefore, we studied serum leptin, insulin-like growth factor I, and other endocrine parameters in female anorectics before and after gaining weight and in female normal body weight controls. Leptin levels in untreated anorectics were significantly lower than those in normal body weight controls (3.6 +/- 1.6 vs. 12.0 +/- 6.9 ng/mL; P < 0.001), and they uncoupled from body weight in a nonlinear relationship, suggesting a threshold effect at lowest body weights. Leptin increased significantly with refeeding (5.6 +/- 3.8 ng/mL; P < 0.01). The significant linear correlations of leptin with body mass index in the anorectics after weight gain and in normal body weight controls (r = 0.69; P < 0.001 and r = 0.76; P < 0.001, respectively) are consistent with a normal physiological increase in leptin with weight gain. Leptin and insulin-like growth factor I were highly correlated, even after controlling for body weight (r = 0.63; P = 0.001) during starvation, but were no longer significantly correlated after body weight gain in the anorectics or the normal body weight controls. Further studies are necessary to elucidate the relationship of leptin to neuroendrocrine abnormalities seen in starvation and to determine a possible contribution of leptin to difficulties with weight restoration in anorexia nervosa.

Adolescent↗
PubMed1997

Effect of body weight and caloric restriction on serum complement proteins, including Factor D/adipsin: studies in anorexia nervosa and obesity.

Complement plays important roles in host immune defences, and recent studies suggest that adipose tissue is an important site of production for some complement proteins. Starvation has been associated with low complement levels, but studied populations have usually had concomitant opportunistic infections or other conditions which might affect complement levels. To determine the impact of body weight and changes in body weight on serum complement, we investigated levels of complement proteins in otherwise healthy patients with a wide range of body weights, including patients with anorexia nervosa before and after treatment, obese dieters before and after weight loss, and normal weight controls. We found that complement proteins of the alternative pathway (C3, B, and D), alternative pathway haemolytic activity (AP50) and the inhibitors H and I were low in starving anorectics and normalized with weight gain. C3a levels were comparable in anorectics at low weight and after weight gain, indicating that low serum complement levels were attributable to hypoproduction and not complement cascade activation with consumption. Further, levels of C3, B, AP50, H and I, but not D, were higher than controls in obese patients and decreased toward normal after weight loss. Overall, percentage of ideal body weight, changes in body weight, and serum transferrin were each highly correlated with serum levels of complement proteins. We conclude that levels of alternative pathway complement components are determined in part by factors that influence body weight and by weight changes, possibly due to changes in production in adipose tissue or at other sites.

Adult↗
PubMed1997

Role of gamma interferon in the pathogenesis of bacteremic pneumococcal pneumonia.

Gamma interferon (IFN-gamma) concentrations in blood, but not in lungs, rose significantly at 24 to 48 h after murine pulmonary infection with virulent pneumococci. In contrast, infection with avirulent pneumococcal strains produced minimal rises in serum IFN-gamma concentrations. Compared with that of immunocompetent mice, mortality was appreciably increased after pulmonary infection of IFN-gamma gene knockout mice, suggesting a protective role for IFN-gamma in host response to pneumococcal disease.

Animals↗