A cost-effective training tool for flexor tendon repair: pig's trotters.
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Animals↗
Biomedical subjects
T C Wright
Publications and source records attributed to T C Wright.
Acetyl CoA carboxylase shares control of fatty acid synthesis with fatty acid synthase in bovine mammary homogenate.
The objectives of this research were to determine the flux control coefficients for acetyl CoA carboxylase and fatty acid synthase using an in vitro preparation of bovine mammary homogenate. For an enzyme to be considered rate limiting with the use of metabolic control analysis, its control coefficient would be equal to unity. The hypothesis for this experiment was that the control coefficient for acetyl CoA carboxylase was not equal to unity, and that this enzyme was not, therefore, the rate-limiting step. Mammary tissue was isolated from lactating Holstein cows at slaughter and frozen in liquid nitrogen. Tissue was ground, homogenized, and centrifuged to obtain a postmitochondrial supernatant for use in in vitro incubations containing labeled acetate. Specific inhibitors for acetyl CoA carboxylase and fatty acid synthase were used to fractionally inhibit de novo synthesis for the calculation of flux control coefficients. The composition of fatty acids synthesized in the absence of enzyme inhibitors was similar to the composition of fatty acids in the presence of inhibitors. Calculations following avidin inhibition of acetyl CoA carboxylase determined the flux control coefficient was 0.63 +/- 0.15, which means that 63% of the control of fatty acid synthesis is exerted by acetyl CoA carboxylase. The remaining control (37%) was from fatty acid synthase, which indicates a significant degree of control over the flux of acetate in de novo synthesis resides with this enzyme. The rate-limiting status ascribed to acetyl CoA carboxylase was not supported, because the flux control coefficient was less than unity. Metabolic control analysis, through its use of pathway product measurements, allows for potential interactions in the pathway such as feedback inhibition contribution to the flux control coefficients, which would not otherwise be considered in studies measuring enzyme kinetics with purified enzymes.
Acetates↗
Leakage of liquefied petroleum gas during motor vehicle refuelling--a new cause of cold injury.
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Accidents, Occupational↗
Human papillomavirus testing and screening.
Cervical cancer is a largely preventable disease through the detection, treatment and follow-up of its precursors. Traditionally, this has been accomplished through screening women with cervical cytology, and referring women with abnormal cytology for colposcopy, histological sampling and treatment. In organized programmes that achieve wide coverage of the target population at frequent intervals, this approach has resulted in a considerable reduction in cervical cancer. Recently, however, the development of reliable and reproducible tests for the detection of human papillomavirus (HPV) infection of the cervix (which is now accepted to be causally associated with the development of almost all cervical cancers) has led to the evaluation of HPV de-oxyribonucleic acid (DNA) testing as either an alternative or adjunctive test to cytology for the detection of cervical cancer and its precursors. There is now a large body of data supporting the clinical utility of HPV DNA testing for the prevention of cervical cancer, particularly in the settings of primary screening of women older than 30 years, in the triage of women with equivocal cytology and for the follow-up of women post-treatment.
Adult↗
Anal intraepithelial neoplasia in heterosexual and homosexual HIV-positive men with access to antiretroviral therapy.
BACKGROUND: Studies of human immunodeficiency virus (HIV)-positive men have demonstrated high rates of anal intraepithelial neoplasia (AIN), a precursor to anal carcinoma, mostly in white homosexual men and men not receiving effective antiretroviral therapy (ART). METHODS: Ninety-two participants--53% Latino, 36% African American, and 40% without a history of receptive anal intercourse (RAI)--were evaluated with a behavioral questionnaire, liquid-based anal cytological testing, Hybrid Capture 2 human papillomavirus (HPV) DNA assay and polymerase chain reaction, and anal colposcopy with biopsy of lesions. RESULTS: High-risk HPV DNA was identified in 61%, and this was associated with a history of RAI (78% vs. 33%; P<.001); 47% had abnormal cytological results, and 40% had AIN on biopsy. In multivariate analysis, both were associated with a history of RAI (odds ratio [OR], 10 [P<.001] and OR, 3.6 [P=.02], respectively) and lower nadir CD4(+) cell counts (P=.06 and P=.01). Current ART use was protective (OR, 0.09; P<.01 and OR, 0.18; P=.02). CONCLUSIONS: Although anal infections with high-risk HPV and AIN in HIV-positive men are associated with a history of RAI, both conditions are commonly identified in HIV-positive men without this history. Both lower nadir CD4(+) cell counts and lack of current ART were associated with AIN but not with the detection of anal HPV.
Adult↗
Effect of combinations of fish meal and feather meal on milk fatty acid content and nitrogen utilization in dairy cows.
The effect of supplemental fishmeal in combination with feathermeal at two different proportions in the diet on milk docosahexaenoic acid (DHA) content was investigated. Recently, benefits to human health have been attributed to the consumption of this fatty acid, which is normally present in marine lipids. Six Holstein cows past peak lactation were used in a Latin square design with a 2 x 3 factorial arrangement of treatments. Fish- and feathermeals were prepared as pellets at 4:1 and 1:4 combinations and offered at 3.75, 11.75, and 27% of the diet. The supplements were top-dressed onto a basal diet based on corn silage that was progressively replaced by supplement. Nitrogen balance measures were made during the experiment because of the wide range in crude protein content of experimental diets. Milk protein content increased with level of supplementation in the diet reflecting the protein quality of the supplements used. There was overall higher milk DHA content when cows consumed the supplement containing more fishmeal than feather meal. Milk DHA content increased in a quadratic fashion, as more of either supplement was included in the diet. Apparent transfer efficiency of DHA from diet to milk declined with increasing amount of DHA in the diet. Results from this experiment suggest that transfer of docosahexaenoic acid from diet to milk may depend on diet composition and quantity present in the diet.
Animals↗
Physical and processing properties of milk, butter, and cheddar cheese from cows fed supplemental fish meal.
Physical, chemical, sensory and processing properties of milk produced by feeding a rumen-undegradable fish meal protein supplement to Holstein cows were investigated. The supplement contained (as fed basis) 25% soft-white wheat, 60% herring meal, and 15% feather meal. The total fat level in the milk decreased to 2.43%. For both pasteurized and ultra-high temperature processed drinking milk, no difference was found between fish meal (FM) milk and control milk in terms of color, flavor and flavor stability; in particular, no oxidized flavor was observed. Cheddar cheese made from FM milk ripened faster after 3 mo of ripening and developed a more desirable texture and stronger Cheddar flavor. The yield efficiencies for FM and control cheese, 94.4 (+/- 2.44 SE) and 96.4 (+/- 2.26 SE), respectively, were not different. Relative to controls, average fat globule size was smaller in FM milk and churning time of FM cream was longer. FM butter had softer texture and better cold spreadability, and butter oils from FM enriched milk had lower dropping points compared to control butter oil (average 32.89 versus 34.06 degrees C). These differences in physical properties of butter fat were greater than expected considering that iodine values were not different. This study demonstrates the feasibility of producing high quality products from milk naturally supplemented with FM, but the results also show that dietary changes affect processing properties.
Animal Feed↗
Assessment of the cervix after acetic acid wash: inter-rater agreement using photographs.
OBJECTIVE: To estimate the inter-rater agreement on the assessment of cervical photographs after acetic acid wash, using visual inspection with acetic acid categories. METHODS: Three raters individually assessed 144 photographs as negative, positive, or suspicious for cancer. The inter-rater agreement was analyzed using the unweighted and weighted kappa coefficient. To explore the reasons for concordancy and discordancy, photographs were compared on histologic evidence of cervical intraepithelial neoplasia and on testing for oncogenic types of human papillomavirus. RESULTS: Overall raw agreement among the three raters was 66.7% (96 of 144) with a kappa of 0.57 (95% confidence interval 0.48, 0.66). Pair-wise agreement using unweighted and weighted kappa was moderate to substantial: 0.54-0.60 and 0.56-0.63, respectively. There was concordance on negative in 25.7% (37 of 144) and on positive or suspicious for cancer in 41.0% (59 of 144). Cervical intraepithelial neoplasia II or III was not present on biopsy if photographs were concordant-negative, and the human papillomavirus test was less likely to be positive (relative risk 0.3; 95% confidence interval 0.2, 0.6) in concordant-negatives compared with concordant-positives, including suspicious for cancer. Cervical intraepithelial neoplasia II or III was more common in photographs that were concordant-positive, including suspicious for cancer, compared with discordants (relative risk 3.4, 95% confidence interval 1.5, 7.6). CONCLUSION: Based on photographs of the cervix taken after acetic acid wash, the level of agreement among raters using visual inspection with acetic acid categories was moderate to substantial, consistent with other commonly used tests.
Acetic Acid↗
Inhibition of fatty acid synthesis in bovine mammary homogenate by palmitic acid is not a detergent effect.
Supplemental fat fed to dairy cows affects the fat composition of milk by reducing the yield of mammary synthesized fatty acids. The effect has been attributed to a potential allosteric inhibition of acetyl coenzyme-A, a key enzyme in fatty acid synthesis. In vitro experiments have demonstrated an inhibition of fatty acid synthesis when long-chain fatty acids are added to incubations. However, in vitro inhibition can result from a nonspecific detergent effect arising from an inherent physical property of fatty acids. An allosteric role for palmitic acid has not been tested in bovine mammary tissue. The objective of this experiment was to test the hypothesis that palmitic acid is an allosteric inhibitor of fatty acid synthesis in mammary tissue. We tested for a detergent effect by including a synthetic detergent, sodium dodecyl sulfate, under identical incubation conditions. A subcellular supernatant fraction of mammary tissue was used for incubations in the present experiment. The incubation system produced free fatty acids in a linear fashion for time and protein content. Results indicated that fatty acid synthesis was affected by the addition of palmitic acid to the incubations but not by caprylic acid, a short-chain fatty acid. Sodium dodecyl sulfate did not affect fatty acid synthesis at the concentrations used. The results of the present experiment indicate that palmitic acid inhibited fatty acid synthesis, and the effect was not the result of a detergent effect.
Acetyl Coenzyme A↗
Policy analysis of cervical cancer screening strategies in low-resource settings: clinical benefits and cost-effectiveness.
CONTEXT: Cervical cancer is a leading cause of cancer-related death among women in developing countries. In such low-resource settings, cytology-based screening is difficult to implement, and less complex strategies may offer additional options. OBJECTIVE: To assess the cost-effectiveness of several cervical cancer screening strategies using population-specific data. DESIGN AND SETTING: Cost-effectiveness analysis using a mathematical model and a hypothetical cohort of previously unscreened 30-year-old black South African women. Screening tests included direct visual inspection (DVI) of the cervix, cytologic methods, and testing for high-risk types of human papillomavirus (HPV) DNA. Strategies differed by number of clinical visits, screening frequency, and response to a positive test result. Data sources included a South African screening study, national surveys and fee schedules, and published literature. MAIN OUTCOME MEASURES: Years of life saved (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios (cost per YLS). RESULTS: When analyzing all strategies performed as a single lifetime screen at age 35 years compared with no screening, HPV testing followed by treatment of screen-positive women at a second visit, cost $39/YLS (27% cancer incidence reduction); DVI, coupled with immediate treatment of screen-positive women at the first visit was next most effective (26% cancer incidence reduction) and was cost saving; cytology, followed by treatment of screen-positive women at a second visit was least effective (19% cancer incidence reduction) at a cost of $81/YLS. For any given screening frequency, when strategies were compared incrementally, HPV DNA testing generally was more effective but also more costly than DVI, and always was more effective and less costly than cytology. When comparing all strategies simultaneously across screening frequencies, DVI was the nondominated strategy up to a frequency of every 3 years (incremental cost-effectiveness ratio, $460/YLS), and HPV testing every 3 years (incremental cost-effectiveness ratio, $11 500/YLS) was the most effective strategy. CONCLUSION: Cervical cancer screening strategies that incorporate DVI or HPV DNA testing and eliminate colposcopy may offer attractive alternatives to cytology-based screening programs in low-resource settings.
Adult↗
Cellular replication of human immunodeficiency virus type 1 occurs in vaginal secretions.
Most human immunodeficiency virus type 1 (HIV-1) transmission worldwide is the result of exposure to infectious virus in genital secretions. However, current vaccine candidates are based on virus isolates from blood. In this study, vaginal secretions from HIV-1-infected women were examined for evidence of cellular viral replication that produced virus with properties different from that in blood. Multiply spliced HIV-1 messenger RNA, which is found only in cells replicating virus, was detected in all vaginal lavage samples tested. There was a strong correlation between the amounts of multiply spliced HIV-1 messenger RNA and of cell-free HIV-1 RNA in the lavage samples. In addition, significant genotypic differences were found in cell-free virus from matched blood plasma and vaginal secretions. Moreover, drug resistance-associated mutations appeared in plasma virus several months before appearing in vaginal virus. These findings indicate that cellular replication of HIV-1 occurs in vaginal secretions and can result in a virus population with important differences from that in blood.
Adolescent↗
Cost effectiveness of human papillomavirus testing to augment cervical cancer screening in women infected with the human immunodeficiency virus.
PURPOSE: To determine the cost effectiveness of incorporating molecular testing for high-risk types of human papillomavirus into a cervical cancer screening program for women infected with the human immunodeficiency virus (HIV). SUBJECTS AND METHODS: We developed a Markov model to simulate the natural history of cervical cancer precursor lesions in HIV-infected women. Probabilities of progression and regression of cervical lesions were conditional on transient or persistent infection with human papillomavirus, as well as stage of HIV and effectiveness of antiretroviral therapy. Incorporating data from prospective cohort studies, national databases, and published literature, the model was used to calculate quality-adjusted life expectancy, life expectancy, lifetime costs, and incremental cost-effectiveness ratios for two main strategies: targeted screening-human papillomavirus testing is added to the initial two cervical cytology smears obtained after an HIV diagnosis and subsequent screening intervals are modified based on the test results; and universal screening-no testing for human papillomavirus is performed, and a single cytology screening interval is applied to all women. RESULTS: In HIV-infected women on anti-retroviral therapy, a targeted screening strategy in which cervical cytology screening was conducted every 6 months for women with detected human papillomavirus DNA, and annually for all others, cost $10,000 to $14,000 per quality-adjusted life year gained compared with no screening. A universal screening strategy consisting of annual cervical cytology for all women was 15% less effective and had a less attractive cost-effectiveness ratio. Targeted screening remained economically attractive in multiple sensitivity analyses, although when the overall incidence of cervical cancer precursor lesions was lowered by 75%, the screening interval for women with detected human papillomavirus DNA could be widened to 1 year. CONCLUSIONS: Adding human papillomavirus testing to the two cervical cytology smears obtained in the year after an HIV diagnosis, and modifying subsequent cytology screening intervals based on the results, appears to be an effective and cost-effective modification to current recommendations for annual cytology screening in HIV-infected women.
AIDS-Related Opportunistic Infections↗
Tissue response to the STOP microcoil transcervical permanent contraceptive device: results from a prehysterectomy study.
OBJECTIVE: The present study examines the safety, effectiveness, and local tissue response for a new transcervical fallopian tube permanent contraceptive device, the STOP device (Conceptus, Inc., San Carlos, CA). DESIGN: Nonrandomized prospective evaluation of tubal occlusion and histologic response. SETTING: Inpatient, university and university-affiliated medical centers in the United States and Mexico. PATIENT(S): Premenopausal and perimenopausal women with benign indications for hysterectomy who were able to defer their hysterectomy for 1 to 13 weeks. INTERVENTION(S): A transcervically placed microcoil (STOP device) was inserted into the fallopian tubes of women who were scheduled for hysterectomy, and the device was worn for 1 to 12 weeks. At hysterectomy, hysterosalpingography was done to determine tubal occlusion; subsequently, the tubes containing the STOP devices were processed, sectioned, and evaluated to determine the histologic response. MAIN OUTCOME MEASURE(S): Ability to place a device and evaluate tubal occlusion and tissue response. RESULT(S): Devices were placed in 33 women, representing 57 tubes; the women wore the devices from 1 day to 30 weeks. Histology on 27 women (47 tubes) showed an acute inflammatory and fibrotic response in the short term that, over time, became a chronic inflammatory response with extensive fibrosis. CONCLUSION(S): The localized tissue response and notable absence of any normal tubal architecture in the segment of the fallopian tube containing the STOP device supports the postulated mechanisms of action of the device. Prehysterectomy study findings suggest the usefulness of the STOP device for pregnancy prevention, this is being evaluated in long-term safety and effectiveness studies.
Fallopian Tubes↗
Human immunodeficiency virus 1 expression in the female genital tract in association with cervical inflammation and ulceration.
OBJECTIVES: Determining the source of human immunodeficiency virus 1 in the female genital tract and identifying factors that influence the amount of virus shed are important in the understanding of heterosexual human immunodeficiency virus 1 transmission. STUDY DESIGN: Cervicovaginal human immunodeficiency virus 1 ribonucleic acid shedding was quantified before and after treatment of cervical squamous intraepithelial lesions in 14 women. Genotypic analysis was performed on peptide HIV-1 env gp120 of the major human immunodeficiency virus 1 species in plasma and cervicovaginal lavage of selected samples. RESULTS: At 2 to 4 weeks after treatment, when cervices were inflamed and ulcerated, human immunodeficiency virus 1 ribonucleic acid in lavage samples increased 1.0 to 4.4 log 10. Genotypic analysis showed significant differences between the predominant human immunodeficiency virus 1 species in paired plasma and lavage samples from 2 of 4 women, suggesting that the increase in human immunodeficiency virus 1 was the result of local viral replication. CONCLUSIONS: Cervical inflammation and ulceration are associated with local human immunodeficiency virus 1 expression, which increases as much as 10,000-fold the amount of human immunodeficiency virus 1 shed into genital secretions. This may explain why sexually transmitted diseases are important risk factors for human immunodeficiency virus transmission.
Adult↗
Chlamydia trachomatis and Pap testing from a single, fluid-based sample. A multicenter study.
OBJECTIVE: To determine the potential for both Pap testing and the Chlamydia direct fluorescence assay (DFA) from a single sample using the fluid-based ThinPrep Pap Test method (Cytyc Corporation, Boxborough, Massachusetts). STUDY DESIGN: Conventional DFA was compared to ThinPrep DFA in a direct-to-vial, double-blinded, multicenter protocol. Cervical scrapings were collected for the ThinPrep Pap Test, and then a second swab was used to collect an endocervical sample for a conventional DFA test. The DFA slide prepared from the ThinPrep Test and the conventional DFA sample prepared from the endocervical swab were evaluated independently. Discrepant cases were adjudicated by testing residual specimens using a Chlamydia direct DNA method. RESULTS: Combining 636 adequate cases (94% of the total collected), 582 (91.5%) were negative on both slides, 43 (6.8%) positive by both and 11 (1.7%) discrepant. The prevalence of Chlamydia was 7.9% based on the conventional DFA method (range, 4.3-10.9%). McNemar's two-tailed test indicated the results not to be statistically different (P > .05). Adjudication favored ThinPrep 45% of the time and conventional 55%. Specimen adequacy favored ThinPrep with high statistical significance (McNemar's test, P > .01). CONCLUSION: A second slide prepared from the same vial of cells as that used for the ThinPrep Pap Test can be used for Chlamydia testing by DFA. Fluid-based collection could allow multiple tests from a single sample.
Adolescent↗
Screening for cervical cancer.
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Costs and Cost Analysis↗
Evaluation of alternative methods of cervical cancer screening for resource-poor settings.
BACKGROUND: Noncytologic methods of screening for cervical carcinoma and its precursor lesions are needed for resource-poor settings in which cervical carcinoma continues to be an important cause of morbidity and mortality. METHODS: Two thousand nine hundred forty-four women ages 35-65 years were recruited from Cape Town, South Africa and screened using a combination of a Papanicolaou (Pap) smear, human papillomavirus (HPV) DNA testing, direct visual inspection after the application of a 5% acetic acid solution (DVI), and cervicography. Cervicography was considered primarily as a method with which to quality control the DVI examinations. Women with squamous intraepithelial lesions (SIL) or carcinoma on Pap smear, positive DVI examination (acetowhite lesion or cervical ulcer/growth), high levels of high risk HPV DNA (relative light units [RLU] > 10x positive control), or positive Cervigramtrade mark were referred for colposcopy and cervical biopsy. RESULTS: Pap smears were positive in 8.1% of all women screened and identified 65 (78%) of all cases of biopsy confirmed high grade disease (high grade SIL or invasive carcinoma). DVI and cervicography were classified as positive in 18.1% and 10.5%, respectively, of women screened and identified 58 (67%) and 46 (58%) of all cases of high grade disease, respectively. The results of HPV DNA testing varied depending on the cutoff value used to define a positive result. At the standard cutoff level (RLU > 1x positive control), 16.2% of women screened were classified as high risk HPV DNA positive, as were 63 women with high grade disease (73%). CONCLUSIONS: DVI and HPV DNA testing identified similar numbers of high grade SIL (cervical intraepithelial neoplasia Grade 2,3) and invasive carcinoma cases as Pap smears. However, both classify considerably more women without cervical disease as being test positive.
Adult↗
Correlation between human immunodeficiency virus type 1 RNA levels in the female genital tract and immune activation associated with ulceration of the cervix.
To address the hypothesis that local immune activation resulting from genital ulceration enhances human immunodeficiency virus type 1 (HIV-1) replication and shedding into the genital tract, paired plasma and cervicovaginal lavage (CVL) samples were obtained from 12 HIV-infected women before and after treatment of cervical intraepithelial lesions. Two weeks after treatment, inflammation and ulceration of the cervix were accompanied by major increases in mean concentrations of HIV-1 RNA (200-fold), tumor necrosis factor-alpha, interleukin 6, and soluble markers shed by activated lymphocytes and macrophages (sCD25 and sCD14, respectively) in CVL samples (P<.01 for each), but not plasma. Strong temporal and quantitative correlations were observed between concentrations of immunological markers and HIV-1 load in this compartment during a 10-week follow-up. Furthermore, in the presence of genital ulceration, HIV-1 in CVL samples was more readily captured by antibodies directed against virion-associated HLA-DR, a marker of host-cell activation, compared with virus in plasma. We suggest that local immune activation increases HIV-1 load in genital secretions, potentially increasing the risk of HIV-1 transmission.
Adult↗