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1.  Discordance of Tuberculin Skin Test and Interferon Gamma Release Assay in Recently Exposed Household Contacts of Pulmonary TB Cases in Brazil 
PLoS ONE  2014;9(5):e96564.
Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8–12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.
doi:10.1371/journal.pone.0096564
PMCID: PMC4018294  PMID: 24819060
2.  Influence of Age and Nutritional Status on Flight Performance of the Asian Tiger Mosquito Aedes albopictus (Diptera: Culicidae) 
Insects  2013;4(3):404-412.
The Asian tiger mosquito, Aedes albopictus, is a competent vector for arboviruses and recently was implicated as the vector of the first autochthonous cases of dengue and chikungunya in southern Europe. The objective of this study was to analyze the flight performance of female Ae. albopictus of different ages that were starved, sugar-fed, or sugar-fed and blood-fed, using flight mills. After three days of starvation post emergence, females flew an average distance of 0.7 ± 0.5 km in 1.9 ± 1.5 h during a 16 h trial period, whereas sugar- or sugar- and blood-fed females of this age covered a significantly higher distance of around 3 km with a mean total flight time of around 6 h. The age of females (up to four weeks) had no effect on performance. The average of maximal continuous flight segments of sugar-fed (2.14 ± 0.69 h) and blood-fed (3.17 ± 0.82 h) females was distinctly higher than of starved females (0.38 ± 0.15 h) of which most flyers (83%) performed maximal flight segments that lasted no longer than 0.5 h. Overall, the results for the laboratory monitored flight performance of Ae. albopictus confirm their ability to disperse a few kilometres between breeding site and host.
doi:10.3390/insects4030404
PMCID: PMC3882092  PMID: 24404384
Aedes albopictus; flight potential; distance; vector; mosquito
3.  The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men 
Background.
Concerns about potential adverse effects of testosterone on prostate have motivated the development of selective androgen receptor modulators that display tissue-selective activation of androgenic signaling. LGD-4033, a novel nonsteroidal, oral selective androgen receptor modulator, binds androgen receptor with high affinity and selectivity.
Objectives.
To evaluate the safety, tolerability, pharmacokinetics, and effects of ascending doses of LGD-4033 administered daily for 21 days on lean body mass, muscle strength, stair-climbing power, and sex hormones.
Methods.
In this placebo-controlled study, 76 healthy men (21–50 years) were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days. Blood counts, chemistries, lipids, prostate-specific antigen, electrocardiogram, hormones, lean and fat mass, and muscle strength were measured during and for 5 weeks after intervention.
Results.
LGD-4033 was well tolerated. There were no drug-related serious adverse events. Frequency of adverse events was similar between active and placebo groups. Hemoglobin, prostate-specific antigen, aspartate aminotransferase, alanine aminotransferase, or QT intervals did not change significantly at any dose. LGD-4033 had a long elimination half-life and dose-proportional accumulation upon multiple dosing. LGD-4033 administration was associated with dose-dependent suppression of total testosterone, sex hormone–binding globulin, high density lipoprotein cholesterol, and triglyceride levels. follicle-stimulating hormone and free testosterone showed significant suppression at 1.0-mg dose only. Lean body mass increased dose dependently, but fat mass did not change significantly. Hormone levels and lipids returned to baseline after treatment discontinuation.
Conclusions.
LGD-4033 was safe, had favorable pharmacokinetic profile, and increased lean body mass even during this short period without change in prostate-specific antigen. Longer randomized trials should evaluate its efficacy in improving physical function and health outcomes in select populations.
doi:10.1093/gerona/gls078
PMCID: PMC4111291  PMID: 22459616
Selective androgen receptor modulators; SARMs; Sarcopenia; Function promoting anabolic therapies; Cachexia
4.  Clinical Meaningfulness of the Changes in Muscle Performance and Physical Function Associated With Testosterone Administration in Older Men With Mobility Limitation 
Context.
Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation. Trial’s Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm. The changes in muscle performance and physical function were evaluated in relation to participant’s perception of change.
Methods.
Men aged 65 years and older, with mobility limitation, total testosterone 100–350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months. Primary outcome was leg-press strength. Secondary outcomes included chest-press strength, stair-climb, 40-m walk, muscle mass, physical activity, self-reported function, and fatigue. Proportions of participants exceeding minimally important difference in study arms were compared.
Results.
Of 209 randomized participants, 165 had follow-up efficacy measures. Mean (SD) age was 74 (5.4) years and short physical performance battery score 7.7 (1.4). Testosterone arm exhibited greater improvements in leg-press strength, chest-press strength and power, and loaded stair-climb than placebo. Compared with placebo, significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths (43% vs 18%, p = .01) and stair-climbing power (28% vs 10%, p = .03) more than minimally important difference. Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass. Physical activity, walking speed, self-reported function, and fatigue did not change.
Conclusions.
Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power. Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population.
doi:10.1093/gerona/glr100
PMCID: PMC3202898  PMID: 21697501
Testosterone; Minimally important difference; Mobility limitation; Older men; Function promoting therapies
5.  Adverse Events Associated with Testosterone Administration 
The New England journal of medicine  2010;363(2):109-122.
Background
Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied.
Methods
Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group.
Results
A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load.
Conclusions
In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy.
doi:10.1056/NEJMoa1000485
PMCID: PMC3440621  PMID: 20592293
6.  Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications 
Asian Journal of Andrology  2012;14(2):222-225.
Prostate cancer (PCa) is the most common malignancy in men. Prostate being an androgen responsive tissue, androgen deprivation therapy (ADT) is used in the management of locally advanced (improves survival) and metastatic (improves pain and quality of life) PCa. Over the past two decades, the use of ADT has significantly increased as it is also being used in patients with localized disease and those experiencing biochemical recurrences, though without any evidence of survival advantage. Hypogonadism resulting from ADT is associated with decreased muscle mass and strength, increased fat mass, sexual dysfunction, vasomotor symptoms, decreased quality of life, anemia and bone loss. Insulin resistance, diabetes and cardiovascular disease have recently been added to the list of these complications. As the majority of men with PCa die of conditions other than their primary malignancy, recognition and management of these adverse effects is paramount. Here we review data evaluating metabolic and cardiovascular complications of ADT.
doi:10.1038/aja.2011.109
PMCID: PMC3735099  PMID: 22343494
androgen deprivation therapy; cardiovascular disease; diabetes; hypogonadism; prostate cancer
7.  Generation of Attenuated Mycobacterium bovis Strains by Signature-Tagged Mutagenesis for Discovery of Novel Vaccine Candidates  
Infection and Immunity  2005;73(4):2379-2386.
Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex, has a particularly wide host range and causes tuberculosis in most mammals, including humans. A signature tag mutagenesis approach, which employed illegitimate recombination and infection of guinea pigs, was applied to M. bovis to discover genes important for virulence and to find potential vaccine candidates. Fifteen attenuated mutants were identified, four of which produced no lesions when inoculated separately into guinea pigs. One of these four mutants had nine deleted genes including mmpL4 and sigK and, in guinea pigs with aerosol challenge, provided protection against tuberculosis at least equal to that of M. bovis BCG. Seven mutants had mutations near the esxA (esat-6) locus, and immunoblot analysis of these confirmed the essential role of other genes at this locus in the secretion of EsxA (ESAT-6) and EsxB (CFP10). Mutations in the eight other attenuated mutants were widely spread through the chromosome and included pks1, which is naturally inactivated in clinical strains of M. tuberculosis. Many genes identified were different from those found by signature tag mutagenesis of M. tuberculosis by use of a mouse infection model and illustrate how the use of different approaches enables identification of a wider range of attenuating mutants.
doi:10.1128/IAI.73.4.2379-2386.2005
PMCID: PMC1087418  PMID: 15784584

Results 1-7 (7)