Some factors affecting the response of muscle to insulin.
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ABSTRACT:
SUBMITTER: Manchester KL
PROVIDER: S-EPMC1264912 | biostudies-other | 1966 Mar
REPOSITORIES: biostudies-other
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Project description:Asthma is a frequent disease, mainly characterized by airway inflammation, in which drug therapy is crucial in its management. The potential of pharmacogenomics testing in asthma therapy has been, to date, little explored. In this review, we discuss pharmacogenetic factors affecting asthma treatment, both related to drugs used as controller medications for regular maintenance, such as inhaled corticosteroids, anti-leukotriene agents, long-acting beta-agonists, and the new biologic agents used to treat severe persistent asthma. In addition, we discuss current pharmacogenomics knowledge for rescue medications provided to all patients for as-needed relief, such as short-acting beta-agonists. Evidence for genetic variations as a factor related to drugs response has been provided for the following genes and groups of drugs: Inhaled corticosteroids: FCER2; anti-leukotriene agents: ABCC1, and LTC4S; beta-agonists: ADRB2. However, the following genes require further studies confirming or rejecting association with the response to asthma therapy: ADCY9, ALOX5, ARG1, ARG2, CRHR1, CRHR2, CYP3A4, CYP3A5, CYSLTR1, CYSLTR2, GLCCI1, IL4RA, LTA4H, ORMDL3, SLCO2B1, SPATS2L, STIP1, T, TBX21, THRA, THRB, and VEGFA. Although only a minority of these genes are, at present, listed as associated with drugs used in asthma therapy, in the Clinical Pharmacogenomics Implementation Consortium gene-drug pair list, this review reveals that sufficient evidence to start testing the potential of clinical pharmacogenomics in asthma therapy already exists. This evidence supports the inclusion in pilot pharmacogenetics tests of at least four genes. Hopefully these tests, if proven useful, will increase the efficiency and the safety of asthma therapy.
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Project description:ContextThere is limited research on what factors are most salient to implementation of evidence-based practices (EBPs) among public health agencies in public health emergency preparedness and response (PHPR) and under what conditions EBP implementation will occur.ObjectiveThis study assessed the conditions, barriers, and enablers affecting EBP implementation among the PHPR practice community and identified opportunities to support EBP implementation.DesignA Web-based survey gathered information from public health agencies. Data obtained from 228 participating agencies were analyzed.SettingState, local, and territorial public health agencies across the United States.ParticipantsPreparedness program officials from 228 public health agencies in the United States, including Public Health Emergency Preparedness (PHEP) cooperative agreement awardees (PHEP awardees) and a random sample of local health departments (LHDs).ResultsRespondents indicated that EBP is necessary and improves PHPR functions and tasks and that staff are interested in improving skills for EBP implementation. Top system-level barriers to EBP implementation were insufficient funding, lack of EBP, and lack of clarity regarding which practices are evidence based. PHEP awardees were significantly more likely to report a lack of EBP in the field, whereas LHDs were significantly more likely to report a lack of incentives. The top organizational-level barrier was insufficient staff. Most respondents indicated their agency culture supports EBP; however, LHDs were significantly more likely to report a lack of support from supervisors and leadership. Few respondents reported individual barriers to EBP implementation.ConclusionsFindings indicate an opportunity to improve dissemination strategies, communication efforts, and incentives to support EBP implementation in PHPR. Potential strategies include improving awareness of and accessibility to EBPs through targeted dissemination efforts; building organizational capacity to support EBP implementation, particularly staff capacity, knowledge, and skills; and identifying funding and incentives to promote EBP uptake and sustainment.
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Project description:ObjectivesThe primary goal of this study was to characterize the clinical presentation of feline cutaneous lymphoma. The secondary aims included determining if treatment or initial response to treatment affected the overall survival of patients, and understanding if disease characteristics such as immunophenotype, cell size or the presence of epitheliotropism influenced response to treatment.MethodsVeterinary medical oncologists at four academic veterinary teaching hospitals submitted cases of feline patients with cutaneous lymphoma diagnosed by histopathology or cytology. Signalment, feline leukemia virus (FeLV)/feline immunodeficiency virus (FIV) status, physical examination findings, clinical signs, diagnostic tests, therapy, response and outcome, and necropsy findings, when available, were recorded.ResultsForty-one patients were identified and described. The majority of patients were domestic shorthair cats (n = 29). The median age at diagnosis was 12.3 years. Males were over-represented in the population (n = 30). In the majority of patients (n = 33), the FIV/FeLV status was unknown. Twenty patients were fully staged. Thirty-four patients were treated with a variety of modalities, including surgery, radiation, single-agent or combination chemotherapy, or prednisolone only. In multiple patients, surgery or radiation was combined with a systemic therapy. Of 34 patients treated with some form of therapy, 20 responded (achieving either a partial response or complete remission).Conclusions and relevanceClinical signs and physical examination findings varied among patients. Response to therapy appeared to be associated with survival (P = 0.0025); however, this population was highly censored. Immunophenotype, cell size and the presence of epitheliotropism did not influence treatment response. Results were limited by small numbers of patients, heterogeneous disease manifestations and treatment protocols. Further studies are necessary to evaluate the effect of specific treatment modalities and disease subtype on prognosis.
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Project description:ContextInterruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear.ObjectiveTo test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans.DesignWe conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet.SettingAcademic clinical research center.ParticipantsHealthy, nondiabetic, normotensive volunteers.InterventionsInfusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5-7 days.Main outcome measuresChange in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle.ResultsA low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (-16.0 ± 5.6%; P = .007) and C-peptide responses (-21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (-1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion.ConclusionsLow dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity.
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