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1.
Crit Care Med ; 52(7): 1113-1126, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38236075

ABSTRACT

OBJECTIVES: To provide a narrative review of hospital violence (HV) and its impact on critical care clinicians. DATA SOURCES: Detailed search strategy using PubMed and OVID Medline for English language articles describing HV, risk factors, precipitating events, consequences, and mitigation strategies. STUDY SELECTION: Studies that specifically addressed HV involving critical care medicine clinicians or their practice settings were selected. The time frame was limited to the last 15 years to enhance relevance to current practice. DATA EXTRACTION: Relevant descriptions or studies were reviewed, and abstracted data were parsed by setting, clinician type, location, social media events, impact, outcomes, and responses (agency, facility, health system, individual). DATA SYNTHESIS: HV is globally prevalent, especially in complex care environments, and correlates with a variety of factors including ICU stay duration, conflict, and has recently expanded to out-of-hospital occurrences; online violence as well as stalking is increasingly prevalent. An overlap with violent extremism and terrorism that impacts healthcare facilities and clinicians is similarly relevant. A number of approaches can reduce HV occurrence including, most notably, conflict management training, communication initiatives, and visitor flow and access management practices. Rescue training for HV occurrences seems prudent. CONCLUSIONS: HV is a global problem that impacts clinicians and imperils patient care. Specific initiatives to reduce HV drivers include individual training and system-wide adaptations. Future methods to identify potential perpetrators may leverage machine learning/augmented intelligence approaches.


Subject(s)
Critical Care , Humans , Critical Care/methods , Intensive Care Units , Risk Factors , Workplace Violence/prevention & control , Workplace Violence/statistics & numerical data , Violence/prevention & control
2.
Am J Cardiol ; 190: 98-101, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36608437

ABSTRACT

In the primary prevention of atherosclerotic cardiovascular disease (ASCVD), a significant portion of high-risk patients have diabetes. Two decades ago, patients with or without cardiovascular disease were identified as having coronary heart disease (CHD) risk equivalents because prospective studies showed that they were at risk for future CHD events equivalent to that of patients with established CHD. Thus, for patients with CHD, cholesterol guidelines recommended that patients with diabetes should be treated routinely with statins. However, recently, the treatment of diabetes has been greatly improved, and the risk for ASCVD has decreased. For this reason, it may be appropriate to re-evaluate the recommendations for routine use of statins in patients with diabetes. One of the major advances in the risk assessment for ASCVD is the introduction of coronary artery calcium measurement. This report will examine the role of coronary artery calcium scanning for the decision to initiate statin therapy in the primary prevention for patients with diabetes.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Coronary Artery Disease , Diabetes Mellitus , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Cardiovascular Diseases/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Calcium , Prospective Studies , Diabetes Mellitus/epidemiology , Risk Assessment , Coronary Artery Disease/prevention & control , Risk Factors
3.
J Clin Lipidol ; 17(1): 12-18, 2023.
Article in English | MEDLINE | ID: mdl-36593174

ABSTRACT

Current cholesterol guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) base statin treatment decisions on multiple risk factor algorithms (e.g., Pooled Cohort Equations [PCEs]). By available PCEs, most older middle-aged men are statin eligible. But several studies cast doubt on predictive accuracy of available PCEs for ASCVD risk assessment. Recent studies suggest that accuracy can be improved by measurement of coronary artery calcium (CAC). This method has the advantage of identifying men at low risk in whom statin therapy can be delayed for several years, provided they are monitored periodically for progression of CAC. Thus, there are two approaches to statin therapy in men ≥ 55 years: first all men could be treated routinely, or second, treatment can be based on the extent of coronary calcium. The latter could allow a sizable fraction of men to avoid treatment for several years or indefinitely. Whether with initial CAC scan or with periodic rescanning, a CAC score ≥ 100 Agatston units is high enough to warrant statin therapy. In otherwise high-risk men (e.g., diabetes, severe hypercholesterolemia, 10-year risk by PCE ≥ 20%), a statin is generally indicated without the need for CAC; but in special cases, CAC measurement may aid in treatment decisions.


Subject(s)
Atherosclerosis , Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Vascular Calcification , Male , Middle Aged , Humans , Coronary Artery Disease/prevention & control , Calcium , Coronary Vessels , Risk Factors , Risk Assessment , Primary Prevention/methods
4.
Skeletal Radiol ; 52(2): 157-165, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35978163

ABSTRACT

OBJECTIVE: To standardize a method for 1H MRS intramuscular absolute quantification of carnosine in the thigh, using a surface coil and water as internal reference. MATERIALS AND METHODS: Carnosine spectra were acquired in phantoms (5, 10, and 15 mM) as well as in the right gastrocnemius medialis (GM) and right vastus lateralis (VLM) muscles of young team sports athletes, using volume (VC) and surface (SC) coils on a 3 T scanner, with the same receiver gain. Water spectra were used as internal reference for the absolute quantification of carnosine. RESULTS: Phantom's experiments showed a maximum error of 7%, highlighting the validity of the measurements in the study setup. The carnosine concentrations (mmol/kg ww, mean ± SD) measured in the GM were 6.8 ± 2.2 with the VC (CcarVC) and 10.2 ± 3.0 with the SC (CcarSC) (P = 0.013; n = 9). Therefore, a correction was applied to these measurements (CcarVC = 0.6582*CcarSC), to make coils performance comparable (6.8 ± 2.2 for VC and 6.7 ± 2.0 for SC, P = 0.97). After that, only the SC was used to quantify carnosine in the VLM, where a concentration of 5.4 ± 1.5 (n = 30) was found, with significant differences between men (6.2 ± 1.3; n = 15) and women (4.6 ± 1.2; n = 15). The error in quantitation was 5.3-5.5% with both coils. CONCLUSION: The method using the SC and water as internal reference can be used to quantify carnosine in voluminous muscles and regions of the body in humans, where the VC is not suitable, such as the VLM.


Subject(s)
Carnosine , Male , Humans , Female , Quadriceps Muscle/diagnostic imaging , Water , Muscle, Skeletal/diagnostic imaging , Thigh
5.
J Clin Lipidol ; 16(4): 376-382, 2022.
Article in English | MEDLINE | ID: mdl-35614000

ABSTRACT

By current guidelines, statin treatment decisions depend on multiple risk factor algorithms (e.g., pooled cohort equations [PCEs]). By available PCEs most older middle-aged women are statin eligible. But several studies cast doubt on reliability of available PCEs for ASCVD risk assessment. An alternative method for risk assessment is a coronary artery calcium (CAC) score. Many older women have zero CAC, which equates to low risk for ASCVD; these women can delay statin therapy for several years before re-scanning. When CAC is 1-99 Agatston units, risk is only borderline high and statin delay also is an option until re-scanning. When CAC is > 100 Agatston units, risk is high enough to warrant a statin. In most women, CAC is the best guide to treatment decisions. In high-risk women (e.g., diabetes and severe hypercholesterolemia), generally are indicated, but CAC can assist in risk assessment, but other risk factors also can aid in treatment decisions.


Subject(s)
Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Vascular Calcification , Aged , Calcium , Coronary Artery Disease/drug therapy , Coronary Artery Disease/prevention & control , Coronary Vessels/diagnostic imaging , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Middle Aged , Primary Prevention/methods , Reproducibility of Results , Risk Assessment , Risk Factors , Vascular Calcification/prevention & control
7.
J Clin Lipidol ; 16(1): 66-74, 2022.
Article in English | MEDLINE | ID: mdl-34922882

ABSTRACT

BACKGROUND: Pooled cohort equations (PCEs) estimate 10-year risk for atherosclerotic cardiovascular disease (ASCVD) in US adults. One use is to guide statin eligibility. However, PCEs risk estimate is inaccurate in some US subpopulations. OBJECTIVE: Recent cholesterol guidelines proposed addition of risk enhancing factors to improve risk assessment for selection of statin therapy. This study examines frequencies of several risk enhancing biomarkers in NHANES subjects at intermediate risk (7.5 -<20% 10-year risk for ASCVD) and considers how they may be used to better assess risk for individuals. METHODS: Prevalence of the following biomarkers were determined; elevations in apolipoprotein B-containing lipoproteins, i.e., LDL cholesterol (LDL-C) (160-189 mg/dL), non-HDL-cholesterol (non-HDL-C) (190-219 mg/dL), or total apolipoprotein B (apoB) (≥ 130 mg/dL), serum triglyceride (≥175 mg/dL), hemoglobin A1c (5.7-6.4%), high sensitivity C-reactive protein (2-10 mg/L), and waist circumference ≥ 102 cm, and abnormal estimated glomerular filtration rate (15 - ≤ 60 mg/min/1.73 m2). RESULTS: 25% of NHANES population had intermediate risk. In this subpopulation, 85% had ≥ 1 biomarkers-similarly in women and men-with a third having ≥3 abnormal markers. Frequencies were not age-related, except in those 40-49 years, in whom > 40% had ≥3 abnormal biomarkers. It made little difference whether LDL-C, non-HDL-C or apoB was used as the atherogenic lipoprotein. CONCLUSION: Three or more enhancing risk factors in intermediate risk subjects can complement PCE-estimated 10-year risk and guide the patient-provider discussion toward use of lipid-lowering medication. Future research is needed to integrate risk estimates by PCE and multiple risk enhancers.


Subject(s)
Atherosclerosis , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Adult , Apolipoproteins B , Biomarkers , Cholesterol , Cholesterol, LDL , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lipoproteins , Male , Middle Aged , Nutrition Surveys , Prevalence , Risk Factors , United States/epidemiology
8.
Toxicology ; 459: 152845, 2021 07.
Article in English | MEDLINE | ID: mdl-34246716

ABSTRACT

Serum concentrations of cholesterol are positively correlated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in humans. The associated change in cholesterol is small across a broad range of exposure to PFOA and PFOS. Animal studies generally have not indicated a mechanism that would account for the association in humans. The extent to which the relationship is causal is an open question. Nonetheless, the association is of particular importance because increased serum cholesterol has been considered as an endpoint to derive a point of departure in at least one recent risk assessment. To gain insight into potential mechanisms for the association, both causal and non-causal, an expert workshop was held Oct 31 and Nov 1, 2019 to discuss relevant data and propose new studies. In this report, we summarize the relevant background data, the discussion among the attendees, and their recommendations for further research.


Subject(s)
Cholesterol/blood , Environmental Exposure/adverse effects , Environmental Pollutants/blood , Fluorocarbons/toxicity , Alkanesulfonic Acids/adverse effects , Alkanesulfonic Acids/toxicity , Animals , Caprylates/adverse effects , Caprylates/toxicity , Endpoint Determination , Fluorocarbons/adverse effects , Humans
9.
J Clin Lipidol ; 15(2): 255-265, 2021.
Article in English | MEDLINE | ID: mdl-33663990

ABSTRACT

BACKGROUND: Statins effectively reduce risk for atherosclerotic cardiovascular disease (ASCVD) when 10-year risk is ≥ 7.5%. In many patients at intermediate risk (7.5-<20% risk), there is uncertainty about reliability of risk assessment by current pooled cohort equations (PCE). A decision to initiate statin therapy is favored by several risk enhancing factors not employed in PCEs. OBJECTIVE: This study examines the scope of the metabolic syndrome, a risk enhancing factor, and its principal sequala, diabetes, in 26,796 US adults age 40-75 years from the NHANES survey data, 1999-2016. METHODS: The prevalence of metabolic syndrome without diabetes (MetS+) and of diabetes (DM+) were determined for 10-year risk categories estimated to be low (<7.5%), intermediate (7.5% -< 20%) and high (≥20%). Data were weighted to account for complex study design. RESULTS: 90.4% of the population was free of ASCVD. In subjects projected to be at low risk by PCEs, MetS+ was present in 15.0% and 17.6% of women and men, respectively. MetS + increased to 30.6% of women and 29.6% of men at intermediate risk, and to 21.5% of women and 32.2% of men at high risk. In addition, DM+ was present in 6.1%/5.3% (F/M) of low risk individuals, 20.1%/14.8% (F/M) of intermediate risk subjects, and 44.3%/39.4% (F/M) of high-risk persons. Prevalence of both MetS+ and DM + rose progressively with age in women and men. CONCLUSIONS: MetS+ and DM + are common multiplex risk factors that predispose to higher lifetime risk and support statin therapy in patients at intermediate and high risk.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Atherosclerosis , Humans , Metabolic Syndrome , Risk Factors
10.
J Clin Lipidol ; 15(1): 173-180, 2021.
Article in English | MEDLINE | ID: mdl-33191195

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). American cardiovascular societies consider CKD a risk-enhancing factor that supports statin therapy in intermediate-risk patients aged 40-75 years. In contrast, European cardiovascular societies recommend statins for all middle-aged adults with CKD. The Kidney Disease: Improving Global Outcomes lipid management guideline for CKD recommends statin therapy for all patients with CKD >50 years. Clinical implications for these differences have not been examined. OBJECTIVE: This study examines CKD prevalence and statin eligibility in non-ASCVD adults, representative of the US population, at 3 levels of 10-year risk of ASCVD estimated by pooled cohort equations. METHODS: National Health and Nutrition Examination Surveys 1999-2016 weighted data were evaluated for CKD defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2. Overall prevalence of low, intermediate, and high 10-year risk for ASCVD was determined. RESULTS: A total of 92.5% of all participants had estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2; 7.5% (confidence interval 6.9%, 8.1%) had CKD. Among participants with CKD, 46.3% had 10-year risk for ASCVD <7.5% (low risk); 31.7% had intermediate risk (7.5-< 20%), and 22.0% had high risk (≥20%). In participants with CKD, 62.5% were women. A total of 19.6% of all participants with CKD had diabetes. A total of 46.3% of participants with CKD at intermediate or high risk reported taking cholesterol-lowering drugs. CONCLUSION: A total of 46.3% of patients with CKD aged 40-75 years had 10-year risk <7.5% (low risk) and hence were statin eligible by European and Kidney Disease: Improving Global Outcomes (>50 years) guidelines. US cardiovascular guidelines limit statin eligibility to intermediate- and high-risk CKD. Statin eligibility in lower-risk patients may be best determined by measuring coronary artery calcium.


Subject(s)
Atherosclerosis , Adult , Aged , Anticholesteremic Agents , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Middle Aged , Renal Insufficiency, Chronic , Risk Factors
11.
J Investig Med ; 68(6): 1141-1151, 2020 08.
Article in English | MEDLINE | ID: mdl-32474407

ABSTRACT

Optimal medical management of patients with peripheral arterial disease (PAD) includes statin therapy, which has been shown to decrease the risk of major cardiovascular events. However, the relationship between low-density lipoprotein (LDL) lowering, PAD progression and limb outcomes remains controversial. Although prevention of coronary and cerebrovascular events is a priority, limb outcomes are still important determinants of quality of life and healthcare spending. This review will highlight differences between coronary artery disease (CAD) and PAD, and in particular, the more prevalent role of lipids and LDL cholesterol in CAD versus calcification in PAD. This difference may contribute to the differential impact of LDL cholesterol levels on coronary events and outcomes versus limb outcomes. Beyond LDL lowering, immune modulators have emerged as another agent to treat atherosclerosis in CAD, however similar data in PAD are lacking. Small studies have suggested that other lipids besides LDL cholesterol, such as triglycerides or small dense LDL, may have a greater impact on limb outcomes in patients with PAD. Although statin therapy is central in the management of patients with PAD, current understanding of the distinctions between PAD and CAD suggest that there may be other non-LDL targets for risk reduction that require further study.


Subject(s)
Coronary Artery Disease , Hyperlipidemias/therapy , Peripheral Arterial Disease , Plaque, Atherosclerotic/pathology , Cholesterol, LDL/blood , Coronary Artery Disease/pathology , Coronary Artery Disease/prevention & control , Humans , Peripheral Arterial Disease/etiology , Peripheral Arterial Disease/pathology , Peripheral Arterial Disease/prevention & control , Plaque, Atherosclerotic/etiology , Plaque, Atherosclerotic/prevention & control , Risk Factors
12.
J Clin Lipidol ; 14(4): 425-430, 2020.
Article in English | MEDLINE | ID: mdl-32467016

ABSTRACT

BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) includes atherogenic cholesterol and low-density lipoproteins (LDL) and triglyceride-rich lipoproteins. Patients with diabetes frequently have elevations in non-HDL-C. OBJECTIVE: This study examines temporal trends in the levels of non-HDL-C in free-living subjects with diabetes but a negative history of atherosclerotic cardiovascular disease. METHODS: National Health and Nutrition Examination Surveys conducted between 1999 and 2016 had data from 3,219 adults (aged 40-75 years) with diabetes. Temporal trends in changes in the distribution of total cholesterol, non-HDL-C, LDL cholesterol (LDL-C), and HDL-C were evaluated. Data were weighted to account for complex survey design. RESULTS: Significant decreases were observed in non-HDL-C (20.1%; P < .0001) and total cholesterol (16.1%; P < .0001) levels between 1999 and 2016. No significant changes were noted in HDL-C levels. LDL-C was reduced by 29.6% in a subset of subjects. The reduction in non-HDL-C and LDL-C occurred simultaneously, with an increase of 4.4% of subjects per year taking cholesterol-lowering drugs and statins. In contrast, the fraction of subjects taking antihypertensives or hypoglycemia agents rose at a rate of 2.2% per year. There was also a significant trend for increases in weight gain (P ≤ .013). CONCLUSIONS: In subjects with diabetes, non-HDL-C levels have declined over time in parallel with reported increases in cholesterol-lowering drugs. Nonetheless, treatment targets for lipids in subjects with diabetes lag behind current recommendations. Reported intakes for antihypertensive agents and hypoglycemia agents were relatively high throughout the period of study, with little change over time. However, there was a trend for weight increase in diabetic subjects, which may offset some of the benefits of pharmacotherapy.


Subject(s)
Cholesterol/blood , Diabetes Mellitus/blood , Adult , Aged , Anticholesteremic Agents/therapeutic use , Diabetes Mellitus/drug therapy , Female , Humans , Male , Middle Aged , Nutrition Surveys , Risk Factors , Time Factors
13.
J Investig Med ; 68(2): 378-382, 2020 02.
Article in English | MEDLINE | ID: mdl-31540967

ABSTRACT

Evidence suggests that substantial testosterone therapy is occurring without checking levels of testosterone, presumably based on the presence of symptoms alone. We sought to explore the relationship between total testosterone level and non-specific symptoms, metabolic abnormalities, and sexual dysfunction associated with hypogonadism. This cross-sectional study included 2994 generally healthy men aged 50-79 years examined at a preventive medicine clinic in Dallas, TX from January 2012 to March 2016. Symptoms of hypogonadism were assessed. Screening morning total testosterone levels were measured and categorized into low (<250 ng/dL), low normal (250-399 ng/dL), and normal (≥400 ng/dL). Multiple logistic regression models were used to test the associations between total testosterone and signs and symptoms of hypogonadism. When considering symptoms and signs of hypogonadism, only decreased libido (OR 1.31, 95% CI 1.00 to 1.70), fasting glucose ≥100 mg/dL (OR 1.47, CI 1.15 to 1.88), and hemoglobin A1c over 6% (OR 1.47, 95% CI 1.06 to 2.03) were associated with increased odds of low testosterone after adjustment for age, body mass index, and cardiorespiratory fitness. Testosterone levels were not associated with fatigue, depression, or erectile dysfunction in our study (p>0.6). In this preventive medicine cohort, symptoms commonly attributed to testosterone deficiency were not associated with low total testosterone levels.


Subject(s)
Hypogonadism/blood , Hypogonadism/diagnosis , Preventive Health Services/methods , Testosterone/blood , Aged , Cross-Sectional Studies , Humans , Hypogonadism/epidemiology , Longitudinal Studies , Male , Middle Aged , Texas/epidemiology
14.
J Clin Lipidol ; 13(4): 563-567, 2019.
Article in English | MEDLINE | ID: mdl-31248654

ABSTRACT

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) are targets for prevention of atherosclerotic cardiovascular disease (ASCVD). The American Heart Association and American College of Cardiology recently modified recommendations for clinical management of cholesterol in secondary and primary prevention. Accordingly, the present article examines the need for cholesterol-lowering drugs in the U.S. population with ASCVD. OBJECTIVE: This study examines trends in non-HDL-C and LDL-C levels in a free living population of ASCVD subjects between 1999 and 2016. METHODS: National Health and Nutrition Examination Surveys database included 4920 adults with ASCVD aged 40 to 85 years. Complete data were available for 4226. Trend analysis of changes in lipids is shown in box plots. RESULTS: Mean age was 67 years with 57% males. Over 17 years, LDL-C decreased significantly by 24% and non-HDL-C by 21%. Over the period of study, reported intake of cholesterol-lowering drugs rose from 37% in 1999-2000 to 69% in 2015 to 2016. Over this same period, serum triglycerides decreased by 29% (P < .001) and HDL-C rose by 6%. CONCLUSIONS: The changes in LDL-C and non-HDL-C in patients with ASCVD over a 17-year period probably are related to increased treatment with statins. However, the changes are too small to be explained by widespread use of high-intensity statins, which is the current recommendation for patients with ASCVD. These findings pose a challenge for professional education to support implementation of current guidelines for cholesterol-lowering therapies.


Subject(s)
Cardiovascular Diseases/pathology , Cholesterol, LDL/blood , Cholesterol/blood , Adult , Aged , Aged, 80 and over , Anticholesteremic Agents/therapeutic use , Cardiovascular Diseases/blood , Cardiovascular Diseases/prevention & control , Cholesterol, HDL/blood , Databases, Factual , Female , Humans , Male , Middle Aged , Nutrition Surveys , Primary Prevention/trends , Triglycerides/blood
15.
Med Hypotheses ; 126: 26-37, 2019 May.
Article in English | MEDLINE | ID: mdl-31010495

ABSTRACT

The pregnant woman normally shows clinical manifestations similar to a metabolic syndrome (MS), due to her metabolic and hemodynamic adaptations in order to share nutrients with the child. If those adjustments are surpassed, a kind of pregnancy MS (PregMS) could appear, characterized by excessive insulin resistance and vascular maladaptation. Skeletal muscle (SKM) must be a protagonist in the PregMS: SKM strength and mass have been associated inversely with MS incidence in non-pregnant patients, and in pregnant women muscular activity modulates metabolic and vascular adaptations that favor better outcomes. Of note, a sedentary lifestyle affects exactly in the other way. Those effects may be explained not only by the old paradigm of SKM being a great energy consumer and store, but because it is an endocrine organ whose chronic activity or deconditioning correspondingly releases myokines modulating insulin sensitivity and cardiovascular adaptation, by direct or indirect mechanisms not well understood. In this document, we present evidence to support the concept of a PregMS and hypothesize on the role of the SKM mass, fiber types composition and myokines in its pathophysiology. Also, we discuss some exercise interventions in pregnancy as a way to test our hypotheses.


Subject(s)
Metabolic Syndrome/physiopathology , Muscle, Skeletal/physiopathology , Pregnancy Complications/psychology , Blood Glucose/metabolism , Body Composition , Exercise , Female , Hemodynamics , High-Intensity Interval Training , Humans , Insulin/metabolism , Insulin Resistance , Models, Biological , Muscle Strength , Pregnancy , Sedentary Behavior
16.
J Investig Med ; 67(2): 295-302, 2019 02.
Article in English | MEDLINE | ID: mdl-30530528

ABSTRACT

Survivors of childhood brain tumors may be at risk for early onset of metabolic syndrome, possibly secondary to surgery and/or radiation exposure. This study examines effects of radiation exposure to hypothalamus-pituitary-adrenal axis (HPA) on metabolic risk among survivors of childhood brain tumors. One hundred forty-two met inclusion criteria; 60 had tumor surgery plus radiation exposure (>1 Gray (Gy)) to HPA. The second subgroup of 82 subjects had surgery only and were not exposed to radiation. Both subgroups had survived for approximately 5 years at the time of study. All had clinical evaluation, vital signs, anthropometry, measurement of body composition by dual X-ray absorptiometry and fasting laboratory assays (metabolic panel, insulin, C-peptide, insulin-like growth factor-1, leptin and adiponectin). Body composition data for both subgroups was compared with the National Health and Nutrition Survey (NHANES) subgroup of similar age, gender and body mass index. Cranial surgery was associated with obesity of similar severity in both subgroups. However, survivors exposed to radiation to the HPA also had increased visceral fat mass and high prevalence of growth hormone deficiency and metabolic syndrome. Fat mass alone did not explain the prevalence of the metabolic syndrome in radiation exposure subgroup. Other factors such as growth hormone deficiency may have contributed to metabolic risk. We conclude that prevalence of metabolic syndrome among subjects exposed to hypothalamic radiation was higher than expected from hypothalamic obesity alone. Radiation exposure may exert untoward endocrinopathies due to HPA exposure that worsens metabolic risk. Early screening for metabolic syndrome in this population is indicated.


Subject(s)
Brain Neoplasms/complications , Brain Neoplasms/radiotherapy , Cancer Survivors , Hypothalamus/pathology , Metabolic Syndrome/drug therapy , Metabolic Syndrome/etiology , Obesity/complications , Radiation Exposure/adverse effects , Adolescent , Body Composition , Child , Female , Growth Hormone/therapeutic use , Humans , Male , Phenotype , Risk Factors
17.
Maturitas ; 118: 1-6, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30415749

ABSTRACT

BACKGROUND: Currently, exogenous hormone replacement is used in many men with hypogonadism without clear organic cause. This study examines the contribution of modifiable health behaviors, i.e., physical activity and weight control, to the maintenance of testosterone levels with aging. METHODS: In a cross-sectional study of 2994 healthy men aged 50-79 years examined at a preventive medicine clinic from January 2012 to March 2016, screening morning total testosterone levels were measured and categorized as low (<250 ng/dL), low normal (250-399 ng/dL), and normal (>400 ng/dL). Cardiorespiratory fitness (fitness) was estimated from a maximal exercise treadmill test. Multiple logistic regression models were used to test the associations between low testosterone levels and age, body mass index (BMI), and fitness. FINDINGS: Mean testosterone levels were in the normal range for each age group (50-59, 60-69, and 70-79). There was a similar prevalence of low testosterone in each age group (11·3%, 10%, and 10·5%, respectively). The prevalence of low testosterone was positively associated with BMI and negatively associated with fitness but was not associated with age. INTERPRETATION: This study found no evidence that low testosterone is an inevitable consequence of aging. Maintenance of healthy weight and fitness may help maintain normal testosterone levels.


Subject(s)
Body Mass Index , Body Weight , Cardiorespiratory Fitness/physiology , Testosterone/blood , Age Factors , Aged , Cross-Sectional Studies , Exercise , Exercise Test , Humans , Longitudinal Studies , Male , Mass Screening , Middle Aged , Physical Examination
18.
Diabetologia ; 61(12): 2570-2579, 2018 12.
Article in English | MEDLINE | ID: mdl-30159588

ABSTRACT

AIMS/HYPOTHESIS: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort. METHODS: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed. RESULTS: The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m2. Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, ß = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (ß = -0.14 to -0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (ß = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (ß = -0.06 to -0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors. CONCLUSIONS/INTERPRETATION: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.


Subject(s)
Ceramides/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Insulin Resistance/physiology , Intra-Abdominal Fat/metabolism , Adiposity/physiology , Adult , Body Mass Index , Chromatography, Liquid , Female , Humans , Magnetic Resonance Spectroscopy , Male , Mass Spectrometry , Middle Aged
19.
JAMA Neurol ; 75(9): 1089-1097, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29799940

ABSTRACT

Importance: The pathophysiologic mechanisms of Guillain-Barré syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features. Objective: To identify specific clinical features of GBS associated with ZIKV infection. Design, Setting, and Participants: During the ZIKV epidemic in Puerto Rico, prospective and retrospective strategies were used to identify patients with GBS who had neurologic illness onset in 2016 and were hospitalized at all 57 nonspecialized hospitals and 2 rehabilitation centers in Puerto Rico. Guillain-Barré syndrome diagnosis was confirmed via medical record review using the Brighton Collaboration criteria. Specimens (serum, urine, cerebrospinal fluid, and saliva) from patients with GBS were tested for evidence of ZIKV infection by real-time reverse transcriptase-polymerase chain reaction; serum and cerebrospinal fluid were also tested by IgM enzyme-linked immunosorbent assay. In this analysis of public health surveillance data, a total of 123 confirmed GBS cases were identified, of which 107 had specimens submitted for testing; there were 71 patients with and 36 patients without evidence of ZIKV infection. Follow-up telephone interviews with patients were conducted 6 months after neurologic illness onset; 60 patients with and 27 patients without evidence of ZIKV infection participated. Main Outcomes and Measures: Acute and long-term clinical characteristics of GBS associated with ZIKV infection. Results: Of 123 patients with confirmed GBS, the median age was 54 years (age range, 4-88 years), and 68 patients (55.3%) were male. The following clinical features were more frequent among patients with GBS and evidence of ZIKV infection compared with patients with GBS without evidence of ZIKV infection: facial weakness (44 [62.0%] vs 10 [27.8%]; P < .001), dysphagia (38 [53.5%] vs 9 [25.0%]; P = .005), shortness of breath (33 [46.5%] vs 9 [25.0%]; P = .03), facial paresthesia (13 [18.3%] vs 1 [2.8%]; P = .03), elevated levels of protein in cerebrospinal fluid (49 [94.2%] vs 23 [71.9%]; P = .008), admission to the intensive care unit (47 [66.2%] vs 16 [44.4%]; P = .03), and required mechanical ventilation (22 [31.0%] vs 4 [11.1%]; P = .02). Six months after neurologic illness onset, patients with GBS and evidence of ZIKV infection more frequently reported having excessive or inadequate tearing (30 [53.6%] vs 6 [26.1%]; P = .03), difficulty drinking from a cup (10 [17.9%] vs 0; P = .03), and self-reported substantial pain (15 [27.3%] vs 1 [4.3%]; P = .03). Conclusions and Relevance: In this study, GBS associated with ZIKV infection was found to have higher morbidity during the acute phase and more frequent cranial neuropathy during acute neuropathy and 6 months afterward. Results indicate GBS pathophysiologic mechanisms that may be more common after ZIKV infection.


Subject(s)
Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/virology , Zika Virus Infection/complications , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Guillain-Barre Syndrome/epidemiology , Hispanic or Latino , Humans , Middle Aged , Young Adult , Zika Virus Infection/epidemiology
20.
Eur J Clin Invest ; 48(7): e12941, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29682733

ABSTRACT

BACKGROUND: The metabolic syndrome is a constellation of risk factors including dyslipidemia, dysglycemia, hypertension, a pro-inflammatory state, and a prothrombotic state. All of these factors are accentuated by obesity. However, obesity can be defined by body mass index (BMI), percent body fat, or by body fat distribution. The latter consists of upper body fat (subcutaneous and visceral fat) and lower body fat (gluteofemoral fat). Waist circumference is a common surrogate marker for upper body fat. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2006 was examined for associations of metabolic risk factors with percent body fat, waist circumference, and BMI. RESULTS: Associations between absolute measures of waist circumference and risk factors were similiar for men and women. The similarities of associations between waist circumference and risk factors suggests that greater visceral fat in men does not accentuate the influence of upper body fat on risk factors. CONCLUSIONS: Different waist concumference values should not be used to define abdominal obesity in men and women.


Subject(s)
Intra-Abdominal Fat/pathology , Metabolic Syndrome/pathology , Subcutaneous Fat/pathology , Blood Pressure/physiology , Body Mass Index , C-Reactive Protein/metabolism , Cholesterol, HDL/metabolism , Female , Humans , Male , Metabolic Syndrome/etiology , Metabolic Syndrome/physiopathology , Middle Aged , Obesity/pathology , Risk Factors , Waist Circumference/physiology
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