David A Fryburg

• MD
• Independent Researcher

The healthcare workplace is a high-stress environment. All stakeholders, including patients and providers, display evidence of that stress. High stress has several effects. Even acutely, stress can negatively affect cognitive function, worsening diagnostic acumen, decision-making, and problem-solving. It decreases helpfulness. As stress increases,...

Patients enter the healthcare space shouldering a lot of personal stress. Concurrently, health care providers and staff are managing their own personalstressors as well as workplace stressors. As stress can negatively affect the patient–provider experience and cognitive function of both individuals, it is imperative to try to uplift the health care...

Chronic stress is a ubiquitous problem shouldered by many people worldwide. Although the stressors are myriad (eg, loneliness, finances, health, discrimination), the corporal response to them either causes or exacerbates mental and physical illness, including depression, anxiety, and cardiovascular disease. Identifying efficient ways to help people...

Background and Objectives: Stress is a ubiquitous aspect of modern life that affects both mental and physical health. Clinical care settings can be particularly stressful for both patients and providers. Kindness and compassion are buffers for the negative effects of stress, likely through strengthening positive interpersonal connection. In previou...

Background: The aims of this study were to 1. define the responses of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and peptide YY (PYY) to an oral meal and to intravenous L-arginine; and 2. examine correlation of enteroendocrine hormones with insulin secretion. We hypothesized a relationship betwee...

Standard practice to minimize variability in beta cell function (BCF) measurement is to test in inpatient (IP) settings. IP testing strains trial subjects, investigators, and budgets. Outpatient (OP) testing may be a solution although there are few reports on OP BCF testing variability. We compared variability metrics between OP and IP from a stand...

Objective: Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tole...

Faced with an increasing number of choices for biologic therapies, rheumatologists have a critical need for better tools to inform rheumatoid arthritis (RA) disease management. The ability to identify patients who are unlikely to respond to first-line biologic anti-TNF therapies prior to their treatment would allow these patients to seek alternativ...

Background: The number of biologic therapies approved for use in treating rheumatoid arthritis (RA) has grown steadily over the past 15 years. While many patients are treated with anti-TNF therapies 30-40% of these patients fail to respond adequately as their disease progressively worsens. Tools to guide disease management and identify a priori whi...

A key aspect of research into the prevention and treatment of type 2 diabetes is availability of reproducible clinical research methodology to assess β-cell function. One commonly-used method employs non-glycemic secretagogues like arginine (arg) or glucagon (glgn). This study was designed to quantify the insulin response to arg and glgn and determ...

Societal demand for faster and more accurate assignment of treatments is based in both patient care needs and in health economics. From a patient care standpoint, there needs to be a transformation from the empiric method of therapeutic decision making to avoid unwanted side effects from inefficacious treatments. For health economics, the delay in...

The current drug discovery paradigm is long, costly, and prone to failure. For projects in early development, lack of efficacy in Phase II is a major contributor to the overall failure rate. Efficacy failures often occur from one of two major reasons: either the investigational agent did not achieve the required pharmacology or the mechanism target...

Selventa, Inc. (MA, USA) is a biomarker discovery company that enables personalized healthcare. Originally founded as Genstruct, Inc., Selventa has undergone significant evolution from a technology-based service provider to an active partner in the development of diagnostic tests, functioning as a molecular dashboard of disease activity using a uni...

With the current chances of an efficacious outcome in Phase II for novel mechanisms being in the region of I in 5, we argue the need for personalised drug discovery and development to be executed at the beginning of the process and that the pharmaceutical industry's future successes will likely depend upon effectively enacting this paradigm.

The limited predictability of phase II biomarkers for atherosclerosis outcomes in phase III studies stands in contrast to the number and varied types of biomarkers--soluble, imaging, and functional--that have been used in a diverse array of trials. Although collectively abundant, these biomarker data exist in a fragmented state. Most biomarkers are...

The sections in this article are: In Vitro Actions of Growth Hormone and Insulin‐Like Growth Factor I on Protein Metabolism Effects of Growth Hormone In Vitro Effects of Insulin‐Like Growth Factor I In Vitro In Vitro Actions of Growth Hormone and Insulin‐Like Growth Factor I on Protein Degradation In vivo Actions of Growth Hormone and Insulin‐...

Of the many issues that contribute to the pharmaceutical industry's productivity problems, biases in the drug discovery and development (DDD) process should be included on the list. The dominant bias pervading the early DDD process is the requirement to identify and develop a commercializable molecule, long before the importance of the target in hu...

Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ-induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double-b...

Matrix metalloproteinase (MMP)-9, a member of the MMP superfamily is consistently implicated in the pathophysiology of atherosclerosis and plaque rupture, the most common mechanism responsible for acute coronary syndrome (ACS). To summarize the role of MMP-9 in atherosclerosis and its potential implications in assessment and treatment of coronary a...

What is already known about this subject: Active cigarette smoking is associated with increased permeability of the pulmonary alveolar epithelium, resulting in faster absorption of inhaled drugs such as Exubera (EXU). Absorption of EXU is increased approximately twice to four times as much in chronic smokers compared with nonsmokers. The rate of c...

Biomarkers of atherosclerosis are emerging as a potential tool for assessment of coronary artery disease (CAD) patients. As acute coronary syndrome (ACS), and stable CAD are distinguished in their pathophysiology it is conceivable that they are also characterized by different biomarkers of atherosclerosis. We systematically reviewed the literature...

Identification of variants predicting development of renal dysfunction would offer substantial clinical benefits. There is evidence that coding non-synonymous variants in the gene encoding paraoxonase 2 (PON2) are associated with nephropathy in both type 1 and type 2 diabetes. We examined the relationship between variation at the C311S and A148G po...

For many decades, it has been recognized that insulin, growth hormone, glucocorticoids, insulin-like growth factor 1, thyroid hormones, and other hormones regulate body protein metabolism. It has been more recently recognized, but not understood, that humor factors present in states of acute and chronic inflammation could have a strong impact on pr...

Thermal biofeedback may be a useful adjunctive technique for enhancing cutaneous blood flow in patients with lower-extremity vascular complications of diabetes. However, autonomic, sensory, and/or motor neuropathies may impair vasomotion and limit the ability to alter blood flow and achieve significant foot warming with thermal biofeedback. We exam...

We examined the effects of GH and/or testosterone (T) administration on body composition, performance, mood, sexual function, bone turnover, and muscle-gene expression in healthy older men. Ten men [mean (SEM) age, 68 (2.5) yr; height, 171.5 (2.4) cm; and weight, 80 (3.0) kg] completed each of the following 1-month, double-blind interventions after...

Branched chain amino acids (BCAA) are particularly effective anabolic agents. Recent in vitro studies suggest that amino acids, particularly leucine, activate a signaling pathway that enhances messenger ribonucleic acid translation and protein synthesis. The physiological relevance of these findings to normal human physiology is uncertain. We exami...

We examined the effects of exercise intensity on serum leptin levels. Seven men (age = 27.0 yr; height = 178.3 cm; weight = 82.2 kg) were tested on a control (C) day and on 5 exercise days (EX). Subjects exercised (30 min) at the following intensities: 25% and 75% of the difference between the lactate threshold (LT) and rest (0.25 LT, 0.75 LT), at...

Despite clear anthropomorphic differences, gender differences in human skeletal muscle protein and carbohydrate metabolism have not been carefully examined. We compared postabsorptive forearm glucose, oxygen, and lactate balances and forearm protein kinetics between 40 male and 36 female subjects. Forearm composition was measured in a subset of 17...

The maintenance of lean body mass, particularly skeletal muscle mass, has much relevance to human health because skeletal muscle serves two important functions. First, it is a major protein reservoir and provides amino acids for the synthesis of protein in more critical tissues during periods of caloric depletion and catabolic illness (1,2). Second...

Insulin clearly stimulates skeletal muscle protein synthesis in vitro. Surprisingly, this effect has been difficult to reproduce in vivo. As in vitro studies have typically used much higher insulin concentrations than in vivo studies, we examined whether these concentration differences could explain the discrepancy between in vitro and in vivo obse...

Gonadal steroids are known to alter GH secretion as well as tissue metabolism. The present study was designed to examine the effects of short term (2- to 3-week) alterations in gonadal steroids on basal pulsatile (nonstimulated) and exercise- and GH-releasing hormone-stimulated GH secretion, urinary nitrogen excretion, and basal and exercise-stimul...

Recently published data have provided evidence that nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) are signaling intermediates in the pathway through which muscle contraction stimulates glucose transport. As exercise promotes both NO production and calcium flux, we examined the relationships between NO-stimulated glucose uptake and cal...

In human skeletal muscle, insulin-like growth factor-I (IGF-I) exerts both growth hormone-like (increase in protein synthesis) and insulin-like (decrease in protein degradation and increase in glucose uptake) actions and augments forearm blood flow two- to threefold. This study was designed to address whether (a) the increase in blood flow due to I...

Thermal biofeedback (TBF) increases blood flow and may promote healing of diabetic ulcers, the leading cause of nontraumatic amputation in the U.S. We examined the relationship between nerve function and hand- and foot-warming proficiency during TBF in diabetic patients. Multiple regression techniques revealed that sympathetic and sensory nerve fun...

Insulin inhibits proteolysis in human muscle thereby increasing protein anabolism. In contrast, IGF-I promotes muscle protein anabolism principally by stimulating protein synthesis. As increases or decreases of plasma amino acids may affect protein turnover in muscle and also alter the muscle's response to insulin and/or IGF-I, this study was desig...

Insulin's anabolic action on skeletal muscle and whole body protein is attributable to its action to slow tissue proteolysis. The antimalarial chloroquine inhibits lysosomal proteolysis and is reported to improve glycemia in poorly controlled diabetic patients. We infused chloroquine into the brachial artery of seven healthy postabsorptive voluntee...

Systemic epinephrine infusion causes hypoaminoacidemia and inhibits whole body leucine flux (proteolysis) in humans. Its specific action on muscle protein is not known and is difficult to assess during systemic epinephrine infusions, which affect plasma insulin, amino acid, and free fatty acid concentrations. During a steady-state infusion of L-[ri...

Insulin, growth hormone, and insulin-like growth factor-I (IGF-I) are the three major peptide hormones that modulate somatic cell growth and hyperplasia. In isolated tissues and cells, insulin is necessary to sustain protein synthesis and to restrain proteolysis while growth hormone and IGF-I act primarily to stimulate protein synthesis. In humans,...

Patients with the acquired immunodeficiency syndrome (AIDS) are characterized by a decrease in the number of T helper cells, a defect that is linked to the impaired immunologic competence. Vitamin A and its dietary precursor, beta-carotene, increase absolute T helper cell counts as well as indices of T cell function in both human and animal models....

The effect of a 6-h intra-arterial infusion of recombinant human (rh) insulin-like growth factor I (IGF-I) on forearm muscle metabolism was studied in 19 postabsorptive subjects. Forearm glucose, lactate, and phenylalanine (Phe) balances, as well as estimates of protein degradation (Phe Ra) and synthesis (Phe Rd) were measured before and at 3 and 6...

The purpose of this paper is to describe the management of a previously undiagnosed non-insulin-dependent diabetic patient with a severe burn injury. The hyperglycaemia and glucose intolerance following burn injury was complicated by the hyperglycaemia of diabetes mellitus. Intravenous insulin infusion monitored by hourly glucose levels was require...

In a previous study, a 6-hour local infusion of growth hormone (GH) into the brachial artery of normal subjects stimulated net muscle protein anabolism by augmenting skeletal muscle protein synthesis. In the present study, we examined whether systemically infused GH affects forearm and whole-body protein metabolism. Normal volunteers aged 18 to 24...

Physiologic increases of insulin promote net amino acid uptake and protein anabolism in forearm skeletal muscle by restraining protein degradation. The sensitivity of this process to insulin is not known. Using the forearm perfusion method, we infused insulin locally in the brachial artery at rates of 0.00 (saline control), 0.01, 0.02, 0.035, or 0....

We examined the effects of a combined, local intra-arterial infusion of growth hormone (GH) and insulin on forearm glucose and protein metabolism in seven normal adults. GH was infused into the brachial artery for 6 h with a dose that, in a previous study, stimulated muscle protein synthesis (phenylalanine Rd) without affecting systemic GH, insulin...

The short-term effects of growth hormone (GH) on skeletal muscle protein synthesis and degradation in normal humans are unknown. We studied seven postabsorptive healthy men (age 18-23 yr) who received GH (0.014 micrograms.kg-1.min-1) via intrabrachial artery infusion for 6 h. The effects of GH on forearm amino acid and glucose balances and on forea...

To examine the influence of insulin-dependent diabetes on the metabolic response to insulin-like growth factor I (IGF-I), awake chronically catheterized diabetic and nondiabetic BB/w rats received IGF-I (5 micrograms.kg-1.min-1) or insulin (2 mU.kg-1.min-1) for 2 h while maintaining euglycemia. In nondiabetic rats, IGF-I and insulin produced simila...

Although starvation is known to impair insulin-stimulated glucose disposal, whether it also induces resistance to insulin's antiproteolytic action on muscle is unknown. To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using [3H]phenylalanine (Phe) and...

Although fructose is widely regarded as an insulin-independent fuel source, its in vivo conversion to glucose represents a theoretical limitation to its clinical usefulness in diabetics, particularly if given in large doses. To determine whether small amounts of fructose can be well utilized in the setting of insulinopenia, we administered a low-do...