Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation.

Rationale: Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming.

Objectives: This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects.

Methods: Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally).

Biomechanical properties of Achilles tendon repair augmented with a bioadhesive-coated scaffold.

The Achilles tendon is the most frequently ruptured tendon. Both acute and chronic (neglected) tendon ruptures can dramatically affect a patient's quality of life, and require a prolonged period of recovery before return to pre-injury activity levels. This paper describes the use of an adhesive-coated biologic scaffold to augment primary suture repair of transected Achilles tendons.

Adhesive performance of biomimetic adhesive-coated biologic scaffolds.

Surgical repair of a discontinuity in traumatized or degenerated soft tissues is traditionally accomplished using sutures. A current trend is to reinforce this primary repair with surgical grafts, meshes, or patches secured with perforating mechanical devices (i.e.

Renal transplant patient compliance with free immunosuppressive medications.

Background: Noncompliance with immunosuppressive medications after renal transplantation is believed to be a major cause of allograft rejection and graft loss, with the impressive costs of these agents considered a significant reason for noncompliance. Our purpose was to determine the compliance rates of renal transplant patients who received their immunosuppressant therapy free of charge and evaluate their patterns of compliance.

Methods: All patients who received a renal transplant and received their immunosuppressant medications at our institution for their first year posttransplant were included in the study.

Cost-benefit analysis of a clinical pharmacist-managed medication assistance program in a renal transplant clinic.

Unlabelled: Medicare pays for 80% of the cost of immunosuppressant agents needed within the first 3 years of solid organ transplantation; however, many patients cannot afford the remaining 20%. Furthermore, many patients who are beyond 3 years post-transplantation and have prescription coverage cannot afford the co-payment for these medications. Other patients may not be able to afford their medications due to limited or no insurance coverage.

Medication assistance programs for uninsured and indigent patients.

Pharmaceutical company-sponsored medication assistance programs and the pharmacist's role in obtaining medications for indigent patients are discussed. Information about enrolling in medication assistance programs can be obtained through a variety of sources, including the Internet. Although some eligibility criteria may be common to many programs, each company operates independently, and the eligibility criteria vary, individuals involved in the administration of medication assistance programs should strive to ensure that correct information is reported.

Exaggerated endothelin release in high-altitude pulmonary edema.

Background: Exaggerated pulmonary hypertension is thought to play an important part in the pathogenesis of high-altitude pulmonary edema (HAPE). Endothelin-1 is a potent pulmonary vasoconstrictor peptide that also augments microvascular permeability.

Methods And Results: We measured endothelin-1 plasma levels and pulmonary artery pressure in 16 mountaineers prone to HAPE and in 16 mountaineers resistant to this condition at low (580 m) and high (4559 m) altitudes.

Augmented sympathetic activation during short-term hypoxia and high-altitude exposure in subjects susceptible to high-altitude pulmonary edema.

Background: Pulmonary hypertension is a hallmark of high-altitude pulmonary edema and may contribute to its pathogenesis. Cardiovascular adjustments to hypoxia are mediated, at least in part, by the sympathetic nervous system, and sympathetic activation promotes pulmonary vasoconstriction and alveolar fluid flooding in experimental animals.

Methods And Results: We measured sympathetic nerve activity (using intraneural microelectrodes) in 8 mountaineers susceptible to high-altitude pulmonary edema and 7 mountaineers resistant to this condition during short-term hypoxic breathing at low altitude and at rest at a high-altitude laboratory (4559 m).

Cardiovascular and sympathetic effects of nitric oxide inhibition at rest and during static exercise in humans.

Background: Nitric oxide (NO) regulates vascular tone and blood pressure, and studies in animals suggest that it does so, at least in part, by modulating sympathetic neural outflow. Loss of NO-induced vasodilator tone and restraint on sympathetic vasoconstrictor outflow could lead to exaggerated vasoconstrictor and pressor responses to physical stress in humans.

Methods And Results: To determine the role of NO in the modulation of central sympathetic outflow and vascular tone at rest and during a physical stress, we tested effects of systemic inhibition of NO synthase by N(G)-monomethyl-L-arginine (L-NMMA) infusion (a stereospecific inhibitor of NO synthase) on sympathetic nerve activity (microneurography), regional vascular resistance, and blood pressure at rest and during static handgrip.

Inhaled nitric oxide for high-altitude pulmonary edema.

Background: Pulmonary hypertension is a hallmark of high-altitude pulmonary edema and may contribute to its pathogenesis. When administered by inhalation, nitric oxide, an endothelium-derived relaxing factor, attenuates the pulmonary vasoconstriction produced by short-term hypoxia.

Methods: We studied the effects of inhaled nitric oxide on pulmonary-artery pressure and arterial oxygenation in 18 mountaineers prone to high-altitude pulmonary edema and 18 mountaineers resistant to this condition in a high altitude laboratory (altitude, 4559 m).

Insulin-induced sympathetic activation and vasodilation in skeletal muscle. Effects of insulin resistance in lean subjects.

Insulin-induced stimulation of blood flow and sympathetic nerve activity in skeletal muscle tissue is impaired in obesity, but the underlying mechanism is unknown. To determine whether insulin resistance alters sympathetic and vasodilatory responses to euglycemic hyperinsulinemia, in eight healthy subjects we measured calf blood flow and muscle sympathetic nerve activity (MSNA) (n = 5) during insulin/glucose infusion (euglycemic hyperinsulinemic [6 pmol.kg-1.

Metabolic effects of an increase of sympathetic activity in healthy humans.

Objective: To determine the metabolic effects of catecholamines released at sympathetic nerves ending in the postabsorptive and postprandial states.

Design: Sympathetic activity was acutely increased by lower body negative pressure (LBNP; -15 mmHg) on two occasions in a group of eight healthy volunteers: (1) in the postabsorptive state; and (2) after glucose ingestion.

Measurements: Plasma norepinephrine concentrations were determined by HPLC and energy expenditure and substrate oxidation rates were assessed with indirect calorimetry.

Nitric oxide release accounts for insulin's vascular effects in humans.

Insulin exerts effects on the vasculature that (a) may play a role in the regulation of blood pressure; and (b) by boosting its own delivery to target tissues, also have been proposed to play an integral part in its main action, the promotion of glucose disposal. To study the role of nitric oxide (NO) in the mediation of insulin's effects on the peripheral vasculature, NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the synthesis of endothelium-derived NO, was infused into the brachial arteries of healthy volunteers both before, and at the end of a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp. L-NMMA (but not norepinephrine, an NO-independent vasoconstrictor) caused larger reductions in forearm blood flow during hyperinsulinemia than at baseline.

Mechanisms of dexamethasone-induced insulin resistance in healthy humans.

Insulin resistance may result from decreased muscle blood flow, impaired cellular glucose transport, or intracellular deficits of glucose metabolism. The mechanisms responsible for dexamethasone-induced insulin resistance were investigated in healthy human subjects. During a 2-h hyperinsulinemic clamp, dexamethasone decreased glucose uptake, oxidation, and nonoxidative glucose disposal during the first hour.