Occupational respiratory and skin diseases among workers exposed to metalworking fluids.

Purpose Of Review: To examine respiratory and skin diseases that occur among workers exposed to metalworking fluids (MWFs) used during machining processes.

Recent Findings: Five cases of a severe and previously unrecognized lung disease characterized by B-cell bronchiolitis and alveolar ductitis with emphysema (BADE) were identified among workers at a machining facility that used MWFs, although MWF exposure could not be confirmed as the etiology. In the United Kingdom, MWF is now the predominant cause of occupational hypersensitivity pneumonitis (HP).

Occupational Exposure to Secondhand Cannabis Smoke Among Law Enforcement Officers Providing Security at Outdoor Concert Events.

Objectives: Numerous states within the USA have legalized cannabis for medical or non-medical (adult/recreational) use. With the increased availability and use of cannabis, occupational and environmental exposures to secondhand cannabis smoke (SHCS) raise concerns over whether non-users may be at risk for a 'contact high', impaired neurocognitive function, harm from irritants and carcinogens in smoke, or potentially failing a cannabis screening test. The extent of health effects from potential occupational exposure to SHCS is unknown.

Review of NIOSH Cannabis-Related Health Hazard Evaluations and Research.

Since 2004, the National Institute for Occupational Safety and Health (NIOSH) has received 10 cannabis-related health hazard evaluation (HHE) investigation requests from law enforcement agencies (n = 5), state-approved cannabis grow operations (n = 4), and a coroner's office (n = 1). Earlier requests concerned potential illicit drug exposures (including cannabis) during law enforcement activities and criminal investigations. Most recently HHE requests have involved state-approved grow operations with potential occupational exposures during commercial cannabis production for medicinal and non-medical (recreational) use.

Potential occupational and respiratory hazards in a Minnesota cannabis cultivation and processing facility.

Background: Cannabis has been legalized in some form for much of the United States. The National Institute for Occupational Safety and Health (NIOSH) received a health hazard evaluation request from a Minnesota cannabis facility and their union to undertake an evaluation.

Methods: NIOSH representatives visited the facility in August 2016 and April 2017.

Stability of isoniazid injection in i.v. solutions.

Purpose: Results of an assessment of the chemical stability of isoniazid injection in 0.9% sodium chloride injection and 5% dextrose injection are reported.

Methods: Triplicate solutions of isoniazid (0.

Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate.

Dietary NO (nitrate) and NO (nitrite) support ˙NO (nitric oxide) generation and downstream vascular signaling responses. These nitrogen oxides also generate secondary nitrosating and nitrating species that react with low molecular weight thiols, heme centers, proteins, and unsaturated fatty acids. To explore the kinetics of NOand NOmetabolism and the impact of dietary lipid on nitrogen oxide metabolism and cardiovascular responses, the stable isotopes NaNO and NaNO were orally administered in the presence or absence of conjugated linoleic acid (cLA).

Dose-escalation study of octanoic acid in patients with essential tremor.

Background: Recently, 1-octanol has been shown to have efficacy in treating patients with essential tremor (ET). The primary metabolite of 1-octanol is octanoic acid (OA), which is now thought to be the active substance that mediates tremor suppression. Our aim was to describe the maximum tolerated dose (MTD) of oral OA in patients with ET and assess the pharmacokinetics (PK) and pharmacodynamics (PD) profile of OA.

Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes.

A gap in our understanding of the beneficial systemic responses to dietary constituents nitrate (NO3(-)), nitrite (NO2(-)) and conjugated linoleic acid (cLA) is the identification of the downstream metabolites that mediate their actions. To examine these reactions in a clinical context, investigational drug preparations of (15)N-labeled NO3(-) and NO2(-) were orally administered to healthy humans with and without cLA. Mass spectrometry analysis of plasma and urine indicated that the nitrating species nitrogen dioxide was formed and reacted with the olefinic carbons of unsaturated fatty acids to yield the electrophilic fatty acid, nitro-cLA (NO2-cLA).

Topical sodium nitrite for chronic leg ulcers in patients with sickle cell anaemia: a phase 1 dose-finding safety and tolerability trial.

Background: Well-tolerated and effective treatments are needed for chronic leg ulcers in sickle cell anaemia. Topical sodium nitrite, a known nitric oxide donor, enhances blood flow in ulcers and has known bacteriostatic effects. We aimed to assess the safety, tolerability, and pharmacokinetics of topical sodium nitrite in patients with sickle cell disease and chronic leg ulcers.

A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder caused by gain-of-function mutations in the G protein-coupled chemokine receptor CXCR4. The CXCR4 antagonist plerixafor, which is approved by the US Food and Drug Administration (FDA) for stem cell mobilization in cancer and administered for that indication at 0.24 mg/kg, has been shown in short-term (1- to 2-week) phase 1 dose-escalation studies to correct neutropenia and other cytopenias in WHIM syndrome.

Paranitroanaline poisoning: a failure in basic prevention?

The Occupational Medicine Forum is prepared by the ACOEM Occupational and Environmental Medical Practice Committee and does not necessarily represent an official ACOEM position. The Forum is intended for health professionals and is not intended to provide medical or legal advice, including illness prevention, diagnosis or treatment, or regulatory compliance. Such advice should be obtained directly from a physician and/or attorney.

Stability of alemtuzumab solutions at room temperature.

Purpose: The 24-hour stability of alemtuzumab solutions prepared at concentrations not included in the product label and stored in glass or polyolefin containers at room temperature was evaluated.

Methods: Triplicate solutions of alemtuzumab (6.67, 40, and 120 μg/mL) in 0.

Octanoic acid in alcohol-responsive essential tremor: a randomized controlled study.

Objective: To assess safety and efficacy of an oral, single, low dose of octanoic acid (OA) in subjects with alcohol-responsive essential tremor (ET).

Methods: We conducted a double-blind, placebo-controlled, crossover, phase I/II clinical trial evaluating the effect of 4 mg/kg OA in 19 subjects with ET. The primary outcome was accelerometric postural tremor power of the dominant hand 80 minutes after administration.

An open-label, single-dose, crossover study of the pharmacokinetics and metabolism of two oral formulations of 1-octanol in patients with essential tremor.

Existing therapeutic options for management of essential tremor are frequently limited by poor efficacy and adverse effects. Likely the most potent tremor suppressant used is ethanol, although its use is prohibitive due to a brief therapeutic window, and the obvious implications of excessive alcohol use. Longer-chain alcohols have been shown to suppress tremor in harmaline animal models, and appear to be safe and well tolerated in 2 prior studies in humans.

Physical compatibility of magnesium sulfate and sodium bicarbonate in a pharmacy-compounded hemofiltration solution.

Purpose: The physical compatibility of magnesium sulfate and sodium bicarbonate in a pharmacy-compounded hemofiltration solution was assessed.

Methods: Two bicarbonate-buffered hemofiltration solutions (low- and high-magnesium formulations) were compounded in triplicate. The concentrations of magnesium (15 meq/L) and sodium bicarbonate (50 meq/L) in the high-magnesium formulation were chosen to be somewhat below the concentrations reported as being incompatible in a popular reference.

A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic renal cell carcinoma.

Background: Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the von Hippel-Lindau (VHL) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides.

Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation.

Background: The recent discovery that nitrite is an intrinsic vasodilator and signaling molecule at near-physiological concentrations has raised the possibility that nitrite contributes to hypoxic vasodilation and to the bioactivity of nitroglycerin and mediates the cardiovascular protective effects of nitrate in the Mediterranean diet. However, important questions of potency, kinetics, mechanism of action, and possible induction of tolerance remain unanswered.

Methods And Results: In the present study, we performed biochemical, physiological, and pharmacological studies using nitrite infusion protocols in 20 normal human volunteers and in nonhuman primates to answer these questions, and we specifically tested 3 proposed mechanisms of bioactivation: reduction to nitric oxide by xanthine oxidoreductase, nonenzymatic disproportionation, and reduction by deoxyhemoglobin.

Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration.

Purpose: The safety and pharmacokinetics of a triamcinolone acetonide (TA) preservative-free (TA-PF) formulation were investigated after intravitreal administration in rabbits.

Methods: A TA-PF formulation was prepared as a sterile 40-mg/mL or 160-mg/mL suspension in single-use vials by adding TA powder to 0.5% hydroxypropyl methylcellulose in normal saline.

Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques.

Although replication-competent adenovirus (Ad) vectors are promising in AIDS vaccine design, their safety in immune compromised hosts is unknown. To initially address this question, enteric-coated tablets containing a replicating Ad vector were orally administered to SHIV- and SIV-infected rhesus macaques with normal, intermediate or low CD4 T cell counts and stable disease. The vector was detected within a week after tablet administration in stools of all animals but not in nasal secretions, indicating no spread of virus to the upper respiratory tract.

Injectable formulation of disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), an ultrafast nitric oxide donor prodrug.

PROLI/NO is an agent of structure XN(O)==NONa (X = L-prolyl) whose 2-s half-life for nitric oxide (NO) release at physiological pH makes it an excellent prodrug for localizing NO's therapeutic effects at the site of application, but a difficult one to formulate and certify as pure. Despite its extraordinary thermal and hydrolytic instability, however, PROLI/NO could be formulated as an injectable drug by dissolving it in cold 0.1 M sodium hydroxide containing 5% D-mannitol, then quickly ultrafiltering and lyophilizing it in evacuated septum vials.

Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.

Context: Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm.

Objective: To determine whether infusions of nitrite will prevent delayed cerebral vasospasm.