Range of the perfluorooctanoate (PFOA) safe dose for human health: An international collaboration.

Many government agencies and expert groups have estimated a dose-rate of perfluorooctanoate (PFOA) that would protect human health. Most of these evaluations are based on the same studies (whether of humans, laboratory animals, or both), and all note various uncertainties in our existing knowledge. Nonetheless, the values of these various, estimated, safe-doses vary widely, with some being more than 100,000 fold different.

Dual diagnosis of autosomal dominant polycystic kidney disease and sickle cell disease in a teenage male.

Background: Sickle cell disease (SCD) and autosomal dominant polycystic kidney disease (ADPKD) are relatively common genetic conditions with considerable overlap in clinical presentation. In addition to similarities between the signs and symptoms in sickle cell nephropathy and ADPKD, more than half of SCD patients have kidney cysts. The co-occurrence of these two diseases has not been previously reported in the literature.

Targeting plasma cells with daratumumab aids in the treatment of post-transplant autoimmune-like hepatitis.

Antibody-mediated autoimmune-like hepatitis is a rare and challenging occurrence after hematopoietic cell transplant (HCT). We present the case of a 16-year-old male patient with Ph+ ALL who underwent matched sibling donor HCT and developed autoimmune-like hepatitis after receiving ponatinib for post-HCT maintenance, evidenced by marked plasma cell infiltrate on liver biopsy. He was successfully treated with steroids and daratumumab, an anti-CD38-monoclonal antibody.

Reaching the Hard-to-Reach: Outcomes of the Severe Hypertension Outreach Intervention.

Introduction: Severe hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic) is associated with a twofold increase in the relative risk of death. At the authors' Federally Qualified Health Center in the Southeast, 39% of adults (n=8,695) had hypertension, and 3% (n=235) were severe. The purpose of this project was to lower blood pressure and improve the proportion of patients achieving the Agency for Healthcare Research and Quality goal for blood pressure.

Reducing high-risk medication use through pharmacist-led interventions in an outpatient setting.

Objective: This study aimed to reduce high-risk medication (HRM) prescribing by direct electronic medical record messaging to providers.

Setting: Lincoln Community Health Center is a federally qualified health center in the southeast United States.

Practice Description: This was a single-center, observational study performed with quality improvement methodology including define, measure, analyze, improve, and control phases.

Quality Improvement Interventions across a Network of Pediatric Hematology-Oncology Clinics.

Introduction: Achieving improvement in quality among different institutions is challenging. Immunocompromised children with febrile neutropenia are at high risk of severe infection. Pediatric hematology-oncology patients frequently experience central line-associated bloodstream infections (CLABSIs) associated with implanted catheters.

Sickle Cell Clinical Research and Intervention Program (SCCRIP): A lifespan cohort study for sickle cell disease progression from the pediatric stage into adulthood.

Background: Previous natural history studies have advanced the understanding of sickle cell disease (SCD), but generally have not included sufficient lifespan data or investigation of the role of genetics in clinical outcomes, and have often occurred before the widespread use of disease-modifying therapies, such as hydroxyurea and chronic erythrocyte transfusions. To further advance knowledge of SCD, St. Jude Children's Research Hospital established the Sickle Cell Clinical Research and Intervention Program (SCCRIP), to conduct research in a clinically evaluated cohort of individuals with SCD across their lifetime.

Salvage Treatment of Mucormycosis Post-Liver Transplant With Posaconazole During Sirolimus Maintenance Immunosuppression.

We describe the first successful case of posaconazole salvage therapy for mucormycosis with concomitant sirolimus (SRL) maintenance immunosuppression following liver transplantation, despite black box drug interaction following intolerance to first-line tacrolimus and amphotericin due to nephrotoxicity and neurotoxicity. This case describes a 55-year-old female who developed rhinocerebral mucormycosis 108 days after liver transplantation. After 3 months of posaconazole therapy, the patient remains free of disease at 3 years posttransplant.

Hydroquinone PBPK model refinement and application to dermal exposure.

A physiologically based pharmacokinetic (PBPK) model for hydroquinone (HQ) was refined to include an expanded description of HQ-glucuronide metabolites and a description of dermal exposures to support route-to-route and cross-species extrapolation. Total urinary excretion of metabolites from in vivo rat dermal exposures was used to estimate a percutaneous permeability coefficient (K(p); 3.6×10(-5) cm/h).

Carcinogenicity and chronic toxicity of di-2-ethylhexyl terephthalate (DEHT) following a 2-year dietary exposure in Fischer 344 rats.

The carcinogenicity and chronic toxicity potential of di-2-ethylhexyl terephthalate (DEHT) was assessed in F-344 rats (50/sex/dose) by dietary exposure for 104 weeks. Exposure levels of 0, 1500, 6000 or 12,000 ppm resulted in average daily doses of 79, 324 and 666 mg/kg/day for males and 102, 418 and 901 mg/kg/day for females. Animals were observed daily for clinical signs and detailed physical examinations were performed weekly.

Developmental toxicity and uterotrophic studies with di-2-ethylhexyl terephthalate.

Background: These studies were conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) exposure on in utero development in mice and rats. In addition, a uterotrophic assay for estrogenic activity was conducted in sexually immature rats.

Methods: In the developmental toxicity studies, diet containing DEHT was fed to four groups of mated female Crl:CD(SD)IGS BR rats (25/group) from gestation day (GD) 0-20 or Crl:CD1(ICR) mice (25/group) from GD 0-18.

Two-generation reproduction study of di-2-ethylhexyl terephthalate in Crl:CD rats.

Background: This study was conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) on reproductive capability from exposure of F(0) and F(1) parental animals.

Methods: Four groups of male and female Crl:CD (SD)IGS BR rats (30/gender/group) were exposed to 0, 0.3%, 0.

Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another.

Medulloblastoma outcome is adversely associated with overexpression of EEF1D, RPL30, and RPS20 on the long arm of chromosome 8.

Background: Medulloblastoma is the most common malignant brain tumor of childhood. Improvements in clinical outcome require a better understanding of the genetic alterations to identify clinically significant biological factors and to stratify patients accordingly. In the present study, we applied cytogenetic characterization to guide the identification of biologically significant genes from gene expression microarray profiles of medulloblastoma.

Subchronic toxicity of ethylene glycol in Wistar and F-344 rats related to metabolism and clearance of metabolites.

Ethylene glycol (CAS RN 107-21-1) can cause kidney toxicity via the formation of calcium oxalate crystals in a variety of species, including humans. Numerous repeated dose studies conducted in rats have indicated that male rats are more susceptible than female rats. Furthermore, subchronic and chronic studies using different dietary exposure regimens have indicated that male Wistar rats may be more sensitive to renal toxicity than male Fischer-344 (F-344) rats.

Review of subchronic/chronic toxicity of antimony potassium tartrate.

Subchronic/chronic toxicity studies on antimony potassium tartrate (APT) have been reviewed. One of the older studies (H. A.

drp, a novel protein expressed at high cell density but not during growth arrest.

Contact is a vital mechanism used by cells to interact with their environment. Contact with living and nonliving elements adjacent to a cell is the basis for many common biological events ranging from growth regulation to metastasis to embryonic pattern formation. We describe the cloning and characterization of a novel density-regulated protein (drp) whose expression is increased in cultured cells at high density compared with cells at low density.

English plantain and psyllium: lack of cross-allergenicity by crossed immunoelectrophoresis.

Background: English plantain (Plantago lanceolata) weed pollen and psyllium (Plantago ovata) husk dust are inhalant allergens. Because of the phylogenetic relationship between these plant species, cross-allergenicity has been a concern.

Objective: The purpose of this study was to investigate the possible cross-allergenicity of plantain and psyllium.

Role of metabolism in monocrotaline-induced immunotoxicity in C57BL/6 mice.

Monocrotaline (MCT) is a pyrrolizidine alkaloid which has been shown to induce immunotoxicity in mice. We hypothesized that metabolic activation of MCT by mixed-function oxygenases (MFO) to dehydromonocrotaline (MCTP) is a prerequisite for its immunotoxicity, as has been shown for other toxic effects of MCT. To test this hypothesis, we compared the in vitro immunotoxic potency of MCT and MCTP to suppress the in vitro antibody response to SRBC and the blastogenic response to B and T cell mitogens.

Polychlorinated biphenyl-induced immune suppression: castration, but not adrenalectomy or RU 38486 treatment, partially restores the suppressed cytotoxic T lymphocyte response to alloantigen.

The cytotoxic T lymphocyte (CTL) response to allogeneic P815 tumor in C57bl/6 mice is dose-dependently suppressed after treatment with 3,3',4,4',5,5'-hexachlorobiphenyl (HxCB). Elevation of plasma corticosterone (CS) is also observed coincident with CTL suppression. Because immune suppression is inducible by glucocorticoid administration, the role of elevated CS was investigated as an indirect mechanism of HxCB-induced immunotoxicity.

Tier-2 studies on monocrotaline immunotoxicity in C57BL/6 mice.

Monocrotaline (MCT) is a member of a class of naturally occurring phytotoxins known as pyrrolizidine alkaloids, and is a toxicological concern to both man and his livestock. The purpose of these studies was to evaluate the effect of a 14-day oral MCT (0-100 mg/kg per day) exposure on the functional integrity of various immunocyte effector systems in C57BL/6 mice, as well as to investigate potential mechanisms for its immunotoxicity. Decreases in lymphoid organ weights and cellularity, and resident peritoneal exudate cell (PEC) number were only observed after exposure to the highest dose of 100 mg/kg MCT.

Influence of the Ah locus on the humoral immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: evidence for Ah-receptor-dependent and Ah-receptor-independent mechanisms of immunosuppression.

There are conflicting reports in the literature regarding the role of the Ah locus in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) immunotoxicity. The present studies have utilized two congenic strains of C57Bl/6 mice that differ only at this locus to assess its influence on TCDD-induced suppression of antibody responses. Mice were given a single oral dose of TCDD 2 days prior to challenge with sheep red blood cells (SRBC) or trinitrophenyl-lipopolysaccharide (TNP-LPS).

Immunotoxicity of the pyrrolizidine alkaloid monocrotaline following subchronic administration to C57Bl/6 mice.

Monocrotaline (MCT) is a member of a class of compounds known as pyrrolizidine alkaloids (PAs). PAs are found in the leaves and seeds of a variety of plant species. The potential intoxication of livestock and man through the ingestion of contaminated grains and other foods makes PAs a significant toxicological concern.