Secondhand cannabis smoke exposure and respiratory symptoms among adults living in a state with legalized medical cannabis with limited smoke-free protections.

Background: Little is known about the demographic and health correlates of secondhand cannabis smoke (SHCS) exposure, despite increased availability and use of cannabis across the U.S. This study examined the prevalence and correlates of SHCS exposure in a sample of N=5,410 adults living in Oklahoma and the association of SHCS exposure with self-reported respiratory problems.

The Price of Always Saying Yes: A Cost Analysis of Secondary Overtriage to an Urban Level I Trauma Center.

Level I trauma centers serve as a community resource, with most centers using an inclusive transfer policy that may result in overtriage. The financial burden this imparts on an urban trauma system has not been well examined. We sought to examine the incidence of secondary overtriage (SOT) at an urban Level I trauma center.

Wiser with Age? Increased Per-Surgeon Elderly Patient Volume Is Associated with Lower Postinjury Complications.

We hypothesize that higher elderly patient volume per trauma surgeon is associated with fewer clinical complications. This is a retrospective cohort study which included elderly patients admitted to trauma surgery service within a five-year period, from 2009 to 2013, at two Level I trauma centers in Florida. Trauma surgeons were stratified into three groups depending on patient volume.

Money well spent? A cost and utilization analysis of prophylactic inferior vena cava filter placement in high-risk trauma patients.

Background: Inferior vena cava filters (IVCF) for venous thromboembolic prophylaxis in high-risk trauma patients is a controversial practice. Utilization of IVCF prophylaxis was evaluated at a level 1 trauma center. Daily cost of IVCF prophylaxis, time to IVCF, duration between IVCF and chemoprophylaxis, and number of patients needed to treat (NNT) to prevent pulmonary embolism (PE) was calculated.

In by helicopter out by cab: the financial cost of aeromedical overtriage of trauma patients.

Background: Helicopter transport of injured patients is controversial and costly. This study aims to show that a complex trauma algorithm leads to significant aeromedical overtriage at substantial cost. Our secondary outcomes were to compare adjusted mortality and outcomes between air and ground transport and determine predictors of overtriage.

The G60 Trauma Center: A Future Consideration?

With a considerably increasing elderly population, we sought to determine whether the volume of elderly trauma patients treated impacted outcomes at two different Level I trauma centers. This is a retrospective review of all elderly patients (>60 years) at two state-verified Level I trauma centers over the past five years. The elderly trauma center (ETC) saw a greater proportion (52%) of elderly patients than the reference trauma center (30%, TC).

Probable cause in helicopter emergency medical services crashes: what role does ownership play?

Background: The National Transportation Safety Board (NTSB) ranks helicopter emergency medical services (HEMS) as one of the most perilous occupations in the United States, with improvements in its safety of highest priority. As many injured patients are transported by helicopter, this is of particular concern to the trauma community. The use of HEMS is associated with a heightened degree of inherent risk.

Health sector reform and reproductive health in Latin America and the Caribbean: strengthening the links.

Many countries in Latin America and the Caribbean (LAC) are currently reforming their national health sectors and also implementing a comprehensive approach to reproductive health care. Three regional workshops to explore how health sector reform could improve reproductive health services have revealed the inherently complex, competing, and political nature of health sector reform and reproductive health. The objectives of reproductive health care can run parallel to those of health sector reform in that both are concerned with promoting equitable access to high quality care by means of integrated approaches to primary health care, and by the involvement of the public in setting health sector priorities.

The development of a quality information system: a case study of Mexico.

One of the primary obstacles in the implementation of continuous quality improvement (CQI) programmes in developing countries is the lack of timely and appropriate information for decentralized decision-making. The integrated quality information system (QIS) described herein demonstrates Mexico's unique effort to package four separate, yet mutually reinforcing, tools for the generation and use of quality-related information at all levels of the Mexican national health care system. The QIS is one element of the continuous quality improvement programme administered by the Secretariat of Health in Mexico.

Effects of SCH 59228, an orally bioavailable farnesyl protein transferase inhibitor, on the growth of oncogene-transformed fibroblasts and a human colon carcinoma xenograft in nude mice.

The products of the Ha-, Ki-, and N-ras proto-oncogenes comprise a family of 21 kDa guanine nucleotide-binding proteins which play a crucial role in growth factor signal transduction and in the control of cellular proliferation and differentiation. Activating mutations in the ras oncogenes occur in a wide variety of human tumors. Ras proteins undergo a series of posttranslational processing events.

Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice.

We have been developing a series of nonpeptidic, small molecule farnesyl protein transferase inhibitors that share a common tricyclic nucleus and compete with peptide/protein substrates for binding to farnesyl protein transferase. Here, we report on pharmacological and in vivo studies with SCH 66336, a lead compound in this structural class. SCH 66336 potently inhibits Ha-Ras processing in whole cells and blocks the transformed growth properties of fibroblasts and human tumor cell lines expressing activated Ki-Ras proteins.

Human smooth muscle alpha-actin gene is a transcriptional target of the p53 tumor suppressor protein.

Smooth muscle (sm) alpha-actin is expressed in vascular smooth muscle cells and fibroblast cells. Its expression is regulated by cell proliferation and repressed during oncogenic transformation. In this study, we demonstrate that p53 activation is associated with a dramatic increase in organized microfilament bundles and an increase in sm alpha-actin mRNA level.

Inhibitors of farnesyl protein transferase. 4-Amido, 4-carbamoyl, and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine.

The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl) piperazine to explore the SAR of this series of FPT inhibitors is described. This resulted in the synthesis of the 4- and 3-pyridylacetyl analogues 45a and 50a, respectively, both of which were orally active but were found to be rapidly metabolized in vivo. Identification of the principal metabolites led to the synthesis of a variety of new compounds that would be less readily metabolized, the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and 83a.

Structure-activity relationship of 3-substituted N-(pyridinylacetyl)-4- (8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene )- piperidine inhibitors of farnesyl-protein transferase: design and synthesis of in vivo active antitumor compounds.

Novel tricyclic Ras farnesyl-protein transferase (FPT) inhibitors are described. A comprehensive structure-activity relationship (SAR) study of compounds arising from substitution at the 3-position of the tricyclic pyridine ring system has been explored. In the case of halogens, the chloro, bromo, and iodo analogues 19, 22, and 28 were found to be equipotent.

Biochemical characterization of the binding of echistatin to integrin alphavbeta3 receptor.

Echistatin is a 49-amino-acid peptide belonging to the family of disintegrins that are derived from snake venoms and are potent inhibitors of platelet aggregation and cell adhesion. Integrin alphavbeta3 receptor plays a critical role in several physiological processes such as tumor-induced angiogenesis, tumor cell metastasis, osteoporosis and wound repair. In this study, we have characterized the binding of echistatin to purified integrin alphavbeta3 receptor and the form expressed on human embryonic kidney 293 cells.

K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors.

The association of mutant forms of Ras protein with a variety of human cancers has stimulated intense interest in therapies based on inhibiting oncogenic Ras signaling. Attachment of Ras proteins to the plasma membrane is required for effective Ras signaling and is initiated by the enzyme farnesyl protein transferase. We found that in the presence of potent farnesyl protein transferase inhibitors, Ras proteins in the human colon carcinoma cell line DLD-1 were alternatively prenylated by geranylgeranyl transferase-1.

Efficacy of p53 adenovirus-mediated gene therapy against human breast cancer xenografts.

In response to DNA damage, p53 protein accumulates in the cell nucleus causing cells to undergo DNA repair or apoptosis, programmed cell death. Reintroduction of wild-type p53 into tumors with null or mutant p53 offers a novel strategy for controlling tumor growth, by inducing apoptotic death in neoplastic cells. The efficacy of a replication-deficient p53 adenovirus construct was tested against three human breast cancer cell lines expressing mutant p53, MDA-MB-231, -468, and -435.

Ras oncoprotein inhibitors: the discovery of potent, ras nucleotide exchange inhibitors and the structural determination of a drug-protein complex.

The nucleotide exchange process is one of the key activation steps regulating the ras protein. This report describes the development of potent, non-nucleotide, small organic inhibitors of the ras nucleotide exchange process. These inhibitors bind to the ras protein in a previously unidentified binding pocket, without displacing bound nucleotide.

Discovery of novel nonpeptide tricyclic inhibitors of Ras farnesyl protein transferase.

A comprehensive structure-activity relationship (SAR) study of novel tricyclic amides has been undertaken. The discovery of compounds that are potent FPT inhibitors in the nanomolar range has been achieved. These compounds are nonpeptidic and do not contain sulfhydryl groups.

Antitumor 8-chlorobenzocycloheptapyridines: a new class of selective, nonpeptidic, nonsulfhydryl inhibitors of ras farnesylation.

Ras farnesylation by farnesyl protein transferase (FPT) is an intracellular event that facilitates the membrane association of the ras protein and is involved in the signal transduction process. FPT inhibition could be a novel, noncytotoxic method of treating ras dependent tumor growth. We report here three structural classes of 8-chlorobenzocycloheptapyridines as novel, nonpeptidic, nonsulfhydryl FPT inhibitors having antitumor activity in mice when dosed orally.