Physician Beliefs about Physical and Mental Competency of Patients Applying for Concealed Weapon Permits.

Law enforcement officials have asked health care providers to evaluate patient applications for concealed weapon permits. The current study was designed to examine physician beliefs regarding competency to carry a concealed weapon for patients with specific physical and mental conditions. Among 222 North Carolina physicians who participated in this survey (40% response rate), large variation and uncertainty existed for determining competency. Physicians most frequently chose mild dementia, post-traumatic stress disorder, and recent depression as conditions that would render a patient not competent to carry a concealed weapon. Male physicians and those owning a gun were more likely to deem a patient competent. Almost a third of physicians were unsure about competence for most conditions. Physicians asked to assess competency of patients to carry a concealed weapon have quite disparate views on competency and little confidence in their decisions. If physicians are expected to assess patient competence to carry a concealed weapon, more objective criteria and training are needed.

Coronary artery stents and antiplatelet therapy in patients with cirrhosis.

GOALS: To describe our experience with coronary artery stenting and antiplatelet therapy in cirrhotic patients and compare rates of bleeding with a control group. BACKGROUND: Although there are data on cardiac evaluation and perioperative cardiac risk in cirrhotic patients, there is a paucity of information on outcomes in cirrhotic patients with coronary artery stents. Cirrhotic patients may be at increased risk for complications, including gastrointestinal bleeding as a result of antiplatelet therapy prescribed after stenting. STUDY: We performed a retrospective study of complications in cirrhotics that received a coronary artery stent followed by clopidogrel and aspirin prescribed to prevent stent occlusion. Cirrhotics with stents were compared with an age and sex-matched control group with cirrhosis without stents and not on aspirin. RESULTS: Among 423 cirrhotic patients who underwent liver transplant evaluation, 16 patients (3.8%) received a stent of which 9 underwent liver transplant. Two patients with varices (12.5%) in the stent group had fatal variceal bleeding and 2 controls (6.3%) had nonfatal variceal bleeding during follow-up while on antiplatelet therapy (P=0.86). There were no significant differences in transfusion requirements between the 9 liver transplant recipients with stents compared with the control group, P=0.69 for packed red blood cells. CONCLUSIONS: In our experience, it is safe for cirrhotic patients without varices to receive a coronary artery stent and for cirrhotic patients with coronary artery stents to be considered for liver transplantation. Larger prospective studies are needed to confirm these results and evaluate the risk of bleeding in cirrhotics with varices who receive coronary artery stents and antiplatelet therapy.

A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism.

BACKGROUND: Opioids are the most widely used analgesics for the treatment of clinical pain. They produce their therapeutic effects by binding to mu-opioid receptors (MORs), which are 7 transmembrane domain (7TM) G-protein-coupled receptors (GPCRs), and inhibiting cellular activity. However, the analgesic efficacy of opioids is compromised by side-effects such as analgesic tolerance, dependence and opioid-induced hyperalgesia (OIH). In contrast to opioid analgesia these side effects are associated with cellular excitation. Several hypotheses have been advanced to explain these phenomena, yet the molecular mechanisms underlying tolerance and OIH remain poorly understood. RESULTS: We recently discovered a new human alternatively spliced isoform of MOR (MOR1K) that is missing the N-terminal extracellular and first transmembrane domains, resulting in a 6TM GPCR variant. To characterize the pattern of cellular transduction pathways activated by this human MOR1K isoform, we conducted a series of pharmacological and molecular experiments. Results show that stimulation of MOR1K with morphine leads to excitatory cellular effects. In contrast to stimulation of MOR1, stimulation of MOR1K leads to increased Ca2+ levels as well as increased nitric oxide (NO) release. Immunoprecipitation experiments further reveal that unlike MOR1, which couples to the inhibitory Galphai/o complex, MOR1K couples to the stimulatory Galphas complex. CONCLUSION: The major MOR1 and the alternative MOR1K isoforms mediate opposite cellular effects in response to morphine, with MOR1K driving excitatory processes. These findings warrant further investigations that examine animal and human MORK1 expression and function following chronic exposure to opioids, which may identify MOR1K as a novel target for the development of new clinically effective classes of opioids that have high analgesic efficacy with diminished ability to produce tolerance, OIH, and other unwanted side-effects.

Molecular assays for characterization of alternatively spliced isoforms of the u opioid receptor (MOR).

Mu-opioid receptor (MOR) belongs to a family of heptahelical G-protein-coupled receptors (GPCRs). Studies in humans and rodents demonstrated that the OPRM1 gene coding for MOR undergoes extensive alternative splicing afforded by the genetic complexity of OPRM1. Evidence from rodent studies also demonstrates an important role of these alternatively spliced forms in mediating opiate analgesia via their differential signaling properties. MOR signaling is predominantly G(ia) coupled. Release of the alpha subunit from G-protein complex results in the inhibition of adenylyl cyclase/cAMP pathway, whereas release of the betagamma subunits activates G-protein-activated inwardly rectifying potassium channels and inhibits voltage-dependent calcium channels. These molecular events result in the suppression of cellular activities that diminish pain sensations. Recently, a new isoform of OPRM1, MOR3, has been identified that shows an increase in the production of nitric oxide (NO) upon stimulation with morphine. Hence, there is a need to describe molecular techniques that enable the functional characterization of MOR isoforms. In this review, we describe the methodologies used to assay key mediators of MOR activation including cellular assays for cAMP, free Ca(2+), and NO, all of which have been implicated in the pharmacological effects of MOR agonists.

Effect of polyelectrolytes and quaternary ammonium compounds on the anaerobic biological treatment of poultry processing wastewater.

Quaternary ammonium compounds (QACs) and polyelectrolytes are extensively used in poultry processing facilities as sanitizing agents and flocculants, respectively. These chemicals may affect the performance of biological treatment systems resulting in low effluent quality. The impact of these chemicals on the anaerobic treatment of poultry processing wastewater (PPWW) samples, collected before and after a solids separation process, was tested in batch assays using a mixed, mesophilic (35 degrees C) methanogenic culture. The results of this study showed that Vigilquat (VQ), a commercial mixture of four QACs, has a high affinity for the organic solids in the PPWW. Cationic and anionic polyelectrolytes, alone or in combination, did not have any adverse effect on the anaerobic biodegradation of PPWW at concentrations typically used in poultry processing facilities (20 and 5 mg/L, respectively). In spite of the high affinity of VQ for the PPWW solids, VQ at a concentration of 50mg/L and above adversely affected the anaerobic degradation of the PPWW, which resulted in a significantly reduced methane production and accumulation of volatile fatty acids. In the absence of any inhibition, the methane yield varied from 0.76 to 0.98 L methane at STP per g volatile solids added. VQ was not biodegraded under the batch, methanogenic conditions used in this study.

Fate and effect of quaternary ammonium compounds on a mixed methanogenic culture.

The potential inhibitory effect of four quaternary ammonium compounds (QACs) and Vigilquat, a commercial sanitizer which is a mixture of the four QACs, was investigated at concentrations up to 100 mg/L using a mixed, mesophilic (35 degrees C) methanogenic culture. Dextrin and peptone were used as the carbon and energy sources. A batch assay conducted at a range of QAC concentrations showed that QACs were inhibitory to methanogens at and above 25 mg/L. Methanogenesis was more susceptible to QAC inhibition than acidogenesis. Adsorption of QACs on biomass was successfully simulated with the Freundlich isotherm equation. The inhibitory effect of Vigilquat on the mixed methanogenic culture was also investigated in a batch reactor fed with dextrin and peptone. Methanogens were inhibited when the total QAC concentration reached 30 mg/L and volatile fatty acids (VFAs) accumulated. However, methane production recovered in 57 days of incubation, and all VFAs were consumed, suggesting that a prolonged incubation period is necessary for the methanogens to overcome the transient inhibition at a relatively low QAC concentration. None of the QACs tested in this study was biodegraded under methanogenic conditions.

Fate and effect of the antioxidant ethoxyquin on a mixed methanogenic culture.

The potential inhibitory effect of ethoxyquin, an antioxidant commonly used as a preservative in the food processing industry (e.g., for stabilizing dissolved air flotation residuals), was evaluated at concentrations up to 300 mg/L using a mixed, mesophilic (35 degrees C) methanogenic culture and dextrin, peptone and methanol as the carbon source. A batch assay conducted with a range of ethoxyquin concentrations did not result in any inhibition up to an ethoxyquin concentration of 75 mg/L, but severe inhibition of methanogenesis was observed at concentrations higher than 150 mg/L. Ethoxyquin addition to a batch reactor with the same mixed, methanogenic culture, at ethoxyquin concentrations gradually increasing over 100 days, resulted in a transient and a complete inhibition of methanogenesis at ethoxyquin concentrations of 150 and 300 mg/L, respectively. Acidogens were not significantly impacted, whereas aceticlastic and methanol degrading methylotrophic methanogens were impacted the most. Acclimation of the methanogenic culture to ethoxyquin was not observed over an incubation period of more than 100 days. Long-term (>100 days) incubation at sub-inhibitory ethoxyquin concentrations did not result in ethoxyquin biotransformation. Similarly, ethoxyquin biotransformation was not evident over an 8-day aeration period in a laboratory-scale activated sludge reactor operated under fully aerobic conditions. Ethoxyquin phase distribution tests conducted with the mixed, methanogenic culture at 1.61 g/L volatile solids concentration and nominal ethoxyquin concentrations equal to or higher than 300 mg/L resulted in solid phase/liquid phase ethoxyquin ratios equal to or higher than 1.0. The combined effect of ethoxyquin recalcitrance under anaerobic conditions along with its phase distribution, which favors biosolids, will result in ethoxyquin accumulation in anaerobic treatment systems used by the food processing industry. Such accumulation may pose concerns relative to inhibitory effects in these treatment systems and the disposal of ethoxyquin-bearing biosolids.

Hip function in adults with severe cerebral palsy.

BACKGROUND: The reported prevalence of hip pain in patients with severe cerebral palsy has varied widely. It is unclear whether surgical treatment is indicated for progressive hip subluxation in immature patients with severe involvement. In the present study, we evaluated seventy-seven adults who were profoundly affected with cerebral palsy to determine if either spastic hip displacement (subluxation or dislocation) or osteoarthritis was associated with hip pain and/or diminished function. METHODS: Data regarding the medical history, level of function, pain, and use of analgesics were obtained from a review of medical records and from caregiver interviews. The range of motion of the hip, the degree of spasticity, the presence of pressure ulcers, and changes in vital signs as well as in the Face, Legs, Activity, Cry, and Consolability behavioral pain score were documented. Radiographs of the pelvis and spine were blindly evaluated for evidence of osteoarthritis and subluxation or dislocation. Statistical analysis was performed in order to identify associations between the medical history, the physical examination findings, and the radiographic measurements. RESULTS: The study group included seventy-seven adult subjects (thirty-eight men and thirty-nine women) with a mean age of forty years. Twenty-three (15%) of the 154 hips in these subjects were dislocated, eighteen (12%) were subluxated, and thirty-five (23%) had radiographic evidence of osteoarthritis. Twenty-eight (18%) of the 154 hips were definitely painful, and sixty-nine (45%) were definitely not painful. Increased hip pain and problems with perineal care were noted in patients with decreased hip abduction (<30 degrees ) (p = 0.01), windswept hip deformities (p = 0.02), and flexion contractures of >30 degrees (p = 0.07). Increased spasticity was associated with higher rates of osteoarthritis, dislocation, pain, and pressure ulcers. Spastic hip subluxation or dislocation was significantly associated with osteoarthritis (p = 0.0001), but not with hip pain. There was no association between radiographic evidence of osteoarthritis and hip pain. CONCLUSIONS: Neither hip displacement (i.e., subluxation or dislocation) nor osteoarthritis was found to be associated with hip pain or diminished function. Because the prevalence of hip pain is low and is not associated with hip displacement or osteoarthritis, we suggest that surgical treatment of the hip in severely affected patients be based on the presence of pain or contractures and not on radiographic signs of hip displacement or osteoarthritis. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.