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Objective. Chronic regional pain syndrome (CRPS) is a severe pain condition that usually results from an injury or surgical procedure. The pain in CRPS often spreads from the site of injury, and with time becomes refractory to conventional therapy. The present study was undertaken to evaluate the effects of 5-day continuous intravenous lidocaine treatment in patients afflicted with CRPS. Methods. Intravenous lidocaine was administered in an escalating dose schedule to 49 severely affected CRPS patients in a monitored setting over 5 days. Evaluation of pain parameters and other signs and symptoms of CRPS were obtained during the infusion and at 1, 3, and 6 months following therapy. Results. The majority of patients demonstrated a significant decrease in pain parameters and other symptoms and signs of CRPS. The pain reduction lasted an average of 3 months. Lidocaine may be particularly effective for thermal and mechanical allodynia. Less clinically significant effects were documented on the motor aspects of the syndrome. Discussion. Intravenous lidocaine administration titrated to 5 mg/L demonstrated: 1) a significant decrease in mechanical and thermal allodynia for three months, 2) lessened associated inflammatory components of CRPS, and 3) only minimal side effects and no severe complications.

Objective To examine the frequency of allergic sensitization to staphylococcal superantigens in young children with mild to moderate atopic dermatitis (AD). Study design AD severity was assessed with objective Scoring AD. Serum IgE to staphylococcal enterotoxin (SE) A, SEB, SEC, SED, and toxic shock syndrome toxin-1 were measured with ImmunoCAP. Comparisons between mild AD and moderate AD were performed by using logistic regressions. Results The prevalence of allergic sensitization to staphylococcal superantigens in patients with mild and moderate AD was 38% and 63%, respectively. Allergic sensitization to staphylococcal superantigens, particularly SEA and SED, was found to be associated with moderate AD, compared with mild AD. Conclusions Our results suggest that allergic sensitization to staphylococcal superantigens is common even in young children with mild to moderate AD, and such sensitization may contribute to the disease severity of these patients.

ObjectivesThis study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC).MethodsA retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group).ResultsOf 27 patients, 17 had optimal CRS before RT. The actuarial survival at 5 and 10 years (in parenthesis) from date of radiation were LRFS (70% and 60%), overall survival (30% and 19%), and disease-free survival (33% and 20%). None of the NIFRT patients survived beyond 5 years from initiation of salvage chemotherapy.ConclusionsLong-term follow-up in this selected series confirmed the benefit of IFRT (±CRS) in localized ROC. Chemotherapy salvage in a similar NIFRT group was not equivalent, suggesting a role for locoregional therapies in selected patients with ROC.

A series of indole-O-glucosides and C-glucosides was synthesized and evaluated in SGLT1 and SGLT2 cell-based functional assays. Compounds 2a and 2o were identified as potent SGLT2 inhibitors and screened in ZDF rats.

This study identified courses in the pre-professional portion of the curriculum at the St. Louis College of Pharmacy that predicted success in the professional pharmacy curriculum, as measured by their impact on both cumulative grade point average (GPA) for their pre-professional work as well as their GPA before entering clinical externships. Transcripts of the class that started their pre-professional coursework in 1997 at the St. Louis College of Pharmacy underwent multiple regression modeling using SPSS software to analyze the effect of pre-professional science and math courses on pre-professional and pre-clinical academic performance. The basic math and science skills taught in general chemistry, biology, physiology, physics and organic chemistry had the strongest correlation with pre-professional success. Successful entry into the externship phase of the pharmacy curriculum depended primarily on biology, organic chemistry and physiology.

A series of P1/P1' substituted cyclic urea analogues were prepared in an attempt to increase the intra-cellular antiviral potency of the nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851. The effect of alkyl substitution of the P1/P1' residues on cellular antiviral potency, protein binding, resistance profile and pharmacokinetics are described.

Immunizations are the most effective way to reduce incidence of vaccine-preventable diseases. Immunization information systems (IISs) are confidential, population-based, computerized databases that record all vaccination doses administered by participating providers to people residing within a given geopolitical area. They facilitate consolidation of vaccination histories for use by health care providers in determining appropriate client vaccinations. Immunization information systems also provide aggregate data on immunizations for use in monitoring coverage and program operations and to guide public health action.Methods for conducting systematic reviews for the Guide to Community Preventive Services were used to assess the effectiveness of IISs. Reviewed evidence examined changes in vaccination rates in client populations or described expanded IIS capabilities related to improving vaccinations. The literature search identified 108 published articles and 132 conference abstracts describing or evaluating the use of IISs in different assessment categories.Studies described or evaluated IIS capabilities to (1) create or support effective interventions to increase vaccination rates, such as client reminder and recall, provider assessment and feedback, and provider reminders; (2) determine client vaccination status to inform decisions by clinicians, health care systems, and schools; (3) guide public health responses to outbreaks of vaccine-preventable disease; (4) inform assessments of vaccination coverage, missed vaccination opportunities, invalid dose administration, and disparities; and (5) facilitate vaccine management and accountability.Findings from 240 articles and abstracts demonstrate IIS capabilities and actions in increasing vaccination rates with the goal of reducing vaccine-preventable disease.

The solubility of 4 analogues of efavirenz was studied as a function of pH. The study evaluated the ionization behavior and determined the relative contribution of electronegative substituents versus resonance effects on the pK(a) value of the cyclic carbamate. The most profound lowering effect on the pK(a) was due to the presence of multiple electronegative substituents and in particular the trifluoromethyl and acetylene groups. The presence of chlorine on the benzoxazinone ring was found to have a slight impact on the pK(a), although to a lesser extent. In the absence of any functional groups on the benzoxazinone ring system, the pKa shifted to a value of 13.2, which is 3 pH units above that of efavirenz and more closely correlates with typical literature values for cyclic carbamates.

You are half way through a usability test session, and the participant s cell phone rings. She answers it and says it s her child calling and she has to leave immediately, but she ll be back in 45 minutes to finish the test What should you do? In the course of running hundreds of product evaluations, we have encountered some awkward and unusual situations. These situations involve issues with participants, with the software or product being tested, and with the test protocol. Among the factors that we consider when resolving these issues include the participant s rights and psychological well-being, the cost to replace the participant s test session, the importance of adhering strictly to the recruiting criteria, and how eliminating the test session might affect the integrity of the protocol or data. In this paper, we describe some real-life sticky testing situations and discuss the factors we considered in resolving each issue.

The preparation of unsymmetrical cyclic ureas bearing novel biaryl indazoles as P2/P2' substituents was undertaken, utilizing a Suzuki coupling reaction as the key step. Compound 6i was equipotent to the lead compound of the series SE063.

Two series of benzoxazinones differing in the aromatic substitution pattern were prepared and evaluated as HIV-1 reverse transcriptase inhibitors. The 5-fluoro (5a-d) and 6-nitro (5e-h) substituted compounds displayed activity comparable or better than Efavirenz, the lead structure of the series.

Two series of cyclic ureas modified at the P1/P1′ residue were prepared and evaluated for HIV protease inhibition and whole cell antiviral activity. Compounds 8b, 10 (3- and 4-pyridylmethyl analogs) and 6b (4-methoxy analog) showed significant improvement in antiviral activity relative to lead compounds DMP323 and DMP 450.

A novel series of spirobenzazepines was synthesized and evaluated for V1a and V2 receptor antagonist activity. Compounds 8b, 8i, and 8k have shown selective V1a receptor antagonist activity. Compounds 8p and 8q were shown to be dual V1a/V2 receptor antagonists.

BackgroundA new version of international standard (ISO 15197) and CLSI Guideline (POCT12) with more stringent accuracy criteria are near publication. We evaluated the glucose test performance of the FreeStyle Precision Pro system, a new blood glucose monitoring system (BGMS) designed to enhance accuracy for point-of-care testing (POCT).MethodsPrecision, interference and system accuracy with 503 blood samples from capillary, venous and arterial sources were evaluated in a multicenter study. Study results were analyzed and presented in accordance with the specifications and recommendations of the final draft ISO 15197 and the new POCT12.ResultsThe FreeStyle Precision Pro system demonstrated acceptable precision (CV

Educational collaboratives offer a promising approach to disseminate educational resources and provide faculty development to advance residents' training, especially in areas of novel curricular content; however, their impact has not been clearly described. Advocacy training is a recently mandated requirement of the Accreditation Council for Graduate Medical Education that many programs struggle to meet.The authors describe the formation (in 2007) and impact (from 2008 to 2010) of 13 California pediatric residency programs working in an educational collaboration ("the Collaborative") to improve advocacy training. The Collaborative defined an overarching mission, assessed the needs of the programs, and mapped their strengths. The infrastructure required to build the collaboration among programs included a social networking site, frequent conference calls, and face-to-face semiannual meetings. An evaluation of the Collaborative's activities showed that programs demonstrated increased uptake of curricular components and an increase in advocacy activities. The themes extracted from semistructured interviews of lead faculty at each program revealed that the Collaborative (1) reduced faculty isolation, increased motivation, and strengthened faculty academic development, (2) enhanced identification of curricular areas of weakness and provided curricular development from new resources, (3) helped to address barriers of limited resident time and program resources, and (4) sustained the Collaborative's impact even after formal funding of the program had ceased through curricular enhancement, the need for further resources, and a shared desire to expand the collaborative network.

The polymyxins (polymyxin B and E) are bactericidal polypeptide antibiotics first discovered in 1947 and used for the treatment of gram-negative bacterial infections. Renal and neurologic toxicities coupled with the increasing availability of effective alternatives led to declining use in the 1960s. The emergence of multidrug-resistant organisms in the past decade has resulted in a resurgence in the use of polymyxins in critically ill patients, yet the side effects are not well known. We report two cases of respiratory arrest likely due to polymyxin B infusions in the context of a 10-fold increase in the use of polymyxin B in our institution over the past 10 years.

The effect of hypoxia on 3T3-L1 cell differentiation was examined in confluent cultures incubated with differentiation medium (DM) followed by incubation in growth medium (GM). Control cultures remained in GM throughout the incubation period. Eight days after the incubation, cells were assessed either for changes in morphology by staining with Oil Red O/hematoxylin or harvested to measure protein kinase C activity. Morphological examination of stained cells showed almost complete differentiation of normoxic cells to adipocytes when exposed to DM. By contrast hypoxia caused a dramatic inhibition of differentiation under similar media conditions with only 34 ± 4% of cells accumulating fat deposits. Cultures sustained in GM under normoxic or hypoxic conditions were devoid of any fat deposits, reflecting an undifferentiated phenotype. Normoxic cells exposed to DM exhibited a significantly lower membrane to cytosolic ratio of protein kinase C in comparison with cells maintained in GM, which is consistent with differentiated and undifferentiated phenotypes, respectively. In comparison with normoxic cells incubated in DM, cells exposed to hypoxia under similar media conditions exhibited a significantly higher membrane to cytosolic ratio of protein kinase C, indicating sustained activation of the enzyme. In addition, cells in differentiation medium exposed to hypoxia in the presence of the protein kinase C inhibitors staurosporine or H7 exhibited a significant increase in the number of fat accumulating cells when compared with hypoxic controls. These studies indicate that chronic hypoxia impairs the differentiation of 3T3-L1 cells to adipocytes in association with the sustained activation of protein kinase C, which appears to play a role in mediating this process. © 1994 Wiley-Liss, Inc.

A series of 4,4-disubstituted quinolinones was prepared and evaluated as HIV-1 reverse transcriptase inhibitors. The C-3 substituted compound 9h displayed improved antiviral activity against clinically significant single (K103N) and double (K103N/L100I) mutant viruses.

a new strip, designed to enhance the ease of use and minimize interference of non-glucose sugars, has been developed to replace the current FreeStyle (Abbott Diabetes Care, Alameda, CA) blood glucose test strip. We evaluated the performance of this new strip.laboratory evaluation included precision, linearity, dynamic range, effects of operating temperature, humidity, altitude, hematocrit, interferents, and blood reapplication. System accuracy, lay user performance, and ease of use for finger capillary blood testing and accuracy for venous blood testing were evaluated at clinics. Lay users also compared the speed and ease of use between the new strip and the current FreeStyle strip.for glucose concentrations75 mg/dL, 73%, 100%, and 100% of the individual capillary blood glucose results obtained by lay users fell within ± 5, 10, and 15 mg/dL, respectively, of the reference. For glucose concentrations ≥75 mg/dL, 68%, 95%, 99%, and 99% of the lay user results fell within ± 5%, 10%, 15%, and 20%, respectively, of the reference. Comparable accuracy was obtained in the venous blood study. Lay users found the new test strip easy to use and faster and easier to use than the current FreeStyle strip. The new strip maintained accuracy under various challenging conditions, including high concentrations of various interferents, sample reapplication up to 60 s, and extremes in hematocrit, altitude, and operating temperature and humidity.our results demonstrated excellent accuracy of the new FreeStyle test strip and validated the improvements in minimizing interference and enhancing ease of use.

Treatment of heterocyclic o-aminonitriles and o-aminoesters 1a-5a with dibromotriphenylphosphorane gives iminophosphoranes 1b-5b which undergo a facile aza-Wittig reaction at room temperature with phenyl isocyanate to provide the carbodiimides 1c-5c. Treatment of the latter intermediates with ammonia leads to intramolecular ring closure of the initially formed guanidines to provide the fused 4-aminopyrimidines and 4(3H)-pyrimidinones 1d-Sd.

Two series of cyclic ureas modified at the P1/P1′ residue were prepared and evaluated for HIV protease inhibition and whole cell antiviral activity. Compounds 8b, 10 (3- and 4-pyridylmethyl analogs) and 6b (4-methoxy analog) showed significant improvement in antiviral activity relative to lead compounds DMP323 and DMP 450.

A series of 4,4-disubstituted quinolinones was prepared and evaluated as HIV-1 reverse transcriptase inhibitors. The C-3 substituted compound 9h displayed improved antiviral activity against clinically significant single (K103N) and double (K103N/L100I) mutant viruses.

The synthesis and biological activity of novel 5-desmethylene analogues of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF, a potent antitumor agent presently indergoing clinical trails, are desscribed; These compounds are representative of a new series of optically pure analogues of DDATHF

Treatment of heterocyclic o-aminonitriles and o-aminoesters 1a-5a with dibromotriphenylphosphorane gives iminophosphoranes 1b-5b which undergo a facile aza-Wittig reaction at room temperature with phenyl isocyanate to provide the carbodiimides 1c-5c. Treatment of the latter intermediates with ammonia leads to intramolecular ring closure of the initially formed guanidines to provide the fused 4-aminopyrimidines and 4(3H)-pyrimidinones 1d-Sd.

on communication in the older adult patients they care for. Understand that rates of formal training and knowledge about hearing loss management is low. Original Research Background. Age-related hearing loss can impair patient-provider communication about symptom management, goals of care, and endof-life decision making. Research Objectives. To determine whether hospice and palliative care providers screen for or received training about hearing loss, believe it impacts patient care, and use strategies to optimize communication. Methods. National survey of hospice andpalliative care providers. Survey questions were pilot-tested with multidisciplinary providers in San Francisco. We solicited responses via emails to professional contacts and AAHPM members, the GeriPal blog, twitter, and Facebook. Responses were collected using an online survey tool. Results. Of 510 responses (55% age 50+, 65% female, 63% inpractice 5+ years, 55%practice primarily in inpatient/outpatient palliative care, 45% in hospice), 315 were physicians, 50 nurses, 48 NPs, 58 social workers, and 39 chaplains. Ninety-one percent reported that hearing loss has some or great impact on the quality of care for older adults. Eighty-eight percent recalled a specific instance of hearing loss impairing communication with a patient, and 56% remembered it impairing communication with a caregiver. Eighty-seven percent of physicians, nurses, and NPs reported not screening for hearing loss. While 62% felt comfortable with their communication skills for patients with hearing loss, only 21% reported receiving formal training in its management, 31%were unfamiliar with resources for patients with hearing loss, and 38%had never heard of a pocket talker amplification device. Conclusion. Hospice and palliative medicine providers believe age-related hearing loss impacts care, yet most do not screen. While they feel they are managingwell, fewhave formal training, and knowledge about management approaches and resources is sub-optimal. Implications for Research, Policy or Practice. The lack of research in this area is glaring relative to its importance. Universal screening should be considered. Training in management strategies is needed.

Objectives Reflect on current neonatal intensive care practice for the seriously ill and or dying neonate. Explore the role of the primary palliative care clinician. Discuss palliative educational goals for intensive care clinicians. Introduction: This session will be an interactive discussion with presenters (parent, palliative care nurse scientist/educator/author/neonatologist/palliative care pediatric nurse consultant). Our assumption is that primary palliative care is integral to the life-supporting care of neonates and their families on admission to the neonatal intensive care unit (NICU). Background: In keeping with the recommendations of the 2014 Institute of Medicine’s Dying in America report, primary palliative care must be included in the basic curriculum for every clinician who cares for patients with advanced or serious illness. Clinicians practicing in the NICU fall squarely in this category as demonstrated by the life-supporting measures required by sick newborns while addressing the vulnerable traumatized emotional state of parents, especially mothers. Few parents are able to grasp the enormity of the situations they are now facing. Two-thirds of infant deaths (birth-1 year) occur in the neonatal period (birth-28 days). Other neonates remain with a significant degree of prognostic uncertainty, hovering between life and death for weeks or months. If an infant dies, parents are often unprepared and, in turn, the intensive care team is unprepared to respond to the intense suffering of parents.

We have continued to explore spirobenzazepines as vasopressin receptor antagonists to follow up on RWJ-339489 (2), which had advanced into preclinical development. Further structural modifications were pursued to find a suitable backup compound for human clinical studies. Thus, we identified carboxylic acid derivative 3 (RWJ-676070; JNJ-17158063) as a potent, balanced vasopressin V(1a)/V(2) receptor antagonist with favorable properties for clinical development. Compound 3 is currently undergoing human clinical investigation.

A series of indole-O-glucosides and C-glucosides was synthesized and evaluated in SGLT1 and SGLT2 cell-based functional assays. Compounds 2a and 2o were identified as potent SGLT2 inhibitors and screened in ZDF rats.

A series of benzo-fused heteroaryl-O-glucosides was synthesized and evaluated in SGLT1 and 2 cell-based functional assays. Indole-O-glucoside 10a and benzimidazole-O-glucoside 18 exhibited potent in vitro SGLT2 inhibitory activity.

A series of benzo-fused heteroaryl-O-glucosides was synthesized and evaluated in SGLT1 and 2 cell-based functional assays. Indole-O-glucoside 10a and benzimidazole-O-glucoside 18 exhibited potent in vitro SGLT2 inhibitory activity.

This review describes the role of nuclear receptors in the regulation of genes involved in cholesterol transport and synthetic modulators of these receptors. Increasing the efflux of cholesterol from peripheral cells, such as lipid-laden macrophages, through a process called reverse cholesterol transport (RCT) requires HDL. Increasing the circulating levels of HDL, as well as the efficiency of the RCT process, could result in a reduction in the development of coronary artery disease and atherosclerosis. Nuclear receptors of the RXR heterodimer family have recently been shown to regulate key genes involved in HDL metabolism and reverse cholesterol transport. These include the PPARs (peroxisome proliferator activated receptors), the LXR (liver X receptor) and the farnesoid X receptor (FXR). The synthesis of specific and potent ligands for these receptors has aided in ascertaining the physiological role of these receptors as lipid sensors and the potential therapeutic utility of modulators of these receptors in dyslipidemias and cardiovascular disease.

A series of substituted spirobenzazepines was prepared and evaluated as V1a and V2 dual vasopressin receptor antagonists. Compounds 7p and 7q have been shown to be not only potent inhibitors of vasopressin receptors, but also have exhibited an excellent overall pharmaceutical suitability profile.

The practical and highly diastereoselective syntheses of CF3-substituted dihydroquinazolinones via 1,4-additions of nucleophiles to chiral auxiliary substituted 2(3H)-quinazolinones is described. This methodology is applied to the syntheses of the NNRTIs (nonnucleoside reverse transcriptase inhibitors) DPC 961 (1) and DPC 083 (2), which are useful for the treatment of HIV (human immunodeficiency virus). The synthesis of DPC 961 (1) requires three steps, proceeds in >55% overall yield from the keto-aniline 9, and gives synthetic access to DPC 083 (2). In addition, the scope of the new diastereoselective 1,4-addition chemistry is investigated. The first preparation of DPC 961 (1) described in this paper is a derivatization fractional crystallization protocol.