Synchrotron radiation-based far-infrared spectroscopic ellipsometer with full Mueller-matrix capability.

We developed far-IR spectroscopic ellipsometer at the U4IR beamline of the National Synchrotron Light Source in Brookhaven National Laboratory. This ellipsometer is able to measure both, rotating analyzer and full-Mueller matrix spectra using rotating retarders, and wire-grid linear polarizers. We utilize exceptional brightness of synchrotron radiation in the broad spectral range between about 20 and 4000 cm(-1). Fourier-transform infrared (FT-IR) spectrometer is used for multi-wavelength data acquisition. The sample stage has temperature variation between 4.2 and 450 K, wide range of θ-2θ angular rotation, χ tilt angle adjustment, and X-Y-Z translation. A LabVIEW-based software controls the motors, sample temperature, and FT-IR spectrometer and also allows to run fully automated experiments with pre-programmed measurement schedules. Data analysis is based on Berreman's 4 × 4 propagation matrix formalism to calculate the Mueller matrix parameters of anisotropic samples with magnetic permeability µ ≠ 1. A nonlinear regression of the rotating analyzer ellipsometry and∕or Mueller matrix (MM) spectra, which are usually acquired at variable angles of incidence and sample crystallographic orientations, allows extraction of dielectric constant and magnetic permeability tensors for bulk and thin-film samples. Applications of this ellipsometer setup for multiferroic and ferrimagnetic materials with µ ≠ 1 are illustrated with experimental results and simulations for TbMnO3 and Dy3Fe5O12 single crystals. We demonstrate how magnetic and electric dipoles, such as magnons and phonons, can be distinguished from a single MM measurement without adducing any modeling arguments. The parameters of magnetoelectric components of electromagnon excitations are determined using MM spectra of TbMnO3.

Computer simulation to aid the risk assessment of wheelchair and special seating systems used in transport.

The crashworthiness of occupied proprietary wheelchairs, which are transported in motor vehicles, is currently assessed by physical crash testing in accordance with ISO 7176-19. If such wheelchairs are modified to meet the needs of the occupant, e.g. the addition of special seating, environmental control systems or life support equipment, then those making the modifications take on the manufacturer's responsibilities, one of these being the assessment of the modified wheelchair's ability to withstand vehicle crash forces. Destructively testing bespoke wheelchair designs is not practical so, currently, the transport-related risk is assessed using best engineering judgement. To improve this process virtual crash testing of the wheelchair and occupant was used. A modified crash criteria from ISO 7176-19 is proposed to enable assessment of the wheelchair's crashworthiness and provide the clinical engineer with an informed judgement of how both wheelchair alone and occupant and wheelchair together will behave in a crash.

Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomised controlled trial.

BACKGROUND: This randomised, double-blind, double-dummy, parallel-group multicentre study assessed the impact of a total daily dose of 60-80 mg oral oxycodone prolonged-release (PR)/naloxone PR (OXN PR) as fixed-ratio combination for patients with opioid-induced constipation (OIC) having moderate-to-severe, non-malignant pain. METHODS: During pre-randomisation patients receiving opioids for moderate-to-severe non-malignant pain were converted to oxycodone PR (OXY PR) and titrated to an effective analgesic dose. During randomisation 265 patients on a stable OXY PR dose (60-80 mg/day) and with OIC were included in the full analysis population to receive OXN PR or OXY PR alone. Primary outcome was improvement in symptoms of constipation as measured by the Bowel Function Index (BFI). Secondary/exploratory outcomes examined analgesic efficacy and other bowel function parameters. RESULTS: After 4 weeks of treatment, patients receiving OXN PR showed a significant improvement in bowel function compared with those in the OXY PR group (-14.9; 95% CI: -17.9, -11.9; p<0.0001) as measured by BFI which was seen after only 1 week of treatment continuing to the end of the study. After 4 weeks of treatment, patients receiving OXN PR had a median number of 3.0 complete spontaneous bowel movements (CSBM) per week compared with only 1.0 for OXY PR alone. Laxative intake was lower in the OXN PR than the OXY PR group. Furthermore, improvements in bowel function were achieved without loss of analgesic efficacy; pain intensity scores were comparable between the groups and consistent for duration of the study. Most frequently reported adverse events were consistent with those reported for opioid analgesics; no new or unexpected adverse reactions attributable to OXN PR used in higher doses were observed. CONCLUSION: This study shows that the fixed-ratio combination of OXN PR is superior to OXY PR alone in terms of bowel function, while providing effective equivalent analgesia.

A proteomic approach to understanding the development of multidrug-resistant Candida albicans strains.

Resistance of the pathogenic yeast Candida albicans to the antifungal agent fluconazole is often caused by the overexpression of genes that encode multidrug efflux pumps ( CDR1, CDR2, or MDR1). We have undertaken a proteomic approach to gain further insight into the regulatory network controlling efflux pump expression and drug resistance in C. albicans. Three pairs of matched fluconazole-susceptible and resistant clinical C. albicans isolates, in which drug resistance correlated with stable activation of MDR1 or CDR1/2, were analyzed for differences in their protein expression profiles. In two independent, MDR1-overexpressing, strains, additional up-regulated proteins were identified, which are encoded by the YPR127 gene and several members of the IFD ( YPL088) gene family. All are putative aldo-keto reductases of unknown function. These proteins were not up-regulated in a fluconazole-resistant strain that overexpressed CDR1 and CDR2 but not MDR1, indicating that expression of the various efflux pumps of C. albicans is controlled by different regulatory networks. To investigate the possible role of YPR127 in the resistance phenotype of the clinical isolates, we constitutively overexpressed the gene in a C. albicans laboratory strain. In addition, the gene was deleted in a C. albicans laboratory strain and in one of the drug-resistant clinical isolates in which it was overexpressed. Neither forced overexpression nor deletion of YPR127 affected the susceptibility of the strains to drugs and other toxic substances, suggesting that the regulatory networks which control the expression of efflux pumps in C. albicans also control genes involved in cellular functions not related to drug resistance.

Differential transcription factor expression in human mononuclear cells in response to amphotericin B: identification with complementary DNA microarray technology.

STUDY OBJECTIVE: To identify genes differentially expressed in human monocytic cells exposed to amphotericin B in vitro. DESIGN: In vitro experiment. SETTING: Hospital laboratory. MATERIAL: Human mononuclear cell line, THP-1. INTERVENTION: Human mononuclear cells were exposed to amphotericin B or media alone for 6 hours. After exposure, total RNA was isolated and reverse transcribed to complementary DNA. Differences in probe hybridization observed during blotting were measured, and genes with altered regulation were described by using human complementary DNA microarray technology. MEASUREMENTS AND MAIN RESULTS: Of 588 genes represented on the array, 16 transcripts were found to be upregulated and 4 transcripts were downregulated in response to amphotericin B. These findings suggest that amphotericin B alters the expression of genes in human monocytic cells that play a role in many cellular functions, including immune response, signal transduction, and cell differentiation. CONCLUSION: Amphotericin B induces alterations in human cell gene transcription. These changes could be used to evaluate differences in toxicity or efficacy observed in patients receiving this agent.

Intravenous itraconazole.

OBJECTIVE: To review the pharmacology, mycology, chemistry, pharmacokinetics, efficacy, safety, tolerability, dosage, administration, and economic issues of intravenous itraconazole. DATA SOURCES: A MEDLINE search from 1978 to June 2000 of the English-language literature and an extensive review of meeting abstracts was conducted. Due to the paucity of published information concerning the pharmacokinetics, efficacy, and safety of the intravenous formulation of intravenous itraconazole, additional information was obtained from the manufacturer. DATA EXTRACTION: Data from in vitro and preclinical studies, as well as Phase II and III clinical trials, were included. DATA SYNTHESIS: The triazole antifungal agent itraconazole is available in a cyclodextrin-based intravenous formulation. Intravenous itraconazole is indicated for the treatment of pulmonary and extrapulmonary blastomycosis; histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis; and pulmonary and extrapulmonary aspergillosis in patients who are intolerant of or who are refractory to amphotericin B. This formulation provides quicker and more consistent therapeutic concentrations than the oral formulations. Clinical data comparing the efficacy of intravenous itraconazole with that of amphotericin B are lacking. CONCLUSIONS: Intravenous itraconazole offers a less toxic alternative for patients with pulmonary and extrapulmonary blastomycosis, histoplasmosis, and aspergillosis who cannot receive oral medications or who are intolerant of or refractory to amphotericin B.

Beyond sexual assessment: lessons learned from couples post radical prostatectomy.

PURPOSE: To share selected experiences of advanced practice nurses (APNs) who implemented a home-based nursing protocol related to psychosexual function for couples following radical surgery for prostate cancer. DATA SOURCES: Selected research-based articles, the PLISSIT Model for sexual rehabilitation counseling, and the authors' experiences. CONCLUSIONS: Five lessons related to communicating about sexuality and intimacy were synthesized from the experience, including examining knowledge and self-awareness regularly, using a structured interview guide to facilitate the process, developing a trusting relationship with the couple, attending to verbal and nonverbal cues, and providing information about the full range of sexual expression. IMPLICATIONS FOR PRACTICE: Include an assessment of sexual health as an integral part of a general health assessment. Patients do not generally volunteer information about their sexual concerns unless the subject is introduced by the APN.

Comparison of the caudal and lumbar approaches to the epidural space.

OBJECTIVES: To investigate the accuracy of placement of epidural injections using the lumbar and caudal approaches. To identify which factors, if any, predicted successful placement. METHODS: 200 consecutive patients referred to a pain clinic for an epidural injection of steroid were randomly allocated to one of two groups. Group L had a lumbar approach to the epidural space and group C a caudal approach to the epidural space. Both groups then had epidurography performed using Omnipaque and an image intensifier to determine the position of the needle. RESULTS: Body mass index (BMI), grade of operator, and route of injection were predictors of a successful placement. 93% of lumbar and 64% of caudal epidural injections were correctly placed (p< 0.001). 97% of lumbar and 85% of caudal epidural injections clinically thought to be correctly placed were confirmed radiographically. For epidural injections where the clinical impression was "maybe", 91% of lumbar injections, but only 45% of caudal injections were correctly placed. Obesity was associated with a reduced chance of successful placement (odds ratio (OR) 0.34 (95% confidence interval (CI) 0.17 to 0.72) BMI >30 v BMI <30). A more senior grade of operator was associated with a reduced chance of successful placement (OR 0.16 (95% CI 0.03 to 0.89) consultant v other). However, small numbers may have accounted for the latter result. CONCLUSIONS: The weight of the patient and intended approach need to be considered when deciding the method used to enter the epidural space. In the non-obese patient, lumbar epidural injections can be accurately placed without x ray screening, but caudal epidural injections, to be placed accurately, require x ray screening no matter what the weight of the patient.

Amphotericin B induces expression of genes encoding chemokines and cell adhesion molecules in the human monocytic cell line THP-1.

Amphotericin B is known to elicit immunomodulatory effects on neutrophil, monocyte, and lymphocyte function. It also has been shown to induce the release of proinflammatory cytokines from human monocytes and macrophages. Release of these cytokines has been associated with the infusion-related toxicity observed after administration of this drug. The present study demonstrates that amphotericin B increases mRNA for the chemokines interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1beta, as well as the cell adhesion molecules intercellular adhesion molecule (ICAM)-1 and CD44 in the human monocytic cell line THP-1. Amphotericin B increased the concentrations of IL-8, MCP-1, and MIP-1beta in a dose-dependent fashion. Amphotericin B also induced expression of ICAM-1 but not CD44 in these cells. Production of these proteins in response to amphotericin B may play a role in the immunomodulatory activity and toxicity of this antifungal agent.

American Academy of Pediatrics. Committee on Substance Abuse. Marijuana: A continuing concern for pediatricians.

Marijuana, the common name for products derived from the plant Cannabis sativa, is the most common illicit drug used by children and adolescents in the United States.(1) Despite growing concerns by the medical profession about the physical and psychological effects of its active ingredient, Delta-9-tetrahydrocannabinol, survey data continue to show that increasing numbers of young people are using the drug as they become less concerned about its dangers.(1)

Stability of cefepime in peritoneal dialysis solution.

OBJECTIVE: To determine the stability of cefepime in peritoneal dialysis solution. DESIGN: Cefepime HCl was added to premade bags of Delflex peritoneal dialysis solution with 1.5% dextrose to produce a cefepime concentration of approximately 100 microg/mL. Peritoneal dialysis solution bags were stored at 4, 25, and 37 degrees C to simulate refrigeration, room temperature, and body temperature, respectively. Samples were drawn at scheduled times up to 336, 168, and 48 hours, respectively, after the addition of cefepime HCl. Cefepime concentrations were measured by HPLC. SETTING: This study was performed at a university-affiliated tertiary care hospital. OUTCOME MEASURE: If the mean concentration of the samples at a given time and condition was >90% of the initial concentration, cefepime was considered stable at that time and condition. RESULTS: The mean HPLC results for samples drawn at each time and condition were all >90%. CONCLUSIONS: Cefepime is stable in peritoneal dialysis solution with dextrose 1.5% for 14 days refrigerated, seven days at room temperature, and 48 hours at 37 degrees C.

Amphotericin B-induced interleukin-1beta expression in human monocytic cells is calcium and calmodulin dependent.

Amphotericin B remains the agent of choice for treatment of severe fungal infections. Its use is hindered by adverse effects, including infusion-related fever, chills, and hypotension, as well as nephrotoxicity with secondary anemia, hypokalemia, and hypomagnesemia. Amphotericin B-induced transcription and expression of interleukin (IL)-1beta by human monocytes is believed to be involved in mediating infusion-related adverse effects. It is shown here that agents that increase intracellular calcium [Ca++]i (A23187 and thapsigargin) in human monocytic cells also induce IL-1beta expression. Furthermore, amphotericin B-induced IL-1beta expression is attenuated by the calmodulin antagonist calmidazolium. Amphotericin B 5.41 microM increases [Ca++]i by up to 300 nM in these cells. In the presence of a nominal calcium buffer or EGTA, amphotericin B-induced IL-1beta expression is attenuated. Thus, amphotericin B acts as an ionophore to increase [Ca++]i and activates calmodulin-mediated expression of IL-1beta in human monocytes.

Amphotericin B activation of human genes encoding for cytokines.

Amphotericin B has been shown to cause release of cytokines, including interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), from monocytes and macrophages. Human and murine monocytic cell lines were used to evaluate the effects of amphotericin B on the transcription of IL-1alpha, IL-1beta, and TNF-alpha and the transcription and production of soluble IL-1 receptor antagonist (sIL-1Ra). The effects of inhibitors of transcription and translation on amphotericin B-induced IL-1beta expression in a human monocytic cell line were also evaluated. Amphotericin B markedly increased IL-1beta and TNF-alpha mRNA levels, with peak levels occurring by 4 h. Amphotericin B induced production of sIL-1Ra in a dose-dependent fashion and induced sIL-1Ra mRNA, with peak levels at 24 h. Cycloheximide and actinomycin D resulted in a dose-dependent decrease in amphotericin B-induced IL-1beta expression at 2 h. Thus, amphotericin B induces gene expression for IL-1beta, TNF-alpha, and IL-1Ra in human and murine monocytic cells.

Antifungal therapy during pregnancy.

Careful consideration of the benefit to the mother and the risk to the fetus is required when prescribing antifungal therapy in pregnancy. Imidazoles are considered safe as topical therapy for fungal skin infections during pregnancy. Nystatin is minimally absorbed and is effective for vaginal therapy. Although vaginal use of the imidazoles is probably safe during the later stages of pregnancy, their systemic absorption is higher than when applied to the skin. The systemic antifungal drug with which there has been the most experience in pregnancy is amphotericin B. There have been no reports of teratogenesis attributed to this agent. There is evidence to suggest that fluconazole exhibits dose-dependent teratogenic effects; however, it appears to be safe at lower doses (150 mg/day). Ketoconazole, flucytosine, and griseofulvin have been shown to be teratogenic and/or embryotoxic in animals. Iodides have been associated with congenital goiter and should not be used during pregnancy.

Susceptibilities of clinical and laboratory isolates of Blastomyces dermatitidis to ketoconazole, itraconazole, and fluconazole.

Eighteen isolates of Blastomyces dermatitidis were evaluated for their in vitro susceptibilities to ketoconazole, itraconazole, and fluconazole. The MIC ranges were 0.1 to 0.4 microg/ml for ketoconazole, < or =0.018 to 0.07 microg/ml for itraconazole, and 2.5 to 4.0 microg/ml for fluconazole. The ranges for the minimal lethal concentrations were 0.2 to 0.8 microg/ml for ketoconazole, < or =0.018 to 0.07 microg/ml for itraconazole, and 10 to 40 microg/ml for fluconazole. Itraconazole was the most active agent against B. dermatitidis in vitro, while fluconazole was the least active. These results correlate with the clinical efficacies noted to date with doses of these agents used to treat blastomycosis.

Cimetidine in the treatment of acute intermittent porphyria.

Treatment options for AIP remain limited. Although no single therapy has been proven superior in clinical trials, intravenous hemin appears to be more effective than increased carbohydrate intake, and remains the treatment of choice. At usual dosages the average wholesale price of hemin is $120-475 per day (for a patient weighing 70 kg), compared with $2.50 per day for cimetidine. Cimetidine may offer a more cost-effective and easily administered alternative to hemin therapy. The optimal dosage and duration of treatment with cimetidine have not been established and are likely to be patient-specific. Oral doses of 800 mg/d have been used. In addition to its potential for treatment, cimetidine may also have a role in prophylaxis of acute episodes by maintaining a baseline suppression of ALA synthase activity. Until well-designed, controlled clinical trials demonstrate its efficacy and compare it with other treatment options, cimetidine should be reserved for use only after standard treatment modalities have failed.

The assessment of the identified substance-abusing adolescent.

When an adolescent has been identified as abusing drugs, alcohol, or both, a complete assessment of this young person must be completed by qualified health professionals before the level of treatment is chosen. With our present state of knowledge of substance-abusing adolescents, this assessment must focus on every sphere of the child's life, not just the quantity and frequency of the drug use. Most substance-abusing young people have experienced deep psychological trauma that must be identified and eventually treated. A family evaluation and psychological testing are crucial to the evaluation of these adolescents. When choosing a treatment facility for a substance-abusing adolescent, it is best to select a treatment program that requires family involvement. An adolescent treatment program should include treatment of both the family and the child, and it must include the goal of abstinence from mood-altering substances as a major component of recovery.

Alcohol and adolescents.

Alcohol use has persisted over time as the number one drug problem among youth in the United States. Many primary care physicians underestimate the seriousness and prevalence of teenage alcohol use. The epidemiology of alcohol use among adolescents is discussed, as are its dangers and society's attitude toward drinking. The effects of alcohol on adolescents are listed. Several types of alcoholism are discussed.