High numerical aperture holographic microscopy reconstruction with extended z range.

A holographic microscopy reconstruction method compatible with a high numerical aperture microscope objective (MO) up to NA=1.4 is proposed. After off-axis and reference field curvature corrections, and after selection of the +1 grating order holographic image, a phase mask that transforms the optical elements of the holographic setup into an afocal device is applied in the camera plane. The reconstruction is then made by the angular spectrum method. The field is first propagated in the image half-space from the camera to the afocal image of the MO optimal plane (the plane for which the MO has been designed) by using a quadratic kernel. The field is then propagated from the MO optimal plane to the object with the exact kernel. Calibration of the reconstruction is made by imaging a calibrated object such as a USAF resolution target for different positions along z. Once the calibration is done, the reconstruction can be made with an object located in any plane z. The reconstruction method has been validated experimentally with a USAF target imaged with a NA=1.4 microscope objective. Near-optimal resolution is obtained over an extended range (±50 µm) of z locations.

Picometer-scale surface roughness measurements inside hollow glass fibres.

A differential profilometry technique is adapted to the problem of measuring the roughness of hollow glass fibres by use of immersion objectives and index-matching liquid. The technique can achieve picometer level sensitivity. Cross validation with AFM measurements is obtained through use of vitreous silica step calibration samples. Measurements on the inner surfaces of fibre-sized glass capillaries drawn from high purity suprasil F300 tubes show a sub-nanometer roughness, and the roughness power spectrum measured in the range [5 · 10(-3) m(-1) 10(-1) m(-1)] is consistent with the description of the glass surface as a superposition of frozen capillary waves. The surface roughness spectrum of two capillary tubes of differing compositions can be quantitatively distinguished.

Imaging the three-dimensional scattering pattern of plasmonic nanodisk chains by digital heterodyne holography.

Nanoantennas have the unique ability to affect the emission pattern of a dipole in free space. We present a technique based on full-field heterodyne holography for the mapping of the scattered field of plasmonic gold nanodisk chains in all three dimensions. A spectroscopic study allowed us to determine the resonant and nonresonant wavelengths at which we conducted a full characterization of the scattered field on a chosen nanodisk chain.

Multiple wavelength reflectance microscopy to study the multiphysical behavior of microelectromechanical systems.

In order to characterize surface chemomechanical phenomena driving microelectromechanical systems behavior, we propose herein a method to simultaneously obtain a full kinematic field describing the surface displacement and a map of its chemical modification from optical measurements. Using a microscope, reflected intensity fields are recorded for two different illumination wavelengths. Decoupling the wavelength-independent and -dependent contributions to the measured relative intensity changes then yields the sought fields. This method is applied to the investigation of the electroelastic coupling, providing images of both the local surface electrical charge density and the device deformation field.

Imaging gold nanoparticles in living cell environments using heterodyne digital holographic microscopy.

This paper describes an imaging microscopic technique based on heterodyne digital holography where subwavelength-sized gold colloids can be imaged in cell environments. Surface cellular receptors of 3T3 mouse fibroblasts are labeled with 40 nm gold nanoparticles, and the biological specimen is imaged in a total internal reflection configuration with holographic microscopy. Due to a higher scattering efficiency of the gold nanoparticles versus that of cellular structures, accurate localization of a gold marker is obtained within a 3D mapping of the entire sample's scattered field, with a lateral precision of 5 nm and 100 nm in the x,y and in the z directions respectively, demonstrating the ability of holographic microscopy to locate nanoparticles in living cell environments.

Photothermal heterodyne holography of gold nanoparticles.

We report a method based on heterodyne numerical holography associated to photothermal excitation for full field and three-dimensional localisation of metallic nanoparticles. A modulated pump laser (lambda = 532 nm) heats several particles, creating local refractive index changes. This modulation is detected using a probe and a local oscillator beam (lambda = 785 nm), frequency-shifted to create a hologram beating at low frequency. Tens of particles, down to diameters of 10 nm, can be localised simultaneously and selectively in three dimensions with near- diffraction resolution by a numerical reconstruction of a single hologram acquired in 5 s.

Thermo-optical dynamics in an optically pumped Photonic Crystal nano-cavity.

Linear and non-linear thermo-optical dynamical regimes were investigated in a photonic crystal cavity. First, we have measured the thermal relaxation time in an InP-based nano-cavity with quantum dots in the presence of optical pumping. The experimental method presented here allows one to obtain the dynamics of temperature in a nanocavity based on reflectivity measurements of a cw probe beam coupled through an adiabatically tapered fiber. Characteristic times of 1.0+/-0.2 micros and 0.9+/-0.2 micros for the heating and the cooling processes were obtained. Finally, thermal dynamics were also investigated in a thermo-optical bistable regime. Switch-on/off times of 2 micros and 4 micros respectively were measured, which could be explained in terms of a simple non-linear dynamical representation.

Intraductal optical coherence tomography during endoscopic retrograde cholangiopancreatography for investigation of biliary strictures.

BACKGROUND AND STUDY AIMS: Optical coherence tomography (OCT) uses infrared light reflectance to produce high-resolution cross-sectional tissue images. The aim of this study was to demonstrate the feasibility of biliary intraductal OCT during endoscopic retrograde cholangiopancreatography (ERCP) and to assess the potential of the method to detect malignant biliary strictures. PATIENTS AND METHODS: Thirty-seven patients with biliary strictures were studied during therapeutic ERCP. Malignant strictures were defined as those that demonstrated malignant cells in brushing and/or biopsy specimens, and/or endoscopic ultrasound-guided fine-needle aspiration and/or surgery. Strictures that did not have malignant cells in resected specimens and were without clinical/radiological evidence of disease progression for at least a 12-month follow-up period were considered as benign. Two OCT criteria for malignancy were considered: unrecognizable layer architecture; and presence of large, nonreflective areas compatible with tumor vessels. Sensitivity and specificity for brushings/biopsies as well as OCT criteria were calculated. RESULTS: Nineteen patients had malignant and 16 had benign strictures. In two patients, OCT assessment could not be performed due to tight strictures. Malignancy was confirmed by biliary brushings/biopsies in 12/19 (63 %) patients. OCT revealed that two malignancy criteria were encountered in 10/19 (53 %) and at least one criterion in 15/19 (79 %) patients with malignant strictures. No patient with benign stricture met both criteria and 5/16 met one criterion (31 %). Combining brushings/biopsy with the observation of at least one OCT criterion resulted in the diagnosis of malignancy in 16/19 (84 %) patients. CONCLUSIONS: OCT may improve the sensitivity and diagnostic accuracy of biliary brushings/biopsies alone.

Health among commercial airline pilots.

BACKGROUND: The airline pilot works within a complex exposure environment that may present physiological challenges to long-term health. METHODS: This study investigated self-reported disease outcomes among a large group of active and retired commercial airline pilots in the United States and Canada. A survey methodology was used, including the collection of historical information. RESULTS: Of 10,678 surveys mailed, 6609 were returned (6533 men, 63 women). Given the limitations of survey methodology, increased disease rates among pilots were suggested for melanoma, motor neuron disease, and cataracts. However, rates for other diseases were in general lower than those for the U.S. population. CONCLUSIONS: Further study has been initiated to verify and follow reported cases, to expand the study to a larger group, and to collect more in-depth information on flight histories, occupational exposures, and lifestyle factors.

Tools used to help community pharmacists implement comprehensive pharmaceutical care.

OBJECTIVE: To describe the tools and processes used in the practice enhancement program (PEP) of the Pharmaceutical Care Research and Education Project to enable community pharmacists to acquire the necessary skills, knowledge, and attitudes to deliver comprehensive pharmaceutical care to elderly ambulatory patients. SETTING: Independent community pharmacies in Alberta. PRACTICE DESCRIPTION: The PEP was designed to allow self-directed learning in a problem-based environment. The intent was for pharmacists to apply the knowledge they gained to improve drug therapy outcomes. PRACTICE INNOVATION: As a systematic approach to providing care, several tools were adapted to help pharmacists execute tasks required by the nine steps of the pharmaceutical care process proposed by Helper and Strand. These tools and processes facilitated (1) self-directed learning about diseases and drugs, (2) acquisition of relevant patient data, (3) a consistent and stepwise approach to the identification and resolution of drug-related problems, (4) documentation of care provided, and (5) continuity of care. RESULTS: To help pharmacists in the PEP acquire the necessary competency to provide pharmaceutical care, they were required to use the tools and processes described herein to work up and resolve patient problems. Initially, patient problems were presented as paper cases covering a range of acute and chronic problems, including topics applicable to geriatric patients. This was followed by a practicum phase wherein patient problems represented individuals from among their clientele. CONCLUSION: The tools and processes used in the project increased community pharmacists' competency for providing pharmaceutical care, by helping them develop the needed skills, knowledge, and attitudes.

Alzheimer's disease: a review of the disease, its epidemiology and economic impact.

This article consists of a critical review of Canadian, American and European studies published between 1976 and 1997 on the subject of Alzheimer's disease (AD), and its epidemiology, patterns of care, prognostic factors, and economic impact. As the population ages in North America and Europe, significant increases in the prevalence of AD over the next decades have been projected. The elderly population represents the largest consumer group of health care resources and the management of common diseases occurring in this population will have major medical, social, and economic implications. As a result, researchers will need to integrate the ever-increasing knowledge on AD when addressing governmental and societal concerns regarding its impact. Described herein is the study findings, limitations, and differences observed following the review of the diagnostic criteria, prevalence rates, incidence rates and risk factors. Highlighted are the areas where data is lacking. To refine current models of disease progression, and better address where health care resources and new therapies would be most beneficial, the review of predictors of institutionalization and predictive models of disease progression and survival, was performed. New research questions are indicated.

Economic evaluation of zuclopenthixol acetate compared with injectable haloperidol in schizophrenic patients with acute psychosis.

Zuclopenthixol acetate is a rapid-acting, injectable neuroleptic drug with a duration of action that allows for administration once every 2 to 3 days, in contrast to injectable haloperidol, which may require administration more than once daily. To assess the place of zuclopenthixol acetate in the treatment of acute episodes of schizophrenia, a cost-consequence analysis was performed comparing this new medication with short-acting, injectable haloperidol. The perspective of the Quebec health care system was adopted. The study population comprised patients diagnosed with schizophrenia who experienced an acute episode of psychosis and who were treated with intramuscular (i.m.) haloperidol. The study assessed patients for 9 days after the start of treatment. The literature was the principal source of comparative data about the clinical outcomes of the two treatments. The total cost associated with zuclopenthixol acetate i.m. or haloperidol i.m. was modeled using a decision tree built around the number of i.m. injections required to achieve stabilization. To establish costs, expert panels were consulted and patients' files were reviewed for a sample of schizophrenic patients who had been hospitalized in a large psychiatric or general hospital subsequent to a visit to the emergency department and had received a short-acting i.m. neuroleptic drug. Only a direct medical records costs were considered. Because zuclopenthixol acetate was not on the market at the time of the study, the file review did not allow for a direct estimate of its related costs but did provide an account of haloperidol use. The literature shows that zuclopenthixol acetate is similar to haloperidol with respect to the control of psychotic episodes; however, zuclopenthixol acetate is associated with increased sedation and a lower incidence of extrapyramidal symptoms. Using the base-case estimate for the number of injections required for stabilization, the incremental cost of zuclopenthixol acetate 50 mg over haloperidol was $25.00 (1995 Canadian dollars) per patient at the psychiatric hospital and $21.00 per patient at the general hospital. The results were sensitive to the estimate of the number of injections and the number of minutes of nursing care required by agitated patients. Zuclopenthixol acetate resulted in cost savings over haloperidol if it permits a reduction of 25% in minutes of nursing care or if 85% of patients require 2 injections or less (45% requiring 1 injection and 40% requiring 2). However, whichever drug is used, the cost of the injectable neuroleptic represents a small fraction of the cost of care for acutely psychotic patients.

Reference-based pricing in British Columbia: implications for cardiologists--an analysis.

Under the reference-based pricing (RBP) policy, British Columbia will fund drug therapies based on the cost of the 'gold standard' therapy that meets the needs of the majority of patients with a specific condition. Hence, Pharmacare will pay for the lowest cost drug within a cluster of related but different drugs, regardless of the indication. When evaluating the impact of drugs on health care expenditure, one must consider that their costs are more than offset by the clinical and economic benefits they provide. Pharmaceutical expenditure accounts for a small proportion of health care expenditure and should be viewed as an essential and interactive component in the global health care budget rather than as an independent constituent. In that respect, insight should be gained from many countries in which RBP has been implemented A wealth of data converge to the same conclusion: price controls and restricted access to drugs do not reduce prescription drug expenditures but actually increase health care costs. Furthermore, cost containment being the main issue behind RBP in British Columbia, the contentious issue of therapeutic substitution has not been taken fully into consideration, nor has its impact on the quality of care of the patient. The case of diltiazem once-a-day versus diltiazem tablets for hypertensive and angina patients illustrates the important considerations that must be taken into account in writing the overall financial equation that drives the implementation of the RBP policy. If pharmacotherapy is to be an appropriate treatment to attain optimal cost effective health care, its benefit can only be optimized with a strategy that entails the right therapy, for the right patient, in the right dosage form and at the right time. Accordingly, RBP in British Columbia should be analyzed in light of patient welfare and appropriate use of collective resources.

Ion transport properties of fetal sheep alveolar epithelial cells in monolayer culture.

Alveolar type II cells were isolated from late-term fetal sheep to investigate ion transport across fetal distal lung epithelium. In Ussing chambers, basal transepithelial potential difference (PD; reference apical side), equivalent short-circuit current (Ieq), and resistance were -0.10 +/- 0.05 mV, 0.10 +/- 0.08 microA/cm2, and 821.5 +/- 38.8 omega .cm2, respectively. Epinephrine (100 nM) increased PD from -0.13 +/- 0.19 to -1.37 +/- 0.20 mV and Ieq from 0.18 +/- 0.26 to 1.47 +/- 0.28 microA/cm2. Propranolol (100 nM) inhibited responses to epinephrine. Forskolin (10 microM) increased PD to -0.81 +/- 0.08 mV and Ieq to 1.02 +/- 0.12 microA/cm2. Mucosal amiloride (200 microM) and serosal bumetanide (10 microM) decreased the forskolin-stimulated PD by 23.42 +/- 4.73 and 25.57 +/- 3.9%, respectively. We conclude that in fetal sheep distal lung epithelium amiloride-inhibitable sodium absorption and bumetanide-sensitive chloride secretion are stimulated by forskolin and that epinephrine effects on ion transport are mediated by beta-adrenergic receptors.

The economic effects of introducing vigabatrin, a new antiepileptic medication.

Epilepsy is a common disorder, the prevalence of which is estimated at between 0.1 and 1% of the population. Although there are a number of medications available for treating the disorder, 20 to 35% of affected individuals are resistant to standard treatments. Many of these patients could benefit from a new anti-epileptic, vigabatrin. Because the current indication for vigabatrin is as an adjunct in a specific subgroup of epileptic patients, which implies an increased cost of drug therapy, an ex ante economic appraisal of the expected consequences of its introduction in the treatment of epilepsy is valuable. This would provide decision makers with information to complement standard clinical data. Using administrative records of healthcare services utilisation by epileptic patients, we performed a simulation of the expected economic repercussions of vigabatrin use on direct costs related to disease management. The results show that whether or not the introduction of vigabatrin results in an increase or a reduction in costs to the healthcare system depends largely on 3 factors: (i) the administered dosage of vigabatrin; (ii) the effect that vigabatrin has on hospital admissions; and (iii) the proportion of epileptic patients who take the drug. Moreover, this study underlines the usefulness of administrative data in forecasting the economic impact of new health technologies.

Cost utility of chemotherapy and best supportive care in non-small cell lung cancer.

Polychemotherapy is the therapeutic option recommended for nonresectable, non-small cell lung cancer (NSCLC). However, the modest gains in survival, and the frequent and often serious adverse effects, associated with chemotherapy should also be considered when deciding on therapy. We therefore performed a cost-utility analysis of chemotherapy and best supportive care in NSCLC. Effectiveness and costs were analysed on 70 patients who were randomised to receive one of 3 treatments: VP (vindesine and cisplatin), CAP (cyclophosphamide, doxorubicin and cisplatin), or best supportive care. Subsequently, an assessment of the value of polychemotherapy and best supportive care was performed by oncology personnel using the time trade-off technique. Polychemotherapy was found to be more effective than best supportive care, but was also more costly and had a lower value score. Because of its cost utility and its higher value, best supportive care should not be discarded as an alternative for the treatment of NSCLC.

Quality of life of subjects with occupational asthma.

BACKGROUND: The aim of the study was to assess the quality of life in subjects with occupational asthma after removal from exposure to the offending agent by comparison with a group of subjects paired for clinical and functional indices in order to show the separation between the two groups of subjects with a hypothesized different quality of life and relate the impairment in quality of life to anthropometric, clinical, and functional variables. METHODS: A previously described asthma quality of life questionnaire (Juniper EF, et al. Thorax 1992;47:76-83) was administered to two groups of subjects in a prospective manner. Information on the clinical and functional severity of asthma was obtained from each subject. Two groups of subjects were assessed: group 1, 134 subjects with occupational asthma who were seen more than 2 years after the diagnosis was confirmed, and group 2, 91 subjects who were seen in specialized asthma clinics of tertiary care hospitals for treatment of nonoccupational asthma and matched with 91 of the 134 subjects with occupational asthma from group 1 according to need for medication and (when available), baseline forced expiratory volume in 1 second (FEV1), and level of bronchial responsiveness. RESULTS: A statistically significant difference was seen in the four domains (asthma symptoms, limitation of activities, emotional dysfunction, environmental stimuli) and in the total score of the quality of life questionnaire between the two groups of matched subjects; the mean difference in the total score was 0.6 on a scale of 1 (no limitation or none of the time) to 7 (severe limitation or all the time). A weak but statistically significant correlation between the total score and several indices (FEV1, bronchial responsiveness and asthma severity) was generally obtained. CONCLUSION: The quality of life of subjects with occupational asthma is slightly less satisfactory than that of subjects paired for clinical and functional indices, although the magnitude of the difference is small; and quality of life is weakly correlated with clinical and functional indices.

Mucosal histamine inhibits Na absorption and stimulates Cl secretion across equine tracheal epithelium.

When the equine tracheal epithelium is mounted in Ussing chambers and bathed in plasma-like Ringer solution, the tissue generates a lumen-negative transepithelial potential (PD) of 22 mV and a short-circuit current (Isc) of 70-200 microA/cm2. Mucosal addition of 10 microM histamine produces a transient increase in the Isc followed by a return to baseline or below. Mucosal addition of 2 microM diphenhydramine inhibits the Isc response to mucosal histamine, whereas 100 microM mucosal cimetidine produces no effect. The average initial increases in Isc over time for mucosal vs. serosal histamine addition are significantly different (17.32 +/- 2.8 and 3.76 +/- 0.69 microA/min, respectively). Pretreatment with mucosal amiloride significantly prolongs the effect of mucosal histamine on Isc over a 20-min period from 4.73 +/- 0.33 to 15.48 +/- 3.16 microA. When Cl is replaced by gluconate, mucosal histamine addition results in a gradual decrease in Isc and significantly reduces the effect of mucosal amiloride on Isc from 80.8% to 54.9%. Mucosal histamine inhibits the net transepithelial Na flux by 42% and stimulates the secretion of Cl by 106%. Subsequent addition of serosal bumetanide decreases net Cl secretion by 70% These results suggest that histamine stimulates bumetanide-sensitive Cl secretion and inhibits amiloride-sensitive Na absorption; these effects are mediated by H1 receptors at the apical membrane surface.

Modulation of equine tracheal smooth muscle contractility by epithelial-derived and cyclooxygenase metabolites.

The role of epithelium in the modulation of contractile responses to electrical field stimulation (EFS), acetylcholine (ACh), and KCl were studied in vitro in strips of equine tracheal smooth muscle (TSM). EFS with 0.5 ms pulses of voltage (70 V) resulted in frequency dependent contractions of equine TSM that were sensitive to tetrodotoxin (TTX) and atropine. In TSM without epithelium, preincubation with indomethacin significantly potentiated contractile responses to EFS. The potentiating effect of indomethacin on EFS contractions was abolished by the addition of 3 nM prostaglandin E2 (PGE2). ACh and KCl cumulative concentration-response curves were shifted to the left by removal of epithelium from equine TSM strips with a significant decrease in the 50% effective concentration (EC50) for both ACh and KCl. The mean EC50 (+/- SE) for ACh in TSM without epithelium was 0.51 +/- 0.09 microM vs 4.30 +/- 1.03 microM in TSM with epithelium. Similarly, the mean EC50 (+/- SE) for KCl in TSM without epithelium was 22.20 +/- 2.61 mM vs 32.35 +/- 2.66 mM in TSM with epithelium. The addition of indomethacin (3 microM) had no effect on the ACh concentration-response curves in TSM strips with or without epithelium. Our results suggest that in the equine airway there is (1) an epithelial-derived relaxant factor that modulates tracheal smooth muscle contractility postsynaptically, and (2) a nonepithelial-derived inhibitory factor, possibly PGE2, that modulates ACh release from nerves presynaptically.

Mechanisms of sodium and chloride transport across equine tracheal epithelium.

Equine tracheal epithelium, stripped of serosal muscle, mounted in Ussing chambers, and bathed in plasmalike Ringer solution generates a serosa-positive transepithelial potential of 10-22 mV and a short-circuit current (Isc) of 70-200 microA/cm2. Mucosal amiloride (10 microM) causes a 40-60% decrease in Isc and inhibits the net transepithelial Na flux by 95%. Substitution of Cl with gluconate resulted in a 30% decrease in basal Isc. Bicarbonate substitution with 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid decreased the Isc by 21%. The Cl-dependent Isc was inhibited by serosal addition of 1 mM amiloride. Bicarbonate replacement or serosal amiloride (1 mM) inhibits the net Cl flux by 72 and 69%, respectively. Bicarbonate replacement significantly reduces the effects of serosal amiloride (1 mM) on Isc, indicating its effect is HCO3 dependent. Addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP; 100 microM) causes a 40% increase in Isc. This effect is inhibited by subsequent addition of 10 microM serosal bumetanide. Bumetanide (10 microM) reduces net Cl secretion following stimulation with 8-BrcAMP (100 microM). Serosal addition of BaCl2 (1 mM) causes a reduction in Isc equal to that following Cl replacement in the presence or absence of 100 microM cAMP. These results suggest that 1) Na absorption depends on amiloride-inhibitable Na channels in the apical membrane, 2) Cl influx across the basolateral membrane occurs by both a Na-H/Cl-HCO3 parallel exchange mechanism under basal conditions and by a bumetanide-sensitive Na-(K?)-Cl cotransport system under cAMP-stimulated conditions, and 3) basal and cAMP-stimulated Cl secretion depends on Ba-sensitive K channels in the basolateral membrane.