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Prediction of drug dissolution from tablets using near-infrared diffuse reflectance spectroscopy as a nondestructive method.

The goal of this study is to use near-infrared (NIR) reflectance spectroscopy to measure the percentage drug dissolution from a series of tablets compacted at different compressional forces, calibrate NIR data vs. laboratory equipment data, develop a model equation, validate the model, and test the model predictive ability. Seven theophylline tablet formulations of the same composition but with different dissolution profiles were prepared. Laboratory dissolution profiles were compared with NIR diffuse reflectance data. Linear regression, quadratic, cubic, and partial least-square techniques were used to determine the relationship between dissolution profiles data and NIR spectra. The results demonstrated that a decrease in the amount of drug dissolution produced an increase in NIR absorbance. A series of model equations, depending on the mathematical technique used for regression, were developed from the calibration of the percentage of drug dissolution by using laboratory equipment vs. the NIR diffuse reflectance for each formulation. The results of NIR dissolution data were similar to laboratory tests. The NIR diffuse reflectance spectroscopy method is an alternative, nondestructive method for measurement of drug dissolution from tablets.

Algorithms↗

Prediction of tablets disintegration times using near-infrared diffuse reflectance spectroscopy as a nondestructive method.

The goals of this study are to user near-infrared reflectance (NIR) spectroscopy to measure the disintegration time of a series of tablets compacted at different compressional forces, calibrate NIR data vs. laboratory equipment data, develop a model equation, validate the model, and test the model's predictive ability. Seven theophylline tablet formulations of the same composition but with different disintegration time values (0.224, 1.141, 2.797, 5.492, 9.397, 16.8, and 30.092 min) were prepared along with five placebo tablet formulations with different disintegration times. Laboratory disintegration time was compared to near-infrared diffuse reflectance data. Linear regression, quadratic, cubic, and partial least square techniques were used to determine the relationship between disintegration time and near-infrared spectra. The results demonstrated that an increase in disintegration time produced an increase in near-infrared absorbance. Series of model equations, which depended on the mathematical technique used for regression, were developed from the calibration of disintegration time using laboratory equipment vs. the near-infrared diffuse reflectance for each formulation. The results of NIR disintegration time were similar to laboratory tests. The near-infrared diffuse reflectance spectroscopy method is an alternative nondestructive method for measurement of disintegration time of tablets.

Algorithms↗

Pulse wave reflection in currently and previously preeclamptic women.

OBJECTIVE: Disturbed maternal endothelial function is believed to be central in the pathogenesis of preeclampsia and has been observed to persist for several years following the preeclamptic pregnancy. Endothelial dysfunction has been reported to cause increased pulse wave reflection, a measure of systemic arterial stiffness. This study tested the hypothesis that preeclampsia and a history of preeclampsia are associated with increased pulse wave reflection. DESIGN AND METHODS: We carried out a cross-sectional case-control study of 26 pregnant women with preeclampsia, 26 pregnant controls, 22 normotensive nonpregnant previously preeclamptic women, and 22 nonpregnant controls. Pulse wave reflection was assessed by applanation tonometry on the radial artery. RESULTS: Pregnant preeclamptic women had a significantly higher heart rate-adjusted augmentation index than did pregnant controls (23 +/- 1 vs. 8 +/- 1%, P < 0.001). The augmentation index of women with a history of preeclampsia was similar to that of the nonpregnant controls (9 +/- 2 vs. 9 +/- 2%, P = 0.78). In a multiple linear regression analysis (R2 = 0.76) the augmentation index of pregnant women was independently associated with a diagnosis of preeclampsia (P < 0.001) and heart rate (P < 0.001), but not with mean arterial blood pressure (P = 0.59). CONCLUSIONS: This study demonstrates that pulse wave reflection and, thus, systemic arterial stiffness are increased in pregnant women with preeclampsia, but not in normotensive nonpregnant women with a history of preeclampsia. The results support the concept of generalized vascular dysfunction in preeclampsia.

Adult↗

Structural organization of interphase 3T3 fibroblasts studied by total internal reflection fluorescence microscopy.

We studied the laminar organization of 3T3 fibroblast cells growing on glass slides by use of total internal reflection illumination to excite fluorescence emission (TIRF) from labeled molecules and stained cellular compartments that are very close to the cell-substrate contact region. Mitochondria, distant from the contact regions and stained with the water-soluble cationic dye, dil-C3-(3), fluoresced only as the glass/cytoplasm critical angle was approached. A similar result was obtained when the nuclei were stained with Hoechst dye 33342. From this measured angle a cytoplasmic refractive index in the range 1.358-1.374 was computed. The plasma membrane of 3T3 cells was stained with dil-C18-(3), and the cytoplasmic compartment was stained with fluoresceinyl-dextran (FTC-dextran) or with carboxyfluorescein. We have demonstrated a high degree of correspondence between the low-reflectance zones in the reflection interference image of a live cell and the TIRF images of both the plasma membrane and cytoplasmic compartment. TIRF photometry of selected contact regions of cells provided data from which the absolute separation of cell and substrate was computed. From a population of 3T3 cells microinjected with fluorescein-labeled actin, motile and adherent interphase cells were selected for study. For adherent cells, which displayed fluorescent stress fibers, the TIRF image was composed of intense patches and less intense regions that corresponded, respectively, to the focal contact and close-contact zones of the reflection-interference image. The intense patches corresponded to the endpoints of the stress fibers. Cells of motile morphology, which formed some focal contacts and extensive close-contact zones, gave AF-actin TIRF images of relatively even intensity. Thin lamellar regions of the cytoplasm were found to contain concentrations of actin not significantly different from other close-contact regions of the cell. The major analytical problem of TIRF microscopy is separation of the effects of proximity to substrate, refractive index, and fluorescent probe concentration on the local brightness of the TIRF image. From our results, it appears possible to use TIRF microscopy to measure the proximity of different components of substrate contact regions of cells.

Actins↗

Reflections on tissue characterisation.

Theoretical predictions that absorption and velocity dispersion, in addition to characteristic acoustic impedance mismatch, mediate the reflectivity of a planar interface are explored. A technique to measure the frequency dependence of the reflectivity is described: a special hydrophone, purpose-built to this end, is utilised in order to show that perspex/water and neoprene/water reflectivities are not inconsistent with the general predictions of the theory. An approach towards displaying, simultaneously, both the temporal and spectral properties of ultrasound pulses is described, and its potential utility in both reflectivity measurement and investigation of non-linear propagation is proposed.

Acoustics↗

A portable diffuse reflectance spectrophotometer for the rapid and automatic measurement of meat pigments.

A portable reflectance spectrophotometry system, which can measure a wide range of absorbance and has an adhesive pad type fibre optic probe, was developed to improve the availability of non-invasive reflectance spectrophotometry. A Czerny-Turner type spectrometer, which can be connected to an optical fibre probe, was developed, and a linear charge coupled device (CCD) was used as its light detector to increase data acquisition speed. The scanning time of the linear CCD is automatically controlled in accordance with the reflectance of meat to increase the dynamic range of absorption. We tried to apply this instrument to samples of meat pigments in order to demonstrate whether reflectance spectrophotometry is suitable for evaluating the freshness of meat. We examined the myoglobin solution in the form of the met-derivative in order to detect the concentration of myoglobin. The absorbance spectrum of myoglobin in the range of 0-4 mg dl(-1) was successfully distinguished with this instrument.

Animals↗

Determination of the optical properties of semi-infinite turbid media from frequency-domain reflectance close to the source.

We investigate theoretically the errors in determining the reduced scattering and absorption coefficients of semi-infinite turbid media from frequency-domain reflectance measurements made at small distances between the source and the detector(s). The errors are due to the uncertainties in the measurement of the phase, the modulation and the steady-state reflectance as well as to the diffusion approximation which is used as a theoretical model to describe light propagation in tissue. Configurations using one and two detectors are examined for the measurement of the phase and the modulation and for the measurement of the phase and the steady-state reflectance. Three solutions of the diffusion equation are investigated. We show that measurements of the phase and the steady-state reflectance at two different distances are best suited for the determination of the optical properties close to the source. For this arrangement the errors in the absorption coefficient due to typical uncertainties in the measurement are greater than those resulting from the application of the diffusion approximation at a modulation frequency of 200 MHz. A Monte Carlo approach is also examined; this avoids the errors due to the diffusion approximation.

Biophysical Phenomena↗

Influence of refractive index matching on the photon diffuse reflectance.

Photon migration in a randomly inhomogeneous, highly scattering and absorbing semi-infinite medium with a plane boundary is considered by a Monte Carlo (MC) technique. The employed MC technique combines the statistical weight scheme and real photon paths simulation, allowing the exclusion of the energy conservation problem. The internal reflection of the scattered radiation on the medium interface is taken into account by allowing the trajectories of photon packets to be split into reflected and transmitted parts. The spatial photon sensitivity profile (SPSP), spatially resolved diffuse reflectance and angular and spatial photon detector weight distributions are considered in terms of Fresnel's reflection/refraction on the boundary of the medium. The effect of the refractive index match is predicted correctly by the MC method and by the diffusion approximation. The results demonstrate that matching of the refractive index of the medium significantly improves the contrast and spatial resolution of the spatial photon sensitivity profile (SPSP). The results of simulation of the spatially resolved diffuse reflectance agree well with the results predicted by the diffusion approximation and the experimental results reported earlier.

Absorption↗

Innovative reflecting interview: effect on high-utilizing patients with medically unexplained symptoms.

This pilot study was conducted to determine the effect of an innovative reflecting interview on the health care utilization, physical health, mental function, and health care satisfaction of high-utilizing primary care patients with medically unexplained physical symptoms. Twenty-four high-utilizing patients met study selection criteria and were randomly assigned to a no-intervention control group or a reflecting interview intervention group. Outcomes were measured at 4 weeks, 6 months, and 1 year after the date of study enrollment. Results indicated that high-utilizing patients with medically unexplained physical symptoms who participated in a reflecting interview had reduced total health care costs, primarily through the reduction of hospitalization or inpatient expenses, despite a modest increase in outpatient primary care clinic visits. These data suggest that participation in a reflecting interview and regular visits with a primary care clinician can decrease health care utilization without adversely affecting patient satisfaction.

Adult↗

Reflective blankets used for reduction of heat loss during regional anaesthesia.

We have studied the ability of reflective blankets to reduce net loss of body heat during regional anaesthesia for total hip arthroplasty. Thirty patients were allocated randomly to either the study group (insulated with reflective blankets) or the control group (no reflective blankets). Surgical and operation room draping, theatre temperature and i.v. fluid administration were standardized for all patients. Total body heat was deduced from core temperature (aural canal) and mean skin temperature (four measuring sites). After 2 h of surgery, loss of body heat was reduced significantly in patients wrapped in reflective blankets (26 kJ) compared with those in the control group (95 kJ).

Adult↗

Neural correlates of self-reflection.

The capacity to reflect on one's sense of self is an important component of self-awareness. In this paper, we investigate some of the neurocognitive processes underlying reflection on the self using functional MRI. Eleven healthy volunteers were scanned with echoplanar imaging using the blood oxygen level-dependent contrast method. The task consisted of aurally delivered statements requiring a yes-no decision. In the experimental condition, participants responded to a variety of statements requiring knowledge of and reflection on their own abilities, traits and attitudes (e.g. 'I forget important things', 'I'm a good friend', 'I have a quick temper'). In the control condition, participants responded to statements requiring a basic level of semantic knowledge (e.g. 'Ten seconds is more than a minute', 'You need water to live'). The latter condition was intended to control for auditory comprehension, attentional demands, decision-making, the motoric response, and any common retrieval processes. Individual analyses revealed consistent anterior medial prefrontal and posterior cingulate activation for all participants. The overall activity for the group, using a random-effects model, occurred in anterior medial prefrontal cortex (t = 13.0, corrected P = 0.05; x, y, z, 0, 54, 8, respectively) and the posterior cingulate (t = 14.7, P = 0.02; x, y, z, -2, -62, 32, respectively; 967 voxel extent). These data are consistent with lesion studies of impaired awareness, and suggest that the medial prefrontal and posterior cingulate cortex are part of a neural system subserving self-reflective thought.

Adult↗

Reflected pressure waves in the ascending aorta: effect of glyceryl trinitrate.

Reflected pressure waves returning to the ascending aorta are an important contribution to aortic systolic pressure and thus the load on the left ventricle. The effect of glyceryl trinitrate on pressure wave reflections in the ascending aorta was studied using the transmission of arterial pressure between two high fidelity pressure transducers. Glyceryl trinitrate 0.3 mg sublingually reduced systolic arterial pressure by 11 mmHg owing to a reduction of the late systolic pressure peak. Mean arterial pressure fell 2 mmHg, but heart rate and aortic flow did not change. The aortic input impedance was reduced at the first harmonic (control 18.4(4.1); glyceryl trinitrate 10.8(2.4) kPa.s.litre-1; p less than 0.005) but characteristic impedance was not changed (control 12.7(3.8); glyceryl trinitrate 14.2(3.3) kPa.s.litre-1). The first two harmonics of apparent phase velocity were reduced by glyceryl trinitrate (1.05 Hz: control 3314(798); glyceryl trinitrate 1772(495) cm.s-1; p less than 0.01; 2.1 Hz: control 1246(269); glyceryl trinitrate 754(127) cm.s-1; p less than 0.05), yet the foot to foot wave velocity was unchanged (control 688(112); glyceryl trinitrate 726(112) cm.s-1). There was a significant reduction in the amplitude of the global reflection coefficient at 1.05 Hz (control 0.70(0.09); glyceryl trinitrate 0.48(0.08); p less than 0.001) and at 2.1 Hz (control 0.48(0.07); glyceryl trinitrate 0.23(0.06); p less than 0.005) with no significant change in phase. Glyceryl trinitrate reduces cardiac pulsatile load by diminishing the amplitude of wave reflections arriving back in the aorta during systole yet has no effect on aortic compliance or arteriolar resistance. This study demonstrates a method of evaluating the effect of vasoactive drugs on cardiac pulsatile load.

Adult↗

Promoting reflection on professionalism: a comparison trial of educational interventions for medical students.

PURPOSE: To determine whether writing, one-on-one interviews with faculty, or a combination of these interventions effectively elicited reflection on professionalism for medical students. METHOD: The study was a randomized trial conducted in 2001 at Harborview Medical Center, Seattle, Washington, with fourth-year medical students on a four-week clinical clerkship in emergency medicine. Three interventions were evaluated: the critical incident report (CIR), the CIR followed by a one-on-one interview with a faculty member, and one-on-one interview with no CIR. Quality and quantity of professional issues raised were addressed. RESULTS: All students (n = 68) agreed to participate; 66 completed the study components. On average, the students addressed significantly more issues of professionalism in their interviews alone than in their CIRs, 15.9 (95% confidence interval [CI] 18.2-13.6) and 7.15 (CI 8.88-5.40) issues respectively (p <.0001). Interviews preceded by CIRs were not significantly different from interviews with no CIR (13.5 versus 15.9 professionalism issues raised, respectively). In-depth explorations, including problem solving and projection to the future, occurred 2.59 times in interviews alone (CI 3.62-1.56) and 0.794 times in CIRs (CI 1.12-0.46) (p <.001). When analyzed as a proportion of total statements, the groups had similar ratios of in-depth statements (11.2% in CIRs and 15.7% in interviews alone). CONCLUSION: Writing did not significantly affect the quantity or quality of reflection in interviews. One-on-one interviews with a faculty mentor most effectively elicited reflection on professionalism. Future studies should examine how reflective exercises such as those evaluated can be used to promote professional development.

Adult↗

Caring for self: becoming a self-reflective nurse.

Grounded in teaching experiences with nursing students, Dewey's educational philosophy, principles of adult learning, and phenomenologic perspectives, the article presents a model of self-reflection discovered in the educational/learning process of caring for self. Self-reflection as a process is operationalized as a bending back of attention and a focus on self to uncover silence and meanings or essences of personal and professional experience. Critical outcomes of this process are increased awareness, increased depth and breadth of understanding, and expanded consciousness. The thesis that self-reflection is a critical process in caring for others is presented. The background for the work and the nursing course where students develop a clinical experience of caring for self are discussed. The article includes graphic representations of the reflective process and proposes that, through caring for self, transformation in caring experiences is possible.

Adult↗

Arterial mechanics and wave reflection with antihypertensive therapy.

PURPOSE: To describe a logical therapy for hypertension, based on functional elements of structural changes. EFFECTS OF STRUCTURAL CHANGES: Structural changes to large blood vessels in hypertension include medial degenerative changes, which stiffen arteries and increase pulse wave velocity, and intimal atherosclerotic changes, which narrow arterial segments. The former cause early wave reflection with increased systolic pressure in central arteries and the left ventricle. The latter compromise blood flow to vital organs. LOGIC OF VASODILATOR THERAPY: Vasodilator drugs with arterial dilating properties are the most logical and effective therapy. These agents decrease wave reflection from peripheral sites and so reduce systolic pressure in the left ventricle and central arteries; this effect is achieved both by decreasing the stiffness of peripheral arteries and by a differential effect on arterial calibre at branching sites. Arterial vasodilators also tend to dilate stenoses and collateral vessels and thereby minimize vascular 'steal', whereas arterial vasodilators (such as dipyridamole, hydralazine, prazosin) have little or no significant effect on wave reflection, and so fail to reduce the ill-effects of early wave reflection on the left ventricle and central arteries. Furthermore, by dilating arterioles in normal tissue, arteriolar vasodilators can cause vascular 'steal' in the heart or brain. CONCLUSIONS: The most effective vasodilators are those with both arterial- and arteriolar-dilating properties. Differential effects of vasodilators on arteries and arterioles can explain some differing effects of antihypertensive agents in clinical trials, as well as differing clinical responses in individual patients.

Arteries↗

Simultaneous determination of fecal fat, nitrogen, and water by near-infrared reflectance spectroscopy.

BACKGROUND: Determinations of fecal fat and nitrogen reveal evidence of malabsorption and assist in estimating the efficacy of pancreatic enzyme treatment. Seventy-two-hour stool collection, with chemical analysis of fecal fat, and Kjeldahl's method for measurement of fecal nitrogen are generally accepted as standard methods for making these determinations. However, these traditional methods are expensive, time-consuming, and cumbersome. This study evaluated the efficiency and validity of an alternative method, using near-infrared reflectance spectroscopy (NIRS) and compared results with those of the standard methods. METHODS: Near-infrared reflectance spectroscopy is a secondary method: The instrument first has to be calibrated with samples analyzed by the standard method. Sixty-three stool samples with known fat content (range 4.79-292.5 mg/g), 24 samples with known nitrogen content (range 5.36-19.38 mg/g), and 24 samples with known water concentration (range 60.1-82.22%) served for calibration. A further 69 samples were analyzed to validate the procedure. RESULTS: There was a satisfactory correlation between the measurements produced by near-infrared reflectance spectroscopy and those produced by standard methods: fat r = 0.97; nitrogen r = 0.94; water r = 0.96. CONCLUSIONS: Near-infrared reflectance spectroscopy appears to be a reliable, simple, and rapid method of measuring different fecal components-as precise and accurate as the standard methods. Stool samples should be analyzed immediately after collecting or stored only a few days before analyzing.

Adolescent↗

Reflective journaling: developing an online journal for distance education.

Reflective journal writing can be a useful heuristic tool to foster critical thinking skills and develop reflective clinical practice in nursing. When combined with a distance education delivery format, the online journal helps to leverage the strengths of reflective learning with educational technology as well as provide a seamless record of learning outcomes across the curriculum. The authors discuss the incorporation of an online reflective journal into a distance education clinical course and provide guidelines for educators considering a similar approach.

Attitude of Health Personnel↗

Comparison of the accuracy of glucose reflectance meters in pregnant insulin-dependent diabetics.

Home monitoring of blood glucose by reflectance meters has been shown to be accurate in the nonpregnant diabetic and is currently used for outpatient glucose control in the pregnant diabetic as well. Beckman ASTRA glucose results from samples collected into sodium fluoride were used as the standard for this study. Comparisons were then made to four glucose reflectance meters: Accu-Check II, One Touch, DiaScan S, and ExacTech. Although the reflectance meters appeared to be useful for assessing blood glucose trends in the pregnant diabetic, the results obtained from these meters would be unacceptable in the laboratory setting. Unfortunately, because of the erratic combination of proportional and constant bias, correction factors are not easily ascertained. Laboratories and physicians should reconsider the use of these reflectance meters for inpatient evaluation and general population screening of pregnant women.

Blood Glucose Self-Monitoring↗