Validated spectrophotometric and spectrofluorimetric methods for determination of chloroaluminum phthalocyanine in nanocarriers

UV-VIS-Spectrophotometric and spectrofluorimetric methods have been developed and validated allowing the quantification of chloroaluminum phthalocyanine (CIAIPc) in nanocarriers. In order to validate the methods, the linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, and selectivity were examined according to USP 30 and ICH guidelines. Linearities range were found between 0.50-3.00 mu g.mL(-1) (Y=0.3829 X [CIAIPc, mu g.mL(-1)] + 0.0126; r=0.9992) for spectrophotometry, and 0.05-1.00 mu g.mL(-1) (Y=2.24 x 10(6) X [CIAIPc, mu g.L(-1)] + 9.74 x 10(4); r=0.9978) for spectrofluorimetry. In addition, ANOVA and Lack-of-fit tests demonstrated that the regression equations were statistically significant (p<0.05), and the resulting linear model is fully adequate for both analytical methods. The LOD values were 0.09 and 0.01 mu g.mL(-1), while the LOCI were 0.27 and 0.04 mu g.mL(-1) for spectrophotometric and spectrofluorimetric methods, respectively. Repeatability and intermediate precision for proposed methods showed relative standard deviation (RSD) between 0.58% to 4.80%. The percent recovery ranged from 98.9% to 102.7% for spectrophotometric analyses and from 94.2% to 101.2% for spectrofluorimetry. No interferences from common excipients were detected and both methods were considered specific. Therefore, the methods are accurate, precise, specific, and reproducible and hence can be applied for quantification of CIAIPc in nanoemulsions (NE) and nanocapsules (NC).

Numerical modelling of chemical effects of magma solidification problems in porous rocks

The solidification of intruded magma in porous rocks can result in the following two consequences: (1) the heat release due to the solidification of the interface between the rock and intruded magma and (2) the mass release of the volatile fluids in the region where the intruded magma is solidified into the rock. Traditionally, the intruded magma solidification problem is treated as a moving interface (i.e. the solidification interface between the rock and intruded magma) problem to consider these consequences in conventional numerical methods. This paper presents an alternative new approach to simulate thermal and chemical consequences/effects of magma intrusion in geological systems, which are composed of porous rocks. In the proposed new approach and algorithm, the original magma solidification problem with a moving boundary between the rock and intruded magma is transformed into a new problem without the moving boundary but with the proposed mass source and physically equivalent heat source. The major advantage in using the proposed equivalent algorithm is that a fixed mesh of finite elements with a variable integration time-step can be employed to simulate the consequences and effects of the intruded magma solidification using the conventional finite element method. The correctness and usefulness of the proposed equivalent algorithm have been demonstrated by a benchmark magma solidification problem. Copyright (c) 2005 John Wiley & Sons, Ltd.

Molecular epidemiology: A multidisciplinary approach to understanding parasitic zoonoses

Sound application of molecular epidemiological principles requires working knowledge of both molecular biological and epidemiological methods. Molecular tools have become an increasingly important part of studying the epidemiology of infectious agents. Molecular tools have allowed the aetiological agent within a population to be diagnosed with a greater degree of efficiency and accuracy than conventional diagnostic tools. They have increased the understanding of the pathogenicity, virulence, and host-parasite relationships of the aetiological agent, provided information on the genetic structure and taxonomy of the parasite and allowed the zoonotic potential of previously unidentified agents to be determined. This review describes the concept of epidemiology and proper study design, describes the array of currently available molecular biological tools and provides examples of studies that have integrated both disciplines to successfully unravel zoonotic relationships that would otherwise be impossible utilising conventional diagnostic tools. The current limitations of applying these tools, including cautions that need to be addressed during their application are also discussed.(c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection

Because CD4(+) T cells play a key role in aiding cellular immune responses, we wanted to assess whether increasing numbers of gene-engineered antigen-restricted CD4(+) T cells could enhance an antitumor response mediated by similarly gene-engineered CD8(+) T cells. In this study, we have used retroviral transduction to generate erbB2-reactive mouse T-cell populations composed of various proportions of CD4(+) and CD8(+) cells and then determined the antitumor reactivity of these mixtures. Gene-modified CD4(+) and CD8(+) T cells were shown to specifically secrete Tc1 (T cytotoxic-1) or Tc2 cytokines, proliferate, and lyse erbB2(+) tumor targets following antigen ligation in vitro. In adoptive transfer experiments using severe combined immunodeficient (scid) mice, we demonstrated that injection of equivalent numbers of antigen-specific engineered CD8(+) and CD4(+) T cells led to significant improvement in survival of mice bearing established lung metastases compared with transfer of unfractionated (largely CD8(+)) engineered T cells. Transferred CD4(+) T cells had to be antigen-specific (not just activated) and secrete interferon gamma (IFN-gamma) to potentiate the antitumor effect. Importantly, antitumor responses in these mice correlated with localization and persistence of gene-engineered T cells at the tumor site. Strikingly, mice that survived primary tumor challenge could reject a subsequent re-challenge. Overall, this study has highlighted the therapeutic potential of using combined transfer of antigen-specific gene-modified CD8(+) and CD4(+) T cells to significantly enhance T-cell adoptive transfer strategies for cancer therapy.

Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial

Background Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. This study investigated whether an antisense inhibitor of apolipoprotein B synthesis, mipomersen, is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease. Methods This randomised, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics in seven countries. Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks. Randomisation was computer generated and stratified by weight (<50 kg vs >= 50 kg) in a centralised blocked randomisation, implemented with a computerised interactive voice response system. All clinical, medical, and pharmacy personnel, and patients were masked to treatment allocation. The primary endpoint was percentage change in LDL cholesterol concentration from baseline. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00607373. Findings 34 patients were assigned to mipomersen and 17 to placebo; data for all patients were analysed. 45 patients completed the 26-week treatment period (28 mipomersen, 17 placebo). Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (-24.7%, 95% CI 31.6 to 17.7) than with placebo (-3.3%, 12.1 to 5.5; p=0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal. Interpretation Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins.

Anemia screening in potential female blood donors: comparison of two different quantitative methods

Anemia screening before blood donation requires an accurate, quick, practical, and easy method with minimal discomfort for the donors. The aim of this study was to compare the accuracy of two quantitative methods of anemia screening: the HemoCue 201(+) (Aktiebolaget Leo Diagnostics) hemoglobin (Hb) and microhematocrit (micro-Hct) tests. Two blood samples of a single fingerstick were obtained from 969 unselected potential female donors to determine the Hb by HemoCue 201(+) and micro-Hct using HemataSTAT II (Separation Technology, Inc.), in alternating order. From each participant, a venous blood sample was drawn and run in an automatic hematology analyzer (ABX Pentra 60, ABX Diagnostics). Considering results of ABX Pentra 60 as true values, the sensitivity and specificity of HemoCue 201(+) and micro-Hct as screening methods were compared, using a venous Hb level of 12.0 g per dL as cutoff for anemia. The sensitivities of the HemoCue 201(+) and HemataSTAT II in detecting anemia were 56 percent (95% confidence interval [CI], 46.1%-65.5%) and 39.5 percent (95% CI, 30.2%-49.3%), respectively (p < 0.001). Analyzing only candidates with a venous Hb level lower than 11.0 g per dL, the deferral rate was 100 percent by HemoCue 201(+) and 77 percent by HemataSTAT II. The specificities of the methods were 93.5 and 93.2 percent, respectively. The HemoCue 201(+) showed greater discriminating power for detecting anemia in prospective blood donors than the micro-Hct method. Both presented equivalent deferral error rates of nonanemic potential donors. Compared to the micro-Hct, HemoCue 201(+) reduces the risk of anemic female donors giving blood, specially for those with lower Hb levels, without increasing the deferral of nonanemic potential donors.

Numerical simulation of double-diffusion driven convective flow and rock alteration in three-dimensional fluid-saturated geological fault zones

Numerical methods are used to simulate the double-diffusion driven convective pore-fluid flow and rock alteration in three-dimensional fluid-saturated geological fault zones. The double diffusion is caused by a combination of both the positive upward temperature gradient and the positive downward salinity concentration gradient within a three-dimensional fluid-saturated geological fault zone, which is assumed to be more permeable than its surrounding rocks. In order to ensure the physical meaningfulness of the obtained numerical solutions, the numerical method used in this study is validated by a benchmark problem, for which the analytical solution to the critical Rayleigh number of the system is available. The theoretical value of the critical Rayleigh number of a three-dimensional fluid-saturated geological fault zone system can be used to judge whether or not the double-diffusion driven convective pore-fluid flow can take place within the system. After the possibility of triggering the double-diffusion driven convective pore-fluid flow is theoretically validated for the numerical model of a three-dimensional fluid-saturated geological fault zone system, the corresponding numerical solutions for the convective flow and temperature are directly coupled with a geochemical system. Through the numerical simulation of the coupled system between the convective fluid flow, heat transfer, mass transport and chemical reactions, we have investigated the effect of the double-diffusion driven convective pore-fluid flow on the rock alteration, which is the direct consequence of mineral redistribution due to its dissolution, transportation and precipitation, within the three-dimensional fluid-saturated geological fault zone system. (c) 2005 Elsevier B.V. All rights reserved.

Special issue on methods and learning in functional MRI: Introductory remarks

This special issue represents a further exploration of some issues raised at a symposium entitled “Functional magnetic resonance imaging: From methods to madness” presented during the 15th annual Theoretical and Experimental Neuropsychology (TENNET XV) meeting in Montreal, Canada in June, 2004. The special issue’s theme is methods and learning in functional magnetic resonance imaging (fMRI), and it comprises 6 articles (3 reviews and 3 empirical studies). The first (Amaro and Barker) provides a beginners guide to fMRI and the BOLD effect (perhaps an alternative title might have been “fMRI for dummies”). While fMRI is now commonplace, there are still researchers who have yet to employ it as an experimental method and need some basic questions answered before they venture into new territory. This article should serve them well. A key issue of interest at the symposium was how fMRI could be used to elucidate cerebral mechanisms responsible for new learning. The next 4 articles address this directly, with the first (Little and Thulborn) an overview of data from fMRI studies of category-learning, and the second from the same laboratory (Little, Shin, Siscol, and Thulborn) an empirical investigation of changes in brain activity occurring across different stages of learning. While a role for medial temporal lobe (MTL) structures in episodic memory encoding has been acknowledged for some time, the different experimental tasks and stimuli employed across neuroimaging studies have not surprisingly produced conflicting data in terms of the precise subregion(s) involved. The next paper (Parsons, Haut, Lemieux, Moran, and Leach) addresses this by examining effects of stimulus modality during verbal memory encoding. Typically, BOLD fMRI studies of learning are conducted over short time scales, however, the fourth paper in this series (Olson, Rao, Moore, Wang, Detre, and Aguirre) describes an empirical investigation of learning occurring over a longer than usual period, achieving this by employing a relatively novel technique called perfusion fMRI. This technique shows considerable promise for future studies. The final article in this special issue (de Zubicaray) represents a departure from the more familiar cognitive neuroscience applications of fMRI, instead describing how neuroimaging studies might be conducted to both inform and constrain information processing models of cognition.

A comparison of methods to identify open-lung PEEP

Purpose: Many methods exist in the literature for identifying PEEP to set in ARDS patients following a lung recruitment maneuver (RM). We compared ten published parameters for setting PEEP following a RM. Methods: Lung injury was induced by bilateral lung lavage in 14 female Dorset sheep, yielding a PaO(2) 100-150 mmHg at F(I)O(2) 1.0 and PEEP 5 cmH(2)O. A quasi-static P-V curve was then performed using the supersyringe method; PEEP was set to 20 cmH(2)O and a RM performed with pressure control ventilation (inspiratory pressure set to 40-50 cmH(2)O), until PaO(2) + PaCO(2) > 400 mmHg. Following the RM, a decremental PEEP trial was performed. The PEEP was decreased in 1 cmH(2)O steps every 5 min until 15 cmH(2)O was reached. Parameters measured during the decremental PEEP trial were compared with parameters obtained from the P-V curve. Results: For setting PEEP, maximum dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), and minimum shunt calculated during the decremental PEEP trial, and the lower Pflex and point of maximal compliance increase on the inflation limb of the P-V curve (Pmci,i) were statistically indistinguishable. The PEEP value obtained using the deflation upper Pflex and the point of maximal compliance decrease on the deflation limb were significantly higher, and the true inflection point on the inflation limb and minimum PaCO(2) were significantly lower than the other variables. Conclusion: In this animal model of ARDS, dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), minimum shunt, inflation lower Pflex and Pmci,i yield similar values for PEEP following a recruitment maneuver.

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective ""CORE-64"" trial (""Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors""). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Ventilation Patterns Influence Airway Secretion Movement

BACKGROUND: Retention of airway secretions is a common and serious problem in ventilated patients. Treating or avoiding secretion retention with mucus thinning, patient-positioning, airway suctioning, or chest or airway vibration or percussion may provide short-term benefit. METHODS: In a series of laboratory experiments with a test-lung system we examined the role of ventilator settings and lung-impedance on secretion retention and expulsion. Known quantities of a synthetic dye-stained mucus simulant with clinically relevant properties were injected into a transparent tube the diameter of an adult trachea and exposed to various mechanical-ventilation conditions. Mucus-simulant movement was measured with a photodensitometric technique and examined with image-analysis software. We tested 2 mucus-simulant viscosities and various peak flows, inspiratory/ expiratory flow ratios, intrinsic positive end-expiratory pressures, ventilation waveforms, and impedance values. RESULTS: Ventilator settings that produced flow bias had a major effect on mucus movement. Expiratory How bias associated with intrinsic positive end-expiratory pressure generated by elevated minute ventilation moved mucus toward the airway opening, whereas intrinsic positive end-expiratory pressure generated by increased airway resistance moved the mucus toward the lungs. Inter-lung transfer of mucus simulant occurred rapidly across the ""carinal divider"" between interconnected test lungs set to radically different compliances; the mucus moved out of the low-compliance lung and into the high-compliance lung. CONCLUSIONS: The movement of mucus simulant was influenced by the ventilation pattern and lung impedance. Flow bias obtained with ventilator settings may clear or embed mucus during mechanical ventilation.

Hemihypoglossal-facial neurorrhaphy after mastoid dissection of the facial nerve: Results in 24 patients and comparison with the classic technique

OBJECTIVE: Hypoglossal-facial neurorrhaphy has been widely used for reanimation of paralyzed facial muscles after irreversible proximal injury of the facial nerve. However, complete section of the hypoglossal nerve occasionally results in hemiglossal dysfunction and interferes with swallowing and speech. To reduce this morbidity, a modified technique with partial section of the hypoglossal nerve after mastoid dissection of the facial nerve (HFM) has been used. We report our experience with the HFM technique, retrospectively comparing the outcome with results of the classic hypoglossal-facial neurorrhaphy. METHODS: A retrospective review was performed in 36 patients who underwent hypoglossal-facial neurorrhaphy with the classic (n = 12) or variant technique (n = 24) between 2000 and 2006. Facial Outcome was evaluated with the House-Brackmann grading system, and tongue function was evaluated with a new scale proposed to quantify Postoperative tongue alteration. The results were compared, and age and time between nerve injury and surgery were correlated with the outcome. RESULTS: There was no significant difference between the two techniques concerning facial reanimation. A worse outcome of tongue function, however, was associated with the classic technique (Mann-Whitney U test; P < 0.05). When HFM was used, significant correlations defined by the Spearman test were identified between preoperative delay (p = 0.59; P = 0.002) or age (p = 0.42; P = 0.031) and results of facial reanimation evaluated with the House-Brackmann grading system. CONCLUSION: HFM is as effective as classic hypoglossal-facial neurorrhaphy for facial reanimation, and it has a much lower morbidity related to tongue function. Better results are obtained in younger patients and with a shorter interval between facial nerve injury and surgery.

Diagnostic Performance of Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-MDCT: The CT Angiography and Perfusion Methods of the CORE320 Multicenter Multinational Diagnostic Study

OBJECTIVE. Coronary MDCT angiography has been shown to be an accurate noninvasive tool for the diagnosis of obstructive coronary artery disease (CAD). Its sensitivity and negative predictive value for diagnosing percentage of stenosis are unsurpassed compared with those of other noninvasive testing methods. However, in its current form, it provides no information regarding the physiologic impact of CAD and is a poor predictor of myocardial ischemia. CORE320 is a multicenter multinational diagnostic study with the primary objective to evaluate the diagnostic accuracy of 320-MDCT for detecting coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected CAD compared with the reference standard of conventional coronary angiography and SPECT myocardial perfusion imaging. CONCLUSION. We aim to describe the CT acquisition, reconstruction, and analysis methods of the CORE320 study.

Optical Quality in Eyes Implanted With Aspheric and Spherical Intraocular Lenses Assessed by NIDEK OPD-Scan: A Randomized, Bilateral, Clinical Trial

PURPOSE: To determine whether implantation of an intraocular lens (IOL) with an aspheric surface (Akreos AO, Bausch & Lomb Inc) results in reduced ocular aberrations (spherical aberration) and improved Strehl ratio and modulation transfer function (MTF) after cataract surgery. METHODS: In an intraindividual, randomized, double-masked, prospective study of 50 eyes (25 patients) with bilateral cataract, an IOL with modified anterior and posterior surfaces (Akreos AO) was implanted in one eye and a biconvex IOL with spherical surfaces (Akreos Fit, Bausch & Lomb Inc) implanted in the fellow eye. Ocular aberrations, Strehl ratio, and MTF curve with 4.5-, 5.0-, and 6.0-mm pupils were measured with a NIDEK OPD-Scan dynamic retinoscopy aberrometer 3 months after surgery. Uncorrected and corrected distance visual acuity (UDVA and CDVA, respectively) were also measured. RESULTS: No statistically significant difference was noted between eyes in postoperative UDVA and CDVA at 1 month. At 3 months, the Akreos AO IOL group obtained statistically significant lower values of higher order and spherical aberrations with 4.5-, 5.0-, and 6.0-mm pupil diameters than the Akreos Fit IOL group (P<.05). The value of Strehl ratio was statistically significantly higher in eyes with the Akreos AO IOL for 4.5- and 6.0-mm pupils (P<.05). The MTF curve was better in the Akreos AO IOL group in 4.5-, 5.0-, and 6.0-mm pupils (P<.05). CONCLUSIONS: The aspheric Akreos AO IOL induced significantly less spherical aberration than the Akreos Fit IOL for 4.5-, 5.0-, and 6.0-mm pupils. Modulation transfer function and Strehl ratio were also better in eyes implanted with the Akreos AO IOL than the Akreos Fit. [J Refract Surg. 2011;27(4):287-292.] doi:10.3928/1081597X-20100714-01