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Experimental and clinical results of Er:YAG laser stapedotomy.

BACKGROUND AND OBJECTIVE: At the beginning of the 1980s, different laser types were used for stapes surgery to reduce potential harm to inner ear structures through manipulation with conventional instruments during stapedotomy. Most clinical studies were carried out with the CO2 or the argon laser. The Er:YAG laser has been used rarely in patients with otosclerosis. STUDY DESIGN/MATERIALS AND METHODS: In an experimental study on 54 human petrous bones, the optimal laser energy parameter for dissection of the posterior stapes crus and the footplate perforation were determined. With these parameters, stapedotomy was carried out with the Er:YAG laser in 29 patients with otosclerosis with a conventional dissection of the incudostapedial joint and the stapedius muscle tendon. The Er:YAG laser was used (60 or 100 mJ, 3-6 pulses) for dissection of the posterior stapes crus and footplate perforation. RESULTS: No intra- or postoperative complications were observed in all 29 patients. Vertigo and hearing loss were not observed intra- or postoperatively. The postoperative hearing results (improvement of the air-bone gap) was in all cases satisfactory (median remaining air bone gap, 8.1 dB). The median operation time was 29 minutes (15-42 minutes) and did not show a significant prolongation in comparison to the conventional technique. In 1 of the 29 patients, the footplate perforation needed to be carried out conventionally. CONCLUSION: For the first time, Er:YAG laser parameters have been optimized and refined in a human petrous bone model and were then used in a clinical setting. According to the presented results, the Er:YAG laser seemed to be a very suitable instrument for stapedotomy.

Adult↗

Mass spectrometric characteristics of decabromodiphenyl ether and the application of isotopic dilution in the electron capture negative ionization mode for the analysis of polybrominated diphenyl ethers.

The mass spectrometric properties of (12)C-and (13)C-labeled decabromodiphenyl ether (BDE-209) in the low-resolution mass spectrometry electron capture negative ionization mode (ECNI-MS) is described in detail and are compared with those of polybrominated diphenyl ethers (PBDEs) with a lower degree of bromination. The mass spectrometric properties of BDE-209 make it possible to apply (13)C-labeled BDE-209 as an internal surrogate standard for the determination of BDE-209 by isotopic dilution. A combination of the [Br](-) and [C(6)Br(5)O](-) fragment ions is proposed for the detection with ECNI-MS in the selected ion monitoring mode to increase selectivity, sensitivity and accuracy in the determination of decabromodiphenyl ether together with other polybrominated diphenyl ethers. The importance of optimizing the instrument parameters to obtain optimal response from the mass spectrometer in the analysis of PBDEs is discussed in detail.

Journal Article↗

Improved method for preparation and use of 9-anthryldiazomethane for derivatization of hydroxycarboxylic acids. Application to diarrhetic shellfish poisoning toxins.

Application of a method for the "in situ" generation of 9-anthryldiazomethane (ADAM) to the derivatization of the carboxyl function in diarrhetic shellfish poisoning (DSP) toxins revealed the formation of artifact products. Using liquid chromatography-mass spectrometry, it was determined that these artifacts were due to base-catalyzed reactions between the solvent, ethyl acetate, and the hydroxyl groups of the analyte to produce O-acetylated ADAM derivatives. Using a new formulation, with tetrahydrofuran as solvent, it was possible to eliminate these artifact reactions. Various reaction parameters have also been re-optimized to ensure quantitative derivatizations. An assessment method was developed that was useful not only for optimizing reaction parameters, but also for evaluating the reagent potency before use on important samples. Finally, application of the method to the determination of DSP toxins in plankton and mussel tissue was demonstrated.

Anthracenes↗

3-D deformable image registration: a topology preservation scheme based on hierarchical deformation models and interval analysis optimization.

This paper deals with topology preservation in three-dimensional (3-D) deformable image registration. This work is a nontrivial extension of, which addresses the case of two-dimensional (2-D) topology preserving mappings. In both cases, the deformation map is modeled as a hierarchical displacement field, decomposed on a multiresolution B-spline basis. Topology preservation is enforced by controlling the Jacobian of the transformation. Finding the optimal displacement parameters amounts to solving a constrained optimization problem: The residual energy between the target image and the deformed source image is minimized under constraints on the Jacobian. Unlike the 2-D case, in which simple linear constraints are derived, the 3-D B-spline-based deformable mapping yields a difficult (until now, unsolved) optimization problem. In this paper, we tackle the problem by resorting to interval analysis optimization techniques. Care is taken to keep the computational burden as low as possible. Results on multipatient 3-D MRI registration illustrate the ability of the method to preserve topology on the continuous image domain.

Algorithms↗

Liposomal doxorubicin.

Doxorubicin is a potent antineoplastic agent with activity against numerous human cancers. Encapsulation of doxorubicin inside a liposome alters bioavailability, biodistribution and thus its biological activity significantly. The physical properties of the liposome (size, lipid components and lipid dose) play a major role in determining drug retention and pharmacokinetics. The therapeutic benefits of liposomal doxorubicin will therefore depend on these physical characteristics. Here we review the toxicity and efficacy of liposomal doxorubicin determined for various liposome compositions (size, lipid composition and drug-to-lipid ratio). These physical properties can be independently varied using the transmembrane pH gradient-dependent drug encapsulation procedure. The results show that the toxicity of the formulation is related to drug retention in the circulation. The antitumor activity is more sensitive to the size of the liposomes. By optimizing these parameters, liposomal doxorubicin formulations can be optimized for improved therapeutic activity.

Antibiotics, Antineoplastic↗

Method dependence of proton spin-lattice relaxation analysis in biologic tissues.

Spin-lattice proton relaxation times (T1) in several biologic and phantom samples have been measured and analysed by using standard inversion recovery (IR) and spin echo (SE) sequences at 0.02 T. The average T1 of the sample was measured with the two-data point method. In the case of bi-exponential relaxation the value of a single T1 is strongly dependent on the TI and TR selected. With short TI the T1 value obtained by using the two point method is approximately equal to the weighted average of the two relaxation time components (T1s and T1l), while at long inversion times TI the single T1 is more dependent on the long component T1l. The more the true short and long relaxation time components T1s and T1l of the bi-exponential relaxation differ from each other, the greater is the potential error, provided that the weights ws and wl do not differ very much. When two-data point analyzing method is used, the possible multi-exponential behaviour of the relaxation in tissues will be missed. For more reliable T1 values a series of images with as many values of TI as possible should be taken. Knowledge of true multi-exponential relaxation parameters helps in optimizing the sequence parameters and the image contrast between the various tissues.

Animals↗

Estimation of the electrical parameters of spinal motoneurons using impedance measurements.

Electrical parameters of spinal motoneurons were estimated by optimizing the parameters of motoneuron models to match experimentally determined impedance functions with those of the models. The model was described by soma area, somatic and dendritic membrane resistivities, and the diameter of an equivalent dendritic cable having a standard profile. The impedance functions of motoneurons and optimized models usually differed (rms error) by <2% of input resistance. Consistent estimates for most parameters were obtained from repeated impedance determinations in individual motoneurons; estimates of dendritic resistivity were most variable. The few cells that could not be fit well had reduced impedance phase lag consistent with dendritic penetrations. Most fits were improved by inclusion of a voltage-dependent conductance G(V) with time constant tau(V). A uniformly distributed G(V) with tau(V) >5 ms provided a better fit for most cells. The magnitude of this conductance decreased with depolarization. Impedance functions of other cells were adequately fit by a passive model or by a model with a somatic G(V) and tau(V) <5 ms. Most of these neurons (7/8) had resting potentials positive to -60 mV. The electrotonic parameters rho, tau, and L, estimated from model parameters, were consistent with published distributions. Most motoneuron parameters obtained in somatic shunt and sigmoidal models were well correlated, and parameters were moderately affected by changes in dendritic profile. These results demonstrate the utility and limitations of impedance measurements for estimating motoneuron parameters and suggest that voltage-dependent conductances are a substantial component of resting electrical properties.

Animals↗

Optimization of the principal parameters for the ultrarapid electrophoretic separation of reduced and oxidized glutathione by capillary electrophoresis.

Several factors can influence the analytical efficiency and rapidity of the quantitative determination of erythrocyte glutathione by capillary zone electrophoresis (CZE). We optimized the time, efficiency and resolution of the electrophoretic separation of reduced (GSH) and oxidized (GSSG) glutathione by studying the influence of the most important factors affecting the separation, i.e. the pH and ionic strength of the electrolyte solution, the capillary length and temperature. Best results in the shortest time are obtained at 25 degrees C, using an uncoated 37 cm x 75 microm i.d. capillary and a 300 mmol/l borate buffer pH 7.8. These conditions give a good reproducibility of the corrected peak areas (R.S.D. 1.41 and 1.31%) and of the migration time (R.S.D. 0.22 and 0.26%) for GSH and GSSG, respectively. The high concentration buffer, besides permitting a good resolution of standard GSH and GSSG mix, allows also N-nitrosoglutathione detection. By shortening the capillary length to 27 cm, the separation time of GSH and GSSG can be further decreased to less than 60s. This shortened method, the most rapid described in literature, can detect and quantify GSH in red blood cells despite a loss of sensitivity. To compare the new method here described with the Beutler colorimetric method, the data relative to the GSH content of red blood cells from young normal subjects were analyzed by the Passing and Bablok regression and the Bland-Altman test.

Electrophoresis, Capillary↗

[Role of the pharmacokinetic parameters of carbamazepine in optimizing epilepsy treatment].

In 14 epileptic patients the authors determined concentrations of carbamazepine, its total and relative clearance, the period of half-elimination and the elimination constant. Blood levels of carbamazepine were assayed by gas liquid chromatography. The pharmacokinetic parameters have been found to be important for specifying the causes of dissociation between the level of blood anticonvulsant and the therapeutic effect when the attacks cannot be controlled or there were signs of intoxication. The mean diagrams of fluctuations of blood concentrations of the drug in the interval between single doses indicate the dependence of the clinical effect on the amplitude of fluctuations and create the prerequisites for the optimization of anticonvulsive therapy.

Adult↗

Are higher vancomycin doses needed in ventricle-external shunted patients?

OBJECTIVE: Hydrocephalus is usually resolved by diverting cerebrospinal fluid through a surgically implanted intra-ventricular catheter (shunt). The aim of this study was to characterize vancomycin pharmacokinetic (PK) parameters and optimal dosage in shunted patients under vancomycin treatment. SETTING: Intensive Care and Neurosurgical Units. University Hospital. METHODS: Retrospective data of vancomycin blood concentrations, demographics and biochemical parameters, from a Therapeutic Drug Monitoring (TDM) program, in ventricle-external shunted patients (Group A) and controls (Group B) were collected. In all subjects, several blood samples at steady state conditions were drawn. Individual PK parameters such as drug clearance (CL) and volume of distribution (V) were estimated by using an one-compartmental PK model and later, dosage regimens were individually adjusted by Bayesian analysis. The obtained CL and V mean +/- standard deviation were compared between both groups (A versus B). Vancomycin dosage regimens between both groups were also compared. MAIN OUTCOME MEASURES: Patients demographics, clinical records, creatinine clearance by Cockcroft-Gault, vancomycin blood levels, vancomycin pK parameters and optimal initial IV vancomycin dosage. RESULTS: Forty-five patients were included in the study: 15 patients in group A and 30 subjects in group B. Significant differences between CL(A) and CL(B) means were observed, while not between V(A) and V(B). In shunted patients, the required vancomycin daily dose to reach target concentrations was significantly higher than the dose needed in the control group (49.25 +/- 12.28 mg/kg/day vs. 31.74 +/- 6.70 mg/kg/day; P < 0.0005). CONCLUSIONS: Greater vancomycin clearance was found in our shunted patients, thus they required higher vancomycin daily doses compared to the control group. Consequently, vancomycin TDM in shunted patients should be advisable in order to guarantee antibiotic blood concentrations within the recommended therapeutic range.

Adult↗

[Detectability of cerebral aneurysms and surrounding vessels by three-dimensional evaluation using helical scanning CT (HES-CT)].

Helical scanning CT (HES-CT) is a new technique to enable high-speed volumetric data acquisition. We have applied HES-CT to the diagnosis of cerebral vascular diseases. In our experience, the relationship between the scanning parameters of HES-CT and image quality was complex and reciprocal, so that optimization of the parameters according to the clinical demands was essential. We compared HES-CT with conventional cerebral angiography to determine the detectability of the aneurysm and surrounding vessels, and sought the optimal parameters to delineate small vessels. All aneurysms were detected in multiplanar reconstruction (MPR) images. The smallest one was 3 x 4 mm. MPR images were found to have some advantages over conventional cerebral angiography in delineation of intracranial aneurysms: 1) scanning was over in a short time (30s), 2) the relationship between the aneurysm and surrounding vessels was easily recognized, 3) the diameter of the neck could be measured, because the neck of the aneurysm and parent artery could be imaged on the same plane without overlapping another vessel, 4) calcified lesions on the aneurysmal wall were detected, and 5) HES-CT was done safety without arterial puncture. However, the detectability of unknown aneurysm was less than the detectability of known aneurysm in MPR images. The 180 degrees interpolation algorithm and 1 mm slice were effective in detecting small vessels. However, vessels with a diameter less than 1 mm could not be detected by HES-CT. HES-CT was considered to be useful as a supplementary examination to conventional angiography for the diagnosis of intracranial aneurysms.

Adolescent↗

Application of backpropagation neural networks to diagnosis of breast and ovarian cancer.

Neural network programs have been developed in an attempt to improve the diagnosis of breast and ovarian cancer using a group of laboratory tests and the age of the patient. The laboratory tests employed in this study include albumin, cholesterol, HDL-cholesterol, triglyceride, apolipoproteins A1 and B, NMR linewidth (the Fossel Index) and a tumor marker (i.e., CA 15-3 or CA 125). The breast cancer study involved 104 patients (45 malignant and 59 benign subjects). The ovarian cancer study involved 98 individuals (35 malignant, 36 benign and 27 control subjects). Methods are outlined for identification of the most influential input parameters and optimization of network structure and training. Network characteristics were contrasted with the test results of the appropriate serum tumor marker assay. For the breast cancer study, the best neural network program, using six input parameters, had a sensitivity of only 55.6% and a specificity of 72.9%. The tumor marker CA 15-3 alone gave results of 61.3% and 64.4%, respectively. For the ovarian cancer study, the best neural network program, using six input parameters, had a sensitivity of 80.6% and a specificity of 85.5%. The tumor marker CA 125 alone gave results of 77.8% and 82.3%, respectively. These methods provide an objective approach to neural network optimization and parameter selection applicable to other data bases of clinical and laboratory data.

Biomarkers, Tumor↗

MarkerMatch: A Proximity-Based Probe-Matching Algorithm for Joint Analysis of Copy-Number Variants from Different Genotyping Arrays.

MOTIVATION: Copy-number variants (CNVs) are a form of genetic structural variation with increasing importance in complex human disorders. Both DNA sequencing and microarray data can be used to call CNVs, which can be used in association tests, such as association between CNV number and disease status. Unlike genotypes, CNV detection in microarrays requires the use of observed intensity signals at each probe, which limits the imputability for analyses that span multiple array types. Thus far, a consensus set of probes (the intersection encompassing the probes that occur in common on all arrays) has been used to circumvent the problem of differing array-specific sensitivities. This has, however, led to excessive reduction in overall sensitivity of CNV calls as arrays can have an undesirably low overlap of probe sets. To overcome this limitation, we developed MarkerMatch, a proximity-based algorithm that matches probes across different genotyping microarrays to maximize the number of probes considered in the CNV calling algorithm, thereby increasing the resolution and sensitivity while preserving precision. RESULTS: By analyzing CNV calls from 4,906 individuals genotyped across three different arrays (Global Screening Array, Omni2.5 array, and Omni Express Exome array), we show that the MarkerMatch approach improves sensitivity by increasing the density of probes available for CNV calling while maintaining precision or improving it relative to the current practice (e.g., use of consensus probes only). We further demonstrate that MarkerMatch exceeds the output from current practice in terms of F1 score, Fowlkes-Mallows index, and Jaccard index. We also optimize MarkerMatch parameters, D MAX and Method, and find an optimal D MAX setting at 10kb, with no clear optimal candidate based on Method, indicating that parameters for this metric should be determined on a use case basis.

Journal Article↗

Controlled release of a self-emulsifying formulation from a tablet dosage form: stability assessment and optimization of some processing parameters.

The objective of this study was to evaluate the effect of some processing parameters on the release of lipid formulation from a tablet dosage form. A 17-run, face-centered cubic design was employed to evaluate the effect of colloidal silicates (X(1)), magnesium stearate mixing time (X(2)), and compression force (X(3)) on flow, hardness, and dissolution of Coenzyme Q(10) (CoQ(10)) lipid formulation from a tablet dosage form. The optimized formulation was subsequently subjected to a short-term accelerated stability study. All preparations had a flowability index values ranging from 77 to 90. The cumulative percent of CoQ(10) released within 8h (Y(5)) ranged from 40.6% to 90% and was expressed by the following polynomial equation: Y(5)=49.78-16.36X(1)+2.90X(2)-3.11X(3)-0.37X(1)X(2)+1.06X(1)X(3)-1.02X(2)X(3)+11.98X(1)(2)+10.63X(2)(2)-7.10X(3)(2). When stored at 4 degrees C, dissolution rates were retained for up to 3 months. Storage at higher temperatures, however, accelerated lipid release and caused leakage, and loss of hardness. Processing parameters have a profound effect on the release of lipid formulations from their solid carriers. While optimized controlled release formulations could be attained, further considerations should be made to prepare "liquisolids" that are physically stable at higher storage temperatures.

Coenzymes↗

[Integral evaluation of optimal microclimate and human thermoregulation].

The article presents integral parameters of heat comfort determined numerically through parameters of microclimate and human heat state. The authors defined human heat state classes that necessitate differentiated evaluation of heat comfort depending on energy expenditure. The materials also cover regression equations to calculate criterial parameters for optimal heat state.

Body Temperature Regulation↗

Optimal cryogen spray cooling parameters for pulsed laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: In dermatologic laser therapy, cryogen spray cooling (CSC) is a means to protect the epidermis while leaving dermal structures susceptible to thermal damage. The purpose of this study was to determine optimal spurt duration, tau(s), and optimal delay, tau(d), between the cryogen spurt and laser pulse when using CSC in treatment of port wine stain birthmarks. STUDY DESIGN/MATERIALS AND METHODS: A finite difference method is used to compute temperature distributions in human skin in response to CSC. Optimal tau(s) and tau(d) are determined by maximizing the temperature difference between a modeled basal layer and an imaginary target chromophore. RESULTS: The model predicts an optimal tau(s) of 170-300 msec and approximately 400 msec for shallow (150 microm) and deeper (400 microm) targets, respectively. Spraying for longer than the optimal tau(s) does not critically impair cooling selectivity. For a spurt duration of 100 msec, optimal delays are 5-10 msec and 25-70 msec for a shallow and deep basal layer, respectively. CONCLUSION: In the absence of knowledge about the lesion anatomy, using a tau(s) of 100-200 msec and no delay is a good compromise. A delay is justified only when basal layer and target chromophore are relatively deep and the optimal spurt duration cannot be applied, e.g., to avoid frostbite.

Cryotherapy↗

DNAOPT: a computer program to aid optimization of DNA gel electrophoresis and SDS-PAGE.

Several methods and computer programs have been developed for estimating the size of DNA fragments from gel electrophoresis. However, methods are lacking that may facilitate in optimization of gel conditions. In this article, a computer program called DNAOPT is described, which was developed to assist researchers in tuning the gel conditions of gel electrophoresis. The DNAOPT program fits the reciprocal of the migration distance vs. the size of the DNA fragments using the hyperbolic regression method and computes the hyperbolic parameters such as signal, flatness and capacity (optimization parameters). The program further manipulates these parameters obtained by running gel electrophoresis under various conditions (i) to determine the relationship between the gel conditions (temperature, buffer concentration, electric field strength, etc.) and optimization parameters; (ii) to demonstrate gel electrophoresis curves and optimization parameters graphically; and (iii) to represent the optimizing parameters at different gel conditions in tabular form. The above-mentioned program options aid the users in selecting optimum gel conditions by running the gel repeatedly under various conditions in which the agarose concentration, electric field strength, temperature, buffer concentration and so on are varied in a systematic way for each set of gel conditions. Similarly, this program can also be used to optimize gel conditions of sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Algorithms↗

MRI of the neonatal brain: optimization of spin-echo parameters.

OBJECTIVE: Our aim was to measure the relaxation times of the neonatal brain and to use these to derive pulse sequence parameters that enhance the signal-to-noise ratio (SNR) and contrast of MRI scans of the neonatal brain. SUBJECTS AND METHODS: The transverse (T2) and longitudinal (T1) relaxation times were measured for 10 healthy neonates, and the average relaxation times were calculated for both gray and white matter. Simulations using these values were then performed to estimate the optimal pulse sequence parameters. Images were obtained in three neonates using both the optimized and conventional sequence parameters. RESULTS: The measured (mean +/- SD) relaxation times of the neonatal brain at 1.5 T were T1 equals 1712 +/- 235 msec and T2 equals 394 +/- 52 msec in white matter and T1 equals 1144 +/- 245 msec and T2 equals 206 +/- 26 msec in gray matter. The optimized T1-weighted imaging used a turbo spin-echo sequence with an echo-train length of 3 and TR/TE of 850/11 msec and showed increases in both the contrast and the SNR. The optimized T2-weighted sequence used a TE of 270 msec and markedly increased the contrast but at the expense of a reduction in the SNR. CONCLUSION: Parameters of MRI turbo spin-echo sequences for scanning neonates are different from those required for adult studies, and appropriate protocols should be used.

Artifacts↗