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PubMed2007

Plasma protein binding affinity and its relationship to molecular structure: an in-silico analysis.

In-silico plasma protein binding (PPB) models have been generated on human and rat in-house datasets, and on a human dataset sourced from the literature. From the results reported herein, it is apparent that models built on datasets relevant to the chemotypes under investigation in lead optimization programs will perform considerably better in this role than those generated on diverse compounds sourced from the literature. The in-house human and rat partial least-squares regression (PLS) models have cross-validated q2 values of 0.53 and 0.42 on the training sets, respectively. On the independent test and validation sets, they display similar predictive ability, with logK prediction errors of approximately 0.5 log units. This compares to approximately 0.25 log units variability expected for experiment. Given the considerable interspecies PPB differences, the prediction of PPB in one species using measurements in the other is no better than a prediction from an in-silico model generated on that species.

Analysis of Variance↗

PubMed1998

An intriguing controversy over protein structural class prediction.

A recent report by Bahar et al. [(1997), Proteins 29, 172-185] indicates that the coupling effects among different amino acid components as originally formulated by K. C. Chou [(1995), Proteins 21, 319-344] are important for improving the prediction of protein structural classes. These authors have further proposed a compact lattice model to illuminate the physical insight contained in the component-coupled algorithm. However, a completely opposite result was concluded by Eisenhaber et al. [(1996), Proteins 25, 169 179], using a different dataset constructed according to their definition. To address such an intriguing controversy, tests were conducted by various approaches for the datasets from an objective database, the SCOP database [Murzin et al. (1995), J. Mol. Biol. 247, 536-540]. The results obtained by both self-consistency and jackknife tests indicate that the overall rates of correct prediction by the algorithm incorporating the coupling effect among different amino acid components are significantly higher than those by the algorithms without counting such an effect. This is fully consistent with the physical reality that the folding of a protein is the result of a collective interaction among its constituent amino acid residues, and hence the coupling effects of different amino acid components must be incorporated in order to improve the prediction quality. It was found by a revisiting the calculation procedures by Eisenhaber et al. that there was a conceptual mistake in constructing the structural class datasets and a systematic mistake in applying the component-coupled algorithm. These findings are informative for understanding and utilizing the component-coupled algorithm to study the structural classes of proteins.

Algorithms↗

PubMed2004

Longitudinal data analysis. A comparison between generalized estimating equations and random coefficient analysis.

The analysis of data from longitudinal studies requires special techniques, which take into account the fact that the repeated measurements within one individual are correlated. In this paper, the two most commonly used techniques to analyze longitudinal data are compared: generalized estimating equations (GEE) and random coefficient analysis. Both techniques were used to analyze a longitudinal dataset with six measurements on 147 subjects. The purpose of the example was to analyze the relationship between serum cholesterol and four predictor variables, i.e., physical fitness at baseline, body fatness (measured by sum of the thickness of four skinfolds), smoking and gender. The results showed that for a continuous outcome variable, GEE and random coefficient analysis gave comparable results, i.e., GEE-analysis with an exchangeable correlation structure and random coefficient analysis with only a random intercept were the same. There was also no difference between both techniques in the analysis of a dataset with missing data, even when the missing data was highly selective on earlier observed data. For a dichotomous outcome variable, the magnitude of the regression coefficients and standard errors was higher when calculated with random coefficient analysis then when calculated with GEE-analysis. Analysis of a dataset with missing data with a dichotomous outcome variable showed unpredictable results for both GEE and random coefficient analysis. It can be concluded that for a continuous outcome variable, GEE and random coefficient analysis are comparable. Longitudinal data-analysis with dichotomous outcome variables should, however, be interpreted with caution, especially when there are missing data.

Adipose Tissue↗

PubMed2026

Beyond benchmarking: an expert-guided consensus approach to spatially aware clustering.

Spatial omics technologies have revolutionized the study of tissue architecture and cellular heterogeneity by integrating molecular profiles with spatial localization. In spatially resolved transcriptomics, delineating higher-order anatomical structures is critical for understanding how cellular organization affects function. However, the reliability of current benchmarks of spatially aware clustering (SAC) methods is undermined by their narrow focus on Visium and brain tissue datasets and the incorrect interpretation of manual annotation as ground truth. Here we present SACCELERATOR, a community-driven, extensible framework that standardizes data formatting, method integration and metric evaluation, enabling rapid inclusion of new methods and datasets. Our analysis revealed substantial limitations in the generalizability and reproducibility of SAC methods and shows that anatomical labels commonly used as ground truths are often biased, error prone and unsuitable for benchmarking. Rather than ranking methods, we propose a consensus-guided workflow where descriptive spatial metrics highlight high-entropy regions of method disagreement, enabling targeted feedback for tissue experts. Applied to brain and cancer datasets, this approach uncovered biologically meaningful patterns overlooked by individual SAC methods and manual annotations, highlighting the need for iterative, expert-in-the-loop evaluation.

Benchmarking↗

PubMed1999

Readmission for group B streptococci or Escherichia coli infection among full-term, singleton, vaginally delivered neonates after early discharge from Florida hospitals for births from 1992 through 1994.

BACKGROUND: In Florida during the period 1992 through 1994, there was a major drop in the length of stay for full-term, singleton, vaginally delivered newborn babies in the hospital. A major concern on the part of clinicians has been the potential of an increased risk of sepsis (manifesting itself after discharge) associated with earlier newborn discharge from the hospital. We used the Florida hospital discharge dataset to study the frequency of readmission with sepsis after early newborn discharge to home. METHODS: Using the Florida Agency for Health-Care Administration Acute Care Hospital Discharge Dataset, we used a multivariate, probabilistic matching algorithm to merge newborn discharge records for births from 1992 through 1994 with readmission discharge records (including hospital-to-hospital transfers and multiple readmissions) during the first 28 days of life. We used the resulting merged dataset to study bacterial infection diagnoses on newborn and readmission records and to examine relationships between readmission diagnoses and timing of newborn discharge among the 364,528 full-term, singleton, vaginally delivered babies (FTSVDBs) without congenital anomalies from 1992 through 1994 in Florida acute-care hospitals. RESULTS: Overall, 86.3% of all FTSVDBs born in Florida acute-care hospitals were discharged between day of life (DOL) 0 (born and discharged the same day) and DOL 2 (discharged two calendar days after birth). The group B streptococci (GBS) infection code was found on the newborn discharge records of 9.2 per 10,000 FTSVDBs over the 3-year period, 5.9% of which involved hospital-to-hospital transfer of the baby. Escherichia coli infection codes were found on the records of 3.4 per 10,000 FTSVDBs over the 3-year period, 2.3% of which involved hospital-to-hospital transfer of the baby. Of those FTSVDBs discharged to home without infection codes during DOL 1 to 2, 0.8 per 10,000 were readmitted within 7 days (inclusive) with GBS infection, and 2.0 per 10,000 with E. coli infection. When the data for readmitted babies were pooled for 1992 through 1994, the odds ratio for probability of readmission comparing discharges on DOL 1 to DOL 2 for GBS was 2.27 (95% confidence interval, 1.83 to 2.70), and for E. coli 2.16 (95% confidence interval, 1.46 to 2.85). Over this 3-year period, for babies discharged on DOL 1, there was a 115% increase in the rate of readmission for GBS from 1992 through 1994 (p < 0.01) and a 36.5% increase in the rate of readmission for E. coli (p < 0.05). However, among FTSVDBs discharged on DOL 2, the rate of readmission for both GBS and E. coli did not change during the period 1992 through 1994. There were no deaths among FTSVDBs as either newborns, transfers, or readmissions within 7 days of discharge, with either GBS or E. coli infection codes on their discharge record. CONCLUSION: From 1992 through 1994, the increased number of babies discharged early in Florida was temporally associated with an increased rate of readmission during the week after discharge for both GBS and E. coli infection among babies discharged on the calendar day after birth. With an increase in both the number of babies exposed to the risks of early discharge, and an increased rate of these serious infections during the week after discharge from the hospital, the number of these babies grew to exceed, by several fold, the number of babies with inborn errors of metabolism picked up by state screening programs.

Age Factors↗

PubMed2001

Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples.

Molecular genetic studies in attention deficit hyperactivity disorder (ADHD) have focussed on candidate genes within the dopamine system, which is thought to be the main site of action of stimulant drugs, the primary pharmacological treatment of the disorder. Of particular interest are findings with the dopamine transporter gene (DAT1), since stimulant drugs interact directly with the transporter protein. To date, there have been eight published association studies of ADHD with a 480 base-pair allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the gene, five that support an association and three against. We have analysed the same VNTR marker in a dataset of UK Caucasian children and an independent dataset of Turkish Caucasian children with DSM-IV ADHD, using the transmission disequilibrium test (TDT). Results from the UK (chi(2) = 8.97, P = 0.001, OR = 1.95), but not the Turkish sample (chi(2) = 0.93, P = 0.34) support association and linkage between genetic variation at the DAT1 locus and ADHD. When considered alongside evidence from other published reports, there is only modest evidence for the association, consistent with a very small main effect for the 480-bp allele (chi(2) = 3.45, P = 0.06, OR = 1.15), however we find significant evidence of heterogeneity between the combined dataset (chi(2) = 22.64, df = 8, P = 0.004).

3' Untranslated Regions↗

PubMed2000

Age and mortality among white male problem drinkers.

AIMS: This study is designed to determine the relative risk of mortality for white male problem drinkers compared to white males in the general population, and to identify any variation in relative risk of problem drinking in three age groups (18-29, 30-49 and 50-79 years). DESIGN: The research design is prospective, using historical administrative datasets from treatment programs in conjunction with vital records datasets. PARTICIPANTS: Participants include all white men aged 18-79 treated for alcohol-related problems in community mental health substance abuse programs in Vermont during 1991. The treatment group includes 1853 service recipients; the comparison group includes 196,443 adult white male residents of Vermont. MEASUREMENT: Measurement of mortality rates for problem drinkers was based on probabilistic determination of overlap between treatment and vital record datasets. FINDINGS: Mortality for problem drinkers is greater than the general population in all three age groups. The estimated relative risk of mortality in the oldest age group was lower than the other groups, but substantially higher than found in recently published research. The estimated relative risk of mortality in the youngest age group, which has rarely been addressed in previous research, was higher than the relative risk in the middle age group. CONCLUSION: The application of a public health research model in which problem drinkers are compared to the general population has potential to inform public policy. In this case, the public health approach identified an elevated risk of mortality associated with problem drinking among older adults that had not been evident in the previous research.

Adolescent↗

PubMed2000

Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children.

AIMS: This analysis was performed to validate a previously developed population pharmacokinetic model for lamotrigine in order to establish a basis for dosage recommendations for children. METHODS: (a) The importance of the covariates in the final model was confirmed using the model validation dataset. Population and individual (Bayesian estimate) pharmacokinetic parameters were estimated using both the initial model, which included none of the covariates, and the final model. Accuracy and precision of parameter estimation and of concentration prediction were compared between the two models. (b) The performance in predicting the validation concentrations by the final model parameters obtained previously from the model development dataset was assessed. (c) The parameters of the final model were refined using a dataset combining both the development and validation data. RESULTS: Prediction performance of the final pharmacostatistical model was superior to that of the initial model. The results of the validation confirmed that concomitant antiepileptic drugs that increased or reduced lamotrigine clearance in adults had similar effects in children. The validation also verified the linear relationship between weight and clearance. The previously seen small sex effect on clearance was found statistically insignificant. CONCLUSIONS: The current analysis confirmed the previous findings. To achieve the same concentrations, children receiving enzyme-inducing antiepileptic drugs without valproate require higher doses than those receiving valproate; and heavier children require higher doses.

Adolescent↗

PubMed2003

Basal cell carcinoma: a dermatopathological and molecular biological update.

The ideal classification of basal cell carcinoma (BCC) should be able to identify subtypes which correlate with clinical behaviour and treatment requirements. Unfortunately, however, such a classification has yet to be defined. In the interim, the currently most favoured classification is one based predominantly on histological growth pattern. This classification contributes to the useful concept of low- and high-risk histological subtypes of BCC. The latter are characterized by an increased probability of subclinical extension and/or incomplete excision and/or aggressive local invasive behaviour and/or local recurrence. The Royal College of Pathologists has published a minimum dataset for the histopathological reporting of BCC and this has been written to be compatible with the British Association of Dermatologists' management guidelines. Growth patterns to be reported include nodular, superficial, infiltrative/morphoeic and micronodular types, together with differentiation when of severely atypical or malignant squamous type (basosquamous carcinoma). Deep and peripheral excision margins will be reported to be either involved or clear. The latter will include a comment of a clearance of less than 1 mm for close margins and a measured distance in whole millimetres for other excisions. Clinical assessment and histology remain the 'gold standard' for evaluating BCC and cancers in general. However, in the postgenomic era emphasis is changing from the gathering and archiving of genomic data to its analysis and use in guiding clinical practice. In this context, a current goal is to define cancer phenotype in terms of molecular abnormalities and use this as a new gold standard. One way to assess whether this goal is being achieved for BCC is to determine whether our knowledge of its molecular pathology has any relevance to the minimum dataset for histological reporting. Knowledge of BCC molecular pathology has been fuelled by the recent discovery that deregulation of the Hedgehog (Hh) signalling pathway, a key player in embryonic patterning, appears to be fundamental to tumour growth. But despite accrual of a large amount of data concerning Hh pathway molecular alterations in neoplasia, little is known about the functional consequences of these changes in BCC, how they lead to tumour development, or how they relate to non-Hh pathway alterations such as TP53 mutation. Recent work suggests that the cellular localization of beta-catenin gives a degree of credence to the growth pattern classification of BCC. Furthermore, it is possible that beta-catenin may have a pathogenetic role in the invasive behaviour of BCC. This review draws on current evidence to discuss these issues and assess whether they are relevant to the minimum dataset.

Basal Cell Carcinoma↗

PubMed2004

Support vector machines for prediction of peptidyl prolyl cis/trans isomerization.

A new method for peptidyl prolyl cis/trans isomerization prediction based on the theory of support vector machines (SVM) was introduced. The SVM represents a new approach to supervised pattern classification and has been successfully applied to a wide range of pattern recognition problems. In this study, six training datasets consisting of different length local sequence respectively were used. The polynomial kernel functions with different parameter d were chosen. The test for the independent testing dataset and the jackknife test were both carried out. When the local sequence length was 20-residue and the parameter d = 8, the SVM method archived the best performance with the correct rate for the cis and trans forms reaching 70.4 and 69.7% for the independent testing dataset, 76.7 and 76.6% for the jackknife test, respectively. Matthew's correlation coefficients for the jackknife test could reach about 0.5. The results obtained through this study indicated that the SVM method would become a powerful tool for predicting peptidyl prolyl cis/trans isomerization.

Artificial Intelligence↗

PubMed2000

Estimating the prevalence of diagnosed diabetes in a health district of Wales: the importance of using primary and secondary care sources of ascertainment with adjustment for death and migration.

AIMS: To determine diagnosed diabetic prevalence within our district (population 434398) in 1996 using data from two sources. METHODS: A general practice audit comprising data on patients with diabetes from 61 (82%) of 74 general practices was linked to a record linkage-derived patient index in which data from secondary care and other sources underwent a process of probability matching to identify records relating to the same patient and to flag those with diabetes. By linking this dataset to a mortality dataset, patients known to have died before 1996 could be excluded. Age and sex-stratified emigration rates were applied to those identified by the hospital dataset for each year from 1991 onwards. RESULTS: A total of 386988 residents (89.1%) were listed with a general practitioner participating in the audit, of whom 6050 patients were identified as having diabetes in 1996; a prevalence rate of 1.56%. From the hospital-based source, 7639 patients were identified who were alive in 1996, a period prevalence of 1.76%. By combining the two sources, and extrapolating the general practice audit to the population as a whole, a total of 10 530 patients were identified of whom 8735 were confirmed as still resident within South Glamorgan during 1996. This represented a period prevalence of between 2.01% to 2.42%. By applying age and sex-stratified migration rates to the diabetic population identified by hospital sources, a diagnosed diabetic population of 10,004 was identified, a prevalence of 2.3%. CONCLUSIONS: This study demonstrates that to calculate the true prevalence of diagnosed diabetes from health sources, it is necessary to use both primary and secondary care sources.

Adolescent↗

PubMed1997

Sonographic prediction of malignancy in adnexal masses using multivariate logistic regression analysis.

The aim of the study was to assign a probability of malignancy for any patient with an adnexal tumor by the application of multivariate logistic regression analysis to variables recorded at the time of pelvic sonography. Sixty-seven women with known adnexal masses were examined using transvaginal B-mode and color Doppler imaging. For each patient the variables included: (1) age, (2) maximum tumor diameter, (3) tumor volume, (4) unilocularity (presence (0) or absence(1)), (5) papillary projections (presence (1) or absence (0)), (6) random echogenicity (presence (1) or absence (0)), (7) highest peak systolic velocity (PSV), (8) time-averaged maximum velocity (TAMXV), (9) pulsatility index (PI) and (10) resistance index (RI). The TAMXV, PI and RI were those associated with the highest PSV. These ten independent variables and the final histological diagnosis for each patient (the dependent variable) were used for the regression analysis. Approximately 75% of the entire dataset was randomly selected for generating the regression model. The remaining 25% was used as the testing set for cross-validation of the model. In the entire dataset there were 52 women with benign, three with borderline and 12 with invasive ovarian tumors. Regression analysis on the ten variables resulted in the retention of only 'age', 'papillary projection score' and 'TAMXV' as significantly contributing to predicting the presence or absence of malignancy. The probability of malignancy for any patient was given by solving the equation: Probability = 1/(1 + e-z) where e is the base value for natural logarithms and z = (0.1273 x Age) + (0.2794 x TAMXV) + (4.4136 x Papillary projections score) - 14.2046. Cross-validation of the model on the test set of data gave a 100% sensitivity and specificity. However, for the entire dataset the best sensitivity and specificity were 93.3 and 90.4%, respectively, at a cut-off value of 25% probability of malignancy. In conclusion, multivariate logistic regression analysis enables the calculation of probability of malignancy for any patient with a known adnexal mass. The accuracy of this prediction appears to be better than that of morphological or Doppler criteria when the latter are used independently. The value of this model needs to be tested prospectively.

Adult↗

PubMed2005

Genetic association studies in complex disease: disentangling additional predisposing loci from associated neutral loci using a constrained - permutation approach.

In the process of genetically mapping a complex disease, the question may arise whether a certain polymorphism is the only causal variant in a region. A number of methods can answer this question, but unfortunately these methods are optimal for bi-allelic loci only. We wanted to develop a method that is more suited for multi-allelic loci, such as microsatellite markers. We propose the Additional Disease Loci Test (ADLT): the alleles at an additional locus are permuted within the subsample of haplotypes that have identical alleles at the predisposing locus. The hypothesis being tested is, whether the predisposing locus is the sole factor predisposing to the trait that is in LD with the additional locus under study. We applied ADLT to simulated datasets and a published dataset on Type 1 Diabetes, genotyped for microsatellite markers in the HLA-region. The method showed the expected number of false-positive results in the absence of additional loci, but proved to be more powerful than existing methods in the presence of additional disease loci. ADLT was especially superior in datasets with less LD or with multiple predisposing alleles. We conclude that the ADLT can be useful in identifying additional disease loci.

Diabetes Mellitus, Type 1↗

PubMed2002

Quantitative assessment of aortic stenosis by three-dimensional anyplane and three-dimensional volume-rendered echocardiography.

Aortic stenosis is a challenge for three-dimensional (3-D) echocardiographic image resolution. This is the first study evaluating both 3-D anyplane and 3-D volume-rendered echocardiography in the quantification of aortic stenosis. In 31 patients, 3-D echocardiography was performed using a multiplane transesophageal probe. Within the acquired volume dataset, five parallel cross sections were generated through the aortic valve. Subsequently, volume-rendered images of the five cross sections were reconstructed. The smallest orifice areas of both series were compared with the results obtained by two-dimensional (2-D) transesophageal planimetry and those calculated by Doppler continuity equation. No significant differences were found between Doppler (0.76 +/- 0.18 cm(2)), 2-D echocardiography (0.78 +/- 0.24 cm(2)), and 3-D anyplane echocardiography (0.72 +/- 0.29 cm(2)). The orifice area measured smaller (0.54 =/- 0.31 cm(2), P < 0.001) by 3-D volume-rendered echocardiography. Bland-Altmann analysis indicated that for 3-D anyplane echocardiography, the mean difference from Doppler and 2-D echocardiography was - 0.04 +/- 0.24 cm(2) and - 0.06 +/- 0.23 cm(2), respectively. For 3-D volume-rendered echocardiography, the mean difference was -0.23 +/- 0.24 cm(2) and - 0.25 +/- 0.26 cm(2), respectively. In the subgroup with good resolution in the 3-D dataset, close limits of agreement were obtained between 3-D echocardiography and each of the reference methods, while the subgroup with poor resolution showed wide limits of agreement. In conclusion, planimetry of the stenotic aortic orifice by 3-D volume-rendered echocardiography is feasible but tends to underestimate the orifice area. Three-dimensional anyplane echocardiography shows better agreement with the reference methods. Accuracy is influenced strongly by the structural resolution of the stenotic orifice in the 3-D dataset.

Adult↗

PubMed2005

Inferring gene regulatory networks with time delays using a genetic algorithm.

Recently a state-space model with time delays for inferring gene regulatory networks was proposed. It was assumed that each regulation between two internal state variables had multiple time delays. This assumption caused underestimation of the model with many current gene expression datasets. In biological reality, one regulatory relationship may have just a single time delay, and not multiple time delays. This study employs Boolean variables to capture the existence of the time-delayed regulatory relationships in gene regulatory networks in terms of the state-space model. As the solution space of time delayed relationships is too large for an exhaustive search, a genetic algorithm (GA) is proposed to determine the optimal Boolean variables (the optimal time-delayed regulatory relationships). Coupled with the proposed GA, Bayesian information criterion (BIC) and probabilistic principle component analysis (PPCA) are employed to infer gene regulatory networks with time delays. Computational experiments are performed on two real gene expression datasets. The results show that the GA is effective at finding time-delayed regulatory relationships. Moreover, the inferred gene regulatory networks with time delays from the datasets improve the prediction accuracy and possess more of the expected properties of a real network, compared to a gene regulatory network without time delays.

Algorithms↗

PubMed2002

Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore throat. Clinical proof of concept.

UNLABELLED: Acute oro-pharyngeal catarrh is characterised by mild to severe sore throat, such as pain on swallowing, feeling of scratchiness, burning and urge to cough. The present study was conducted to explore whether the test compound is going to show clinical relevance and is a suitable medication for the relief of these symptoms. OBJECTIVE: Description and comparison of the efficacy and tolerability of lozenges containing 20 mg ambroxol hydrochloride (trans-4-[(2-amino-3,5-dibrombenzyl)amino]cyclohexano hydrochloride, CAS 18683-91-5) in relieving acute sore throat, in comparison to placebo. DESIGN: Multi-centre, prospective, placebo-controlled, randomised, double-blind trial involving two days of treatment with up to 6 lozenges containing 20 mg ambroxol hydrochloride per day. SUBJECTS: Two-hundred-eighteen (218) patients were enrolled (97 males, 121 females, average age: 39.4 +/- 15 years, range: 17-81 years); 215 were treated: 107 with 20 mg ambroxol and 108 with placebo; 26 discontinued prematurely (13 in each treatment group). 208 patients constituted the intent-to-treat (ITT) dataset (105 and 103 for treatment with ambroxol and placebo, respectively); 196 patients constituted the perprotocol (PP) dataset (97 and 99, respectively); all treated patients were part of the dataset for safety analysis. TREATMENTS: Double-blind treatment with up to 6 lozenges per day containing 20 mg ambroxol hydrochloride or placebo (a lozenge with a distinct minty flavour). MAIN OUTCOME MEASURES: The time-weighted average pain relief over the first 3 h after the first lozenge as a ratio of the baseline pain intensity of sore throat (SPIDnorm) and the patients' evaluation of efficacy and tolerability at the end of each day of treatment. RESULTS: Both treatments led to a reduction of pain intensity; the mean (+/- SD) SPIDnorm after the 1st lozenge were 0.39 +/- 0.27 and 0.28 +/- 0.25 for 20 mg ambroxol hydrochloride and placebo, respectively; the treatment effect of ambroxol was statistically significantly superior compared to placebo (p: 0.0029; 95% confidence interval estimate of the mean treatment difference for ambroxol minus placebo: 0.04 to 0.18). At the end of each subsequent ambulatory treatment day with up to 6 lozenges per day, a statistically significantly higher proportion of patients scored a higher level of efficacy for the active treatments with ambroxol hydrochloride compared to placebo. The investigational treatments were equally well tolerated. CONCLUSIONS: Sucking lozenges containing 20 mg ambroxol hydrochloride has a beneficial pain relieving effect in patients with acute sore throat, superior to that which otherwise can be achieved by sucking a placebo lozenge. This finding confirms that the preclinical local anaesthetic properties of ambroxol hydrochloride may have beneficial clinical implications.

Administration, Oral↗

PubMed2006

Integration of intraoperative 3D-ultrasound in a commercial navigation system.

STUDY AIMS: The purpose of this study was the integration of three-dimensional ultrasound data into a neuronavigation system, in order to allow a guided intraoperative resection control during neurosurgical interventions. MATERIAL AND METHODS: A system for iterative neuronavigation based on 3D-ultrasound (US) has been developed. The main components of the system are the ultrasound device Voluson 730 (GE Healthcare) with a 5 - 9 MHz probe, the navigation system VectorVision2 (BrainLAB AG) and a standard PC with Windows XP. The ultrasound data are transferred via DICOM from the ultrasound device to an external computer, where they are processed with a C++ program for representation in the neuronavigation coordinate system. The data transfer between the navigation system and the external computer is performed via the VVLink interface from BrainLAB. The feasibility test of the system was performed with an ultrasound phantom RMI 403GS (Gammex-RMI GmbH). RESULTS: The error of homologous points mapping from US datasets to a CT dataset in the neuronavigation system was determined to be 1.9 +/- 0.97 mm. The maximum time required to technically integrate the ultrasound data into the navigation system was 1.5 min. CONCLUSIONS: The developed system allows 3D-ultrasound based navigation to be carried out with a commercially available navigation system. The functionality of this system has been proven by technical tests. Recording and integration of the ultrasound data can be repeated at any time during surgery and can be used to update anatomical data and consequently for resection control. Another application is the intraoperative adaptation of preoperative datasets (MRI or CT) in order to compensate for "brain shift" during neurosurgical operations.

Algorithms↗

PubMed2006

Application of intraoperative 3D ultrasound during navigated tumor resection.

Intraoperative 3D ultrasound (3D-iUS) may enhance the quality of neuronavigation by adding information about brain shift and tumor remnants. The aim of our study was to prove the concept of 3D ultrasound on the basis of technical and human effects. A 3D-ultrasound navigation system consisting of a standard personal computer containing a video grabber card in combination with an optical tracking system (NDI Polaris) and a standard ultrasound device (Siemens Omnia) with a 7.5 MHz probe was used. 3D-iUS datasets were acquired after craniotomy, at different subsequent times of the procedure and overlaid with preoperative MRI. All patients underwent early postoperative 3D MRI including contrast agent within 24 hours after surgery. Acquisition of 3D iUS and the fusion with preoperative MRI was successful in 22/23 patients. The expenditure of time was at least 5 minutes for one intraoperative 3D US dataset. The technique was used three to seven times during surgery. The quality of the ultrasound images was superior in cases of metastasis, meningeoma and angioma over those in malignant glioma. Brain shifting ranged from 2-25 mm depending on localization and kind of tumor. A resection control was possible in 78%. All six neurosurgeons demonstrated a learning curve. The introduction of 3D ultrasound has increased the value of neuronavigation substantially, making it possible to update several times during surgery and minimize the problem of brain shift. Configuration of both the 3D iUS based on a standard ultrasound system and the MR navigation system is time- and especially cost-effective. Faster navigational datasets and more intuitive image-guided surgery enable novel and user-friendly display techniques.

Adult↗