SEARCH · PubMed Health

Results for “Intelligent agents”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources

PubMed2006

Computational Methods for analysis of foci: validation for radiation-induced gamma-H2AX foci in human cells.

Observation and counting of gamma-H2AX foci in untreated cells as well as in cells exposed to cytotoxic agents is a widely used method for documenting the presence of double-strand breaks (DSBs) in the DNA and for analysis of their repair. Similar methods are employed to analyze formation of foci by a variety of proteins implicated in the cellular responses to DNA damage. Despite the wide application of the approach, the manual counting that is frequently used is prone to inaccuracies and investigator-related biases and artifacts. To alleviate this limitation, we developed and describe here personal computer-based algorithms, operating as utilities on available software, that allow an objective and quantitative analysis of foci from confocal images. The algorithms allow focus counting as well as size definition and correct for focus coincidence due to the overlap normally occurring with an increasing number of foci per nucleus. Furthermore, the software allows measurement of the integrated optical density (IOD) of each individual focus, which enables analysis of properties of foci as a function of time. Finally, the information generated by the above analysis algorithms can be employed to evaluate colocalization between foci formed by different proteins. A validation of the software is presented for radiation-induced gamma-H2AX foci in three widely used human cell lines and colocalization tested with RAD51 and gamma-H2AX foci. The computational methods presented extend to images generated by digital cameras.

Artificial Intelligence↗

PubMed2007

Economics of new oncology drug development.

PURPOSE: Review existing studies and provide new results on the development, regulatory, and market aspects of new oncology drug development. METHODS: We utilized data from the US Food and Drug Administration (FDA), company surveys, and publicly available commercial business intelligence databases on new oncology drugs approved in the United States and on investigational oncology drugs to estimate average development and regulatory approval times, clinical approval success rates, first-in-class status, and global market diffusion. RESULTS: We found that approved new oncology drugs to have a disproportionately high share of FDA priority review ratings, of orphan drug designations at approval, and of drugs that were granted inclusion in at least one of the FDA's expedited access programs. US regulatory approval times were shorter, on average, for oncology drugs (0.5 years), but US clinical development times were longer on average (1.5 years). Clinical approval success rates were similar for oncology and other drugs, but proportionately more of the oncology failures reached expensive late-stage clinical testing before being abandoned. In relation to other drugs, new oncology drug approvals were more often first-in-class and diffused more widely across important international markets. CONCLUSION: The market success of oncology drugs has induced a substantial amount of investment in oncology drug development in the last decade or so. However, given the great need for further progress, the extent to which efforts to develop new oncology drugs will grow depends on future public-sector investment in basic research, developments in translational medicine, and regulatory reforms that advance drug-development science.

Antineoplastic Agents↗

PubMed2006

A multiagent evolutionary algorithm for constraint satisfaction problems.

With the intrinsic properties of constraint satisfaction problems (CSPs) in mind, we divide CSPs into two types, namely, permutation CSPs and nonpermutation CSPs. According to their characteristics, several behaviors are designed for agents by making use of the ability of agents to sense and act on the environment. These behaviors are controlled by means of evolution, so that the multiagent evolutionary algorithm for constraint satisfaction problems (MAEA-CSPs) results. To overcome the disadvantages of the general encoding methods, the minimum conflict encoding is also proposed. Theoretical analyzes show that MAEA-CSPs has a linear space complexity and converges to the global optimum. The first part of the experiments uses 250 benchmark binary CSPs and 79 graph coloring problems from the DIMACS challenge to test the performance of MAEA-CSPs for nonpermutation CSPs. MAEA-CSPs is compared with six well-defined algorithms and the effect of the parameters is analyzed systematically. The second part of the experiments uses a classical CSP, n-queen problems, and a more practical case, job-shop scheduling problems (JSPs), to test the performance of MAEA-CSPs for permutation CSPs. The scalability of MAEA-CSPs along n for n-queen problems is studied with great care. The results show that MAEA-CSPs achieves good performance when n increases from 10(4) to 10(7), and has a linear time complexity. Even for 10(7)-queen problems, MAEA-CSPs finds the solutions by only 150 seconds. For JSPs, 59 benchmark problems are used, and good performance is also obtained.

Algorithms↗

PubMed2004

Computerized interpretation of breast MRI: investigation of enhancement-variance dynamics.

The advantages of breast MRI using contrast agent Gd-DTPA in the diagnosis of breast cancer have been well established. The variation of interpretation criteria and absence of interpretation guidelines, however, is a major obstacle for applications of MRI in the routine clinical practice of breast imaging. Our study aims to increase the objectivity and reproducibility of breast MRI interpretation by developing an automated interpretation approach for ultimate use in computer-aided diagnosis. The database in this study contains 121 cases: 77 malignant and 44 benign masses as revealed by biopsy. Images were obtained using a T1-weighted 3D spoiled gradient echo sequence. After the acquisition of the precontrast series, Gd-DTPA contrast agent was injected intravenously by power injection with a dose of 0.2 mmol/kg. Five postcontrast series were then taken with a time interval of 60 s. Each series contained 64 coronal slices with a matrix of 128 x 256 pixels and an in-plane resolution of 1.25 x 1.25 mm2. Slice thickness ranged from 2 to 3 mm depending on breast size. The lesions were delineated by an experienced radiologist as well as independently by computer using an automatic volume-growing algorithm. Fourteen features that were extracted automatically from the lesions could be grouped into three categories based on (I) morphology, (II) enhancement kinetics, and (III) time course of enhancement-variation over the lesion. A stepwise feature selection procedure was employed to select an effective subset of features, which were then combined by linear discriminant analysis (LDA) into a discriminant score, related to the likelihood of malignancy. The classification performances of individual features and the combined discriminant score were evaluated with receiver operating characteristic (ROC) analysis. With the radiologist-delineated lesion contours, stepwise feature selection yielded four features and an Az value of 0.80 for the LDA in leave-one-out cross-validation testing. With the computer-segmented lesion volumes, it yielded six features and an Az value of 0.86 for the LDA in the leave-one-out testing.

Algorithms↗

PubMed2004

One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men.

The results of several recent studies suggest that estrogen and testosterone play an important role in the modulation of mood and cognitive function in women, and preliminary evidence indicates that these hormones may also modulate the levels of beta-amyloid (Abeta), a 4 Kilo Dalton peptide that is likely to be involved in the pathogenesis of Alzheimer's disease. However, the physiological and clinical effects of reversible castration remain unclear and no systematic data is currently available for men. We designed the present study to investigate the effects of reversible chemical castration on the mood and cognitive performance of men treated for prostate cancer, as well as its impact on the levels of plasma Abeta. Forty men with prostate cancer were clinically treated with androgen blockade therapy (flutamide and leuprolide) for 36 weeks and subsequently followed up for another 18 weeks after treatment was discontinued. All subjects received a comprehensive clinical, neuropsychological and biochemical evaluation that included the use of the Beck Depression (BDI) and Anxiety Inventories (BAI), several subtests of the Wechsler Memory and Intelligence Scales (Word Lists-WL, Verbal Paired Associates-VPA, Visual Reproduction-VR and Block Design-BD), and biochemical monitoring of changes in estrogen, testosterone and Abeta levels. Chemical castration was associated with a rapid and marked decline in the levels of testosterone and estradiol, and significant increase in plasma Abeta levels. Treatment was associated with increased BDI (p = 0.004) and BAI scores (p < 0.001), although such changes were of questionable clinical significance (i.e., few subjects had scores > or = 13). CAMCOG (p = 0.046) and WL recall total scores (p < 0.001) improved significantly after androgen blockade treatment was discontinued, but visuospatial abilities, as assessed by BD, was not influenced by the introduction or discontinuation of treatment. There was a significant negative correlation between changes in Abeta levels and subjects' WL total score change between weeks 36 and 54 (r = -0.452, p = 0.012). The results of this naturalistic study indicate that chemical castration is associated with a significant rise in the plasma levels of Abeta and, clinically, with increased depression and anxiety scores. The discontinuation of treatment is associated with better cognitive performance, most noticeably of verbal memory. The performance of subjects on the WL test was negatively correlated with plasma levels of Abeta, but the clinical significance of this finding remains to be determined.

Adult↗

PubMed1988

Cognitive sequelae of tardive dyskinesia.

Severity and location of tardive dyskinesia (TD) symptoms and diagnosis were related to neurocognitive dysfunction as measured by the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale using schizophrenic and affective patients. Diagnosis, severity, and location of TD symptoms were related to cognitive dysfunction. Total symptom severity correlated significantly negatively with 10 of 14 WAIS scores and with four of seven Wechsler Memory scores in the total group with combined schizophrenic and affective patients. The magnitude of the relationships between TD symptom severity and cognitive deficit was strongly affected by the location of the symptoms and the diagnosis of the patient. In the total group, severity of facial TD symptoms correlated significantly negatively with 11 of 14 WAIS scores and with all eight memory scores. TD symptoms in the extremities correlated significantly negatively with only two WAIS and two memory scores, whereas truncal TD symptoms did not correlate significantly negatively with any WAIS or memory scores. Patients diagnosed as schizophrenic showed significant negative correlations of total TD symptom severity with 12 of 14 WAIS scores and with seven of eight Wechsler Memory Scale scores. Patients diagnosed as having affective disorder showed only one significant correlation between total TD symptom severity and WAIS or memory scores. Length of institutionalization has been found to be related to TD symptoms in schizophrenic but not affective patients. In the present study, institutionalization was negatively correlated with severity of facial TD symptoms but not with severity of TD symptoms of the trunk or extremities.(ABSTRACT TRUNCATED AT 250 WORDS)

Antipsychotic Agents↗

PubMed2000

Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population.

Acquired cerebellar lesions in adults have been shown to produce impairments in higher function as exemplified by the cerebellar cognitive affective syndrome. It is not yet known whether similar findings occur in children with acquired cerebellar lesions, and whether developmental factors influence their presentation. In studies to date, survivors of childhood cerebellar tumours who demonstrate long-term deficits in cognitive functions have undergone surgery as well as cranial irradiation or methotrexate treatment. Investigation of the effects of the cerebellar lesion independent of the known deleterious effects of these agents is important for understanding the role of the cerebellum in cognitive and affective development and for informing treatment and rehabilitation strategies. If the cerebellar contribution to cognition and affect is significant, then damage in childhood may influence a wide range of psychological processes, both as an immediate consequence and as these processes fail to develop normally later on. In this study we evaluated neuropsychological data in 19 children who underwent resection of cerebellar tumours but who received neither cranial irradiation nor methotrexate chemotherapy. Impairments were noted in executive function, including planning and sequencing, and in visual-spatial function, expressive language, verbal memory and modulation of affect. These deficits were common and in some cases could be dissociated from motor deficits. Lesions of the vermis in particular were associated with dysregulation of affect. Behavioural deficits were more apparent in older than younger children. These results reveal that clinically relevant neuropsychological changes may occur following cerebellar tumour resection in children. Age at the time of surgery and the site of the cerebellar lesion influence the neurobehavioural outcome. The results of the present study indicate that the cerebellar cognitive affective syndrome is evident in children as well as in adults, and they provide further clinical evidence that the cerebellum is an essential node in the distributed neural circuitry subserving higher-order behaviours.

Adolescent↗

PubMed2003

Change in cognitive function over time in very low-birth-weight infants.

CONTEXT: Preterm very low-birth-weight (VLBW) infants have a high prevalence of neurodevelopmental disability when evaluated during the first several years of life. However, recent experimental data suggest that the developing brain may recover from or compensate for injury. OBJECTIVE: To determine if there is cognitive improvement throughout early and middle childhood following VLBW birth. DESIGN, SETTING, AND PARTICIPANTS: Follow-up data of 296 infants born weighing 600 to 1250 g who participated in a prospective, randomized, placebo-controlled intraventricular hemorrhage (IVH) prevention study performed at 3 northeastern US hospitals between September 1989 and August 1992 and who were serially evaluated at 36, 54, 72, and 96 months of corrected age (CA). MAIN OUTCOME MEASURES: The age-normed Peabody Picture Vocabulary Test-Revised (PPVT-R) score and measures of intelligence. RESULTS: Overall, the median PPVT-R score increased from 88 at 36 months of CA to 99 at 96 months of CA; when data from 36 and 96 months of CA were compared, 45% of children gained 10 points or more and 12.5% showed a 5- to 9-point increase in test scores. Similar findings were noted for full-scale and verbal IQ scores. Multivariate analyses demonstrated that increasing age, residence in a 2-parent household, and higher levels of maternal education were all significantly associated with higher PPVT-R scores (for each, P<.001). In addition, early intervention led to greater increases over time in PPVT-R scores among children whose mothers had less than a high school education compared with those with a high school education level or greater (P =.03 by test for interaction). Although most children showed improvement in PPVT-R scores with increasing CA, children with early-onset IVH and subsequent significant central nervous system injury had the lowest PPVT-R scores initially and the scores declined over time (P =.009 by test for interaction). CONCLUSIONS: The majority of VLBW children had improvement in verbal and IQ test scores over time. Only children with early-onset IVH followed by significant central nervous system injury had low PPVT-R scores that declined over time.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Prediction of tacrolimus blood levels by using the neural network with genetic algorithm in liver transplantation patients.

The neural network (NN) is a technique using an artificial intelligent concept in predicting outcomes by using various input variables. Tacrolimus pharmacokinetics has wide inter- and intra-subject variability and it is often difficult to predict its blood concentrations by dose alone. The objectives of this study are to select the clinically significant variables and to predict the blood concentration of tacrolimus in liver transplant patients by NN combined with genetic algorithm (GA). A total of thirty-two adult liver transplant patients from the University of Iowa Hospitals and Clinics were selected and the patients' data were retrospectively collected. These patient were randomly assigned into two groups: either the training group (n = 10), or testing group (n = 22). A back propagation (BP) NN was developed which contained two hidden layers. A dynamic BP NN based on the time series concept was trained by using the current and previous data sets to predict the trough levels of tacrolimus. The mean of the NN prediction for tacrolimus blood levels was not significantly different from the observed value by a paired t-test comparison (12.05+/-2.67 ng/ml vs. 12.14+/-2.64 ng/ml, p = 0.80). The average difference of the testing sets between the observed and predicted levels was 1.74 ng/ml with a range from 0.08 to 5.26 ng/ml which is clinically acceptable range. Thirty-seven out of 44 data sets (84%) in the testing group were within 3.0 ng/ml of the observed values. This study demonstrated that tacrolimus blood concentrations are precisely predictable in liver transplant patients using patients variables by NN.

Adult↗

PubMed2000

Outcome of children in the indomethacin intraventricular hemorrhage prevention trial.

BACKGROUND: For preterm infants, intraventricular hemorrhage (IVH) may be associated with adverse neurodevelopmental outcome. We have demonstrated that early low-dose indomethacin treatment is associated with a decrease in both the incidence and severity of IVH in very low birth weight preterm infants. In addition, we hypothesized that the early administration of low-dose indomethacin would not be associated with an increase in the incidence of neurodevelopmental handicap at 4.5 years of age in our study children. METHODS: To test this hypothesis, we provided neurodevelopmental follow-up for the 384 very low birth weight survivors of the Multicenter Randomized Indomethacin IVH Prevention Trial. Three hundred thirty-seven children (88%) were evaluated at 54 months' corrected age, and underwent neurodevelopmental examinations, including the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Peabody Picture Vocabulary Test-Revised (PPVT-R), and standard neurologic examinations. RESULTS: Of the 337 study children, 170 had been randomized to early low-dose indomethacin therapy and 167 children had received placebo. Twelve (7%) of the 165 indomethacin children and 11 (7%) of the 158 placebo children who underwent neurologic examinations were found to have cerebral palsy. For the 233 English-monolingual children for whom cognitive outcome data follow, the mean gestational age was significantly younger for the children who received indomethacin than for those who received placebo. In addition, although there were no differences in the WPPSI-R or the PPVT-R scores between the 2 groups, analysis of the WPPSI-R full-scale IQ by function range demonstrated significantly less mental retardation among those children randomized to early low-dose indomethacin (for the indomethacin study children, 9% had an IQ <70, 12% had an IQ of 70-80, and 79% had an IQ >80, compared with the placebo group, for whom 17% had an IQ <70, 18% had an IQ of 70-80, and 65% had an IQ >80). Indomethacin children also experienced significantly less difficulty with vocabulary skills as assessed by the PPVT-R when compared with placebo children. CONCLUSIONS: These data suggest that, for preterm neonates, the early administration of low-dose indomethacin therapy is not associated with adverse neurodevelopmental function at 54 months' corrected age.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Detection of preclinical scrapie from serum by infrared spectroscopy and chemometrics.

In this study we describe a methodology for diagnosing preclinical scrapie infection in hamsters from serum by a combination of Fourier-transform infrared (FT-IR) spectroscopy and chemometrics. Syrian hamsters (Mesocricetus auratus) were orally inoculated with the 263K scrapie agent, or mock-infected, and sera were obtained at 70, 100 and 130 days post infection (dpi) and at the terminal stage of scrapie (160 +/- 10 dpi). The analysis of hamster sera by FT-IR spectroscopy and artificial neural networks (ANN) confirmed results from earlier studies which had indicated the existence of disease-related structural and compositional alterations in the sera of infected donors in the terminal stage of scrapie [Schmitt et al. (2002) Anal Chem 74:3865-3868]. Experimental data from sera of animals in the preclinical stages of scrapie revealed subtle but reproducible spectral variations that permitted the identification of a preclinical scrapie infection at 100 dpi and later, but not at 70 dpi. The IR spectral features that were discriminatory for the preclinical stages differed from those of the terminally ill individuals. In order to reliably identify scrapie-negative as well as preclinical (100 and 130 dpi) and terminal scrapie-positive animals, a hierarchical classification system of independent artificial neural networks (ANN) was established. A "toplevel" ANN was designed which discriminates between animals in the terminal stage of scrapie and preclinical scrapie-positive or control animals. Spectra identified by the "toplevel" ANN as preclinical or controls were then further analyzed by a second classifier, the "sublevel" ANN. Using independent external validation procedures, the toplevel classifier produced an overall classification accuracy of 98%, while the sublevel classifier yielded an accuracy of 93%, indicating that scrapie-specific serum markers were also present for preclinical disease stages. Possible spectral markers responsible for the discrimination capacity of the two different ANNs are discussed.

Animals↗

PubMed2004

Integration of knowledge-based metabolic predictions with liquid chromatography data-dependent tandem mass spectrometry for drug metabolism studies: application to studies on the biotransformation of indinavir.

Despite recent advances in the application of data-dependent liquid chromatography/tandem mass spectrometry (LC/MS/MS) to the identification of drug metabolites in complex biological matrixes, a prior knowledge of the likely routes of biotransformation of the therapeutic agent of interest greatly facilitates the detection and structural characterization of its metabolites. Thus, prediction of the [M + H]+ m/z values of expected metabolites allows for the construction of user-defined MS(n) protocols that frequently reveal the presence of minor drug metabolites, even in the presence of a vast excess of coeluting endogenous constituents. However, this approach suffers from inherent user bias, as a result of which additional "survey scans" (e.g., precursor ion and constant neutral loss scans) are required to ensure detection of as many drug-related components in the sample as possible. In the present study, a novel approach to this problem has been evaluated, in which knowledge-based predictions of metabolic pathways are first derived from a commercial database, the output from which is used to formulate a list-dependent LC/MS(n) data acquisition protocol. Using indinavir as a model drug, a substructure similarity search on the MDL metabolism database with a similarity index of 60% yielded 188 "hits", pointing to the possible operation of two hydrolytic, two N-dealkylation, three N-glucuronidation, one N-methylation, and several aromatic and aliphatic oxidation pathways. Integration of this information with data-dependent LC/MS(n) analysis using an ion trap mass spectrometer led to the identification of 18 metabolites of indinavir following incubation of the drug with human hepatic postmitochondrial preparations. This result was accomplished with only a single LC/MS(n) run, representing significant savings in instrument use and operator time, and afforded an accurate view of the complex in vitro metabolic profile of this drug.

Artificial Intelligence↗

PubMed2006

Automatic identification and classification of characteristic kinetic curves of breast lesions on DCE-MRI.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast is being used increasingly in the detection and diagnosis of breast cancer as a complementary modality to mammography and sonography. Although the potential diagnostic value of kinetic curves in DCE-MRI is established, the method for generating kinetic curves is not standardized. The inherent reason that curve identification is needed is that the uptake of contrast agent in a breast lesion is often heterogeneous, especially in malignant lesions. It is accepted that manual region of interest selection in 4D breast magnetic resonance (MR) images to generate the kinetic curve is a time-consuming process and suffers from significant inter- and intraobserver variability. We investigated and developed a fuzzy c-means (FCM) clustering-based technique for automatically identifying characteristic kinetic curves from breast lesions in DCE-MRI of the breast. Dynamic contrast-enhanced MR images were obtained using a T1-weighted 3D spoiled gradient echo sequence with Gd-DTPA dose of 0.2 mmol/kg and temporal resolution of 69 s. FCM clustering was applied to automatically partition the signal-time curves in a segmented 3D breast lesion into a number of classes (i.e., prototypic curves). The prototypic curve with the highest initial enhancement was selected as the representative characteristic kinetic curve (CKC) of the lesion. Four features were then extracted from each characteristic kinetic curve to depict the maximum contrast enhancement, time to peak, uptake rate, and washout rate of the lesion kinetics. The performance of the kinetic features in the task of distinguishing between benign and malignant lesions was assessed by receiver operating characteristic analysis. With a database of 121 breast lesions (77 malignant and 44 benign cases), the classification performance of the FCM-identified CKCs was found to be better than that from the curves obtained by averaging over the entire lesion and similar to kinetic curves generated from regions drawn within the lesion by a radiologist experienced in breast MRI.

Adult↗

PubMed2005

A double-blinded, placebo-controlled, randomized trial of the neuropsychologic efficacy of cranberry juice in a sample of cognitively intact older adults: pilot study findings.

OBJECTIVES: The aim of this research was to conduct the first known clinical trial of the short-term (i.e., 6 weeks) efficacy of cranberry juice on the neuropsychologic functioning of cognitively intact older adults. PARTICIPANTS: Fifty (50) community-dwelling, cognitively intact volunteers, > or = 60 years old, who reported no history of dementia or significant neurocognitive impairments, participated in this study. DESIGN: A 6-week, double-blind, placebo-controlled, randomized, parallel-group, clinical trial was utilized. Participants were randomly assigned to receive either 32 ounces/day of a beverage containing 27% cranberry juice per volume (n = 25) or placebo (n = 25) for 6 weeks, and administered a series of neuropsychologic tests at both pretreatment baseline and again after 6 weeks of either cranberry juice or placebo treatment to assess treatment-related changes. OUTCOME MEASURES: Efficacy measures consisted of participants' raw scores on the following standardized neuropsychologic tests: Selective Reminding Test, Wechsler Memory Scale-III Faces I and Faces II subtests, Trail Making Test (Parts A and B), Stroop Color and Word Test, and the Wechsler Adult Intelligence Scale- III Digit Symbol-Coding subtest. A subjective Follow-up Self-report Questionnaire was also administered to participants at the conclusion of the end-of-treatment phase assessments. RESULTS: Two-factor, mixed analyses of variance (ANOVA) revealed no significant group (cranberry juice and placebo) by trial (pretreatment baseline and end-of-treatment assessments) interactions across all of the neuropsychologic tests and measures utilized in this study when a Bonferroni corrected alpha level was used to correct for multiple comparisons (i.e., .05/17 group by trial comparisons = .003). Pearson Chi-Square analyses of the groups' self-reported changes over the 6-week treatment phase in their abilities to remember, thinking processes, moods, energy levels, and overall health on the Follow-up Self-report Questionnaire revealed no significant relationships. However, a nonsignificant trend (X2(1) = 2.373, p = 0.123) was noted for participants' self-reported overall abilities to remember from pretreatment baseline to the end-of-treatment assessment. Specifically, more than twice as many participants in the cranberry group (n = 9, 37.5%) rated their overall abilities to remember by treatment end as "improved" as compared to placebo controls (n = 4, 17.4%). CONCLUSIONS: Taken together, no significant interactions were found between the cranberry and placebo groups and their pretreatment baseline and end-of-treatment phase (after 6 weeks) standardized neuropsychologic assessments. A nonsignificant trend was noted, however, on a subjective, self-report questionnaire where twice as many participants in the cranberry group rated their overall abilities to remember by treatment end as "improved" compared to placebo controls.

Aged↗

PubMed1975

Pyritinol hydrochloride and cognitive functions: influence on children in slow learner classes.

Pyritinol-HCl was tested for its impact on the cognitive functions of children with learning disabilities. This study is a contribution to scientific discussion on the complicated methodologic problems in evaluating the clinical efficacy of psychopharmacologic agents. Sixty-seven pupils of slow learner classes between the ages of 11 and 16 years were treated for 6 months with 300 mg pyritinol-HCl/24 hr or placebo under strict double-blind conditions. Drug intake was stimulated and controlled by means of intense psychosocial interaction with the mothers of the subjects. The dependence variables used to test medication effects were 22 parameters of cognitive performance measured in psychologic tests for perceptual and intellectual functions which were administered immediately before and after the medication phase. First the gainscores before and after treatment with pyritinol or placebo within the 22 cognitive parameters were statistically compared. In addition, an analysis of covariance on the corrected results of the second test (treating the results of first testing as covariates) and a two group discriminant analysis for overall differences were performed. None of the 22 parameters showed statistically significant treatment effects with respect to average performance (t (pyritinol - placebo) = 1.96 to 1.31), neither could the two groups be separated by discriminant analysis (Hotelling's T2 = 35.4, df - 22 and 43, P = 0.465). With respect to a variability of gainscores, however, in four parameters there was a significantly higher variance in the pyritinol group (F = 1.85-2.33, P less than 0.05, less than 0.02, respectively). This fact may signify that pyritinol-HCl had different effects on different subjects. By means of prognostic stratification we therefore attempted to define objective criteria for a selection of subjects with probable positive treatment effects. None of the 15 tested criteria, such as body weight, age, perceptual handicaps, or reduced short term memory, IQ range, proved, however, to be critical for a prognosis of pyritinol effects within the present test population.

Adolescent↗

PubMed2005

Polymorphisms of genes controlling homocysteine levels and IQ score following the treatment for childhood ALL.

INTRODUCTION: One of the causes of long-term morbidity associated with the treatment of acute lymphoblastic leukemia (ALL) is late neurotoxicity manifesting as impairment of higher cognitive functions. Cranial radiation therapy (CRT) and chemotherapeutic agents, particularly methotrexate (MTX), are often suggested to be major contributing factors for its development. Homocysteinemia that arises as a result of MTX-induced folate depletion was proposed to play a role in MTX-related neurotoxicity. Several enzymes are essential to maintain the homocysteine levels. Their different functional forms, associated with common genetic polymorphisms, may modulate homocysteine levels and thereby influence MTX-associated neurotoxicity. OBJECTIVES: To test this hypothesis we assessed whether the variants of the methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), cystathionine beta-synthase (CBS) and endothelial nitric acid synthase (eNOS, NOS3) genes, acting either independently or in conjunction with other risk factors, influenced the cognitive functioning in ALL patients. The influence of the genes was measured by estimating the change in IQ scores over a period of 4 years post ALL diagnosis. RESULTS: Two variants, the CBS 844ins68 polymorphism and NOS3 894T homozygosity, were associated with a change in IQ scores (p = 0.01 and 0.007, respectively). A multivariate model obtained through step-wise selection pointed to the importance of the NOS3 894TT genotype only. This effect appears to be dependent on CRT; IQ decline was apparent among individuals with the 894TT genotype who received radiation therapy (p = 0.03). Furthermore, additional factors affecting IQ were identified, including the treatment administered (i.e., CRT; p = 0.02) and a younger age at diagnosis (p = 0.003), and the modifying effect of the treatment protocols was also noted (p = 0.04). CONCLUSION: The results suggest that NOS3 genotyping might identify individuals that are susceptible to intellectual impairment following ALL treatment.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed1977

Physiological principles of therapy in head and neck cutaneous wounds.

It is essential that surgeons treating soft tissue wounds about the head and neck have a basic understanding of skin anatomy and physiology. The quality as well as the rate of healing is usually dependent on the type and extent of the original injury. Having a practical working knowledge of the pathophysiology of the various types of head and neck soft tissue injuries allows an intelligent choice of the most appropriate approach to a particular wound. The best functional and cosmetic results routinely are achieved by the wound's undergoing primary healing. Skin tapes and various sutures each exhibit certain benefits and disadvantages in primary closure of wounds. Skin tapes cause less inflammatory reaction but fail to close the subepithelial wound spaces. The inflammatory reaction and subsequent scarring caused by the various sutures depends upon the size of the suture needle, the diameter of the suture material and whether it is a monofilament or a woven suture. The essential nutrition of the wound must be maintained with the body providing adequate amounts of carbohydrates, proteins, trace elements and vitamins. The lack of adequate wound tissue perfusion by a normal or reversed oxygen gradient will lead to tissue necrosis and infection. The size of the inoculum of micro-organisms, the virulence of the organisms and host antimicrobial defense mechanisms determine if an infection will develop. The pharmacological action of each antibiotic must be understood in order to choose the proper antibiotic, its route of administration and to avoid unwanted side effects. Crushing tissue injuries, high velocity projectile tissue injuries and major burns of tissue may require several days to exhibit the true scope of the original injury. Most of these injuries must be treated by the open delayed method of wound treatment until the proper tissue conditions exist for healing. The proper timing and correct choice of autografts and tissue flaps from the surgeon's personal experience, study and conferring with other qualified surgeons. Upon gaining insight into the cellular and humoral antimicrobial defense system, the surgeon is able to provide the best conditions to allow these systems to function properly. Studies in the ultrastructures of skin along with the recently developed microbioassay techniques will allow a closer monitoring during the process of wound healing that will provide the basis for future techniques in the beneficial manipulation of wound healing.

Anti-Bacterial Agents↗

PubMed2003

CBP 1011: Colirest, Hematrol.

InKine Pharmaceutical Co. is developing an oral compound, CBP 1011, for the treatment of immune thrombocytopenic purpura (ITP) [Hematrol] and for the treatment of inflammatory bowel disorders, ulcerative colitis and Crohn's disease (Colirest). This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. CBP 1011 or medroxyprogesterone, is a progesterone agonist and inhibits pro-inflammatory mediators such as interleukin-6 and tumour necrosis factor (TNF). CBP 1011 was originally developed by CorBec Pharmaceuticals, which in 1997 was aquired by Panax and then intergrated into InKine Pharmaceuticals. According to a company spokesperson, InKline is pursuing outlicensing opportunities for Hematrol since the company's current commercial focus is on gastrointestinal products. In June 2000, InKine announced the completion of a study comparing the bioavailability of a commercially viable tablet formulation of CBP 1011 to the original capsule formulation that is currently being used in the company's phase III studies in patients with idiopathic thrombocytopenic purpura. Preliminary results from this study indicate that the bioavailability of the tablet formulation does not differ significantly from that of the capsule formulation. The trial enrolled ITP patients (i) who are HIV positive, (ii) who are chronic ITP sufferers despite having had a splenectomy, (iii) who are older, or (iv) who have less severe thrombocytopenia. In preclinical trials, CBP 1011 was shown to decrease lymphocyte infiltration into the bowel compared with the control. Studies also show that it possibly offers safety benefits over steroid therapies. In June 2001, InKine commenced enrolment for a pivotal phase III trial in the treatment of Crohn's disease. This randomised, double-blind trial will enrol approximately 250 patients and will compare two doses of CBP 1011 (400 and 1000mg) with placebo. In April 2003, the US Patent and Trademark Office granted InKine Pharmaceutical a 'Notice of Allowance' for the 'Method of Treating Inflammatory Conditions with Progesterone or Progesterone Analogs'. This patent for medroxyprogesterone (Colirest) provides InKine patent protection for the use of Colirest in treating patients with Crohn's disease, ulcerative colitis, proctitis, microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, drug-induced oesophagitis, coeliac disease, recurrent polyps and haemorrhoids. The patent protection also covers Colirest in a variety of delivery forms such as tablet, enema, suppository, foam, gel, ointment and suspension.

Administration, Oral↗