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PubMedDate not supplied

Chemotherapy for patients with recurrent or refractory neuroblastoma: a POG Phase II study.

PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of three different salvage regimens (Rx) in children with recurrent or refractory neuroblastoma. PATIENTS AND METHODS: Forty-six children with recurrent or refractory neuroblastoma received treatment according to one of three regimens: Rx 1 (five patients), high-dose cisplatin (HDP) (200 mg/m2) with concurrent sodium thiosulfate (STS) (9.9 g/m2) as a nephroprotectant and etoposide (VP-16) (200 mg/m2/day for 3 days); Rx 2 (22 patients), high-dose carboplatin (HD-CBDCA) (500 mg/m2/day for 2 days) and VP-16 (100 mg/m2/day for 3 days); Rx 3 (19 patients), ifosfamide (1.5 g/m2/day for 3 days) followed by CBDCA (400 mg/m2) on day 4. Chemotherapy was administered every 3-4 weeks. Responses were assessed following four courses with or without surgery. Patients achieving less than a partial response (PR) on their primary treatment were crossed over to the next regimen (i.e., Rx 1 --> Rx 2 <--> Rx 3). RESULTS: Rx 1 was ended early owing to grade 4 nephrotoxicity in two patients following their first course. Ten of 22 evaluated patients (45%) primarily (n = 19) or secondarily (n = 3) treated by Rx 2 responded [five complete response (CR) and five PRs]. Nine of the 23 evaluated patients (39%) on Rx 3 as primary (n = 18) or secondary (n = 5) treatment responded (one CR and eight PRs). Grades 3-4 neutropenia and thrombocytopenia occurred after 80% and 50% of courses administered on Rx 2 and Rx 3, respectively. Central venous line infections were the most commonly documented infections on these regimens. CONCLUSIONS: Rx 2 and Rx 3 are active combinations in patients with recurrent or refractory neuroblastoma and are associated with manageable toxicity. HDP administered as a short i.v. infusion with concurrent STS infusion cannot be safely given to children with neuroblastoma pretreated with cisplatin.

Adolescent↗
PubMedDate not supplied

Topotecan in pediatric patients with recurrent and progressive solid tumors: a Pediatric Oncology Group phase II study.

PURPOSE: A phase II study was designed to determine the efficacy of topotecan, an inhibitor of topoisomerase I, in the treatment of patients with progressive or recurrent pediatric extracranial solid tumors (STs). PATIENTS AND METHODS: Patients younger than 21 years at the time of initial diagnosis with refractory STs were treated with 2 mg/m2 topotecan given by 30-minute infusions for 5 days repeated every 3 weeks. Granulocyte colony stimulating factor (G-CSF) was added to the regimen only after occurrence of severe neutropenia or therapy delay due to sustained neutropenia. RESULTS: One hundred forty-one patients were treated with 539 courses of topotecan. Responses were seen in 34 patients (3 had complete responses [CRs], 2 had partial responses [PRs], and 24 had minor responses [MRs] or stable disease [SD]). The number of administered courses in patients with SD varied between 5 and 24, with a median of 10. The median time on the study for patients with SD was approximately 8.5 months. In patients without bone marrow involvement, the most frequent toxicity was myelosuppression: hemoglobin < 8 g/dl in 83 of 341 courses, absolute granulocyte count < 1,000/microl in 221 of 341 courses, and platelet count < 50,000/microl in 162 of 341 courses. Nausea and vomiting were infrequent; many patients were pretreated with ondansetron or granisetron. A recurrent rash developed in 16 patients and was usually well controlled with diphenhydramine and hydrocortisone. G-CSF was administered in 203 of 539 courses because of neutropenia. Therapy was delayed over 1 week in 33 instances. CONCLUSION: In previously treated patients, topotecan produced CRs and PRs in patients with neuroblastoma, Ewing's tumor, and retinoblastoma. In hepatoblastoma, rhabdomyosarcoma, and a few rare tumors, long-lasting MRs and SDs with excellent symptom control were seen. The toxicity of topotecan, predominantly myelosuppression, was tolerable.

Adolescent↗
PubMedDate not supplied

Reliability and validity of visual assessments of gait using a modified physician rating scale for crouch and foot contact.

This study evaluates the visual assessment of gait using portions of the Physicians' Rating Scale (PRS). Thirty children with pathologic gait were evaluated "live" and using full- and slow-speed video. Interobserver reliability (weighted kappa) was 0.57 to 0.74 for foot contact, 0.69 to 0.71 for crouch, 0.30 to 0.40 for hip flexion, 0.57 to 0.65 for knee flexion, and 0.42 to 0.52 for dorsiflexion in stance. Intraobserver reliability (comparing the three conditions) was 0.50 to 0.78 for foot contact, 0.71 to 0.80 for crouch, 0.26 to 0.44 for hip flexion, 0.60 to 0.86 for knee flexion, and 0.39 to 0.61 for dorsiflexion. Observers were correct only 12% to 32% of the time when reporting less than 0 degrees of dorsiflexion and 0% to 29% of the time when reporting more than 20 degrees of hip flexion due to overestimation of hip flexion and underestimation of ankle dorsiflexion. These errors could lead some clinicians to presume the presence of contractures that do not actually exist. Visual assessment using the PRS does not appear to accurately measure what it is most commonly used to assess: ankle position in stance.

Adolescent↗
PubMed2005

Parry-Romberg syndrome.

The authors report an unusual case of Parry-Romberg syndrome (PRS). Magnetic resonance imaging and computed tomography scan of the craniofacial region and surgical correction of enophthalmos were performed. Results after the operative intervention included persistent palpebral edema and ecchymosis and transient choroid vasculitis of the right eye, highlighted with echography and fluorescein angiography. The fundus oculi examination showed retinal choroid folds. Immunological test results were weakly positive. The authors conclude enophthalmos, associated with right side hemi atrophy, and the transient choroids vasculitis support the diagnosis of PRS. Furthermore, it is suggested the case had an autoimmune etiology, rather than a hemi facial asymmetry caused by a facial trauma that occurred in puberty.

Adult↗
PubMed2026

Integrative genomic and transcriptomic analysis of hypertension in a Taiwanese population.

OBJECTIVES: Hypertension is highly prevalent in Asian populations and represents a major cardiovascular risk factor. However, most genome-wide association studies (GWASs) and transcriptome-wide association studies (TWASs) have focused primarily on Caucasian cohorts. This study aimed to identify genetic loci and gene expression signatures associated with hypertension in an Asian population. METHODS: We analyzed 10 739 hypertensive patients and 49 668 controls from the Taiwan Biobank, testing 4 512 191 genome-wide single nucleotide polymorphisms (SNPs). Integrated GWAS, TWAS, and expression quantitative trait locus (eQTL) analyses were conducted to characterize genetic risk. Additionally, a polygenic risk score (PRS) was constructed using a split-sample design to evaluate genetic risk stratification. RESULTS: We identified 14 loci significantly associated with hypertension, including a novel locus at 5p13.1. eQTL analysis linked this locus to DAB2 expression in whole blood. TWAS detected 55 hypertension-associated genes, with 20 (36%) overlapping GWAS loci. Several novel genes outside GWAS loci, including FBXL15, KCNIP2, and CRIP3, were highly significant and implicated in vascular biology and hypertension mechanisms. PRS analysis effectively differentiated hypertension risk, with individuals in the top 10% showing a > 3.5-fold increased risk compared to the bottom 10%. CONCLUSIONS: Our findings provide new insights into the genetic and transcriptomic landscape of hypertension in Asians. The identification of novel loci and genes advances understanding of disease biology and may guide precision medicine approaches for risk prediction and therapeutic development.

Female↗
PubMed1988

Mutants of Bacillus subtilis defective in protein export.

We have isolated a set of strains with mutations (designated prs) that decrease secretion of alpha-amylase and have a pleiotropic effect on secretion of other exoproteins. The seven mutants were selected in a strain of Bacillus subtilis which overproduces alpha-amylase due to the presence of an alpha-amylase gene on a multicopy plasmid. The mutations were mapped to four different chromosomal loci. The phenotype of the mutants, especially their pleiotropic effects and the accumulation of alpha-amylase precursor, indicated that they have defects in the mechanism of protein export. Double mutants with certain pairwise combinations of mutations in different loci had additive effects on secretion, suggesting that these prs genes encode different components of the secretion pathway.

Bacillus subtilis↗
PubMed1996

Molecular analysis of an operon in Bacillus subtilis encoding a novel ABC transporter with a role in exoprotein production, sporulation and competence.

The levels of exoamylase and other exoenzymes of Bacillus subtilis are pleiotropically decreased by the ecs-26 (prs-26) and ecs-13 (prs-13) mutations. These mutations also cause a competence- and sporulation-deficient phenotype. In the present work, the ecs locus, which has been defined by the ecs-26 and ecs-13 mutations, was cloned and sequenced. Sequence analysis revealed a putative operon of three ORFs (ecsA, ecsB and ecsC). ecsA can encode a putative polypeptide of 248 amino acid residues containing an ATP-binding site. The polypeptide shows about 30% sequence similarity with the ATP-binding components of numerous membrane transporters of the ABC-type (ATP-binding cassette transporters or traffic ATPases). The ecs-26 mutation was found to result from a transition of one base pair chaning the glycine164 of EcsA to a glutamic acid residue in the vicinity of the putative ATP-binding pocket. ecsB was predicted to encode a hydrophobic protein with six membrane-spanning helices in a pattern found in other hydrophobic components of ABC transporters. The properties deduced for the ecsA and ecsB gene products are consistent with the interpretation that ecs encodes a novel ABC-type membrane transporter of B. subtilis. The third ORF, ecsC, can encode a putative polypeptide of 237 amino acid residues. The polypeptide does not resemble components of ABC transporters.

ATP-Binding Cassette Transporters↗
PubMed2004

Effect of interactions on the nutrient status of a tropical soil treated with green manures and inorganic phosphate fertilizers.

Integrated nutrient management systems using plant residues and inorganic P fertilizers have high potential for increasing crop production and ensuring sustainability in the tropics, but their adoption requires in-depth understanding of nutrient dynamics in such systems. This was examined in a highly weathered tropical soil treated with green manures (GMs) and P fertilizers in two experiments conducted in the laboratory and glasshouse. The treatments were factorial combinations of the GMs (Calopogonium caeruleum, Gliricidia sepium, and Imperata cylindrica) and P fertilizers (phosphate rocks [PRs] from North Carolina, China, and Algeria, and triple superphosphate) replicated thrice. Olsen P, mineral N, pH, and exchangeable K, Ca, and Mg were monitored in a laboratory incubation study for 16 months. The change in soil P fractions and available P was also determined at the end of the study. Phosphorus available from the amendments was quantified at monthly intervals for 5 months by 33P-32P double isotopic labeling in the glasshouse using Setaria sphacelata as test crop. The GMs were labeled with 33P to determine their contribution to P taken up by Setaria, while that from the P fertilizers was indirectly measured by labeling the soil with 32P. The P fertilizers hardly changed Olsen P and exchangeable cations during 16 months of incubation. The legume GMs and legume GM+P did not change Olsen P, lowered exchangeable Ca, and increased exchangeable K about threefold (4.5 cmol[+]kg(-1) soil) in the first 4 months, even as large amounts of NH4-N accumulated (approximately 1000 mg kg soil(-1)) and soil pH increased to more than 6.5. Afterwards, Olsen P and exchangeable Ca and Mg increased (threefold) as NH4+-N and soil pH declined. The legume GMs also augmented reversibly sorbed P in Al-P and Fe-P fractions resulting in high residual effect in the soil, while fertilizer-P was irreversibly retained. The GMs increased PR-P utilization by 40 to over 80%, mobilized soil P, and markedly enhanced uptake of N, K, Ca, and Mg. Thus GMs+PRs is an appropriate combination for correcting nutrient deficiencies in tropical soils.

Agriculture↗
PubMed2025

Prematurity and Genetic Liability for Autism Spectrum Disorder.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by diverse presentations and a strong genetic component. Environmental factors, such as prematurity, have also been linked to increased liability for ASD, though the interaction between genetic predisposition and prematurity remains unclear. This study aims to investigate the impact of genetic liability and preterm birth on ASD conditions. METHODS: We analyzed phenotype and genetic data from two large ASD cohorts, the Simons Foundation Powering Autism Research for Knowledge (SPARK) and Simons Simplex Collection (SSC), encompassing 78,559 individuals for phenotype analysis, 12,519 individuals with genome sequencing data, and 8,104 individuals with exome sequencing data. Statistical significance of differences in clinical measures was evaluated between individuals with different ASD and preterm status. We assessed the rare variants burden using generalized estimating equations (GEE) models and polygenic load using ASD-associated polygenic risk score (PRS). Furthermore, we developed a machine learning model to predict ASD in preterm children using phenotype and genetic features available at birth. RESULTS: Individuals with both preterm birth and ASD exhibit more severe phenotypic outcomes despite similar levels of genetic liability for ASD across the term and preterm groups. Notably, preterm ASD individuals showed an elevated rate of de novo variants identified in exome sequencing (GEE model, p=0.005) in comparison to the non-ASD preterm group. Additionally, a GEE model showed that a higher ASD PRS, preterm birth, and male sex were positively associated with a higher predicted probability for ASD, reaching a probability close to 90% in SPARK. Lastly, we developed a machine learning model using phenotype and genetic features available at birth with limited predictive power (AUROC = 0.65). CONCLUSIONS: Preterm birth may exacerbate the multimorbidity present in ASD, which was not due to the ASD genetic factors. However, increased genetic factors may elevate the likelihood of a preterm child being diagnosed with ASD. Additionally, a polygenic load of ASD-associated variants had an additive role with preterm birth in the predicted probability for ASD, especially for boys. We propose that incorporating genetic assessment into neonatal care could benefit early ASD identification and intervention for preterm infants.

Autism Spectrum Disorder↗
PubMed2005

On using prototype reduction schemes and classifier fusion strategies to optimize kernel-based nonlinear subspace methods.

In Kernel-based Nonlinear Subspace (KNS) methods, the length of the projections onto the principal component directions in the feature space, is computed using a kernel matrix, K, whose dimension is equivalent to the number of sample data points. Clearly this is problematic, especially, for large data sets. In this paper, we solve this problem by subdividing the data into smaller subsets, and utilizing a Prototype Reduction Scheme (PRS) as a preprocessing module, to yield more refined representative prototypes. Thereafter, a Classifier Fusion Strategy (CFS) is invoked as a postprocessing module, to combine the individual KNS classification results to derive a consensus decision. Essentially, the PRS is used to yield computational advantage, and the CFS, in turn, is used to compensate for the decreased efficiency caused by the data set division. Our experimental results demonstrate that the proposed mechanism significantly reduces the prototype extraction time as well as the computation time without sacrificing the classification accuracy. The results especially demonstrate a significant computational advantage for large data sets within a parallel processing philosophy.

Algorithms↗
PubMed2005

A method of "weak resonance" for quality factor and coupling coefficient measurement in piezoelectrics.

In the absolute-immittance spectrum of a piezoelectric resonator (PR), if the relative resonance-antiresonance frequency interval of a high-intensity resonance is basically determined by the coefficient of electromechanical coupling (CEMC), the relative resonance-antiresonance frequency interval of a low-intensity resonance with the resonance-antiresonance attenuation less than 15 dB, regardless of the reason, is determined by the quality factor Q of the resonance, and its intensity is proportional to the CEMC. The technique for the quality factor and CEMC determination based on the "weak resonance" (WR) concept has been formulated and then applied to low-Q and/or low-CEMC piezoelectrics, including the initial stage of piezoceramics polarization, and to piezotransducers under electrical or mechanical loading with maximum efficiency. The WR method allows one to determine the quality factor on PRs under specific conditions, such as arbitrary PR shape resulting to a broken frequency spectrum; PRs with an extremely large or extremely low electrical capacitance; at high-order PR harmonics; electrodeless piezoelements under mechanically contactless electrical excitation; determining the local thickness-mode material quality factor value and its distribution along the surface of a thin electrodeless piezoplate--all this where the traditional methods show a poor performance or do not work at all.

Ceramics↗
PubMedDate not supplied

Subdural hygroma in a patient with Parry-Romberg syndrome.

Parry-Romberg syndrome (PRS) is a poorly understood disorder characterized by progressive hemifacial atrophy. A number of neurologic associations have been reported. We describe a rare association of seizures, PRS, and subdural hygroma. To the best of our knowledge, this association has not been reported in the literature.

Child, Preschool↗
PubMedDate not supplied

Phase II study of weekly paclitaxel for docetaxel-resistant metastatic breast cancer in Japan.

The purpose of the study was to evaluate the efficacy of weekly paclitaxel (PTX) against metastatic breast cancer (MBC) that was resistant to docetaxel (DTX) given every 3 weeks. A multicenter phase II study was performed. Women with MBC resistant to DTX were eligible for enrollment. DTX resistance was defined as no tumor response to DTX and stable disease, partial response, or complete response to DTX preceding disease progression. PTX 80 mg/m(2) was administered over 1 hour once a week for 3 weeks per 4-week cycle. Among 47 enrolled patients, 46 patients were assessable for response and toxicity. The overall objective response rate (complete responses [CRs] and partial responses [PRs]) was 17.4% and overall clinical benefit rate (CRs, PRs, and stable disease >or=24 weeks) was 26.1%. The median time to progression was 11 weeks. There were a few severe hematologic toxicities related to the therapy, with grade 4 neutropenia (4.3%) and thrombocytopenia (2.2%). Grade 3 anaphylaxis and grade 3 neuropathy were observed in one patient (2.2%) each. The median delivered dose intensity was 77.6 mg/m(2)/week, 97.1% of the planned dose intensity. Weekly PTX has activity in patients with MBC resistant to DTX every 3 weeks.

Adult↗
PubMed2004

Different SAR86 subgroups harbour divergent proteorhodopsins.

Proteorhodopsins (PRs), bacterial photoactive proton pumps, were originally detected in the uncultured marine gamma-proteobacterial SAR86 group. PRs are now known to occur in both the gamma and alpha marine proteobacterial lineages. Recent environmental shotgun sequence analysis in the Sargasso Sea has added yet more diversity, and a potentially broader taxonomic distribution, to the PR family. Much remains to be learned, however, about within-taxon PR variability and the broader organismal distribution of different PR types. We report here genomic analyses of large genome fragments from different subgroups of the SAR86 lineage, recovered from naturally occurring bacterioplankton populations in coastal Red Sea and open ocean Pacific waters. Sequence comparisons were performed on large bacterial artificial chromosomes (BACs) bearing both rRNA and PR genes, derived from different SAR86 subgroups. Our analyses indicated the presence of different PR sequence types within the same SAR86 rRNA subgroup. The data suggested that the distribution of particular PR types does not necessarily parallel the phylogenetic relationship inferred from highly conserved genes such as rRNA. Further analyses of the genomic regions flanking PR also revealed a potential pathway for the biosynthesis of retinal, the PR chromophore that is required to generate the functionally active photoprotein. Finally, comparison of our results with recently reported Sargasso Sea environmental shotgun sequence assemblies demonstrated the utility of BAC clones for interpreting environmental shotgun sequence data, much of which is represented in short contigs that have an overall low depth of coverage.

Amino Acid Sequence↗
PubMed2005

Parry-Romberg syndrome in association with anti-dsDNA antibodies: a case report.

Parry-Romberg syndrome (PRS) is a rare and puzzling disorder that is characterized by progressive hemifacial atrophy. It involves mainly some or all tissues of one side of the face. A case of 21-year-old Caucasian man with hemifacial atrophy in the right facial region is reported. Serological studies with anti-single-stranded DNA (anti-ssDNA), anti-double-stranded DNA (anti-dsDNA), anticentromere (ACA) and antinuclear (ANA) antibodies were done. Anti-dsDNA antibodies was found positive, but the others were negative. Rheumatoid factor (RF) was also negative. Since PRS is rare and its association with anti-dsDNA antibodies was not reported before, this case appears to be the first report.

Adult↗
PubMed2004

The reliability and validity of tasks measuring perception of rapid sequences in children with dyslexia.

BACKGROUND: Claims that children with reading and oral language deficits have impaired perception of sequential sounds are usually based on psychophysical measures of auditory temporal processing (ATP) designed to characterise group performance. If we are to use these measures (e.g., the Tallal, 1980, Repetition Test) as the basis for intervention in language and literacy deficits, we need to demonstrate that they can effectively quantify individual differences. Therefore, questions of standardisation, reliability and construct validity can no longer be ignored. METHOD: We explored these issues in three studies: (i) 52 Dyslexics and Good Readers aged 8 to 11 years performed a task requiring perception of rapid sequences (PRS) based on the Tallal Repetition Test; (ii) a subgroup of the initial sample was retested on the task three to four months later, and after extended practice; (iii) a further subgroup then completed a rate of auditory processing task using a backward recognition masking paradigm. RESULTS: With a standardised methodology, we were able to replicate previous results with the PRS task, and demonstrate moderate reliability of measurement across time and practice. However, there were large effects of exposure and practice, and the task did not seem useful for identifying absolute and continuing deficits in given individuals. CONCLUSIONS: Our results call into question the use of this type of task as an individual measure of ATP. Neither is it certain that it is capturing what is currently understood as ATP.

Auditory Perception↗
PubMed1983

Studies on the effect of mode of delivery on the renin-angiotensin system in mother and fetus at term.

Plasma renin substrate (PRS) and renin (PRC) concentrations were measured in the paired umbilical artery and vein blood of 54 babies and in the venous blood of 23 of their mothers at vaginal delivery. Similar samples were collected from 31 babies and their mothers at elective caesarean section. Fetal renin concentrations in both umbilical artery and vein blood were markedly increased at vaginal delivery compared with values at operative delivery. Renin substrate concentration was correlated with the length of second stage of labour. Umbilical vein PRC and PRS were greater than corresponding umbilical artery values at vaginal, but not at operative delivery, suggesting that some factor associated with delivery might stimulate the placenta to produce renin and renin substrate during vaginal delivery. Maternal and umbilical concentrations of both renin and renin substrate were unrelated, supporting the view that the maternal and fetal compartments are independent. It is suggested that hyperactivity of the renin-angiotensin system may be an integral part of the marked changes in cardiovascular homeostasis which occur at birth.

Adult↗
PubMed1995

Development of the perceptions of racism scale.

Racism may be a factor in low-birth-weight (LBW) and preterm delivery in African American childbearing women. Because no satisfactory measure of racism existed, the Perception of Racism Scale (PRS) was developed. The PRS was pilot tested on 109 participants from churches and community organizations. The scale was then used in a study of 136 childbearing women to investigate LBW and preterm delivery. Twenty items rated on a 4-point Likert-type scale were scored with 1 as the lowest and 4 as the highest perception of racism. Alpha reliabilities were .88 for the pilot and .91 for the study. Content validity was strengthened by expert panel critique. Reliability, content validity, and construct validity were demonstrated and no undue participant burden was observed. The scale is an effective instrument to measure perceptions of racism by African American women.

Adolescent↗