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Neuropsychological differentiation of subnormal arithmetic abilities in children.

For the neuropsychological diagnosis of a Specific disorder of arithmetic skills the standard is defined worldwide by the diagnostic guidelines of the two major classification systems of psychiatric disorders, the ICD- 10 and the DSM-IV, both of which use the discrepancy criterion as the key feature of the diagnosis. It becomes clear that following such guidelines can only mean an extensive diagnostic assessment of patients with subnormal arithmetic abilities, including the social and previous medical history followed by the exclusion of a present disorder or disability, often necessitating laboratory, neuroimaging and neurophysiological tests. In the neuropsychological diagnosis of a Specific disorder of arithmetical skills we found a stepwise approach including previously obtained test results to be most practical and economical. The assessment instruments such as intelligence tests, neuropsychological test batteries, academic achievement tests, specific neuropsychological tests, test batteries for arithmetic abilities or error analysis are discussed. An overview of case studies in the literature is given; however, the overwhelming majority of case reports on patients with arithmetic disabilities are casuistics of adult patients with an acquired loss of arithmetic abilities. The importance of a differentiated neuropsychological diagnosis is demonstrated by four of our own cases: of borderline deficient intelligence, a combined disorder of academic skills, congenital brain dysfunction, and a specific disorder of arithmetic skills. Especially the new quality in assessing arithmetic abilities with the NUCALC battery is demonstrated; diagnostic and therapeutic consequences are discussed.

Adolescent↗

In vitro and in vivo methods to determine the interactions of osteogenic cells with biomaterials.

To assess new biomaterials for possible use as bone graft substitutes, a number of techniques allow interactions with osteoblastic cells to be studied, with respect to effects on proliferation and differentiation of osteoprogenitors. In vitro models include the use of bone explant cultures, fetal rat calvarial-derived osteoblast cells, primary stromal populations, transformed and non-transformed cell lines and immortalized osteoblast cell lines. However, these assessments are limited by the extent of osteogenic differentiation and bone formation that can be observed in vitro, species differences and phenotypic drift of cells cultured in vitro. The use of in vivo experimental systems such as the segmental/calvarial bone defect model, the subcutaneous implant model and the diffusion chamber implantation model circumvent some of these issues and, in the appropriate model, provide data on efficacy, biocompatibility and osteointegration of a biomaterial. The combination of in vitro and in vivo approaches together with the development of new cell labeling techniques, in particular the ability to genetically mark and select specific human bone cell populations provides new avenues for their potential evaluation in combination with appropriate biomaterials for clinical use. These in vitro and in vivo techniques are reviewed and those recently developed for assessment of human osteogenic cells should be applicable to many other cell systems where knowledge of specific human tissue or cell interactions with biomaterials is required.

Journal Article↗

Specific hybridization arrest of dihydrofolate reductase mRNA in vitro using anti-sense RNA or anti-sense oligonucleotides.

Three anti-sense RNAs and ten synthetic anti-sense oligonucleotides were tested for their ability specifically to arrest translation of human dihydrofolate reductase (DHFR) mRNA in a nuclease-treated rabbit reticulocyte lysate. Quantitative hybrid arrest of DHFR mRNA by anti-sense RNA required that the RNA hybridize to the 5' end of DHFR mRNA. Oligonucleotides of length 11-20, complementary to various sites near the 5' end of DHFR mRNA, also could cause specific inhibition of DHFR mRNA translation. Oligonucleotide length and concentration were shown to be important variables in hybrid arrest of DHFR mRNA. Neither the exact oligonucleotide binding site position near the 5' end of the mRNA nor prehybridization conditions were important variables. The combination of short oligonucleotides with contiguous binding sites was shown to synergize their ability to inhibit specifically DHFR mRNA translation.

Humans↗

Bioluminescence imaging of systemic tumor targeting using a prostate-specific lentiviral vector.

Developments in vector design using tissue-specific and tumor-specific promoters have led to significant improvements in tumor-targeting strategies. These developments combined with the ability to monitor gene expression by molecular imaging have facilitated the detection and prolonged monitoring of disease progression in small-animal models. Bioluminescence imaging offers a convenient and sensitive platform for monitoring gene expression patterns in preclinical models of gene therapy. Targeting a specific subset of cells/tissues via systemic delivery of vectors would be highly beneficial in gene therapy protocols. Using a two-step transcriptional amplification (TSTA)-based lentiviral vector (LV-TSTA), we demonstrate specific targeting of prostate tumors in vivo after systemic administration of lentivirus. Four days after intravenous administration of LV-TSTA into adult severe combined immunodeficient (SCID) mice (n=5) carrying subcutaneous prostate tumors, we found significant levels of transduction at the tumor site when compared with other organs (p<0.05). Gene expression was sustained in the tumor for up to 3 weeks (7.3x10(4)+/-2x10(4) photons/ sec/cm2/steradian (p/sec/cm2/sr) on day 4 and 7.0x10(4)+/-4x10(4) p/sec/cm2/sr on day 21). Low levels of transduction were also observed in the spleen and liver (5.0x10(2)+/-1.7x10(2) p/sec/cm2/sr). The results from this study support the use of TSTA-based lentiviral vectors for prostate tumor targeting after systemic delivery. Noninvasive imaging using such vectors should be useful for monitoring long-term gene expression in gene therapy applications.

Animals↗

Mixed chimerism induces donor-specific T-cell tolerance across a highly disparate xenogeneic barrier.

Induction of tolerance is likely to be essential for successful xenotransplantation because immune responses across xenogeneic barriers are vigorous. Although mixed hematopoietic chimerism leads to stable donor-specific tolerance in allogeneic and closely related xenogeneic (eg, rat-to-mouse) combinations, the ability of this approach to induce tolerance across a highly disparate xenogeneic barrier has not yet been demonstrated. In this study, we investigated the immune responses of murine T cells that developed in mice with pre-established porcine hematopoietic chimerism. Our results show for the first time that induction of porcine hematopoietic chimerism can eliminate the development of antiporcine donor responses in a highly disparate xenogeneic species. Porcine hematopoietic chimeras showed donor-specific nonresponsiveness in the mixed lymphocyte reaction, lack of antidonor IgG antibody production, and acceptance of donor skin grafts. Thus, mixed chimerism is capable of inducing tolerance in a highly disparate xenogeneic combination and may have clinical potential to prevent xenograft rejection. (Blood. 2002;99:3823-3829)

Animals↗

Analyses of carbohydrate recognition by legume lectins: size of the combining site loops and their primary specificity.

Recognition of cell-surface carbohydrates by lectins has wide implications in important biological processes. The ability of plant lectins to detect subtle variations in carbohydrate structures found on molecules, cells and organisms have made them a paradigm for protein-carbohydrate recognition. Legume lectins, one of the most well studied family of plant proteins, display a considerable repertoire of carbohydrate specificities owing perhaps to the sequence hypervariability in the loops constituting their combining site. However, lack of a rigorous framework to explain their carbohydrate binding specificities has precluded a rational approach to alter their ligand binding activity in a meaningful manner. This study reports an extensive analysis of sequences and structures of several legume lectins and shows that despite the hypervariability of their combining regions they exhibit within a significant pattern of uniformity. The results show that the size of the binding site loop D is invariant in the Man/Glc specific lectins and is possibly a primary determinant of the monosaccharide specificities of the legume lectins. Analyses of size and sequence variability of loops reveal the existence of a common theme that subserves to define their binding specificities. These results thus provide not only a framework for understanding the molecular basis of carbohydrate recognition by legume lectins but also a rationale for redesign of their ligand binding propensities.

Acetylgalactosamine↗

Prediction of hyperbilirubinemia in near-term and term infants.

OBJECTIVE: The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life. METHODS: From 9 multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998, through February 22, 1999. Measurements of both ETCOc and STB were performed at 30 +/- 6 hours of life; STB also was measured at 96 +/- 12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study. RESULTS: A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breastfed infants was 8.92 +/- 4.37 mg/dL at 96 hours versus 7.63 +/- 3.58 mg/dL in those fed formula only. The mean ETCOc at 30 +/- 6 hours for the total population was 1.48 +/- 0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45 +/- 0.47 ppm and 1.81 +/- 0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30 +/- 6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB >/=95th percentile. When infants with STB >95th percentile at <36 hours of age were excluded, the STB at 30 +/- 6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these 2 measurements at 30 +/- 6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV. Conclusions. This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant's risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30 +/- 6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

Bilirubin↗

Prediction of hyperbilirubinemia in near-term and term infants.

OBJECTIVE: The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life. METHODS: From nine multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998 through February 22, 1999. Measurements of both ETCOc and STB were performed at 30+/-6 hours of life; STB also was measured at 96+/-12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study. RESULTS: A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breast-fed infants was 8.92+/-4.37 mg/dl at 96 hours versus 7.63+/-3.58 mg/dl in those fed formula only. The mean ETCOc at 30+/-6 hours for the total population was 1.48+/-0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45+/-0.47 and 1.81+/-0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30+/-6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB > or =95th percentile. When infants with STB > or =95th percentile at <36 hours of age were excluded, the STB at 30+/-6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these two measurements at 30+/-6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV. CONCLUSIONS: This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant's risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30+/-6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

Bilirubin↗

Neuronal plasticity in memory and learning abilities: theoretical position and selective review.

Neural plasticity of modality-nonspecific and modality-specific memory and learning abilities pertains to fluid intelligence and crystallized intelligence, respectively. The limbic system with the novelty neurons of the hippocampus interacts with the prefrontal cortex optimization of the orienting reflex and voluntary attention. Brain-derived neurotrophic factor produced by novelty neurons of the hippocampus contributes to long-term memory formation and improves learning abilities in a wide range of disciplines. Synergistic combination of stimulation with "analytical-specific visual perceptual patterns" and "optimally high" physiological activation of the bilateral electrodermal system optimizes the limbic system and prefrontal cortex activity as demonstrated by enhanced prefrontal N450 ERPs to a memory workload paradigm. This is accompanied by improvements in auditory retention tasks, word memorization, higher school achievement and marks, and an amelioration of "analytical-specific perceptual skills" as measured by the Mangina-Test. Intracerebral ERPs to a memory workload paradigm contributed to the elucidation of limbic structures and neocortical sites involved in memory workload processes. The progressive degeneration of these same structures causes the gradual decline of memory functions observed in early Alzheimer's disease. Research findings indicate that ERPs elicited by a memory workload paradigm are sensitive markers for diagnosis, treatment and clinical follow-up of early Alzheimer's patients. In addition, ERPs provide objective measurement of cholinergic medication effects on cerebral functions involved in memory processes through neuropsychophysiological parameters.

Animals↗

Prostate-specific antigen: critical issues for the practicing physician.

BACKGROUND: Serum prostate-specific antigen (PSA), when used in combination with existing detection methods, improves the clinician's ability to detect early and potentially curable prostate cancer. FINDINGS: This report describes clinically important issues about use of the serum PSA concentration for detecting early prostate cancer. Other PSA-related factors--PSA density, PSA velocity, and age-specific reference ranges--seem to enhance the ability of clinicians to distinguish benign prostatic conditions from early prostate cancer. Because digital rectal examination only minimally affects the serum PSA concentration, delaying a determination after this examination is unnecessary. Finasteride therapy for benign prostatic hyperplasia should be initiated only after the prostate has been evaluated for cancer because this 5 alpha-reductase inhibitor lowers the serum PSA value by approximately 50%; however, reassessment of the prostate for cancer is necessary if the PSA level fails to decrease as expected or increases to more than 2 ng/mL during finasteride treatment. CONCLUSION: Currently, PSA is the most important, accurate, and clinically useful tumor marker for prostate cancer.

Adult↗

The discriminative ability of peripheral and axial bone measurements to identify proximal femoral, vertebral, distal forearm and proximal humeral fractures: a case control study.

Previous studies evaluating peripheral bone measurement devices have often used discontinued technologies, compared single devices, only evaluated a single fracture syndrome or failed to make a comparison with central densitometry, which is currently the gold standard for fracture discrimination. We have used a case control study to evaluate the ability of different peripheral and central bone techniques to discriminate between fracture cases and controls, determine the impact of different measurement sites, evaluate the role of measuring the cortical or trabecular envelopes using quantitative computed tomography (QCT) and determine the impact of using combinations of sites and techniques on fracture discrimination. We recruited postmenopausal women with proximal femoral (n=53), vertebral (n=73), distal forearm (n=78) or proximal humeral (n=75) fractures, and 500 population-based women (age 55-80 years). All subjects had measurements of the spine, total hip and distal forearm with dual-energy X-ray absorptiometry (DXA), distal forearm QCT and quantitative ultrasound (QUS) of the heel (four devices), finger (two devices), radius and metatarsal. The association of each device with fracture was expressed as the age-adjusted standardized odds ratios (sOR) per 1-SD decrease of population variance. The association of bone measurements with fracture was site-specific. We found the hip (sOR up to 3.40) and vertebral (sOR up to 4.67) fractures were more closely associated with central bone measurements than upper limb fractures (sOR 1.96 and 2.05). The performance of heel broadband ultrasound attenuation (sOR 2.09-2.41), heel speed of sound (sOR 1.79-2.28) and peripheral BMD (sOR 2.07 and 2.24) was comparable with total hip (sOR 2.46) and lumbar spine DXA (sOR 2.31) in discriminating all types of osteoporotic fracture. In general, measuring cortical or trabecular envelopes did not increase sOR. However, combining different measurement sites or technologies provided additional information, which was independent of total hip BMD. The ability of different bone measurements to discriminate between fracture cases and controls is device- and site-specific, with additional information obtained by combining measurement sites and technologies.

Absorptiometry, Photon↗

Detection of rubella virus-specific polymeric immunoglobulin A by enzyme-linked immunosorbent assay in combination with streptococcal pretreatment of serum.

An enzyme-linked immunosorbent assay combined with streptococcal treatment of serum was assessed for its ability to detect serum polymeric immunoglobulin A. This technique detects rubella virus-specific polymeric immunoglobulin A antibody, which appears for only a short time after infection, and it is useful for serodiagnosis of recent rubella virus infection.

Antibodies, Viral↗

Hepatitis C virus-specific T-cell reactivity during interferon and ribavirin treatment in chronic hepatitis C.

BACKGROUND & AIMS: The role of virus-specific T-helper lymphocyte reactivity in determining the therapeutic response in chronic hepatitis C virus (HCV) infection is not fully understood. METHODS: We studied CD4(+) T lymphocyte proliferation together with interferon (IFN)-gamma and interleukin (IL)-10 production from peripheral blood mononuclear cells in response to 4 HCV antigens (core, NS3, NS4, and NS5) in 25 patients with chronic hepatitis C undergoing antiviral therapy with IFN alone or in combination with ribavirin, prospectively, before, during, and after treatment. RESULTS: HCV-specific T-cell reactivity was uncommon at baseline but increased markedly during antiviral therapy, peaking around treatment weeks 4-8. Resolution of hepatitis C viremia was significantly more likely in patients who developed HCV-specific T-cell proliferation with increased IFN-gamma production. The main difference in T-cell reactivity of patients treated with IFN plus ribavirin was a significantly lower production of IL-10, whereas lymphocyte proliferation was similar to that in patients receiving IFN monotherapy. CONCLUSIONS: Treatment-induced control of hepatitis C viremia is associated with the development of HCV-specific T-cell responses with enhanced IFN-gamma and low IL-10 production. The greater efficacy of combination therapy with IFN-alpha plus ribavirin may be related to its ability to suppress HCV-specific IL-10 production.

Adult↗

[Performance testing in mountaineering].

Laboratory ergometry to exhaustion allows cardiopulmonal risk assessment for the prevention of health problems related to mountaineering. Moreover, exercise testing evaluates functional status, so permitting individualized training programs and evaluation of training effects. Additionally, mountaineering-specific performance diagnosis allows individual as well as group-specific determination of exercise performance related to field conditions. Laboratory tests are standardized, easy to perform and cost effective. Treadmill ergometry with constant walking speed and increasing inclination is suggested to be predictive for mountaineering performance. On the other hand, the validity for the specific conditions for mountaineering is questionable. Standardized laboratory exercise tests combined with sport-specific exercise tests provide rough information on the ability to sustain real-situation strain. To compare individual exercise performance, published data tables obtained from field tests may be used. It must, however, be mentioned that high-altitude-adaptation is independent of exercise performance evaluated separately.

Acclimatization↗

A micromethod for the estimation of oligosaccharides containing glycosidically linked sialic acid or hexoses, or both, in glycoproteins.

The peeling reaction, the process by which oligosaccharides are degraded in alkali, was used as the basis for an assay to provide structural information about glycosidically linked oligosaccharides in glycoproteins. Glycoproteins were treated with 0.05 M NaOH at 50 degrees to induce release, and subsequent degradation ("peeling"), of glycosidically linked, but not of N-glycosydically linked, oligosaccharides. Among the degradation products generated from O-linked chains were three 3-deoxy sugar acids whose formation was correlated with certain structural features of the oligosaccharides. N-Acetylneuraminic acid was released from terminal positions in the oligosaccharides, and iso- and meta-saccharinic acids were derived from the degradation of 4-O- and 3-O-substituted hexoses, respectively. All of these sugar acids were detected colorimetrically by periodate oxidation and reaction of the product with 2-thiobarbituric acid. The ability of the method to generate 3-deoxy sugar acids was tested in 8 alkali-treated glycoproteins. 3-Deoxy sugar acids were detected only in those glycoproteins whose glycosidically linked carbohydrates contained N-acetylneuraminic acid, or 3-O- or 4-O-substituted hexoses, or both. As little as 0.12 microgram of 3-deoxy sugar acid produced from 5 micrograms of human chorionic gonadotropin was sufficient for detection. This method is novel in its ability to distinguish sialylation of glycosidically linked carbohydrates. Furthermore, it combines the specificity of beta-elimination with the sensitivity of the 2-thiobarbituric acid assay in targeting degradation products of the peeling reaction as candidates for an assay method.

Glycoproteins↗

A hospital staff support program: design and evaluation.

The literature indicates that nurses on special care units experience stress resulting from the role conflict and ambiguity to which they are exposed. Role theory predicts that such individuals will become dissatisfied with their work and will decrease their confidence in supervisors and co-workers. Consequently, it was hypothesized that a staff support program designed to assist nurses to cope with role conflict and ambiguity would result in reduced stress; increased satisfaction with work, supervision, and co-workers; and decreased staff turnover. A nine week staff support program was implemented on a hospice unit in a large, private, general hospital. The program utilized an insight-oriented approach focused on specific sources of stress combined with structured exercises designed to facilitate nurses' ability to cope with stress resulting from a role conflict and ambiguity. Data were collected from two groups to hospice nurses using a Nursing Stress Scale developed for this study, the Job Description Index, and personnel records. A quasi-experimental research design was used to assess the validity and generalizability of the results of the program. Data were analyzed in four stages: (i) pre-program levels of stress and job satisfaction were analyzed using a multivariate profile analysis; (ii) correlated t-tests were used to test for significant differences between pre- and post-program levels of stress; (iii) a repeated measures ANOVA was used to examine the effect of the program on job satisfaction; (iv) turnover among the nursing staff on four other hospital units was compared to the hospice unit. Results of the evaluation indicated that the support program was effective in reducing nursing stress, increasing job satisfaction, and decreasing staff turnover. The implications of the study for the design and evaluation of hospital staff support programs are discussed.

Conflict, Psychological↗

Regulation of energy intake in relation to metabolic state and nutritional status.

Inadequate energy intake can be an important contributor to weight loss in older individuals. This review highlights recent studies on possible causes of negative energy balance in older individuals. Studies of the regulation of food intake suggest that aging is associated with a significant impairment in the regulation of food intake that inhibits appropriate short-term and long-term compensation for imposed alterations in energy intake. The combination of a reduced ability to regulate energy intake, decreased sensory-specific satiety, and disadvantageous social factors such as functional limitations, social isolation and depression, increases the risk of negative energy balance leading to weight loss in older individuals.

Aged↗

Intrabodies: turning the humoral immune system outside in for intracellular immunization.

Antibodies have long been used in biomedical science as in vitro tools for the identification, purification and functional manipulation of target antigens; they have been exploited in vivo for diagnostic and therapeutic applications as well. Recent advances in antibody engineering have now allowed the genes encoding antibodies to be manipulated so that the antigen binding domain can be expressed intracellularly. The specific and high-affinity binding properties of antibodies, combined with their ability to be stably expressed in precise intracellular locations inside mammalian cells, has provided a powerful new family of molecules for gene therapy applications. These intracellular antibodies are termed 'intrabodies'. Two clinical protocols have been approved by the RAC for the use of intrabodies in the treatment of an oncologic and an infectious disease. Their clinical use will in all likelihood become widespread if these initial studies show 'proof in principle'. In this article, the studies from laboratories that have used intrabodies as molecular reagents for cancer therapy and for the control of infectious diseases will be reviewed and future directions of this technology will be discussed.

Acquired Immunodeficiency Syndrome↗