Exercise training improves activity in adolescents with congenital heart disease.

OBJECTIVES: To ascertain if motivational techniques and a structured exercise programme can increase activity in adolescents afflicted with congenital heart disease (CHD). DESIGN: Prospective randomised controlled trial. SETTING: One hundred and forty-three patients aged 12-20 years attending the tertiary centre for paediatric cardiology in Northern Ireland. MAIN OUTCOME MEASURES: Increase in exercise capacity as assessed by duration of exercise stress test, and number of minutes spent in moderate to vigorous physical activity (MVPA) per day. RESULTS: Eighty-six patients were men (60%), mean age was 15.60 ± 2.27 years. Seventy-three percent were considered to have major CHD. Seventy-two participants were randomised to the intervention group. Following intervention, duration of exercise test increased by 1 min 5 s for the intervention group (p value 0.02) along with increase in predicted VO2Max (p value 0.02). There was a significant increase in minutes of MVPA per day for the intervention group from baseline to reassessment (p value <0.001) while MVPA remained much the same for the control group. Fourteen patients met the current recommendation for more than 60 min MVPA per day at baseline. This doubled to 29 participants at reassessment. There were no adverse effects or mortalities reported. CONCLUSIONS: Exercise training is safe, feasible and beneficial in adolescents with CHD. Psychological techniques can be employed to maximise the impact of interventions. TRIAL REGISTRATION NUMBER: ISRCTN27986270.

Primitive hepatic venous plexus in a child with scimitar syndrome and pulmonary sequestration.

We report a case of scimitar syndrome with pulmonary sequestration, persistent primitive hepatic venous plexus and stenosis of the inferior vena cava in a child presenting with failure to thrive. Such associations are rare but may have implications when planning interventions for patients with complex congenital heart disease.

Examination of the physical and psychosocial determinants of health behaviour in 4-5-year-old children with congenital cardiac disease.

OBJECTIVES: To assess the general health and activity levels of 4- and 5-year-old children after intervention for congenital cardiac disease. METHODS: Health behaviour outcomes were assessed in 91 children who had surgery or catheter intervention for congenital cardiac disease. The children were classified into four groups according to severity. The main parameters of classification were the presence of residual symptoms, frequency of visits to general practitioner or the Accident and Emergency Department, and ability to participate in physical activity according to a calculated "activity score". RESULTS: Children had very few residual symptoms after "corrective surgery". Those with complex congenital cardiac disease post-Fontan-type repair still had symptoms on average 18.2 days per month. Surprisingly, the complex group had fewer days "sick" from non-cardiac causes and had fewer visits to general practitioner or Accident and Emergency Departments. Regression analysis indicates that three variables had significant relevance to the general practitioner or Accident and Emergency visits: complex congenital cardiac disease, fewer visits; Townsend score - more deprivation - more visits; and maternal worry - higher maternal worry score - more visits. Regression analysis indicates that lower activity score is significantly related to complex cardiac disease and higher maternal worry score. CONCLUSIONS: The majority of this group of 4- and 5-year-old children had few residual symptoms and had good exercise tolerance. Maternal worry is a significant factor in influencing both activity levels and frequency of unscheduled health service demands - general practitioner or Accident and Emergency visits.

Evaluation of sequentially crosslinked ultra-high molecular weight polyethylene.

This study was undertaken to investigate the effect of crosslinking ultra-high molecular weight polyethylene (UHMWPE) in a sequential manner to the final desired dose and to compare the results to single-dose crosslinking. To verify these results, an explanted, commercially available, sequentially crosslinked component was characterized. Finally, additional tensile testing was conducted to determine if tensile-sample thickness has a significant effect on the mechanical properties of UHMWPE. Based upon this well-controlled study with the same starting material, there is no apparent benefit of sequential crosslinking over crosslinking by single dose in any of the mechanical, thermophysical, physical, or oxidative properties evaluated in this study. In contrast, the soak temperature of the postirradiation heat treatment was more influential and exhibited statistically significant effects on the stability, structure, and properties of the resultant material. Compared to virgin material, crosslinking always resulted in decreases in tensile strength, elongation, and impact strength. These results were confirmed by characterization of a retrieved, sequentially crosslinked (X3) cup. All of the metrics derived for the retrieved cup were virtually identical to the sequential- and single-dose-crosslinked materials produced in this study. Examination of the effect of tensile-sample thickness demonstrated that there are significant effects on the resultant properties. In particular, the ultimate tensile strength of UHMWPE can be elevated by conducting tensile tests with thin specimens.

Phenotypic changes in mitochondrial membrane potential (Delta psi(m)) during valinomycin-induced depolarisation and apoptosis.

A large body of evidence has implicated mitochondria in control of cell death, where key apoptotic mechanisms involve change in mitochondrial membrane permeability and depolarisation of mitochondrial membrane potential (Delta psi(m)). Assessment of Delta psi(m) is traditionally conducted using the lipophilic cation JC-1 on the flow cytometer or by fluorescent microscopy. Here we assess JC-1 aggregation using the novel tool of digital texture analysis to establish mitochondrial phenotypic changes induced by the K+ ionophore, valinomycin in a unique model comprising SW480 and SW620 cell lines. This provides an opportunity to study these phenomena in the context of colorectal cancer. Valinomycin-induced apoptosis was detected using morphology and analysis of DNA content. Cells were treated with valinomycin, images digitally recorded on a calibrated video photometer and subjected to high resolution digital texture analysis. This demonstrated that the HARAM texture features (Mean of the Haralick texture features) were highly valuable in describing the transition of Delta psi(m) as the cell undergoes apoptosis. In conclusion this study illustrates the potential of texture analysis as a novel and additional technique for quantifying JC-1 aggregation and revealing the spectrum of collapse of Delta psi(m) during apoptosis.

The electrochemical evaluation of a Zr-based bulk metallic glass in a phosphate-buffered saline electrolyte.

Bulk metallic glasses (BMGs) represent an emerging class of materials with an amorphous structure and a unique combination of properties. The objectives of this investigation were to define the electrochemical behavior of a specific Zr-based BMG alloy in a physiologically relevant environment and to compare these properties to standard, crystalline biomaterials as well as other Zr-based BMG compositions. Cyclic-anodic-polarization studies were conducted with a Zr52.5Cu17.9Ni14.6Al10.0Ti5.0 (at %) BMG in a phosphate-buffered saline electrolyte with a physiologically relevant oxygen content at 37 degrees C. The results were compared to three common, crystalline biomaterials: CoCrMo, 316L stainless steel, and Ti-6Al-4V. The BMG alloy was found to have a lower corrosion penetration rate (CPR), as compared to the 316L stainless steel, and an equivalent CPR, as compared to the CoCrMo and Ti-6Al-4V alloys. Furthermore, the BMG alloy demonstrated better localized corrosion resistance than the 316L stainless steel. However, the localized corrosion resistance of the BMG alloy was not as high as those of the CoCrMo and Ti-6Al-4V alloys in the tested environment. The excellent electrochemical properties demonstrated by the BMG alloy are combined with a low modulus and unparalleled strength. This unique combination of properties dramatically demonstrates the potential for amorphous alloys as a new generation of biomaterials.

Expert system support using a Bayesian belief network for the classification of endometrial hyperplasia.

Accurate morphological classification of endometrial hyperplasia is crucial as treatments vary widely between the different categories of hyperplasia and are dependent, in part, on the histological diagnosis. However, previous studies have shown considerable inter-observer variation in the classification of endometrial hyperplasias. The aim of this study was to develop a decision support system (DSS) for the classification of endometrial hyperplasias. The system used a Bayesian belief network to distinguish proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. These diagnostic outcomes were held in the decision node. Four morphological features were selected as diagnostic clues used routinely in the discrimination of endometrial hyperplasias. These represented the evidence nodes and were linked to the decision node by conditional probability matrices. The system was designed with a computer user interface (CytoInform) where reference images for a given clue were displayed to assist the pathologist in entering evidence into the network. Reproducibility of diagnostic classification was tested on 50 cases chosen by a gynaecological pathologist. These comprised ten cases each of proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. The DSS was tested by two consultant pathologists, two junior pathologists and two medical students. Intra- and inter-observer agreement was calculated following conventional histological examination of the slides on two occasions by the consultants and junior pathologists without the use of the DSS. All six participants then assessed the slides using the expert system on two occasions, enabling inter- and intra-observer agreement to be calculated. Using unaided conventional diagnosis, weighted kappa values for intra-observer agreement ranged from 0.645 to 0.901. Using the DSS, the results for the four pathologists ranged from 0.650 to 0.845. Both consultant pathologists had slightly worse weighted kappa values using the DSS, while both junior pathologists achieved slightly better values using the system. The grading of morphological features and the cumulative probability curve provided a quantitative record of the decision route for each case. This allowed a more precise comparison of individuals and identified why discordant diagnoses were made. Taking the original diagnoses of the consultant gynaecological pathologist as the 'gold standard', there was excellent or moderate to good inter-observer agreement between the 'gold standard' and the results obtained by the four pathologists using the expert system, with weighted kappa values of 0.586-0.872. The two medical students using the expert system achieved weighted kappa values of 0.771 (excellent) and 0.560 (moderate to good) compared to the 'gold standard'. This study illustrates the potential of expert systems in the classification of endometrial hyperplasias.

A longitudinal study of Sin Nombre virus prevalence in rodents, southeastern Arizona.

We determined the prevalence of Sin Nombre virus antibodies in small mammals in southeastern Arizona. Of 1,234 rodents (from 13 species) captured each month from May through December 1995, only mice in the genus Peromyscus were seropositive. Antibody prevalence was 14.3% in 21 white-footed mice (P. leucopus), 13.3% in 98 brush mice (P. boylii), 0.8% in 118 cactus mice (P. eremicus), and 0% in 2 deer mice (P. maniculatus). Most antibody-positive mice were adult male Peromyscus captured close to one another early in the study. Population dynamics of brush mice suggest a correlation between population size and hantavirus-antibody prevalence.

Feasibility and marketing studies of health sciences librarianship education programs.

The University of North Carolina at Chapel Hill evaluated five curricular models designed to improve education for health sciences librarianship. Three of the models enhanced existing degree and certificate programs, and two were new programs for working information professionals. Models were developed with input from experts and a Delphi study; the marketability of the models was tested through surveys of potential students and employers; and recommendations were made as a guide to implementation. The results demonstrated a demand for more specialized curricula and for retraining opportunities. Marketing data showed a strong interest from potential students in a specialized master's degree, and mid-career professionals indicated an interest in postmaster's programs that provided the ability to maintain employment. The study pointed to the opportunity for a center of excellence in health sciences information education to enable health sciences librarians to respond to their evolving roles.

Preparing tomorrow's health sciences librarians: feasibility and marketing studies.

The University of North Carolina at Chapel Hill is devising and evaluating five curricular models designed to improve education for health sciences librarianship. These models fit into a continual learning process from the initial professional preparation to lifelong learning opportunities. Three of them enhance existing degree and certificate programs in the School of Information and Library Science (SILS) with a health sciences specialization, and two are new programs for working information professionals. The approaches involve partnerships among SILS, the Health Sciences Library, and the program in Medical Informatics. The planning process will study the feasibility of the proposed programs, test the marketability of the models to potential students and employers, and make recommendations about implementation.

Grandparent-headed families: new therapeutic challenges.

In today's complex society where dissolution of the nuclear family has become commonplace, grandparents are playing an increasingly significant role in the nurturing of their young grandchildren. The authors studied twelve randomly selected grandparent-headed families from the case files of a suburban child guidance clinic. Comparisons were made among the cases in terms of a number of factors, most significantly, elements of treatment including therapeutic issues, modalities and outcomes. The authors stress a multi-modal and intergenerational approach to the treatment of these families.

Mutations in the zinc fingers of ADR1 that change the specificity of DNA binding and transactivation.

ADR1 is a yeast transcription factor that contains two zinc fingers of the Cys-2-His-2 (C2H2) class. Mutations that change the specificity of DNA binding of ADR1 to its target site, upstream activation sequence 1 (UAS1), have been identified at three positions in the first zinc finger. Mutations Arg-115 to Gln, His-118 to Thr, and Arg-121 to Asn led to new specificities of DNA binding at adjacent positions 10, 9, and 8 (3'-GAG-5') in UAS1. Arg-115 is at the finger tip, and His-118 and Arg-121 are at positions 3 and 6, respectively, in the alpha helix of finger 1. One double mutant displayed the binding specificity expected from the properties of its constituent new-specificity mutations. Mutations in the second finger that allowed its binding site to be identified through loss-of-contact phenotypes were made. These mutations imply a tail-to-tail orientation of the two ADR1 monomers on their adjacent binding sites. Finger 1 is aligned on UAS1 in an amino-to-carboxyl-terminal orientation along the guanine-rich strand in a 3'-to-5' direction. One of the ADR1 mutants was functional in vivo with both its cognate binding site and wild-type UAS1, but the other two mutants were defective in transactivation despite their ability to bind with high affinity to their cognate binding sites.

Alanine scanning site-directed mutagenesis of the zinc fingers of transcription factor ADR1: residues that contact DNA and that transactivate.

To identify functionally important amino acids in the two zinc fingers of transcription factor ADR1 [alcohol dehydrogenase (ADH) II synthesis regulator], oligonucleotide-directed mutagenesis was used to substitute alanine for the original amino acid at each position in both fingers. The effects of these mutations on DNA binding and thermal stability of ADR1 in vitro and on activation of ADH2 expression in vivo were measured. The DNA binding activity was remarkably heatstable. Amino acids that are candidates for DNA contact sites were identified in the finger-tip and alpha-helical region of each finger, three in the first finger and two in the second. Unexpectedly, an acidic residue in the first finger was essential for transactivation, but its replacement by alanine had no effect on DNA binding. Substitution at several highly conserved positions did not affect ADR1 functions. The ADR1 zinc fingers appear to make relatively few energetically significant contacts to DNA, perhaps as few as three in the first finger and one in the second.

Survey of birds and lizards for ixodid ticks (Acari) and spirochetal infection in northern California.

A total of 138 birds (24 species) was captured in an oak woodland between December 1988 and June 1989 at the University of California, Sierra Foothill Range Field Station, Yuba County, Calif. Ticks were not found on 71 birds captured between December 1988 and March 1989. Five subadult Ixodes pacificus Cooley & Kohls were removed from 3 of 67 birds caught between April and June 1989. These three birds, an orange-crowned warbler (Vermivora celata (Say], a lazuli bunting (Passerina amoena (Say], and a chipping sparrow (Spizella passerina (Bechstein], represent new host records for I. pacificus in California. Tissues from two ticks and thick blood films prepared from 126 birds tested negative for spirochetes by direct immunofluorescence (DI). A total of 172 larval and 197 nymphal I. pacificus was removed from 15 of 16 western fence lizards (Sceloporus occidentalis Baird & Girard) caught between April and June 1989 in the same location as were birds. Thick blood films prepared from all 16 lizards and tissue smears from 334 of the ticks (143 larvae and 191 nymphs) were DI test-negative for spirochetes. One (1.1%) of 93 adult I. pacificus collected at the bird-lizard capture site in February 1989 was infected with spirochetes that resembled B. burgdorferi.

Statistics of Natural Populations. II. Estimating an Allele Probability in Families Descended from Cryptic Mothers.

In population studies, adults are frequently difficult or inconvenient to identify for genotype, but a family profile of genotypes can be obtained from an unidentified female crossed with a single unidentified male. The problem is to estimate an allele frequency in the cryptic parental gene pool from the observed family profiles. For example, a worker may wish to estimate inversion frequencies in Drosophila; inversion karyotypes are cryptic in adults but visible in salivary gland squashes from larvae. A simple mixture model, which assumes the Hardy-Weinberg law, Mendelian laws and a single randomly chosen mate per female, provides the vehicle for studying three competing estimators of an allele frequency. A simple, heuristically appealing estimator called the Dobzhansky estimator is compared with the maximum likelihood estimator and a close relative called the grouped profiles estimator. The Dobzhansky estimator is computationally simple, consistent and highly efficient and is recommended in practice over its competitors.