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Proper evaluation of clinical innovations and of the process of their diffusion is essential for the development of sound health care policy. This case study examines transcutaneous oxygen monitoring in neonatal intensive care, a procedure that was rapidly adopted in the late 1970s as a scientific breakthrough of great promise, then all but abandoned within a decade in favor of pulse oximetry, a still more recent technology. The study incorporates the results of interviews with representatives of industry as well as biomedical researchers and clinicians involved with these devices. Factors in technology diffusion are analyzed, with special attention to those susceptible to change by policy makers. Participants in the diffusion process also include nurses, hospital administrators, the legal profession, the news media, and the public, but the pivotal role--and hence ultimate responsibility--is seen to be that of the physician. The discussion is presented in the context of a proposed "ethics of evidence" pertinent to medical decision making. [ABSTRACT FROM AUTHOR]

Objective: A positive significant association has been found between behavior problems and lower cognition in very low birthweight (VLBW) preterm children at school age, but there is relatively little information about whether such an association exists in toddlers and on the continuity of this association. The aim of this study was to assess if there is a relationship between behavior problems and cognitive performance in VLBW preterm children at 18 months post conception and 3 years old, independent of socioeconomic status and sex., Method: Parents of 124 preterm children completed a behavior rating questionnaire (Child Behavior Checklist 1.5-5) to measure behavior problems characteristic of preterm children (Withdrawn, Anxious/Depressed, and Attention Problems). Children completed the Cognitive Scale of the Bayley Scales of Infant Development-III at 18 months and the Wechsler Preschool and Primary Scale (III or IV) at 36 months old. Socioeconomic status (SES), sex, and diagnoses of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) at 3 years were recorded for each child., Results: Withdrawn problems at 18 months were associated with lower cognitive scores at 18 months and both Withdrawn problems at 18 months and 36 months were associated with lower cognitive scores at 36 months. Increases in Attention Problems scores from 18 to 36 months were associated with decreases in cognitive scores over that period. Lower SES was associated with lower cognitive scores at 36 months and decreases in cognitive scores between 18 and 36 months. Sex was not related to behavior problems or cognition. Diagnoses of ASD and ADHD were significantly associated with increased Withdrawn behavior and Attention Problems, respectively., Conclusions: The early association of Withdrawn behaviors with less favorable cognitive performance at 18 months and 36 months and the relationship between increases in Attention Problems with decreases in cognitive scores between the toddler and preschool period indicate the need for early assessment of and intervention for behavior problems, as well as concurrent cognitive delays, in VLBW preterm children., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Learning Objectives: After participating in this CME activity, the clinician will be better able to:• Interpret classifications of neuropsychiatric systemic lupus erythematosus (NPSLE).• Identify determining factors of neuropsychiatric events.• Analyze current evidence regarding disease pathways for NPSLE., (Copyright © 2022 President and Fellows of Harvard College.)

We report here five new localities across the distribution of the lizard Sphaerodactylus samanensis , extending its current geographic range to the west, in the Cordillera Central of Hispaniola. We also report phenotypic variation in the color pattern and scutellation on throat and pelvic regions of males from both eastern and western populations, which is described below. Furthermore, based on these new data, we confirm that the species is not fitting in its current IUCN category, and in consequence propose updating its conservation status., Competing Interests: Joaquín A. Ugarte-Núñez is employed by Knight Piésold Consulting., (©2021 Chávez et al.)

One hundred and nine preterm infants were studied to examine the relative effects of biologic/neurologic factors (length of hospital stay, 18 month cognitive status) and environment (socioeconomic status) on cognition in the toddler (18 months) and preschool periods (3 years). Length of hospital stay was significantly related to toddler cognitive outcome, and less so to preschool outcome. Socioeconomic status predicted only preschool cognitive outcome and not toddler outcome. Cognitive status at 18 months significantly predicted 3 year outcome, and there was relatively little change between those periods. Together, cognitive status at 18 months and socioeconomic status significantly predicted preschool IQ, accounting for 34% of the variance. Results showed that perinatal biologic risks became less salient while socioeconomic status became increasingly important at the preschool period. Relative lack of change in cognitive status indicated the importance of early cognitive evaluation in preterm infants., (© 2019 Wiley Periodicals, Inc.)

Background: Life expectancy of patients with transfusion-dependent thalassemias has increased with the development of improved treatment over the last few decades. However, β-thalassemia disorder still has considerable lifetime treatment demands and heightened risk of frequent complications due to transfusion-transmitted infections and iron overload, which may affect thalassemic patients' functioning in different domains., Objectives: The vast majority of published studies on thalassemic patients have focused on children and adolescent functioning, and little research has examined adults. Hence, the current study was planned to examine the functioning and resilience of adult thalassemic patients in a comprehensive way., Methods: We examined multidimensional resilience and functioning across different domains (psychological adjustment, treatment adherence, social functioning and occupational functioning). We also examined demographic and medical variables that may relate to resilience and functioning. Participants were adult patients [n = 38; age M = 31·63, standard deviation (SD) = 7·72; 72% female] with transfusion-dependent thalassemia in treatment in a hospital in the northeastern United States., Results: The results suggest that most adult thalassemic patients tend to be resilient, demonstrating good functioning in four main domains: psychological adjustment, treatment adherence, social functioning and occupational functioning., Conclusion: Despite the considerable demands of their illness, adult thalassemic patients appeared to be adapting well, demonstrating evidence of multidimensional resilience., (© 2016 British Blood Transfusion Society.)

Background: Very low birthweight (VLBW) premature infant follow-up studies report on single developmental outcome variables but do not assess profiles of development., Aims: To identify developmental profiles of VLBW premature infants based on cognitive and language development and their association with demographic, perinatal, and behavior variables., Study Design: Retrospective chart review., Subjects: 117 children<1250 g BW seen at 18 months post-term on the Bayley Scales-III and Child Behavior Checklist 1 ½-5 (CBCL 1 ½-5), a behavior problem questionnaire. Demographic and perinatal variables were obtained from medical records., Outcome Measures: Bayley Cognitive, Expressive Language, and Receptive Language scores were used to cluster the subjects into developmental profiles. Demographic, perinatal, and CBCL variables were analyzed as they related to clusters., Results: Children were clustered into 4 groups based on their Bayley Cognitive, Expressive Language, and Receptive Language scores: Consistently High, Consistently Average, Average with Delayed Expressive Language, and Consistently Low. Socioeconomic status, bronchopulmonary dysplasia, Grades III-IV intraventricular hemorrhage, and summary Behavior Problems and Attention Deficit/Hyperactivity (ADHD) Problems scores were significantly related to clusters., Conclusion: Cluster analysis defined distinct outcome groups in VLBW premature children and provides an informative means of identifying factors related to developmental outcome. This approach may be useful in predicting later outcome and determining which groups of children will require early intervention., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Deforestation is one of the major threats to habitats in the Dominican Republic. In this work we present a forest baseline for the year 2000 and a deforestation map for the year 2011. Maps were derived from Moderate Resolution Imaging Radiometer (MODIS) products at 250 m resolution. The vegetation continuous fields product (MOD44B) for the year 2000 was used to produce the forest baseline, while the vegetation indices product (MOD13Q1) was used to detect change between 2000 and 2011. Major findings based on the data presented here are reported in the manuscript "Habitat suitability and protection status of four species of amphibians in the Dominican Republic" (Sangermano et al., Appl. Geogr.,) [7].63, 2015, 55-65.

Background: Although research has demonstrated the detrimental effects of excessive negative affect on treatment adherence and morbidity in chronic illness, rarely have researchers investigated the benefits of awareness of negative emotional experiences during treatment., Purpose: In this investigation, we examined the association of negative affect differentiation (the ability to report negative emotional experiences as separate and distinct from each other,) to treatment adherence in adult patients with the congenital blood disorder thalassemia., Method: Negative affect differentiation was assessed during a 12-16-week treatment-based diary and adherence was operationalized as attendance at routine screenings over 12 months. Participants were adult patients (n = 32; age M = 31.63, SD = 7.72; 72 % female) with transfusion-dependent thalassemia in treatment in a large metropolitan hospital in the Northeastern USA., Results: The results indicate that negative affect differentiation is significantly associated with greater adherence to treatment, even when controlling for disease burden and level of psychological distress., Conclusion: Although preliminary, this investigation suggests that differentiated processing of negative emotional experiences during illness can lead to adaptive treatment-related behavior. As such, it may present a new avenue for research and intervention targeting the improvement of adherence during treatment for chronic illness.

Background: Discordant birth weight twins have been shown to have high rates of adverse perinatal outcomes, but little is known about their growth and development., Aim: To determine whether smaller and larger birth weight premature twins in concordant and discordant birth weight groups differ on measures of physical growth and intelligence at 3 years., Study Design: Prospective cohort study. Eight-four children, 52 concordant and 32 discordant birth weight twin pairs, were measured for height, weight, and head circumference and on intelligence at 3 years. Perinatal and demographic variables, including birth weight, head circumference, small for gestational age, zygosity, in vitro fertilization, gender and social class were recorded., Results: Smaller and larger birth weight twins did not differ significantly from each other on any growth parameters in either concordant or discordant birth weight groups at 3 years of age. Smaller birth weight twins in the discordant birth weight group performed significantly less well on Verbal, Performance, and Full Scale IQ scores (Verbal IQ for smaller twins was 8.6 points lower, p<0.005; Performance IQ, 11.9 points lower, p<0.03; Full Scale IQ, 12.4 points lower, p<0.004), but there were no significant intra-twin differences between larger and smaller birth weight concordant twins., Conclusions: Smaller discordant birth weight twins performed significantly less well on intelligence, although they did not differ significantly from their larger twins on growth parameters at 3 years old. We conclude that smaller discordant birth weight twins had less optimal intra-uterine environments than their larger birth weight twin, which affected both their birth weights and brain development., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To assess the prevalence of neurocognitive impairment (NCI) in childhood-onset systemic lupus erythematosus (cSLE) by comparing published classification criteria, and to examine associations between NCI, disease characteristics, psychosocial well-being, and intelligence., Methods: cSLE patients and ethnicity- and age-matched healthy controls completed a neuropsychological research battery, and results were categorized by 3 different NCI classification criteria with different cutoff scores (e.g., >2, 1.5, or 1 SD below the mean) and the number of required abnormal tests or domains., Results: Forty-one cSLE subjects and 22 controls were included. Subjects were predominantly female (~70%) and Hispanic (∼70%). Executive functioning, psychomotor speed, and fine motor speed were most commonly affected. Method 1 classified 34.1% of cSLE subjects with NCI compared to method 2 (14.6% with decline and 7.3% with NCI) and method 3 (63.4% with NCI). The prevalence of NCI was not significantly different between the controls and patients using any of the categorization methods. NCI was not associated with SLE disease activity or characteristics or with depression. Using method 3, patients in the cognitive impairment group reported significantly lower quality of life estimates (69.7 versus 79.3; P = 0.03). Below average intellectual functioning (intelligence quotient <90) differentiated the number of test scores >1 and >1.5 SDs, but not >2 SDs below the mean., Conclusion: NCI was prevalent in cSLE, but varied according to the chosen categorization method. A similar proportion of cSLE patients and controls had NCI, reinforcing the importance of studying an appropriate control group. Categorical classification (i.e., impaired/nonimpaired) may oversimplify the commonly observed deficits in cSLE., (Copyright © 2011 by the American College of Rheumatology.)

Objective: To develop and propose a standardized battery of neuropsychological tests for the assessment of cognitive functioning of children and adolescents with pediatric systemic lupus erythematosus (SLE)., Methods: A committee of health care professionals involved in the assessment of pediatric SLE patients reviewed the literature to identify cognitive domains most commonly affected in pediatric SLE and in adult SLE. They then reviewed the standardized tests available for children and adolescents that assess the cognitive domains identified. Through a structured consensus formation process, the committee considered the psychometric characteristics and durations of the tests., Results: A test battery was developed that appears suitable to provide a comprehensive assessment of cognitive domains commonly affected by pediatric SLE within a 2.5-hour period., Conclusion: It is hoped that the consistent use of this reliable and efficient battery increases the practicality of routine evaluations in pediatric SLE, enabling between-cohort comparisons and facilitating the longitudinal assessment of individual patients over time.

Background: Kiwifruit (Actinidia spp.) are a relatively new, but economically important crop grown in many different parts of the world. Commercial success is driven by the development of new cultivars with novel consumer traits including flavor, appearance, healthful components and convenience. To increase our understanding of the genetic diversity and gene-based control of these key traits in Actinidia, we have produced a collection of 132,577 expressed sequence tags (ESTs)., Results: The ESTs were derived mainly from four Actinidia species (A. chinensis, A. deliciosa, A. arguta and A. eriantha) and fell into 41,858 non redundant clusters (18,070 tentative consensus sequences and 23,788 EST singletons). Analysis of flavor and fragrance-related gene families (acyltransferases and carboxylesterases) and pathways (terpenoid biosynthesis) is presented in comparison with a chemical analysis of the compounds present in Actinidia including esters, acids, alcohols and terpenes. ESTs are identified for most genes in color pathways controlling chlorophyll degradation and carotenoid biosynthesis. In the health area, data are presented on the ESTs involved in ascorbic acid and quinic acid biosynthesis showing not only that genes for many of the steps in these pathways are represented in the database, but that genes encoding some critical steps are absent. In the convenience area, genes related to different stages of fruit softening are identified., Conclusion: This large EST resource will allow researchers to undertake the tremendous challenge of understanding the molecular basis of genetic diversity in the Actinidia genus as well as provide an EST resource for comparative fruit genomics. The various bioinformatics analyses we have undertaken demonstrates the extent of coverage of ESTs for genes encoding different biochemical pathways in Actinidia.

Purpose: The association between language delay and behavior problems in toddlers was examined in 2 studies, 1 conducted in a developmental clinic in New Jersey (Study 1; N = 83) and the other conducted in a developmental clinic in New York (Study 2; N = 103)., Method: In both clinics, parents of 18- to 35-month-olds completed the Language Development Survey (LDS) and the Child Behavior Checklist/1.5-5 (CBCL). In Study 2, the Preschool Language Scale-Fourth Edition (PLS-4) was also administered. Neurodevelopmental delay (ND) and pervasive developmental disorder (PDD) symptoms were also assessed in both studies but were done so using different measures., Results: In Study 1, LDS Vocabulary score and CBCL Total Problems, Internalizing, and Withdrawn scores were significantly correlated. However, when children with ND and/or suspected PDD were excluded, only the correlation between LDS Vocabulary and Withdrawn remained significant. In Study 2, only the correlation between LDS Vocabulary and Withdrawn approached significance. Children delayed in language on the PLS-4 had higher CBCL scores than typically developing toddlers only on the CBCL Withdrawn syndrome., Conclusion: Significant associations between language delays and behavior problems were not found in 2 samples of 18- to 35-month-olds when children with ND and PDD were excluded, except that toddlers with language delays appeared to show elevated social withdrawal relative to typically developing toddlers.

The domestic apple (Malus domestica; also known as Malus pumila Mill.) has become a model fruit crop in which to study commercial traits such as disease and pest resistance, grafting, and flavor and health compound biosynthesis. To speed the discovery of genes involved in these traits, develop markers to map genes, and breed new cultivars, we have produced a substantial expressed sequence tag collection from various tissues of apple, focusing on fruit tissues of the cultivar Royal Gala. Over 150,000 expressed sequence tags have been collected from 43 different cDNA libraries representing 34 different tissues and treatments. Clustering of these sequences results in a set of 42,938 nonredundant sequences comprising 17,460 tentative contigs and 25,478 singletons, together representing what we predict are approximately one-half the expressed genes from apple. Many potential molecular markers are abundant in the apple transcripts. Dinucleotide repeats are found in 4,018 nonredundant sequences, mainly in the 5'-untranslated region of the gene, with a bias toward one repeat type (containing AG, 88%) and against another (repeats containing CG, 0.1%). Trinucleotide repeats are most common in the predicted coding regions and do not show a similar degree of sequence bias in their representation. Bi-allelic single-nucleotide polymorphisms are highly abundant with one found, on average, every 706 bp of transcribed DNA. Predictions of the numbers of representatives from protein families indicate the presence of many genes involved in disease resistance and the biosynthesis of flavor and health-associated compounds. Comparisons of some of these gene families with Arabidopsis (Arabidopsis thaliana) suggest instances where there have been duplications in the lineages leading to apple of biosynthetic and regulatory genes that are expressed in fruit. This resource paves the way for a concerted functional genomics effort in this important temperate fruit crop.

Managing surgical wounds healing by primary intention is likely to become less problematic with the development of more effective advanced wound dressings; increasingly effective methods of medicated pain management; education; and advances in minimal access surgical (MAS) techniques. Future research is likely to focus on management of patients with surgical wounds healing by secondary intention. If so, management of surgical wound pain must become an integral part of assessment. Theatre practitioners, clinical nurses and surgical practitioners, working as part of the multidisciplinary team, are ideally placed to undertake this work and to include multimodal, holistic approaches to caring for surgical wounds and controlling surgical wound pain (Gould, 1999). Patient support and education is likely to become an increasing priority, particularly in view of the significant move from inpatient care to short-stay and day-case surgery.

Multigene families are common in higher organisms. However, due to the close similarities between members, it is often difficult to assess the individual contribution of each gene to the overall expression of the family. In Arabidopsis thaliana, there are four genes encoding the small subunits (SSU) of ribulose-1.5-bisphosphate carboxylase oxygenase (rubisco) whose nucleotide sequences are up to 98.4% identical. In order to overcome the technical limitations associated with gene-specific probes (or primers) commonly used in existing methods, we developed a new gene expression assay based on the RACE (rapid amplification of cDNA ends) technique with a single pair of primers. With this RACE gene expression assay, we were able to determine the relative transcript levels between four Arabidopsis SSU genes. We found that the relative SSU gene expression differed significantly between plants grown at different temperatures. Our observation raises the possibility that an adaptation of rubisco to the environment may be achieved through the specific synthesis of the SSU proteins, which is determined by the relative expression levels between the SSU genes., (Copyright 2001 Academic Press.)

In kiwifruit, much of the softening process occurs prior to the respiratory climacteric and production of ethylene. This fruit therefore represents an excellent model system for dissecting the process of softening in the absence of endogenous ethylene production. We have characterized the expression of three polygalacturonase (PG) cDNA clones (CkPGA, B and C) isolated from fruit of Actinidia chinensis. Expression of CkPGA and B was detected by northern analysis only in fruit producing endogenous ethylene, and by RT-PCR in other tissues including flower buds, petals at anthesis, and senescent petals. CkPGA promoter fragments of 1296, 860 and 467 bp fused to the beta-glucuronidase (uidA) reporter gene directed fruit-specific gene expression during the climacteric in transgenic tomato. CkPGC gene expression was observed in softening fruit, and reached maximum levels (50-fold higher than for CkPGA and B) as fruit passed through the climacteric. However, expression of this gene was also readily detected during fruit development and in fruit harvested prior to the onset of softening. Using RT-PCR, expression of CkPGC was also detected at low levels in root tips and in senescent petals. These results suggest that PG expression is required not only during periods of cell wall degeneration, but also during periods of cell wall turnover and expansion.

This work addresses the role of calcitonin gene-related peptide (CGRP) in the physiological maintenance of acetylcholinesterase (AChE) molecular forms in motor endplate regions of adult Sprague-Dawley rat fast-twitch anterior gracilis muscles. Results show that: (a) CGRP is present in obturator nerve motor neurons which supply the gracilis muscle, as well as in the corresponding motor endplate regions where high levels of both AChE activity and acetylcholine receptors (AChRs) are detected; (b) endplate-associated CGRP declines with muscle denervation several hours before any changes in AChE forms are detected; (c) a single subcutaneous injection of CGRP reversibly reduces the activities of all AChE forms in endplate regions of normally innervated and otherwise untreated gracilis muscles; and (d) similar treatment with hCGRP(8-37), a potent and selective CGRP antagonist, produces the opposite effects, i.e., it reversibly elevates the activities of all AChE forms. These and other findings indicate that CGRP and hCGRP(8-37) influence the mechanism(s) by which AChE forms are maintained in intact adult gracilis muscles. Indeed, the findings lend strong support to the hypothesis that nerve-derived CGRP plays a key role in the trophic regulation of AChE forms at the neuromuscular junction.

A cDNA encoding polygalacturonase-inhibiting protein (PGIP) from mature apple fruit has been cloned and characterized. The open reading frame encodes a polypeptide of 330 amino acids, in which 24 amino acids at the N-terminus comprise the signal peptide. Apple PGIP contains 10 imperfect leucine-rich repeat sequence motifs averaging 24 amino acids in length. In addition to the 1.3 kb PGIP transcript, the cloned cDNA also hybridized to RNA molecules with sizes of 3.2 and 5.0 kb. Genomic DNA analysis revealed that the apple PGIP probably belongs to a small family of genes. PGIP transcript levels varied in fruit collected at different maturities, suggesting the gene is developmentally regulated. Very high PGIP transcript levels were detected in decayed areas and the tissue adjacent to the inoculation sites of Penicillium expansum and Botrytis cinerea. However, no increase in the amount of PGIP transcript in tissue distant from the decayed region was observed. Wounding on fruit also induced PGIP gene expression but to a much lessser extent when compared with decayed areas. After storage at 0 degrees C for 1 month, the abundance of PGIP transcript in ripe fruit was substantially increased. The PGIP gene in immature and ripe fruit was rapidly up-regulated by fungal infections, while in stored fruit the induction was very limited and concurred with an increase of fruit susceptibility to fungal colonization. Since PGIP gene expression is regulated by fruit development and responds to wounding, fungal infection and cold storage, these observations suggest that apple PGIP may have multiple roles during fruit development and stress response.

Levels of 1-aminocyclopropane-1-carboxylate (ACC) oxidase and polygalacturonase (PG) mRNAs were characterized during ripening of Royal Gala, Braeburn and Granny Smith apples. Both ACC-oxidase and PG mRNAs were up-regulated in ripening fruit of all three cultivars. Expression in Royal Gala was detected earlier than in Braeburn and Granny Smith, relative to internal ethylene concentration. Genomic clones corresponding to the ACC-oxidase and PG mRNAs expressed in ripe apple fruit were isolated and ca. 2 kb of each promoter was sequenced. The start point of transcription in each gene was mapped by primer extension, and sequences homologous to elements in other ethylene-responsive or PG promoters were identified. The fruit specificity of the apple ACC-oxidase and PG promoters was investigated in transgenic tomato plants using a nested set of promoter fragments fused to the beta-glucuronidase (gusA) reporter gene. For the ACC-oxidase gene, 450 bp of 5' promoter sequence was sufficient to drive GUS expression, although this expression was not specific to ripening fruit. Larger fragments of 1966 and 1159 bp showed both fruit and ripening specificity. For the PG gene, promoter fragments of 1460 and 532 bp conferred ripening-specific expression in transgenic tomato fruit. However GUS expression was down-regulated by 2356 bp of promoter, suggesting the presence of a negative regulatory element between positions -1460 and -2356.

A 71-year-old woman presented with gastrointestinal bleeding. She had been stabilized on warfarin for the previous few months. Terbinafine had been started 32 days prior to this episode for the treatment of onychomycosis. The patient had been on cimetidine for the previous 2 years and on other medications for the last 10 years. At the time of admission for the gastrointestinal bleeding, the coagulation indices were all above the therapeutic range. Endoscopy of the gastrointestinal tract exhibited diffuse intestinal 'oozing' consistent with coagulopathy as the cause of bleeding. Terbinafine may have had an effect on the metabolism of warfarin since both are metabolized through the liver and cimetidine can reduce terbinafine clearance by 33% resulting in higher concentrations of the antifungal agent. Our experience suggests that caution should be exercised when prescribing terbinafine to a patient receiving warfarin.

This case study presents an industry perspective on medical innovation. Introduced as a scientific breakthrough in the late 1970s, transcutaneous oxygen monitoring was rapidly adopted for routine use in neonatal intensive care. But plagued by technical problems, it was within a decade being replaced by pulse oximetry, a still more recent technology. Its use in efforts to prevent retinopathy of prematurity, an eye disease of preterm newborns often leading to blindness, proved disappointing. The project included interviews with executives and design engineers of companies marketing the device, with investigators who had pioneered the technology, and with senior practicing neonatologists. The findings, reflecting complexity and uncertainty, are relevant to issues concerning health care in the United States and other developed nations. They centre on the key role and ultimate responsibility of the medical profession, with a need for greater attention to the scientific training of health care workers, as perceived by members of the medical device industry. The views of senior investigators are integrated into the picture, with discussion of major challenges faced by the medical community.

In an attempt to identify important predictors of failure of passive immunoglobulin transfer (< 800 mg of IgG/dl), identify calves with failure of passive immunoglobulin transfer, and determine the effects of a colostrum supplement, blood samples were collected from 263 calves at postpartum hours 10 and 24. Calves of dams diagnosed with mastitis had lower mean plasma protein and IgG concentrations at 10 (P < 0.05) and 24 (P < 0.01) hours. Plasma protein and IgG concentrations were similar for single and twin calves at 10 hours, but IgG concentration at 24 hours was higher (P < 0.01) in twin calves. Calves born to dams that had dystocia had numerically lower mean plasma protein and IgG concentrations than did calves born to dams that had normal delivery. However, observed differences were small and, after adjustment for other important factors, these differences were not significant. Age of dam was associated with plasma protein (P < 0.05) and IgG (P < 0.10) concentrations at 10 hours, but had no effect at 24 hours. Plasma protein and IgG concentrations decreased as calves were born later in the calving season, although the association of birth date with IgG concentration at 24 hours was marginal (P = 0.07). Calf sex, dam body condition score, and birth weight were not related to plasma protein or IgG values. The sensitivity and specificity of a cutoff value of 4.8 g of protein/dl of plasma, measured at 10 hours, for diagnosing failure of passive immunoglobulin transfer at 10 hours were 78 and 94%, and for diagnosing failure of passive immunoglobulin transfer at 24 hours were 88 and 73%, respectively. A colostrum supplement administered to calves with low plasma protein concentration at 10 hours had no effect on plasma protein or IgG values at 24 hours or on preweaning morbidity and mortality.

The main component of Alzheimer's disease (AD) amyloid deposits is amyloid beta-peptide (A beta), a fragment of the larger amyloid precursor protein (APP). The cellular source of A beta is not known, but a circulatory origin has been postulated. We studied human blood from healthy individuals and found that platelets account for almost 90% of the total anti-A beta immunoreactivity detected in whole blood. Using reverse-phase HPLC, we identified a platelet peptide which corresponds to A beta by three criteria: (a) it shares a retention time with the synthetic A beta 1-40 peptide in two consecutive HPLC tests; (b) it interacts with two anti-A beta antibodies in separate ELISAs; and, (c) its partial N-terminal amino acid sequence closely matches that of A beta. The detection of this peptide in platelets indicates that, aside from the well-known non-amyloidogenic (secretory) pathway, the processing of APP in platelets from healthy individuals also involves an amyloidogenic pathway. These findings are consistent with the view that platelets are one of the major sources of A beta in the circulation.

A full-length cDNA clone encoding apple (Malus domesticus) polyphenol oxidase (PPO) was isolated from a fruit peel cDNA library. Southern analysis indicated that apple PPO is encoded by a divergent multigene family. By northern analysis, PPO mRNA was only detected in a fruit sample taken one week after full bloom. PPO mRNA accumulated in wounded tissues, and also in peel tissue showing the symptoms of superficial scald, a post-harvest disorder. The induction of PPO mRNA provides the first evidence for transcriptional control of PPO expression after wounding or the manifestation of a physiological disorder.

A beta-galactosidase was purified from cortical tissue of ripe apples (Malus domestica Borkh. cv Granny Smith) using a procedure involving affinity chromatography on lactosyl-Sepharose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that two polypeptides of 44 and 32 kD were present in the fraction that showed activity against the synthetic substrate p-nitrophenol-beta-D-galactopyranoside. The enzyme preparation was incubated with polysaccharide extracts from apple cell walls containing beta-(1-->4)-linked galactans, and products of digestion were analyzed by gas chromatography. Small amounts of monomeric galactose were released during incubation, showing that the enzyme was active against native substrates. Amino acid sequence information was obtained from the purified protein, and this showed high homology with the anticipated polypeptide coded by the ethylene-regulated SR12 gene in carnation (K.G. Raghothama, K.A. Lawton, P.B. Goldborough, W.R. Woodson [1991] Plant Mol Biol 17: 61-71) and a harvest-related pTIP31 cDNA from asparagus (G. King, personal communication). Using the asparagus cDNA clone as a probe, an apple homolog (pABG1) was isolated. This clone contains a 2637-bp insert, including an open reading frame that codes for a polypeptide of 731 amino acids. Cleavage of an N-terminal signal sequence would leave a predicted polypeptide of 78.5 kD. Genomic DNA analysis and the isolation of other homologous apple clones suggest that pABG1 represents one member of an apple beta-galactosidase gene family. Northern analysis during fruit development and ripening showed accumulation of pABG1-homologous RNA during fruit ripening. Enzyme activity as measured in crude extracts increased during fruit development to a level that was maintained during ripening.

Divalproex sodium (DVS; Depakote) is a commonly used antiepileptic agent that increases the levels of gamma aminobutyric acid. Spasticity from different causes may be due to a deficiency of inhibitory transmitters like gamma aminobutyric acid or an excess of excitatory neurotransmitters. Spasticity also may be accompanied by pain. The authors administered DVS orally for pain and spasticity in three patients with a history of spinal cord injury and one patient with a history of head injury. Three patients had marked improvement in spasticity and pain. One patient, who had some symptomatic improvement in spasticity, could not tolerate DVS because of gastric irritation. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used, no such side effects were detected with DVS. It is suggested that a possible enhancement by DVS of gamma aminobutyric acid-ergic postsynaptic inhibition of motor reflex arc in the spinal cord may represent a new nonsedating, management approach for spasticity as a result of traumatic spinal cord and head injuries.

Six steer calves, surgically fitted with a permanent cannula in the rumen, omasoabomasal orifice, abomasum, and duodenum were used to determine total digesta flow and volatile fatty acid (VFA) concentration at various points in the digestive tract. The omasoabomasal cannula had a flexible nylon sleeve that could be exteriorized through the abomasal cannula to collect omasal effluent. Three experiments were conducted: 95% concentrate fed at maintenance (2,670 g of organic matter intake/d); 95% concentrate fed ad libitum (3,484 g of organic matter intake/d); and brome hay fed ad libitum (2,927 g of organic matter intake/d). Calves were offered the diet in 12 portions daily. Each experiment included a 14-day adaptation period and a 2-day sample collection period during which chromic oxide was used as a digesta flow marker. In all 3 experiments, VFA concentration was greatest in the rumen sample (84 to 109 mM), intermediate in the omasal sample (32 to 40 mM), and lowest in the duodenal sample (7 to 14 mM, P < 0.01). Total fluid flow at the duodenum was 13 to 18 L/d greater than flow at the omasum (P < 0.10). Omasal VFA flow was twofold greater than duodenal VFA flow (P < 0.05). There was a net fluid increase and net disappearance of VFA across the abomasum. The cannulation technique was useful for repeated collection of omasal effluent for at least 3 months.

Neonatal extracorporeal membrane oxygenation (ECMO), a technology for the treatment of respiratory failure in newborns, is used as a case study to examine statistical and ethical aspects of clinical trials and to illustrate a proposed 'ethics of evidence', an approach to medical uncertainty within the context of contemporary biomedical ethics. Discussion includes the twofold aim of the ethics of evidence: to clarify the role of uncertainty and scientific evidence in medical decision-making, and to call attention to the need to confront the irreducible nature of uncertainty.

A case of a 57-year-old man with hypertension and stable angina, on aspirin therapy, who was treated for epistaxis with intranasal cocaine, and who subsequently suffered a non-Q wave myocardial infarction is reported. Of note, the cocaine was administered in a manner which differs from that advocated in standard references. Specifically, intranasal packing soaked with 4% cocaine was left in place with continuous nasal mucous membrane contact over 5 to 6 hours. The authors speculate that myocardial infarction occurred on the basis of coronary artery spasm. This case should alert practitioners to myocardial ischemia occurring as a complication of the therapeutic use of intranasal cocaine for the treatment of epistaxis.

We report the isolation of a ripening-related apple cDNA which is complementary to a mRNA which may be involved in ethylene production. Poly(A)+ RNA was extracted from cortical tissue of ripe apple fruit (Malus domestica Borkh cv. Golden Delicious) and a cDNA library constructed in the plasmid vector pSPORT. The library was screened with pTOM13, a tomato cDNA clone thought to code for ACC oxidase in that fruit. An apple cDNA clone (pAP4) was isolated and sequenced. The 1182 bp cDNA insert includes an open reading frame of 942 bp, and shows strong homology with reported tomato and avocado sequences, both at the nucleic acid and amino acid levels. The polypeptide has a calculated molecular mass of 35.4 kDa and a calculated pI of 5.15. In apple cortical tissue, expression of pAP4-complementary RNA increased with ethylene production by the fruit during ripening. Expression was also enhanced in both ethylene-treated and wounded fruit.

Pneumocystis carinii pneumonia is often difficult to diagnose in an ambulatory care setting. Previous reports have identified elements of the clinical history, physical examination, and clinical testing that are useful predictors of P carinii pneumonia. We analyzed published data on these predictors and measured them against methodologic standards for clinical prediction rules. Variables with high negative or positive predictive value for P carinii pneumonia, low error rates, or compelling biologic credibility were then selected to develop an untested clinical prediction rule for P carinii pneumonia. We suggest that dyspnea, oral lesions, chest roentgenographic examination, and pulse oximetry may be used to select patients requiring sputum testing and/or bronchoscopy for the diagnosis of P carinii pneumonia. The role of pulse oximetry in the diagnosis of P carinii pneumonia merits further study.

A 62-year-old man who presented with gross hematuria was found to have a severe and prolonged coagulopathy. The workup involved mixing studies, which suggested an acquired factor deficiency, and specific factor assays, which demonstrated isolated defects in vitamin K-dependent factors. With vitamin K deficiency excluded, and serum warfarin levels undetectable, so-called superwarfarin ingestion was suspected. This diagnosis was subsequently proved by biochemical evidence (an increase in the serum vitamin K epoxide-vitamin K ratio) and compatible history. This case illustrates how a logical workup can lead to a diagnosis of superwarfarin ingestion, even without a history of such an ingestion. New serum assays for specific superwarfarins are also mentioned. This case report should increase clinicians' awareness of long-acting rodenticide ingestions.

Sixty heifers were infected with bluetongue virus (BTV) by the bites of the vector and by inoculation with insect origin virus. During the acute and convalescent stages of the infection, embryos were collected nonsurgically from these animals and washed according to the recommendations of the International Embryo Transfer Society (1). No BTV was isolated from 77 of these embryos when they were inoculated onto cell culture and into embryonating chicken eggs. There was no evidence of lateral BTV transmission when 231 of these embryos were transferred into susceptible recipients, nor was there evidence of vertical BTV transmission to the 88 calves resulting from these transfers. Another six donors that were assumed to have recovered from a natural infection of BTV, were added to the study to increase the probability of obtaining embryos from a persistently infected BTV carrier. However, it was determined later that these animals had not been infected with BTV but with the closely-related epizootic hemorrhagic disease virus (EHDV). Embryos were collected from these donors and washed as above. Neither BTV nor EHDV was isolated from 26 of these embryos by the inoculation of cell culture and embryonating chicken eggs. There was no evidence of lateral BTV or EHDV transmission to recipients of 15 of these embryos or of vertical BTV or EHDV transmission to the resulting 7 calves. However, two recipients of embryos from one of these donors developed antibodies to BTV 6 to 9 months after transfer. Passive antibodies to BTV were also detected in their calves. There is good evidence that these two recipients acquired BTV from natural exposure to infected insect vectors and not from the transferred embryos.

Poly(A)(+) RNA was extracted from cortical tissue of apple fruit (Malus domestica Borkh. cv Golden Delicious), and in vitro translation products were analyzed by two-dimensional gel electrophoresis. As fruit internal ethylene concentration increased from a basal level of 0.0 to 0.1 microliter per liter to 1 to 5 microliters/liter, substantial changes in the pattern of in vitro translation products were observed. More subtle changes were observed as fruit continued to ripen and internal ethylene concentration increased to 80 to 100 microliters/liter. Overall, the levels of at least six mRNAs were found to increase, while one mRNA decreased. Analysis of proteins extracted from ripening fruit indicated that the level of at least three proteins increased with ripening.

Thirty-two castrated male crossbred growing pigs (average initial wt 26.9 kg) were used to determine the effect of a high level of dietary protein (37%) compared with a normal level of protein (15%) on enterobacteria and Campylobacter sp. inhabitation in the large intestine and on visceral organ hypertrophy and the interrelationships between these two factors. Pigs were kept in pairs (eight pens of two pigs/diet) and fed their respective diets and libitum. Eight pigs (two pens of two pigs fed each diet) were killed at wk 4, 8, 12 and 16 without fasting. Fecal samples were obtained every 2 wk from animals scheduled for necropsy at 16 wk, and colon contents were obtained from all pigs at necropsy; samples were enumerated individually for enterobacteria and Campylobacter sp. Weights of heart, lungs, liver, kidneys, perirenal fat and empty stomach, small intestine and large intestine were recorded at necropsy. Stomach, cecum and proximal colon were sectioned for histopathologic examination. Daily body weight gain was depressed by high dietary protein, but liver and kidneys were heavier in the high protein group than in controls at each time interval. Mild lymphoid hyperplasia of Peyer's patches in the small intestine in some pigs in both groups was indicative of antigenic stimulation but not of pathologic significance. There was no effect of diet on counts of enterobacteria or Campylobacter sp. in feces or colon contents during the 16-wk experiment. We conclude that the hypertrophic response of the tissues of growing pigs to high dietary protein is not the result of the presence of Campylobacter sp. or enterobacteria in the colon contents.

Bovine viral diarrhea virus (BVDV) infections resulting in clinical disease developed in calves, despite vaccination of dams and high maternal BVDV antibody titers in calves. Eight persistently infected (PI) calves born to immunocompetent dams were identified in the herd. Neutralizing BVDV antibody titers of PI calves had decreased greatly by the time the calves were 1 to 2 months old. Antibody titers of PI calves decreased more rapidly than antibody titers of calves that were not PI. Reduced antibody titers in PI calves allowed detection of BVDV in serum specimens of all PI calves by the time they were 8 weeks old. Persistent infection in suspect calves was detectable serologically and was confirmed by virologic examination of serum specimens 4 months after weaning, when the calves were 9 months old. Growth rates were reduced in viremic calves.

This study reports on two aspects of outcome in a sample of infants whose birth weights ranged from 500 to 799 gm. First, maternal and early neonatal variables were analyzed by means of stepwise logistic regression. Five-minute Apgar score and initial pH were the only variables that predicted mortality at p less than or equal to 0.05. Second, the surviving infants were examined at ages ranging from 17 months to 7 years. The majority (72%) had neurologic and/or developmental examinations in the suspect or abnormal range and required rehabilitation or early intervention services.

This study determined the lower brainstem sites at which electrical stimulation elicits stepping movements of the forelimbs and hindlimbs. Rats (N = 45), anesthetized with nembutal, were fixed in a stereotaxic apparatus so that their limbs contacted a moving treadmill belt. Electrical stimulation (100 microA, 10-sec trains, 0.5-msec cathodal pulses, 50-Hz pulse frequency) was applied every 200 micron through 173 movable electrodes. Well coordinated quadrupedal stepping was elicited by stimulation at dorsal posterior mesencephalic sites including the inferior collicular commissure, the central gray, the nucleus cuneiformis and lateral aspects of the pedunculopontine tegmental nucleus. Caudal and ventral to this general region, sites supporting quadrupedal stepping appeared mainly in or near the spinal trigeminal nucleus. Stepping with only the forelimb and hindlimb contralateral to the stimulation site was associated with the corticospinal tract, the lateral pontis oralis, the lateral pontis caudalis and the ventral reticular nucleus of the medulla. Bilateral forelimb stepping was associated with the trigeminal system and the gigantocellular reticular nucleus. At the level of the rostral medulla, systems involved in bilateral forelimb stepping and contralateral hindlimb stepping appear to be located medially. Systems concerned with bilateral hindlimb stepping appear to be located laterally.

The Coulter Counter model TA II was evaluated as a gynecologic cytodiagnostic tool. The instrument produces particle size histograms as plots of percent volume versus particle volume in 16 channels with each channel corresponding to twice the volume of the next lower channel. Cell volume distributions were obtained using cell suspensions from patients with cervicitis, inflammation, dysplasia or carcinoma and were compared with those from normal subjects. Although this method is superior to other methods of volume distribution analysis, it does not satisfy the stringent requirements of a cervical cancer mass screening method.

The literature on mother-infant separation involving healthy newborn infants is discussed, and the validity of extrapolating these findings to high-risk infants is examined. The author suggests that factors other than separation are operative in parental response to the infant at risk, and that the quality of mother-infant interactions is ultimately more important than the early onset of these interactions.

In human subjects cortisol raises the osmotic threshold for vasopressin release. The presumption that this results from a direct inhibitory action of cortisol on osmotically stimulated vasopressin release has been tested in conscious rhesus monkeys. Preparatory surgical procedures included chronic bladder catheterization, placement of cannulae in the right atrium, the left jugular vein and the stomach and stereotaxic insertion of metal cannulae in both supraoptic nuclei. The osmotic threshold for vasopressin release was defined as the plasma osmolality at the beginning of the 3 min urine sample in which free water clearance first fell by greater than 2 SD below the mean control level, in response to 5% saline infusion during constant hydration. Compared with control substances (0.9% saline solution or 11-deoxycortisol crystals), cortisol solution or crystals introduced into both supraoptic nuclei significantly lowered the plasma osmolality during the water-induced pre-saline diuresis, so that a larger amount of 5% NaCl infusion was required to reach the osmotic threshold. Thus, cortisol introduced into the supraoptic nuclei prolonged the duration of 5% saline infusion needed to reach the osmotic threshold, and raised the increment in plasma osmolality needed to reach the threshold but cortisol did not significantly raise the absolute level of the threshold.