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Biomedical subjects

J Harding

Publications and source records attributed to J Harding.

At least 37 records · Page 2Linked to original sources

Combining descriptive and experimental analyses of young children with behavior problems in preschool settings.

This investigation shows the merits of preceding experimental analyses with descriptive analyses of functional variables with preschool children who engage in problematic behavior. A two-phase descriptive analysis was conducted in daycare settings with three children. In Phase 1, the authors assessed the relation between child behavior and structural events. During Phase 2, the same behavior was replotted by functional variables. The results showed that when the descriptive data were plotted via functional variables, specific hypotheses could be generated regarding the variables controlling appropriate behavior. This procedure permitted the subsequent use of very brief experimental analyses to further identify functional relations. The use of descriptive analyses of functional rather than structural variables may be an important component in the assessment of problem behavior in community settings.

Behavior Therapy↗

Reproduction of lesions of postweaning multisystemic wasting syndrome in gnotobiotic piglets.

Neonatal gnotobiotic piglets were inoculated with tissue homogenates and low- and high-passage cell culture material to determine if the lesions of the newly described porcine postweaning multisystemic wasting syndrome (PMWS) could be reproduced. For this, 17 3-day-old gnotobiotic piglets were inoculated intranasally with pelleted chloroform-treated, filtered extracts from cell cultures, filter-sterilized homogenates of lymphoid tissue from PMWS-affected piglets, or control materials. Piglets were maintained in germ-free isolators for up to 5 weeks after infection prior to euthanasia and collection of samples for analysis. All piglets inoculated with the viral inocula developed lesions typical of PMWS, including generalized lymphadenopathy, hepatitis, nephritis, interstitial pneumonia, myocarditis, and gastritis. Porcine circovirus (PCV), as well as porcine parvovirus (PPV), was detected in tissues by virus reisolation, polymerase chain reaction analysis, or immunohistochemistry. All infected piglets developed moderate to high titers of antibody to PCV and moderate titers to PPV. No lesions, virus, or virus-specific antibodies were detected in sham-inoculated or uninoculated control piglets. These studies demonstrate that the lesions of PMWS can be experimentally reproduced in gnotobiotic piglets using filterable viral agents derived from pigs with PMWS and provide an experimental basis for further investigation into the pathogenesis and control of this emerging infectious disease in swine.

Animals↗

Evaluation of antecedent stimulus parameters for the treatment of escape-maintained aberrant behavior.

We evaluated a methodology for identifying the range of stimulus features of antecedent stimuli associated with aberrant behavior in demand contexts in natural settings. For each participant, an experimental analysis of antecedents (Phase 1) was conducted to confirm the hypothesis that task instructions occasioned increases in aberrant behavior. During Phase 2, specific stimulus features associated with the presentation of task instructions were assessed by evaluating the child's behavior across two distinct settings, therapists, and types of tasks in a sequential fashion. Aberrant behavior occurred immediately across settings and therapists, presumably because the presence of a discriminative stimulus for escape-maintained behavior (the delivery of a task instruction) occasioned aberrant behavior. However, aberrant behavior decreased initially across tasks, suggesting that familiarity with the task might be a variable. During Phase 3, an experimental (functional) analysis of consequences was conducted with 2 participants to verify that aberrant behavior was maintained by negative reinforcement. During Phase 4, a treatment package that interspersed play with task instructions was conducted to disrupt the ongoing occurrence of aberrant behavior. Immediate and durable treatment effects occurred for 2 of the 3 participants.

Aggression↗

Lack of evidence of conserved lentiviral sequences in pigs with post weaning multisystemic wasting syndrome.

In order to investigate the role of retroviruses in the recently described porcine postweaning multisystemic wasting syndrome (PMWS) serum and leukocytes were screened for reverse transcriptase (RT) activity, and tissues were examined for the presence of conserved lentiviral sequences using degenerate primers in a polymerase chain reaction (PCR). Serum and stimulated leukocytes from the blood and lymph nodes from pigs with PMWS, as well as from control pigs had RT activity that was detected by the sensitive Amp-RT assay. A 257-bp fragment was amplified from DNA from the blood and bone marrow of pigs with PMWS. This fragment was identical in size to conserved lentiviral sequences that were amplified from plasmids containing DNA from several lentiviruses. Cloning and sequencing of the fragment from affected pigs, however, did not reveal homology with the recognized lentiviruses. Together the results of these analyses suggest that the RT activity present in tissues from control and affected pigs is the result of endogenous retrovirus expression, and that a lentivirus is not a primary pathogen in PMWS.

Amino Acid Sequence↗

Is a normally functioning gastrointestinal tract necessary for normal growth in late gestation?

It is known that neonates with congenital abnormalities of the intestine tend to be growth-retarded. We wished to explore the hypothesis that normal fetal gut function is needed for normal growth in late gestation. If this is true, then different populations of babies with different congenital gut abnormalities would be expected to have similar impairments of growth and be small at birth. This growth retardation would be more marked in term than in preterm babies and would be independent of other congenital anomalies. To test these hypotheses, we examined 43 babies born with gastroschisis (GS) in Auckland, New Zealand; 69 babies born with GS in Birmingham, England; and 60 babies born with intestinal atresia (IA) in Auckland. For Auckland babies with GS, the mean weight standard deviation score (WSDS) (i.e., birth weight relative to the mean birth weight for gestation) for term babies was lower than that for preterm babies (-0.932+/-0.180 vs -0.064+/-0.237, P=0.014). This was also true for Birmingham babies with GS (-0.991+/-0.193 vs -0.36 +/-0.153, P=0.028). For babies with IA, the mean WSDS for term babies was lower than that for preterm babies (-0.627+/-0.266 vs 0. 057+/-0.211, P=0.034). There was no significant difference between the mean WSDS of babies with and without major congenital abnormalities (-0.402+/-0.201 vs -0.271, P=0.70). Our results demonstrate that term babies born with GS are significantly growth-retarded compared with premature babies born with GS. Term babies born with a proximal IA are also growth-retarded. This strongly suggests that in late gestation, the normal growth is dependent on a normally functioning gastrointestinal tract that allows exposure of the proximal intestinal mucosa to ingested amniotic fluid.

Abdominal Muscles↗

Methodology for the study and projection of surgical and anaesthetic workforce.

The Australian Medical Workforce Advisory Committee has studied the specialties of anaesthesia, general surgery, orthopaedics, ophthalmology and urology in Australia. A methodology is presented for rationalizing various data sources to establish numbers and characteristics of the existing workforce, for applying a variety of information to establish opinion about current adequacy, to project future needs and to advise the mechanisms to ensure delivery of services. This study emphasizes the importance of the cooperative input of governments, health administrations and professional bodies, careful gathering of fundamental data, the studied application of uneven pieces of evidence, recognition of changes in needs and demands, the overlap of sectors of the medical workforce in service delivery, and the requirement for continued study and monitoring. The current size of the workforce in these surgical specialties is found to be satisfactory overall but with some uneven distribution. The anaesthetic workforce is found to be slightly deficient in number overall. The growth of future demand for these specialties was estimated between 1% and 3% per annum and requirements for increases in trainee numbers to meet these projected future demands are defined.

Anesthesia↗

Antenatal indomethacin--adverse fetal effects confirmed.

We examined the association between antenatal indomethacin exposure and adverse neonatal outcome in a matched retrospective cohort study of infants born to 72 mothers at less than 31 weeks' gestation. Indomethacin-exposed mothers were matched to controls by gestational age at delivery, antenatal corticosteroid exposure, prolonged spontaneous rupture of membranes, multiple pregnancy, thyrotrophin releasing hormone (TRH) exposure, and neonatal sex. Periventricular haemorrhage was significantly increased for infants delivered within 48 hours of maternal indomethacin exposure (Grade 1 and 2 19% versus 6%, and Grades 3 and 4 28% versus 3% (p<0.03)). Persistent patent ductus arteriosus was more common in those infants delivered within 48 hours of maternal indomethacin exposure (40% versus 20% (p<0.04)). More neonates exposed to antenatal indomethacin failed to respond to postnatal indomethacin to close a patent ductus arteriosus, 60% versus 0% (p<0.04). There were no adverse effects demonstrated of indomethacin administered greater than 48 hours from delivery. We have confirmed a probable association between antenatal indomethacin administration and an increased incidence of neonatal periventricular haemorrhage, patent ductus arteriosus, and impaired renal function. The adverse neonatal effects appear to be greatest when indomethacin is administered within 48 hours of delivery. We recommend that indomethacin should be used with caution as a tocolytic agent for the treatment of preterm labour at gestations less than 31 weeks.

Cerebral Hemorrhage↗

Isolation of circovirus from lesions of pigs with postweaning multisystemic wasting syndrome.

Postweaning multisystemic wasting syndrome (PMWS), an apparently new disease, has been recognized in swine herds in western Canada. Young pigs with this disease have progressive weight loss, tachypnea, dyspnea, and jaundice, accompanied by interstitial pneumonia, lymphadenopathy, hepatitis, and nephritis. We examined more than 400 pigs from more than 70 herds in Alberta, Saskatchewan, and Manitoba with cases of PMWS. A small virus was isolated from a range of tissues from 8 of 8 affected pigs examined. The agent was identified as a circovirus-like virus using electron microscopy, immunohistochemical staining with porcine and rabbit immune serum, and in situ hybridization. Immunohistochemical examination of tissues from more than 100 affected pigs has revealed widespread viral antigen, often contained in circovirus-like inclusion bodies, in lesions from numerous organs. Although Koch's postulates remain to be fulfilled, these results demonstrate a high degree of association between the presence of the circovirus-like virus and PMWS in affected swine.

Alberta↗

Feelings and attitudes of gifted students.

Differences between the self-perceptions of gifted high school freshmen (n = 62) and nongifted peers (n = 162) were assessed regarding intimacy with family and peers, social support, family responsibilities, self-esteem, depression, and risk-taking behavior. Gifted students perceived themselves as being more intimate with friends, assuming fewer family responsibilities, and taking more risks (both sports- and danger-related risks). Contrary to the literature suggesting delays in the social development of gifted students, these data indicate that gifted students may be socially precocious when compared with their nongifted peers. Gifted students and their teachers were also administered the Perceptions about Giftedness Scale. Gifted students reported feeling the same as, or better than, their peers about their academic and social skills, and their teachers closely agreed. However, the teachers rated the gifted students as being less happy than the students rated themselves.

Achievement↗

Additional congenital anomalies in babies with gut atresia or stenosis: when to investigate, and which investigation.

A wide variety of additional congenital anomalies occur in babies born with a gut atresia or stenosis. The specific pattern of anomalies depends on the location of the atresia. The serious nature of many of them makes perioperative diagnosis imperative. Eighty-six babies born with pure oesophageal atresia (OA), duodenal atresia (DA) or stenosis, or jejuno-ileal atresia (JIA) have been studied. These, combined with over 2,000 cases in the literature, have been used to develop a protocol to optimally investigate babies with gut atresia for associated anomalies. The authors recommend routinely obtaining anterio-posterior and lateral chest and abdominal radiographs for babies with pure OA, DA and intestinal atresia, making sure the entire spine can be visualised. Cardiac and renal ultrasonography (US) should be routine in all babies with pure OA or DA. A micturating cystourethrogram should be done in those babies with abnormal urinary tract US or an associated anorectal anomaly. A sweat test should be obtained in babies with JIA, and a rectal biopsy should be taken in babies with the combination of Down's syndrome and DA to exclude Hirschsprung's disease.

Abnormalities, Multiple↗

The effects of kainic acid lesions on dopaminergic responses to haloperidol and clozapine.

The antipsychotic drugs haloperidol and clozapine have the common action of increasing dopamine metabolism in the striatum (nucleus accumbens, caudate-putamen) of the rat. Intracerebroventricular administration of kainic acid (KA) produces neuronal loss in limbic-cortical brain regions which project directly or indirectly to the striatum. In the present study, dopamine metabolism in subregions of the striatum was examined in rats with KA lesions after acute and chronic haloperidol or clozapine administration. The main findings was that the elevating effect of acute haloperidol treatment on the dopamine metabolite, DOPAC, was blocked in the nucleus accumbens shell and diminished in medial and laterodorsal caudate-putamen of the KA-lesioned rats. In addition, the elevating effects of both acute and chronic haloperidol treatment on dopamine turnover were attenuated in the laterodorsal caudate-putamen of KA-lesioned rats. The levels of dopamine, DOPAC, and HVA after chronic clozapine treatment were greater in KA-lesioned than control rats. These results indicate that dopaminergic responses to haloperidol may be diminished by limbic-cortical neuropathology, while such pathology does not significantly alter dopaminergic responses to clozapine.

Animals↗

The long-term effects of functional communication training in home settings.

A four-phase study was conducted in the homes of 4 young children who displayed aberrant behavior. Phases 1 and 2 consisted of a series of descriptive and experimental analyses to identify the environmental antecedents and consequences that controlled aberrant behavior. Phases 3 and 4 evaluated the short- and long-term effects of treatment on aberrant behavior, target mands, and collateral (social and toy play) behaviors. The effects of treatment were monitored for up to 27 months to assess long-term suppression of aberrant behavior. The assessment results successfully identified environmental events that occasioned and maintained aberrant behavior for all children. The short-term treatment resulted in immediate decreases in aberrant behavior for 3 of 4 children. Long-term treatment was successful for all children and was correlated with substantial response generalization. These results are interpreted in relation to functional equivalence, pivotal responding, and response generalization.

Behavior Therapy↗

Adolescents' perceptions of family responsibility-taking.

A scale was developed to solicit adolescents' perceptions of their family responsibility-taking (defined as helping out and being supportive). Four hundred adolescents were administered this scale together with self-report measures of intimacy with parents and peers as well as other psychological variables (self-esteem, depression, risk-taking, and drug use). The results revealed that adolescents who felt they assumed more family responsibility reported less depression, more intimate relationships with their parents, and higher self-esteem.

Adolescent↗

NMR spectroscopic and theoretical chemistry studies on the internal acyl migration reactions of the 1-O-acyl-beta-D-glucopyranuronate conjugates of 2-, 3-, and 4-(trifluoromethyl) benzoic acids.

High resolution 19F NMR spectroscopy has been used to investigate the kinetics of internal acyl migration and hydrolysis of the synthetic beta -1-O-acyl-D-glucopyranuronates of 2-, 3-, and 4-(trifluoromethyl) benzoic acids (TFMBAs) in phosphate buffer solutions at 30 degrees C as models of drug ester glucuronides. Apparent first-order degradation of the 1-O-acyl glucuronide and the sequential appearance of 2-, 3-, and 4-O-acyl isomers as both alpha- and beta-anomeric forms were observed for each TFMBA isomer. The overall degradation rate constants of the 2-, 3-, and 4-TFMBA 1-O-acyl isomers were 0.065 h-1, 0.25 h-1, and 0.52 h-1. In order to probe the reasons for these differences in reactivity, theoretical structural and electronic parameters for the beta-anomers of the 1-O-acyl glucuronides, their beta-2-O-acyl isomers, and both structures of the postulated ortho-acid ester intermediate were computed using semiempirical molecular orbital (AM1 and PM3) methods. The distinction between the slowly reacting 2-TFMBA glucuronide and the much faster reacting 3- and 4-TFMBA glucuronides could be observed by calculation of the relative bond order of the C-O bonds in the ortho-acid ester intermediates. The slow internal acyl migration rate of the 2-TFMBA isomer was also partly attributed to the high degree of steric hindrance of the trifluoromethyl group obstructing attack by the glucuronic acid 2-hydroxy group on the carbonyl carbon to form the ortho-acid ester intermediate. Some calculated molecular orbital properties, namely, dipole moment, energy of the lowest unoccupied molecular orbital (LUMO), LUMO density, and nucleophilic frontier density on the carbonyl carbon, were also shown to be related to the measured half-lives. This work gives insight into the molecular physicochemical properties that influence the acyl migration kinetics of simple model drug glucuronides and is of potential importance in understanding more complex drug glucuronide acyl migration reactions of toxicological interest.

Acylation↗