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Biomedical subjects

M Cooper

Publications and source records attributed to M Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1998

Myocardial nuclear factor-kappaB activity and nitric oxide production in rejecting cardiac allografts.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a rapid response transcription factor for genes whose products are critical for inflammation and immunity. In a rat model of heterotopic cardiac transplantation, we studied NF-kappaB DNA binding activity and nitric oxide (.NO) production in untreated allografts and whether inhibition of NF-kappaB suppresses .NO production and prolongs graft survival. METHODS: In allograft recipients and isograft controls, NF-kappaB was assayed by electrophoretic mobility shift assay, daily from transplant until rejection. Myocardial .NO was directly detected in explanted allografts by electron spin resonance spectroscopy on day 6 after transplant. The potent inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC; 250 mg/kg s.c.) was administered daily from transplant until day of rejection. The extent of graft lymphocytic infiltrate was assessed by routine hematoxylin and eosin staining. Immunohistochemical staining of NF-kappaB was per formed to identify the cell type responsible for NF-kappaB activity. RESULTS: A time-dependent increase in myocardial NF-kappaB activity was seen in untreated allografts as compared with isografts as determined by PhosphorImage analysis. Peak NF-kappaB activity occurred in allografts on day 4 with a ninefold increase as compared with isografts (24.0+/-3.7% vs. 2.7+/-0.5; P<0.05). On posttransplant day 6, electron spin resonance spectroscopy analysis of allografts demonstrated .NO identified by a triplet nitrogen signal centered at g=2.012 with hyperfine splitting of 17.5 Gauss, which is consistent with nitrosoheme formation and low-field signals at g=2.08 and g=2.03 consistent with nitrosomyoglobin. These signals were not seen in native hearts of allograft recipients. With PDTC administration, a threefold decrease in NF-kappaB activity within the transplanted heart was observed on posttransplant day 5 as compared with untreated allografts (9.7+/-1.6% vs. 23.5+/-2.5%; P<0.01). PDTC prolonged graft survival as compared with untreated allografts (11.7+/-0.3 vs. 6.6+/-0.2 days; P<0.05) and reduced the intensity of the nitrosoheme and nitrosomyoglobin signals. Allograft mononuclear cell infiltrate correlated with peak NF-kappaB activity with peak infiltrate on posttransplant day 4. PDTC treatment had no effect on the extent of infiltrate. Immunohistochemical staining localized NF-kappaB to the infiltrating mononuclear cells on posttransplant day 5. CONCLUSION: These data support a role for NF-kappaB in allograft rejection.

Animals↗
PubMed1998

Core beliefs and underlying assumptions in bulimia nervosa and depression.

In a pilot study, core beliefs and underlying assumptions were investigated in patients with bulimia nervosa, patients with depression and female controls, using a new self-report measure. The patients with bulimia nervosa did not differ from the patients with depression in negative self beliefs but they did differ in assumptions concerned with weight, shape and eating. Both groups of patients also differed from the female controls, with the exception of one comparison including the depressed patients. The findings support recent developments in cognitive theories of eating disorders. Treatment implications are briefly discussed.

Adult↗
PubMed1998

Expansion and division of conjoined twins.

Omphalopagus conjoined twins were born by cesarean section after their 24-year-old gravida 2, para 1 mother went into labor at 35 weeks' gestation. Initial studies included roentenograms, an upper gastrointestinal study, small bowel follow-through, and computerized tomography with intravenous contrast from neck through pelvis. Results of these studies showed that the twins had very little shared vasculature, but did share a pericardium and liver parenchyma. The infants were allowed to gain weight and grow. After 3 weeks, tissue expanders were placed subcutaneously and were rapidly expanded in 2 weeks. The infants were then separated. An Argon Beam Coagulator was used to aid the separation of the liver. The abdominal fascia was closed primarily on each infant, and the skin easily closed without tension. During the first 36 hours of the postoperative course, both infants required significant ventilatory support including inhaled nitric oxide. After this period, the ventilatory support decreased dramatically and rapidly. The infants were discharged 9 days after their surgical separation. Conjoined omphalopagus twins, the use of tissue expanders and the Argon Beam Coagulator, and the postoperative course are discussed.

Contrast Media↗
PubMed1998

Computers in midwifery practice: a view from the labour ward.

Concern continues to exist about the lack of integration of research into clinical practice. One of the reasons which has been suggested for this, is that practitioners may either not know about, or understand, the research findings. The availability of a database which contains systematic reviews of research such as the Cochrane Pregnancy and Childbirth Database, should go some way to overcome such obstacles associated with the implementation of research into practice. As part of a national audit on Caesarean section, a computer with the Cochrane Database was installed in the labour ward of each consultant maternity unit in Scotland. The purpose of this study was to determine if midwives working in labour wards make use of this accessible source of research findings to inform their practice. Anecdotal evidence suggested that although midwives were keen to use the databases, they did not have the requisite computer skills to do so. This study examined the computer literacy of midwives and their perceived educational needs. A questionnaire was distributed to all labour ward midwives in 22 consultant maternity hospitals in Scotland (n = 850). This questionnaire considered issues such as the preparation of midwives to use computers, midwives' perceptions and use of computers and their perceived educational needs. The response rate was 74%. Following analysis of the questionnaire labour ward managers were interviewed by telephone to ascertain their views regarding the Cochrane Database and their perception of its effectiveness. The results highlighted that only 27% of midwives claimed to use the Cochrane Database on a regular basis. Overall midwives had a positive attitude towards information technology but claimed they did not have the requisite computer skills to use these tools. Managers agreed that there was a need for further instruction and support for midwives. The findings of this study have important implications for the future professional preparation and continuing education of midwives.

Adult↗
PubMed1998

QU-GENE: a simulation platform for quantitative analysis of genetic models.

MOTIVATION: Classical quantitative genetics theory makes a number of simplifying assumptions in order to develop mathematical expressions that describe the mean and variation (genetic and phenotypic) within and among populations, and to predict how these are expected to change under the influence of external forces. These assumptions are often necessary to render the development of many aspects of the theory mathematically tractable. The availability of high-speed computers today provides opportunity for the use of computer simulation methodology to investigate the implications of relaxing many of the assumptions that are commonly made. RESULTS: QU-GENE (QUantitative-GENEtics) was developed as a flexible computer simulation platform for the quantitative analysis of genetic models. Three features of the QU-GENE software that contribute to its flexibility are (i) the core E(N:K) genetic model, where E is the number of types of environment, N is the number of genes, K indicates the level of epistasis and the parentheses indicate that different N:K genetic models can be nested within types of environments, (ii) the use of a two-stage architecture that separates the definition of the genetic model and genotype-environment system from the detail of the individual simulation experiments and (iii) the use of a series of interactive graphical windows that monitor the progress of the simulation experiments. The E(N:K) framework enables the generation of families of genetic models that incorporate the effects of genotype-by-environment (G x E) interactions and epistasis. By the design of appropriate application modules, many different simulation experiments can be conducted for any genotype-environment system. The structure of the QU-GENE simulation software is explained and demonstrated by way of two examples. The first concentrates on some aspects of the influence of G x E interactions on response to selection in plant breeding, and the second considers the influence of multiple-peak epistasis on the evolution of a four-gene epistatic network. AVAILABILITY: QU-GENE is available over the Internet at (http://pig.ag.uq.edu.au/qu-gene/) CONTACT: m.cooper@mailbox.uq.edu. au

Computer Simulation↗
PubMed1998

Intrathecal sufentanil dose response in nulliparous patients.

BACKGROUND: Intrathecal sufentanil provides effective analgesia during the first stage of labor. A range of doses has been reported to provide adequate pain relief. This study determined the dose of intrathecal sufentanil that produced acceptable pain relief in 50% of nulliparous patients (ED50) who requested labor analgesia. METHODS: With institutional review board approval, 50 nulliparous patients requesting spinal opioid labor analgesia were enrolled into this prospective, randomized, double-blinded study. Each patient was in spontaneous labor at <5 cm cervical dilation. Patients received one of the following doses of intrathecal sufentanil: 1, 2, 3, 5, or 10 microg in 3 ml preservative-free saline (n = 10 for each dose). Pain, pain relief, hemodynamic, respiratory, and side effect data were collected at times 0, 2, 5, 10, 15, 20, 25, and 30 min. Probit analysis of the number of patients in each group who requested additional pain medicine at 30 min was used to determine the ED50. RESULTS: The groups were demographically similar. The ED50 of intrathecal sufentanil was 1.8 microg (SE, 0.6 microg; 95% CI, 2.96 to 0.54 microg). The incidence of side effects was similar among the groups. CONCLUSIONS: This is the first study to determine the ED50 of intrathecal sufentanil in spontaneously laboring nulliparous patients. As dose-response curves are determined for other labor analgesics, future studies can compare equianalgesic doses or dose combinations.

Adult↗
PubMed1998

The immediate-early gene product encoded by open reading frame 57 of herpesvirus saimiri modulates gene expression at a posttranscriptional level.

The herpesvirus saimiri (HVS) immediate-early gene product encoded by open reading frame (ORF) 57 shares limited amino acid homology with HSV-1 ICP27 and Epstein-Barr virus BMLF1, both regulatory proteins. The ORF 57 gene has been proposed to be spliced based on the genome sequence, and here we confirm the intron-exon structure of the gene. We also demonstrate that a cDNA construct of the ORF 57 gene product represses the transactivating capability of the ORF 50a gene product (which is produced from a spliced transcript), but activates that of ORF 50b (an unspliced transcript). Further analyses with cotransfection experiments show that ORF 57 can either activate or repress expression from a range of both early and late HVS promoters, depending on the target gene. These results indicate that repression of gene expression mediated by the ORF 57 gene product is dependent on the presence of an intron within the target gene encoding region. Furthermore, Northern blot analysis demonstrates that the levels of mRNA transcribed from genes not containing an intron are not significantly affected in the presence of the ORF 57 gene product. This suggests that it regulates gene expression through a posttranscriptional mechanism.

Animals↗
PubMed1998

The open reading frame (ORF) 50a gene product regulates ORF 57 gene expression in herpesvirus saimiri.

We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptional regulating genes in herpesvirus saimiri. ORF 50, a homolog of Epstein-Barr virus R protein, is a sequence-specific transactivator, whereas ORF 57 acts posttranscriptionally. In this report, we demonstrate that the ORF 57 gene is regulated by the ORF 50a gene product. We show that the ORF 57 gene is expressed at basal levels early in the virus replication cycle and that thereafter it is transactivated by the ORF 50a gene product, due to an increase in RNA levels. As it has been shown that the ORF 57 gene product downregulates ORF 50a due to the presence of its intron, these combined observations identify a feedback mechanism modulating gene expression in herpesvirus saimiri, whereby ORF 50a transcription is downregulated by the ORF 57 gene product, a gene which it specifically transactivates. Furthermore, we propose that the intron-containing ORF 57 gene downregulates itself by the same mechanism as that for ORF 50a, as both genes are downregulated at similar times during the replication cycle.

Animals↗
PubMed1998

Exposure to commonly prescribed drugs and the etiology of cryptogenic fibrosing alveolitis: a case-control study.

Cryptogenic fibrosing alveolitis is an interstitial lung disease of unknown etiology. Since pulmonary fibrosis is a recognized, if rare, complication of certain drug exposures, including antidepressants, betablockers, antibiotics, anticonvulsants, and nonsteroidal antiinflammatory drugs (NSAIDs), we tested the hypothesis that exposure to these drugs might contribute to the etiology of cryptogenic fibrosing alveolitis. Lifetime drug exposure data were collected from general practitioner records for 141 cases of cryptogenic fibrosing alveolitis and 246 age-, sex-, and community-matched control subjects from the Trent region of England. Additional data on lifetime smoking habits were obtained by postal questionnaire. The odds of disease in relation to ever exposure to antidepressants, betablockers, antibiotics, anticonvulsants, and NSAIDs were calculated by conditional logistic regression. For drug groups significantly associated with cryptogenic fibrosing alveolitis, subset analyses were performed to investigate the effects of individual drugs. Cryptogenic fibrosing alveolitis was associated with exposure to antidepressants (odds ratio [OR] 1.79 [95% CI 1.09-2.95], p = 0.022) and specifically to imipramine (OR 4.79 [1.50-15.3], p = 0.01), dothiepin (OR 2.37 [0.99-5.69], p = 0.05), and mianserin (OR 3.27 [1.11-9.61], p = 0.03). The magnitude of the overall effect of antidepressants was not changed by excluding all drug exposures within the 5 yr preceding the diagnosis of cryptogenic fibrosing alveolitis (OR 1.62 [0.94-2.77], p = 0.081), nor were the strong individual effects of imipramine (OR 5.72 [1.54-21.2], p = 0.009) and dothiepin (OR 5.58 [1.12-27.8], p = 0.036). These estimates were not appreciably affected by controlling for smoking history. The attributable risk for antidepressant exposure was in the region of 9-14%. No significant association was noted between cryptogenic fibrosing alveolitis and the four other drug groups in the primary hypothesis. The results of this study suggest that some antidepressant drugs can cause cryptogenic fibrosing alveolitis.

Adrenergic beta-Antagonists↗
PubMed1998

Increasing prevalence of wheeze and asthma in Nottingham primary schoolchildren 1988-1995.

The prevalence of asthma in children has increased substantially in many countries in recent decades, but it is not clear how much this trend has continued into the 1990s. This study aimed to estimate the current prevalence of asthma and wheeze in British primary schoolchildren and to determine whether there has been any increase in the prevalence of these conditions since 1988. The prevalence of self-reported wheeze and asthma was measured by parental questionnaire in 22,968 children aged 4-11 yrs attending primary schools in the Nottingham area of England in 1995, and these estimates were compared with data from a subsample of the same schools in 1988. In 1995, wheezing ever was reported in 24.0% of children, wheezing in the past year in 15.1% and diagnosed asthma symptomatic in the past year in 8.8%. All measures have increased in prevalence since 1988, in absolute terms by 7.7% for wheeze ever, by 2.6% for wheeze in the past year and by 2.7% for asthma. The increases were greater in females than males, but did not vary with age. In conclusion, the prevalence of asthma has continued to rise in British schoolchildren since the late 1980s, particularly in females, and across all ages.

Asthma↗
PubMed1998

Antibodies to toluene diisocyanate in an environmentally exposed population.

Residents living near a polyurethane foam manufacturing facility expressed concern to health officials over chemical emissions from the plant. Environmental monitoring of ambient air near the plant indicated the presence of toluene diisocyanate (TDI), which was used in foam production. Health officials collected blood samples from 113 residents and analyzed the blood sera for antibodies to TDI and related diisocyanates. Ten of the 113 residents (9%) had elevated levels of IgG or IgE antibodies specific for one or more diisocyanates. Exposure histories were taken from antibody-positive individuals to identify possible occupational exposure to TDI or the use of diisocyanate-containing consumer products. Exposure to TDI in ambient air may be responsible for the positive antibody responses detected in some residents of the community.

Adolescent↗
PubMed1998

Evaluation of a nursery based language intervention in a socially disadvantaged area.

This longitudinal study was designed to evaluate the impact of a community-based speech and language project, set in an area of Plymouth known for its high levels of social disadvantage. The interventions include a specifically designed nursery programme, known as Wise Words for Nursery, and a modular series of parenting groups for the parents of pre-school children. The data were collected from five consecutive year groups entering a single primary school for the years 1993-1997. Each of the five cohorts underwent a battery of tests to collect data on their lexical development, information recall, reception of grammar, sentence length and speech clarity. Statistical analysis of the data showed a significant difference in the communication abilities of the most recent cohort when compared to the previous years. The findings provide considerable support for the efficacy of the approach employed.

Analysis of Variance↗
PubMed1998

Interclass drug effects and changes in regional brain glucose metabolism.

We have developed an innovative use of positron emission tomography that has broad applications in drug development. Based on the FDG method (Phelps et al. 1979) for assessing glucose metabolism, the method requires rigorous experimental control of subjects and standardized data acquisition and analyses. In localizing net metabolic drug effects, measured in quantifiable terms, we have derived a new conceptual basis for examining pharmacologically induced changes in brain function and a new model for predicting drug effectiveness. We applied this method to studies of drugs in three different classes and noted marked differences in distribution and magnitude of metabolic effects. This approach presents an opportunity to selectively examine measurements of the glucose metabolic changes induced by specific pharmacological probes on intermediary metabolic pathways, including regulation of gene expression and the metabolic consequences of neurotransmitter alteration in pharmacologically targeted neuronal systems. Development of these methods provides new approaches for studying neurobiological mechanisms, and can contribute significantly to the process of new drug development.

Brain↗
PubMed1998

Teaching the microscopic examination of urine sediment to second year medical students using the Urinalysis-Tutor computer program.

The microscopic examination of urine sediment is a common diagnostic tool taught to medical students, medical technologists, and others. The urine microscopic exam is difficult to teach because supervised instruction and textbook-based teaching suffer from numerous drawbacks. Here, we describe Urinalysis-Tutor, a computer program that uses digitized microscope images and computer-based teaching techniques to systematically teach the urine microscopic exam. In addition, we report the results of a 2-year study that evaluated the effectiveness of the program in 314 second year medical students who were required to use the program. The program contained two, 20-question exams. In the first year of the study (1996), one of the exams was chosen as the pretest and the other as the posttest; the pretest had to be completed before the students viewed the contents of the program, and the posttest was taken after finishing the tutorial. In 1997, the order of the two exams was reversed. In 1996, 159 students completed the study. The mean pretest score was 34% (SD, 14%), the mean posttest score was 71% (SD, 13%), and the improvement was significant (P <0.001, paired t-test). In 1997, 155 students participated. The mean pretest score was 41% (SD, 11%), the mean posttest score was 71% (SD, 13%), and the improvement was significant (P <0.001, paired t-test). The study shows that Urinalysis-Tutor helps medical students learn to interpret the microscopic appearance of urine sediment and that it is feasible to implement this tutorial in a medical school class.

Computer-Assisted Instruction↗