Neoral cyclosporine as maintenance immunosuppression in pediatric small bowel transplantation.
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Administration, Oral↗
Biomedical subjects
S Williams
Publications and source records attributed to S Williams.
Results of pediatric small bowel transplantation in Canada.
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Child↗
Emergency department senior house officers' consultation difficulties: implications for training.
STUDY OBJECTIVE: We investigated the types of patient presentations that cause senior house officers (SHOs) most difficulty during their tenure in emergency departments and report the extent to which such difficulties are related to SHOs' communication problems, stress, or perceived lack of skills or knowledge. METHODS: We conducted a questionnaire survey of 171 newly appointed SHOs employed in 27 EDs in the South Thames region of England. Subjects were asked to describe the presentation that gave them greatest difficulty during three subsequent shifts at the end of the first and fourth months of their ED appointment. RESULTS: A total of 132 (77%) and 110 (64%) respondents returned questionnaires at the end of the first and fourth months, respectively; 61% (105) responded to both questionnaires. The respondents described 537 of a possible total of 726 cases (74%). Communication problems caused difficulty in 406 (76%) cases, SHOs' experience of stress in 352 (66%) cases, and a perceived lack of knowledge or skills in 281 (52%) cases. Communication problems and the experience of stress occurred in 141 (26%) cases. Patients presenting with mental or behavioral disorders and symptoms most frequently gave rise to communication problems, perceived lack of skills, and the experience of stress. The difficulties described at the two time periods were very similar indicating that experience alone had little effect on these problems. CONCLUSION: ED SHOs may benefit from communication skills training, the opportunity to review difficult case presentations, and the alleviation of organizational stress factors.
Adult↗
CNS location of uterine-related neurons revealed by trans-synaptic tracing with pseudorabies virus and their relation to estrogen receptor-immunoreactive neurons.
Retrograde, transneuronal tracing with Bartha's strain of pseudorabies virus was used in rats to identify spinal cord, brainstem and hypothalamic loci of uterine-related neurons that could function in the regulation of uterine activity. Based on the premise that estrogen might influence such uterine-related neurons, the existence of estrogen receptors in neurons in these same loci was examined. Viral injections were made into the uterine cervix, body and cervical end of the uterine horns, and the rats allowed to survive for four to six days. After four days, mainly the spinal cord, medulla and pons contained virus-infected neurons. After longer survival times, progressively higher levels of the neuraxis contained viral-labeled neurons, so that by six days hypothalamic uterine-related neurons were identified. First-order virus-infected neurons were visualized by immunohistochemistry in the pelvic paracervical parasympathetic ganglia and in inferior mesenteric sympathetic ganglia. Preganglionic and putative interneurons were labeled in the lumbosacral spinal cord and thoracic spinal cord mainly in the lateral horn area (sacral parasympathetic nucleus and intermediolateral nucleus), lateral aspect of the dorsal horn, intermediate gray, lamina X and dorsal gray commissural area. In the brainstem, labeling was most evident and consistent in the nucleus tractus solitarius, ventrolateral medulla, raphe magnus and pallidus nuclei, parapyramidal area, A5 cell group, Barrington's nucleus of the pons and periaqueductal gray of the midbrain. In the hypothalamus, virus-infected neurons were most marked in the paraventricular nucleus, with fewer in the medial preoptic area and ventromedial hypothalamic nucleus. Estrogen receptor-immunoreactive neurons were most often present among the virus-labeled uterine-related neurons of the spinal cord, nucleus tractus solitarius, ventrolateral medulla, periaqueductal gray, medial preoptic area and ventromedial hypothalamic nucleus. These results identify a multisynaptic pathway of neurons whose eventual output is involved in uterine functions, whose distribution is similar to that revealed by pseudorabies virus tracing from other visceral organs, and which are often mixed among estrogen-responsive neurons.
Afferent Pathways↗
GABAergic input to cholinergic nucleus basalis neurons.
The potential influence of GABAergic input to cholinergic basalis neurons was studied in guinea-pig basal forebrain slices. GABA and its agonists were applied to electrophysiologically-identified cholinergic neurons, of which some were labelled with biocytin and confirmed to be choline acetyltransferase-immunoreactive. Immunohistochemistry for glutamate decarboxylase was also performed in some slices and revealed GABAergic varicosities in the vicinity of the biocytin-filled soma and dendrites of electrophysiologically-identified cholinergic cells. From rest (average - 63 mV), the cholinergic cells were depolarized by GABA. The depolarization was associated with a decrease in membrane resistance and diminution in firing. The effect was mimicked by muscimol, the specific agonist for GABA(A) receptors, and not by baclofen, the specific agonist for GABA(B) receptors, which had no discernible effect. The GABA- and muscimol-evoked depolarization and decrease in resistance were found to be postsynaptic since they persisted in the presence of solutions containing either high Mg2+/low Ca2+ or tetrodotoxin. They were confirmed as being mediated by a GABA(A) receptor, since they were antagonized by bicuculline. The reversal potential for the muscimol effect was estimated to be approximately -45 mV, which was -15 mV above the resting membrane potential. Finally, in some cholinergic cells, spontaneous subthreshold depolarizing synaptic potentials (average 5 mV in amplitude), which were rarely associated with action potentials, were recorded and found to persist in the presence of glutamate receptor antagonists but to be eliminated by bicuculline. These results suggest that GABAergic input may be depolarizing, yet predominantly inhibitory to cholinergic basalis neurons.
2-Amino-5-phosphonovalerate↗
Phosphorylation of the Grb2- and phosphatidylinositol 3-kinase p85-binding p36/38 by Syk in Lck-negative T cells.
Activation of the mitogen-activated protein kinase (MAPK) pathway by the T-cell antigen receptor (TCR) in T cells involves a positive role for phosphatidylinositol 3-kinase (PI3K) activity. We recently reported that over-expression of the Syk protein tyrosine kinase in the Lck-negative JCaM1 cells enabled the TCR to induce a normal activation of the Erk2 MAPK and enhanced transcription of a reporter gene driven by the nuclear factor of activated T cells and AP-1. Because this system allows us to analyse the targets for Syk in receptor-mediated signalling, we examined the role of PI3K in signalling events between the TCR-regulated Syk and the downstream activation of Erk2. We report that inhibition of PI3K by wortmannin or an inhibitory p85 construct, p85deltaiSH2, reduced the TCR-induced Syk-dependent activation of Erk2, as well as the appearance of phospho-Erk and phospho-Mek. At the same time, expression of Syk resulted in the activation-dependent phosphorylation of three proteins that bound to the src homology 2 (SH2) domains of PI3K p85. The strongest of these bands had an apparent molecular mass of 36-38 kDa on SDS gels, and it was quantitatively removed from the lysates by adsorption to a fusion protein containing the SH2 domain of Grb2. The appearance of this band was Syk dependent, and it was seen only upon triggering of the TCR complex. Thus, p36/38 was phosphorylated by Syk or a Syk-regulated kinase, and this protein may provide a link to the recruitment and activation of PI3K, as well as to the Ras-MAPK pathway, in TCR-triggered T cells.
Adaptor Proteins, Signal Transducing↗
Expression and immunolocalisation of the snowdrop lectin, GNA in transgenic rice plants.
Transgenic rice (Oryza sativa L.) plants generated through particle bombardment expressed high levels of an insecticidal protein (the snowdrop lectin, GNA) directed against sap-sucking insects. Engineered plants expressed GNA either constitutively or in a tissue specific manner, depending on the nature of the promoter used to drive expression of the gene. We used specific antibodies raised against GNA to localize its expression in phloem tissue in plants engineered with the rice sucrose synthase promoter driving GNA expression. We report here molecular, biochemical and immunological analyses for fifteen independently-derived transformants out of more than 200 plants we generated.
Gene Expression↗
Keratinocyte growth factor decreases pulmonary edema, transforming growth factor-beta and platelet-derived growth factor-BB expression, and alveolar type II cell loss in bleomycin-induced lung injury.
Keratinocyte growth factor (KGF), a potent growth factor for type II pneumocytes and Clara cells, has been shown to prevent the end-stage pulmonary fibrosis and mortality in a rat model of bleomycin-induced lung injury. In this study, protective effects of KGF were explored during the earlier course of bleomycin-induced lung injury by studying protein exudation in alveolar edema fluids, pulmonary expression of transforming growth factor-beta (TGF beta) and platelet-derived growth factor-BB (PDGF-BB), and changes in type II pneumocytes and Clara cells after i.t. (intratracheal) bleomycin injection following KGF- or saline-pretreatment in rats. Total protein in bronchoalveolar lavage (BAL) fluids after bleomycin injury from KGF-pretreated rats was significantly lower than the levels in saline-pretreated rats. TGF beta protein in BAL fluids which peaked at day 3 after i.t. bleomycin in saline-pretreated lungs was not significantly increased at any time points in KGF-pretreated rats. PDGF-BB protein in whole lung tissues of KGF-pretreated rats also remained near normal throughout the course after i.t. bleomycin, in contrast to the significant increase in saline-pretreated rats. Numbers of type II pneumocytes and Clara cells in KGF-pretreated lungs after a high dose of bleomycin were close to the normal in intact lungs. At the same dose of bleomycin injury, type II pneumocytes in saline-pretreated lungs were markedly decreased, while the number of Clara cells in these rats was relatively preserved as the pre-injury level. In conclusion, KGF prevents bleomycin-induced end-stage pulmonary injury and mortality probably at least partly by decreasing protein-rich pulmonary edema, protein expression of fibrogenic cytokines TGF beta and PDGF-BB, and type II cell loss during the course of lung injury.
Animals↗
Measuring occupational stress: development of the pressure management indicator.
The study of occupational stress is hindered by the lack of compact and comprehensive standardized measurement tools. The Pressure Management Indicator (PMI) is a 120-item self-report questionnaire developed from the Occupational Stress Indicator (OSI). The PMI is more reliable, more comprehensive, and shorter than the OSI. It provides an integrated measure of the major dimensions of occupational stress. The outcome scales measure job satisfaction, organizational satisfaction, organizational security, organizational commitment, anxiety--depression, resilience, worry, physical symptoms, and exhaustion. The stressor scales cover pressure from workload, relationships, career development, managerial responsibility, personal responsibility, home demands, and daily hassles. The moderator variables measure drive, impatience, control, decision latitude, and the coping strategies of problem focus, life work balance, and social support.
Adaptation, Psychological↗
The anatomy of conscious vision: an fMRI study of visual hallucinations.
Despite recent advances in functional neuroimaging, the apparently simple question of how and where we see--the neurobiology of visual consciousness--continues to challenge neuroscientists. Without a method to differentiate neural processing specific to consciousness from unconscious afferent sensory signals, the issue has been difficult to resolve experimentally. Here we use functional magnetic resonance imaging (fMRI) to study patients with the Charles Bonnet syndrome, for whom visual perception and sensory input have become dissociated. We found that hallucinations of color, faces, textures and objects correlate with cerebral activity in ventral extrastriate visual cortex, that the content of the hallucinations reflects the functional specializations of the region and that patients who hallucinate have increased ventral extrastriate activity, which persists between hallucinations.
Brain Mapping↗
Is mental health in childhood a major predictor of smoking in adolescence?
AIMS: To test an extended version of Pomerleau's (1997) hypothesis that children with mental health problems are at higher risk of smoking in preadolescence and adolescence. DESIGN: Information concerning mental health from 5 to 13 years, smoking at ages 11 and 15, and family disadvantage at age 7 was available for 773 children enrolled in a longitudinal study of children and adolescents. PARTICIPANTS: Participants were enrolled into the Dunedin Multidisciplinary Health and Development Study, which is a longitudinal investigation of the health, development and behaviour of a large group of New Zealand children born between 1 April 1972 and 31 March 1973. MEASUREMENTS: Assessment of mental health problems in childhood was based upon parent and teacher reports of behavioural and emotional problems. In pre-adolescence, mental health was assessed by self, parent and teacher report. Smoking was assessed by self-report. FINDINGS: None of the potential risk factors of gender, childhood disadvantage or childhood mental health problems predicted onset of smoking in pre-adolescence. Daily smoking at age 15 was best predicted by smoking in preadolescence, being female and experiencing childhood disadvantage. Pre-adolescent mental health was only weakly predictive of later smoking and this association appeared to be confounded with background disadvantage. CONCLUSIONS: We found little support for the extension of Pomerleau's (1997) hypothesis to childhood mental health. Our findings also run counter to recent suggestions for targeting smoking prevention at groups of children with mental health disorders.
Adolescent↗
Treatment of oropharyngeal carcinoma by irradiation or by surgery.
Of previously untreated patients with squamous cell carcinoma of the oropharynx, 145 are reviewed in this study. All were treated in the Department of Head and Neck Surgery at the University of Liverpool from 1990 to 1997. Seventy-seven patients were treated with irradiation, 28 patients by surgery and 40 patients were deemed not suitable for any curative treatment. Univariate analysis showed no difference in the two groups treated by curative modalities but multivariate analysis did suggest that the surgical group tended to have larger neck node metastases. The 5-year tumour specific actuarial survival for all patients was 53%, 65% for the radiotherapy group and 51% for the surgery group. The difference was not statistically significant (chi (1)2 = 1.5070). The modality of treatment had no affect on either the development of a primary or neck node recurrence or the survival after such a recurrence. Where neck node disease was present it was treated as appropriate. As is generally standard practice, lymph nodes over 2 cm were treated with radical neck dissection whether the patient was having irradiation therapy or surgery. If the patient was having irradiation therapy, the neck dissection was carried out before and irradiation after operation, both on the primary and on the neck, if appropriate. It is concluded that irradiation therapy in properly selected cases in combined head and neck clinics is a safe and effective treatment for squamous cell carcinoma of the oropharynx. Neck node disease should be treated appropriately, but there is no support for the old adage that whatever form of treatment is being used for the neck node should also be used for the primary site.
Analysis of Variance↗
Expression of snowdrop lectin (GNA) in transgenic rice plants confers resistance to rice brown planthopper.
Snowdrop lectin (Galanthus nivalis agglutinin; GNA) has been shown previously to be toxic towards rice brown planthopper (Nilaparvata lugens; BPH) when administered in artificial diet. BPH feeds by phloem abstraction, and causes 'hopper burn', as well as being an important virus vector. To evaluate the potential of the gna gene to confer resistance towards BPH, transgenic rice (Oryza sativa L.) plants were produced, containing the gna gene in constructs where its expression was driven by a phloem-specific promoter (from the rice sucrose synthase RSs1 gene) and by a constitutive promoter (from the maize ubiquitin ubi1 gene). PCR and Southern analyses on DNA from these plants confirmed their transgenic status, and that the transgenes were transmitted to progeny after self-fertilization. Western blot analyses revealed expression of GNA at levels of up to 2.0% of total protein in some of the transgenic plants. GNA expression driven by the RSs1 promoter was tissue-specific, as shown by immunohistochemical localization of the protein in the non-lignified vascular tissue of transgenic plants. Insect bioassays and feeding studies showed that GNA expressed in the transgenic rice plants decreased survival and overall fecundity (production of offspring) of the insects, retarded insect development, and had a deterrent effect on BPH feeding. gna is the first transgene to exhibit insecticidal activity towards sap-sucking insects in an important cereal crop plant.
Animals↗
The serotonin inhibition of high-voltage-activated calcium currents is relieved by action potential-like depolarizations in dissociated cholinergic nucleus basalis neurons of the guinea-pig.
The aim of the present study was to investigate whether the voltage-dependent inhibition of calcium currents by serotonin 5-HT1A agonists can be alleviated (facilitated) by action potential-like depolarizations. In dissociated cholinergic basal forebrain neurons using whole-cell recordings, it is shown that a selective serotonin 5-HT1A agonist (8-OH-DPAT) predominantly blocks N-type HVA calcium current, although a minor reduction of P-type current was also observed. The inhibition may principally occur through Gi-Go subtypes of G-proteins because it was prevented by N-ethylmaleimide, a substance known to block specifically pertussis-sensitive G-proteins. The inhibitory effect of 8-OH-DPAT on calcium currents is voltage-dependent because it was alleviated by long-lasting depolarizing prepulses. Interestingly, the inhibition could also be reversed by prepulses made-up of action potential-like depolarizations that were given at a frequency of 200 Hz. This observation may have important implications during periods of high-frequency rhythmic bursts, a firing pattern that is prevalent in cholinergic basal forebrain neurons.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Better increase in fibrin gel porosity by low dose than intermediate dose acetylsalicylic acid.
AIM: To investigate the influence on plasma fibrin gel structure of low and intermediate doses of acetylsalicylic acid in healthy individuals. The influence of acetylsalicylic acid on thrombin formation, fibrinolytic capacity and plasminogen inhibitor-1 in plasma was also investigated. METHODS: Nineteen subjects were treated with 75 mg and 11 with 320 mg acetylsalicylic acid daily; eight subjects received both doses. Fibrin gel structure was determined by a permeability technique yielding a porosity constant (Ks), and the thromboxane metabolite 11-dehydro-thromboxane B2 (TxM) was determined by an ELISA. RESULTS: Acetylsalicylic acid increased fibrin porosity by 65% at 75 mg (P<0.001, n=19), whereas lower increases were found at 320 mg (+22%, P<0.05, n=11). One week after withdrawal Ks had essentially returned to baseline (ns). Urinary thromboxane metabolites were suppressed during treatment (-61%, P<0.001 at 75 mg, n=19; -46%, P<0.01 at 320 mg, n=11). The intra-individual comparison showed similar results (Ks +92%, TxM -62% at 75 mg; Ks +5%, TxM -52% at 320 mg). Fibrinolytic capacity, plasminogen inhibitor-1 levels and thrombin generation (in platelet-poor citrated plasma) were not influenced. CONCLUSION: Low dose acetylsalicylic acid causes the greatest increase in fibrin gel porosity; this may well be of therapeutic importance.
Adult↗
Doctor-patient communication and patient satisfaction: a review.
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Communication↗
Women and abortion in 1930s Britain: a survey and its data.
This paper examines over 3,000 questionnaires on abortion that were distributed through the National Birthday Trust Fund, a non-governmental orrganization, to working-class women in municipal hospitals in 1930s Britain. The aim of the survey was to "discover the proportion of induced to spontaneous abortions". Although the study was abandoned due to weaknesses in its design, the collected data contain a mass of detailed information about the lives and reproductive history of working-class women in this period. The background to the survey is discussed, setting it within the development of research on poverty and women's health, as well as contemporary debate on the issue of abortion. The survey data, which are both qualitative and quantitative, are analysed and presented in figures with accompanying commentary. Issues covered include the impact of poverty, overcrowding, reasons for avoiding pregnancy, and contraception.
Abortion, Spontaneous↗
Effects of glibenclamide on blood pressure and cardiovascular responsiveness in non-insulin dependent diabetes mellitus.
OBJECTIVE: To compare the effects of chronic glibenclamide therapy and placebo on blood pressure and cardiovascular responsiveness in patients with non-insulin-dependent diabetes. DESIGN AND METHODS: Fourteen patients with non-insulin-dependent diabetes mellitus, seven of whom were receiving angiotensin converting enzyme inhibitor therapy, received glibenclamide or placebo for 1 month in a double-blind, randomized crossover study. At the end of each treatment period patients attended for studies of forearm vascular responsiveness to intra-brachial arterial infusions of angiotensin II, acetylcholine, sodium nitroprusside and noradrenaline, responses of blood pressure to intravenous infusions of noradrenaline and angiotensin II and 24 h ambulatory blood pressure monitoring. RESULTS: Administration of glibenclamide produced significantly better glycaemic control than placebo (fasting blood glucose level 8.5 +/- 2.4 versus 13.5 +/- 4.5 mmol/l, P < 0.001) and plasma insulin levels were significantly higher during glibenclamide treatment than they were with placebo (12.9 +/- 4.4 versus 9.2 +/- 4.1 mU/l, P < 0.05). Body weights at the ends of the glibenclamide treatment and placebo phases were similar (92.1 +/- 14.3 versus 91.1 +/- 14.3 kg, P = 0.085). Night-time systolic blood pressures were significantly higher during glibenclamide treatment than they were with placebo (128 +/- 17 versus 118 +/- 10 mmHg, P < 0.05) due to there being a smaller day-night difference in systolic blood pressure during glibenclamide treatment that appeared to occur mainly in patients receiving angiotensin converting enzyme inhibitors. Responses of diastolic blood pressure to intravenous infusion of angiotensin II and forearm vascular responses to intra-brachial arterial infusion of angiotensin II were significantly greater during glibenclamide treatment than they were with placebo (P < 0.05). However, the enhancement of forearm vascular responses during glibenclamide treatment appeared to be restricted to patients receiving angiotensin converting enzyme inhibitors. Responses of blood pressure to intravenous infusion of noradrenaline and forearm vascular responses to infusions of noradrenaline, acetylcholine and nitroprusside did not differ between glibenclamide treatment and placebo; neither did basal forearm vascular resistance. CONCLUSIONS: Glibenclamide therapy is associated with greater responses of blood pressure and forearm vascular responses to infusion of angiotensin and higher nocturnal blood pressures. This effect appears to be influenced by concomitant angiotensin converting enzyme inhibition.
Acetylcholine↗