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Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 127 records · Page 7Linked to original sources
PubMed1998

Management of psychiatric symptoms in medically ill patients in the homecare setting.

Nurses with critical care knowledge and experience increasingly provide technologically advanced care to patients at home who often present comorbid psychiatric symptoms. Failure to accurately recognize and provide appropriate intervention can be devastating for patients because these symptoms can exacerbate the medical condition and may lead to mortality. The Biopsychosocial Model and the Transactional Model of Stress were presented as guides for nursing practice. Practice is directed at 1) understanding the patient's perception of events, 2) involving the caregiver(s) in the patient's recovery, and 3) enhancing the individual's adaptive coping efforts and resources. The article attempts to guide nurses in making decisions on when to consult and collaborate with an APPN to achieve desired patient outcomes.

Community Health Nursing↗
PubMed1997

Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel.

Synaptotagmins are synaptic vesicle proteins containing two calcium-binding C2 domains which are involved in coupling calcium influx through voltage-gated channels to vesicle fusion and exocytosis of neurotransmitters. The interaction of synaptotagmins with native P/Q-type calcium channels was studied in solubilized synaptosomes from rat cerebellum. Antibodies against synaptotagmins I and II, but not IV co-immunoprecipitated [125I]omega-conotoxin MVIIC-labelled calcium channels. Direct interactions were studied between in vitro-translated [35S]synaptotagmin I and fusion proteins containing cytoplasmic loops of the alpha1A subunit (BI isoform). Gel overlay revealed the association of synaptotagmin I with a single region (residues 780-969) located in the intracellular loop connecting homologous domains II and III. Saturable calcium-independent binding occurred with equilibrium dissociation constants of 70 nM and 340 nM at 4 degrees C and pH 7.4, and association was blocked by addition of excess recombinant synaptotagmin I. Direct synaptotagmin binding to the pore-forming subunit of the P/Q-type channel may optimally locate the calcium-binding sites that initiate exocytosis within a zone of voltage-gated calcium entry.

Amino Acid Sequence↗
PubMed1997

Identification of brainstem neurons responding to hypoxia in fetal and newborn sheep.

Hypoxia causes a reversible decrease in the level of respiratory, oculomotor and postural muscle activity in fetal sheep, an effect not seen in newborn lambs. We have used Fos immunohistochemistry to identify neurons which are activated by hypoxia and which may mediate this motor inhibition in the fetus. Pregnant sheep of either 117 or 138 days gestation were made hypoxic by allowing them to breathe 8-9% O2 for 2 h. Compared to age-matched control fetuses, hypoxia caused a significant increase in Fos-immunoreactivity in several medullary nuclei including the nucleus tractus solitarius, lateral reticular nucleus and the rostral ventrolateral medulla and also in the lateral parabrachial nucleus, locus coeruleus and subcoeruleus region in the pons. Hypoxia in newborn lambs, 7-18 days old, resulted in Fos staining in the same medullary and pontine nuclei with the exception of the subcoeruleus region which was devoid of Fos-immunoreactivity. In newborn lambs in which the carotid sinus nerves had been sectioned bilaterally, Fos-immunoreactivity was increased in the nucleus tractus solitarius in the medulla and in the locus coeruleus, lateral parabrachial and Kölliker-Fuse nuclei in the pons when compared to intact control newborn lambs. When carotid sinus nerve denervated-lambs were subjected to hypoxia the pattern of Fos-ir was similar to the pattern seen in the denervated control lambs but in addition staining was present in the subcoeruleus. These results suggest that a specific set of pontine neurons are activated by low oxygen levels in the fetus but not in the newborn lamb in the presence of an intact innervation from the carotid sinus. We hypothesise that: (a) in the fetus hypoxia activates neurons in the region of the subcoeruleus and this causes cessation of breathing movements and muscle atonia; and (b) that after birth stimulation of the carotid chemoreceptors by hypoxia normally inhibits activation of these subcoeruleus neurons.

Aging↗
PubMed1997

Direct binding of G-protein betagamma complex to voltage-dependent calcium channels.

Voltage-dependent Ca2+ channels play a central role in controlling neurotransmitter release at the synapse. They can be inhibited by certain G-protein-coupled receptors, acting by a pathway intrinsic to the membrane. Here we show that this inhibition results from a direct interaction between the G-protein betagamma complex and the pore-forming alpha1 subunits of several types of these channels. The interaction is mediated by the cytoplasmic linker connecting the first and second transmembrane repeats. Within this linker, binding occurs both in the alpha1 interaction domain (AID), which also mediates the interaction between the alpha1 and beta subunits of the channel, and in a second downstream sequence. Further analysis of the binding site showed that several amino-terminal residues in the AID are critical for Gbetagamma binding, defining a site distinct from the carboxy-terminal residues shown to be essential for binding the beta-subunit of the Ca2+ channel. Mutation of an arginine residue within the N-terminal motif abolished betagamma binding and rendered the channel refractory to G-protein modulation when expressed in Xenopus oocytes, showing that the interaction is indeed responsible for G-protein-dependent modulation of Ca2+ channel activity.

Amino Acid Sequence↗
PubMed1997

Report of a collaborative study to establish the international standard for parvovirus B19 serum IgG.

With the introduction of commercial test kits and the wider availability of parvovirus B19 antibody testing, greater standardization is required. Moreover, with a B19 vaccine in the early stages of development, there will be long-term need of accurate measurement of parvovirus B19 antibody levels following natural infection and vaccination. A collaborative study was carried out to assess the suitability of a freeze-dried preparation designated 93/724 to serve as the International Standard for parvovirus B19 serum IgG. The proposed standard, which is a pool of sera from six U.K. blood donors, was assayed along with three coded samples. One was the proposed standard (Preparation A), one a pool of three donor sera (Preparation B) and the third an individual donor serum (Preparation C). These preparations were sent to nine laboratories in seven countries who tested them in 10 different enzyme immunoassays. There were no differences in the antibody content expressed relative to that of the proposed standard in assays using native or recombinant antigen. However, antibody was not detected in serum from an individual blood donor (Preparation C) in assays performed using kits which contained recombinant VP1 but not VP2. This highlights the differences which may be obtained in commercial kits which contain different antigens. The results of this study demonstrated that the proposed standard coded 93/724 is suitable to serve as the International Standard for parvovirus B19 serum IgG and this material has been established as the International Standard for parvovirus B19 IgG by the World Health Organization with an assigned unitage of 100 lU per ampoule. The standard, which is a pool of what can be assumed to be convalescent sera, will be suitable for standardizing diagnostic tests for use in seroprevalence studies and for assessing immunity. An additional standard will be required to standardise tests specifically for the detection of IgM and the diagnosis of acute infection.

Antibodies, Viral↗
PubMed1997

Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro.

PURPOSE: The relative contribution of the small and large intestine to paracellular absorption is a subject of some controversy. Direct comparison of paracellular permeability in different epithelia is complicated by variations in junctional density and/or the absorptive surface area. METHODS: This study used a combination of morphometric analyses and in vitro absorption studies to define permeability characteristics in relation to the amount of paracellular pathway present in rat ileum, colon and the model epithelium, Caco-2. RESULTS: Mucosal to serosal amplification was higher in ileum (3.9) than colon (1.9) or Caco-2 (1). Tight junctional density (lp) of ileal crypts was approximately 3 fold greater (91 m/cm2) than that measured in ileal villi, colonic surface and crypt cells or Caco-2 monolayers (34-37 m/cm2). However, when the relative contributions of the crypts and villi was taken into account there was no significant difference in the mean lp per mucosal area for the three epithelia studied. Using these data to correct for morphometric differences the permeabilities of a range of small hydrophilic molecules (atenolol, D-PheAsp and PEG oligomers MW 282-634) was measured. Permeability of rat ileum and colon were virtually identical for all compounds studied. In contrast, Caco-2 monolayers showed a significantly lower permeability than intestinal tissues with the difference increasing markedly with molecular size. CONCLUSIONS: These studies suggest the importance of accounting for morphological variation when comparing the permeability characteristics of different epithelial systems.

Animals↗
PubMed1997

Influence of proxy respondents and mode of administration on health status assessment following central nervous system tumours in childhood.

Central nervous system (CNS) tumours account for 20% of childhood cancers. Survivors often experience severe physical, neuropsychological and social sequelae of the disease and its treatment. Health status assessment in these individuals is an essential clinical outcome measure, yet little consensus exists regarding the optimum methodology. The influence of proxy respondents (parents, physiotherapists and doctors) and mode of administration (home and clinic) in which assessments is performed has been evaluated in a cohort of 37 survivors of childhood CNS tumours. A health-related quality of life (HRQOL) questionnaire, incorporating the Mark II and III Health Utilities Indices, was completed at home and in clinic by patients and parents. Doctors and physiotherapists completed this questionnaire plus Lansky Play-Performance and Karnofsky Performance scores. No significant differences between raters for single attribute scores occurred either at home or in clinic, although a wide range of agreement (kappa = 0.05-1.00, percentage agreement 53-100%) between observers was revealed. Most agreement occurred between parents and patients: this was greatest on home completion (kappa = 0.48-1.00, percentage agreement 53-100%). Doctors and physiotherapists agreed less on subjective attributes (emotion, cognition and pain). Better if responses were classified as normal and abnormal. Inter-observer agreement was greater for the HRQOL questionnaire than for Karnofsky and Lansky scores. Home completion of questionnaires provides a reliable, acceptable and convenient method of assessing health status.

Adolescent↗
PubMed1997

Sequence-specific inhibition of the tumor necrosis factor-alpha receptor I gene by oligodeoxynucleotides containing N7 modified 2'-deoxyguanosine.

Tumor necrosis factor-alpha (TNF-alpha) is a highly pleiotropic cytokine produced mainly by activated macrophages. This cytokine has been found to mediate the growth of certain tumors, the replication of HIV-1, septic shock, cachexia, graft-versus-host disease, and autoimmune diseases. The binding of TNF-alpha to the p55 tumor necrosis factor receptor type I (TNFRI) is considered one of the initial steps responsible for the multiple physiologic effects mediated by TNF-alpha. The role of TNF-alpha as an inflammatory mediator through TNFRI makes both of these genes attractive targets for intervention in both acute and chronic inflammatory diseases. We have designed antisense oligodeoxynucleotides (ODNs) containing chemically modified purine and pyrimidine bases that specifically inhibit TNFRI expression and functions. These ODNs were designed to hybridize to the 3'-polyadenylation signal region of the TNFRI gene. In cell-based assays, gene-specific antisense inhibition occurred in a dose-dependent fashion at submicromolar concentrations in the presence of cellular uptake enhancing agents. Within ODN sets with a common pattern of stabilizing backbone substitution, the inhibition of the gene expression is found to be correlated with the affinity of the ODNs for their cognate mRNA target sites, providing direct evidence for an antisense mechanism of action. In addition, events triggered by the binding of TNF-alpha to TNFRI, such as the production of IL-6 and IL-8, were significantly reduced by treatment of cells with the anti-TNFRI ODN. Therefore, antisense ODNs can be used to control biologic processes mediated by TNF-alpha and may be useful as therapeutic agents to treat conditions resulting from overproduction of TNF-alpha.

Antigens, CD↗
PubMed1997

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination.

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH-stimulated patients.

Chorionic Gonadotropin↗
PubMed1997

Intrathecal sufentanil for labor analgesia does not cause a sympathectomy.

BACKGROUND: Intrathecal sufentanil (ITS) is frequently used to provide analgesia during labor. Decreases in blood pressure and sensory changes in this circumstance suggest that ITS may have a local anesthetic effect and thus cause a sympathectomy. To determine whether ITS given to laboring women causes a sympathectomy, the authors evaluated central and lower extremity temperature changes after ITS administration. These findings were compared with those in a control group of women having spinal anesthesia with bupivacaine for elective cesarean section in whom an extensive sympathectomy was expected. METHODS: Twenty parturients classified as American Society of Anesthesiologists' physical status 1 or 2 had temperatures measured centrally, at the calf, and at the great toe at frequent intervals after receiving 10 microg ITS for labor analgesia (sufentanil group, n = 10), or hyperbaric bupivacaine 12 mg in their spinal anesthetic for cesarean section (bupivacaine group, n = 10). Calf-to-toe temperature indices (C-T) were calculated by subtracting toe temperature from calf temperature. A decrease in this index means that the toe had warmed compared with the calf and is an indication of vasodilation and a sympathectomy. RESULTS: There was no significant change in the C-T indices or central temperature in the sufentanil group, but the C-T indices and central temperature decreased significantly in the bupivacaine group. CONCLUSIONS: The decreases in the C-T index and central temperature in the bupivacaine group indicate the presence of a sympathectomy. The lack of change in the C-T indices and central temperature in the sufentanil group indicates that no significant vasodilation occurred. Therefore, the decrease in blood pressure seen after ITS administration for labor analgesia is unlikely to be the result of a sympathectomy.

Adult↗
PubMed1997

Type B lactic acidosis following cardiopulmonary bypass.

OBJECTIVE: To describe, characterize, and identify the associations of postcardiac surgical lactic acidosis occurring in the absence of clinical evidence of tissue hypoperfusion. DESIGN: The preliminary study is a report of a series of observations in 12 patients. The prospective study is also observational, involving the structured collection of hemodynamic and metabolic variables in a prescribed series of patients. SETTING: Cardiac surgical intensive care unit of a university teaching hospital. PATIENTS: Twelve patients who developed an unexplained lactic acidosis after cardiac surgery are reported in the preliminary study. The prospective study involved observations in 112 consecutive patients undergoing cardiopulmonary bypass for cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preliminary study: Cardiac index was increased before, during and after recovery from lactic acidosis. Recovery from lactic acidosis was associated with a decrease in oxygen transport index and significant increases in oxygen consumption index and oxygen extraction ratio. PROSPECTIVE STUDY: Hemodynamic, oxygen transport, and oxygen consumption variables, together with arterial blood gas and lactate concentrations, were assessed every 6 hrs for 24 hrs after surgery. Sixteen patients developed lactic acidosis (peak lactate concentration > 5.0 mmol/L). Compared with the remainder of the patients, this subgroup had longer duration of cardiopulmonary bypass (116 +/- 31 vs. 76 +/- 31 mins, p < .01), greater intraoperative hypothermia (24.9 +/- 2.0 degrees vs. 26.6 +/- 2.3 degrees C, p < .01), more frequent requirement for vasopressor agents (14/16 vs. 35/96, p < .05) and a higher frequency of hyperglycemia (15/16 vs. 28/96, p < .01). Hemodynamic variables, including cardiac index, were remarkably similar in the acidotic and nonacidotic groups. All of the acidotic patients, in both parts of this study, recovered from their acidosis. Eleven of the patients in the preliminary study and all of the 16 acidotic patients in the prospective study were ultimately discharged from the hospital. CONCLUSIONS: This report documents the occurrence of lactic acidosis in a subgroup of patients undergoing cardiopulmonary bypass. The pathogenesis of this disorder is uncertain, but it appears to not relate to inadequate oxygen delivery. Systemic vasodilation and reduced oxygen extraction appear to be features of this disorder, which has an excellent prognosis.

Acidosis, Lactic↗
PubMed1997

Protein characterization of Australian spotted fever group rickettsiae and monoclonal antibody typing of Rickettsia honei.

Rickettsial proteins rOmp A and rOmp B exist in both Rickettsia australis and Rickettsia honei but differ in molecular weight and antigenicity; in addition, they produce distinct immunogenic responses and appear to be to conformationally dependent antigens. Species-specific monoclonal antibodies for other spotted fever group rickettsial species did not react with R. honei. A PCR product of the repeat region of the rOmp A gene from R. honei was amplified and calculated to contain 11 repeat units.

Antibodies, Bacterial↗