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Biomedical subjects

D Jordan

Publications and source records attributed to D Jordan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Differences in serological IgA responses to recombinant baculovirus-derived human papillomavirus E2 protein in the natural history of cervical neoplasia.

Infection with certain types of human papillomavirus (HPV) presents a high risk for the subsequent development of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. Immunological mechanisms are likely to play a role in control of cervical HPV lesions. The HPV E2 protein has roles in virus replication and transcription, and loss of E2 functions may be associated with progression of cervical neoplasia. Accordingly, it is of interest to monitor immune responses to the E2 protein, and previous studies have reported associations between serological reactivity to E2 peptide antigens and cervical neoplasia. In order to investigate serological responses to native, full-length E2 protein, we expressed HPV-16 E2 proteins with and without an N-terminal polyhistidine tag using the baculovirus system. Purified HPV-16 E2 protein was used to develop enzyme-linked immunosorbent assays to detect serological IgG and IgA responses in cervical neoplasia patients and controls. We found that serum IgA levels against the E2 protein were elevated in CIN patients relative to normal control subjects but were not elevated in cervical cancer patients. Moreover, there appeared to be a gradient of response within cervical neoplasia such that the highest antibody levels were seen in lower grades of neoplasia up to CIN 2, whereas lower levels were observed in CIN 3 and still lower levels in cervical carcinoma. These findings suggest that the IgA antibody response to E2 may associate with stage and progression in cervical neoplasia.

Adult↗
PubMed1997

Evaluation of an intercostal myoneurovascular transposition as a lower esophageal neosphincter.

Previous work has shown promising results for an intercostal myoneurovascular transposition in the prevention of gastroesophageal reflux following esophagectomy. A first study evaluated the intercostal transposition procedure and compared it with the Nissen fundoplication using a rabbit model of gastroesophageal reflux. Group A underwent partial cardiomyectomy to produce gastroesophageal reflux. Group B underwent cardiomyectomy, and intercostal transposition around the gastric cardia. Group C underwent Nissen fundoplication and cardiomyectomy. All animals had preoperative and 1-week and 4-week postoperative intraesophageal manometry and pH studies. At the 4-week interval, macroscopic and microscopic esophageal histopathology was assessed. The mean change in values from preoperative to 4 weeks postoperative were compared. Group B showed significantly lower reflux time (P < 0.001) and grade of esophagitis (P < 0.005), and significantly greater average lower esophageal sphincter basal pressure (P < 0.001) and abdominal length of sphincter (P < 0.01) when compared with Group A. There was no statistical significance between the results of Group B and Group C. A second study assessed whether reflux was prevented by an anatomical structure, or a muscle flap acting in a physiological manner. At autopsy, the ten rabbits from Group B underwent removal of the intercostal wrap, and the right 11th intercostal muscle as a control. There was a significant difference in the quantity of viable muscle tissue between muscle flaps and controls (P < 0.001), the muscle flaps having generally little viable muscle left 4 weeks after surgery. A further experiment to evaluate this result found that loss of muscle tissue was due to excessive stretch and not due to damage of the intercostal neurovascular bundle during mobilization. Two groups of animals underwent electromyographic studies. The first group underwent recordings of all intercostal muscles. The second group underwent intercostal transposition around the gastric cardia, and insertion of recording electrodes into the muscle flap. The electromyographic activity of the muscle flap was recorded at 0, 2, and 4 weeks after surgery. The second group demonstrated activity in the muscle flaps simultaneous with diaphragmatic contractions. This activity, although much reduced, was still present 4 weeks after surgery. These studies showed that the intercostal transposition and Nissen fundoplication procedures are equally effective in preventing experimental gastroesophageal reflux. The antireflux properties of the intercostal transposition were possibly the result of anatomical buttressing of the gastroesophageal junction, and not due to a fully viable contracting muscle flap.

Animals↗
PubMed1997

Insights into the increased oxygen demand during chest physiotherapy.

OBJECTIVES: To determine the mechanism responsible for the increase in oxygen consumption (VO2) during chest physical therapy. Specifically, to examine the hypothesis that muscular activity is the major contributor to the increase in oxygen demand. DESIGN: Prospective, observational study. SETTING: University hospital surgical intensive care unit. PATIENTS: Phase one included 13 patients who were mechanically ventilated after coronary artery bypass surgery. Phase two involved seven mechanically ventilated patients who had undergone major vascular or abdominal surgery. INTERVENTIONS: Phase one involved turning patients to the lateral decubitus position. During the second phase, patients were given midazolam (0.15 microg/kg) 2 mins before an initial chest physiotherapy session and midazolam plus vecuronium (0.7 mg/kg) before a subsequent session. Physiologic measurements were made during the resting periods before and following each session, as well as at the completion of the intervention. MEASUREMENTS AND MAIN RESULTS: Turning patients to the lateral position resulted in significant increases in oxygen uptake and CO2 elimination (VCO2). VO2 increased from 219 +/- 21 (SD) mL/min at rest to 324 +/- 58 mL/min (p <.05) with turning. These increases in oxygen demand were met by increases in both oxygen delivery (852 +/- 238 mL/min at rest to 1116 +/- 430 mL/min, p < .05) and extraction (0.27 +/- 0.7 at rest to 0.32 +/- 0.09, p < .05). There were associated increases in hemodynamic and respiratory variables including heart rate and systolic blood pressure. The administration of vecuronium completely suppressed the 50% increases in VO2 and VCO2 seen without the use of a muscle relaxant. The increases in systolic blood pressure were unaffected by vecuronium. The magnitude of the increase in PaCO2 (32 +/- 5 torr [4.3 +/- 0.7 kPa] at rest to 36 +/- 5 torr [4.8 +/- 0.7 kPa] during therapy, p < .05), was not accentuated by vecuronium (30 +/- 4 torr [4.0 +/- 0.5 kPa] to 35 +/- 6 torr [4.7 +/- 0.8 kPa], p < .05) despite a lack of any increase in minute ventilation or respiratory rate. This change was due to the parallel suppression of VCO2. CONCLUSIONS: The increase in metabolic demand during chest physiotherapy is the result of increased muscular activity as evidenced by the suppression of VO2 following the administration of the muscle relaxant and the observation that turning a patient into the lateral decubitus position produces similar increases in VO2. The increases in blood pressure and cardiac output are due to another mechanism, most likely enhanced sympathetic output. The increase in physiologic activity produced by chest physiotherapy is thus secondary to both exercise-like and stress-like responses.

Aged↗
PubMed1997

Continuity of do-not resuscitate orders between hospital and nursing home settings.

OBJECTIVE: To determine the relationship between interinstitutional communication and continuity of advance directives from hospital to nursing home (NH) settings. DESIGN: Retrospective chart review of discharges to hospital affiliated or community NHs. SETTING: Teaching Veterans Affairs Hospital and affiliated and community nursing homes. MEASUREMENTS: Demographic characteristics, medical diagnoses, presence of advance directives, and documentation that relates to the topic. RESULTS: A total of 83 patients were discharged to either setting. Before discharge to a NH, the prevalence of chronic obstructive pulmonary disease and cancer was higher among those who had a DNR order. Overall, subsequent discussions about advance directives were equally common in NHs. Having a hospital discussion about advance directives or having a hospital DNR order were associated with a higher rate of advance directive discussions in NHs. Hospital DNR orders were continued for 93% and 41% of patients admitted to the hospital-affiliated NH compared with community NHs, respectively (P < .001). Specific communication of hospital DNR status to the receiving NH was associated with better continuity of DNR orders (49% vs 9%, P = .001). Factors that predicted continuity of DNR orders in logistic regression analysis correctly included hospital DNR status, communication of advance directives to the receiving NH, and NH advance directive discussions. CONCLUSIONS: There is higher continuation rate of DNR orders between the hospital under study and its affiliated NH than to community NHs despite a similar frequency of confirmation discussions. Completing advance directives before patients are discharged to NHs, communication of advance directives to the receiving NH, and follow-up discussions at the NH may improve the continuity of advance directives between hospitals and nursing homes.

Advance Directives↗
PubMed1996

Crystal structure of the ternary complex of 1,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea with NADPH and an active-site inhibitor.

BACKGROUND: The enzyme 1,3,8-trihydroxynaphthalene reductase (THNR) catalyzes an essential reaction in the biosynthesis of melanin, a black pigment crucial for the pathogenesis of the rice blast fungus, Magnaporthe grisea. The enzyme is the biochemical target of several commercially important fungicides which are used to prevent blast disease in rice plants. We have determined the structure of the ternary complex of THNR with bound NADPH and a fungicide, tricyclazole. RESULTS: Crystallographic analysis showed four identical subunits of THNR to form a tetramer with 222 symmetry. The enzyme subunit consists of a single domain comprising a seven-stranded beta sheet flanked by eight alpha helices; the subunit contains a dinucleotide-binding fold which binds the coenzyme, NADPH. Tricyclazole, an inhibitor of the enzyme, binds at the active site in the vicinity of the NADPH nicotinamide ring. The active site contains a Ser-Tyr-Lys triad which is proposed to participate in catalysis. Coenzyme specificity is partly conferred by the interaction of a single basic residue, Arg39, with the 2' phosphate group of NADPH. CONCLUSIONS: The structural model reveals THNR to belong to the family of short chain dehydrogenases. Despite the diversity of the chemical reactions catalyzed by this family of enzymes, their tertiary structures are very similar. In particular THNR has many amino acid sequence identities, and thus most probably high structural similarities, to enzymes involved in fungal aflatoxin synthesis. The structure of THNR in complex with NADPH and tricyclazole provides new insights into the structural basis of inhibitor binding. This new information may aid in the design of new inhibitors for rice crop protection.

Amino Acid Sequence↗
PubMed1996

Crystallization and preliminary x-ray diffraction study of 1 ,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea.

1,3,8-Trihydroxynaphthalene reductase was crystallized in the presence of NADPH and the inhibitor tricyclazole. The crystals are trigonal, space group P3(1)21 or its enantiomorph P3(2)21. Two crystal forms with slightly different cell dimensions were obtained. Form A has unit cell dimensions a = b = 142.6 angstrom, c = 70.1 angstrom and form B cell dimensions a = b = 142.6 angstrom, c = 72.9 angstrom. The diffraction pattern of the latter crystal form extends to 2.5 angstrom resolution.

Ascomycota↗
PubMed1996

Evidence for multiple opioid receptors in the human posterior pituitary.

The distribution and quantification of opioid receptor types in post-mortem human pituitary cryostat sections was determined by quantitative in vitro receptor autoradiography. Highly specific radioligands were used for each opioid receptor type i.e. [125l]-FK-33-824 for mu-opioid sites, [125l][D.Ala2]-Deltorphin-l for delta-opioid sites and 3H-U69,593 for kappa-opioid sites. None of the five specimens tested exhibited any labeling in the anterior lobe of the pituitary for the three radioligands. As for the posterior pituitary, all 5 specimens contained both mu and kappa-opioid binding sites whereas none of them showed delta-binding sites. The presence of both mu- and kappa-opioid binding sites in the human posterior pituitary contrasts with previous findings in the rat where only kappa-sites have been found. The present study could contribute to understanding of the functional action of opioids in the human pituitary.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Mediation by 5-HT3 receptors of an excitatory effect of 5-HT on dorsal vagal preganglionic neurones in anaesthetized rats: an ionophoretic study.

1. Extracellular recording were made from 141 vagal preganglionic neurones in the dorsal vagal nucleus (DVN). The effects of ionophoretic administration of 5-hydroxytryptamine (5-HT), the 5-HT3 receptor agonist, phenylbiguanide (PBG) and the antagonists, granisetron and tropisetron (ICS 205-930) on these vagal preganglionic neurones were studied in pentobarbitone sodium anaesthetized rats. 2. Ionophoretic application of 5-HT at low currents (< 10 nA) increased the activity in 46 (73%) of 63 neurones tested. Application of granisetron (5-20 nA) or tropisetron (5-20 nA) abolished or attenuated the 5-HT excitatory responses in 8 out of 11 and 5 out of 5 neurones respectively. At the currents used, neither antagonist had any effect on baseline firing rate. 3. Ionophoresis of the selective 5-HT3 receptor agonist, phenylbiguanide (0-40 nA) excited 54 (82%) of the 66 vagal neurones tested, whilst the remaining 12 neurones were unaffected. 4. Granisetron applied either ionophoretically (8/11) or intravenously (3/3),abolished or attenuated the excitations evoked by PBG. Similarly, tropisetron administered either ionophoretically (2/3) or intravenously (2/2), attenuated the PBG excitation. In contrast, the PBG excitations were unaffected by the 5-HT2 receptor antagonist, cinanserin (2/2), and the selective 5-HT1A receptor antagonist, WAY- 100802 (6/6). 5. In conclusion, excitation of vagal preganglionic neurones evoked by ionophoretic application of 5- HT is mediated in part by 5-HT3 receptors and activation of 5-HT3 receptors on and/or in the vicinity of vagal motoneurones causes excitation of these neurones.

Anesthesia, General↗
PubMed1996

Aggregate testing for the evaluation of Johne's disease herd status.

This paper examines methods for evaluating herd Johne's disease status that could be used in a survey of the cattle industry. Emphasis is placed on aggregate testing, a process whereby a random sample of cattle from a herd is assessed using an imperfect test, such as an ELISA for detecting antibody in serum. Important aggregate test parameters discussed include: sample size, herd-level sensitivity, herd-level specificity, the number of reactors used for declaring a positive herd result, and the expected within-herd prevalence of disease. Aggregate testing may be useful for several livestock diseases. However, problems arise when it is applied to Johne's disease because of the poor sensitivity of the available diagnostic tests, the low within herd prevalence of infection, and clustering of false positives within a herd.

Animals↗
PubMed1996

Factors associated with the effectiveness of antibiotic treatment for ovine virulent footrot.

Factors associated with the proportion of sheep cured of virulent footrot after antibiotic treatment were studied in a field trial under dry environmental conditions. From 2 similar flocks, 1091 Merino sheep weighing about 50 kg and infected with virulent footrot received an intramuscular injection of either 12 mL of a mixture of penicillin (250 mg/mL) and streptomycin (250 mg/mL), 6 mL of long acting oxytetracycline (200 mg/mL) or 6 mL of a mixture of lincomycin (50 mg/mL) and spectinomycin (100 mg/mL). Variables that were significantly associated with the proportion of sheep cured were: the type of antibiotic used, the number of feet infected and the flock from which the sheep came. There was an interaction between antibiotic type and number of feet infected and between antibiotic type and flock in association with the proportion of sheep cured. The extent of paring and the occurrence of blowfly strike in footrot lesions treated with diazinon had no significant association with the proportion of sheep cured.

Animals↗
PubMed1996

Smoking-related knowledge and attitudes of senior Australian medical students.

OBJECTIVE: To assess the smoking-related knowledge and attitudes of senior medical students and to compare knowledge and attitude changes in students exposed to four different smoking cessation skills training interventions. DESIGN: A survey questionnaire, assessing knowledge and attitudes, was administered pre- and post-intervention for each of the four intervention conditions. SUBJECTS: A cohort of 219 fifth-year medical students at the University of Sydney. INTERVENTIONS: Students were randomised into one of four intervention conditions: (1) a traditional didactic lecture mode (control group); (2) the use of role plays and audiotaped feedback; (3) role plays with peer feedback; and (4) video feedback. MAIN OUTCOME MEASURES: Knowledge on morbidity and mortality associated with smoking, intervention strategies, intervention effectiveness, and cessation practices; anticipated clinical behaviour related to smoking; and attitudes towards medical practitioner involvement in smoking cessation. RESULTS: Smoking knowledge was significantly greater at post-test (mean unweighted scores of 69% before and 74% after intervention). All groups had improved knowledge levels at post-test. However, after controlling for pre-test differences, the control group, video feedback, and peer feedback groups were found to have improved significantly over the audio feedback group. Scores were higher on items related to morbidity and mortality and intervention effectiveness than for items on intervention strategies and cessation practices. Positive student attitudes towards their role in smoking cessation were also found. There was an almost universally held view that doctors can have a significant impact on reducing smoking levels. Although most students perceived smoking intervention to be a worthwhile activity, they remained pessimistic about the ease with which patients' smoking behaviour could be changed. CONCLUSIONS: Positive smoking cessation knowledge changes can be readily achieved through training. However, specific smoking cessation training is needed for medical trainees to develop appropriate skills and strategies. Attention to particular weaknesses related to specific intervention strategies and cessation practices is required to develop competence in this area and to maximise the chances of new medical graduates fully using the opportunities available to them.

Adult↗
PubMed1996

MAGIC: an experimental system for generating multimedia briefings about post-bypass patient status.

We describe MAGIC, an experimental system for generating multimedia briefings about the clinical status of post-bypass patients entering a cardiac ICU. MAGIC is a distributed system whose components use knowledge-based techniques for planning and generating briefings in text, speech, and graphics. These briefings are coordinated together by reasoning with dynamically generated temporal and spatial constraints. Formative evaluation using system mock-ups with ICU nurses and residents have been used to determine the general format and content of these briefings. We present an overview of MAGIC's architecture and show what it can currently generate.

Computer Systems↗
PubMed1995

Heart rate responses to selective stimulation of cardiac vagal C fibres in anaesthetized cats, rats and rabbits.

1. The contribution of cardiac vagal C fibres to vagal chronotropic control in anaesthetized cats, rats and rabbits was analysed using electrical stimulation of the vagus nerve with a selective anodal block technique. 2. After bilateral vagotomy and pretreatment with atenolol, 10 Hz continuous selective stimulation of unmyelinated fibres in the cut peripheral end of the cervical vagus evoked a bradycardia in anaesthetized rats, cats and rabbits. With this stimulation protocol the three species exhibited a similar lengthening of the heart period (R-R interval) when expressed as a percentage of their basal cardiac interval. 3. The mechanism of action of the selective blocking technique was analysed by recording eighty-nine single A- (n = 12), B- (n = 22) and C-fibre (n = 55) vagal-projecting neurones in the medulla of the rat. This demonstrated that the technique can selectively block conduction in myelinated fibres and that 'break excitation' is seen mainly in unmyelinated fibres. Although thirty C fibres showed break excitation sixteen did not and this difference could not be correlated with their axonal conduction velocity, chronaxie or initial segment frequency following. 4. Using the anodal block technique the vagal effects on heart rate were reanalysed in the cat by incorporating a collision technique. B fibres were activated orthodromically to evoke cardioinhibition and simultaneously antidromically to collide with errant B-fibre spikes activated at the electrode producing anodal block. With this protocol it was noted that the B- and C-fibre bradycardias were not additive. Using a double anodal block and collision technique, it was demonstrated that this phenomenon was likely to be due to occlusion of the effects of B and C fibres. 5. In conclusion, in addition to the well-defined effects of vagal B fibres on heart rate, selective stimulation of vagal C fibres also had a cardioinhibitory effect in all three species studied. However, since the effects of cardiac C fibres on heart rate was small, these neurones alone cannot account for the cardioinhibition of the pulmonary chemoreflex. It is likely that activation of both B- and C-fibre cardiac vagal preganglionic neurones accounts for this reflex cardioinhibition.

Animals↗
PubMed1995

Regional distribution of substance P binding sites in the brainstem of the human newborn.

The distribution of [3H]substance P ([3H]SP) binding sites in the brainstem of the human newborn was investigated in eleven cases (aged 1 h to 6 months) by in vitro quantitative receptor autoradiography. The binding of [3H]SP to newborn brainstem tissue was found to be saturable (for the eight cases examined, Kd and Bmax (M +/- S.E.M.) were 0.29 +/- 0.03 nM and 206 +/- 21 fmol/mg tissue, respectively). Competition studies showed unlabeled SP to be the most potent peptide for displacing [3H]SP binding from tissue sections. The desaturating effect of GTP on the specific binding of [3H]SP was also investigated, but was not found to be significant. Autoradiographic analysis showed that the neurokinin-1 (NK-1)/SP binding sites were widely but unevenly distributed, and that they varied with age. The highest densities of (NK-1)/SP binding sites were observed in the locus coeruleus, olivaris inferior nuclei, raphe magnus and obscurus nuclei, while low to moderate densities were observed in other brainstem structures. These findings support the idea that SP is involved in cardiovascular regulation, and that it may interact with the catecholaminergic and/or serotonergic system.

Autoradiography↗
PubMed1995

Effects of 5-HT and 5-HT1A receptor agonists and antagonists on dorsal vagal preganglionic neurones in anaesthetized rats: an ionophoretic study.

1. Effects of ionophoretic administration of 5-hydroxytryptamine (5-HT) and selective 5-HT1A receptor agonists and antagonists on identified dorsal vagal preganglionic and dorsal raphe neurones were studied in pentobarbitone sodium or chloral hydrate-anaesthetized rats, respectively. 2. Extracellular recordings were made from 176 preganglionic neurones in the dorsal vagal nucleus (DVN). Application of 5-HT at low currents (< or = 10 nA) increased the activity of these neurones. However, at increased currents (10-60 nA), it had a predominantly depressant effect. Application of selective 5-HT1A receptor antagonists, (+/-)-pindolol or WAY-100635, attenuated the excitatory responses evoked by 5-HT. 3. Ionophoresis of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-30 nA) increased the firing rate of 19 and decreased that of 67 of the 104 vagal neurones tested. Other 5-HT1A receptor agonists, flesinoxan and N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT) also had predominantly depressant effects. 4. (+/-)-Pindolol attenuated excitations but not inhibitions evoked by 8-OH-DPAT. Surprisingly, WAY-100635 and 8-OH-DPAT produced the same effect on these neurones and when applied together, WAY-100635 failed to attenuate the 8-OH-DPAT responses. 5. Dorsal raphe neurones were identified by their low, regular firing rate and their subsequent histological localization. 8-OH-DPAT reversibly reduced the activity in all 7 neurones tested and this was antagonized by WAY-100635 in all 3 neurones tested. 6. In conclusion, 5-HT applied to vagal preganglionic neurones evokes excitatory and inhibitory responses. The excitatory, but not the inhibitory responses may be mediated, at least in part, by activation of 5-HT1A receptors.

Anesthesia↗