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Biomedical subjects

C Thornton

Publications and source records attributed to C Thornton.

At least 37 records · Page 2Linked to original sources

Adverse effects and sero-responses to an acellular pertussis/diphtheria/tetanus vaccine when combined with Haemophilus influenzae type b vaccine in an accelerated schedule.

UNLABELLED: Acellular pertussis vaccines provide protection against pertussis with few adverse effects. Differences in the reactogenicity and immunogenicity of available pertussis vaccines may be influenced by the immunisation schedule employed. We assessed responses to an acellular pertussis, diphtheria, tetanus vaccine mixed with Haemophilus influenzae type b (Hib) vaccine, (PRP-T) given at age 2, 3 and 4 months. Parents kept a symptom diary for 3 days after each immunisation. Antibodies to diphtheria, tetanus, pertussis toxin and filamentous haemagglutinin were measured by enzyme immunoassay at 2 and 5 months. Results were compared with historical controls who received a combination whole-cell pertussis, diphtheria, tetanus/PRP-T vaccine in the same schedule. A total of 262 infants were recruited, of whom 251 were fully evaluated after three doses of vaccine. Systemic and most local reactions were less frequent following the acellular combination. Fever > or = 38 degrees C was reported after only 0.6% of doses. Redness or swelling > or = 2.5 cm were unusual after the first two doses (2-5%), but rates rose to 13% after the third dose. Antibody responses to diphtheria and tetanus toxoids were lower, while those to pertussis antigens were higher, more uniform and less attenuated by pre-immunisation antibody than in infants who received the whole-cell combination. All infants achieved protective antibody titres of at least 0.1 IU/ml for diphtheria and 0.01 IU/ml for tetanus. CONCLUSION: The acellular combination vaccine was immunogenic for diphtheria, tetanus and pertussis components and was associated with low rates of fever following immunisation.

Analysis of Variance↗

Effective health care for people with learning disabilities: a formal carers' perspective.

This paper explores the perceptions and experiences of formal carers, working in three different geographical locations in the south of England, in accessing primary health care for people with learning disabilities. The sample included six multidisciplinary, community learning disability teams and 11 managers of small homes for residents who had learning disabilities. Data were collected through focus group and individual semistructured interviews. Levels of collaboration between primary health care groups and the community learning disability teams and the managers of small homes were assessed. Questions were focused upon the importance of primary health care and the key care provider within the community setting. Although some good experiences were recorded, the overall levels of collaboration were poor. Health care was perceived as very important by all of the respondents. The general practitioner (GP) as the coordinator of health care was perceived as the normal model within our health care system but the majority of respondents questioned the effectiveness in relation to their own experiences of accessing health care for people with learning disabilities. The relocation of this role to the learning disability nurse was perceived as a possible solution.

Attitude of Health Personnel↗

The myotonic dystrophies.

Myotonic dystrophy, or dystrophia myotonica (DM), is the most common inherited muscle disorder in adults. DM is a multisystem disease in which the most disabling feature is muscle wasting that begins in the distal limb and cranial muscles. The genetic basis for DM is an expanded CTG repeat in the DMPK gene on chromosome 19. The size of the expanded repeat, and the severity of the disease, tend to increase in successive generations. The mechanism by which this unusual mutation leads to muscle wasting, myotonia, cataracts, heart block, and neurobehavioral abnormalities has not been clearly defined. Identification of the DM gene has made it easier to delineate other DM-like disorders that are clinically and genetically distinct. The most common of these is proximal myotonic myopathy (PROMM), which is characterized by early involvement of proximal limb muscles. The genetic locus for another DM-like disorder, called DM type 2, was recently mapped to chromosome 3.

Anticipation, Genetic↗

Dissociation, abuse and the eating disorders: evidence from an Australian population.

OBJECTIVE: A number of European and Northern American studies have investigated a possible association between dissociative phenomena, eating disorders, child sexual abuse and self-mutilation. However, there has been little confirmation from other countries and cultures, and the Australian experience of these interrelationships has not previously been studied. METHOD: Dissociative symptomatology and self-reported history of abusive experiences, physical and sexual, were retrospectively studied in a sample of Australian eating disordered patients using a self-report measure, the Dissociation Questionnaire (DIS-Q). RESULTS: As hypothesised, dissociative symptoms were particularly frequent in those who reported child and adult sexual abuse and in those who self-mutilated. A correlation between multiple forms of abuse and higher dissociation scores was only partially upheld. CONCLUSIONS: Interrelationships between victimisation and dissociation are discussed within the context of current knowledge in the field, and brief suggestions for therapeutic strategies are offered.

Adolescent↗

The induction of immunologic memory after vaccination with Haemophilus influenzae type b conjugate and acellular pertussis-containing diphtheria, tetanus, and pertussis vaccine combination.

The significance of reduced antibody responses to the Haemophilus influenzae type b (Hib) component of acellular pertussis-containing combination vaccines (DTaP-Hib) is unclear. A DTaP-Hib vaccine evaluated in infants vaccinated at ages 2, 3, and 4 months showed reduced anti-Hib polysaccharide IgG (geometric mean concentration [GMC], 1.23 microgram/mL; 57%, >1.0 microgram/mL). Polyribitolribosyl phosphate (PRP) and Hib conjugate (PRP-T) vaccine given as a booster during the second year of life was evaluated for the presence of immunological memory. After boosting, most children achieved anti-PRP IgG >1.0 microgram/mL, although the GMC was higher with PRP-T (88.5 microgram/mL) than with PRP vaccine (7.86 microgram/mL, P<.001). The GMC of the PRP group was higher than anticipated for naive PRP recipients of the same age. PRP-specific IgG avidity was significantly higher after boosting than after priming, providing further evidence for the generation of memory. Despite reduced immunogenicity, DTaP-Hib combination vaccines appear to prime for immunologic memory.

Antibodies, Bacterial↗

Effect of a bolus dose of midazolam on the auditory evoked response in humans.

We have studied the effect of a bolus dose of midazolam on the auditory evoked response (AER) of the electroencephalogram (EEG) in nine patients. We measured the AER in the awake patient, at the point of loss of the eyelash reflex and when airway support was required. The eyelash reflex was lost at mean 1.78 (SD 0.5) min after administration of the midazolam bolus dose. Time to airway support in the seven patients who required it was 2.74 (1.26) min. Mean Nb latency in awake patients was 44.3 ms (95% CI 41.9-46.9) which was significantly shorter than Nb latency at the clinical end-points (P < 0.001). When the eyelash reflex was lost, Nb latency was 55.7 ms (95% CI 51.4-60.3) and when airway support was needed, it was 50.9 ms (95% CI 48.6-53.2). We conclude that loss of consciousness after midazolam was associated with an increase in mean Nb latency.

Adult↗

Effect of bolus doses of alfentanil on the arousal response to intubation, as assessed by the auditory evoked response.

We have studied the effect of bolus doses of alfentanil on the arousal response to intubation, using the auditory evoked response (AER) of the electroencephalogram (EEG) in 45 anaesthetized patients. After induction of anaesthesia with propofol and 20 min of positive pressure ventilation via a laryngeal mask airway with 0.6 MAC of isoflurane and 50% nitrous-oxide in oxygen, patients received saline (control), or alfentanil 15 or 50 micrograms kg-1 before intubation. The early cortical AER before and after intubation in each group was measured and compared. After intubation, Pa amplitude increased in the saline group by 60% (95% CI +10 to +130), decreased in the low-dose alfentanil group by 11% (-38 to +29) and decreased further in the high-dose alfentanil group by 26% (-49 to +7). There were significant (P < 0.005) linear trends in the three group means for Pa amplitude. Similarly, Nb latency increased in the saline group by 30% (-2 to +73), decreased in the low-dose alfentanil group by 10% (-32 to +19) and decreased further in the high-dose alfentanil group by 19% (-39 to +7). There were significant (P = 0.02) linear trends in the three group means for Nb amplitude. Systolic and diastolic arterial pressures increased after intubation in the control group, and to a lesser extent in the low-dose alfentanil group, but decreased after high-dose alfentanil. Heart rate increased after intubation in the control group but decreased in both alfentanil groups, decreasing to a greater degree in the high-dose group. There were significant (P < 0.001) linear trends for all three haemodynamic variables in the three groups. We conclude that the increase in Pa amplitude after intubation was blocked by bolus administration of alfentanil and that this effect was dose dependent.

Adolescent↗

Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with anaesthetic-sparing effects. We have determined the pharmacodynamic and pharmacokinetic interactions between dexmedetomidine and isoflurane in volunteers. Nine male subjects were allocated randomly to receive isoflurane anaesthesia preceded by infusion of dexmedetomidine on three separate occasions, 2 weeks apart. Dexmedetomidine target plasma concentrations were 0.0 (placebo), 0.3 ng ml-1 (low-dex) and 0.6 ng ml-1 (high-dex). End-tidal isoflurane concentrations at which gross purposeful movement and response to verbal commands occurred were identified. In the recovery period, sedation scores and digit symbol substitution tests were recorded. Venous blood samples were obtained before, during and after anaesthesia at predetermined intervals for measurement of plasma concentrations of dexmedetomidine and calculation of standard pharmacokinetic indices (AUC, Cl, Vss, T1/2 alpha, T1/2 beta). The end-tidal isoflurane concentration at which 50% of subjects first responded to the tetanic stimulus was 1.05% in the placebo group, 0.72% in the low-dex group and 0.52% in the high-dex group. We conclude that dexmedetomidine decreased isoflurane requirements in a dose-dependent manner and reduced heart rate, systolic and diastolic arterial pressures. Sedation and slight impairment of cognitive function persisted for several hours after anaesthesia and the end of infusion of dexmedetomidine. Isoflurane did not appear to influence the pharmacokinetics of dexmedetomidine.

Adrenergic alpha-Agonists↗

Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 2: Auditory and somatosensory evoked responses.

The anaesthetic-sparing activity of dexmedetomidine during isoflurane anaesthesia was examined, using the end-point of lack of response to tetanic nerve stimulation. Nine subjects were given two doses of dexmedetomidine (target plasma concentrations of 0.3 ng ml-1 and 0.6 ng ml-1, respectively) and saline on separate occasions. We measured auditory (AER) and somatosensory (SER) evoked responses at end-tidal isoflurane concentrations of 0.2-1.4%. Pa and P25-N35 amplitudes increased as isoflurane concentration was reduced (P < 0.001). Dexmedetomidine had no significant effect on this relationship. In contrast, P15-N20 (SER) amplitude increased (P < 0.001) as isoflurane concentration was reduced. The dose of dexmedetomidine had a significant interaction with this trend (P < 0.002). Decreasing the concentration of isoflurane at the high dose of dexmedetomidine had less impact on P15-N20 amplitude than decreasing isoflurane at the low dose or with saline. The mechanism by which dexmedetomidine spares isoflurane is discussed in the light of these evoked response changes.

Adrenergic alpha-Agonists↗

Middle latency auditory evoked responses and electroencephalographic derived variables do not predict movement to noxious stimulation during 1 minimum alveolar anesthetic concentration isoflurane/nitrous oxide anesthesia.

UNLABELLED: The electroencephalogram (EEG) and middle latency auditory evoked responses (MLAER) have been proposed for assessment of the depth of anesthesia. However, a reliable monitor of the adequacy of anesthesia has not yet been defined. In a multicenter study, we tested whether changes in the EEG and MLAER after a tetanic stimulus applied to the wrist could be used to predict subsequent movement in response to skin incision in patients anesthetized with 1 minimum alveolar anesthetic concentration (MAC) isoflurane in N2O. We also investigated whether the absolute values of any of these variables before skin incision was able to predict subsequent movement. After the induction of anesthesia with propofol and facilitation of tracheal intubation with succinylcholine, 82 patients received 1 MAC isoflurane (0.6%) in N2O 50% without an opioid or muscle relaxant. Spontaneous EEG and MLAER to auditory click-stimulation were recorded from a single frontoparietal electrode pair. MLAER were severely depressed at 1 MAC isoflurane. At least 20 min before skin incision, a 5-s tetanic stimulus was applied at the wrist, and the changes in EEG and MLAER were recorded. EEG and MLAER values were evaluated before and after skin incision for patients who did not move in response to tetanic stimulation. Twenty patients (24%) moved after tetanic stimulation. The changes in the EEG or MLAER variables were unable to predict which patients would move in response to skin incision. Preincision values were not different between patients who did and did not move in response to skin incision for any of the variables. MLAER amplitude increased after skin incision. We conclude that it is unlikely that linear EEG measures or MLAER variables can be of practical use in titrating isoflurane anesthesia to prevent movement in response to noxious stimulation. IMPLICATIONS: Reliable estimation of anesthetic adequacy remains a challenge. Changes in spontaneous or auditory evoked brain activity after a brief electrical stimulus at the wrist could not be used to predict whether anesthetized patients would subsequently move at the time of surgical incision.

Adolescent↗

Antibody response to accelerated Hib immunisation in preterm infants receiving dexamethasone for chronic lung disease.

AIM: To study the effect of dexamethasone on the routine immunisation of preterm infants with chronic lung disease. METHODS: Serum samples were obtained before and after immunisation from an unselected cohort of 59 preterm infants. Haemophilus influenzae antibodies were measured using an ELISA method and differences in the geometric mean values between the two groups of babies analysed. RESULTS: Sixteen infants received no dexamethasone. Before and after immunisation antibody titres for those receiving no dexamethasone were 0.16 and 4.63 mcg IgG/ml. Corresponding values for those receiving dexamethasone were 0.10 and 0.51 mcg IgG/ml, respectively. CONCLUSION: Dexamethasone used in the treatment of chronic lung disease seems to significantly affect the antibody response of preterm infants to immunisation against Haemophilus influenzae.

Anti-Inflammatory Agents↗

Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle.

The AMP-activated protein kinase (AMPK) is a member of a growing family of related kinases, including the SNF1 complex in yeast, which respond to nutritional stress. AMPK is a heterotrimeric complex of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), and proteins related to all three subunits have been identified in the SNF1 complex. We have used the two-hybrid system in order to identify proteins interacting with the catalytic subunit (alpha2). Using this approach, we have isolated a novel AMPKbeta isoform, which we designate AMPKbeta2. The N-terminal region of beta2 differs significantly from that of the previously characterized isoform (beta1), suggesting that this region could play a role in isoform-specific AMPK activity. Comparison of the C-terminal sequences of beta1 and beta2 with their related proteins in yeast identifies two highly conserved regions predicted to be involved in binding of the alpha and gamma subunits. The expression of beta1 and beta2 was examined in a number of tissues, revealing that the beta1 isoform is highly expressed in liver with low expression in skeletal muscle, whereas the opposite pattern is observed for the beta2 isoform. These results suggest that the beta isoforms have tissue-specific roles, which may involve altered responses to upstream signaling and/or downstream targeting of the AMPK complex.

AMP-Activated Protein Kinases↗

Does the Composite International Diagnostic Interview underdiagnose the eating disorders?

OBJECTIVE: A study was undertaken to assess the procedural validity of the Composite International Diagnostic Interview (CIDI) for the diagnosis of eating disorders. METHOD: The CIDI was administered to 44 patients consecutively admitted to an eating disorders unit. CIDI-generated diagnoses were compared with clinical diagnoses documented in patient files. Discrepancies between diagnoses were examined in detail. RESULTS: A significant level of disagreement was apparent, particularly for anorexia nervosa patients. A large number of patients with symptoms requiring inpatient treatment did not reach criteria using CIDI's diagnostic algorithm. CONCLUSION: Considerable difficulties remain in the use of standardized assessments, such as the CIDI, to diagnose eating disorders. While presenting features of the illness, for example, ego syntonic nature of the illness, secrecy, and denial, may be part of the reason, the questions used by the CIDI appear to be in need of some refinement.

Anorexia Nervosa↗

Perceptions of bed rest by anorexic patients.

OBJECTIVE: Few studies have investigated perceptions of operant conditioning programs by anorexic patients. This study examined patients' perceptions of the Bed Rest (BR) component which is employed in some operant conditioning programs. METHODS: A sample of 48 anorexic inpatients was administered a survey to elicit their attitudes towards BR. RESULTS: Results from the survey suggested that most patients perceived BR in a negative way. The main complaint, however, was not punishment or humiliation, as predicted, but isolation and boredom. A number of patients concluded that they wanted more individualization and distraction and less restriction while on BR. DISCUSSION: The findings justify the use of BR within a humane framework in the inpatient treatment of anorexia nervosa, but suggest that patients' perceptions of BR warrant systematic scrutiny.

Adolescent↗

Effect of remifentanil on the auditory evoked response and haemodynamic changes after intubation and surgical incision.

We have observed the effect of intubation and incision, as measured by the auditory evoked response (AER) and haemodynamic variables, in 12 patients undergoing hernia repair or varicose vein surgery who received remifentanil as part of either an inhaled anaesthetic technique using isoflurane or as part of a total i.v. technique using propofol. Anaesthesia was induced with remifentanil 1 microgram kg-1 and propofol, neuromuscular block was achieved with atracurium 0.6 mg kg-1 before intubation, and anaesthesia was maintained with a continuous infusion of remifentanil in combination with either a continuous infusion of propofol or inhaled isoflurane. The AER and haemodynamic variables were measured before and after intubation and incision. The effects of intubation and incision on the AER and haemodynamic variables were not significantly different between the remifentanil-propofol and remifentanil-isoflurane groups. However, the study had a low power for this comparison. When the data for the two anaesthetic combinations were pooled, the only significant effects were increases in diastolic arterial pressure and heart rate immediately after intubation; these were not seen 5 min after intubation. There were no cardiovascular responses to incision. There were no significant changes in the AER after intubation or incision.

Analgesics, Opioid↗

Automation, task difficulty, and aircrew performance.

The effects of an automated system on team processes and performance were assessed in a laboratory simulation. Two-person crews were required to fly a complex emergency-response scenario under conditions of low and high workload. These flights were completed with or without the aid of an autopilot. The results indicated that the autopilot was effective in reducing subjective workload. However, the automation was associated with improved performance on only 1 of 4 performance measures. Furthermore, it was observed that problem-solving performance was worse in the autopilot condition during the high-workload flights. Investigation of crew process data indicated that workload savings afforded by the autopilot might have been invested in more explicit coordination. The results are discussed in terms of their implications for military aviators' performance, system design, and team training.

Adult↗