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Biomedical subjects

C A Morgan

Publications and source records attributed to C A Morgan.

At least 55 records · Page 3Linked to original sources

Fear-potentiated startle in posttraumatic stress disorder.

Exaggerated startle is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD); however, objective studies have given conflicting results as to whether or not startle is increased in PTSD. The present study investigated startle in PTSD during the threat of shock (fear-potentiated startle). The eyeblink component of the startle reflex was measured at various times preceding and following the anticipation of unpleasant electric shocks in 9 PTSD subjects and 10 age-matched, healthy controls. Startle amplitude was significantly greater during baseline and during shock anticipation in the PTSD subjects, compared to the controls. Habituation of the startle reflex was normal. Because other studies in the literature, as well as in our own laboratory, have failed to find exaggerated startle at baseline (i.e., absence of stress) in PTSD patients, it is unlikely that the present results reflect a chronic elevation of startle in this group. Instead, the higher levels of startle in the PTSD group probably resulted from a greater conditioned emotional response in this group, triggered by anticipation of electric shocks that generalized to the unfamiliar experimental context in which testing occurred. Hence, emotionally charged test procedures may be especially informative in distinguishing PTSD patients from other psychiatric diagnostic groups.

Adult↗

A p53-dependent mouse spindle checkpoint.

Cell cycle checkpoints enhance genetic fidelity by causing arrest at specific stages of the cell cycle when previous events have not been completed. The tumor suppressor p53 has been implicated in a G1 checkpoint. To investigate whether p53 also participates in a mitotic checkpoint, cultured fibroblasts from p53-deficient mouse embryos were exposed to spindle inhibitors. The fibroblasts underwent multiple rounds of DNA synthesis without completing chromosome segregation, thus forming tetraploid and octaploid cells. Deficiency of p53 was also associated with the development of tetraploidy in vivo. These results suggest that murine p53 is a component of a spindle checkpoint that ensures the maintenance of diploidy.

Animals↗

Yohimbine facilitated acoustic startle in combat veterans with post-traumatic stress disorder.

Preclinical and clinical studies have suggested that the acoustic startle reflex (ASR) is a useful model to investigate the neurochemical basis of anxiety and fear states. This work has revealed that the anxiogenic alpha-2 receptor antagonist, yohimbine, increases the amplitude of the ASR in laboratory animals and in healthy human controls. Because of the growing body of data that support the hypothesis that severe stress results in substantial alterations in noradrenergic neuronal reactivity, the present investigation evaluated the effects of yohimbine on the ASR of 18 patients with PTSD and 11 healthy combat controls. Subjects received IV yohimbine (0.4 mg/kg) or saline placebo on 2 separate days in a randomized double blind placebo control design. A trial of two tone frequencies with varied intensity (90, 96, 102, 108, 114 dB) white noise and instantaneous rise time, was delivered binaurally through headphones. Tones were delivered every 25-60 s, for a 40-ms duration. Startle testing was performed 80 min post-infusion and lasted 15-20 min. Yohimbine significantly increased the amplitude, magnitude and probability of the ASR in combat veterans with PTSD, but did not do so in combat controls. Overall startle was significantly larger in the PTSD subjects; however, this did not account for the differential effect of yohimbine, since yohimbine had no significant effect in the control group. This study demonstrates an excitatory effect of yohimbine on the amplitude, magnitude and probability of the ASR in PTSD patients that is not seen in combat controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Trauma-related symptoms in veterans of Operation Desert Storm: a 2-year follow-up.

OBJECTIVE: This study was a 2-year follow-up in an ongoing prospective examination of development of trauma-related symptoms over time in a community group of veterans of Operation Desert Storm. METHOD: Sixty-two National Guard reservists, from one medical and one military police unit, completed the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder and a DSM-III-R-based posttraumatic stress disorder (PTSD) symptom scale 1 month, 6 months, and 2 years after returning from the Middle East. Differences in symptom severity over time were analyzed by using repeated measure analyses of variance. RESULTS: Scores on the Mississippi scale, but not the DSM-III-R PTSD scale, increased significantly over time. Symptoms of hyperarousal were more severe at all time points than were symptoms of reexperiencing or avoidance. Level of combat exposure, as reflected by the Desert Storm trauma questionnaire, was significantly associated with the score on the Mississippi scale at 2 years but not at 1 month or 6 months. All subjects who met the Mississippi scale's diagnostic criteria for PTSD at 1 or 6 months still met the criteria at 2 years. CONCLUSIONS: Although symptoms were relatively mild, there was an overall increase in PTSD symptoms over 2 years. The statistical relationship between level of combat exposure and PTSD symptoms at 2 years, and not before, suggests that it may take time for the consequences of traumatic exposure to become apparent. Moreover, degree of exposure may be important in predicting the eventual development of symptoms. Continued follow-up will address the evolution of PTSD symptoms in Gulf War veterans.

Female↗

Abnormal noradrenergic function in posttraumatic stress disorder.

To evaluate possible abnormal noradrenergic neuronal regulation in patients with posttraumatic stress disorder (PTSD), the behavioral, biochemical, and cardiovascular effects of intravenous yohimbine hydrochloride (0.4 mg/kg) were determined in 18 healthy male subjects and 20 male patients with PTSD. A subgroup of patients with PTSD were observed to experience yohimbine-induced panic attacks (70% [14/20]) and flashbacks (40% [8/20]), and they had larger yohimbine-induced increases in plasma 3-methoxy-4-hydroxyphenylglycol levels, sitting systolic blood pressure, and heart rate than those in healthy subjects. In addition, in the patients with PTSD, yohimbine induced significant increases in core PTSD symptoms, such as intrusive traumatic thoughts, emotional numbing, and grief. These data were consistent with a large body of preclinical data that indicated that uncontrollable stress produces substantial increases in noradrenergic neuronal function. We discuss the implications of these abnormalities in noradrenergic functional regulation in relation to the long-term neurobiological sequelae of severe uncontrollable stress and the pathophysiological relationship between PTSD and other anxiety disorders, such as panic disorder.

Adult↗

Yohimbine-facilitated acoustic startle reflex in humans.

Preclinical studies have suggested the acoustic startle reflex (ASR) may be a useful animal model to investigate the neurochemical basis of anxiety and fear states. This work has revealed that the anxiogenic alpha-2 receptor antagonist, yohimbine, increases the amplitude of the ASR in laboratory animals. The present investigation evaluated the effects of yohimbine on the ASR in healthy subjects. Seven healthy subjects received IV yohimbine (0.4 mg/kg) or saline placebo on two separate days in a randomized double blind placebo control design. A trial of 2 tone frequencies with varied intensity (90, 96, 102, 108, 114 dB) white noise, instantaneous rise time, was delivered binaurally through headphones. Tones were delivered every 25-60 sec, for a 30 ms duration. Startle testing was done 80 minutes post infusion and lasted 15-20 minutes. Sign rank testing indicated yohimbine caused an overall increase in startle amplitude, as well as significant augmentation of startle amplitude at 96, 102, 108, 114 decibels but not at the 90 dB intensity. Sign rank tests indicated a significant reduction of startle latency by yohimbine at only the 96 dB intensity. Significant correlations were observed between startle and peak anxiety, startle and plasma MHPG, peak anxiety and plasma MHPG. This study demonstrates in healty human subjects an excitatory effect of yohimbine on the magnitude of the ASR and a decrease in its latency. In the context of the key role of this reflex in the alarm response, this finding adds to the array of documented behavioral, biochemical and cardiovascular effects of yohimbine in humans which support the relationship between increased noradrenergic function and anxiety states.

Acoustic Stimulation↗

The Australian Incident Monitoring Study: an analysis of 2000 incident reports.

The Australian Patient Safety Foundation was formed in 1987; it was decided to set up and co-ordinate the Australian Incident Monitoring Study as a function of this Foundation; 90 hospitals and practices joined the study. Participating anaesthetists were invited to report, on an anonymous and voluntary basis, any unintended incident which reduced, or could have reduced, the safety margin for a patient. Any incident could be reported, not only those which were deemed "preventable" or were thought to involve human error. The Mark I AIMS form was developed which incorporated features and concepts from several other studies. All the incidents in this symposium were reported using this form, which contains general instructions to the reporter, key words and space for a narrative of the incident, structured sections for what happened (with subsections for circuitry incidents, circuitry involved, equipment involved, pharmacological incidents and airway incidents), why it happened (with subsections for factors contributing to the incident, factors minimising the incident and suggested corrective strategies), the type of anaesthesia and procedure, monitors in use, when and where the incident happened, the experience of the personnel involved, patient age and a classification of patient outcome. Enrollment, reporting and data-handling procedures are described. Data on patient outcome are presented; this is correlated with the stages at which the incident occurred and with the ASA status of the patients. The locations at which the incidents occurred and the types of procedures, the sets of incidents analysed in detail and a breakdown of the incidents due to drugs are also presented.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗

The Australian Incident Monitoring Study. Cardiac arrest--an analysis of 2000 incident reports.

Eighty-seven cases of cardiac arrest from the first 2000 incidents reported to the Australian Incident Monitoring Study were reviewed. "Cardiac arrest" was taken to include patients who were either pulseless or had electrocardiographic asystole or ventricular fibrillation. Cases were grouped by primary cause--drug administration (19), vagal stimulation (16), hypoventilation (15), bleeding (13), anaphylaxis (6), direct cardiac stimulation (4) and miscellaneous (14). Overall, 20 patients died (23% of the 87 cases); all of these were in the hypoventilation, bleeding, or miscellaneous groups (4, 9 and 7 patients, respectively). Cardiac compression was performed in 66% of patients; 20% were defibrillated; adrenaline was given to 42% and bicarbonate to 3%. There was a clear anaesthetic cause for 46% of this series of arrests, and with hindsight, a preventable factor was present in over half (58%) of these. Preventative strategies regarding staffing, equipment, policy and procedures are suggested.

Anesthesia↗

Open prospective trial of fluoxetine for posttraumatic stress disorder.

Twenty-seven patients with combat-related posttraumatic stress disorder (PTSD) entered an open, prospective, 10-week trial of fluoxetine, beginning with 20 mg/day and increasing to 80 mg/day until response was optimal or side effects prohibited dose increase. Nineteen patients completed 3 or more weeks and were included in the data analysis. Total Clinician-Administered PTSD Scale scores decreased from a mean of 64.5 at baseline to 42.7 at endpoint (F = 7.17, p < 0.001), and improvement was significant in each of the three PTSD subscales (reexperiencing, avoidance/numbing, and hyperarousal). Depression and anxiety ratings showed similar improvements, and suicidality ratings did not increase. Global improvement scores decreased from 4.0 at baseline to 2.67 at endpoint (F = 12.08, p < 0.001); however, improvement in social and occupational functioning was minimal. Appreciable improvement tended to occur after 6 weeks, suggesting that higher fluoxetine doses and/or duration than that used for depression may be indicated in this population. Panic attack frequency decreased by at least 50% in six of eight patients who kept panic diaries. The high dropout rate reflects problems with side effects, anxiety symptoms, external events, and substance abuse. Our data suggest that fluoxetine is effective in reducing reexperiencing, avoidance, and hyperarousal symptoms of PTSD, and this improvement is independent of comorbid panic disorder. In addition, fluoxetine appears to be effective in reducing panic attacks in PTSD patients. The efficacy of fluoxetine for some PTSD patients is interesting in light of emerging neuropharmacologic data suggesting serotonergic dysregulation in some PTSD patients. Noradrenergic hypotheses are also discussed. The findings should be confirmed by double-blind, placebo-controlled studies.

Adult↗

Perimenopausal risk of falling and incidence of distal forearm fracture.

A postal survey of 2000 women and 2000 men sampled from the electoral roll in Oxford was undertaken to ascertain whether changes with age in the risk of falling might explain the stepwise increases in age specific incidence rates of distal forearm fracture which occur in women at around the age of 50. Corrected response rates were 83% for women and 72% for men. In women, but not in men, there was a rise in the risk of falling from 45 years, peaking in the 55-59 year age group, and sinking to a nadir at ages 70-74. In both sexes rates rose in extreme old age. These variations were not attributable to preferential response from people who had suffered a fracture. It is concluded that changes in the risk of falling interact with osteoporosis to produce a perimenopausal rise in the incidence of forearm fractures and contribute to the fluctuations in incidence of these fractures in old age.

Accidental Falls↗

Host origin of marrow stromal cells obtained from marrow transplant recipients and transformed in vitro by simian virus-40.

We evaluated the karyotypes of marrow-derived stromal cell lines established by simian virus-40 (SV-40) transformation of long-term cultures from four men who received marrow transplants from women donors. In all cases a normal female karyotype was found in marrow cells. In contrast, a Y chromosome was identified in metaphase cells from the stromal lines, suggesting that following successful marrow transplantation, cells in the marrow microenvironment susceptible to SV-40 transformation remain host in origin.

Bone Marrow Cells↗

An ongoing surveillance study of persistent crying and hypotonic-hyporesponsive episodes following routine DTP immunization: a preliminary report.

Hypotonic-hyporesponsive episodes and persistent crying are specific complications of pertussis immunization. Hyperinsulinemia, hypoglycemia, and leukocytosis have been noted after pertussis vaccine administration in a murine model. Five children with hypotonic-hyporesponsive episodes and 6 children with persistent crying following DTP immunization were studied. The children were found to have leukocytosis acutely, similar to findings reported in children following routine DTP immunization. No abnormalities were noted in plasma insulin or serum glucose. Five of 6 children with persistent crying had severe local reactions, suggesting that localized inflammation may be a cause of persistent crying.

Crying↗

Respiratory adaptation to chronic hypoxia in newborn rats.

Newborn rats were maintained in an hypoxic chamber (10% O2 in N2) from the day of birth up to 2 wk of postnatal life. Body weight (BW) and nose-tail length were less in the hypoxic exposed (H) rats than in control (C) animals growing in air. Hematocrit rose from about 37% to about 51%. Oxygen consumption (VO2), measured with a manometric method, was lower in H than in C rats; the difference remained at 5-7 days even after normalization by BW. At 5-7 days ventilation, measured with an airflow plethysmograph, was much more elevated in H rats (whether breathing 10% O2 or air) than in C rats, with an increase in both tidal volume and frequency. This indicates that the biphasic ventilatory response, characterized by an initial rise and then a fall of ventilation toward normoxic values, commonly observed in newborns during acute hypoxic challenge is an immediate but only transient response. The dry lung weight-to-BW ratio and alveolar size were larger in H than in C rats. Lung volumes at 20 cmH2O were similar, despite the smaller BW of the H rats. Hence, in the rat, chronic hypoxia in the immediate postnatal period increases O2-carrying capacity, decreases metabolic demands, increases alveolar O2 availability, and promotes structural changes in the lung that protect the gas exchange area and optimize the structure-function relationship of the lung. These results may also suggest that the lung structural alterations with chronic hypoxia should not be attributed to changes in VO2 but, eventually, to the ventilatory action of the organ.

Acclimatization↗

Lithium accelerates the development of tolerance to alcohol in rats.

Thirty male Wistar rate, trained on the moving belt test, were used to test the effect of acute and chronic lithium administration on tolerance to alcohol. Over the first 11 days, a group receiving lithium (1.5 mequiv./kg, i.p.) 4 h before and alcohol (2 g/kg, i.p.) 17 min before three daily 2-min test trials on the moving belt showed accelerated development of tolerance to alcohol compared with a group receiving saline (instead of lithium) and the same dose of alcohol. There were no differences between the groups in the level of tolerance finally reached and no differences could be detected in the effects of lithium on physiological as opposed to behaviorally augmented tolerance. Also, 12 days of lithium pretreatment did not increase tolerance to an initial dose of alcohol or modify the expected blood alcohol level. Conversely, tolerance, as a result of 12 days of chronic alcohol pretreatment, was not increased further by a single lithium administration. Drug-free performance at the end of the experiment showed that the injection procedure per se did not influence performance.

Alcoholism↗

Drugs in obstetric anaesthesia.

From the anaesthetist's viewpoint, pharmacokinetics of pregnancy, drugs affecting uterine muscle tension and foetal effects of anaesthetic drugs are reviewed.

Albuterol↗