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Biomedical subjects

D Healy

Publications and source records attributed to D Healy.

At least 19 recordsLinked to original sources

Analysis of the importance of controllable versus uncontrollable stress on subsequent behavioral and physiological functioning.

Original observations of the effects of stress exposure on behavioral, physiological and pathological indices were documented in the mid 1960s [J.B. Overmier, Interference with avoidance behavior: failure to avoid traumatic shock, J. Exp. Psychol. 78 (1968) 340-343 [12]; J.B. Overmier, M.E.P. Seligman, Effects of inescapable shock upon subsequent escape and avoidance learning, J. Comp. Physiol. Psychol. 63 (1967) 28-33 [13]; M.E.P. Seligman, S.F. Maier, Failure to escape traumatic shock, J. Exp. Psychol. 74 (1967) 1-9 [15]; J.M. Weiss, Effects of coping responses on stress, J. Comp. Physiol. Psychol. 65 (1968) 251-260 [18]]. Studies employing the triadic design (e.g. escapable stress, yoked-inescapable stress and no stress) indicated that the deficits following stress exposure were not caused by stress per se, rather the uncontrollability of the stress was the critical determinant. In this paradigm, the first group (escape) receives exposure to an environmental event that it can "control" by performing a behavioral response. Stress control or coping behavior includes the ability to alter the onset, duration, intensity or pattern of an aversive experience [S.F. Maier, M.E.P. Seligman, Learned helplessness: theory and evidence, J. Exp. Psychol.: Gen. 105 (1976) 3-46 [10]]. The second group is "yoked" to its escape partner and receives the identical physical stressor as its escape counterpart, but there is no behavioral response that the yoked subject can make to alter the outcome. The third group (naive) receives no stress exposure and is either restrained in the experimental apparatus or remains in the home cage until subsequent testing. Researchers using this triadic design should be aware of the concerns of certain investigators [R.M. Church, Systematic effect of random error in the yoked control design, Psychol. Bull. 62 (1964) 122-131 [3]; E.A. Wasserman, Response bias in the yoked control procedure, Behav. Brain Sci. 11 (1988) 477-478 [17]] who have raised important issues about the validity of the yoked control design because of the possibility of systematic biases. For example, individual differences in stress reactivity may result in random error in the yoked control group. This point will be addressed further in Section 5. This procedure allows the investigator to analyze the contributions of the importance of psychological dynamics of stress on a variety of dependent measures including: behavioral, pharmacological, neurochemical and immunological indices.

Animals

Low intraovarian vascular resistance: a marker for severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess intraovarian blood flow in relation to the severity of ovarian hyperstimulation syndrome (OHSS) after controlled ovarian hyperstimulation. DESIGN: A prospective study. SETTING: Monash IVF, Clayton, Victoria, Australia. PATIENT(S): Thirty patients with OHSS after embryo or gamete transfer who also had sonographic evidence of ascites. MAIN OUTCOME MEASURE(S): The resistance to blood flow within the ovaries of 11 patients with severe OHSS and 19 patients with mild OHSS was measured by using transabdominal ultrasonography with color flow and pulsed Doppler imaging. RESULT(S): The pulsatility index (PI), resistance index (RI), and the S-D ratio, all measures of downstream vascular impedance, were significantly lower in those patients with severe OHSS. In cases with RI < 0.48, more than two thirds of the patients had a pleural effusion, whereas patients with either PI < 0.75 or S-D < 1.92 had pleural effusion in over one half of the cases. It was notable that blood flow velocity did not differ significantly between the two groups despite the changes in vascular impedance. CONCLUSION(S): There appears to be a close correlation between the severity of OHSS and the resistance to blood flow within the stimulated ovaries. Measurement of intraovarian vascular resistance before gamete transfer or ET in patients undergoing controlled ovarian hyperstimulation may help in predicting those patients at particular risk of developing severe OHSS.

Adult

Short-term immobilization-induced cancellous bone loss is limited to regions undergoing high turnover and/or modeling in mature rats.

Estrogen and calcium deficiencies increase both bone resorption and formation, whereas immobilization mainly decreases bone formation. How these functionally different risk factors for bone loss interact in cancellous bone undergoing modeling or remodeling activity is not well understood. Mature (6-month-old) female rats were subjected to sham operation (sham), ovariectomy (ovx), dietary calcium deficiency (LoCa, 0.1% Ca), and sciatic and femoral denervation (IM), ovx+IM, or LoCa+IM for 4 weeks. The primary spongiosa, the region of active modeling within 1 mm of the growth plate, in ovx, LoCa, and IM groups showed a decrease in cancellous bone volume, trabecular number, and connectivity when compared to sham controls. Groups combining two risk factors exhibited additive changes when compared with single risk factor groups. In the secondary spongiosa, an area with little modeling activity, ovx and LoCa groups, as expected, lost bone. In contrast with the primary spongiosa, IM alone did not induce bone loss in the secondary spongiosa, and the groups with a combination of IM and ovx or IM and LoCa showed a greater bone loss than either ovx or LoCa alone. Ovx and LoCa groups showed increases in both bone formation rate and eroded surface in the secondary spongiosa, while IM groups showed a decrease in bone formation rate. Combining IM with either ovx or LoCa resulted in increased eroded surface. The effects on cortical bone were assessed at the tibio-fibular junction. A trend toward decreased percentage of cortical bone area and an increase in marrow cavity area were observed in the combined deficiency groups only. These changes were the result of a statistically significant increase in endosteal eroded surface in IM+ovx and IM+LoCa groups. Our results demonstrate that immobilization-induced bone loss is restricted to the primary spongiosa where most modeling events occur. However, the inhibitory effect of IM on bone formation in the secondary spongiosa is unmasked in remodeling sites when a high turnover state is provided by either estrogen or dietary calcium deficiency. These results suggest that the presence of a risk factor, such as immobilization, which in the short-term causes inhibition of bone formation, does not predispose the skeleton to rapid cancellous bone loss except when accompanied by modeling or high turnover.

Animals

Probabilistic reasoning in obsessive-compulsive and delusional disorders.

BACKGROUND: Delusional disorder (DD) and obsessive-compulsive disorder (OCD) have been investigated in previous studies using probabilistic reasoning paradigms and abnormalities in each group have been reported. No study to date has compared results between these groups. This study compares patients with these disorders with those who have both phenomena. METHODS: Thirty subjects with DD, 29 with OCD and 16 with obsessive and delusional features were compared with 30 normal controls in a study of probabilistic reasoning using two different computer-based tasks involving a Bayesian paradigm. RESULTS: Deluded subjects showed a 'jump to conclusions' reasoning style, but on a test that added a consequence to their choices did not differ from normals. OCD subjects deviated from Bayesian and control norms to a greater degree than did DD subjects. In subjects with mixed psychopathology, the presence of both phenomena appeared to 'normalize' these probability estimates. CONCLUSIONS: Our findings extend those of others but require cautious interpretation as to the role of probabilistic reasoning in the genesis of delusions or obsessions. Obsessionals in both the OCD and Mixed groups, showed substantial deviation from Bayesian norms, suggesting that obsessionality leads to a reasoning style that is less 'normal' than that of delusionals. Further work is required to investigate clinical correlates of these findings which provide modest support for the proposal that the combination of obsessions and delusions confers greater functional advantages than simply having delusions or obsessions.

Adult

Cumulative pregnancy rates in couples with anovulatory infertility compared with unexplained infertility in an ovulation induction programme.

Using a retrospective analysis, we compared cumulative pregnancy rates, early pregnancy failure rates and multiple pregnancy rates in couples with polycystic ovarian syndrome (PCOS) (n = 148), hypogonadotrophic or eugonadotrophic hypogonadism (n = 91) and unexplained infertility (n = 117), who were treated in an ovulation induction clinic between January 1991 and December 1995. The women were treated with either human menopausal gonadotrophin (HMG) or purified follicle stimulating hormone (FSH). The cumulative pregnancy rate (derived from life-table analysis) after four ovulatory treatment cycles was 70% in the PCOS group, 74% in the hypogonadism group and 38% in the unexplained infertility group. The cumulative pregnancy rate in the unexplained infertility group was significantly lower than the other groups (P < 0.001) but there was no significant difference between PCOS and hypogonadism using the log rank test. The early pregnancy failure rate was 25% in the PCOS group, 27% in the hypogonadism group and 26% in the unexplained infertility group (chi(2) = 0.132, not significant). The multiple pregnancy rate was 20% in the PCOS group, 30% in the hypogonadism group and 17% in the unexplained infertility group (chi(2) = 2.105, not significant). Treatment of anovulatory infertility using HMG or FSH is effective irrespective of the cause. Couples with unexplained infertility are less successfully treated using HMG: correction of unexplained infertility may involve more than simple correction of possible subtle ovulatory defects.

Adult

The enhancement of social functioning as a therapeutic principle in the management of depression.

It has long been considered that depression is a biochemical disorder resulting from dysfunction of monoamine systems in the brain and that antidepressants act upon these systems as 'magic bullets' to correct the lesion. An alternative hypothesis is that antidepressants act upon intact monoamine systems to produce functional changes that are not necessarily a reversal of the initial cause. If this is the case, one would expect that currently available classes of antidepressants would have overlapping spectra of therapeutic effects and that, while all may be effective in the majority of patients, some will be more useful according to individual needs. To date, the assessment of recovery from depression, using scales such as the Hamilton Rating Scale for Depression, has been physician centred. Such assessments leave open the possibility that patients may not have recovered in terms of their social adaptation and that, accordingly, the patients themselves and their relatives may not perceive them as having recovered. Findings of differences between antidepressants on the Social Adaptation Self-evaluation Scale highlight the importance of patient perception of treatment efficacy. These differences may indicate differences in efficacy not detected by conventional instruments, differences in tolerability, differences in the speed of onset of antidepressant activity, or differences in the behavioural profile produced by different classes of antidepressants.

Antidepressive Agents

Delusional phenomenology--dimensions of change.

Although the application of cognitive techniques to both the measurement and modification of delusional beliefs has recently been developed in more theoretical detail (e.g. Chadwick & Lowe, 1994, Behaviour Research and Therapy, 32, 355-367) there has not been an effort to examine the variability of delusional phenomenology across time. In the present study we report on the treatment of 6 individuals who fulfilled DSM-III-R (American Psychiatric Association, 1987) criteria for Delusional Disorder and who received cognitive therapy targeted specifically on the single symptom of their delusional belief(s). Single-case time-series methodology was used to examine the associations between different aspects of delusional phenomenology through baseline and intervention study phases. Belief maintenance factors were found to be significantly associated with conviction in all 3 individuals who responded to the intervention. Negative behaviours, affect associated with the belief, preparedness to talk to others about the belief and insight were associated with conviction in some individuals but not others. Preoccupation and acting on the belief were aspects of delusional phenomenology that were found to systematically vary independent of belief conviction. The results support a multidimensional view of delusional phenomenology and the process of change during cognitive intervention.

Adult

Double-blind placebo controlled study: human biosynthetic growth hormone for assisted reproductive technology.

OBJECTIVE: To study whether the effect of cotreatment with human biosynthetic GH improves the outcome of poor IVF responders. DESIGN: A double-blind placebo-controlled study using a GnRH agonist (GnRH-a) and gonadotropin in a "boost" flare-up protocol for ovarian stimulation together with either placebo, 4, or 12 IU of human GH followed by oocyte retrieval and IVF-ET. PATIENTS: Twenty-two patients with previously demonstrated poor responses in at least two assisted reproductive technology cycles were recruited. INTERVENTIONS: Pretreatment and post-treatment blood samples and daily morning blood samples during ovarian stimulation were collected after an overnight fast. Human GH or placebo and GnRH-a were administered SC; gonadotropin was administered IM. Oocytes were collected by ultrasound-guided transvaginal aspiration of follicles. Embryos were cultured in vitro and transferred transcervically. MAIN OUTCOME MEASURES: Serum E2, FSH, GH, insulin-like growth factor-I (IGF-1), IGF binding protein 1 (IGFBP-1), and IGFBP-3 concentrations. Number of FSH ampules, follicles, oocytes, embryos, and pregnancies. RESULTS: No improvement in cycle outcome was demonstrated with daily adjuvant human GH administration with either 4 or 12 IU. Serum IGF-I levels were highest in the 12 IU human GH group and lowest in the placebo group. Serum IGFBP-3 levels increased 2 days after IGF-I levels in the 12 IU human GH group only. Serum IGFBP-1 levels were unchanged in all groups. CONCLUSION: Poor IVF responders do not benefit from cotreatment with human GH during their ovarian stimulation.

Adult

Interpersonal sensitivity predicts depressive symptom response to the circadian rhythm disruption of nightwork.

This paper reports the results of a study designed to explore the validity of a shiftwork model of affective disorders. Fifty-five student nurses doing nightwork for the first time were recruited to a study designed both to replicate an earlier study of the effects of nightwork on cognitive, emotional and neurovegetative measures and to assess the effects of nightwork on personality measures and the role of personality factors and nightwork induced disturbances in predicting accommodation to nightwork. As in the earlier study, concentration, interest, energy, sleep and appetite were significantly disturbed by nightwork and there was an increased perception of recent criticism from other. The findings from both studies were, therefore, aggregated to explore further possible relations between outcomes and the pre-nightwork level of affective symptoms and sensitivity to interpersonal criticism. These predicted poor response. In contrast, measures of cognitive style and symptom interpretation did not predict outcome. The findings are not inconsistent with proposals that disturbance of circadian rhythms consequent on psychosocial disruptions may play a part in the genesis of or maintenance of depression. They also support a proposal that nightwork induced changes may be a suitable human model for investigation of aspects of the affective disorders.

Adult

Cognitive processes in delusional disorders.

BACKGROUND: Studies of schizophrenics with persecutory delusions have shown cognitive biases in subjects who are deluded. It has been suggested that their delusions defend against depression. This study challenges the assumption that delusional disorder (DD) patients are covertly depressed. METHOD: Clinical and demographic data, and responses to questionnaires designed to assess schizotypy, depression, dysfunctional attitudes, attributional and attention biases were collected from 29 patients satisfying DSM-III-R criteria for DD. These were compared with 20 matched normal controls and results from published studies of schizophrenics. RESULTS: DD subjects did not show abnormal levels of overt or covert depression or schizotypy. They showed high levels of dysfunctional attitudes (P < 0.0001), a distinctive attributional style (P = 0.01), and increased attention to threat-related stimuli (P = 0.01). CONCLUSIONS: DD is a distinct disorder predicated upon sensitivity to threat and biases of attention and attribution. These findings may have implications for the cognitive therapy of these disorders.

Adult

Breast and ovarian cancer incidence after infertility and in vitro fertilisation.

Concern has been expressed that exposure to fertility drugs might be associated with a risk of ovarian cancer. We have examined the incidence of breast and ovarian cancer in a cohort of 10,358 women referred for in-vitro fertilisation (IVF) treatment in Victoria, Australia, between 1978 and 1992. The "exposed" group (n = 5564) had had ovarian stimulation to induce multiple folliculogenesis and the "unexposed" group (n = 4794) had been referred for IVF but were untreated or had had "natural cycle" treatment without ovarian stimulation. Duration of follow-up ranged from 1 to 15 years. Cases of cancer were determined by record linkage with data from population-based cancer registries. 34 cases of invasive breast cancer and 6 of invasive ovarian cancer were observed. A comparison with the expected numbers, derived by applying age-standardised general population rates to the cohort gave standardised incidence ratios (SIR) for breast cancer of 0.89 (95% CI 0.55-1.46) in the exposed group and 0.98 (0.62-1.56) in the unexposed group, and for ovarian cancer SIRs were 1.70 (0.55-5.27) and 1.62 (0.52-5.02), respectively. Rates of all cancers were not significantly different from general population rates. The relative risk (RR) of cancer, adjusted for age and infertility type, was, in the treated group compared with the untreated group, 1.11 (95% CI 0.56-2.20) for breast cancer and 1.45 (0.28-7.55) for ovarian cancer. The risk of body of uterus cancer was increased in the exposed and unexposed groups combined (SIR 2.84 [1.18-6.81]). Women with unexplained infertility, independent of IVF exposure, had significantly increased risks of ovarian cancer (RR = 19.19 [2.23-165.0]) and body of uterus cancer (RR = 6.34 [1.06-38.0]) compared with women with known causes of infertility. This relatively short-term follow-up suggests that ovarian stimulation with IVF is not associated with an increased risk of breast cancer. Although there was no significantly increased risk of ovarian cancer after ovarian stimulation with IVF the small number of cases limits the conclusions that can be drawn. Longer-term follow-up of large cohorts of women who have been in IVF programmes will be necessary.

Adult

The circadian system and the therapeutics of the affective disorders.

Establishing that a circadian rhythm is abnormal tells us little about the cause, which can arise from changes in the patient's lifestyle, irregularities of the body clock or a malfunction in the process of entrainment of the clock. In a clinical context, such a range of possible explanations implies differences in the most appropriate mode of treatment. Against this background, the conventional view that the underlying abnormality in endogenous depression is due to a disorder of the body clock is challenged. The challenge is based on difficulties of interpretation of the clinical data and the results of studies on circadian rhythms in patients. It is suggested that the state of the circadian system in depression resembles its state in healthy individuals after time-zone transitions or in shift work maladaptation syndrome and that this disturbance should be seen as resulting from changes in the phasing of external zeitgebers rather than from an abnormality in the clock itself.

Animals

Urinary vascular endothelial growth factor concentrations in women undergoing gonadotrophin treatment.

A recently identified cytokine, vascular endothelial growth factor (VEGF, vascular permeability factor) has been implicated in ovarian hyperstimulation syndrome in women undergoing assisted reproduction. We postulate that circulating and urinary VEGF values increase following gonadotrophin stimulation, in parallel with the increased ovarian vascularity. A VEGF radioimmunoassay was developed using iodinated VEGF as tracer, a goat anti-VEGF serum as antiserum and recombinant human VEGF as standard. The specificity of the assay was confirmed by comparing the reverse phase high-performance liquid chromatography (HPLC) pattern of VEGF immunoactivity in urine and urine spiked with recombinant VEGF. Urine was concentrated 5-fold prior to measurement by the radioimmunoassay. VEGF:creatinine ratios in early morning urine samples were used to monitor daily urinary VEGF concentrations based on its high correlation (r = 0.77, P < 0.001) with VEGF concentrations in 24 h urine collections. No diurnal variation in VEGF:creatinine ratios was detected. VEGF:creatinine ratios were determined daily from nine women undergoing gonadotrophin-releasing hormone (GnRH) agonist/gonadotrophin treatment. In a further 16 women, early morning urine samples were collected in the peri-ovulatory period. A significant increase (P < 0.005, n = 25) was observed in VEGF:creatinine ratios following human chorionic gonadotrophin (HCG) administration. VEGF:creatinine ratios correlated poorly (r < 0.34) with plasma oestradiol, follicle number and size. It is concluded that urinary VEGF/creatinine ratios increase following HCG stimulation.

Chorionic Gonadotropin

Prognostic role of antioxidant enzymes in sepsis: preliminary assessment.

The prognostic potential of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was evaluated in sepsis. Enzyme concentrations were determined in samples obtained from septic patients at time of diagnosis. Statistically significant increases in activities of total plasma SOD (P < 0.003, n = 32), erythrocyte (RBC) SOD (P < 0.007, n = 16), plasma CAT (P < 0.0001, n = 32), and RBC CAT (P < 0.005, n = 16) were found in septic patients when compared with healthy adult controls (n = 7). Further, within the group of septic patients, statistically significant differences were found for total plasma SOD (P < 0.05) and plasma CAT (P < 0.009) (but not for RBC determinations) when survivors (n = 15) were compared with nonsurvivors (n = 17). No significant differences were found for either plasma or RBC enzyme concentrations when patients who developed adult respiratory distress syndrome were compared with those who did not. The most striking finding was that plasma total SOD values of > 10 kU/L were found in 7 of 21 (30%) patients who did not survive their sepsis and that these values did not overlap with any surviving patients or controls. However, while high total plasma SOD activity appears to have some potential as a prognostic indicator, lower values (0.0-8.8 kU/L) do not. For plasma CAT, despite finding statistically significant differences between survivors and nonsurvivors, the substantial overlap in the values obtained for the two groups limits the practical prognostic potential of this enzyme.

Adult

The attitudes and general health of student nurses before and immediately after their first eight weeks of nightwork.

A group of 43 student nurses were studied before and immediately after their first eight weeks of nightwork. Volunteers answered questions about their general health, sleep, and eating habits, as well as their social lives and relationships with friends. In all measures there was a deterioration produced by nightwork. About half the subjects volunteered the view that the forthcoming nightwork would cause a decline in the standard of their lifestyle or that it would improve now that nightwork had finished. This subgroup showed a significantly greater deterioration in interpersonal relationships, even though general health status was not significantly different. These results indicate that the problems associated with nightwork can arise before coping mechanisms can be expected to have been devised, and even in anticipation of nightwork. They imply that counselling is needed before nightwork is actually started.

Adolescent