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Biomedical subjects

J M Rey

Publications and source records attributed to J M Rey.

At least 55 records · Page 3Linked to original sources

Expression of oestrogen receptor-alpha splicing variants and oestrogen receptor-beta in endometrium of infertile patients.

Endometrium is one of the main target tissues of oestrogens. Although homozygous inactivation of oestrogen receptor-alpha leads to infertility in transgenic mice, oestrogen receptor-alpha is detected in endometrium of patients with unexplained infertility. Oestrogen receptor-alpha splicing variants and oestrogen receptor-beta have been studied in oestrogen target tissues, but their expression in endometrium throughout the menstrual cycle and in unexplained infertility is unknown. Using reverse transcription-polymerase chain reaction (RT-PCR), we studied the expression of oestrogen receptor-alpha splicing variants and oestrogen receptor-beta in uterine biopsies from 12 patients with endometriosis and 15 patients with unexplained infertility. A control group included 19 women who had had a previous pregnancy. Our study gave evidence of exon 2, 3, 4 or 7 deleted oestrogen receptor-alpha variants co-existing with the wild-type receptor. We did not find any exon 5 or 6-deleted variants. Exon 4 or 7-deleted variants were detected in all samples. Exon 2 or 3-deleted variants were detected at a similar frequency in fertile women (58 and 68% respectively), endometriotic patients (67 and 83% respectively) and infertile patients (73 and 80% respectively). During the follicular phase, there was a non-significant trend towards a lower frequency of exon-2 deleted variants in the fertile group when compared with the hypofertile group. Oestrogen receptor-beta was detected in all samples. Our preliminary study showed that altered expression of oestrogen receptor-alpha variants and oestrogen receptor-beta may not explain the hypofertility state.

Alternative Splicing↗

FRA-1 expression level modulates regulation of activator protein-1 activity by estradiol in breast cancer cells.

We compared the effect of estradiol on activator protein-1 (AP-1) activity in estrogen receptor positive (ER alpha+) and estrogen receptor negative (ER alpha-) human breast cancer cell lines transiently transfected with the AP-1-responsive reporter plasmid AP-1-TK-CAT and an ER alpha expression vector. While estradiol increased AP-1 activity in the ER alpha+ cell lines MCF7, ZR75.1, and T47D, it decreased (MDA-MB231 and BT20 cells) or had no significant effect (MDA-MB435 cells) on AP-1-mediated transcription in ER alpha- cells. Estradiol also inhibited AP-1 activity in ER alpha-MDA-MB231 cells stably transfected with ER alpha and in which ER alpha levels are close to those found in MCF7. Use of ER alpha mutant expression vectors demonstrated that the DNA-binding domain of ER alpha was needed for stimulation or inhibition of AP-1 activity by estradiol but suggested that ER alpha binding to estrogen-responsive elements was not required for these effects. Changes in regulation paralleled quantitative and qualitative changes in protein binding to AP-1 sites, as demonstrated by gel shift assay: protein binding was greater and DNA/protein complexes migrated faster for ER alpha--than for ER alpha+ cells. In fact, by Northern blot, a high level of Fra-1 mRNA was found in BT20 and MDA-MB231 cells as compared with ER alpha+ cells, and MDA-MB435 cells showed an intermediary level of expression. The differential expression of Fra-1 in MCF7 and MDA-MB231 cells was confirmed at the protein level by supershift experiments. In addition, overexpression of Fra-1 in MCF7 cells decreased the positive effect of estradiol while inhibition of Fra-1 expression in MDA-MB231 cells, by transient transfection of the Fra-1 antisense expression vector, abolished the negative effect of the hormone. In conclusion, we demonstrated that ER alpha- breast cancer cell lines differ from ER+ cells by a high level of AP-1 DNA-binding activity due, at least in part, to high Fra-1 constitutive expression. High Fra-1 concentration is crucial for the negative regulation of AP-1 activity by estradiol and thus may take part in estradiol-induced inhibition of cell proliferation in ER alpha- breast cancer cells transfected with ER alpha expression construct.

Blotting, Northern↗

Attitudes of mental health personnel towards rating outcome.

Outcome measurement is becoming an integral part of health-care delivery. The attitudes of staff towards this development are important as they may influence ratings themselves, improve the design of measures and indicate how outcome assessment should be introduced into services. In this preliminary study, we surveyed staff from Central Sydney Mental Health Services who had taken part in a Commonwealth-funded project which had required them to rate patient outcome. The major concern expressed by respondents was that rating outcome was too time-consuming. More than half were not in favor of measuring outcome routinely even if it meant providing a better service to patients. The study methodology had limitations. However, if our findings are corroborated, attention will need to be paid to staff attitudes to outcome assessment so that ratings are more reliable and valid, properly inform treatment and meaningfully influence resource allocation.

Attitude of Health Personnel↗

A global scale to measure the quality of the family environment.

BACKGROUND: Simple, reliable measures of the quality of the environment in which a child was reared that can be used in clinical research and practice are lacking. METHOD: The reliability and validity of a global scale to retrospectively appraise the quality of that environment were examined. Fifty-three clinicians from 4 centers in Australia and 1 in Hong Kong, People's Republic of China, used the scale to rate 7 case vignettes; 4 clinicians rated 20 medical records, and 49 rated 211 subjects after clinical interviews. RESULTS: Interrater reliability (intraclass correlation coefficient) was 0.82 (time 1) and 0.84 (time 2) for case vignettes, 0.90 for medical records, and 0.89 for clinical interviews. Consistency in time was high (r = 0.91). Lower ratings, indicative of a less adequate environment, were associated with a clinical diagnosis of oppositional defiant or conduct disorder. CONCLUSIONS: Our simple-to-use scale appears to measure reliably a relevant clinical construct and fills a gap among the instruments available. Ratings may be useful as a cost-effective index to consider in outcome studies, when examining response to treatment, or in other clinical research.

Adolescent↗

An epidemiological study of the use of ECT in adolescents.

OBJECTIVE: There is little knowledge about the use of electroconvulsive therapy (ECT) in adolescents. Given the prevalence and severity of psychiatric disorders in this age group, it is important to determine the frequency, indications, effectiveness, and side effects of ECT. METHOD: Persons younger than 19 years who received ECT between 1990 and 1996 in the Australian state of New South Wales were identified. Detailed information about diagnosis, treatment, and outcome was then obtained. RESULTS: Forty-two patients aged 14 to 18 years underwent a total of 49 courses comprising 450 ECTs (0.93% of all treatments given to all persons). Marked improvement or resolution of symptoms occurred in half of the completed courses. Mood disorders derived most benefit from ECT. Side effects were transient and minor. Prolonged seizures were observed in 0.4% of treatments. Comorbid personality disorder predicted poorer response, and the anesthetic propofol was associated with shorter seizures. CONCLUSIONS: Although ECT is an effective treatment for some mental disorders in adolescents and has few side effects, it is seldom used. Indications, response, and unwanted effects were similar to those observed in adults. The use of propofol may reduce the risk of prolonged seizures.

Adolescent↗

Half a century of ECT use in young people.

OBJECTIVE: Pharmacological treatments for certain psychiatric disorders in young people are often ineffective and may cause major side effects; thus, it is important to investigate other treatments. This article reviews the literature on the efficacy and safety of ECT in this age group and examines the evidence for the suggestion that it may be used inappropriately. METHOD: All studies published in English and other languages on the use of ECT in persons 18 years of age or younger were obtained. The reports were systematically reviewed and rated according to the quality of the information in several domains, yielding an overall quality score for each study. Individual cases from each report were then examined and grouped according to diagnosis and response to ECT. RESULTS: Sixty reports describing ECT in 396 patients were identified; most (63%) were single case reports. The overall quality was poor but improved in the more recent studies. There were no controlled trials. Rates of improvement across studies were 63% for depression, 80% for mania, 42% for schizophrenia, and 80% for catatonia. Serious complications were very rare, whereas minor, transient side effects appeared common. CONCLUSIONS: ECT in the young seems similar in effectiveness and side effects to ECT in adults. However, this conclusion is qualified by the lack of systematic evidence. More research and education of professionals and the public are needed. It is suggested that ECT registers be set up, that surveys and controlled trials be conducted, and that seizure thresholds, the optimal anesthetic, effects of concurrent medications, and cognitive consequences of ECT in the young be investigated.

Adolescent↗

Experience, knowledge and attitudes of child psychiatrists regarding electroconvulsive therapy in the young.

OBJECTIVE: To ascertain the experience, knowledge and attitudes of Australian and New Zealand child psychiatrists in relation to electroconvulsive therapy (ECT) in the young in order to determine whether they would be willing and able to provide an opinion if consulted about children or adolescents in whom ECT is proposed. METHOD: A 28-item questionnaire was posted to all members of the Faculty of Child and Adolescent Psychiatry living in Australia or New Zealand. RESULTS: Eighty-three percent (n = 206) answered the questionnaire. Forty percent rated their knowledge about ECT in the young as nil or negligible. Having had patients treated with ECT was the best predictor of possessing some knowledge. Thirty-nine percent believed that ECT was unsafe in children compared to 17% for adolescents and 3% for adults. Almost all (92%) respondents believed child psychiatrists should be consulted in all cases of persons under 19 in whom ECT was recommended. The vast majority believed the Faculty or College should have guidelines relating to ECT use in this group and that it would be useful to have a national register of young persons treated with ECT. CONCLUSIONS: Child and adolescent psychiatrists wish to be involved in the process of ECT treatment in young people. At the same time, there are gaps in their knowledge. This will need to be remedied, particularly if formal guidelines advocating their involvement are introduced.

Adolescent↗

Juvenile obsessive-compulsive disorder.

OBJECTIVE: To describe the characteristics of a series of children and adolescents with obsessive-compulsive disorder (OCD) and evaluate the outcome of treatment. METHOD: Type of symptoms, severity before and after treatment and factors associated with outcome were examined in a large group (n = 82) of consecutive OCD cases referred for treatment. RESULTS: Most children (95%) had both obsessions and compulsions. Symptoms had been present for 2 years on average. Seventy-one per cent (n = 57) of all eligible patients completed a combined behavioural and pharmacological protocol. Among these, there was a 68% remission rate and a 60% decrease of symptoms at 4 weeks. Comorbidity with oppositional defiant disorder and high aggression scores were associated with poor outcome. CONCLUSIONS: Juvenile OCD can be treated effectively in a standard clinical setting. Treatment programs of the kind described are accepted by young people. It remains to be seen whether in this age group a combined treatment produces better results than medication alone or cognitive-behaviour therapy alone.

Adolescent↗

Referred adolescents as young adults: the relationship between psychosocial functioning and personality disorder.

OBJECTIVE: To examine the functioning of young adults who had been referred for psychiatric treatment during adolescence. METHOD: A group of 145 adolescents referred at a mean age of 14 years were interviewed at a mean age of 20 years to ascertain their functioning and whether they suffered from a personality disorder. RESULTS: Having a personality disorder was associated with poor functioning at follow-up independently of adolescent diagnosis. Antisocial personalities were typified by problems with the law, a poor work record and early cohabitation, while other personality disorders were characterised by social isolation and problems in interpersonal relationships. Poor quality of the family environment and having received treatment during the follow-up period were the only developmental variables associated with poor functioning. CONCLUSIONS: Developing a personality disorder and having a poor family environment, rather than having an adolescent disorder, appear to be the factors that result in poor functioning in young adults.

Adolescent↗

Perceptions of poor maternal care are associated with adolescent depression.

This study sought to ascertain if depressed adolescents perceived their parents as less caring and more controlling than patients with other diagnoses, as reported for adults. Associations between perceptions of parenting, as measured by the Parental Bonding Instrument, and diagnosis were studied using groups of referred adolescents with major depression (n = 19), dysthymia (n = 41), oppositional disorder (n = 51), conduct disorder (n = 122), attention deficit disorder with hyperactivity (n = 55), separation anxiety (n = 38) and other anxiety disorders (n = 36). When the effects of other variables were statistically controlled, only adolescents with major depression showed an association with low maternal care.

Adolescent↗

Functional enuresis: is desmopressin the answer?

OBJECTIVE: The efficacy of desmopressin in the treatment of functional enuresis, known for 15 years, has received very little attention in the psychiatric literature. This review seeks to remedy this and to asses critically its effectiveness, risks and side effects, as well as the implications for the understanding and management of enuresis. METHOD: Treatment trials, reports of unwanted effects, and literature on mechanisms of action were reviewed. RESULTS: Desmopressin is more effective than placebo in controlled trials, but only one quarter of patients become "dry." Individuals who wet the bed 4 nights per week or more can expect a one-third reduction in their wet nights with a single intranasal dose of desmopressin before bedtime. Relapse rates upon cessation of treatment are very high, while side effects appear to be few. However, there are increasing reports of hyponatremic seizures. There is a group of patients in which bed-wetting appears to be the result of insufficient nocturnal secretion of vasopressin. CONCLUSIONS: Desmopressin is a simple-to-use and effective drug for the treatment of nocturnal enuresis; it has opened important new avenues of inquiry, but more information is required about its long-term effectiveness and unwanted side effects.

Child↗

Bedwetting and psychopathology in adolescents.

OBJECTIVE: To ascertain whether nocturnal enuresis in adolescents is associated with depression, hyperactivity, oppositionality, conduct and peer problems. METHODOLOGY: This was investigated cross-sectionally in adolescents aged 12-16 years from a community sample (n = 528) and a clinically referred cohort (n = 2325) using parents' reports. RESULTS: Referred adolescents were 7 times more likely to wet the bed than their community counterparts. There was a small but significant association between nocturnal enuresis and hyperactivity. Depressed adolescents were half as likely to wet the bed as those without depression. Bedwetters had more problems relating to peers but were not disliked more often. There was no association between bedwetting, oppositionality, conduct problems and gender. Gender differences disappeared when the effect of hyperactivity was controlled. CONCLUSIONS: Clinicians need to inquire about symptoms of attention deficit hyperactivity disorder in adolescents who present with enuresis and vice versa.

Adolescent↗

Inter-rater reliability of global assessment of functioning in a clinical setting.

Four studies on the inter-rater reliability of a proposed Axis V version for DSM-IV and of the CGAS involving 162 child and adolescent patients and 20 clinicians showed moderate agreement (intraclass correlation: 0.53-0.66). This was comparable to previous versions of Axis V, but lower than that reported for the CGAS. More detailed description of anchor points did not increase reliability nor there were differences in agreement when rating current or previous functioning.

Achievement↗

Continuities between psychiatric disorders in adolescents and personality disorders in young adults.

OBJECTIVE: Personality disorders are a major mental health problem, but little information about their etiology and natural history is available. This study examined continuities between axis I disorders in adolescents and personality disorders in young adults. METHOD: The authors interviewed 145 young adults (mean age, 19.6 years) who had been diagnosed with a variety of DSM-III emotional and disruptive disorders during adolescence (mean age, 13.7 years). The Personality Disorder Examination was used to establish whether the subjects currently suffered from personality disorders. RESULTS: Subjects who had had disruptive disorders during adolescence showed high rates of all types of personality disorders (40% had a personality disorder at follow-up), while subjects who had had emotional disorders had a lower rate of personality disorders (12%). Men were more likely to have cluster A personality disorders, and women were more likely to have cluster C personality disorders. Disruptive diagnoses were associated with cluster B personality disorders, but emotional disorders did not show an association with cluster C personality disorders. Oppositional disorder did not increase the likelihood of passive-aggressive personality disorder. There was an association between attention deficit disorder with hyperactivity and borderline personality disorder. CONCLUSIONS: The rate of personality disorders was lower among young adults who had had emotional disorders during adolescence than among those who had had disruptive disorders, suggesting either that treatment for emotional disorders is more effective or that the personality psychopathology in these adolescents is not as severe as that in adolescents with disruptive disorders.

Adolescent↗

Comorbidity between disruptive disorders and depression in referred adolescents.

Parent questionnaires from large Australian (N = 2093) and American (N = 500) clinic cohorts of adolescents were used to diagnose depression, attention deficit disorder with hyperactivity, and oppositional and conduct disorders. Co-occurrence of diagnoses was very high. Comorbidity between depression and conduct disorder was not higher than that expected for any psychiatric disorder (odds ratios = 1.20 and 1.45 respectively for each cohort) while comorbidity between attention deficit disorder with hyperactivity and oppositional disorder was higher than expected (odds ratios = 7.03 and 9.02) but comparable to that between conduct and oppositional disorder (odds ratios = 7.35 and 6.14). Co-occurrence of depression with other disorders did not increase the likelihood of comorbid conduct disorder.

Adolescent↗

Child and adolescent psychiatric services: case audit and patient satisfaction.

A system for the monitoring and review of a large number of cases seen for assessment and outpatient treatment by a multidisciplinary child and adolescent psychiatric service is described. The system permits monitoring of all cases to closure, and clinical review of treatment for those cases whose outcomes are judged unsatisfactory by the treating clinician. It also allows monitoring of those cases in which there was patient dissatisfaction with the service, as expressed in a patient satisfaction questionnaire. The system of review has gained the acceptance of the clinical team, who are involved in its continued improvement.

Adolescent↗