Female sex preponderance for idiopathic familial premature ovarian failure suggests an X chromosome defect: opinion.

Premature ovarian failure (POF) is defined as ovarian failure occurring before the age of 40 years. A genetic aetiology is suggested by the occurrence of families with two or more affected females. We have characterised the pattern of inheritance of 41 cases of familial POF and compared them to published pedigrees. In eleven families a clear genetic association of POF could be identified. In the remaining 30 families the mechanism of inheritance was obscure. We found a female sex preponderance in the siblings of 30 families with idiopathic POF and in previously published series of idiopathic familial POF. In contrast, other known causes of POF, such as blepharophimosis ptosis epicanthus and inversus and autosomal recessive gonadal dysgenesis, had no altered sex ratio. One of our series of 30 pedigrees demonstrated transmission of POF susceptibility through fathers, which we believe is the first to be described in the literature. We present a group of five consanguineous families where we assume the mode of inheritance is autosomal recessive and where there was no female sex preponderance. Female sex preponderance for idiopathic familial POF suggests an X chromosome defect is inherited as a major cause of ovarian failure.

Mapping of the POF1 locus and identification of putative genes for premature ovarian failure.

We have identified a breakpoint on the X chromosome which is associated with premature ovarian failure (POF). Using polymerase chain reaction (PCR) probes of polymorphic microsatellites and fluorescent in-situ hybridization (FISH), this breakpoint has been narrowed to a region of 300 kb spanned by two P1 artificial chromosomes (PAC). Computer exon prediction and gene homology programs revealed three genes in this area. Our results suggest that two of these genes, HS6ST and E2F, and LINE 1 elements may be involved in ovarian development. Interruption of these genes could be the cause of POF. This study demonstrates how various molecular techniques and bioinformatic searches can complement each other in order to solve a clinical problem.

Clinical presentation of PCOS following development of an insulinoma: case report.

A 24 year old woman presented with a prolonged clinical history of fasting and exertional hypoglycaemia, and was subsequently diagnosed with an insulinoma. Concurrent symptoms of oligomenorrhoea and hyperandrogenism of similar duration were noted. Biochemically, hyperinsulinaemia was observed in association with a raised serum luteinizing hormone (LH), raised testosterone and androstendione concentrations. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS) but minimal change was observed in the ovarian ultrasound appearances. This case demonstrates the role of insulin in mediating the hypersecretion of both LH and androgens in women with polycystic ovaries. We suggest that hyperinsulinaemia converted occult 'polycystic ovaries' to become clinically manifest as 'polycystic ovary syndrome'. This paradigm has clear implications for women with insulin dependent diabetes mellitus who presumably have systemic hyperinsulinaemia.

Quality of life and posttraumatic stress disorder: a pilot study assessing changes in SF-36 scores before and after treatment in a placebo-controlled trial of fluoxetine.

In this small pilot study, we evaluated quality of life for 16 posttraumatic stress disorder (PTSD) patients by administering the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at baseline and endpoint during a 12-week double-blind trial of fluoxetine and placebo. At baseline, our subjects reported greater impairment relative to subjects with major depression or obsessive-compulsive disorder on several SF-36 domains. Significant effects of fluoxetine relative to placebo were observed for vitality, social functioning, and mental health. Overall, PTSD was associated with greatly reduced quality of life, but considerable improvement was achieved through treatment.

A familial case of X chromosome deletion ascertained by cytogenetic screening of women with premature ovarian failure.

The association between X chromosome deletions and premature ovarian failure is well established. Previous anecdotal reports however, have not documented the prevalence of X deletions in women with premature ovarian failure. We therefore performed cytogenetic analyses on 79 women with primary or secondary amenorrhoea to assess the utility of screening for a genetic marker for familial premature ovarian failure. A normal karyotype was found in 77 women. One woman with primary amenorrhoea had an XY karyotype and a woman with secondary amenorrhoea had a deletion at Xq 26.1. This second case had a family history of premature ovarian failure, and her mother who underwent premature ovarian failure at 28 years shared this deletion. The early diagnosis of familial X deletions causing premature ovarian failure allowed for the prediction of impending menopause and the implementation of manoeuvres to advance conception. Although cytogenetic aberrations are rare in secondary amenorrhoea, the ability to predict premature ovarian failure can be vital.

New approaches to insulin resistance in polycystic ovarian syndrome.

The aetiology of the polycystic ovarian syndrome together with new advances in the molecular genetics and possible candidate genes for the inheritance of the syndrome is discussed. The possible role of leptin in the obesity of polycystic ovarian syndrome is reviewed. Hyperinsulinaemia acts not only as the trigger for hyperandrogenaemia and infertility, but also by stimulating plasminogen activator inhibitor type 1; hyperinsulinaemia may also promote atherogenesis in polycystic ovarian syndrome. The long-term effects of the metabolic derangements accompanying hyperinsulinaemia are reviewed. Special emphasis is placed on the use of novel insulin sensitizers such as troglitazone which promise new treatment opportunities in polycystic ovarian syndrome for both fertility and long-term disease prevention.

Assessment of a new self-rating scale for post-traumatic stress disorder.

BACKGROUND: In post-traumatic stress disorder (PTSD) there is a need for self-rating scales that are sensitive to treatment effects and have been tested in a broad range of trauma survivors. Separate measures of frequency and severity may also provide an advantage. METHODS: Three hundred and fifty-three men and women completed the Davidson Trauma Scale (DTS), a 17-item scale measuring each DSM-IV symptom of PTSD on 5-point frequency and severity scales. These subjects comprised war veterans, survivors of rape or hurricane and a mixed trauma group participating in a clinical trial. Other scales were included as validity checks as follows: Global ratings, SCL-90-R, Eysenck Scale, Impact of Event Scale and Structured Clinical Interview for DSM-III-R. RESULTS: The scale demonstrated good test-retest reliability (r = 0.86), internal consistency (r = 0.99). One main factor emerged for severity and a smaller one for intrusion. In PTSD diagnosed subjects, and the factor structure more closely resembled the traditional grouping of symptoms. Concurrent validity was obtained against the SCID, with a diagnostic accuracy of 83% at a DTS score of 40. Good convergent and divergent validity was obtained. The DTS showed predictive validity against response to treatment, as well as being sensitive to treatment effects. CONCLUSIONS: The DTS showed good reliability and validity, and offers promised as a scale which is particularly suited to assessing symptom severity, treatment outcome and in screening for the likely diagnosis of PTSD.

Abscisic-acid content of xylem sap.

Abscisic acid (ABA) has been identified by gas chromatography in xylem sap of the woody species apple, peach, willow, sugar maple, Tecomaria capensis and Actinidia chinensis. The amounts of ABA present in each species are markedly different, varying from 9 to over 1000 ng/100 ml of sap.