Permanent Genetic Resources added to Molecular Ecology Resources Database 1 June 2011-31 July 2011.

This article documents the addition of 112 microsatellite marker loci and 24 pairs of single nucleotide polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Agelaius phoeniceus, Austrolittorina cincta, Circus cyaneus, Circus macrourus, Circus pygargus, Cryptocoryne × purpurea Ridl. nothovar. purpurea, Mya arenaria, Patagioenas squamosa, Prochilodus mariae, Scylla serrata and Scytalopus speluncae. These loci were cross-tested on the following species: Cryptocoryne × purpurea nothovar. purpurea, Cryptocoryne affinis, Cryptocoryne ciliata, Cryptocoryne cordata var. cordata, Cryptocoryne elliptica, Cryptocoryne griffithii, Cryptocoryne minima, Cryptocoryne nurii and Cryptocoryne schulzei. This article also documents the addition of 24 sequencing primer pairs and 24 allele-specific primers or probes for Aphis glycines.

Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy.

These neuroendocrine studies were part of a series of studies testing the hypotheses that 1) there may be reduced activity of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome and 2) low-dose augmentation with hydrocortisone therapy would improve the core symptoms. We measured ACTH and cortisol responses to human CRH, the insulin stress test, and D-fenfluramine in 37 medication-free patients with CDC-defined chronic fatigue syndrome but no comorbid psychiatric disorders and 28 healthy controls. We also measured 24-h urinary free cortisol in both groups. All patients (n = 37) had a pituitary challenge test (human CRH) and a hypothalamic challenge test [either the insulin stress test (n = 16) or D-fenfluramine (n = 21)]. Baseline cortisol concentrations were significantly raised in the chronic fatigue syndrome group for the human CRH test only. Baseline ACTH concentrations did not differ between groups for any test. ACTH responses to human CRH, the insulin stress test, and D- fenfluramine were similar for patient and control groups. Cortisol responses to the insulin stress test did not differ between groups, but there was a trend for cortisol responses both to human CRH and D-fenfluramine to be lower in the chronic fatigue syndrome group. These differences were significant when ACTH responses were controlled. Urinary free cortisol levels were lower in the chronic fatigue syndrome group compared with the healthy group. These results indicate that ACTH responses to pituitary and hypothalamic challenges are intact in chronic fatigue syndrome and do not support previous findings of reduced central responses in hypothalamic-pituitary-adrenal axis function or the hypothesis of abnormal CRH secretion in chronic fatigue syndrome. These data further suggest that the hypocortisolism found in chronic fatigue syndrome may be secondary to reduced adrenal gland output. Thirty-two patients were treated with a low-dose hydrocortisone regime in a double-blind, placebo-controlled cross-over design, with 28 days on each treatment. They underwent repeated 24-h urinary free cortisol collections, a human CRH test, and an insulin stress test after both active and placebo arms of treatment. Looking at all subjects, 24-h urinary free cortisol was higher after active compared with placebo treatments, but 0900-h cortisol levels and the ACTH and cortisol responses to human CRH and the insulin stress test did not differ. However, a differential effect was seen in those patients who responded to active treatment (defined as a reduction in fatigue score to the median population level or less). In this group, there was a significant increase in the cortisol response to human CRH, which reversed the previously observed blunted responses seen in these patients. We conclude that the improvement in fatigue seen in some patients with chronic fatigue syndrome during hydrocortisone treatment is accompanied by a reversal of the blunted cortisol responses to human CRH.

Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer.

We ascertained 184 Ashkenazi Jewish women with breast/ovarian cancer (171 breast and 13 ovarian cancers, two of the former also had ovarian cancer) in a self-referral study. They were tested for germline founder mutations in BRCA1 (185delAG, 5382insC, 188del11) and BRCA2 (6174delT). Personal/family histories were correlated with mutation status. Logistic regression was used to develop a model to predict those breast cancer cases likely to be germline BRCA1/BRCA2 mutation carriers in this population. The most important factors were age at diagnosis, personal/family history of ovarian cancer, or breast cancer diagnosed before 60 years in a first degree relative. A total of 15.8% of breast cancer cases, one of 13 ovarian cancer cases (7.7%), and both cases with ovarian and breast cancer carried one of the founder mutations. Age at diagnosis in carriers (44.6 years) was significantly lower than in non-carriers (52.1 years) (p<0.001), and was slightly lower in BRCA1 than BRCA2 carriers. Thirty three percent of carriers had no family history of breast or ovarian cancer in first or second degree relatives. Conversely, 12% of non-mutation carriers had strong family histories, with both a first and a second degree relative diagnosed with breast or ovarian cancer. The predicted values from the logistic model can be used to define criteria for identifying Ashkenazi Jewish women with breast cancer who are at high risk of carrying BRCA1 and BRCA2 mutations. The following criteria would identify those at approximately 10% risk: (1) breast cancer <50 years, (2) breast cancer <60 years with a first degree relative with breast cancer <60 years, or (3) breast cancer <70 years and a first or second degree relative with ovarian cancer.

Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial.

BACKGROUND: Reports of mild hypocortisolism in chronic fatigue syndrome led us to postulate that low-dose hydrocortisone therapy may be an effective treatment. METHODS: In a randomised crossover trial, we screened 218 patients with chronic fatigue. 32 patients met our strict criteria for chronic fatigue syndrome without co-morbid psychiatric disorder. The eligible patients received consecutive treatment with low-dose hydrocortisone (5 mg or 10 mg daily) for 1 month and placebo for 1 month; the order of treatment was randomly assigned. Analysis was by intention to treat. FINDINGS: None of the patients dropped out. Compared with the baseline self-reported fatigue scores (mean 25.1 points), the score fell by 7.2 points for patients on hydrocortisone and by 3.3 points for those on placebo (paired difference in mean scores 4.5 points [95% CI 1.2-7.7], p=0.009). In nine (28%) of the 32 patients on hydrocortisone, fatigue scores reached a predefined cut-off value similar to the normal population score, compared with three (9%) of the 32 on placebo (Fisher's exact test p=0.05). The degree of disability was reduced with hydrocortisone treatment, but not with placebo. Insulin stress tests showed that endogenous adrenal function was not suppressed by hydrocortisone. Minor side-effects were reported by three patients after hydrocortisone treatment and by one patient after placebo. INTERPRETATION: In some patients with chronic fatigue syndrome, low-dose hydrocortisone reduces fatigue levels in the short term. Treatment for a longer time and follow-up studies are needed to find out whether this effect could be clinically useful.