Synpolydactyly and HOXD13 polyalanine repeat: addition of 2 alanine residues is without clinical consequences

Background  

Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in HOXD13, resulting in an addition of ≥ 7 alanine residues to the polyalanine repeat. It has been suggested that expansions ≤ 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype.     

Diurnal cortisol dysregulation,functional disability,and depression in women with ovarian cancer

BACKGROUND:

Multiple alterations in circadian rhythms have been observed in cancer patients, including the diurnal rhythm of the adrenal hormone cortisol. Diurnal cortisol alterations have been associated with cancer‐related physiological processes as well as psychological stress. Here we investigate alterations in diurnal cortisol rhythm in ovarian cancer patients, and potential links with depression, life stress, and functional disability.

METHODS:

Women (n = 177) with suspected ovarian cancer completed questionnaires and collected salivary cortisol 3× daily for 3 consecutive days before surgery. One hundred women were subsequently diagnosed with ovarian cancer and 77 with benign disease. In addition, healthy women (n = 33) not scheduled for surgery collected salivary cortisol at the same time points.

RESULTS:

Ovarian cancer patients demonstrated significantly elevated nocturnal cortisol (P = .022) and diminished cortisol variability (P = .023) compared with women with benign disease and with healthy women (all P values <.0001). Among ovarian cancer patients, higher levels of nocturnal cortisol and less cortisol variability were significantly associated with greater functional disability, fatigue, and vegetative depression, but not with stress, distress, or depressed affect. There were no significant associations between functional or psychological variables and diurnal cortisol in women with benign disease.

CONCLUSIONS:

Nocturnal cortisol and cortisol variability show significant dysregulation in ovarian cancer patients, and this dysregulation was associated with greater functional disability, fatigue, and vegetative depression. These findings suggest potential hypothalamic‐pituitary‐adrenal involvement in functional disability in ovarian cancer, and may have implications for disease progression. Cancer 2010. © 2010 American Cancer Society.     

Comprehensive Australasian multicentre dosimetric intercomparison: Issues,logistics and recommendations

The present paper describes the logistics of the 2004–2008 Australasian Level III Dosimetry Intercomparison. Dosimetric intercomparisons (or ‘audits’) can be used in radiotherapy to evaluate the accuracy and quality of radiation delivery. An intercomparison was undertaken in New Zealand and Australia to evaluate the feasibility and logistics of ongoing dosimetric intercomparisons that evaluate all steps in the radiotherapy treatment process, known as a ‘Level III’ intercomparison. The study commenced in 2002 with the establishment of a study team, definition of the study protocol, acquisition of appropriate equipment and recruitment of participating radiotherapy centres. Measurements were undertaken between October 2004 and March 2008, and included collation of data on time, costs and logistics of the study. Forty independent Australian and New Zealand radiotherapy centres agreed to participate. Measurement visits were made to 37 of these centres. Data is presented on the costs of the study and the level of support required. The study involved the participation of 16 staff at the study centre who invested over 4000 hours in the study, and of over 200 professionals at participating centres. Recommendations are provided for future phantom‐based intercomparisons. It is hoped that the present paper will be of benefit to any centres or groups contemplating similar activities by identifying the processes involved in establishing the study, the potential hazards and pitfalls, and expected resource requirements.     

Impact of experimentally induced serotonin deficiency by tryptophan depletion on saliva cortisol concentrations

BACKGROUND: Tryptophan depletion (TD) has been shown to induce a transient mood-lowering effect in psychiatric patients and susceptible healthy subjects. We investigated the effects of TD on cortisol secretion in psychiatric patients and healthy subjects based on the hypothesis that the potential mood-lowering effects may be associated with increased activity of the hypothalamic-pituitary-adrenal axis, thus leading to a rise of cortisol secretion. METHODS: After TD at 18.00 h, salivary cortisol was sampled in the evening and on the following morning. The first study was a randomized, placebo-controlled, crossover study in healthy subjects. Two further open trials in patients with obsessive-compulsive disorder (OCD) and primary insomnia compared the effects of TD on cortisol with baseline conditions. RESULTS: In healthy subjects, TD significantly diminished cortisol the next morning compared with placebo. In OCD patients and primary insomniacs, cortisol the morning after TD was lowered compared with baseline. Evening cortisol was not affected by TD in any of the groups. CONCLUSIONS: Contrary to expectation, TD led to a comparable decrease of morning cortisol in all groups investigated. However, these findings are consistent with former studies analyzing the impact of antiserotonergic drugs on cortisol secretion. The results underline that the antiserotonergic effects caused by TD may influence cortisol secretion.     

No morning cortisol response in patients with severe global amnesia

Activity of the hypothalamus pituitary adrenal (HPA) axis is characterized by a pronounced circadian rhythm. An acute increase in cortisol levels occurs after awakening in the morning with continuously declining levels over the course of the remaining day. The morning cortisol increase probably reflects an activational response of the HPA axis aimed at preparing the body for the day. Some studies found patterns of enhanced or blunted waking cortisol responses observed under chronic stress, burnout, or post traumatic stress disorder. The present study wanted to characterize the morning cortisol response and the circadian cortisol day profile in a sample of six male patients with severe amnesia due to hypoxia, herpes simplex encephalitis or closed head injury. Age and gender matched relatives or friends served as controls. Cortisol was measured from saliva samples collected at home on two consecutive days. The patients were woken up in the morning by their partners or caregivers. The morning cortisol increase typically observed in healthy subjects and also observed in the control group was absent in the amnesic patients. In contrast, a normal circadian day profile was found in the amnesic patients, with a pronounced circadian cortisol decrease. Further studies are needed to understand the neurological or psychological mechanisms leading to a missing morning cortisol response in amnesic patients.