A meta-analysis of cortisol response to challenge in human aging: importance of gender

An increased cortisol response to challenge is associated with a variety of age-related disorders such as Alzheimer's disease, depression, diabetes, metabolic syndrome, and hypertension. Among the healthy elderly, an increased cortisol response to challenge may be a risk factor for developing these age-related disorders. We searched Pubmed, Embase, PsychInfo, Biosis, and Digital Dissertations (January 1966-June 2003) and included 45 parallel-group (young vs. old subjects) studies that used either a pharmacological or psychological challenge in healthy volunteers and measured cortisol response to challenge. We calculated effect sizes (Cohen's d) for the standardized mean differences between groups. Compared to younger controls (n=670, mean age 28 years +/-5), older subjects (n=625, 69+/-6) showed a larger cortisol response to challenge defined as stronger response to stimulation or less inhibition after a suppression test (d=0.42, 95% confidence interval (CI), 0.26-0.57). The effect of age on cortisol release was significantly stronger in women (d=0.65, 95% CI 0.34-0.97) than men (d=0.24, 95% CI 0.02-0.47). Our results demonstrate that aging increases the cortisol response to challenge. This effect of age on cortisol response is almost three-fold stronger in women than men. Prospective studies should explore whether the higher cortisol response in the elderly is a risk factor for developing neuropsychiatric and medical disorders.     

Polymorphisms of haemostasis genes as risk factors for preterm delivery

Clinical trials evaluating the potential benefit of anticoagulant treatment in pregnant women with inherited thrombophilia are based on the observation that a genetic predisposition to thrombosis is associated with frequent abortions and preterm birth. It was the aim of our study to delineate the impact of genetic polymorphisms with prothrombotic and antithrombotic effects on the occurrence of preterm birth in a large cohort of very-low-birth-weight (VLBW)-infants and their mothers. We examined the factor V Leiden and the prothrombin G20210A mutation, the factor VII 121del/ins and the factor XIII Val34Leu polymorphism in preterm very-low-birth-weight (VLBW, n=593) and term-born-infants (n=278) and their mothers (n=785). The primary outcome was preterm vs.term birth. From all polymorphisms tested, the maternal factor VII-121del/ins polymorphism (26.2 vs. 17.6 %; p=0.009) and the infant's factor VII-121del/ins polymorphism (29.0 vs. 20.0 %; p=0.009) were more frequent in singleton VLBW and their mothers compared to term infants and their mothers. Furthermore, the frequency of the factor XIII-Val34Leu polymorphism was significantly lower in singleton VLBW than in term infant controls (5.1 vs. 9.6%, p=0.025). In a multivariate regression analysis, previous preterm delivery (OR=3.8, 95% CI: 1.7-8.4), the maternal carrier status of the factor-VII-121del/ins polymorphism (OR=1.7, 95% CI: 1.12-2.5, p=0.007) and the lower frequency of infant's factor-XIII-Val34Leu polymorphism (OR=0.53; 95% CI: 0.29-0.96; p=0.038) were found to be independently associated with preterm delivery. InVLBW mothers with pathological CTG as cause of preterm delivery, the frequency of factor V Leiden mutation was significantly increased compared to VLBW mothers without pathological CTG (14.1 vs. 6.1%, p=0.01). The investigated haemostasis gene polymorphisms have a much lower impact on subsequent preterm delivery than known risk factors such as previous preterm birth. The reported association of the factor-VII-121del/ins polymorphism on preterm delivery and its clinical relevance needs to be further elucidated.     

Maternal death after oocyte donation at high maternal age: case report

Background  

The percentage of women giving birth after the age of 35 increased in many western countries. The number of women remaining childless also increased, mostly due to aging oocytes. The method of oocyte donation offers the possibility for infertile older women to become pregnant. Gestation after oocyte-donation-IVF, however, is not without risks for the mother, especially at advanced age.     

In-vitro-Maturation - „PRO“

In the past few years, knowledge acquired in reproductive medicine has led to the development of a wide range of methods of assisted reproduction (ART). Ovarian hyperstimulation using gonadotrophins is a standardized and highly efficient treatment option for inducing polyfollicular development to obtain a large number of oocytes and guarantee acceptable pregnancy rates. However, this technique has various disadvantages, and alternative new methods of assisted reproduction are thus being sought. In vitro maturation (IVM) is designed to aspirate immature cumulus-enclosed oocytes from small antral follicles in order to support their maturation from the germinal vesicle stage to the fertilizable metaphase 2 stage in vitro. IVM is now a simple and cost-saving technique. The technical framework has also been considerably improved. The data obtained to date suggest that IVM is safe. Due to the relatively short time in which IVM has been developed, this technique cannot yet approach the IVF/ICSI method, and it produces fewer pregnancies. However, IVM has great potential for development.     

Foot fractures in restrained front seat car occupants: a long-term study over twenty-three years

OBJECTIVES: To analyze the mechanism of injury for foot and ankle fractures resulting from automobile accidents to create a basis for developing an improved design for protection. DESIGN: Retrospective. SETTING: Level I trauma center with accident research unit. PATIENTS: Automobile accident reports and medical records of individuals injured in the accidents. MAIN OUTCOME MEASUREMENTS: Technical indicators (collision type, impulse angle, deltav, and extent of vehicle deformation) and clinical data (injury location and severity [abbreviated injury scale and injury severity score] and long-term outcome). RESULTS: From 1973 to 1996, 15,559 car accidents were analyzed. Two hundred sixty-one front seat occupants sustained fractures of the foot and ankle (ankle, 41 percent; forefoot, 29 percent; midfoot, 20 percent; and hindfoot, 10 percent). Seventy-five percent of the fractures were classified abbreviated injury scale(foot) 2. The incidence, location, and abbreviated injury scale(foot) category of fractures were similar between driver (n = 210) and front seat passenger (n = 51). Fifty percent of the fractures occurred in head-on collisions and 34 percent occurred in accidents with multiple collisions. The deltav ranged in 82 percent of car crashes between fifteen and sixty kilometers per hour. The deltav and extent of foot compartment deformation correlated with the abbreviated injury scale. During our investigation, deltav increased; the injury severity score decreased; and the extent of deformation did not differ significantly. CONCLUSIONS: Although overall car passenger safety has improved, the relative incidence of foot and ankle fractures has increased. Comparing drivers and front seat passengers, the foot pedals, steering wheel, or the asymmetric design of the dashboard did not influence injury incidence, mechanism, or severity. Foot fractures are mainly caused by the foot compartment deformation in head-on collisions, and therefore improvements in foot compartments are essential for fracture prevention.     

Elevated right ventricular pressures are not a contraindication to liver transplantation in Alagille syndrome

BACKGROUND: Elevated right ventricle pressure resulting from pulmonary artery stenoses may affect outcome and survival after liver transplantation in patients with Alagille syndrome. METHODS AND RESULTS: Between 1984 and 1997, among 444 pediatric liver transplant recipients, 17 had liver transplantation for Alagille syndrome (mean age 3.5 years, range 1.2-13 years), mainly because of poor quality of life with intractable pruritus, and failure to thrive. All patients had pulmonary artery stenosis. In 10 patients considered to have elevated RV pressure on ECG and/or Doppler-echocardiography, a cardiac catheterization was performed before liver transplantation. Mean RV systolic pressure was 55 mmHg (median 49.5 mmHg, range 35-98 mm Hg), mean RV to left ventricular systolic pressure ratio 0.53 (median 0.53, range 0.29-0.78) with a ratio above 0.5 in 6 patients (median 0.66, range 0.5-0.8). All patients underwent successful liver transplantation. Five patients died 1 to 9 months after transplantation from noncardiac causes. In two of them, cardiac catheterization before transplantation showed a RV to left ventricular pressure ratio of 0.51 in one and 0.37 in the second. In the three others, echocardiography before transplantation estimated RV pressures below 0.5 systemic pressures. At follow-up (median 6 years, range 1.5-15 years), liver tests were normal in all, none complained of pruritus and body weight was normalized in 70%. None of the patients presented cardiac symptoms, arrhythmias, or worsening of their cardiac status. CONCLUSIONS: Liver transplantation can be performed safely in children with Alagille syndrome, even in the presence of elevated right ventricular pressure.     

Hypothalamic-pituitary-adrenal axis activity and sleep in posttraumatic stress disorder.

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis and sleep disturbances have been described separately in post-traumatic stress disorder (PTSD). It is not known if HPA alterations and sleep disturbances are associated in PTSD. This study examined sleep and HPA activity in 20 male medication-free subjects with PTSD and 16 matched healthy controls. Two nights of polysomnography were obtained and 24-h urinary cortisol was collected during day 2. Subjects self-administered a low-dose (0.5 mg) salivary dexamethasone test at home. Compared with controls, PTSD subjects had higher 24-h urinary microg cortisol/g creatinine (mean+/-SD 40+/-17 vs 28+/-12, p=0.03) but not significantly higher 24-h urinary cortisol (mean+/-SD 52+/-15 microg/day vs 43+/-23, p=0.19). PTSD subjects showed a trend towards less cortisol suppression after dexamethasone (73%+/-18 vs 83%+/-10, p=0.06). In the combined sample, delta sleep was significantly and negatively correlated with 24-h urinary cortisol (r=-0.36, p=0.04), and with 24-h urinary cortisol/g creatinine on a trend level (r=-0.34, p=0.06). Our results suggest that increased cortisol is negatively associated with delta sleep. This may contribute to sleep abnormalities in conditions associated with elevated cortisol, possibly including PTSD. Future studies should explore the temporal relationship between HPA activity, sleep disturbances, and psychopathology after a traumatic event.     

Insulin-like growth factor type 1 receptor expression correlates to good prognosis in highly malignant soft tissue sarcoma.

PURPOSE: To evaluate known and suggested prognostic markers, especially insulin-like growth factor type 1 receptor (IGF-1R), in highly malignant soft tissue sarcomas (STS). EXPERIMENTAL DESIGN: A cohort of 101 patients with primary STS of high malignancy grade was studied with respect to development of metastasis, local recurrence, and survival during a minimum of 5 years follow-up. All tumors were analyzed by immunohistochemistry for expression of Ki-67, p53, p27, Bcl-2, IGF-1R, and microvessel density. The traditional clinical variables size, malignancy grade (3 or 4), necrosis, mitotic frequency, infiltrative tumor growth, vascular invasion, depth, and surgical margins were also evaluated. RESULTS: A significant association was shown between high expression of IGF-1R and favorable outcome. Among STS with positive IGF-1R immunoreactivity, cases with high expression (76-100% positive cells) had the best outcome, whereas cases with the lowest expression (1-25% positive cells) had the worst. As expected, large tumor size (>11 cm), presence of necrosis, high mitotic count, intralesional surgery, and deep location were all significantly associated with poor outcome, both in univariate and multivariate analyses. No difference in outcome was observed between cases of malignancy grade 3 versus 4, whereas the included and more objective variables necrosis and mitotic count were found to be reliable prognostic markers. CONCLUSION: IGF-1R expression is a common feature of highly malignant STS. Further elucidation of the role of IGF-1R and the IGF system in STS may both provide a basis for development of new prognostic tools in STS, as well as shed light on the basic mechanisms of the STS development.