Cognition,mood, and physiological concentrations of sex hormones in the early and late postmenopause

Variations in the hormonal milieu after menopause may influence neural processes concerned with cognition, cognitive aging, and mood, but findings are inconsistent. In particular, cognitive effects of estradiol may vary with time since menopause, but this prediction has not been assessed directly using serum hormone concentrations. We studied 643 healthy postmenopausal women not using hormone therapy who were recruited into early (<6 y after menopause) and late (10+ y after menopause) groups. Women were administered a comprehensive neuropsychological battery and assessed with the Center for Epidemiologic Studies Depression Scale. They provided serum for free estradiol, estrone, progesterone, free testosterone, and sex hormone binding globulin measurements. Cognitive outcomes were standardized composite measures of verbal episodic memory, executive functions, and global cognition. Covariate-adjusted linear regression analyses were conducted for each hormone separately and after adjustment for other hormone levels. Endogenous sex steroid levels were unassociated with cognitive composites, but sex hormone binding globulin was positively associated with verbal memory. Results for early and late groups did not differ significantly, although progesterone concentrations were significantly positively associated with verbal memory and global cognition in early group women. Hormone concentrations were not significantly related to mood. Results fail to support the hypothesis that temporal proximity to menopause modifies the relation between endogenous serum levels of estradiol and verbal memory, executive functions, or global cognition. Physiological variations in endogenous postmenopausal levels of sex steroid hormones are not substantially related to these aspects of cognition or mood; positive associations for progesterone and sex hormone binding globulin merit additional study.Nuclear and nonnuclear receptors for estrogens, androgens, and progesterone are widely distributed in the brain and expressed within discrete neural populations (1–5), and sex steroids may influence brain function through other mechanisms. Variations in the hormonal milieu after menopause have the potential to affect cognitive function and mood as well as physiological processes linked to cognitive aging and late-life disorders, such as Alzheimer’s disease (6, 7). A number of studies have examined associations between serum concentrations of sex steroids and cognition after menopause. Most have focused on 17β-estradiol (E2) (8), which is produced cyclically by the ovaries in women of reproductive age. After menopause, the depletion of ovarian follicles leads to permanent reductions in circulating levels of E2 as well as estrone (E1) and progesterone (P4). Findings related to cognition are inconsistent because of, in part, limited measures of cognitive abilities, measurement of only a single sex steroid, and restricted age range. Age is potentially quite important, because some hormonal effects on cognitive outcomes are proposed to vary by age or timing in relation to the final menstrual period (9–12). The timing, or critical window, hypothesis is best developed with regard to exogenous E2; no research has examined this hypothesis in relation to endogenous hormone concentrations.The ongoing Early versus Late Intervention Trial with Estradiol (ELITE) targets two groups of women: women in early postmenopause and women in late postmenopause (Protocol Plan). The randomized interventions are oral E2 or placebo, and the goal is to assess whether time since menopause (as represented by postmenopause group) modifies the effect of E2 therapy on specified health outcomes, including cognitive change (ELITE-Cog). This large trial provides the additional opportunity to test in a well-characterized cohort of postmenopausal women the hypothesis that the relation of endogenous E2 levels to cognitive skills differs by temporal proximity to menopause and assess other hormone associations with cognition and mood.In younger women, verbal episodic memory is reported to be sensitive to estrogen effects (13, 14), and verbal memory impairment is potentially important, given its association with Alzheimer’s disease risk (15). Episodic memory depends on integrity of the hippocampus and adjacent medial temporal lobe structures (16), and studies in rodents document robust effects of E2 on hippocampal synaptic plasticity, hippocampal long-term potentiation, and hippocampal-mediated cognitive behaviors (17, 18).Here, we report—for early and late postmenopausal women not using hormone therapy—prerandomization associations between verbal memory and other cognitive measures and serum concentrations of E2, E1, P4, and testosterone (T) as well as sex hormone binding globulin (SHBG). At the same time, we also examined the relation between serum hormone concentrations and mood or possible depression. Our primary hypothesis was that the association of E2 levels with verbal episodic memory would differ between postmenopause strata, with higher concentrations associated with better memory performance in the early group but not the late group.     

Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes

Aims/hypothesis

Type 1 diabetes is an autoimmune disease resulting from the destruction of insulin-producing beta cells. Along with advances in generating replacement beta cells for treating diabetes, there is also increasing demand for non-invasive tools to evaluate the recurrence of autoimmune attack on transplanted tissue. Here, we examined the anterior chamber of the eye as a potential islet transplant site, and also evaluated whether in vivo imaging of the islets transplanted in the eye could enable real-time visualisation of autoimmune processes underway in the pancreas.

Methods

Syngeneic islet equivalents were transplanted into the eye or kidney capsule of streptozotocin-induced diabetic C57BL/6 mice to compare islet dose (25–125 islet equivalents) and function across transplant sites. Autoimmune attack of syngeneic islets was evaluated in the pancreas and eye tissues of NOD and NOD-severe combined immunodeficient (SCID) mice given diabetogenic splenocytes.

Results

Islet transplantation in the eye decreased fasting plasma glucose levels and increased weight gain and survival in an islet-dose-dependent manner. Even 50 islets in the eye reduced blood glucose levels, whereas ≥200 islets were required in the kidney for a similar effect. Autoimmune destruction of pancreatic islets in the eye mirrored that in the pancreas and could be visualised in real time by non-invasive imaging.

Conclusions/interpretation

We found that far fewer islets were required to restore normoglycaemia when transplanted into the anterior chamber of the eye vs the kidney capsule. However, our results suggest that islets are not protected against autoimmune attack in the eye, making this a suitable site for visualising autoimmune processes against transplanted tissue.     

Cutaneous embryonal rhabdomyosarcoma presenting as a nodule on cheek; a case report and review of literature

We report a case of primary cutaneous rhabdomyosarcoma, solid embryonal type, presenting as a rapidly enlarging nodule on the right cheek of a 7-year-old boy. This lesion had begun as a pea-sized nodule 8 months previously, and, with suspected abscess, had been incised. It recurred 2 months later; at that time, incisional biopsy was consistent with malignant round cell tumor. Wide local excision of the tumor was then completed. Subsequent immunohistochemical staining with desmin and myoglobin confirmed embryonal rhabdomyosarcoma. The patient underwent radiation therapy followed by chemotherapy and continues to be disease free at 14 months after his wide local excision. Rhabdomyosarcoma presenting as a dermal nodule is rare. It usually presents as an asymptomatic papule without distinctive clinical features and therefore may result in delayed diagnosis unless a biopsy is performed.     

Prognosis of acute renal failure in children

Acute renal failure (ARF) is the acute loss of renal function over a period of hours or days. Given the poor prognosis of ARF among children, there is some urgency to identifying more effective prognostic indicators for detecting disease onset. Such indicators would help provide the means of selecting patients who would benefit the most from early aggressive treatment. In this study we assessed the etiologic and prognostic indicators of ARF, including several risk factors such as sepsis, respiratory distress, age, among others, in 300 children who were admitted to the Ali Asghar Children’s Hospital, Tehran, Iran, from 1990 to 2003. Statistical analysis was performed using multiple regression and chi-square methods, and a score to determine the prognosis of ARF in children was developed. Result: Based on the results of this study the three common causes of ARF are acute tubular necrosis (ATN, 38%), acute glumerulonephritis (24%) and hemolytic uremic syndrome (24.1%). The overall mortality rate among our patients was 24.7%, with the highest risk group being those patients suffering from ischemic ATN. In addition, the correlation (p<0.0005) between the etiology and mortality rate was particularly high in patients with ischemic ATN. Mortality was also high (68%) in children younger than 2 years. Multiple regression models revealed that among those factors that significantly differed between the survivors and nonsurvivors, only the necessity of dialysis (p<0.0005), the use of mechanical ventilation (p=0.05) and disseminated intravascular coagulation (p=0.038) can be regarded as independent determinants of ARF prognosis in children.     

Experimental evaluation of ileal patch in delayed primary repair of penetrating colon injuries: An animal study

Primary repair of traumatic colonic perforation is progressively gaining acceptance as the best method of management. However, when delayed, the risk of infection-related complications may increase. Here, we present a new method of repairing colon perforation in the presence of peritonitis. Acute colon injury was simulated in 22 German shepherd dogs. The dogs were randomly divided into two groups of 11 and after 24 hours they were operated on. The perforations were repaired by subserosal suture technique. In the first group (group A), ileal patch was used. In the other group (group B), the colon was closed by debridement and anastomosis. After 6 weeks, the repairs were assessed on the basis of survival, gross and histological assessments. Nine (82%) dogs in group A and six (56%) in group B survived. Ileal patch utilization significantly decreased the mortality rate (p < 0.05). The cause of death in two group A dogs and five group B dogs was peritonitis and intra-abdominal abscess formation. None of the surviving dogs showed evidence of anastomotic leakage or breakdown. Small bowel patch used in primary repair of colon injury in the presence of peritonitis may decrease the risk of postoperative infection-related complications and the mortality rate.     

Surgical management of carotid body tumours: a 24-year surgical experience

BACKGROUND: Carotid body tumours (CBT) are rare tumours, best treated by complete surgical resection. However, there is no uniform agreement on the method of resection. The aim of this study was to review our 24 years' experience of meticulous subadventitial excision of CBT. METHODS: A retrospective study, from March 1980 to September 2004 of patients with CBT was undertaken, detailing presentation, diagnosis and treatment and postoperative complications. RESULTS: Twenty-five patients (six men and 19 women) with an age range of 23-72 years had been operated on, and all were treated by surgical excision. All patients had neck mass. No patient had a positive family history. Angiography was the main method of diagnosis. All of the patients had unilateral tumours. There was no postoperative permanent neurological deficit. Temporary neurological problems developed in only four patients. External carotid artery was ligated in three patients to facilitate excision of the tumour. Surgical care limited blood loss to an average of 480 mL. CONCLUSIONS: Subadventitial excision, carried out meticulously, allowed complete resection to be achieved in all of the patients with minimal morbidity and no surgical mortalities. This method is therefore recommended. Facilities for shunting and arterial repair should always be available.