Luteinizing hormone sensitivity to naloxone in maturing male chimpanzees.

We have systematically investigated the involvement of endogenous opioids in gonadotropin secretion during primate sexual maturation by examining LH/FSH responses to gonadotropin-releasing hormone (GnRH) and changes in LH secretion during infusions of saline or naloxone, an opiate antagonist, in ten male chimpanzees between one and nine years of age. Animals were anesthetized with ketamine (10 mg/kg) and injected or infused IV with GnRH, naloxone or saline. Circulating levels of serum LH were elevated to the same extent (approximately 400%) in response to GnRH (100 micrograms) in animals 1-5 years old (juvenile) and in animals 6-9 years old (pubertal). No differences were noted between the two groups in GnRH-stimulated levels of serum FSH. During treatment with naloxone (0.14 mg/kg bolus followed by 0.2 mg/kg/h maintenance infusion for 3 h), serum LH levels in pubertal animals were significantly (p less than 0.05) elevated by as much as 95% over LH levels found during treatment with saline. Juvenile animals, on the other hand, failed to demonstrate significant increases in serum LH following naloxone at the doses tested. A strong correlation (r = .84) was found between circulating testosterone and serum LH levels during naloxone treatment. These data indicate that opioid inhibition of LH secretion can be reversed by naloxone only when puberty is reached in chimpanzees and suggest an alteration in opioid regulation of GnRH near the time of puberty. The strong correlation between testosterone levels and LH responses to naloxone suggests that steroids may participate in the maturation of opioid control of LH during puberty of nonhuman primates.     

Nuclear estrogen receptor beta in lung cancer: expression and survival differences by sex.

PURPOSE: A role for estrogens in determining lung cancer risk and prognosis is suggested by reported sex differences in susceptibility and survival. Archival lung tissue was evaluated for the presence of nuclear estrogen receptor (ER)-alpha and ER-beta and the relationship between ER status, subject characteristics, and survival. EXPERIMENTAL DESIGN: Paraffin-embedded lung tumor samples were obtained from 214 women and 64 men from two population-based, case-control studies as were 10 normal lung autopsy samples from patients without cancer. Nuclear ER-alpha and ER-beta expression was determined by immunohistochemistry. Logistic regression was used to identify factors associated with ER positivity and Cox proportional hazards models were used to measure survival differences by ER status. RESULTS: Neither tumor (0 of 94) nor normal (0 of 10) lung tissue stained positive for ER-alpha. Nuclear ER-beta positivity was present in 61% of tumor tissue samples (170 of 278; 70.3% in men and 58.3% in women) and 20% of normal tissue samples (2 of 10; P = 0.01). In multivariate analyses, females were 46% less likely to have ER-beta-positive tumors than males (odds ratio, 0.54; 95% confidence interval, 0.27-1.08). This relationship was stronger and statistically significant in adenocarcinomas (odds ratio, 0.40; 95% confidence interval, 0.18-0.89). Women with ER-beta-positive tumors had a nonsignificant 73% (P = 0.1) increase in mortality, whereas men with ER-beta-positive tumors had a significant 55% (P = 0.04) reduction in mortality compared with those with ER-beta-negative tumors. CONCLUSIONS: This study suggests differential expression by sex and influence on survival in men of nuclear ER-beta in lung cancer, particularly in adenocarcinomas.     

Effects of early reperfusion on the mechanical and biochemical characteristics of ischemic myocardium

Coronary reperfusion of ischemic myocardium may be beneficial but is highly dependent upon occlusion and reperfusion times. To study the effects of early reperfusion on ischemic myocardium, 24 open chest pigs underwent coronary occlusion; one group was occluded for 40 min, and the other was occluded for 30 min followed by 10 min of reperfusion. Left ventricular wall thickness during systole and diastole was determined by ultrasound. Mitochondrial energy production and calcium content were evaluated from ischemic and nonischemic areas. Results showed: There was an absence of systolic thickness, a slight decrease of diastolic thickness from baseline, and a decrease in energy production in the ischemic myocardium. Reperfusion resulted in a diverse pattern of systolic and diastolic wall thickness in the ischemic area and a variable Ca2+ accumulation and mitochondrial ATP production. The variability of myocardial Ca2+ accumulation in the ischemic reperfused group correlated inversely with mitochondrial ATP production (r = -0.94) and directly with diastolic wall thickness (r = 0.65). Similarly, calcium accumulation, ATP production, and diastolic wall thickness correlated with mean blood pressure during reperfusion. These results suggest that many factors including individual characteristics of the animal and experimental conditions such as the level of blood pressure and the degree of calcium accumulation may determine outcome of reperfusion even in as brief a period as 10 min.     

Treatment of myofascial trigger points in common shoulder disorders by physical therapy: A randomized controlled trial [ISRCTN75722066]

Background  

Shoulder disorders are a common health problem in western societies. Several treatment protocols have been developed for the clinical management of persons with shoulder pain. However available evidence does not support any protocol as being superior over others. Systematic reviews provide some evidence that certain physical therapy interventions (i.e. supervised exercises and mobilisation) are effective in particular shoulder disorders (i.e. rotator cuff disorders, mixed shoulder disorders and adhesive capsulitis), but there is an ongoing need for high quality trials of physical therapy interventions. Usually, physical therapy consists of active exercises intended to strengthen the shoulder muscles as stabilizers of the glenohumeral joint or perform mobilisations to improve restricted mobility of the glenohumeral or adjacent joints (shoulder girdle). It is generally accepted that a-traumatic shoulder problems are the result of impingement of the subacromial structures, such as the bursa or rotator cuff tendons. Myofascial trigger points (MTrPs) in shoulder muscles may also lead to a complex of symptoms that are often seen in patients diagnosed with subacromial impingement or rotator cuff tendinopathy. Little is known about the treatment of MTrPs in patients with shoulder disorders.     

Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing.

Recent data suggest that Alzheimer's patients who discontinue treatment with cholinesterase inhibitors have a significantly delayed cognitive decline as compared to patients receiving placebo. Such observations suggest cholinesterase inhibitors to provide a disease-modifying effect as well as symptomatic relief and, moreover, that this benefit remains after drug withdrawal. Consistent with this suggestion, we now demonstrate that chronic administration of tacrine, nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memory-associated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability. As a combination of both interventions failed to further increase basal polysialylated cell frequency, complex environment rearing and chronic drug regimens most likely enhanced cognitive performance by the same mechanism(s). These findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease modifying action of drugs such as cholinesterase inhibitors. Moreover, the molecular and cellular events underpinning neuroplastic responses are identified as novel targets in the search for interventive drug strategies for the treatment of neurodegenerative and neuropsychiatric disorders.     

Peripheral pulmonary artery aneurysm in a patient with limited respiratory reserve: controlled resection using cardiopulmonary bypass

Pulmonary artery aneurysms are rare lesions for which operative management is not frequently undertaken. When operation is indicated, central lesions involving the pulmonary trunk, right main pulmonary artery, or left main pulmonary artery are repaired using cardiopulmonary bypass. Peripheral aneurysms in segmental intrapulmonary arteries have been managed most frequently by lobectomy, but occasionally by aneurysmectomy and pulmonary arterial repair. We used cardiopulmonary bypass for peripheral pulmonary aneurysmectomy in a patient with limited respiratory reserve because he had undergone prior contralateral bilobectomy; this allowed controlled resection while preserving a maximal amount of pulmonary parenchyma.