The occurrence of late asthmatic response to exercise after allergen challenge

OBJECTIVES: To evaluate the correlation between the pathological findings of stereotactic core needle biopsy (SCNB) and the prebiopsy mammographic findings, as well as the pathological findings of lesions that were subsequently removed by surgical excision. DESIGN: A retrospective review of 97 consecutive patients who underwent 100 SCNBs of suspicious nonpalpable mammographic lesions. The criterion standard is surgical excisional biopsy with needle localization. Mammographic findings were graded according to the American College of Radiology Breast Imaging Reporting and Data System. The pathological findings of SCNB were categorized into 4 groups: benign and specific, benign and nonspecific, premalignant, and malignant. Surgical excision of the lesion was performed if the pathological finding on SCNB was nonconcordant with the prebiopsy mammogram and when premalignant or malignant lesions were found. The pathological findings of lesions that were subsequently removed by surgical excision were compared with those of SCNB. SETTING: Community-based private multispecialty ambulatory practice. PATIENTS: A population-based sample composed of 97 patients who had grade III, IV, or V lesions on routine screening mammograms. INTERVENTION: Stereotactic core needle biopsy of nonpalpable mammographic lesions. MAIN OUTCOME MEASURES: Percentage of patients whose SCNB results were concordant with the mammographic findings and the pathological findings on subsequent surgical excision. RESULTS: Concordance between SCNB and mammography occurred in 97% of biopsy specimens. Concordance between the pathological findings of SCNB and those of surgically excised lesions occurred in 92.5% of biopsy specimens. We had 1 false-negative result. We had no false-positive diagnosis of cancer with SCNB. CONCLUSION: On the basis of accumulating literature and our own initial experience, SCNB is a promising, safe, and cost-effective procedure.     

Evidence that increased calcium intake does not prevent early postmenopausal bone loss

Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose baseline calcium intake was <500 mg/d were advised to increase their calcium intake. Mean (+/- SE) BMD decreased by 1.9% +/- 0.16% at the lumbar spine and 1.6% +/- 0.14% at the hip over the 24-month period. Despite wide variations in baseline calcium intake and changes in calcium intake, these measures were not significantly associated with changes in BMD or bone turnover. Even women whose total calcium intake was >1333 mg/d (the highest tertile of total calcium intake) showed a decline in BMD of almost 2%, similar to declines in the lower two tertiles of total calcium intake (<869 and 869-1333 mg/d, respectively). Increased calcium intake resulted in modest mean increases of approximately 200 mg/d. We were unable to demonstrate that increases of this magnitude or much greater (1 g/d) were protective against declines in BMD at any site, even in women who had the lowest calcium intake at baseline. In addition to adequate calcium intake, more effective therapy appears to be required when the therapeutic goal is to increase or maintain BMD.     

Female sex is associated with increased mortality and morbidity early, but not late, after coronary artery bypass grafting

OBJECTIVE: To describe mortality and morbidity during a period of 2 years after coronary artery bypass grafting in relation to gender. DESIGN: Prospective follow-up study. SETTING: Two regional cardiothoracic centres which performed all the coronary artery bypass operations in western Sweden at the time. SUBJECTS: A total of 2129 (1727 (81%) men and 402 (19%) women) consecutive patients undergoing coronary artery bypass surgery between June 1988 and June 1991 without concomitant procedures. RESULTS: Females were older and more frequently had a history of hypertension, diabetes mellitus, congestive heart failure, renal dysfunction and obesity. In a multivariate analysis, taking account of age, history of cardiovascular diseases and renal dysfunction, female sex appeared as a significant independent predictor of mortality during the 30 days after coronary artery bypass grafting (P < 0.05), but not thereafter. Various postoperative complications including neurological deficit, hydro- and pneumo-thorax, perioperative myocardial damage and the need for assist devices and prolonged reperfusion were more common in females than males. CONCLUSION: Females run an increased risk of early death and the development of postoperative complications after coronary artery bypass surgery as compared with males. Late mortality does not appear to be influenced by gender and the long-term benefit of the coronary artery bypass graft operation is similar in men and women.     

Effect of inhaled cyclosporin A on the allergen-induced late asthmatic response and increased in airway hyperresponsiveness in a guinea pig model of asthma

Oral administration of cyclosporin (CsA), a potent inhibitor of helper T cell function, prevents the allergen-induced late asthmatic response (LAR) and the increase in airway hyperresponsiveness (AH) seen in actively sensitized guinea pigs. The systemic administration of this agent in humans has been associated with serious side effect, therefore, the effects of inhaled CsA were therefore examined in guinea pigs that were actively sensitized by repeated exposure to nebulized ovalbumin. Respiratory resistance (Rrs) of the animals was measured by an oscillation method and the extent of AH was inferred from the inhaled concentration of histamine required to increase Rrs by 200%. The magnitude of ovalbumin-induced immediate bronchoconstriction after sensitization was similar in CsA-treated and nontreated control animals. However, a LAR was observed in 4/5 control animals but in 0/5 CsA-treated animals. The increase in AH observed 24 hours after antigen exposure in control animals was significantly inhibited by prior CsA inhalation. Significant CsA concentrations were detected by radioimmunoassay in the lungs of CsA-treated animals. Thus, inhaled CsA should be further investigated because it may be useful treating asthma while avoiding side effects.     

Increased LTB4 metabolites and PGD2 in BAL fluid after methacholine challenge in asthmatic subjects

The bronchoconstrictor potency of inhaled methacholine is widely used to assess airway responsiveness. However, evidence has accumulated that methacholine inhalation challenge may lead to an inflammatory response in the lower respiratory tract. We therefore compared cellular, leukotriene and prostanoid profiles in bronchoalveolar lavages (BAL) obtained five hours after methacholine challenge to control lavages without prior challenge. Eight subjects with asymptomatic to mild bronchial asthma and nine nonatopic healthy controls were enrolled in the study. Without prior challenge, the percentage of BAL eosinophils was higher in the asthmatic subjects ((mean +/- SD), 1.1 +/- 0.9%) than in the control subjects (0.1 +/- 0.1%. Leukotriene B4 (LTB4), and its omega-oxidation products (20-OH-LTB4 and 20-COOH-LTB4) were the only leukotrienes detectable in the baseline BAL fluids in five of the eight asthmatic patients. After methacholine challenge, no change in BAL cell profile occurred, but in the asthmatic patients, the total amounts of LTB4 and its omega-oxidation products rose from 0.52 +/- 0.50 ng.ml-1 (pre-challenge) to 1.55 +/- 1.32 ng.ml-1 (post-challenge), and prostaglandin D2 (PGD2) rose from 49.1 +/- 15.7 (pre-challenge) to 94.4 +/- 25.4 pg.ml-1 (post-challenge), with no change in 6-keto-PGF1 alpha, thromboxane B2 (TXB2), and prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2). In the healthy controls, no consistent change in BAL cell profile and mediators occurred after methacholine provocation. We conclude that inhaled methacholine stimulates LTB4 and PGD2 release in asthmatics, but not in healthy controls, without affecting the number of inflammatory cells in BAL fluid.     

Pulmonary metabolism of beta-endorphin in asthmatic patients in asymptomatic periods and after bronchospasm induced by methacholine

Blood concentration of endogenous beta-endorphines can change during the clinical evolution of chronic bronchopneumopathies. The authors assessed the beta-endorphine concentrations in the pulmonary arterial and systemic arterial blood in 8 asthmatic patients during a symptom-free period and after methacholine-induced bronchospasm. The beta-endorphine analysis was performed in duplicate dor each sample, by means of a RIA assay. There is not difference in the systemic arterial blood concentration of beta-endorphines between asthmatic patients and normal subjects. Furthermore, there is no change in the beta-endorphine blood concentration during the passage through the pulmonary tissue after methacoline-induced bronchospasm.     

Nicotine given intracerebroventricularly does not inhibit the preovulatory surge of LH and PRL secretion in female rats

Twenty-three cases of Little Leaguer's shoulder were reviewed including the history and physical examination findings, as well as bilateral internal and external rotation anteroposterior comparison radiographs of the proximal humerus. The average follow-up was 9.6 months (range, 1.5 to 54), and all patients were observed until they had either returned to baseball or their symptoms had resolved. The average age of the patients in this series was 14 years. The chief complaint in all patients was pain localizing to the proximal humerus during the act of throwing. The average duration of symptoms was 7.7 months. Nineteen patients (83%) were pitchers. Physical examination revealed tenderness to palpation over the proximal humerus in 20 patients (87%), with 16 (70%) demonstrating specific tenderness over the lateral aspect of the proximal humerus. Swelling, weakness, atrophy, and loss of motion were uncommon findings. All 23 patients demonstrated radiographic widening of the proximal humeral physis of the throwing arm on internal and external rotation comparison anteroposterior radiographs of the shoulder. All patients were treated with rest from baseball throwing for an average of 3 months. Twenty-one of the 23 patients (91%) returned to playing baseball and were asymptomatic. The classic radiographic finding of widening of the proximal humeral physis can easily be seen on bilateral anteroposterior internal and external rotation radiographs of the proximal humerus. Rest from throwing for at least 3 months is recommended, followed by a gradual return to throwing in an asymptomatic shoulder.     

Social stress inhibits the nitric oxide effect on the corticotropin-releasing hormone- but not vasopressin-induced pituitary-adrenocortical responsiveness

Putative involvement of endogenous nitric oxide (NO) in the corticotropin-releasing hormone (CRH, 1 microg/kg i.p.)- and vasopressin (AVP, 5 microg/kg i.p.)-induced ACTH and corticosterone secretion was investigated in both non-stressed and crowded rats. The NO synthase blocker Nomega-nitro-l-arginine (l-NNA, 2 mg/kg i.p. ) significantly augmented the AVP-induced ACTH and corticosterone secretion in control and stressed rats, but it increased the CRH-induced ACTH response only in control rats. Crowding stress did not affect the l-NNA evoked increase in AVP-induced hormone responses, but it abolished the CRH-induced ACTH response.     

Loss of normal cyclical beta 2 adrenoceptor regulation and increased premenstrual responsiveness to adenosine monophosphate in stable female asthmatic patients

BACKGROUND: A study was undertaken to investigate the influence of the menstrual cycle on airway responsiveness and beta 2 adrenoceptor function in female asthmatic patients. It has previously been shown that normal women exhibit cyclical changes in beta 2 adrenoceptor function with an increase in beta 2 adrenoceptor density in the luteal phase during the premenstrual period. METHODS: Fifteen women with stable, well controlled asthma (mean forced expiratory volume in one second (FEV1) 2.971 (93.8% predicted)) were evaluated. Measurements were made at the follicular phase (days 1-6) and the luteal phase (days 21-24) of the menstrual cycle. Airway responsiveness was assessed using adenosine 5'-monophosphate (AMP) and expressed as PC20 AMP. Beta 2 adrenoceptor function was evaluated by measuring lymphocyte beta 2 adrenoceptor parameters and constructing dose-response curves to salbutamol (100-1600 micrograms). The levels of female sex hormones were also measured at both phases of the cycle. RESULTS: There were significant increases in serum levels of both oestradiol (2.2-fold, p < 0.001) and progesterone (7.2-fold, p < 0.05) between the follicular and luteal phases. Geometric mean PC20 AMP was 19.0 mg/ml and 7.6 mg/ml during the follicular and luteal phases, respectively (p < 0.05), a 2.51-fold difference (95% CI 1.19 to 5.30) amounting to 1.33 doubling doses of AMP. There was no change in lymphocyte beta 2 adrenoceptor parameters or in airway beta 2 adrenoceptor responses to salbutamol between the two phases. CONCLUSIONS: Despite an appropriate rise in female sex hormones during the luteal period, beta 2 adrenoceptor regulation in female asthmatic subjects shows a loss of the normal cyclical pattern. In addition, there were cyclical changes in airway responsiveness to AMP which was highest during the premenstrual period. Thus, drugs such as theophylline which block adenosine receptors warrant investigation in premenstrual asthma.     

Increasing the difficulty of response selection does not increase the switch cost.

Several theories of task switching assume that basic task processes such as stimulus identification and response selection do not contribute to task-switch costs. This conclusion is mainly based on the finding that stimulus-identification manipulations have no influence on the size of the switch cost. The present study tested the influence of response-selection manipulations on the size of the switch cost. The authors manipulated the difficulty of response selection by using a semantically based response-side effect that is associated with numerical-judgement tasks, namely the Spatial Numerical Association of Response Codes (SNARC) effect. The authors observed a SNARC effect and a switch cost, but no interaction between the two: the task-switch cost did not differ between SNARC-compatible and -incompatible responses. The authors conclude that response selection does not contribute to the switch cost on the current trial, which provides further support for the idea that basic task processes and task-switch processes are separate. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apoptosis in late stage Drosophila nurse cells does not require genes within the H99 deficiency

A reversed-phase high performance liquid chromatographic (HPLC) assay developed for the CP-93,393-1 drug substance was adapted for use with CP-93,393-1 tablets. Using a novel experimental matrix, validation was performed to obtain linearity, reproducibility and recovery and to meet current regulatory requirements. Deviations in the sample preparation procedure were performed to demonstrate the ruggedness of the assay.     

Faith is not enough: A response to the Baltes-Schaie claim that intelligence does not wane.

Faith has been defined as unfounded belief in the occurrence of the improbable. This seems to describe well the adherence of P. B. Baltes and K. W. Schaie (see PA, Vol 52:5053; also Schaie—Vol 53:7133) to a claim that little or no important age-related intellectual decline occurs. In replying to criticisms of their arguments that such decline is myth, the present paper argues that Baltes and Schaie (1976) have (a) obscured the basic points at issue by raising diversionary questions about plasticity and "dialectical posture"; (b) advanced the untenable argument that the search for lawful explanation of complex phenomena is futile; (c) fallaciously argued that criticisms are suspect unless they are based on a "theory-free" inductive interpretation of findings; (d) ignored results indicating decline and positive bias in the very data cited to support their argument for the myth of intellectual decline; (e) failed to explain what is systematic about the significance of the omnibus F test for cohort "effects," beyond what can parsimoniously be accounted for in terms of the confounded age variable; (f) not responded to reasoning suggesting that between-cohort differences in education, if these account for important intellectual variation, should be reflected in a manner contrary to what is actually observed; and (g) asserted that no statistically reliable age decrement occurs in a set of data for which analyses demonstrate statistically significant linear decline. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antigen-specific immunoglobulin-A prevents increased airway responsiveness and lung eosinophilia after airway challenge in sensitized mice

The aim of this study was to examine the role of dopamine neurotransmission in the effects of morphine in the learned helplessness paradigm in rats, a generally recognized model of depression. In this model, rats first exposed to inescapable shocks (stressed rats) exhibited an escape deficit in a subsequent shuttle-box test performed 48 h later for 3 consecutive days. The numbers of escape failures and intertrial crossings (motor activity during each intertrial interval) were recorded. Morphine was injected twice daily for 5 days (6 mg/kg/day, s.c.), and haloperidol, a preferential D2-dopamine receptor antagonist, was injected i.p. 15 min before each shuttle-box session. At the highest dose tested (150 microg/kg) haloperidol mimicked the behavioral deficit produced by inescapable shocks. A 37.5 microg/kg dose of haloperidol, which was ineffective by itself, reversed the morphine-induced improvement of escape behavior in previously stressed rats and the morphine-induced increase in intertrial activity in both stressed and nonstressed animals. These results support roles (a) for a dysregulation of dopaminergic neuronal activity in the expression of escape deficit subsequent to an inescapable aversive situation, and (b) for a dopaminergic mediation in the effects of morphine in the learned helplessness paradigm.     

Blood markers of early and late airway responses to allergen in asthmatic subjects. Relationship with functional findings

Resistance exercise has been suggested to increase blood volume, increase the sensitivity of the carotid baroreceptor cardiac reflex response (BARO), and decrease leg compliance, all factors that are expected to improve orthostatic tolerance. To further test these hypotheses, cardiovascular responses to standing and to pre-syncopal limited lower body negative pressure (LBNP) were measured in two groups of sedentary men before and after a 12-week period of either exercise (n = 10) or no exercise (control, n = 9). Resistance exercise training consisted of nine isotonic exercises, four sets of each, 3 days per week, stressing all major muscle groups. After exercise training, leg muscle volumes increased (P < 0.05) by 4-14%, lean body mass increased (P = 0.00) by 2.0 (0.5) kg, leg compliance and BARO were not significantly altered, and the maximal LBNP tolerated without pre-syncope was not significantly different. Supine resting heart rate was reduced (P = 0.03) without attenuating the heart rate or blood pressure responses during the stand test or LBNP. Also, blood volume (125I and 51Cr) and red cell mass were increased (P < 0.02) by 2.8% and 3.9%, respectively. These findings indicate that intense resistance exercise increases blood volume but does not consistently improve orthostatic tolerance.     

Synaptic plasticity and the organization of behaviour after early and late brain injury.

D. O. Hebb (1949) proposed that synaptic change underlies behavioural and cognitive plasticity. When applied to recovery from brain injury, the general hypothesis is that if there is recovery following brain injury, then there ought to be a correlated synaptic change, which is presumed to be responsible for recovery. In contrast, if recovery fails to occur, or expected recovery is blocked in some manner, then the synaptic change will likely not be present. Systematic study of functional recovery and synaptic change following brain injury at different ages supports these predictions. Good recovery is always correlated with enhanced connectivity whereas poor recovery is always correlated with an absence of reorganized connectivity. Furthermore, factors that stimulate recovery, such as neurotrophins or experience, stimulate synaptic change and functional recovery. Factors that retard recovery, such as depletion of neuromodulators, also block synaptic change. These results thus support Hebb's general idea that synaptic plasticity is related to behavioural change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood

Forty-five male patients with planned coronary artery bypass operation were randomized in a double blind fashion to receive either 6 million kallikrein inactivator units of aprotinin (high-dose group), 2 million kallikrein inactivator units of aprotinin (low-dose group), or placebo (control group). Postoperative bleeding was significantly decreased in both aprotinin groups in comparison to that in the control group (590 ml [290 to 1800 ml] high-dose group and 650 ml [280 to 1900 ml] low-dose group versus 920 ml (350 to 2700 ml) control group, p < 0.001). There was no difference between the two aprotinin groups. The need for postoperative blood transfusion was significantly lower in the aprotinin groups (1.46 [0 to 4] blood units high-dose group and 1.65 [0 to 5] blood units low-dose group versus 2.43 [0 to 7] blood units control group, p < 0.05). All patients underwent coronary angiography between the seventh and twelfth postoperative day. No difference was found among the three groups in patency of vein grafts-93.8% in the high-dose group, 94.5% in the low-dose groups, and 93.3% in the control group. Therefore, aprotinin significantly reduced postoperative bleeding and transfusion requirement after coronary artery bypass grafting without influencing early graft patency.     

D-cycloserine facilitates extinction but does not eliminate renewal of the conditioned emotional response.

The effect of D-cycloserine (DCS), an NMDA partial agonist, on extinction of fear was investigated in rats using the conditioned emotional response preparation. Fear extinction was facilitated when the first 4 trials occurred with a 30-mg/kg dose of DCS. However, extinguished fear was "renewed" regardless of the drug treatment when the rats were returned to the context in which fear had been conditioned. Additional results suggest that DCS's facilitation of extinction is a small but meaningful effect in the current method. The results suggest caution regarding the use of DCS as an adjunct to extinction: Although the drug may modestly facilitate extinction learning, it does not necessarily destroy the potential for relapse. Behavioral mechanisms are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)