Geographic variations in breast cancer mortality: do higher rates imply elevated incidence or poorer survival?

A 46-year-old women presented with an inoperable low-grade endometrial stromal sarcoma. Two doses of Depo-Lupron, 7.5 mg, and Megace, 160 mg/day, were given to control uterine bleeding and shrink the tumor mass. In 9 weeks, significant reduction in the tumor occurred allowing for surgical resection. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the mainstay for primary treatment. The role of chemotherapy, radiation therapy, and hormonal therapy is poorly defined. This is a case report of neoadjuvant hormonal therapy which may improve outcomes in patients with endometrial stromal sarcomas. Additional research is needed to define the exact role of these agents.     

The expression of murine B cell CD23, in vivo, is regulated by its ligand, IgE

CD23, the low-affinity IgE receptor, is believed to participate in immune responses by mediating antigen capture for presentation by B cells and by shedding fragments with immunomodulatory properties. The number of CD23 molecules on B cells is increased during allergic responses and infection with helminths. This can be attributed in part to regulation of CD23 expression by cytokines, including IL-4. In addition, there is evidence that CD23 can be induced on cultured B cells by its ligand, IgE. In the current study we use IgE-deficient (IgE-/-) mice to establish the effects of IgE on CD23 expression by B cells in vivo, in the absence of allergic or parasitic stimuli. The spleens of IgE-/- and wild-type mice contained similar proportions of CD23+ B lymphocytes. However, cells from IgE-/- mice were found to have nearly 3-fold less CD23 on their surface. The mutant B cells had a corresponding defect in their ability to bind IgE. CD23 could be normally induced on IgE-/- B cells after culture with IL-4 or CD40 ligand, indicating that these cells had no inherent defect in CD23 biosynthesis. CD23 expression and IgE-binding capacity were both restored when splenocytes from IgE-/- mice were cultured in the presence of IgE. IgE-induced up-regulation of CD23 could be elicited in vivo as well. In IgE-/- mice, i.v. infusion of IgE corrected CD23 expression to wild-type levels. Our results demonstrate that IgE directly participates in CD23 regulation in vivo. This positive feedback loop may constitute a mechanism for the amplification of ongoing allergic responses.     

Antecedents of pre-competition achievement goals in elite junior tennis players

The aim of this study was to integrate both dispositional and situational factors to examine their interactive ability to predict pre-competitive goal states of task and ego involvement in a sample of National junior tennis players. The Task and Ego Orientation in Sport Questionnaire (Chi and Duda, 1995) and a set of single-item assessments of match goal orientation represented the dispositional measures in the study. These were administered at home, away from the tennis environment. The situational antecedents of pre-match task and ego involvement were assessed by an 11-item Match Context Questionnaire, which was administered to the players (n = 119) within 1 h of their singles match start time at the National Junior Championships. The Match Context Questionnaire also measured the personal task- and ego-involved goal states of the player with respect to the upcoming singles match (i.e. 'state' goals). Factor analysis of this questionnaire revealed three situational factors which cumulatively accounted for 64.7% of variance in the match context: social/personal perceptions of ability; perceived state goal preference of significant others; and match value. Moderated hierarchical regression analyses revealed significant main effects of the dispositional and situational factors on the different goal types. Specifically, perceptions of significant others, the achievement value of the match and perceptions of ability were the major predictors of task involvement. The pre-match intensity of ego involvement was predicted by ego orientation combining with perceptions of significant others and match value. These findings reinforce the need for researchers to consider the importance of both dispositional and situational variables when predicting goal involvement in competitive contexts.     

Endogenous opioid tone in patients with rheumatoid arthritis

A monoclonal antibody giving a dominant reaction with the group-specific polysaccharide of streptococcus group B in an ELISA test has been developed. The purified polysaccharide exhibited a high positivity with reference anti B streptococcal antiserum in the ELISA test. Cross-tests of antibodies with other groups of streptococci provided a minimum cross-reaction only in the case of G streptococci. Monoclonal antibodies were prepared using Streptococcus agalactiae S 589 MT strain isolated from a case of bovine mastitis which does not express Ia, Ib, II, III, IV and V type antigens, nor C, R and X protein antigens.     

Selective metabotropic receptor agonists distinguish non-ionotropic glutamate binding sites

Metabotropic glutamate receptors (mGluRs) are thought to mediate diverse processes in brain including synaptic plasticity and excitotoxicity. These receptors are often divided into three groups by their pharmacological profiles. [3H]Glutamate binding in the presence of compounds selective for ionotropic glutamate receptors can be used as a general assay for these receptors; subtypes of this non-ionotropic [3H]glutamate binding differ in both pharmacology and anatomical distribution, and are differentially sensitive to quisqualate. The characteristics of these binding sites are consistent with those of group 1 (high-affinity quisqualate) and group 2 (low-affinity quisqualate) mGluRs. Under our assay conditions, no [3H]glutamate binding to group 3-like (L-AP4 sensitive) sites could be demonstrated. We have attempted to characterize particular agents which may selectively measure [3H]glutamate binding to mGluR subtypes. We used two isomers of 2-(carboxycyclopropyl)glycine, L-CCG-I and L-CCG-II, and the (2S,1'R,2'R,3'R) isomer of 2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) as competitors of non-ionotropic [3H]glutamate binding sites. DCG-IV clearly distinguishes two binding sites. Quantitative levels of DCG-IV binding by anatomic region correlate with quisqualate-defined binding subtypes: high-affinity DCG-IV binding correlates with low-affinity quisqualate binding, whereas low-affinity DCG-IV binding correlates with high-affinity quisqualate binding. L-CCG-II displaces only one type of non-ionotropic [3H]glutamate binding, corresponding to high-affinity quisqualate binding. Therefore DCG-IV and L-CCG-II at appropriate concentrations appear to distinguish binding to putative group 2 vs. group 1 mGluRs. L-CCG-I displaces both high- and low-affinity quisqualate binding sites, but unlike the other two compounds, does not clearly distinguish between them.     

Overview of the epidemiology of colorectal cancer

The surgical treatment for strabismus in infants generally results in microtropia or subnormal binocular vision. Although the clinical characteristics of these conditions are well established, there are important questions about the mechanisms of binocular vision in these patients that can best be investigated in an appropriate animal model. In the present psychophysical investigations, spatial frequency response functions for disparity-induced fusional vergence and for local stereopsis were studied in macaque monkeys, who demonstrated many of the major visual characteristics of patients whose eyes were surgically aligned during infancy. In six rhesus monkeys, unilateral esotropia was surgically induced at various ages (30-184 days of age). However, over the next 12 months, all of the monkeys recovered normal eye alignment. Behavioral measurements at 4-6 years of age showed that the monkeys' prism-induced fusional vergence responses were indistinguishable from those of control monkeys or humans with normal binocular vision. Investigations of stereo-depth discrimination demonstrated that each of the experimental monkeys also had stereoscopic vision, but their stereoacuities varied from being essentially normal to severely stereo-deficient. The degree of stereo-deficiency was not related to the age at which surgical esotropia was induced, or to the presence or absence of amblyopia, and was not dependent on the spatial frequency of the test stimulus. Altogether, these experiments demonstrate that a temporary, early esotropia can affect the binocular disparity responses of motor and sensory components of binocular vision differently, probably because of different sensitive periods of development for the two components.     

The impact of beta-receptor blocker addition to high-dose angiotensin-converting enzyme inhibitor-nitrate therapy in heart failure

BACKGROUND: The natural history of heart failure is one of continued worsening of cardiac function. Beta-receptor blocker therapy has been effective in improving clinical status and left ventricular function in patients with heart failure. Similarly, high doses of angiotensin-converting enzyme (ACE) inhibitors with nitrates partially reverse the ventricular remodeling of heart failure. HYPOTHESIS: We tested the hypothesis that beta-blocker therapy added to high-dose ACE inhibitor-nitrates would potentiate the reversal of heart failure. METHODS: Thirteen patients, aged 52 +/- 8 years, with moderate to severe heart failure, 12 of whom were referred for transplant consideration, with heart failure duration of 4.8 +/- 2.2 years, were prospectively followed for 12 months. Baseline echocardiographic ejection fraction was 19 +/- 8%, and presenting New York Heart Association class was 2.9 +/- 0.7. Angiotensin-converting enzyme inhibitors and nitrates were uptitrated over 6 months to a final dose of lisinopril 53 +/- 31 mg/day, and isosorbide dinitrate 217 +/- 213 mg/day. At 6 months, beta-blocker therapy with atenolol was initiated and titrated to a final dose of 46 +/- 23 mg/day. Two-dimensional Doppler echocardiography and metabolic stress testing were performed at baseline, at 6 months on lisinopril-nitrates only, and at 12 months on combined ACE inhibitor-nitrate and beta-blocker therapy. RESULTS: New York Heart Association classification improved from 2.9 +/- 0.7 to 1.8 +/- 0.8 on lisinopril-nitrates (p < 0.05), and to 1.5 +/- 0.5 with the addition of beta blockade (p = NS). On follow-up, peak oxygen consumption rose from 17 +/- 7 ml O2/kg/min at baseline to 21 +/- 5 ml O2/kg/min at 6 months on lisinopril-nitrates (p = 0.06) without further change on beta blockade. Ejection fraction rose from 19 +/- 8 to 33 +/- 14% on lisinopril-nitrates at 6 months (p = 0.005) and to 36 +/- 18% on beta blockade at 12 months (p = NS). CONCLUSION: High-dose ACE inhibitor-nitrate therapy significantly improved patient clinical status and left ventricular systolic function in heart failure. The addition of beta-receptor blockade over and above high-dose ACE inhibitor-nitrates was well tolerated but had no further impact on symptomatic status, exercise tolerance, or left ventricular systolic function. The potential for pharmacologic reversal of heart failure remodeling may be finite despite the use of complementary therapies. Larger placebo-controlled and randomized trials of beta-receptor blockade added to high-dose ACE inhibitor-nitrate therapy are needed to confirm these observations.     

4-Alkylpiperidines related to SR-48968: potent antagonists of the neurokinin-2 (NK2) receptor

A series of 4-alkylpiperidine derivatives related to the potent neurokinin-2 (NK2) receptor antagonist SR-48968 (1) is described. Simple aliphatic derivatives were found to be poorly active, but appropriate placement of an alcohol functional group afforded compounds that were of similar activity to 1. Several representatives in this series, such as the 4-(1-hydroxy-1-ethylpropyl)piperidine (14), were found to exhibit oral activity in a model of labored abdominal breathing in guinea pigs. These results expand the latitude of substituents available in this region of this series of NK2 receptor antagonists.