Tools for making correct decisions regarding hormone therapy. Part II. Organ response and clinical applications

OBJECTIVE: To review existing scientific knowledge of the complicated and variable behavior and response to hormone therapy (HT) of different organs during aging, and to summarize long-term consequences on human health. DESIGN: A MEDLINE computer search was performed to identify relevant articles. RESULT(S): Five body organs were evaluated. [1]. Physiologic aging of the bone has deleterious consequences on women's health and quality of life. Bone fractures could be attributed to the combination of estrogen depletion and osteoporosis, mechanisms of applied forces, and disturbed brain function, partially reversible by timely estrogen administration. [2]. Estrogen seems to have a profound neuroprotective effect. As physiologic aging of the brain is an unhealthy phenomenon, possible intervention is justified. The therapeutic time window seems crucial. [3]. The differentiation between response of a healthy or already damaged organ to sex hormones is the key factor to understanding the possible cardioprotective effects. [4]. Based on doubling time of tumor cells, intracrinology, epidemiological data on breast cancer, and behavior of breast cancer survivors in response to estrogen treatment, estrogen seems to be mainly a promoter and even a protector of breast cancer survivors. [5]. Colon cancer appears to be an estrogen-dependent tumor with a wide therapeutic window, as every report regardless of age and dose demonstrates protective effects. CONCLUSION(S): Knowledge of each organ's response to aging and sex hormone substitutions demonstrates that the organs could benefit from properly designed intervention. In the wake of the publication of the Women's Health Initiative study, which shocked the medical community, we suggest that the results be reevaluated according to the aforementioned principles, and that menopausal medicine could play an important role.     

Long-term serological outcome of infants who received frozen-thawed milk from human T-lymphotropic virus type-I positive mothers

AIM: Human T-lymphotropic virus type-I (HTLV-I) infection occurs via mothers' milk during feeding. However, freeze-thaw processing can eliminate the infectivity of the mother's milk of HTLV-I carriers. METHODS: A long-term follow-up survey was conducted to investigate the HTLV-I infectivity of frozen-thawed mothers' milk among infants whose mothers were HTLV-I seropositive. RESULTS: Infants fed frozen-thawed mothers' milk did not become HTLV-I antibody-positive up until 1 year old, and all children followed up until an age of 11-12 years were antibody negative. CONCLUSIONS: This study showed that freeze-thaw processing can eliminate the HTLV-I infectivity of mothers' milk, and that HTLV-I carriers can indirectly feed their infants using frozen-thawed mothers' milk as a way to prevent HTLV-I infection.     

Immediate and delayed incorporations of events into dreams: further replication and implications for dream function

The incorporation of memories into dreams is characterized by two types of temporal effects: the day-residue effect, involving immediate incorporations of events from the preceding day, and the dream-lag effect, involving incorporations delayed by about a week. This study was designed to replicate these two effects while controlling several prior methodological problems and to provide preliminary information about potential functions of delayed event incorporations. Introductory Psychology students were asked to recall dreams at home for 1 week. Subsequently, they were instructed to select a single dream and to retrieve past events related to it that arose from one of seven randomly determined days prior to the dream (days 1-7). They then rated both their confidence in recall of events and the extent of correspondence between events and dreams. Judges evaluated qualities of the reported events using scales derived from theories about the function of delayed incorporations. Average ratings of correspondences between dreams and events were high for predream days 1 and 2, low for days 3 and 4 and high again for days 5-7, but only for participants who rated their confidence in recall of events as high and only for females. Delayed incorporations were more likely than immediate incorporations to refer to events characterized by interpersonal interactions, spatial locations, resolved problems and positive emotions. The findings are consistent with the possibility that processes with circaseptan (about 7 days) morphology underlie dream incorporation and that these processes subserve the functions of socio-emotional adaptation and memory consolidation.     

硝普钠对豚鼠耳蜗外毛细胞能动性影响的初步研究

目的研究硝普钠(sodium nitroprusside,SNP)对耳蜗OHC在电压刺激下的能动性的改变情况.方法运用全细胞膜片钳电压钳技术,在正常细胞内外液的条件下,观察不同浓度SNP对电压性刺激引起OHC能动性的影响情况.结果在SNP浓度低于100 μMol/L时,SNP对OHC能动性的影响不明显,但当SNP浓度高于100 μMol/L时,SNP对OHC的能动性有明显的抑制作用,结果有统计学意义(P<0.05).结论 SNP对OHC的能动性有抑制作用,作用呈一定的浓度效应关系.     

Modulation of autonomous contractile activity in the isolated whole bladder of the guinea pig

OBJECTIVE: To investigate the actions of the nonhydrolysable analogue of ATP, alpha,beta-methylene ATP (alpha,beta-MATP) and the sensory peptide, substance P, on the phasic activity generated by muscarinic stimulation in the isolated whole bladder. Isolated bladder can generate complex contractions resulting in phasic rises in intravesical pressure (the autonomous bladder): activity thought to underlie nonmicturition activity in vivo and which may be important in generating bladder sensations. MATERIALS AND METHODS: Experiments were conducted on whole isolated bladders from female guinea pigs (270-300 g). Bladders were cannulated via the urethra, suspended in a heated chamber containing oxygenated solution at 33-36 degrees C and intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface of the bladder. RESULTS: When alpha,beta-MATP (30-3000 nmol/L) or substance P (30-300 nmol/L) was added to resting bladders there were small rises in intravesical pressure (<2 cmH2O). However, in the presence of phasic activity generated by exposing the bladder to the muscarinic agonist arecaidine (100-300 nmol/L) or the nicotinic ligand lobeline (10-30 micromol/L) similar or lower concentrations of alpha,beta-MATP or substance P produced more dramatic effects: alpha,beta-MATP and substance P (both at 100 nmol/L) activated a rise in basal pressure of > 15 cmH2O and increased the frequency of the phasic activity. On removing alpha,beta-MATP or substance P, there was a slowing of phasic activity indicative of an inhibitory mechanism. CONCLUSION: In addition to direct effects on smooth muscle the agonists alpha,beta-MATP and substance P appear to be potent regulators of the mechanisms generating phasic activity. A developing concept is that the mechanisms responsible for generating phasic activity underlie nonmicturition activity are the target for excitatory and inhibitory inputs. Regulating such activity may be a factor in generating or modifying bladder sensation. Inappropriate or exaggerated phasic activity could underpin the pathological changes which cause the overactive bladder, thus adding another hypothesis to the neurogenic and myogenic hypotheses of bladder overactivity, i.e. that of the autonomous bladder.     

Use of the Paired-Comparison Technique to Determine the Most Valued Qualities of the McMaster Medical Programme Admissions Process

The Undergraduate Medical Programme at McMaster University selects students using a comprehensive set of tools. Attempts to modify the selection process over many years have been impeded by an inability to reconcile very strongly held views among stakeholders as to the importance of the selection tools and, indeed, the very purposes of the admission process. The objective of this study was to identify key 'qualities' of the selection process and to measure their relative importance to admissions process assessors. Through a qualitative review of internal research documents, Medical Programme Admissions Committee meeting minutes, memos and accreditation surveys eight qualities of the admissions process were identified: validity, fairness, accessibility, comprehensiveness, affordability, legal defensibility, contribution to class diversity and the role of the process as a public statement of the Programme's values. Faculty, students and community admissions assessors were surveyed, by mail, using a paired-comparisons technique. The overall response rate was 58%. By a wide margin, all three groups of admissions assessors valued validity and fairness most highly. The least valued qualities were affordability and the role of the process as a statement of our values. Possible applications of this approach to the admissions process deliberations are discussed.     

The Lore of Admissions Policies: Contrasting Formal and Informal Understandings of the Residency Selection Process

PURPOSE: The selection process for residency positions is sometimes seen as being "opaque" and unfair by students, and can be a significant source of student stress. Yet efforts to clarify the process may not have helped reduce student stress for a number of reasons. This paper examines the nature of the knowledge that students possess and describes the implications for future efforts at addressing this knowledge. METHODS: The current study assessed the perceptions of three groups (selection committee members, faculty advisors, and students) at a single institution using two evaluation methods (ranking of a context-free list of variables, and an assessment of the legitimacy of 20 "common language" opinion statements comparing the variables). RESULTS: For the context-free ranking of variables, ICC's were moderately high for all three groups (0.479-0.584) and the disattenuated correlations were very high (0.872 to 0.946). By contrast, when more contextually relevant opinion statements were evaluated, the ICC's were much more variable (less than 0 to 0.279), the correlations (where calculable) were lower (0.449 to 0.547), and inconsistencies of opinion regarding particular variables became apparent. CONCLUSIONS: To properly understand the true nature of the opinions that are being held by the various groups it is necessary to use statements that reflect the vernacular of the "rumour mills" that are the common source of student information.     

Heterogeneity and potentiation of AMPA type of glutamate receptors in rat cultured microglia

alpha-amino-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor in rat cultured microglia were analyzed precisely using flop- and flip-preferring allosteric modulators of AMPA receptors, 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide (PEPA) and cyclothiazide (CTZ), respectively. Glutamate (Glu)- or kainite (KA)-induced currents were completely inhibited by a specific blocker of AMPA receptor, LY300164, indicating that functional Glu-receptors in cultured microglia are mostly AMPA receptor but not KA receptor in many cells. Glu- and KA-induced currents were potentiated by PEPA and CTZ in a concentration-dependent manner. The ratio of the potentiation by PEPA to the potentiation by cyclothiazide varied with cells between 0.1 and 0.9, suggesting cell-to-cell heterogeneity of AMPA receptor subunits expressed in microglia. Quantitative RT-PCR revealed that GluR1-3 mainly occurred in the flip forms, which agreed with the stronger potentiation of receptor currents by CTZ vs. PEPA. Finally, the potentiation of microglial AMPA receptors by PEPA and CTZ inhibited the Glu-induced release of tumor necrosis factor-alpha (TNF-alpha) unpredictably. The increase in TNF-alpha release by Glu or KA required extracellular Na+ and Ca2+ ions but not mitogen-activated protein kinase (MAPK), suggesting the effects of PEPA and CTZ were not due to the inhibition of MAPK. These results suggest that potentiation of microglial AMPA receptors serves as a negative feedback mechanism for the regulation of TNF-alpha release and may contribute to the ameliorating effects of allosteric modulators of AMPA receptors.