妊娠期乳腺癌的治疗进展

妊娠期乳腺癌是一种特殊类型的乳腺癌。妊娠对乳腺癌的生物学行为可能的影响及诊疗措施对胎儿的影响,使得妊娠期乳腺癌的临床表现、诊断和治疗等有其特殊性。由于妊娠相关的乳腺的生理改变,妊娠期乳腺癌的诊断极具挑战性,导致诊断延误非常普遍。妊娠期乳腺癌患者的治疗策略需要多学科专家一起参与决定,在考虑胎儿安全性的同时尽量与非妊娠乳腺癌患者的标准治疗一致。妊娠期间都可以安全的行乳腺手术。妊娠第一孕期和第二孕期早期可以考虑放疗,但要注意检测胎儿暴露的放射剂量。研究证据越来越支持14孕周后可以安全的行化疗。曲妥单抗和他莫昔芬有潜在的胎儿毒性,不推荐用于妊娠期患者。     

Chromosome Analysis before Birth and its Value in Genetic Counselling

Chromosome analysis of amniotic cell cultures was achieved in 29 out of 30 consecutive patients who were referred for genetic counselling during pregnancy. Amniocentesis was performed without any apparent untoward maternal or fetal complication. The only pregnancy terminated was that of a carrier of X-linked granulomatous disease, in whom the amniotic cells showed that the fetus was male and also had Down''s syndrome (trisomy G). Chromosome analysis in the remaining 28 patients showed normal karyotypes. The interval between amniocentesis and a definitive karyotype varied from 7 to 31 (average 18·4) days.The reliability of chromosome analysis from amniotic cell culture and of fetal sex determination by means of the sex chromatin and Y-fluorescence techniques was studied further in amniotic fluid from cases of therapeutic abortion and of rhesus incompatibility. The fetal sex was correctly determined in all cases. It is concluded that antenatal diagnosis of genetic disease by amniocentesis now permits a more practical approach to genetic counselling.     

Who should Decide for the Unrepresented?

Unrepresented patients lack the capacity to make medical decisions for themselves, have no clear documentation of preferences for medical treatment, and have no surrogate decision maker or obvious candidate for that role. There is no consensus about who should serve as the decision maker for these patients, particularly regarding whether to continue or to limit life‐sustaining treatment. Several authors have argued that ethics committees should play this role rather than the patient's treating physician, a common current default. We argue that concerns about the adequacy of physicians as surrogates are either empirically unfounded or apply equally to ethics committees. We suggest that physicians should be the primary decision maker for the unrepresented because of their fiduciary duties toward their patients. As part of the process of fulfilling these duties, they should seek the advice of third parties such as ethic committees; but final end‐of‐life decision‐making for the unrepresented should rest with the treating physician.     

Female fetal cells in maternal blood: use of DNA polymorphisms to prove origin

The nucleated erythrocyte (NRBC) is one of the target fetal cell types for noninvasive genetic diagnosis using maternal peripheral blood. However, it is now known that pregnancy can stimulate the production of maternal NRBCs. When isolating female gamma-positive NRBCs, fluorescence in situ hybridization (FISH) analysis may show two X chromosome signals per nucleus, and therefore it cannot be conclusively determined whether the isolated cells are fetal or maternal in origin. The purpose of this study was to develop a means of verifying that a female cell is fetal on the basis of polymorphic short tandem repeat markers. Peripheral blood samples were obtained from women who had just undergone termination of pregnancy. Nucleated candidate fetal cells were isolated by flow-sorting using antibody to the gamma-chain of fetal hemoglobin and Hoechst 33342. FISH analysis was performed using X and Y chromosome specific probes. Female gamma-positive cells and leukocytes were micromanipulated separately and subjected to fluorescent polymerase chain reaction amplification of chromosome 21 and/or 18 STR markers (D21S11, D21S1411, D21S1412, and D18S535). In all ten cases analyzed, the gamma-positive female candidate fetal cells were determined to be fetal in origin by the presence of shared and nonshared DNA polymorphisms when compared with maternal leukocytes. These results show that genetic analysis can be performed on all fetal NRBCs, including female fetal cells that cannot be distinguished from maternal cells based on FISH analysis alone.     

Identifying and treating pregnant patients at risk from alcohol.

Heavy alcohol consumption during pregnancy has been associated with retardation of fetal growth and abnormal fetal development. Pregnant women whose offspring are at risk because of alcohol abuse can be identified and counselled by health professional providing prenatal care. Offspring born to women who had been drinking heavily and subsequently abstained from or reduced their intake of alcohol before the third trimester demonstrated improvements in growth and in regulation of sleep-awake states. The existing health care delivery system can be modified in a cost-effective manner to treat pregnant women who are problem drinkers. Physicians'' attitudes and behaviour are critical for the success of this strategy.     

Baby on board: olfactory cues indicate pregnancy and fetal sex in a non-human primate

Olfactory cues play an integral, albeit underappreciated, role in mediating vertebrate social and reproductive behaviour. These cues fluctuate with the signaller''s hormonal condition, coincident with and informative about relevant aspects of its reproductive state, such as pubertal onset, change in season and, in females, timing of ovulation. Although pregnancy dramatically alters a female''s endocrine profiles, which can be further influenced by fetal sex, the relationship between gestation and olfactory cues is poorly understood. We therefore examined the effects of pregnancy and fetal sex on volatile genital secretions in the ring-tailed lemur (Lemur catta), a strepsirrhine primate possessing complex olfactory mechanisms of reproductive signalling. While pregnant, dams altered and dampened their expression of volatile chemicals, with compound richness being particularly reduced in dams bearing sons. These changes were comparable in magnitude with other, published chemical differences among lemurs that are salient to conspecifics. Such olfactory ‘signatures’ of pregnancy may help guide social interactions, potentially promoting mother–infant recognition, reducing intragroup conflict or counteracting behavioural mechanisms of paternity confusion; cues that also advertise fetal sex may additionally facilitate differential sex allocation.     

Relationship Factors and Trajectories of Intimate Partner Violence among South African Women during Pregnancy and the Postpartum Period

Intimate partner violence (IPV) is a significant public health problem in South Africa. However, there is limited research on whether and how IPV changes during pregnancy and the postpartum period and on the factors that might affect women''s risk during this time. In this study, we describe the mean trajectories of physical and psychological IPV during pregnancy and the postpartum period and examine whether relationship power, partner social support, and relationship stress are associated with women''s trajectories of IPV. Data come from a longitudinal study with 1,480 women recruited during pregnancy between May 2008 and June 2010 at a public clinic in Durban. Women completed behavioral assessments at their first antenatal visit, at fourteen weeks and at nine months postpartum. Women''s experiences of IPV were measured at all three time points and relationship power, partner social support and relationship stress were each measured at the baseline assessment. We used multilevel random coefficients growth modeling to build our models. The mean trajectory for both types of IPV was flat which means that, on average, there was not significant change in levels of IPV over pregnancy and the postpartum period. However, there was significant individual variability in trajectories of IPV over the study period. Women who had higher relationship power had lower levels of physical and psychological IPV over time than women with lower relationship power. Additionally, women with higher relationship stress and lower partner support had higher levels of psychological IPV at pregnancy. Interventions that maximize women''s relationship power and partner social support and minimize relationship stress during this transformative time are needed.     

Plasma active and inactive renin and fetal complications in women with high risk pregnancies.

To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full-term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it.     

建立胎儿生长受限动物模型的研究进展

动物模型法对于人类疾病病因学及病理生理学的研究有着独特的作用。将动物模型法引入对胎儿生长受限（fetal growth restriction,FGR）的探索,不仅可以让我们观察FGR患者及胎儿在不同孕期各自的表现,还可以让我们对发病胎儿在出生后不同年龄阶段的自然表现进行继续研究。人们在FGR动物模型的建立和利用方面已经积累了大量的宝贵经验,这为进一步阐明FGR的病因学及发病机制创造了条件。     

Randomized Controlled Trials of Maternal‐Fetal Surgery: A Challenge to Clinical Equipoise

This article focuses on maternal‐fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be used as a criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence‐based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable.     

Maternal nutrition in early and late pregnancy in relation to placental and fetal growth.

OBJECTIVE: To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth. DESIGN: Prospective observational study. SETTING: Princess Anne Maternity Hospital, Southampton. SUBJECTS: 538 mothers who delivered at term. MAIN OUTCOME MEASURES: Placental and birth weights adjusted for the infant''s sex and duration of gestation. RESULTS: Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g(95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother''s height and body mass index and of strong relations between the mother''s birth weight and the placental and birth weights of her offspring. CONCLUSION: These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring''s risk of cardiovascular disease.     

Elective Delivery at Term after a Previous Unexplained Intra-Uterine Fetal Death: Audit of Delivery Outcome at Tygerberg Hospital,South Africa

Objectives

To assess the delivery outcome in a pregnancy with a previous unexplained intra-uterine death by elective induction of labour at term.

Methods

An audit of the pregnancy outcome of all women within the catchment area with a current singleton pregnancy; and a previous unexplained or unexplored singleton fetal demise ≥24 weeks (or 500 grams birth weight if gestation unknown) after planned routine induction of labour at full term (39-40 weeks).

Results

During the audit period, 306 patients with a previous intra-uterine fetal death were referred for further management. Of these, 161 had a clear indication for earlier intervention and were excluded from the protocol. Of the remaining 145 patients, 9 met further exclusion criteria and there were 2 patients who defaulted. Forty-two of the remaining study patients (with no known previous medical problems) developed complications during their antenatal course that necessitated a change in clinical management and earlier (<39 weeks) delivery. Of the remaining 92 patients in the audit, 47 (51%) went into spontaneous labour before their induction date; all 92 women delivered without major complications. There were no intra-uterine deaths prior to induction.

Conclusions

Careful follow up at a high risk clinic identifies new or concealed maternal or fetal complications in 29% of patients with a previous intra-uterine death and no obvious maternal or fetal disease in the index pregnancy. When all risks are excluded and the pregnancy allowed to progress to full term (39-40 weeks) before an induction is offered, 50% will go into spontaneous labour.     

Production and appreciation of humor as sexually selected traits

Both men and women prefer someone with a “good sense of humor” as a relationship partner. However, two recent studies have shown that men are not attracted to funny women, suggesting the sexes use the phrase good sense of humor differently. To investigate this question, we measured the importance participants placed on a partner's production of humor vs. receptivity to their own humor. Men emphasized the importance of their partners' receptivity to their own humor, whereas women valued humor production and receptivity equally. In a second task, participants chose whether they preferred a person who only produced humor or a person who only appreciated their own humor for several types of relationships. Women preferred those who produced humor for all types of relationships, whereas men preferred those who were receptive to their own humor, particularly for sexual relationships. Our results suggest that sexual selection may have operated on men's and women's preferences during humorous interaction in dramatically different ways.     

Influence of ACTH secreting tumor (MtTF4) on fetal rat adrenal gland steroidogenesis in vitro in prolonged pregnancy

Pregnant female rats with ACTH secreting tumor (MtTF4) have prolonged pregnancy and cannot deliver. The fetuses of tumor bearing females have in prolonged pregnancy on days 24 and 25 of pregnancy greater body weight and smaller adrenal weight as compared to intact fetuses of the 22nd day of pregnancy. The fetal adrenal glands converted to vitro 4-14C progesterone to radioactive 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), 18-hydroxy-corticosterone (18-OH-B) and aldosterone. Fetal adrenal glands in prolonged pregnancy synthetized in vitro less amount of radioactive DOC, B and 18-OH-DOC. A negative relationship exists between the maternal corticosterone which passes the placenta to fetuses and corticosteroidogenesis of fetal adrenal glands. These results indicate the possibility that fetal rat adrenal glands with their corticosteroids participate in pregnancy and influence normal delivery.     

High risk maternal factors related to fetal wastage in rural Bangladesh

An analysis of the relationship between fetal mortality (early fetal death and stillbirth), pregnancy order, maternal age, and previous fetal deaths in a rural Bangladesh population characterized by high fertility and mortality and the virtual absence of obstetric and other medical care indicates that early fetal wastage and stillbirth are higher among pregnancy orders 1 and 6, or higher than among orders 2 and 3, with the increased risk particularly apparent among those pregnancies following 2 or more previous fetal deaths. The data consist of the 21,144 pregnancies that occurred to the women in Matlab, Bangladesh, 1966-1969. By a multiple regression technique allowing for pregnancy order and previous fetal deaths, adjustments were made for age of the mother, and after allowances were made for previous fetal deaths, adjustments were made for pregnancy order. Results show the fewest fetal deaths in 2nd and 3rd pregnancies, and most at the highest parities. 10% of all pregnancy terminations 1966-1969 were registered as fetal deaths. Women in the higher pregnancy orders who have not experienced previous fetal deaths or only 1 fetal death have only a slight increase in the risk of fetal death compared to women in pregnancy orders 2 and 3. It is concluded that the virtual absence of medical care facilities is responsible for the large numbers of fetal deaths due to complications of gestation, delivery, and environmental influences. It also results in a higher maternal mortality of women with pregnancy complications related to fetal deaths. This absence of obstetric care and the high maternal mortality in this population may allow only women without reproductive impairments to reach the higher pregnancy orders.     

An evolutionary perspective on the association between grandmother-mother relationships and maternal mental health among a cohort of pregnant Latina women

Grandmothers are often critical helpers during a mother's reproductive career. Studies on the developmental origins of health and disease demonstrate how maternal psychological distress can negatively influence fetal development and birth outcomes, highlighting an area in which soon-to-be grandmothers (henceforth “grandmothers”) can invest to improve both mother and offspring well-being. Here, we examine if and how a pregnant woman's mental health– specifically, depression, state-anxiety, and pregnancy-related anxiety– is influenced by her relationship with her fetus' maternal and paternal grandmother, controlling for relationship characteristics with her fetus' father. In a cohort of pregnant Latina women in Southern California (N = 216), we assessed social support, geographic proximity, and communication between the fetus' grandmothers and pregnant mother. We assessed maternal mental health with validated questionnaire-based instruments. We find that both social support from and communication with the maternal grandmother were statistically associated with less depression, while no paternal grandmother relationship characteristics were statistically significant in association with any mental health variable. These results align with the idea that maternal grandmothers are more adaptively incentivized to invest in their daughters' well-being during pregnancy than paternal grandmothers are for their daughters-in-law. Results suggest that the positive association of maternal grandmothers with mothers' mental health may not hinge on geographic proximity, but rather, potentially function through emotional support. This work represents a novel perspective describing a psychological and prenatal grandmaternal effect.     

Rawlsian Justice and Palliative Care

Palliative care serves both as an integrated part of treatment and as a last effort to care for those we cannot cure. The extent to which palliative care should be provided and our reasons for doing so have been curiously overlooked in the debate about distributive justice in health and healthcare. We argue that one prominent approach, the Rawlsian approach developed by Norman Daniels, is unable to provide such reasons and such care. This is because of a central feature in Daniels' account, namely that care should be provided to restore people's opportunities. Daniels' view is both unable to provide pain relief to those who need it as a supplement to treatment and, without justice‐based reasons to provide palliative care to those whose opportunities cannot be restored. We conclude that this makes Daniels' framework much less attractive.     

The use of infants in drug research when there is no direct benefit to them: a survey of Canadian health care professionals serving on ethics committees.

Canadian health care professionals and lawyers serving on ethics committees were questioned about their views on pharmacokinetic research in newborn infants who are not likely to benefit directly from the results. Of the 50 respondents 13 felt that blood samples should be taken only for therapeutic reasons; 10 of the 13 argued that additional blood samples should not be taken, because there is no direct benefit to the infant; and 8 felt that proxy consent cannot be given for invasive nontherapeutic research. Four of the five participating lawyers would not permit additional blood samples to be taken. Of the 37 respondents who would permit additional blood samples to be taken, 27 felt that the number of samples taken should depend on the researcher''s justification for that number of samples; only 7 of the respondents had a clear idea of what the "upper limit" of the number of blood samples should be.     

THE VISUAL ACUITY OF THE HONEY BEE

1. Bees respond by a characteristic reflex to a movement in their visual field. By confining the field to a series of parallel dark and luminous bars it is possible to determine the size of bar to which the bees respond under different conditions and in this way to measure the resolving power or visual acuity of the eye. The maximum visual acuity of the bee is lower than the lowest human visual acuity. Under similar, maximal conditions the fineness of resolution of the human eye is about 100 times that of the bee. 2. The eye of the bee is a mosaic composed of hexagonal pyramids of variable apical angle. The size of this angle determines the angular separation between adjacent ommatidia and therefore sets the structural limits to the resolving power of the eye. It is found that the visual angle corresponding to the maximum visual acuity as found experimentally is identical with the structural angular separation of adjacent ommatidia in the region of maximum density of ommatidia population. When this region of maximum ommatidia population is rendered non-functional by being covered with an opaque paint, the maximum visual acuity then corresponds to the angular separation of those remaining ommatidia which now constitute the maximum density of population. 3. The angular separation of adjacent ommatidia is much smaller in the vertical (dorso-ventral) axis than in the horizontal (anterio-posterior) axis. The experimentally found visual acuity varies correspondingly. From this and other experiments as well as from the shape of the eye itself, it is shown that the bee''s eye is essentially an instrument for uni-directional visual resolution, functional along the dorso-ventral axis. The resolution of the visual pattern is therefore determined by the vertical angular separation of those ocular elements situated in the region of maximum density of ommatidia population. 4. The visual acuity of the bee varies with the illumination in much the same way that it does for the human eye. It is low at low illuminations; as the intensity of illumination increases it increases at first slowly and then rapidly; and finally at high intensities it becomes constant. The resolving power of a structure like the bee''s eye depends on the distance which separates the discrete receiving elements. The data then mean that at low illuminations the distance between receiving elements is large and that this distance decreases as the illumination increases. Since such a moving system cannot be true anatomically it must be interpreted functionally. It is therefore proposed that the threshold of the various ommatidia are not the same but that they vary as any other characteristic of a population. The visual acuity will then depend on the distance apart of those elements whose thresholds are such that they are functional at the particular illumination under investigation. Taking due consideration of the angular separation of ommatidia it is possible to derive a distribution curve for the thresholds of the ommatidia which resembles the usual probability curves, and which describes the data with complete fidelity.