Density of mu-opioid receptors in the hippocampus of adult male and female rats is altered by prenatal morphine exposure and gonadal hormone treatment

The present in vitro autoradiography study demonstrates that prenatal exposure to morphine alters the density of mu-opioid receptors in the hippocampus of adult female but not adult male rats. Prenatal morphine exposure increased the mu-opioid receptor density in the CA1 of ovariectomized (OVX) females and in the CA3 of OVX, estradiol benzoate-plus progesterone (EB+P)-treated females, but decreased it in CA3 of OVX females. There were also hormonal effects on mu-opioid receptor density in adult female rats. In the CA1, only morphine-exposed but not saline-exposed, hormone-treated females (EB, P, or EB+P) had a decrease in mu-opioid receptor density relative to OVX females. Both saline-exposed and morphine-exposed, OVX females after gonadal hormone replacement had a lower density of mu-opioid receptors in the CA3 and in the dentate gyrus (DG) than OVX females. In male rats, there was a decrease in mu-opioid receptor density in the CA1 and CA3 of gonadectomized (GNX), testosterone 17beta-proprionate (TP)-treated males relative to GNX males regardless of prenatal morphine exposure. In the DG, the mu-opioid receptor density was reduced only in morphine-exposed but not in saline-exposed, TP-treated males compared with GNX males. Thus, our data demonstrate that mu-opioid receptor density in the hippocampus is affected by prenatal morphine exposure and by male and female gonadal hormones.     

Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia

Comorbid schizophrenia and dementia is a common clinical phenomenon; however, management of the coexisting illnesses remains incomplete. Donepezil, a cholinesterase inhibitor, may be beneficial for the management of symptoms of Alzheimer's disease, a disease in which cholinergic pathways in the cerebral cortex and basal forebrain are well known to be compromised. Furthermore, impaired cognition in elderly schizophrenic patients has been observed to be more than two thirds; however, there are no published controlled studies reporting the use of cholinesterase inhibitors in the management of schizophrenia in patients with associated dementia. In this study, six patients with chronic schizophrenia and comorbid dementia were administered donepezil, 5 mg, in single-blind fashion as augmentation to their standard antipsychotic medication for a 4-week period. Patients were evaluated with the Mini Mental State Examination (MMSE); Alzheimer's Disease Assessment Scale, Cognitive subscale; Positive and Negative Symptom Scale (PANSS); and the Clinical Global Impression (CGI) scales. A significant improvement was noted in MMSE scores (P < 0.01) and for CGI scores (P < 0.01). In addition, three patients demonstrated improvement on the PANSS. Donepezil appears to be an effective treatment for the management of symptoms of dementia accompanying patients with comorbid schizophrenia and dementia. Since cholinergic dysfunction may be present in some patients with schizophrenia, the authors' findings further demonstrate the possibility that this disorder may be managed with cholinergic medications as augmenting agents, at least in this specific subpopulation of patients with comorbid dementia. To confirm the findings of this preliminary trial, further investigation is mandated with a larger sample of subjects in the context of a double-blind medication trial.     

Association of a woman's own birth weight with her subsequent risk for pregnancy-induced hypertension

Studies have linked low birth weight to elevated risk for adult hypertension and insulin resistance. However, the relation between birth weight and later risk for pregnancy-induced hypertension (PIH), a disorder associated with insulin resistance and predictive of chronic hypertension, has not been well studied. This case-control study used linked hospital discharge and vital record data from New York State. Subjects were healthy women born in New York State who completed a first pregnancy there between 1994 and 1998. Records from each woman's own birth (1970-1985) were linked to those from her first pregnancy. Cases were 2,180 women diagnosed with PIH. Controls were the 22,955 remaining women with no record of PIH. Birth weight showed a U-shaped relation to risk for PIH, with the highest risks associated with very low and very high birth weights. Relative to women born at 3.5-4.0 kg, odds ratios adjusted for gestational age were 2.1 (95% confidence interval (CI): 1.1, 3.9) and 1.6 (95% CI: 1.1, 2.4), respectively, for women with birth weights less than 1.5 kg and greater than 4.5 kg. Adjustment for other perinatal factors reduced the association with high birth weight to 1.1 (95% CI: 0.7, 1.7) but strengthened that with lower birth weights, leaving a strong, inverse relation between birth weight and PIH risk (p for trend < 0.0001). These findings support a possible role for early life factors, particularly fetal growth, in the etiology of PIH.     

The Harvard Twin Study of Substance Abuse: what we have learned

The Harvard Twin Study of Substance Abuse was carried out with the members of the Vietnam Era Twin (VET) Registry. The VET Registry comprises over 8000 male twins who served in the United States military between 1965 and 1975 and were subsequently interviewed regarding their use of licit and illicit substances, as well as various types of psychopathology. Our research has demonstrated significant influences by genetic, shared environmental, and unique environmental factors on the abuse of illicit substances. Multivariate analyses have indicated that the co-occurrence of abuse of various types of illicit drugs reflects a common vulnerability, influenced by both genetic and environmental factors, that cuts across all categories of illicit drugs. We have also demonstrated that some drugs have unique determinants, both genetic and environmental, that are not shared with other drugs. In part, the genetic influence on marijuana abuse is mediated by genetic influence on subjective effects in response to the drug. The determinants of transitions from one stage of drug use to another differ depending on which drug or which transition is examined. We determined significant genetic influences on several aspects of nicotine and alcohol use separately, as well as genetic influences shared by both substances. We found that the co-occurrence of illicit drug abuse and major depression is due to unique environmental influences. The phenotypic association between symptoms of conduct disorder and alcohol and marijuana dependence is due largely to shared environmental influences. Our results, thus far, indicate a complex pattern of genetic and environmental influences on substance use and abuse.     

Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis

BACKGROUND: Cyclosporine (CsA) therapy must often be continued during pregnancy to maintain maternal health in such conditions as organ transplantation and autoimmune disease. This meta-analysis was performed to determine whether CsA exposure during pregnancy is associated with an increased risk of congenital malformations, preterm delivery, or low birthweight. METHODS: Various health science databases were searched to identify relevant articles. Articles selected for inclusion in the study were required to be free of any apparent selection bias and report outcomes in at least 10 newborns exposed to CsA in utero, specifically commenting on the presence or absence of congenital malformations. Article selection and data extraction were performed by two independent reviewers, with adjudication in cases of disagreement. To assess risks of CsA exposure, a summary odds ratio was calculated. Prevalence of malformations was calculated as a rate for all cyclosporine-exposed live births and for the subgroups identified. Ninety-five percent confidence intervals were constructed for both the odds ratio and prevalence rates. RESULTS: Fifteen studies (6 with control groups of transplant without use of cyclosporine; total patients: 410) met the inclusion criteria for major malformations, 10 for preterm delivery (4 with control groups; total patients: 379) and 5 for low birth weight (1 with control groups; total number of patients: 314). The calculated odds ratio of 3.83 for malformations did not achieve statistical significance (CI 0.75-19.6). The overall prevalence of major malformations in the study population (4.1%) also did not vary substantially from that reported in the general population. OR for prematurity [1.52 (CI 1.00-2.32)] did not reach statistical significance although the overall prevalence rate was 56.3%. The OR for low birth weight [1.5 (CI 0.95-2.44 based on 1 study)]. CONCLUSIONS: CsA does not appear to be a major human teratogen. It may be associated with increased rates of prematurity. More research is needed to evaluate whether cyclosporine increases teratogenic risk.     

Clinical and histologic characteristics of breast cancers in women with previous pathologic diagnosis of benign breast disease in Spain

Women with a benign breast disease (BBD) have an increased risk of subsequent breast carcinoma. Information is scarce regarding the characteristics of breast carcinomas diagnosed after a BBD. Our aim was to point out the differences in clinical and histologic characteristics of breast carcinomas diagnosed in women with and without a previous pathologic diagnosis of BBD in the context of population‐based mammography screening. Retrospective cohort study of all women aged 50‐69 years who were screened at least once in a population‐based screening program in Spain, between 1994 and 2011 and followed up until December 2012. The mean follow‐up was 6.1 years. We analyzed 6645 breast carcinomas, of whom 238 had a previous pathologic diagnosis of BBD. Information on clinical and histologic characteristics was collected from pathology reports. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (95%CI) of occurrence of selected histologic characteristics of breast carcinomas in women with and without a previous BBD. Women with a previous BBD had a higher proportion of ductal carcinoma in situ (DCIS) compared with women without a BBD (22.1% and 13.6%, respectively). Among those diagnosed with an invasive breast carcinoma, women with previous BBD were more likely to be diagnosed with carcinomas sized >2 cm (OR = 1.46; 95%CI = 1.03‐2.08), metastatic positive (OR = 2.66; 95%CI = 1.21‐5.86), and with a high Ki‐67 proliferation rate (OR = 1.93; 95%CI = 1.24‐2.99). No differences were found across histologic subtypes of BBD. Screening participants with a previous pathologic diagnosis of BBD had a higher proportion of DCIS. However, invasive carcinomas detected in women with a BBD were associated with clinical and histologic characteristics conferring a worst prognosis.     

Does female age affect embryo morphology?

Deteriorating oocyte quality is commonly believed to be the primary determinant of the decreased implantation potential in older women. We assessed the influence of age on embryo morphology in standard in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) modalities. All 6350 consecutive embryos (2990 IVF, 3360 ICSI) obtained in our Assisted Reproductive Technology Unit from January 1996 through June 1997 were included. High quality embryos were defined as those with equal-sized blastomeres and < 10% fragmentations and a cleavage rate of four cells on day 2 or eight cells on day 3 transfers. The results were analyzed for the standard IVF group, the ICSI group, and the ICSI subgroup with severe male factor infertility (< or = 1 x 10(6) total motile spermatozoa in the ejaculate). For standard IVF, a positive association was observed between female age and increased proportion of good quality embryos. No such association was detected for the ICSI cycles (whole group or subgroup). We conclude that in standard IVF, embryo quality, as reflected by embryo morphology, does not deteriorate with increased maternal age.     

Predictive value of a single early fetal weight estimate in normal pregnancies

OBJECTIVES: To evaluate the accuracy of ultrasound-based fetal weight estimates made at 28-34 weeks of gestation in predicting small- and large-for-gestational-age infants (SGA, LGA) at term. METHODS: Two-hundred and fifty-nine patients with a healthy, singleton pregnancy in whom fetal biometry measurements were routinely performed between 28 and 34 weeks' gestation, were recruited at term delivery. The sonographic estimated fetal weight (EFW) and the birth weight were converted to percentiles on the basis of locally developed growth charts and compared. Multivariate linear stepwise regression analysis was used to predict the birth weight and birth weight percentile. The resulting equation (projectile formula) was used to determine the calculated birth weight, and that value was compared with the actual birth weight. The Bland and Altman plot and Passing and Bablok regression were used to compare between the calculated birth weight and the actual birth weight. RESULTS: Mean gestational age at ultrasound examination was 32+/-1.6 weeks (28-34), and mean age at delivery was 39+/-1.7 weeks (37-42). The multivariate correlation between the calculated birth weight and the birth weight (R2 = 0.524) was higher than the correlation between the sonographic EFW and the birth weight (R2 = 0.083). Both the sonographic EFW and the calculated birth weight are characterized by low positive predictive values in predicting SGA or LGA infants. The calculated birth weight was more accurate in excluding SGA and LGA infants (negative predictive values of 99.5% and 100%, respectively). On method comparison tests, the calculated birth weight was not significantly different than the actual birth weight. CONCLUSIONS: Fetal weight estimation at the early third trimester poorly predicts the birth weight centile at term. It remains uncertain, however, if it would be useful to use the calculated birth weight in pregnancies with clinically suspected SGA or LGA fetuses.     

Concentrating stroke care provision in the Czech Republic: The establishment of Stroke Centres in 2011 has led to improved outcomes

This article describes policy processes that have led to the re-organisation of stroke care in the Czech Republic since 2011, which has been part of a broader process of care concentration in several medical fields. Currently, stroke care is provided by 13 Comprehensive and 32 Primary Stroke Centres. The paper explains factors that supported the reform implementation, reviews implications, and discusses future challenges.Mandatory reporting of quality indicators, the introduction of a benchmarking system, integration with pre-hospital emergency care, and the introduction of countrywide patient triage have supported more timely treatment for stroke patients and better quality of care. Data from the Stroke Care Quality Indicators of the Czech Stroke Society show positive trends in many areas: the number of patients treated with intravenous thrombolysis quadrupled in eight years, with 26.4 % of all acute stroke patients receiving thrombolysis in 2018. Czech Republic now ranks third in Europe in the number of thrombolysis per population and second in the number of mechanical thrombectomies per population. The Czech experience provides an example of positive outcomes of concentrated stroke care, while highlighting the importance of proper implementation processes. In particular, it is essential to involve stakeholders and to provide reputational incentives through continuous benchmarking.