The Iowa Perinatal Letter, 2012, Vol. 32, no. 1

This newsletter from The Department of Public Health about perinatal health care and statistics.

Multicenter Study on the Clinical Effectiveness, Pharmacokinetics, and Pharmacogenetics of Mirtazapine in Depression.

ABSTRACT: Pharmacogenetic tests and therapeutic drug monitoring may considerably improve the pharmacotherapy of depression. The aim of this study was to evaluate the relationship between the efficacy of mirtazapine (MIR) and the steady-state plasma concentrations of its enantiomers and metabolites in moderately to severely depressed patients, taking their pharmacogenetic status into account. Inpatients and outpatients (n = 45; mean age, 51 years; range, 19-79 years) with major depressive episode received MIR for 8 weeks (30 mg/d on days 1-14 and 30-45 mg/d on days 15-56). Mirtazapine treatment resulted in a significant improvement in mean Hamilton Depression Rating Scale total score at the end of the study (P < 0.0001). There was no evidence for a significant plasma concentration-clinical effectiveness relationship regarding any pharmacokinetic parameter. The enantiomers of MIR and its hydroxylated (OH-MIR) and demethylated (DMIR) metabolites in plasma samples on days 14 and 56 were influenced by sex and age. Nonsmokers (n = 28) had higher mean MIR plasma levels than smokers (n = 17): S(+)-enantiomer of MIR, 9.4 (SD, 3.9) versus 6.2 (SD, 5.5) ng/mL (P = 0.005); R(-)-enantiomer of MIR, 24.4 (SD, 6.5) versus 18.5 (SD, 4.1) ng/mL (P = 0.003). Only in nonsmokers, plasma levels of S(+)-enantiomer of MIR and metabolites depended on the CYP2D6 genotype. Therefore, high CYP1A2 activity seen in smokers seems to mask the influence of the CYP2D6 genotype. In patients presenting the CYP2B6 *6/*6 genotype (n = 8), S-OH-MIR concentrations were higher those in the other patients (n = 37). Although it is not known if S-OH-MIR is associated with the therapeutic effect of MIR, the reduction of the Hamilton scores was significantly (P = 0.016) more pronounced in the CYP2B6 *6/*6-genotyped patients at the end of the study. The role of CYP2B6 in the metabolism and effectiveness of MIR should be further investigated.

Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation.

Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded tissue that is conducive to their survival and proliferation. However, the factors that render tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. Here we have shown that during murine gestation, metastasis is enhanced regardless of tumor type, and that decreased NK cell activity is responsible for the observed increase in experimental metastasis. Gene expression changes in pregnant mouse lung and liver were shown to be similar to those detected in premetastatic sites and indicative of myeloid cell infiltration. Indeed, myeloid-derived suppressor cells (MDSCs) accumulated in pregnant mice and exerted an inhibitory effect on NK cell activity, providing a candidate mechanism for the enhanced metastatic tumor growth observed in gestant mice. Although the functions of MDSCs are not yet understood in the context of pregnancy, our observations suggest that they may represent a shared mechanism of immune suppression occurring during gestation and tumor growth.

Sorafenib fourth-line treatment in imatinib-, sunitinib-, and nilotinib-resistant metastatic GIST : a retrospective analysis : 10564

Background: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors usually caused by mutations in the KIT or PDGFRA gene. Advanced disease generally cannot be cured by surgery nor by tyrosine kinase inhibitors (TKI), but TKIs have considerably improved outcome for patients (pts) with advanced GIST. Patients failing TKI treatment with imatinib (IM), sunitinib (SU) or nilotinib (NI) have a poor prognosis. Sorafenib is a multi kinase inhibitor that blocks not only receptor tyrosine kinases such as KIT, VEGFR and PDGFR but also serine/threonine kinases along the RAS/RAF/MEK/ERK pathway. Recently, clinical activity of sorafenib in third-line treatment in patients with GIST after IM and SU failure has been shown (Wiebe et al. ASCO 2008, #10502). Methods: We report herein preliminary data of 32 pts treated with sorafenib in nine European centers. Centers were selected based on their previous and known experience in GIST and reported all pts treated. Pts received sorafenib after failure of IM, SU and NI in fourth-line treatment. Baseline characteristics and treatment details have been retrieved via questionary. Results: Median age at sorafenib treatment start was 62 years (range 33-81 y), and the majority of pts were male (63 %). Primary tumor site was gastric or small intestine in 25% and 41% of pts, respectively. All pts had failed IM, SU, NI. 19 % of pts achieved partial remission and 44% disease stabilization. Approximately half of the pts had an improvement of symptoms and/or performance. Half of the pts were on treatment longer than 4 months (actuarial data) and 41% of pts continue to receive sorafenib. Median progression-free survival is 20 weeks and median overall survival 42 weeks (Kaplan-Meier), at a median follow-up of 22 weeks (range 3-54). Conclusions: This is the largest series assessing efficacy of sorafenib fourth-line treatment for IM, SU and NI refractory GIST reported yet. Sorafenib displays significant clinical activity in this heavily pretreated group of patients.

Gene expression profiles in rat mesenteric lymph nodes upon supplementation with Conjugated Linoleic Acid during gestation and suckling

Background Diet plays a role on the development of the immune system, and polyunsaturated fatty acids can modulate the expression of a variety of genes. Human milk contains conjugated linoleic acid (CLA), a fatty acid that seems to contribute to immune development. Indeed, recent studies carried out in our group in suckling animals have shown that the immune function is enhanced after feeding them with an 80:20 isomer mix composed of c9,t11 and t10,c12 CLA. However, little work has been done on the effects of CLA on gene expression, and even less regarding immune system development in early life. Results The expression profile of mesenteric lymph nodes from animals supplemented with CLA during gestation and suckling through dam's milk (Group A) or by oral gavage (Group B), supplemented just during suckling (Group C) and control animals (Group D) was determined with the aid of the specific GeneChip® Rat Genome 230 2.0 (Affymettrix). Bioinformatics analyses were performed using the GeneSpring GX software package v10.0.2 and lead to the identification of 89 genes differentially expressed in all three dietary approaches. Generation of a biological association network evidenced several genes, such as connective tissue growth factor (Ctgf), tissue inhibitor of metalloproteinase 1 (Timp1), galanin (Gal), synaptotagmin 1 (Syt1), growth factor receptor bound protein 2 (Grb2), actin gamma 2 (Actg2) and smooth muscle alpha actin (Acta2), as highly interconnected nodes of the resulting network. Gene underexpression was confirmed by Real-Time RT-PCR. Conclusions Ctgf, Timp1, Gal and Syt1, among others, are genes modulated by CLA supplementation that may have a role on mucosal immune responses in early life.

Enhanced kangaroo mother care for heel lance in preterm neonates: a crossover trial.

OBJECTIVE: To test if enhancing maternal skin-to-skin contact, or kangaroo mother care (KMC) by adding rocking, singing and sucking is more efficacious than simple KMC for procedural pain in preterm neonates. STUDY DESIGN: Preterm neonates (n=90) between 32 0/7 and 36 0/7 weeks' gestational age participated in a single-blind randomized crossover design. The infant was held in KMC with the addition of rocking, singing and sucking or the infant was held in KMC without additional stimulation. The Premature Infant Pain Profile was the primary outcome with time to recover as the secondary outcome. A repeated-measures analysis of covariance was employed for analyses. RESULT: There were no significant differences in any of the 30 s time periods over the 2 min of blood sampling nor in time to return to baseline. Compared to historical controls of the same age in incubator, the pain scores were lower and comparable to other studies of KMC. There were site differences related to lower scores with the use of sucrose in one site and higher scores in younger, sicker infants in another site. CONCLUSION: The sensorial stimulations from skin-to-skin contact that include tactile, olfactory sensations from the mother are sufficient to decrease pain response in premature neonates. Other studies showing that rocking, sucking and music were efficacious were independent of skin-to-skin contact, which, when used alone has been shown to be effective as reported across studies.

Iowa Crop and Weather Report, October 9, 2012, Vol. 12. no. 32

Report produced by the The Department of Agriculture and Land Stewardship, Climatology Bureau. Iowa Secretary of Agriculture Bill Northey today commented on the Iowa Crops and Weather report released by the USDA National Agricultural Statistical Service. The report is released weekly from April through October.

Changes in volume, surface estimate, three-dimensional shape and total number of neurons of the human primary visual cortex from midgestation until old age.

Macroscopic features such as volume, surface estimate, thickness and caudorostral length of the human primary visual cortex (Brodman's area 17) of 46 human brains between midgestation and 93 years were studied by means of camera lucida drawings from serial frontal sections. Individual values were best fitted by a logistic function from midgestation to adulthood and by a regression line between adulthood and old age. Allometric functions were calculated to study developmental relationships between all the features. The three-dimensional shape of area 17 was also reconstructed from the serial sections in 15 cases and correlated with the sequence of morphological events. The sulcal pattern of area 17 begins to develop around 21 weeks of gestation but remains rather simple until birth, while it becomes more convoluted, particularly in the caudal part, during the postnatal period. Until birth, a large increase in cortical thickness (about 83% of its mean adult value) and caudorostral length (69%) produces a moderate increase in cortical volume (31%) and surface estimate (40%) of area 17. After birth, the cortical volume and surface undergo their maximum growth rate, in spite of a rather small increase in cortical thickness and caudorostral length. This is due to the development of the pattern of gyrification within and around the calcarine fissure. All macroscopic features have reached the mean adult value by the end of the first postnatal year. With aging, the only features to undergo significant regression are the cortical surface estimate and the caudorostral length. The total number of neurons in area 17 shows great interindividual variability at all ages. No decrease in the postnatal period or in aging could be demonstrated.

Mis à l'écart et laissé-pour-compte: l'adéquation dans l'article 32 de la LAMal (commentaire de l'article de Georg Marckmann: "Marktorientierung und Gerechtigkeit: Prinzipen im Widerspruch?")

Commentaire de: Marckmann G. Marktorientierung und Gerechtigkeit: Prinzipen im Widerspruch? SGBEbulletinSSEB 2010;(61):5-12.

"A renewed sense of purpose": Mothers' and fathers' experience of having a child following a recent stillbirth.

Background Most research has focused on mothers¿ experiences of perinatal loss itself or on the subsequent pregnancy, whereas little attention has been paid to both parents¿ experiences of having a child following late perinatal loss and the experience of parenting this child. The current study therefore explored mothers¿ and fathers' experiences of becoming a parent to a child born after a recent stillbirth, covering the period of the second pregnancy and up to two years after the birth of the next baby.MethodIn depth interviews were conducted with 7 couples (14 participants). Couples were eligible if they previously had a stillbirth (after 24 weeks of gestation) and subsequently had another child (their first live baby) who was now under the age of 2 years. Couples who had more than one child after experiencing a stillbirth and those who were not fluent in English were excluded. Qualitative analysis of the interview data was conducted using Interpretive Phenomenological Analysis.ResultsFive superordinate themes emerged from the data: Living with uncertainty; Coping with uncertainty; Relationship with the next child; The continuing grief process; Identity as a parent. Overall, fathers' experiences were similar to those of mothers', including high levels of anxiety and guilt during the subsequent pregnancy and after the child was born. Coping strategies to address these were identified. Differences between mothers and fathers regarding the grief process during the subsequent pregnancy and after their second child was born were identified. Despite difficulties with bonding during pregnancy and at the time when the baby was born, parents' perceptions of their relationship with their subsequent child were positive.ConclusionsFindings highlight the importance of tailoring support systems not only according to mothers' but also to fathers' needs. Parents¿, and particularly fathers', reported lack of opportunities for grieving as well as the high level of anxiety of both parents about their baby's wellbeing during pregnancy and after birth implies a need for structured support. Difficulties experienced in bonding with the subsequent child during pregnancy and once the child is born need to be normalised.

Placental immaturity, endocardial fibroelastosis and fetal hypoxia.

We describe a term newborn who, after a normal gestational course, presented at birth with absent cardiac activity and no spontaneous breathing. Death occurred within 30 h. Autopsy revealed placental villous immaturity, multiple acute hypoxic lesions, but also chronic hypoxic lesions like endocardial fibroelastosis. This striking association of endocardial fibroelastosis and placental villous immaturity is reviewed and correlated with 2 other cases of placental villous immaturity that led to in utero death at 39 and 41 weeks of gestation. Placental villous immaturity must be suspected and looked for by both pediatricians and obstetricians in every case of stillbirth or perinatal asphyxia of unclear origin. In order to minimize the risk of recurrence in further pregnancies, elective cesarean section may be considered.

Ciência da Informação: 32 anos (1972-2004) no caminho da história e horizontes de um periódico científico brasileiro

Análise da revista Ciência da Informação, do IBICT, nas suas qualidades extrínsecas e intrínsecas. As primeiras, relativas à forma, incluem as seções, padrões bibliográficos e sistema de avaliação. As características intrínsecas abrangem a análise de conteúdo dos artigos, a produtividade de autores e padrões de autoria, tendo sido constatada tanto a sua repercussão nacional quanto internacional. O processo evolutivo da Ciência da Informação, na sua transformação para formato eletrônico , potencializou a disseminação e acesso universal à informação. Os resultados demonstram que o periódico Ciência da Informação é um espaço de discussão de temas relevantes e atuais da área, nos seus avanços, contribuindo para a consolidação e expansão da Ciência da Informação no Brasil.

Iowa Board of Nursing Newsletter, February-March-April, 2013 Vol. 32, no. 1

Newsletter produced by the Iowa Board of Nursing for nurses to keep them informed to CE classes, renewals, board meetings, etc. Produced 4 times a year. Also known as Nursing Newsletter.

Iowa Board of Nursing Newsletter, May-June-July, 2013 Vol. 32, no. 2

Newsletter produced by the Iowa Board of Nursing for nurses to keep them informed to CE classes, renewals, board meetings, etc. Produced 4 times a year. Also known as Nursing Newsletter.