Population-based study of antiepileptic drug exposure in utero—Influence on head circumference in newborns

PurposeTo study the effect of AED exposure on head circumference in the newborn.MethodsData on all Swedish singletons births between 1995 and 2005, over 900,000 births, were obtained from the Swedish Medical Birth Registry. The effects of AEDs on birth-weight-adjusted mean head circumference (bw-adj-HC) were estimated by comparison with data from all births in an analysis which was adjusted for year of birth, maternal age, parity, maternal smoking, and maternal body mass index.ResultsA significant reduction of mean bw-adj-HC was seen after both carbamazepine (CBZ) (standard deviation scores (SDS) = 0.15, p < 0.001) and valproic acid (VPA) (SDS = 0.10, p = 0.04) in monotherapy. No effect on mean bw-adj-HC was seen for phenytoin, clonazepam, lamotrigine and gabapentin. There was a significant increase in the occurrence of microcephaly (bw-adj-HC smaller than 2 SD below the mean) after any AED polytherapy (OR = 2.85, 95% CI: 1.74–4.78) but not after AED monotherapy or monotherapy with CBZ or VPA. CBZ or VPA was taken by 71% of the pregnant mothers on AED, and the usage increased over time.ConclusionsCBZ and VPA in monotherapy during pregnancy reduce mean bw-adj-HC. AED polytherapy increases the rate of microcephaly but no significant effect is seen of AED monotherapy. The possible significance for the further development of the child is uncertain but should be explored.     

Bronchoalveolar lavage in sarcoidosis

There is no single cell type present in bronchoalveolar lavage (BAL) fluid that appears to be predictive for sarcoidosis. However, BAL fluid analysis can be very helpful in the differential diagnosis. A grouping of features, an elevated total cell count, predominantly lymphocytes, together with a nearly normal percentage of eosinophils and polymorphonuclear neutrophils and the absence of plasma cells, distinguish the most likely diagnosis of sarcoidosis from the most common interstitial lung diseases, extrinsic allergic alveolitis (EAA), nonspecific interstitial pneumonia (NSIP), and idiopathic pulmonary fibrosis (IPF). In sarcoidosis the majority of cases have an increased number of lymphocytes and a normal amount of eosinophils and neutrophils. Disease presentation or activity at the time the BAL is performed as well as the smoking status is crucial for interpretation of individual BAL fluid analysis results. In severe cases the number of neutrophils can be increased as well. For an individual case the CD4:CD8 ratio is of less importance because it can be increased, normal, and even decreased. In the follow-up depicting prognosis and response to treatment, BAL fluid analysis has less clinical relevance.     

Coping strategies in immigrant men and women with type 2 diabetes

The aim of this study was to assess coping strategies of foreign-born men and women with type 2 diabetes in relation to demographic (sex, age, time in Sweden), medical, and socio-economic situation, and as compared with Swedish-born patients. Participants were foreign-born type 2 diabetic patients of European and non-European origin in primary health care in Stockholm County, comprising 41 men and 36 women aged 35-64 years, compared with Swedish-born type 2 diabetes patients, 121 men and 111 women. The General Coping Questionnaire, which measures five main orientations, dichotomised into "positive" and "negative" factors, i.e. 10 coping strategies, was used in the assessment. Medical and socio-economic data were obtained from medical records and postal questionnaires. Foreign-born men showed an impact on 6 of 10 coping strategies, and foreign-born women on 2 of 10 coping strategies, as compared to Swedish-born subjects. Longer time since migration and higher educational level were associated with lower scores for stressful coping strategies, while having financial problems and receiving a disability pension were associated with higher scores. In conclusion, the most stressful coping strategies were found among foreign-born men. It seems to be essential to improve and adjust diabetes care for immigrants, also including the psycho-social perspective.     

Symptomatic carotid artery occlusion: flow territories of major brain-feeding arteries

PURPOSE: To prospectively investigate the extent of flow territories of the contralateral internal carotid artery (ICA) and vertebrobasilar arteries in patients with symptomatic ICA occlusion. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Flow territory mapping of the ICA contralateral to the occluded ICA and mapping of the vertebrobasilar arteries were performed by using selective arterial spin-labeling magnetic resonance imaging in 23 functionally independent patients (22 men, one woman; mean age, 58 years +/- 8 [standard deviation]) with symptomatic ICA occlusion. The control group consisted of 68 subjects (57 men, 11 women; mean age, 59 years +/- 9) without hemodynamically significant ICA obstruction. Voxel-based chi(2) testing with Bonferroni correction was performed to analyze significant differences in the extent of the flow territories. RESULTS: Flow territory maps in patients with symptomatic ICA occlusion showed significant differences in the flow territories of the contralateral ICA and vertebrobasilar arteries compared with those in control subjects (P < .05). CONCLUSION: In functionally independent patients with symptomatic ICA occlusion, the middle cerebral artery flow territory ipsilateral to the occluded ICA is mainly supplied by the vertebrobasilar arteries, whereas the anterior cerebral artery flow territory on the occluded side is mainly supplied by the contralateral ICA.     

Cellular senescence of human mammary epithelial cells (HMEC) is associated with an altered MMP-7/HB-EGF signaling and increased formation of elastin-like structures

The extracellular matrix (ECM) and a complex interplay of cell-to-cell and cell-to-matrix (ECM) interactions provide important platforms to determine cellular senescence and a potentially tumorigenic transformation of normal human mammary epithelial cells (HMEC). An enhanced formation of extracellular filaments, consisting of elastin-like structures, in senescent post-selection HMEC populations was paralleled by a significantly increased expression of its precursor protein tropoelastin and matched with a markedly elevated activity of the cross-linking enzyme family of lysyl oxidases (LOX). RNAi experiments revealed both the ECM metalloproteinase MMP-7 and the growth factor HB-EGF as potential effectors of an increased tropoelastin expression. Moreover, co-localization of MMP-7 and HB-EGF as well as a concomittant downstream signaling via Fra-1 indicated a possible association between the reduced MMP-7 enzyme activity and an impaired HB-EGF processing, resulting in an enhanced tropoelastin synthesis during senescence of HMEC. In agreement with previous work, these findings suggested an important influence of the extracellular proteinase MMP-7 on the aging process of HMEC, affecting both extracellular remodeling as well as intracellular signaling pathways.     

In vitro and in vivo treatments of echinococcus protoscoleces and metacestodes with artemisinin and artemisinin derivatives

In vitro treatment of Echinococcus multilocularis and Echinococcus granulosus larval stages with the antimalarials dihydroartemisinin and artesunate (10 to 40 μM) exhibited promising results, while 6 weeks of in vivo treatment of mice infected with E. multilocularis metacestodes (200 mg/kg of body weight/day) had no effect. However, combination treatments of both drugs with albendazole led to a substantial but statistically not significant reduction in parasite weight compared to results with albendazole alone.     

Risk of emotional disorder in offspring of depressed parents: gender differences in the effect of a second emotionally affected parent

In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring of parents with major depressive disorder, this study examined the effects of a second affected parent, offspring gender, gender of the depressed parent and their interactions on risk of depression and anxiety disorder. We found that daughters had a higher risk of depression and anxiety than sons and that offspring of depressed mothers had a higher risk of anxiety than offspring of depressed fathers. In addition to these main effects, we found an interaction between parent and offspring gender inasmuch that sons of depressed fathers had the lowest risk of depression and anxiety relative to the other groups. A second affected parent tended to increase risk of depression and significantly increased risk of anxiety. However, this effect of a second affected parent on offspring anxiety was most prominent in daughters when the second affected parent was the father, whereas risk in sons did not increase if the father was affected as well. Our results indicate that paternal and maternal depression similarly and additively increase daughters' risk of emotional disorder, but that sons' risk only increases with maternal depression. Intergenerational transmission of emotional disorder seems strongest when the female gender is involved, either in the form of a daughter or a depressed mother.     

Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Introduction

Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods

We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results

Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion

Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.