Effects of intra-animal nephron heterogeneity on studies of glomerular dynamics

Effects of intra-animal nephron heterogeneity on studies of glomerular dynamics. Quintuplicate determinations of the parameters measured in studies of glomerular dynamics revealed that the intra-animal coefficients of variation for Bowman's space and star vessel pressures, nephron filtration rate, and filtration fractions were 54 to 72% larger than the corresponding interanimal coefficients of variation; those for glomerular capillary pressure were more nearly equal. With a net efferent filtration pressure (ΔPE) of 10.6 ± SEM 1.92mm Hg, the rats were far from filtration pressure equilibrium and the calculated ultrafiltration coefficient (Kf) of 2.1 ± SEM 0.2 nl/min ·2mm Hg was lower than in many other studies. Statistical analysis revealed that the precision of estimates of both the measured and the derived parameters in glomerular dynamic studies is affected appreciably by ignoring the intra-animal effect. The importance of the intra-animal variance in glomerular dynamic studies is greatest when only one or two samples of each measured parameter are obtained in every rat (k = 1 or 2) and least when k is large. Triplicate sampling provides combined SEMS that are not greatly larger than those obtained with k = 5, however, and offers the greatest economy in studies of glomerular dynamics. The number of animals required to provide values with ΔPE and Kf that are within ± 20% of the “true” values is rather large.Effets de l'hétérogénéité néphronique intra-animale sur les études de la dynamique glomérulaire. Des déterminations en quintuple des paramètres mesurés dans les études de la dynamique glomérulaire ont révélé que les coefficients de variation intra-animale pour les pressions dans l'espace de Bowman et les vaisseaux étoilés, le débit de filtration glomérulaire et les fractions de filtration étaient 54 à 74% plus grandes que les coefficients de variation inter-animale correspondants; ceux de la pression capillaire glomérulaire étaient plus proches. Avec une pression de filtration effèrente nette (ΔPE) de 10,6 ± SEM 1,92mm Hg, les rats étaient loin d'une pression de filtration en équilibre, et le coefficient d'ultrafiltration calculé (Kf) de 2,1 ± SEM 0,2 nl/min ·2mm Hg était plus faible que lors de nombreuses autres études. L'analyse statistique a révélé que la précision des paramètres mesurés et déduits des études de la dynamique glomérulaire est affectée de façon appréciable en ignorant l'effet intra-animal. L'importance de la variance intra-animale dans les études de la dynamique glomérulaire est très grande lorsque seulement un ou deux échantillons de chaque paramètre mesuré sont obtenus chez chaque rat (k = 1 ou 2), et moindre lorsque k est élevé. Un échantillon-age triple offre cependant des SEM combinés qui ne sont pas beaucoup plus grands que ceux obtenus pour k = 5, cependant, et offre la plus forte économie lors des mesures de la dynamique glomérulaire. Le nombre d'animaux nécessaires pour obtenir des valeurs avec ΔE et Kf entre ± 20% des valeurs “vraies” est assez grand

The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders

Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs—valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine—in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs)

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.Peer reviewe

A pilot randomized controlled trial to promote healthful fish consumption during pregnancy: The Food for Thought Study

Background: Nutritionists advise pregnant women to eat fish to obtain adequate docosahexaenoic acid (DHA), an essential nutrient important for optimal brain development. However, concern exists that this advice will lead to excess intake of methylmercury, a developmental neurotoxicant. Objective: Conduct a pilot intervention to increase consumption of high-DHA, low-mercury fish in pregnancy. Methods: In April-October 2010 we recruited 61 women in the greater Boston, MA area at 12–22 weeks gestation who consumed = 200mg/d of DHA from fish, compared with 33% in the Advice arm (p=0.005) and 53% in the Advice+GC arm (p=0.0002). We did not detect any differences in mercury intake or in biomarker levels of mercury and DHA between groups. Conclusions: An educational intervention increased consumption of fish and DHA but not mercury. Future studies are needed to determine intervention effects on pregnancy and childhood health outcomes. Trial registration Registered on clinicaltrials.gov as NCT0112676

IRAS sky survey atlas: Explanatory supplement

This Explanatory Supplement accompanies the IRAS Sky Survey Atlas (ISSA) and the ISSA Reject Set. The first ISSA release in 1991 covers completely the high ecliptic latitude sky, absolute value of beta is greater than 50 deg, with some coverage down to the absolute value of beta approx. equal to 40 deg. The second ISSA release in 1992 covers ecliptic latitudes of 50 deg greater than the absolute value of beta greater than 20 deg, with some coverage down to the absolute value of beta approx. equal to 13 deg. The remaining fields covering latitudes within 20 deg of the ecliptic plane are of reduced quality compared to the rest of the ISSA fields and therefore are released as a separate IPAC product, the ISSA Reject Set. The reduced quality is due to contamination by zodiacal emission residuals. Special care should be taken when using the ISSA Reject images. In addition to information on the ISSA images, some information is provided in this Explanatory Supplement on the IRAS Zodiacal History File (ZOHF), Version 3.0, which was described in the December 1988 release memo. The data described in this Supplement are available at the National Space Science Data Center (NSSDC) at the Goddard Space Flight Center. The interested reader is referred to the NSSDC for access to the IRAS Sky Survey Atlas (ISSA)

Body Composition Measurements from Birth through 5 Years: Challenges, Gaps, and Existing & Emerging Technologies—A National Institutes of Health workshop

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156150/2/obr13033_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156150/1/obr13033.pd

A rare case of giant leiomyosarcoma in a filarial scrotum: a case report

Giant leiomyosarcoma of scrotum is a rare tumour. A case of scrotum leiomyosarcoma is presented in a 67 year old patient with scrotal filariasis which was managed successfully with total scrotectomy with bilateral orchidectomy, degloved penis reconstructed with rotation advancement supra pubic fasciocutaneous flap. We made a literature search proving the rarity of this lesion type. Only 36 cases have been described and the first case in a filarial scrotu

Multimodality Treatment with Conventional Transcatheter Arterial Chemoembolization and Radiofrequency Ablation for Unresectable Hepatocellular Carcinoma

Background/Aims: To evaluate the efficacy of multimodality treatment consisting of conventional transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable hepatocellular carcinoma (HCC). Methods: In this retrospective study, 85 consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE followed by RFA between 2001 and 2010. The mean number of tumors per patient was 1.6 +/- 0.7 with a mean size of 3.0 +/- 0.9 cm. Both local efficacy and patient survival were evaluated. Results: Of 120 treated HCCs, 99 (82.5%) showed a complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted. Patients with solitary HCC revealed CR in 91% (51/56); in patients with multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis revealed a significant difference in survival between Barcelona Clinic Liver Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP) score and tumor distribution pattern. Conclusion: TACE combined with RFA provides an effective treatment approach with high local tumor control rates and promising survival data, especially for BCLC A patients. Randomized trials are needed to compare this multimodality approach with a single modality approach for early-stage HCC. Copyright (C) 2011 S. Karger AG, Base

Plasma metabolite profiles in children with current asthma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146270/1/cea13183.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146270/2/cea13183_am.pd