[Osteostimulating effect of bone xenograft on bone tissue regeneration].

PubMed

Balin, V N; Balin, D V; Iordanishvili, A K; Musikin, M I

2015-01-01

The aim of experimental case-control study performed in 28 dogs divided in 2 groups was to assess local tissue reactions on bone xenograft transplantation; dynamics of bone remodeling and formation at the site of bone defect wall contacting with bone xenograft; dynamics and mechanisms of xenograft remodeling. Transplantation of xenograft in conventional bone defects did not cause inflammatory of destructive reactions because of high biocompatibility of the material. At transplantation site active fibrous bone trabeculae formation filling the spaces between xenograft participles was observed. On the 90th day newly formed bone showed lammelar structure. Simultaneously from the 42d day the invasion of cell elements from recipient bed into the material was seen leading to xenograft resorption. The observed dynamics may be assessed as gradual substitution of xenograft with newly formed host bone structures.

Dorsal arachnoid web.

PubMed

McCormick, Paul C

2014-09-01

Dorsal thoracic arachnoid web is a rare but often overlooked cause of progressive myelopathy. Syringomyelia, either above or below the compressive arachnoid band, may also be present. Dorsal arachnoid cyst and ventral spinal cord herniation may be mistaken for this condition. This video demonstrates the microsurgical identification and techniques of resection of a dorsal arachnoid band producing a progressive myelopathy in a 63-year-old man. The video can be found here: http://youtu.be/KDNTqiyW6yo.

Lumbar dorsal ramus syndrome.

PubMed

Bogduk, N

1980-11-15

Low back pain, referred pain in the lower limbs, and spasm of the back, gluteal, and hamstring muscles are clinical features which can be induced in normal volunteers by stimulating structures which are innervated by the lumbar dorsal rami. Conversely, they can be relieved in certain patients by selective interruption of conduction along dorsal rami. These facts permit the definition of a lumbar dorsal ramus syndrome, which can be distinguished from the intervertebral disc syndrome and other forms of low back pain. The distinguishing feature is that, in lumbar dorsal ramus syndrome, all the clinical features are exclusively mediated by dorsal rami and do not arise from nerve-root compression. The pathophysiology, pathology, and treatment of this syndrome are described. Recognition of this syndrome, and its treatment with relatively minor procedures, can obviate the need for major surgery which might otherwise be undertaken.

The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats

PubMed Central

Solís, Karina H.; Méndez, Laura I.; García-López, Guadalupe; Díaz, Néstor F.; Portillo, Wendy; De Nova-Ocampo, Mónica; Molina-Hernández, Anayansi

2017-01-01

Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E) 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R) which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2) and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers) and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon of embryos from

Superficial dorsal vein injury/thrombosis presenting as false penile fracture requiring dorsal venous ligation.

PubMed

Rafiei, Arash; Hakky, Tariq S; Martinez, Daniel; Parker, Justin; Carrion, Rafael

2014-12-01

Conditions mimicking penile fracture are extremely rare and have been seldom described. To describe a patient with false penile fracture who presented with superficial dorsal vein injury/thrombosis managed with ligation. A 33-year-old male presented with penile swelling and ecchymosis after intercourse. A penile ultrasound demonstrated a thrombosed superficial dorsal vein but also questionable fracture of the tunica albuginea. As the thrombus was expanding, he was emergently taken to the operating room for exploration and required only dorsal venous ligation. Postoperatively, patient's Sexual Health Inventory for Men score was 23, and he had no issues with erections or sexual intercourse. Early exploration of patients with suspected penile fracture provides excellent results with maintenance of erectile function. Also, in the setting of dorsal vein thrombosis, ligation preserves the integrity of the penile tissues and avoids unnecessary complications from conservative management. Rafiei A, Hakky TS, Martinez D, Parker J, and Carrion R. Superficial dorsal vein injury/thrombosis presenting as false penile fracture requiring dorsal venous ligation.

Superficial Dorsal Vein Injury/Thrombosis Presenting as False Penile Fracture Requiring Dorsal Venous Ligation

PubMed Central

Rafiei, Arash; Hakky, Tariq S; Martinez, Daniel; Parker, Justin; Carrion, Rafael

2014-01-01

Introduction Conditions mimicking penile fracture are extremely rare and have been seldom described. Aim To describe a patient with false penile fracture who presented with superficial dorsal vein injury/thrombosis managed with ligation. Methods A 33-year-old male presented with penile swelling and ecchymosis after intercourse. A penile ultrasound demonstrated a thrombosed superficial dorsal vein but also questionable fracture of the tunica albuginea. As the thrombus was expanding, he was emergently taken to the operating room for exploration and required only dorsal venous ligation. Results Postoperatively, patient's Sexual Health Inventory for Men score was 23, and he had no issues with erections or sexual intercourse. Conclusion Early exploration of patients with suspected penile fracture provides excellent results with maintenance of erectile function. Also, in the setting of dorsal vein thrombosis, ligation preserves the integrity of the penile tissues and avoids unnecessary complications from conservative management. Rafiei A, Hakky TS, Martinez D, Parker J, and Carrion R. Superficial dorsal vein injury/thrombosis presenting as false penile fracture requiring dorsal venous ligation. PMID:25548650

Vitrification and xenografting of human ovarian tissue.

PubMed

Amorim, Christiani Andrade; Dolmans, Marie-Madeleine; David, Anu; Jaeger, Jonathan; Vanacker, Julie; Camboni, Alessandra; Donnez, Jacques; Van Langendonckt, Anne

2012-11-01

To assess the efficiency of two vitrification protocols to cryopreserve human preantral follicles with the use of a xenografting model. Pilot study. Gynecology research unit in a university hospital. Ovarian biopsies were obtained from seven women aged 30-41 years. Ovarian tissue fragments were subjected to one of three cryopreservation protocols (slow freezing, vitrification protocol 1, and vitrification protocol 2) and xenografted for 1 week to nude mice. The number of morphologically normal follicles after cryopreservation and grafting and fibrotic surface area were determined by histologic analysis. Apoptosis was assessed by the TUNEL method. Morphometric analysis of TUNEL-positive surface area also was performed. Follicle proliferation was evaluated by immunohistochemistry. After xenografting, a difference was observed between the cryopreservation procedures applied. According to TUNEL analysis, both vitrification protocols showed better preservation of preantral follicles than the conventional freezing method. Moreover, histologic evaluation showed a significantly higher proportion of primordial follicles in vitrified (protocol 2)-warmed ovarian tissue than in frozen-thawed tissue. The proportion of growing follicles and fibrotic surface area was similar in all groups. Vitrification procedures appeared to preserve not only the morphology and survival of preantral follicles after 1 week of xenografting, but also their ability to resume folliculogenesis. In addition, vitrification protocol 2 had a positive impact on the quiescent state of primordial follicles after xenografting. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Plantar-to-dorsal compared to dorsal-to-plantar screw fixation for proximal chevron osteotomy: a biomechanical analysis.

PubMed

Sharma, Krishn M; Parks, Brent G; Nguyen, Augustine; Schon, Lew C

2005-10-01

A change in screw orientation in fixing the chevron proximal first metatarsal osteotomy was noted anecdotally to improve fixation strength. The authors hypothesized that plantar-to-dorsal screw orientation would be more stable than the conventional dorsal-to-plantar screw orientation for fixation of the chevron osteotomy. The purpose of this study was to determine if the load-to-failure and stiffness of the chevron type proximal first metatarsal osteotomy stabilized using plantar-to-dorsal screw fixation were greater than with the more conventional dorsal-to-plantar screw fixation method. One foot from each of eight matched cadaver pairs was randomly assigned to one of two groups: 1) fixation with a dorsal-to-plantar lag screw or 2) fixation with a plantar-to-dorsal lag screw. A proximal chevron osteotomy was then created using standard technique and the metatarsal was fixed according to previously established method. The bone was potted in polyester resin, and the construct was fitted into a materials testing system machine in which load was applied to the plantar aspect of the metatarsal until failure. The two groups were compared using a two-tailed Student t test. The average load-to-failure and stiffness of the chevron osteotomy fixed with the plantar-to-dorsal lag screw were significantly greater (p < 0.05) than the group fixed with more conventional dorsal-to-plantar lag screws. Plantar-to-dorsal screw orientation was more stable than the conventional dorsal-to-plantar screw orientation for fixation of the proximal chevron osteotomy. Plantar-to-dorsal screw orientation should be considered when using the chevron proximal first metatarsal osteotomy.

In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

PubMed

Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

2017-03-01

Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

Fetal Research

NASA Astrophysics Data System (ADS)

Hansen, John T.; Sladek, John R.

1989-11-01

This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

Versatility of the ventral approach in bulbar urethroplasty using dorsal, ventral or dorsal plus ventral oral grafts.

PubMed

Palminteri, Enzo; Berdondini, Elisa; Fusco, Ferdinando; De Nunzio, Cosimo; Giannitsas, Kostas; Shokeir, Ahmed A

2012-06-01

To investigate the versatility of the ventral urethrotomy approach in bulbar reconstruction with buccal mucosa (BM) grafts placed on the dorsal, ventral or dorsal plus ventral urethral surface. Between 1999 and 2008, 216 patients with bulbar strictures underwent BM graft urethroplasty using the ventral-sagittal urethrotomy approach. Of these patients, 32 (14.8%; mean stricture 3.2 cm, range 1.5-5) had a dorsal graft urethroplasty (DGU), 121 (56%; mean stricture 3.7, range 1.5-8) a ventral graft urethroplasty (VGU), and 63 (29.2%; mean stricture 3.4, range 1.5-10) a dorsal plus ventral graft urethroplasty (DVGU). The strictured urethra was opened by a ventral-sagittal urethrotomy and BM graft was inserted dorsally or ventrally or dorsal plus ventral to augment the urethral plate. The median follow-up was 37 months. The overall 5-year actuarial success rate was 91.4%. The 5-year actuarial success rates were 87.8%, 95.5% and 86.3% for the DGU, VGU and DVGU, respectively. There were no statistically significant differences among the three groups. Success rates decreased significantly only with a stricture length of >4 cm. In BM graft bulbar urethroplasties the ventral urethrotomy access is simple and versatile, allowing an intraoperative choice of dorsal, ventral or combined dorsal and ventral grafting, with comparable success rates.

Next generation patient-derived prostate cancer xenograft models

PubMed Central

Lin, Dong; Xue, Hui; Wang, Yuwei; Wu, Rebecca; Watahiki, Akira; Dong, Xin; Cheng, Hongwei; Wyatt, Alexander W; Collins, Colin C; Gout, Peter W; Wang, Yuzhuo

2014-01-01

There is a critical need for more effective therapeutic approaches for prostate cancer. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease. This review particularly focuses on the development of prostate cancer xenograft models based on subrenal capsule grafting of patients’ tumor tissue into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues. The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease. These xenograft models could therefore be viewed as next-generation models of prostate cancer. PMID:24589467

[Dorsal capsular imbrication for dorsal instability of the distal radioulnar joint].

PubMed

Unglaub, F; Manz, S; Bruckner, T; Leclère, F M; Hahn, P; Wolf, M B

2013-12-01

To stabilize the distal radioulnar joint (DRUJ) by performing dorsal capsular imbrication in patients presenting with dorsal instability. The goal was to reduce pain and prevent the occurrence of posttraumatic arthrosis. Posttraumatic dorsal instability of the DRUJ with missing block while performing translational activities in the DRUJ or subluxation while actively rotating the forearm. Cases, in which other stabilizing techniques, such as, sutures of the triangular fibrocartilage complex failed. DRUJ arthrosis, previous surgical interventions to the capsule area of the DRUJ, instabilities due to osseous reasons (malposition or pseudarthrosis) should already have been treated. Dorsal approach and opening of the 5th extensor compartment to expose the dorsal joint capsule. A longitudinal division of the capsule was performed and sufficient tissue on the radial and ulnar border was retained to ensure a solid suture technique. Then 2 U-shaped sutures using FiberWire suture material were made. Correction of the malposition and repositioning the forearm into supination. Tightening of the prepared capsule sutures and closing of the retinaculum with a resorbable suture. Patients wore a long-arm cast with the forearm being in supination for a period of 4 weeks. Following cast removal, patients wore a forearm splint for a period of 4 weeks to limit forearm pronation/supination at 45°. Full load on the wrist was allowed after 12 weeks. The subjective and functional outcomes of 20 patients having received capsular imbrication using this technique were good and entailed no significant complications. The postoperative DASH was 15.8 points. Of the 20 patients, 17 patients (85%) had a reduction of pain. Symptoms of DRUJ instability could be reduced in 18 patients (90%). Pronation/supination of the wrist was not restricted postoperatively.

Versatility of the ventral approach in bulbar urethroplasty using dorsal, ventral or dorsal plus ventral oral grafts

PubMed Central

Palminteri, Enzo; Berdondini, Elisa; Fusco, Ferdinando; Nunzio, Cosimo De; Giannitsas, Kostas; Shokeir, Ahmed A.

2012-01-01

Objectives To investigate the versatility of the ventral urethrotomy approach in bulbar reconstruction with buccal mucosa (BM) grafts placed on the dorsal, ventral or dorsal plus ventral urethral surface. Patients and methods Between 1999 and 2008, 216 patients with bulbar strictures underwent BM graft urethroplasty using the ventral-sagittal urethrotomy approach. Of these patients, 32 (14.8%; mean stricture 3.2 cm, range 1.5–5) had a dorsal graft urethroplasty (DGU), 121 (56%; mean stricture 3.7, range 1.5–8) a ventral graft urethroplasty (VGU), and 63 (29.2%; mean stricture 3.4, range 1.5–10) a dorsal plus ventral graft urethroplasty (DVGU). The strictured urethra was opened by a ventral-sagittal urethrotomy and BM graft was inserted dorsally or ventrally or dorsal plus ventral to augment the urethral plate. Results The median follow-up was 37 months. The overall 5-year actuarial success rate was 91.4%. The 5-year actuarial success rates were 87.8%, 95.5% and 86.3% for the DGU, VGU and DVGU, respectively. There were no statistically significant differences among the three groups. Success rates decreased significantly only with a stricture length of >4 cm. Conclusions In BM graft bulbar urethroplasties the ventral urethrotomy access is simple and versatile, allowing an intraoperative choice of dorsal, ventral or combined dorsal and ventral grafting, with comparable success rates. PMID:26558013

Lessons from the first dorsal fin in atheriniforms—A new mode of dorsal fin development and its phylogenetic implications

PubMed Central

Richter, Philipp

2017-01-01

Abstract The median fins in extant actinopterygians are the product of millions of years of evolution. During this time, different developmental patterns for the dorsal and anal fins emerged leading to a high variation in median fin morphology and ontogeny. In this study, the development of anal and dorsal fins in atheriniforms is described and its consequences for the current phylogenetic hypothesis are discussed. Developmental series of five atheriniform species were investigated using clearing and staining as well as antibody staining. The skeletal elements of the second dorsal fin and the anal fin emerge in a bidirectional pattern. The first dorsal fin, however, arises separately in front of the second dorsal fin after this one is almost completely formed. The pterygiophores of the first dorsal fin, including the interdorsal pterygiophores, develop from caudal to rostral, but the fin‐spines of the first dorsal fin form in the opposite direction. This new mode of fin development has been found in all examined atheriniform species with two dorsal fins. Several morphological characters of atheriniforms, including interdorsal pterygiophores, are also found in one other taxon: the Mugiliformes. Thus, several dorsal fin characteristics may provide evidence for a closer relationship of these two taxa. PMID:28370120

Radiographic Outcomes of Dorsal Distraction Distal Radius Plating for Fractures With Dorsal Marginal Impaction.

PubMed

Huish, Eric G; Coury, John G; Ibrahim, Mohamed A; Trzeciak, Marc A

2017-04-01

The purpose of this study is to compare radiographic outcomes of patients treated with dorsal spanning plates with previously reported normal values of radiographic distal radius anatomy and compare the results with prior publications for both external fixation and internal fixation with volar locked plates. Patients with complex distal radius fractures including dorsal marginal impaction pattern necessitating dorsal distraction plating at the discretion of the senior authors (M.A.T. and M.A.I.) from May 30, 2013, to December 29, 2015, were identified and included in the study. Retrospective chart and radiograph review was performed on 19 patients, 11 male and 8 female, with mean age of 47.83 years (22-82). No patients were excluded from the study. All fractures united prior to plate removal. The average time the plate was in place was 80.5 days (49-129). Follow-up radiographs showed average radial inclination of 20.5° (13.2°-25.5°), radial height of 10.7 mm (7.5-14 mm), ulnar variance of -0.3 mm (-2.1 to 3.1 mm), and volar tilt of 7.9° (-3° to 15°). One patient had intra-articular step-off greater than 2 mm. Dorsal distraction plating of complex distal radius fractures yields good radiographic results with minimal complications. In cases of complex distal radius fractures including dorsal marginal impaction where volar plating is not considered adequate, a dorsal distraction plate should be considered as an alternative to external fixation due to reduced risk for infection and better control of volar tilt.

β-Arrestins Negatively Regulate the Toll Pathway in Shrimp by Preventing Dorsal Translocation and Inhibiting Dorsal Transcriptional Activity*

PubMed Central

Sun, Jie-Jie; Lan, Jiang-Feng; Shi, Xiu-Zhen; Yang, Ming-Chong; Niu, Guo-Juan; Ding, Ding; Zhao, Xiao-Fan; Yu, Xiao-Qiang; Wang, Jin-Xing

2016-01-01

The Toll signaling pathway plays an important role in the innate immunity of Drosophila melanogaster and mammals. The activation and termination of Toll signaling are finely regulated in these animals. Although the primary components of the Toll pathway were identified in shrimp, the functions and regulation of the pathway are seldom studied. We first demonstrated that the Toll signaling pathway plays a central role in host defense against Staphylococcus aureus by regulating expression of antimicrobial peptides in shrimp. We then found that β-arrestins negatively regulate Toll signaling in two different ways. β-Arrestins interact with the C-terminal PEST domain of Cactus through the arrestin-N domain, and Cactus interacts with the RHD domain of Dorsal via the ankyrin repeats domain, forming a heterotrimeric complex of β-arrestin·Cactus·Dorsal, with Cactus as the bridge. This complex prevents Cactus phosphorylation and degradation, as well as Dorsal translocation into the nucleus, thus inhibiting activation of the Toll signaling pathway. β-Arrestins also interact with non-phosphorylated ERK (extracellular signal-regulated protein kinase) through the arrestin-C domain to inhibit ERK phosphorylation, which affects Dorsal translocation into the nucleus and phosphorylation of Dorsal at Ser276 that impairs Dorsal transcriptional activity. Our study suggests that β-arrestins negatively regulate the Toll signaling pathway by preventing Dorsal translocation and inhibiting Dorsal phosphorylation and transcriptional activity. PMID:26846853

A human lung xenograft mouse model of Nipah virus infection.

PubMed

Valbuena, Gustavo; Halliday, Hailey; Borisevich, Viktoriya; Goez, Yenny; Rockx, Barry

2014-04-01

Nipah virus (NiV) is a member of the genus Henipavirus (family Paramyxoviridae) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%). NiV can cause Acute Lung Injury (ALI) in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7) TCID50/gram lung tissue) as early as 3 days post infection (pi). NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

Nitrous acid pretreatment of tendon xenografts cross-linked with glutaraldehyde and sterilized with gamma irradiation.

PubMed

Johnson, K A; Rogers, G J; Roe, S C; Howlett, C R; Clayton, M K; Milthorpe, B K; Schindhelm, K

1999-06-01

Collagenous xenografts made from kangaroo tail tendon cross-linked with glutaraldehyde have a potential application in the reconstruction of massive digital tendon deficits. However, a limitation to the clinical use of these xenografts has been the optimization of collagen cross-linking, and subsequent bio-incorporation and retention of mechanical properties following implantation. The purpose of this study was to evaluate the effect of nitrous acid on modulating the biologic and mechanical properties of tendon xenografts cross-linked with glutaraldehyde. Tendon xenografts were pretreated with 0.1 or 0.01 M nitrous acid solution, prior to cross-linking in 2% glutaraldehyde and sterilization by gamma irradiation. Xenografts were implanted intramuscularly in rabbits to examine biocompatability, and also used to repair ovine digital extensor tendon deficits to evaluate functional incorporation. Histologically, intramuscularly implanted nitrous acid pretreated xenografts in rabbits had a greater degree of diffuse cellular infiltration into interstitial splits in the graft than controls after 12 weeks. Xenografts implanted in an ovine extensor tendon deficit were evaluated after 26 and 52 weeks. Rate of failure of tenorrhaphies between host tendon and xenografts overall (15/21) was significantly greater (P < 0.05) than for autografts (1/21), suggesting that the holding power of sutures in xenografts was inferior to that obtained in autografts. Tensile failure stress of midsections of both nitrous acid pretreated and control xenografts was about 100 MPa prior to implantation (time zero). After 26 and 52 weeks, failure stress of both types of xenografts was significantly less than at time zero (P < 0.05). At 52 weeks, failure stress of nitrous acid pretreated xenografts (47.4 +/- 3.1 MPa) was significantly less than control xenografts (63.7 +/- 5.4 MPa); (P < 0.05). However, nitrous acid pretreated xenografts were similar to control xenografts in failure load (357 +/- 29

Dorsal onlay (Barbagli technique) versus dorsal inlay (Asopa technique) buccal mucosal graft urethroplasty for anterior urethral stricture: a prospective randomized study.

PubMed

Aldaqadossi, Hussein; El Gamal, Samir; El-Nadey, Mohamed; El Gamal, Osama; Radwan, Mohamed; Gaber, Mohamed

2014-02-01

To compare both the dorsal onlay technique of Barbagli and the dorsal inlay technique of Asopa for the management of long anterior urethral stricture. From January 2010 to May 2012, a total of 47 patients with long anterior urethral strictures were randomized into two groups. The first group included 25 patients who were managed by dorsal onlay buccal mucosal graft urethroplasty. The second group included 22 patients who were managed by dorsal inlay buccal mucosal graft urethroplasty. Different clinical parameters, postoperative complications and success rates were compared between both groups. The overall success rate in the dorsal onlay group was 88%, whereas in the dorsal inlay group the success rate was 86.4% during the follow-up period. The mean operative time was significantly longer in the dorsal onlay urethroplasty group (205 ± 19.63 min) than in the dorsal inlay urethroplasty group (128 ± 4.9 min, P-value <0.0001). The average blood loss was significantly higher in the dorsal onlay urethroplasty group (228 ± 5.32 mL) than in the dorsal inlay urethroplasty group (105 ± 12.05 mL, P-value <0.0001). The dorsal onlay technique of Barbagli and the dorsal inlay technique of Asopa buccal mucosal graft urethroplasty provide similar success rates. The Asopa technique is easy to carry out, provides shorter operative time and less blood loss, and it is associated with fewer complications for anterior urethral stricture repair. © 2013 The Japanese Urological Association.

Establishing prostate cancer patient derived xenografts: lessons learned from older studies.

PubMed

Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W C; Williams, Elizabeth D; Raghavan, Derek

2015-05-01

Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding. Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43-46, XY, dic(1;12)(p11;p11

Establishing Prostate Cancer Patient Derived Xenografts: Lessons Learned From Older Studies

PubMed Central

Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W-C; Williams, Elizabeth D; Raghavan, Derek

2015-01-01

Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding. Results Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43�

The effect of fetal sex on customized fetal growth charts.

PubMed

Rizzo, Giuseppe; Prefumo, Federico; Ferrazzi, Enrico; Zanardini, Cristina; Di Martino, Daniela; Boito, Simona; Aiello, Elisa; Ghi, Tullio

2016-12-01

To evaluate the effect of fetal sex on singleton pregnancy growth charts customized for parental characteristics, race, and parity Methods: In a multicentric cross-sectional study, 8070 ultrasonographic examinations from low-risk singleton pregnancies between 16 and 40 weeks of gestation were considered. The fetal measurements obtained were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Quantile regression was used to examine the impact of fetal sex across the biometric percentiles of the fetal measurements considered together with parents' height, weight, parity, and race. Fetal gender resulted to be a significant covariate for BDP, HC, and AC with higher values for male fetuses (p ≤ 0.0009). Minimal differences were found among sexes for FL. Parity, maternal race, paternal height and maternal height, and weight resulted significantly related to the fetal biometric parameters considered independently from fetal gender. In this study, we constructed customized biometric growth charts for fetal sex, parental, and obstetrical characteristics using quantile regression. The use of gender-specific charts offers the advantage to define individualized normal ranges of fetal biometric parameters at each specific centile. This approach may improve the antenatal identification of abnormal fetal growth.

The neural and vascular effects of killed Su-Streptococcus pyogenes (OK-432) in preterm fetal sheep

PubMed Central

Cowie, R. V.; Stone, P. R.; Barrett, R.; Naylor, A. S.; Blood, A. B.; Gunn, A. J.

2010-01-01

Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is derived from gram-negative bacteria. Intrapleural injections of OK-432, a killed Su-strain of Streptococcus pyogenes, has been used to treat fetal chylothorax. In this study, we evaluated the neural and cardiovascular effects of OK-432 in preterm fetal sheep (104 ± 1 days, term 147 days). OK-432 (0.1 mg, n = 6) or saline vehicle (n = 7) was infused in the fetal pleura, and fetuses were monitored for 7 days. Blood samples were taken routinely for plasma nitrite measurement. Fetal brains were taken for histological assessment at the end of the experiment. Between 3 and 7 h postinjection, OK-432 administration was associated with transient suppression of fetal body and breathing movements and electtroencephalogram activity (P < 0.05), increased carotid and femoral vascular resistance (P < 0.05), but no change in blood pressure. Brain activity and behavior then returned to normal except in one fetus that developed seizures. OK-432 fetuses showed progressive, sustained vasodilatation (P < 0.05), with lower blood pressure after 4 days (P < 0.05), but normal heart rate. There were no changes in plasma nitrite levels. Histological studies showed bilateral infarction in the dorsal limb of the hippocampus of the fetus that developed seizures, but no injury in other fetuses. We conclude that a single low-dose injection of OK-432 can be associated with risk of focal cerebral injury in the preterm fetus and chronic central and peripheral vasodilatation that does not appear to be mediated by nitric oxide. PMID:20484698

The neural and vascular effects of killed Su-Streptococcus pyogenes (OK-432) in preterm fetal sheep.

PubMed

Bennet, L; Cowie, R V; Stone, P R; Barrett, R; Naylor, A S; Blood, A B; Gunn, A J

2010-08-01

Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is derived from gram-negative bacteria. Intrapleural injections of OK-432, a killed Su-strain of Streptococcus pyogenes, has been used to treat fetal chylothorax. In this study, we evaluated the neural and cardiovascular effects of OK-432 in preterm fetal sheep (104 +/- 1 days, term 147 days). OK-432 (0.1 mg, n = 6) or saline vehicle (n = 7) was infused in the fetal pleura, and fetuses were monitored for 7 days. Blood samples were taken routinely for plasma nitrite measurement. Fetal brains were taken for histological assessment at the end of the experiment. Between 3 and 7 h postinjection, OK-432 administration was associated with transient suppression of fetal body and breathing movements and electtroencephalogram activity (P < 0.05), increased carotid and femoral vascular resistance (P < 0.05), but no change in blood pressure. Brain activity and behavior then returned to normal except in one fetus that developed seizures. OK-432 fetuses showed progressive, sustained vasodilatation (P < 0.05), with lower blood pressure after 4 days (P < 0.05), but normal heart rate. There were no changes in plasma nitrite levels. Histological studies showed bilateral infarction in the dorsal limb of the hippocampus of the fetus that developed seizures, but no injury in other fetuses. We conclude that a single low-dose injection of OK-432 can be associated with risk of focal cerebral injury in the preterm fetus and chronic central and peripheral vasodilatation that does not appear to be mediated by nitric oxide.

Fetal endocrinology

PubMed Central

Kota, Sunil Kumar; Gayatri, Kotni; Jammula, Sruti; Meher, Lalit Kumar; Kota, Siva Krishna; Krishna, S. V. S.; Modi, Kirtikumar D.

2013-01-01

Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition. PMID:23961471

Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

PubMed

Ahn, Julie; Bishop, Justin A; Akpeng, Belinda; Pai, Sara I; Best, Simon R A

2015-02-01

Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis. © The Author(s) 2014.

Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

PubMed

Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2016-08-01

Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Correlation of fetal oxygen saturation to fetal heart rate patterns. Evaluation of fetal pulse oximetry with two different oxisensors.

PubMed

Luttkus, A K; Friedmann, W; Homm-Luttkus, C; Dudenhausen, J W

1998-03-01

The purpose of this study was the correlation of fetal oxygen saturation values to various fetal heart rate patterns, as well as to oxygen saturation values obtained by fetal blood analysis. These objectives need to be evaluated from the perspective that two generations of fetal oxisensors have been used. Two different oxisensor systems (FS10: 660+890 nm and FS14: 735+890 nm) and a blinded pulse oximeter (type N400, Nellcor Puritan Bennett) were utilized to monitor 112 fetuses. All data, including oxygen saturation, fetal heart rate patterns, signal and contact quality were stored on a personal computer and evaluated after delivery. The following median fetal oxygen saturation values were obtained: during reassuring fetal heart rate sequences 54% with the oxisensor FS10 and 48% with the newer FS14 oxisensor, during intervals of variable decelerations 43% with the FS10 oxisensor and 40% with the FS14 oxisensor. These differences between values obtained during normal and abnormal fetal heart rate patterns are significant. Due to non-reassuring fetal heart rate patterns 81 fetal blood analyses were performed. The values of pulse oximetry were 9% higher (6% for the FS14) than those of spectrophotometry. Correlation of both methods was r=0.66 (0.74 for the FS14). In combination with fetal heart rate monitoring, fetal pulse oximetry promises a better differentiation between low and high risk heart rate patterns. Oxygen saturation values from intermittent fetal blood sampling reassure the clinician concerning the accuracy of this new method of intrapartum fetal surveillance and underline the increased quality of the new generation of oxisensor using light of a wavelength of 735 and 890 nm.

Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

PubMed

Melamed, Nir; Whittle, Wendy; Kelly, Edmond N; Windrim, Rory; Seaward, P Gareth R; Keunen, Johannes; Keating, Sarah; Ryan, Greg

2015-06-01

Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection. A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration. Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT. Copyright © 2015. Published by

Serological aspects of rat tumour xenograft growth in athymic nude mice.

PubMed Central

Pimm, M. V.; Baldwin, R. W.

1979-01-01

The serum of athymic nude mice bearing rat tumour xenografts has been examined for tumour-specific antigen. With a sarcoma and a hepatoma, tumour-specific antigen expression continued in xenograft growths, and sera of tumour-bearing mice contained free antigen, assayed by its ability to neutralise reactivity of tumour-immune rat sera against tumour target cells in an indirect membrane-immunofluorescence test. In contrast, no anti-rat antibody was detectable in sera of mice bearing the xenografts, or rejecting cells injected in admixture with BCG. PMID:373782

A Comparative Study of Dorsal Buccal Mucosa Graft Substitution Urethroplasty by Dorsal Urethrotomy Approach versus Ventral Sagittal Urethrotomy Approach.

PubMed

Pahwa, Mrinal; Gupta, Sanjeev; Pahwa, Mayank; Jain, Brig D K; Gupta, Manu

2013-01-01

Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG) substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as described by Asopa. Operative time, success rate, satisfaction rate, and complications were compared between the two groups. Mean follow-up was 12 months (6-24 months). Results. Ventral urethrotomy group had considerably lesser operative time although the difference was not statistically significant. Patients in dorsal group had mean maximum flow rate of 19.6 mL/min and mean residual urine of 27 mL, whereas ventral group had a mean maximum flow rate of 18.8 and residual urine of 32 mL. Eighteen out of twenty patients voided well in each group, and postoperative imaging study in these patients showed a good lumen with no evidence of leak or extravasation. Conclusion. Though ventral sagittal urethrotomy preserves the blood supply of urethra and intraoperative time was less than dorsal urethrotomy technique, there was no statistically significant difference in final outcome using either technique.

A Comparative Study of Dorsal Buccal Mucosa Graft Substitution Urethroplasty by Dorsal Urethrotomy Approach versus Ventral Sagittal Urethrotomy Approach

PubMed Central

Pahwa, Mrinal; Gupta, Sanjeev; Pahwa, Mayank; Jain, Brig D. K.; Gupta, Manu

2013-01-01

Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG) substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as described by Asopa. Operative time, success rate, satisfaction rate, and complications were compared between the two groups. Mean follow-up was 12 months (6–24 months). Results. Ventral urethrotomy group had considerably lesser operative time although the difference was not statistically significant. Patients in dorsal group had mean maximum flow rate of 19.6 mL/min and mean residual urine of 27 mL, whereas ventral group had a mean maximum flow rate of 18.8 and residual urine of 32 mL. Eighteen out of twenty patients voided well in each group, and postoperative imaging study in these patients showed a good lumen with no evidence of leak or extravasation. Conclusion. Though ventral sagittal urethrotomy preserves the blood supply of urethra and intraoperative time was less than dorsal urethrotomy technique, there was no statistically significant difference in final outcome using either technique. PMID:24194754

Frequent Infection of Human Cancer Xenografts with Murine Endogenous Retroviruses in Vivo

PubMed Central

Naseer, Asif; Terry, Anne; Gilroy, Kathryn; Kilbey, Anna; Watts, Ciorsdaidh; Mackay, Nancy; Bell, Margaret; Mason, Susan; Blyth, Karen; Cameron, Ewan; Neil, James C.

2015-01-01

Infection of human cancer xenografts in mice with murine leukemia viruses (MLVs) is a long-standing observation, but the likelihood of infection in vivo and its biological consequences are poorly understood. We therefore conducted a prospective study in commonly used xenograft recipient strains. From BALB/c nude mice engrafted with MCF7 human mammary carcinoma cells, we isolated a virus that was virtually identical to Bxv1, a locus encoding replication-competent xenotropic MLV (XMLV). XMLV was detected in 9/17 (53%) independently isolated explants. XMLV was not found in primary leukemias or in THP1 leukemia cells grown in Bxv1-negative NSG (NOD/SCID/γCnull) mice, although MCF7 explants harbored replication-defective MLV proviruses. To assess the significance of infection for xenograft behavior in vivo, we examined changes in growth and global transcription in MCF7 and the highly susceptible Raji Burkitt lymphoma cell line chronically infected with XMLV. Raji cells showed a stronger transcriptional response that included up-regulation of chemokines and effectors of innate antiviral immunity. In conclusion, the risk of de novo XMLV infection of xenografts is high in Bxv1 positive mice, while infection can have positive or negative effects on xenograft growth potential with significant consequences for interpretation of many xenograft studies. PMID:25912714

A biomechanical comparison of four fixed-angle dorsal plates in a finite element model of dorsally-unstable radius fracture.

PubMed

Knežević, Josip; Kodvanj, Janoš; Čukelj, Fabijan; Pamuković, Frane; Pavić, Arsen

2017-11-01

To compare the finite element models of two different composite radius fracture patterns, reduced and stabilised with four different fixed-angle dorsal plates during axial, dorsal and volar loading conditions. Eight different plastic models representing four AO/ASIF type 23-A3 distal radius fractures and four AO/ASIF 23-C2 distal radius fractures were obtained and fixed each with 1 of 4 methods: a standard dorsal non-anatomical fixed angle T-plate (3.5mm Dorsal T-plate, Synthes), anatomical fixed-angle double plates (2.4mm LCP Dorsal Distal Radius, Synthes), anatomical fixed angle T-plate (2.4mm Acu-Loc Dorsal Plate, Acumed) or anatomical variable-angle dorsal T-plate (3.5mm, Dorsal Plate, Zrinski). Composite radius with plate and screws were scanned with a 3D optical scanner and later processed in Abaqus Software to generate the finite element model. All models were axially loaded at 3 points (centrally, volarly and dorsally) with 50 N forces to avoid the appearance of plastic deformations of the models. Total displacements at the end of the bone and the stresses in the bones and plates were determined and compared. Maximal von Mises stress in bone for 3-part fracture models was very similar to that in 2-part fracture models. The biggest difference between models and the largest displacements were seen during volar loading. The stresses in all models were the highest above the fracture gap. The best performance in all parameters tested was with the Zrinski plate and the most modest results were with the Synthes T-plate. There was no significant difference between 2-part (AO/ASIF type 23-A3) and 3-part (AO/ASIF 23-C2) fracture models. Maximal stresses in the plates appeared above the fracture gap; therefore, it is worth considering the development of plates without screw holes above the gap. © 2017 Elsevier Ltd. All rights reserved.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, III, Robert A. (Inventor)

1996-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, Robert A., III (Inventor)

1994-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate is presented. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Fetal Surgery

PubMed Central

Laberge, Jean-Martin

1986-01-01

Fetal surgery has come of age. For decades experimental fetal surgery proved essential in studying normal fetal physiology and development, and pathophysiology of congenital defects. Clinical fetal surgery started in the 1960s with intrauterine transfusions. In the 1970s, the advent of ultrasonography revolutionized fetal diagnosis and created a therapeutic vacuum. Fetal treatment, medical and surgical, is slowly trying to fill the gap. Most defects detected are best treated after birth, some requiring a modification in the time, mode and place of delivery for optimal obstetrical and neonatal care. Surgical intervention in utero should be considered for malformations that cause progressive damage to the fetus, leading to death or severe morbidity; that can be corrected or palliated in utero with a reasonable expectation of normal postnatal development; that cannot wait to be corrected after birth, even considering pre-term delivery; that are not accompanied by chromosomal or other major anomalies. At present, congenital hydronephrosis is the most common indication for fetal surgery, followed by obstructive hydrocephalus. Congenital diaphragmatic hernia also fulfills the criteria, but its correction poses more problems, and no clinical attempts have been reported so far. In the future many other malformations or diseases may become best treated in utero. The ethical and moral issues are complex and need to be discussed as clinical and experimental progress is made. PMID:21267309

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

PubMed Central

Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

2016-01-01

Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms

The quality of fetal arm movements as indicators of fetal stress.

PubMed

Reissland, Nadja; Francis, Brian

2010-12-01

Although a number of studies have found that maternal stress affects the fetus, it is unclear whether jerky fetal movements observed on ultrasound scans are indicative of fetal stress, or whether they are part of normal development. The present study was designed to examine the relationship between jerky fetal arm movements in relation to fetal age and stress. Video recordings were made of routine ultrasound scans of 57 fetuses (age range 8 to 33 weeks) classified into three age groups: 1st trimester (8-12 weeks, N=9), 2nd trimester (13-24 weeks, N=38), and 3rd trimester (26-33 weeks, N=10). Following previous research on stress behaviour in neonates, a fetal index of stress was derived from frequency of hiccup, back arch and rhythmical mouthing. Results indicated that while stress level was unrelated to fetal age, jerkiness of arm movements was significantly associated with the fetal stress index but not age. Our findings suggest that jerky arm movements in fetuses are suggestive of fetal stress. Copyright © 2010 Elsevier Ltd. All rights reserved.

Personal authentication through dorsal hand vein patterns

NASA Astrophysics Data System (ADS)

Hsu, Chih-Bin; Hao, Shu-Sheng; Lee, Jen-Chun

2011-08-01

Biometric identification is an emerging technology that can solve security problems in our networked society. A reliable and robust personal verification approach using dorsal hand vein patterns is proposed in this paper. The characteristic of the approach needs less computational and memory requirements and has a higher recognition accuracy. In our work, the near-infrared charge-coupled device (CCD) camera is adopted as an input device for capturing dorsal hand vein images, it has the advantages of the low-cost and noncontact imaging. In the proposed approach, two finger-peaks are automatically selected as the datum points to define the region of interest (ROI) in the dorsal hand vein images. The modified two-directional two-dimensional principal component analysis, which performs an alternate two-dimensional PCA (2DPCA) in the column direction of images in the 2DPCA subspace, is proposed to exploit the correlation of vein features inside the ROI between images. The major advantage of the proposed method is that it requires fewer coefficients for efficient dorsal hand vein image representation and recognition. The experimental results on our large dorsal hand vein database show that the presented schema achieves promising performance (false reject rate: 0.97% and false acceptance rate: 0.05%) and is feasible for dorsal hand vein recognition.

Contribution of fetal brain MRI in management of severe fetal anemia.

PubMed

Ghesquière, L; Houfflin-Debarge, V; Verpillat, P; Fourquet, T; Joriot, S; Coulon, C; Vaast, P; Garabedian, C

2018-06-06

Intrauterine transfusion (IUT) has changed fetal anemia prognosis. However, long-term neurodevelopmental outcome is altered in 5% of children. Our objective was to study the contribution of fetal MRI to diagnosis brain lesions in case of fetal anemia. Retrospective monocentric descriptive study from 2005 to 2016, including all patients followed for fetal anemia requiring IUT. The indications for MRI were: hydrops fetalis and / or hemoglobin <5 g / dL and / or more than 3 IUTs and / or acute severe anemia and / or ultrasound abnormality. Fetal and neonatal outcome and pediatric neurological monitoring were studied. 89 patients were followed for fetal anemia with IUT and 28 (29.1%) had fetal MRI, 12 of which were abnormal. Two out of twelve had abnormal ultrasound. Seven out of twelve had poor neurological prognosis: 2 medical terminations of pregnancy were performed; 2 children had severe developmental delay and 3 children had schooling difficulties. Five out of twelve children had favorable neurological prognosis. MRI of the fetal brain makes it possible to better detect brain lesions than ultrasound does in the management of severe fetal anemia and seems particularly appropriate in cases of acute anemia. Copyright © 2018 Elsevier B.V. All rights reserved.

Fetal acoustic stimulation test for early intrapartum fetal monitoring.

PubMed

Goonewardene, M; Hanwellage, K

2011-03-01

The fetal acoustic stimulation test (FAST) is a simple cost effective screening test for antenatal fetal monitoring. The aim of the study was to evaluate the FAST as a screening test for early intrapartum fetal well being. An initial non stress test (NST) followed by a FAST using corometric model 146 was carried out in 486 participants in early labour with uncomplicated singleton pregnancies and > 32 weeks gestation. A repeat NST was recorded in the participants who had an initial non reactive NST. The results of the NST and FAST were compared with fetal outcome. Maternal perception of fetal movements after FAST, results of NST before and after FAST, and the babies' 5 minute APGAR scores were measured. Of the 486 participants 413 (85%) noticed fetal movements after FAST. Initial NST was non reactive in 203 (42%) but 149 (31%) became reactive after FAST. Compared to the NST, FAST had a better sensitivity (97% vs 62%, p < 0.001), specificity (100% vs 87%, p = 0.017), positive predictive value (100% vs 98%, p = 0.024), negative predictive value (79% vs 17%, p < 0.001) and accuracy (99%vs 64%, p < 0.001) in predicting 5 minute APGAR < 7 in the baby. FAST is a reliable screening test for assessing fetal well being in early labour. It complements the NST and is better than the NST alone.

Comparative anatomy of the dorsal hump in mature Pacific salmon.

PubMed

Susuki, Kenta; Ban, Masatoshi; Ichimura, Masaki; Kudo, Hideaki

2017-07-01

Mature male Pacific salmon (Genus Oncorhynchus) demonstrate prominent morphological changes, such as the development of a dorsal hump. The degree of dorsal hump formation depends on the species in Pacific salmon. It is generally accepted that mature males of sockeye (O. nerka) and pink (O. gorbuscha) salmon develop most pronounced dorsal humps. The internal structure of the dorsal hump in pink salmon has been confirmed in detail. In this study, the dorsal hump morphologies were analyzed in four Pacific salmon species inhabiting Japan, masu (O. masou), sockeye, chum (O. keta), and pink salmon. The internal structure of the dorsal humps also depended on the species; sockeye and pink salmon showed conspicuous development of connective tissue and growth of bone tissues in the dorsal tissues. Masu and chum salmon exhibited less-pronounced increases in connective tissues and bone growth. Hyaluronic acid was clearly detected in dorsal hump connective tissue by histochemistry, except for in masu salmon. The lipid content in dorsal hump connective tissue was richer in masu and chum salmon than in sockeye and pink salmon. These results revealed that the patterns of dorsal hump formation differed among species, and especially sockeye and pink salmon develop pronounced dorsal humps through both increases in the amount of connective tissue and the growth of bone tissues. In contrast, masu and chum salmon develop their dorsal humps by the growth of bone tissues, rather than the development of connective tissue. © 2017 Wiley Periodicals, Inc.

Fetal behavioral teratology.

PubMed

Visser, Gerard H A; Mulder, Eduard J H; Tessa Ververs, F F

2010-10-01

Ultrasound studies of fetal motor behavior provide direct – in vivo – insight in the functioning of the motor component of the fetal central nervous system. In this article, studies are reviewed showing changes in the first timetable of appearance of fetal movements, changes in quality and/or quantity of movements and disturbances in the development of fetal behavioral states in case of endogenous malfunctions, maternal diseases and exogenous behavioral teratogens.

Widespread neuronal degeneration in rats following oral administration of methylmercury during the postnatal developing phase: a model of fetal-type minamata disease.

PubMed

Sakamoto, M; Wakabayashi, K; Kakita, A; Hitoshi Takahashi; Adachi, T; Nakano, A

1998-02-16

The neurotoxicity of methylmercury (MeHg) treatment during the postnatal developing phase in rats was studied. Rats on postnatal day 1 were orally administered 5 mg/kg/day methylmercury chloride (MMC) for more than 30 consecutive days. Body weight loss began 26 days after MMC was administered, and severe paralysis of the hind-limbs and unsteadiness appeared subsequently. Histopathologically, the widespread neuronal degeneration was observed in the cerebral neocortex, neostriatum, red nucleus, brainstem, cerebellum and spinal dorsal root ganglia on day 32. The widespread distribution of the lesions was quite similar to that in fetal cases of MeHg intoxication in Minamata, Japan. These findings suggest that MMC treatment during the postnatal development phase in rats produce a good model of fetal-type Minamata disease. Copyright 1998 Elsevier Science B.V.

Ethics of fetal tissue transplantation.

PubMed Central

Sanders, L M; Giudice, L; Raffin, T A

1993-01-01

Now that the Clinton Administration has overturned the ban on federal funding for fetal tissue transplantation, old ethical issues renew their relevance and new ethical issues arise. Is fetal tissue transplantation necessary and beneficial? Are fetal rights violated by the use of fetal tissue in research? Is there a moral danger that the potential of fetal tissue donation will encourage elective abortions? Should pregnant women be allowed to designate specific fetal transplant recipients? What criteria should be used to select fetal tissue transplants? Whose consent should be required for the use of fetal tissue for transplantation? We review the current state of clinical research with fetal tissue transplantation, the legal history of fetal tissue research, the major arguments against the use of fetal tissue for transplantation, and the new postmoratorium ethical dilemmas. We include recommendations for guidelines to govern the medical treatment of fetal tissue in transplantation. Images PMID:8236984

Fetal and maternal outcomes in pregnancies complicated with fetal macrosomia.

PubMed

Alsammani, Mohamed Alkahatim; Ahmed, Salah Roshdy

2012-06-01

Fetal macrosomia remains a considerable challenge in current obstetrics due to the fetal and maternal complications associated with this condition. This study was designed to determine the prevalence of fetal macrosomia and associated fetal and maternal morbidity and mortality in the Al Qassim Region of Saudi Arabia. This register-based study was conducted from January 1, 2011 through December 30, 2011 at the Maternity and Child Hospital, Qassim, Saudi Arabia. Macrosomia was defined as birth weight of 4 kg or greater. Malformed babies and those born dead were excluded. The total number of babies delivered was 9241; of these, 418 were macrosomic. Thus, the prevalence of fetal macrosomia was 4.5%. The most common maternal complications were postpartum hemorrhage (5 cases, 1.2%), perineal tear (7 cases, 1.7%), cervical lacerations (3 cases, 0.7%), and shoulder dystocia (40 cases, 9.6%) that resulted in 4 cases of Erb's palsy (0.96%), and 6 cases of bone fractures (1.4%). The rate of cesarean section among women delivering macrosomic babies was 47.6% (199), while 52.4% (219) delivered vaginally. Despite extensive efforts to reduce fetal and maternal complications associated with macrosomia, considerable fetal and maternal morbidity remain associated with this condition.

Sunscreen Use on the Dorsal Hands at the Beach

PubMed Central

Warren, Donald B.; Riahi, Ryan R.; Hobbs, Jason B.; Wagner, Richard F.

2013-01-01

Background. Since skin of the dorsal hands is a known site for the development of cutaneous squamous cell carcinoma, an epidemiologic investigation was needed to determine if beachgoers apply sunscreen to the dorsal aspect of their hands as frequently as they apply it to other skin sites. Aim. The aim of the current study was to compare the use of sunscreen on the dorsal hands to other areas of the body during subtropical late spring and summer sunlight exposure at the beach. Materials and Methods. A cross-sectional survey from a convenience sample of beachgoers was designed to evaluate respondent understanding and protective measures concerning skin cancer on the dorsal hands in an environment with high natural UVR exposure. Results. A total of 214 surveys were completed and analyzed. Less than half of subjects (105, 49%) applied sunscreen to their dorsal hands. Women applied sunscreen to the dorsal hands more than men (55% women versus 40% men, P = 0.04). Higher Fitzpatrick Skin Type respondents were less likely to protect their dorsal hands from ultraviolet radiation (P = 0.001). Conclusions. More public education focused on dorsal hand protection from ultraviolet radiation damage is necessary to reduce the risk for squamous cell carcinomas of the hands. PMID:23840956

Temporal morphologic changes in human colorectal carcinomas following xenografting.

PubMed

Barkla, D H; Tutton, P J

1983-03-01

The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

Fetal electrocardiogram (ECG) for fetal monitoring during labour.

PubMed

Neilson, James P

2015-12-21

Hypoxaemia during labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably the relation of the PR to RR intervals, and elevation or depression of the ST segment. Technical systems have therefore been developed to monitor the fetal ECG during labour as an adjunct to continuous electronic fetal heart rate monitoring with the aim of improving fetal outcome and minimising unnecessary obstetric interference. To compare the effects of analysis of fetal ECG waveforms during labour with alternative methods of fetal monitoring. The Cochrane Pregnancy and Childbirth Group's Trials Register (latest search 23 September 2015) and reference lists of retrieved studies. Randomised trials comparing fetal ECG waveform analysis with alternative methods of fetal monitoring during labour. One review author independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. One review author assessed the quality of the evidence using the GRADE approach. Seven trials (27,403 women) were included: six trials of ST waveform analysis (26,446 women) and one trial of PR interval analysis (957 women). The trials were generally at low risk of bias for most domains and the quality of evidence for ST waveform analysis trials was graded moderate to high. In comparison to continuous electronic fetal heart rate monitoring alone, the use of adjunctive ST waveform analysis made no obvious difference to primary outcomes: births by caesarean section (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.96 to 1.08; six trials, 26,446 women; high quality evidence); the number of babies with severe metabolic acidosis at birth (cord arterial pH less than 7.05 and base deficit greater than 12 mmol/L) (average RR 0.72, 95% CI 0.43 to 1.20; six trials, 25,682 babies; moderate quality evidence); or babies with neonatal encephalopathy (RR 0.61, 95% CI 0.30 to 1.22; six trials, 26,410 babies; high quality evidence). There were, however, on average

Dorsal Augmentation with Homologous Rib.

PubMed

Kridel, Russell W H; Sturm, Angela K

2017-04-01

Dorsal augmentation grafts are used to reconstruct and raise the nasal dorsum in patients with dorsal saddling due to trauma, infection, or previous nasal surgery, as well as in patients with a narrow, congenitally low, and/or wide dorsum. Alloplastic implants and various biomaterials are available for grafting, each with advantages and disadvantages. Although autologous septal cartilage is a preferable and often convenient source of cartilage, it is frequently not sufficient for large volume dorsal augmentation, nor is it available in patients who have had septoplasty, infection, previous rhinoplasty with grafting, or significant trauma. Ear cartilage may be used but it is difficult to make homogenous and smooth, and dorsal irregularities can be seen in the long term especially in thin-skinned patients. For these reasons, we frequently use irradiated costal cartilage from tissue banks as our grafting source, thereby eliminating the morbidity of harvesting the patient's own rib. Proper surgical techniques, the use of antibiotics, and proper sculpting and placement of the cartilage limits complications such as warping, resorption, infection, and extrusion. Irradiated homograft costal cartilage grafts have been used successfully in large numbers of patients with long-term follow-up with low complication rates and serve as a welcome alternative to harvesting a patient's rib cartilage. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Incidence of fetal macrosomia: maternal and fetal morbidity].

PubMed

Rodríguez-Rojas, R R; Cantú-Esquivel, M G; Benavides-de la Garza, L; Benavides-de Anda, L

1996-06-01

The macrosomia is an obstetric eventuality associated to high maternal-fetal morbidity-mortality. This assay was planned in order to know the incidence of macrosomia in our institution, the relation between vaginal and abdominal deliveries and the fetal-maternal morbidity we reviewed 3590 records and we found 5.6% incidence of macrosomia in the global obstetric population. There was 58% of vaginal deliveries, 68% of the newborn were male. The main complications were in the C. sections, 2 laceration of the hysterectomy, and 2 peroperative atonias. In the vaginal deliveries, the lacerations of III and IV grade were 9 of each grade. The main fetal complications were 5 slight to severe asphyxia and 4 shoulder dystocias. This assay concludes that the macrosomia in our service is similar to the already published ones, a 42% were C. section and the maternal-fetal morbidity was low.

The use of non-invasive fetal electrocardiography in diagnosing second-degree fetal atrioventricular block.

PubMed

Lakhno, Igor; Behar, Joachim A; Oster, Julien; Shulgin, Vyacheslav; Ostras, Oleksii; Andreotti, Fernando

2017-01-01

Complete atrioventricular block in fetuses is known to be mostly associated with autoimmune disease and can be irreversible if no steroids treatment is provided. Conventional methods used in clinical practice for diagnosing fetal arrhythmia are limited since they do not reflect the primary electrophysiological conduction processes that take place in the myocardium. The non-invasive fetal electrocardiogram has the potential to better support fetal arrhythmias diagnosis through the continuous analysis of the beat to beat variation of the fetal heart rate and morphological analysis of the PQRST complex. We present two retrospective case reports on which atrioventricular block diagnosis could have been supported by the non-invasive fetal electrocardiogram. The two cases comprised a 22-year-old pregnant woman with the gestational age of 31 weeks and a 25-year-old pregnant woman with the gestational age of 41 weeks. Both women were admitted to the Department of Maternal and Fetal Medicine at the Kyiv and Kharkiv municipal perinatal clinics. Patients were observed using standard fetal monitoring methods as well as the non-invasive fetal electrocardiogram. The non-invasive fetal electrocardiographic recordings were analyzed retrospectively, where it is possible to identify the presence of the atrioventricular block. This study demonstrates, for the first time, the feasibility of the non-invasive fetal electrocardiogram as a supplementary method to diagnose of the fetal atrioventricular block. Combined with current fetal monitoring techniques, non-invasive fetal electrocardiography could support clinical decisions.

Surgical Strategy and Techniques for Low-Profile Dorsal Plating in Treating Dorsally Displaced Unstable Distal Radius Fractures

PubMed Central

Hamada, Yoshitaka; Gotani, Hiroyuki; Hibino, Naohito; Tanaka, Yoshitaka; Satoh, Ryousuke; Sasaki, Kousuke; Kanchanathepsak, Thepparat

2016-01-01

Background The low-profile dorsal locking plating (DLP) technique is useful for treating dorsally comminuted intra-articular distal radius fractures; however, due to the complications associated with DLP, the technique is not widely used. Methods A retrospective review of 24 consecutive cases treated with DLP were done. Results All cases were classified into two types by surgical strategy according to the fracture pattern. In type 1, there is a volar fracture line distal to the watershed line in the dorsally displaced fragment, and this type is treated by H-framed DLP. In type 2, the displaced dorsal die-punch fragment is associated with a minimally displaced styloid shearing fracture or a transverse volar fracture line. We found that the die-punch fragment was reduced by the buttress effect of small l-shaped DLP after stabilization of the styloid shearing for the volar segment by cannulated screws from radial styloid processes. At 6 months after surgery, outcomes were good or excellent based on the modified Mayo wrist scores with no serious complications except one case. The mean range of motion of each type was as follows: the palmar flexion was 50, 65 degrees, dorsiflexion was 70, 75 degrees, supination was 85, 85 degrees, and pronation was 80, 80 degrees; in type 1 and 2, respectively. Conclusion DLP is a useful technique for the treatment of selected cases of dorsally displaced, comminuted intra-articular fractures of the distal radius with careful soft tissue coverage. PMID:28428920

Agenesis of the dorsal pancreas

PubMed Central

Schnedl, Wolfgang J; Piswanger-Soelkner, Claudia; Wallner, Sandra J; Krause, Robert; Lipp, Rainer W

2009-01-01

During the last 100 years in medical literature, there are only 54 reports, including the report of Pasaoglu et al (World J Gastroenterol 2008; 14: 2915-2916), with clinical descriptions of agenesis of the dorsal pancreas in humans. Agenesis of the dorsal pancreas, a rare congenital pancreatic malformation, is associated with some other medical conditions such as hyperglycemia, abdominal pain, pancreatitis and a few other diseases. In approximately 50% of reported patients with this congenital malformation, hyperglycemia was demonstrated. Evaluation of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose, oral glucose tolerance test, glycated hemoglobin and medical treatment would be a future goal. Since autosomal dominant transmission has been suggested in single families, more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this disease. With this letter to the editor, we aim to increase available information for the better understanding of this rare disease. PMID:19140241

Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia.

PubMed

Wang, Xu-Yang; Gu, Pei-Yuan; Chen, Shi-Wen; Gao, Wen-Wei; Tian, Heng-Li; Lu, Xiang-He; Zheng, Wei-Ming; Zhuge, Qi-Chuan; Hu, Wei-Xing

2015-11-01

In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1-5 and L7-S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

Uterine artery blood flow, fetal hypoxia and fetal growth

PubMed Central

Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

2015-01-01

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

[Expressional change of nitric oxide synthases in dorsal root ganglia of cats after selective dorsal rhizotomy].

PubMed

Qin, Hua-li; Zhou, Xue; Zhang, Wei; Chen, Si-xiu

2004-01-01

To examine the expressional change of nitric oxide synthase (NOS) in the injured dorsal root ganglia (DRG) and the ipsilateral adjacent uninjured DRG after selective dorsal rhizotomy. Immunochemical ABC method was used to detect the distribution of immunoreaction complex of NOS isoforms--nNOS and eNOS, and quantitative analysis was conducted to get the number of nNOS-immunoreactivity (nNOS-IR) neurons in normal DRG, dorsal rhizotomized DRG and spared DRG from adult cats on the 6th day after operation. This operating model was made by rhizotomizing unilateral L1-L5 dorsal roots and leaving L6 as a spared root. nNOS-immunoreactants were mainly distributed in the small-sized neurons in the DRG of cat. The percentage of nNOS-expressing small-sized neurons increased in the deafferentated L5 DRG (29.74%) when compared with the contralateral DRG (19.35%), and it also increased in the spared DRG (24.22%), compared with the contralateral DRG (18.61%). eNOS-IR was not observed in the DRG of adult cats. nNOS/NO up-regulated in DRG neurons is involved in a wide variety of biological functions under physiological and lesion-induced pathophysiological conditions in nerve system.

Antenatal fetal heart rate and "maternal intuition" as predictors of fetal sex.

PubMed

Genuis, S; Genuis, S K; Chang, W C

1996-06-01

To determine if the antenatal fetal heart rate is a reliable predictor of fetal sex, if there is any correlation between "maternal intuition" and fetal gender, and if maternal intuition favors one sex over the other. Two hundred twelve consecutive maternity patients with singleton gestations underwent a total of 2,261 antepartum visits. Fetal heart rate assessment was carried out between 14 and 41 weeks of gestation. At 32 weeks, participants were asked if they had a strong intuitive feeling regarding the fetal gender. Following birth, data on the infant were recorded, and the information was analyzed. There was no significant difference in the baseline fetal heart rate between male and female fetuses at any recorded gestational age. One hundred ten patients (51.9%) in the sample indicated a strong belief about the sex of their fetuses, with the majority (63.6%) predicting a male. The accuracy of maternal intuition, however, was not significantly different from that of random guessing. In the current era of declining family size, an increased focus on absolute reproductive choice and proliferating reproductive technological services, prenatal sex determination and sex selection will continue to provoke increasing attention. Fetal heart rate determination and maternal intuition, however, are not valid predictors of fetal gender.

Internal fetal monitoring (image)

MedlinePlus

Internal fetal monitoring involves placing a electrode directly on the fetal scalp through the cervix. This test is performed to evaluate fetal heart rate and variability between beats, especially ...

Expressing Constitutively Active Rheb in Adult Dorsal Root Ganglion Neurons Enhances the Integration of Sensory Axons that Regenerate Across a Chondroitinase-Treated Dorsal Root Entry Zone Following Dorsal Root Crush

PubMed Central

Wu, Di; Klaw, Michelle C.; Kholodilov, Nikolai; Burke, Robert E.; Detloff, Megan R.; Côté, Marie-Pascale; Tom, Veronica J.

2016-01-01

While the peripheral branch of dorsal root ganglion neurons (DRG) can successfully regenerate after injury, lesioned central branch axons fail to regrow across the dorsal root entry zone (DREZ), the interface between the dorsal root and the spinal cord. This lack of regeneration is due to the limited regenerative capacity of adult sensory axons and the growth-inhibitory environment at the DREZ, which is similar to that found in the glial scar after a central nervous system (CNS) injury. We hypothesized that transduction of adult DRG neurons using adeno-associated virus (AAV) to express a constitutively-active form of the GTPase Rheb (caRheb) will increase their intrinsic growth potential after a dorsal root crush. Additionally, we posited that if we combined that approach with digestion of upregulated chondroitin sulfate proteoglycans (CSPG) at the DREZ with chondroitinase ABC (ChABC), we would promote regeneration of sensory axons across the DREZ into the spinal cord. We first assessed if this strategy promotes neuritic growth in an in vitro model of the glial scar containing CSPG. ChABC allowed for some regeneration across the once potently inhibitory substrate. Combining ChABC treatment with expression of caRheb in DRG significantly improved this growth. We then determined if this combination strategy also enhanced regeneration through the DREZ after dorsal root crush in adult rats in vivo. After unilaterally crushing C4-T1 dorsal roots, we injected AAV5-caRheb or AAV5-GFP into the ipsilateral C5-C8 DRGs. ChABC or PBS was injected into the ipsilateral dorsal horn at C5-C8 to digest CSPG, for a total of four animal groups (caRheb + ChABC, caRheb + PBS, GFP + ChABC, GFP + PBS). Regeneration was rarely observed in PBS-treated animals, whereas short-distance regrowth across the DREZ was observed in ChABC-treated animals. No difference in axon number or length between the ChABC groups was observed, which may be related to intraganglionic inflammation induced by the

A Real-Time Non-invasive Auto-bioluminescent Urinary Bladder Cancer Xenograft Model.

PubMed

John, Bincy Anu; Xu, Tingting; Ripp, Steven; Wang, Hwa-Chain Robert

2017-02-01

The study was to develop an auto-bioluminescent urinary bladder cancer (UBC) xenograft animal model for pre-clinical research. The study used a humanized, bacteria-originated lux reporter system consisting of six (luxCDABEfrp) genes to express components required for producing bioluminescent signals in human UBC J82, J82-Ras, and SW780 cells without exogenous substrates. Immune-deficient nude mice were inoculated with Lux-expressing UBC cells to develop auto-bioluminescent xenograft tumors that were monitored by imaging and physical examination. Lux-expressing auto-bioluminescent J82-Lux, J82-Ras-Lux, and SW780-Lux cell lines were established. Xenograft tumors derived from tumorigenic Lux-expressing auto-bioluminescent J82-Ras-Lux cells allowed a serial, non-invasive, real-time monitoring by imaging of tumor development prior to the presence of palpable tumors in animals. Using Lux-expressing auto-bioluminescent tumorigenic cells enabled us to monitor the entire course of xenograft tumor development through tumor cell implantation, adaptation, and growth to visible/palpable tumors in animals.

Fetal Abuse.

ERIC Educational Resources Information Center

Kent, Lindsey; And Others

1997-01-01

Five cases of fetal abuse by mothers suffering from depression are discussed. Four of the women had unplanned pregnancies and had considered termination of the pregnancy. Other factors associated with fetal abuse include pregnancy denial, pregnancy ambivalence, previous postpartum depression, and difficulties in relationships. Vigilance for…

Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace.

PubMed

East, Christine E; Leader, Leo R; Sheehan, Penelope; Henshall, Naomi E; Colditz, Paul B; Lau, Rosalind

2015-05-01

Fetal scalp blood sampling for lactate estimation may be considered following identification of an abnormal or non-reassuring fetal heart rate pattern. The smaller volume of blood required for this test, compared with the more traditional pH estimation, may improve sampling rates. The appropriate use of this practice mandates systematic review of its safety and clinical effectiveness prior to widespread introduction. To evaluate the effectiveness and risks of fetal scalp lactate sampling in the assessment of fetal well-being during labour, compared with no testing or alternative testing. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015). All published and unpublished randomised and quasi-randomised trials that compared fetal scalp lactate testing with no testing or alternative testing to evaluate fetal status in the presence of a non-reassuring cardiotocograph during labour. We used the standard methodological procedures of the Cochrane Pregnancy and Childbirth Group. Two review authors independently assessed the studies. The search identified two completed randomised controlled trials (RCTs) and two ongoing trials. The two published RCTs considered outcomes for 3348 mother-baby pairs allocated to either lactate or pH estimation of fetal blood samples when clinically indicated in labour. Overall, the published RCTs were of low or unclear risk of bias. There was a high risk of performance bias, because it would not have been feasible to blind clinicians or participants.No statistically significant between-group differences were found for neonatal encephalopathy (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.32 to 3.09, one study, 2992 infants) or death. No studies reported neonatal seizures. We had planned to report death with other morbidities, for example, neonatal encephalopathy; however, the data were not available in a format suitable for this, therefore death due to congenital abnormality was considered alone

Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.

PubMed

Cho, Yong Beom; Hong, Hye Kyung; Choi, Yoon-La; Oh, Ensel; Joo, Kyeung Min; Jin, Juyoun; Nam, Do-Hyun; Ko, Young-Hyeh; Lee, Woo Yong

2014-04-01

Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples. Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts. From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor. Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Morphology and morphometry of fetal liver at 16-26 weeks of gestation by magnetic resonance imaging: Comparison with embryonic liver at Carnegie stage 23.

PubMed

Hamabe, Yui; Hirose, Ayumi; Yamada, Shigehito; Uwabe, Chigako; Okada, Tomohisa; Togashi, Kaori; Kose, Katsumi; Takakuwa, Tetsuya

2013-06-01

Normal liver growth was described morphologically and morphometrically using magnetic resonance imaging (MRI) data of human fetuses, and compared with embryonic liver to establish a normal reference chart for clinical use. MRI images from 21 fetuses at 16-26 weeks of gestation and eight embryos at Carnegie stage (CS)23 were investigated in the present study. Using the image data, the morphology of the liver as well as its adjacent organs was extracted and reconstructed three-dimensionally. Morphometry of fetal liver growth was performed using simple regression analysis. The fundamental morphology was similar in all cases of the fetal livers examined. The liver tended to grow along the transversal axis. The four lobes were clearly recognizable in the fetal liver but not in the embryonic liver. The length of the liver along the three axes, liver volume and four lobes correlated with the bodyweight (BW). The morphogenesis of the fetal liver on the dorsal and caudal sides was affected by the growth of the abdominal organs, such as the stomach, duodenum and spleen, and retroperitoneal organs, such as the right adrenal gland and right kidney. The main blood vessels such as inferior vena cava, portal vein and umbilical vein made a groove on the surface of the liver. Morphology of the fetal liver was different from that of the embryonic liver at CS23. The present data will be useful for evaluating the development of the fetal liver and the adjacent organs that affect its morphology. © 2012 The Japan Society of Hepatology.

Fetal short time variation during labor: a non-invasive alternative to fetal scalp pH measurements?

PubMed

Schiermeier, Sven; Reinhard, Joscha; Hatzmann, Hendrike; Zimmermann, Ralf C; Westhof, Gregor

2009-01-01

To determine whether short time variation (STV) of fetal heart beat correlates with scalp pH measurements during labor. From 1279 deliveries, 197 women had at least one fetal scalp pH measurement. Using the CTG-Player, STVs were calculated from the electronically saved cardiotocography (CTG) traces and related to the fetal scalp pH measurements. There was no correlation between STV and fetal scalp pH measurements (r=-0.0592). Fetal STV is an important parameter with high sensitivity for antenatal fetal acidosis. This study shows that STV calculations do not correlate with fetal scalp pH measurements during labor, hence are not helpful in identifying fetal acidosis.

Fetal bile salt metabolism

PubMed Central

Smallwood, R. A.; Lester, R.; Piasecki, G. J.; Klein, P. D.; Greco, R.; Jackson, B. T.

1972-01-01

Bile salt metabolism was studied in fetal dogs 1 wk before term. The size and distribution of the fetal bile salt pool were measured, and individual bile salts were identified. The hepatic excretion of endogenous bile salts was studied in bile fistula fetuses, and the capacity of this excretory mechanism was investigated by the i.v. infusion of a load of sodium taurocholate-14C up to 20 times the endogenous pool size. The total fetal bile salt pool was 30.9±2.7 μmoles, of which two-thirds was in the fetal gallbladder. Expressed on a body weight basis, this was equal to approximately one-half the estimated pool size in the adult dog (119.2±11.3 vs. 247.5±33.1 μmoles/kg body wt). Measurable quantities of bile salt were found in small bowel (6.0±1.8 μmoles), large bowel (1.1±0.3 μmoles), liver (1.2±0.5 μmoles), and plasma (0.1±0.03 μmoles). Plasma bile salt levels were significantly greater in fetal than in maternal plasma (1.01±0.24 μg/ml vs. 0.36±0.06 μg/ml; P < 0.05). Fetal hepatic bile salt excretion showed a fall over the period of study from 2.04±0.34 to 0.30±0.07 μmoles/hr. The maximal endogenous bile salt concentration in fetal hepatic bile was 18.7±1.5 μmoles/ml. The concentration in fetal gallbladder bile was 73.9±8.6 μmoles/ml; and, in those studies in which hepatic and gallbladder bile could be compared directly, the gallbladder appeared to concentrate bile four- to fivefold. Taurocholate, taurochenodeoxycholate, and taurodeoxycholate were present in fetal bile, but no free bile salts were identified. The presence of deoxycholate was confirmed by thin-layer chromatography and gas liquid chromatography, and the absence of microorganisms in fetal gut suggests that it was probably transferred from the maternal circulation. After infusion of a taurocholate load, fetal hepatic bile salt excretion increased 30-fold, so that 85-95% of the dose was excreted by the fetal liver during the period of observation. Placental transfer accounted

Actions of (-)-baclofen on rat dorsal horn neurons.

PubMed

Kangrga, I; Jiang, M C; Randić, M

1991-10-25

The actions of a gamma-aminobutyric acid B (GABAB) agonist, (-)-baclofen, on the electrophysiological properties of neurons and synaptic transmission in the spinal dorsal horn (laminae I-IV) were examined by using intracellular recordings in spinal cord slice from young rats. In addition, the effects of baclofen on the dorsal root stimulation-evoked outflow of glutamate and aspartate from the spinal dorsal horn were examined by using high performance liquid chromatography (HPLC) with flourimetric detection. Superfusion of baclofen (5 nM to 10 microM) hyperpolarized, in a stereoselective and bicuculline-insensitive manner, the majority (86%) of tested neurons. The hyperpolarization was associated with a decrease in membrane resistance and persisted in a nominally zero-Ca2+, 10 mM Mg(2+)- or a TTX-containing solution. Our findings indicate that the hyperpolarizing effect of baclofen is probably due to an increase in conductance to potassium ions. Baclofen decreased the direct excitability of dorsal horn neurons, enhanced accommodation of spike discharge, and reduced the duration of Ca(2+)-dependent action potentials. Baclofen depressed, or blocked, excitatory postsynaptic potentials evoked by electrical stimulation of the dorsal roots. Spontaneously occurring synaptic potentials were also reversibly depressed by baclofen. Whereas baclofen did not produce any consistent change in the rate of the basal outflow of glutamate and aspartate, the stimulation-evoked release of the amino acids was blocked. The present results suggest that baclofen, by activating GABAB receptors, may modulate spinal afferent processing in the superficial dorsal horn by at least two mechanisms: (1) baclofen depresses excitatory synaptic transmission primarily by a presynaptic mechanism involving a decrease in the release of excitatory amino acids, and (2) at higher concentrations, the hyperpolarization and increased membrane conductance may contribute to the depressant effect of baclofen on

Prospective evaluation of the fetal heart using Fetal Intelligent Navigation Echocardiography (FINE).

PubMed

Garcia, M; Yeo, L; Romero, R; Haggerty, D; Giardina, I; Hassan, S S; Chaiworapongsa, T; Hernandez-Andrade, E

2016-04-01

To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart. In all women between 19 and 30 weeks' gestation with a normal fetal heart, an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: (1) fetal spine located between 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of fetal breathing, hiccups, or movement; and (4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated. One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance. In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS-Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. Published 2015. This article is a U.S. Government work and is in

Feature integration and object representations along the dorsal stream visual hierarchy

PubMed Central

Perry, Carolyn Jeane; Fallah, Mazyar

2014-01-01

The visual system is split into two processing streams: a ventral stream that receives color and form information and a dorsal stream that receives motion information. Each stream processes that information hierarchically, with each stage building upon the previous. In the ventral stream this leads to the formation of object representations that ultimately allow for object recognition regardless of changes in the surrounding environment. In the dorsal stream, this hierarchical processing has classically been thought to lead to the computation of complex motion in three dimensions. However, there is evidence to suggest that there is integration of both dorsal and ventral stream information into motion computation processes, giving rise to intermediate object representations, which facilitate object selection and decision making mechanisms in the dorsal stream. First we review the hierarchical processing of motion along the dorsal stream and the building up of object representations along the ventral stream. Then we discuss recent work on the integration of ventral and dorsal stream features that lead to intermediate object representations in the dorsal stream. Finally we propose a framework describing how and at what stage different features are integrated into dorsal visual stream object representations. Determining the integration of features along the dorsal stream is necessary to understand not only how the dorsal stream builds up an object representation but also which computations are performed on object representations instead of local features. PMID:25140147

Superficial Dorsal Vein Rupture Imitating Penile Fracture

PubMed Central

Topsakal, Medih; Kavukcu, Ender; Karadeniz, Tahir

2011-01-01

Dorsal vein rupture of the penis is a rare condition, and few cases have been reported in the literature. Herein we report a 41-year-old man who presented with mildly painful and acute swollen penis, which initially imitated a penile fracture but was surgically explored and shown to be a superficial dorsal vein rupture. PMID:21556219

Pancreatitis and agenesis of the dorsal pancreas.

PubMed

Oldenburg, B; van Leeuwen, M S; van Berge Henegouwen, G P; Koningsberger, J C

1998-10-01

We report a case of agenesis of the dorsal pancreas, complicated by pancreatitis and diabetes mellitus. A 39-year-old woman was referred for evaluation of a chronic pancreatitis. Abdominal spiral CT and ERP and MRCP demonstrated agenesis of the dorsal pancreas. The pathogenesis, clinical features and diagnosis of this very rarely reported disease are discussed.

Temporal morphologic changes in human colorectal carcinomas following xenografting.

PubMed Central

Barkla, D. H.; Tutton, P. J.

1983-01-01

The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:6829710

Value of amniocentesis versus fetal tissue for cytogenetic analysis in cases of fetal demise.

PubMed

Bryant Borders, Ann E; Greenberg, Jessica; Plaga, Stacey; Shepard-Hinton, Megan; Yates, Carin; Elias, Sherman; Shulman, Lee P

2009-01-01

Use of fetal tissue for cytogenetic analysis in cases of second- and third-trimester fetal demise frequently results in unacceptably high failure rates. We reviewed our ongoing use of amniocentesis prior to uterine evacuation to determine if this provided a better source of cells for cytogenetic analysis. We compared cytogenetic results using fetal tissues obtained following uterine evacuation to our ongoing use of amniotic fluid cell obtained by transabdominal amniocentesis prior to uterine evacuation from 2003 to 2008. In 49 of the 63 cases evaluated by fetal tissue biopsies performed after uterine evacuation, a karyotypic analysis was obtained (77.8%). Among the 38 cases evaluated by amniocentesis, an amniotic fluid sample and fetal cytogenetic results were obtained in all 38 (100%) cases. Our findings indicate that amniocentesis is a more reliable source of cytogenetic information than fetal tissue in cases of second- and third-trimester fetal demise.

Evaluation of Cytarabine Against Ewing Sarcoma Xenografts by the Pediatric Preclinical Testing Program

PubMed Central

Houghton, Peter J.; Morton, Christopher L.; Kang, Min; Reynolds, C. Patrick; Billups, Catherine A.; Favours, Edward; Payne-Turner, Debbie; Tucker, Chandra; Smith, Malcolm A.

2015-01-01

Treatment with the nucleoside analog cytarabine has been shown to mimic changes in gene expression associated with down-regulation of the EWS-FLI1 oncogene in Ewing sarcoma cell lines, selectively inhibit their growth in vitro, and cause tumor regression in athymic nude mice. For this report cytarabine was studied in vitro against a panel of 23 pediatric cancer cell lines and in vivo against 6 Ewing sarcoma xenografts. Acute lymphoblastic leukemia cell lines were the most sensitive to cytarabine in vitro (median IC50 9 nM), while Ewing sarcoma cell lines showed intermediate sensitivity (median IC50 232 nM). Cytarabine at a dose of 150 mg/kg administered daily 5× failed to significantly inhibit growth of five xenograft models, but reduced growth rate of the A673 xenograft by 50%. Cytarabine shows no differential in vitro activity against Ewing sarcoma cell lines and is ineffective in vivo against Ewing sarcoma xenografts at the dose and schedule studied. PMID:20979180

Human Fetal Brain Connectome: Structural Network Development from Middle Fetal Stage to Birth

PubMed Central

Song, Limei; Mishra, Virendra; Ouyang, Minhui; Peng, Qinmu; Slinger, Michelle; Liu, Shuwei; Huang, Hao

2017-01-01

Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20–40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20–35 PMW than during 35–40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural

Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers.

PubMed

Gaccioli, Francesca; Aye, Irving L M H; Sovio, Ulla; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-02-01

Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ultrasound screening for fetal growth restriction in the third trimester, but the evidence base is not strong. Implementation of universal ultrasound screening in low-risk women in France failed to reduce the risk of complications among small-for-gestational-age infants but did appear to cause iatrogenic harm to false positives. One strategy to making progress is to improve screening by developing more sensitive and specific tests with the key goal of differentiating between healthy small fetuses and those that are small through fetal growth restriction. As abnormal placentation is thought to be the major cause of fetal growth restriction, one approach is to combine fetal biometry with an indicator of placental dysfunction. In the past, these indicators were generally ultrasonic measurements, such as Doppler flow velocimetry of the uteroplacental circulation. However, another promising approach is to combine ultrasonic suspicion of small-for-gestational-age infant with a blood test indicating placental dysfunction. Thus far, much of the research on maternal serum biomarkers for fetal growth restriction has involved the secondary analysis of tests performed for other indications, such as fetal aneuploidies. An exemplar of this is pregnancy-associated plasma protein A. This blood test is performed primarily to assess the risk of Down syndrome, but women with low first-trimester levels are now serially scanned in later pregnancy due to associations with placental causes of

Unexpected fetal death during pregnancy--a problem of unrecognized fetal disorders during antenatal care?

PubMed

Künzel, Wolfgang; Misselwitz, Björn

2003-09-22

To investigate the causes of ante partum fetal death (APFD) and to evaluate the diagnostic methods for prevention. A population-based retrospective study was conducted in 293091 deliveries from 1996 to 2000 in the State of Hesse, Germany. The investigations focus on mortality of infants during pregnancy, separated between singletons of 37-42 weeks (n=361) and 23-36 weeks (n=550), and multiple births (n=76). In 44 cases, the gestational age was unknown and in 19 cases lower than 23 weeks or greater than 43 weeks. In total 1006 cases remained and were subject for evaluation. Perinatal mortality (PM) was 0.56%. APFD occurred in 1050 cases (0.3%), i.e. 63.5% of PM. Risk factors from the medical history during pregnancy could be identified in 515 cases (51.2%). Significant risk factors were social burden (odds ratio (OR) 58.3), diabetes mellitus (OR 5.4) and gestational diabetes (OR 2.1), psychological burden (OR 4.8), proteinuria (OR 2.8), maternal age (OR 1.7) and maternal smoking, depending on the number of cigarettes. The risk factors show a difference in significance, if related to the gestational age and multiple pregnancies. The contribution of malformations to APFD was 7.8%. There was however a number of unexpected fetal deaths with unidentified risk factors: n=415 (41.3%). In this group, fetal growth restriction was observed in 38.1%. Compared to control, APFD was three to five times higher in fetal growth retardation below the 10th percentile. Fetal death was closely related to fetal surveillance, i.e. the number of antenatal visits, ultrasound measurements, and fetal heart rate monitoring. Fetal ante partum fetal death can be reduced at least by 50%, if the available methods for fetal surveillance are employed aiming to detect indications of fetal oxygen deprivation at an early stage.

Impact of fetal death reporting requirements on early neonatal and fetal mortality rates and racial disparities.

PubMed

Tyler, Crystal P; Grady, Sue C; Grigorescu, Violanda; Luke, Barbara; Todem, David; Paneth, Nigel

2012-01-01

Racial disparities in infant and neonatal mortality vary substantially across the U.S. with some states experiencing wider disparities than others. Many factors are thought to contribute to these disparities, but state differences in fetal death reporting have received little attention. We examined whether such reporting requirements may explain national variation in neonatal and fetal mortality rates and racial disparities. We used data on non-Hispanic white and non-Hispanic black infants from the U.S. 2000-2002 linked birth/infant death and fetal death records to determine the degree to which state fetal death reporting requirements explain national variation in neonatal and fetal mortality rates and racial disparities. States were grouped depending upon whether they based the lower limit for fetal death reporting on birthweight alone, gestational age alone, both birthweight and gestational age, or required reporting of all fetal deaths. Traditional methods and the fetuses-at-risk approach were used to calculate mortality rates, 95% confidence intervals, and relative and absolute racial disparity measures in these four groups. States with birthweight-alone fetal death thresholds substantially underreported fetal deaths at lower gestations and slightly overreported neonatal deaths at older gestations. This finding was reflected by these states having the highest neonatal mortality rates and disparities, but the lowest fetal mortality rates and disparities. Using birthweight alone as a reporting threshold may promote some shift of fetal deaths to newborn deaths, contributing to racial disparities in neonatal mortality. The adoption of a uniform national threshold for reporting fetal deaths could reduce systematic differences in live birth and fetal death reporting.

[Autopsies for fetal anomalies].

PubMed

Kidron, Debora; Eidel, Jouly; Aviram, Rami

2013-06-01

Fetal autopsies are effective in identifying the cause and/or mechanisms leading to death in cases of intrauterine fetal death. Autopsies for fetal anomalies are different. To summarize our experience with 569 autopsies of fetal anomalies which were performed during an 18-year period. A retrospective analysis of 569 autopsies of fetal anomalies was conducted, out of a total of 1067 fetal autopsies. The pregnancy weeks were 14 - 41. Among 569 cases, 88% were termination of pregnancies, 10% intrauterine death and 2% perinatal deaths. The diagnosis of a syndrome or disease process was made when a constellation of gross and/or histologic findings was met. Specific diagnoses were offered in cases of cystic diseases of kidneys, types of dwarfism, tumors and fetal hydrops. Teratogenic (acquired) processes, such as congenital infections, thrombosis and cerebral hemorrhages, were differentiated from malformations. In cases of multiple congenital anomalies, documentation of the entire spectrum of malformations facilitated the genetic counseling. First and foremost, the autopsy is performed in the interest of the parents, with their written consent and in accordance with limitations and requests which they pose. Autopsy results provide feedback to the prenatal imaging. They assist in focusing the genetic counseling. Autopsy reports provide tools of control for the health authorities. Autopsies for fetal anomalies are time consuming. They require skill and experience. They are helpfuL when the prenatal diagnosis raises differential diagnosis. They are Less helpful when the diagnosis is clear, i.e. chromosomal trisomy.

Acquisition of the dorsal structures in chordate amphioxus.

PubMed

Morov, Arseniy R; Ukizintambara, Tharcisse; Sabirov, Rushan M; Yasui, Kinya

2016-06-01

Acquisition of dorsal structures, such as notochord and hollow nerve cord, is likely to have had a profound influence upon vertebrate evolution. Dorsal formation in chordate development thus has been intensively studied in vertebrates and ascidians. However, the present understanding does not explain how chordates acquired dorsal structures. Here we show that amphioxus retains a key clue to answer this question. In amphioxus embryos, maternal nodal mRNA distributes asymmetrically in accordance with the remodelling of the cortical cytoskeleton in the fertilized egg, and subsequently lefty is first expressed in a patch of blastomeres across the equator where wnt8 is expressed circularly and which will become the margin of the blastopore. The lefty domain co-expresses zygotic nodal by the initial gastrula stage on the one side of the blastopore margin and induces the expression of goosecoid, not-like, chordin and brachyury1 genes in this region, as in the oral ectoderm of sea urchin embryos, which provides a basis for the formation of the dorsal structures. The striking similarity in the gene regulations and their respective expression domains when comparing dorsal formation in amphioxus and the determination of the oral ectoderm in sea urchin embryos suggests that chordates derived from an ambulacrarian-type blastula with dorsoventral inversion. © 2016 The Authors.

Acquisition of the dorsal structures in chordate amphioxus

PubMed Central

Morov, Arseniy R.; Ukizintambara, Tharcisse; Sabirov, Rushan M.

2016-01-01

Acquisition of dorsal structures, such as notochord and hollow nerve cord, is likely to have had a profound influence upon vertebrate evolution. Dorsal formation in chordate development thus has been intensively studied in vertebrates and ascidians. However, the present understanding does not explain how chordates acquired dorsal structures. Here we show that amphioxus retains a key clue to answer this question. In amphioxus embryos, maternal nodal mRNA distributes asymmetrically in accordance with the remodelling of the cortical cytoskeleton in the fertilized egg, and subsequently lefty is first expressed in a patch of blastomeres across the equator where wnt8 is expressed circularly and which will become the margin of the blastopore. The lefty domain co-expresses zygotic nodal by the initial gastrula stage on the one side of the blastopore margin and induces the expression of goosecoid, not-like, chordin and brachyury1 genes in this region, as in the oral ectoderm of sea urchin embryos, which provides a basis for the formation of the dorsal structures. The striking similarity in the gene regulations and their respective expression domains when comparing dorsal formation in amphioxus and the determination of the oral ectoderm in sea urchin embryos suggests that chordates derived from an ambulacrarian-type blastula with dorsoventral inversion. PMID:27307516

Natural killer T cell facilitated engraftment of rat skin but not islet xenografts in mice.

PubMed

Gordon, Ethel J; Kelkar, Vinaya

2009-01-01

We have studied cellular components required for xenograft survival mediated by anti-CD154 monoclonal antibody (mAb) and a transfusion of donor spleen cells and found that the elimination of CD4(+) but not CD8(+) cells significantly improves graft survival. A contribution of other cellular components, such as natural killer (NK) cells and natural killer T (NKT) cells, for costimulation blockade-induced xenograft survival has not been clearly defined. We therefore tested the hypothesis that NK or NKT cells would promote rat islet and skin xenograft acceptance in mice. Lewis rat islets or skin was transplanted into wild type B6 mice or into B6 mice that were Jalpha18(null), CD1(null), or beta2 microglobulin (beta2M)(null) NK 1.1 depleted, or perforin(null). Graft recipients were pretreated with an infusion of donor derived spleen cells and a brief course of anti-CD154 mAb treatments. Additional groups received mAb or cells only. We first observed that the depletion of NK1.1 cells does not significantly interfere with graft survival in C57BL/6 (B6) mice. We used NKT cell deficient B6 mice to test the hypothesis that NKT cells are involved in islet and skin xenograft survival in our model. These mice bear a null mutation in the gene for the Jalpha18 component of the T-cell receptor. The component is uniquely associated with NKT cells. We found no difference in islet xenograft survival between Jalpha18(null) and wild type B6 mice. In contrast, median skin graft survival appeared shorter in Jalpha18(null) recipients. These data imply a role for Jalpha18(+) NKT cells in skin xenograft survival in treated mice. In order to confirm this inference, we tested skin xenograft survival in B6 CD1(null) mice because NKT cells are CD1 restricted. Results of these trials demonstrate that the absence of CD1(+) cells adversely affects rat skin graft survival. An additional assay in beta2M(null) mice demonstrated a requirement for major histocompatibility complex (MHC) class I

[Effects of baicalin on HL-60 cell xenografts in nude mice and its mechanism].

PubMed

Zheng, Jing; Hu, Jian-Da; Huang, Yi; Chen, Ying-Yu; Li, Jing; Chen, Bu-Yuan

2012-10-01

This study was aimed to investigate the effects of baicalin on HL-60 cell xenografts in nude mice in vivo and explore its mechanism. Xenograft tumor model of HL-60 cells in nude mice was established, which was divided randomly into 6 groups: negative control group (injection of 5% NaHCO(3)), 25, 50 and 100 mg/kg baicalin groups, combination group (50 mg/kg baicalin + 2 mg/kg VP16) and positive control group (VP16 4 mg/kg). The nude mice with HL-60 cell xenografts were treated with drugs via intraperitoneal injection daily. After treatment for 14 days average weigh and inhibitory rate of transplanted tumor stripped from 5 nude mice in each group were calculated, and the ultrastructure change of xenografts cells were tested by transmission electron microscopy. Histopathologic examination was used to observed the change of main organs in nude mice. The expression of signaling molecular PI3K/Akt proteins extracted from xenografts was detected by Western blot. The effects of baicalin on overall survival time in nude mice with HL-60 cell xenografts were evaluated. The results showed that baicalin could inhibit the growth of transplanted tumors in dose-dependent manner. There were more necrotic and apoptotic cells in mice of baicalin-treated groups and combination group than that in mice of negative control group. Baicalin could inhibit the proliferation of HL-60 cells in vivo by down-regulating the PI3K/Akt/mTOR signal pathway, where the expressions of p-Akt, mTOR and p-mTOR proteins decreased compared with negative control group, and no significant difference of Akt expression was found between different groups. Compared with negative control group, the median survival time of mice in combination group was more prolongated (P < 0.05). It is concluded that baicalin can inhibit growth and induce apoptosis of HL-60 cell xenografts in nude mice, and prolong median survival time of nude mice. The possible mechanisms may be related to inhibition of Akt activity and down

Predicting intrapartum fetal compromise using the fetal cerebro-umbilical ratio.

PubMed

Sabdia, S; Greer, R M; Prior, T; Kumar, S

2015-05-01

The aim of this study was to explore the association between the cerebro-umbilical ratio measured at 35-37 weeks and intrapartum fetal compromise. This retrospective cross sectional study was conducted at the Mater Mothers' Hospital in Brisbane, Australia. Maternal demographics and fetal Doppler indices at 35-37 weeks gestation for 1381 women were correlated with intrapartum and neonatal outcomes. Babies born by caesarean section or instrumental delivery for fetal compromise had the lowest median cerebro-umbilical ratio 1.60 (IQR 1.22-2.08) compared to all other delivery groups (vaginal delivery, emergency delivery for failure to progress, emergency caesarean section for other reasons or elective caesarean section). The percentage of infants with a cerebro-umbilical ratio <10th centile that required emergency delivery (caesarean section or instrumental delivery) for fetal compromise was 22%, whereas only 7.3% of infants with a cerebro-umbilical ratio between the 10th-90th centile and 9.6% of infants with a cerebro-umbilical ratio > 90th centile required delivery for the same indication (p < 0.001). A lower cerebro-umbilical ratio was associated with an increased risk of emergency delivery for fetal compromise, OR 2.03 (95% CI 1.41-2.92), p < 0.0001. This study suggests that a low fetal cerebro-umbilical ratio measured at 35-37 weeks is associated with a greater risk of intrapartum compromise. This is a relatively simple technique which could be used to risk stratify women in diverse healthcare settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms

PubMed Central

Monsma, David J; Cherba, David M; Eugster, Emily E; Dylewski, Dawna L; Davidson, Paula T; Peterson, Chelsea A; Borgman, Andrew S; Winn, Mary E; Dykema, Karl J; Webb, Craig P; MacKeigan, Jeffrey P; Duesbery, Nicholas S; Nickoloff, Brian J; Monks, Noel R

2015-01-01

Variable clinical responses, tumor heterogeneity, and drug resistance reduce long-term survival outcomes for metastatic melanoma patients. To guide and accelerate drug development, we characterized tumor responses for five melanoma patient derived xenograft models treated with Vemurafenib. Three BRAFV600E models showed acquired drug resistance, one BRAFV600E model had a complete and durable response, and a BRAFV600V model was expectedly unresponsive. In progressing tumors, a variety of resistance mechanisms to BRAF inhibition were uncovered, including mutant BRAF alternative splicing, NRAS mutation, COT (MAP3K8) overexpression, and increased mutant BRAF gene amplification and copy number. The resistance mechanisms among the patient derived xenograft models were similar to the resistance pathways identified in clinical specimens from patients progressing on BRAF inhibitor therapy. In addition, there was both inter- and intra-patient heterogeneity in resistance mechanisms, accompanied by heterogeneous pERK expression immunostaining profiles. MEK monotherapy of Vemurafenib-resistant tumors caused toxicity and acquired drug resistance. However, tumors were eradicated when Vemurafenib was combined the MEK inhibitor. The diversity of drug responses among the xenograft models; the distinct mechanisms of resistance; and the ability to overcome resistance by the addition of a MEK inhibitor provide a scheduling rationale for clinical trials of next-generation drug combinations. PMID:26101714

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

Dorsal metacarpal veins: anatomic variation and potential clinical implications.

PubMed

Elmegarhi, Sara S; Amarin, Justin Z; Hadidi, Maher T; Badran, Darwish H; Massad, Islam M; Bani-Hani, Amjad M; Shatarat, Amjad T

2018-03-01

The dorsal metacarpal veins are frequently cannulated. Cannulation success is determined by several variable anatomic features. The objective of this study is to classify, for the first time, the anatomic variants of the dorsal metacarpal veins. In this cross-sectional study, 520 university students and staff were conveniently recruited. The dorsal metacarpal veins in 1040 hands were studied. Venous visibility was enhanced by either tourniquet application or near-infrared illumination. Variant patterns of the dorsal metacarpal veins were classified. The final analysis included 726 hands, for an exclusion rate of 30 %. Eight pattern types were identified. Three anatomic features informed the variation. Bilateral symmetry of the dorsal metacarpal veins was present in 352 participants (83 % of the total). The overall frequency distribution of variants in both hands was similar (P = 0.8). The frequency distribution of variants was subject to sexual dimorphism (P = 0.001), ethnic variation (P < 0.001), and technical variation (P < 0.001). The anatomic variants of the dorsal metacarpal veins were sorted into decreasingly frequent primary, secondary, and tertiary groups. The groups may signify a progressive increase in difficulty of peripheral cannulation, in the mentioned order. As such, primary patterns are the most common and likely the easiest to cannulate, while tertiary patterns are the least common and likely the most difficult to cannulate. The preceding premise, in tandem with the bilateral asymmetry of the veins, is clinically significant. With cannulation difficulty likely signifying an underlying tertiary pattern, the contralateral dorsal metacarpal veins are probabilistically characterized by a primary pattern and are, as such, the easier option for peripheral venous cannulation.

Size-dependent regulation of dorsal-ventral patterning in the early Drosophila embryo

PubMed Central

Garcia, Mayra; Nahmad, Marcos; Reeves, Gregory T.; Stathopoulos, Angelike

2013-01-01

How natural variation in embryo size affects patterning of the Drosophila embryo dorsal-ventral (DV) axis is not known. Here we examined quantitatively the relationship between nuclear distribution of the Dorsal transcription factor, boundary positions for several target genes, and DV axis length. Data were obtained from embryos of a wild-type background as well as from mutant lines inbred to size select embryos of smaller or larger sizes. Our data show that the width of the nuclear Dorsal gradient correlates with DV axis length. In turn, for some genes expressed along the DV axis, the boundary positions correlate closely with nuclear Dorsal levels and with DV axis length; while the expression pattern of others is relatively constant and independent of the width of the Dorsal gradient. In particular, the patterns of snail (sna) and ventral nervous-system defective (vnd) correlate with nuclear Dorsal levels and exhibit scaling to DV length; while the pattern of intermediate neuroblasts defective (ind) remains relatively constant with respect to changes in Dorsal and DV length. However, in mutants that exhibit an abnormal expansion of the Dorsal gradient which fails to scale to DV length, only sna follows the Dorsal distribution and exhibits overexpansion; in contrast, vnd and ind do not overexpand suggesting some additional mechanism acts to refine the dorsal boundaries of these two genes. Thus, our results argue against the idea that the Dorsal gradient works as a global system of relative coordinates along the DV axis and suggest that individual targets respond to changes in embryo size in a gene-specific manner. PMID:23800450

Fetal Alcohol Syndrome and Fetal Alcohol Effects in Child Development.

ERIC Educational Resources Information Center

Pancratz, Diane R.

This literature review defines Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) and considers their causes, diagnoses, prevalence, and educational ramifications. Effects of alcohol during each of the trimesters of pregnancy are summarized. Specific diagnostic characteristics of FAS are listed: (1) growth deficiency, (2) a…

The influence of betamethasone on fetal heart rate variability, obtained by non-invasive fetal electrocardiogram recordings.

PubMed

Verdurmen, Kim M J; Warmerdam, Guy J J; Lempersz, Carlijn; Hulsenboom, Alexandra D J; Renckens, Joris; Dieleman, Jeanne P; Vullings, Rik; van Laar, Judith O E H; Oei, S Guid

2018-04-01

Betamethasone is widely used to enhance fetal lung maturation in case of threatened preterm labour. Fetal heart rate variability is one of the most important parameters to assess in fetal monitoring, since it is a reliable indicator for fetal distress. To describe the effect of betamethasone on fetal heart rate variability, by applying spectral analysis on non-invasive fetal electrocardiogram recordings. Prospective cohort study. Patients that require betamethasone, with a gestational age from 24 weeks onwards. Fetal heart rate variability parameters on day 1, 2, and 3 after betamethasone administration are compared to a reference measurement. Following 68 inclusions, 12 patients remained with complete series of measurements and sufficient data quality. During day 1, an increase in absolute fetal heart rate variability values was seen. During day 2, a decrease in these values was seen. All trends indicate to return to pre-medication values on day 3. Normalised high- and low-frequency power show little changes during the study period. The changes in fetal heart rate variability following betamethasone administration show the same pattern when calculated by spectral analysis of the fetal electrocardiogram, as when calculated by cardiotocography. Since normalised spectral values show little changes, the influence of autonomic modulation seems minor. Copyright © 2018 Elsevier B.V. All rights reserved.

Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ.

PubMed

Joo, Kyeung Min; Kim, Jinkuk; Jin, Juyoun; Kim, Misuk; Seol, Ho Jun; Muradov, Johongir; Yang, Heekyoung; Choi, Yoon-La; Park, Woong-Yang; Kong, Doo-Sik; Lee, Jung-Il; Ko, Young-Hyeh; Woo, Hyun Goo; Lee, Jeongwu; Kim, Sunghoon; Nam, Do-Hyun

2013-01-31

Frequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable "patient tumor's phenocopy" that represents molecular and functional heterogeneity of GBMs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Dissociation between dorsal and ventral hippocampal theta oscillations during decision-making.

PubMed

Schmidt, Brandy; Hinman, James R; Jacobson, Tara K; Szkudlarek, Emily; Argraves, Melissa; Escabí, Monty A; Markus, Etan J

2013-04-03

Hippocampal theta oscillations are postulated to support mnemonic processes in humans and rodents. Theta oscillations facilitate encoding and spatial navigation, but to date, it has been difficult to dissociate the effects of volitional movement from the cognitive demands of a task. Therefore, we examined whether volitional movement or cognitive demands exerted a greater modulating factor over theta oscillations during decision-making. Given the anatomical, electrophysiological, and functional dissociations along the dorsal-ventral axis, theta oscillations were simultaneously recorded in the dorsal and ventral hippocampus in rats trained to switch between place and motor-response strategies. Stark differences in theta characteristics were found between the dorsal and ventral hippocampus in frequency, power, and coherence. Theta power increased in the dorsal, but decreased in the ventral hippocampus, during the decision-making epoch. Interestingly, the relationship between running speed and theta power was uncoupled during the decision-making epoch, a phenomenon limited to the dorsal hippocampus. Theta frequency increased in both the dorsal and ventral hippocampus during the decision epoch, although this effect was greater in the dorsal hippocampus. Despite these differences, ventral hippocampal theta was responsive to the navigation task; theta frequency, power, and coherence were all affected by cognitive demands. Theta coherence increased within the dorsal hippocampus during the decision-making epoch on all three tasks. However, coherence selectively increased throughout the hippocampus (dorsal to ventral) on the task with new hippocampal learning. Interestingly, most results were consistent across tasks, regardless of hippocampal-dependent learning. These data indicate increased integration and cooperation throughout the hippocampus during information processing.

Interactions between dorsal and ventral streams for controlling skilled grasp

PubMed Central

van Polanen, Vonne; Davare, Marco

2015-01-01

The two visual systems hypothesis suggests processing of visual information into two distinct routes in the brain: a dorsal stream for the control of actions and a ventral stream for the identification of objects. Recently, increasing evidence has shown that the dorsal and ventral streams are not strictly independent, but do interact with each other. In this paper, we argue that the interactions between dorsal and ventral streams are important for controlling complex object-oriented hand movements, especially skilled grasp. Anatomical studies have reported the existence of direct connections between dorsal and ventral stream areas. These physiological interconnections appear to be gradually more active as the precision demands of the grasp become higher. It is hypothesised that the dorsal stream needs to retrieve detailed information about object identity, stored in ventral stream areas, when the object properties require complex fine-tuning of the grasp. In turn, the ventral stream might receive up to date grasp-related information from dorsal stream areas to refine the object internal representation. Future research will provide direct evidence for which specific areas of the two streams interact, the timing of their interactions and in which behavioural context they occur. PMID:26169317

Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts of nude mice.

PubMed

Yoshiyuki, T; Shimizu, Y; Onda, M; Tokunaga, A; Kiyama, T; Nishi, K; Mizutani, T; Matsukura, N; Tanaka, N; Akimoto, M

1990-02-15

Thirty-two surgical specimens and three cell lines of human gastric cancers were used for subcutaneous transplantation into nude mice, resulting in the establishment of eight (25%) xenografts from the surgical specimens and two (67%) from the cell lines. The localization of epidermal growth factor (EGF) in the surgical specimens and cell lines of the gastric cancers and their xenografts in nude mice was then investigated immunohistochemically. Epidermal growth factor was stained in the cytoplasm of the cancer cells, being detected in 16 (50%) of the 32 surgical specimens and in all of the cell lines. Seven (44%) of the sixteen EGF-positive surgical specimens and one (6%) of the 16 EGF-negative ones were tumorigenic in nude mice. All of the xenografts in nude mice were positive for EGF. The tumorigenicity of human gastric cancer xenografts in nude mice may, therefore, be correlated with the presence of EGF in cancer cells.

Special Tests for Monitoring Fetal Health

MedlinePlus

... a nonstress test? The nonstress test measures the fetal heart rate in response to fetal movement over time. The ... A belt with a sensor that measures the fetal heart rate is placed around your abdomen. The fetal heart ...

Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse.

PubMed

Clappier, Emmanuelle; Gerby, Bastien; Sigaux, François; Delord, Marc; Touzri, Farah; Hernandez, Lucie; Ballerini, Paola; Baruchel, André; Pflumio, Françoise; Soulier, Jean

2011-04-11

Genomic studies in human acute lymphoblastic leukemia (ALL) have revealed clonal heterogeneity at diagnosis and clonal evolution at relapse. In this study, we used genome-wide profiling to compare human T cell ALL samples at the time of diagnosis and after engraftment (xenograft) into immunodeficient recipient mice. Compared with paired diagnosis samples, the xenograft leukemia often contained additional genomic lesions in established human oncogenes and/or tumor suppressor genes. Mimicking such genomic lesions by short hairpin RNA-mediated knockdown in diagnosis samples conferred a selective advantage in competitive engraftment experiments, demonstrating that additional lesions can be drivers of increased leukemia-initiating activity. In addition, the xenograft leukemias appeared to arise from minor subclones existing in the patient at diagnosis. Comparison of paired diagnosis and relapse samples showed that, with regard to genetic lesions, xenograft leukemias more frequently more closely resembled relapse samples than bulk diagnosis samples. Moreover, a cell cycle- and mitosis-associated gene expression signature was present in xenograft and relapse samples, and xenograft leukemia exhibited diminished sensitivity to drugs. Thus, the establishment of human leukemia in immunodeficient mice selects and expands a more aggressive malignancy, recapitulating the process of relapse in patients. These findings may contribute to the design of novel strategies to prevent or treat relapse.

Anesthesia for fetal surgery.

PubMed

Hoagland, Monica A; Chatterjee, Debnath

2017-04-01

Fetal therapy is an exciting and growing field of medicine. Advances in prenatal imaging and continued innovations in surgical and anesthetic techniques have resulted in a wide range of fetal interventions including minimally invasive, open mid-gestation, and ex-utero intrapartum treatment procedures. The potential for maternal morbidity is significant and must be carefully weighed against claimed benefits to the fetus. Appropriate patient selection is critical, and a multidisciplinary team-based approach is strongly recommended. The anesthetic management should focus on maintaining uteroplacental circulation, achieving profound uterine relaxation, optimizing surgical conditions, monitoring fetal hemodynamics, and minimizing maternal and fetal risk. © 2017 John Wiley & Sons Ltd.

184AA3: a xenograft model of ER+ breast adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hines, William C.; Kuhn, Irene; Thi, Kate

Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER +) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER + adenocarcinomas that had a high proliferative rate and other features consistentmore » with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44 High  subpopulation was discovered, yet their tumor forming ability was far less than CD44 Low  cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER +  cancers. In conclusion, this model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development.« less

184AA3: a xenograft model of ER+ breast adenocarcinoma

DOE PAGES

Hines, William C.; Kuhn, Irene; Thi, Kate; ...

2015-12-12

Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER +) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER + adenocarcinomas that had a high proliferative rate and other features consistentmore » with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44 High  subpopulation was discovered, yet their tumor forming ability was far less than CD44 Low  cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER +  cancers. In conclusion, this model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development.« less

Even Better Than the Real Thing? Xenografting in Pediatric Patients with Scald Injury.

PubMed

Diegidio, Paul; Hermiz, Steven J; Ortiz-Pujols, Shiara; Jones, Samuel W; van Duin, David; Weber, David J; Cairns, Bruce A; Hultman, Charles Scott

2017-07-01

This article reviews a single burn center experience with porcine xenografts to treat pediatric scald injuries, over a 10-year period. The authors compare xenografting to autografting, as well as wound care only, and provide outcome data on length of stay, incidence of health care-associated infections, and need for reconstructive surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Dorsal Plating of Unstable Scaphoid Fractures and Nonunions.

PubMed

Bain, Gregory I; Turow, Arthur; Phadnis, Joideep

2015-09-01

Achieving stable fixation of displaced acute and chronic nonunited scaphoid fractures continues to be a challenge for the treating surgeon. The threaded compression screw has been the mainstay of treatment of these fractures for the last 3 decades; however, persistent nonunion after screw fixation has prompted development of new techniques. Recent results of volar buttress plating have been promising. We describe a novel technique of dorsal scaphoid plating. In contrast to volar plating, the dorsal plate is biomechanically more favorable as it utilizes the tension side of the scaphoid bone for dynamic compression. Dorsal scaphoid plating provides a more stable construct than the traditional Herbert screw and mitigates the need for vascular or corticocancellous bone grafting in most cases.

Fetal blood drawing.

PubMed

Hobbins, J C; Mahoney, M J

1975-07-19

A small sample of fetal blood suitable for studies of haemoglobin synthesis was obtained from a placental vessel under endoscopic visualisation in 23 of 26 patients in whom the procedure was attempted prior to second-trimester abortion. Fetal blood loss, calculated in 23 cases, was between 0-2 ml. and 2-5 ml., and fetal blood-volume depletion varied from 0-5% to 15%. No short-term ill-effects were demonstrated in mother or fetus in any of 16 patients in whom the injection of aborti-facient was postponed for between 16 and 24 hours after the procedure.

Examiner's finger-mounted fetal tissue oximetry.

PubMed

Kanayama, Naohiro; Niwayama, Masatsugu

2014-06-01

The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor's finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO₂) with the new tissue oximeter. Neonatal StO₂ was measured at any position of the head regardless of amount of hair. Neonatal StO₂ was found to be around 77%. Fetal StO₂ was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO₂ without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO₂ in any condition of the fetus.

Examiner's finger-mounted fetal tissue oximetry

NASA Astrophysics Data System (ADS)

Kanayama, Naohiro; Niwayama, Masatsugu

2014-06-01

The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor's finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO2) with the new tissue oximeter. Neonatal StO was measured at any position of the head regardless of amount of hair. Neonatal StO was found to be around 77%. Fetal StO was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO in any condition of the fetus.

Fetal pain perception and pain management.

PubMed

Van de Velde, Marc; Jani, Jacques; De Buck, Frederik; Deprest, J

2006-08-01

This paper gives an overview of current science related to the concept of fetal pain. We have answered three important questions: (1) does fetal pain exist? (2) does management of fetal pain benefit the unborn child? and (3) which techniques are available to provide good fetal analgesia?

Fetal and neonatal thyrotoxicosis

PubMed Central

Batra, Chandar Mohan

2013-01-01

Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20th week of pregnancy and reaches its maximum by 30th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

Prenatal Depression Restricts Fetal Growth

PubMed Central

Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

2009-01-01

Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

Comparison of Two Xenograft Materials Used in Sinus Lift Procedures: Material Characterization and In Vivo Behavior

PubMed Central

Ramírez Fernández, María Piedad; Mazón, Patricia; Gehrke, Sergio A.; Calvo-Guirado, Jose Luis; De Aza, Piedad N.

2017-01-01

Detailed information about graft material characteristic is crucial to evaluate their clinical outcomes. The present study evaluates the physico-chemical characteristics of two xenografts manufactured on an industrial scale deproteinized at different temperatures (non-sintered and sintered) in accordance with a protocol previously used in sinus lift procedures. It compares how the physico-chemical properties influence the material’s performance in vivo by a histomorphometric study in retrieved bone biopsies following maxillary sinus augmentation in 10 clinical cases. An X-ray diffraction analysis revealed the typical structure of hydroxyapatite (HA) for both materials. Both xenografts were porous and exhibited intraparticle pores. Strong differences were observed in terms of porosity, crystallinity, and calcium/phosphate. Histomorphometric measurements on the bone biopsies showed statistically significant differences. The physic-chemical assessment of both xenografts, made in accordance with the protocol developed on an industrial scale, confirmed that these products present excellent biocompatibilitity, with similar characteristics to natural bone. The sintered HA xenografts exhibited greater osteoconductivity, but were not completely resorbable (30.80 ± 0.88% residual material). The non-sintered HA xenografts induced about 25.92 ± 1.61% of new bone and a high level of degradation after six months of implantation. Differences in the physico-chemical characteristics found between the two HA xenografts determined a different behavior for this material. PMID:28772984

A Primary Xenograft Model of Small Cell Lung Cancer Reveals Irreversible Changes in Gene Expression Imposed by Culture In-Vitro

PubMed Central

Daniel, Vincent C.; Marchionni, Luigi; Hierman, Jared S.; Rhodes, Jonathan T.; Devereux, Wendy L.; Rudin, Charles M.; Yung, Rex; Parmigani, Giovanni; Dorsch, Marion; Peacock, Craig D.; Watkins, D. Neil

2009-01-01

Traditional approaches to the preclinical investigation of cancer therapies rely on the use of established cell lines maintained in serum-based growth media. This is particularly true of small cell lung cancer (SCLC), where surgically resected tissue is rarely available. Recent attention has focused on the need for better models that preserve the integrity of cancer stem cell populations, as well as three-dimensional tumor-stromal interactions. Here we describe a primary xenograft model of SCLC in which endobronchial tumor specimens obtained from chemo-naive patients are serially propagated in vivo in immunodeficient mice. In parallel, cell lines grown in conventional tissue culture conditions were derived from each xenograft line, passaged for 6 months, and then re-implanted to generate secondary xenografts. Using the Affymetrix platform, we analyzed gene expression in primary xenograft, xenograft-derived cell line, and secondary xenograft, and compared these data to similar analyses of unrelated primary SCLC samples and laboratory models. When compared to normal lung, primary tumors, xenografts and cell lines displayed a gene expression signature specific for SCLC. Comparison of gene expression within the xenograft model identified a group of tumor-specific genes expressed in primary SCLC and xenografts that was lost during the transition to tissue culture, and that was not regained when the tumors were re-established as secondary xenografts. Such changes in gene expression may be a common feature of many cancer cell culture systems, with functional implications for the use of such models for preclinical drug development. PMID:19351829

[Regional anatomy of the dorsal penile nerve and its clinical significance].

PubMed

Zhang, Chun-Ying; Li, Xing-Hua; Yuan, Tan; Zhang, Hai-Feng; Liu, Ji-Hong; Ye, Zhang-Qun

2009-02-01

To investigate the number, course and distribution of normal dorsal penile nerves and their clinical significance for selective neurectomy of the dorsal penile nerve in the treatment of primary premature ejaculation. We dissected 38 cadaveric adult penises and recorded the number, course and distribution of the dorsal penile nerves. A total of 314 cases of primary premature ejaculation underwent selective neurectomy of the dorsal penile nerve. The patients ranged between 20 and 45 years in age and from 1 to 22 years in disease course. The dorsal penile nerves were distributed in parallel bilaterally in all the cadaveric penises and branched into the ventral side in 4 of them. The total number of dorsal penile nerves was (3.6 +/- 1.2) in the 38 cadaveric penises, 7 in 1 case, 6 in 1 case, 5 in 6 cases, 4 in 9 cases, 3 in 14 cases and 2 in 7 cases, while that of the 314 patients with primary premature ejaculation was (7.0 +/- 1.9), 5 in 64 cases, 6 in 56 cases, 7 in 52 cases, 8 in 40 cases, 9 in 33 cases, 10 in 28 cases, 11 in 25 cases, 12 in 11 cases and 13 in 5 cases. Selective neurectomy of the dorsal penile nerve achieved an intravaginal ejaculation latency of (4.31 +/- 1.87) minutes and sexual satisfaction rate of (61 +/- 17) %, significantly different from those before the operation ([1.24 +/- 0.32] min, [23 +/- 6] %; all P < 0.01). The abnormal increase of dorsal penile nerves possibly lies at the bottom of the pathogenesis of primary premature ejaculation. Selective neurectomy of the dorsal penile nerve is safe and effective for the treatment of primary premature ejaculation.

Aortic valve replacement with the Biocor PSB stentless xenograft.

PubMed

Bertolini, P; Luciani, G B; Vecchi, B; Pugliese, P; Mazzucco, A

1998-08-01

The midterm clinical results after aortic valve replacement with the Biocor PSB stentless xenograft on all patients operated between October 1992 and October 1996 were reviewed. One hundred six patients, aged 70+/-6 years, had aortic valve replacement for aortic stenosis (67%), regurgitation (11%), or both (22%). Associated procedures were done in 49 patients (46%), including coronary artery bypass in 30 patients, mitral valve repair/replacement in 16, and ascending aorta replacement in 5 patients. Aortic cross-clamp and cardiopulmonary bypass times were 96+/-24 and 129+/-31 minutes, respectively. There were 3 (3%) early deaths due to low output (2 patients) and cerebrovascular accident (1 patient). Follow-up of survivors ranged from 6 to 66 months (mean, 39+/-14 months). Survival was 94%+/-2% and 90%+/-3% at 1 and 5 years. There were 5 late deaths due to cardiac cause (2), cancer (2), and pulmonary embolism (1 patient). No patient had structural valve deterioration, whereas 100% and 95%+/-3% were free from valve-related events at 1 and 5 years. There were two reoperations due to narrowing of the left coronary ostium and endocarditis, with an actuarial freedom from reoperation of 99%+/-1% and 98+/-1% at 1 and 5 years, respectively. Functional results demonstrated a mean peak transprosthetic gradient of 16+/-12 mm Hg, with only 1 patient (1%) with a 55 mm Hg gradient. No cases of valve regurgitation greater than mild were recorded at follow-up. Assessment of New York Heart Association functional class demonstrated a significant improvement (2.9+/-0.6 versus 1.4+/-0.7; p=0.01). All patients were free from anticoagulation. Aortic valve replacement using the Biocor PSB stentless xenograft offers excellent midterm survival, negligible valve deterioration, and a very low rate of valve-related events, which are comparable to estimates reported with other models of stentless xenografts and currently available stented xenografts. Hemodynamic performance is favorable and

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

PubMed Central

Tutton, P. J.; Barkla, D. H.

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours. PMID:7362778

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

PubMed

Tutton, P J; Barkla, D H

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

Long-Term Survival and Freedom From Reoperation After Placement of a Pulmonary Xenograft Valved Conduit.

PubMed

Alfieris, George M; Swartz, Michael F; Lehoux, Juan; Bove, Edward L

2016-08-01

The optimal choice for pulmonary valve replacement (PVR) remains controversial. This study hypothesized that xenografts used for PVR would result in prolonged long-term survival and freedom from reoperation. Children and adults with congenital heart disease requiring PVR using a xenograft from 1980 to 1985 were reviewed. In all cases, the xenograft valve was either sewn or manufactured into a Dacron conduit, and the conduit was sewn to the pulmonary artery bifurcation. Clinical data were analyzed, and survival and freedom from reoperation were determined using Kaplan-Meier analysis. Twenty-four patients received a xenograft for PVR at 14.6 ± 5.6 years. Conduit size ranged from 21 to 27 mm. Most patients received a Carpentier-Edwards valved conduit (n = 17), followed by a Hancock valved conduit (n = 5) and an Ionescu-Shiley valve sewn into a Dacron graft (n = 2). No perioperative deaths occurred. Reoperation was required mainly for pulmonary stenosis (72.7%), followed by pulmonary insufficiency (18.2%), or both stenosis and insufficiency (9%). Freedom from reoperation was 90%, 56%, 43%, and 14% at 10, 20, 25, and 30 years, respectively. At most recent follow-up the was only death, which was related to severe biventricular failure 25 years after conduit implant. PVR using a xenograft valved conduit results in prolonged freedom from reoperation and excellent long-term survival. These data, which provide long-term follow-up information on xenograft valves after PVR. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

'What' Is Happening in the Dorsal Visual Pathway.

PubMed

Freud, Erez; Plaut, David C; Behrmann, Marlene

2016-10-01

The cortical visual system is almost universally thought to be segregated into two anatomically and functionally distinct pathways: a ventral occipitotemporal pathway that subserves object perception, and a dorsal occipitoparietal pathway that subserves object localization and visually guided action. Accumulating evidence from both human and non-human primate studies, however, challenges this binary distinction and suggests that regions in the dorsal pathway contain object representations that are independent of those in ventral cortex and that play a functional role in object perception. We review here the evidence implicating dorsal object representations, and we propose an account of the anatomical organization, functional contributions, and origins of these representations in the service of perception. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal perception of fetal movements in late pregnancy is affected by type and duration of fetal movement.

PubMed

Brown, Rebecca; Higgins, Lucy E; Johnstone, Edward D; Wijekoon, Jayawan H; Heazell, Alexander E P

2016-01-01

A reduction in fetal movements has been proposed to identify pregnancies at risk of stillbirth. The utility of this approach is limited by variability in maternal perception of fetal movements. We aimed to determine the proportion of fetal movements observed by ultrasound that were maternally perceived and identify factors that affected maternal perception. During 30-min recordings, women (n = 21) depressed a trigger upon perception of a fetal movement, while an ultrasound operator recorded observed movements according to the fetal parts involved. Women perceived between 2.4% and 81.0% (median 44.8%) of movements observed on scan. Synchronous movement of the fetal trunk and limbs was more likely to be recognized than either part in isolation (60.5% versus 37.5% and 30%, respectively). The ultrasound operator judged the fetus to be moving for a significantly greater proportion of the time than mothers (median 1.5% of total recording time versus 0.7%). There was no significant relationship between the ability to perceive fetal activity and placental site, parity, amniotic fluid index or maternal body mass index. Variations in maternal perception of fetal movements may affect detection of a clinically significant reduction in fetal movements for some women.

Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model.

PubMed

Kim, Y; Gelehrter, S K; Fifer, C G; Lu, J C; Owens, G E; Berman, D R; Williams, J; Wilkinson, J E; Ives, K A; Xu, Z

2011-04-01

Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. The experiments involved 11 gravid sheep at 102-129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (< 10 µs) delivered by an external 1-MHz focused ultrasound transducer at a 0.2-1-kHz pulse-repetition rate and 10-16 MPa peak negative pressure. Procedures were monitored and guided by real-time ultrasound imaging. Treated organs were examined by gross and histological inspection for location and degree of tissue injury. Hyperechoic, cavitating bubble clouds were successfully generated in 19/31 (61%) treatment attempts in 27 fetal organs beneath up to 8 cm of overlying tissue and fetal bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Fetal Neurobehavioral Development.

ERIC Educational Resources Information Center

DiPietro, Janet A.; And Others

1996-01-01

Investigated the ontogeny of fetal autonomic, motoric, state, and interactive functioning in 31 healthy fetuses from 20 weeks through term. Found that male fetuses were more active than female fetuses, and that greater maternal stress appraisal was associated with reduced fetal heart rate variability. Found that an apparent period of…

Fetal hydrops and other variables associated with the fetal hematocrit decrease after the first intrauterine transfusion for red cell alloimmunization.

PubMed

Lobato, Gustavo; Soncini, Cristina Silveira

2008-01-01

To evaluate the influence of fetal hydrops and other variables on fetal hematocrit (Hct) decrease after the first intrauterine transfusion (IUT) in alloimmunized pregnancies. From 1996 to 2006, the data of all alloimmunized pregnancies submitted to IUT were assessed. Exclusion criteria included: fetuses submitted to intraperitoneal transfusion; pregnancies complicated by other fetal abnormalities; pregnancies submitted to only one IUT, and cases in which posttransfusion or pretransfusion blood samples were not obtained. Linear regression models were implemented to assess the relationship between the rate of Hct fall after the first IUT and the following variables: fetal hydrops; antibody titer; gestational age at the first IUT; number of days between the first and second IUT; pretransfusion and posttransfusion fetal Hct values. Fifty fetuses fulfilled the study criteria. The fetal Hct decrease after the first IUT was 1.21 (range 0.18-2.3) %/day. The variables independently associated with the fetal Hct drop after the first IUT were the fetal hydrops (p = 0.000), the pretransfusion fetal Hct (p = 0.001) and the posttransfusion fetal Hct (p = 0.016). Fetal hydrops, pretransfusion fetal Hct and posttransfusion fetal Hct seem to influence the fetal Hct decrease between the first and second IUT. These findings may be helpful for estimating the rate of fetal Hct drop and programming the following IUT. Copyright 2008 S. Karger AG, Basel.

Hydrodynamic function of dorsal fins in spiny dogfish and bamboo sharks during steady swimming.

PubMed

Maia, Anabela; Lauder, George V; Wilga, Cheryl D

2017-11-01

A key feature of fish functional design is the presence of multiple fins that allow thrust vectoring and redirection of fluid momentum to contribute to both steady swimming and maneuvering. A number of previous studies have analyzed the function of dorsal fins in teleost fishes in this context, but the hydrodynamic function of dorsal fins in freely swimming sharks has not been analyzed, despite the potential for differential functional roles between the anterior and posterior dorsal fins. Previous anatomical research has suggested a primarily stabilizing role for shark dorsal fins. We evaluated the generality of this hypothesis by using time-resolved particle image velocimetry to record water flow patterns in the wake of both the anterior and posterior dorsal fins in two species of freely swimming sharks: bamboo sharks ( Chiloscyllium plagiosum ) and spiny dogfish ( Squalus acanthias ). Cross-correlation analysis of consecutive images was used to calculate stroke-averaged mean longitudinal and lateral velocity components, and vorticity. In spiny dogfish, we observed a velocity deficit in the wake of the first dorsal fin and flow acceleration behind the second dorsal fin, indicating that the first dorsal fin experiences net drag while the second dorsal fin can aid in propulsion. In contrast, the wake of both dorsal fins in bamboo sharks displayed increased net flow velocity in the majority of trials, reflecting a thrust contribution to steady swimming. In bamboo sharks, fluid flow in the wake of the second dorsal fin had higher absolute average velocity than that for first dorsal fin, and this may result from a positive vortex interaction between the first and second dorsal fins. These data suggest that the first dorsal fin in spiny dogfish has primarily a stabilizing function, while the second dorsal fin has a propulsive function. In bamboo sharks, both dorsal fins can contribute thrust and should be considered as propulsive adjuncts to the body during steady

Diagnosis and Treatment of Fetal Arrhythmia

PubMed Central

Wacker-Gussmann, Annette; Strasburger, Janette F.; Cuneo, Bettina F.; Wakai, Ronald T.

2014-01-01

Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythmare regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques. PMID:24858320

Antitumor effect of bevacizumab in a xenograft model of canine hemangiopericytoma.

PubMed

Michishita, Masaki; Uto, Tatsuya; Nakazawa, Ryota; Yoshimura, Hisashi; Ogihara, Kikumi; Naya, Yuko; Tajima, Tsuyoshi; Azakami, Daigo; Kishikawa, Seigo; Arai, Toshiro; Takahashi, Kimimasa

2013-01-01

Canine hemangiopericytoma (CHP) is characterized by frequent local recurrence and increased invasiveness. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis in tumors. The aim of the present study was to investigate the effect of a single dose of bevacizumab on a xenograft model of CHP. VEGF protein was secreted from cultured CHP cells and interacted with bevacizumab. Bevacizumab treatment suppressed tumor growth by inhibiting tumor angiogenesis, whereas no significant differences were observed in the proliferation index and apoptosis rates of treated and untreated mice. Thus, bevacizumab had antitumor effects in a xenograft model of CHP.

Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies.

PubMed

Buck Louis, Germaine M; Grewal, Jagteshwar; Albert, Paul S; Sciscione, Anthony; Wing, Deborah A; Grobman, William A; Newman, Roger B; Wapner, Ronald; D'Alton, Mary E; Skupski, Daniel; Nageotte, Michael P; Ranzini, Angela C; Owen, John; Chien, Edward K; Craigo, Sabrina; Hediger, Mary L; Kim, Sungduk; Zhang, Cuilin; Grantz, Katherine L

2015-10-01

Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts

PubMed Central

Zhu, Yin; Cheng, Ming; Yang, Zhen; Zeng, Chun-Yan; Chen, Jiang; Xie, Yong; Luo, Shi-Wen; Zhang, Kun-He; Zhou, Shu-Feng; Lu, Nong-Hua

2014-01-01

Mesenchymal stem cells (MSCs) have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met) which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP). Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS), MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor tissues after systemic injection. The microvessel density of tumor xenografts was decreased, and tumor cellular apoptosis was significantly induced in the mice treated with MSCs-NK4 compared to control mice. These findings demonstrate that MSC-based NK4 gene therapy can obviously inhibit the growth of gastric cancer xenografts, and MSCs are a better vehicle for NK4 gene therapy than lentiviral vectors. Further studies are warranted to explore the efficacy and safety of the MSC-based NK4 gene therapy in

Adaptation of an articulated fetal skeleton model to three-dimensional fetal image data

NASA Astrophysics Data System (ADS)

Klinder, Tobias; Wendland, Hannes; Wachter-Stehle, Irina; Roundhill, David; Lorenz, Cristian

2015-03-01

The automatic interpretation of three-dimensional fetal images poses specific challenges compared to other three-dimensional diagnostic data, especially since the orientation of the fetus in the uterus and the position of the extremities is highly variable. In this paper, we present a comprehensive articulated model of the fetal skeleton and the adaptation of the articulation for pose estimation in three-dimensional fetal images. The model is composed out of rigid bodies where the articulations are represented as rigid body transformations. Given a set of target landmarks, the model constellation can be estimated by optimization of the pose parameters. Experiments are carried out on 3D fetal MRI data yielding an average error per case of 12.03+/-3.36 mm between target and estimated landmark positions.

Central vagal sensory and motor connections: human embryonic and fetal development.

PubMed

Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

2004-07-30

The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

Dorsal scapular neuropathy causing rhomboids palsy and scapular winging.

PubMed

Argyriou, Andreas A; Karanasios, Panagiotis; Makridou, Alexandra; Makris, Nicolaos

2015-01-01

Most cases of scapular winging (SW) are attributed to either long thoracic or spinal accessory nerve lesions. Dorsal scapular nerve lesions are quite rare and the literature contains very few case reports of SW secondary to rhomboid paralysis. We are reporting the unusual case of a young patient who developed right-side scapular winging due to dorsal scapular neuropathy and rhomboids palsy, and we highlight the role of conservative treatment and rehabilitation for cases of mild/medium injury to the dorsal scapular nerve or to the rhomboid muscles. For those cases, physiotherapy is recommended, and this is mainly aimed at strengthening the trapezius in order to compensate for rhomboids weakness.

Fetal Alcohol Syndrome and Fetal Alcohol Effects-- Support for Teachers and Families.

ERIC Educational Resources Information Center

Duckworth, Susanna V.; Norton, Terry L.

2000-01-01

Reviews genesis of fetal alcohol syndrome and fetal alcohol effects in children. Identifies physical characteristics and behavioral indicators found and provides three checklists of observable signs for both disorders. Recommends seven steps for educators to follow in seeking assistance with these conditions. (DLH)

Asymmetric distribution of Echinoid defines the epidermal leading edge during Drosophila dorsal closure

PubMed Central

Laplante, Caroline

2011-01-01

During Drosophila melanogaster dorsal closure, lateral sheets of embryonic epidermis assemble an actomyosin cable at their leading edge and migrate dorsally over the amnioserosa, converging at the dorsal midline. We show that disappearance of the homophilic cell adhesion molecule Echinoid (Ed) from the amnioserosa just before dorsal closure eliminates homophilic interactions with the adjacent dorsal-most epidermal (DME) cells, which comprise the leading edge. The resulting planar polarized distribution of Ed in the DME cells is essential for the localized accumulation of actin regulators and for actomyosin cable formation at the leading edge and for the polarized localization of the scaffolding protein Bazooka/PAR-3. DME cells with uniform Ed fail to assemble a cable and protrude dorsally, suggesting that the cable restricts dorsal migration. The planar polarized distribution of Ed in the DME cells thus provides a spatial cue that polarizes the DME cell actin cytoskeleton, defining the epidermal leading edge and establishing its contractile properties. PMID:21263031

Opposing dorsal/ventral stream dynamics during figure-ground segregation.

PubMed

Wokke, Martijn E; Scholte, H Steven; Lamme, Victor A F

2014-02-01

The visual system has been commonly subdivided into two segregated visual processing streams: The dorsal pathway processes mainly spatial information, and the ventral pathway specializes in object perception. Recent findings, however, indicate that different forms of interaction (cross-talk) exist between the dorsal and the ventral stream. Here, we used TMS and concurrent EEG recordings to explore these interactions between the dorsal and ventral stream during figure-ground segregation. In two separate experiments, we used repetitive TMS and single-pulse TMS to disrupt processing in the dorsal (V5/HMT⁺) and the ventral (lateral occipital area) stream during a motion-defined figure discrimination task. We presented stimuli that made it possible to differentiate between relatively low-level (figure boundary detection) from higher-level (surface segregation) processing steps during figure-ground segregation. Results show that disruption of V5/HMT⁺ impaired performance related to surface segregation; this effect was mainly found when V5/HMT⁺ was perturbed in an early time window (100 msec) after stimulus presentation. Surprisingly, disruption of the lateral occipital area resulted in increased performance scores and enhanced neural correlates of surface segregation. This facilitatory effect was also mainly found in an early time window (100 msec) after stimulus presentation. These results suggest a "push-pull" interaction in which dorsal and ventral extrastriate areas are being recruited or inhibited depending on stimulus category and task demands.

Fetal Topographical Anatomy of the Pancreatic Head and Duodenum with Special Reference to Courses of the Pancreaticoduodenal Arteries

PubMed Central

Jin, Zhe Wu; Cho, Baik Hwan; Kim, Hyoung Tae; Kimura, Wataru; Fujimiya, Mineko; Murakami, Gen

2010-01-01

Purpose The purpose of this study is to provide better understanding as to how the "double" vascular arcades, in contrast to other intestinal marginal vessels, develop along the right margin of the pancreatic head. Materials and Methods In human fetuses between 8-30 weeks, we described the topographical anatomy of the vessels, bile duct, duodenum as well as the ventral and dorsal primordia of the pancreatic head with an aid of pancreatic polypeptide immunohisto-chemistry. Results The contents of the hepatoduodenal ligament crossed the superior side of the pylorus. Moreover, the right hepatic artery originating from the superior mesenteric artery ran along the superior aspect of the pancreatic head. An arterial arcade, corresponding to the posterior pancreaticoduodenal arteries, encircled the superior part of the pancreatic head, whereas another arcade, corresponding to the anterior pancreaticoduodenal arteries, surrounded the inferior part. The dorsal promordium of the pancreas surrounded and/or mixed the ventral primordium at 13-16 weeks. Thus, both arterial arcades were likely to attach to the dorsal primordium. Conclusion The fetal anatomy of the pancreaticoduodenal vascular arcades as well as that of the hepatoduodenal ligament were quite different from adults in topographical relations. Thus, in the stage later than 30 weeks, further rotation of the duodenum along a horizontal axis seemed to be required to move the pylorus posterosuperiorly and to reflect the superior surface of the pancreatic head posteriorly. However, to change the topographical anatomy of the superior and inferior arterial arcades into the final position, re-arrangement of the pancreatic parenchyma might be necessary in the head. PMID:20376893

Fetal MRI: head and neck.

PubMed

Mirsky, David M; Shekdar, Karuna V; Bilaniuk, Larissa T

2012-08-01

Abnormalities of the fetal head and neck may be seen in isolation or in association with central nervous system abnormalities, chromosomal abnormalities, and syndromes. Magnetic resonance imaging (MRI) plays an important role in detecting associated abnormalities of the brain as well as in evaluating for airway obstruction that may impact prenatal management and delivery planning. This article provides an overview of the common indications for MRI of the fetal head and neck, including abnormalities of the fetal skull and face, masses of the face and neck, and fetal goiter. Copyright © 2012 Elsevier Inc. All rights reserved.

Insect Wing Membrane Topography Is Determined by the Dorsal Wing Epithelium

PubMed Central

Belalcazar, Andrea D.; Doyle, Kristy; Hogan, Justin; Neff, David; Collier, Simon

2013-01-01

The Drosophila wing consists of a transparent wing membrane supported by a network of wing veins. Previously, we have shown that the wing membrane cuticle is not flat but is organized into ridges that are the equivalent of one wing epithelial cell in width and multiple cells in length. These cuticle ridges have an anteroposterior orientation in the anterior wing and a proximodistal orientation in the posterior wing. The precise topography of the wing membrane is remarkable because it is a fusion of two independent cuticle contributions from the dorsal and ventral wing epithelia. Here, through morphological and genetic studies, we show that it is the dorsal wing epithelium that determines wing membrane topography. Specifically, we find that wing hair location and membrane topography are coordinated on the dorsal, but not ventral, surface of the wing. In addition, we find that altering Frizzled Planar Cell Polarity (i.e., Fz PCP) signaling in the dorsal wing epithelium alone changes the membrane topography of both dorsal and ventral wing surfaces. We also examined the wing morphology of two model Hymenopterans, the honeybee Apis mellifera and the parasitic wasp Nasonia vitripennis. In both cases, wing hair location and wing membrane topography are coordinated on the dorsal, but not ventral, wing surface, suggesting that the dorsal wing epithelium also controls wing topography in these species. Because phylogenomic studies have identified the Hymenotera as basal within the Endopterygota family tree, these findings suggest that this is a primitive insect character. PMID:23316434

Patient-derived xenografts as preclinical neuroblastoma models.

PubMed

Braekeveldt, Noémie; Bexell, Daniel

2018-05-01

The prognosis for children with high-risk neuroblastoma is often poor and survivors can suffer from severe side effects. Predictive preclinical models and novel therapeutic strategies for high-risk disease are therefore a clinical imperative. However, conventional cancer cell line-derived xenografts can deviate substantially from patient tumors in terms of their molecular and phenotypic features. Patient-derived xenografts (PDXs) recapitulate many biologically and clinically relevant features of human cancers. Importantly, PDXs can closely parallel clinical features and outcome and serve as excellent models for biomarker and preclinical drug development. Here, we review progress in and applications of neuroblastoma PDX models. Neuroblastoma orthotopic PDXs share the molecular characteristics, neuroblastoma markers, invasive properties and tumor stroma of aggressive patient tumors and retain spontaneous metastatic capacity to distant organs including bone marrow. The recent identification of genomic changes in relapsed neuroblastomas opens up opportunities to target treatment-resistant tumors in well-characterized neuroblastoma PDXs. We highlight and discuss the features and various sources of neuroblastoma PDXs, methodological considerations when establishing neuroblastoma PDXs, in vitro 3D models, current limitations of PDX models and their application to preclinical drug testing.

Thermal effects of dorsal head immersion in cold water on nonshivering humans.

PubMed

Giesbrecht, Gordon G; Lockhart, Tamara L; Bristow, Gerald K; Steinman, Allan M

2005-11-01

Personal floatation devices maintain either a semirecumbent flotation posture with the head and upper chest out of the water or a horizontal flotation posture with the dorsal head and whole body immersed. The contribution of dorsal head and upper chest immersion to core cooling in cold water was isolated when the confounding effect of shivering heat production was inhibited with meperidine (Demerol, 2.5 mg/kg). Six male volunteers were immersed four times for up to 60 min, or until esophageal temperature = 34 degrees C. An insulated hoodless dry suit or two different personal floatation devices were used to create four conditions: 1) body insulated, head out; 2) body insulated, dorsal head immersed; 3) body exposed, head (and upper chest) out; and 4) body exposed, dorsal head (and upper chest) immersed. When the body was insulated, dorsal head immersion did not affect core cooling rate (1.1 degrees C/h) compared with head-out conditions (0.7 degrees C/h). When the body was exposed, however, the rate of core cooling increased by 40% from 3.6 degrees C/h with the head out to 5.0 degrees C/h with the dorsal head and upper chest immersed (P < 0.01). Heat loss from the dorsal head and upper chest was approximately proportional to the extra surface area that was immersed (approximately 10%). The exaggerated core cooling during dorsal head immersion (40% increase) may result from the extra heat loss affecting a smaller thermal core due to intense thermal stimulation of the body and head and resultant peripheral vasoconstriction. Dorsal head and upper chest immersion in cold water increases the rate of core cooling and decreases potential survival time.

Fetal damage after accidental polio vaccination of an immune mother

PubMed Central

Burton, A. E.; Robinson, E. T.; Harper, W. F.; Bell, E. J.; Boyd, J. F.

1984-01-01

Irreparable damage to the anterior horn cells of the cervical and thoracic cord was found in a 20-week-old fetus whose mother was immune to poliomyelitis before conceiving but who was inadvertently given oral polio vaccine at 18 weeks gestation. Polio neutralizing antibody titres in sera, taken before and after pregnancy, were identical and were at levels normally regarded as providing protection. Unsuccessful attempts were made to isolate poliovirus from extracts of fetal brain, lung, liver and placenta. Fluorescent antibody tests were performed on various levels of the central nervous system and on the left and right extensor forearm muscles. Specific positive fluorescence to poliovirus 2 and 3 antigens was detected at dorsal spinal cord level only. One positive result was seen with Coxsackie A9 antiserum and fresh guinea-pig complement in the inflammatory cells in the right extensor forearm muscles. This experience, as yet unexplained, underlines the importance of ensuring that women are not pregnant prior to oral polio vaccination. ImagesFigure 1.Figure 2. PMID:6747944

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

PubMed Central

Ribatti, D; Nico, B; Pezzolo, A; Vacca, A; Meazza, R; Cinti, R; Carlini, B; Parodi, F; Pistoia, V; Corrias, M V

2006-01-01

Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-γ (IFN-γ) gene transfer dampens ACN tumorigenicity. As IFN-γ represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-γ and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-γ xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-γ xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-γ was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds. PMID:16721359

Pim Kinases Promote Migration and Metastatic Growth of Prostate Cancer Xenografts

PubMed Central

Santio, Niina M.; Eerola, Sini K.; Paatero, Ilkka; Yli-Kauhaluoma, Jari; Anizon, Fabrice; Moreau, Pascale; Tuomela, Johanna; Härkönen, Pirkko; Koskinen, Päivi J.

2015-01-01

Background and methods Pim family proteins are oncogenic kinases implicated in several types of cancer and involved in regulation of cell proliferation, survival as well as motility. Here we have investigated the ability of Pim kinases to promote metastatic growth of prostate cancer cells in two xenograft models for human prostate cancer. We have also evaluated the efficacy of Pim-selective inhibitors to antagonize these effects. Results We show here that tumorigenic growth of both subcutaneously and orthotopically inoculated prostate cancer xenografts is enhanced by stable overexpression of either Pim-1 or Pim-3. Moreover, Pim-overexpressing orthotopic prostate tumors are highly invasive and able to migrate not only to the nearby prostate-draining lymph nodes, but also into the lungs to form metastases. When the xenografted mice are daily treated with the Pim-selective inhibitor DHPCC-9, both the volumes as well as the metastatic capacity of the tumors are drastically decreased. Interestingly, the Pim-promoted metastatic growth of the orthotopic xenografts is associated with enhanced angiogenesis and lymphangiogenesis. Furthermore, forced Pim expression also increases phosphorylation of the CXCR4 chemokine receptor, which may enable the tumor cells to migrate towards tissues such as the lungs that express the CXCL12 chemokine ligand. Conclusions Our results indicate that Pim overexpression enhances the invasive properties of prostate cancer cells in vivo. These effects can be reduced by the Pim-selective inhibitor DHPCC-9, which can reach tumor tissues without serious side effects. Thus, Pim-targeting therapies with DHPCC-9-like compounds may help to prevent progression of local prostate carcinomas to fatally metastatic malignancies. PMID:26075720

Meiotic activity in orthotopic xenografts derived from human postpubertal testicular tissue.

PubMed

Van Saen, D; Goossens, E; Bourgain, C; Ferster, A; Tournaye, H

2011-02-01

Grafting of frozen-thawed testicular tissue has been suggested as a novel fertility preservation method for patients undergoing gonadotoxic treatments. However, this technique still needs further optimization before any clinical application. So far, grafting of human testicular tissue has only been performed to the back skin of nude mice and has shown spermatogonial stem-cell survival and occasionally differentiation up to primary spermatocytes. In this study, orthotopic grafting to mouse testes was evaluated as an alternative, and the effect of freezing and the donor's age was studied. Human testicular tissue was obtained from two prepubertal (aged 3 and 5) and two postpubertal (aged 12 and 13) boys. Both fresh and frozen-thawed testicular tissue was grafted to the testis of immuno-deficient nude mice. Four and nine months after transplantation, testes were analyzed by histology and immunohistochemistry. Four and nine months after transplantation, spermatogonial stem cells were observed in all tissue grafts. Germ cell survival was found to be higher in xenografts from the older boys when compared with that from younger donors. Furthermore, no differentiation was observed in the xenografts from younger patients, but the grafts of two older donors showed differentiation up to the primary spermatocyte level, with the presence of secondary spermatocytes in the oldest donor 9 months after transplantation. This xenografting study shows that intratesticular grafting results in high germ cell survival. In grafts derived from the older boys, meiotic activity was maintained in the xenografts for at least 9 months. Although difficult to conduct due to the scarcity of the tissue, more comparative research is needed to elucidate an optimal grafting strategy.

Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.

PubMed

Koohestani, Faezeh; Qiang, Wenan; MacNeill, Amy L; Druschitz, Stacy A; Serna, Vanida A; Adur, Malavika; Kurita, Takeshi; Nowak, Romana A

2016-07-01

Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. Uterine leiomyomas are the most common benign tumors of the female reproductive tract. HF can suppress the growth of human uterine leiomyoma cells in vitro. The mouse xenograft model reflects the characteristics of human leiomyomas. Primary leiomyoma smooth muscle cells from eight patients were xenografted under the renal capsule of adult, ovariectomized NOD-scid IL2Rγ(null) mice (NSG). Mice were treated with two different doses of HF or vehicle for 4 weeks with six to eight mice per group. Mouse body weight measurements and immunohistochemical analysis of body organs were carried out to assess the safety of HF treatment. Xenografted tumors were measured and analyzed for cellular and molecular changes induced by HF. Ovarian steroid hormone receptors were evaluated for possible modulation by HF. Treatment of mice carrying human UL xenografts with HF at 0.25 or 0.50 mg/kg body weight for 4 weeks resulted in a 35-40% (P < 0.05) reduction in tumor volume. The HF-induced volume reduction was accompanied by increased apoptosis and decreased cell proliferation. In contrast, there was no significant change in the collagen content either at the transcript or protein level between UL xenografts in control and HF groups. HF treatment did not change the expression level of ovarian steroid hormone receptors. No adverse pathological effects were observed in other tissues from mice undergoing treatment at these doses. While this study did test the effects of HF on human leiomyoma cells in an in vivo model, HF was administered to mice whose tolerance and metabolism of the drug may differ from that in humans. Also, the longer term effects of HF treatment are yet unclear. The results of this study showing the effectiveness of HF in

Development of the Avian Dorsal Thalamus: Patterns and Gradients of Neurogenesis.

PubMed

Lynn, Allison M; Schneider, Danielle A; Bruce, Laura L

2015-01-01

The dorsal thalamus is a region of the diencephalon that relays sensory and motor information between areas of the brain stem and the telencephalon. Although a dorsal thalamic region is recognized in all vertebrates and believed to be homologous, little is known about how the regions within it evolved and whether some or all regions within the dorsal thalamus are homologous among different vertebrate species. To characterize the gradients and patterns of neurogenesis of the avian dorsal thalamus, a single application of a low dose of bromodeoxyuridine (BrdU) was delivered to each chick between embryonic day (E)3 and E8 (stages 21 and 34), and chicks were followed up to E8 or E10 (stage 34 or 36). Comparisons of anti-BrdU labeling patterns across the different injection days suggest that nearly all dorsal thalamic neurons are born early in chick embryogenesis, between E3 and E8. Furthermore, neurons in the lateral, dorsal, and posterior parts of the dorsal thalamus are generally born earlier than those in the medial, ventral, and anterior parts. Analyses of the birth dates for nine regions show that the general pattern of neurogenesis in the avian dorsal thalamus resembles that of homologous regions within the rodent thalamus, with the exception of the auditory region, the nucleus ovoidalis, which is born later than the mammalian auditory medial geniculate nucleus. The similar pattern of neurogenesis in birds and mammals may represent a highly conserved developmental pattern that was present in the common ancestor of living birds and mammals, or may represent independently derived states. Additional studies in reptiles and amphibians are needed to distinguish between these evolutionary histories. © 2015 S. Karger AG, Basel.

Digital atlas of fetal brain MRI.

PubMed

Chapman, Teresa; Matesan, Manuela; Weinberger, Ed; Bulas, Dorothy I

2010-02-01

Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C#, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download from http://radiology.seattlechildrens.org/teaching/fetal_brain . Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development.

Synthetic progestins induce growth and metastasis of BT-474 human breast cancer xenografts in nude mice.

PubMed

Liang, Yayun; Benakanakere, Indira; Besch-Williford, Cynthia; Hyder, Ryyan S; Ellersieck, Mark R; Hyder, Salman M

2010-01-01

Previous studies have shown that sequential exposure to estrogen and progesterone or medroxyprogesterone acetate (MPA) stimulates vascularization and promotes the progression of BT-474 and T47-D human breast cancer cell xenografts in nude mice (Liang et al, Cancer Res 2007, 67:9929). In this follow-up study, the effects of progesterone, MPA, norgestrel (N-EL), and norethindrone (N-ONE) on BT-474 xenograft tumors were compared in the context of several different hormonal environments. N-EL and N-ONE were included in the study because synthetic progestins vary considerably in their biological effects and the effects of these two progestins on the growth of human tumor xenografts are not known. Estradiol-supplemented intact and ovariectomized immunodeficient mice were implanted with BT-474 cells. Progestin pellets were implanted simultaneously with estradiol pellets either 2 days before tumor cell injection (ie, combined) or 5 days after tumor cell injections (ie, sequentially). Progestins stimulated the growth of BT-474 xenograft tumors independent of exposure timing and protocol, MPA stimulated the growth of BT-474 xenograft tumors in ovariectomized mice, and progestins stimulated vascular endothelial growth factor elaboration and increased tumor vascularity. Progestins also increased lymph node metastasis of BT-474 cells. Therefore, progestins, including N-EL and N-ONE, induce the progression of breast cancer xenografts in nude mice and promote tumor metastasis. These observations suggest that women who ingest progestins for hormone therapy or oral contraception could be more at risk for developing breast cancer because of proliferation of existing latent tumor cells. Such risks should be considered in the clinical setting.

Fetal Heart Rate Monitoring during Labor

MedlinePlus

... of monitoring? • How is auscultation performed? • How is electronic fetal monitoring performed? • How is external monitoring performed? • ... method of periodically listening to the fetal heartbeat. Electronic fetal monitoring is a procedure in which instruments ...

Recent advances in fetal near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

D'Antona, Donato; Aldrich, Clive J.; O'Brien, Patrick; Lawrence, Sally; Delpy, David T.; Wyatt, John S.

1997-01-01

Fetal brain injury resulting from hypoxia and ischemia during labor remains an important cause of death and long- term disability. However, little is known about fetal brain oxygenation and hemodynamics. There are currently no satisfactory clinical techniques for fetal monitoring and there remains a need for a new method to assess brain oxygenation. Fetal near infrared spectroscopy (NIRS) is a new technique that allows noninvasive observation of changes in the cerebral concentrations of oxyhemoglobin and deoxyhemoglobin to be made during labor. A specially designed optical probe is inserted through the dilated cervix and placed against the fetal head. It is then possible to compare changes in NIRS data with other observations of fetal conditions, such as fetal heart rate and acid-base status.

Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

PubMed

Dunford, Louise J; Sinclair, Kevin D; Kwong, Wing Y; Sturrock, Craig; Clifford, Bethan L; Giles, Tom C; Gardner, David S

2014-11-01

This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet. © FASEB.

Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.

PubMed

Frasch, M G; Müller, T; Wicher, C; Weiss, C; Löhle, M; Schwab, K; Schubert, H; Nathanielsz, P W; Witte, O W; Schwab, M

2007-03-15

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.

Reliable harvest of a dorsal scapular artery perforator flap by augmenting its perfusion.

PubMed

Kim, So-Young; Lee, Kyeong-Tae; Mun, Goo-Hyun

2016-02-01

Despite confirmation of a reliable perforasome in the dorsal scapular artery in an anatomic study, a true perforator flap has not been recommended in previous clinical studies because of concerns regarding insufficient perfusion in the distal region. In this report, we present two cases of reconstruction for occipital defects caused by tumor extirpation using pedicled dorsal scapular artery perforator flaps without a muscle component. To secure the perfusion of the dorsal scapular artery perforator flap, inclusion of an additional perforator was attempted for perfusion augmentation. The second dorsal scapular artery perforator was harvested in one case. In an additional case, the sixth dorsal intercostal artery perforator with a branch that directly connected with the dorsal scapular artery within the trapezius muscle was additionally harvested. The flaps survived without any perfusion-related complications, including tip necrosis, and no donor site morbidities were observed. We suggest that a perfusion augmented dorsal scapular artery perforator flap by harvesting multiple perforators could be a safe and useful alternative for reconstructive surgery of head and neck defects. © 2014 Wiley Periodicals, Inc.

Professionals' views of fetal-monitoring support the development of devices to provide objective longer-term assessment of fetal wellbeing.

PubMed

Brown, Rebecca; Johnstone, Edward D; Heazell, Alexander E P

2016-01-01

Continuous longer-term fetal monitoring has been proposed to address limitations of current technologies in the detection of fetal compromise. We aimed to assess professionals' views regarding current fetal-monitoring techniques and proposed longer-term continuous fetal monitoring. A questionnaire was designed and validated to assess obstetricians' and midwives' use of current fetal-monitoring techniques and their views towards continuous monitoring. 125 of 173 received responses (72% obstetricians, 28% midwives) were analysed. Professionals had the strongest views about supporting evidence for the most commonly employed fetal-monitoring techniques (maternal awareness of fetal movements, ultrasound assessment of fetal growth and umbilical artery Doppler). 45.1% of professionals agreed that a continuous monitoring device would be beneficial (versus 28.7% who disagreed); this perceived benefit was not influenced by professionals' views regarding current techniques or professional background. Professionals have limited experience of continuous fetal monitoring, but most respondents believed that it would increase maternal anxiety (64.3%) and would have concerns with its use in clinical practice (81.7%). Continuous fetal monitoring would be acceptable to the majority of professionals. However, development of these technologies must be accompanied by extended examination of professionals' and women's views to determine barriers to its introduction.

Therapeutic effects of autologous lymphocytes activated with trastuzumab for xenograft mouse models of human breast cancer.

PubMed

Nakagawa, Shinichiro; Matsuoka, Yusuke; Ichihara, Hideaki; Yoshida, Hitoji; Yoshida, Kenshi; Ueoka, Ryuichi

2013-01-01

Trastuzumab (TTZ) is molecular targeted drug used for metastatic breast cancer patients overexpressing human epidermal growth factor receptor 2 (HER2). Therapeutic effects of lymphocytes activated with TTZ (TTZ-LAK) using xenograft mouse models of human breast cancer (MDA-MB-453) cells were examined in vivo. Remarkable reduction of tumor volume in a xenograft mouse models intravenously treated with TTZ-LAK cells after the subcutaneously inoculated of MDA-MB-453 cells was verified in vivo. The migration of TTZ-LAK cells in tumor of mouse models subcutaneously inoculated MDA-MB-453 cells was observed on the basis of histological analysis using immunostaining with CD-3. Induction of apoptosis in tumor of xenograft mice treated with TTZ-LAK cells was observed in micrographs using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method. It was noteworthy that the therapeutic effects of TTZ-LAK cells along with apoptosis were obtained for xenograft mouse models of human breast tumor in vivo.

Fetal response to maternal hunger and satiation - novel finding from a qualitative descriptive study of maternal perception of fetal movements.

PubMed

Bradford, Billie; Maude, Robyn

2014-08-26

Maternal perception of decreased fetal movements is a specific indicator of fetal compromise, notably in the context of poor fetal growth. There is currently no agreed numerical definition of decreased fetal movements, with the subjective perception of a decrease on the part of the mother being the most significant definition clinically. Both qualitative and quantitative aspects of fetal activity may be important in identifying the compromised fetus.Yet, how pregnant women perceive and describe fetal activity is under-investigated by qualitative means. The aim of this study was to explore normal fetal activity, through first-hand descriptive accounts by pregnant women. Using qualitative descriptive methodology, interviews were conducted with 19 low-risk women experiencing their first pregnancy, at two timepoints in their third trimester. Interview transcripts were later analysed using qualitative content analysis and patterns of fetal activity identified were then considered along-side the characteristics of the women and their birth outcomes. This paper focuses on a novel finding; the description by pregnant women of fetal behaviour indicative of hunger and satiation. Full findings will be presented in later papers. Most participants (74% 14 of 19) indicated mealtimes were a time of increased fetal activity. Eight participants provided detailed descriptions of increased activity around meals, with seven (37% 7 of 19) of these specifying increased fetal activity prior to meals or in the context of their own hunger. These movements were interpreted as a fetal demand for food often prompting the mother to eat. Interestingly, the women who described increased fetal activity in the context of hunger subsequently gave birth to smaller infants (mean difference 364 gm) than those who did not describe a fetal response to hunger. Food seeking behaviour may have a pre-birth origin. Maternal-fetal interaction around mealtimes could constitute an endocrine mediated

Activin-like signal activates dorsal-specific maternal RNA between 8- and 16-cell stages of Xenopus.

PubMed

Hainski, A M; Moody, S A

1996-01-01

In many animals the dorsal-ventral axis forms by an initial localization of maternal molecules, which then regulate the spatial location of signals that directly influence the expression of axis-specific fates. Several recent studies have demonstrated that dorsal-animal blastomeres of the Xenopus morula (8-32 cells) are biased toward dorsal fates prior to mesoderm inductive signaling. In this study we ask whether the dorsal bias is the result of autonomous expression of maternal molecules specifically localized within dorsal cells or of early activating signals. It was found that although 16-cell dorsal-animal blastomeres (D1.1) can differentiate into dorsal tissues when cultured alone, the 8-cell mothers (D1) can not. Likewise, although RNA extracted from D1.1 can induce an extra dorsal axis when injected into vegetal blastomeres, RNA extracted from D1 can not. However, D1 does express dorsal tissues if co-cultured with dorsal-vegetal cells or with culture medium containing a mixture of activins (PIF-medium). Furthermore, short-term culture of D1 in PIF-medium enables the D1 RNA to induce an ectopic dorsal axis. Ventral-animal blastomeres also can express dorsal axial tissues when co-cultured with dorsal-vegetal blastomeres or in PIF-medium, but the RNA from the activin-treated ventral cells cannot induce ectopic dorsal axes. These studies demonstrate that there are maternal RNAs that, shortly after fertilization, are present only in the dorsal-animal region. They do not act cell autonomously, but require an activin-like signal. These RNAs may function by increasing the responsiveness of dorsal-animal blastomeres to the mesoderm inductive signals present in both the morula and the blastula.

Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts.

PubMed

Sudha, Thangirala; Bharali, Dhruba J; Sell, Stewart; Darwish, Noureldien H E; Davis, Paul J; Mousa, Shaker A

2017-06-01

Thyroid hormone as L-thyroxine (T 4 ) stimulates proliferation of glioma cells in vitro and medical induction of hypothyroidism slows clinical growth of glioblastoma multiforme (GBM). The proliferative action of T 4 on glioma cells is initiated nongenomically at a cell surface receptor for thyroid hormone on the extracellular domain of integrin αvβ3. Tetraiodothyroacetic acid (tetrac) is a thyroid hormone derivative that blocks T 4 action at αvβ3 and has anticancer and anti-angiogenic activity. Tetrac has been covalently bonded via a linker to a nanoparticle (Nanotetrac, Nano-diamino-tetrac, NDAT) that increases the potency of tetrac and broadens the anticancer properties of the drug. In the present studies of human GBM xenografts in immunodeficient mice, NDAT administered daily for 10 days subcutaneously as 1 mg tetrac equivalent/kg reduced tumor xenograft weight at animal sacrifice by 50%, compared to untreated control lesions (p < 0.01). Histopathological analysis of tumors revealed a 95% loss of the vascularity of treated tumors compared to controls at 10 days (p < 0.001), without intratumoral hemorrhage. Up to 80% of tumor cells were necrotic in various microscopic fields (p < 0.001 vs. control tumors), an effect attributable to devascularization. There was substantial evidence of apoptosis in other fields (p < 0.001 vs. control tumors). Induction of apoptosis in cancer cells is a well-described quality of NDAT. In summary, systemic NDAT has been shown to be effective by multiple mechanisms in treatment of GBM xenografts.

Ethical challenges in fetal surgery.

PubMed

Smajdor, Anna

2011-02-01

Fetal surgery has been practised for some decades now. However, it remains a highly complex area, both medically and ethically. This paper shows how the routine use of ultrasound has been a catalyst for fetal surgery, in creating new needs and new incentives for intervention. Some of the needs met by fetal surgery are those of parents and clinicians who experience stress while waiting for the birth of a fetus with known anomalies. The paper suggests that the role of technology and visualisation techniques in creating and meeting such new needs is ethically problematic. It then addresses the idea that fetal surgery should be restricted to interventions that are life-saving for the fetus, arguing that this restriction is unduly paternalistic. Fetal surgery poses challenges for an autonomy-based system of ethics. However, it is risky to circumvent these challenges by restricting the choices open to pregnant women, even when these choices appear excessively altruistic.

Genetically Engineered Cancer Models, But Not Xenografts, Faithfully Predict Anticancer Drug Exposure in Melanoma Tumors

PubMed Central

Combest, Austin J.; Roberts, Patrick J.; Dillon, Patrick M.; Sandison, Katie; Hanna, Suzan K.; Ross, Charlene; Habibi, Sohrab; Zamboni, Beth; Müller, Markus; Brunner, Martin; Sharpless, Norman E.

2012-01-01

Background. Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The usefulness of xenograft models for efficacy testing, however, has been questioned, whereas genetically engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may offer some advantages for efficacy assessment. A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human patients has not been performed. Methods. In this work, we evaluated the plasma and tumor dispositions of an antimelanoma agent, carboplatin, in patients with cutaneous melanoma compared with four different murine melanoma models (one GEMM, one human cell line xenograft, and two OSTs). Results. Using microdialysis to sample carboplatin tumor disposition, we found that OSTs and xenografts were poor predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK parameters similar to those seen in human tumors. Conclusions. The tumor PKs of carboplatin in a GEMM of melanoma more closely resembles the tumor disposition in patients with melanoma than transplanted tumor models. GEMMs show promise in becoming an improved prediction model for intratumoral PKs and response in patients with solid tumors. PMID:22993143

Fetal heart rate monitoring.

PubMed

Nageotte, Michael P

2015-06-01

Electronic fetal heart rate monitoring is a widely utilized means of assessment of fetal status during labor. Whereas little evidence exists regarding efficacy, this modality continues to be used extensively in every modern labor and delivery unit in developed countries. It is of importance that all providers of health care to the woman in labor and her newborn have a clear understanding of the basic pathophysiology of fetal heart rate monitoring and an appreciation for labor course and concerns as they arise in order to optimize outcomes and patient safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance.

PubMed

Xu, Yunhua; Zhang, Feifei; Pan, Xiaoqing; Wang, Guan; Zhu, Lei; Zhang, Jie; Wen, Danyi; Lu, Shun

2018-05-09

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively. Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing (WES), and patients and xenograft-bearing mice received targeted treatment (crizotinib or osimertinib) accordingly. Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size. Finally, the pathology of patients biopsies and xenograft tumors were compared histologically. The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients. WES showed that the genotypes of the xenograft and patient tumors were similar (an echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) gene fusion (patient/xenograft: CTC15035 EML4-ALK ) and EGFR L858R and T790M mutations (patient/xenograft: CTC15063 EGFR L858R, T790M )). After continuous crizotinib or osimertinib treatment, WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035 EML4-ALK xenograft, while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B (BRAF) G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha (PIK3C2A) A86fs frame shift mutations led to osimertinib resistance in the CTC15063 EGFR L858R, T790M xenografts. We successfully developed a new method of generating

The dorsal raphe modulates sensory responsiveness during arousal in zebrafish

PubMed Central

Yokogawa, Tohei; Hannan, Markus C.; Burgess, Harold A.

2012-01-01

During waking behavior animals adapt their state of arousal in response to environmental pressures. Sensory processing is regulated in aroused states and several lines of evidence imply that this is mediated at least partly by the serotonergic system. However there is little information directly showing that serotonergic function is required for state-dependent modulation of sensory processing. Here we find that zebrafish larvae can maintain a short-term state of arousal during which neurons in the dorsal raphe modulate sensory responsiveness to behaviorally relevant visual cues. Following a brief exposure to water flow, larvae show elevated activity and heightened sensitivity to perceived motion. Calcium imaging of neuronal activity after flow revealed increased activity in serotonergic neurons of the dorsal raphe. Genetic ablation of these neurons abolished the increase in visual sensitivity during arousal without affecting baseline visual function or locomotor activity. We traced projections from the dorsal raphe to a major visual area, the optic tectum. Laser ablation of the tectum demonstrated that this structure, like the dorsal raphe, is required for improved visual sensitivity during arousal. These findings reveal that serotonergic neurons of the dorsal raphe have a state-dependent role in matching sensory responsiveness to behavioral context. PMID:23100441

Thrombophilic disorders and fetal loss: a meta-analysis.

PubMed

Rey, Evelyne; Kahn, Susan R; David, Michèle; Shrier, Ian

2003-03-15

Our aim was to assess the strength of the controversial association between thrombophilia and fetal loss, and to examine whether it varies according to the timing or definition of fetal loss. We searched Medline and Current Contents for articles published between 1975 and 2002 and their references with terms denoting recurrent fetal and non-recurrent fetal loss combined with various thrombophilic disorders. We included in our meta-analysis case-control, cohort, and cross-sectional studies published in English, the methodological quality of which was rated as moderate or strong. Pooled odds ratios (OR) with 95% CI were generated by random effects models with Cochrane Review Manager software. We included 31 studies. Factor V Leiden was associated with early (OR 2.01, 95% CI 1.13-3.58) and late (7.83, 2.83-21.67) recurrent fetal loss, and late non-recurrent fetal loss (3.26, 1.82-5.83). Exclusion of women with other pathologies that could explain fetal loss strengthened the association between Factor V Leiden and recurrent fetal loss. Activated protein C resistance was associated with early recurrent fetal loss (3.48, 1.58-7.69), and prothrombin G20210A mutation with early recurrent (2.56, 1.04-.29) and late non-recurrent (2.30, 1.09-4.87) fetal loss. Protein S deficiency was associated with recurrent fetal loss (14.72, 0.99-218.01) and late non-recurrent fetal loss (7.39, 1.28-42.63). Methylenetetrahydrofolate mutation, protein C, and antithrombin deficiencies were not significantly associated with fetal loss. The magnitude of the association between thrombophilia and fetal loss varies, according to type of fetal loss and type of thrombophilia.

Maternal hemodynamics, fetal biometry and Dopplers in pregnancies followed up for suspected fetal growth restriction.

PubMed

Roberts, Llinos A; Ling, Hua Zen; Poon, Liona; Nicolaides, Kypros H; Kametas, Nikos A

2018-04-01

To assess whether in a cohort of patients with small for gestational age (SGA) foetuses with estimated fetal weight ≤10 th percentile, maternal hemodynamics, fetal biometry and Dopplers at presentation, can predict the subsequent development of abnormal fetal Dopplers or delivery with birthweight <3 rd percentile. The study population comprised of 86 singleton pregnancies with SGA fetuses presenting at a median gestational age of 32 (range 26-35) weeks. We measured maternal cardiac function with a non-invasive transthoracic bioreactance monitor (NICOM, Cheetah), mean arterial pressure, fetal biometry, umbilical artery (UA), middle cerebral artery (MCA) and uterine artery (UT) pulsatility index (PI) and the deepest vertical pool (DVP) of amniotic fluid. Z-scores of these variables were calculated based on reported reference ranges and the values were compared between those with evidence of abnormal fetal Dopplers at presentation (group 1), those that developed abnormal Dopplers in subsequent visits (group 2) and those who did not develop abnormal Dopplers throughout pregnancy (group 3). Abnormal fetal Dopplers were defined as UAPI >95 th percentile, or MCA PI <5 th percentile. Differences in measured variables at presentation were also compared between pregnancies delivering a baby with birthweight <3 rd and ≥3 rd percentile. Multivariate logistic regression analysis was used to determine significant predictors of birthweight <3 rd percentile and evolution from normal fetal Dopplers to abnormal fetal Dopplers in groups 2 and 3. In the study population 14 (16%) cases were in group 1, 19 (22%) in group 2 and 53 (62%) in group 3. The birthweight was <3 rd percentile in 39 (45%) cases and ≥3 rd percentile in 47 (55%). In the study groups, compared to normal populations, there was decreased cardiac output and stroke volume and increased peripheral vascular resistance and mean arterial pressure (MAP) and the deviations from normal were most marked in group 1

Dorsal CA1 interneurons contribute to acute stress-induced spatial memory deficits.

PubMed

Yu, Jing-Ying; Fang, Ping; Wang, Chi; Wang, Xing-Xing; Li, Kun; Gong, Qian; Luo, Ben-Yan; Wang, Xiao-Dong

2018-06-01

Exposure to severely stressful experiences disrupts the activity of neuronal circuits and impairs declarative memory. GABAergic interneurons coordinate neuronal network activity, but their involvement in stress-evoked memory loss remains to be elucidated. Here, we provide evidence that interneurons in area CA1 of the dorsal hippocampus partially modulate acute stress-induced memory deficits. In adult male mice, both acute forced swim stress and restraint stress impaired hippocampus-dependent spatial memory and increased the density of c-fos-positive interneurons in the dorsal CA1. Selective activation of dorsal CA1 interneurons by chemogenetics disrupted memory performance in the spatial object recognition task. In comparison, anxiety-related behavior, spatial working memory and novel object recognition memory remained intact when dorsal CA1 interneurons were overactivated. Moreover, chemogenetic activation of dorsal CA1 interneurons suppressed the activity of adjacent pyramidal neurons, whereas a single exposure to forced swim stress but not restraint stress increased the activity of CA1 pyramidal neurons. However, chemogenetic inhibition of dorsal CA1 interneurons led to spatial memory impairments and failed to attenuate acute stress-induced memory loss. These findings suggest that acute stress may overactivate interneurons in the dorsal CA1, which reduces the activity of pyramidal neurons and in turn disrupts long-term memory. Copyright © 2018 Elsevier Ltd. All rights reserved.

Passive Fetal Heart Monitoring System

NASA Technical Reports Server (NTRS)

Zuckerwar, Allan J. (Inventor); Mowrey, Dennis L. (Inventor)

2003-01-01

A fetal heart monitoring system and method for detecting and processing acoustic fetal heart signals transmitted by different signal transmission modes. One signal transmission mode, the direct contact mode, occurs in a first frequency band when the fetus is in direct contact with the maternal abdominal wall. Another signal transmission mode, the fluid propagation mode, occurs in a second frequency band when the fetus is in a recessed position with no direct contact with the maternal abdominal wall. The second frequency band is relatively higher than the first frequency band. The fetal heart monitoring system and method detect and process acoustic fetal heart signals that are in the first frequency band and in the second frequency band.

Xenograft transplantation in congenital cardiac surgery at Baskent University: midterm results.

PubMed

Ozkan, S; Akay, T H; Gultekin, B; Sezgin, A; Tokel, K; Aslamaci, S

2007-05-01

Xenograft valved conduits have been used in several cardiac pathologies. In this study we have presented our midterm results of pediatric patients pathologies who were operated with xenograft conduits. Between January 1999 and January 2005, 134 patients underwent open heart surgery with xenograft conduits. The conduits were used to establish the continuity of the right ventricle to the pulmonary artery or aorta, the left ventricle to the pulmonary artery, or aorta due to various types of complex cardiac anomalies. Patients were evaluated by transthoracic echocardiography (ECHO) at 6-month follow-ups. Cardiac catheterization was performed when ECHO demonstrated significant conduit failure. Hospital mortality was observed in 28 patients (20.1%), and 13 patients died upon follow-up (9.7%). Mean follow-up was 24.6 +/- 4 months (range, 13 to 85 months). Among 93 survivors 20 patients (21.5%) were reoperated due to conduit failure. The main reasons for conduit failure were stenosis (n=13), valvular regurgitation (n=2), or both conditions in 5 cases. Mean pulmonary gradient before conduit re-replacement was 47.7 +/- 30.1 mmHg. The 1-, 3-, and 6-year actuarial survival rates were 95 +/- 2%, 91 +/- 3%, and 86 +/- 5%. The 1-, 3-, and 6-year actuarial freedom rates from reoperation were 95 +/- 1%, 90 +/- 3%, and 86 +/- 4%. An increased gradient between the pulmonary artery and the right ventricle and prolonged cardiopulmonary bypass times were observed to be significant risk factors for reoperation. There was no mortality among reoperated patients. Xenograft conduits should be closely followed for calcification and stenosis. Conduit stenosis is the major risk factor for reoperation. In these patients, reoperation for conduit replacement can be performed safely before deterioration of cardiac performance.

Synthetic progestins induce growth and metastasis of BT-474 human breast cancer xenografts in nude mice

PubMed Central

Liang, Yayun; Benakanakere, Indira; Besch-Williford, Cynthia; Hyder, Ryyan S; Ellersieck, Mark R.; Hyder, Salman M

2010-01-01

Objective Previous studies showed that sequential exposure to estrogen and progesterone or medroxyprogesterone acetate (MPA) stimulates vascularization and promotes the progression of BT-474 and T47-D human breast cancer cell xenografts in nude mice (Liang et al, Cancer Res 2007, 67:9929). In this follow-up study, the effects of progesterone, MPA, norgestrel (N-EL) and norethindrone (N-ONE) on BT-474 xenograft tumors were compared in the context of several different hormonal environments. N-EL and N-ONE were included in the study since synthetic progestins vary considerably in their biological effects and the effects of these two progestins on the growth of human tumor xenografts are not known. Methods Estradiol-supplemented intact and ovariectomized Immunodeficient mice were implanted with BT-474 cells. Progestin pellets were implanted either simultaneously with estradiol pellets 2-days prior to tumor cell injection (i.e. combined), or 5-days following tumor cell injections (i.e. sequentially). Results Progestins stimulated the growth of BT-474 xenograft tumors independent of exposure timing and protocol, MPA stimulated the growth of BT-474 xenograft tumors in ovariectomized mice and progestins stimulated VEGF elaboration and increased tumor vascularity. Progestins also increased lymph node metastasis of BT-474 cells. Therefore, progestins, including N-EL and N-ONE, induce the progression of breast cancer xenografts in nude mice and promote tumor metastasis. Conclusions These observations suggests that women who ingest progestins for HT or oral contraception could be more at risk for developing breast cancer as a result of proliferation of existing latent tumor cells. Such risks should be considered in the clinical setting. PMID:20461021

Dorsal buccal mucosa graft urethroplasty for female urethral strictures.

PubMed

Migliari, Roberto; Leone, Pierluigi; Berdondini, Elisa; De Angelis, M; Barbagli, Guido; Palminteri, Enzo

2006-10-01

We describe the feasibility and complications of dorsal buccal mucosa graft urethroplasty in female patients with urethral stenosis. From April 2005 to July 2005, 3 women 45 to 65 years old (average age 53.7) with urethral stricture disease underwent urethral reconstruction using a dorsal buccal mucosa graft. Stricture etiology was unknown in 1 patient, ischemic in 1 and iatrogenic in 1. Buccal mucosa graft length was 5 to 6 cm and width was 2 to 3 cm. The urethra was freed dorsally until the bladder neck and then opened on the roof. The buccal mucosa patch was sutured to the margins of the opened urethra and the new roof of the augmented urethra was quilted to the clitoris corpora. In all cases voiding urethrogram after catheter removal showed a good urethral shape with absent urinary leakage. No urinary incontinence was evident postoperatively. On urodynamic investigation all patients showed an unobstructed Blaivas-Groutz nomogram. Two patients complained about irritative voiding symptoms at catheter removal, which subsided completely and spontaneously after a week. The dorsal approach with buccal mucosa graft allowed us to reconstruct an adequate urethra in females, decreasing the risks of incontinence and fistula.

Fetal motor activity and maternal cortisol

PubMed Central

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Laudenslager, Mark L.

2009-01-01

The contemporaneous association between maternal salivary cortisol and fetal motor activity was examined at 32 and 36 weeks gestation. Higher maternal cortisol was positively associated with the amplitude of fetal motor activity at 32 weeks, r(48) = .39, p < .01, and 36 weeks, r(77)=.27, p < .05, and the amount of time fetuses spent moving at 32 weeks during the 50 minute observation period, r(48) = 33, p < .05. Observation of periods of unusually intense fetal motor activity were more common in fetuses of women with higher cortisol, Mann-Whitney U = 58.5. There were no sex differences in fetal motor activity, but the associations between maternal cortisol and fetal motor amplitude and overall movement were significantly stronger for male than female fetuses. PMID:19630038

Fetal Treatment 2017: the Evolution of Fetal Therapy Centers

PubMed Central

MOON-GRADY, Anita J.; BASCHAT, Ahmet; CASS, Darrell; CHOOLANI, Mahesh; COPEL, Joshua; CROMBLEHOLME, Timothy M.; DEPREST, Jan; EMERY, Stephen P.; EVANS, Mark I.; LUKS, Francois; NORTON, Mary E.; RYAN, Greg; TSAO, Kuojen; WELCH, Ross; HARRISON, Michael

2017-01-01

More than 3 decades ago, a small group of physicians and other practitioners active in what they called “fetal treatment” authored an opinion piece outlining the current status and future challenges anticipated in the field. Many advances in maternal, neonatal, and perinatal care and diagnostic and therapeutic modalities have been made in the intervening years, yet a thoughtful re-assessment of the basic tenets put forth in 1982 has not been published. The present effort will aim to provide a framework for contemporary redefinition of the field of fetal treatment, with brief discussion of the necessary minimum expertise and systems-base for provision of different types of interventions on both a mother and fetus. Our goal will be to present an opinion that encourages the advancement of thoughtful practice, ensuring that current and future patients have realistic access to centers with a range of fetal therapies with appropriate expertise, experience, subspecialty and institutional support while remaining focused on excellence in care, collaborative scientific discovery, and maternal autonomy and safety. PMID:28531885

Weighing the evidence for a dorsal processing bias under continuous flash suppression.

PubMed

Ludwig, Karin; Hesselmann, Guido

2015-09-01

With the introduction of continuous flash suppression (CFS) as a method to render stimuli invisible and study unconscious visual processing, a novel hypothesis has gained popularity. It states that processes typically ascribed to the dorsal visual stream can escape CFS and remain functional, while ventral stream processes are suppressed when stimuli are invisible under CFS. This notion of a CFS-specific "dorsal processing bias" has been argued to be in line with core characteristics of the influential dual-stream hypothesis of visual processing which proposes a dissociation between dorsally mediated vision-for-action and ventrally mediated vision-for-perception. Here, we provide an overview of neuroimaging and behavioral studies that either examine this dorsal processing bias or base their conclusions on it. We show that both evidence for preserved ventral processing as well as lack of dorsal processing can be found in studies using CFS. To reconcile the diverging results, differences in the paradigms and their effects are worthy of future research. We conclude that given the current level of information a dorsal processing bias under CFS cannot be universally assumed. Copyright © 2014 Elsevier Inc. All rights reserved.

The Tribolium castaneum Ortholog of Sex combs reduced Controls Dorsal Ridge Development

PubMed Central

Shippy, Teresa D.; Rogers, Carmelle D.; Beeman, Richard W.; Brown, Susan J.; Denell, Robin E.

2006-01-01

In insects, the boundary between the embryonic head and thorax is formed by the dorsal ridge, a fused structure composed of portions of the maxillary and labial segments. However, the mechanisms that promote development of this unusual structure remain a mystery. In Drosophila, mutations in the Hox genes Sex combs reduced and Deformed have been reported to cause abnormal dorsal ridge formation, but the significance of these abnormalities is not clear. We have identified three mutant allele classes of Cephalothorax, the Tribolium castaneum (red flour beetle) ortholog of Sex combs reduced, each of which has a different effect on dorsal ridge development. By using Engrailed expression to monitor dorsal ridge development in these mutants, we demonstrate that Cephalothorax promotes the fusion and subsequent dorsolateral extension of the maxillary and labial Engrailed stripes (posterior compartments) during dorsal ridge formation. Molecular and genetic analysis of these alleles indicates that the N terminus of Cephalothorax is important for the fusion step, but is dispensable for Engrailed stripe extension. Thus, we find that specific regions of Cephalothorax are required for discrete steps in dorsal ridge formation. PMID:16849608

The "Fetal Reserve Index": Re-Engineering the Interpretation and Responses to Fetal Heart Rate Patterns.

PubMed

Eden, Robert D; Evans, Mark I; Evans, Shara M; Schifrin, Barry S

2018-01-01

Electronic fetal monitoring (EFM) correlates poorly with neonatal outcome. We present a new metric: the "Fetal Reserve Index" (FRI), formally incorporating EFM with maternal, obstetrical, fetal risk factors, and excessive uterine activity for assessment of risk for cerebral palsy (CP). We performed a retrospective, case-control series of 50 term CP cases with apparent intrapartum neurological injury and 200 controls. All were deemed neurologically normal on admission. We compared the FRI against ACOG Category (I-III) system and long-term outcome parameters against ACOG monograph (NEACP) requirements for labor-induced fetal neurological injury. Abnormal FRI's identified 100% of CP cases and did so hours before injury. ACOG Category III identified only 44% and much later. Retrospective ACOG monograph criteria were found in at most 30% of intrapartum-acquired CP patients; only 27% had umbilical or neonatal pH <7.0. In this initial, retrospective trial, an abnormal FRI identified all cases of labor-related neurological injury more reliably and earlier than Category III, which may allow fetal therapy by intrauterine resuscitation. The combination of traditional EFM with maternal, obstetrical, and fetal risk factors creating the FRI performed much better as a screening test than EFM alone. Our quantified screening system needs further evaluation in prospective trials. © 2017 S. Karger AG, Basel.

Core Promoter Functions in the Regulation of Gene Expression of Drosophila Dorsal Target Genes*

PubMed Central

Zehavi, Yonathan; Kuznetsov, Olga; Ovadia-Shochat, Avital; Juven-Gershon, Tamar

2014-01-01

Developmental processes are highly dependent on transcriptional regulation by RNA polymerase II. The RNA polymerase II core promoter is the ultimate target of a multitude of transcription factors that control transcription initiation. Core promoters consist of core promoter motifs, e.g. the initiator, TATA box, and the downstream core promoter element (DPE), which confer specific properties to the core promoter. Here, we explored the importance of core promoter functions in the dorsal-ventral developmental gene regulatory network. This network includes multiple genes that are activated by different nuclear concentrations of Dorsal, an NFκB homolog transcription factor, along the dorsal-ventral axis. We show that over two-thirds of Dorsal target genes contain DPE sequence motifs, which is significantly higher than the proportion of DPE-containing promoters in Drosophila genes. We demonstrate that multiple Dorsal target genes are evolutionarily conserved and functionally dependent on the DPE. Furthermore, we have analyzed the activation of key Dorsal target genes by Dorsal, as well as by another Rel family transcription factor, Relish, and the dependence of their activation on the DPE motif. Using hybrid enhancer-promoter constructs in Drosophila cells and embryo extracts, we have demonstrated that the core promoter composition is an important determinant of transcriptional activity of Dorsal target genes. Taken together, our results provide evidence for the importance of core promoter composition in the regulation of Dorsal target genes. PMID:24634215

Electronic fetal monitoring: family medicine obstetrics.

PubMed

Rodney, John R M; Huntley, Benjamin J F; Rodney, Wm Macmillan

2012-03-01

Electronic fetal monitoring assesses fetal health during the prenatal and intrapartum process. Intermittent auscultation does not detect key elements of fetal risk, such as beat-to-beat variability. Family medicine obstetric fellowships have contributed new knowledge to this process by articulating a method of analysis that builds on evidence-based recommendations from the American College of Obstetrics and Gynecology as well as the National Institute of Child Health and Development. This article summarizes the development, interpretation, and management of electronic fetal heart rate patterns and tracings. Copyright © 2012 Elsevier Inc. All rights reserved.

Findings and differential diagnosis of fetal intracranial haemorrhage and fetal ischaemic brain injury: what is the role of fetal MRI?

PubMed Central

Kennedy, Anne

2017-01-01

Ventriculomegaly (VM) is a non-specific finding on fetal imaging. Identification of the specific aetiology is important, as it affects prognosis and may even change the course of current or future pregnancies. In this review, we will focus on the application of fetal MRI to demonstrate intracranial haemorrhage and ischaemic brain injury as opposed to other causes of VM. MRI is able to identify the specific aetiology of VM with much more sensitivity and specificity than ultrasound and should be considered whenever VM is identified on obstetric ultrasound. Advances in both fetal and neonatal MRI have the potential to shed further light on mechanisms of brain injury and the impact of chronic hypoxia; such information may guide future interventions. PMID:27734711

Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection.

PubMed

Zlotnik, Alexander; Tsesis, Svetlana; Gruenbaum, Benjamin Fredrick; Ohayon, Sharon; Gruenbaum, Shaun Evan; Boyko, Matthew; Sheiner, Eyal; Brotfain, Evgeny; Shapira, Yoram; Teichberg, Vivian Itzhak

2012-09-01

Excess glutamate in the brain is thought to be implicated in the pathophysiology of fetal anoxic brain injury, yet little is known about the mechanisms by which glutamate is regulated in the fetal brain. This study examines whether there are differences between maternal and fetal glutamate concentrations, and whether a correlation between them exists. 10 ml of venous blood was extracted from 87 full-term (>37 weeks gestation) pregnant women in active labor. Immediately after delivery of the neonate, 10 ml of blood from the umbilical artery and vein was extracted. Samples were analyzed for levels of glutamate, glutamate-oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT). Fetal blood glutamate concentrations in both the umbilical artery and vein were found to be significantly higher than maternal blood (p<0.001). Similarly, fetal serum GOT levels in the umbilical artery and vein were found to be significantly higher than maternal GOT levels (p<0.001). The difference in GPT levels between maternal and fetal serum was not statistically significant. There was no difference in fetal glutamate, GOT or GPT between the umbilical artery and vein. There was an association observed between glutamate levels in maternal blood and glutamate levels in both venous (R=0.32, p<0.01) and arterial (R=0.33, p<0.05) fetal blood. This study demonstrated that higher baseline concentrations of blood glutamate are present in fetal blood compared with maternal blood, and this was associated with elevated GOT, but not GPT levels. An association was observed between maternal and fetal blood glutamate levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

Variegated clonality and rapid emergence of new molecular lesions in xenografts of acute lymphoblastic leukemia are associated with drug resistance.

PubMed

Nowak, Daniel; Liem, Natalia L M; Mossner, Maximilian; Klaumünzer, Marion; Papa, Rachael A; Nowak, Verena; Jann, Johann C; Akagi, Tadayuki; Kawamata, Norihiko; Okamoto, Ryoko; Thoennissen, Nils H; Kato, Motohiro; Sanada, Masashi; Hofmann, Wolf-Karsten; Ogawa, Seishi; Marshall, Glenn M; Lock, Richard B; Koeffler, H Phillip

2015-01-01

The use of genome-wide copy-number analysis and massive parallel sequencing has revolutionized the understanding of the clonal architecture of pediatric acute lymphoblastic leukemia (ALL) by demonstrating that this disease is composed of highly variable clonal ancestries following the rules of Darwinian selection. The current study aimed to analyze the molecular composition of childhood ALL biopsies and patient-derived xenografts with particular emphasis on mechanisms associated with acquired chemoresistance. Genomic DNA from seven primary pediatric ALL patient samples, 29 serially passaged xenografts, and six in vivo selected chemoresistant xenografts were analyzed with 250K single-nucleotide polymorphism arrays. Copy-number analysis of non-drug-selected xenografts confirmed a highly variable molecular pattern of variegated subclones. Whereas primary patient samples from initial diagnosis displayed a mean of 5.7 copy-number alterations per sample, serially passaged xenografts contained a mean of 8.2 and chemoresistant xenografts a mean of 10.5 copy-number alterations per sample, respectively. Resistance to cytarabine was explained by a new homozygous deletion of the DCK gene, whereas methotrexate resistance was associated with monoallelic deletion of FPGS and mutation of the remaining allele. This study demonstrates that selecting for chemoresistance in xenografted human ALL cells can reveal novel mechanisms associated with drug resistance. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2.

PubMed

Godel, Tim; Mautner, Victor-Felix; Farschtschi, Said; Pham, Mirko; Schwarz, Daniel; Kronlage, Moritz; Gugel, Isabel; Heiland, Sabine; Bendszus, Martin; Bäumer, Philipp

2018-04-01

Schwannomatosis and neurofibromatosis type 2 are hereditary tumor syndromes, and peripheral neuropathy has been reported in both. We prospectively applied in vivo morphometric measurement of dorsal root ganglia volume in 16 schwannomatosis patients, 14 neurofibromatosis type 2 patients, and 26 healthy controls by magnetic resonance neurography. Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in neurofibromatosis type 2 (L3, + 267%; L4, + 235%; L5, + 241%; S1, + 300%; S2, + 242%; Bonferroni-adjusted p < 0.001) but not in schwannomatosis. Dorsal root ganglia may be a vulnerable site in origination of areflexia and sensory loss and a useful diagnostic marker in neurofibromatosis type 2. Ann Neurol 2018;83:854-857. © 2018 American Neurological Association.

Pregnancy interruption after second trimester diagnosis of fetal structural anomalies: the New Jersey Fetal Abnormalities Registry.

PubMed

Rauch, Eden R; Smulian, John C; DePrince, Kristin; Ananth, Cande V; Marcella, Stephen W

2005-10-01

The purpose of this study was to identify factors that predict a decision to interrupt a pregnancy in which there are fetal anomalies in the second trimester. The New Jersey Fetal Abnormalities Registry prospectively recruits and collects information on pregnancies (> or = 15 weeks of gestation) from New Jersey residents in whom a fetal structural anomaly has been suspected by maternal-fetal medicine specialists. Enrolled pregnancies that have major fetal structural abnormalities identified from 15 to 23 weeks of gestation were included. Outcomes were classified as either elective interruption or a natural pregnancy course, which might include a spontaneous fetal death or live birth. Predictors of elective interruption of pregnancy were examined with univariable and multivariable logistic regression analyses. Of the 97 cases, 33% of the women (n = 32) interrupted the pregnancy. Significant variables in the regression model that were associated with a decision to interrupt a pregnancy were earlier identification of fetal anomalies (19.0 +/- 2 weeks of gestation vs 20.5 +/- 2 weeks of gestation; P = .003), the presence of multiple anomalies (78% [25/32] vs 52% [33/63]; P = .01], and a presumption of lethality (56% [18/32] vs 14% [9/65]; P = .0001). These variables corresponded to an odds ratio for pregnancy interruption of 4.2 (95% CI, 1.0, 17.0) for multiple anomalies, 0.8 (95% CI, 0.7, 1.0) for each week of advancing gestational age, and 36.1 (95% CI, 2.9, 450.7) for presumed lethal abnormalities. Early diagnosis, the identification of multiple abnormalities, and an assessment of likely lethality of fetal anomalies are important factors for the optimization of parental autonomy in deciding pregnancy management.

Physicochemical characterization of porcine bone-derived grafting material and comparison with bovine xenografts for dental applications.

PubMed

Lee, Jung Heon; Yi, Gyu Sung; Lee, Jin Woong; Kim, Deug Joong

2017-12-01

The physicochemical properties of a xenograft are very important because they strongly influence the bone regeneration capabilities of the graft material. Even though porcine xenografts have many advantages, only a few porcine xenografts are commercially available, and most of their physicochemical characteristics have yet to be reported. Thus, in this work we aimed to investigate the physicochemical characteristics of a porcine bone grafting material and compare them with those of 2 commercially available bovine xenografts to assess the potential of xenogenic porcine bone graft materials for dental applications. We used various characterization techniques, such as scanning electron microscopy, the Brunauer-Emmett-Teller adsorption method, atomic force microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and others, to compare the physicochemical properties of xenografts of different origins. The porcine bone grafting material had relatively high porosity (78.4%) and a large average specific surface area (SSA; 69.9 m 2 /g), with high surface roughness (10-point average roughness, 4.47 µm) and sub-100-nm hydroxyapatite crystals on the surface. Moreover, this material presented a significant fraction of sub-100-nm pores, with negligible amounts of residual organic substances. Apart from some minor differences, the overall characteristics of the porcine bone grafting material were very similar to those of one of the bovine bone grafting material. However, many of these morphostructural properties were significantly different from the other bovine bone grafting material, which exhibited relatively smooth surface morphology with a porosity of 62.0% and an average SSA of 0.5 m 2 /g. Considering that both bovine bone grafting materials have been successfully used in oral surgery applications in the last few decades, this work shows that the porcine-derived grafting material possesses most of the key physiochemical characteristics required for its

pO{sub 2} Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellingsen, Christine; Ovrebo, Kirsti Marie; Galappathi, Kanthi

2012-07-15

Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO{sub 2}) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO{sub 2} fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO{sub 2} was measured simultaneously in two positionsmore » in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO{sub 2} fluctuations, the pO{sub 2} fluctuation frequency in these regions, and the relative amplitude of the pO{sub 2} fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO{sub 2} in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO{sub 2} and, thus, protect tumor tissue from cycling hypoxia.« less

Dorsal buccal mucosal graft urethroplasty for anterior urethral stricture by Asopa technique.

PubMed

Pisapati, V L N Murthy; Paturi, Srimannarayana; Bethu, Suresh; Jada, Srikanth; Chilumu, Ramreddy; Devraj, Rahul; Reddy, Bhargava; Sriramoju, Vidyasagar

2009-07-01

Buccal mucosal graft (BMG) substitution urethroplasty has become popular in the management of intractable anterior urethral strictures with good results. Excellent long-term results have been reported by both dorsal and ventral onlay techniques. Asopa reported a successful technique for dorsal placement of BMG in long anterior urethral strictures through a ventral sagittal approach. To evaluate prospectively the results and advantages of dorsal BMG urethroplasty for recurrent anterior urethral strictures by a ventral sagittal urethrotomy approach (Asopa technique). From December 2002 to December 2007, a total of 58 men underwent dorsal BMG urethroplasty by a ventral sagittal urethrotomy approach for recurrent urethral strictures. Forty-five of these patients with a follow-up period of 12-60 mo were prospectively evaluated, and the results were analysed. The urethra was split twice at the site of the stricture both ventrally and dorsally without mobilising it from its bed, and the buccal mucosal graft was secured in the dorsal urethral defect. The urethra was then retubularised in one stage. The overall results were good (87%), with a mean follow-up period of 42 mo. Seven patients developed minor wound infection, and five patients developed fistulae. There were six recurrences (6:45, 13%) during the follow-up period of 12-60 mo. Two patients with a panurethral stricture and four with bulbar or penobulbar strictures developed recurrences and were managed by optical urethrotomy and self-dilatation. The medium-term results were as good as those reported with the dorsal urethrotomy approach. Long-term results from this and other series are awaited. More randomised trials and meta-analyses are needed to establish this technique as a procedure of choice in future. The ventral sagittal urethrotomy approach is easier to perform than the dorsal urethrotomy approach, has good results, and is especially useful in long anterior urethral strictures.

Silencing of Apis mellifera dorsal genes reveals their role in expression of the antimicrobial peptide defensin-1.

PubMed

Lourenço, Anete Pedro; Florecki, Mônica Mazzei; Simões, Zilá Luz Paulino; Evans, Jay Daniel

2018-04-17

Like all other insects, two key signaling pathways (Toll and Imd) regulate the induction of honey bee immune effectors that target microbial pathogens. Among these effectors are antimicrobial peptides (AMPs) that are presumed to be produced by the NF-κB factors Dorsal and Relish from the Toll and Imd pathways, respectively. Using in silico analysis, we previously proposed that the honey bee AMP defensin-1 was regulated by the Toll pathway, while hymenoptaecin was regulated by Imd and abaecin by both the Toll and Imd pathways. Here we use an RNA interference (RNAi) assay to determine the role of Dorsal in regulating abaecin and defensin-1. Honey bees have two dorsal genes (dorsal-1 and dorsal-2) and two splicing isoforms of dorsal-1 (dorsal-1A and dorsal-1B). Accordingly, we used both single and multiple (double or triple) isoform knockdown strategies to clarify the roles of dorsal proteins and their isoforms. Down-regulation of defensin-1 was observed for dorsal-1A and dorsal-2 knockdowns, but abaecin expression was not affected by dorsal RNAi. We conclude that defensin-1 is regulated by Dorsal (Toll pathway). This article is protected by copyright. All rights reserved. © 2018 The Royal Entomological Society.

Fetal microchimeric cells in autoimmune thyroid diseases

PubMed Central

Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

2013-01-01

Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083

Prediction of fetal compromise in labor.

PubMed

Prior, Tomas; Mullins, Edward; Bennett, Phillip; Kumar, Sailesh

2014-06-01

The majority of intrapartum fetal hypoxia occurs in uncomplicated pregnancies. Current intrapartum monitoring techniques have not resulted in a reduction in the incidence of cerebral palsy in term neonates. We report the development of a composite risk score to allow risk stratification of normal pregnancies before labor. Six hundred one women were recruited to this prospective observational study. All women underwent an ultrasound examination before active labor, during which fetal biometry and fetal Doppler flow resistance indices were measured. A composite risk score, amalgamating data from the umbilical artery, middle cerebral artery, and umbilical vein, was then developed and correlated with intrapartum outcomes. In cases with the highest composite risk scores, the incidence of fetal compromise (the primary outcome) was 80.0% compared with just 15.3% in cases with the lowest risk scores (relative risk 5.2, 95% confidence interval 2.7-10.1). These cases were also at increased risk of cesarean delivery (53.3% compared with 3.4%, P<.001) and of developing a fetal heart rate pattern considered pathologic by National Institute for Health and Clinical Excellence criteria (P=.003). No significant variation in Apgar scores or umbilical artery pH was observed. Intrapartum fetal compromise remains a significant global health issue. The composite risk score reported here can identify fetuses at both high risk and low risk of a subsequent diagnosis of intrapartum fetal compromise. This may enable more judicious use of current intrapartum fetal monitoring techniques, which are hampered by low specificity. II.

Fetal electrocardiograph

NASA Astrophysics Data System (ADS)

Rios, Heriberto; Andrade, Armando; Puente, Ernestina; Lizana, Pablo R.; Mendoza, Diego

2002-11-01

The high intra-uterine death rate is due to failure in appropriately diagnosing some problems in the cardiobreathing system of the fetus during pregnancy. The electrocardiograph is one apparatus which might detect problems at an early stage. With electrodes located near the womb and uterus, in a way similar to the normal technique, the detection of so-called biopotential differences, caused by concentrations of ions, can be achieved. The fetal electrocardiograph is based on an ultrasound technique aimed at detecting intrauterine problems in pregnant women, because it is a noninvasive technique due to the very low level of ultrasound power used. With this system, the following tests can be done: Heart movements from the ninth week onwards; Rapid and safe diagnosis of intrauterine fetal death; Location and size of the placenta. The construction of the fetal electrocardiograph requires instrument level components directly mounted on the printed circuit board, in order to avoid stray capacitance in the cabling which prevents the detection of the E.C.G. activity. The low cost of the system makes it affordable to low budget institutions; in contrast, available commercial systems are priced in U.S. Dollars. (To be presented in Spanish.)

Minimal alteration in the ratio of circulatory fetal DNA to fetal corticotropin-releasing hormone mRNA level in preeclampsia.

PubMed

Zhong, Xiao Yan; Holzgreve, Wolfgang; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Gupta, Anurag Kumar; Huppertz, Berthold; Hahn, Sinuhe

2006-01-01

We have recently observed that fetal DNA and fetal corticotropin-releasing hormone (CRH) mRNA are associated with in vitro generated syncytiotrophoblast-derived microparticles, and that the ratio of fetal DNA to mRNA (CRH) varied according to whether the particles were derived by predominantly apoptotic, apo-necrotic or necrotic pathways. Hence, we examined whether these ratios varied in maternal plasma samples taken from normotensive and preeclamptic pregnancies in vivo. Maternal plasma samples were collected from 18 cases with preeclampsia and 29 normotensive term controls. Circulatory fetal CRH mRNA and DNA levels were quantified by real-time PCR and RT-PCR. Circulatory fetal mRNA and fetal DNA levels were significantly elevated in the preeclampsia study group when compared to normotensive controls. Alterations in the fetal mRNA to DNA ratio between the study and control groups were minimal, even when stratified into early (<34 weeks of gestation) and late (>34 weeks of gestation) onset preeclampsia. Our data suggest that although circulatory fetal DNA and mRNA levels are significantly elevated in preeclampsia, the ratios in maternal plasma are not dramatically altered. Copyright 2006 S. Karger AG, Basel.

Mesenchymal stem cells display hepato-protective activity in lymphoma bearing xenografts.

PubMed

Secchiero, Paola; Corallini, Federica; Zavan, Barbara; Tripodo, Claudio; Vindigni, Vincenzo; Zauli, Giorgio

2012-04-01

A disseminated model of non-Hodgkin's lymphoma with prevalent liver metastasis was generated by intraperitoneal (i.p.) injection of EBV(+) B lymphoblastoid SKW6.4 in nude-SCID mice. The survival of SKW6.4 xenografts (median survival = 27 days) was significantly improved when hyaluronan scaffolds embedded with mesenchimal stem cells (MSC) were implanted in the abdominal area 4 days after SKW6.4 injection (median survival = 39.5 days). Mice implanted with MSC showed a significant improvement of hepatic functionality in lymphoma xenografts, as demonstrated by measurement of serum ALT/AST levels. Co-culture of MSC with lymphoma cells enhanced the release of hepatocyte growth factor (HGF) by MSC. These data suggest that hyaluronan-embedded MSC exert anti-lymphoma activity by ameliorating hepatic functionality.

The Different Dynamic Changes of Nerve Growth Factor in the Dorsal Horn and Dorsal Root Ganglion Leads to Hyperalgesia and Allodynia in Diabetic Neuropathic Pain.

PubMed

Gao, Zhifeng; Feng, Yi; Ju, Hui

2017-05-01

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and more than half of the patients with DPN have self-reported symptoms referring to painful diabetic neuropathy (PDN). Nerve growth factor (NGF) is a key factor for the nervous system, but the role of it in the neuropathic pain of diabetic patients is unclear. This study aimed to investigate the relationship between the dynamic expression of NGF in dorsal horn and dorsal root ganglion (DRG) of diabetic rats and hyperalgesia and allodynia in diabetic neuropathic pain. It also aimed to explore the effects of exogenous mouse NGF (mNGF) on NGF expression in dorsal horn, DRG, and mechanical pain threshold. Animal research study. Experimental research laboratory. The model of diabetes was established by a single intraperitoneal injection of streptozocin (STZ 55 mg/kg). Firstly, the rats were randomly divided into 2 groups: control group (n = 10) and diabetes group (n = 40). The diabetes group contained 4 subgroups: diabetes week 1 group (DM1, n = 10), diabetes week 2 group (DM2, n = 10), diabetes week 4 group (DM4, n = 10), and diabetes week 8 group (DM8, n = 10). Then, the other rats were randomly divided into 2 groups: control group (n = 10) and treatment group (n = 30). The treatment group contained 3 subgroups: saline group (n = 10), low dose mNGF group (mNGF1, n = 10), and high dose mNGF group (mNGF2, n = 10). Mechanical pain threshold was assessed using Von Frey hairs, before the establishment of the diabetes model and 1, 2, 4, and 8 weeks after the establishment. The NGF expression in dorsal horn and DRG was measured by western blot. The mechanical pain threshold decreased one week after the establishment of the diabetes model, which continued for 8 weeks. The NGF expression in the dorsal horn was reduced 2 weeks after diabetes induction and the decreased NGF expression continued for 4 weeks. However, the NGF expression in DRG was reduced one week after diabetes induction and

Damage in the dorsal striatum alleviates addictive behavior.

PubMed

Muskens, J B; Schellekens, A F A; de Leeuw, F E; Tendolkar, I; Hepark, S

2012-01-01

The ventral striatum has been assigned a major role in addictive behavior. In addition, clinical lesion studies have described involvement of the insula and globus pallidus. To the best of our knowledge, this is the first report of alleviation of alcohol and nicotine addiction after a cerebrovascular incident in the dorsal striatum. The patient was still abstinent from alcohol and nicotine at follow-up. This observation suggests that the dorsal striatum may play a critical role in addiction to alcohol and nicotine. Copyright © 2012 Elsevier Inc. All rights reserved.

Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones.

PubMed

Rahman, Wahida; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H

2008-06-01

Activity in descending systems from the brainstem modulates nociceptive transmission through the dorsal horn. Intrathecal injection of the neurotoxin saporin conjugated to SP (SP-SAP) into the lumbar spinal cord results in the selective ablation of NK(1) receptor expressing (NK(1)+ve) neurones in the superficial dorsal horn (lamina I/III). Loss of these NK(1)+ve neurones attenuates excitability of deep dorsal horn neurones due to a disruption of both intrinsic spinal circuits and a spino-bulbo-spinal loop, which activates a descending excitatory drive, mediated through spinal 5HT(3) receptors. Descending inhibitory pathways also modulate spinal activity and hence control the level of nociceptive transmission relayed to higher centres. To ascertain the spinal origins of the major descending noradrenergic inhibitory pathway we studied the effects of a selective alpha2-adrenoceptor antagonist, atipamezole, on neuronal activity in animals pre-treated with SP-SAP. Intrathecal application of atipamezole dose dependently facilitated the mechanically evoked neuronal responses of deep dorsal horn neurones to low intensity von Frey hairs (5-15 g) and noxious thermal (45-50 degrees C) evoked responses in SAP control animals indicating a physiological alpha2-adrenoceptor control. This facilitatory effect of atipamezole was lost in the SP-SAP treated group. These data suggest that activity within noradrenergic pathways have a dependence on dorsal horn NK(1)+ve cells. Further, noradrenergic descending inhibition may in part be driven by lamina I/III (NK(1)+ve) cells, and mediated via spinal alpha2-adrenoceptor activation. Since the same neuronal population drives descending facilitation and inhibition, the reduced excitability of lamina V/VI WDR neurones seen after loss of these NK(1)+ve neurones indicates a dominant role of descending facilitation.

bullwinkle and shark regulate dorsal-appendage morphogenesis in Drosophila oogenesis.

PubMed

Tran, David H; Berg, Celeste A

2003-12-01

bullwinkle (bwk) regulates embryonic anteroposterior patterning and, through a novel germline-to-soma signal, morphogenesis of the eggshell dorsal appendages. We screened for dominant modifiers of the bullwinkle mooseantler eggshell phenotype and identified shark, which encodes an SH2-domain, ankyrin-repeat tyrosine kinase. At the onset of dorsal-appendage formation, shark is expressed in a punctate pattern in the squamous stretch cells overlying the nurse cells. Confocal microscopy with cell-type-specific markers demonstrates that the stretch cells act as a substrate for the migrating dorsal-appendage-forming cells and extend cellular projections towards them. Mosaic analyses reveal that shark is required in follicle cells for cell migration and chorion deposition. Proper shark RNA expression in the stretch cells requires bwk activity, while restoration of shark expression in the stretch cells suppresses the bwk dorsal-appendage phenotype. These results suggest that shark plays an important downstream role in the bwk-signaling pathway. Candidate testing implicates Src42A in a similar role, suggesting conservation with a vertebrate signaling pathway involving non-receptor tyrosine kinases.

Fetal motion estimation from noninvasive cardiac signal recordings.

PubMed

Biglari, Hadis; Sameni, Reza

2016-11-01

Fetal motility is a widely accepted indicator of the well-being of a fetus. In previous research, it has be shown that fetal motion (FM) is coherent with fetal heart rate accelerations and an indicator for active/rest cycles of the fetus. The most common approach for FM and fetal heart rate (FHR) assessment is by Doppler ultrasound (DUS). While DUS is the most common approach for studying the mechanical activities of the heart, noninvasive fetal electrocardiogram (ECG) and magnetocardiogram (MCG) recording and processing techniques have been considered as a possible competitor (or complement) for the DUS. In this study, a fully automatic and robust framework is proposed for the extraction, ranking and alignment of fetal QRS-complexes from noninvasive fetal ECG/MCG. Using notions from subspace tracking, two measures, namely the actogram and rotatogram, are defined for fetal motion tracking. The method is applied to four fetal ECG/MCG databases, including twin MCG recordings. By defining a novel measure of causality, it is shown that there is significant coherency and causal relationship between the actogram/rotatogram and FHR accelerations/decelerations. Using this measure, it is shown that in many cases, the actogram and rotatogram precede the FHR variations, which supports the idea of motion-induced FHR accelerations/decelerations for these cases and raises attention for the non-motion-induced FHR variations, which can be associated to the fetal central nervous system developments. The results of this study can lead to novel perspectives of the fetal sympathetic and parasympathetic brain systems and future requirements of fetal cardiac monitoring.

Attention modulates the dorsal striatum response to love stimuli.

PubMed

Langeslag, Sandra J E; van der Veen, Frederik M; Röder, Christian H

2014-02-01

In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved-related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved-distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved-related information per se, but only by beloved-related information that is attended. Copyright © 2012 Wiley Periodicals, Inc.

Fetal scalp pH testing

MedlinePlus

... such as HIV/AIDS or hepatitis C. Normal Results Normal fetal blood sample results are: Normal pH: ... meaning of your specific test results. What Abnormal Results Mean A fetal scalp blood pH level of ...

Incidence of fetal bradycardia and effect of placental injury on fetal heart rate during second-trimester genetic amniocentesis.

PubMed

Hanprasertpong, T; Petpichetchian, C; Ponglopisit, S; Suksai, M; Kor-Anantakul, O; Geater, A; Pruksanusak, N; Hanprasertpong, J

2016-05-01

A prospective study was conducted for comparing the incidence of fetal bradycardia and level of fetal heart rate change following a second-trimester genetic amniocentesis with and without placental injury. A total of 257 and 495 participants in injured and non-injured groups were analysed. The incidence of fetal bradycardia following amniocentesis was not statistically different between the two groups (1.17%, [95% CI 0.24, 3.37] and 0.20%, [95% CI 0.005, 1.12]) in injured and non-injured placenta groups, respectively; p = 0.118). The mean change in baseline fetal heart rate before and after amniocentesis was also not significantly different between the two groups (p = 0.844). No fetal death or pregnancy loss occurred within 4 weeks after the procedure. All 4 bradycardia participants were normal and healthy and had an appropriate weight for their gestational age. We conclude that placental injury during a second-trimester genetic amniocentesis due to advanced maternal age poses only a low risk of fetal bradycardia, and there is no evidence of differences between subjects with injured and non-injured placenta in the changes in fetal heart rate.

spadetail-dependent cell compaction of the dorsal zebrafish blastula.

PubMed

Warga, R M; Nüsslein-volhard, C

1998-11-01

The dorsal marginal zone of the zebrafish blastula, equivalent to the amphibian Spemann organizer, is destined to become the tissues of the notochord and prechordal plate. Preceding gastrulation in the zebrafish, we find that these future mesendodermal cells acquire a cohesive cell behavior characterized by flattening and maximization of intercellular contacts, somewhat resembling cell compaction in mouse blastocysts. This behavior may suppress cell intermingling. Surprisingly, this blastula cell compaction requires normal function of spadetail, a gene known to be necessary for the dorsal convergent cell movement of paraxial mesoderm later in the gastrula. We propose that spadetail-dependent cell compaction subtly controls the early mixing and dispersal of dorsal cells that coalesce into the prospective organizer region. This early process may be necessary for the correct location of the boundary separating axial and paraxial cells. Copyright 1998 Academic Press.

Patient-derived tumor xenografts of lung squamous cell carcinoma alter long non-coding RNA profile but not responsiveness to cisplatin.

PubMed

Lu, Dapeng; Luo, Peng; Zhang, Ju; Ye, Yuanyuan; Wang, Qi; Li, Ming; Zhou, Hangcheng; Xie, Mingran; Wang, Baolong

2018-06-01

Lung squamous cell carcinoma (LSCC), the second most common type of lung cancer, has received limited attention. Patient-derived tumor xenografts (PDTXs) are useful preclinical models to reproduce the diverse heterogeneity of cancer, but it is important to identify potential variations during their establishment. A total of 18 PDTXs were established from 37 the surgical specimens and 16 were serially passaged to third generation. Second- and third-generation xenografts had a faster growth rate in mice. The tumor implantation success rate was associated with poorer differentiation, larger tumor volume and higher expression of Ki-67. The xenografts largely retained histological and key immunophenotypic features (including p53, p63, cytokeratin5/6, and E-cadherin). However, increased Ki-67 expression was identified in partial xenografts. Long non-coding RNA (lncRNA) and mRNA expression in third-generation xenografts differed from that of matched primary tumors. Gene Ontology and pathway analysis showed that mRNAs involved in cell cycle, and metabolism regulation were generally upregulated in xenografts, while those associated with immune responses were typically downregulated. Furthermore, the responses of xenografts to cisplatin were consistent with clinical outcome. In the present study, PDTXs of SCC were successfully established, and closely resembled their original tumor regarding their immunophenotype and response to cisplatin. Overall, PDTXS of LSCC altered the lncRNA profile and increased the proliferative activity of cancer cells, whilst retaining responsiveness to cisplatin.

Fetal heart rate variation after corticosteroids for fetal maturation.

PubMed

Knaven, Olga; Ganzevoort, Wessel; de Boer, Marjon; Wolf, Hans

2017-09-01

Several studies report a decrease of fetal heart rate (FHR) short-term variation (STV) after corticosteroids for improvement of fetal maturity and advice not to deliver a fetus for low STV within 2-3days after corticosteroids. However, literature is not unanimous in this respect. This study intends to asses STV longitudinally after corticosteroid administration. A retrospective cohort study in a tertiary perinatal centre from 2009 to 2015 included all women who had been treated with corticosteroids at gestational age of 26-34 weeks, had a computerized cardiotocography (cCTG) before and after medication and did not deliver within 48h. FHR and STV were stratified over 12-h periods and compared before and after corticosteroids. Women with imminent preterm labour (including PPROM) and women with placental problems (fetal growth restriction (FGR) or preeclampsia) (PE) were analysed separately. The effect of co-medication and gestational age was assessed. The study included 406 women, 211 with imminent preterm labour, 195 with FGR-PE. After corticosteroids STV increased 1-2ms (median 1.4; IQR 0.1-3.1) during the first 36h after start of corticosteroids. Thereafter a small decrease of less than 1ms (median -0,6; IQR -1.6 to 0.3) compared to before CC was seen. The most conspicuous effect of corticosteroids is a short term increase of STV and decrease of FHR. A slight decrease after 48-71h is possible, but abnormally low values should be considered as a sign of fetal distress. The clinical guidance, given by some, not to intervene because of a low STV after corticosteroids appears invalid. Copyright © 2017 Elsevier B.V. All rights reserved.

Relaxin receptor antagonist AT-001 synergizes with docetaxel in androgen-independent prostate xenografts.

PubMed

Neschadim, Anton; Pritzker, Laura B; Pritzker, Kenneth P H; Branch, Donald R; Summerlee, Alastair J S; Trachtenberg, John; Silvertown, Joshua D

2014-06-01

Androgen hormones and the androgen receptor (AR) pathway are the main targets of anti-hormonal therapies for prostate cancer. However, resistance inevitably develops to treatments aimed at the AR pathway resulting in androgen-independent or hormone-refractory prostate cancer (HRPC). Therefore, there is a significant unmet need for new, non-androgen anti-hormonal strategies for the management of prostate cancer. We demonstrate that a relaxin hormone receptor antagonist, AT-001, an analog of human H2 relaxin, represents a first-in-class anti-hormonal candidate treatment designed to significantly curtail the growth of androgen-independent human prostate tumor xenografts. Chemically synthesized AT-001, administered subcutaneously, suppressed PC3 xenograft growth by up to 60%. AT-001 also synergized with docetaxel, standard first-line chemotherapy for HRPC, to suppress tumor growth by more than 98% in PC3 xenografts via a mechanism involving the downregulation of hypoxia-inducible factor 1 alpha and the hypoxia-induced response. Our data support developing AT-001 for clinical use as an anti-relaxin hormonal therapy for advanced prostate cancer.

Fetal deaths in Brazil: a systematic review

PubMed Central

Barbeiro, Fernanda Morena dos Santos; Fonseca, Sandra Costa; Tauffer, Mariana Girão; Ferreira, Mariana de Souza Santos; da Silva, Fagner Paulo; Ventura, Patrícia Mendonça; Quadros, Jesirée Iglesias

2015-01-01

OBJECTIVE To review the frequency of and factors associated with fetal death in the Brazilian scientific literature. METHODS A systematic review of Brazilian studies on fetal deaths published between 2003 and 2013 was conducted. In total, 27 studies were analyzed; of these, 4 studies addressed the quality of data, 12 were descriptive studies, and 11 studies evaluated the factors associated with fetal death. The databases searched were PubMed and Lilacs, and data extraction and synthesis were independently performed by two or more examiners. RESULTS The level of completeness of fetal death certificates was deficient, both in the completion of variables, particularly sociodemographic variables, and in defining the underlying causes of death. Fetal deaths have decreased in Brazil; however, inequalities persist. Analysis of the causes of death indicated maternal morbidities that could be prevented and treated. The main factors associated with fetal deaths were absent or inadequate prenatal care, low education level, maternal morbidity, and adverse reproductive history. CONCLUSIONS Prenatal care should prioritize women that are most vulnerable (considering their social environment or their reproductive history and morbidities) with the aim of decreasing the fetal mortality rate in Brazil. Adequate completion of death certificates and investment in the committees that investigate fetal and infant deaths are necessary. PMID:25902565

Fetal myosin immunoreactivity in human dystrophic muscle.

PubMed

Schiaffino, S; Gorza, L; Dones, I; Cornelio, F; Sartore, S

1986-01-01

We report immunofluorescence observations on normal and dystrophic human muscle using an antibody (anti-bF) raised against bovine fetal myosin and specific for fetal myosin heavy chains. In rat skeletal muscle, anti-bF was previously found to react selectively with myosin isoforms expressed during fetal and early postnatal development and in regenerating muscles. Anti-bF stained most fibers in human fetal and neonatal muscle, whereas only nuclear chain fibers of muscle spindles were labeled in normal adult muscle. In muscle biopsies from patients with Duchenne's muscular dystrophy, numerous extrafusal fibers were stained: some were small regenerating fibers, others were larger fibers presumably resulting from previous regenerative events. Fetal myosin immunoreactivity in Duchenne's dystrophy appears to reflect the reexpression of fetal-specific myosin isoforms and provides a new valuable tool for identifying regenerating fibers and following their destiny in dystrophic muscle.

Preschool Teacher Attitude and Knowledge Regarding Fetal Alcohol Syndrome and Fetal Alcohol Effects.

ERIC Educational Resources Information Center

Mack, Faite R-P.

The Centers for Disease Control estimate that each year more than 8,000 Fetal Alcohol Syndrome (FAS) babies are born, and that many more babies go undiagnosed with Fetal Alcohol Effects (FAE), a less severe condition. FAS and FAE have been identified as major contributors to poor memory, shorter attention spans, lower IQs, diminished achievement…

21 CFR 884.2620 - Fetal electroencephalographic monitor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal electroencephalographic monitor. 884.2620... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2620 Fetal electroencephalographic monitor. (a) Identification. A fetal...

21 CFR 884.2620 - Fetal electroencephalographic monitor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal electroencephalographic monitor. 884.2620... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2620 Fetal electroencephalographic monitor. (a) Identification. A fetal...

21 CFR 884.2620 - Fetal electroencephalographic monitor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal electroencephalographic monitor. 884.2620... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2620 Fetal electroencephalographic monitor. (a) Identification. A fetal...

Dorsal Failures: From Saddle Deformity to Pollybeak.

PubMed

Hamilton, Grant S

2018-06-01

The nasal dorsum is an important component of a rhinoplasty and may be the primary motivation for seeking surgery. The nasal dorsum is a complex three-dimensional shape that is shrouded by local anesthetic and edema during surgery. This makes an accurate assessment of the surgical changes challenging. Complications related to dorsal modification include imbalances from over- or underresection of the structures of the nasal dorsum, inadequate or overaugmentation, an open-roof deformity, pollybeak, saddle nose, inverted-V, warped cartilage, visible grafts, contour problems, graft malposition, and extrusion. This review will discuss the common problems that can occur with dorsal modification during rhinoplasty. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The dorsal "action" pathway.

PubMed

Gallivan, Jason P; Goodale, Melvyn A

2018-01-01

In 1992, Goodale and Milner proposed a division of labor in the visual pathways of the primate cerebral cortex. According to their account, the ventral pathway, which projects to occipitotemporal cortex, constructs our visual percepts, while the dorsal pathway, which projects to posterior parietal cortex, mediates the visual control of action. Although the framing of the two-visual-system hypothesis has not been without controversy, it is clear that vision for action and vision for perception have distinct computational requirements, and significant support for the proposed neuroanatomic division has continued to emerge over the last two decades from human neuropsychology, neuroimaging, behavioral psychophysics, and monkey neurophysiology. In this chapter, we review much of this evidence, with a particular focus on recent findings from human neuroimaging and monkey neurophysiology, demonstrating a specialized role for parietal cortex in visually guided behavior. But even though the available evidence suggests that dedicated circuits mediate action and perception, in order to produce adaptive goal-directed behavior there must be a close coupling and seamless integration of information processing across these two systems. We discuss such ventral-dorsal-stream interactions and argue that the two pathways play different, yet complementary, roles in the production of skilled behavior. Copyright © 2018 Elsevier B.V. All rights reserved.

The dorsal thoracic fascia: anatomic significance with clinical applications in reconstructive microsurgery.

PubMed

Kim, P S; Gottlieb, J R; Harris, G D; Nagle, D J; Lewis, V L

1987-01-01

The anatomic distribution and potential arterial flow patterns of the circumflex scapular artery were investigated by Microfil injection. These studies demonstrated that the circumflex scapular artery lies within the dorsal thoracic fascia, which plays a significant role in the circulation of the overlying skin and subcutaneous tissue. We conclude that scapular/parascapular flaps are fasciocutaneous flaps, the dorsal thoracic fascia can be transferred as a free flap without its overlying skin and subcutaneous tissue, and intercommunication exists between the myocutaneous perforators of the latissimus dorsi myocutaneous flap and the vascular plexus of the dorsal thoracic fascia. We present microvascular cases in which the vascular properties of the dorsal thoracic fascia facilitated wound closure with free fascia flaps or expanded cutaneous or myocutaneous flaps.

In Vivo Activity and Pharmacokinetics of Nemorosone on Pancreatic Cancer Xenografts

PubMed Central

Wolf, Robert J.; Hilger, Ralf A.; Hoheisel, Jörg D.; Werner, Jens; Holtrup, Frank

2013-01-01

Pancreatic cancer is one of the leading cancer-related causes of death in the western world with an urgent need for new treatment strategies. Recently, hyperforin and nemorosone have been described as promising anti-cancer lead compounds. While hyperforin has been thoroughly investigated in vitro and in vivo, in vivo data for nemorosone are still missing. Thus, we investigated the growth-inhibitory potential of nemorosone on pancreatic cancer xenografts in NMRI nu/nu mice and determined basic pharmacokinetic parameters. Xenograft tumors were treated with nemorosone and gemcitabine, the current standard of care. Tumor sections were subjected to H&E as well as caspase 3 and Ki-67 staining. Nemorosone plasma kinetics were determined by HPLC and mass spectrometry. Induction of CYP3A4 and other metabolizing enzymes by nemorosone and hyperforin was tested on primary hepatocytes using qRT-PCR. At a dose of 50 mg/kg nemorosone per day, a significant growth-inhibitory effect was observed in pancreatic cancer xenografts. The compound was well tolerated and rapidly absorbed into the bloodstream with a half-life of approximately 30 min. Different metabolites were detected, possibly resembling CYP3A4-independent oxidation products. It is concluded that nemorosone is a potential anti-cancer lead compound with good bioavailability, little side-effects and promising growth-inhibitory effects, thus representing a valuable compound for a combination therapy approach. PMID:24040280

Fetal immune response to chorioamnionitis

PubMed Central

Kallapur, Suhas G.; Presicce, Pietro; Rueda, Cesar M.; Jobe, Alan H.; Chougnet, Claire A.

2014-01-01

Chorioamnionitis is a frequent cause of preterm birth and is associated with an increased risk for injury responses in the lung, GI tract, brain and other fetal organs. Chorioamnionitis is a polymicrobial non-traditional infectious disease because the organisms causing chorioamnionitis are generally of low virulence and colonize the amniotic fluid often for extended periods, and the host (mother and the fetus) does not have typical infection related symptoms such as fever. In this review, we discuss the effects of chorioamnionitis in experimental animal models that mimic the human disease. Our focus is on the immune changes in multiple fetal organs and the pathogenesis of chorioamnionitis induced injury in different fetal compartments. Since chorioamnionitis disproportionately affects preterm infants, we discuss the relevant developmental context for the immune system. We also provide a clinical context for the fetal responses. PMID:24390922

Transcriptome analysis of the immune reaction of the pearl oyster Pinctada fucata to xenograft from Pinctada maxima.

PubMed

Wei, Jinfen; Fan, Sigang; Liu, Baosuo; Zhang, Bo; Su, Jiaqi; Yu, Dahui

2017-08-01

The pearl oyster Pinctada maxima exhibits great difficulty to culture pearls through nuclear insertion with an allograft, but it is easy for P. fucata to culture pearls after allografting. If P. fucata could be used as a surrogate mother to culture P. maxima pearls, it would benefit the pearl culture industry of P. maxima. However, this is blocked by the immune rejection of P. fucata against P. maxima mantle grafts. In this study, the immune responses of P. fucata hemocyte to allograft and xenograft were investigated after transplantation by transcriptome analysis. In total, 107.93 Gb clean reads were produced and assembled using the reference genome of P. fucata. Gene Ontology Term enrichment and KEGG enrichment analyses indicated that apoptosis, hippo signaling pathway, oxidation-reduction, MAPK signaling pathway, ribosome, protein processing in endoplasmic reticulum, purine metabolism, NF-kappa B signaling pathway, oxidative phosphorylation, Ras signaling pathway, and ubiquitin mediated proteolysis were involved in response to transplantation. Many genes related to oxidation-reduction reactions, the MAPK signaling pathway, and apoptosis were identified by comparison of the allograft group and the xenograft group at 0 h, 6 h, 12 h, 24 h, 48 h, 72 h, and 96 h post-transplantation. Among them, the expression levels of NADH dehydrogenase, succinate dehydrogenase and other dehydrogenases were increased significantly in the xenograft groups compared with allograft groups at 0 h post transplantation, indicating that a respiratory burst of neutrophils occurred immediately after xenograft transplantation. Additionally, HSP70 was highly expressed from 0 h to 96 h in the xenograft groups, indicating an oyster immune response to the xenograft. The genes enriched in the ribosome and hippo-signaling pathways were also identified, and expression patterns of these DEGs were different as compared between transplantation and control groups. Finally, altered

Production of sperm from porcine fetal testicular tissue after cryopreservation and grafting into nude mice.

PubMed

Kaneko, Hiroyuki; Kikuchi, Kazuhiro; Men, Nguyen Thi; Nakai, Michiko; Noguchi, Junko; Kashiwazaki, Naomi; Ito, Junya

2017-03-15

A major goal of testicular xenografting is to salvage germ cells from immature animals that cannot be used for reproduction and generate their offspring. In this study, we investigated whether porcine fetal testicular tissue would acquire the ability to produce sperm with full developmental competence after they had been cryopreserved and grafted into nude mice. Testicular fragments from fetuses at 35, 55 and 90 days postartificial insemination (dpi) were vitrified and stored in liquid nitrogen. Immediately after warming, testicular fragments at each fetal stage were transplanted under the back skin of castrated nude mice (Crlj:CD1-Foxn1 nu ) (35-, 55- and 90-dpi groups, respectively) (day 0 = grafting). Before grafting, the testicular fragments contained seminiferous cords consisting of only gonocytes and Sertoli cells. Histological analyses of the testicular grafts revealed that the differentiation of seminiferous tubules was largely dependent on the time after grafting, and not on donor age. On day 180 in each group, 10-20% of the total number of tubule/cord cross-sections examined had germ cells that had progressed beyond the spermatogonial stage. Fewer than 5% of tubule cross-sections contained elongated spermatids or sperm. Between days 360 and 420, tubule differentiation advanced further, until more than 45% of the tubule cross-sections contained elongated spermatids or sperm. Sperm were recovered for the first time from a single mouse in the 55-dpi group on day 180, although on days 360-420 sperm were recovered from most mice in all of the groups. Serum concentrations of inhibin and testosterone in host mice in all of the groups were higher than those in castrated mice that had received no testicular grafts. Single sperm collected from mice in each group on day 300 or later were injected into individual in vitro-matured oocytes, and these sperm-injected oocytes were transferred to the oviducts of 2 or 3 estrus-synchronized recipient gilts. None of the

Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice

PubMed Central

Yang, Jun; Xie, Sheng-Xue; Huang, Yiling; Ling, Min; Liu, Jihong; Ran, Yali; Wang, Yanlin; Thrasher, J Brantley; Berkland, Cory; Li, Benyi

2012-01-01

Background Prostate cancer is the major cause of cancer death in men and the androgen receptor (AR) has been shown to play a critical role in the progression of the disease. Our previous reports showed that knocking down the expression of the AR gene using a siRNA-based approach in prostate cancer cells led to apoptotic cell death and xenograft tumor eradication. In this study, we utilized a biodegradable nanoparticle to deliver the therapeutic AR shRNA construct specifically to prostate cancer cells. Materials & methods The biodegradable nanoparticles were fabricated using a poly(dl-lactic-co-glycolic acid) polymer and the AR shRNA constructs were loaded inside the particles. The surface of the nanoparticles were then conjugated with prostate-specific membrane antigen aptamer A10 for prostate cancer cell-specific targeting. Results A10-conjugation largely enhanced cellular uptake of nanoparticles in both cell culture- and xenograft-based models. The efficacy of AR shRNA encapsulated in nanoparticles on AR gene silencing was confirmed in PC-3/AR-derived xenografts in nude mice. The therapeutic property of A10-conjugated AR shRNA-loaded nanoparticles was evaluated in xenograft models with different prostate cancer cell lines: 22RV1, LAPC-4 and LNCaP. Upon two injections of the AR shRNA-loaded nanoparticles, rapid tumor regression was observed over 2 weeks. Consistent with previous reports, A10 aptamer conjugation significantly enhanced xenograft tumor regression compared with nonconjugated nanoparticles. Discussion These data demonstrated that tissue-specific delivery of AR shRNA using a biodegradable nanoparticle approach represents a novel therapy for life-threatening prostate cancers. PMID:22583574

Inhibition of gamma-secretase activity impedes uterine serous carcinoma growth in a human xenograft model.

PubMed

Groeneweg, Jolijn W; Hall, Tracilyn R; Zhang, Ling; Kim, Minji; Byron, Virginia F; Tambouret, Rosemary; Sathayanrayanan, Sriram; Foster, Rosemary; Rueda, Bo R; Growdon, Whitfield B

2014-06-01

Uterine serous carcinoma (USC) represents an aggressive subtype of endometrial cancer. We sought to understand Notch pathway activity in USC and determine if pathway inhibition has anti-tumor activity. Patient USC tissue blocks were obtained and used to correlate clinical outcomes with Notch1 expression. Three established USC cell lines were treated with gamma-secretase inhibitor (GSI) in vitro. Mice harboring cell line derived or patient derived USC xenografts (PDXs) were treated with vehicle, GSI, paclitaxel and carboplatin (P/C), or combination GSI and P/C. Levels of cleaved Notch1 protein and Hes1 mRNA were determined in GSI treated samples. Statistical analysis was performed using the Wilcoxon rank sum and Kaplan-Meier methods. High nuclear Notch1 protein expression was observed in 58% of USC samples with no correlation with overall survival. GSI induced dose-dependent reductions in cell number and decreased levels of cleaved Notch1 protein and Hes1 mRNA in vitro. Treatment of mice with GSI led to decreased Hes1 mRNA expression in USC xenografts. In addition, GSI impeded tumor growth of cell line xenografts as well as UT1 USC PDXs. When GSI and P/C were combined, synergistic anti-tumor activity was observed in UT1 xenografts. Notch1 is expressed in a large subset of USC. GSI-mediated Notch pathway inhibition led to both reduced cell numbers in vitro and decreased tumor growth of USC some xenograft models. When combined with conventional chemotherapy, GSI augmented anti-tumor activity in one USC PDX line suggesting that targeting of the Notch signaling pathway is a potential therapeutic strategy for future investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Fetal median sacral artery anatomy study by micro-CT imaging.

PubMed

Meignan, P; Binet, A; Cook, A R; Lardy, H; Captier, G

2018-04-30

The median sacral artery (MSA) is the termination of the dorsal aorta, which undergoes a complex regression and remodeling process during embryo and fetal development. The MSA contributes to the pelvic vascularization and may be injured during pelvic surgery. The embryological steps of MSA development, anastomosis formation and anatomical variations are linked, but not fully understood. The pelvic vascularization and more precisely the MSA of a human fetus at 22 weeks of gestation (GW) were studied using micro-CT imaging. Image treatment included arterial segmentations and 3D visualization. At 22 GW, the MSA was a well-developed straight artery in front of the sacrum and was longer than the abdominal aorta. Anastomoses between the MSA and the internal pudendal arteries and the superior rectal artery were detected. No evidence was found for the existence of a coccygeal glomus with arteriovenous anastomosis. Micro-CT imaging and 3D visualization helped us understand the MSA central role in pelvic vascularization through the ilio-aortic anastomotic system. It is essential to know this anastomotic network to treat pathological conditions, such as sacrococcygeal teratomas and parasitic ischiopagus twins (for instance, fetus in fetu and twin-reversed arterial perfusion sequence).

Fetal auditory evoked responses to onset of amplitude modulated sounds. A fetal magnetoencephalography (fMEG) study.

PubMed

Draganova, R; Schollbach, A; Schleger, F; Braendle, J; Brucker, S; Abele, H; Kagan, K O; Wallwiener, D; Fritsche, A; Eswaran, H; Preissl, H

2018-06-01

The human fetal auditory system is functional around the 25th week of gestational age when the thalamocortical connections are established. Fetal magnetoencephalography (fMEG) provides evidence for fetal auditory brain responses to pure tones and syllables. Fifty-five pregnant women between 31 and 40 weeks of gestation were included in the study. Fetal MEG was recorded during the presentation of an amplitude modulated tone (AM) with a carrier frequency of 500 Hz to the maternal abdomen modulated by low modulation rates (MRs) - 2/s and 4/s, middle MR - 8/s and high MRs - 27/s, 42/s, 78/s and 91/s. The aim was to determine whether the fetal brain responds differently to envelope slopes and intensity change at the onset of the AM sounds. A significant decrease of the response latencies of transient event-related responses (ERR) to high and middle MRs in comparison to the low MRs was observed. The highest fetal response rate was achieved by modulation rates of 2/s, 4/s and 27/s (70%, 57%, and 86%, respectively). Additionally, a maturation effect of the ERR (response latency vs. gestational age) was observed only for 4/s MR. The significant difference between the response latencies to low, middle, and high MRs suggests that still before birth the fetal brain processes the sound slopes at the onset in different integration time-windows, depending on the time for the intensity increase or stimulus power density at the onset, which is a prerequisite for language acquisition. Copyright © 2018 Elsevier B.V. All rights reserved.

Detection of Genes Regulated by Lmx1b During Limb Dorsalization

PubMed Central

Feenstra, Jennifer M.; Kanaya, Kohei; Pira, Charmaine U; Hoffman, Sarah E.; Eppey, Richard J.; Oberg, Kerby C.

2012-01-01

Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs. Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wildtype mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified 54 target genes differentially expressed in all three stages. Several skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the relative abundance of extracellular matrix-related soft tissue targets regulated by Lmx1b, such as collagens and proteoglycans, suggests a mechanism which includes changes in the extracellular matrix composition to accomplish limb dorsalization. Our study provides the most comprehensive characterization of genes regulated by Lmx1b during limb development to-date and provides targets for further investigation. PMID:22417325

Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

PubMed

Spong, C Y; Abebe, D T; Gozes, I; Brenneman, D E; Hill, J M

2001-05-01

Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

Dissociated repetition deficits in aphasia can reflect flexible interactions between left dorsal and ventral streams and gender-dimorphic architecture of the right dorsal stream

PubMed Central

Berthier, Marcelo L.; Froudist Walsh, Seán; Dávila, Guadalupe; Nabrozidis, Alejandro; Juárez y Ruiz de Mier, Rocío; Gutiérrez, Antonio; De-Torres, Irene; Ruiz-Cruces, Rafael; Alfaro, Francisco; García-Casares, Natalia

2013-01-01

Assessment of brain-damaged subjects presenting with dissociated repetition deficits after selective injury to either the left dorsal or ventral auditory pathways can provide further insight on their respective roles in verbal repetition. We evaluated repetition performance and its neural correlates using multimodal imaging (anatomical MRI, DTI, fMRI, and18FDG-PET) in a female patient with transcortical motor aphasia (TCMA) and in a male patient with conduction aphasia (CA) who had small contiguous but non-overlapping left perisylvian infarctions. Repetition in the TCMA patient was fully preserved except for a mild impairment in nonwords and digits, whereas the CA patient had impaired repetition of nonwords, digits and word triplet lists. Sentence repetition was impaired, but he repeated novel sentences significantly better than clichés. The TCMA patient had tissue damage and reduced metabolism in the left sensorimotor cortex and insula. DTI showed damage to the left temporo-frontal and parieto-frontal segments of the arcuate fasciculus (AF) and part of the left ventral stream together with well-developed right dorsal and ventral streams, as has been reported in more than one-third of females. The CA patient had tissue damage and reduced metabolic activity in the left temporoparietal cortex with additional metabolic decrements in the left frontal lobe. DTI showed damage to the left temporo-parietal and temporo-frontal segments of the AF, but the ventral stream was spared. The direct segment of the AF in the right hemisphere was also absent with only vestigial remains of the other dorsal subcomponents present, as is often found in males. fMRI during word and nonword repetition revealed bilateral perisylvian activation in the TCMA patient suggesting recruitment of spared segments of the left dorsal stream and right dorsal stream with propagation of signals to temporal lobe structures suggesting a compensatory reallocation of resources via the ventral streams. The CA

Dissociated repetition deficits in aphasia can reflect flexible interactions between left dorsal and ventral streams and gender-dimorphic architecture of the right dorsal stream.

PubMed

Berthier, Marcelo L; Froudist Walsh, Seán; Dávila, Guadalupe; Nabrozidis, Alejandro; Juárez Y Ruiz de Mier, Rocío; Gutiérrez, Antonio; De-Torres, Irene; Ruiz-Cruces, Rafael; Alfaro, Francisco; García-Casares, Natalia

2013-01-01

Assessment of brain-damaged subjects presenting with dissociated repetition deficits after selective injury to either the left dorsal or ventral auditory pathways can provide further insight on their respective roles in verbal repetition. We evaluated repetition performance and its neural correlates using multimodal imaging (anatomical MRI, DTI, fMRI, and(18)FDG-PET) in a female patient with transcortical motor aphasia (TCMA) and in a male patient with conduction aphasia (CA) who had small contiguous but non-overlapping left perisylvian infarctions. Repetition in the TCMA patient was fully preserved except for a mild impairment in nonwords and digits, whereas the CA patient had impaired repetition of nonwords, digits and word triplet lists. Sentence repetition was impaired, but he repeated novel sentences significantly better than clichés. The TCMA patient had tissue damage and reduced metabolism in the left sensorimotor cortex and insula. DTI showed damage to the left temporo-frontal and parieto-frontal segments of the arcuate fasciculus (AF) and part of the left ventral stream together with well-developed right dorsal and ventral streams, as has been reported in more than one-third of females. The CA patient had tissue damage and reduced metabolic activity in the left temporoparietal cortex with additional metabolic decrements in the left frontal lobe. DTI showed damage to the left temporo-parietal and temporo-frontal segments of the AF, but the ventral stream was spared. The direct segment of the AF in the right hemisphere was also absent with only vestigial remains of the other dorsal subcomponents present, as is often found in males. fMRI during word and nonword repetition revealed bilateral perisylvian activation in the TCMA patient suggesting recruitment of spared segments of the left dorsal stream and right dorsal stream with propagation of signals to temporal lobe structures suggesting a compensatory reallocation of resources via the ventral streams. The

Bacteria of Porcine Skin, Xenografts, and Treatment with Neomycin Sulfate

PubMed Central

Smith, Rodney F.; Evans, Barbara L.

1972-01-01

Homogenized 4-mm punch biopsies were taken from pigs and bacteriologically evaluated to determine the efficacy of surgical scrub procedures and the subsequent treatment of tissue with 0.5% neomycin sulfate-sodium bisulfite (neomycin-bisulfite) as a decontaminating agent. The majority of the lots of porcine skin taken directly from animals for xenografts in the treatment of burns contained viable bacteria at the time of grafting although scrubbing procedures substantially reduced the skin bacteria. The porcine bacteria consisted primarily of coagulase-negative staphylococci with most strains exhibiting caseinolytic and elastase activity. Staphylococci were the only abundant bacteria found in postscrub biopsies and in saline solutions used to wash the dermatome during its use. After an overnight exposure of grafting tissue soaked in neomycin-bisulfite, the spent neomycin-bisulfite solutions were tested for bacteriostatic and bactericidal activity by comparison to unused neomycin. All solutions tested were equal in bacteriostatic strength, but the bactericidal action of some spent solutions was decreased. Neomycin alone exerted a more lethal effect on sensitive bacteria than the neomycin-bisulfite solution. The desirability of having viable porcine skin for a xenograft necessitated using or discarding the tissue after storage in neomycin-bisulfite at 4 C for a maximum of 72 hr. Certain contaminating microorganisms were unaffected by antibiotic treatment, and the prolonged use of neomycin without bisulfite would have primarily eradicated only the porcine coagulase-negative staphylococci. Neither the presence of this group in grafting tissue nor their proteolytic activity had any observed adverse effect on xenografting success. Images PMID:4552886

Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving.

PubMed

Li, Xuan; Carreria, Maria B; Witonsky, Kailyn R; Zeric, Tamara; Lofaro, Olivia M; Bossert, Jennifer M; Zhang, Jianjun; Surjono, Felicia; Richie, Christopher T; Harvey, Brandon K; Son, Hyeon; Cowan, Christopher W; Nestler, Eric J; Shaham, Yavin

2017-12-29

Methamphetamine (meth) seeking progressively increases after withdrawal (incubation of meth craving). We previously demonstrated an association between histone deacetylase 5 (HDAC5) gene expression in the rat dorsal striatum and incubation of meth craving. Here we used viral constructs to study the causal role of dorsal striatum HDAC5 in this incubation. In experiment 1 (overexpression), we injected an adeno-associated virus bilaterally into dorsal striatum to express either green fluorescent protein (control) or a mutant form of HDAC5, which strongly localized to the nucleus. After training rats to self-administer meth (10 days, 9 hours/day), we tested the rats for relapse to meth seeking on withdrawal days 2 and 30. In experiment 2 (knockdown), we injected an adeno-associated virus bilaterally into the dorsal striatum to express a short hairpin RNA either against luciferase (control) or against HDAC5. After training rats to self-administer meth, we tested the rats for relapse on withdrawal days 2 and 30. We also measured gene expression of other HDACs and potential HDAC5 downstream targets. We found that HDAC5 overexpression in dorsal striatum increased meth seeking on withdrawal day 30 but not day 2. In contrast, HDAC5 knockdown in the dorsal striatum decreased meth seeking on withdrawal day 30 but not on day 2; this manipulation also altered other HDACs (Hdac1 and Hdac4) and potential HDAC5 targets (Gnb4 and Suv39h1). Results demonstrate a novel role of dorsal striatum HDAC5 in incubation of meth craving. These findings also set up future work to identify HDAC5 targets that mediate this incubation. Published by Elsevier Inc.

Linear and nonlinear features of fetal heart rate on the assessment of fetal development in the course of pregnancy and the impact of fetal gender.

PubMed

Spyridou, K; Chouvarda, I; Hadjileontiadis, L; Maglaveras, N

2018-01-30

This work aims to investigate the impact of gestational age and fetal gender on fetal heart rate (FHR) tracings. Different linear and nonlinear parameters indicating correlation or complexity were used to study the influence of fetal age and gender on FHR tracings. The signals were recorded from 99 normal pregnant women in a singleton pregnancy at gestational ages from 28 to 40 weeks, before the onset of labor. There were 56 female fetuses and 43 male. Analysis of FHR shows that the means as well as measures of irregularity of FHR, such as approximate entropy and algorithmic complexity, decrease as gestation progresses. There were also indications that mutual information and multiscale entropy were lower in male fetuses in early pregnancy. Fetal age and gender seem to influence FHR tracings. Taking this into consideration would improve the interpretation of FHR monitoring.

Amnioserosa cell constriction but not epidermal actin cable tension autonomously drives dorsal closure.

PubMed

Pasakarnis, Laurynas; Frei, Erich; Caussinus, Emmanuel; Affolter, Markus; Brunner, Damian

2016-11-01

Tissue morphogenesis requires coordination of multiple force-producing components. During dorsal closure in fly embryogenesis, an epidermis opening closes. A tensioned epidermal actin/MyosinII cable, which surrounds the opening, produces a force that is thought to combine with another MyosinII force mediating apical constriction of the amnioserosa cells that fill the opening. A model proposing that each force could autonomously drive dorsal closure was recently challenged by a model in which the two forces combine in a ratchet mechanism. Acute force elimination via selective MyosinII depletion in one or the other tissue shows that the amnioserosa tissue autonomously drives dorsal closure while the actin/MyosinII cable cannot. These findings exclude both previous models, although a contribution of the ratchet mechanism at dorsal closure onset remains likely. This shifts the current view of dorsal closure being a combinatorial force-component system to a single tissue-driven closure event.

Complete dorsal pancreatic agenesis and unilateral renal agenesis.

PubMed

Moreira, Adriana; Carvalho, André; Portugal, Inês; Jesus, José Miguel

2018-02-01

Dorsal pancreatic agenesis is a very rare congenital anomaly. Unilateral renal agenesis, on the other hand, is a relatively common congenital anomaly, although its etiology is not fully understood. Renal and pancreatic embryologic development appears to be nonrelated. We report a case of a 34-year-old man who was referred to our hospital for evaluation of cholestasis and microalbuminuria. Ultrasound and magnetic resonance imaging examinations showed empty right renal fossa and absence of the pancreatic neck, body, and tail. Our case report is the second case of a dorsal pancreatic agenesis and unilateral renal agenesis in a young male patient.

Comparative study of subtalar arthrodesis after calcaneal frature malunion with autologous bone graft or freeze-dried xenograft.

PubMed

Henning, Carlo; Poglia, Gabriel; Leie, Murilo Anderson; Galia, Carlos Roberto

2015-12-01

Calcaneal fracture malunion may evolve into arthrosis and severe foot deformities. The aim of this study was to identify differences in bony union following corrective subtalar arthrodesis with interposition of autologous tricortical bone graft or freeze-dried bovine xenograft. We prospectively evaluated 12 patients who underwent subtalar arthrodesis, six patients received autografts and 6 received freeze-dried bovine xenografts. After a mean followup of 58 weeks, the patients were clinical assessed using AOFAS scale and the visual analog scale (VAS) for pain and for final radiographic parameters measurement. Two blind raters evaluated the length of time required for solid union of the arthrodesis and graft integration by retrospective radiographic examination. In the autograft group, AOFAS score improved from a preoperative average of 37 to 64 points postoperatively (p = 0.02) and mean VAS score improved from 4.7 to 1.9 (p = 0.028). In the xenograft group, AOFAS score improved from 38 to 74 points (p = 0.02) and VAS from 5.5 to 2.7 (p = 0.046). Solid union was achieved in all cases in the autograft group at an average of 5.3 weeks and in five cases in the xenograft group at 8.8 weeks (p = 0.077). Graft integration occurred after an average of 10.7 weeks in the autograft group and 28.8 weeks in the xenograft group (p = 0.016). With the numbers available, no significant difference could be detected in the length of time required for solid union of subtalar arthrodesis between groups, although time to integration of freeze-dried bovine xenografts was statistically higher. Clinical and functional improvement was observed in both groups.

Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

PubMed Central

Vines, Douglass C.; Scollard, Deborah A.; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Besanger, Travis

2017-01-01

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy. PMID:29097943

Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models.

PubMed

Zhang, Libo; Vines, Douglass C; Scollard, Deborah A; McKee, Trevor; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Vali, Reza; Shammas, Amer; Besanger, Travis; Baruchel, Sylvain

2017-01-01

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68 Ga-DOTA-TATE uptake and 177 Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68 Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68 Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177 Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro , NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131 I-MIBG therapy, low 123 I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68 Ga-DOTA-TATE uptake and antitumor efficacy of 177 Lu-DOTA-TATE. 68 Ga-DOTA-TATE PET is superior to 123 I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177 Lu-DOTA-TATE therapy.

21 CFR 884.2620 - Fetal electroencephalographic monitor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal electroencephalographic monitor. 884.2620... Devices § 884.2620 Fetal electroencephalographic monitor. (a) Identification. A fetal electroencephalographic monitor is a device used to detect, measure, and record in graphic form (by means of one or more...

Safe fetal platelet genotyping: new developments.

PubMed

Le Toriellec, Emilie; Chenet, Christophe; Kaplan, Cecile

2013-08-01

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is due to maternal alloimmunization against fetal platelet (PLT) antigens. Antenatal management strategies have been developed to avoid complications such as intracranial hemorrhage. The aim of this study was to set up two reliable, noninvasive fetal genotyping assays to determine the fetal risk in pregnancies in which the father is heterozygous for the offending antigen. This study focused on human PLT antigen (HPA)-1, the most frequently implicated antigen in FNAIT in Caucasians. Two assays based on cell-free fetal DNA extracted from maternal blood samples and on real-time polymerase chain reaction (QPCR) were developed: an allele-specific QPCR specifically targeting the polymorphic sequence in HPA-1 and the study of the variation in the high-resolution melting curve of amplicons containing the polymorphic region. All results from the 49 samples obtained from 29 pregnant women were consistent with expectations. Six women were compatible with their fetuses (three HPA-1aa women and three HPA-1bb women), 41 HPA-1bb women were incompatible with their fetuses, as were two HPA-1aa women. Two fetal PLT genotyping assays on maternal blood samples proved to be reliable as of 15 weeks of gestation, thereby avoiding invasive techniques such as amniocentesis. © 2012 American Association of Blood Banks.

Noninvasive fetal RhCE genotyping from maternal blood.

PubMed

Geifman-Holtzman, O; Grotegut, C A; Gaughan, J P; Holtzman, E J; Floro, C; Hernandez, E

2009-01-01

The successful prevention of RhD disease has brought attention to other red blood cells' antigens causing alloimmunisation including RhC/c and RhE/e. Prenatal diagnosis of fetal Rh genotype from maternal blood is in clinical use in Europe but not in the USA. To estimate the collective reported diagnostic accuracy of fetal RhCE genotyping from peripheral maternal blood and compare the results of genotyping when fetal cells and free fetal DNA (FfDNA) are used. English-written literature describing fetal RhCE determination from maternal blood using fetal cells or FfDNA was performed using medical subject headings and text words. The sources included Pubmed (1966-2007), Ovid (1966-2007), CINAHL, The Cochrane Library, ACP Journal Club and OCLC. Key words were prenatal diagnosis, fetal RhCE, fetal DNA in maternal blood and alloimmunisation. A study was considered eligible if it described fetal RhCE type determination using maternal peripheral blood reported in the English literature. Abstracts were excluded. From each study, we determined the number of samples tested, fetal RhCE genotype, the source of the fetal DNA, gestational age, presence of alloimmunisation and confirmation of fetal RhCE type. Exclusions and inclusions were noted. We calculated composite estimates of accuracy using a weighted random effects model. We assessed the papers against an international quality, STARD checklist which is standards for reporting studies of diagnostic accuracy. We identified 20 protocols in six English-written publications reporting fetal RhC/c (seven protocols) and/or E/e (13 protocols) genotyping using DNA obtained from maternal blood for a total of 369 samples. For RhC/c, 176 samples were tested and for RhE/e, 193 samples were tested. Accuracy was determined for each study and for all studies. The combined accuracy of fetal genotype was 96.3% for RhC/c and 98.2% for RhE/e. Only a few samples of the sorted cells were found to be a source for accurate diagnosis, but plasma was

WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component.

PubMed

Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin; Abdel-Aleem, Hany; Bega, George; Benachi, Alexandra; Carroli, Guillermo; Cecatti, Jose Guilherme; Diemert, Anke; Gonzalez, Rogelio; Hecher, Kurt; Jensen, Lisa N; Johnsen, Synnøve L; Kiserud, Torvid; Kriplani, Alka; Lumbiganon, Pisake; Tabor, Ann; Talegawkar, Sameera A; Tshefu, Antoinette; Wojdyla, Daniel; Platt, Lawrence

2014-05-02

In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component

PubMed Central

2014-01-01

Background In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. Methods This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/− 1 week) to be performed by trained ultrasonographers. The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. Discussion The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use

Sertoli Cell Wt1 Regulates Peritubular Myoid Cell and Fetal Leydig Cell Differentiation during Fetal Testis Development.

PubMed

Wen, Qing; Wang, Yuqian; Tang, Jixin; Cheng, C Yan; Liu, Yi-Xun

2016-01-01

Sertoli cells play a significant role in regulating fetal testis compartmentalization to generate testis cords and interstitium during development. The Sertoli cell Wilms' tumor 1 (Wt1) gene, which encodes ~24 zinc finger-containing transcription factors, is known to play a crucial role in fetal testis cord assembly and maintenance. However, whether Wt1 regulates fetal testis compartmentalization by modulating the development of peritubular myoid cells (PMCs) and/or fetal Leydig cells (FLCs) remains unknown. Using a Wt1-/flox; Amh-Cre mouse model by deleting Wt1 in Sertoli cells (Wt1SC-cKO) at embryonic day 14.5 (E14.5), Wt1 was found to regulate PMC and FLC development. Wt1 deletion in fetal testis Sertoli cells caused aberrant differentiation and proliferation of PMCs, FLCs and interstitial progenitor cells from embryo to newborn, leading to abnormal fetal testis interstitial development. Specifically, the expression of PMC marker genes α-Sma, Myh11 and Des, and interstitial progenitor cell marker gene Vcam1 were down-regulated, whereas FLC marker genes StAR, Cyp11a1, Cyp17a1 and Hsd3b1 were up-regulated, in neonatal Wt1SC-cKO testes. The ratio of PMC:FLC were also reduced in Wt1SC-cKO testes, concomitant with a down-regulation of Notch signaling molecules Jag 1, Notch 2, Notch 3, and Hes1 in neonatal Wt1SC-cKO testes, illustrating changes in the differentiation status of FLC from their interstitial progenitor cells during fetal testis development. In summary, Wt1 regulates the development of FLC and interstitial progenitor cell lineages through Notch signaling, and it also plays a role in PMC development. Collectively, these effects confer fetal testis compartmentalization.

[The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies--will a global change start in Israel?].

PubMed

Bronshtein, Moshe; Solt, Ido; Blumenfeld, Zeev

2014-06-01

Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

Radiographic and functional evaluation of low profile dorsal versus volar plating for distal radius fractures.

PubMed

Kumar, Sanjay; Khan, A N; Sonanis, S V

2016-12-01

Fracture of the distal radius is a common clinical problem. Complex fracture requires open reduction and stabilization with plating to restore anatomy. Dorsal plating has advantages of buttressing the fracture better but often complicated with tendon problems as per literature. The rate of complications however, was not compared between the low-profile dorsal and the volar plates. This was a retrospective study on seventy one patients with dorsally angulated or displaced distal radius fractures, who underwent fixation of fractures with either dorsal or volar locking plate from Jan - Nov 2012. Preoperative radiographs were classified based on Universal and Fernandez classification. Postoperative radiographs were assessed for anatomical restoration of Radial length, radial inclination and volar tilt. Tendon and nerve related complications were assessed and functional evaluation was performed on the basis of PRWE (Patient related wrist evaluation) score. Both groups were matched for their demographic profile and fracture types (p 0.033). Dorsal plating group had 89% excellent/good restoration and fair in 11%. Volar group had 96% excellent/good restoration and fair in 4%. Statistical analysis was performed with unpaired t test for radiographic parameters. Three patients had tendon related complications in dorsal plating group; two patients in volar group had nerve related complications. Functional outcome with PRWE was comparable between two groups. Results with low profile dorsal plating were comparable to volar plating. Therefore dorsal plating can be used as an alternative method when dorsal buttressing of comminuted fracture is required, especially with concomitant osteoporosis.

Establishment and characterization of a human gastrointestinal stromal tumour (GIST) xenograft in athymic nude mice.

PubMed

Revheim, Mona-Elisabeth; Seierstad, Therese; Berner, Jeanne-Marie; Bruland, Oyvind Sverre; Røe, Kathrine; Ohnstad, Hege Oma; Bjerkehagen, Bodil; Bach-Gansmo, Tore

2009-11-01

The majority of gastrointestinal stromal tumours (GISTs) contain oncogenic KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or platelet-derived growth factor-alpha (PDGFRA) receptor tyrosine kinase (TK) mutations and are initially, but only temporarily sensitive to TK inhibitors. The aim of this study was to establish and characterize a human GIST xenograft that could be used for evaluating various molecularly targeted therapies. GIST tissue from four patients was implanted under the skin of athymic nude mice. In one case a tumour line was established. The xenograft showed characteristic GIST morphology and exhibited the same mutation profile as that of the patient. A human GIST xenograft with mutation in KIT exons 11 and 17 has been established and maintained in nude mice for 3 years (13 passages). This model will enable further studies on mechanisms of resistance, combination therapies and allow testing of novel targeted therapies.

Amniocentesis for fetal lung maturity: will it become obsolete?

PubMed

Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

2013-01-01

AMNIOCENTESIS FOR FETAL LUNG MATURITY HAS HISTORICALLY BEEN PERFORMED FOR MANY REASONS: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate.

Human Fetal Behavior: 100 Years of Study.

ERIC Educational Resources Information Center

Kisilevsky, B. S.; Low, J. A.

1998-01-01

Reviews literature on human fetal behavior. Includes descriptions of coupling of body movements and fetal heart rate and behavior maturation from conception to term. Discusses use of stimulus-induced behavior to examine sensory and cognitive development, and spontaneous and stimulus-induced behavior to assess fetal well-being. Notes research focus…

Molecular genetics in fetal neurology.

PubMed

Huang, Jin; Wah, Isabella Y M; Pooh, Ritsuko K; Choy, Kwong Wai

2012-12-01

Brain malformations, particularly related to early brain development, are a clinically and genetically heterogeneous group of fetal neurological disorders. Fetal cerebral malformation, predominantly of impaired prosencephalic development namely agenesis of the corpus callosum and septo-optic dysplasia, is the main pathological feature in fetus, and causes prominent neurodevelopmental retardation, and associated with congenital facial anomalies and visual disorders. Differential diagnosis of brain malformations can be extremely difficult even through magnetic resonance imaging. Advances in genomic and molecular genetics technologies have led to the identification of the sonic hedgehog pathways and genes critical to the normal brain development. Molecular cytogenetic and genetic studies have identified numeric and structural chromosomal abnormalities as well as mutations in genes important for the etiology of fetal neurological disorders. In this review, we update the molecular genetics findings of three common fetal neurological abnormalities, holoprosencephaly, lissencephaly and agenesis of the corpus callosum, in an attempt to assist in perinatal and prenatal diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Influence of sectioning location on age estimates from common carp dorsal spines

USGS Publications Warehouse

Watkins, Carson J.; Klein, Zachary B.; Terrazas, Marc M.; Quist, Michael C.

2015-01-01

Dorsal spines have been shown to provide precise age estimates for Common CarpCyprinus carpio and are commonly used by management agencies to gain information on Common Carp populations. However, no previous studies have evaluated variation in the precision of age estimates obtained from different sectioning locations along Common Carp dorsal spines. We evaluated the precision, relative readability, and distribution of age estimates obtained from various sectioning locations along Common Carp dorsal spines. Dorsal spines from 192 Common Carp were sectioned at the base (section 1), immediately distal to the basal section (section 2), and at 25% (section 3), 50% (section 4), and 75% (section 5) of the total length of the dorsal spine. The exact agreement and within-1-year agreement among readers was highest and the coefficient of variation lowest for section 2. In general, age estimates derived from sections 2 and 3 had similar age distributions and displayed the highest concordance in age estimates with section 1. Our results indicate that sections taken at ≤ 25% of the total length of the dorsal spine can be easily interpreted and provide precise estimates of Common Carp age. The greater consistency in age estimates obtained from section 2 indicates that by using a standard sectioning location, fisheries scientists can expect age-based estimates of population metrics to be more comparable and thus more useful for understanding Common Carp population dynamics.

A Prospective Study of the Use of Fetal Intelligent Navigation Echocardiography (FINE) to Obtain Standard Fetal Echocardiography Views

PubMed Central

Veronese, Paola; Bogana, Gianna; Cerutti, Alessia; Yeo, Lami; Romero, Roberto; Gervasi, Maria Teresa

2016-01-01

Objective To evaluate the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart in generating standard fetal echocardiography views. Methods In this prospective cohort study of patients with normal fetal hearts (19-30 gestational weeks), one or more STIC volume datasets were obtained of the apical four-chamber view. Each STIC volume successfully obtained was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates for standard fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated. Results One or more STIC volumes (n=463 total) were obtained in 246 patients. A single STIC volume per patient was analyzed using the FINE method. In normal cases, FINE was able to generate nine fetal echocardiography views using: 1) diagnostic planes in 76-100% of cases; 2) VIS-Assistance® in 96-100% of cases; and 3) a combination of diagnostic planes and/or VIS-Assistance® in 96-100% of cases. Conclusion FINE applied to STIC volumes can successfully generate nine standard fetal echocardiography views in 96-100% of cases in the second and third trimesters. This suggests that the technology can be used as a method to screen for congenital heart disease. PMID:27309391

Detection of genes regulated by Lmx1b during limb dorsalization.

PubMed

Feenstra, Jennifer M; Kanaya, Kohei; Pira, Charmaine U; Hoffman, Sarah E; Eppey, Richard J; Oberg, Kerby C

2012-05-01

Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs. Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wild type mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified 54 target genes that were differentially expressed in all three stages. Several skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the relative abundance of extracellular matrix-related soft tissue targets regulated by Lmx1b, such as collagens and proteoglycans, suggests a mechanism that includes changes in the extracellular matrix composition to accomplish limb dorsalization. Our study provides the most comprehensive characterization of genes regulated by Lmx1b during limb development to-date and provides targets for further investigation. © 2012 The Authors. Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

A novel autologous scaffold for diced-cartilage grafts in dorsal augmentation rhinoplasty.

PubMed

Bullocks, Jamal M; Echo, Anthony; Guerra, Gerardo; Stal, Samuel; Yuksel, Eser

2011-08-01

Diced-cartilage grafts have been used for dorsal nasal augmentation for several years with good results. However, compounds such as Surgicel and temporalis fascia used as a wrap have inherent problems associated with them, predominantly inflammation and graft resorption. An autologous carrier could provide stabilization of cartilage grafts while avoiding the complications seen with earlier techniques. In our patients, a malleable construct was used for dorsal nasal augmentation in which autologous diced-cartilage grafts were stabilized with autologous tissue glue (ATG) created from platelet-rich plasma (platelet gel) and platelet-poor plasma (fibrin glue). A prospective analysis of 68 patients, who underwent dorsal nasal augmentation utilizing ATG and diced-cartilage grafts between 2005 and 2008, were included in the study. Although there was notable maintenance of the dorsal height, no complications occurred that required explantation over a mean follow-up of 15 months. The use of ATG to stabilize diced-cartilage grafts is a safe, reliable technique for dorsal nasal augmentation. The platelet gel provides growth factors while the fibrin glue creates a scaffold that allows stabilization and diffusion of nutrients to the cartilage graft.

Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts

NASA Astrophysics Data System (ADS)

Merrill, Daniel; An, Ran; Sun, Hao; Yakubov, Bakhtiyor; Matei, Daniela; Turek, John; Nolte, David

2016-01-01

Three-dimensional (3D) tissue cultures are replacing conventional two-dimensional (2D) cultures for applications in cancer drug development. However, direct comparisons of in vitro 3D models relative to in vivo models derived from the same cell lines have not been reported because of the lack of sensitive optical probes that can extract high-content information from deep inside living tissue. Here we report the use of biodynamic imaging (BDI) to measure response to platinum in 3D living tissue. BDI combines low-coherence digital holography with intracellular Doppler spectroscopy to study tumor drug response. Human ovarian cancer cell lines were grown either in vitro as 3D multicellular monoculture spheroids or as xenografts in nude mice. Fragments of xenografts grown in vivo in nude mice from a platinum-sensitive human ovarian cell line showed rapid and dramatic signatures of induced cell death when exposed to platinum ex vivo, while the corresponding 3D multicellular spheroids grown in vitro showed negligible response. The differences in drug response between in vivo and in vitro growth have important implications for predicting chemotherapeutic response using tumor biopsies from patients or patient-derived xenografts.

Amniocentesis for Fetal Lung Maturity: Will It Become Obsolete?

PubMed Central

Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

2013-01-01

Amniocentesis for fetal lung maturity has historically been performed for many reasons: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate. PMID:24826202

Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry

NASA Astrophysics Data System (ADS)

Fernández, Roberto; Garate, Jone; Lage, Sergio; Terés, Silvia; Higuera, Mónica; Bestard-Escalas, Joan; López, Daniel H.; Guardiola-Serrano, Francisca; Escribá, Pablo V.; Barceló-Coblijn, Gwendolyn; Fernández, José A.

2016-02-01

Xenografts are commonly used to test the effect of new drugs on human cancer. However, because of their heterogeneity, analysis of the results is often controversial. Part of the problem originates in the existence of tumor cells at different metabolic stages: from metastatic to necrotic cells, as it happens in real tumors. Imaging mass spectrometry is an excellent solution for the analysis of the results as it yields detailed information not only on the composition of the tissue but also on the distribution of the biomolecules within the tissue. Here, we use imaging mass spectrometry to determine the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl- and plasmenylether derivatives (PC-P/O and PE-P/O) in xenografts of five different tumor cell lines: A-549, NCI-H1975, BX-PC3, HT29, and U-87 MG. The results demonstrate that the necrotic areas showed a higher abundance of Na+ adducts and of PC-P/O species, whereas a large abundance of PE-P/O species was found in all the xenografts. Thus, the PC/PC-ether and Na+/K+ ratios may highlight the necrotic areas while an increase on the number of PE-ether species may be pointing to the existence of viable tumor tissues. Furthermore, the existence of important changes in the concentration of Na+ and K+ adducts between different tissues has to be taken into account while interpreting the imaging mass spectrometry results.

21 CFR 864.7455 - Fetal hemoglobin assay.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal hemoglobin assay. (a) Identification. A fetal hemoglobin assay is a device that is used to determine the presence...

21 CFR 864.7455 - Fetal hemoglobin assay.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal hemoglobin assay. (a) Identification. A fetal hemoglobin assay is a device that is used to determine the presence...

Relocation of mitochondria to the prospective dorsal marginal zone during Xenopus embryogenesis

NASA Technical Reports Server (NTRS)

Yost, H. J.; Phillips, C. R.; Boore, J. L.; Bertman, J.; Whalon, B.; Danilchik, M. V.

1995-01-01

Dorsal-ventral axis formation in Xenopus laevis begins with a cytoplasmic rotation during the first cell cycle and culminates in a series of cell interactions and movements during gastrulation and neurulation that lead to the formation of dorsal-anterior structures. Evidence reported here indicates that mitochondria are differentially redistributed along the prospective dorsal-ventral axis as a consequence of the cortical-cytoplasmic rotation during the first cell cycle. This finding reinvigorates a possibility that has been considered for many years: asymmetries in cytoplasmic components and metabolic activities contribute to the development of morphological asymmetries.

Fetal MRI: A Technical Update with Educational Aspirations

PubMed Central

Gholipour, Ali; Estroff, Judith A.; Barnewolt, Carol E.; Robertson, Richard L.; Grant, P. Ellen; Gagoski, Borjan; Warfield, Simon K.; Afacan, Onur; Connolly, Susan A.; Neil, Jeffrey J.; Wolfberg, Adam; Mulkern, Robert V.

2015-01-01

Fetal magnetic resonance imaging (MRI) examinations have become well-established procedures at many institutions and can serve as useful adjuncts to ultrasound (US) exams when diagnostic doubts remain after US. Due to fetal motion, however, fetal MRI exams are challenging and require the MR scanner to be used in a somewhat different mode than that employed for more routine clinical studies. Herein we review the techniques most commonly used, and those that are available, for fetal MRI with an emphasis on the physics of the techniques and how to deploy them to improve success rates for fetal MRI exams. By far the most common technique employed is single-shot T2-weighted imaging due to its excellent tissue contrast and relative immunity to fetal motion. Despite the significant challenges involved, however, many of the other techniques commonly employed in conventional neuro- and body MRI such as T1 and T2*-weighted imaging, diffusion and perfusion weighted imaging, as well as spectroscopic methods remain of interest for fetal MR applications. An effort to understand the strengths and limitations of these basic methods within the context of fetal MRI is made in order to optimize their use and facilitate implementation of technical improvements for the further development of fetal MR imaging, both in acquisition and post-processing strategies. PMID:26225129

Hormonal Control of Fetal Growth.

ERIC Educational Resources Information Center

Cooke, Paul S.; Nicoll, Charles S.

1983-01-01

Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

Fetal oxygenation measurement using wireless near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Macnab, Andrew; Shadgan, Babak; Janssen, Patricia; Rurak, Dan

2012-03-01

Background: Fetal well-being is determined in large part by how well the placenta is able to supply oxygen and nutrients, but current technology is unable to directly measure how well a placenta functions. Near-infrared spectroscopy (NIRS) utilizes optical methods to measure tissue oxygenation. This pilot project evaluated the feasibility of NIRS for fetal monitoring through the maternal abdominal wall using a sheep model. Methods: A miniature wireless 2-wavelength NIRS device was placed on the abdominal skin over the placenta of a pregnant ewe whose fetus had been chronically catheterized to allow arterial sampling for measurement of arterial oxygen saturation. The NIRS device has 3-paired light emitting diodes and a single photodiode detector; allowing measurement of an index of tissue oxygen saturation (TSI%). Fetal limb TSI% values were compared before and during fetal breathing movements. Correlation was made during these events between arterial values and placental TSI% monitored continuously in real time. Results: Serial measurements were obtained in a single experiment. The correlation between transcutaneous NIRS derived TSI% and direct arterial oxygen saturation was very high (R2=0.86). Measures of fetal limb TSI% were declined after episodes of fetal breathing (P<0.005). Conclusions: This correlation suggests that NIRS is sensitive enough to detect changes in fetal tissue oxygenation noninvasively through the maternal abdominal wall in real-time in a sheep model. NIRS data confirmed that fetal breathing movements decrease arterial oxygen saturation in fetal lambs. If validated by further study this optical methodology could be applied as means of monitoring fetal wellbeing in humans.

Fetal Ultrasound

MedlinePlus

... isn't recommended simply to determine a baby's sex. Similarly, fetal ultrasound isn't recommended solely for the purpose of producing keepsake videos or pictures. If your health care provider doesn' ...

STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.

PubMed

DiPietro, Janet A; Costigan, Kathleen A; Voegtline, Kristin M

2015-09-01

Among the earliest volumes of this monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodrmal activity and fetal heartrate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include:within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physio-logical processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship.We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

PubMed Central

DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

2016-01-01

Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodermal activity and fetal heart rate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include: within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physiological processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship. We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

Ruptured superficial dorsal vein of the penis masquerading as a penile fracture: case report.

PubMed

Perlmutter, Adam E; Roberts, Lawrence; Farivar-Mohseni, Hesam; Zaslau, Stanley

2007-08-01

Acute onset of pain, swelling, and ecchymosis of the penis during sexual intercourse indicate a penile fracture until proven otherwise. However, there have been few case reports of isolated injuries to the dorsal penile artery or dorsal vein mimicking a penile fracture. Presented herein is a rare case of a patient who ruptured his superficial dorsal vein during intercourse.

Biomedical Instruments for Fetal and Neonatal Surveillance

NASA Astrophysics Data System (ADS)

Rolfe, P.; Scopesi, F.; Serra, G.

2006-10-01

Specialised instruments have been developed to aid the care of the fetus and the newborn baby. Miniature sensors using optical, electrical, chemical, mechanical and magnetic principles have been produced for capturing key measurands. These include temperature, pressure, flow and dimension, as well as several specific molecules such as glucose, oxygen and carbon dioxide. During pregnancy ultrasound imaging and blood flow techniques provide valuable information concerning fetal abnormalities, fetal growth, fetal breathing and fetal heart rate. Signal processing and pattern recognition can be useful for deriving indicators of fetal distress and clinical status, based on biopotentials as well as ultrasound signals. Fetal pH measurement is a critical requirement during labour and delivery. The intensive care of ill preterm babies involves provision of an optimal thermal environment and respiratory support. Monitoring of blood gas and acid-base status is essential, and this involves both blood sampling for in vitro analysis as well as the use of invasive or non-invasive sensors. For the future it will be vital that the technologies used are subjected to controlled trials to establish benefit or otherwise.

Novel Dedifferentiated Liposarcoma Xenograft Models Reveal PTEN Down-Regulation as a Malignant Signature and Response to PI3K Pathway Inhibition

PubMed Central

Smith, Kathleen B.; Tran, Linh M.; Tam, Brenna M.; Shurell, Elizabeth M.; Li, Yunfeng; Braas, Daniel; Tap, William D.; Christofk, Heather R.; Dry, Sarah M.; Eilber, Fritz C.; Wu, Hong

2014-01-01

Liposarcoma is a type of soft tissue sarcoma that exhibits poor survival and a high recurrence rate. Treatment is generally limited to surgery and radiation, which emphasizes the need for better understanding of this disease. Because very few in vivo and in vitro models can reproducibly recapitulate the human disease, we generated several xenograft models from surgically resected human dedifferentiated liposarcoma. All xenografts recapitulated morphological and gene expression characteristics of the patient tumors after continuous in vivo passages. Importantly, xenograftability was directly correlated with disease-specific survival of liposarcoma patients. Thus, the ability for the tumor of a patient to engraft may help identify those patients who will benefit from more aggressive treatment regimens. Gene expression analyses highlighted the association between xenograftability and a unique gene expression signature, including down-regulated PTEN tumor-suppressor gene expression and a progenitor-like phenotype. When treated with the PI3K/AKT/mTOR pathway inhibitor rapamycin alone or in combination with the multikinase inhibitor sorafenib, all xenografts responded with increased lipid content and a more differentiated gene expression profile. These human xenograft models may facilitate liposarcoma research and accelerate the generation of readily translatable preclinical data that could ultimately influence patient care. PMID:23416162

Fetal behavior and heart rate in twin pregnancy: a review.

PubMed

Tendais, Iva; Visser, Gerard H A; Figueiredo, Bárbara; Montenegro, Nuno; Mulder, Eduard J H

2013-04-01

Fetal movements and fetal heart rate (FHR) are well-established markers of fetal well-being and maturation of the fetal central nervous system. The purpose of this paper is to review and discuss the available knowledge on fetal movements and heart rate patterns in twin pregnancies. There is some evidence for an association or similarity in fetal movement incidences or FHR patterns between both members of twin pairs. However, the temporal occurrence of these patterns seems to be for the most part asynchronous, especially when stricter criteria are used to define synchrony. The available data suggest that fetal behavior is largely independent of sex combination, fetal position, and presentation. Conversely, chorionicity appears to have some influence on fetal behavior, mainly before 30 weeks of gestation. There is preliminary evidence for the continuity of inter-individual differences in fetal activity and FHR patterns over pregnancy. Comparisons between studies are limited by large methodological differences and absence of uniform concepts and definitions. Future studies with high methodological quality are needed to provide a more comprehensive knowledge of normal fetal behavior in twin pregnancy.

[Fetal echocardiography efficiency. Clinical experience].

PubMed

San Luis Miranda, Raúl; Arias Monroy, Laura Guadalupe; Gutiérrez González, Gladis Alicia; León Avila, José Luis; Cruz Rodríguez, Armando; Osornio Correa, Porfirio Rafael

2008-12-01

Congenital heart disease diagnostic has a high diagnostic precision with fetal echocardiography. This study has been reported in populations with high risk and with a sensibility of 86 to 99% and specificity of 91 to 100%. To know sensibility and specificity of fetal echocardiography in high-risk pregnancies, and to describe types and frequency of congenital heart disease in utero. 229 files of pregnant women with high-risk factors, more than 15 weeks of gestation, and at birth cardiovascular exam were analyzed. This analysis was made by means of simple frequencies, sensibility, specificity, positive and negative predictive value, and truth index calculation. We found 62 (27%) cases with fetal heart disease. Mean of maternal age was 27 +/- 5.5 years, and of gestational age 31 +/- 5 weeks. Risk factors that require study were: four-chamber abnormality in routine ultrasound, dysmorphy, fetal bradicardia, and poll and oligohydramnios. There were 55 (88.7%) high-risk heart diseases, and most frequent were Ebstein's anomaly, unique ventricle, hypoplastic left ventricle syndrome, and tumors. Sensibility was 98.41%, specificity was 97.59%, positive prognostic value was 97.59%, and negative prognostic value was 99.39%. Fetal echocardiography has a high diagnosis certainty in our hospital unit, thus, it has to be a normal prenatal exam in pregnant women with high-risk factors.

Dorsal Phalloplasty to Preserve Penis Length after Penile Prosthesis Implantation

PubMed Central

Shaeer, Osama; Shaeer, Kamal; Rahman, Islam A.

2017-01-01

Objectives Following penile prosthesis implantation (PPI), patients may complain of a decrease in visible penis length. A dorsal phalloplasty defines the penopubic junction by tacking pubic skin to the pubis, revealing the base of the penis. This study aimed to evaluate the efficacy of a dorsal phalloplasty in increasing the visible penis length following PPI. Methods An inflatable penile prosthesis was implanted in 13 patients with severe erectile dysfunction (ED) at the Kamal Shaeer Hospital, Cairo, Egypt, from January 2013 to May 2014. During the surgery, nonabsorbable tacking sutures were used to pin the pubic skin to the pubis through the same penoscrotal incision. Intraoperative penis length was measured before and after the dorsal phalloplasty. Overall patient satisfaction was measured on a 5-point rating scale and patients were requested to subjectively compare their postoperative penis length with memories of their penis length before the onset of ED. Results Intraoperatively, the dorsal phalloplasty increased the visible length of the erect penis by an average of 25.6%. The average length before and after tacking was 10.2 ± 2.9 cm and 13.7 ± 2.8 cm, respectively (P <0.002). Postoperatively, seven patients (53.8%) reported a longer penis, five patients (38.5%) reported no change in length and one patient (7.7%) reported a slightly shorter penis. The mean overall patient satisfaction score was 4.9 ± 0.3. None of the patients developed postoperative complications. Conclusion A dorsal phalloplasty during PPI is an effective method of increasing visible penis length, therefore minimising the impression of a shorter penis after implantation. PMID:28417025

Group B Streptococcus β-hemolysin/Cytolysin Breaches Maternal-Fetal Barriers to Cause Preterm Birth and Intrauterine Fetal Demise in Vivo

PubMed Central

Randis, Tara M.; Gelber, Shari E.; Hooven, Thomas A.; Abellar, Rosanna G.; Akabas, Leor H.; Lewis, Emma L.; Walker, Lindsay B.; Byland, Leah M.; Nizet, Victor; Ratner, Adam J.

2014-01-01

Background. Maternal vaginal colonization with Streptococcus agalactiae (Group B Streptococcus [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in the pathogenesis of ascending infection remains limited. Methods. We used a new murine model to evaluate the contribution of the pore-forming GBS β-hemolysin/cytolysin (βH/C) to vaginal colonization, ascension, and fetal infection. Results. Competition assays demonstrated a marked advantage to βH/C-expressing GBS during colonization. Intrauterine fetal demise and/or preterm birth were observed in 54% of pregnant mice colonized with wild-type (WT) GBS and 0% of those colonized with the toxin-deficient cylE knockout strain, despite efficient colonization and ascension by both strains. Robust placental inflammation, disruption of maternal-fetal barriers, and fetal infection were more frequent in animals colonized with WT bacteria. Histopathologic examination revealed bacterial tropism for fetal lung and liver. Conclusions. Preterm birth and fetal demise are likely the direct result of toxin-induced damage and inflammation rather than differences in efficiency of ascension into the upper genital tract. These data demonstrate a distinct contribution of βH/C to GBS chorioamnionitis and subsequent fetal infection in vivo and showcase a model for this most proximal step in GBS pathogenesis. PMID:24474814

Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory

PubMed Central

Kempadoo, Kimberly A.; Mosharov, Eugene V.; Choi, Se Joon; Sulzer, David; Kandel, Eric R.

2016-01-01

Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory. PMID:27930324

Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory.

PubMed

Kempadoo, Kimberly A; Mosharov, Eugene V; Choi, Se Joon; Sulzer, David; Kandel, Eric R

2016-12-20

Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory.

Maternal-fetal transfer of selenium in the mouse

PubMed Central

Burk, Raymond F.; Olson, Gary E.; Hill, Kristina E.; Winfrey, Virginia P.; Motley, Amy K.; Kurokawa, Suguru

2013-01-01

Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.—Burk, R. F., Olson, G. E., Hill, K. E., Winfrey, V. P., Motley, A. K., and Kurokawa, S. Maternal-fetal transfer of selenium in the mouse. PMID:23651543

Telefetalcare: a first prototype of a wearable fetal electrocardiograph.

PubMed

Fanelli, A; Signorini, M G; Ferrario, M; Perego, P; Piccini, L; Andreoni, G; Magenes, G

2011-01-01

Fetal heart rate monitoring is fundamental to infer information about fetal health state during pregnancy. The cardiotocography (CTG) is the most common antepartum monitoring technique. Abdominal ECG recording represents the most valuable alternative to cardiotocography, as it allows passive, non invasive and long term fetal monitoring. Unluckily fetal ECG has low SNR and needs to be extracted from abdominal recordings using ad hoc algorithms. This work describes a prototype of a wearable fetal ECG electrocardiograph. The system has flat band frequency response between 1-60 Hz and guarantees good signal quality. It was tested on pregnant women between the 30(th) and 34(th) gestational week. Several electrodes configurations were tested, in order to identify the best solution. Implementation of a simple algorithm for FECG extraction permitted the reliable detection of maternal and fetal QRS complexes. The system will allow continuative and deep screening of fetal heart rate, introducing the possibility of home fetal monitoring.

Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment

PubMed Central

Kurtoğlu, Selim; Özdemir, Ahmet

2017-01-01

Fetal and neonatal hyperthyroidism may occur in mothers with Graves’ disease. Fetal thyrotoxicosis manifestation is observed with the transition of TSH receptor stimulating antibodies to the fetus from the 17th–20th weeks of pregnancy and with the fetal TSH receptors becoming responsive after 20 weeks. The diagnosis is confirmed by fetal tachycardia, goiter and bone age advancement in pregnancy and maternal treatment is conducted in accordance. The probability of neonatal hyperthyroidism is high in the babies of mothers that have ongoing antithyroid requirement and higher antibody levels in the last months of pregnancy. Clinical manifestation may be delayed by 7–17 days because of the antithyroid drugs taken by the mother. Neonatal hyperthyroidism symptoms can be confused with sepsis and congenital viral infections. Herein, the diagnosis and therapeutic approach are reviewed in cases of fetal neonatal hyperthyroidism. PMID:28439194

Maternal-fetal transfer of selenium in the mouse.

PubMed

Burk, Raymond F; Olson, Gary E; Hill, Kristina E; Winfrey, Virginia P; Motley, Amy K; Kurokawa, Suguru

2013-08-01

Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.

Fetal lacerations at caesarean section.

PubMed

Wiener, J J; Westwood, J

2002-01-01

Fetal lacerations occurred in 1.5% of caesarean sections carried out in our institution. The incidence was independent of type of caesarean section, fetal presentation, cervical dilatation, presence of intact membranes or operator grade. We advocate that this complication should be included in the preoperative counselling of all patients undergoing caesarean sections.

Registration of 3D fetal neurosonography and MRI☆

PubMed Central

Kuklisova-Murgasova, Maria; Cifor, Amalia; Napolitano, Raffaele; Papageorghiou, Aris; Quaghebeur, Gerardine; Rutherford, Mary A.; Hajnal, Joseph V.; Noble, J. Alison; Schnabel, Julia A.

2013-01-01

We propose a method for registration of 3D fetal brain ultrasound with a reconstructed magnetic resonance fetal brain volume. This method, for the first time, allows the alignment of models of the fetal brain built from magnetic resonance images with 3D fetal brain ultrasound, opening possibilities to develop new, prior information based image analysis methods for 3D fetal neurosonography. The reconstructed magnetic resonance volume is first segmented using a probabilistic atlas and a pseudo ultrasound image volume is simulated from the segmentation. This pseudo ultrasound image is then affinely aligned with clinical ultrasound fetal brain volumes using a robust block-matching approach that can deal with intensity artefacts and missing features in the ultrasound images. A qualitative and quantitative evaluation demonstrates good performance of the method for our application, in comparison with other tested approaches. The intensity average of 27 ultrasound images co-aligned with the pseudo ultrasound template shows good correlation with anatomy of the fetal brain as seen in the reconstructed magnetic resonance image. PMID:23969169

Clinical relevance of fetal hemodynamic monitoring: Perinatal implications.

PubMed

Pruetz, Jay D; Votava-Smith, Jodie; Miller, David A

2015-08-01

Comprehensive assessment of fetal wellbeing involves monitoring of fetal growth, placental function, central venous pressure, and cardiac function. Ultrasound evaluation of the fetus using 2D, color Doppler, and pulse-wave Doppler techniques form the foundation of antenatal diagnosis of structural anomalies, rhythm abnormalities and altered fetal circulation. Accurate and timely prenatal identification of the fetus at risk is critical for appropriate parental counseling, antenatal diagnostic testing, consideration for fetal intervention, perinatal planning, and coordination of postnatal care delivery. Fetal hemodynamic monitoring and serial assessment are vital to ensuring fetal wellbeing, particularly in the setting of complex congenital anomalies. A complete hemodynamic evaluation of the fetus gives important information on the likelihood of a smooth postnatal transition and contributes to ensuring the best possible outcome for the neonate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal and fetal response to fetal persistent infection with bovine viral diarrhea virus.

PubMed

Hansen, Thomas R; Smirnova, Natalia P; Van Campen, Hana; Shoemaker, Megan L; Ptitsyn, Andrey A; Bielefeldt-Ohmann, Helle

2010-10-01

Infection of naïve pregnant cows with non-cytopathic (ncp) bovine viral diarrhea virus (BVDV) results in transplacental infection of the fetus. Infection of the pregnant cow with ncp BVDV late in gestation (after day 150) results in transient infection (TI), as both the dam and fetus can mount an immune response to the virus. In contrast, if the fetus is infected with ncp BVDV early in gestation (before day 150), the fetal immune system is undeveloped and unable to recognize the virus as foreign. This results in induction of immune tolerance to the infecting BVDV strain and persistent infection (PI). Infection of naïve pregnant heifers with ncp BVDV2 on day 75 was hypothesized to induce differential gene expression in white blood cells of the dams and their fetuses, adversely affecting development and antiviral immune responses in PI fetuses. Gene expression differed in maternal blood cells in the presence of PI versus uninfected fetuses. PI adversely affected fetal development and antiviral responses, despite protective immune responses in the dam. Fetal PI with BVDV alters maternal immune function, compromises fetal growth and immune responses, and results in expression of maternal blood biomarkers that can be used to identify cows carrying PI fetuses.

High Tumor Volume to Fetal Weight Ratio Is Associated with Worse Fetal Outcomes and Increased Maternal Risk in Fetuses with Sacrococcygeal Teratoma.

PubMed

Gebb, Juliana S; Khalek, Nahla; Qamar, Huma; Johnson, Mark P; Oliver, Edward R; Coleman, Beverly G; Peranteau, William H; Hedrick, Holly L; Flake, Alan W; Adzick, N Scott; Moldenhauer, Julie S

2018-03-01

Tumor volume to fetal weight ratio (TFR) > 0.12 before 24 weeks has been associated with poor outcome in fetuses with sacrococcygeal teratoma (SCT). We evaluated TFR in predicting poor fetal outcome and increased maternal operative risk in our cohort of SCT pregnancies. This is a retrospective, single-center review of fetuses seen with SCT from 1997 to 2015. Patients who chose termination of pregnancy (TOP), delivered elsewhere, or had initial evaluation at > 24 weeks were excluded. Receiver operating characteristic (ROC) analysis determined the optimal TFR to predict poor fetal outcome and increased maternal operative risk. Poor fetal outcome included fetal demise, neonatal demise, or fetal deterioration warranting open fetal surgery or delivery < 32 weeks. Increased maternal operative risk included cases necessitating open fetal surgery, classical cesarean delivery, or ex utero intrapartum treatment (EXIT). Of 139 pregnancies with SCT, 27 chose TOP, 14 delivered elsewhere, and 40 had initial evaluation at > 24 weeks. Thus, 58 fetuses were reviewed. ROC analysis revealed that at ≤24 weeks, TFR > 0.095 was predictive of poor fetal outcome and TFR > 0.12 was predictive of increased maternal operative risk. This study supports the use of TFR at ≤24 weeks for risk stratification of pregnancies with SCT. © 2018 S. Karger AG, Basel.

Evisceration as fetal destructive operation: an art revisited.

PubMed

Rohilla, Minakshi; Aggarwal, Neelam; Singh, Purnima; Jain, Vanita

2015-03-01

Fetal destructive operation is a vanishing art today. In an era of increasing cesarean deliveries it has become a historic event. Incidence of destructive operation has varied from various Indian hospitals 0.09-0.28%. Evisceration is one of the rarest of all destructive operations, performed in cases of cephalopelvic disproportion with large fetal abdominal or thoracic tumors and fetal malformations, which are incompatible with life. Less than 50 cases of fetal evisceration have been reported in the literature so far. We are presenting a case of gross fetal abdominal malformation in a multigravida woman, which necessitated internal podalic version followed by evisceration and breech extraction.

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia.

PubMed

Khaw, Seong Lin; Suryani, Santi; Evans, Kathryn; Richmond, Jennifer; Robbins, Alissa; Kurmasheva, Raushan T; Billups, Catherine A; Erickson, Stephen W; Guo, Yuelong; Houghton, Peter J; Smith, Malcolm A; Carol, Hernan; Roberts, Andrew W; Huang, David C S; Lock, Richard B

2016-09-08

The clinical success of the BCL-2-selective BH3-mimetic venetoclax in patients with poor prognosis chronic lymphocytic leukemia (CLL) highlights the potential of targeting the BCL-2-regulated apoptotic pathway in previously untreatable lymphoid malignancies. By selectively inhibiting BCL-2, venetoclax circumvents the dose-limiting, BCL-XL-mediated thrombocytopenia of its less selective predecessor navitoclax, while enhancing efficacy in CLL. We have previously reported the potent sensitivity of many high-risk childhood acute lymphoblastic leukemia (ALL) xenografts to navitoclax. Given the superior tolerability of venetoclax, here we have investigated its efficacy in childhood ALL. We demonstrate that in contrast to the clear dependence of CLL on BCL-2 alone, effective antileukemic activity in the majority of ALL xenografts requires concurrent inhibition of both BCL-2 and BCL-XL We identify BCL-XL expression as a key predictor of poor response to venetoclax and demonstrate that concurrent inhibition of both BCL-2 and BCL-XL results in synergistic killing in the majority of ALL xenografts. A notable exception is mixed lineage leukemia-rearranged infant ALL, where venetoclax largely recapitulates the activity of navitoclax, identifying this subgroup of patients as potential candidates for clinical trials of venetoclax in childhood ALL. Conversely, our findings provide a clear basis for progressing navitoclax into trials ahead of venetoclax in other subgroups.

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia

PubMed Central

Khaw, Seong Lin; Suryani, Santi; Evans, Kathryn; Richmond, Jennifer; Robbins, Alissa; Kurmasheva, Raushan T.; Billups, Catherine A.; Erickson, Stephen W.; Guo, Yuelong; Houghton, Peter J.; Smith, Malcolm A.; Carol, Hernan; Roberts, Andrew W.; Huang, David C. S.

2016-01-01

The clinical success of the BCL-2-selective BH3-mimetic venetoclax in patients with poor prognosis chronic lymphocytic leukemia (CLL) highlights the potential of targeting the BCL-2-regulated apoptotic pathway in previously untreatable lymphoid malignancies. By selectively inhibiting BCL-2, venetoclax circumvents the dose-limiting, BCL-XL-mediated thrombocytopenia of its less selective predecessor navitoclax, while enhancing efficacy in CLL. We have previously reported the potent sensitivity of many high-risk childhood acute lymphoblastic leukemia (ALL) xenografts to navitoclax. Given the superior tolerability of venetoclax, here we have investigated its efficacy in childhood ALL. We demonstrate that in contrast to the clear dependence of CLL on BCL-2 alone, effective antileukemic activity in the majority of ALL xenografts requires concurrent inhibition of both BCL-2 and BCL-XL. We identify BCL-XL expression as a key predictor of poor response to venetoclax and demonstrate that concurrent inhibition of both BCL-2 and BCL-XL results in synergistic killing in the majority of ALL xenografts. A notable exception is mixed lineage leukemia–rearranged infant ALL, where venetoclax largely recapitulates the activity of navitoclax, identifying this subgroup of patients as potential candidates for clinical trials of venetoclax in childhood ALL. Conversely, our findings provide a clear basis for progressing navitoclax into trials ahead of venetoclax in other subgroups. PMID:27343252

The added predictive value of biphasic events in ST analysis of the fetal electrocardiogram for intrapartum fetal monitoring.

PubMed

Becker, Jeroen H; Krikhaar, Anniek; Schuit, Ewoud; Mårtendal, Annika; Maršál, Karel; Kwee, Anneke; Visser, Gerard H A; Amer-Wåhlin, Isis

2015-02-01

To study the predictive value of biphasic ST-events for interventions for suspected fetal distress and adverse neonatal outcome, when using ST-analysis of the fetal electrocardiogram (FECG) for intrapartum fetal monitoring. Prospective cohort study. Three academic hospitals in Sweden. Women in labor with a high-risk singleton fetus in cephalic position beyond 36 weeks of gestation. In women in labor who were monitored with conventional cardiotocography, ST-waveform analysis was recorded and concealed. Traces with biphasic ST-events of the FECG (index) were compared with traces without biphasic events of the FECG. The ability of biphasic events to predict interventions for suspected fetal distress and adverse outcome was assessed using univariable and multivariable logistic regression analyses. Interventions for suspected fetal distress and adverse outcome (defined as presence of metabolic acidosis (i.e. umbilical cord pH <7.05 and base deficit in extracellular fluid >12 mmol), umbilical cord pH <7.00, 5-min Apgar score <7, admittance to neonatal intensive care unit or perinatal death). Although the presence of biphasic events of the FECG was associated with more interventions for fetal distress and an increased risk of adverse outcome compared with cases with no biphasic events, the presence of significant (i.e. intervention advised according to cardiotocography interpretation) biphasic events showed no independent association with interventions for fetal distress [odds ratio (OR) 1.71, 95% confidence interval (CI) 0.65-4.50] or adverse outcome (OR 1.96, 95% CI 0.74-5.24). The presence of significant biphasic events did not discriminate in the prediction of interventions for fetal distress or adverse outcome. Therefore, biphasic events in relation to ST-analysis monitoring during birth should be omitted if future studies confirm our findings. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Differential contribution of electrically evoked dorsal root reflexes to peripheral vasodilatation and plasma extravasation

PubMed Central

2011-01-01

Background Dorsal root reflexes (DRRs) are antidromic activities traveling along the primary afferent fibers, which can be generated by peripheral stimulation or central stimulation. DRRs are thought to be involved in the generation of neurogenic inflammation, as indicated by plasma extravasation and vasodilatation. The hypothesis of this study was that electrical stimulation of the central stump of a cut dorsal root would lead to generation of DRRs, resulting in plasma extravasation and vasodilatation. Methods Sprague-Dawley rats were prepared to expose spinal cord and L4-L6 dorsal roots under pentobarbital general anesthesia. Electrical stimulation of either intact, proximal or distal, cut dorsal roots was applied while plasma extravasation or blood perfusion of the hindpaw was recorded. Results While stimulation of the peripheral stump of a dorsal root elicited plasma extravasation, electrical stimulation of the central stump of a cut dorsal root generated significant DRRs, but failed to induce plasma extravasation. However, stimulation of the central stump induced a significant increase in blood perfusion. Conclusions It is suggested that DRRs are involved in vasodilatation but not plasma extravasation in neurogenic inflammation in normal animals. PMID:21356101

Fetal Echocardiography/Your Unborn Baby's Heart

MedlinePlus

... heart for the doctor to evaluate. The sound waves can also detect blood flow throughout the baby's heart. This enables the doctor to evaluate the structure and function of the fetal heart. Who needs one? Fetal ...

Differential effects of human interferon alpha and interferon gamma on xenografted human thyroid tissue in severe combined immunodeficient mice and nude mice.

PubMed

Kawai, K; Enomoto, T; Fornasier, V; Resetkova, E; Volpé, R

1997-03-01

We have studied the in vivo effects of human interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma) administration on human thyroid tissue xenografted into two mouse strains: severe combined immunodeficient (SCID) mice and nude mice. Human lymphocytes survive in SCID mice but are lysed in nude mice. Thyroid tissues from Graves' disease or Hashimoto's thyroiditis, or paranodular [normal, (N)] tissue was xenografted into SCID mice (0.8 g/mouse) pretreated with anti-asialo GM-1 antiserum and radiation and also into nude mice. One week after xenografting, SCID and nude mice were divided into three groups. Group A was treated with IFN-alpha intraperitoneally (2,000 units/mouse) three times weekly; group B was treated with IFN-gamma similarly; group C was treated with phosphate buffered saline (PBS) only (control). Autologous human peripheral blood mononuclear cells (PBMCs) were added to mice receiving N xenografts. Blood was taken every 2 weeks for levels of IgG and thyroid antibodies (TAb). After 6 weeks of treatment, mice were sacrificed, and xenograft thyrocyte histocompatibility leukocyte antigen (HLA-DR) and intercellular adhesion molecule (ICAM-1) expression were measured. In addition, thyrocyte cultures were stimulated in vitro with 200 units/ml of either IFN-alpha or IFN-gamma or PBS (control). SCID mice xenografted with autoimmune thyroid disease (AITD) in group A showed a significantly higher TAb production than group C, whereas in group B, TAb production was not statistically increased compared to control (group C). SCID mice xenografted with N did not produce TAb in any group, nor did nude mice xenografted with AITD. Thyrocyte HLA-DR expression was markedly increased in group A and B in SCID mice xenografted with Graves' disease, Hashimoto's thyroiditis, and N tissue compared to group C. In contrast, only group B (IFN-gamma) showed an increase in thyrocyte HLA-DR in nude mice. In the in vitro studies, only IFN-gamma (not IFN-alpha) stimulated

Online detection of fetal acidemia during labour by testing synchronization of EEG and heart rate: a prospective study in fetal sheep.

PubMed

Wang, Xiaogang; Durosier, L Daniel; Ross, Michael G; Richardson, Bryan S; Frasch, Martin G

2014-01-01

Severe fetal acidemia during labour can result in life-lasting neurological deficits, but the timely detection of this condition is often not possible. This is because the positive predictive value (PPV) of fetal heart rate (FHR) monitoring, the mainstay of fetal health surveillance during labour, to detect concerning fetal acidemia is around 50%. In fetal sheep model of human labour, we reported that severe fetal acidemia (pH<7.00) during repetitive umbilical cord occlusions (UCOs) is preceded ∼60 minutes by the synchronization of electroencephalogram (EEG) and FHR. However, EEG and FHR are cyclic and noisy, and although the synchronization might be visually evident, it is challenging to detect automatically, a necessary condition for bedside utility. Here we present and validate a novel non-parametric statistical method to detect fetal acidemia during labour by using EEG and FHR. The underlying algorithm handles non-stationary and noisy data by recording number of abnormal episodes in both EEG and FHR. A logistic regression is then deployed to test whether these episodes are significantly related to each other. We then apply the method in a prospective study of human labour using fetal sheep model (n = 20). Our results render a PPV of 68% for detecting impending severe fetal acidemia ∼60 min prior to pH drop to less than 7.00 with 100% negative predictive value. We conclude that this method has a great potential to improve PPV for detection of fetal acidemia when it is implemented at the bedside. We outline directions for further refinement of the algorithm that will be achieved by analyzing larger data sets acquired in prospective human pilot studies.

Antitumor and antiangiogenic activities of anti-vascular endothelial growth factor hairpin ribozyme in human hepatocellular carcinoma cell cultures and xenografts.

PubMed

Li, Li-Hua; Guo, Zi-Jian; Yan, Ling-Ling; Yang, Ji-Cheng; Xie, Yu-Feng; Sheng, Wei-Hua; Huang, Zhao-Hui; Wang, Xue-Hao

2007-12-21

To study the effectiveness and mechanisms of anti- human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis, oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted model. The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma cell line SMMC-7,721 and, subsequently, polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) were performed to confirm the ribozyme gene integration and transcription. To determine the effects of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell proliferation. Furthermore,the transfected and control cells were inoculated into nude mice respectively, the growth of cells in nude mice and angiogenesis were observed. VEGF expression was down-regulated sharply by ribozyme in transfected SMMC-7,721 cells and xenografted tumor. Compared to the control group, the transfected cells grew slower in cell cultures and xenografts, and the xenograft formation was delayed as well. In addition, the microvessel density of the xenografted tumor was obviously declined in the transfected group. As demonstrated by microscopy,reduction of VEGF production induced by ribozyme resulted in a significantly higher cell differentiation and less proliferation vigor in xenografted tumor. Anti-hVEGF hairpin ribozyme can effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in vivo. VEGF is functionally related to cell proliferation, differentiation and tumori-genesis in hepatocarcinoma.

Anterior cruciate ligament reconstruction with a novel porcine xenograft: the initial Italian experience

PubMed Central

ZAFFAGNINI, STEFANO; GRASSI, ALBERTO; MUCCIOLI, GIULIO MARIA MARCHEGGIANI; DI SARSINA, TOMMASO ROBERTI; RAGGI, FEDERICO; BENZI, ANDREA; MARCACCI, MAURILIO

2015-01-01

At the current state of the art in anterior cruciate ligament (ACL) reconstruction, multiple techniques have been presented but none has given clearly defined and improved results. One of the main issues concerns the choice of graft. The concept of using xenograft tissue, defined as a graft tissue from one species and destined for implantation in an unlike species, was introduced in order to try to overcome the mechanical and biological concerns associated with synthetic materials and the safety and quality concerns and availability problems of allograft tissue. Xenograft tissue carries the risk of producing an immunological reaction. In order to try to overcome or attenuate the immune response against porcine xenograft tissue, the Z-Process® (Aperion Biologics Inc, San Antonio, Texas, USA) has been developed and used to produce the Z-Lig® family of devices for ACL reconstruction procedures. Z-Lig® is a tendon graft with or without bone blocks, sourced from animal tissue in a manner consistent with what has normally been sourced from human tissue, and processed to overcome anti-Gal-mediated rejection and to attenuate other immunological recognition in humans. All this while ensuring sterility, viral inactivation and preservation of mechanical proprieties appropriate for an ACL reconstruction device. The Z-Lig® device has been tested in skeletally mature monkeys and given interesting and promising results from the preclinical performance and safety profile point of view. On this basis, it was possible to proceed with the first clinical trial involving humans, which gave similar encouraging results. The Z-Lig® device has also been implanted in Italy at the Rizzoli Orthopaedic Institute in Bologna, as a part of international multicenter prospective randomized blinded controlled study aimed at comparing xenograft with allograft tissue. PMID:26605257

Fetal Antecedents of Infant Temperament.

ERIC Educational Resources Information Center

DiPietro, Janet A.; And Others

1996-01-01

Examined fetal heart rate and movement in 31 healthy fetuses from 20 weeks through birth and at age 6 months. Found that more active fetuses were more difficult, unpredictable, unadaptable, and active as infants that were less active fetuses, and that higher fetal heart rate was associated with lower emotional tone, activity level, and…

Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

PubMed

Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

2017-02-01

Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

Multiplex fluorescent PCR for noninvasive prenatal detection of fetal-derived paternally inherited diseases using circulatory fetal DNA in maternal plasma.

PubMed

Tang, Dong-ling; Li, Yan; Zhou, Xin; Li, Xia; Zheng, Fang

2009-05-01

To develop a fluorescent polymerase chain reaction (PCR) assay for the detection of circulating fetal DNA in maternal plasma and use the established multiplex in noninvasive prenatal genetic diagnosis and its further applications in forensic casework. The DNA template was extracted from 47 pregnant women and the whole blood samples from the stated biological fathers were used to detect genotype. Using multiplex fluorescent PCR at 16 different polymorphic short tandem repeat (STR) loci, maternal DNA extracted from plasma samples at early pregnancy, medium pregnancy and late pregnancy were used to detect genotype. Their husbands' DNA was also used for fetal genotype ascertainment. Multiplex fluorescent PCR with 16 polymorphic short tandem repeats revealed the presence of fetal DNA in all cases. Every pregnant women/husband pair was informative in at least 3 of 16 loci. The chances of detecting paternally inherited fetal alleles ranged from 66.67 to 94.12%. They are 66.67% in early pregnancy, 85.71% in medium pregnancy and 94.12% in late pregnancy. The accuracy of Multiplex PCR assay to detect fetal DNA was 100%. Circulating fetal DNA analysis can be used as a possible alternative tool in routine laboratory prenatal diagnosis in the near future; this highly polymorphic STR multiplex has greatly improved the chances of detecting paternally inherited fetal alleles compared with other fetal DNA detection systems that use fetus-derived Y sequences to detect only male fetal DNA in maternal plasma. Our proposed technique can be applied to both female and male fetuses, which provides a sensitive, accurate and efficient method for noninvasive prenatal genetic diagnosis and forensic casework.

Modeling Leukemogenesis in the Zebrafish Using Genetic and Xenograft Models.

PubMed

Rajan, Vinothkumar; Dellaire, Graham; Berman, Jason N

2016-01-01

The zebrafish is a widely accepted model to study leukemia. The major advantage of studying leukemogenesis in zebrafish is attributed to its short life cycle and superior imaging capacity. This chapter highlights using transgenic- and xenograft-based models in zebrafish to study a specific leukemogenic mutation and analyze therapeutic responses in vivo.

Activity of a new nitrosourea (TCNU) in human lung cancer xenografts.

PubMed Central

Fergusson, R. J.; Anderson, L. E.; Macpherson, J. S.; Robins, P.; Smyth, J. F.

1988-01-01

The activity of a new nitrosourea (TCNU) based on the endogenous amino acid taurine was assessed in three human lung cancer xenografts growing in immunodeficient mice. Moderate activity (specific growth delays of 0.63 and 1.13 compared with controls) was seen in two non-small cell tumours after a single oral administration of 20 mg-1kg. This dose was curative in a small cell xenograft. By using high performance liquid chromatography it was possible to detect parent drug in the tumours as well as the plasma and tissues after oral administration of TCNU. Drug sensitivity was correlated inversely with the amount of the DNA repair enzyme 0(6)-methylguanine-DNA methyltransferase assayed from extracts of the tumour cells but not with the levels of parent drug within the tumour. This compound appears to have unique pharmacokinetic properties compared with other chloroethylnitrosoureas. PMID:3390369

EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

PubMed

Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

2011-03-01

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

Fetal in vivo continuous cardiovascular function during chronic hypoxia

PubMed Central

Allison, B. J.; Brain, K. L.; Niu, Y.; Kane, A. D.; Herrera, E. A.; Thakor, A. S.; Botting, K. J.; Cross, C. M.; Itani, N.; Skeffington, K. L.; Beck, C.

2016-01-01

Key points The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology has been available to induce significant and prolonged fetal hypoxia whilst recording longitudinal changes in fetal regional blood flow as the hypoxic pregnancy is developing.We introduce a new technique able to maintain chronically instrumented maternal and fetal sheep preparations under isobaric chronic hypoxia for most of gestation, beyond levels that can be achieved by high altitude and of relevance in magnitude to the human intrauterine growth‐restricted fetus.This technology permits wireless recording in free‐moving animals of longitudinal maternal and fetal cardiovascular function, including beat‐to‐beat alterations in pressure and blood flow signals in regional circulations.The relevance and utility of the technique is presented by testing the hypotheses that the fetal circulatory brain sparing response persists during chronic fetal hypoxia and that an increase in reactive oxygen species in the fetal circulation is an involved mechanism. Abstract Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean PaO2 levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery

Role of the right dorsal anterior insula in the urge to tic in Tourette syndrome.

PubMed

Tinaz, Sule; Malone, Patrick; Hallett, Mark; Horovitz, Silvina G

2015-08-01

The mid-posterior part of the insula is involved in processing bodily sensations and urges and is activated during tic generation in Tourette syndrome. The dorsal anterior part of the insula, however, integrates sensory and emotional information with cognitive valuation and is implicated in interoception. The right dorsal anterior insula also participates in urge suppression in healthy subjects. This study examined the role of the right dorsal anterior insula in the urge to tic in Tourette syndrome. Resting-state functional magnetic resonance imaging was performed in 13 adult Tourette patients and 13 matched controls. The role of the right dorsal anterior insula within the urge-tic network was investigated using graph theory-based neural network analysis. The functional connectivity of the right dorsal anterior insula was also correlated with urge and tic severity. Even though the patients did not exhibit any overt tics, the right dorsal anterior insula demonstrated higher connectivity, especially with the frontostriatal nodes of the urge-tic network in patients compared with controls. The functional connectivity between the right dorsal anterior insula and bilateral supplementary motor area also correlated positively with urge severity in patients. These results suggest that the right dorsal anterior insula is part of the urge-tic network and could influence the urge- and tic-related cortico-striato-thalamic regions even during rest in Tourette syndrome. It might be responsible for heightened awareness of bodily sensations generating premonitory urges in Tourette syndrome. © 2015 International Parkinson and Movement Disorder Society.

Generation of human acute lymphoblastic leukemia xenografts for use in oncology drug discovery

PubMed Central

Holmfeldt, Linda

2015-01-01

The establishment of reproducible mouse models of acute lymphoblastic leukemia (ALL) is necessary to provide in vivo therapeutic models that recapitulate human ALL, and for amplification of limiting amounts of primary tumor material. A frequently used model is the primary xenograft model that utilizes immunocompromised mice and involves injection of primary patient tumor specimens into mice, and subsequent serial passaging of the tumors by retransplants of cells harvested from the mouse bone marrow and spleen. The tumors generated can then be used for genomic profiling, ex vivo compound testing, mechanistic studies and retransplantation. This unit describes detailed procedures for the establishment and maintenance of primary ALL xenograft panels for potential use in basic research or translational studies. PMID:25737157

Prognostic value of three-dimensional ultrasound for fetal hydronephrosis

PubMed Central

WANG, JUNMEI; YING, WEIWEN; TANG, DAXING; YANG, LIMING; LIU, DONGSHENG; LIU, YUANHUI; PAN, JIAOE; XIE, XING

2015-01-01

The present study evaluated the prognostic value of three-dimensional ultrasound for fetal hydronephrosis. Pregnant females with fetal hydronephrosis were enrolled and a novel three-dimensional ultrasound indicator, renal parenchymal volume/kidney volume, was introduced to predict the postnatal prognosis of fetal hydronephrosis in comparison with commonly used ultrasound indicators. All ultrasound indicators of fetal hydronephrosis could predict whether postnatal surgery was required for fetal hydronephrosis; however, the predictive performance of renal parenchymal volume/kidney volume measurements as an individual indicator was the highest. In conclusion, ultrasound is important in predicting whether postnatal surgery is required for fetal hydronephrosis, and the three-dimensional ultrasound indicator renal parenchymal volume/kidney volume has a high predictive performance. Furthermore, the majority of cases of fetal hydronephrosis spontaneously regress subsequent to birth, and the regression time is closely associated with ultrasound indicators. PMID:25667626

The effect of Ramadan fasting on fetal development.

PubMed

Karateke, Atilla; Kaplanoglu, Mustafa; Avci, Fazil; Kurt, Raziye Keskin; Baloglu, Ali

2015-01-01

To evaluate the effects of Ramadan fasting on fetal development and outcomes of pregnancy. We performed this study in Antakya State Hospital of Obstetrics and Child Care, between 28 June 2014 and 27 July 2014 (during the month of Ramadan). A total of two hundred forty healthy pregnant women who were fasting during Ramadan, were included in the groups. The three groups were divided according to the trimesters. The each group was consisted of 40 healthy pregnant women with fasting and 40 healthy pregnant women without fasting. For evaluating the effects of Ramadan on fetus, ultrasonography was performed on all pregnant women in the beginning and the end of Ramadan. We used the essential parameters for the following measurements: increase of fetal biparietal diameter (BPD), increase of fetal femur length (FL), increase of estimated fetal body weight (EFBW), fetal biophysical profile (BPP), amniotic fluid index (AFI), and umbilical artery systole/diastole (S/D) ratio. No significant difference was found between the two groups for the fetal age, maternal weight gain (kilogram), estimated fetal weight gain (EFWG), fetal BPP, AFI, and umbilical artery S/D ratio. On the other hand, a statistically significant increase was observed in maternal weight in the second and third trimesters and a significant increase was observed in the amniotic fluid index in second trimester. In Ramadan there was no bad fetal outcome between pregnant women with fasting and pregnant women without fasting. Pregnant women who want to be with fast, should be examined by doctors, adequately get breakfast before starting to fast and after the fasting take essential calori and hydration. More comprehensive randomized studies are needed to explain the effects of fasting on the pregnancy and fetal outcomes.

Maternal exposure to hurricane destruction and fetal mortality.

PubMed

Zahran, Sammy; Breunig, Ian M; Link, Bruce G; Snodgrass, Jeffrey G; Weiler, Stephan; Mielke, Howard W

2014-08-01

The majority of research documenting the public health impacts of natural disasters focuses on the well-being of adults and their living children. Negative effects may also occur in the unborn, exposed to disaster stressors when critical organ systems are developing and when the consequences of exposure are large. We exploit spatial and temporal variation in hurricane behaviour as a quasi-experimental design to assess whether fetal death is dose-responsive in the extent of hurricane damage. Data on births and fetal deaths are merged with Parish-level housing wreckage data. Fetal outcomes are regressed on housing wreckage adjusting for the maternal, fetal, placental and other risk factors. The average causal effect of maternal exposure to hurricane destruction is captured by difference-in-differences analyses. The adjusted odds of fetal death are 1.40 (1.07-1.83) and 2.37 (1.684-3.327) times higher in parishes suffering 10-50% and >50% wreckage to housing stock, respectively. For every 1% increase in the destruction of housing stock, we observe a 1.7% (1.1-2.4%) increase in fetal death. Of the 410 officially recorded fetal deaths in these parishes, between 117 and 205 may be attributable to hurricane destruction and postdisaster disorder. The estimated fetal death toll is 17.4-30.6% of the human death toll. The destruction caused by Hurricanes Katrina and Rita imposed significant measurable losses in terms of fetal death. Postdisaster migratory dynamics suggest that the reported effects of maternal exposure to hurricane destruction on fetal death may be conservative. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Development of customized fetal growth charts in twins.

PubMed

Ghi, Tullio; Prefumo, Federico; Fichera, Anna; Lanna, Mariano; Periti, Enrico; Persico, Nicola; Viora, Elsa; Rizzo, Giuseppe

2017-05-01

Twin gestations are at significantly higher risk of fetal growth restriction in comparison with singletons. Using fetal biometric charts customized for obstetrical and parental characteristics may facilitate an accurate assessment of fetal growth. The objective of the study was to construct reference charts for the gestation of fetal biometric parameters stratified by chorionicity and customized for obstetrical and parental characteristics. Fetal biometric measurements obtained from serial ultrasound examinations in uncomplicated twin pregnancies delivering after 36 weeks of gestation were collected by 19 Italian fetal medicine units under the auspices of the Società Italiana di Ecografia Ostetrica e Ginecologica. The measurements acquired in each fetus at each examination included biparietal diameter, head circumference, abdominal circumference, and femur length. Multilevel linear regression models were used to adjust for the serial ultrasonographic measurements obtained and the clustering of each fetus in twin pregnancy. The impact of maternal and paternal characteristics (height, weight, ethnicity), parity, fetal sex, and mode of conception was also considered. Models for each parameter were stratified by fetal chorionicity and compared with our previously constructed growth curves for singletons. The data set included 1781 twin pregnancies (dichorionic, n = 1289; monochorionic diamniotic, n = 492) with 8923 ultrasonographic examinations with a median of 5 (range, 2-8) observations per pregnancy in dichorionic and 6 in (range, 2-11) monochorionic pregnancies. Growth curves of twin pregnancies differed from those of singletons, and differences were more marked in monochorionic twins and during the third trimester. A significant influence of parental characteristics was found. Curves of fetal biometric measurements in twins are influenced by parental characteristics. There is a reduction in the growth rate during the third trimester. The reference limits for

Patient-derived xenograft in zebrafish embryos: a new platform for translational research in neuroendocrine tumors.

PubMed

Gaudenzi, Germano; Albertelli, Manuela; Dicitore, Alessandra; Würth, Roberto; Gatto, Federico; Barbieri, Federica; Cotelli, Franco; Florio, Tullio; Ferone, Diego; Persani, Luca; Vitale, Giovanni

2017-08-01

Preclinical research on neuroendocrine tumors usually involves immortalized cell lines and few animal models. In the present study we described an in vivo model based on patient-derived xenografts of neuroendocrine tumor cells in zebrafish (Danio rerio) embryos, allowing a rapid analysis of the angiogenic and invasive potential. Patient-derived neuroendocrine tumor cells were transplanted in 48 hours post-fertilization Tg(fli1a:EGFP) y1 zebrafish embryos that express enhanced green fluorescent protein in the entire vasculature. Neuroendocrine tumor cells, stained with CM-Dil, were injected into the subperidermal (perivitelline) space, close to the developing subintestinal venous plexus. A proper control group, represented by zebrafish injected with only D-PBS, was included in this study. Angiogenic and invasive potentials of each patient-derived xenograft were evaluated by both epifluorescence and confocal microscopes. Six out of eight neuroendocrine tumor samples were successfully transplanted in zebrafish embryos. Although the implanted tumor mass had a limited size (about 100 cells for embryos), patient-derived xenografts showed pro-angiogenic (5 cases) and invasive (6 cases) behaviors within 48 hours post injection. Patient-derived xenograft in zebrafish embryos appears to be a reliable in vivo preclinical model for neuroendocrine tumors, tumors with often limited cell availability. The rapidity of this procedure makes our model a promising platform to perform preclinical drug screening and opens a new scenario for personalized treatment in patients with neuroendocrine tumors.

Novel dedifferentiated liposarcoma xenograft models reveal PTEN down-regulation as a malignant signature and response to PI3K pathway inhibition.

PubMed

Smith, Kathleen B; Tran, Linh M; Tam, Brenna M; Shurell, Elizabeth M; Li, Yunfeng; Braas, Daniel; Tap, William D; Christofk, Heather R; Dry, Sarah M; Eilber, Fritz C; Wu, Hong

2013-04-01

Liposarcoma is a type of soft tissue sarcoma that exhibits poor survival and a high recurrence rate. Treatment is generally limited to surgery and radiation, which emphasizes the need for better understanding of this disease. Because very few in vivo and in vitro models can reproducibly recapitulate the human disease, we generated several xenograft models from surgically resected human dedifferentiated liposarcoma. All xenografts recapitulated morphological and gene expression characteristics of the patient tumors after continuous in vivo passages. Importantly, xenograftability was directly correlated with disease-specific survival of liposarcoma patients. Thus, the ability for the tumor of a patient to engraft may help identify those patients who will benefit from more aggressive treatment regimens. Gene expression analyses highlighted the association between xenograftability and a unique gene expression signature, including down-regulated PTEN tumor-suppressor gene expression and a progenitor-like phenotype. When treated with the PI3K/AKT/mTOR pathway inhibitor rapamycin alone or in combination with the multikinase inhibitor sorafenib, all xenografts responded with increased lipid content and a more differentiated gene expression profile. These human xenograft models may facilitate liposarcoma research and accelerate the generation of readily translatable preclinical data that could ultimately influence patient care. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The short-term effect of smoking on fetal ECG.

PubMed

Péterfi, István; Kellényi, Lóránd; Péterfi, Lehel; Szilágyi, András

2017-10-26

The number of women who smoke during pregnancy is significant even today. The harmful effects of smoking during pregnancy are well known but there are no data on the effects of smoking on fetal electrocardiography (ECG). The lack of data is in connection with the difficulties of recording fetal ECG through the maternal abdomen. Third trimester pregnant women who were not able to give up the harmful passion of smoking despite repeated attempts of persuasion were recruited in the study on voluntary basis. The fetal ECG was recorded non-invasively through the maternal abdomen before, during and after smoking, then the data were processed offline. The electrophysiological measurements were performed by a self developed ECG device, which allowed the examination of the morphological differences in "true-to-form" fetal ECG in addition to studying the variability of fetal heart rate. The study involved nine pregnant women. The observed changes are presented through case studies of those pregnant women who showed the most significant anomalies. Compared with the resting state fetal heart rate was increased during smoking. The short-term variability of fetal heart rate was narrowed, while the mother's heart rate did not change significantly - which was an indication of direct fetal stress. No explicit ischemic signs were detected in fetal ECG during smoking, however, in the increasing period of the fetal heart rate, the T wave morphology changed slightly, then it returned to normal. Demonstrable by the electrophysiological methods, smoking has a direct effect on fetal cardiac function. The fetal heart rate variability shows a pattern during smoking which is a typical sign of stress conditions among adults. The results may have educational consequences as well. Understanding those, hopefully will help pregnant women give up this harmful addiction.

Assessing effects of BL67 points stimulation on fetal heart rate parameters and fetal movements during nonstress test.

PubMed

Pirhadi, Masume; Valiani, Mahboube

2017-01-01

One of the main goals of antenatal testing is to identify fetuses at the risk of neurologic injury or death so that these adverse outcomes can be prevented. We want to assess the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements during nonstress test (NST). We did a quasi-experimental design in Shahid Beheshti Hospital in Isfahan in 2011. This study aims to assessment of the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements. We did a randomized controlled clinical trial in Shahid Beheshti Hospital in Isfahan in 2011. This study is a quasi-experimental design that was conducted in one group and the two steps (before-after study). Participants were pregnant women (primigravida) who were 35-18 years that refer to Shahid Beheshti Hospital in Isfahan in 2011 to receive routine prenatal care. The 32 pregnant women were selected for acupressure during the second NST. The statistical processing was performed by descriptive, paired t -test through SPSS version 20. There was no significant difference in mean number of accelerations in fetal heart rate and mean number of fetal movement before and after intervention; however, there was a significant difference in mean time to the second acceleration before and after the intervention ( P = 0.04). No difference between parameters of the fetal heart rate before and after stimulation and lack of uterine response by this method is a significant advantage and is probably why stimulating this point could not create a risk to the fetuses.

Near-term fetal response to maternal spoken voice

PubMed Central

Voegtline, Kristin M.; Costigan, Kathleen A.; Pater, Heather A.; DiPietro, Janet A.

2013-01-01

Knowledge about prenatal learning has been largely predicated on the observation that newborns appear to recognize the maternal voice. Few studies have examined the process underlying this phenomenon; that is, whether and how the fetus responds to maternal voice in situ. Fetal heart rate and motor activity were recorded at 36 weeks gestation (n = 69) while pregnant women read aloud from a neutral passage. Compared to a baseline period, fetuses responded with a decrease in motor activity in the 10-seconds following onset of maternal speech and a trend level decelerative heart rate response, consistent with an orienting response. Subsequent analyses revealed that the fetal response was modified by both maternal and fetal factors. Fetuses of women who were previously awake and talking (n = 40) showed an orienting response to onset of maternal reading aloud, while fetuses of mothers who had previously been resting and silent (n = 29) responded with elevated heart rate and increased movement. The magnitude of the fetal response was further dependent on baseline fetal heart rate variability such that largest response was demonstrated by fetuses with low variability of mothers who were previously resting and silent. Results indicate that fetal responsivity is affected by both maternal and fetal state and have implications for understanding fetal learning of the maternal voice under naturalistic conditions. PMID:23748167

Sildenafil Citrate in Fetal Growth Restriction

PubMed Central

Panda, Subrat; Das, Ananya; Md Nowroz, Hossain

2014-01-01

Background Pregnancies with early onset fetal growth restriction have poor perinatal outcome. Sildenafil citrate (PDE -5 inhibitor) as a vasodilator increases utero-placental blood flow and potentiates fetal growth. Case Presentation In this study, a case was examined and Sildenafil was administered for her. It was found that Sildenafil improved the uterine blood flow with a favorable fetal outcome at delivery. Conclusion Sildenafil, as a vasodilator has emerged as a potential management option in the treatment of Intra Uterine Growth Retardation (IUGR) and preeclampsia by later normalization in velocimetric profile. PMID:25202677

Basal Cell Carcinoma of the Dorsal Foot: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany Y; Rubin, Ashley G; Jiang, Shang I Brian

2017-01-01

Ultraviolet radiation is a well-known risk factor for basal cell carcinoma (BCC). Therefore, the high incidence of BCCs in sun-exposed areas such as the head and neck is unsurprising. However, unexpectedly, BCCs on the sun-protected dorsal foot have also been reported, and tumor occurrence here suggests that other factors besides ultraviolet radiation may play a role in BCC pathogenesis. Because only few dorsal foot BCCs have been reported, data on their clinical features and management are limited. To perform an updated review of the literature on clinical characteristics and treatment of dorsal foot BCCs. We conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal foot," "basal cell carcinoma foot," and "basal cell carcinoma toe." We identified 20 cases of dorsal foot BCCs in the literature, 17 of which had sufficient data for analysis. Only 1 case was treated with Mohs micrographic surgery. We present 8 additional cases of dorsal foot BCCs treated with Mohs micrographic surgery. Basal cell carcinomas on the dorsal foot are rare, and potential risk factors include Caucasian descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment option.

Basal Cell Carcinoma of the Dorsal Hand: An Update and Comprehensive Review of the Literature.

PubMed

Loh, Tiffany Y; Rubin, Ashley G; Brian Jiang, Shang I

2016-04-01

Excessive ultraviolet radiation (UVR) exposure is the primary predisposing factor for basal cell carcinoma (BCC). However, surprisingly, BCCs occur very rarely on the dorsal hand, which is subject to intense sun exposure, and their infrequent presentation in this location suggests that other factors besides UVR may play a role in BCC pathogenesis. Because dorsal hand BCCs are uncommon, knowledge of their characteristics is limited, and more data are needed to describe their clinical presentation and treatment. To perform an updated review of the literature on the management of dorsal hand BCCs. The authors conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal hand," "basal cell carcinoma hand," and "basal cell carcinoma finger," and "basal cell carcinoma thumb." The authors identified 176 cases of dorsal hand BCCs in the literature, 120 of which had sufficient data for analysis. Only 4 cases were treated with Mohs micrographic surgery (MMS). The authors present 14 additional cases of dorsal hand BCCs treated with MMS. Basal cell carcinomas on the dorsal hand occur infrequently, and potential risk factors include being a male of white descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment method.

Imaging Axl expression in pancreatic and prostate cancer xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nimmagadda, Sridhar, E-mail: snimmag1@jhmi.edu; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287; Pullambhatla, Mrudula

2014-01-10

Highlights: •Axl is overexpressed in a variety of cancers. •Axl overexpression confers invasive phenotype. •Axl imaging would be useful for therapeutic guidance and monitoring. •Axl expression imaging is demonstrated in pancreatic and prostate cancer xenografts. •Graded levels of Axl expression imaging is feasible. -- Abstract: The receptor tyrosine kinase Axl is overexpressed in and leads to patient morbidity and mortality in a variety of cancers. Axl–Gas6 interactions are critical for tumor growth, angiogenesis and metastasis. The goal of this study was to investigate the feasibility of imaging graded levels of Axl expression in tumors using a radiolabeled antibody. We radiolabeledmore » anti-human Axl (Axl mAb) and control IgG1 antibodies with {sup 125}I with high specific radioactivity and radiochemical purity, resulting in an immunoreactive fraction suitable for in vivo studies. Radiolabeled antibodies were investigated in severe combined immunodeficient mice harboring subcutaneous CFPAC (Axl{sup high}) and Panc1 (Axl{sup low}) pancreatic cancer xenografts by ex vivo biodistribution and imaging. Based on these results, the specificity of [{sup 125}I]Axl mAb was also validated in mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring subcutaneous 22Rv1 (Axl{sup low}) or DU145 (Axl{sup high}) prostate tumors by ex vivo biodistribution and imaging studies at 72 h post-injection of the antibody. Both imaging and biodistribution studies demonstrated specific and persistent accumulation of [{sup 125}I]Axl mAb in Axl{sup high} (CFPAC and DU145) expression tumors compared to the Axl{sup low} (Panc1 and 22Rv1) expression tumors. Axl expression in these tumors was further confirmed by immunohistochemical studies. No difference in the uptake of radioactivity was observed between the control [{sup 125}I]IgG1 antibody in the Axl{sup high} and Axl{sup low} expression tumors. These data demonstrate the feasibility of imaging Axl expression in

Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

PubMed

Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

2018-01-01

Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p < .05), but this was prolonged in CMS versus control ewes (74 vs. 30 min, p < .05). CMS increased fetal circulating baseline and stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

The Normal Fetal Pancreas.

PubMed

Kivilevitch, Zvi; Achiron, Reuven; Perlman, Sharon; Gilboa, Yinon

2017-10-01

The aim of the study was to assess the sonographic feasibility of measuring the fetal pancreas and its normal development throughout pregnancy. We conducted a cross-sectional prospective study between 19 and 36 weeks' gestation. The study included singleton pregnancies with normal pregnancy follow-up. The pancreas circumference was measured. The first 90 cases were tested to assess feasibility. Two hundred ninety-seven fetuses of nondiabetic mothers were recruited during a 3-year period. The overall satisfactory visualization rate was 61.6%. The intraobserver and interobserver variability had high interclass correlation coefficients of of 0.964 and 0.967, respectively. A cubic polynomial regression described best the correlation of pancreas circumference with gestational age (r = 0.744; P < .001) and significant correlations also with abdominal circumference and estimated fetal weight (Pearson r = 0.829 and 0.812, respectively; P < .001). Modeled pancreas circumference percentiles for each week of gestation were calculated. During the study period, we detected 2 cases with overgrowth syndrome and 1 case with an annular pancreas. In this study, we assessed the feasibility of sonography for measuring the fetal pancreas and established a normal reference range for the fetal pancreas circumference throughout pregnancy. This database can be helpful when investigating fetomaternal disorders that can involve its normal development. © 2017 by the American Institute of Ultrasound in Medicine.

Prenatal Alcohol Exposure Alters Fetal Iron Distribution and Elevates Hepatic Hepcidin in a Rat Model of Fetal Alcohol Spectrum Disorders123

PubMed Central

Huebner, Shane M; Blohowiak, Sharon E; Kling, Pamela J; Smith, Susan M

2016-01-01

Background: Prenatal alcohol exposure (PAE) causes neurodevelopmental disabilities, and gestational iron deficiency (ID) selectively worsens learning and neuroanatomical and growth impairments in PAE. It is unknown why ID worsens outcomes in alcohol-exposed offspring. Objective: We hypothesized that PAE alters maternal-fetal iron distribution or its regulation. Methods: Nulliparous, 10-wk-old, Long-Evans rats were mated and then fed iron-sufficient (100 mg Fe/kg) or iron-deficient (≤4 mg Fe/kg) diets. On gestational days 13.5–19.5, dams received either 5.0 g ethanol/kg body weight (PAE) or isocaloric maltodextrin by oral gavage. On gestational day 20.5, maternal and fetal clinical blood counts, tissue mineral and iron transport protein concentrations, and hepatic hepcidin mRNA expression were determined. Results: In fetal brain and liver (P < 0.001) and in maternal liver (P < 0.005), ID decreased iron (total and nonheme) and ferritin content by nearly 200%. PAE reduced fetal bodyweight (P < 0.001) and interacted with ID (P < 0.001) to reduce it by an additional 20%. Independent of maternal iron status, PAE increased fetal liver iron (30–60%, P < 0.001) and decreased brain iron content (total and nonheme, 15–20%, P ≤ 0.050). ID-PAE brains had lower ferritin, transferrin, and transferrin receptor content (P ≤ 0.002) than ID-maltodextrin brains. PAE reduced fetal hematocrit, hemoglobin, and red blood cell numbers (P < 0.003) independently of iron status. Unexpectedly, and also independent of iron status, PAE increased maternal and fetal hepatic hepcidin mRNA expression >300% (P < 0.001). Conclusions: PAE altered fetal iron distribution independent of maternal iron status in rats. The elevated iron content of fetal liver suggests that PAE may have limited iron availability for fetal erythropoiesis and brain development. Altered fetal iron distribution may partly explain why maternal ID substantially worsens growth and behavioral outcomes in PAE. PMID

The incidence of bent dorsal fins in free-ranging cetaceans.

PubMed

Alves, F; Towers, J R; Baird, R W; Bearzi, G; Bonizzoni, S; Ferreira, R; Halicka, Z; Alessandrini, A; Kopelman, A H; Yzoard, C; Rasmussen, M H; Bertulli, C G; Jourdain, E; Gullan, A; Rocha, D; Hupman, K; Mrusczok, M-T; Samarra, F I P; Magalhães, S; Weir, C R; Ford, J K B; Dinis, A

2018-02-01

Laterally bent dorsal fins are rarely observed in free-ranging populations of cetaceans, contrary to captivity, where most killer whale Orcinus orca adult males have laterally collapsed fins. This topic has been poorly explored, and data/information on its occurrence and possible causes are limited. The present study: (i) undertakes a review of the available information on bent dorsal fins in free-ranging cetaceans, and updates it with new records, (ii) reports on the proportion of bent fins in different study populations, and (iii) discusses possible causes. An empirical approach based on bibliographic research and compilation of 52 new records collected worldwide resulted in a total of 17 species of cetaceans displaying bent dorsal fins. The species with the highest number of records (64%) and from most locations was O. orca. On average, individuals with bent dorsal fins represent < 1% of their populations, with the exception of false killer whales Pseudorca crassidens and O. orca. While line injuries associated with fisheries interactions may be the main cause for P. crassidens, and the vulnerability to health issues caused by the evolutionary enlargement of the fin may be the cause for O. orca adult males, factors contributing to this abnormality for other species are still unclear. The occurrence of bent dorsals could be influenced by a set of variables rather than by a single factor but, irrespective of the cause, it is suggested that it does not directly affect the animals' survivorship. While still rare in nature, this incident is more common (at least 101 known cases) and widespread (geographically and in species diversity) than hypothesized, and is not confined only to animals in captive environments. Investigation into the occurrence of bent fins may be an interesting avenue of research. © 2017 Anatomical Society.

Damage to ventral and dorsal language pathways in acute aphasia

PubMed Central

Hartwigsen, Gesa; Kellmeyer, Philipp; Glauche, Volkmar; Mader, Irina; Klöppel, Stefan; Suchan, Julia; Karnath, Hans-Otto; Weiller, Cornelius; Saur, Dorothee

2013-01-01

Converging evidence from neuroimaging studies and computational modelling suggests an organization of language in a dual dorsal–ventral brain network: a dorsal stream connects temporoparietal with frontal premotor regions through the superior longitudinal and arcuate fasciculus and integrates sensorimotor processing, e.g. in repetition of speech. A ventral stream connects temporal and prefrontal regions via the extreme capsule and mediates meaning, e.g. in auditory comprehension. The aim of our study was to test, in a large sample of 100 aphasic stroke patients, how well acute impairments of repetition and comprehension correlate with lesions of either the dorsal or ventral stream. We combined voxelwise lesion-behaviour mapping with the dorsal and ventral white matter fibre tracts determined by probabilistic fibre tracking in our previous study in healthy subjects. We found that repetition impairments were mainly associated with lesions located in the posterior temporoparietal region with a statistical lesion maximum in the periventricular white matter in projection of the dorsal superior longitudinal and arcuate fasciculus. In contrast, lesions associated with comprehension deficits were found more ventral-anterior in the temporoprefrontal region with a statistical lesion maximum between the insular cortex and the putamen in projection of the ventral extreme capsule. Individual lesion overlap with the dorsal fibre tract showed a significant negative correlation with repetition performance, whereas lesion overlap with the ventral fibre tract revealed a significant negative correlation with comprehension performance. To summarize, our results from patients with acute stroke lesions support the claim that language is organized along two segregated dorsal–ventral streams. Particularly, this is the first lesion study demonstrating that task performance on auditory comprehension measures requires an interaction between temporal and prefrontal brain regions via the

Hypoxia: From Placental Development to Fetal Programming.

PubMed

Fajersztajn, Lais; Veras, Mariana Matera

2017-10-16

Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O 2 consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood. In this review, the role of hypoxia in fetal development, placentation, and fetal programming is summarized. Hypoxia is a basic mechanism involved in different pregnancy disorders and fetal health developmental complications. Although there are scientific data showing that hypoxia mediates changes in the growth trajectory of the fetus, modulates gene expression by epigenetic mechanisms, and determines the health status later in adulthood, more mechanistic studies are needed. Furthermore, if we consider that intrauterine hypoxia is not a rare event, and can be a consequence of unavoidable exposures to air pollution, nutritional deficiencies, obesity, and other very common conditions (drug addiction and stress), the health of future generations may be damaged and the incidence of some diseases will markedly increase as a consequence of disturbed fetal programming. Birth Defects Research 109:1377-1385, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Dorsal and ventral hippocampal adult-born neurons contribute to context fear memory.

PubMed

Huckleberry, Kylie A; Shue, Francis; Copeland, Taylor; Chitwood, Raymond A; Yin, Weiling; Drew, Michael R

2018-06-02

The hippocampus contains one of the few neurogenic niches within the adult brain-the subgranular zone of the dentate gyrus. The functional significance of adult-born neurons in this region has been characterized using context fear conditioning, a Pavlovian paradigm in which animals learn to associate a location with danger. Ablation or silencing of adult-born neurons impairs both acquisition and recall of contextual fear conditioning, suggesting that these neurons contribute importantly to hippocampal memory. Lesion studies indicate that CFC depends on neural activity in both the dorsal and ventral hippocampus, subregions with unique extrahippocampal connectivity and behavioral functions. Because most studies of adult neurogenesis have relied on methods that permanently ablate neurogenesis throughout the entire hippocampus, little is known about how the function of adult-born neurons varies along the dorsal-ventral axis. Using a Nestin-CreER T2 mouse line to target the optogenetic silencer Archaerhodopsin to adult-born neurons, we compared the contribution of dorsal and ventral adult-born neurons to acquisition, recall, and generalization of CFC. Acquisition of CFC was impaired when either dorsal or ventral adult-born neurons were silenced during training. Silencing dorsal or ventral adult-born neurons during test sessions decreased context-evoked freezing but did not impair freezing in a hippocampus-independent tone-shock freezing paradigm. Silencing adult-born neurons modestly reduced generalization of fear. Our data indicate that adult-born neurons in the dorsal and ventral hippocampus contribute to both memory acquisition and recall. The comparatively large behavioral effects of silencing a small number of adult-born neurons suggest that these neurons make a unique and powerful contribution to hippocampal function.

Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.

PubMed

Miranda, Joana O; Ramalho, Carla; Henriques-Coelho, Tiago; Areias, José Carlos

2017-11-01

Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

Two different streams form the dorsal visual system: anatomy and functions.

PubMed

Rizzolatti, Giacomo; Matelli, Massimo

2003-11-01

There are two radically different views on the functional role of the dorsal visual stream. One considers it as a system involved in space perception. The other is of a system that codes visual information for action organization. On the basis of new anatomical data and a reconsideration of previous functional and clinical data, we propose that the dorsal stream and its recipient parietal areas form two distinct functional systems: the dorso-dorsal stream (d-d stream) and the ventro-dorsal stream (v-d stream). The d-d stream is formed by area V6 (main d-d extrastriate visual node) and areas V6A and MIP of the superior parietal lobule. Its major functional role is the control of actions "on line". Its damage leads to optic ataxia. The v-d stream is formed by area MT (main v-d extrastriate visual node) and by the visual areas of the inferior parietal lobule. As the d-d stream, v-d stream is responsible for action organization. It, however, also plays a crucial role in space perception and action understanding. The putative mechanisms linking action and perception in the v-d stream is discussed.

Does rat fetal DNA induce preeclampsia in pregnant rats?

PubMed

Konečná, B; Borbélyová, V; Celec, P; Vlková, B

2015-02-01

Cell-free fetal DNA in maternal circulation is higher during preeclampsia. It is unclear whether it is the cause or the consequence of the disease. The aim of this study was to prove whether injected rat fetal DNA induces preeclampsia-like symptoms in pregnant Wistar rats. They received daily i.p. injections of water or rat fetal DNA (400 μg) from gestation day 14 to 18. Blood pressure, proteinuria, placental and fetal weight were measured at gestation day 19. Plasma DNase activity, proteinuria and creatinine clearance were assessed. There was no significant difference in any of the measured parameters. The results of this study do not confirm the hypothesis that fetal DNA might induce preeclampsia. This is in contrast to others using human fetal DNA in mice. Further studies should be focused on the effects of fetal DNA from the same species protected from DNase activity.

The evolution of the dorsal thalamus of jawed vertebrates, including mammals: cladistic analysis and a new hypothesis.

PubMed

Butler, A B

1994-01-01

The evolution of the dorsal thalamus in various vertebrate lineages of jawed vertebrates has been an enigma, partly due to two prevalent misconceptions: the belief that the multitude of nuclei in the dorsal thalamus of mammals could be meaningfully compared neither with the relatively few nuclei in the dorsal thalamus of anamniotes nor with the intermediate number of dorsal thalamic nuclei of other amniotes and a definition of the dorsal thalamus that too narrowly focused on the features of the dorsal thalamus of mammals. The cladistic analysis carried out here allows us to recognize which features are plesiomorphic and which apomorphic for the dorsal thalamus of jawed vertebrates and to then reconstruct the major changes that have occurred in the dorsal thalamus over evolution. Embryological data examined in the context of Von Baerian theory (embryos of later-descendant species resemble the embryos of earlier-descendant species to the point of their divergence) supports a new 'Dual Elaboration Hypothesis' of dorsal thalamic evolution generated from this cladistic analysis. From the morphotype for an early stage in the embryological development of the dorsal thalamus of jawed vertebrates, the divergent, sequential stages of the development of the dorsal thalamus are derived for each major radiation and compared. The new hypothesis holds that the dorsal thalamus comprises two basic divisions--the collothalamus and the lemnothalamus--that receive their predominant input from the midbrain roof and (plesiomorphically) from lemniscal pathways, including the optic tract, respectively. Where present, the collothalamic, midbrain-sensory relay nuclei are homologous to each other in all vertebrate radiations as discrete nuclei. Within the lemnothalamus, the dorsal lateral geniculate nucleus of mammals and the dorsal lateral optic nucleus of non-synapsid amniotes (diapsid reptiles, birds and turtles) are homologous as discrete nuclei; most or all of the ventral nuclear group

Fetal stem cell transplantation: Past, present, and future

PubMed Central

Ishii, Tetsuya; Eto, Koji

2014-01-01

Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson’s disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem (ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements. PMID:25258662

Slack KNa Channels Influence Dorsal Horn Synapses and Nociceptive Behavior.

PubMed

Evely, Katherine M; Pryce, Kerri D; Bausch, Anne E; Lukowski, Robert; Ruth, Peter; Haj-Dahmane, Samir; Bhattacharjee, Arin

2017-01-01

The sodium-activated potassium channel Slack (Kcnt1, Slo2.2) is highly expressed in dorsal root ganglion neurons where it regulates neuronal firing. Several studies have implicated the Slack channel in pain processing, but the precise mechanism or the levels within the sensory pathway where channels are involved remain unclear. Here, we furthered the behavioral characterization of Slack channel knockout mice and for the first time examined the role of Slack channels in the superficial, pain-processing lamina of the dorsal horn. We performed whole-cell recordings from spinal cord slices to examine the intrinsic and synaptic properties of putative inhibitory and excitatory lamina II interneurons. Slack channel deletion altered intrinsic properties and synaptic drive to favor an overall enhanced excitatory tone. We measured the amplitudes and paired pulse ratio of paired excitatory post-synaptic currents at primary afferent synapses evoked by electrical stimulation of the dorsal root entry zone. We found a substantial decrease in the paired pulse ratio at synapses in Slack deleted neurons compared to wildtype, indicating increased presynaptic release from primary afferents. Corroborating these data, plantar test showed Slack knockout mice have an enhanced nociceptive responsiveness to localized thermal stimuli compared to wildtype mice. Our findings suggest that Slack channels regulate synaptic transmission within the spinal cord dorsal horn and by doing so establishes the threshold for thermal nociception.

Fetal heart rate and fetal heart rate variability in Lipizzaner broodmares.

PubMed

Baska-Vincze, Boglárka; Baska, Ferenc; Szenci, Ottó

2015-03-01

Monitoring fetal heart rate (FHR) and fetal heart rate variability (FHRV) helps to understand and evaluate normal and pathological conditions in the foal. The aim of this study was to establish normal heart rate reference values for the ongoing equine pregnancy and to perform a heart rate variability (HRV) time-domain analysis in Lipizzaner mares. Seventeen middle- and late-term (days 121-333) pregnant Lipizzaner mares were examined using fetomaternal electrocardiography (ECG). The mean FHR (P = 0.004) and the standard deviation of FHR (P = 0.012) significantly decreased during the pregnancy. FHR ± SD values decreased from 115 ± 35 to 79 ± 9 bpm between months 5 and 11. Our data showed that HRV in the foal decreased as the pregnancy progressed, which is in contrast with the findings of earlier equine studies. The standard deviation of normal-normal intervals (SDNN) was higher (70 ± 25 to 166 ± 108 msec) than described previously. The root mean square of successive differences (RMSSD) decreased from 105 ± 69 to 77 ± 37 msec between the 5th and 11th month of gestation. Using telemetric ECG equipment, we could detect equine fetal heartbeat on day 121 for the first time. In addition, the large differences observed in the HR values of four mare-fetus pairs in four consecutive months support the assumption that there might be 'high-HR' and 'low-HR' fetuses in horses. It can be concluded that the analysis of FHR and FHRV is a promising tool for the assessment of fetal well-being but the applicability of these parameters in the clinical setting and in studs requires further investigation.

Nicotine Promotes Cholangiocarcinoma Growth in Xenograft Mice.

PubMed

Martínez, Allyson K; Jensen, Kendal; Hall, Chad; O'Brien, April; Ehrlich, Laurent; White, Tori; Meng, Fanyin; Zhou, Tianhao; Greene, John; Bernuzzi, Francesca; Invernizzi, Pietro; Dostal, David E; Lairmore, Terry; Alpini, Gianfranco; Glaser, Shannon S

2017-05-01

Nicotine, the main addictive substance in tobacco, is known to play a role in the development and/or progression of a number of malignant tumors. However, nicotine's involvement in the pathogenesis of cholangiocarcinoma is controversial. Therefore, we studied the effects of nicotine on the growth of cholangiocarcinoma cells in vitro and the progression of cholangiocarcinoma in a mouse xenograft model. The predominant subunit responsible for nicotine-mediated proliferation in normal and cancer cells, the α7 nicotinic acetylcholine receptor (α7-nAChR), was more highly expressed in human cholangiocarcinoma cell lines compared with normal human cholangiocytes. Nicotine also stimulated the proliferation of cholangiocarcinoma cell lines and promoted α7-nAChR-dependent activation of proliferation and phosphorylation of extracellular-regulated kinase in Mz-ChA-1 cells. In addition, nicotine and PNU282987 (α7-nAChR agonist) accelerated the growth of the cholangiocarcinoma tumors in our xenograft mouse model and increased fibrosis, proliferation of the tumor cells, and phosphorylation of extracellular-regulated kinase activation. Finally, α7-nAChR was expressed at significantly higher levels in human cholangiocarcinoma compared with normal human control liver samples. Taken together, results of this study suggest that nicotine acts through α7-nAChR and plays a novel role in the pathogenesis of cholangiocarcinoma. Furthermore, nicotine may act as a mitogen in cholestatic liver disease processes, thereby facilitating malignant transformation. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Equine fetal adrenal, gonadal and placental steroidogenesis.

PubMed

Legacki, Erin L; Ball, Barry A; Corbin, C Jo; Loux, Shavahn C; Scoggin, Kirsten E; Stanley, Scott D; Conley, Alan J

2017-10-01

Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data. CYP17A1 was higher in fetal gonads than adrenals or allantochorion, and HSD3B1 was higher in fetal adrenals and allantochorion than gonads. CYP11A1 transcript was also significantly higher in adrenals and gonads than allantochorion and CYP19 and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. Low CYP11A1 but high HSD3B1 and SRD5A1 transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion. © 2017 Society for Reproduction and Fertility.

Assessing dorsal scute microchemistry for reconstruction of shortnose sturgeon life histories

USGS Publications Warehouse

Altenritter, Matthew E.; Kinnison, Michael T.; Zydlewski, Gayle B.; Secor, David H.; Zydlewski, Joseph D.

2015-01-01

The imperiled status of sturgeons worldwide places priority on the identification and protection of critical habitats. We assessed the micro-structural and micro-chemical scope for a novel calcified structure, dorsal scutes, to be used for reconstruction of past habitat use and group separation in shortnose sturgeon (Acipenser brevirostrum). Dorsal scutes contained a dual-layered structure composed of a thin multi-layered translucent zone lying dorsally above a thicker multi-layered zone. Banding in the thick multi-layered zone correlated strongly with pectoral fin spine annuli supporting the presence of chronological structuring that could contain a chemical record of past environmental exposure. Trace element profiles (Sr:Ca), collected using both wavelength dispersive electron microprobe analysis and laser ablation inductively coupled mass spectrometry, suggest scutes record elemental information useful for tracing transitions between freshwater and marine environments. Moreover, mirror-image like Sr:Ca profiles were observed across the dual-zone structuring of the scute that may indicate duplication of the microchemical profile in a single structure. Additional element:calcium ratios measured in natal regions of dorsal scutes (Ba:Ca, Mg:Ca) suggest the potential for further refinement of techniques for identification of river systems of natal origin. In combination, our results provide proof of concept that dorsal scutes possess the necessary properties to be used as structures for reconstructions of past habitat use in sturgeons. Importantly, scutes may be collected non-lethally and with less injury than current structures, like otoliths and fin spines, affording an opportunity for broader application of microchemical techniques.

Rat brain xenografts reverse hypogonadism in mice immunosuppressed with anti-CD4 monoclonal antibody.

PubMed

Honey, C R; Charlton, H M; Wood, K J

1991-01-01

This study examines the effect of immunosuppression with monoclonal antibodies (MAb) against the murine CD4 (L3T4), a cell surface glycoprotein expressed primarily on helper T-lymphocytes, on the viability and function of rat neural xenografts placed in the third ventricle of hypogonadal (hpg) mice. The hpg mouse fails to synthesize hypothalamic gonadotrophin releasing hormone (GnRH) and consequently there is a drastic reduction in pituitary gonadotrophic hormone content and a failure of postnatal gonadal development (Cattanach et al. 1977). Three groups of male hpg mice received xenografts of day 1 post natal rat preoptic area (POA) tissue, a source of GnRH neurons, to their third ventricle. Those immunosuppressed with anti-CD4 MAb all showed surviving graft tissue thirty days post-transplant and half of this group had enlarged testes with all stages of spermatogenesis. In those hpg mice which were injected with saline alone, or with an anti-CD8 (Lyt-2) antibody there was no xenograft survival. These results suggest that the injection of monoclonal antibodies against the T-helper subset may provide an alternative means of immunosuppression aimed at the enhancement of survival of tissue grafts in the CNS.

Influence of histamine and serotonin antagonists on the growth of xenografted human colorectal tumors.

PubMed

Barkla, D H; Tutton, P J

1981-12-01

Four lines of human colorectal cancer were established and serially propagated as subcutaneous xenographs in immunosuppressed inbred CBA/Lac mice. Established xenografts were then used to investigate the influence of a serotonin antagonist (BW 501c) and a histamine H2 receptor antagonists (Cimetidine) on xenograft growth. The growth of each of the four tumor lines was significantly inhibited by BW 501c throughout the treatment, whereas the growth of only two tumor lines was significantly inhibited by Cimetidine treatment. The response of individual tumor lines was not predictable on the basis of either tumor histopathology or the natural growth rate of the untreated xenograft. A number of alternative, but not mutually exclusive, hypotheses are suggested to explain the results. One hypothesis proposes that colorectal tumors are composed of subpopulations of tumor cells that are variously dependent on or independent of amine hormones. Another hypothesis is that tumor cells exhibit temporal changes in hormone sensitivity to amine hormones during treatment. Finally, it is suggested that serotonin and/or histamine H2 antagonists may be useful in preventing the repopulation of colorectal carcinomas following antineoplastic therapy with the use of conventional drugs.

Passive Fetal Heart Monitoring System

NASA Technical Reports Server (NTRS)

Bryant, Timothy D. (Inventor); Wynkoop, Mark W. (Inventor); Holloway, Nancy M. H. (Inventor); Zuckerwar, Allan J. (Inventor)

2004-01-01

A fetal heart monitoring system preferably comprising a backing plate having a generally concave front surface and a generally convex back surface, and at least one sensor element attached to the concave front surface for acquiring acoustic fetal heart signals produced by a fetus within a body. The sensor element has a shape that conforms to the generally concave back surface of the backing plate. In one embodiment, the at least one sensor element comprises an inner sensor, and a plurality of outer sensors surrounding the inner sensor. The fetal heart monitoring system can further comprise a web belt, and a web belt guide movably attached to the web belt. The web belt guide being is to the convex back surface of the backing plate.

Fetal effects of psychoactive drugs.

PubMed

Salisbury, Amy L; Ponder, Kathryn L; Padbury, James F; Lester, Barry M

2009-09-01

Psychoactive drug use by pregnant women has the potential to effect fetal development; the effects are often thought to be drug-specific and gestational age dependent. This article describes the effects of three drugs with similar molecular targets that involve monoaminergic transmitter systems: cocaine, methamphetamine, and selective serotonin re-uptake inhibitors (SSRIs) used to treat maternal depression during pregnancy. We propose a possible common epigenetic mechanism for their potential effects on the developing child. We suggest that exposure to these substances acts as a stressor that affects fetal programming, disrupts fetal placental monoamine transporter expression and alters neuroendocrine and neurotransmitter system development. We also discuss neurobehavioral techniques that may be useful in the early detection of the effects of in utero drug exposure.

Simultaneous monitoring of maternal and fetal heart rate variability during labor in relation with fetal gender.

PubMed

Gonçalves, Hernâni; Fernandes, Diana; Pinto, Paula; Ayres-de-Campos, Diogo; Bernardes, João

2017-11-01

Male gender is considered a risk factor for several adverse perinatal outcomes. Fetal gender effect on fetal heart rate (FHR) has been subject of several studies with contradictory results. The importance of maternal heart rate (MHR) monitoring during labor has also been investigated, but less is known about the effect of fetal gender on MHR. The aim of this study is to simultaneously assess maternal and FHR variability during labor in relation with fetal gender. Simultaneous MHR and FHR recordings were obtained from 44 singleton term pregnancies during the last 2 hr of labor (H 1, H 2 ). Heart rate tracings were analyzed using linear (time- and frequency-domain) and nonlinear indices. Both linear and nonlinear components were considered in assessing FHR and MHR interaction, including cross-sample entropy (cross-SampEn). Mothers carrying male fetuses (n = 22) had significantly higher values for linear indices related with MHR average and variability and sympatho-vagal balance, while the opposite occurred in the high-frequency component and most nonlinear indices. Significant differences in FHR were only observed in H 1 with higher entropy values in female fetuses. Assessing the differences between FHR and MHR, statistically significant differences were obtained in most nonlinear indices between genders. A significantly higher cross-SampEn was observed in mothers carrying female fetuses (n = 22), denoting lower synchrony or similarity between MHR and FHR. The variability of MHR and the synchrony/similarity between MHR and FHR vary with respect to fetal gender during labor. These findings suggest that fetal gender needs to be taken into account when simultaneously monitoring MHR and FHR. © 2017 Wiley Periodicals, Inc.

Fetal Growth and Neurobehavioral Outcomes in Childhood

PubMed Central

Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

2014-01-01

Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

Maternal physical activity mode and fetal heart outcome.

PubMed

May, Linda E; Suminski, Richard R; Berry, Andrew; Langaker, Michelle D; Gustafson, Kathleen M

2014-07-01

Maternal leisure-time physical activity (LTPA) improves cardiac autonomic function in the fetus. The specific physical activity attributes (e.g., mode) that produce this benefit are not well understood. To determine if more time spent performing non-continuous LTPA during pregnancy is significantly associated with lower fetal heart rate (HR) and increased heart rate variability (HRV). This paper presents a retrospective analysis of previously reported data. Fetal magnetocardiograms (MCG) were recorded from 40 pregnant women at 36-wk gestational age. Metrics of fetal HR and HRV, self-reported min of continuous and non-continuous LTPA performed during the 3-months preceding the 36-wk assessment point and covariates (maternal weight change pre to 36-wk, age, and resting HR and fetal activity state during MCG recordings. Positive correlations were significant (p<0.05) between min of continuous LTPA, the time domain metrics that describe fetal overall HRV, short-term HRV and a frequency domain metric that reflects vagal activity. Time spent in non-continuous LTPA was positively correlated (p<0.05) with two HRV metrics that reflect fetal overall HRV. In the multiple regression analyses, minutes of non-continuous LTPA remained associated with fetal vagal activity (p<0.05) and the relationships between minutes of non-continuous LTPA and fetal overall HRV (p<0.005) persisted. These data suggest non-continuous physical activity provides unique benefits to the fetal autonomic nervous system that may give the fetus an adaptive advantage. Further studies are needed to understand the physiological mechanisms and long-term health effects of physical activity (both non-continuous and continuous) performed during pregnancy to both women and their offspring. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sonographic large fetal head circumference and risk of cesarean delivery.

PubMed

Lipschuetz, Michal; Cohen, Sarah M; Israel, Ariel; Baron, Joel; Porat, Shay; Valsky, Dan V; Yagel, Oren; Amsalem, Hagai; Kabiri, Doron; Gilboa, Yinon; Sivan, Eyal; Unger, Ron; Schiff, Eyal; Hershkovitz, Reli; Yagel, Simcha

2018-03-01

Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm

Lumbosacral Dorsal Rhizotomy for Spastic Cerebral Palsy: A Health Technology Assessment

PubMed Central

Pron, Gaylene; Chan, Brian; Tu, Hong Anh; Xie, Xuanqian; Weir, Mark; Wells, David; Higgins, Caroline

2017-01-01

Background Cerebral palsy, a spectrum of neuromuscular conditions caused by abnormal brain development or early damage to the brain, is the most common cause of childhood physical disability. Lumbosacral dorsal rhizotomy is a neurosurgical procedure that permanently decreases spasticity and is always followed by physical therapy. The objectives of this health technology assessment were to evaluate the clinical effectiveness, safety, cost effectiveness, and family perspectives of dorsal rhizotomy. Methods We performed a systematic literature search until December 2015 with auto-alerts until December 2016. Search strategies were developed by medical librarians, and a single reviewer reviewed the abstracts. The health technology assessment included a clinical review based on functional outcomes, safety, and treatment satisfaction; an economic study reviewing cost-effective literature; a budget impact analysis; and interviews with families evaluating the intervention. Results Eighty-four studies (1 meta-analysis, 5 randomized controlled studies [RCTs], 75 observational pre-post studies, and 3 case reports) were reviewed. A meta-analysis of RCTs involving dorsal rhizotomy and physical therapy versus physical therapy confirmed reduced lower-limb spasticity and increased gross motor function (4.5%, P = .002). Observational studies reported statistically significant improvements in gross motor function over 2 years or less (12 studies, GRADE moderate) and over more than 2 years (10 studies, GRADE moderate) as well as improvements in functional independence in the short term (10 studies, GRADE moderate) and long term (4 studies, GRADE low). Major operative complications, were infrequently reported (4 studies). Bony abnormalities and instabilities monitored radiologically in the spine (15 studies) and hip (8 studies) involved minimal or clinically insignificant changes after surgery. No studies evaluated the cost effectiveness of dorsal rhizotomy. The budget impact of

Lumbosacral Dorsal Rhizotomy for Spastic Cerebral Palsy: A Health Technology Assessment.

PubMed

2017-01-01

Cerebral palsy, a spectrum of neuromuscular conditions caused by abnormal brain development or early damage to the brain, is the most common cause of childhood physical disability. Lumbosacral dorsal rhizotomy is a neurosurgical procedure that permanently decreases spasticity and is always followed by physical therapy. The objectives of this health technology assessment were to evaluate the clinical effectiveness, safety, cost effectiveness, and family perspectives of dorsal rhizotomy. We performed a systematic literature search until December 2015 with auto-alerts until December 2016. Search strategies were developed by medical librarians, and a single reviewer reviewed the abstracts. The health technology assessment included a clinical review based on functional outcomes, safety, and treatment satisfaction; an economic study reviewing cost-effective literature; a budget impact analysis; and interviews with families evaluating the intervention. Eighty-four studies (1 meta-analysis, 5 randomized controlled studies [RCTs], 75 observational pre-post studies, and 3 case reports) were reviewed. A meta-analysis of RCTs involving dorsal rhizotomy and physical therapy versus physical therapy confirmed reduced lower-limb spasticity and increased gross motor function (4.5%, P = .002). Observational studies reported statistically significant improvements in gross motor function over 2 years or less (12 studies, GRADE moderate) and over more than 2 years (10 studies, GRADE moderate) as well as improvements in functional independence in the short term (10 studies, GRADE moderate) and long term (4 studies, GRADE low). Major operative complications, were infrequently reported (4 studies). Bony abnormalities and instabilities monitored radiologically in the spine (15 studies) and hip (8 studies) involved minimal or clinically insignificant changes after surgery. No studies evaluated the cost effectiveness of dorsal rhizotomy. The budget impact of funding dorsal rhizotomy for

Placental hormones, nutrition, and fetal development.

PubMed

Mulay, S; Browne, C A; Varma, D R; Solomon, S

1980-02-01

Fetal growth retardation due to maternal malnutrition is widespread especially in the Third World. Little is known about the mechanisms that regulate the growth of the fetus and placenta during protein malnutrition. It is known that the placental size and levels of circulating placental hormones such as human chorionic gonadotrophins (hCG), human placental lactogen (hPL), and estrogens are affected by the nutritional status of the mother. There is suggestive evidence that during malnutrition, hPL may increase lipolysis and exert a glucose sparing effect in the mother, thereby promoting glucose availability to the fetus. We have studied the influence of dietary protein deficiency on the binding of dexamethasone to the specific cytosol receptors in adult and fetal tissues. A low protein diet in adult male rats is associated with a decrease in dexamethasone binding to liver cytosol receptors. On the other hand, protein deprivation in pregnant female rats leads to an increase in dexamethasone binding to liver cytosol receptors of both the mother and fetus. However, the influences of maternal protein deprivation on dexamethasone receptors in the fetal liver and lungs are not similar. At 21 days gestation the binding of dexamethasone to fetal lung receptors of protein-deficient mothers is lower than that in the controls. These differences at a critical time in the fetal lung development indicate that a fall in receptors for dexamethasone may lead to impaired phospholipid synthesis in fetuses of protein-deficient mothers and point to the importance of nutritional factors in the biochemistry of fetal development.

[Anatomical study of muscular latissimus dorsi surface vascularized by the transverse branch of thoraco-dorsal artery].

PubMed

Boucher, F; Pinatel, B; Shipkov, H; Mertens, P; Rouviere, O; Braye, F; Mojallal, A

2014-10-01

The latissimus dorsi muscle flap is a type V according to Mathes and Nahai. It is vascularized by a proximal main pedicle represented by the thoraco-dorsal pedicle and pedicle distal accessory represented by the dorsal branches of the posterior intercostal arteries. The main thoraco-dorsal pedicle has a descending branch and a transverse branch. This anatomical study clarifies the muscular territory vascularized by the transverse branch of thoraco-dorsal artery for a secondary use after harvesting a thoraco-dorsal artery perforator flap or a muscle-sparing latissimus dorsi flap. Our study focused on ten dissections latissimus dorsi muscle taken from five fresh cadavers chest, carried out within the University Department of Anatomy. The descending branch of thoraco-dorsal artery was ligated, the transverse branch was cannulated and injected with a mixture of barium sulfate/gelatin. After freezing, a static angiotomodensitometry (3D) of each flap was performed. The average muscular surface vascularized by the transverse branch is measured at 80% (77% minimum value, maximum value 83%) of the complete latissimus dorsi muscle. Intermuscular connections between the two branches of thoraco-dorsal pedicle were shown. The use of a ipsilateral latissimus dorsi muscle is a therapeutic option after harvesting a thoraco-dorsal artery perforator flap (TAP) or a muscle-sparing latissimus dorsi flap (MSLD-flap). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Fetal Brain Behavior and Cognitive Development.

ERIC Educational Resources Information Center

Joseph, R.

2000-01-01

Presents information on prenatal brain development, detailing the functions controlled by the medulla, pons, and midbrain, and the implications for cognitive development. Concludes that fetal cognitive motor activity, including auditory discrimination, orienting, the wake-sleep cycle, fetal heart rate accelerations, and defensive reactions,…

Responses of spinal dorsal horn neurons to foot movements in rats with a sprained ankle

PubMed Central

Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

2011-01-01

Acute ankle injuries are common problems and often lead to persistent pain. To investigate the underlying mechanism of ankle sprain pain, the response properties of spinal dorsal horn neurons were examined after ankle sprain. Acute ankle sprain was induced manually by overextending the ankle of a rat hindlimb in a direction of plantarflexion and inversion. The weight-bearing ratio (WBR) of the affected foot was used as an indicator of pain. Single unit activities of dorsal horn neurons in response to plantarflexion and inversion of the foot or ankle compression were recorded from the medial part of the deep dorsal horn, laminae IV-VI, in normal and ankle-sprained rats. One day after ankle sprain, rats showed significantly reduced WBRs on the affected foot, and this reduction was partially restored by systemic morphine. The majority of deep dorsal horn neurons responded to a single ankle stimulus modality. After ankle sprain, the mean evoked response rates were significantly increased, and afterdischarges were developed in recorded dorsal horn neurons. The ankle sprain-induced enhanced evoked responses were significantly reduced by morphine, which was reversed by naltrexone. The data indicate that movement-specific dorsal horn neuron responses were enhanced after ankle sprain in a morphine-dependent manner, thus suggesting that hyperactivity of dorsal horn neurons is an underlying mechanism of pain after ankle sprain. PMID:21389306

Adjustable fetal phantom for pulse oximetry

NASA Astrophysics Data System (ADS)

Stubán, Norbert; Niwayama, Masatsugu

2009-05-01

As the measuring head of a fetal pulse oximeter must be attached to the head of the fetus inside the mother's uterus during labor, testing, and developing of fetal pulse oximeters in real environment have several difficulties. A fetal phantom could enable evaluation of pulse oximeters in a simulated environment without the restrictions and difficultness of medical experiments in the labor room. Based on anatomic data we developed an adjustable fetal head phantom with three different tissue layers and artificial arteries. The phantom consisted of two arteries with an inner diameter of 0.2 and 0.4 mm. An electronically controlled pump produced pulse waves in the arteries. With the phantom we investigated the sensitivity of a custom-designed wireless pulse oximeter at different pulsation intensity and artery diameters. The results showed that the oximeter was capable of identifying 4% and 2% changes in diameter between the diastolic and systolic point in arteries of over 0.2 and 0.4 mm inner diameter, respectively. As the structure of the phantom is based on reported anatomic values, the results predict that the investigated custom-designed wireless pulse oximeter has sufficient sensitivity to detect the pulse waves and to calculate the R rate on the fetal head.

Early Evaluation of the Fetal Heart.

PubMed

Hernandez-Andrade, Edgar; Patwardhan, Manasi; Cruz-Lemini, Mónica; Luewan, Suchaya

2017-01-01

Evaluation of the fetal heart at 11-13 + 6 weeks of gestation is indicated for women with a family history of congenital heart defects (CHD), a previous child with CDH, or an ultrasound finding associated with cardiac anomalies. The accuracy for early detection of CHD is highly related to the experience of the operator. The 4-chamber view and outflow tracts are the most important planes for identification of an abnormal heart, and can be obtained in the majority of fetuses from 11 weeks of gestation onward. Transvaginal ultrasound is the preferred route for fetal cardiac examination prior to 12 weeks of gestation, whereas, after 12 weeks, the fetal heart can be reliably evaluated by transabdominal ultrasound. Cardiac defects, such as ventricular septal defects, tetralogy of Fallot, Ebstein's anomaly, or cardiac tumors, are unlikely to be identified at ≤14 weeks of gestation. Additional ultrasound techniques such as spatiotemporal image correlation and the evaluation of volumes by a fetal-heart expert can improve the detection of congenital heart disease. The evaluation of the fetal cardiac function at 11-13 + 6 weeks of gestation can be useful for early identification of fetuses at risk of anemia due to hemoglobinopathies, such as hemoglobin Bart's disease. © 2017 S. Karger AG, Basel.

Monitoring of fetal radiation exposure during pregnancy.

PubMed

Chandra, Venita; Dorsey, Chelsea; Reed, Amy B; Shaw, Palma; Banghart, Dawn; Zhou, Wei

2013-09-01

One unique concern of vascular surgeons and trainees is radiation exposure associated with increased endovascular practice. The safety of childbearing is a particular worry for current and future women in vascular surgery. Little is known regarding actual fetal radiation exposure. This multi-institutional study aimed to evaluate the radiation dosages recorded on fetal dosimeter badges and compare them to external badges worn by the same cohort of women. All women who declared pregnancy with potential radiation exposure were required to wear two radiation monitors at each institution, one outside and the other inside the lead apron. Maternal (external) and fetal monitor dosimeter readings were analyzed. Maternal radiation exposures prior to, during, and postpregnancy were also assessed to determine any associated behavior modification. Eighty-one women declared pregnancy from 2008 to 2011 and 32 had regular radiation exposure during pregnancy. Maternal whole-body exposures ranged from 21-731 mrem. The average fetal dosimeter recordings for the cohort rounded to zero. Only two women had positive fetal dosimeter recordings; one had a single recording of 3 mrem and the other had a single recording of 7 mrem. There was no significant difference between maternal exposures prior to, during, and postpregnancy. Lack of knowledge of fetal radiation exposure has concerned many vascular surgeons, prompting them to wear double lead aprons during pregnancy, and perhaps prevented numerous other women from entering the field. Our study showed negligible radiation exposure on fetal monitoring suggesting that with the appropriate safety precautions, these concerns may be unwarranted. Published by Mosby, Inc.

Fetal Treatment 2017: The Evolution of Fetal Therapy Centers - A Joint Opinion from the International Fetal Medicine and Surgical Society (IFMSS) and the North American Fetal Therapy Network (NAFTNet).

PubMed

Moon-Grady, Anita J; Baschat, Ahmet; Cass, Darrell; Choolani, Mahesh; Copel, Joshua A; Crombleholme, Timothy M; Deprest, Jan; Emery, Stephen P; Evans, Mark I; Luks, Francois I; Norton, Mary E; Ryan, Greg; Tsao, Kuojen; Welch, Ross; Harrison, Michael

2017-01-01

More than 3 decades ago, a small group of physicians and other practitioners active in what they called "fetal treatment" authored an opinion piece outlining the current status and future challenges anticipated in the field. Many advances in maternal, neonatal, and perinatal care and diagnostic and therapeutic modalities have been made in the intervening years, yet a thoughtful reassessment of the basic tenets put forth in 1982 has not been published. The present effort will aim to provide a framework for contemporary redefinition of the field of fetal treatment, with a brief discussion of the necessary minimum expertise and systems base for the provision of different types of interventions for both the mother and fetus. Our goal will be to present an opinion that encourages the advancement of thoughtful practice, ensuring that current and future patients have realistic access to centers with a range of fetal therapies with appropriate expertise, experience, and subspecialty and institutional support while remaining focused on excellence in care, collaborative scientific discovery, and maternal autonomy and safety. © 2017 S. Karger AG, Basel.

Dorsal hippocampus contributes to model-based planning.

PubMed

Miller, Kevin J; Botvinick, Matthew M; Brody, Carlos D

2017-09-01

Planning can be defined as action selection that leverages an internal model of the outcomes likely to follow each possible action. Its neural mechanisms remain poorly understood. Here we adapt recent advances from human research for rats, presenting for the first time an animal task that produces many trials of planned behavior per session, making multitrial rodent experimental tools available to study planning. We use part of this toolkit to address a perennially controversial issue in planning: the role of the dorsal hippocampus. Although prospective hippocampal representations have been proposed to support planning, intact planning in animals with damaged hippocampi has been repeatedly observed. Combining formal algorithmic behavioral analysis with muscimol inactivation, we provide causal evidence directly linking dorsal hippocampus with planning behavior. Our results and methods open the door to new and more detailed investigations of the neural mechanisms of planning in the hippocampus and throughout the brain.

Fetal Programming and Cardiovascular Pathology

PubMed Central

Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

2016-01-01

Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

A prospective cohort study of fetal heart rate monitoring: deceleration area is predictive of fetal acidemia.

PubMed

Cahill, Alison G; Tuuli, Methodius G; Stout, Molly J; López, Julia D; Macones, George A

2018-05-01

Intrapartum electronic fetal monitoring is the most commonly used tool in obstetrics in the United States; however, which electronic fetal monitoring patterns predict acidemia remains unclear. This study was designed to describe the frequency of patterns seen in labor using modern nomenclature, and to test the hypothesis that visually interpreted patterns are associated with acidemia and morbidities in term infants. We further identified patterns prior to delivery, alone or in combination, predictive of acidemia and neonatal morbidity. This was a prospective cohort study of 8580 women from 2010 through 2015. Patients were all consecutive women laboring at ≥37 weeks' gestation with a singleton cephalic fetus. Electronic fetal monitoring patterns during the 120 minutes prior to delivery were interpreted in 10-minute epochs. Interpretation included the category system and individual electronic fetal monitoring patterns per the Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria as well as novel patterns. The primary outcome was fetal acidemia (umbilical artery pH ≤7.10); neonatal morbidities were also assessed. Final regression models for acidemia adjusted for nulliparity, pregestational diabetes, and advanced maternal age. Area under the receiver operating characteristic curves were used to assess the test characteristics of individual models for acidemia and neonatal morbidity. Of 8580 women, 149 (1.7%) delivered acidemic infants. Composite neonatal morbidity was diagnosed in 757 (8.8%) neonates within the total cohort. Persistent category I, and 10-minute period of category III, were significantly associated with normal pH and acidemia, respectively. Total deceleration area was most discriminative of acidemia (area under the receiver operating characteristic curves, 0.76; 95% confidence interval, 0.72-0.80), and deceleration area with any 10 minutes of tachycardia had the greatest discriminative ability for neonatal

Establishment and characterization of a human papillomavirus type 16-positive tonsillar carcinoma xenograft in BALB/c nude mice.

PubMed

Letsolo, Boitelo T; Faust, Helena; Ekblad, Lars; Wennerberg, Johan; Forslund, Ola

2016-03-01

Among head and neck cancers, human papillomavirus type 16 (HPV16) is associated with tonsillar carcinomas. Despite this, no HPV16-positive tonsillar cancer cell line has been established in nude mice. Fresh tonsillar carcinoma biopsies were obtained from 23 patients and implanted subcutaneously into nude mice (BALB/c, nu/nu). After 7 months, one xenograft was established. The primary tumor harbored 2.7 copies (95% confidence interval = 2.4-2.9) of HPV16/cell and displayed 99.9% (7904/7906) nucleotide identity to HPV16 (EU118173.1). The xenograft showed increased methylation in two E2-binding sites of the HPV16 genome. Both episomal and integrated HPV16 were detected in the original tumor and in 14 xenografts from the second passage. From this passage, a viral load of 6.4 copies/cell (range = 4.6-9.6) and 3.7 (range = 1.0-5.5) E7-mRNA transcripts/HPV16-genome were detected. This xenograft represents the first established HPV16-positive tonsillar tumor in nude mice and could provide an experimental system of HPV16-positive tonsillar cancers. © 2015 Wiley Periodicals, Inc.

Fetal growth: a review of terms, concepts and issues relevant to obstetrics.

PubMed

Mayer, C; Joseph, K S

2013-02-01

The perinatal literature includes several potentially confusing and controversial terms and concepts related to fetal size and growth. This article discusses fetal growth from an obstetric perspective and addresses various issues including the physiologic mechanisms that determine fetal growth trajectories, known risk factors for abnormal fetal growth, diagnostic and prognostic issues related to restricted and excessive growth and temporal trends in fetal growth. Also addressed are distinctions between fetal growth 'standards' and fetal growth 'references', and between fetal growth charts based on estimated fetal weight vs those based on birth weight. Other concepts discussed include the incidence of fetal growth restriction in pregnancy (does the frequency of fetal growth restriction increase or decrease with increasing gestation?), the obstetric implications of studies showing associations between fetal growth and adult chronic illnesses (such as coronary heart disease) and the need for customizing fetal growth standards. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Fetal monitoring during nonobstetric surgery: revisiting guidelines: a case report.

PubMed

Rothschild, Tod J; Morel, Bruce; Pace, Benjamin; Fuks, Aleksandr M

2015-01-01

Nonobstetric surgery during pregnancy is not an infrequent occurrence. Guidelines for fetal monitoring during nonobstetric surgery are limited. We describe a case of appendectomy during third trimester, complicated by in utero fetal demise (IUFD). A 30-year-old, Caucasian woman underwent open appendectomy for suspected acute appendicitis. The procedure was complicated by IUFD. Fetal monitoring was done prior to but not during surgery. Guidelines for fetal monitoring were revised, recommending continuous electronic fetal monitoring when possible during third trimester nonobstetric surgery after appropriate patient counseling. A subsequent series of 5 uncomplicated appendectomies demonstrated no difficulty in implementing these guidelines. Continuous electronic fetal monitoring during third trimester nonobstetric surgery should be available and implemented after appropriate patient counseling. This approach reduces the risk of fetal mortality.

Innexin 3, a New Gene Required for Dorsal Closure in Drosophila Embryo

PubMed Central

Giuliani, Fabrizio; Giuliani, Giuliano; Bauer, Reinhard; Rabouille, Catherine

2013-01-01

Background Dorsal closure is a morphogenetic event that occurs during mid-embryogenesis in many insects including Drosophila, during which the ectoderm migrates on the extraembryonic amnioserosa to seal the embryo dorsally. The contribution of the ectoderm in this event has been known for a long time. However, amnioserosa tension and contractibility have recently been shown also to be instrumental to the closure. A critical pre-requisite for dorsal closure is integrity of these tissues that in part is mediated by cell-cell junctions and cell adhesion. In this regard, mutations impairing junction formation and/or adhesion lead to dorsal closure. However, no role for the gap junction proteins Innexins has so far been described. Results and Discussion Here, we show that Innexin 1, 2 and 3, are present in the ectoderm but also in the amnioserosa in plaques consistent with gap junctions. However, only the loss of Inx3 leads to dorsal closure defects that are completely rescued by overexpression of inx3::GFP in the whole embryo. Loss of Inx3 leads to the destabilisation of Inx1, Inx2 and DE-cadherin at the plasma membrane, suggesting that these four proteins form a complex. Accordingly, in addition to the known interaction of Inx2 with DE-cadherin, we show that Inx3 can bind to DE-cadherin. Furthermore, Inx3-GFP overexpression recruits DE-cadherin from its wildtype plasma membrane domain to typical Innexin plaques, strengthening the notion that they form a complex. Finally, we show that Inx3 stability is directly dependent on tissue tension. Taken together, we propose that Inx3 is a critical factor for dorsal closure and that it mediates the stability of Inx1, 2 and DE-cadherin by forming a complex. PMID:23894431

Monitoring the fetal heart rate variability during labor.

PubMed

Moslem, B; Mohydeen, A; Bazzi, O

2015-08-01

In respect to the main goal of our ongoing work for estimating the heart rate variability (HRV) from fetal electrocardiogram (FECG) signals for monitoring the health of the fetus, we investigate in this paper the possibility of extracting the fetal heart rate variability (HRV) directly from the abdominal composite recordings. Our proposed approach is based on a combination of two techniques: Periodic Component Analysis (PiCA) and recursive least square (RLS) adaptive filtering. The Fetal HRV of the estimated FECG signal is compared to a reference value extracted from an FECG signal recorded by using a spiral electrode attached directly to the fetal scalp. The results obtained show that the fetal HRV can be directly evaluated from the abdominal composite recordings without the need of recording an external reference signal.

Fetal Alcohol Syndrome: An International Concern.

ERIC Educational Resources Information Center

Asetoyer, Charon

1987-01-01

Describes Fetal Alcohol Effects (FAE) and Fetal Alcohol Syndrome (FAS) in infants, caused by mothers' consumption of alcohol during pregnancy. Both disabilities found in relatively high proportions of American Indian children. Discusses impact of disabilities on education. Discusses parent education programs in United States and abroad. (TES)

Fetal distress and the condition of newborn infants.

PubMed Central

Sykes, G S; Molloy, P M; Johnson, P; Stirrat, G M; Turnbull, A C

1983-01-01

In a prospective audit of the obstetric management of 1210 consecutive deliveries the association was investigated between the need for operative delivery for fetal distress during labour and the condition of the newborn infant. Operative delivery was performed for only 11.5% of the newborn infants with severe acidosis at birth (umbilical artery pH less than 7.12, base deficit greater than 12 mmol (mEq)/1), 24.1% of those with an Apgar score less than 7 at one minute, and 15.8% of those with both severe acidosis and a one minute Apgar score less than 7. Most of the infants delivered operatively were in a vigorous condition at birth and did not have severe acidosis. Fetal blood sampling was done in 4.0% of labours. As none of the fetal blood values were less than 7.20 and only three of the infants sampled in utero suffered severe acidosis at birth, fetal blood sampling would have had to be performed much more often to provide a useful guide to metabolic state at birth. While the large majority of "at risk" fetuses had continuous fetal heart rate monitoring in labour, this had not been provided in 48.7% of the labours of infants with severe acidosis, 38.7% of infants with a one minute Apgar score less than 7, and 47.4% of infants with both severe acidosis and a one minute Apgar score less than 7. Continuous fetal heart rate monitoring was associated with a much higher incidence of operative delivery for fetal distress than was intermittent fetal heart rate auscultation. These results suggest an urgent need to review present methods for assessing the intrapartum condition of the fetus, making the diagnosis of fetal distress, and assessing the condition of the infant at birth. PMID:6412897

Piracetam for fetal distress in labour.

PubMed

Hofmeyr, G Justus; Kulier, Regina

2012-06-13

Piracetam is thought to promote the metabolism of brain cells when they are hypoxic. It has been used to prevent adverse effects of fetal distress. The objective of this review was to assess the effects of piracetam for suspected fetal distress in labour on method of delivery and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 February 2012). Randomised trials of piracetam compared with placebo or no treatment for suspected fetal distress in labour. Both review authors assessed eligibility and trial quality. One study of 96 women was included. Piracetam compared with placebo was associated with a trend to reduced need for caesarean section (risk ratio 0.57, 95% confidence interval 0.32 to 1.03). There were no statistically significant differences between the piracetam and placebo group for neonatal morbidity (measured by neonatal respiratory distress) or Apgar score. There is not enough evidence to evaluate the use of piracetam for fetal distress in labour.

The large-scale organization of shape processing in the ventral and dorsal pathways

PubMed Central

Culham, Jody C; Plaut, David C; Behrmann, Marlene

2017-01-01

Although shape perception is considered a function of the ventral visual pathway, evidence suggests that the dorsal pathway also derives shape-based representations. In two psychophysics and neuroimaging experiments, we characterized the response properties, topographical organization and perceptual relevance of these representations. In both pathways, shape sensitivity increased from early visual cortex to extrastriate cortex but then decreased in anterior regions. Moreover, the lateral aspect of the ventral pathway and posterior regions of the dorsal pathway were sensitive to the availability of fundamental shape properties, even for unrecognizable images. This apparent representational similarity between the posterior-dorsal and lateral-ventral regions was corroborated by a multivariate analysis. Finally, as with ventral pathway, the activation profile of posterior dorsal regions was correlated with recognition performance, suggesting a possible contribution to perception. These findings challenge a strict functional dichotomy between the pathways and suggest a more distributed model of shape processing. PMID:28980938

Reproducibility of Differential Proteomic Technologies in CPTAC Fractionated Xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tabb, David L.; Wang, Xia; Carr, Steven A.

2016-03-04

The NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) employed a pair of reference xenograft proteomes for initial platform validation and ongoing quality control of its data collection for The Cancer Genome Atlas (TCGA) tumors. These two xenografts, representing basal and luminal-B human breast cancer, were fractionated and analyzed on six mass spectrometers in a total of 46 replicates divided between iTRAQ and label-free technologies, spanning a total of 1095 LC-MS/MS experiments. These data represent a unique opportunity to evaluate the stability of proteomic differentiation by mass spectrometry over many months of time for individual instruments or across instruments running dissimilarmore » workflows. We evaluated iTRAQ reporter ions, label-free spectral counts, and label-free extracted ion chromatograms as strategies for data interpretation. From these assessments we found that differential genes from a single replicate were confirmed by other replicates on the same instrument from 61-93% of the time. When comparing across different instruments and quantitative technologies, differential genes were reproduced by other data sets from 67-99% of the time. Projecting gene differences to biological pathways and networks increased the similarities. These overlaps send an encouraging message about the maturity of technologies for proteomic differentiation.« less

Phenformin as prophylaxis and therapy in breast cancer xenografts

PubMed Central

Appleyard, M V C L; Murray, K E; Coates, P J; Wullschleger, S; Bray, S E; Kernohan, N M; Fleming, S; Alessi, D R; Thompson, A M

2012-01-01

Background: Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231. Methods: Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis. Results: Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation. Conclusion: Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer. PMID:22361631

Phenformin as prophylaxis and therapy in breast cancer xenografts.

PubMed

Appleyard, M V C L; Murray, K E; Coates, P J; Wullschleger, S; Bray, S E; Kernohan, N M; Fleming, S; Alessi, D R; Thompson, A M

2012-03-13

Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231. Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis. Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation. Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer.

Dorsal column stimulator applications

PubMed Central

Yampolsky, Claudio; Hem, Santiago; Bendersky, Damián

2012-01-01

Background: Spinal cord stimulation (SCS) has been used to treat neuropathic pain since 1967. Following that, technological progress, among other advances, helped SCS become an effective tool to reduce pain. Methods: This article is a non-systematic review of the mechanism of action, indications, results, programming parameters, complications, and cost-effectiveness of SCS. Results: In spite of the existence of several studies that try to prove the mechanism of action of SCS, it still remains unknown. The mechanism of action of SCS would be based on the antidromic activation of the dorsal column fibers, which activate the inhibitory interneurons within the dorsal horn. At present, the indications of SCS are being revised constantly, while new applications are being proposed and researched worldwide. Failed back surgery syndrome (FBSS) is the most common indication for SCS, whereas, the complex regional pain syndrome (CRPS) is the second one. Also, this technique is useful in patients with refractory angina and critical limb ischemia, in whom surgical or endovascular treatment cannot be performed. Further indications may be phantom limb pain, chronic intractable pain located in the head, face, neck, or upper extremities, spinal lumbar stenosis in patients who are not surgical candidates, and others. Conclusion: Spinal cord stimulation is a useful tool for neuromodulation, if an accurate patient selection is carried out prior, which should include a trial period. Undoubtedly, this proper selection and a better knowledge of its underlying mechanisms of action, will allow this cutting edge technique to be more acceptable among pain physicians. PMID:23230533

Midterm results after aortic valve replacement with freehand stentless xenografts: a comparison of three prostheses.

PubMed

Luciani, G B; Bertolini, P; Vecchi, B; Mazzucco, A

1998-06-01

The ideal substitute for the diseased aortic valve is yet to be found. For the assessment and comparison of the midterm results after aortic valve replacement with three different types of freehand stentless xenografts, all patients who underwent the operation between October 1992 and April 1997 were reviewed. Of 231 patients undergoing aortic valve replacement, 106 patients (group 1) were given the Biocor PSB (Biocor Industria e Pesquisa Ltda, Belo Horizonte, MG, Brazil); 76 patients (group 2) were given the Toronto SPV (St. Jude Medical, Inc., St. Paul, Minn.), and 49 patients (group 3) were given the O'Brien-Angell valve (Bravo Cardiovascular model 300, Cryolife, Inc., Marietta, Ga.). The first two xenografts require inflow and outflow suturelines; the third xenograft needs a single-sutureline implantation. Mean age (70 +/- 6 years; 70 +/- 7 years; 72 +/- 9 years; p = 0.6), prevalence of male sex (56 patients, 53%; 37 patients, 49%; 22 patients, 45%; p = 0.7), of aortic stenosis (72 patients, 68%; 54 patients, 71%; 37 patients, 73%; p = 0.6), and need for associated procedures (51 patients, 48%; 30 patients, 40%; 21 patients, 43%; p = 0.1) were comparable among groups. Mean aortic crossclamp time was shorter in group 3 (96 +/- 24 minutes; 100 +/- 23 minutes; 88 +/- 25 minutes;p = 0.01). Early deaths were 3 of 106 (3%) in group 1, 2 of 76 (3%) in group 2, and 2 of 49 (4%) in group 3. Follow-up of survivors ranged from 1 to 54 months (mean 32 +/- 13 months). Survival at 4 years was 90% +/- 3% in group 1, 95% +/- 3% in group 2, 85% +/- 8% in group 3 (p = 0.3). At 4 years, freedom from valve-related events was 95% +/- 6%, 100%, 70% +/- 8% (p = 0.004), while freedom from valve deterioration was 99% +/- 1%, 100%, 73% +/- 8% (p = 0.001), in group 1, 2, and 3, respectively (p = 0.001). At follow-up, reintervention on the xenograft was necessary in one patient (endocarditis) in group 1, none in group 2, and six in group 3 (technical cause, group 3; valve tear, group 2

ACR Appropriateness Criteria Assessment of Fetal Well-Being.

PubMed

Simpson, Lynn; Khati, Nadia J; Deshmukh, Sandeep P; Dudiak, Kika M; Harisinghani, Mukesh G; Henrichsen, Tara L; Meyer, Benjamin J; Nyberg, David A; Poder, Liina; Shipp, Thomas D; Zelop, Carolyn M; Glanc, Phyllis

2016-12-01

Although there is limited evidence that antepartum testing decreases the risk for fetal death in low-risk pregnancies, women with high-risk factors for stillbirth should undergo antenatal fetal surveillance. The strongest evidence supporting antepartum testing pertains to pregnancies complicated by intrauterine fetal growth restriction secondary to uteroplacental insufficiency. The main ultrasound-based modalities to determine fetal health are the biophysical profile, modified biophysical profile, and duplex Doppler velocimetry. In patients at risk for cardiovascular compromise, fetal echocardiography may also be indicated to ensure fetal well-being. Although no single antenatal test has been shown to be superior, all have high negative predictive values. Weekly or twice-weekly fetal testing has become the standard practice in high-risk pregnancies. The timing for the initiation of assessments of fetal well-being should be tailored on the basis of the risk for stillbirth and the likelihood of survival with intervention. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (the RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

[Inhibitory effect of Biejiajian pills on HepG2 cell xenograft growth and expression of β-catenin and Tbx3 in nude mice].

PubMed

Wen, Bin; Sun, Hai-Tao; He, Song-Qi; LA, Lei; An, Hai-Yan; Pang, Jie

2016-02-01

To explore the molecular mechanism by which Biejiajian pills inhibit hepatocellular carcinoma in a nude mouse model bearing HepG2 cell xenograft. The inhibitory effect of Biejiajian pills on the growth of HepG2 cell xenograft in nude mice was observed. Immunohistochemical method was used to examine proliferating cell nuclear antigen (PCNA) expression in HepG2 cell xenograft, and TUNEL method was employed to detect the cell apoptosis; the expression levels of β-catenin and Tbx3 were measured by Western blotting. Biejiajian pills significantly suppressed the growth of HepG2 cell xenograft in nude mice. The tumor-bearing mice treated with a high and a moderate dose of Biejiajian pills showed significantly increased apoptosis rate of the tumor cells [(22.9±1.220)% and (14.7±0.50)%, respectively] compared with the control group [(5.5±0.90)%, P<0.05]. Treatment with Biejiajian pills significantly decreased the expressions of PNCA, β-catenin, and Tbx3 in the cell xenograft (P<0.05). Biejiajian pills can inhibit the growth of HepG2 cell xenograft in nude mice and promote tumor cell apoptosis possibly by inhibiting PNCA expression and the Wnt/β-catenin signaling pathway.

A novel patient-derived xenograft model for claudin-low triple-negative breast cancer.

PubMed

Matossian, Margarite D; Burks, Hope E; Bowles, Annie C; Elliott, Steven; Hoang, Van T; Sabol, Rachel A; Pashos, Nicholas C; O'Donnell, Benjamen; Miller, Kristin S; Wahba, Bahia M; Bunnell, Bruce A; Moroz, Krzysztof; Zea, Arnold H; Jones, Steven D; Ochoa, Augusto C; Al-Khami, Amir A; Hossain, Fokhrul; Riker, Adam I; Rhodes, Lyndsay V; Martin, Elizabeth C; Miele, Lucio; Burow, Matthew E; Collins-Burow, Bridgette M

2018-06-01

Triple-negative breast cancer (TNBC) subtypes are clinically aggressive and cannot be treated with targeted therapeutics commonly used in other breast cancer subtypes. The claudin-low (CL) molecular subtype of TNBC has high rates of metastases, chemoresistance and recurrence. There exists an urgent need to identify novel therapeutic targets in TNBC; however, existing models utilized in target discovery research are limited. Patient-derived xenograft (PDX) models have emerged as superior models for target discovery experiments because they recapitulate features of patient tumors that are limited by cell-line derived xenograft methods. We utilize immunohistochemistry, qRT-PCR and Western Blot to visualize tumor architecture, cellular composition, genomic and protein expressions of a new CL-TNBC PDX model (TU-BcX-2O0). We utilize tissue decellularization techniques to examine extracellular matrix composition of TU-BcX-2O0. Our laboratory successfully established a TNBC PDX tumor, TU-BCX-2O0, which represents a CL-TNBC subtype and maintains this phenotype throughout subsequent passaging. We dissected TU-BCx-2O0 to examine aspects of this complex tumor that can be targeted by developing therapeutics, including the whole and intact breast tumor, specific cell populations within the tumor, and the extracellular matrix. Here, we characterize a claudin-low TNBC patient-derived xenograft model that can be utilized for therapeutic research studies.

Routine screening for fetal anomalies: expectations.

PubMed

Goldberg, James D

2004-03-01

Ultrasound has become a routine part of prenatal care. Despite this, the sensitivity and specificity of the procedure is unclear to many patients and healthcare providers. In a small study from Canada, 54.9% of women reported that they had received no information about ultrasound before their examination. In addition, 37.2% of women indicated that they were unaware of any fetal problems that ultrasound could not detect. Most centers that perform ultrasound do not have their own statistics regarding sensitivity and specificity; it is necessary to rely on large collaborative studies. Unfortunately, wide variations exist in these studies with detection rates for fetal anomalies between 13.3% and 82.4%. The Eurofetus study is the largest prospective study performed to date and because of the time and expense involved in this type of study, a similar study is not likely to be repeated. The overall fetal detection rate for anomalous fetuses was 64.1%. It is important to note that in this study, ultrasounds were performed in tertiary centers with significant experience in detecting fetal malformations. The RADIUS study also demonstrated a significantly improved detection rate of anomalies before 24 weeks in tertiary versus community centers (35% versus 13%). Two concepts seem to emerge from reviewing these data. First, patients must be made aware of the limitations of ultrasound in detecting fetal anomalies. This information is critical to allow them to make informed decisions whether to undergo ultrasound examination and to prepare them for potential outcomes.Second, to achieve the detection rates reported in the Eurofetus study, ultrasound examination must be performed in centers that have extensive experience in the detection of fetal anomalies.

Prenatal diagnosis of congenital fetal heart abnormalities and clinical analysis.

PubMed

Li, Hui; Wei, Jun; Ma, Ying; Shang, Tao

2005-09-01

To study the value of detecting fetal congenital heart disease (CHD) using the five transverse planes technique of fetal echocardiography. Nine hundred and eighty-two high-risk pregnancies for fetal CHD were included in this study, the fetal heart was scanned with the five transverse planes technique of fetal echocardiography described by Yagel, autopsy was conducted when pregnancy was terminated. Blood from fetal heart was collected for fetal chromosome analysis. A close follow-up was given for normal fetal heart pregnancies and neonatal echocardiography was performed to check the accuracy of prenatal diagnosis. (1) Forty-six cases (4.68%) were found to have fetal heart abnormalities in this study, 69.56% of them were diagnosed by single four-chamber view, another 30.43% fetal CHD were found by combining other views; (2) Forty-one parents of prenatal fetuses with CHD chose to terminate pregnancy, thirty-two of them gave consent to conduct autopsy, 93.75% of which yielded unanimous conclusion between prenatal fetal echocardiography and autopsy; (3) Thirty-two of 46 cases underwent fetal chromosome analysis, 8 cases (25%) were found to have abnormal chromosome; (4) Five cases were found to have right ventricle and atrium a little bigger than those on the left side, with the unequal condition being the same after birth, but there were no clinical manifestations and they are healthy for the time being; (5) Nine hundred and thirty-six cases were not found with abnormality in this study, but one case was diagnosed with ventricular septal defect after birth, one case was diagnosed with patent ductus arteriosus, one case had atrial septal defect after birth. (1) The detected CHD rate was 4.68% by screening fetal heart with five transverse planes according to Yagel's description of high risk population basis for CHD. The coinciding rate of prenatal diagnosis and autopsy was 93.75%; (2) The sensitivity of detecting fetal heart abnormality is 92%, the specificity is 99

Tracking fetal development through molecular analysis of maternal biofluids☆

PubMed Central

Edlow, Andrea G.; Bianchi, Diana W.

2015-01-01

Current monitoring of fetal development includes fetal ultrasonography, chorionic villus sampling or amniocentesis for chromosome analysis, and maternal serum biochemical screening for analytes associated with aneuploidy and open neural tube defects. Over the last 15 years, significant advances in noninvasive prenatal diagnosis (NIPD) via cell-free fetal (cff) nucleic acids in maternal plasma have resulted in the ability to determine fetal sex, RhD genotype, and aneuploidy. Cff nucleic acids in the maternal circulation originate primarily from the placenta. This contrasts with cff nucleic acids in amniotic fluid, which derive from the fetus, and are present in significantly higher concentrations than in maternal blood. The fetal origin of cff nucleic acids in the amniotic fluid permits the acquisition of real-time information about fetal development and gene expression. This review seeks to provide a comprehensive summary of the molecular analysis of cff nucleic acids in maternal biofluids to elucidate mechanisms of fetal development, physiology, and pathology. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure. PMID:22542507

Signal separation by nonlinear projections: The fetal electrocardiogram

NASA Astrophysics Data System (ADS)

Schreiber, Thomas; Kaplan, Daniel T.

1996-05-01

We apply a locally linear projection technique which has been developed for noise reduction in deterministically chaotic signals to extract the fetal component from scalar maternal electrocardiographic (ECG) recordings. Although we do not expect the maternal ECG to be deterministic chaotic, typical signals are effectively confined to a lower-dimensional manifold when embedded in delay space. The method is capable of extracting fetal heart rate even when the fetal component and the noise are of comparable amplitude. If the noise is small, more details of the fetal ECG, like P and T waves, can be recovered.

Importance of the levator labii alaeque nasi muscle in dorsal septal deviations.

PubMed

Tellioğlu, Ali Teoman; Özakpinar, Hülda Rifat; Cakir, Bariş; Tekdemir, Ibrahim

2011-03-01

Deviated cartilages structures of the nose can be affected by nasal muscles, and deviation becomes conspicuous when the patient smiles. This condition depends on activity of nasal muscles, particularly the levator labii alaeque nasi muscle. A total of 124 septorhinoplasty operations were performed to correct dorsal concave septal deviation between 2005 and 2009 years. The 70 women and 54 men included in the study had an average age of 28 years. The average follow-up period was 12 months. Open septorhinoplasty was preferred in all cases. The medial part of the levator labii alaeque nasi muscle was extensively dissected from the lateral crus and surrounding tissues. The lateral crura of the alar cartilages were separated from the upper lateral cartilages in the scroll area. The dorsal septal deviation was corrected by combination of bilateral spreader grafts, which reinforced cartilage with horizontal control sutures. Early postoperative period was uneventful. Nasal obstruction was reduced after surgery, and significant subjective postoperative improvements were observed in all patients. Comparison of preoperative and postoperative photographs demonstrated improved dorsal nasal contour. Revision operation was performed in 3 cases. The corrected septal cartilage was in a good position in all revised cases; therefore, septal surgery was not performed in the revision operations. In conclusion, surgical disruption of the anatomic relationship between the muscle with the dorsal septal cartilage and reinforcement of the dorsal septal cartilage with spreader grafts and horizontal control sutures can decrease risk of recurrence.

21 CFR 884.2685 - Fetal scalp clip electrode and applicator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Monitoring Devices § 884.2685 Fetal scalp clip electrode and applicator. (a) Identification. A fetal scalp clip electrode and applicator is a device designed to establish electrical contact between fetal skin... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal scalp clip electrode and applicator. 884...

21 CFR 884.2685 - Fetal scalp clip electrode and applicator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Monitoring Devices § 884.2685 Fetal scalp clip electrode and applicator. (a) Identification. A fetal scalp clip electrode and applicator is a device designed to establish electrical contact between fetal skin... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal scalp clip electrode and applicator. 884...

21 CFR 884.2685 - Fetal scalp clip electrode and applicator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Monitoring Devices § 884.2685 Fetal scalp clip electrode and applicator. (a) Identification. A fetal scalp clip electrode and applicator is a device designed to establish electrical contact between fetal skin... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal scalp clip electrode and applicator. 884...

21 CFR 884.2685 - Fetal scalp clip electrode and applicator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Monitoring Devices § 884.2685 Fetal scalp clip electrode and applicator. (a) Identification. A fetal scalp clip electrode and applicator is a device designed to establish electrical contact between fetal skin... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal scalp clip electrode and applicator. 884...

21 CFR 884.2685 - Fetal scalp clip electrode and applicator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Monitoring Devices § 884.2685 Fetal scalp clip electrode and applicator. (a) Identification. A fetal scalp clip electrode and applicator is a device designed to establish electrical contact between fetal skin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal scalp clip electrode and applicator. 884...

Cetuximab intensifies the ADCC activity of adoptive NK cells in a nude mouse colorectal cancer xenograft model.

PubMed

Chen, Shanshan; Li, Xuechun; Chen, Rongming; Yin, Mingang; Zheng, Qiuhong

2016-09-01

Natural killer (NK) cells, discovered ~40 years ago, are believed to be the most effective cytotoxic lymphocytes to counteract cancer; however, adoptive NK cell therapy in vivo has encountered certain limitations, including a lack of specificity. The drug cetuximab can mediate antibody dependent cell mediated cytotoxicity (ADCC) activity through NK cells in vivo , and has been approved for the first-line treatment of epidermal growth factor receptor (EGFR)-positive metastatic colorectal cancer (CRC). However, the ADCC activity of adoptive NK cells, induced by cetuximab in a nude mouse CRC xenograft model, has not been previously reported. The aim of the present study was to explore the ADCC activity of cetuximab combined with adoptive NK cells in CRC xenograft models with various EGFR expressions. The nude mouse xenograft models were established by subcutaneously injecting LOVO or SW620 cells. The mice were then randomly divided into 6 groups: Phosphate-buffered saline, cetuximab, human immunoglobulin G (hIgG), NK cells, hIgG plus NK cells and cetuximab plus NK cells. The ADCC antitumor activity was evaluated in these CRC models. The results indicated that the cetuximab plus NK cells group showed the greatest tumor inhibition effect compared with the NK cells group in LOVO xenograft tumor models with positive EGFR expression. However, the combination of cetuximab and NK cells did not show a stronger tumor inhibitory effect against the SW620 xenograft tumor models compared with the efficiency of NK cells. In conclusion, cetuximab could intensify the ADCC antitumor activity of adoptive NK cells towards CRC with an increased EGFR expression. The combination of cetuximab and NK cells may be a potential immunotherapy for metastatic CRC patients with positive EGFR expression.

Fetal heart and uterine contraction monitor (image)

MedlinePlus

The fetal heart monitor and uterine contraction monitor provide a continuous record of the baby's heart rate and the mother's contraction rate as labor progresses. This device can provide early warning of fetal distress.

[Usefulness of the examination of fetal blood oxygen saturation (FSpO2) and fetal heart rate (FHR) as a prognostic factor of the newborn outcome].

PubMed

Skoczylas, Michał; Laudański, Tadeusz

2003-10-01

Cardiotocography has become the standard for fetal monitoring in labor. False-positive findings during electronic fetal heart rate monitoring may were not associated with neonatal acidemia. Because of the poor specificity of fetal heart rate monitoring in predicting fetal distress, new methods are being investigated as a way to improve the accuracy of assessing the infant's condition during labor. The aim of this study was to determinate the efficiency of fetal blood oxygen saturation (FSpO2) and computer analysis of the fetal heart rate (Co-CTG) in the late 1-st stage of labor as a prognostic factor of newborn acidemia. Total 62 subjects were studied. During labors and deliveries fetal oxygen saturation was continuously recorded, with use of Nellecor N-400 fetal pulse oximeter and continous CTG were performed by Hewlett Packard 50A. Transdermal fetal oxygen saturation measurements and CTG results obtained during the labors was analyzed using MONAKO system (ITAM Zabrze). The results were compared with the values of pH and base deficit in the umbilical artery measured just after delivery. The sensitivity, specificity, negative, positive predictive values and Youden factor based on FHR and FSpO2, for prognosis of neonatal acidosis were: 65%, 80%, 16%, 97.5% 60% and 0.135 respectively FHR; and 100%, 60%, 100%, 96.8% and 0.968 respectively FSpO2. 1. The examination of fetal blood oxygen saturation in the labor is a useful prognostic factor of the newborn outcome. 2. The best predictive value for intrapartum fetal asphyxia with metabolic acidosis was found when fetal pulse oximetry is added to cardiotocography.

Chorioamnionitis-induced changes of fetal extramedullar hematopoiesis in the second trimester of gestation. Is diagnosis from fetal autopsy possible?

PubMed

Pfisterer, Cora; Faber, Renaldo; Horn, Lars-Christian

2005-02-01

Chorioamnionitis, as the most frequent cause of second trimester abortions, is commonly diagnosed by histomorphological examination of placental tissue. We determined whether chorioamnionitis induces a fetal extramedullary hematopoietic response and estimated whether chorioamnionitis can be diagnosed from fetal liver alone. Clinical data and morphological and histological findings of 39 second trimester abortions, caused by chorioamnionitis, were compared with 32 age-matched control cases. Using hematoxylin and eosin staining, naphtol-ASD-chloracetate esterase and "Berliner Blau" reaction, total hematopoiesis, erythropoiesis, myelopoiesis and intracytoplasmatic iron of fetal liver were examined. In the study group, total hematopoiesis was increased compared with the controls (94.9% versus 84.4%). The same was seen in erythropoiesis (69.2% versus 56.2%, P>0.05). Chorioamnionitis resulted in a significant increase of fetal myelopoiesis with clustering of leukocytes in 56.4% (P=0.001). Neutrophiles were located predominantly intrasinusoidal and periportal (74.4%), while an isolated periportal location was often observed in controls (50.0%). Isolated perivenous iron storing was more often seen with chorioamnionitis (28.3% versus 3.1%) and correlated with the increasing severity of chorioamnionitis. It can be stated that infectious diseases, such as chorioamnionitis, increase fetal intrahepatic myelopoiesis as one defense mechanism. The morphology of fetal intrahepatic hematopoiesis and iron storing might also be helpful in the diagnosis of chorioamnionitis, especially when the placenta is not available for examination.

Society for Maternal-Fetal Medicine (SMFM) Consult Series #45: Mild fetal ventriculomegaly: Diagnosis, evaluation, and management.

PubMed

Fox, Nathan S; Monteagudo, Ana; Kuller, Jeffrey A; Craigo, Sabrina; Norton, Mary E

2018-04-26

Ventriculomegaly is defined as dilation of the fetal cerebral ventricles and is a relatively common finding on prenatal ultrasound. The purpose of this document is to review the diagnosis, evaluation, and management of mild fetal ventriculomegaly. When enlargement of the lateral ventricles (≥10 mm) is identified, a thorough evaluation should be performed, including detailed sonographic evaluation of fetal anatomy, amniocentesis for karyotype and chromosomal microarray analysis (CMA), and a workup for fetal infection. In some cases, fetal magnetic resonance imaging (MRI) may identify other central nervous system abnormalities and should be considered when this technology as well as expert interpretation is available. Follow-up ultrasound examination should be performed to assess for progression of the ventricular dilation. In the setting of isolated ventriculomegaly of 10 to 12 mm, the likelihood of survival with normal neurodevelopment is greater than 90%. With moderate ventriculomegaly (13-15 mm), the likelihood of normal neurodevelopment is 75-93%. The following are Society for Maternal-Fetal Medicine recommendations: we suggest that ventriculomegaly be characterized as mild (10-12 mm), moderate (13-15 mm), or severe (>15 mm) for the purposes of patient counseling, given that the chance of an adverse outcome and potential for other abnormalities are higher when the ventricles measure 13-15 mm versus 10-12 mm (GRADE 2B); we recommend that diagnostic testing (amniocentesis) with CMA should be offered, when ventriculomegaly is detected (GRADE 1B); we recommend testing for CMV and toxoplasmosis when ventriculomegaly is detected, regardless of known exposure or symptoms (GRADE 1B); we suggest that MRI be considered in cases of mild or moderate fetal ventriculomegaly when this modality and expert radiologic interpretation are available; an MRI is likely to be of less value if the patient has had a detailed ultrasound performed by an individual with specific

[Inhibitory effect of VEGF antisense phosphorothioate oligodeoxynucleotides on the growth of human salivary adenoid cystic carcinoma xenografts in nude mice].

PubMed

Li, Xiao-guang; Wang, Xu-xia; Li, Teng-yu; Wang, Yan-xiu; Gao, Jing; Ni, Chun-xiao

2012-12-01

To investigate the inhibitory effect of VEGF antisense phosphorothioate oligodeoxynucleoiides on the growth of human salivary adenoid cystic carcinoma (SACC) xenografts in nude mice. The VEGF-ASODN was synthesised artificially. After the model of human SACC xenografts in nude mice was established, they were random1y divided into three groups: antisense group, scrambled group and normal saline group. A control group without cancer was also established. Antisense(66 μg), scrambled sequence(66 μg) and normal saline(once every 3 days and 7 times in all) were injected in three experimental groups, respectively. Two days after therapy, the mice were sacrificed. Serums were used for detection of VEGF protein. All tumors were measured and weighted. The quantity of VEGF mRNA and protein and PLI, MVD was detected by hybridization in situ and immunohistochemistry. SPSS13.0 software package was used for statistical analysis. The VEGF-ASODN could suppress the expression of VEGF in human SACC xenografts in nude mice and reduce VEGF protein in serum of nude mice significantly. It cou1d also reduce the volume and weight of xenografts and could reduce the expression of VEGF mRNA and its protein, PCNA and CD34. By inhibiting the expression of VEGF, VEGF-ASODN can inhabit proliferation of human SACC xenografts in nude mice.

Sexual Dimorphism and Geographic Variation in Dorsal Fin Features of Australian Humpback Dolphins, Sousa sahulensis.

PubMed

Brown, Alexander M; Bejder, Lars; Parra, Guido J; Cagnazzi, Daniele; Hunt, Tim; Smith, Jennifer L; Allen, Simon J

2016-01-01

Determining the sex of free-ranging cetaceans can be challenging. Sexual dimorphism among external features may allow inferences on sex, but such patterns may be difficult to detect and are often confounded by age and geographic variation. Dorsal fin images of 107 female and 54 male Australian humpback dolphins, Sousa sahulensis, from Western Australia (WA) and Queensland (QLD) were used to investigate sex, age and geographic differences in colouration, height/length quotient and number of notches. Adult males exhibited more dorsal fin notches (p<0.001) and a significantly greater loss of pigmentation on the upper half of their dorsal fins (p<0.001) than did adult females. These differences likely reflect that males experience a higher frequency and/or intensity of intraspecific aggression than females. In QLD, heavily spotted dorsal fins were more frequent among females than males (p<0.001). Logistic regression analyses revealed that dorsal fin spotting and loss of pigmentation on the upper half of the dorsal fin provided the best model parameters for predicting the sex of sampled adults, with 97% accuracy. This technique offers a rapid, non-invasive method for predicting sex in Australian humpback dolphins, which could potentially be applied to populations throughout their range. In contrast to adults, presumed immature animals showed little or no loss of pigmentation or spotting; however, the rate of development of these features remains unknown. There were pronounced differences between QLD and WA in the intensity of spotting on dorsal fins and the extent of pigmentation loss around the posterior insertion and trailing edge of the dorsal fin. While based on a limited sample size, these geographic differences may have conservation implications in terms of population subdivision and should be investigated further. © 2016 Elsevier Ltd. All rights reserved.

[Biomaterials for bone filling: comparisons between autograft, hydroxyapatite and one highly purified bovine xenograft].

PubMed

Chappard, D; Zhioua, A; Grizon, F; Basle, M F; Rebel, A

1993-12-01

Bone grafts are becoming increasingly common in orthopaedics, neurosurgery and periodontology. Twenty one New Zealand rabbits were used in the present study comparing several materials usable as bone substitutes. A 4.5 mm hole was drilled in the inner femoral condyles. Holes were filled with either an autograft (from the opposite condyle), an hydroxylapatite (Bioapatite), or a highly purified bovine xenograft (T650 Lubboc). Animals were sacrificed at 1, 3 and 6 months post implantation and a quantitative analysis of newly-formed bone volume (BNF/IV) and remaining biomaterials (BMAT/IV) was done. In addition, some holes were left unfilled and served as controls. At 6 months, there was no tendency for spontaneous repair in the control animals. The autografted animals have repaired their trabecular mass and architecture within the first month. Hydroxylapatite appeared unresorbed at six months and only thin and scanty new trabeculae were observed. The xenograft induced woven bone trabeculae formation on the first month. This was associated with resorption of the material by two multinucleated cell populations. At six months, the epiphyseal architecture was restored and the biomaterial has disappeared in most cases. Xenografts appear a promising alternative to autografts and allografts, whose infectious risks and ethical problems should always be borne in mind.

Sonography in Fetal Birth Weight Estimation

ERIC Educational Resources Information Center

Akinola, R. A.; Akinola, O. I.; Oyekan, O. O.

2009-01-01

The estimation of fetal birth weight is an important factor in the management of high risk pregnancies. The information and knowledge gained through this study, comparing a combination of various fetal parameters using computer assisted analysis, will help the obstetrician to screen the high risk pregnancies, monitor the growth and development,…

Here, there and everywhere: higher visual function and the dorsal visual stream.

PubMed

Cooper, Sarah Anne; O'Sullivan, Michael

2016-06-01

The dorsal visual stream, often referred to as the 'where' stream, represents the pathway taken by visual information from the primary visual cortex to the posterior parietal lobe and onwards. It partners the ventral or 'what' stream, the subject of a previous review and largely a temporal-based system. Here, we consider the dorsal stream disorders of perception (simultanagnosia, akinetopsia) along with their consequences on action (eg, optic ataxia and oculomotor apraxia, along with Balint's syndrome). The role of the dorsal stream in blindsight and hemispatial neglect is also considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Fetal Intelligent Navigation Echocardiography (FINE): a novel method for rapid, simple, and automatic examination of the fetal heart.

PubMed

Yeo, Lami; Romero, Roberto

2013-09-01

To describe a novel method (Fetal Intelligent Navigation Echocardiography (FINE)) for visualization of standard fetal echocardiography views from volume datasets obtained with spatiotemporal image correlation (STIC) and application of 'intelligent navigation' technology. We developed a method to: 1) demonstrate nine cardiac diagnostic planes; and 2) spontaneously navigate the anatomy surrounding each of the nine cardiac diagnostic planes (Virtual Intelligent Sonographer Assistance (VIS-Assistance®)). The method consists of marking seven anatomical structures of the fetal heart. The following echocardiography views are then automatically generated: 1) four chamber; 2) five chamber; 3) left ventricular outflow tract; 4) short-axis view of great vessels/right ventricular outflow tract; 5) three vessels and trachea; 6) abdomen/stomach; 7) ductal arch; 8) aortic arch; and 9) superior and inferior vena cava. The FINE method was tested in a separate set of 50 STIC volumes of normal hearts (18.6-37.2 weeks of gestation), and visualization rates for fetal echocardiography views using diagnostic planes and/or VIS-Assistance® were calculated. To examine the feasibility of identifying abnormal cardiac anatomy, we tested the method in four cases with proven congenital heart defects (coarctation of aorta, tetralogy of Fallot, transposition of great vessels and pulmonary atresia with intact ventricular septum). In normal cases, the FINE method was able to generate nine fetal echocardiography views using: 1) diagnostic planes in 78-100% of cases; 2) VIS-Assistance® in 98-100% of cases; and 3) a combination of diagnostic planes and/or VIS-Assistance® in 98-100% of cases. In all four abnormal cases, the FINE method demonstrated evidence of abnormal fetal cardiac anatomy. The FINE method can be used to visualize nine standard fetal echocardiography views in normal hearts by applying 'intelligent navigation' technology to STIC volume datasets. This method can simplify

Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

PubMed

Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

2017-01-03

Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic...

21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic...

21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic...

Enzyme markers of maternal malnutrition in fetal rat brain.

PubMed

Shambaugh, G E; Mankad, B; Derecho, M L; Koehler, R R

1987-01-01

The impact of maternal starvation in late gestation on development of some enzymatic mechanisms concerned with neurotransmission and polyamine synthesis was studied in fetal rat brain. Between 17 and 20 d, acetylcholinesterase and choline acetyltransferase activity increased in fetal brains of fed dams, whereas maternal starvation from day 17 to day 20 resulted in heightened acetylcholinesterase but not choline acetyltransferase activity. Ornithine decarboxylase activity on a per-gram wet-weight basis fell between 17 and 20 d in fetal brain from fed dams. Increasing the duration of maternal starvation resulted in a progressive increase in fetal brain ornithine decarboxylase. Arginine and putrescine levels in the brain were lower in fetuses of starved mothers while spermidine and spermine concentrations were unchanged. Since the Km of ornithine decarboxylase for ornithine was found to vary directly with levels of putrescine in fetal brain, lower concentrations of putrescine and greater ornithine decarboxylase activity in fetal brains from starved mothers suggested that levels of this enzyme may be controlled in part by putrescine. Changes in the maternal nutritional state had no effect on the activity of glutamate decarboxylase in fetal brain, and tissue levels of the product, gamma-aminobutyric acid, were unchanged. Thus changes in ornithine decarboxylase and acetylcholinesterase activity in fetal brain may uniquely reflect biochemical alterations consequent to maternal starvation.

Growth assessment in diagnosis of Fetal Growth Restriction. Review

PubMed Central

Albu, AR; Horhoianu, IA; Dumitrascu, MC; Horhoianu, V

2014-01-01

Abstract The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the truly growth restricted fetus who is predisposed to perinatal complications, even if its parameters are above the cut-off limits established. In this article, we present the clinical tools of fetal growth assessment: Symphyseal-Fundal Height (SFH) measurement, the fetal ultrasound parameters widely taken into consideration when discussing fetal growth: Abdominal Circumference (AC) and Estimated Fetal Weight (EFW); several types of growth charts and their characteristics: populational growth charts, standard growth charts, individualized growth charts, customized growth charts and growth trajectories. Abbreviations: FGR = Fetal growth restriction; IUGR = Intrauterine Growth Restriction; SGA = small for gestational age fetus; EFW = estimated fetal weight; AC = abdominal circumference; SD = Standard Deviation; SFH = Symphyseal-fundal height; US = ultrasound; 2D = bidimensional; 3D = tridimensional; RCOG = Royal College of Obstetricians and Gynecologists; FL = femur length; BPD = biparietal diameter; BW = birth weight; IGA = Individualized Growth Assessment; PIH = Pregnancy Induced hypertension; PE = Preeclampsia; NICU = Neonatal Intensive Care Unit. PMID:25408718

Dual HER2 targeting impedes growth of HER2 gene-amplified uterine serous carcinoma xenografts.

PubMed

Groeneweg, Jolijn W; Hernandez, Silvia F; Byron, Virginia F; DiGloria, Celeste M; Lopez, Hector; Scialabba, Vanessa; Kim, Minji; Zhang, Ling; Borger, Darrell R; Tambouret, Rosemary; Foster, Rosemary; Rueda, Bo R; Growdon, Whitfield B

2014-12-15

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that commonly harbors HER2 gene amplification. We investigated the effectiveness of HER2 inhibition using lapatinib and trastuzumab in vitro and in xenografts derived from USC cell lines and USC patient-derived xenografts. Immunohistochemistry and FISH were performed to assess HER2 expression in 42 primary USC specimens. ARK1, ARK2, and SPEC2 cell lines were treated with trastuzumab or lapatinib. Cohorts of mice harboring xenografts derived from ARK2 and SPEC2 cell lines and EnCa1 and EnCa2 primary human USC samples were treated with either vehicle, trastuzumab, lapatinib, or the combination of trastuzumab and lapatinib. Acute and chronic posttreatment tumor samples were assessed for downstream signaling alterations and examined for apoptosis and proliferation. HER2 gene amplification (24%) correlated significantly with HER2 protein overexpression (55%). All models were impervious to single-agent trastuzumab treatment. Lapatinib decreased in vitro proliferation of all cell lines and in vivo growth of HER2-amplified xenografts (ARK2, EnCa1). In addition, dual therapy with trastuzumab and lapatinib resulted in significant antitumor activity only in ARK2 and EnCa1 tumors. Dual HER2 therapy induced on target alteration of downstream MAPK and PI3K pathway mediators only in HER2-amplified models, and was associated with increased apoptosis and decreased proliferation. Although trastuzumab alone did not impact USC growth, dual anti-HER2 therapy with lapatinib led to improved inhibition of tumor growth in HER2-amplified USC and may be a promising avenue for future investigation. ©2014 American Association for Cancer Research.

CABOZANTINIB IS EFFECTIVE IN A SUBSET OF XENOGRAFT GBM TUMORS AND AFFECTS MULTIPLE SIGNALING PATHWAYS

PubMed Central

Mikkelsen, Tom; deCarvalho, Ana C.; Arnold, Kimberly; Mueller, Claudius; Petricoin, Emanuel F; Poisson, Laila M.; Irtenkauf, Susan; Hasselbach, Laura

2014-01-01

BACKGROUND: (blind field). METHODS: Neurospheres enriched in CSCs were cultured from resected GBM tumors. Sensitivity to cabozantinib was determined in vitro. Cells were treated (IC40) in triplicate, and cell lysates were analyzed by reverse phase protein microarrays (RPPAs). GBM CSCs were implanted intracranially into nude mice. Cabozantinib was administered by oral gavage at a dose of 60 mg/kg for 4 weeks (5 days/week) as a single agent or in combination with 40 mg/kg TMZ. Tumor growth and response to treatment were monitored by non-invasive in vivo bioluminescence imaging (BLI) using the Xenogen IVIS System (Caliper Life Sciences), and overall survival. RESULTS: Sensitivity to cabozantinib treatment varied for the different GBM CSCs. From 70 proteins and phosphoproteins measured, 29 distributed among several signaling pathways were significantly altered after treatment in both resistant and sensitive GBM CSCs, including Met, Ret, AKT, MAPK/ERK. Cabozantinib single agent treatment reduced GBM tumor growth and increased mouse survival in two xenograft lines. Cabozantinib monotherapy reduced tumor size, as measured by BLI, but had no significant effect on overall survival for another xenograft line, however, the combination treatment resulted in sensitization of these xenografts to TMZ treatment. RPPA confirmed downregulation of the described targets for XL184, including activated Met, VEGFR2 and Ret (in vitro). CONCLUSIONS: Consistent with the clinical experience, both sensitive and resistant GBMs are represented in our CSC xenografts. More extensive evaluation will likely identify baseline biomarkers which might be valuable in identifying potentially sensitive sub-populations for subsequent clinical trials. RPPA and next-gen sequencing (NGS) on terminal tumors is underway. SECONDARY CATEGORY: Tumor Biology.

Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model.

PubMed

Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko

2016-09-01

Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Automated Fetal Heart Rate Analysis in Labor: Decelerations and Overshoots

NASA Astrophysics Data System (ADS)

Georgieva, A. E.; Payne, S. J.; Moulden, M.; Redman, C. W. G.

2010-10-01

Electronic fetal heart rate (FHR) recording is a standard way of monitoring fetal health in labor. Decelerations and accelerations usually indicate fetal distress and normality respectively. But one type of acceleration may differ, namely an overshoot that may atypically reflect fetal stress. Here we describe a new method for detecting decelerations, accelerations and overshoots as part of a novel system for computerized FHR analysis (OxSyS). There was poor agreement between clinicians when identifying these FHR features visually, which precluded setting a gold standard of interpretation. We therefore introduced `modified' Sensitivity (SE°) and `modified' Positive Predictive Value (PPV°) as appropriate performance measures with which the algorithm was optimized. The relation between overshoots and fetal compromise in labor was studied in 15 cases and 15 controls. Overshoots showed promise as an indicator of fetal compromise. Unlike ordinary accelerations, overshoots cannot be considered to be reassuring features of fetal health.

Aspects of Fetal Learning and Memory

ERIC Educational Resources Information Center

Dirix, Chantal E. H.; Nijhuis, Jan G.; Jongsma, Henk W.; Hornstra, Gerard

2009-01-01

Ninety-three pregnant women were recruited to assess fetal learning and memory, based on habituation to repeated vibroacoustic stimulation of fetuses of 30-38 weeks gestational age (GA). Each habituation test was repeated 10 min later to estimate the fetal short-term memory. For Groups 30-36, both measurements were replicated in a second session…

Are special read alignment strategies necessary and cost-effective when handling sequencing reads from patient-derived tumor xenografts?

PubMed

Tso, Kai-Yuen; Lee, Sau Dan; Lo, Kwok-Wai; Yip, Kevin Y

2014-12-23

Patient-derived tumor xenografts in mice are widely used in cancer research and have become important in developing personalized therapies. When these xenografts are subject to DNA sequencing, the samples could contain various amounts of mouse DNA. It has been unclear how the mouse reads would affect data analyses. We conducted comprehensive simulations to compare three alignment strategies at different mutation rates, read lengths, sequencing error rates, human-mouse mixing ratios and sequenced regions. We also sequenced a nasopharyngeal carcinoma xenograft and a cell line to test how the strategies work on real data. We found the "filtering" and "combined reference" strategies performed better than aligning reads directly to human reference in terms of alignment and variant calling accuracies. The combined reference strategy was particularly good at reducing false negative variants calls without significantly increasing the false positive rate. In some scenarios the performance gain of these two special handling strategies was too small for special handling to be cost-effective, but it was found crucial when false non-synonymous SNVs should be minimized, especially in exome sequencing. Our study systematically analyzes the effects of mouse contamination in the sequencing data of human-in-mouse xenografts. Our findings provide information for designing data analysis pipelines for these data.

Thalamic reticular nucleus in Caiman crocodilus: Relationship with the dorsal thalamus.

PubMed

Pritz, M B

2016-05-13

The thalamic reticular nucleus was investigated in one group of crocodilians, Caiman crocodilus. This neuronal aggregate is composed of two parts: a compact portion and a diffuse region made up of scattered cells within the forebrain bundles. In Caiman, both the lateral and medial forebrain bundles project to the telencephalon and the thalamic reticular nucleus is associated with each fiber tract. In the lateral forebrain bundle, the compact area is termed the nucleus of the dorsal peduncle (dorsal peduncular nucleus) while the diffuse part is called the perireticular area. In the medial forebrain bundle, the interstitial nucleus comprises one part of the compact area while another region without a specific neuronal label is also present. Similar to the perireticular cells of the lateral forebrain bundle, scattered cells are also present in the medial forebrain bundle. Morphological features of the thalamic reticular nucleus are revealed with stains for the following: fibers; cells; succinic acid dehydrogenase; and acetylcholinesterase. Regardless of which dorsal thalamic nucleus was injected, a localized region of the thalamic reticular nucleus contained retrogradely labeled cells and anterogradely labeled axons and terminals. This grouping was termed clusters and was felt to represent the densest interconnection between the dorsal thalamus and the reticular nucleus. Using clusters as an index of interconnections, the reticular nucleus was divided into sectors, each of which was associated with a specific dorsal thalamic nucleus. An organization similar to that found in Caiman is present in other sauropsids as well as in mammals. These data suggest that a thalamic reticular nucleus is present in all amniotes and has morphological properties similar to those described in this analysis. Lastly, a hypothesis is presented to explain how the external shape of the reticular nucleus in Caiman might be transformed into the homologous area in a representative bird and

Does the Use of Diagnostic Technology Reduce Fetal Mortality?

PubMed

Grytten, Jostein; Skau, Irene; Sørensen, Rune; Eskild, Anne

2018-01-19

To examine the effect that the introduction of new diagnostic technology in obstetric care has had on fetal death. The Medical Birth Registry of Norway provided detailed medical information for approximately 1.2 million deliveries from 1967 to 1995. Information about diagnostic technology was collected directly from the maternity units, using a questionnaire. The data were analyzed using a hospital fixed-effects regression with fetal mortality as the outcome measure. The key independent variables were the introduction of ultrasound and electronic fetal monitoring at each maternity ward. Hospital-specific trends and risk factors of the mother were included as control variables. The richness of the data allowed us to perform several robustness tests. The introduction of ultrasound caused a significant drop in fetal mortality rate, while the introduction of electronic fetal monitoring had no effect on the rate. In the population as a whole, ultrasound contributed to a reduction in fetal deaths of nearly 20 percent. For post-term deliveries, the reduction was well over 50 percent. The introduction of ultrasound made a major contribution to the decline in fetal mortality at the end of the last century. © Health Research and Educational Trust.

Increasingly complex representations of natural movies across the dorsal stream are shared between subjects.

PubMed

Güçlü, Umut; van Gerven, Marcel A J

2017-01-15

Recently, deep neural networks (DNNs) have been shown to provide accurate predictions of neural responses across the ventral visual pathway. We here explore whether they also provide accurate predictions of neural responses across the dorsal visual pathway, which is thought to be devoted to motion processing and action recognition. This is achieved by training deep neural networks to recognize actions in videos and subsequently using them to predict neural responses while subjects are watching natural movies. Moreover, we explore whether dorsal stream representations are shared between subjects. In order to address this question, we examine if individual subject predictions can be made in a common representational space estimated via hyperalignment. Results show that a DNN trained for action recognition can be used to accurately predict how dorsal stream responds to natural movies, revealing a correspondence in representations of DNN layers and dorsal stream areas. It is also demonstrated that models operating in a common representational space can generalize to responses of multiple or even unseen individual subjects to novel spatio-temporal stimuli in both encoding and decoding settings, suggesting that a common representational space underlies dorsal stream responses across multiple subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

[Study based on ICA of "dorsal attention network" in patients with temporal lobe epilepsy].

PubMed

Yang, Zhigen; Wang, Huinan; Zhang, Zhiqiang; Zhong, Yuan; Chen, Zhili; Lu, Guangming

2010-02-01

Many functional magnetic resonance imaging (fMRI) studies have revealed the deactivation phenomenon of default mode network in the patients with epilepsy; however, nearly not any of the reports has focused on the dorsal attention network of epilepsy. In this paper, independent component analysis (ICA) was used to isolate the dorsal attention network of 16 patients with temporal lobe epilepsy (TLE) and of 20 healthy normals; and a goodness-of-fit analysis was applied at the individual subject level to choose the interesting component. Intra-group analysis and inter-group analysis were performed. The results indicated that the dorsal attention network included bilateral intraparietal sulcus, middle frontal gyrus, human frontal eye field, posterior lobe of right cerebellum, etc. The TLE group showed decreased functional connectivity in most of the dorsal attention regions with the predominance in the bilateral intraparietal sulcus, middle frontal gyrus, and posterior lobe of right cerebellum. These data suggested that the intrinsic organization of the brain function might be disrupted in TLE. In addition, the decrease of goodness-of-fit scores suggests that activity in the dorsal attention network may ultimately prove a sensitive biomarker for TLE.

Comparison of the Surgical Outcomes of Dorsal Augmentation Using Expanded Polytetrafluoroethylene or Autologous Costal Cartilage.

PubMed

Joo, Yeon Hee; Jang, Yong Ju

2016-09-01

Dorsal augmentation material includes alloplastic implants and autologous tissues. However, there has been no comparison to date of dorsal augmentation using different materials performed by the same surgeon. To compare the aesthetic outcomes and complications of dorsal augmentation using expanded polytetrafluoroethylene (ePTFE) and autologous costal cartilage (ACC) in rhinoplasty. A retrospective review of the medical records of 244 patients who underwent dorsal augmentation performed by the same surgeon at the Asan Medical Center using ePTFE or ACC from March 1, 2003, through September 31, 2015. Patient demographics and surgical procedures were analyzed. The aesthetic outcomes were scored from 1 (worst) to 4 (best) by 3 otolaryngologists. Changes in dorsal height and radix height were measured by comparing preoperative and postoperative profile views. Postoperative complications were also evaluated. A total of 244 patients who underwent augmentation rhinoplasty were reviewed in this study, including 141 men (57.8%) and 103 women (42.2%). The ePTFE group included 176 patients, and the ACC group comprised 68 patients. In the ePTFE and ACC groups, 96 patients (54.5%) and 45 patients (66.2%) were male, respectively. The patient ages ranged from 11 to 69 years, with a mean (SD) age of 30.3 (11.49) years in the ePTFE group and 36.04 (12.65) years in the ACC group. The mean (SD) aesthetic outcome scores were comparable between the 2 groups: 2.99 (0.05) in the ePTFE group and 2.99 (0.06) in the ACC group (P = .93). The change of dorsal (2.64% in ePTFE group and 5.82% in ACC group) and radix (3.62% in ePTFE group and 3.77% in ACC group) heights were significantly increased after augmentation in both groups (P < .001) even though the dorsal height of the ACC group after augmentation showed a significantly greater increase compared to the ePTFE group (P < .001). However, the complication rate was significantly higher in the ACC group: 4.0% in ePTFE group and

Inter-observer variability in fetal biometric measurements.

PubMed

Kilani, Rami; Aleyadeh, Wesam; Atieleh, Luay Abu; Al Suleimat, Abdul Mane; Khadra, Maysa; Hawamdeh, Hassan M

2018-02-01

To evaluate inter-observer variability and reproducibility of ultrasound measurements for fetal biometric parameters. A prospective cohort study was implemented in two tertiary care hospitals in Amman, Jordan; Prince Hamza Hospital and Albashir Hospital. 192 women with a singleton pregnancy at a gestational age of 18-36 weeks were the participants in the study. Transabdominal scans for fetal biometric parameter measurement were performed on study participants from the period of November 2014 to March 2015. Women who agreed to participate in the study were administered two ultrasound scans for head circumference, abdominal circumference and femur length. The correlation coefficient was calculated. Bland-Altman plots were used to analyze the degree of measurement agreement between observers. Limits of agreement ± 2 SD for the differences in fetal biometry measurements in proportions of the mean of the measurements were derived. Main outcome measures examine the reproducibility of fetal biometric measurements by different observers. High inter-observer inter-class correlation coefficient (ICC) was found for femur length (0.990) and abdominal circumference (0.996) where Bland-Altman plots showed high degrees of agreement. The highest degrees of agreement were noted in the measurement of abdominal circumference followed by head circumference. The lowest degree of agreement was found for femur length measurement. We used a paired-sample t-test and found that the mean difference between duplicate measurements was not significant (P > 0.05). Biometric fetal parameter measurements may be reproducible by different operators in the clinical setting with similar results. Fetal head circumference, abdominal circumference and femur length were highly reproducible. Large organized studies are needed to ensure accurate fetal measurements due to the important clinical implications of inaccurate measurements. Copyright © 2018. Published by Elsevier B.V.

Fetal programming of appetite and obesity.

PubMed

Breier, B H; Vickers, M H; Ikenasio, B A; Chan, K Y; Wong, W P

2001-12-20

Obesity and related metabolic disorders are prevalent health issues in modern society and are commonly attributed to lifestyle and dietary factors. However, the mechanisms by which environmental factors modulate the physiological systems that control weight regulation and the aetiology of metabolic disorders, which manifest in adult life, may have their roots before birth. The 'fetal origins' or 'fetal programming' paradigm is based on the observation that environmental changes can reset the developmental path during intrauterine development leading to obesity and cardiovascular and metabolic disorders later in life. The pathogenesis is not based on genetic defects but on altered genetic expression as a consequence of an adaptation to environmental changes during fetal development. While many endocrine systems can be affected by fetal programming recent experimental studies suggest that leptin and insulin resistance are critical endocrine defects in the pathogenesis of programming-induced obesity and metabolic disorders. However, it remains to be determined whether postnatal obesity is a consequence of programming of appetite regulation and whether hyperphagia is the main underlying cause of the increased adiposity and the development of metabolic disorders.

Computerized intrapartum electronic fetal monitoring: analysis of the decision to deliver for fetal distress.

PubMed

Georgieva, Antoniya; Payne, Stephen J; Moulden, Mary; Redman, Christopher W G

2011-01-01

We applied computerized methods to assess the Electronic Fetal Monitoring (EFM) in labor. We analyzed retrospectively the last hour of EFM for 1,370 babies, delivered by emergency Cesarean sections before the onset of pushing (data collected at the John Radcliffe Hospital, Oxford, UK). There were two cohorts according to the reason for intervention: (a) fetal distress, n(1) = 524 and (b) failure to progress and/or malpresentation, n(2) = 846. The cohorts were compared in terms of classical EFM features (baseline, decelerations, variability and accelerations), computed by a dedicated Oxford system for automated analysis--OxSys. In addition, OxSys was employed to simulate current clinical guidelines for the classification of fetal monitoring, i.e. providing in real time a three-tier grading system of the EFM (normal, indeterminate, or abnormal). The computerized features and the simulated guidelines corresponded well to the clinical management and to the actual labor outcome (measured by umbilical arterial pH).

Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization

USDA-ARS?s Scientific Manuscript database

The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nico...

Understanding fetal physiology and second line monitoring during labor.

PubMed

Garabedian, C; De Jonckheere, J; Butruille, L; Deruelle, P; Storme, L; Houfflin-Debarge, V

2017-02-01

Cardiotocography (CTG) is a technique used to monitor intrapartum fetal condition and is one of the most common obstetric procedures. Second line methods of fetal monitoring have been developed in an attempt to reduce unnecessary interventions due to continuous cardiotocography and to better identify fetuses at risk of intrapartum asphyxia. The acid-base balance of the fetus is evaluated by fetal blood scalp samples, the modification of the myocardial oxygenation by the fetal ECG ST-segment analysis (STAN) and the autonomic nervous system by the power spectral analysis of the fetal heart variability. To correctly interpret the features observed on CTG traces or second line methods, it seems important to understand normal physiology during labor and the compensatory mechanisms of the fetus in case of hypoxemia. Therefore, the aim of this review is first to describe fetal physiology during labor and then to explain the modification of the second line monitoring during labor. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Growth assessment in diagnosis of Fetal Growth Restriction. Review.

PubMed

Albu, A R; Horhoianu, I A; Dumitrascu, M C; Horhoianu, V

2014-06-15

The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the truly growth restricted fetus who is predisposed to perinatal complications, even if its parameters are above the cut-off limits established. In this article, we present the clinical tools of fetal growth assessment: Symphyseal-Fundal Height (SFH) measurement, the fetal ultrasound parameters widely taken into consideration when discussing fetal growth: Abdominal Circumference (AC) and Estimated Fetal Weight (EFW); several types of growth charts and their characteristics: populational growth charts, standard growth charts, individualized growth charts, customized growth charts and growth trajectories.

Investigating category- and shape-selective neural processing in ventral and dorsal visual stream under interocular suppression.

PubMed

Ludwig, Karin; Kathmann, Norbert; Sterzer, Philipp; Hesselmann, Guido

2015-01-01

Recent behavioral and neuroimaging studies using continuous flash suppression (CFS) have suggested that action-related processing in the dorsal visual stream might be independent of perceptual awareness, in line with the "vision-for-perception" versus "vision-for-action" distinction of the influential dual-stream theory. It remains controversial if evidence suggesting exclusive dorsal stream processing of tool stimuli under CFS can be explained by their elongated shape alone or by action-relevant category representations in dorsal visual cortex. To approach this question, we investigated category- and shape-selective functional magnetic resonance imaging-blood-oxygen level-dependent responses in both visual streams using images of faces and tools. Multivariate pattern analysis showed enhanced decoding of elongated relative to non-elongated tools, both in the ventral and dorsal visual stream. The second aim of our study was to investigate whether the depth of interocular suppression might differentially affect processing in dorsal and ventral areas. However, parametric modulation of suppression depth by varying the CFS mask contrast did not yield any evidence for differential modulation of category-selective activity. Together, our data provide evidence for shape-selective processing under CFS in both dorsal and ventral stream areas and, therefore, do not support the notion that dorsal "vision-for-action" processing is exclusively preserved under interocular suppression. © 2014 Wiley Periodicals, Inc.

Fetal abuse and neglect: an emerging controversy.

PubMed

Landwirth, J

1987-04-01

Advances in fetal medicine have expanded opportunities for protection of fetal health and intrauterine management of an increasing number of fetal disorders. The legal rights and duties of parents to provide necessary medical treatment for the child may extend to the prenatal period. Resolution of the conflict between the rights of the fetus to be born healthy and the pregnant woman's right of privacy is difficult and controversial. It is suggested that intrusion into a woman's individual fundamental rights for the potential benefit of her fetus should be permissible only in narrowly defined circumstances.

The Organization of Dorsal Frontal Cortex in Humans and Macaques

PubMed Central

Mars, Rogier B.; Noonan, MaryAnn P.; Neubert, Franz-Xaver; Jbabdi, Saad; O'Reilly, Jill X.; Filippini, Nicola; Thomas, Adam G.; Rushworth, Matthew F.

2013-01-01

The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for “new” regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed. PMID:23884933

Human nasal polyp microenvironments maintained in a viable and functional state as xenografts in NOD-scid IL2rgamma(null) mice.

PubMed

Bernstein, Joel M; Brooks, Stephen P; Lehman, Heather K; Pope, Liza; Sands, Amy; Shultz, Leonard D; Bankert, Richard B

2009-12-01

The objective was to develop a model with which to study the cellular and molecular events associated with nasal polyp progression. To accomplish this, we undertook to develop a system in which nondisrupted human nasal polyp tissue could be successfully implanted into severely immunocompromised mice, in which the histopathology of the original nasal polyp tissue, including inflammatory lymphocytes, epithelial and goblet cell hyperplasia, and subepithelial fibrosis, could be preserved for prolonged periods. Small, non-disrupted pieces of human nasal polyp tissues were subcutaneously implanted into NOD-scid IL2rgamma(null) mice. Xenografts at 8 to 12 weeks after implantation were examined histologically and immunohistochemically to identify human inflammatory leukocytes and to determine whether the characteristic histopathologic characteristics of the nasal polyps were maintained for a prolonged period. The xenografts, spleen, lung, liver, and kidneys were examined histologically and immunohistochemically and were evaluated for changes in volume. The sera of these mice were assayed for human cytokines and immunoglobulin. Xenografts of human nasal polyp tissues were established after their subcutaneous implantation into NOD-scid IL2rgamma(null) mice. The xenografts were maintained in a viable and functional state for up to 3 months, and retained a histopathologic appearance similar to that of the original tissue, with a noticeable increase in goblet cell hyperplasia and marked mucus accumulation in the submucosal glands compared to the original nasal polyp tissue. Inflammatory lymphocytes present in the polyp microenvironment were predominantly human CD8+ T cells with an effector memory phenotype. Human CD4+ T cells, CD138+ plasma cells, and CD68+ macrophages were also observed in the xenografts. Human immunoglobulin and interferon-gamma were detected in the sera of xenograft-bearing mice. The polyp-associated lymphocytes proliferated and were found to migrate from