Science.gov

Sample records for septum causing severe

  1. An unusual cause of necrosis and nasal septum perforation after septoplasty: Enterobacter cloacae.

    PubMed

    Binar, M; Arslan, F; Tasli, H; Karakoc, O; Kilic, A; Aydin, U

    2015-11-01

    A 20-year-old man with nasal obstruction underwent septoplasty due to nasal septal deviation. Nasal packs were inserted at the end of surgery and removed 48 hours after surgery. Twenty-four hours after removal of nasal packs, there was necrosis in both sides of septal mucosa and in bilateral inferior turbinates. Nasal swab culture was performed from both nasal cavities. Enterobacter cloacae was isolated from samples. Two weeks after surgery, nasal septum perforation was unavoidable. To our knowledge, this is the first case in literature describing septal mucosal necrosis caused by this pathogen after septoplasty. Mucosal necrosis and perforation as septoplasty complications should be kept in mind, the result of causes both common and, as in the present case, unusual.

  2. Repeated mild traumatic brain injury causes focal response in lateral septum and hippocampus

    PubMed Central

    Acabchuk, Rebecca; Briggs, Denise I; Angoa-Pérez, Mariana; Powers, Meghan; Wolferz, Richard; Soloway, Melanie; Stern, Mai; Talbot, Lillian R; Kuhn, Donald M; Conover, Joanne C

    2016-01-01

    Aim To advance our understanding of regional and temporal cellular responses to repeated mild traumatic brain injury (rmTBI), we used a mouse model of rmTBI that incorporated acceleration, deceleration and rotational forces. Materials & methods A modified weight-drop method was used to compare two inter-injury intervals, rmTBI-short (five hits delivered over 3 days) and rmTBI-long (five hits delivered over 15 days). Regional investigations of forebrain and midbrain histological alterations were performed at three post-injury time points (immediate, 2 weeks and 6 weeks). Results The rmTBI-short protocol generated an immediate, localized microglial and astroglial response in the dorsolateral septum and hippocampus, with the astroglial response persisting in the dorsolateral septum. The rmTBI-long protocol showed only a transitory astroglial response in the dorsolateral septum. Conclusion Our results indicate that the lateral septum and hippocampus are particularly vulnerable regions in rmTBI, possibly contributing to memory and emotional impairments associated with repeated concussions. PMID:28078102

  3. Sylvius aqueduct septum.

    PubMed

    Coolen, T; Médart, L; Tebache, M; Collignon, L

    2013-01-01

    We present a case of chronic hydrocephalus discovered in adulthood through an episode of acute decompensation. Multimodal imaging revealed the cause of this hydrocephalus to be a membranous septum of the aqueduct of Sylvius, a condition for which few reports exist.

  4. Conditional deletion of WT1 in the septum transversum mesenchyme causes congenital diaphragmatic hernia in mice

    PubMed Central

    Carmona, Rita; Cañete, Ana; Cano, Elena; Ariza, Laura; Rojas, Anabel; Muñoz-Chápuli, Ramon

    2016-01-01

    Congenital diaphragmatic hernia (CDH) is a severe birth defect. Wt1-null mouse embryos develop CDH but the mechanisms regulated by WT1 are unknown. We have generated a murine model with conditional deletion of WT1 in the lateral plate mesoderm, using the G2 enhancer of the Gata4 gene as a driver. 80% of G2-Gata4Cre;Wt1fl/fl embryos developed typical Bochdalek-type CDH. We show that the posthepatic mesenchymal plate coelomic epithelium gives rise to a mesenchyme that populates the pleuroperitoneal folds isolating the pleural cavities before the migration of the somitic myoblasts. This process fails when Wt1 is deleted from this area. Mutant embryos show Raldh2 downregulation in the lateral mesoderm, but not in the intermediate mesoderm. The mutant phenotype was partially rescued by retinoic acid treatment of the pregnant females. Replacement of intermediate by lateral mesoderm recapitulates the evolutionary origin of the diaphragm in mammals. CDH might thus be viewed as an evolutionary atavism. DOI: http://dx.doi.org/10.7554/eLife.16009.001 PMID:27642710

  5. Some observations on the septum pellucidum.

    PubMed

    Pearce, J M S

    2008-01-01

    The thin, vertically placed partition consisting of two laminae separated by a narrow chink constitutes the cavity of the septum pellucidum, known from the time of Sylvius. Traumatic lesions in boxers, rare congenital expanding cysts causing hydrocephalus, and a number of septo-optic dysplasias give clinical significance to the septum and its related cavum.

  6. Dissection of the interventricular septum

    PubMed Central

    Gu, Xiaoyan; He, Yihua; Luan, Shurong; Zhao, Ying; Sun, Lin; Zhang, Hongjia; Nixon, J.V. Ian

    2017-01-01

    Abstract Dissection of the interventricular septum (IVS) is an extremely rare entity. An institutional echocardiographic database was retrospectively reviewed; 13 patients with a diagnosis of IVS dissection were found and confirmed by cardiac surgery. The purposes of the study were: to determine the value of transthoracic echocardiography (TTE) in establishing the diagnosis of IVS dissection, and to detail the TTE features of IVS dissection. Thirteen patients with IVS dissection diagnosed by TTE, 8 males and 5 females were taken from 789,114 TTE studies performed between 1985 and 2014. All underwent cardiac surgery during which their diagnosis was confirmed. The etiology, location, 2-dimensional morphology, and color Doppler findings of IVS dissection were noted. The right sinus of Valsalva (SOV) was involved in 11 of the 13 patients. In 5 patients, a single aneurysm of the right SOV was seen dissecting into the IVS. One patient with a combination of a bicuspid aortic valve and a right SOV aneurysm dissected into the IVS. In 4 patients, aortic valve infective endocarditis resulted in IVS dissection. In 1 patient, mechanical aortic valve prosthetic replacement was complicated by annular detachment and a severe paravalvular leak causing IVS dissection. In all 11 patients, TTE showed a dissecting cystic-like mass in the IVS from the base to the mid-septum or confined to the septal base. The path of the dissection in these 11 patients was traced to the right SOV and communications between the IVS dissection and the aortic root were identified. In the remaining 2 patients, IVS dissection followed septal rupture due to a myocardial infarction, and communication was seen between the IVS dissection and the right ventricle. The study showed that most of the dissections of the IVS commence in the right SOV, due to either congenital anomalies or infective endocarditis, or following aortic valve replacement or myocardial infarction. The TTE characteristic of IVS dissection is

  7. THE AGS ELECTROSTATIC SEPTUM.

    SciTech Connect

    HOCK,J.RUSSO,T.GLEN,J.BROWN,K.

    2003-05-12

    The previous slow beam extraction electro static septum in the AGS was designed in 1981. Research documented at the Fermi Laboratory was used as the base line for this design. The septum consisted of a ground plane of .002 inch diameter wire tungsten-rhenium alloy (75%W 25%Re) with a hollow welded titanium cathode assembly. The vacuum chamber is stationary and the septum is moved with a pair of high vacuum linear feed throughs. After years of beam time, the frequency of failures increased. The vacuum system design was poor by today's standards and resulted in long pump down times after repairs. The failures ranged from broken septum wires to a twisted cathode. In addition to the failures, the mechanical drive system had too much backlash, making the operating position difficult to repeat. The new septum needed to address all of these issues in order to become a more reliable septum.

  8. Severe hyponatremia caused by hypothalamic adrenal insufficiency.

    PubMed

    Shibata, T; Oeda, T; Saito, Y

    1999-05-01

    A 60-year-old woman was admitted with severe hyponatremia. Basal values of adrenocorticotropic hormone (ACTH), thyroid hormone and cortisol were normal on admission. Impairment of water diuresis was observed by water loading test. Initially, we diagnosed her condition as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). By provocation test, we finally confirmed that the hyponatremia was caused by hypothalamic adrenal insufficiency. The basal values of ACTH and cortisol might not be sufficient to exclude the possibility of adrenal insufficiency. Therefore, it is necessary to evaluate adrenal function by provocation test or to re-evaluate it after recovery from hyponatremia.

  9. Severe Vitamin D Deficiency Causing Kyphoscoliosis.

    PubMed

    Singhai, Abhishek; Banzal, Subodh

    2013-01-01

    Vitamin D deficiency is common among Indian population. Women are especially at risk for severe vitamin D deficiency. The risk is higher for those who are multiparous and postmenopausal. Poor exposure to sunlight, higher latitude, winter season, inadequate diet, older age, obesity and malabsorption are also important risk factors. Symptoms of hypovitaminosis D, including diffuse or migratory pain affecting several sites (especially the shoulder, pelvis, ribcage and lower back) have also been misdiagnosed as musculoskeletal disorders, including fibromyalgia, polymyalgia rheumatica and ankylosing spondylitis. Here, we report two cases presented with kyphoscoliosis, diagnosed to have severe vitamin D deficiency.

  10. Severe Vitamin D Deficiency Causing Kyphoscoliosis

    PubMed Central

    Singhai, Abhishek; Banzal, Subodh

    2013-01-01

    Vitamin D deficiency is common among Indian population. Women are especially at risk for severe vitamin D deficiency. The risk is higher for those who are multiparous and postmenopausal. Poor exposure to sunlight, higher latitude, winter season, inadequate diet, older age, obesity and malabsorption are also important risk factors. Symptoms of hypovitaminosis D, including diffuse or migratory pain affecting several sites (especially the shoulder, pelvis, ribcage and lower back) have also been misdiagnosed as musculoskeletal disorders, including fibromyalgia, polymyalgia rheumatica and ankylosing spondylitis. Here, we report two cases presented with kyphoscoliosis, diagnosed to have severe vitamin D deficiency. PMID:26664847

  11. Urinothorax: an unexpected cause of severe dyspnea.

    PubMed

    Tortora, Alessandra; Casciani, Emanuele; Kharrub, Zaher; Gualdi, Gianfranco

    2006-05-01

    We report an unusual cause of the pleural effusion due to extravasation of urine from the retroperitoneal space into the thoracic cavity. In our case, the urinoma occurred owing to obstructing urinary tract lesion due to opaque stone. Although rare, urinothorax should be considered when pleural effusion occurs in patients with urinary tract obstruction accompanied by retroperitoneal urinoma.

  12. Reproductive Outcome Following Hysteroscopic Treatment of Uterine Septum

    PubMed Central

    Esmaeilzadeh, Seddigheh; Delavar, Mouloud Agajani; Andarieh, Maryam Ghanbari

    2014-01-01

    Background: Septate uterus is the most common uterine anomaly and a cause for miscarriage and infertility. Existing data suggested a better reproductive outcome of uterine septum following hysteroscopic septum resection. Objective: Current study was administered to share our experience in hystroscopic septum resection for reproductive outcome following hysteroscopic treatment of uterine septum and specifically focusing on different treatment protocols after hysteroscopic septum resection. Methods& materials: This study was a cross-sectional study based on secondary data that was obtained from medical records of infertile women who had undergone transvaginal hysteroscopy and used different treatment protocols after hysteroscopic correction of uterine septum in Infertility and Reproductive Health Research Center between April 2005 and February 2014. Results: The total number of infertile women underwent hysteroscopy uterine septoplasty was 106. The hysteroscopy septoplasty resulted in an overall pregnancy rate of 67% and a live birth 57.5%. Pregnancy rate for patients who had not male infertility was 92.1%. The chi-square test did not reveal any statistically significant difference in side affect, pregnancy, live birth, abortion, preterm deliveries, and term deliveries rate between these patients either with consistent hormone therapy plus IUD insertion or with alternate hormone therapy plus IUD after hysteroscopic metroplasty. Conclusion: The findings of the present study indicated hysteroscopic septum resection to remove a uterine septum in women with infertility is safe and may be an efficacious procedure. Treatment following hysteroscopic septum resection, either the consistent or the alternate protocol is both beneficial to improve pregnancy rate. PMID:25685079

  13. Lipomatous hypertrophy of the interatrial septum: a pathological and clinical approach.

    PubMed

    Xanthos, Theodoros; Giannakopoulos, Nikodimos; Papadimitriou, Lila

    2007-09-14

    Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare benign disorder that is characterized by accumulation and deposition of fat in the interatrial septum. Its etiology is still unknown, despite the theories that have been suggested. It usually occurs in older, obese people with a higher incidence in women. In most cases, it remains asymptomatic, thus its diagnosis is rarely made during a person's lifetime and it is made incidentally or during autopsy. LHIS can cause atrial arrhythmias, obstructive flow symptoms and sometimes death. The diagnosis of LHIS can be made by the use of imaging techniques, with the best results given by multislice-CT (MSCT) scanning. Surgical intervention is usually avoided and the best management is early diagnosis, reassurance and inactivity. However, in cases of severe superior vena cava obstruction or intractable rhythm disturbance, surgical excision is performed together with reconstruction of the interatrial septum.

  14. Rhabdomyolysis following severe hypokalemia caused by familial hypokalemic periodic paralysis

    PubMed Central

    Jung, Young-Lee; Kang, Jae-Young

    2017-01-01

    Rhabdomyolysis continues to appear with increasing frequency and represents a medical emergency requiring rapid appropriate treatment. One of the unusual causes of nontraumatic rhabdomyolysis is hypokalemic periodic paralysis without secondary causes. Primary hypokalemic periodic paralysis is a rare genetic disease characterized by episodic attacks of muscle weakness due to decreases in serum potassium. A 30-year-old woman who had 3 episodic attacks of hypokalemic periodic paralysis was admitted in emergency room with sudden onset symmetrical muscle weakness. After several hours, she started to complain myalgia and severe ache in both calves without any changes. Laboratory test showed markedly elevated creatine phosphokinase, lactic dehydrogenase levels with hypokalemia, rhabdomyolysis resulting from hypokalemia was diagnosed. Here, we report an unusual case of rhabdomyolysis caused by severe hypokalemia, which was suggested a result of familial hypokalemic periodic paralysis. PMID:28255549

  15. AIDS in an infant causing severe failure to thrive.

    PubMed

    Elias-Jones, A C; Larcher, V F; Price, E H

    1987-07-01

    A nine-month-old female Jamaican infant presented with a history of severe failure to thrive, recurrent pneumonia and developmental delay. She was found to have hepatosplenomegaly, generalised lymphadenopathy and hypotonia. Investigations revealed polyclonal hypergammaglobulinaemia, cytomegalovirus in her urine, and patchy lung infiltrates on her chest radiographs. Three separate tests were positive for human immunodeficiency virus in both the infant and her mother, suggesting vertical transmission, and confirming AIDS as the cause of the severe failure to thrive.

  16. [Tubercular meningitis with severe hyponatraemia caused by cerebral salt wasting].

    PubMed

    Tinggaard, Jeanette; Schmidt, Ida Maria; Kristensen, Kim

    2011-09-12

    We describe two children, who were admitted with severe hyponatraemia and dehydration. In both children the hyponatraemia was due to cerebral salt wasting caused by tubercular meningitis. Differential diagnosis and pathophysiology is discussed. It is important to discriminate between cerebral salt wasting and inappropriate secretion of antidiuretic hormone since the therapy required is completely different in the two conditions.

  17. Chondrosarcoma of the nasal septum

    PubMed Central

    Bahgat, Mohammed; Bahgat, Yassin; Bahgat, Ahmed; Elwany, Yasmine

    2012-01-01

    Chondrosarcoma of the nasal septum is a rare malignancy. When it occurs, early diagnosis is difficult because patients generally present with common, non-specific sinonasal complaints. This is the report of a 62-year-old woman who presented with a 1-month history of nasal obstruction, headache and anosmia. Nasal endoscopy showed a nasal mass obstructing both nasal cavities not separable from the septum. A wedge biopsy of the nasal mass was taken. Histopathology was suggestive of chondrosarcoma. The tumour was removed by an endoscopic approach. The clinical presentation, diagnosis and treatment of this case as well as a review of the literature are discussed. PMID:22669930

  18. Quilting sutures for nasal septum.

    PubMed

    Hari, C; Marnane, C; Wormald, P J

    2008-05-01

    Suturing of the nasal septum after septal surgery is a commonly performed procedure designed to prevent complications such as septal haematoma and bleeding. It is also useful for closing any inadvertent tears of the septal mucosa and providing additional support for the cartilage pieces retained in septoplasty. In addition, the suture can be placed through the middle turbinates, stabilising them during the healing process. Placing knots for interrupted sutures in the posterior and middle part of the nasal septum can be technically difficult. We describe a continuous suturing technique for approximating the mucosal flaps following septal surgery.

  19. [Severe phimosis as cause of urosepsis with Actinobaculum schaalii].

    PubMed

    Jöhnk, Maria Louise; Olsen, Anne Buchhave; Prag, Jørgen Brorson; Søby, Karen Marie

    2012-05-28

    Actinobaculum schaalii is a small, Gram-positive, facultative anaerobic, CO2-requiring rod. It is now an acknowledged uropathogen, but often overlooked because of its slow growth. It is part of the normal bacterial flora in the urogenital area, but can be the cause of both local and invasive infections. We present a case of A. schaalii urosepsis in a 68-year-old male with phimosis caused by a severe lichen sclerosus et atrophicus. The only bacteria found in blood and urine was A. schaalii.

  20. Severe Chromoblastomycosis-Like Cutaneous Infection Caused by Chrysosporium keratinophilum

    PubMed Central

    Mijiti, Juhaer; Pan, Bo; de Hoog, Sybren; Horie, Yoshikazu; Matsuzawa, Tetsuhiro; Yilifan, Yilixiati; Liu, Yong; Abliz, Parida; Pan, Weihua; Deng, Danqi; Guo, Yun; Zhang, Peiliang; Liao, Wanqing; Deng, Shuwen

    2017-01-01

    Chrysosporium species are saprophytic filamentous fungi commonly found in the soil, dung, and animal fur. Subcutaneous infection caused by this organism is rare in humans. We report a case of subcutaneous fungal infection caused by Chrysosporium keratinophilum in a 38-year-old woman. The patient presented with severe chromoblastomycosis-like lesions on the left side of the jaw and neck for 6 years. She also got tinea corporis on her trunk since she was 10 years old. Chrysosporium keratinophilum was isolated from the tissue on the neck and scales on the trunk, respectively. The patient showed satisfactory response to itraconazole therapy, although she discontinued the follow-up. PMID:28179902

  1. Complete Atrioventricular Block Presenting With Syncope Caused by Severe Hypothyroidism

    PubMed Central

    Seol, Sang-Hoon; Kim, Doo-Il; Park, Bo-Min; Kim, Dong-Kie; Song, Pil-Sang; Kim, Ki-Hun; Jin, Han-Young; Seo, Jeong-Sook; Jang, Jae-Sik; Yang, Tae-Hyun; Kim, Dae-Kyeong; Kim, Dong-Soo

    2012-01-01

    A 75-year-old man was admitted to our hospital with syncope. Electrocardiogram showed complete atrioventricular block and bradycardia with the minimum heart rate of 22 beats/ min. There was a possible indication for temporary cardiac pacemaker implantation. Laboratory data on admission revealed high TSH level with low free T4 level. To rule out functional atrioventricular block, we treated several days with thyroxine. A follow-up electrocardiogram showed improved heart rate without any atrioventricular block. We found that severe hypothyroidism caused a complete atrioventricular block with syncope, and thyroxine replacement completely improved these conditions.

  2. Electrostatic septum for kilowatt heavy ion beams

    NASA Astrophysics Data System (ADS)

    Alfredson, S.; Marti, F.; Miller, P.; Poe, D.; Stork, G.

    2001-12-01

    A septum of improved design has replaced the standard tungsten septum with uniform thickness used in the deflector for the K1200 cyclotron at Michigan State University [1]. A V-notch in the leading edge enhanced radiation cooling, and an increased septum thickness away from the median plane enhanced conduction of heat to the water cooled housing. Previously observed degradation of beam transmission attributed to thermally induced deformation of the septum was greatly improved with the new septum. The demonstrated power dissipation with an Ar beam was 900 W.

  3. Novel NEK8 Mutations Cause Severe Syndromic Renal Cystic Dysplasia through YAP Dysregulation

    PubMed Central

    Grampa, Valentina; Odye, Gweltas; Thomas, Sophie; Elkhartoufi, Nadia; Filhol, Emilie; Niel, Olivier; Silbermann, Flora; Lebreton, Corinne; Collardeau-Frachon, Sophie; Rouvet, Isabelle; Alessandri, Jean-Luc; Devisme, Louise; Dieux-Coeslier, Anne; Cordier, Marie-Pierre; Capri, Yline; Khung-Savatovsky, Suonavy; Sigaudy, Sabine; Salomon, Rémi; Antignac, Corinne; Gubler, Marie-Claire; Benmerah, Alexandre; Terzi, Fabiola; Attié-Bitach, Tania; Jeanpierre, Cécile; Saunier, Sophie

    2016-01-01

    Ciliopathies are a group of genetic multi-systemic disorders related to dysfunction of the primary cilium, a sensory organelle present at the cell surface that regulates key signaling pathways during development and tissue homeostasis. In order to identify novel genes whose mutations would cause severe developmental ciliopathies, >500 patients/fetuses were analyzed by a targeted high throughput sequencing approach allowing exome sequencing of >1200 ciliary genes. NEK8/NPHP9 mutations were identified in five cases with severe overlapping phenotypes including renal cystic dysplasia/hypodysplasia, situs inversus, cardiopathy with hypertrophic septum and bile duct paucity. These cases highlight a genotype-phenotype correlation, with missense and nonsense mutations associated with hypodysplasia and enlarged cystic organs, respectively. Functional analyses of NEK8 mutations in patient fibroblasts and mIMCD3 cells showed that these mutations differentially affect ciliogenesis, proliferation/apoptosis/DNA damage response, as well as epithelial morphogenesis. Notably, missense mutations exacerbated some of the defects due to NEK8 loss of function, highlighting their likely gain-of-function effect. We also showed that NEK8 missense and loss-of-function mutations differentially affect the regulation of the main Hippo signaling effector, YAP, as well as the expression of its target genes in patient fibroblasts and renal cells. YAP imbalance was also observed in enlarged spheroids of Nek8-invalidated renal epithelial cells grown in 3D culture, as well as in cystic kidneys of Jck mice. Moreover, co-injection of nek8 MO with WT or mutated NEK8-GFP RNA in zebrafish embryos led to shortened dorsally curved body axis, similar to embryos injected with human YAP RNA. Finally, treatment with Verteporfin, an inhibitor of YAP transcriptional activity, partially rescued the 3D spheroid defects of Nek8-invalidated cells and the abnormalities of NEK8-overexpressing zebrafish embryos

  4. Upflow bioreactor with septum and pressure release mechanism

    DOEpatents

    Hansen, Conly L.; Hansen, Carl S.; Pack, Kevin; Milligan, John; Benefiel, Bradley C.; Tolman, C. Wayne; Tolman, Kenneth W.

    2010-04-20

    An upflow bioreactor includes a vessel having an inlet and an outlet configured for upflow operation. A septum is positioned within the vessel and defines a lower chamber and an upper chamber. The septum includes an aperture that provides fluid communication between the upper chamber and lower chamber. The bioreactor also includes means for releasing pressure buildup in the lower chamber. In one configuration, the septum includes a releasable portion having an open position and a closed position. The releasable portion is configured to move to the open position in response to pressure buildup in the lower chamber. In the open position fluid communication between the lower chamber and the upper chamber is increased. Alternatively the lower chamber can include a pressure release line that is selectively actuated by pressure buildup. The pressure release mechanism can prevent the bioreactor from plugging and/or prevent catastrophic damage to the bioreactor caused by high pressures.

  5. Severe hypercalcaemia and colon ischaemia: dehydration as an unusual cause?

    PubMed Central

    Fernandes, Liliana Gil; Ferreira, Nuno Ribeiro; Cardiga, Rosa; Póvoa, Pedro

    2015-01-01

    Hypercalcaemia is an emergency with severe consequences. Dehydration can be an uncommon cause of hypercalcaemia, as seen in this case. A 63-year-old woman with type 2 diabetes mellitus, hypothyroidism and osteoporosis, was admitted to the emergency room with abdominal distension and vomiting for 24 h. Initial evaluation was Hg 18.5 g/dL, Htc 56.2%, creatinine 2 mg/dL, metabolic acidaemia, lactate 8.3 mmol/L, anion gap 19, total Ca2+ 17.7 mg/dL and PO4+ 6.6 mg/dL. CT revealed colonic distension without obstruction or ischaemia. Renal replacement therapy and pamidronate were initiated. The patient's clinical condition deteriorated with septic shock in the context of toxic megacolon and she underwent an emergency subtotal colectomy (10 kg). Hypercalcaemia was corrected in 24 h with aggressive fluid replacement (8 L NaCl 0.9% first 12 h), with a reduction of total Ca2+ to 8.2 mg/dL. Other causes of hypercalcaemia were excluded. ‘Hypercalcaemic crisis’ secondary to severe acute dehydration is not mentioned in the literature. PMID:25809432

  6. MECP2 duplication: possible cause of severe phenotype in females.

    PubMed

    Scott Schwoerer, Jessica; Laffin, Jennifer; Haun, Joanne; Raca, Gordana; Friez, Michael J; Giampietro, Philip F

    2014-04-01

    MECP2 duplication syndrome, originally described in 2005, is an X-linked neurodevelopmental disorder comprising infantile hypotonia, severe to profound intellectual disability, autism or autistic-like features, spasticity, along with a variety of additional features that are not always clinically apparent. The syndrome is due to a duplication (or triplication) of the gene methyl CpG binding protein 2 (MECP2). To date, the disorder has been described almost exclusively in males. Female carriers of the duplication are thought to have no or mild phenotypic features. Recently, a phenotype for females began emerging. We describe a family with ∼290 kb duplication of Xq28 region that includes the MECP2 gene where the proposita and affected family members are female. Twin sisters, presumed identical, presented early with developmental delay, and seizures. Evaluation of the proposita at 25 years of age included microarray comparative genomic hybridization (aCGH) which revealed the MECP2 gene duplication. The same duplication was found in the proposita's sister, who is more severely affected, and the proband's mother who has mild intellectual disability and depression. X-chromosome inactivation studies showed significant skewing in the mother, but was uninformative in the twin sisters. We propose that the MECP2 duplication caused for the phenotype of the proband and her sister. These findings support evidence for varied severity in some females with MECP2 duplications.

  7. Severe adverse reactions caused by omeprazole: A case report

    PubMed Central

    Yu, Meiling; Qian, Jianghua; Guo, Daohua; Li, Li; Liu, Xiaolin

    2016-01-01

    A 61-year-old female patient was admitted to hospital following development of a whole-body rash for 10 days, diarrhea for 7 days, and unconsciousness and oliguria for 1 day. The patient had developed stomach discomfort following the oral administration of non-steroidal anti-inflammatory drugs, the exact nature of which was unknown, for the treatment of arthritic pain for >1 month. The patient was then prescribed omeprazole enteric-coated tablets (20 mg twice daily) for treatment of this symptom. However, the patient developed a whole-body rash 7 days after administering omeprazole, 10 days prior to admission. This symptom was followed by severe diarrhea with nausea and vomiting after 10 days, then shock. The shock occurred after administering omeprazole for 16 days. The patient developed a whole body rash 7 days after administering omeprazole, then 3 days later (after administering omeprazole for 10 days) severe diarrhea with nausea and vomiting occurred. The shock remained until administering omeprazole on the 16th day, with severe diarrhea with nausea and vomiting occurring 6 days later. The patient's condition did not improve following treatment for allergies, low blood pressure and oliguria in the Intensive Care Unit (ICU) department at Suzhou Municipal Hospital. For further diagnosis and treatment, the patient was admitted to the ICU department of The First Affiliated Hospital of Bengbu Medical College and was given a fluid infusion, antibiotics and phlegm-reducing treatment, a plasma infusion, blood filtration, and anti-diarrheal and anti-allergy treatment. The patient's vital signs were stable, with a normal temperature and hemogram results, and improved kidney function and deflorescence. Genetic screening revealed that the patient poorly metabolized omeprazole. Therefore, severe adverse reactions (allergic shock, rash and diarrhea) experienced by the patient were caused by the accumulation of omeprazole metabolites resulting from its slow metabolism in

  8. Tune Variations due to Septum Stray Field F. Pederson &

    SciTech Connect

    Rinolfi, L.

    1986-10-12

    Two types of antiproton instabilities due to trapped ions are harmful in the AA. One is a coherent instability occurring when an ion pocket resonates with a 3-Q mode (hiccups), the other is excitation of 11th and 15th order non-linear resonances due to the non-linear focusing fields from localized ion clouds trapped in uncleared potential well pockets. Accumulation with a good injection yield of antiprotons forces us to locate the tune of the dense core in the general area of the array of 15th order resonances. To avoid harmful blow-up of the dense core the tune is located between the resonances 11Q{sub H} + 4Q{sub V} = 34, 10Q{sub H} + 5Q{sub V} = 34, and 11Q{sub H} = 25, requiring a tune of Q{sub H} = 2.2722 to be maintained with a precision of a few 10{sup -4} (Fig. 4). Different angles of the injection and ejection trajectories require the septum current to be changed from 3860 A during accumulation to 3920 A, during ejection mode. Variations in the septum stray field due to these changes in current cause tune changes in the order of 10{sup -3}. In addition, at a given septum current, a pronounced hysteresis of the stray field causes tune variations of about the same order of magnitude, so also the past history of the septum excitation must be carefully controlled to obtain a reproducible tune.

  9. Missiles caused by severe pressurized-water reactor accidients

    SciTech Connect

    Krieg, R.

    1995-07-01

    For future pressurized-water reactors, which should be designed against core-meltdown accidents, missiles generated inside the containment present a severe problem for its integrity. The masses and geometries of the missiles, as well as their velocities, may vary to a great extent. Therefore a reliable proof of the containment integrity is very difficult. In this article the potential sources of missiles are discussed, and the conclusion was reached that the generation of heavy missiles must be prevented. Steam explosions must not damage the reactor vessel head. Thus fragments of the head cannot become missiles that endanger the containment shell. Furthermore, during a melt-through failure of the reactor vessel under high pressure, the resulting forces must not catapult the whole vessel against the containment shell. Only missiles caused by hydrogen explosions may be tolerable, but shielding structures that protect the containment shell may be required. Further investigations are necessary. Finally, measures are described showing that the generation of heavy missiles can indeed be prevented. Investigations are currently being carried out that will confirm the strength of the reactor vessel head. In addition, a device for retaining the fragments of a failing reactor vessel is discussed.

  10. Heterozygous Mutations of OTX2 Cause Severe Ocular Malformations

    PubMed Central

    Ragge, Nicola K.; Brown, Alison G.; Poloschek, Charlotte M.; Lorenz, Birgit; Henderson, R. Alex; Clarke, Michael P.; Russell-Eggitt, Isabelle; Fielder, Alistair; Gerrelli, Dianne; Martinez-Barbera, Juan Pedro; Ruddle, Piers; Hurst, Jane; Collin, J. Richard O.; Salt, Alison; Cooper, Simon T.; Thompson, Pamela J.; Sisodiya, Sanjay M.; Williamson, Kathleen A.; FitzPatrick, David R.; Heyningen, Veronica van; Hanson, Isabel M.

    2005-01-01

    Major malformations of the human eye, including microphthalmia and anophthalmia, are examples of phenotypes that recur in families yet often show no clear Mendelian inheritance pattern. Defining loci by mapping is therefore rarely feasible. Using a candidate-gene approach, we have identified heterozygous coding-region changes in the homeobox gene OTX2 in eight families with ocular malformations. The expression pattern of OTX2 in human embryos is consistent with the eye phenotypes observed in the patients, which range from bilateral anophthalmia to retinal defects resembling Leber congenital amaurosis and pigmentary retinopathy. Magnetic resonance imaging scans revealed defects of the optic nerve, optic chiasm, and, in some cases, brain. In two families, the mutations appear to have occurred de novo in severely affected offspring, and, in two other families, the mutations have been inherited from a gonosomal mosaic parent. Data from these four families support a simple model in which OTX2 heterozygous loss-of-function mutations cause ocular malformations. Four additional families display complex inheritance patterns, suggesting that OTX2 mutations alone may not lead to consistent phenotypes. The high incidence of mosaicism and the reduced penetrance have implications for genetic counseling. PMID:15846561

  11. Severe osteomyelitis caused by Myceliophthora thermophila after a pitchfork injury

    PubMed Central

    Destino, Lauren; Sutton, Deanna A; Helon, Anna L; Havens, Peter L; Thometz, John G; Willoughby, Rodney E; Chusid, Michael J

    2006-01-01

    Background Traumatic injuries occurring in agricultural settings are often associated with infections caused by unusual organisms. Such agents may be difficult to isolate, identify, and treat effectively. Case report A 4-year-old boy developed an extensive infection of his knee and distal femur following a barnyard pitchfork injury. Ultimately the primary infecting agent was determined to be Myceliophthora thermophila, a thermophilic melanized hyphomycete, rarely associated with human infection, found in animal excreta. Because of resistance to standard antifungal agents including amphotericin B and caspofungin, therapy was instituted with a prolonged course of terbinafine and voriconazole. Voriconazole blood levels demonstrated that the patient required a drug dosage (13.4 mg/kg) several fold greater than that recommended for adults in order to attain therapeutic blood levels. Conclusion Unusual pathogens should be sought following traumatic farm injuries. Pharmacokinetic studies may be of critical importance when utilizing antifungal therapy with agents for which little information exists regarding drug metabolism in children. PMID:16961922

  12. A 77-118 GHz RESONANCE-FREE SEPTUM POLARIZER

    SciTech Connect

    Chen, Yen-Lin; Chiueh, Tzihong; Teng, Hsiao-Feng

    2014-03-01

    Measurements of polarized radiation often reveal specific physical properties of emission sources, such as the strengths and orientations of magnetic fields offered by synchrotron radiation and Zeeman line emission, and the electron density distribution caused by free-free emission. Polarization-capable, millimeter/sub-millimeter telescopes are normally equipped with either septum polarizers or ortho-mode transducers (OMT) to detect polarized radiation. Though the septum polarizer is limited to a significantly narrower bandwidth than the OMT, it possesses advantageous features unparalleled by the OMT when it comes to determining astronomical polarization measurements. We design an extremely wide-band circular waveguide septum polarizer, covering 42% bandwidth, from 77 GHz to 118 GHz, without any undesired resonance, challenging the conventional bandwidth limit. Stokes parameters, constructed from the measured data between 77 GHz and 115 GHz, show that the leakage from I to Q and U is below ±2%, and the Q – U mutual leakage is below ±1%. Such a performance is comparable to other modern polarizers, but the bandwidth of this polarizer can be at least twice as wide. This extremely wide-band design removes the major weakness of the septum polarizer and opens up a new window for future astronomical polarization measurements.

  13. Tricuspid regurgitation: noninvasive techniques for determining causes and severity.

    PubMed

    DePace, N L; Ross, J; Iskandrian, A S; Nestico, P F; Kotler, M N; Mintz, G S; Segal, B L; Hakki, A H; Morganroth, J

    1984-06-01

    Tricuspid regurgitation is often not apparent on physical examination and several methods are now available to aid in this difficult assessment. Cardiac catheterization using right ventriculography, previously considered the diagnostic standard, has several limitations. Currently available noninvasive tools such as M-mode and two-dimensional echocardiography (with or without contrast), Doppler techniques and even radionuclide cardiologic imaging have added significantly to the precise assessment of the presence and severity of tricuspid regurgitation. This review examines the comparative use and limitations of these various techniques.

  14. Cochlear implantation for severe sensorineural hearing loss caused by lightning.

    PubMed

    Myung, Nam-Suk; Lee, Il-Woo; Goh, Eui-Kyung; Kong, Soo-Keun

    2012-01-01

    Lightning strike can produce an array of clinical symptoms and injuries. It may damage multiple organs and cause auditory injuries ranging from transient hearing loss and vertigo to complete disruption of the auditory system. Tympanic-membrane rupture is relatively common in patients with lightning injury. The exact pathogenetic mechanisms of auditory lesions in lightning survivors have not been fully elucidated. We report the case of a 45-year-old woman with bilateral profound sensorineural hearing loss caused by a lightning strike, who was successfully rehabilitated after a cochlear implantation.

  15. Hysteroscopic Transcervical Resection of Uterine Septum

    PubMed Central

    Shi, Xiaoyan; Hua, Xiangdong; Gu, Xiaoyan; Yang, Dazhen

    2013-01-01

    Objective: To explore the method of diagnosis for uterine septum and the clinical effect of hysteroscopic transcervical resection of the septum. Methods: One-hundred ninety cases of patients with uterine septum who were diagnosed and treated at our hospital during 2007–2011 were selected, and their general information, perioperative status, postoperative recovery treatment, and postoperative pregnancy rates were statistically analyzed. Results: All 190 patients were cured with one surgery, with an average hysteroscopic operating time of 22.60 ± 10.67 minutes and intraoperative blood loss of 15.74 ± 9.64 mL. There were no complications such as uterine perforation, water intoxication, infection, or heavy bleeding. Among the 115 patients that we followed up, 86 became pregnant and delivered infants, 81 of which were born at term and 5 that were born premature. Conclusion: The combination of hysteroscopy and laparoscopy is still the most reliable method for the diagnosis of uterine septum. With a shorter operative time, less blood loss, a significantly increased postoperative pregnancy rate and live birth rate, and a significantly lower spontaneous abortion rate, transcervical resection of the septum was the preferred method for the treatment of uterine septum, and surgical instruments and skills were critical to the prognosis of uterine septum. PMID:24398191

  16. [Hyponatraemia as the cause of severe cerebral symptoms].

    PubMed

    Sonne, David P; Overgaard-Steensen, Christian

    2013-09-23

    Hyponatraemia with severe symptoms is a medical emergency that warrants swift action. Treatment can be delayed and/or insufficient if a systematic approach fails. We present two cases of severe symptomatic hyponatraemia: 1) Seizures treated with antiepileptics and isotonic saline, which fails to increase the plasma [Na+]/reveal the symptoms and 2) coma treated successfully with infusions of hypertonic saline boluses. Effective treatment is simple and involves management of airway, breathing and circulation together with bolus infusions of hypertonic saline to ensure controllable plasma [Na+] increase.

  17. Ameboma: an unusual cause of gastrointestinal bleeding during severe leptospirosis

    PubMed Central

    2014-01-01

    Background Severe leptospirosis occurs mainly in a tropical environment and includes icterus, acute renal failure and hemorrhages. These bleedings, which are mainly a consequence of acute homeostatic disturbances, can also reveal simultaneous diseases. Coinfections with other tropical diseases have been previously reported during leptospirosis. To our knowledge, invasive amebiasis, which can induce gastrointestinal bleedings, has never been described in the course of severe leptospirosis. Case presentation In this report, we describe a case of a 60 year-old man living in Reunion Island (Indian Ocean, France) admitted to our intensive care unit for severe Leptospira interrogans serovar icterohaemorrhagiae infection with neurological, renal, liver and hematological involvement. Two lower gastrointestinal bleedings occurred 7 and 15 days after admission. The first episode was promoted by hemostatic disturbances while the second bleeding occurred during low-dose heparin therapy. Colonoscopy revealed a pseudo-tumoral inflammatory mass of the recto-sigmoid junction. Histological examination found trophozoites inside mucinous exudate suggestive of Entamoeba histolytica. Amoebic serology was strongly positive whereas careful detection of cysts or trophozoites on saline-wet mount was negative in three consecutive samples of stools. Amoxicillin followed by metronidazole therapy, combined with supportive care, led to an improvement in the clinical and biological patient’s condition and endoscopic appearances. Conclusion Clinicians should be aware that gastrointestinal bleeding during severe leptospirosis could not solely be the consequences of hemostatic disturbances. Careful endoscopic evaluation that may reveal curable coinfections should also be considered. PMID:24894109

  18. Severe Hypothermia Causing Ventricular Arrhythmia in Organophosphorus Poisoning.

    PubMed

    Munta, Kartik; Santosh, Paiullah; Surath, Manimala Rao

    2017-02-01

    Organophosphorus poisoning cases are routinely treated across all Intensive Care Units adjoining the rural areas where agriculture is the main source of income. We present a unique case of severe hypothermia seen in a case of organophosphorus poisoning, which led to electrocardiogram disturbances and life-threatening arrhythmias.

  19. Severe Hypothermia Causing Ventricular Arrhythmia in Organophosphorus Poisoning

    PubMed Central

    Munta, Kartik; Santosh, Paiullah; Surath, Manimala Rao

    2017-01-01

    Organophosphorus poisoning cases are routinely treated across all Intensive Care Units adjoining the rural areas where agriculture is the main source of income. We present a unique case of severe hypothermia seen in a case of organophosphorus poisoning, which led to electrocardiogram disturbances and life-threatening arrhythmias. PMID:28250607

  20. Piriformis syndrome surgery causing severe sciatic nerve injury.

    PubMed

    Justice, Phillip E; Katirji, Bashar; Preston, David C; Grossman, Gerald E

    2012-09-01

    Piriformis syndrome is a controversial entrapment neuropathy in which the sciatic nerve is thought to be compressed by the piriformis muscle. Two patients developed severe left sciatic neuropathy after piriformis muscle release. One had a total sciatic nerve lesion, whereas the second had a predominantly high common peroneal nerve lesion. Follow-up studies showed reinnervation of the hamstrings only. We conclude that piriformis muscle surgery may be hazardous and result in devastating sciatic nerve injury.

  1. CD45-deficient severe combined immunodeficiency caused by uniparental disomy

    PubMed Central

    Roberts, Joseph L.; Buckley, Rebecca H.; Luo, Biao; Pei, Jianming; Lapidus, Alla; Peri, Suraj; Wei, Qiong; Shin, Jinwook; Parrott, Roberta E.; Dunbrack, Roland L.; Testa, Joseph R.; Zhong, Xiao-Ping; Wiest, David L.

    2012-01-01

    Analysis of the molecular etiologies of SCID has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein-tyrosine phosphatase CD45, we used SNP arrays and whole-exome sequencing. The patient’s mother was heterozygous for an inactivating mutation in CD45 but the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Nonlymphoid blood cells and other mesoderm- and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient, who had undergone successful bone marrow transplantation. Exome sequencing revealed mutations in seven additional genes bearing nonsynonymous SNPs predicted to have deleterious effects. These findings are unique in representing a reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases. PMID:22689986

  2. [Bartter syndrome--a rare cause of severe polyhydramnios].

    PubMed

    Media, Jean; Hoseth, Gerd Eva

    2006-12-11

    We report a case of a 25-year-old woman, gravida II, Para I, in pregnancy week 26 + 4 with severe polyhydramnios. The amniotic fluid index was about 39. Type 2 scanning showed a large urinary bladder only. Treated in pregnancy with repeated aminodrinage, total 21 litres. In week 33 + 5, a Caesarean section was performed. A girl with Apgar score 10/1, 0/10 was born, weight 1,804 grammes. Immediately after birth the child developed polyuria with diuresis, about 8-10 ml/kg/hour, electrolyte disturbance, and vomiting, treated with Losec, Gaviscon, indometacin, and Vioxx. The diagnosis was Bartter syndrome.

  3. Severe apoptotic enteropathy caused by methotrexate treatment for rheumatoid arthritis.

    PubMed

    Toquet, Ségolène; Nguyen, Yohan; Sabbagh, Adel; Djerada, Zoubir; Boulagnon, Camille; Bani-Sadr, Firouzé

    2016-03-01

    The folic acid antagonist methotrexate is a cornerstone treatment of rheumatoid arthritis. Its use is limited chiefly by gastrointestinal toxicity, which is among the main reasons for methotrexate discontinuation. Here, we report the case of a 40-year-old man on chronic methotrexate therapy in whom life-threatening apoptotic enteropathy with watery diarrhea and hypovolemic shock developed after he was switched from the oral to the intramuscular route, with no change in dosage. Colonic biopsies suggested drug-induced colitis, showing a nonspecific, mildly inflammatory infiltrate of lymphocytes and plasma cells, dilated damaged crypts, and a marked increase in basal crypt apoptosis (>20 apoptotic bodies/100 crypts). Clinicians should be aware that methotrexate can cause life-threatening apoptotic enteropathy. Increased basal crypt apoptosis in colonic biopsies with more than 5 apoptotic bodies/100 crypts should routinely suggest drug-induced enteropathy.

  4. Acute alloxan toxicity causes granulomatous tubulointerstitial nephritis with severe mineralization

    PubMed Central

    Zhang, Lianshan; Terayama, Yui; Nishimoto, Taiki; Kodama, Yasushi; Ozaki, Kiyokazu

    2016-01-01

    Alloxan had been recognized as having a direct nephrotoxic effect different from its diabetogenic action. We encountered previously unreported granulomatous tubulointerstitial nephritis with severe luminal and interstitial mineralization in one diabetic rat after one week of alloxan administration. Histopathologically, many dilated and occluded proximal and distal tubules were segmentally observed in the cortex and outer medulla. The tubular lumen contained minerals and cell debris. Tubular epithelial cells were degenerated and piled up, and they protruded into the lumen, where they enveloped minerals. Mineralization was observed mainly in the tubular lumen, and to some extent in the subepithelium and interstitium. The mineralization beneath the tubular epithelium was often continuous from the subepithelium to the interstitium. In these lesions, the tubular basement membrane was disrupted by mineralization, and a granuloma with multinuclear foreign-body giant cells was formed in the interstitial areas. PMID:27821911

  5. Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction.

    PubMed

    Yan, Hong; Mao, Qingxiang; Ma, Yongda; Wang, Li; Chen, Xian; Hu, Yi; Ge, Hengjiang

    2016-01-01

    This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group), or burn injury combined with seawater immersion (BI group), or only immersion in seawater (I group), or control animals with no injury or immersion (C group). The circulating endothelial cell (CEC) count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P < 0.05). The von Willebrand factor (vWF) activity, plasminogen activator inhibitor (PAI-1), and the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1α (6-K-PGF1α ) in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA) in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

  6. [Scorpionism causing severe acute flaccid paralysis. Case report].

    PubMed

    Villa-Manzano, Alberto I; Vázquez-Solís, Ma Guadalupe; Zamora-López, Xochitl Xitlalli; Arias-Corona, Fernando; Palomera-Ávila, Francisco Miguel; Pulido-Galaviz, Carlos; Pacifuentes-Orozco, Adán

    2016-01-01

    Introducción: el alacranismo es un problema de salud pública en diversas regiones del mundo, siendo México el país que tiene mayor número de casos. Las manifestaciones clínicas oscilan desde sintomatología local hasta cuadros graves con repercusiones a nivel cardiovascular, respiratorio y neurológico, e incluso la muerte. No existen reportes de parálisis flácida como una manifestación del cuadro clínico por picadura del alacrán del género Centruroides, familia Buthidae, especie altamente tóxica, endémica y causante de altos índices de morbimortalidad en nuestra región. Caso clínico: documentamos un caso de alacranismo grave, provocado por escorpión de la familia Buthidae del género Centruroides, que causó parálisis flácida aguda, posterior a resolución de otras manifestaciones severas. Solo existe un reporte de caso de alacranismo que produce parálisis flácida aguda en la literatura médica, pero relacionado con el escorpión de la familia Parabuthus, endémico de Sudáfrica, el cual no es endémico en México. Conclusiones: conocer esta complicación, nueva para nuestra región, permitirá maximizar esfuerzos para diagnosticar y manejar oportunamente esta entidad con la aplicación temprana de faboterápico específico y soporte vital avanzado.

  7. Kif14 Mutation Causes Severe Brain Malformation and Hypomyelination

    PubMed Central

    Fujikura, Kohei; Setsu, Tomiyoshi; Tanigaki, Kenji; Abe, Takaya; Kiyonari, Hiroshi; Terashima, Toshio; Sakisaka, Toshiaki

    2013-01-01

    We describe a novel spontaneous mouse mutant, laggard (lag), characterized by a flat head, motor impairment and growth retardation. The mutation is inherited as an autosomal recessive trait, and lag/lag mice suffer from cerebellar ataxia and die before weaning. lag/lag mice exhibit a dramatic reduction in brain size and slender optic nerves. By positional cloning, we identify a splice site mutation in Kif14. Transgenic complementation with wild-type Kif14-cDNA alleviates ataxic phenotype in lag/lag mice. To further confirm that the causative gene is Kif14, we generate Kif14 knockout mice and find that all of the phenotypes of Kif14 knockout mice are similar to those of lag/lag mice. The main morphological abnormality of lag/lag mouse is severe hypomyelination in central nervous system. The lag/lag mice express an array of myelin-related genes at significantly reduced levels. The disrupted cytoarchitecture of the cerebellar and cerebral cortices appears to result from apoptotic cell death. Thus, we conclude that Kif14 is essential for the generation and maturation of late-developing structures such as the myelin sheath, cerebellar and cerebral cortices. So far, no Kif14-deficient mice or mutation in Kif14 has ever been reported and we firstly define the biological function of Kif14 in vivo. The discovery of mammalian models, laggard, has opened up horizons for researchers to add more knowledge regarding the etiology and pathology of brain malformation. PMID:23308235

  8. Two-piece nasal septum prosthesis for a large nasal septum perforation: a clinical report.

    PubMed

    Sashi Purna, C R; Annapurna, P D; Ahmed, Syed Basheer; Vurla, Samyuktha; Nalla, Sandeep; Abhishek, S M

    2013-02-01

    Nasal septum perforation presents with the symptoms of epistaxis and crusting. Obturation of the defect will decrease the symptoms and increase patient comfort. Prosthetic closure is more predictable and thus the treatment of choice in larger defects. This article describes a procedure for construction of a magnet-retained, heat-processed acrylic nasal septum prosthesis. The two-piece nasal septum prosthesis was processed and joined together in situ by magnets. Each piece of the septum prosthesis conforms to the remaining medial wall of each nostril and forms the missing half of the nasal septum. The prosthesis not only alleviates symptoms, but also provides structural support to the saddle-shaped nose and improves esthetics.

  9. Effect of Deviated Nasal Septum on Mean Platelet Volume: A Prospective Study.

    PubMed

    Poorey, Vijay Kumar; Thakur, Pooja

    2014-12-01

    In E.N.T clinical practice, patients with nasal obstruction due to deviated nasal septum is a common presentation. Nasal airway obstruction is a common cause of upper airway obstruction further leading to obstructive and hypoxic manifestations. Mean platelet volume (MPV) levels increase in hypoxic conditions. MPV is one of the platelet activation index which reflects the platelet production rate. Present prospective study conducted in the department of Otorhinolaryngology and Head and Neck surgery, Gandhi Medical College and Hamidia Hospital, Bhopal, on 63 patients with the clinical evidence of DNS and 63 healthy age matched subjects as control group, aimed to evaluate the relationship between MPV levels and nasal obstruction due to deviated nasal septum (DNS). The diagnosis of patients with DNS was based on anterior rhinoscopy and endoscopic nasal examination. Blood samples were collected before surgical correction. In present study, the authors found that there is preponderance of DNS in the age group of 25-45 years being the most active age group, males having the higher incidence. Majority of cases of DNS being left sided and of obstructed type. MPV were significantly higher in patients with DNS than the control group. Among the cases MPV being higher in females and in the impacted type of DNS. Present study reemphasized the concept that MPV is increased in chronic nasal obstruction due to DNS and this increase is in accordance with the severity of DNS.

  10. A New Septum in the Female Breast

    PubMed Central

    Awad, Mostafa Abdel Rahman; Sherif, Mahmoud Magdi; Sadek, Eaman Yahya; Hamid, Wafaa Raafat Abdel

    2017-01-01

    Background Understanding the female breast fascial system is of paramount importance in breast surgery. Little was written about breast ligaments. Most articles refer to Cooper's work without further anatomical studies. Lately, a horizontal septum has been described conveying nerves and vessels to the nipple areola complex. Methods During the surgical dissection of the lower part of the breast, in supero-medial technique for breast reduction operations, a fascial septum between the lower two quadrants was detected. This fibrous septum was studied through anatomic dissection of breast tissues during routine breast reshaping procedures that was done on 30 female patients. Magnetic resonance imaging (MRI) was performed preoperatively in all cases and correlated with the intraoperative findings. In the other five cases, outside the clinical study, the imaging was done during routine investigation for breast swellings. Results A vertical septum was identified in the lower part of the breast, lying at the breast meridian between the two lower quadrants. It is a tough bi-laminated structure that extends from the middle of the infra-mammary crease caudally to nipple-areola complex cranially and from the pectoral fascia posteriorly to the overlying skin anteriorly. This was proved by MRI findings. Conclusions This study describes a new inferior vertical septum which separates the lower half of the breast into two definite anatomical compartments: medial and lateral. PMID:28352598

  11. Comparison of Nasal Septum and Ear Cartilage as a Graft for Lower Eyelid Reconstruction.

    PubMed

    Suga, Hirotaka; Ozaki, Mine; Narita, Keigo; Kurita, Masakazu; Shiraishi, Tomohiro; Ohura, Norihiko; Takushima, Akihiko; Harii, Kiyonori

    2016-03-01

    In lower eyelid reconstruction, several types of grafts from the nasal septum, ear cartilage, buccal mucosa, and hard palate mucosa have been used for an inner layer of the lower eyelid, but there have been no studies comparing these grafts. The authors retrospectively reviewed our cases of lower eyelid reconstruction, and compared chondromucosal grafts from the nasal septum (N = 8) and ear cartilage grafts (N = 10) for an inner layer of the lower eyelid. The authors observed no significant difference in operative time, blood loss, or length of hospital stay between the "nasal septum" and "ear cartilage" groups. The final results were aesthetically and functionally satisfactory in both groups. In the nasal septum group, 1 patient suffered from perforation of the nasal septum and another patient suffered from nasal bleeding postoperatively. There were no donor site complications in the ear cartilage group. These findings indicate that both a chondromucosal graft from the nasal septum and an ear cartilage graft are good grafts for an inner layer of the lower eyelid. Regarding the donor site, however, an ear cartilage graft has the advantage of a lower complication rate.

  12. Papillary muscle approximation to septum for functional tricuspid regurgitation.

    PubMed

    Lohchab, Shamsher Singh; Chahal, Ashok Kumar; Agrawal, Nilesh

    2015-07-01

    Current techniques for repair of functional tricuspid regurgitation are associated with a significant degree of residual or recurrent regurgitation. We describe a technique of anterior papillary muscle attachment to the septum to correct residual tricuspid regurgitation persisting after annuloplasty. In our early experience in 15 patients (6 men and 9 women) with a mean age of 32 ± 11 years, who underwent annuloplasty for severe functional tricuspid regurgitation secondary to rheumatic mitral valve disease, this technique effectively eliminated residual tricuspid regurgitation.

  13. The cdc7 protein kinase is a dosage dependent regulator of septum formation in fission yeast.

    PubMed Central

    Fankhauser, C; Simanis, V

    1994-01-01

    Mutation of the Schizosaccharomyces pombe cdc7 gene prevents formation of the division septum and cytokinesis. We have cloned the cdc7 gene and show that it encodes a protein kinase which is essential for cell division. In the absence of cdc7 function, spore germination, DNA synthesis and mitosis are unaffected, but cells are unable to initiate formation of the division septum. Overexpression of p120cdc7 causes cell cycle arrest; cells complete mitosis and then undergo multiple rounds of septum formation without cell cleavage. This phenotype, which is similar to that resulting from inactivation of cdc16 protein, requires the kinase activity of p120cdc7. Mutations inactivating the early septation gene, cdc11, suppress the formation of multiple septa and allow cells to proliferate normally. If formation of the division septum is prevented by inactivation of either cdc14 or cdc15, p120cdc7 overproduction does not interfere with other events in the mitotic cell cycle. Septation is not induced by overexpression of p120cdc7 in G2 arrested cells, indicating that it does not bypass the normal dependency of septation upon initiation of mitosis. These findings indicate that the p120cdc7 protein kinase plays a key role in initiation of septum formation and cytokinesis in fission yeast and suggest that p120cdc7 interacts with the cdc11 protein in the control of septation. Images PMID:8039497

  14. Cavum Septum Pellucidum in Retired American Pro-Football Players

    PubMed Central

    Hess, Christopher P.; Brus-Ramer, Marcel; Possin, Katherine L.; Cohn-Sheehy, Brendan I.; Kramer, Joel H.; Berger, Mitchel S.; Yaffe, Kristine; Miller, Bruce; Rabinovici, Gil D.

    2016-01-01

    Abstract Previous studies report that cavum septum pellucidum (CSP) is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. Further, rates of CSP among American pro-football players have not been described previously. We sought to characterize MRI features of the septum pellucidum in a series of retired pro-football players with a history of repeated concussive/subconcussive head traumas compared with controls. We retrospectively assessed retired American pro-football players presenting to our memory clinic with cognitive/behavioral symptoms in whom structural MRI was available with slice thickness ≤2 mm (n=17). Each player was matched to a memory clinic control patient with no history of TBI. Scans were interpreted by raters blinded to clinical information and TBI/football history, who measured CSP grade (0–absent, 1–equivocal, 2–mild, 3–moderate, 4–severe) and length according to a standard protocol. Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI. PMID:25970145

  15. Cavum Septum Pellucidum in Retired American Pro-Football Players.

    PubMed

    Gardner, Raquel C; Hess, Christopher P; Brus-Ramer, Marcel; Possin, Katherine L; Cohn-Sheehy, Brendan I; Kramer, Joel H; Berger, Mitchel S; Yaffe, Kristine; Miller, Bruce; Rabinovici, Gil D

    2016-01-01

    Previous studies report that cavum septum pellucidum (CSP) is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. Further, rates of CSP among American pro-football players have not been described previously. We sought to characterize MRI features of the septum pellucidum in a series of retired pro-football players with a history of repeated concussive/subconcussive head traumas compared with controls. We retrospectively assessed retired American pro-football players presenting to our memory clinic with cognitive/behavioral symptoms in whom structural MRI was available with slice thickness ≤2 mm (n=17). Each player was matched to a memory clinic control patient with no history of TBI. Scans were interpreted by raters blinded to clinical information and TBI/football history, who measured CSP grade (0-absent, 1-equivocal, 2-mild, 3-moderate, 4-severe) and length according to a standard protocol. Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI.

  16. The malar septum: the anatomic basis of malar mounds and malar edema.

    PubMed

    Pessa, J E; Garza, J R

    1997-01-01

    The anatomy of malar mounds and malar edema is evaluated in a series of 18 fresh cadaver dissections. Dye injection, histologic evaluation, and gross anatomic dissection are used to identify a previously unrecognized fascial structure of the lower eyelid and cheek. The malar septum originates from orbital rim periosteum superiorly and inserts into cheek skin 2.5 to 3 cm inferior to the lateral canthus. This fascial structure acts as a relatively impermeable barrier that allows tissue edema and hemoglobin pigment to accumulate above its cutaneous insertion. The malar septum, which acts as both a functional and a structural barrier, defines the lower boundary of several clinical entities: malar mounds, malar edema, malar festoons, and periorbital ecchymosis. The permeability characteristics of the malar septum suggest that, at least in some persons, malar mounds may be accentuated by chronic lower eyelid edema, and these characteristics may imply a time course in the progressive development from malar edema to malar mounds and, ultimately, to malar festoons. The anatomy of the malar septum is clinically relevant because it defines the four anatomic compartments of the malar mound that should be considered during surgery: the superior compartment of suborbicularis oculi fat, orbicularis oculi muscle, and superficial cheek fat and cheek skin superior to the cutaneous insertion of the malar septum.

  17. Lipomatous Hypertrophy of the Atrial Septum in a Patient Undergoing Coronary Artery Bypass Surgery

    PubMed Central

    Weyand, Michael; Agaimy, Abbas

    2016-01-01

    Background. Lipomatous hypertrophy of the atrial septum (LHAS) is a rare entity characterized by mass-forming deposition of fatty tissue within the atrial septum. To date, <300 cases have been reported; many of them were autopsy findings. The clinical presentation of LHAS varies from incidental asymptomatic mass (most frequent form) to severe life-threatening cardiovascular complications necessitating emergency cardiac surgery. Case Presentation. Here, we present the successful surgical resection of such a massive LHAS which was found incidentally on preoperative investigation of a 71-year-old patient with progressive coronary heart disease. Histology confirmed the diagnosis of lipomatous hypertrophy of the atrial septum. Conclusions. The described case report illustrates an unusual example of LHAS in a patient undergoing a planned coronary artery bypass surgery. In this case, surgical intervention was justified to avoid later outflow obstructions. PMID:28078155

  18. Nasal septum injury in preterm infants using nasal prongs 1

    PubMed Central

    Bonfim, Suely de Fátima Santos Freire; de Vasconcelos, Maria Gorete Lucena; de Sousa, Nayara Francisca Cabral; da Silva, Daiana Vieira Câmara; Leal, Luciana Pedrosa

    2014-01-01

    OBJECTIVE: to assess the incidence and risk factors associated with nasal septum injury in premature infants using reused and new nasal prongs. METHOD: the study was a cohort from an open therapeutic intervention. The sample included 70 infants with a gestational age inferior to 37 weeks, who used nasal prongs and were hospitalized at the neonatal service of a hospital in Recife-PE, in the Northeast of Brazil. The data were collected in patient files through the assessment of the application of the device and of the nasal septum. Multinomial Logistic Regression and Survival analyses were applied. RESULTS: the incidence of nasal injury corresponded to 62.9%. In the multiple analysis, only the length of the infant's treatment was a determinant factor for the occurrence and severity of the injuries. CONCLUSION: the type of nasal prong does not serve as a risk factor for the nasal injury. The high incidence of nasal injury indicates the need to adapt the nursing care with emphasis on prevention. PMID:25493679

  19. A Case of Fetal Intestinal Volvulus Without Malrotation Causing Severe Anemia

    PubMed Central

    Nakagawa, Tomoko; Tachibana, Daisuke; Kitada, Kohei; Kurihara, Yasushi; Terada, Hiroyuki; Koyama, Masayasu; Sakae, Yukari; Morotomi, Yoshiki; Nomura, Shiho; Saito, Mika

    2015-01-01

    Fetal intestinal volvulus without malrotation is a rare, life-threatening disease. Left untreated, hemorrhage from necrotic bowel tissue will lead to severe fetal anemia and even intrauterine death. We encountered a case of fetal intestinal volvulus causing severe anemia, which was diagnosed postnatally and successfully treated with surgical intervention. PMID:25628516

  20. Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

    PubMed Central

    Meca, Olga; Cruz, María-Jesús; Sánchez-Ortiz, Mónica; González-Barcala, Francisco-Javier; Ojanguren, Iñigo; Munoz, Xavier

    2016-01-01

    Introduction The aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests. Methods Seventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed. Results OA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136–11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0–16), compared with patients with OA caused by HMW agents (0.87, range 0–72), (p = 0.024). Conclusions OA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents. PMID:27280473

  1. Monitoring Chitin Deposition During Septum Assembly in Budding Yeast.

    PubMed

    Arcones, Irene; Roncero, Cesar

    2016-01-01

    The synthesis of the septum is a critical step during cytokinesis in the fungal cell. Moreover, in Saccharomyces cerevisiae septum assembly depends mostly on the proper synthesis and deposition of chitin and, accordingly, on the timely regulation of chitin synthases. In this chapter, we will see how to follow chitin synthesis by two complementary approaches: monitoring chitin deposition in vivo at the septum by calcofluor staining and fluorescence microscopy, and measuring the chitin synthase activities responsible for this synthesis.

  2. Comparison of echocardiography and angiography in determining the cause of severe aortic regurgitation.

    PubMed

    DePace, N L; Nestico, P F; Kotler, M N; Mintz, G S; Kimbiris, D; Goel, I P; Glazier-Laskey, E E; Ross, J

    1984-01-01

    To assess the accuracy of echocardiography in determining the cause of aortic regurgitation M mode and cross sectional echocardiography were compared with angiography in 43 patients with predominant aortic regurgitation. Each patient had all three investigations performed during the same admission to hospital. In each instance, the cause of aortic regurgitation was confirmed at surgery or necropsy. Seventeen patients had rheumatic aortic valve disease, 13 bacterial endocarditis with a perforated or partially destroyed cusp, five a bicuspid aortic valve (four with a history of endocarditis), and eight aortic regurgitation secondary to aortic root dilatation or aneurysm. Overall sensitivity of echocardiography and aortography was 84% in determining the cause of aortic regurgitation. Thus, rheumatic valve disease and endocarditis appear to be the most common causes of severe aortic regurgitation in this hospital based population. Furthermore, echocardiography is a sensitive non-invasive technique for determining the cause of aortic regurgitation and allows differentiation of valvular from root causes of aortic regurgitation.

  3. Comparison of echocardiography and angiography in determining the cause of severe aortic regurgitation.

    PubMed Central

    DePace, N L; Nestico, P F; Kotler, M N; Mintz, G S; Kimbiris, D; Goel, I P; Glazier-Laskey, E E; Ross, J

    1984-01-01

    To assess the accuracy of echocardiography in determining the cause of aortic regurgitation M mode and cross sectional echocardiography were compared with angiography in 43 patients with predominant aortic regurgitation. Each patient had all three investigations performed during the same admission to hospital. In each instance, the cause of aortic regurgitation was confirmed at surgery or necropsy. Seventeen patients had rheumatic aortic valve disease, 13 bacterial endocarditis with a perforated or partially destroyed cusp, five a bicuspid aortic valve (four with a history of endocarditis), and eight aortic regurgitation secondary to aortic root dilatation or aneurysm. Overall sensitivity of echocardiography and aortography was 84% in determining the cause of aortic regurgitation. Thus, rheumatic valve disease and endocarditis appear to be the most common causes of severe aortic regurgitation in this hospital based population. Furthermore, echocardiography is a sensitive non-invasive technique for determining the cause of aortic regurgitation and allows differentiation of valvular from root causes of aortic regurgitation. Images PMID:6689919

  4. Out of phase: relevance of the medial septum for directional hearing and phonotaxis in the natural habitat of field crickets.

    PubMed

    Hirtenlehner, Stefan; Römer, Heiner; Schmidt, Arne K D

    2014-02-01

    A modified tracheal system is the anatomical basis for a pressure difference receiver in field crickets, where sound has access to the inner and outer side of the tympanum of the ear in the forelegs. A thin septum in the midline of a connecting trachea coupling both ears is regarded to be important in producing frequency-dependent interaural intensity differences (IIDs) for sound localization. However, the fundamental role of the septum in directional hearing has recently been challenged by the finding that the localization ability is ensured even with a perforated septum, at least under controlled laboratory conditions. Here, we investigated the influence of the medial septum on phonotaxis of female Gryllus bimaculatus under natural conditions. Surprisingly, even with a perforated septum, females reliably tracked a male calling song in the field. Although reduced by 5.2 dB, IIDs still averaged at 7.9 dB and provided a reliable proximate basis for the observed behavioural performance of operated females in the field. In contrast, in the closely related species Gryllus campestris the same septum perforation caused a dramatic decline in IIDs over all frequencies tested. We discuss this discrepancy with respect to a difference in the phenotype of their tracheal systems.

  5. Management of Recurrent Stricture Formation after Transverse Vaginal Septum Excision

    PubMed Central

    Gupta, Ridhima; Bozzay, Joseph D.; Williams, David L.; DePond, Robert T.; Gantt, Pickens A.

    2015-01-01

    Background. A transverse vaginal septum (TVS) is a rare obstructing anomaly, caused due to improper fusion of Müllerian ducts and urogenital sinus during embryogenesis. Case. A 15-year-old girl presented with primary amenorrhea. She had multiple congenital anomalies. Initial examination and imaging investigation revealed the presence of a unicornuate uterus and a TVS. The TVS was excised; however the patient was unable to perform vaginal dilation postoperatively leading to recurrent stricture formation. She underwent multiple surgeries for excision of the stricture. The patient was eventually evaluated every day in the clinic until she was able to demonstrate successful vaginal dilatation in the presence of a clinician. Summary and Conclusion. Properly guided regular and intensive vaginal dilation after TVS excision may decrease the need of reoperations due to recurrent stricture formation. PMID:26078895

  6. Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review.

    PubMed

    Versluis, A; Knulst, A C; Kruizinga, A G; Michelsen, A; Houben, G F; Baumert, J L; van Os-Medendorp, H

    2015-02-01

    Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary.

  7. Gastroesophageal reflux as a cause of chronic cough, severe asthma, and migratory pulmonary infiltrates

    PubMed Central

    Ribó, Paula; Pacheco, Adalberto; Arrieta, Paola; Teruel, Carlos; Cobeta, Ignacio

    2014-01-01

    Gastroesophageal reflux (GER), asthma-type cough and upper airway disease are the most common causes of chronic cough syndrome. We present a case in which impedance–pH monitoring indicated severe mixed acid–nonacid esophageal reflux reaching the upper third of the esophagus in 75% of nonacid events. GER and the associated aspiration episodes were shown to be the cause of severe asthma attacks and migratory pulmonary infiltrates. GER was caused by a sleeve gastrectomy, which seriously disabled the mechanisms preventing reflux from reaching the airways. Respiratory symptoms improved notably after abdominal surgery to correct the GER, suggesting a close causal relationship between GER and all the symptoms, including asthma. However, this issue remains unresolved in the literature. PMID:25473547

  8. Severe Cenani-Lenz syndrome caused by loss of LRP4 function.

    PubMed

    Kariminejad, Ariana; Stollfuß, Barbara; Li, Yun; Bögershausen, Nina; Boss, Karin; Hennekam, Raoul C M; Wollnik, Bernd

    2013-06-01

    Limb patterning and growth are complex embryonic processes in which the elaborately orchestrated interplay of diverse endocrine and paracrine factors is crucial to limb integrity. LRP4 is a lipoprotein receptor known for its regulatory effects on LRP5- and LRP6-mediated Wnt signaling, a pathway that plays a pivotal role in limb development. Recessive mutations in LRP4 have been shown to cause Cenani-Lenz syndrome, which is characterized by severe limb malformations, an unusual face, and renal abnormalities. We report on a child with severe Cenani-Lenz syndrome caused by a novel homozygous nonsense mutation in LRP4. The severity of the phenotype in a patient with absent residual LRP4 function may point to a genotype-phenotype correlation.

  9. DESIGN OF BEAM-EXTRACTION SEPTUM MAGNET FOR THE SNS.

    SciTech Connect

    TSOUPAS,N.; LEE,Y.Y.; RANK,J.; TUOZZOLO,J.

    2001-06-18

    The beam-extraction process from the SNS accumulator ring [1,2] requires a Lambertson septum magnet. In this paper we discuss the geometrical and magnetic field requirements of the magnet and present results obtained from two and three dimensional magnetic field calculations that shows the field quality in the regions of interest of the septum magnet.

  10. Nasal septum giant pyogenic granuloma after a long lasting nasal intubation: case report.

    PubMed

    Neves-Pinto, Roberto M; Carvalho, Adolpho; Araujo, Elizabeth; Alberto, Carlos; Basilio-De-Oliveira; De Carvalho, Gustavo Adolpho

    2005-03-01

    The authors present a case of Pyogenic Granuloma (PG) arising from the nasal septum in the posterior nasal cavity of a patient male sex, caucasian, 32 years old, with a previous history of cranioencephalic trauma, several neurosurgeries for different subsequent neurological problems and the use of a nasogastric tube for feeding (nasal intubation) during 30 days. He underwent surgery in St. Vincent de Paul Hospital (Rio de Janeiro) on May 18, 1993, for the tumor removal and straightening of the nasal septum. Under endoscopic guidance the complete excision of the tumor mass was perfectly done thanks to the excellent exposure of the lesion, provided by the enlarged telescopic view, and the wide access afforded by the septum straighttening plus the cartilaginous septum mobilization through the maxilla-premaxilla approach of Cottle, allied to the lateralization and volume reduction of the right inferior nasal concha, simultaneously performed, thus making lateral rhinotomy or "degloving" unnecessary. The patient is until now (2004) completely free of the lesion operated on. This is the first report in the literature of such a lesion associated to nasal intubation as the triggering agent.

  11. Mutation in TNXB gene causes moderate to severe Ehlers-Danlos syndrome

    PubMed Central

    Kaufman, Carolyn S; Butler, Merlin G

    2016-01-01

    We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A > T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classified as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient’s symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome (EDS). At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X deficiency, but the variant identified in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A > T nucleotide transition in the TNXB gene may be classified as disease-causing for EDS due to tenascin-X deficiency.

  12. Laparoscopic Treatment of Median Arcuate Ligament Syndrome: A Rare Cause of Chronic Severe Abdominal Pain

    PubMed Central

    Divarci, Emre; Celtik, Ulgen; Dokumcu, Zafer; Celik, Ahmet; Ergun, Orkan

    2017-01-01

    Median arcuate ligament syndrome is a rare disorder characterized by chronic postprandial abdominal pain and weight loss caused by compression on celiac artery. A 17-year-old girl with chronic severe abdominal pain and weight loss was referred to our clinic. Other causes of chronic abdominal pain were investigated and excluded. The compression on celiac artery was detected on Doppler ultrasound and diagnosis was confirmed by computed tomography angiography. The patient underwent laparoscopic release of median arcuate ligament. There were no intraoperative complications; however, partial pain response was observed postoperatively that necessitated para-spinal ganglion blockage. The patient is symptom-free in 1-year follow-up period. PMID:28082779

  13. Nonlinear excited waves on the interventricular septum

    NASA Astrophysics Data System (ADS)

    Bekki, Naoaki; Harada, Yoshifumi; Kanai, Hiroshi

    2012-11-01

    Using a novel ultrasonic noninvasive imaging method, we observe some phase singularities in propagating excited waves on a human cardiac interventricular septum (IVS) for a healthy young male. We present a possible physical model explaining one-dimensional dynamics of phase singularities in nonlinearly excited waves on the IVS. We show that at least one of the observed phase singularities in the excited waves on the IVS can be explained by the Bekki-Nozaki hole solution of the complex Ginzburg-Landau equation without any adjustable parameters. We conclude that the complex Ginzburg-Landau equation is such a suitable model for one-dimensional dynamics of cardiac phase singularities in nonlinearly excited waves on the IVS.

  14. Medial septum regulates the hippocampal spatial representation

    PubMed Central

    Mamad, Omar; McNamara, Harold M.; Reilly, Richard B.; Tsanov, Marian

    2015-01-01

    The hippocampal circuitry undergoes attentional modulation by the cholinergic medial septum. However, it is unclear how septal activation regulates the spatial properties of hippocampal neurons. We investigated here what is the functional effect of selective-cholinergic and non-selective septal stimulation on septo-hippocampal system. We show for the first time selective activation of cholinergic cells and their differential network effect in medial septum of freely-behaving transgenic rats. Our data show that depolarization of cholinergic septal neurons evokes frequency-dependent response from the non-cholinergic septal neurons and hippocampal interneurons. Our findings provide vital evidence that cholinergic effect on septo-hippocampal axis is behavior-dependent. During the active behavioral state the activation of septal cholinergic projections is insufficient to evoke significant change in the spiking of the hippocampal neurons. The efficiency of septo-hippocampal processing during active exploration relates to the firing patterns of the non-cholinergic theta-bursting cells. Non-selective septal theta-burst stimulation resets the spiking of hippocampal theta cells, increases theta synchronization, entrains the spiking of hippocampal place cells, and tunes the spatial properties in a timing-dependent manner. The spatial properties are augmented only when the stimulation is applied in the periphery of the place field or 400–650 ms before the animals approached the center of the field. In summary, our data show that selective cholinergic activation triggers a robust network effect in the septo-hippocampal system during inactive behavioral state, whereas the non-cholinergic septal activation regulates hippocampal functional properties during explorative behavior. Together, our findings uncover fast septal modulation on hippocampal network and reveal how septal inputs up-regulate and down-regulate the encoding of spatial representation. PMID:26175674

  15. Medial septum regulates the hippocampal spatial representation.

    PubMed

    Mamad, Omar; McNamara, Harold M; Reilly, Richard B; Tsanov, Marian

    2015-01-01

    The hippocampal circuitry undergoes attentional modulation by the cholinergic medial septum. However, it is unclear how septal activation regulates the spatial properties of hippocampal neurons. We investigated here what is the functional effect of selective-cholinergic and non-selective septal stimulation on septo-hippocampal system. We show for the first time selective activation of cholinergic cells and their differential network effect in medial septum of freely-behaving transgenic rats. Our data show that depolarization of cholinergic septal neurons evokes frequency-dependent response from the non-cholinergic septal neurons and hippocampal interneurons. Our findings provide vital evidence that cholinergic effect on septo-hippocampal axis is behavior-dependent. During the active behavioral state the activation of septal cholinergic projections is insufficient to evoke significant change in the spiking of the hippocampal neurons. The efficiency of septo-hippocampal processing during active exploration relates to the firing patterns of the non-cholinergic theta-bursting cells. Non-selective septal theta-burst stimulation resets the spiking of hippocampal theta cells, increases theta synchronization, entrains the spiking of hippocampal place cells, and tunes the spatial properties in a timing-dependent manner. The spatial properties are augmented only when the stimulation is applied in the periphery of the place field or 400-650 ms before the animals approached the center of the field. In summary, our data show that selective cholinergic activation triggers a robust network effect in the septo-hippocampal system during inactive behavioral state, whereas the non-cholinergic septal activation regulates hippocampal functional properties during explorative behavior. Together, our findings uncover fast septal modulation on hippocampal network and reveal how septal inputs up-regulate and down-regulate the encoding of spatial representation.

  16. Severe ARDS may cause right heart failure with extreme hepatomegaly but without hepatic failure.

    PubMed

    Søreide, E; Harboe, S; Søndenaa, K

    2002-08-01

    A young trauma patient developed severe adult respiratory distress syndrome (ARDS), right heart failure, hepatic congestion and an extreme hepatomegaly but no hepatic failure. The patient needed 100% oxygen during ventilatory support for 80 days and was weaned from the ventilator after more than 100 days. The hepatomegaly gradually disappeared. Four months after the injury, the anatomical shape of the lungs, heart and liver were normalized. This case illustrates that severe ARDS may cause right heart failure and extreme hepatomegaly due to venous congestion in the liver and spleen, but without hepatic failure.

  17. A case of odontogenic orbital cellulitis causing blindness by severe tension orbit.

    PubMed

    Park, Chang Hyun; Jee, Dong Hyun; La, Tae Yoon

    2013-02-01

    We report a very rare case of odontogenic orbital cellulitis causing blindness by severe tension orbit. A 41-yr old male patient had visited the hospital due to severe periorbital swelling and nasal stuffiness while he was treated for a periodontal abscess. He was diagnosed with odontogenic sinusitis and orbital cellulitis, and treated with antibiotics. The symptoms were aggravated and emergency sinus drainage was performed. On the next day, a sudden decrease in vision occurred with findings of ischemic optic neuropathy and central retinal artery occlusion. Deformation of the eyeball posterior pole into a cone shape was found from the orbital CT. A high-dose steroid was administered immediately resulting in improvements of periorbital swelling, but the patient's vision had not recovered. Odontogenic orbital cellulitis is relatively rare, but can cause blindness via rapidly progressing tension orbit. Therefore even the simplest of dental problems requires careful attention.

  18. Recurrent Acute Decompensated Heart Failure Owing to Severe Iron Deficiency Anemia Caused by Inappropriate Habitual Bloodletting

    PubMed Central

    Lim, Woo-Hyun; Kim, Hack-Lyoung; Kim, Ki-Hwan; Na, Sang Hoon; Lee, Hyun-Jung; Kang, Eun Gyu; Seo, Jae-Bin; Chung, Woo-Young; Zo, Joo-Hee; Hong, Jung Ae; Kim, Kwangyoun; Kim, Myung-A

    2015-01-01

    A 68-year-old woman visited the emergency department twice with symptoms of acute heart failure including shortness of breath, general weakness, and abdominal distension. Laboratory findings showed extremely low level of serum hemoglobin at 1.4 g/dL. Echocardiographic examination demonstrated dilated left ventricular cavity with systolic dysfunction and moderate amount of pericardial effusion. In this patient, acute heart failure due to severe iron deficiency anemia was caused by inappropriate habitual bloodletting. PMID:26755934

  19. Root causes and impacts of severe accidents at large nuclear power plants.

    PubMed

    Högberg, Lars

    2013-04-01

    The root causes and impacts of three severe accidents at large civilian nuclear power plants are reviewed: the Three Mile Island accident in 1979, the Chernobyl accident in 1986, and the Fukushima Daiichi accident in 2011. Impacts include health effects, evacuation of contaminated areas as well as cost estimates and impacts on energy policies and nuclear safety work in various countries. It is concluded that essential objectives for reactor safety work must be: (1) to prevent accidents from developing into severe core damage, even if they are initiated by very unlikely natural or man-made events, and, recognizing that accidents with severe core damage may nevertheless occur; (2) to prevent large-scale and long-lived ground contamination by limiting releases of radioactive nuclides such as cesium to less than about 100 TBq. To achieve these objectives the importance of maintaining high global standards of safety management and safety culture cannot be emphasized enough. All three severe accidents discussed in this paper had their root causes in system deficiencies indicative of poor safety management and poor safety culture in both the nuclear industry and government authorities.

  20. [The very severe sensorineural deafness patients caused by rubella virus infection: two cases report].

    PubMed

    Ma, Jing; Wan, Lang; Xu, Fen

    2015-09-01

    To explore the audiological features in children who were sever sensorineural hearing loss infected with rubella virus. There were two cases of rubella virus infection in children who were deaf, they conducted the distortion product otoacoustic emission, ABR and auditory steady-state evoked response (ASSR) examination, then analyzed the results comprehensively. Two patients' mothers were prompted to have infected rubella virus during the early three months pregnant period by history and laboratory tests. The two patients were not detected deafness gene mutation. Audiology results implied the two patients were very severe binaural sensorineural deafness, so they were recommended to equipped with hearing aids and cochlear implant surgery. Early pregnancy women infected with rubella virus can cause very severe offspring sensorineural deafness. The crowd whose mother were suspected to infect with rubella virus in early pregnancy, that should be tracked and detected hearing in order to achieve early detection, early intervention and early treatment.

  1. A severe red tide (Tampa Bay, 2005) causes an anomalous decrease in biological sound.

    PubMed

    Indeck, Katherine L; Simard, Peter; Gowans, Shannon; Lowerre-Barbieri, Susan; Mann, David A

    2015-09-01

    Although harmful algal blooms (HABs) are known to cause morbidity and mortality in marine organisms, their sublethal effects are poorly understood. The purpose of this study was to compare ambient noise levels during a severe HAB event in Tampa Bay, Florida, to those during non-HAB periods. Passive acoustic monitoring was conducted using bottom-mounted autonomous acoustic recorders during a severe HAB in summer 2005, and in summers 2006, 2011 and 2012 (non-severe HAB years). Ambient noise levels were significantly higher during the non-HAB years due to an abundance of snapping shrimp (Alpheidae) sounds and fish chorusing. The difference of sound intensity between the study years is most likely attributable to effects of the HAB on the abundance and/or behaviour of fish and snapping shrimp as a result of mortality and stress-induced behavioural modifications.

  2. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy.

    PubMed

    Ravenscroft, Gianina; Miyatake, Satoko; Lehtokari, Vilma-Lotta; Todd, Emily J; Vornanen, Pauliina; Yau, Kyle S; Hayashi, Yukiko K; Miyake, Noriko; Tsurusaki, Yoshinori; Doi, Hiroshi; Saitsu, Hirotomo; Osaka, Hitoshi; Yamashita, Sumimasa; Ohya, Takashi; Sakamoto, Yuko; Koshimizu, Eriko; Imamura, Shintaro; Yamashita, Michiaki; Ogata, Kazuhiro; Shiina, Masaaki; Bryson-Richardson, Robert J; Vaz, Raquel; Ceyhan, Ozge; Brownstein, Catherine A; Swanson, Lindsay C; Monnot, Sophie; Romero, Norma B; Amthor, Helge; Kresoje, Nina; Sivadorai, Padma; Kiraly-Borri, Cathy; Haliloglu, Goknur; Talim, Beril; Orhan, Diclehan; Kale, Gulsev; Charles, Adrian K; Fabian, Victoria A; Davis, Mark R; Lammens, Martin; Sewry, Caroline A; Manzur, Adnan; Muntoni, Francesco; Clarke, Nigel F; North, Kathryn N; Bertini, Enrico; Nevo, Yoram; Willichowski, Ekkhard; Silberg, Inger E; Topaloglu, Haluk; Beggs, Alan H; Allcock, Richard J N; Nishino, Ichizo; Wallgren-Pettersson, Carina; Matsumoto, Naomichi; Laing, Nigel G

    2013-07-11

    Nemaline myopathy (NEM) is a common congenital myopathy. At the very severe end of the NEM clinical spectrum are genetically unresolved cases of autosomal-recessive fetal akinesia sequence. We studied a multinational cohort of 143 severe-NEM-affected families lacking genetic diagnosis. We performed whole-exome sequencing of six families and targeted gene sequencing of additional families. We identified 19 mutations in KLHL40 (kelch-like family member 40) in 28 apparently unrelated NEM kindreds of various ethnicities. Accounting for up to 28% of the tested individuals in the Japanese cohort, KLHL40 mutations were found to be the most common cause of this severe form of NEM. Clinical features of affected individuals were severe and distinctive and included fetal akinesia or hypokinesia and contractures, fractures, respiratory failure, and swallowing difficulties at birth. Molecular modeling suggested that the missense substitutions would destabilize the protein. Protein studies showed that KLHL40 is a striated-muscle-specific protein that is absent in KLHL40-associated NEM skeletal muscle. In zebrafish, klhl40a and klhl40b expression is largely confined to the myotome and skeletal muscle, and knockdown of these isoforms results in disruption of muscle structure and loss of movement. We identified KLHL40 mutations as a frequent cause of severe autosomal-recessive NEM and showed that it plays a key role in muscle development and function. Screening of KLHL40 should be a priority in individuals who are affected by autosomal-recessive NEM and who present with prenatal symptoms and/or contractures and in all Japanese individuals with severe NEM.

  3. Mutations in KLHL40 Are a Frequent Cause of Severe Autosomal-Recessive Nemaline Myopathy

    PubMed Central

    Ravenscroft, Gianina; Miyatake, Satoko; Lehtokari, Vilma-Lotta; Todd, Emily J.; Vornanen, Pauliina; Yau, Kyle S.; Hayashi, Yukiko K.; Miyake, Noriko; Tsurusaki, Yoshinori; Doi, Hiroshi; Saitsu, Hirotomo; Osaka, Hitoshi; Yamashita, Sumimasa; Ohya, Takashi; Sakamoto, Yuko; Koshimizu, Eriko; Imamura, Shintaro; Yamashita, Michiaki; Ogata, Kazuhiro; Shiina, Masaaki; Bryson-Richardson, Robert J.; Vaz, Raquel; Ceyhan, Ozge; Brownstein, Catherine A.; Swanson, Lindsay C.; Monnot, Sophie; Romero, Norma B.; Amthor, Helge; Kresoje, Nina; Sivadorai, Padma; Kiraly-Borri, Cathy; Haliloglu, Goknur; Talim, Beril; Orhan, Diclehan; Kale, Gulsev; Charles, Adrian K.; Fabian, Victoria A.; Davis, Mark R.; Lammens, Martin; Sewry, Caroline A.; Manzur, Adnan; Muntoni, Francesco; Clarke, Nigel F.; North, Kathryn N.; Bertini, Enrico; Nevo, Yoram; Willichowski, Ekkhard; Silberg, Inger E.; Topaloglu, Haluk; Beggs, Alan H.; Allcock, Richard J.N.; Nishino, Ichizo; Wallgren-Pettersson, Carina; Matsumoto, Naomichi; Laing, Nigel G.

    2013-01-01

    Nemaline myopathy (NEM) is a common congenital myopathy. At the very severe end of the NEM clinical spectrum are genetically unresolved cases of autosomal-recessive fetal akinesia sequence. We studied a multinational cohort of 143 severe-NEM-affected families lacking genetic diagnosis. We performed whole-exome sequencing of six families and targeted gene sequencing of additional families. We identified 19 mutations in KLHL40 (kelch-like family member 40) in 28 apparently unrelated NEM kindreds of various ethnicities. Accounting for up to 28% of the tested individuals in the Japanese cohort, KLHL40 mutations were found to be the most common cause of this severe form of NEM. Clinical features of affected individuals were severe and distinctive and included fetal akinesia or hypokinesia and contractures, fractures, respiratory failure, and swallowing difficulties at birth. Molecular modeling suggested that the missense substitutions would destabilize the protein. Protein studies showed that KLHL40 is a striated-muscle-specific protein that is absent in KLHL40-associated NEM skeletal muscle. In zebrafish, klhl40a and klhl40b expression is largely confined to the myotome and skeletal muscle, and knockdown of these isoforms results in disruption of muscle structure and loss of movement. We identified KLHL40 mutations as a frequent cause of severe autosomal-recessive NEM and showed that it plays a key role in muscle development and function. Screening of KLHL40 should be a priority in individuals who are affected by autosomal-recessive NEM and who present with prenatal symptoms and/or contractures and in all Japanese individuals with severe NEM. PMID:23746549

  4. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome.

    PubMed

    Brown, Kyla; Selfridge, Jim; Lagger, Sabine; Connelly, John; De Sousa, Dina; Kerr, Alastair; Webb, Shaun; Guy, Jacky; Merusi, Cara; Koerner, Martha V; Bird, Adrian

    2016-02-01

    Rett syndrome is caused by mutations in the X-linked MECP2 gene, which encodes a chromosomal protein that binds to methylated DNA. Mouse models mirror the human disorder and therefore allow investigation of phenotypes at a molecular level. We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice. Together these three alleles comprise ∼25% of all RTT mutations in humans, but they vary significantly in average severity. This spectrum is mimicked in the mouse models; R133C being least severe, T158M most severe and R306C of intermediate severity. Both R133C and T158M mutations cause compound phenotypes at the molecular level, combining compromised DNA binding with reduced stability, the destabilizing effect of T158M being more severe. Our findings contradict the hypothesis that the R133C mutation exclusively abolishes binding to hydroxymethylated DNA, as interactions with DNA containing methyl-CG, methyl-CA and hydroxymethyl-CA are all reduced in vivo. We find that MeCP2[T158M] is significantly less stable than MeCP2[R133C], which may account for the divergent clinical impact of the mutations. Overall, this allelic series recapitulates human RTT severity, reveals compound molecular aetiologies and provides a valuable resource in the search for personalized therapeutic interventions.

  5. Severe maternal morbidity from direct obstetric causes in West Africa: incidence and case fatality rates.

    PubMed Central

    Prual, A.; Bouvier-Colle, M. H.; de Bernis, L.; Bréart, G.

    2000-01-01

    Data on maternal morbidity make it possible to assess how many women are likely to need essential obstetric care, and permit the organization, monitoring and evaluation of safe motherhood programmes. In the present paper we propose operational definitions of severe maternal morbidity and report the frequency of such morbidity as revealed in a population-based survey of a cohort of 20,326 pregnant women in six West African countries. The methodology and questionnaires were the same in all areas. Each pregnant woman had four contacts with the obstetric survey team: at inclusion, between 32 and 36 weeks of amenorrhoea, during delivery and 60 days postpartum. Direct obstetric causes of severe morbidity were observed in 1215 women (6.17 cases per 100 live births). This ratio varied significantly between areas, from 3.01% in Bamako to 9.05% in Saint-Louis. The main direct causes of severe maternal morbidity were: haemorrhage (3.05 per 100 live births); obstructed labour (2.05 per 100), 23 cases of which involved uterine rupture (0.12 per 100); hypertensive disorders of pregnancy (0.64 per 100), 38 cases of which involved eclampsia (0.19 per 100); and sepsis (0.09 per 100). Other direct obstetric causes accounted for 12.2% of cases. Case fatality rates were very high for sepsis (33.3%), uterine rupture (30.4%) and eclampsia (18.4%); those for haemorrhage varied from 1.9% for antepartum or peripartum haemorrhage to 3.7% for abruptio placentae. Thus at least 3-9% of pregnant women required essential obstetric care. The high case fatality rates of several complications reflected a poor quality of obstetric care. PMID:10859853

  6. Multiple Magnetic Foreign Bodies Causing Severe Digestive Tract Injuries in a Child

    PubMed Central

    Si, Xinmin; Du, Baofeng; Huang, Lei

    2016-01-01

    Foreign body (FB) ingestion is a common emergency as well as a major cause of accidental injury and represents a severe public health problem in childhood, especially in infants. Most cases of FB ingestion reported in children aged between 6 months and 3 years depend primarily on the fact that young children are more likely to explore objects using their mouth and are not able to distinguish edible objects from nonedible ones, their teeth are physiologically lacking, and they have poor swallowing coordination. Although, sometimes it can cause serious complications, FB ingestion generally has a low mortality rate. However, accidental ingestion of magnetic toys, as a rare kind of FB mostly encountered in children, has now become more common due to the increased availability of objects and toys with magnetic elements. The majority of magnetic FB traverse the gastrointestinal (GI) system spontaneously without complication, but in rare cases may cause severe damages to the GI tract due to its special pathogenesis [Kay and Wyllie: Curr Gastroenterol Rep 2005;7: 212-218]. Ingestion of multiple magnets may be related to increased morbidity resulting in a delay of recognition of FB injury that can lead to serious complications and require surgical resolution. PMID:28100992

  7. SVA retrotransposition in exon 6 of the coagulation factor IX gene causing severe hemophilia B.

    PubMed

    Nakamura, Yuki; Murata, Moe; Takagi, Yuki; Kozuka, Toshihiro; Nakata, Yukiko; Hasebe, Ryo; Takagi, Akira; Kitazawa, Jun-ichi; Shima, Midori; Kojima, Tetsuhito

    2015-07-01

    Hemophilia B is an X-linked recessive bleeding disorder caused by abnormalities of the coagulation factor IX gene (F9). Insertion mutations in F9 ranging from a few to more than 100 base pairs account for only a few percent of all hemophilia B cases. We investigated F9 to elucidate genetic abnormalities causing severe hemophilia B in a Japanese subject. We performed PCR-mediated analysis of F9 and identified a large insertion in exon 6. Next, we carried out direct sequencing of a PCR clone of the whole insert using nested deletion by exonuclease III and S1 nuclease. We identified an approximately 2.5-kb SINE-VNTR-Alu (SVA)-F element flanked by 15-bp duplications in the antisense orientation in exon 6. Additionally, we carried out exontrap analysis to assess the effect of this retrotransposition on mRNA splicing. We observed that regular splicing at exons 5 and 6 of F9 was disturbed by the SVA retrotransposition, suggesting that abnormal FIX mRNA may be reduced by nonsense-mediated mRNA decay. In conclusion, this is the first report of SVA retrotransposition causing severe hemophilia B; only five cases of LINE-1 or Alu retrotranspositions in F9 have been reported previously.

  8. B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ.

    PubMed

    Salzer, Elisabeth; Santos-Valente, Elisangela; Klaver, Stefanie; Ban, Sol A; Emminger, Wolfgang; Prengemann, Nina Kathrin; Garncarz, Wojciech; Müllauer, Leonhard; Kain, Renate; Boztug, Heidrun; Heitger, Andreas; Arbeiter, Klaus; Eitelberger, Franz; Seidel, Markus G; Holter, Wolfgang; Pollak, Arnold; Pickl, Winfried F; Förster-Waldl, Elisabeth; Boztug, Kaan

    2013-04-18

    Primary B-cell disorders comprise a heterogeneous group of inherited immunodeficiencies, often associated with autoimmunity causing significant morbidity. The underlying genetic etiology remains elusive in the majority of patients. In this study, we investigated a patient from a consanguineous family suffering from recurrent infections and severe lupuslike autoimmunity. Immunophenotyping revealed progressive decrease of CD19(+) B cells, a defective class switch indicated by low numbers of IgM- and IgG-memory B cells, as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site mutation in protein C kinase δ (PRKCD), causing the absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate was decreased, and mRNA levels of nuclear factor interleukin (IL)-6 and IL-6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B-cell deficiency with severe autoimmunity.

  9. Depletion of WRN protein causes RACK1 to activate several protein kinase C isoforms.

    PubMed

    Massip, L; Garand, C; Labbé, A; Perreault, E; Turaga, R V N; Bohr, V A; Lebel, M

    2010-03-11

    Werner's syndrome (WS) is a rare autosomal disease characterized by the premature onset of several age-associated pathologies. The protein defective in patients with WS (WRN) is a helicase/exonuclease involved in DNA repair, replication, transcription and telomere maintenance. In this study, we show that a knock down of the WRN protein in normal human fibroblasts induces phosphorylation and activation of several protein kinase C (PKC) enzymes. Using a tandem affinity purification strategy, we found that WRN physically and functionally interacts with receptor for activated C-kinase 1 (RACK1), a highly conserved anchoring protein involved in various biological processes, such as cell growth and proliferation. RACK1 binds strongly to the RQC domain of WRN and weakly to its acidic repeat region. Purified RACK1 has no impact on the helicase activity of WRN, but selectively inhibits WRN exonuclease activity in vitro. Interestingly, knocking down RACK1 increased the cellular frequency of DNA breaks. Depletion of the WRN protein in return caused a fraction of nuclear RACK1 to translocate out of the nucleus to bind and activate PKCdelta and PKCbetaII in the membrane fraction of cells. In contrast, different DNA-damaging treatments known to activate PKCs did not induce RACK1/PKCs association in cells. Overall, our results indicate that a depletion of the WRN protein in normal fibroblasts causes the activation of several PKCs through translocation and association of RACK1 with such kinases.

  10. Depletion of WRN protein causes RACK1 to activate several protein kinase C isoforms

    PubMed Central

    Massip, L; Garand, C; Labbé, A; Perreault, È; Turaga, RVN; Bohr, VA; Lebel, M

    2015-01-01

    Werner’s syndrome (WS) is a rare autosomal disease characterized by the premature onset of several age-associated pathologies. The protein defective in patients with WS (WRN) is a helicase/exonuclease involved in DNA repair, replication, transcription and telomere maintenance. In this study, we show that a knock down of the WRN protein in normal human fibroblasts induces phosphorylation and activation of several protein kinase C (PKC) enzymes. Using a tandem affinity purification strategy, we found that WRN physically and functionally interacts with receptor for activated C-kinase 1 (RACK1), a highly conserved anchoring protein involved in various biological processes, such as cell growth and proliferation. RACK1 binds strongly to the RQC domain of WRN and weakly to its acidic repeat region. Purified RACK1 has no impact on the helicase activity of WRN, but selectively inhibits WRN exonuclease activity in vitro. Interestingly, knocking down RACK1 increased the cellular frequency of DNA breaks. Depletion of the WRN protein in return caused a fraction of nuclear RACK1 to translocate out of the nucleus to bind and activate PKCδ and PKCβII in the membrane fraction of cells. In contrast, different DNA-damaging treatments known to activate PKCs did not induce RACK1/PKCs association in cells. Overall, our results indicate that a depletion of the WRN protein in normal fibroblasts causes the activation of several PKCs through translocation and association of RACK1 with such kinases. PMID:19966859

  11. Severe Hypernatremia Caused by Acute Exogenous Salt Intake Combined with Primary Hypothyroidism

    PubMed Central

    Jung, Woo Jin; Park, Su Min; Park, Jong Man; Rhee, Harin; Kim, Il Young; Lee, Dong Won; Lee, Soo Bong; Seong, Eun Young; Kwak, Ihm Soo

    2016-01-01

    This report describes a case of severe hypernatremia with a serum sodium concentration of 188.1mmol/L caused by exogenous salt intake. A 26-year-old man diagnosed with Crohn's disease 5 years previously visited our clinic due to generalized edema and personality changes, with aggressive behavior. He had compulsively consumed salts, ingesting approximately 154 g of salt over the last 4 days. Despite careful fluid management that included not only hypotonic fluid therapy for 8 hours but also hypertonic saline administration, his serum sodium level decreased sharply at 40.6 mmol/L; however, it returned to normal within 72-hour of treatment without any neurological deficits. Primary hypothyroidism was also diagnosed. He was discharged after 9 days from admission, with a stable serum sodium level. We have described the possibility of successful treatment in a patient with hypernatremia caused by acute salt intoxication without sustained hypotonic fluid therapy. PMID:28275385

  12. Beamstrahlung Photon Load on the TESLA Extraction Septum Blade(LCC-0104)

    SciTech Connect

    Seryi, A

    2003-10-02

    This note describes work performed in the framework of the International Linear Collider Technical Review Committee [1] to estimate the power load on the TESLA extraction septum blade due to beamstrahlung photons. It is shown, that under realistic conditions the photon load can be several orders of magnitude higher than what was estimated in the TESLA TDR [2] for the ideal Gaussian beams, potentially representing a serious limitation of the current design.

  13. Causes of non-adherence to therapeutic guidelines in severe community-acquired pneumonia

    PubMed Central

    Gattarello, Simone; Ramírez, Sergio; Almarales, José Rafael; Borgatta, Bárbara; Lagunes, Leonel; Encina, Belén; Rello, Jordi

    2015-01-01

    Objective To assess the adherence to Infectious Disease Society of America/American Thoracic Society guidelines and the causes of lack of adherence during empirical antibiotic prescription in severe pneumonia in Latin America. Methods A clinical questionnaire was submitted to 36 physicians from Latin America; they were asked to indicate the empirical treatment in two fictitious cases of severe respiratory infection: community-acquired pneumonia and nosocomial pneumonia. Results In the case of communityacquired pneumonia, 11 prescriptions of 36 (30.6%) were compliant with international guidelines. The causes for non-compliant treatment were monotherapy (16.0%), the unnecessary prescription of broad-spectrum antibiotics (40.0%) and the use of non-recommended antibiotics (44.0%). In the case of nosocomial pneumonia, the rate of adherence to the Infectious Disease Society of America/American Thoracic Society guidelines was 2.8% (1 patient of 36). The reasons for lack of compliance were monotherapy (14.3%) and a lack of dual antibiotic coverage against Pseudomonas aeruginosa (85.7%). If monotherapy with an antipseudomonal antibiotic was considered adequate, the antibiotic treatment would be adequate in 100% of the total prescriptions. Conclusion The compliance rate with the Infectious Disease Society of America/American Thoracic Society guidelines in the community-acquired pneumonia scenario was 30.6%; the most frequent cause of lack of compliance was the indication of monotherapy. In the case of nosocomial pneumonia, the compliance rate with the guidelines was 2.8%, and the most important cause of non-adherence was lack of combined antipseudomonal therapy. If the use of monotherapy with an antipseudomonal antibiotic was considered the correct option, the treatment would be adequate in 100% of the prescriptions. PMID:25909312

  14. Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.

    PubMed

    Moulson, Casey L; Fong, Loren G; Gardner, Jennifer M; Farber, Emily A; Go, Gloriosa; Passariello, Annalisa; Grange, Dorothy K; Young, Stephen G; Miner, Jeffrey H

    2007-09-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare precocious aging syndrome caused by mutations in LMNA that lead to synthesis of a mutant form of prelamin A, generally called progerin, that cannot be processed to mature lamin A. Most HGPS patients have a recurrent heterozygous de novo mutation in exon 11 of LMNA, c.1824C>T/p.G608G; this synonymous mutation activates a nearby cryptic splice donor site, resulting in synthesis of the mutant prelamin A, progerin, which lacks 50 amino acids within the carboxyl-terminal domain. Abnormal splicing is incomplete, so the mutant allele produces some normally-spliced transcripts. Nevertheless, the synthesis of progerin is sufficient to cause misshapen nuclei in cultured cells and severe disease phenotypes in affected patients. Here we present two patients with extraordinarily severe forms of progeria caused by unusual mutations in LMNA. One had a splice site mutation (c.1968+1G>A; or IVS11+1G>A), and the other had a novel synonymous coding region mutation (c.1821G>A/p.V607V). Both mutations caused very frequent use of the same exon 11 splice donor site that is activated in typical HGPS patients. As a consequence, the ratios of progerin mRNA and protein to wild-type were higher than in typical HGPS patients. Fibroblasts from both patients exhibited nuclear shape abnormalities typical of HGPS, and cells treated with a protein farnesyltransferase inhibitor exhibited fewer misshapen nuclei. Thus, farnesyltransferase inhibitors may prove to be useful even when progerin expression levels are higher than those in typical HGPS patients.

  15. The onion skin-like organization of the septum arises from multiple embryonic origins to form multiple adult neuronal fates.

    PubMed

    Wei, B; Huang, Z; He, S; Sun, C; You, Y; Liu, F; Yang, Z

    2012-10-11

    In the past several decades, tremendous progress has been achieved through developmental studies of the central nervous system structures such as the cerebral cortex. The septum, which receives reciprocal connections from a variety of brain structures, contains diverse projection neurons but few interneurons. However, the mechanisms underlying its development remain poorly understood. Here we show that the septum is organized into an onion skin-like structure composed of five groups of neurons. These neurons are parvalbumin, choline acetyltransferase, neuronal nitric oxide synthase, calretinin and calbindin immunoreactive. Using the BrdU birth-dating method, we found that these five groups of neurons in the septum are grossly generated following an outside-in pattern. Interestingly, the distinct molecular identities of these neuronal subtypes correspond to their heterogeneous subpallial origins. Using three specific transgenic mouse lines and focal in utero electroporation of Cre-reporter plasmid, we showed that septal neurons originate from not only local progenitor regions but also neighboring progenitor regions including the medial ganglionic eminence and preoptic area. Thus, the neuronal diversity of the septum is achieved through both temporal and spatial control. Our results also suggest that multiple neuronal subtypes arrive to the septum through both radial and tangential migration. Based on these findings, we proposed a novel developmental model involving multiple spatial-temporal origins of septal neurons. This study presents new perspectives for comprehensively exploring septal functions in brain circuits.

  16. X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene.

    PubMed

    Brockmann, Knut; Dumitrescu, Alexandra M; Best, Thomas T; Hanefeld, Folker; Refetoff, Samuel

    2005-06-01

    We previously reported two unrelated boys aged 3 and 8 years with mutations in the thyroid hormone transporter gene MCT8 resulting in severe global retardation and an uncommon pattern of thyroid hormone abnormalities. We now further describe an unusual neurological phenotype associated with these mutations, namely paroxysmal kinesigenic dyskinesias (PKD), provoked by certain stimuli including changing of their clothes or diapers. It is not clear how the MCT8 defect causes PKDs. PKDs have been previously noted in patients with thyroid abnormalities. This novel X-linked condition widens the spectrum of secondary PKDs.

  17. Severe oropharyngeal trauma caused by toothbrush--case report and review of 13 cases.

    PubMed

    Kumar, S; Gupta, R; Arora, R; Saxena, S

    2008-10-25

    Foreign body trauma to the oral cavity is fairly common. However, severe injuries caused by a toothbrush are rarely reported. We report a case of a 35-year-old epileptic patient who suffered seizures while brushing his teeth. During this episode, he self-inflicted a grievous injury to his oro-pharynx with his toothbrush which went unnoticed for 11 months. Thirteen cases of toothbrush induced trauma to this area are reviewed and a classification of these injuries is proposed. Complications related to these injuries are highlighted and their management discussed.

  18. Two cases of severe sepsis caused by Bacillus pumilus in neonatal infants.

    PubMed

    Kimouli, Maria; Vrioni, Georgia; Papadopoulou, Magdalini; Koumaki, Vasiliki; Petropoulou, Dimitra; Gounaris, Antonios; Friedrich, Alexander W; Tsakris, Athanassios

    2012-04-01

    Bacillus pumilus is an environmental contaminant that has been rarely associated with clinical infections. Here, two cases of severe sepsis caused by B. pumilus are described in two full-term neonates; one in a female infant with no factors predisposing her to infection and the other in a male infant requiring mechanical ventilation and an intravenous catheter. In both cases, the micro-organism was recovered from repeated blood cultures and was identified using biochemical assays and 16S rRNA gene sequencing. Both infants were successfully treated with vancomycin. This report reveals the potential role of B. pumilus as a bloodstream pathogen during infancy.

  19. Low-Velocity Nail-Gun Injuries to the Interventricular Septum: Report of Two Cases, One in a Child

    PubMed Central

    Michalsen, Kara L.; Iguidbashian, John P.; Kyser, James P.

    2015-01-01

    Nail-gun injury to the heart is rare. Nail-gun injury to the interventricular septum is rarer: we could find only 5 reported cases, and none involving a child. We report 2 additional cases, in which nails penetrated the interventricular septum without causing acute pericardial tamponade, heart block, or shunt across the septum. Transesophageal echocardiography provides a dynamic way to evaluate the patient preoperatively, intraoperatively, and postoperatively. In the cases reported here, both the adult with multiple interventricular nails and the child with a single nail underwent foreign-object removal via median sternotomy. The child needed cardiopulmonary bypass for removal of the nail. There were no short-term or long-term sequelae from these interventricular septal injuries. PMID:26413027

  20. First Report of Oryctes rhinoceros nudivirus (Coleoptera: Scarabaeidae) Causing Severe Disease in Allomyrina dichotoma in Korea

    PubMed Central

    Lee, Seokhyun; Park, Kwan-Ho; Nam, Sung-Hee; Kwak, Kyu-Won; Choi, Ji-Young

    2015-01-01

    Oryctes rhinoceros nudivirus (OrNV) has been known to cause severe disease in coconut palm rhinoceros beetle, Oryctes rhinoceros, in Southeastern Asia and is used as a biological control to reduce the pest population. Here, we report for the first time that the OrNV may have landed on Korea and may be the major pathogen for diseased larvae of Korean horn beetle, Allomyrina dichotoma. After peroral inoculation, over 60% of infected larvae perished in 6 wk. This viral disease spreads very fast in several locations throughout Korea. This threat not only makes economic loss of local farms rearing A. dichotoma larvae but also may disturb the ecosystem by transmitting to wild A. dichotoma. PMID:25765317

  1. Multilobular tumour of the caudal cranium causing severe cerebral and cerebellar compression in a dog.

    PubMed

    Psychas, Vassilios; Loukopoulos, Panayiotis; Polizopoulou, Zoe S; Sofianidis, Georgios

    2009-03-01

    Multilobular tumour of bone (MTB) is an uncommon tumour and is usually located in the skull. A 13-year-old mixed breed dog was presented with a two-week history of progressively worsening vestibular dysfunction and cognitive abnormalities; it appeared demented and showed asymmetric ataxia and hypermetria of all limbs. The owner opted to have the animal euthanised. Necropsy revealed a large mass occupying the right occipital, parietal and temporal bones, severely compressing the cerebellum and the right occipital lobe. Histologically, it was characterised by the presence of multiple lobules containing osteoid or cartilage and separated by fibrous septae, features typical of MTB. Lung metastases were evident. To our knowledge, this is the first report of an MTB causing both severe cerebral and cerebellar compression and the second detailed report of an MTB of the occipital bone. MTB should be included in the differential diagnosis of bone tumours as well as in cases with central vestibular disease.

  2. Evidence of increasing drought severity caused by temperature rise in southern Europe

    NASA Astrophysics Data System (ADS)

    Vicente-Serrano, Sergio M.; Lopez-Moreno, Juan-I.; Beguería, Santiago; Lorenzo-Lacruz, Jorge; Sanchez-Lorenzo, Arturo; García-Ruiz, José M.; Azorin-Molina, Cesar; Morán-Tejeda, Enrique; Revuelto, Jesús; Trigo, Ricardo; Coelho, Fatima; Espejo, Francisco

    2014-04-01

    We use high quality climate data from ground meteorological stations in the Iberian Peninsula (IP) and robust drought indices to confirm that drought severity has increased in the past five decades, as a consequence of greater atmospheric evaporative demand resulting from temperature rise. Increased drought severity is independent of the model used to quantify the reference evapotranspiration. We have also focused on drought impacts to drought-sensitive systems, such as river discharge, by analyzing streamflow data for 287 rivers in the IP, and found that hydrological drought frequency and severity have also increased in the past five decades in natural, regulated and highly regulated basins. Recent positive trend in the atmospheric water demand has had a direct influence on the temporal evolution of streamflows, clearly identified during the warm season, in which higher evapotranspiration rates are recorded. This pattern of increase in evaporative demand and greater drought severity is probably applicable to other semiarid regions of the world, including other Mediterranean areas, the Sahel, southern Australia and South Africa, and can be expected to increasingly compromise water supplies and cause political, social and economic tensions among regions in the near future.

  3. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion

    PubMed Central

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-01-01

    Abstract Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date. We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy. Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited. PMID:27368013

  4. Superior Mesenteric Vein Occlusion Causing Severe Gastrointestinal Haemorrhage in Two Paediatric Cases

    PubMed Central

    Fox, Anna L.; Jones, Matthew; Healey, Andrew; Auth, Marcus K. H.

    2012-01-01

    Reports about superior mesenteric vein thrombosis in childhood are very rare and have not been associated with gastrointestinal bleeding. We describe two cases of severe bleeding from the upper and lower gastrointestinal tract in children who had undergone complex abdominal surgery at considerable time before. The first child had a tracheoesophageal fistula, corrected by division, gastrostomy insertion, and repair of duodenal rupture. The child presented with severe bleeding from the gastrostomy site and was diagnosed with a thrombosis of the proximal superior mesenteric vein. The second child had a gastroschisis and duodenal atresia, and required duodenoplasty, gastrostomy insertion, hemicolectomy, and adhesiolysis. The child presented with intermittent severe lower gastrointestinal bleeding, resulting from collateral vessels at location of the surgical connections. He was diagnosed with a thrombosis of the superior mesenteric vein. In both children, the extensive previous surgery and anastomosis were considered the cause of the mesenteric thrombosis. CT angiography confirmed the diagnosis in both cases, in addition to characteristic findings on endoscopy. Paediatricians should suspect this condition in children with severe gastrointestinal bleeding, particularly in children with previous, complex abdominal surgery. PMID:23198238

  5. Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in Patients with Type 2 Diabetes

    PubMed Central

    Cha, Seon-Ah; Yun, Jae-Seung; Lim, Tae-Seok; Hwang, Seawon; Yim, Eun-Jung; Song, Ki-Ho; Yoo, Ki-Dong; Park, Yong-Moon; Ahn, Yu-Bae

    2016-01-01

    Background We investigated the association between severe hypoglycemia (SH) and the risk of cardiovascular (CV) or all-cause mortality in patients with type 2 diabetes. Methods The study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR), who consecutively enrolled (n=1,260) from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis. Results Among the 906 participants (71.9%) who completed follow-up, 85 patients (9.4%) had at least one episode of SH, and 86 patients (9.5%) died (9.1 per 1,000 patient-years). Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P=0.003) and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P=0.002) after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use. Conclusion We found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes. PMID:27098504

  6. Fabrication techniques for septum magnets at the APS.

    SciTech Connect

    Jaski, M.; Thompson, K.; Kim, S.; Friedsam, H.; Toter, W.; Humbert, J.

    2002-09-16

    The design, construction, and installation of pulsed septum magnets for particle accelerators presents many challenges for the magnet engineer. Issues associated with magnet core structure design, component alignment, weldment design, and electrical insulation choices are among those requiring careful attention. The designs of the six septum magnets required for the APS facility have evolved since operation began in 1996. Improvements in the designs have provided better injection/extraction performance parameters and extended the machine reliability to meet the requirements of a world-class, third-generation synchrotron radiation facility. Details of the techniques used to address issues involved in producing septum magnets at the APS are described here to aid magnet engineers in the fabrication of future septum magnets.

  7. All-Cause Mortality in Women With Severe Postpartum Psychiatric Disorders

    PubMed Central

    Johannsen, Benedicte Marie Winther; Larsen, Janne Tidselbak; Laursen, Thomas Munk; Bergink, Veerle; Meltzer-Brody, Samantha; Munk-Olsen, Trine

    2017-01-01

    Objective The postpartum period is associated with a high risk of psychiatric episodes. The authors studied mortality in women with first-onset severe psychiatric disorders following childbirth and compared their mortality rates with those in women from the background population including other female psychiatric patients (mothers and childless women). Method In a register-based cohort study with linked information from Danish population registers, the authors identified women with first psychiatric inpatient or outpatient contacts 0–3 months postpartum. The main outcome measure was mortality rate ratios (MRRs): deaths from natural causes (diseases and medical conditions) or unnatural causes (suicides, accidents, and homicides). The cohort included 1,545,857 women representing 68,473,423 person-years at risk. Results In total, 2,699 women had first-onset psychiatric disorders 0–3 months postpartum, and 96 of these died during follow-up. Women with postpartum psychiatric disorders had a higher MRR (3.74; 95% CI=3.06–4.57) than non-postpartum-onset mothers (MRR=2.73; 95% CI=2.67–2.79) when compared with mothers with no psychiatric history. However, childless women with psychiatric diagnoses had the highest MRR (6.15; 95% CI=5.94–6.38). Unnatural cause of death represented 40.6% of fatalities among women with postpartum psychiatric disorders, and within the first year after diagnosis, suicide risk was drastically increased (MRR=289.42; 95% CI=144.02–581.62) when compared with mothers with no psychiatric history. Conclusions Women with severe postpartum psychiatric disorders had increased MRRs compared with mothers without psychiatric diagnoses, and the first year after diagnosis represents a time of particularly high relative risk for suicide in this vulnerable group. PMID:26940804

  8. Severe visual impairment and blindness in infants: causes and opportunities for control.

    PubMed

    Gogate, Parikshit; Gilbert, Clare; Zin, Andrea

    2011-04-01

    Childhood blindness has an adverse effect on growth, development, social, and economic opportunities. Severe visual impairment (SVI) and blindness in infants must be detected as early as possible to initiate immediate treatment to prevent deep amblyopia. Although difficult, measurement of visual acuity of an infant is possible. The causes of SVI and blindness may be prenatal, perinatal, and postnatal. Congenital anomalies such as anophthalmos, microphthalmos, coloboma, congenital cataract, infantile glaucoma, and neuro-ophthalmic lesions are causes of impairment present at birth. Ophthalmia neonatorum, retinopathy of prematurity, and cortical visual impairment are acquired during the perinatal period. Leukocoria or white pupillary reflex can be cause by congenital cataract, persistent hyperplastic primary vitreous, or retinoblastoma. While few medical or surgical options are available for congenital anomalies or neuro-ophthalmic disorders, many affected infants can still benefit from low vision aids and rehabilitation. Ideally, surgery for congenital cataracts should occur within the first 4 months of life. Anterior vitrectomy and primary posterior capsulotomy are required, followed by aphakic glasses with secondary intraocular lens implantation at a later date. The treatment of infantile glaucoma is surgery followed by anti-glaucoma medication. Retinopathy of prematurity is a proliferation of the retinal vasculature in response to relative hypoxia in a premature infant. Screening in the first few weeks of life can prevent blindness. Retinoblastoma can be debulked with chemotherapy; however, enucleation may still be required. Neonatologists, pediatricians, traditional birth attendants, nurses, and ophthalmologists should be sensitive to a parent's complaints of poor vision in an infant and ensure adequate follow-up to determine the cause. If required, evaluation under anesthesia should be performed, which includes funduscopy, refraction, corneal diameter

  9. Severe Visual Impairment and Blindness in Infants: Causes and Opportunities for Control

    PubMed Central

    Gogate, Parikshit; Gilbert, Clare; Zin, Andrea

    2011-01-01

    Childhood blindness has an adverse effect on growth, development, social, and economic opportunities. Severe visual impairment (SVI) and blindness in infants must be detected as early as possible to initiate immediate treatment to prevent deep amblyopia. Although difficult, measurement of visual acuity of an infant is possible. The causes of SVI and blindness may be prenatal, perinatal, and postnatal. Congenital anomalies such as anophthalmos, microphthalmos, coloboma, congenital cataract, infantile glaucoma, and neuro-ophthalmic lesions are causes of impairment present at birth. Ophthalmia neonatorum, retinopathy of prematurity, and cortical visual impairment are acquired during the perinatal period. Leukocoria or white pupillary reflex can be cause by congenital cataract, persistent hyperplastic primary vitreous, or retinoblastoma. While few medical or surgical options are available for congenital anomalies or neuro-ophthalmic disorders, many affected infants can still benefit from low vision aids and rehabilitation. Ideally, surgery for congenital cataracts should occur within the first 4 months of life. Anterior vitrectomy and primary posterior capsulotomy are required, followed by aphakic glasses with secondary intraocular lens implantation at a later date. The treatment of infantile glaucoma is surgery followed by anti-glaucoma medication. Retinopathy of prematurity is a proliferation of the retinal vasculature in response to relative hypoxia in a premature infant. Screening in the first few weeks of life can prevent blindness. Retinoblastoma can be debulked with chemotherapy; however, enucleation may still be required. Neonatologists, pediatricians, traditional birth attendants, nurses, and ophthalmologists should be sensitive to a parent’s complaints of poor vision in an infant and ensure adequate follow-up to determine the cause. If required, evaluation under anesthesia should be performed, which includes funduscopy, refraction, corneal diameter

  10. Severe gingival recession caused by traumatic occlusion and mucogingival stress: a case report.

    PubMed

    Ustun, Kemal; Sari, Zafer; Orucoglu, Hasan; Duran, Ismet; Hakki, Sema S

    2008-04-01

    Gingival recession is displacement of the soft tissue margin apically leading to root surface exposure. Tooth malpositions, high muscle attachment, frenal pull have been associated with gingival tissue recession. Occlusal trauma is defined as injury resulting in tissue changes within the attachment apparatus as a result of occlusal forces. Trauma from occlusion may cause a shift in tooth position and the direction of the movement depends on the occlusal force. We present the clinical and radiological findings and the limitation of periodontal treatment of a severe gingival recession in a case with traumatic occlusion. A 16 years old male, systemically healthy and non-smoking patient presented to our clinic with severe gingival recession of mandibular canines and incisors. Clinical evaluation revealed extensive gingival recession on the vestibules of mandibular anterior segment. Patient has an Angle class III malocclusion and deep bite. To maintain the teeth until orthodontic therapy and maxillofacial surgery, mucogingival surgeries were performed to obtain attached gingiva to provide oral hygiene and reduce inflammation. After mucogingival surgeries, limited attached gingiva was gained in this case. Regular periodontal maintenance therapy was performed at 2 month intervals to preserve mandibular anterior teeth. Multidisciplinary approach should be performed in this kind of case for satisfactory results. Unless occlusal relationship was corrected, treatment of severe gingival recession will be problematic. For satisfactory periodontal treatment, early diagnosis of trauma from occlusion and its treatment is very important.

  11. Severe Gingival Recession Caused by Traumatic Occlusion and Mucogingival Stress: A Case Report

    PubMed Central

    Ustun, Kemal; Sari, Zafer; Orucoglu, Hasan; Duran, Ismet; Hakki, Sema S.

    2008-01-01

    Gingival recession is displacement of the soft tissue margin apically leading to root surface exposure. Tooth malpositions, high muscle attachment, frenal pull have been associated with gingival tissue recession. Occlusal trauma is defined as injury resulting in tissue changes within the attachment apparatus as a result of occlusal forces. Trauma from occlusion may cause a shift in tooth position and the direction of the movement depends on the occlusal force. We present the clinical and radiological findings and the limitation of periodontal treatment of a severe gingival recession in a case with traumatic occlusion. A 16 years old male, systemically healthy and non-smoking patient presented to our clinic with severe gingival recession of mandibular canines and incisors. Clinical evaluation revealed extensive gingival recession on the vestibules of mandibular anterior segment. Patient has an Angle class III malocclusion and deep bite. To maintain the teeth until orthodontic therapy and maxillofacial surgery, mucogingival surgeries were performed to obtain attached gingiva to provide oral hygiene and reduce inflammation. After mucogingival surgeries, limited attached gingiva was gained in this case. Regular periodontal maintenance therapy was performed at 2 month intervals to preserve mandibular anterior teeth. Multidisciplinary approach should be performed in this kind of case for satisfactory results. Unless occlusal relationship was corrected, treatment of severe gingival recession will be problematic. For satisfactory periodontal treatment, early diagnosis of trauma from occlusion and its treatment is very important. PMID:19212523

  12. Staphylococcus aureus seroproteomes discriminate ruminant isolates causing mild or severe mastitis.

    PubMed

    Le Maréchal, Caroline; Jardin, Julien; Jan, Gwenaël; Even, Sergine; Pulido, Coralie; Guibert, Jean-Michel; Hernandez, David; François, Patrice; Schrenzel, Jacques; Demon, Dieter; Meyer, Evelyne; Berkova, Nadia; Thiéry, Richard; Vautor, Eric; Le Loir, Yves

    2011-02-15

    Staphylococcus aureus is a major cause of mastitis in ruminants. In ewe mastitis, symptoms range from subclinical to gangrenous mastitis. S. aureus factors or host-factors contributing to the different outcomes are not completely elucidated. In this study, experimental mastitis was induced on primiparous ewes using two S. aureus strains, isolated from gangrenous (strain O11) or subclinical (strain O46) mastitis. Strains induced drastically distinct clinical symptoms when tested in ewe and mice experimental mastitis. Notably, they reproduced mild (O46) or severe (O11) mastitis in ewes. Ewe sera were used to identify staphylococcal immunoreactive proteins commonly or differentially produced during infections of variable severity and to define core and accessory seroproteomes. Such SERological Proteome Analysis (SERPA) allowed the identification of 89 immunoreactive proteins, of which only 52 (58.4%) were previously identified as immunogenic proteins in other staphylococcal infections. Among the 89 proteins identified, 74 appear to constitute the core seroproteome. Among the 15 remaining proteins defining the accessory seroproteome, 12 were specific for strain O11, 3 were specific for O46. Distribution of one protein specific for each mastitis severity was investigated in ten other strains isolated from subclinical or clinical mastitis. We report here for the first time the identification of staphylococcal immunogenic proteins common or specific to S. aureus strains responsible for mild or severe mastitis. These findings open avenues in S. aureus mastitis studies as some of these proteins, expressed in vivo, are likely to account for the success of S. aureus as a pathogen of the ruminant mammary gland.

  13. The Relationship between Large Cavum Septum Pellucidum and Antisocial Behavior, Callous-Unemotional Traits and Psychopathy in Adolescents

    ERIC Educational Resources Information Center

    White, Stuart F.; Brislin, Sarah; Sinclair, Stephen; Fowler, Katherine A.; Pope, Kayla; Blair, R. James R.

    2013-01-01

    Background: The presence of a large cavum septum pellucidum (CSP) has been previously associated with antisocial behavior/psychopathic traits in an adult community sample. Aims: The current study investigated the relationship between a large CSP and symptom severity in disruptive behavior disorders (DBD; conduct disorder and oppositional defiant…

  14. Severe endobronchitis and airway stricture caused by inhalation of cosmetic talc.

    PubMed

    Ong, Thun How; Takano, Angela

    2012-08-01

    Pulmonary disease caused by talc is well described, but previous reports mainly describe lung parenchymal involvement. We describe what is, to our knowledge, the first case in which inhalation of cosmetic talc led to intense endobronchitis and airway stricture. A 70-year-old woman presented with new-onset wheezing and was found to have right upper lobe collapse on chest radiography. CT imaging of the thorax showed right upper lobe collapse with occlusion of the right upper lobe. Bronchoscopy showed severe endobronchitis with thickened mucosa throughout the right and left main stem bronchi and a fibrotic stricture occluding the right upper lobe. Bronchial biopsy specimens showed foreign-body granulomatosis encasing birefringent crystalline material. Spectral analysis confirmed the crystals to be consistent with cosmetic talc used by the patient. We hypothesize that the patient inhaled a large amount of talc, which was trapped in the larger airways and resulted in intense foreign-body granulomatosis, leading to an airway stricture.

  15. Severe methemoglobinemia caused by continuous lidocaine infusion in a term neonate.

    PubMed

    Bohnhorst, Bettina; Hartmann, Hans; Lange, Matthias

    2016-12-28

    Neonates and young infants are especially prone to develop drug-induced methemoglobinemia. Therefore, lidocaine is not licensed as local anesthetic in children below the age of 3 months. However, its systemic use is advocated for neonatal seizures. Cardiac arrhythmia has been reported as sole major side effect. Here we report a case of severe methemoglobinemia caused by continuous infusion of lidocaine in a term neonate with neonatal seizures. The increase of methemoglobin up to 13.8% was accompanied by hypoxemia and cyanosis, necessitating additional inspired oxygen and CPAP ventilation. After stopping lidocaine infusion methemoglobin levels fell and the neonate could be weaned from ventilation. Neonates treated with lidocaine for seizures must be monitored for the occurrence of methemoglobinemia.

  16. Neospora caninum causes severe economic losses in cattle in the humid pampa region of Argentina.

    PubMed

    Moore, Dadin; Reichel, Michael; Spath, Ernesto; Campero, Carlos

    2013-06-01

    This work estimates the economic losses due to Neospora abortions in the humid pampa region of Argentina.The total dairy and beef cattle population at risk of abortion is 1,771,326 and 9,726,684 head, respectively. In dairy cattle, there was an 8 % risk of experiencing abortion due to a variety of causes, but 16.5 % of them were due to Neospora caninum. The economic losses were estimated at US$1,415 (1,400-1,431) per abortion, which equates to a total loss of US$33,097,221 (15,622,600-119,349,693) for the dairy industry at the humid pampa region of Argentina. In beef cattle, the overall risk of abortion was estimated to be 4.5 % for all pregnancies,whereas 6.7 % are specifically due to N. caninum, with an economic loss of US$440 (range, 150-730) per abortion.This amounts to an annual loss to the beef industry of US$12,903,440 (range, 1,130,700-42,070,630) in the same area. The results of this study show that Neospora infections and thus abortions cause severe economic impacts in the dairy and beef industries in the humid pampa region of Argentina, which is one the most important areas of cattle production in the world [corrected].

  17. Mutations in LOXHD1 gene cause various types and severities of hearing loss

    PubMed Central

    Mori, Kentaro; Moteki, Hideaki; Kobayashi, Yumiko; Azaiez, Hela; Booth, Kevin T; Nishio, Shin-ya; Sato, Hiroaki; Smith, Richard J H; Usami, Shin-ichi

    2015-01-01

    Objective We present two families that were identified with novel mutations in LOXHD1, as a cause of non-progressive hearing loss. Methods One thousand three hundred fourteen (1,314) Japanese subjects with sensorineural hearing loss from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known non-syndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results Two patients in one family affected with homozygous mutation; c.879+1G>A in LOXHD1, showed profound congenital hearing loss, whereas two patients in the other family with compound heterozygous mutations; c.5869G>T (p.E1957X) and c.4480C>T (p.R1494X) showed moderate to severe hearing loss. Conclusion Mutations in LOXHD1 are extremely rare, and these cases are the first identified in a Japanese population. The genotype-phenotype correlation in LOXHD1 is still unclear. The differences of phenotypes in each patient might be the result of the nature of the mutations, or the location at the gene, or be influenced by genetic modifier. PMID:25792669

  18. Cytolethal distending toxin-producing Escherichia coli strains causing severe diarrhoea in young Mexican children

    PubMed Central

    Maldonado-Puga, Samantha; Huerta-Cantillo, Jazmin; Chavez-Dueñas, Lucia; Navarro-Garcia, Fernando

    2017-01-01

    Introduction. Cytolethal distending toxins (CDTs), encoded by cdt genes, have DNase activity leading to cellular and nuclear distension, resulting in irreversible cell cycle arrest and apoptosis of target cells. cdt-positive Escherichia coli strains have been isolated from children with diarrhoea. There is, however, scant information on the prevalence and clinical presentation of diarrhoeal disease caused by these strains. Furthermore, toxin production of cdt-positive strains is rarely confirmed. We report five young children with diarrhoea caused by CDT-producing E. coli in whom stools were negative for other bacterial or enteric pathogens. Case presentation. On admission to hospital, all children presented watery diarrhoea with high stool output (range 7–20 stools/24 h); five had fever of 38 °C or more and four presented vomiting. Dehydration was present in four patients, one of whom had hypovolaemic shock; one child also presented hyponatraemia and hypokalaemia. In two children, cdt-positive strains were classified as typical and atypical enteropathogenic E. coli, and the remaining three harboured cdt-positive strains that did not belong to any diarrhoeagenic pathogroup. One cdt-positive strain from each case was characterized by a CDT cytotoxic assay and a cdt type-specific PCR. All strains produced the characteristic cellular intoxication due to CDT. Two strains carried the cdt-I, one cdt-III, one cdt-IV, and one concurrently had cdt-I, cdt-II and cdt-III genes. Conclusion. Our results suggest that CDT-producing E. coli strains are an infrequent, albeit significant, cause of severe diarrhoeal illness in children. Future research should measure the true burden of cdt-positive E. coli diarrhoea among children. PMID:28348804

  19. Why do lesions in the rodent anterior thalamic nuclei cause such severe spatial deficits?

    PubMed

    Aggleton, John P; Nelson, Andrew J D

    2015-07-01

    Lesions of the rodent anterior thalamic nuclei cause severe deficits to multiple spatial learning tasks. Possible explanations for these effects are examined, with particular reference to T-maze alternation. Anterior thalamic lesions not only impair allocentric place learning but also disrupt other spatial processes, including direction learning, path integration, and relative length discriminations, as well as aspects of nonspatial learning, e.g., temporal discriminations. Working memory tasks, such as T-maze alternation, appear particularly sensitive as they combine an array of these spatial and nonspatial demands. This sensitivity partly reflects the different functions supported by individual anterior thalamic nuclei, though it is argued that anterior thalamic lesion effects also arise from covert pathology in sites distal to the thalamus, most critically in the retrosplenial cortex and hippocampus. This two-level account, involving both local and distal lesion effects, explains the range and severity of the spatial deficits following anterior thalamic lesions. These findings highlight how the anterior thalamic nuclei form a key component in a series of interdependent systems that support multiple spatial functions.

  20. Why do lesions in the rodent anterior thalamic nuclei cause such severe spatial deficits?

    PubMed Central

    Aggleton, John P.; Nelson, Andrew J.D.

    2015-01-01

    Lesions of the rodent anterior thalamic nuclei cause severe deficits to multiple spatial learning tasks. Possible explanations for these effects are examined, with particular reference to T-maze alternation. Anterior thalamic lesions not only impair allocentric place learning but also disrupt other spatial processes, including direction learning, path integration, and relative length discriminations, as well as aspects of nonspatial learning, e.g., temporal discriminations. Working memory tasks, such as T-maze alternation, appear particularly sensitive as they combine an array of these spatial and nonspatial demands. This sensitivity partly reflects the different functions supported by individual anterior thalamic nuclei, though it is argued that anterior thalamic lesion effects also arise from covert pathology in sites distal to the thalamus, most critically in the retrosplenial cortex and hippocampus. This two-level account, involving both local and distal lesion effects, explains the range and severity of the spatial deficits following anterior thalamic lesions. These findings highlight how the anterior thalamic nuclei form a key component in a series of interdependent systems that support multiple spatial functions. PMID:25195980

  1. [Severe anemia caused by haemorrhoids: the casae of a young man with toxic cirrhosis].

    PubMed

    Kovács, Erzsébet; Palatka, Károly; Németh, Attila; Pásztor, Éva; Pfliegler, György

    2013-03-10

    A 38-year-old alcoholic man with severe iron deficient anaemia, and bloody-mucous stool was found to have haemorrhoidal bleeding. In spite of intravenous iron supplements haemoglobin levels were falling. He was admitted because of deteriorating condition, jaundice, severe anaemia (haemoglobin, 38 g/l) and iron deficiency. Except of toxic (alcohol) agent all other causes of liver disease could be excluded. Sclero-, and medical therapy, and abstinence resulted in a rapid improvement in his condition and subsequently rectal bleeding also disappeared. Bleeding from the upper gastrointestinal tract is a well known and serious complication in liver cirrhosis, however, a voluminous blood loss resulting in a life-threatening anaemia from lower gastrointestinal tract or haemorrhoids, as it was detected in this patient, is quite rare. Sclerotherapy seems to be an effective method with only minor complications when compared with other invasive techniques. However, the patient's compliance even in liver cirrhosis with haemorrhoidal nodes is essential for long-term success.

  2. Plasma from human mothers of fetuses with severe arthrogryposis multiplex congenita causes deformities in mice

    PubMed Central

    Jacobson, Leslie; Polizzi, Agata; Morriss-Kay, Gillian; Vincent, Angela

    1999-01-01

    Arthrogryposis multiplex congenita (AMC) is characterized by fixed joint contractures and other deformities, sometimes resulting in fetal death. The cause is unknown in most cases, but some women with fetuses affected by severe AMC have serum antibodies that inhibit fetal acetylcholine receptor (AChR) function, and antibodies to fetal antigens might play a pathogenic role in other congenital disorders. To investigate this possibility, we have established a model by injecting pregnant mice with plasma from four anti-AChR antibody–positive women whose fetuses had severe AMC. We found that human antibodies can be transferred efficiently to the mouse fetus during the last few days of fetal life. Many of the fetuses of dams injected with AMC maternal plasmas or Ig were stillborn and showed fixed joints and other deformities. Moreover, similar changes were found in mice after injection of a serum from one anti-AChR antibody–negative mother who had had four AMC fetuses. Thus, we have confirmed the role of maternal antibodies in cases of AMC associated with maternal anti-AChR, and we have demonstrated the existence of pathogenic maternal factors in one other case. Importantly, this approach can be used to look at the effects of other maternal human antibodies on development of the fetus. PMID:10194476

  3. Severe burn injuries caused by bioethanol-design fireplaces-an overview on recreational fire threats.

    PubMed

    Kraemer, Robert; Knobloch, Karsten; Lorenzen, Johan; Breuing, Karl H; Koennecker, Soeren; Rennekampff, Hans-Oliver; Vogt, Peter M

    2011-01-01

    Commercially available bioethanol-fueled fireplaces have become increasingly popular additions for interior home decoration in Europe and more recently in the United States. These fireplaces are advertised as smokeless, ecologically friendly, and do not require professional installation, formal gas lines, or venting. Although manufacturers and businesses promote their safety, recent presentations of injuries have alerted the authors to the relevant danger bioethanol fireplaces can pose for the incautious user. Are bioethanol fireplaces going to become the future threat in domestic burn accidents beside common barbeque burns? A Medline literature search on barbeque and domestic fireplace accidents was performed to compare and stratify the injury patterns reported and to identify a risk profile for contemporary bioethanol-fueled fireplaces. To exemplify, two representative clinical cases of severe burn accidents caused by bioethanol-fueled fireplaces, both treated in the burn unit of the authors, are being presented. Design fireplaces are being recognized as an increasing source of fuel and fire-related danger in the home. This risk may be underestimated by the uninformed customer, resulting in severe burn injuries. Because bioethanol-fueled fireplaces have become more commonplace, they may overtake barbecue-related injury as the most common domestic burn injury.

  4. Diagnosing the Causes and Severity of One-sided Message Contention

    SciTech Connect

    Tallent, Nathan R.; Vishnu, Abhinav; van Dam, Hubertus; Daily, Jeffrey A.; Kerbyson, Darren J.; Hoisie, Adolfy

    2015-02-11

    Two trends suggest network contention for one-sided messages is poised to become a performance problem that concerns application developers: an increased interest in one-sided programming models and a rising ratio of hardware threads to network injection bandwidth. Unfortunately, it is difficult to reason about network contention and one-sided messages because one-sided tasks can either decrease or increase contention. We present effective and portable techniques for diagnosing the causes and severity of one-sided message contention. To detect that a message is affected by contention, we maintain statistics representing instantaneous (non-local) network resource demand. Using lightweight measurement and modeling, we identify the portion of a message's latency that is due to contention and whether contention occurs at the initiator or target. We attribute these metrics to program statements in their full static and dynamic context. We characterize contention for an important computational chemistry benchmark on InfiniBand, Cray Aries, and IBM Blue Gene/Q interconnects. We pinpoint the sources of contention, estimate their severity, and show that when message delivery time deviates from an ideal model, there are other messages contending for the same network links. With a small change to the benchmark, we reduce contention up to 50% and improve total runtime as much as 20%.

  5. Cause and predictability for the severe haze pollutions in downtown Beijing during November-December 2015.

    PubMed

    Zhang, Ziyin; Gong, Daoyi; Kim, Seong-Joong; Mao, Rui; Xu, Jing; Zhao, Xiujuan; Ma, Zhiqiang

    2017-02-15

    When severe haze pollutions hit downtown Beijing during period of November-December 2015, Beijing issued the red alert for the heavy pollution for the first time in history. Based on the hourly PM2.5 concentration and meteorological variable records and the ERA-Interim reanalysis data, a series of diagnostic analyses were conducted to explore the possible meteorological causes for the severe haze pollutions. Using the online-coupled WRF-Chem model and GFS data, the predictability of hourly and daily PM2.5 concentration was evaluated. The results showed that, in the context of pollutants emission, the severe haze pollutions in downtown Beijing during November-December 2015 were mainly attributed to the anomalous local meteorological conditions (i.e., the decreased wind speed and boundary layer height and the increased relative humidity and thermal inversion in the lower troposphere), which were caused and strengthened by the anomalous large-scale atmospheric circulations (i.e., the anomalous southeastern winds associated with the weakened land-sea thermal contrast at the lower troposphere, and the weakened East Asian trough at the middle troposphere and East Asian Jet stream at the upper troposphere, and the anomalous strong water vapor over most of northern China). The abnormal changes at upper troposphere appeared to trigger the anomalies in middle-lower troposphere and local conditions. The numerical simulations well capture the spatial distribution patterns of PM2.5 concentrations in predicting 1 to 10days in advance. The trends of PM2.5 concentration in downtown Beijing were generally in good agreement with prediction on both daily and hourly time-scales, although the predictability decreased gradually as the leading times prolonged. The predictability of the daily mean PM2.5 concentration was slightly higher than that of the hourly. The statistical indices suggested that the predictions of daily and hourly mean PM2.5 concentration were generally skillful and

  6. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.

    PubMed

    Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-10-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas.

  7. Rho1-GEFs Rgf1 and Rgf2 are involved in formation of cell wall and septum, while Rgf3 is involved in cytokinesis in fission yeast.

    PubMed

    Mutoh, Tadashi; Nakano, Kentaro; Mabuchi, Issei

    2005-12-01

    The Rho GTPase acts as a binary molecular switch by converting between a GDP-bound inactive and a GTP-bound active conformational state. The guanine nucleotide exchange factors (GEFs) are critical activators of Rho. Rho1 has been shown to regulate actin cytoskeleton and cell wall synthesis in the fission yeast Schizosaccharomyces pombe. Here we studied function of fission yeast RhoGEFs, Rgf1, Rgf2, and Rgf3. It was shown that these proteins have similar molecular structures, and function as GEFs for Rho1. Disruption of either rgf1 or rgf2 did not show a serious effect on the cell. On the other hand, disruption of rgf3 caused severe defects in contractile ring formation, F-actin patch localization, and septation during cytokinesis. Rgf1 and Rgf2 were localized to the cell ends during interphase and the septum. Rgf3 formed a ring at the division site, which was located outside the contractile ring and inside the septum where Rho1 was accumulated. In summary, Rgf1 and Rgf2 show functional redundancy, and roles of these RhoGEFs are likely to be different from that of Rgf3. Rho1 is likely to be activated by Rgf3 at the division site, and involved in contractile ring formation and/or maintenance and septation.

  8. Septum development in Neurospora crassa: the septal actomyosin tangle.

    PubMed

    Delgado-Álvarez, Diego Luis; Bartnicki-García, Salomón; Seiler, Stephan; Mouriño-Pérez, Rosa Reyna

    2014-01-01

    Septum formation in Neurospora crassa was studied by fluorescent tagging of actin, myosin, tropomyosin, formin, fimbrin, BUD-4, and CHS-1. In chronological order, we recognized three septum development stages: 1) septal actomyosin tangle (SAT) assembly, 2) contractile actomyosin ring (CAR) formation, 3) CAR constriction together with plasma membrane ingrowth and cell wall construction. Septation began with the assembly of a conspicuous tangle of cortical actin cables (SAT) in the septation site >5 min before plasma membrane ingrowth. Tropomyosin and myosin were detected as components of the SAT from the outset. The SAT gradually condensed to form a proto-CAR that preceded CAR formation. During septum development, the contractile actomyosin ring remained associated with the advancing edge of the septum. Formin and BUD-4 were recruited during the transition from SAT to CAR and CHS-1 appeared two min before CAR constriction. Actin patches containing fimbrin were observed surrounding the ingrowing septum, an indication of endocytic activity. Although the trigger of SAT assembly remains unclear, the regularity of septation both in space and time gives us reason to believe that the initiation of the septation process is integrated with the mechanisms that control both the cell cycle and the overall growth of hyphae, despite the asynchronous nature of mitosis in N. crassa.

  9. Septum Development in Neurospora crassa: The Septal Actomyosin Tangle

    PubMed Central

    Delgado-Álvarez, Diego Luis; Bartnicki-García, Salomón; Seiler, Stephan; Mouriño-Pérez, Rosa Reyna

    2014-01-01

    Septum formation in Neurospora crassa was studied by fluorescent tagging of actin, myosin, tropomyosin, formin, fimbrin, BUD-4, and CHS-1. In chronological order, we recognized three septum development stages: 1) septal actomyosin tangle (SAT) assembly, 2) contractile actomyosin ring (CAR) formation, 3) CAR constriction together with plasma membrane ingrowth and cell wall construction. Septation began with the assembly of a conspicuous tangle of cortical actin cables (SAT) in the septation site >5 min before plasma membrane ingrowth. Tropomyosin and myosin were detected as components of the SAT from the outset. The SAT gradually condensed to form a proto-CAR that preceded CAR formation. During septum development, the contractile actomyosin ring remained associated with the advancing edge of the septum. Formin and BUD-4 were recruited during the transition from SAT to CAR and CHS-1 appeared two min before CAR constriction. Actin patches containing fimbrin were observed surrounding the ingrowing septum, an indication of endocytic activity. Although the trigger of SAT assembly remains unclear, the regularity of septation both in space and time gives us reason to believe that the initiation of the septation process is integrated with the mechanisms that control both the cell cycle and the overall growth of hyphae, despite the asynchronous nature of mitosis in N. crassa. PMID:24800890

  10. Analysis of cardiac interventricular septum motion in different respiratory states

    NASA Astrophysics Data System (ADS)

    Tautz, Lennart; Feng, Li; Otazo, Ricardo; Hennemuth, Anja; Axel, Leon

    2016-03-01

    The interaction between the left and right heart ventricles (LV and RV) depends on load and pressure conditions that are affected by cardiac contraction and respiration cycles. A novel MRI sequence, XD-GRASP, allows the acquisition of multi-dimensional, respiration-sorted and cardiac-synchronized free-breathing image data. In these data, effects of the cardiac and respiratory cycles on the LV/RV interaction can be observed independently. To enable the analysis of such data, we developed a semi-automatic exploration workflow. After tracking a cross-sectional line positioned over the heart, over all motion states, the septum and heart wall border locations are detected by analyzing the grey-value profile under the lines. These data are used to quantify septum motion, both in absolute units and as a fraction of the heart size, to compare values for different subjects. In addition to conventional visualization techniques, we used color maps for intuitive exploration of the variable values for this multi-dimensional data set. We acquired short-axis image data of nine healthy volunteers, to analyze the position and the motion of the interventricular septum in different breathing states and different cardiac cycle phases. The results indicate a consistent range of normal septum motion values, and also suggest that respiratory phase-dependent septum motion is greatest near end-diastolic phases. These new methods are a promising tool to assess LV/RV ventricle interaction and the effects of respiration on this interaction.

  11. External validity of a randomised controlled trial on the treatment of severe infections caused by MRSA

    PubMed Central

    Paul, Mical; Bronstein, Ella; Yahav, Dafna; Goldberg, Elad; Bishara, Jihad; Leibovici, Leonard

    2015-01-01

    Objectives To assess the external validity of a pragmatic, investigator-initiated RCT on treatment of severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA), we compared patient characteristics and treatment effect estimates for patients included in the RCT versus those excluded. Participants and outcomes The RCT included hospitalised patients with documented or highly-probable invasive MRSA infections who were randomised to vancomycin versus trimethoprim-sulfamethoxazole (TMP-SMX) treatment, between 2007 and 2014. A concomitant observational study prospectively included all consecutive patients, between 2008 and 2011, who were excluded from the RCT due to no consent, meningitis, left-sided endocarditis, severe neutropaenia, chronic renal dialysis or treatment with study medications for longer than 48 h. The primary outcomes were clinical failure at day 7 and 30-day mortality for both studies. We compared baseline and infection characteristics, outcome rates and treatment effect estimates for included versus excluded patients. Results The RCT included 252 patients who were compared with 220 excluded patients who were observed. Inability to provide informed consent was the main reason for patient exclusion. Excluded patients’ functional and cognitive performance was significantly poorer than that of included patients. Sepsis was more severe among excluded patients (higher rates of mechanical ventilation, indwelling catheters, septic shock and organ failure). Clinical failure occurred in 83/252 (32.9%) versus 175/220 (79.5%) and deaths in 32 (12.7%) versus 64 (29.1%) for included versus excluded patients, p<0.001 for both comparisons. Comparing vancomycin to TMP-SMX, in the RCT mortality, was non-significantly lower with vancomycin (OR 0.76, 95% CIs 0.36 to 1.62), while in the observational analysis of excluded patients, mortality was significantly higher with vancomycin (OR 2.63, 1.04 to 6.65), p=0.04 for the difference. Conclusions

  12. De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment

    PubMed Central

    Hempel, Maja; Cremer, Kirsten; Ockeloen, Charlotte W.; Lichtenbelt, Klaske D.; Herkert, Johanna C.; Denecke, Jonas; Haack, Tobias B.; Zink, Alexander M.; Becker, Jessica; Wohlleber, Eva; Johannsen, Jessika; Alhaddad, Bader; Pfundt, Rolph; Fuchs, Sigrid; Wieczorek, Dagmar; Strom, Tim M.; van Gassen, Koen L.I.; Kleefstra, Tjitske; Kubisch, Christian; Engels, Hartmut; Lessel, Davor

    2015-01-01

    CHAMP1 encodes a protein with a function in kinetochore-microtubule attachment and in the regulation of chromosome segregation, both of which are known to be important for neurodevelopment. By trio whole-exome sequencing, we have identified de novo deleterious mutations in CHAMP1 in five unrelated individuals affected by intellectual disability with severe speech impairment, motor developmental delay, muscular hypotonia, and similar dysmorphic features including short philtrum and a tented upper and everted lover lip. In addition to two frameshift and one nonsense mutations, we found an identical nonsense mutation, c.1192C>T (p.Arg398∗), in two affected individuals. All mutations, if resulting in a stable protein, are predicted to lead to the loss of the functionally important zinc-finger domains in the C terminus of the protein, which regulate CHAMP1 localization to chromosomes and the mitotic spindle, thereby providing a mechanistic understanding for their pathogenicity. We thus establish deleterious de novo mutations in CHAMP1 as a cause of intellectual disability. PMID:26340335

  13. Iliac arteriovenous fistula due to spinal disk surgery. Causes severe hemodynamic repercussion with pulmonary hypertension.

    PubMed Central

    Machado-Atías, I; Fornés, O; González-Bello, R; Machado-Hernández, I

    1993-01-01

    We present a case of a 46-year-old man with a pulsatile mass in the left inferior abdominal quadrant that irradiated a continuous murmur extending to the left lumbar region. Despite an 8-year history of cardiomegaly, he appeared to be asymptomatic except for the mass and could recollect no traumatic injury or surgery that might have caused it. Near the vertebral column, we found a small scar, the result of spinal disk surgery 11 years before. Following chest radiography and electrocardiography, we located the suspected arteriovenous fistula by selective angiography of the aorta and its branches: a communication of the left iliac artery with the left iliac vein had resulted in a very large left-to-right shunt and a severely dilated inferior vena cava. We then divided and isolated the arterial segment containing the fistula, but left this segment in continuity with the left iliac vein by over-sewing both ends. To avoid injury to surrounding structures, dissection was limited to the area of maximal thrill. Hemodynamic improvement was immediate, and the postoperative course was uneventful. At the present time, almost 3 years postoperatively, the patient is asymptomatic. Images PMID:8508067

  14. Dumping syndrome: an unusual cause of severe hyperinsulinemic hypoglycemia in neurologically impaired children with gastrostomy.

    PubMed

    Bizzarri, C; Cervoni, M; Crea, F; Cutrera, R; Schiavino, A; Schiaffini, R; Cappa, M

    2011-02-01

    This paper describes severe hyperinsulinemic hypoglycemia during bolus enteral feeding in two neurologically impaired children. Both children were affected by dysphagia with swallowing difficulties; caloric intake was inadequate. For these reasons, percutaneous endoscopic gastrostomy had been positioned during the first months of life. In one patient due to persisting vomiting, after a few months, a gastrojejunal tube (PEG-J) was inserted. Hypoglycemia was revealed by routine blood tests, without evidence of specific symptoms. Continuous subcutaneous glucose monitoring showed wide glucose excursions, ranging from hypoglycemia to hyperglycemia. Extremely high levels of insulin were detected at the time of hypoglycemia. A diagnosis of dumping syndrome (DS) was suspected in both children. In the child with PEG, the tip of the gastrostomy catheter was found to be lying in the bulbus duodeni. Once this had been pulled back, hypoglycemic episodes disappeared. The child with PEG-J needed continuous enteral feeding to reach a normal glucose balance. DS is a relatively common complication in children with gastrostomy, but extremely irregular glucose levels, ranging from hypoglycemia to hyperglycemia, and increased insulin secretion had not been previously demonstrated. The incidence of DS is probably underestimated in children receiving enteral feeding for neurological impairment. In these patients intensive monitoring of blood glucose levels should be performed to calibrate meals. Repeated underestimated hypoglycemic episodes could worsen neurological damage and cause a deterioration in clinical conditions.

  15. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

    PubMed Central

    Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

    2006-01-01

    Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder

  16. Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype.

    PubMed

    Alston, Charlotte L; Compton, Alison G; Formosa, Luke E; Strecker, Valentina; Oláhová, Monika; Haack, Tobias B; Smet, Joél; Stouffs, Katrien; Diakumis, Peter; Ciara, Elżbieta; Cassiman, David; Romain, Nadine; Yarham, John W; He, Langping; De Paepe, Boel; Vanlander, Arnaud V; Seneca, Sara; Feichtinger, René G; Płoski, Rafal; Rokicki, Dariusz; Pronicka, Ewa; Haller, Ronald G; Van Hove, Johan L K; Bahlo, Melanie; Mayr, Johannes A; Van Coster, Rudy; Prokisch, Holger; Wittig, Ilka; Ryan, Michael T; Thorburn, David R; Taylor, Robert W

    2016-07-07

    Complex I deficiency is the most common biochemical phenotype observed in individuals with mitochondrial disease. With 44 structural subunits and over 10 assembly factors, it is unsurprising that complex I deficiency is associated with clinical and genetic heterogeneity. Massively parallel sequencing (MPS) technologies including custom, targeted gene panels or unbiased whole-exome sequencing (WES) are hugely powerful in identifying the underlying genetic defect in a clinical diagnostic setting, yet many individuals remain without a genetic diagnosis. These individuals might harbor mutations in poorly understood or uncharacterized genes, and their diagnosis relies upon characterization of these orphan genes. Complexome profiling recently identified TMEM126B as a component of the mitochondrial complex I assembly complex alongside proteins ACAD9, ECSIT, NDUFAF1, and TIMMDC1. Here, we describe the clinical, biochemical, and molecular findings in six cases of mitochondrial disease from four unrelated families affected by biallelic (c.635G>T [p.Gly212Val] and/or c.401delA [p.Asn134Ilefs(∗)2]) TMEM126B variants. We provide functional evidence to support the pathogenicity of these TMEM126B variants, including evidence of founder effects for both variants, and establish defects within this gene as a cause of complex I deficiency in association with either pure myopathy in adulthood or, in one individual, a severe multisystem presentation (chronic renal failure and cardiomyopathy) in infancy. Functional experimentation including viral rescue and complexome profiling of subject cell lines has confirmed TMEM126B as the tenth complex I assembly factor associated with human disease and validates the importance of both genome-wide sequencing and proteomic approaches in characterizing disease-associated genes whose physiological roles have been previously undetermined.

  17. Divergent Simian Arteriviruses Cause Simian Hemorrhagic Fever of Differing Severities in Macaques

    PubMed Central

    Moncla, Louise H.; Weiler, Andrea M.; Charlier, Olivia; Rojas, Oscar; Byrum, Russell; Ragland, Dan R.; Cohen, Melanie; Sanford, Hannah B.; Qin, Jing

    2016-01-01

    ABSTRACT Simian hemorrhagic fever (SHF) is a highly lethal disease in captive macaques. Three distinct arteriviruses are known etiological agents of past SHF epizootics, but only one, simian hemorrhagic fever virus (SHFV), has been isolated in cell culture. The natural reservoir(s) of the three viruses have yet to be identified, but African nonhuman primates are suspected. Eleven additional divergent simian arteriviruses have been detected recently in diverse and apparently healthy African cercopithecid monkeys. Here, we report the successful isolation in MARC-145 cell culture of one of these viruses, Kibale red colobus virus 1 (KRCV-1), from serum of a naturally infected red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) sampled in Kibale National Park, Uganda. Intramuscular (i.m.) injection of KRCV-1 into four cynomolgus macaques (Macaca fascicularis) resulted in a self-limiting nonlethal disease characterized by depressive behavioral changes, disturbance in coagulation parameters, and liver enzyme elevations. In contrast, i.m. injection of SHFV resulted in typical lethal SHF characterized by mild fever, lethargy, lymphoid depletion, lymphoid and hepatocellular necrosis, low platelet counts, increased liver enzyme concentrations, coagulation abnormalities, and increasing viral loads. As hypothesized based on the genetic and presumed antigenic distance between KRCV-1 and SHFV, all four macaques that had survived KRCV-1 injection died of SHF after subsequent SHFV injection, indicating a lack of protective heterotypic immunity. Our data indicate that SHF is a disease of macaques that in all likelihood can be caused by a number of distinct simian arteriviruses, although with different severity depending on the specific arterivirus involved. Consequently, we recommend that current screening procedures for SHFV in primate-holding facilities be modified to detect all known simian arteriviruses. PMID:26908578

  18. Suppression of severe lesions, myonecrosis and hemorrhage, caused by Protobothrops flavoviridis venom with its serum proteins.

    PubMed

    Chijiwa, Takahito; So, Shuhei; Hattori, Shosaku; Yoshida, Aichi; Oda-Ueda, Naoko; Ohno, Motonori

    2013-12-15

    Protobothrops flavoviridis serum proteins precipitated with ammonium sulfate were chromatographed on a DEAE-Toyopearl 650M column at pH 7.5 with stepwise increase or with linear gradient of NaCl concentration. Peaks 3 and 4 serum proteins, obtained by linear gradient elution and named Fr(de3) and Fr(de4), contained Habu serum factors (HSF) and phospholipase A2 (PLA2) inhibitors (PfPLI), respectively. The serum proteins eluted at 0.2 M NaCl by stepwise elution, named Fr(0.2NaCl), effectively suppressed myonecrosis and hemorrhage caused by P. flavoviridis venom in rat or mouse thigh muscles. The Fr(0.2NaCl) were fractionated by HPLC and the fractions, after SDS-PAGE, underwent far-western blot analysis with PLA2 ([Asp(49)]PLA2) and BPI ([Lys(49)]PLA2) as the probes. Four PfPLIs, namely, PfαPLI-A, PfαPLI-B, PfγPLI-A and PfγPLI-B, were identified together with their selective binding specificities to PLA2 species. In addition, a new 9 kDa protein, which is specifically bound to BPI, was found. Suppression of P. flavoviridis venom-induced severe lesions, such as myonecrosis, hemorrhage and edema, with its serum proteins was histopathologically observed in the present work for the first time. The cooperative use of P. flavoviridis antivenom and its serum proteins as medication for P. flavoviridis snake bites is discussed.

  19. LocZ Is a New Cell Division Protein Involved in Proper Septum Placement in Streptococcus pneumoniae

    PubMed Central

    Holečková, Nela; Molle, Virginie; Buriánková, Karolína; Benada, Oldřich; Kofroňová, Olga; Ulrych, Aleš; Branny, Pavel

    2014-01-01

    ABSTRACT How bacteria control proper septum placement at midcell, to guarantee the generation of identical daughter cells, is still largely unknown. Although different systems involved in the selection of the division site have been described in selected species, these do not appear to be widely conserved. Here, we report that LocZ (Spr0334), a newly identified cell division protein, is involved in proper septum placement in Streptococcus pneumoniae. We show that locZ is not essential but that its deletion results in cell division defects and shape deformation, causing cells to divide asymmetrically and generate unequally sized, occasionally anucleated, daughter cells. LocZ has a unique localization profile. It arrives early at midcell, before FtsZ and FtsA, and leaves the septum early, apparently moving along with the equatorial rings that mark the future division sites. Consistently, cells lacking LocZ also show misplacement of the Z-ring, suggesting that it could act as a positive regulator to determine septum placement. LocZ was identified as a substrate of the Ser/Thr protein kinase StkP, which regulates cell division in S. pneumoniae. Interestingly, homologues of LocZ are found only in streptococci, lactococci, and enterococci, indicating that this close phylogenetically related group of bacteria evolved a specific solution to spatially regulate cell division. PMID:25550321

  20. Severe peritonitis caused by Citrobacter freundii and successful treatment with double antibiotic coverage.

    PubMed

    Kataria, A; Saad, E

    2015-01-01

    Serratia, Pseudomonas/Providencia, indole-positive Proteus/Acinetobacter/Morganella, Citrobacter, Enterobacter and Hafnia group of organisms cause peritoneal dialysis (PD)-related peritonitis with high morbidity and mortality. Peritonitis caused by Citrobacter freundii is uncommon, and it may lead to catheter removal despite antimicrobial treatment. We describe a case of PD-related peritonitis caused by C. freundii, which was successfully treated with double antibiotic coverage.

  1. The Causes of Blindness in Childhood; A Study of 776 Children with Severe Visual Handicaps.

    ERIC Educational Resources Information Center

    Fraser, G.R.; Friedman, A.I.

    To investigate causes of blindness in childhood, 776 children (infancy to 20 years old) in special schools were seen in 1963. Examinations, parent questionnaires, and correspondence with health personnel were used to obtain etiological data. Causes of blindness mainly of genetic determination described are choroido-retinal degenerations,…

  2. Disruption of Germination and Seedling Development in Brassica napus by Mutations Causing Severe Seed Hormonal Imbalance.

    PubMed

    Nguyen, Tung C T; Obermeier, Christian; Friedt, Wolfgang; Abrams, Suzanne R; Snowdon, Rod J

    2016-01-01

    The Brassica napus (oilseed rape) accession 1012-98 shows a disturbed germination phenotype that was thought to be associated with its lack of testa pigmentation and thin seed coat. Here, we demonstrate that the disturbed germination and seedling development are actually due to independent mutations that disrupt the balance of hormone metabolites and their regulators in the seeds. High-throughput UPLC-MS/MS hormone profiling of seeds and seedlings before and after germination revealed that 1012-98 has a severely disturbed hormone balance with extremely atypical, excessive quantities of auxin and ABA metabolites. The resulting hypersensitivity to abscisic acid (ABA) and a corresponding increase in dormancy often results in death of the embryo after imbibition or high frequencies of disturbed, often lethal developmental phenotypes, resembling Arabidopsis mutants for the auxin regulatory factor gene ARF10 or the auxin-overproducing transgenic line iaaM-OX. Molecular cloning of Brassica ARF10 orthologs revealed four loci in normal B. napus, two derived from the Brassica A genome and two from the C genome. On the other hand, the phenotypic mutant 1012-98 exhibited amplification of C-genome BnaC.ARF10 copy number along with a chimeric allele originating from recombination between homeologous A and C genome loci which lead to minor increase of Bna.ARF10 transcription on the critical timepoint for seed germination, the indirect regulator of ABI3, the germinative inhibitor. Bna.GH3.5 expression was upregulated to conjugate free auxin to IAA-asp between 2 and 6 DAS. Functional amino acid changes were also found in important DNA binding domains of one BnaC.ARF10 locus, suggesting that regulatory changes in Bna.ARF10 are collectively responsible for the observed phenotpyes in 1012-98. To our knowledge, this study is the first to report disruption of germination and seedling development in Brassica napus caused by the crosstalk of auxin-ABA and the corresponding regulators Bna

  3. Disruption of Germination and Seedling Development in Brassica napus by Mutations Causing Severe Seed Hormonal Imbalance

    PubMed Central

    Nguyen, Tung C. T.; Obermeier, Christian; Friedt, Wolfgang; Abrams, Suzanne R.; Snowdon, Rod J.

    2016-01-01

    The Brassica napus (oilseed rape) accession 1012-98 shows a disturbed germination phenotype that was thought to be associated with its lack of testa pigmentation and thin seed coat. Here, we demonstrate that the disturbed germination and seedling development are actually due to independent mutations that disrupt the balance of hormone metabolites and their regulators in the seeds. High-throughput UPLC-MS/MS hormone profiling of seeds and seedlings before and after germination revealed that 1012-98 has a severely disturbed hormone balance with extremely atypical, excessive quantities of auxin and ABA metabolites. The resulting hypersensitivity to abscisic acid (ABA) and a corresponding increase in dormancy often results in death of the embryo after imbibition or high frequencies of disturbed, often lethal developmental phenotypes, resembling Arabidopsis mutants for the auxin regulatory factor gene ARF10 or the auxin-overproducing transgenic line iaaM-OX. Molecular cloning of Brassica ARF10 orthologs revealed four loci in normal B. napus, two derived from the Brassica A genome and two from the C genome. On the other hand, the phenotypic mutant 1012-98 exhibited amplification of C-genome BnaC.ARF10 copy number along with a chimeric allele originating from recombination between homeologous A and C genome loci which lead to minor increase of Bna.ARF10 transcription on the critical timepoint for seed germination, the indirect regulator of ABI3, the germinative inhibitor. Bna.GH3.5 expression was upregulated to conjugate free auxin to IAA-asp between 2 and 6 DAS. Functional amino acid changes were also found in important DNA binding domains of one BnaC.ARF10 locus, suggesting that regulatory changes in Bna.ARF10 are collectively responsible for the observed phenotpyes in 1012-98. To our knowledge, this study is the first to report disruption of germination and seedling development in Brassica napus caused by the crosstalk of auxin-ABA and the corresponding regulators Bna

  4. Severe Community-Acquired Pneumonia with Bacteremia Caused by Herbaspirillum aquaticum or Herbaspirillum huttiense in an Immune-Competent Adult

    PubMed Central

    Kimball, Joanna; Smith, L. Patrick; Salzer, William

    2015-01-01

    Herbaspirillum spp. are Gram-negative bacteria that inhabit soil and water. Infections caused by these organisms have been reported in immunocompromised hosts. We describe severe community-acquired pneumonia and bacteremia caused by Herbaspirillum aquaticum or H. huttiense in an immunocompetent adult male. PMID:26179298

  5. Operative balloon dilatation for pulmonary atresia with intact ventricular septum.

    PubMed Central

    Hamilton, J R; Fonseka, S F; Wilson, N; Dickinson, D F; Walker, D R

    1987-01-01

    In six infants with pulmonary atresia and intact ventricular septum operative balloon dilatation was used to achieve continuity between the right ventricle and the main pulmonary artery as the initial procedure. Two of the six subsequently needed an aortico pulmonary shunt. All six are alive and well. Images Fig PMID:3676024

  6. [Use of Solcoseryl DAP after nasal septum surgery].

    PubMed

    Krzeski, A; Makowska, W

    1991-01-01

    Solcoseryl is a biological agent, which accelerates the healing tissue procedure. This influence was studied during the nasal septum surgery. In 25 patients the postoperational nasal plug was inserted with the Solcoseryl and in 10 (control) with the paraffin. The cytologic verifications were performed before and after the surgery. In the solcoseryl group the mucosa regeneration procedure was accelerated and the inflammation reduced.

  7. Prenatal sonographic diagnosis of urorectal septum malformation sequence and chromosomal microarray analysis

    PubMed Central

    Pei, Yan; Wu, Qingqing; Liu, Yan; Sun, Lijuan; Zhi, Wenxue; Zhang, Puqing

    2016-01-01

    Abstract Introduction: Urorectal septum malformation sequence (URSMS) is a rare congenital abnormal syndrome that is caused by the incomplete division of the cloaca. Based on whether the cloaca membrane breaks down or not, the URSMS are classified as full and partial forms. The prenatal diagnosis of URSMS remains challenging because of poor recognition to this malformation and the relatively non-specific sonographic features. We report a prenatally sonographic diagnosed case of the partial URSMS, and review the literature to summarize the prenatal features. Case report and review: A 37-year old woman was referred at 24 weeks of gestation for fetal abdominal cyst. Detailed sonographic examination was done and revealed the vesicocolic fistula, distended colon, absence of perianal hypoechoic ring, pyelectasis, and small stomach bubble. The URSMS was suspected. Amniocentesis was done and karyotyping revealed 46,XY. Furthermore, chromosomal microarray analysis (CMA) was performed for the first time in URSMS and an alteration of 111.8Kb deletion was detected in 16p13.3 which was located inside the RBFOX1 gene. Parental studies showed that the deletion was inherited from the father who has nomal clinical phenotype. The woman elected to terminate the pregnancy at 25 weeks gestation and postmortem examination confirmed the diagnosis of partial URSMS. The published studies were reviewed and 28 cases of URSMS with conducted prenatal ultrasonography were collected in this report. The most common sonographic description, as suspicious signs of URSMS, were severe oligohydramnios or anhydramnios, urinary tract anomalies, fetal intra-abdominal cysts, and dilated bowel. Also, enterolithiasis and vesicocolic fistula were relatively infrequent but highly specific feature of URSMS. Conclusions: URSMS is difficult to be diagnosed prenatally. However, it has characteristic features that can be detected by fetal ultrasonography, and a precise prenatal sonographic examination is crucial

  8. [Evaluation of severity of harm to health caused by trauma aggravating a preceding disease].

    PubMed

    Kapustin, A V

    2003-01-01

    A severity of damage made to the health condition by an injury aggravating a preceding pathology is under discussion. It was demonstrated that such criteria as the time period of temporary disablement as well as the permanent disablement ensure, with respect for clinical data, an objective assessment of a severity done to the health in the discussed cases.

  9. Trends and causes of severity, size, and number of fires in northwestern California, USA.

    PubMed

    Miller, J D; Skinner, C N; Safford, H D; Knapp, E E; Ramirez, C M

    2012-01-01

    Research in the last several years has indicated that fire size and frequency are on the rise in western U.S. forests. Although fire size and frequency are important, they do not necessarily scale with ecosystem effects of fire, as different ecosystems have different ecological and evolutionary relationships with fire. Our study assessed trends and patterns in fire size and frequency from 1910 to 2008 (all fires > 40 ha), and the percentage of high-severity in fires from 1987 to 2008 (all fires > 400 ha) on the four national forests of northwestern California. During 1910-2008, mean and maximum fire size and total annual area burned increased, but we found no temporal trend in the percentage of high-severity fire during 1987-2008. The time series of severity data was strongly influenced by four years with region-wide lightning events that burned huge areas at primarily low-moderate severity. Regional fire rotation reached a high of 974 years in 1984 and fell to 95 years by 2008. The percentage of high-severity fire in conifer-dominated forests was generally higher in areas dominated by smaller-diameter trees than in areas with larger-diameter trees. For Douglas-fir forests, the percentage of high-severity fire did not differ significantly between areas that re-burned and areas that only burned once (10% vs. 9%) when re-burned within 30 years. Percentage of high-severity fire decreased to 5% when intervals between first and second fires were > 30 years. In contrast, in both mixed-conifer and fir/high-elevation conifer forests, the percentage of high-severity fire was less when re-burned within 30 years compared to first-time burned (12% vs. 16% for mixed conifer; 11% vs. 19% for fir/high-elevation conifer). Additionally, the percentage of high-severity fire did not differ whether the re-burn interval was less than or greater than 30 years. Years with larger fires and greatest area burned were produced by region-wide lightning events, and characterized by less winter

  10. Hookworm infestation as a cause of melena and severe anaemia in farmer.

    PubMed

    Tariq, Marvi; Muzammil, Syeda Maria; Shaikh, Fareed Ahmed; Pal, K M Inam

    2017-02-01

    Hookworm infections remain a major cause of morbidity in the developing world. Prevalence is highest in agricultural areas, where use of waste water for irrigation and poor hygiene increases infection rates among farmers. Infections present with gastrointestinal symptoms and chronic anaemia, and there are usually no signs of overt blood loss. The following report describes a case of melena in a middle-aged farmer, where the diagnosis of hookworm infestation was delayed due to the unusual presentation. The patient underwent multiple blood transfusions before referral to the Aga Khan University Hospital (AKUH), Karachi and was managed conservatively with mebendazole at our hospital after exclusion of other possible causes of gastrointestinal bleeding. This case highlights the importance of considering hookworm infestations as a cause of melena in the older age group, where other critical differentials such as peptic ulcer disease and occult malignancy may result in delay in initiation of treatment and a significant financial burden on the patient.

  11. RFT1-congenital disorder of glycosylation (CDG) syndrome: a cause of early-onset severe epilepsy.

    PubMed

    Aeby, Alec; Prigogine, Cynthia; Vilain, Catheline; Malfilatre, Geneviève; Jaeken, Jaak; Lederer, Damien; Van Bogaert, Patrick

    2016-03-01

    RFT1-congenital disorder of glycosylation (CDG) syndrome, a recessive N-glycosylation disorder caused by mutation in the RFT1 gene, is a very rare subtype of CDG syndrome associated with deafness, developmental delay, and non-specific epilepsy. The aim of this report is to describe the electroclinical presentation of epilepsy associated with this condition. [Published with video sequences online].

  12. Smokers Beware: Study Shows Increased Cadmium Levels in the Brain May Cause Severe Neurological Disorders

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Tobacco is one crop that accumulates cadmium, making smokers susceptible to higher levels of the metal in their bodies. The findings suggest that even a low-level exposure to a heavy metal like cadmium is likely to cause a change in the functions of neurons in the brain and the behavioral response to drugs of abuse.

  13. Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia

    PubMed Central

    Yang, Yan; Tang, Hong

    2016-01-01

    Influenza A virus (IAV) infects the respiratory tract in humans and causes significant morbidity and mortality worldwide each year. Aggressive inflammation, known as a cytokine storm, is thought to cause most of the damage in the lungs during IAV infection. Dysfunctional coagulation is a common complication in pathogenic influenza, manifested by lung endothelial activation, vascular leak, disseminated intravascular coagulation and pulmonary microembolism. Importantly, emerging evidence shows that an uncontrolled coagulation system, including both the cellular (endothelial cells and platelets) and protein (coagulation factors, anticoagulants and fibrinolysis proteases) components, contributes to the pathogenesis of influenza by augmenting viral replication and immune pathogenesis. In this review, we focus on the underlying mechanisms of the dysfunctional coagulatory response in the pathogenesis of IAV. PMID:27041635

  14. DID A SEVERE FLOOD IN THE MIDWEST CAUSE AN INCREASE IN THE INCIDENCE OF GASTROINTESTINAL ILLNESS?

    EPA Science Inventory

    Severe flooding occurred in the midwestern United States in 2001. Since November 2000, coincidentally, data on gastrointestinal symptoms had been collected for a drinking water intervention study in a community along the Mississippi River that was affected by the flood. After t...

  15. Therapeutic efficacy of lysophosphatidylcholine in severe infections caused by Acinetobacter baumannii.

    PubMed

    Smani, Younes; Domínguez-Herrera, Juan; Ibáñez-Martínez, José; Pachón, Jerónimo

    2015-07-01

    Due to the significant increase in antimicrobial resistance of Acinetobacter baumannii, immune system stimulation to block infection progression may be a therapeutic adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC), a major component of phospholipids in eukaryotic cells, is involved in immune cell recruitment and modulation. The aim of this study was to show if LPC could be useful for treating infections caused by A. baumannii. A. baumannii ATCC 17978 was used in this study. Levels of serum LPC and levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-10 were determined by spectrophotometric assay and enzyme-linked immunosorbent assay (ELISA), respectively, using a murine peritoneal sepsis model in which mice were inoculated with 5.3 log CFU/ml of A. baumannii. The therapeutic efficacy of LPC against A. baumannii in murine peritoneal sepsis and pneumonia models was assessed for 48 h after bacterial infection. At early time points in the murine model of peritoneal sepsis caused by A. baumannii, LPC was depleted and was associated with an increase of inflammatory cytokine release. Preemptive therapy with LPC in murine peritoneal sepsis and pneumonia models markedly enhanced spleen and lung bacterial clearance and reduced the numbers of positive blood cultures and the mouse mortality rates. Moreover, treatment with LPC reduced proinflammatory cytokine production. These data demonstrate that LPC is efficacious as a preemptive treatment in experimental models of peritoneal sepsis and pneumonia caused by A. baumannii.

  16. Therapeutic Efficacy of Lysophosphatidylcholine in Severe Infections Caused by Acinetobacter baumannii

    PubMed Central

    Domínguez-Herrera, Juan; Ibáñez-Martínez, José; Pachón, Jerónimo

    2015-01-01

    Due to the significant increase in antimicrobial resistance of Acinetobacter baumannii, immune system stimulation to block infection progression may be a therapeutic adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC), a major component of phospholipids in eukaryotic cells, is involved in immune cell recruitment and modulation. The aim of this study was to show if LPC could be useful for treating infections caused by A. baumannii. A. baumannii ATCC 17978 was used in this study. Levels of serum LPC and levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-10 were determined by spectrophotometric assay and enzyme-linked immunosorbent assay (ELISA), respectively, using a murine peritoneal sepsis model in which mice were inoculated with 5.3 log CFU/ml of A. baumannii. The therapeutic efficacy of LPC against A. baumannii in murine peritoneal sepsis and pneumonia models was assessed for 48 h after bacterial infection. At early time points in the murine model of peritoneal sepsis caused by A. baumannii, LPC was depleted and was associated with an increase of inflammatory cytokine release. Preemptive therapy with LPC in murine peritoneal sepsis and pneumonia models markedly enhanced spleen and lung bacterial clearance and reduced the numbers of positive blood cultures and the mouse mortality rates. Moreover, treatment with LPC reduced proinflammatory cytokine production. These data demonstrate that LPC is efficacious as a preemptive treatment in experimental models of peritoneal sepsis and pneumonia caused by A. baumannii. PMID:25896698

  17. A Giant Brunneroma Causing Gastrointestinal Bleeding and Severe Anemia Requiring Transfusion and Surgery

    PubMed Central

    Laclé, Miangela M.; Borel Rinkes, Inne H. M.

    2017-01-01

    Brunner's gland hamartoma, also called hyperplasia, adenoma, and Brunneroma, is an extremely rare benign proliferative lesion of Brunner's glands in the duodenum. While being mostly small and asymptomatic, they can result in gastrointestinal bleeding and obstruction. We report the case of a 54-year-old man presenting with melena and severe anemia requiring blood transfusion. CT scans showed a large mass of 8 cm in diameter, presumably arising in the duodenum. Endoscopic biopsies were not conclusive. As we were unable to determine the nature of the mass preoperatively and due to the severe symptoms, its size, and the uncertain malignant potential, a classic Whipple procedure was performed. The resected specimen showed extensive proliferation of Brunner's glands without signs of malignancy. PMID:28299229

  18. A Giant Brunneroma Causing Gastrointestinal Bleeding and Severe Anemia Requiring Transfusion and Surgery.

    PubMed

    Frenkel, Nicola C; Laclé, Miangela M; Borel Rinkes, Inne H M; Molenaar, Izaak Q; Hagendoorn, Jeroen

    2017-01-01

    Brunner's gland hamartoma, also called hyperplasia, adenoma, and Brunneroma, is an extremely rare benign proliferative lesion of Brunner's glands in the duodenum. While being mostly small and asymptomatic, they can result in gastrointestinal bleeding and obstruction. We report the case of a 54-year-old man presenting with melena and severe anemia requiring blood transfusion. CT scans showed a large mass of 8 cm in diameter, presumably arising in the duodenum. Endoscopic biopsies were not conclusive. As we were unable to determine the nature of the mass preoperatively and due to the severe symptoms, its size, and the uncertain malignant potential, a classic Whipple procedure was performed. The resected specimen showed extensive proliferation of Brunner's glands without signs of malignancy.

  19. Can esophageal dilation be avoided in the treatment of severe esophageal stricture caused by eosinophilic esophagitis?

    PubMed

    Silva, D; Santos, F; Piedade, S; Morais-Almeida, M

    2015-07-01

    Eosinophilic esophagitis (EoE) is an inflammatory immune-mediated disease with predominant eosinophilic inflammation characterized by the presence of esophageal dysfunction symptoms. Treatment delay can be associated with disease complications, like esophageal strictures, that can justify the use of invasive procedures which are not deprived of side effects. We present a case report of a 14 year old child with severe esophageal stricture secondary to EoE, that was treated with topical and systemic corticosteroid before any invasive procedure was considered. After 26 weeks of medical treatment, significant improvement of esophageal dysfunction occurred with histological remission and stricture resolution. In patients with severe esophageal strictures secondary to EoE, the need for esophageal dilation procedures should be considered only after anti-inflammatory treatment.

  20. [Dientamoeba fragilis infection as cause of severe abdominal discomfort and flatulence].

    PubMed

    Halkjær, Sofie; Stensvold, Christen Rune; Petersen, Andreas Munk

    2015-01-26

    The clinical significance of Dientamoeba fragilis infection is controversial. We describe a case-history of a 16-year-old patient, who had suffered severe abdominal discomfort and flatulence through his lifetime. He was eventually diagnosed with D. fragilis infection, and eradication of D. fragilis with high-dose metronidazole kept him without symptoms for one year. Recurrence of the symptoms and recurrence of the D. fragilis infection was thereafter treated successfully with paromomycin.

  1. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    PubMed

    Baird, J K; Basri, H; Weina, P; MaGuire, J D; Barcus, M J; Picarema, H; Elyazar, I R F; Ayomi, E; Sekartuti

    2003-08-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P < 0.0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR > 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection.

  2. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    PubMed Central

    Baird, J. K.; Basri, H.; Weina, P.; MaGuire, J. D.; Barcus, M. J.; Picarema, H.; Elyazar, I. R. F.; Ayomi, E.; Sekartuti

    2003-01-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P < 0.0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR > 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection. PMID:12948380

  3. Severe exfoliative dermatitis caused by strontium ranelate: two cases of a new drug reaction.

    PubMed

    Smith, Emma V; Shipley, Debbie R V

    2010-05-01

    Strontium ranelate is a relatively new drug used as a second-line treatment for osteoporosis, often targeted at older patients. It is known to cause skin rash and rarely drug reaction with eosinophilia and systemic symptoms, but there are no reports of exfoliative dermatitis as a reaction in the literature. We present the first two cases of this adverse effect of the drug, combined with eosinophilia but no systemic symptoms. We illustrate the significant morbidity involved and use of systemic steroid treatment required, highlighting the need for awareness of this reaction in medical and particularly in elderly care communities.

  4. Injury Severity and Causes of Death from Operation Iraqi Freedom and Operation Enduring Freedom: 2003-2004 Versus 2006

    DTIC Science & Technology

    2008-02-01

    on the chitosan -based hemostatic dressing : experience in current combat operations. J Trauma. 2006;60:655–658. 5. Holcomb JB. The 2004 Fitts Lecture...Defense has enacted numerous evidence-based pol- icies and clinical practice guidelines. We hypothesized that the severity of wounds has increased over...injury severity and number of wounds per casualty. Truncal hemorrhage is the leading cause of poten- tially survivable deaths. Arguably, the suc- cess of

  5. Severe aromatic hydrocarbon pollution in the Arctic town of Longyearbyen (Svalbard) caused by snowmobile emissions.

    PubMed

    Reimann, Stefan; Kallenborn, Roland; Schmidbauer, Norbert

    2009-07-01

    The aromatic hydrocarbons benzene, toluene and C2-benzenes (ethyl benzene and m,p,o-xylene) (BTEX) were measured during a 2-month monitoring campaign in 2007 in the Arctic town of Longyearbyen (Spitsbergen, Svalbard). Reflecting the remoteness of the location, very low mixing ratios were observed during night and in windy conditions. In late spring (April-May), however, the high frequency of guided snowmobile tours resulted in "rush-hour" maximum values of more than 10 ppb of BTEX. These concentration levels are comparable to those in European towns and are caused predominately by the outdated 2-stroke engines, which are still used by approximately 30% of the snowmobiles in Longyearbyen. During summer, peak events were about a factor of 100 lower compared to those during the snowmobile season. Emissions in summer were mainly caused by diesel-fueled heavy duty vehicles (HDVs), permanently used for coal transport from the adjacent coal mines. The documented high BTEX mixing ratios from snowmobiles in the Arctic provide an obvious incentive to change the regulation practice to a cleaner engine technology.

  6. Cameron Ulcer Causing Severe Anemia in a Patient with Diaphragmatic Hernia

    PubMed Central

    Gupta, Prashant; Suryadevara, Madhu; Das, Avash; Falterman, James

    2015-01-01

    Patient: Female, 51 Final Diagnosis: Cameron’s ulcer Symptoms: — Medication: — Clinical Procedure: Endoscopy Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology Background: Cameron lesions are linear gastric erosions on the mucosal folds at the diaphragmatic impressions found in patients with large hiatal hernias. While usually asymptomatic, hiatal hernias can result in serious sequelae, as this case report will clearly illustrate. Cameron lesions are clinically significant because of their ability to cause significant acute, chronic, or obscure gastrointestinal bleeding, often requiring blood transfusions. Case Report: In this report, we present the case of a 51-year-old white woman who originally presented to the Emergency Department with complaints of a runny nose, dry cough, generalized weakness, and muscle cramping ascribed to a viral infection. However, closer examination revealed substantial pallor with pale conjunctiva prompting further workup that revealed substantial anaemia. Upon further inquiry of her past medical history, she revealed the need for previous blood transfusions, and meticulous review of her medical record indicated a previous diagnosis of hiatal hernia with the presence of Cameron lesions based on esophagogastroduodenoscopy 2 years prior. Conclusions: This case emphasizes the need for a high index of suspicion for Cameron lesions as a causative agent of substantial blood loss in patients with hiatal hernias after other common causes of gastrointestinal bleeding have been ruled out. PMID:26467083

  7. [Successful treatment of people with severe body injuries caused rabid animal bites].

    PubMed

    Golubović, S

    1998-01-01

    Seven patients were presented with severe injuries seeking medical help 3-10 days after being bitten by rabid animals. Just one of those subjects underwent timely and correct surgical management. Three patients were with complete, and four with incomplete antirabic prophylaxis. Two patients did not receive human rabies immunoglobulin, and another two did not receive HDC-RV vaccine. At least 3 patients were expected to develop rabies, but it did not happen. The course of these cases could be explained by the existence of less pathogenic strains of virus in Banja Luka region.

  8. A founder mutation causing a severe methylenetetrahydrofolate reductase (MTHFR) deficiency in Bukharian Jews.

    PubMed

    Ben-Shachar, Shay; Zvi, Tal; Rolfs, Arndt; Breda Klobus, Andrea; Yaron, Yuval; Bar-Shira, Anat; Orr-Urtreger, Avi

    2012-11-01

    Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. A novel homozygous MTHFR c.474A>T (p.G158G) mutation was detected in two unrelated children of Jewish Bukharian origin. This mutation generates an abnormal splicing and early termination codon. A carrier frequency of 1:39 (5/196) was determined among unrelated healthy Bukharian Jews. Given the disease severity and allele frequency, a population screening for individuals of this ancestry is warranted in order to allow prenatal, or preimplantation diagnosis.

  9. Myelodysplastic syndrome in pregnancy--a rare cause of severe anaemia in pregnancy.

    PubMed

    Biswas, Arati; Sanyal, Pradipta

    2006-11-01

    A 28-year-old woman presented with severe anaemia in pregnancy at a period of gestation of 20 weeks. She was immediately admitted and after proper investigation it was seen that her Hb was 3.5 g/dl and platelet count was 62,000/cmm, RBC showed normocytic, normochromic morphology. There was neither hepatosplenomegaly nor any purpuric spot over the body. Bone marrow showed dyserythropoiesis and its chromosomal study revealed monosomy-7. Her pregnancy was continued till term with repeated packed cell and platelet concentrate transfusions. Normal healthy baby was delivered by caesarean section and she was discharged after 6 days.

  10. Isolated gonadotropin deficiency secondary to glioma in septum pellucidum.

    PubMed

    Kitamura, M; Namiki, M; Okuyama, A; Arita, N; Mizutani, S; Sonoda, T

    1988-01-01

    A 21-year-old man, who had had normal sexuality beforehand, noticed a decrease in libido and potency, as well as loss of ejaculation. Endocrine evaluation showed normal serum levels of gonadotropins but a low testosterone level. The response to clomiphene citrate was poor while those to luteinizing hormone-releasing hormone and human chorionic gonadotropin were within normal limits. A tumor found in the septum pellucidum through brain-computerized tomography was resected. Histologically it proved to be a mixed tumor composed of astrocytoma and oligodendroglioma. Three months after the operation the patient had recovered normal sexual functions and endocrine evaluations, including the responsiveness to clomiphene citrate, had been restored. This case suggests the existence of some stimulatory fiber for the secretion of luteinizing hormone in the septum pellucidum.

  11. Echinococcal Cyst of the Interventricular Septum with Right Ventricular Protrusion

    PubMed Central

    Eren, E. Ergin; Aykut, Serap; Kayihan, Attila; Aydogan, Hakki; Dagsali, Sabri

    1989-01-01

    Although echinococcosis (echinococcal hydatidosis) is common in sheep-raising countries such as Turkey, cardiac involvement is rare; the presence of a hydatid cyst in the interventricular septum is rarer still. We report a case of hydatid cyst of the interventricular septum that was first revealed by 2-dimensional echocardiography and then confirmed by right ventricular angiography. The cyst was removed surgically under cardiopulmonary bypass. Within the context of the medical literature concerning this rare lesion, we discuss this case and 10 other cases of cardiac hydatidosis, previously unreported in the world literature, that we have treated from January 1967 through January 1987. (Texas Heart Institute Journal 1989;16:292-5) Images PMID:15227384

  12. SMN deficiency in severe models of spinal muscular atrophy causes widespread intron retention and DNA damage.

    PubMed

    Jangi, Mohini; Fleet, Christina; Cullen, Patrick; Gupta, Shipra V; Mekhoubad, Shila; Chiao, Eric; Allaire, Norm; Bennett, C Frank; Rigo, Frank; Krainer, Adrian R; Hurt, Jessica A; Carulli, John P; Staropoli, John F

    2017-03-21

    Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease, is the leading monogenic cause of infant mortality. Homozygous loss of the gene survival of motor neuron 1 (SMN1) causes the selective degeneration of lower motor neurons and subsequent atrophy of proximal skeletal muscles. The SMN1 protein product, survival of motor neuron (SMN), is ubiquitously expressed and is a key factor in the assembly of the core splicing machinery. The molecular mechanisms by which disruption of the broad functions of SMN leads to neurodegeneration remain unclear. We used an antisense oligonucleotide (ASO)-based inducible mouse model of SMA to investigate the SMN-specific transcriptome changes associated with neurodegeneration. We found evidence of widespread intron retention, particularly of minor U12 introns, in the spinal cord of mice 30 d after SMA induction, which was then rescued by a therapeutic ASO. Intron retention was concomitant with a strong induction of the p53 pathway and DNA damage response, manifesting as γ-H2A.X positivity in neurons of the spinal cord and brain. Widespread intron retention and markers of the DNA damage response were also observed with SMN depletion in human SH-SY5Y neuroblastoma cells and human induced pluripotent stem cell-derived motor neurons. We also found that retained introns, high in GC content, served as substrates for the formation of transcriptional R-loops. We propose that defects in intron removal in SMA promote DNA damage in part through the formation of RNA:DNA hybrid structures, leading to motor neuron death.

  13. SMN deficiency in severe models of spinal muscular atrophy causes widespread intron retention and DNA damage

    PubMed Central

    Jangi, Mohini; Fleet, Christina; Cullen, Patrick; Gupta, Shipra V.; Mekhoubad, Shila; Chiao, Eric; Allaire, Norm; Bennett, C. Frank; Rigo, Frank; Krainer, Adrian R.; Hurt, Jessica A.; Carulli, John P.; Staropoli, John F.

    2017-01-01

    Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease, is the leading monogenic cause of infant mortality. Homozygous loss of the gene survival of motor neuron 1 (SMN1) causes the selective degeneration of lower motor neurons and subsequent atrophy of proximal skeletal muscles. The SMN1 protein product, survival of motor neuron (SMN), is ubiquitously expressed and is a key factor in the assembly of the core splicing machinery. The molecular mechanisms by which disruption of the broad functions of SMN leads to neurodegeneration remain unclear. We used an antisense oligonucleotide (ASO)-based inducible mouse model of SMA to investigate the SMN-specific transcriptome changes associated with neurodegeneration. We found evidence of widespread intron retention, particularly of minor U12 introns, in the spinal cord of mice 30 d after SMA induction, which was then rescued by a therapeutic ASO. Intron retention was concomitant with a strong induction of the p53 pathway and DNA damage response, manifesting as γ-H2A.X positivity in neurons of the spinal cord and brain. Widespread intron retention and markers of the DNA damage response were also observed with SMN depletion in human SH-SY5Y neuroblastoma cells and human induced pluripotent stem cell-derived motor neurons. We also found that retained introns, high in GC content, served as substrates for the formation of transcriptional R-loops. We propose that defects in intron removal in SMA promote DNA damage in part through the formation of RNA:DNA hybrid structures, leading to motor neuron death. PMID:28270613

  14. Severe Abdominal Pain Caused by Lead Toxicity without Response to Oral Chelators: A Case Report

    PubMed Central

    Vossoughinia, Hassan; Pourakbar, Ali; Esfandiari, Samaneh; Sharifianrazavi, Masoud

    2016-01-01

    A 19-year-old woman was referred to the Emergency Surgery Department with severe abdominal pain, icterus, and anemia. The patient’s clinical and paraclinical findings in addition to her occupational and social history, convinced us to assay blood lead level (BLL), which was 41/5 μg/dL. Therefore toxicology consult was performed to treat lead toxicity. Recheck of the BLL showed the level as 53/7 μg/dL. So oral chelator with succimer was started. Despite consumption of oral chelator, there was no response and the pain continued. Because our repeated evaluations were negative, we decided to re-treat lead poisoning by intravenous and intramuscular chelators. Dimercaprol (BAL) + calcium EDTA was started, and after 5 days, the pain relieved dramatically and the patient was discharged. We recommend more liberal lead poisoning therapy in symptomatic patients, and also suggest parenteral chelator therapy, which is more potent, instead of oral chelators in patients with severe symptoms. PMID:26933485

  15. Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation.

    PubMed Central

    McNally, E. M.; Passos-Bueno, M. R.; Bönnemann, C. G.; Vainzof, M.; de Sá Moreira, E.; Lidov, H. G.; Othmane, K. B.; Denton, P. H.; Vance, J. M.; Zatz, M.; Kunkel, L. M.

    1996-01-01

    Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein gamma-sarcoglycan. The previous mutation analysis of gamma-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the gamma-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding gamma-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the gamma-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of alpha-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the gamma-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from gamma-sarcoglycan gene mutations. Images Figure 2 Figure 5 PMID:8900232

  16. A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP).

    PubMed

    Pons, Véronique; Rolland, Corinne; Nauze, Michel; Danjoux, Marie; Gaibelet, Gérald; Durandy, Anne; Sassolas, Agnès; Lévy, Emile; Tercé, François; Collet, Xavier; Mas, Emmanuel

    2011-07-01

    Abetalipoproteinemia is a rare autosomal recessive disease characterized by low lipid levels and by the absence of apoB-containing lipoproteins. It is the consequence of microsomal triglyceride transfer protein (MTTP) deficiency. We report two patients with new MTTP mutations. We studied their functional consequences on the triglyceride transfer function using duodenal biopsies. We transfected MTTP mutants in HepG2 and HeLa cells to investigate their association with protein disulfide isomerase (PDI) and their localization at the endoplasmic reticulum. These children have a severe abetalipoproteinemia. Both of them had also a mild hypogammaglobulinemia. They are compound heterozygotes with c.619G>T and c.1237-28A>G mutations within the MTTP gene. mRNA analysis revealed abnormal splicing with deletion of exon 6 and 10, respectively. Deletion of exon 6 (Δ6-MTTP) introduced a frame shift in the reading frame and a premature stop codon at position 234. Despite the fact that Δ6-MTTP and Δ10-MTTP mutants were not capable of binding PDI, both MTTP mutant proteins normally localize at the endoplasmic reticulum. However, these two mutations induce a loss of MTTP triglyceride transfer activity. These two mutations lead to abnormal truncated MTTP proteins, incapable of binding PDI and responsible for the loss of function of MTTP, thereby explaining the severe abetalipoproteinemia phenotype of these children.

  17. Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency.

    PubMed

    Yang, W; Lee, P P W; Thong, M-K; Ramanujam, T M; Shanmugam, A; Koh, M-T; Chan, K-W; Ying, D; Wang, Y; Shen, J J; Yang, J; Lau, Y L

    2015-12-01

    Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.

  18. Severe Abdominal Pain Caused by Lead Toxicity without Response to Oral Chelators: A Case Report.

    PubMed

    Vossoughinia, Hassan; Pourakbar, Ali; Esfandiari, Samaneh; Sharifianrazavi, Masoud

    2016-01-01

    A 19-year-old woman was referred to the Emergency Surgery Department with severe abdominal pain, icterus, and anemia. The patient's clinical and paraclinical findings in addition to her occupational and social history, convinced us to assay blood lead level (BLL), which was 41/5 μg/dL. Therefore toxicology consult was performed to treat lead toxicity. Recheck of the BLL showed the level as 53/7 μg/dL. So oral chelator with succimer was started. Despite consumption of oral chelator, there was no response and the pain continued. Because our repeated evaluations were negative, we decided to re-treat lead poisoning by intravenous and intramuscular chelators. Dimercaprol (BAL) + calcium EDTA was started, and after 5 days, the pain relieved dramatically and the patient was discharged. We recommend more liberal lead poisoning therapy in symptomatic patients, and also suggest parenteral chelator therapy, which is more potent, instead of oral chelators in patients with severe symptoms.

  19. A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality.

    PubMed

    Crimi, Marco; Papadimitriou, Alexandros; Galbiati, Sara; Palamidou, Phani; Fortunato, Francesco; Bordoni, Andreina; Papandreou, Urania; Papadimitriou, Dimitra; Hadjigeorgiou, George M; Drogari, Eurydiki; Bresolin, Nereo; Comi, Giacomo Pietro

    2004-05-01

    We describe a new mitochondrial DNA mutation in a male infant who presented clinical and magnetic resonance imaging features of Leigh syndrome and died at the age of 9 mo. The patient's development was reportedly normal in the first months of life. At the age of 5 mo, he presented severe generalized hypotonia, nystagmus, and absent eye contact. Laboratory examination showed increased lactate and pyruvate in both serum and cerebrospinal fluid. Brain magnetic resonance imaging revealed multiple necrotic lesions in the basal ganglia, brain stem, and thalamus. Muscle histopathology was unremarkable, whereas respiratory chain enzyme analysis revealed a severe complex I deficiency. The patient died after an acidotic coma at age 9 mo. Sequence analysis of the entire mtDNA disclosed a new T10158C mutation with variable tissue heteroplasm (muscle: 83%; blood: 48%). The mutation was undetectable in the blood of his unaffected mother. The transition changes a serine residue into a proline, in a highly conserved region of the NADH dehydrogenase subunit 3 (ND3). This is the first description of a mitochondrial ND3 gene in Leigh syndrome with early lethality.

  20. Mild and severe muscular dystrophy caused by a single {gamma}-sarcoglycan mutation

    SciTech Connect

    McNally, E.M.; Boennemann, C.G.; Lidov, H.G.W.

    1996-11-01

    Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein {gamma}-sarcoglycan. The previous mutation analysis of {gamma}-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the {gamma}-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding {gamma}-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the {gamma}-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of {alpha}-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the {gamma}-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from {gamma}-sarcoglycan gene mutations. 19 refs., 5 figs., 3 tabs.

  1. Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN.

    PubMed

    Kumar, Santhosh V R; Kulkarni, Onkar P; Mulay, Shrikant R; Darisipudi, Murthy N; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen; Anders, Hans-Joachim

    2015-10-01

    Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN.

  2. A novel mutation in the GCM2 gene causing severe congenital isolated hypoparathyroidism

    PubMed Central

    Doyle, Daniel; Kirwin, Susan M.; Sol-Church, Katia; Levine, Michael A.

    2013-01-01

    Objective To investigate the GCM2 gene in three siblings with congenital hypoparathyroidism and perform functional analysis. Materials and methods We sequenced the GCM2 gene by PCR and analyzed the functional consequence of the mutation by transient transfection studies. Haplotype analysis was performed. Results We identified a nucleotide change, c.408C>A, in exon 3 that is predicted to truncate the Gcm2 protein (p.Tyr136Ter). All three affected siblings were homozygous and both parents were heterozygous for the mutation. Transfection studies revealed the mutant mRNA but not expression of the Gcm2 protein. Haplotype analysis revealed that the two mutant GCM2 alleles shared genotypes on chromosome 6p24.2. Conclusions We describe the first GCM2 mutation in exon 3 in patients with severe congenital hypoparathyroidism. Informative genetic markers could not exclude identity by descent for the mutant alleles. Gcm2 protein was not detected after transfection, suggesting that complete lack of Gcm2 action accounts for severe hypoparathyroidism. PMID:23155703

  3. det1, cop1, and cop9 mutations cause inappropriate expression of several gene sets.

    PubMed Central

    Mayer, R; Raventos, D; Chua, N H

    1996-01-01

    Genetic studies using Arabidopsis offer a promising approach to investigate the mechanisms of light signal transduction during seedling development. Several mutants, called det/cop, have been isolated based on their deetiolated/constitutive photomorphogenic phenotypes in the dark. This study examines the specificity of the det/cop mutations with respect to their effects on genes regulated by other signal transduction pathways. Steady state mRNA levels of a number of differently regulated gene sets were compared between mutants and the wild type. We found that det2, cop2, cop3, and cop4 mutants displayed a gene expression pattern similar to that of the wild type. By contrast, det1, cop1, and cop9 mutations exhibited pleiotropic effects. In addition to light-responsive genes, genes normally inducible by plant pathogens, hypoxia, and developmental programs were inappropriately expressed in these mutants. Our data provide evidence that DET1, COP1, and COP9 most likely act as negative regulators of several sets of genes, not just those involved in light-regulated seedling development. PMID:8953766

  4. det1, cop1, and cop9 mutations cause inappropriate expression of several gene sets.

    PubMed

    Mayer, R; Raventos, D; Chua, N H

    1996-11-01

    Genetic studies using Arabidopsis offer a promising approach to investigate the mechanisms of light signal transduction during seedling development. Several mutants, called det/cop, have been isolated based on their deetiolated/constitutive photomorphogenic phenotypes in the dark. This study examines the specificity of the det/cop mutations with respect to their effects on genes regulated by other signal transduction pathways. Steady state mRNA levels of a number of differently regulated gene sets were compared between mutants and the wild type. We found that det2, cop2, cop3, and cop4 mutants displayed a gene expression pattern similar to that of the wild type. By contrast, det1, cop1, and cop9 mutations exhibited pleiotropic effects. In addition to light-responsive genes, genes normally inducible by plant pathogens, hypoxia, and developmental programs were inappropriately expressed in these mutants. Our data provide evidence that DET1, COP1, and COP9 most likely act as negative regulators of several sets of genes, not just those involved in light-regulated seedling development.

  5. Crisscross heart with dextrocardia and intact interventricular septum.

    PubMed

    Muneer, P Kader; Kalathingathodika, Sajeer; Chakanalil, Govindan Sajeev; Sony, Manuel M

    2014-01-01

    Crisscross heart is a rare congenital heart disease characterized by a twisted atrioventricular connection, as a result of rotation of the ventricular mass along its long axis. We report an asymptomatic 48-year-old woman referred to us for evaluation of a cardiac murmur. Further evaluation showed situs solitus, dextrocardia with normal atrioventricular and ventriculoarterial connection, and a crisscross relation of the atrioventricular valves. Unlike the usual case of crisscross heart, our patient had an intact ventricular septum.

  6. Cystic choroid plexus papilloma in the cavum septum pellucidum.

    PubMed

    Tuchman, Alexander; Kalhorn, Stephen P; Mikolaenko, Irina; Wisoff, Jeffrey H

    2009-12-01

    A choroid plexus papilloma is a rare CNS neoplasm arising from the neuroepithelial lining of the choroid plexus. A third ventricular location of a choroid plexus papilloma is rare compared with the more common sites in the lateral and fourth ventricles. Cystic choroid plexus papilloma represents an infrequent subtype that may present diagnostic ambiguity. The authors present a case of cystic choroid plexus papilloma within a cavum septum pellucidum that radiographically mimicked neurocysticercosis.

  7. As the Nasal Spine Goes, So Goes the Septum

    PubMed Central

    Jagade, Mohan; Kale, Vitthal; Attakil, Anoop; Kar, Rajesh; Singhal, Arpita; Rao, Karthik; Gupta, Pallavi

    2016-01-01

    Introduction "As the septum goes, so goes the nose". A well-known phrase by Maurice Cottle forms the pillar of septoplasty. Since the inception of septal surgeries, numerous methods of septoplasty have been described. But, if not performed meticulously, may lead to deformity. For a successful surgery, understanding the anatomy and addressing the anterior nasal spine and maintaining the tip integrity is vital. Aim To study the outcomes of “ROUND ABOUT technique” to correct deviated nasal septum which focuses on the importance of anterior spine and hence maintain the tip integrity. Materials and Methods This was a prospective, single-centre outcome study of 35 patients with symptomatic nasal obstruction. Here, we describe a method of elevating the mucoperichondrial and mucoperiosteal flaps bilaterally, without transecting the quadrilateral cartilage of the septum. The Sino Nasal Outcome Test-22 (SNOT-22) Questionnaire was administered pre-operatively and after 3 months following surgery. The post-operative follow-up period ranged from 3 to 6 months (mean= 4.5 months) to evaluate the functional and aesthetic outcomes of the performed procedure. Results A total of 35 patients underwent surgery by this technique who presented with deviated nasal septum and variable degrees of nasal obstruction. To assess the statistical outcome, Paired t-test was applied. Mean SNOT-22 scores decreased significantly from 40.02 pre-operatively to 18.65 three months after surgery. The results sustained after 6 months (p-value <0.0001), 85% of these patients had improved breathing post-operatively and none of the patients complained any aesthetic criticisms. The patients were content and the requirement of medications post-operatively were minimal. Conclusion The ROUND ABOUT technique is a very effective and safe method in correcting the septal deviations especially the ones with caudal or dorsal deflections. It also helps in maintaining the tip integrity and addressing the anterior

  8. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor c...

  9. Severe acute respiratory distress syndrome caused by unintentional sewing machine lubricant ingestion: A case report

    PubMed Central

    Kishore, Sunil; Chandelia, Sudha; Patharia, Neha; Swarnim

    2016-01-01

    Sewing machine oil ingestion is rare but is possible due to its availability at home. Chemically, it belongs to hydrocarbon family which is toxic if aspirated, owing to their physical properties such as high volatility and low viscosity. On the contrary, sewing machine lubricant has high viscosity and low volatility which makes it aspiration less likely. The main danger of hydrocarbon ingestion is chemical pneumonitis which may be as severe as acute respiratory distress syndrome (ARDS). We report a case of a 5-year-old girl with accidental ingestion of sewing machine lubricant oil, who subsequently developed ARDS refractory to mechanical ventilation. There was much improvement with airway pressure release ventilation mode of ventilation, but the child succumbed to death due to pulmonary hemorrhage. PMID:27994384

  10. Multi-drug-resistant hypertension caused by severe aortic coarctation presenting in late adulthood.

    PubMed

    Meller, Stephanie M; Fahey, John T; Setaro, John F; Forrest, John K

    2015-04-01

    Aortic coarctation, a congenital narrowing in the region of the ligamentum arteriosium, is a rare etiology for multi-drug-resistant hypertension in adulthood; however, advances in stenting modalities may offer long-term improvements in morbidity and possibly even cure. We report on a female patient in her late 50s presenting with refractory hypertension and severely elevated renin levels, ultimately diagnosed with aortic coarctation and treated with percutaneous stent implantation, which resulted in successful blood pressure control with verapamil monotherapy. This case highlights the efficacy of endovascular stent implantation for the treatment of coarctation and the need for clinicians to consider this disease entity in the differential diagnosis of refractory hypertension even in late adulthood.

  11. Severe necrotizing myocarditis caused by serratia marcescens infection in an axolotl (Ambystoma mexicanum).

    PubMed

    Del-Pozo, J; Girling, S; Pizzi, R; Mancinelli, E; Else, R W

    2011-05-01

    This report provides the first account of the pathological changes associated with infection by Serratia marcescens in an adult male axolotl. The infection resulted in septicaemia with severe multifocal necrotizing myocarditis. The latter lesion evolved to cardiac rupture, haemopericardium and death resulting from cardiac tamponade. This animal was exposed to higher than usual temperatures (24-25 °C) 2 weeks before the onset of disease and this may have resulted in immunocompromise and opportunistic bacterial infection. S. marcescens was isolated from the coelomic and pericardial cavity. Both isolates were identical and were resistant to β-lactam antibiotics, but not to aminoglycosides or fluoroquinolones. The production of red prodigiosin pigment by the bacterium suggested an environmental origin. Overall, the clinical and histopathological presentation suggests that S. marcescens should be included in the list of aetiological agents of the 'red-leg'/bacterial dermatosepticaemia syndrome of amphibians.

  12. Severe Pleuropulmonary Paragonimiasis Caused by Paragonimus mexicanus Treated as Tuberculosis in Ecuador.

    PubMed

    Calvopina, Manuel; Romero-Alvarez, Daniel; Macias, Rubén; Sugiyama, Hiromu

    2017-01-11

    A 30-year-old male, from a subtropical region of Ecuador, was hospitalized with a 5-year history of persistent cough with rusty brown sputum, chest pain, and progressive dyspnea. The patient underwent thoracic surgery 3 years ago for pleural effusion and subsequently received a 9-month regimen treatment of tuberculosis. However, there was no clinical resolution and symptoms became progressively worse. A chest radiograph and computerized tomography scan showed several small nodules in both lungs. Eggs of Paragonimus spp. were observed in sputum smears, but the smears were negative for acid-fast bacilli. Molecular characterization of eggs by the internal transcribed spacer-2 regions identified them as Paragonimus mexicanus The patient was treated with praziquantel and tested negative parasitologically for 12 months. There was clinical resolution of the cough and expectoration, but dyspnea and chest pain persisted.

  13. Severe anemia caused by babesiosis in a maned wolf (Chrysocyon brachyurus).

    PubMed

    Phair, Kristen A; Carpenter, James W; Smee, Nicole; Myers, Carl B; Pohlman, Lisa M

    2012-03-01

    An 8-yr-old, captive, spayed, female maned wolf (Chrysocyon brachyurus) developed progressive lethargy and weakness over a 24-hr period. Clinical signs included vomiting, recumbency, horizontal nystagmus, possible blindness, pale icteric mucus membranes, and port-wine colored urine. A complete blood cell count revealed severe anemia (packed cell volume [PCV], 6%) and intraerythrocytic piroplasms consistent with a Babesia species. Polymerase chain reaction testing later confirmed babesiosis. The wolf was treated with imidocarb dipropionate, antibiotics, and fluid therapy. A whole-blood transfusion from a sibling maned wolf also was performed. Despite aggressive treatment, the wolf failed to improve and was euthanized. To the authors' knowledge, this is the first documented case of babesiosis in a captive maned wolf in North America. Surveillance of infectious diseases in captive and wild maned wolf populations should be expanded to include screening for Babesia species. Tick control also should be implemented to prevent and decrease transmission of the disease to this endangered species.

  14. An outbreak in 1965 of severe respiratory illness caused by the Legionnaires' disease bacterium.

    PubMed

    Thacker, S B; Bennett, J V; Tsai, T F; Fraser, D W; McDade, J E; Shepard, C C; Williams, K H; Stuart, W H; Dull, H B; Eickhoff, T C

    1978-10-01

    In January 1977 an unsolved outbreak of infection at St. Elizabeth's Hospital (Washington, D.C.) that occurred in 1965 was linked with Legionnaires' disease. The link was made by fluorescent antibody testing with the bacterium isolated from tissues of persons with Legionnaires' disease in the 1976 outbreak in Philadelphia. In July and August 1965, an epidemic of severe respiratory disease characterized by abrupt onset of high fever, weakness, malaise, and nonproductive cough, frequently accompanied by radiographic evidence of pneumonia, affected at least 81 patients at St. Elizabeth's Hospital, a general psychiatric hospital. Fourteen (17%) of the affected patients died. Intensive epidemiologic and laboratory investigations in 1965 did not determine the etiology. The etiologic organism may have become airborne from sites of soil excavation.

  15. TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment.

    PubMed

    Delplanque, Jérôme; Devos, David; Huin, Vincent; Genet, Alexandre; Sand, Olivier; Moreau, Caroline; Goizet, Cyril; Charles, Perrine; Anheim, Mathieu; Monin, Marie Lorraine; Buée, Luc; Destée, Alain; Grolez, Guillaume; Delmaire, Christine; Dujardin, Kathy; Dellacherie, Delphine; Brice, Alexis; Stevanin, Giovanni; Strubi-Vuillaume, Isabelle; Dürr, Alexandra; Sablonnière, Bernard

    2014-10-01

    Autosomal dominant cerebellar ataxia corresponds to a clinically and genetically heterogeneous group of neurodegenerative disorders that primarily affect the cerebellum. Here, we report the identification of the causative gene in spinocerebellar ataxia 21, an autosomal-dominant disorder previously mapped to chromosome 7p21.3-p15.1. This ataxia was firstly characterized in a large French family with slowly progressive cerebellar ataxia, accompanied by severe cognitive impairment and mental retardation in two young children. Following the recruitment of 12 additional young family members, linkage analysis enabled us to definitively map the disease locus to chromosome 1p36.33-p36.32. The causative mutation, (c.509C>T/p.P170L) in the transmembrane protein gene TMEM240, was identified by whole exome sequencing and then was confirmed by Sanger sequencing and co-segregation analyses. Index cases from 368 French families with autosomal-dominant cerebellar ataxia were also screened for mutations. In seven cases, we identified a range of missense mutations (c.509C>T/p.P170L, c.239C>T/p.T80M, c.346C>T/p.R116C, c.445G>A/p.E149K, c.511C>T/p.R171W), and a stop mutation (c.489C>G/p.Y163*) in the same gene. TMEM240 is a small, strongly conserved transmembrane protein of unknown function present in cerebellum and brain. Spinocerebellar ataxia 21 may be a particular early-onset disease associated with severe cognitive impairment.

  16. A nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice.

    PubMed

    Ishii, Akihiro; Ueno, Keisuke; Orba, Yasuko; Sasaki, Michihito; Moonga, Ladslav; Hang'ombe, Bernard M; Mweene, Aaron S; Umemura, Takashi; Ito, Kimihito; Hall, William W; Sawa, Hirofumi

    2014-12-02

    Bats can carry important zoonotic pathogens. Here we use a combination of next-generation sequencing and classical virus isolation methods to identify novel nairoviruses from bats captured from a cave in Zambia. This nairovirus infection is highly prevalent among giant leaf-nosed bats, Hipposideros gigas (detected in samples from 16 individuals out of 38). Whole-genome analysis of three viral isolates (11SB17, 11SB19 and 11SB23) reveals a typical bunyavirus tri-segmented genome. The strains form a single phylogenetic clade that is divergent from other known nairoviruses, and are hereafter designated as Leopards Hill virus (LPHV). When i.p. injected into mice, the 11SB17 strain causes only slight body weight loss, whereas 11SB23 produces acute and lethal disease closely resembling that observed with Crimean-Congo Haemorrhagic Fever virus in humans. We believe that our LPHV mouse model will be useful for research on the pathogenesis of nairoviral haemorrhagic disease.

  17. A nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice

    PubMed Central

    Ishii, Akihiro; Ueno, Keisuke; Orba, Yasuko; Sasaki, Michihito; Moonga, Ladslav; Hang’ombe, Bernard M.; Mweene, Aaron S.; Umemura, Takashi; Ito, Kimihito; Hall, William W.; Sawa, Hirofumi

    2014-01-01

    Bats can carry important zoonotic pathogens. Here we use a combination of next-generation sequencing and classical virus isolation methods to identify novel nairoviruses from bats captured from a cave in Zambia. This nairovirus infection is highly prevalent among giant leaf-nosed bats, Hipposideros gigas (detected in samples from 16 individuals out of 38). Whole-genome analysis of three viral isolates (11SB17, 11SB19 and 11SB23) reveals a typical bunyavirus tri-segmented genome. The strains form a single phylogenetic clade that is divergent from other known nairoviruses, and are hereafter designated as Leopards Hill virus (LPHV). When i.p. injected into mice, the 11SB17 strain causes only slight body weight loss, whereas 11SB23 produces acute and lethal disease closely resembling that observed with Crimean–Congo Haemorrhagic Fever virus in humans. We believe that our LPHV mouse model will be useful for research on the pathogenesis of nairoviral haemorrhagic disease. PMID:25451856

  18. Mucormycosis as a rare cause of severe gastrointestinal bleeding after multivisceral transplantation.

    PubMed

    Irtan, S; Lamerain, M; Lesage, F; Verkarre, V; Bougnoux, M-E; Lanternier, F; Zahar, J R; Salvi, N; Talbotec, C; Lortholary, O; Lacaille, F; Chardot, C

    2013-12-01

    Mucormycosis, an emerging fungal infection in solid organ transplant patients, is mostly located in rhino-orbito-cerebral, pulmonary, and cutaneous areas, or disseminated with poor prognosis. A 4-year-old girl with chronic intestinal pseudo-obstruction syndrome underwent a modified multivisceral transplantation, including half of the stomach, the duodeno-pancreas, the small bowel, and the right colon. On postoperative day 5, a digestive perforation was suspected. Surgical exploration found a small necrotic area on the native stomach, which was externally drained. The next day, massive gastric bleeding occurred. During the emergency laparotomy, 2 hemorrhagic ulcers were found and resected from the transplanted stomach. Pathology and fungal culture showed mucormycosis caused by Lichtheimia (formerly Absidia) ramosa in both the transplanted and native stomach. High-dose intravenous liposomal amphotericin B was immediately started. No other site of fungal infection was found. The child recovered, and 3 years after transplantation, is alive and well, off parenteral nutrition. The originality of this case is the very early presentation after transplantation, the unusual site, and the complete recovery after rapid medico-surgical management. The origin of the fungus and treatment are discussed.

  19. Airbag-Associated Severe Blunt Eye Injury Causes Choroidal Rupture and Retinal Hemorrhage: A Case Report

    PubMed Central

    Wang, Shih Hao; Lim, Chen Chee; Teng, Yu Ti

    2017-01-01

    A case of choroidal rupture caused by airbag-associated blunt eye trauma and complicated with massive subretinal hemorrhage and vitreous hemorrhage that was successfully treated with intravitreal injection of expansile gas and bevacizumab is presented. A 53-year-old man suffered from loss of vision in his right eye due to blunt eye trauma by a safety airbag after a traffic accident. On initial examination, the patient had no light perception in his right eye. Dilated ophthalmoscopy revealed massive subretinal hemorrhage with macular invasion and faint vitreous hemorrhage. We performed intravitreal injection of pure sulfur hexafluoride twice for displacement, after which visual acuity improved to 0.03. For persistent subretinal hemorrhage and suspicion of choroidal neovascularization (CNV), intravitreal bevacizumab (1.25 mg/0.05 mL) injection was administered. After 3 weeks, the visual acuity of his right eye recovered to 0.4. For early-stage choroidal rupture-induced subretinal hemorrhage and complications of suspected CNV, intravitreal injection of expandable gas and intraocular injection of antiangiogenesis drugs seem to be an effective treatment. PMID:28203191

  20. Severe disseminated phaeohyphomycosis in an immunocompetent patient caused by Veronaea botryosa.

    PubMed

    Bonifaz, Alexandro; Davoudi, Mehrnaz Mohammad; de Hoog, G S; Padilla-Desgarennes, Carmen; Vázquez-González, Denisse; Navarrete, Gisela; Meis, Jacques F; Badali, Hamid

    2013-06-01

    We present a severe case of disseminated phaeohyphomycosis due to Veronaea botryosa. A 32-year-old female, native from Cuautla, Morelos, Mexico, presented a chronic dermatosis which started 10 years earlier with multiple exophytic, multilobulated, soft, and pedunculated or sessile neoformations of diverse sizes from 2 to 10 cm in diameter, which became verrucose and increased in size. The patient was immunocompetent, and no hereditary or familiar precedents of importance were known. No treatment was given, and the dermatosis remained relatively stable until the patient became pregnant in 2001 and 2003. The infection then exacerbated and worsened, leading to dissemination to the extremities, trunk, and face. The initial diagnosis was chromoblastomycosis which was treated with terbinafine and itraconazole but without visible improvement. Histopathology revealed pigmented, irregular, unbranched, and septate hyphae. Veronaea botryosa was isolated (CBS 127264 = JX566723), and its identity was confirmed by sequencing the internal transcribed spacer (ITS) rDNA. Therapy with posaconazole (800 mg/day) was started showing a gradual improvement of lesions with a reduction in size and flattening of the eruptions.

  1. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy.

    PubMed

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velde, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2017-01-05

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia, psychomotor delay, refractory epilepsy, and elevated lactate in the blood and cerebrospinal fluid. Functional studies in fibroblasts from affected subjects showed both an apparently complete loss of MDH2 levels and MDH2 enzymatic activity close to null. Metabolomics analyses demonstrated a significant concomitant accumulation of the MDH substrate, malate, and fumarate, its immediate precursor in the Krebs cycle, in affected subjects' fibroblasts. Lentiviral complementation with wild-type MDH2 cDNA restored MDH2 levels and mitochondrial MDH activity. Additionally, introduction of the three missense mutations from the affected subjects into Saccharomyces cerevisiae provided functional evidence to support their pathogenicity. Disruption of the Krebs cycle is a hallmark of cancer, and MDH2 has been recently identified as a novel pheochromocytoma and paraganglioma susceptibility gene. We show that loss-of-function mutations in MDH2 are also associated with severe neurological clinical presentations in children.

  2. TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy specifically disturb several steps during transcription.

    PubMed

    Singh, Amita; Compe, Emanuel; Le May, Nicolas; Egly, Jean-Marc

    2015-02-05

    Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD-A) subunits of the transcription and DNA-repair factor TFIIH lead to three autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases were originally associated with defects in DNA repair, transcription deficiencies might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2) as a model in several cells bearing mutations in genes encoding TFIIH subunits, we observed that (1) the recruitment of the TFIIH complex was altered at the activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide excision repair (NER) factors during transcription in a manner different from that observed during NER, and (3) the different TFIIH variants disturbed transcription by having distinct consequences on post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The transition from heterochromatin to euchromatin was disrupted depending on the variant, illustrating the fact that TFIIH, by contributing to NER factor recruitment, orchestrates chromatin remodeling. The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals.

  3. Severe combined immunodeficiency caused by a new homozygous RAG1 mutation with progressive encephalopathy.

    PubMed

    Dhingra, Nivedita; Yadav, Satya Prakash; de Villartay, Jean-Pierre; Picard, Capucine; Sabharwal, R K; Dinand, Veronique; Ghuman, Samarjit Singh; Sachdeva, Anupam

    2014-03-01

    We describe an unusual case of severe combined immunodeficiency (SCID) with neutropenia and central nervous system (CNS) manifestations in which a novel RAG1 mutation was identified. A 15-month-old boy presented with failure to thrive, neutropenia and recurrent infections. He was diagnosed with T-B-NK+ SCID. He subsequently developed right partial seizures with ipsilateral hemiparesis and became comatose. Magnetic resonance imaging (MRI) of the brain revealed an inflammatory lesion in the left thalamus which later progressed to diffuse meningo-encephalitis on serial imaging. No CNS infection was documented. Genetic work-up in the child revealed a novel homozygous deleterious mutation in the RAG1 gene (c:2881T>C; p:I794T), for which both parents were heterozygous. He underwent a haploidentical bone marrow transplant without conditioning and died on day +35 with no improvement in his neurological status. The features of neutropenia and progressive encephalopathy could be linked to the novel genetic defect but more data is required to establish this conclusively.

  4. Severe mandibuloacral dysplasia caused by novel compound heterozygous ZMPSTE24 mutations in two Japanese siblings

    PubMed Central

    Miyoshi, Y; Akagi, M; Agarwal, AK; Namba, N; Kato-Nishimura, K; Mohri, I; Yamagata, M; Nakajima, S; Mushiake, S; Shima, M; Auchus, RJ; Taniike, M; Garg, A; Ozono, K

    2009-01-01

    Mandibuloacral dysplasia (MAD) is a rare autosomal recessive progeroid syndrome, characterized by mandibular hypoplasia, acroosteolysis affecting distal phalanges and clavicles, delayed closure of the cranial sutures, atrophic skin, and lipodystrophy. Recently, mutations in lamin A/C (LMNA) and zinc metalloprotease (ZMPSTE24), involved in post-translational processing of prelamin A to mature lamin A, have been identified in MAD kindreds. We now report novel compound heterozygous mutations in exon 1 (c.121C>T; p.Q41X) and exon 6 (c.743C>T; p.P248L) in ZMPSTE24 in two Japanese sisters, 7- and 3-year old, with severe MAD and characteristic facies and atrophic skin. The older sister had lipodystrophy affecting the chest and thighs but sparing abdomen. Their parents and a brother, who were healthy, had heterozygous mutations. The missense mutation, P248L, was not found in 100 normal subjects of Japanese origin. The mutant Q41X was inactive in a yeast halo assay; however, the mutant P248L retained near normal ZMPSTE24 activity. Immunoblots demonstrated accumulation of prelamin A in the patients’ cell lysates from lymphoblasts. The lymphoblasts from the patients also revealed less intense staining for lamin A/C on immunofluorescence. We conclude that ZMPSTE24 deficiency results in accumulation of farnesylated prelamin A, which may be responsible for cellular toxicity and the MAD phenotype. PMID:18435794

  5. Magnetic resonance imaging of AMS (Aneurysm of the Membranous Septum), review of the literature and case report.

    PubMed

    Di Cesare, Ernesto; Di Sibio, Alessandra; Lanni, Giuseppe; Gennarelli, Antonio; Masciocchi, Carlo

    2014-05-01

    Aneurysm of the Membranous Septum (AMS) is a rare cardiac disease, mostly associated with other cardiac anomalies, very rare in the absence of other congenital heart defects. A prompt diagnosis is important, due to severe potential complications, but remain challenging. Most of the cases were earlier diagnosed using ventriculography, but, with the availability of echocardiography and cardiovascular magnetic resonance (CMR), this disease can be accurately assessed non-invasively. We report a case of a 62 years old female patient, without other cardiac congenital disease, who was incidentally diagnosed, by means of CMR with a true and isolated AMS. Our report underlines CMR usefulness in AMS diagnosis, thanks to accurate evaluation (both morphologic and functional) provided by this diagnostic tool, which is able to demonstrate clearly the presence of AMS (aneurysm of the membranous septum) and depict its features.

  6. Mycoplasma ovipneumoniae - A Primary Cause of Severe Pneumonia Epizootics in the Norwegian Muskox (Ovibos moschatus) Population

    PubMed Central

    Handeland, Kjell; Tengs, Torstein; Kokotovic, Branko; Vikøren, Turid; Ayling, Roger D.; Bergsjø, Bjarne; Sigurðardóttir, Ólöf G.; Bretten, Tord

    2014-01-01

    The Norwegian muskox (Ovibos moschatus) population lives on the high mountain plateau of Dovre and originates from animals introduced from Greenland. In the late summers of 2006 and 2012, severe outbreaks of pneumonia with mortality rates of 25-30% occurred. During the 2012 epidemic high quality samples from culled sick animals were obtained for microbiological and pathological examinations. High throughput sequencing (pyrosequencing) of pneumonic lung tissue revealed high concentrations of Mycoplasma ovipneumoniae in all six animals examined by this method and Pasteurella multocida subsp. multocida in four animals, whereas no virus sequences could be identified. Mycoplasma ovipneumoniae and P. multocida multocida were also isolated by culture. Using real time PCR on lung swabs, M. ovipneumoniae was detected in all of the 19 pneumonic lungs examined. Gross pathological examination revealed heavy consolidations primarily in the cranial parts of the lungs and it also identified one case of otitis media. Histologically, lung lesions were characterized as acute to subacute mixed exudative and moderately proliferative bronchoalveolar pneumonia. Immunohistochemical (IHC) examination revealed high load of M. ovipneumoniae antigens within lung lesions, with particularly intensive staining in the neutrophils. Similar IHC finding were observed in archived lung tissue blocks from animals examined during the 2006 epidemic. An M. ovipneumoniae specific ELISA was applied on bio-banked muskox sera from stray muskoxen killed in the period 2004–2013 and sick muskoxen culled, as well as sera from wild reindeer (Rangifer tarandus tarandus) on Dovre and muskoxen from Greenland. Serology and mycoplasma culturing was also carried out on sheep that had been on pasture in the muskox area during the outbreak in 2012. Our findings indicated separate introductions of M. ovipneumoniae infection in 2006 and 2012 from infected co-grazing sheep. Salt licks shared by the two species were a

  7. Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

    PubMed Central

    Zanon, Tyler; Kappell, Anthony D.; Petrella, Lisa N.; Andersen, Erik C.; Hristova, Krassimira R.

    2016-01-01

    Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits

  8. Ethanol and High Cholesterol Diet Causes Severe Steatohepatitis and Early Liver Fibrosis in Mice

    PubMed Central

    Krishnasamy, Yasodha; Ramshesh, Venkat K.; Gooz, Monika; Schnellmann, Rick G.; Lemasters, John J.; Zhong, Zhi

    2016-01-01

    Background and Aim Because ethanol consumption is commonly associated with a high cholesterol diet, we examined whether combined consumption of ethanol and high cholesterol increases liver injury and fibrosis. Methods Male C57BL/6J mice were fed diets containing: 1) 35% of calories from corn oil (CTR), 2) CTR plus 0.5% (w/v) cholesterol (Chol), 3) CTR plus ethanol (27% of calories) (EtOH), or 4) EtOH+Chol for 3 months. Results In mice fed Chol or EtOH alone, ALT increased to ~160 U/L, moderate hepatic steatosis occurred, and leukocyte infiltration, necrosis, and apoptosis increased modestly, but no observable fibrosis developed. By contrast in mice fed EtOH+Chol, ALT increased to ~270 U/L, steatosis was more extensive and mostly macrovesicular, and expression of proinflammatory molecules (HMGB-1, TLR4, TNFα, ICAM-1) and leukocyte infiltration increased substantially. Necrosis and apoptosis also increased. Trichrome staining and second harmonic generation microscopy revealed hepatic fibrosis. Fibrosis was mostly sinusoidal and/or perivenular, but in some mice bridging fibrosis occurred. Expression of smooth muscle α-actin and TGF-β1 increased slightly by Chol, moderately by EtOH, and markedly by EtOH+Chol. TGF-β pseudoreceptor BAMBI increased slightly by Chol, remained unchanged by EtOH and decreased by EtOH+Chol. MicroRNA-33a, which enhances TGF-β fibrotic effects, and phospho-Smad2/3, the down-stream signal of TGF-β, also increased more greatly by EtOH+Chol than Chol or EtOH. Metalloproteinase-2 and -9 were decreased only by EtOH+Chol. Conclusion High dietary cholesterol and chronic ethanol consumption synergistically increase liver injury, inflammation, and profibrotic responses and suppress antifibrotic responses, leading to severe steatohepatitis and early fibrosis in mice. PMID:27676640

  9. Severe Human Illness Caused by Rift Valley Fever Virus in Mauritania, 2015

    PubMed Central

    Fall-Malick, Fatima Zahra; Ould Baba, Sidi El Wafi; Ould Salem, Mohamed Lemine; Belizaire, Marie Roseline Darnycka; Ledib, Hamade; Ould Baba Ahmed, Mohamed Mahmoud; Basco, Leonardo Kishi; Ba, Hampaté

    2016-01-01

    Background. Rift Valley Fever epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications.Objectives. The aim of the present prospective study was to describe severe clinical signs and symptoms of Rift Valley Fever in southern Mauritania. Patients and methods. Suspected cases were enrolled in Kiffa (Assaba) and Aleg (Brakna) Hospital Centers from September 1 to November 7, 2015, based on the presence of fever, hemorrhagic or meningoencephalitic syndromes, and probable contact with sick animals. Suspected cases were confirmed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR). Results. There were thirty-one confirmed cases. The sex ratio M/F and the average age were 2.9 and 25 years old [range, 4-70 years old], respectively. Mosquito bites, direct contact with aborted or dead animals, and frequent ingestion of milk from these animals were risk factors observed in all patients. Hemorrhagic and neurological manifestations were observed in 81% and 13% of cases, respectively. The results of laboratory analysis showed high levels of transaminases, creatinine, and urea associated with thrombocytopenia, anemia, and leukopenia. All patients who died (42%) had a hemorrhagic syndrome and 3 of them had a neurological complication. Among the cured patients, none had neurologic sequelae. Conclusion. The hemorrhagic form was the most common clinical manifestation of RVF found in southern Mauritania and was responsible for a high mortality rate. Our results justify the implementation of a continuous epidemiological surveillance. PMID:27844026

  10. Severe forms of Baraitser–Winter syndrome are caused by ACTB mutations rather than ACTG1 mutations

    PubMed Central

    Di Donato, N; Rump, A; Koenig, R; Der Kaloustian, V M; Halal, F; Sonntag, K; Krause, C; Hackmann, K; Hahn, G; Schrock, E; Verloes, A

    2014-01-01

    ACTB and ACTG1 mutations have recently been reported to cause Baraitser–Winter syndrome (BRWS) – a rare condition characterized by ptosis, colobomata, neuronal migration disorder, distinct facial anomalies and intellectual disability. One of the patients carrying an ACTB mutation was previously diagnosed with Fryns–Aftimos syndrome (FAS), which is a rare and severe, multiple congenital anomaly (MCA) syndrome whose symptoms partially overlap with that of BRWS. However, several patients with Fryns–Aftimos were considered not to fit into the ACTB and ACTG1 spectrum because of their severe impairment and additional malformations. We report on three patients who had been diagnosed with FAS. All three patients carry a mutation in the ACTB gene. On the basis of the ACTB mutations and analysis of the clinical findings, we reclassify the diagnosis of these patients as severe BRWS. We suggest that mutations in ACTB cause a distinctly more severe phenotype than ACTG1 mutations, despite the structural similarity of beta- and gamma-actins and their overlapping expression pattern. We expand the spectrum of BRWS and confirm that FAS is not a separate entity but an early and severe manifestation of BRWS. PMID:23756437

  11. A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs.

    PubMed

    Burk, Raymond F; Christensen, Joani M; Maguire, Mark J; Austin, Lori M; Whetsell, William O; May, James M; Hill, Kristina E; Ebner, Ford F

    2006-06-01

    A short period of combined deficiency of vitamins E and C causes profound central nervous system (CNS) dysfunction in guinea pigs. For this report, CNS histopathology was studied to define the nature and extent of injury caused by this double deficiency. Weanling guinea pigs were fed a vitamin E-deficient or -replete diet for 14 d. Then vitamin C was withdrawn from the diet of some guinea pigs. Four diet groups were thus formed: replete, vitamin E deficient, vitamin C deficient, and both vitamin E and C deficient. From 5 to 11 d after institution of the doubly deficient diet, 9 of 12 guinea pigs developed paralysis, and 2 more were found dead. The remaining guinea pig in the doubly deficient group and all animals in the other 3 groups survived without clinical impairment until the experiment was terminated at 13-15 d. Brains and spinal cords were serially sectioned and stained for examination. Only the combined deficiency produced damage in the CNS. The damage consisted mainly of nerve cell death, axonal degeneration, vascular injury, and associated glial cell responses. The spinal cord and the ventral pons in the brainstem were most severely affected, often exhibiting asymmetric cystic lesions. Several features of the lesions suggest that the primary damage was to blood vessels. These results indicate that the paralysis and death caused by combined deficiency of vitamins E and C in guinea pigs is caused by severe damage in the brainstem and spinal cord.

  12. CyDiv, a Conserved and Novel Filamentous Cyanobacterial Cell Division Protein Involved in Septum Localization

    PubMed Central

    Mandakovic, Dinka; Trigo, Carla; Andrade, Derly; Riquelme, Brenda; Gómez-Lillo, Gabriela; Soto-Liebe, Katia; Díez, Beatriz; Vásquez, Mónica

    2016-01-01

    Cell division in bacteria has been studied mostly in Escherichia coli and Bacillus subtilis, model organisms for Gram-negative and Gram-positive bacteria, respectively. However, cell division in filamentous cyanobacteria is poorly understood. Here, we identified a novel protein, named CyDiv (Cyanobacterial Division), encoded by the all2320 gene in Anabaena sp. PCC 7120. We show that CyDiv plays a key role during cell division. CyDiv has been previously described only as an exclusive and conserved hypothetical protein in filamentous cyanobacteria. Using polyclonal antibodies against CyDiv, we showed that it localizes at different positions depending on cell division timing: poles, septum, in both daughter cells, but also in only one of the daughter cells. The partial deletion of CyDiv gene generates partial defects in cell division, including severe membrane instability and anomalous septum localization during late division. The inability to complete knock out CyDiv strains suggests that it is an essential gene. In silico structural protein analyses and our experimental results suggest that CyDiv is an FtsB/DivIC-like protein, and could therefore, be part of an essential late divisome complex in Anabaena sp. PCC 7120. PMID:26903973

  13. CyDiv, a Conserved and Novel Filamentous Cyanobacterial Cell Division Protein Involved in Septum Localization.

    PubMed

    Mandakovic, Dinka; Trigo, Carla; Andrade, Derly; Riquelme, Brenda; Gómez-Lillo, Gabriela; Soto-Liebe, Katia; Díez, Beatriz; Vásquez, Mónica

    2016-01-01

    Cell division in bacteria has been studied mostly in Escherichia coli and Bacillus subtilis, model organisms for Gram-negative and Gram-positive bacteria, respectively. However, cell division in filamentous cyanobacteria is poorly understood. Here, we identified a novel protein, named CyDiv (Cyanobacterial Division), encoded by the all2320 gene in Anabaena sp. PCC 7120. We show that CyDiv plays a key role during cell division. CyDiv has been previously described only as an exclusive and conserved hypothetical protein in filamentous cyanobacteria. Using polyclonal antibodies against CyDiv, we showed that it localizes at different positions depending on cell division timing: poles, septum, in both daughter cells, but also in only one of the daughter cells. The partial deletion of CyDiv gene generates partial defects in cell division, including severe membrane instability and anomalous septum localization during late division. The inability to complete knock out CyDiv strains suggests that it is an essential gene. In silico structural protein analyses and our experimental results suggest that CyDiv is an FtsB/DivIC-like protein, and could therefore, be part of an essential late divisome complex in Anabaena sp. PCC 7120.

  14. Nasal septum changes in adolescent patients treated with rapid maxillary expansion

    PubMed Central

    Aziz, Tehnia; Wheatley, Francis Carter; Ansari, Kal; Lagravere, Manuel; Major, Michael; Flores-Mir, Carlos

    2016-01-01

    Objective: To analyze cone-beam computed tomography (CBCT) scans to measure changes in nasal septal deviation (NSD) after rapid maxillary expansion (RME) treatment in adolescent patients. Methods: This retrospective study involved 33 patients presenting with moderate to severe nasal septum deviation as an incidental finding. Out of these 33 patients, 26 were treated for transverse maxillary constriction with RME and seven, who did not undergo RME treatment, were included in the study as control group. CBCT scans were taken before appliance insertion and after appliance removal. These images were analyzed to measure changes in nasal septum deviation (NSD). Analysis of variance for repeated measures (ANOVA) was used. Results: No significant changes were identified in NSD regardless of the application or not of RME treatment and irrespective of the baseline deviation degree. Conclusion: This study did not provide strong evidence to suggest that RME treatment has any effect on NSD in adolescent patients; however, the results should be interpreted with caution, due to the small sample size and large variation amongst individual patient characteristics. PMID:27007761

  15. Direct carotid cavernous fistula after submucous resection of the nasal septum.

    PubMed

    Bizri, A R; al-Ajam, M; Zaytoun, G; al-Kutoubi, A

    2000-01-01

    A carotid cavernous fistula (CCF) is an abnormal arteriovenous anastomosis between the carotid artery and the cavernous sinus. Etiologies of this condition reported in the literature so far include facial trauma, rupture of an intracavernous aneurysm of the carotid artery, Ehler-Danlos syndrome and fibromuscular dysplasia of the cerebral arteries. Such fistulae were reported as complications of rhinoplasty, transsphenoidal surgery, embolization of cavernous sinus meningioma, and rhinocerebral mucormycosis. CCF may also occur spontaneously in children or as a congenital malformation. However, to our knowledge, submucous resection of the nasal septum has not been reported before to cause direct carotid-cavernous fistula. CT and angiographic findings are presented and a review of the literature for reported causes of CCF is made as well as a brief discussion of the possible pathophysiology.

  16. Surgical treatment of severe chronic venous insufficiency caused by pulsatile varicose veins in a patient with tricuspid regurgitation.

    PubMed

    Casian, D; Gutsu, E; Culiuc, V

    2009-04-01

    A case of severe chronic venous insufficiency caused by pulsatile varicose veins in a 46-year-old man with tricuspid regurgitation is presented. Active venous leg ulcer complicated with recurrent venous bleeding and inefficacy of conservative management serve as indications for surgical treatment. This case demonstrates the possibility of radical surgical correction of pathological venous reflux by means of saphenofemoral ligation, foam sclerotherapy and subfascial endoscopic perforator surgery.

  17. [The effect of physical therapy on the most severe forms of knee structral changes caused by osteoarthritis].

    PubMed

    Kapidzić-Basić, Nedima; Dzananović, Dzevad; Kapidzić-Duraković, Suada; Kikanović, Sahza; Mulić-Bacić, Suada; Hotić-Hadziefendić, Asja

    2011-01-01

    In the most severe form of structural changes on knee caused by osteoarthritis non-surgical treatment provide minimal results and a question of its purpose is being raised. Aim of the study was to examine the possibilities of physical treatment of patients with the most severe degree of structural changes caused by knee osteoarthritis. Examination was conducted on 60 patients that were on physical treatment because of the knee OA. Structural changes are evaluated by Kellgren-Lawrence scale, functional ability by Lequesne index, and pain by Visual analog scale. Physical treatment lasted for 4 weeks. After the physical treatment there was a significant improvement of functional ability (p = 1.78E-07), but the size of improvement was reduced by the level of structural changes. It was significantly lower in IV class in relation to III and II class (p < 0.05). Physical treatment has lower affect by patients with the most severe form of structural changes caused by knee osteoarthritis, but it still can help patients to ease the appearance of complete dependence on other people's help.

  18. Photoelectrolysis of water in semiconductor septum electrochemical photovoltaic cells

    SciTech Connect

    Tien, H.T.; Chen, J.W. )

    1992-01-01

    Producing hydrogen from water has been the dream of generations of energy-conscious scientists and engineers. That dream may at last be realized in the semiconductor septum electrochemical photovoltaic (SC-SEP) cell, which is modeled after nature's photosynthetic thylakoid membrane. The novel SC-SEP cell arose from studies of pigmented bilayer lipid membranes. The cell is easy to construct and simple to operate. It appears to offer a practical approach to the photochemical conversion and storage of solar energy. This report describes how hydrogen is produced from artificial sea water when an SC-SEP cell is irradiated by the visible light of the solar spectrum.

  19. Postnatal Deletion of the Type II TGF-Beta Receptor in Smooth Muscle Cells Causes Severe Aortopathy in Mice

    PubMed Central

    Hu, Jie Hong; Wei, Hao; Jaffe, Mia; Airhart, Nathan; Du, Liang; Angelov, Stoyan N.; Yan, James; Allen, Julie K.; Kang, Inkyung; Wight, Thomas; Fox, Kate; Smith, Alexandra; Enstrom, Rachel; Dichek, David A.

    2016-01-01

    Objective Prenatal deletion of the type II TGF-β receptor (TBRII) prevents normal vascular morphogenesis and smooth muscle cell (SMC) differentiation, causing embryonic death. The role of TBRII in adult SMC is less well studied. Clarification of this role has important clinical implications because TBRII deletion should ablate TGF-β signaling and blockade of TGF-β signaling is envisioned as a treatment for human aortopathies. We hypothesized that postnatal loss of SMC TBRII would cause aortopathy. Approach and Results We generated mice with either of two tamoxifen-inducible SMC-specific Cre (SMC-CreERT2) alleles and homozygous floxed Tgfbr2 alleles. Mice were injected with tamoxifen, and their aortas examined 4 and 14 weeks later. Both SMC-CreERT2 alleles efficiently and specifically rearranged a floxed reporter gene and efficiently rearranged a floxed Tgfbr2 allele, resulting in loss of aortic medial TBRII protein. Loss of SMC TBRII caused severe aortopathy including hemorrhage, ulceration, dissection, dilation, accumulation of macrophage markers, elastolysis, abnormal proteoglycan accumulation, and aberrant SMC gene expression. All areas of the aorta were affected, with the most severe pathology in the ascending aorta. Cre-mediated loss of SMC TBRII in vitro ablated both canonical and noncanonical TGF-β signaling and reproduced some of the gene expression abnormalities detected in vivo. Conclusions SMC TBRII plays a critical role in maintaining postnatal aortic homeostasis. Loss of SMC TBRII disrupts TGF-β signaling, acutely alters SMC gene expression, and rapidly results in severe and durable aortopathy. These results suggest that pharmacologic blockade of TGF-β signaling in humans could cause aortic disease rather than prevent it. PMID:26494233

  20. Vitamin B12 and Vitamin D Deficiencies: An Unusual Cause of Fever, Severe Hemolytic Anemia and Thrombocytopenia

    PubMed Central

    Mishra, Vikas A.; Harbada, Rishit; Sharma, Akhilesh

    2015-01-01

    The array of diagnostic workup for pyrexia of unknown origin (PUO) generally revolves in searching for infections, inflammatory/autoimmune, and endocrine etiologies. A differential diagnosis of fever, hemolytic anemia, and thrombocytopenia can have etiologies varying from infections like malaria, dengue, cytomegalovirus, Ebstein barr virus, Parvovirus, infective endocarditis, to autoimmune disorder (systemic lupus erythromatosis), vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), autoimmune hemolytic anemia/Evan's syndrome, paroxysmal nocturnal hemoglobinuri (PNH), or drugs. Nutritional deficiencies (especially vitamin B12 deficiency) as a cause of fever, hemolytic anemia, and thrombocytopenia are very rare and therefore rarely thought of. Severe vitamin B12 deficiency may cause fever and if accompanied by concurrent hyper-homocysteinemia and hypophosphatemia can sometimes lead to severe hemolysis mimicking the above-mentioned conditions. We present a case that highlights vitamin B12 and vitamin D deficiency as an easily treatable cause of PUO, hemolytic anemia, and thrombocytopenia, which should be actively looked for and treated before proceeding with more complicated and expensive investigation or starting empiric treatments. PMID:25811010

  1. Prevalence, seasonality and severity of disease caused by pathogenic Escherichia coli in children with diarrhoea in Bolivia.

    PubMed

    Gonzales, Lucia; Joffre, Enrique; Rivera, Rosario; Sjöling, Åsa; Svennerholm, Ann-Mari; Iñiguez, Volga

    2013-11-01

    The prevalence of infection caused by different categories of diarrhoeagenic E. coli (DEC) strains, including enteroaggregative (EAEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and enterohaemorrhagic (EHEC) E. coli, in children who suffered from diarrhoea (n = 3943) or did not have diarrhoea (n = 1026) were analysed in two areas in Bolivia over a period of 4 years. We also analysed the seasonality of DEC infections and severity of diarrhoea in children with DEC infection and compared antibiotic resistance in DEC strains isolated from children with and without diarrhoea. Stool samples were analysed for the presence of DEC by culturing followed by PCR. The most prevalent DEC categories in samples from the children were: EAEC (11.2 %); ETEC (6.6 %); EPEC (5.8 %); and EIEC and EHEC (<1 %). DEC strains were isolated significantly more often from diarrhoea cases (21.6 %) than from controls (17.6 %; P = 0.002). The number of children with diarrhoea associated with EAEC, EPEC and ETEC infections peaked in the Bolivian winter (April-September), although the proportion of DEC-positive stool samples was higher during the warm rainy season (October-March). High levels of antibiotic resistance were detected among the DEC strains. In particular, resistance to tetracycline and sulfamethoxazole-trimethoprim was significantly higher in strains isolated from individuals with diarrhoea than in samples from controls. The severity of disease in children infected with EAEC, EPEC and ETEC varied from mild to severe diarrhoea, although disease severity did not differ significantly between the different DEC categories. ETEC, EPEC and EAEC are commonly found in Bolivia and may cause severe disease in children.

  2. A combined LDL receptor/LDL receptor adaptor protein 1 mutation as the cause for severe familial hypercholesterolemia.

    PubMed

    Soufi, Muhidien; Rust, Stephan; Walter, Michael; Schaefer, Juergen R

    2013-05-25

    Familial hypercholesterolemia (FH) results from impaired catabolism of plasma low density lipoproteins (LDL), thus leading to high cholesterol, atherosclerosis, and a high risk of premature myocardial infarction. FH is commonly caused by defects of the LDL receptor or its main ligand apoB, together mediating cellular uptake and clearance of plasma LDL. In some cases FH is inherited by mutations in the genes of PCSK9 and LDLRAP1 (ARH) in a dominant or recessive trait. The encoded proteins are required for LDL receptor stability and internalization within the LDLR pathway. To detect the underlying genetic defect in a family of Turkish descent showing unregular inheritance of severe FH, we screened the four candidate genes by denaturing gradient gel electrophoresis (DGGE) mutation analysis. We identified different combinatory mixtures of LDLR- and LDLRAP1-gene defects as the cause for severe familial hypercholesterolemia in this family. We also show for the first time that a heterozygous LDLR mutation combined with a homozygous LDLRAP1 mutation produces a more severe hypercholesterolemia phenotype in the same family than a homozygous LDLR mutation alone.

  3. Revascularization in a 17-Year-Old Girl with Neurofibromatosis and Severe Hypertension Caused by Renal Artery Stenosis

    PubMed Central

    Geavlete, Oliviana D.; Botezatu, Simona; Postu, Marin; Popescu, Bogdan A.; Ginghina, Carmen; Coman, Ioan M.

    2017-01-01

    Renal artery stenosis caused by neurofibromatosis is a rare cause of renovascular hypertension. This hypertension can develop during childhood and is one of the leading causes of poor outcome. We report the case of a 17-year-old girl who was incidentally diagnosed with severe hypertension. During her examination for secondary hypertension, we reached a diagnosis of neurofibromatosis type 1 on the basis of a cluster of typical findings: optic nerve glioma, café au lait spots, nodular neurofibromas, and axillary freckling. Renal angiograms revealed a hemodynamically significant left renal artery stenosis (70%). Renal angioplasty with a self-expanding stent was performed one month later for rapidly progressive renal artery stenosis (90%) and uncontrolled blood pressure. Excellent blood pressure control resulted immediately and was maintained as of the 2-year follow-up evaluation. We think that percutaneous transluminal renal angioplasty can be effective in select patients who have neurofibromatosis type 1 and refractory hypertension caused by renal artery stenosis. PMID:28265213

  4. Disinhibition of rat hippocampal pyramidal cells by GABAergic afferents from the septum.

    PubMed Central

    Tóth, K; Freund, T F; Miles, R

    1997-01-01

    1. Slices were prepared from rat forebrain to include both the septum and the hippocampus in order to examine the effects of septal stimulation on hippocampal inhibitory circuits. 2. Repetitive stimulation of septo-hippocampal fibres caused a maintained decrease in the frequency of spontaneous IPSPs recorded from CA3 pyramidal cells in the presence of antagonists of excitatory amino acid receptors and of muscarine receptors. 3. In records made from pyramidal cells with CsCl-filled electrodes, IPSPs were examined at potentials both more positive and more negative than their reversal potential. Single septal stimuli hyperpolarized pyramidal cells when IPSPs were depolarizing events and depolarized them when IPSPs were hyperpolarizing. The GABAA receptor antagonist picrotoxin abolished the effects of septal stimulation. 4. Activation of septal afferents initiated an IPSP in hippocampal inhibitory cells but not in pyramidal cells. Septal IPSPs had similar kinetics to those initiated by local hippocampal stimulation and could suppress inhibitory cell discharge. 5. In pyramidal cells recorded with potassium acetate-filled electrodes, septal stimuli initiated a depolarization that increased with the driving force for Cl- and that could cause firing. 6. Rhythmic stimulation of septo-hippocampal fibres at 5 Hz initiated, in the hippocampus, a maintained out-of-phase oscillation of pyramidal cell discharge and inhibitory cell firing, as detected by the occurrence of spontaneous IPSPs. 7. These results suggest that GABAergic septo-hippocampal afferents selectively inhibit hippocampal inhibitory cells and so disinhibit pyramidal cells. This disinhibition could contribute to the transmission of the theta rhythm from the septum to the hippocampus. Images Figure 1 PMID:9147330

  5. Characterizing Septum Inhibition in Mycobacterium tuberculosis for Novel Drug Discovery

    SciTech Connect

    Respicio,L.; Nair, P.; Huang, Q.; Anil, B.; Tracz, S.; Truglio, J.; Kisker, C.; Raleigh, D.; Ojima, I.; et al

    2008-01-01

    A temperature sensitive mutation in the cell division protein FtsZ was used in combination with transcriptional analysis to identify biomarkers for inhibition of septum formation. Crystallography and modeling revealed that the glycine for aspartate substitution at amino acid 210 was located in helix 8 of the protein, adjacent to the T7 synergy loop. To verify the molecular behavior of FtsZD210G, the in vitro activity and structural stability were evaluated as a function of temperature. These analyses confirmed that the FtsZD210G mutant had reduced GTPase and polymerization activity compared to wild-type FtsZ, and CD spectroscopy demonstrated that both FtsZD210G and wild-type FtsZ had similar structure and stability. Significantly, the FtsZD210G merodiploid strain of M. tuberculosis had compromised growth at 37 C, substantiating the suitability of FtsZD210G as a molecular tool for global analysis in response to improper FtsZ polymerization and septum inhibition. Advanced model-based bioinformatics and transcriptional mapping were used to identify high-content multiple features that provide biomarkers for the development of a rational drug screening platform for discovering novel chemotherapeutics that target cell division.

  6. Pseudothrombosis with T2-weighted fast spin-echo MR images caused by static portal venous flow in severe cirrhosis.

    PubMed

    Matsuo, Masayuki; Kanematsu, Masayuki; Nishigaki, Youichi; Kondo, Hiroshi; Goshima, Satoshi; Maeda, Sunaho; Tomita, Eiichi; Hoshi, Hiroaki

    2002-02-01

    Unenhanced T2-weighted fast spin-echo images obtained in a 65-year-old woman with severe cirrhosis showed an area of high signal intensity occupying the left second-order portal vein branch, suggesting portal vein thrombosis in cirrhosis. Doppler sonography, which revealed virtually no blood flow in the vessel, also supported the diagnosis. Gadolinium-enhanced MRI subsequently revealed the patency of the vessel. The extremely slow portal venous flow was considered to be the cause of false-positive findings with unenhanced MRI and sonography.

  7. Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

    PubMed

    Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H

    2011-03-01

    Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.

  8. A severe case of esophageal ulcer causing a tight stricture despite long-term D-penicillamine treatment.

    PubMed

    Yapali, Suna; Turan, Ilker; Ozutemiz, Omer; Tekesin, Oktay

    2014-12-01

    D-penicillamine has long been used in the management of rheumatic diseases due to the effects on inhibition of collagen synthesis. Herein, we report a severe case of esophageal ulcer causing a tight stricture extending through the distal esophagus despite the long-term D-penicillamine treatment in a patient with Wilson's disease. D-penicillamine would theoretically be expected to contribute to the healing of an esophageal ulcer. However, the drug failed to have a favorable outcome, which is notable and worth reporting.

  9. Pregnancy-related severe pelvic girdle pain caused by unilateral noninfectious sacroiliitis. A case report and literature review.

    PubMed

    Mahovic, D; Laktasic-Zerjavic, N; Tudor, K I; Mercep, I; Prutki, M; Anic, B

    2014-09-01

    Pelvic girdle pain during and after pregnancy is the clinical syndrome of persistent musculoskeletal pain localized in the posterior and/or anterior aspect of the pelvis originating from sacroiliac joints and/or pubic symphysis due to dynamic instability. We report the case of severe and disabling postpartum pelvic girdle pain caused by unilateral noninfectious sacroiliitis which resolved after 2 months by nonsteroidal anti-inflammatory drug and physical therapy. A short literature review is given on epidemiology, etiology, clinical presentation, therapy, and prognosis of pregnancy-related pelvic girdle pain.

  10. Prevalence and Characteristics of Cavum Septum Pellucidum in Schizophrenia: A 16 Slice Computed Tomography Study

    PubMed Central

    Khanra, Sourav; Srivastava, Naveen Kumar; Chail, Vivek; Khess, Christoday Raja Jayant

    2016-01-01

    Objective: Several significant midline abnormalities including cavum septum pellucidum (CSP) have been reported in schizophrenia. However, not all studies were able to replicate similar findings. Furthermore, very few of them were conducted with large samples. Methods: CSP was identified and graded with 16 slice computed tomography (CT) machine in 138 patients of schizophrenia and 64 controls. Results: We found 21.0% of patients in schizophrenia group had abnormal CSP compared to only 9.4% in control group (P = 0.047). Grade III was most frequent type (19.6%) in schizophrenia group. Conclusions: Our study adds to the existing literature suggesting abnormal CSP may reflect neurodevelopmental process in schizophrenia. The strength of our study was larger sample size. Limitations were use of CT, male predominance in schizophrenia group, the inclusion of nonpsychiatric patients in control group. PMID:27833230

  11. The Embryonic Septum and Ventral Pallium, New Sources of Olfactory Cortex Cells

    PubMed Central

    de Carlos, Juan A.

    2012-01-01

    The mammalian olfactory cortex is a complex structure located along the rostro-caudal extension of the ventrolateral prosencephalon, which is divided into several anatomically and functionally distinct areas: the anterior olfactory nucleus, piriform cortex, olfactory tubercle, amygdaloid olfactory nuclei, and the more caudal entorhinal cortex. Multiple forebrain progenitor domains contribute to the cellular diversity of the olfactory cortex, which is invaded simultaneously by cells originating in distinct germinal areas in the dorsal and ventral forebrain. Using a combination of dye labeling techniques, we identified two novel areas that contribute cells to the developing olfactory cortices, the septum and the ventral pallium, from which cells migrate along a radial and then a tangential path. We characterized these cell populations by comparing their expression of calretinin, calbindin, reelin and Tbr1 with that of other olfactory cell populations. PMID:22984546

  12. Severe haematoperitoneum caused by ovarian bleeding after transvaginal oocyte retrieval: a retrospective analysis and systematic literature review.

    PubMed

    Nouri, Kazem; Walch, Katharina; Promberger, Regina; Kurz, Christine; Tempfer, Clemens B; Ott, Johannes

    2014-12-01

    A case series of haematoperitoneum caused by ovarian bleeding after transvaginal oocyte retrieval (TVOR) is presented and all published cases summarized. In a retrospective case series, four patients with ovarian bleeding after TVOR were included. In addition, a pooled analysis of all published cases (n = 32) who underwent surgical intervention for severe haematoperitoneum caused by ovarian bleeding after TVOR was carried out. Main outcome measures were incidence, risk factors, course and intraoperative findings. In the pooled analysis, the incidence was 0.08%. The first sign of haematoperitoneum was evident in 33.3% within the first postoperative hour, and, cumulatively, in 93.3% within 24 h. The median time between TVOR and surgical intervention was 10 h. In four patients, the ovary could not be preserved, which was associated with a longer time interval between TVOR and the onset of symptoms (median 18 h versus 2.5 h; P = 0.004) as well as between TVOR and surgical intervention (median 21.5 h versus 8.5 h; 0.004). In conclusion, severe haematoperitoneum occurs in 0.08% after TVOR. Late-onset bleeding is common. A longer time interval between TVOR and surgical intervention might put a patient at risk of ovariectomy.

  13. Quinine allergy causing acute severe systemic illness: report of 4 patients manifesting multiple hematologic, renal, and hepatic abnormalities

    PubMed Central

    2003-01-01

    Quinine is widely used for the common symptom of leg cramps. Quinine tablets require a prescription, but quinine and the product from which it is derived, cinchona, are also available without prescription. They are components of over-the-counter remedies for many common symptoms, of nutrition products, and of beverages such as tonic water and bitter lemon. Although quinine has been used for centuries, initially as an extract from the bark of the cinchona tree, allergic reactions to quinine can be severe and can affect multiple organs. These allergic reactions can cause thrombocytopenia, neutropenia, anemia, disseminated intravascular coagulation, acute renal failure, liver toxicity, and neurological abnormalities. Because quinine use is often intermittent, defining quinine as a cause of an acute disorder may be difficult. Moreover, since quinine use is often self-regulated, patients may not mention it in response to direct questions about medication use, adding to diagnostic difficulty. The diversity and severity of quinine-associated disorders and the difficulties of diagnosis are illustrated by the presentation of 4 case histories. Awareness of the variety of potential quinine-associated reactions is important for accurate diagnosis and critical for prevention of recurrent illness. PMID:16278718

  14. Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: heart failure causes severe lung disease.

    PubMed

    Chen, Yingjie; Guo, Haipeng; Xu, Dachun; Xu, Xin; Wang, Huan; Hu, Xinli; Lu, Zhongbing; Kwak, Dongmin; Xu, Yawei; Gunther, Roland; Huo, Yuqing; Weir, E Kenneth

    2012-06-01

    Chronic left ventricular failure causes pulmonary congestion with increased lung weight and type 2 pulmonary hypertension. Understanding the molecular mechanisms for type 2 pulmonary hypertension and the development of novel treatments for this condition requires a robust experimental animal model and a good understanding of the nature of the resultant pulmonary remodeling. Here we demonstrate that chronic transverse aortic constriction causes massive pulmonary fibrosis and remodeling, as well as type 2 pulmonary hypertension, in mice. Thus, aortic constriction-induced left ventricular dysfunction and increased left ventricular end-diastolic pressure are associated with a ≤5.3-fold increase in lung wet weight and dry weight, pulmonary hypertension, and right ventricular hypertrophy. Interestingly, the aortic constriction-induced increase in lung weight was not associated with pulmonary edema but resulted from profound pulmonary remodeling with a dramatic increase in the percentage of fully muscularized lung vessels, marked vascular and lung fibrosis, myofibroblast proliferation, and leukocyte infiltration. The aortic constriction-induced left ventricular dysfunction was also associated with right ventricular hypertrophy, increased right ventricular end-diastolic pressure, and right atrial hypertrophy. The massive lung fibrosis, leukocyte infiltration, and pulmonary hypertension in mice after transverse aortic constriction clearly indicate that congestive heart failure also causes severe lung disease. The lung fibrosis and leukocyte infiltration may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. Thus, the effective treatment of left ventricular failure may require additional efforts to reduce lung fibrosis and the inflammatory response.

  15. Dissociated Roles for the Lateral and Medial Septum in Elemental and Contextual Fear Conditioning

    ERIC Educational Resources Information Center

    Calandreau, Ludovic; Jaffard, Robert; Desmedt, Aline

    2007-01-01

    Extensive evidence indicates that the septum plays a predominant role in fear learning, yet the direction of this control is still a matter of debate. Increasing data suggest that the medial (MS) and lateral septum (LS) would be differentially required in fear conditioning depending on whether a discrete conditional stimulus (CS) predicts, or not,…

  16. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency

    PubMed Central

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A.; Fliegauf, Manfred; Sayar, Esra H.; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S¸ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-01-01

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease—all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients. PMID:26476407

  17. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.

    PubMed

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A; Fliegauf, Manfred; Sayar, Esra H; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S Ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-12-20

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients.

  18. Causes of the Change in the Rates of Mortality and Severe Complications of Diabetes Mellitus: 1992 – 2012

    PubMed Central

    Yashkin, Arseniy P.; Picone, Gabriel

    2015-01-01

    Objective To quantify the causes of the changes in the rates of mortality and select severe complications of diabetes mellitus, type 2 (T2D) among the elderly between 1992 and 2012. Research Design A retrospective cohort study design based on Medicare 5% administrative claims data from 1992 to 2012 was used. Traditional fee-for-service Medicare beneficiaries, age 65 and older, diagnosed with T2D and living in the United States between 1992 and 2012 were included in the study. Blinder-Oaxaca decomposition was used to quantify the potential causes of the change in the rates of death, congestive heart failure (CHF) and/or acute myocardial infarction (AMI), stroke, amputation of lower extremity and end stage renal disease (ESRD) between 1992 and 2012. Results The number of beneficiaries in the analysis sample diagnosed with T2D increased from 152,191 in 1992 to 289,443 in 2012. Over the same time period, rates of mortality decreased by 1.2, CHF and/or AMI by 2.6, stroke by 1.6, amputation by 0.6 while rates of ESRD increased by 1.5 percentage points. Improvements in the management of precursor conditions and utilization of recommended health care services, not population composition, were the primary causes of the change. Conclusions With the exception of ESRD, outcomes among Medicare beneficiaries diagnosed with T2D improved. Analysis suggests that persons diagnosed with T2D are living longer with fewer severe complications. Much of the improvement in outcomes likely reflects more regular contact with health professionals and better management of care. PMID:25675404

  19. Prevalence and causes of avoidable blindness and severe visual impairment in a tribal district of Maharashtra, India

    PubMed Central

    Dhake, Praful V.; Dole, Kuldeep; Khandekar, Rajiv; Deshpande, Madan

    2011-01-01

    Background: We present the outcomes of a survey conducted in Nandurbar, a tribal district of Maharashtra, India. It was based on “Rapid Assessment for Avoidable Blindness” methodology and conducted in 2009 in Nandurbar, a tribal district of Maharashtra, India. Materials and Methods: We examined persons of 50 years and older ages. Ophthalmic assistants noted the distant vision [best corrected vision (BCV) and as presented]. Ophthalmologist examined eyes of persons with vision less than 6/18. The principal cause of impairment in each eye and the most “preventable” or “treatable” cause were assigned. We calculated the prevalence rates of bilateral blindness, severe visual impairment (SVI), and moderate visual impairment (MVI). Result: We examined 2,005/2,300 persons (response rate 87.2%). The prevalence of blindness, SVI, and MVI for the BCV was 1.63% (95% CI 1.11–2.15), 5.93% (95% CI 4.96–6.90), and 14.6% (95% CI 13.2–16.1), respectively. The prevalence of blindness, SVI, and MVI for the presented vision was 1.87% (1.32–2.42), 6.72% (95% CI 5.70–7.74), and 19% (95% CI 17.4–20.6), respectively. Unoperated cataract was responsible for 77% of different visual disabilities. The coverage of existing cataract surgery service was 9.4%. Lack of knowledge about cataract surgery was the main cause of unoperated cataract among 41% of interviewed participants with cataract and SVI. Conclusion: Unoperated cataract was the main curable cause of visual disabilities in tribal population of India. Increasing awareness and offering cataract surgeries at affordable cost in the district would reduce visual disabilities. PMID:22279401

  20. A 10-bp deletion in the apolipoprotein epsilon gene causing apolipoprotein E deficiency and severe type III hyperlipoproteinemia.

    PubMed Central

    Feussner, G.; Dobmeyer, J.; Gröne, H. J.; Lohmer, S.; Wohlfeil, S.

    1996-01-01

    Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2. We identified a 30-year-old male German of Hungarian ancestry with severe type III HLP and apo E deficiency. The disease was expressed in an extreme phenotype with multiple cutaneous xanthomas. Apo E was detectable only in trace amounts in plasma but not in the different lipoprotein fractions. Direct sequencing of PCR-amplified segments of the apo epsilon gene identified a 10-bp deletion in exon 4 (bp 4037-4046 coding for amino acids 209-212 of the mature protein). The mutation is predictive for a reading frameshift introducing a premature stop codon (TGA) at amino acid 229. By western blot analysis, we found small amounts of a truncated apo E in the patient's plasma. Family analysis revealed that the proband was homozygous--and 10 of 24 relatives were heterozygous--for the mutation. Heterozygotes had, as compared to unaffected family members, significantly higher triglycerides (TG), very low-density lipoprotein (VLDL) cholesterol and a significantly higher VLDL cholesterol-to-serum TG ratio, which is indicative of a delayed remnant catabolism. We propose that the absence of a functionally active apo E is the cause of the severe type III HLP in the patient and that the mutation, even in a single dose in heterozygotes, predisposes in variable severity to the phenotypic expression of the disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8571954

  1. Mutations Affecting the SAND Domain of DEAF1 Cause Intellectual Disability with Severe Speech Impairment and Behavioral Problems

    PubMed Central

    Vulto-van Silfhout, Anneke T.; Rajamanickam, Shivakumar; Jensik, Philip J.; Vergult, Sarah; de Rocker, Nina; Newhall, Kathryn J.; Raghavan, Ramya; Reardon, Sara N.; Jarrett, Kelsey; McIntyre, Tara; Bulinski, Joseph; Ownby, Stacy L.; Huggenvik, Jodi I.; McKnight, G. Stanley; Rose, Gregory M.; Cai, Xiang; Willaert, Andy; Zweier, Christiane; Endele, Sabine; de Ligt, Joep; van Bon, Bregje W.M.; Lugtenberg, Dorien; de Vries, Petra F.; Veltman, Joris A.; van Bokhoven, Hans; Brunner, Han G.; Rauch, Anita; de Brouwer, Arjan P.M.; Carvill, Gemma L.; Hoischen, Alexander; Mefford, Heather C.; Eichler, Evan E.; Vissers, Lisenka E.L.M.; Menten, Björn; Collard, Michael W.; de Vries, Bert B.A.

    2014-01-01

    Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1. PMID:24726472

  2. Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems.

    PubMed

    Vulto-van Silfhout, Anneke T; Rajamanickam, Shivakumar; Jensik, Philip J; Vergult, Sarah; de Rocker, Nina; Newhall, Kathryn J; Raghavan, Ramya; Reardon, Sara N; Jarrett, Kelsey; McIntyre, Tara; Bulinski, Joseph; Ownby, Stacy L; Huggenvik, Jodi I; McKnight, G Stanley; Rose, Gregory M; Cai, Xiang; Willaert, Andy; Zweier, Christiane; Endele, Sabine; de Ligt, Joep; van Bon, Bregje W M; Lugtenberg, Dorien; de Vries, Petra F; Veltman, Joris A; van Bokhoven, Hans; Brunner, Han G; Rauch, Anita; de Brouwer, Arjan P M; Carvill, Gemma L; Hoischen, Alexander; Mefford, Heather C; Eichler, Evan E; Vissers, Lisenka E L M; Menten, Björn; Collard, Michael W; de Vries, Bert B A

    2014-05-01

    Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1.

  3. Diarrheagenic Escherichia coli carrying supplementary virulence genes are an important cause of moderate to severe diarrhoeal disease in Mexico.

    PubMed

    Patzi-Vargas, Sandra; Zaidi, Mussaret Bano; Perez-Martinez, Iza; León-Cen, Magda; Michel-Ayala, Alba; Chaussabel, Damien; Estrada-Garcia, Teresa

    2015-03-01

    Diarrheagenic Escherichia coli (DEC) cause acute and persistent diarrhoea worldwide, but little is known about their epidemiology in Mexico. We determined the prevalence of bacterial enteropathogens in 831 children with acute diarrhoea over a four-year period in Yucatan, Mexico. Six DEC supplementary virulence genes (SVG), mainly associated with enteroaggregative E. coli (EAEC), were sought in 3100 E. coli isolates. DEC was the most common bacterial enteropathogen (28%), surpassing Salmonella (12%) and Shigella (9%). Predominant DEC groups were diffusely adherent E. coli (DAEC) (35%), EAEC (24%), and enteropathogenic E. coli (EPEC) (19%). Among children with DEC infections, 14% had severe illness mainly caused by EPEC (26%) and DAEC (18%); 30% had moderate diarrhoea mainly caused by DAEC (36%), mixed DEC infections (33%) and EAEC (32%). DAEC was most prevalent during spring, while ETEC, EAEC and EPEC predominated in summer. EAEC was more frequent in children 6-24 months old than in those younger than 6 months of age (P = 0.008, OR = 4.2, 95% CI, 1.3-13.9). The presence of SVG dispersin, (aatA), dispersin-translocator (aatA), enteroaggregative heat-stable toxin 1 (astA), plasmid encoded toxin (pet), cytolethal distending toxin (cdt) was higher in DEC than non-DEC strains, (36% vs 26%, P <0.0001, OR = 1.5, 95% CI, 1.3-1.8). 98% of EAEC-infected children harboured strains with SVG; 85% carried the aap-aatA gene combination, and 33% of these also carried astA. 28% of both EPEC and ETEC, and 6% of DAEC patients had strains with SVG. 54% of EPEC patients carried pet-positive strains alone or in combination with astA; only this DEC group harboured cdt-positive isolates. All ETEC patients carried astA- or astA-aap-positive strains. astA and aap were the most common SVG in DAEC (3% and 2%) and non-DEC strains (21% and 13%). DEC carrying SVG are an important cause of moderate to severe bacterial diarrhoea in Mexican children.

  4. Assessing factors causing severe injuries in crashes of high-deck buses in long-distance driving on freeways.

    PubMed

    Chu, Hsing-Chung

    2014-01-01

    High-deck buses that have a higher center of gravity traveling at an excessive speed have a higher likelihood of causing serious and fatal accidents when drivers lose control of the vehicle. In addition, drivers who suffer from fatigue in long-distance driving increase the likelihood of serious accident. This paper examines the effects of risk factors contributing to severe crashes associated with high-deck buses used for long-distance driving on freeways. An ordered logit and latent class models are used to examine significant factors on the severity of injuries in crashes related to high-deck buses. Driver fatigue, drivers or passengers not wearing a seat belt, reckless driving, drunk driving, crashes occurred between midnight and dawn, and crashes occurred at interchange ramps were found to significantly affect the severity of injuries in crashes involving high-deck buses. Safety policies to prevent severe injuries in crashes involving high deck buses used for long-distance runs on freeways include: (1) restricting drivers from exceeding the limit of daily driving hours and mandating sufficient rest breaks; (2) installing an automatic sleep-warning device in the vehicle; (3) drivers with obstructive sleep apnea syndrome or sleep disorders should be tested and treated before they are allowed to perform long hours of driving tasks; (4) educating the public or even amending the seatbelt legislation to require all passengers to wear a seat belt and thus reduce the chance of ejection from a high-deck bus and prevent serious injuries in a crash while traveling at a higher speed on freeways.

  5. Early depictions of the human anterior nasal septum.

    PubMed

    Pirsig, Wolfgang; Sokiranski, Roman

    2006-06-01

    In the literature, remarks on the depiction of the anterior nasal septum in prehistoric times cannot be found. Studying works of art from some archaeological sites of Asia, Asia Minor, Near East, Egypt, and Southeastern Europe the anatomical depiction of the columella and the nostrils in human figures are shown. These figures or heads, partly appearing as masks, were made of ivory, stone, marble, terracotta, steatite, reeds and clay, or of burned limestone. Faces and figures sculpted in the time between the Upper Palaeolithic (30,000 - 25,000 BC) and the Early Bronze Age (3,300 - 2,400 BC) are presented as examples of our ancestors' outstanding skill to create works of art with an astonishing ability to observe anatomical details. The tendency to create a human nose in a natural manner can already be recognized in the figurines of the Upper Palaeolithic.

  6. Hemangioma of the Interatrial Septum: CT and MRI Features

    SciTech Connect

    Hrabak-Paar, Maja; Huebner, Marisa; Stern-Padovan, Ranka; Lusic, Mario

    2011-02-15

    Hemangioma of the heart is a rare primary benign tumor mainly appearing as enhancing, homogenous, well-circumscribed mass. We report a case of a 61-year-old asymptomatic woman, whose echocardiography showed a cardiac mass, which was described as the atypical myxoma of the right atrium. For further imaging, contrast-enhanced computed tomography and cardiac magnetic resonance imaging were undertaken, which showed a tumor located in the interatrial septum with imaging characteristics of hemangioma. In the literature, cardiac hemangioma is usually described as an intensely enhancing mass. In our opinion, early peripheral puddling of contrast material with filling in on delayed images is a typical pattern of its enhancement. This characteristic, in addition to high signal intensity on T2-weighted images, allows differentiation of a hemangioma from other benign and malignant tumors.

  7. Fusarium Wilt of Banana Is Caused by Several Pathogens Referred to as Fusarium oxysporum f. sp. cubense.

    PubMed

    Ploetz, Randy C

    2006-06-01

    ABSTRACT Fusarium wilt of banana (also known as Panama disease) is caused by Fusarium oxysporum f. sp. cubense. Where susceptible cultivars are grown, management is limited to the use of pathogen-free planting stock and clean soils. Resistant genotypes exist for some applications, but resistance is still needed in other situations. Progress has been made with this recalcitrant crop by traditional and nontraditional improvement programs. The disease was first reported in Australia in 1876, but did the greatest damage in export plantations in the western tropics before 1960. A new variant, tropical race 4, threatens the trades that are now based on Cavendish cultivars, and other locally important types such as the plantains. Phylogenetic studies indicate that F. oxysporum f. sp. cubense had several independent evolutionary origins. The significance of these results and the future impact of this disease are discussed.

  8. A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family.

    PubMed

    Saglar, Emel; Deniz, Ferhat; Erdem, Beril; Karaduman, Tugce; Yönem, Arif; Cagiltay, Eylem; Mergen, Hatice

    2014-05-01

    X-linked nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by mutations in arginine vasopressin type 2 receptor (AVPR2) and characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel 388 bp deletion starting in intron 1 and ending in exon 2 in the AVPR2 gene in a patient with NDI and in his family. We have revealed that this mutation is a de novo mutation for the mother of the proband patient. Prospective clinical data were collected for all family members. The water deprivation test confirmed the diagnosis of diabetes insipidus. The patient has severe symptoms like deep polyuria nocturia, polydipsia, and fatigue. He was given arginine vasopressin treatment while he was a child. However, he could not get well due to his nephrogenic type of illness. Both of his nephews have the same complains in addition to failure to grow. We have sequenced all exons and intron-exon boundaries of the AVPR2 gene of all family members. The analyses of bioinformatics and comparative genomics of the deletion were done via considering the DNA level damage. AVPR2 gene mutation results in the absence of the three transmembrane domains, two extracellular domains, and one cytoplasmic domain. Three-dimensional protein structure prediction was shown. We concluded that X-linked NDI and severity of illness in this family is caused by a novel 388 bp deletion in the AVPR2 gene that is predicted to truncate the receptor protein, and also this deletion may lead to dysfunctioning in protein activity and inefficient or inadequate binding abilities.

  9. Aging causes partial loss of basal forebrain but no loss of pontine reticular cholinergic neurons.

    PubMed

    Baskerville, Karen A; Kent, Caroline; Nicolle, Michelle M; Gallagher, Michela; McKinney, Michael

    2006-11-27

    Cholinergic degeneration occurs in several neurodegenerative diseases. To investigate whether normal aging causes selective neurodegeneration, we compared counts of cholinergic neurons in the medial septum/vertical limb of the diagonal band and pedunculopontine and laterodorsal tegmental nuclei of the brainstem in young and aged Long-Evans rats characterized for their spatial learning ability in the Morris water maze. A subset of aged rats (aged-unimpaired) learned the spatial learning task as young rats, whereas another group (age-impaired) showed poorer learning than young animals. In the medial septum/diagonal band, there was a significant loss (-23%, P < 0.02) of cholinergic neurons in aged-impaired animals compared with young subjects. In the brainstem, there were no significant differences in cholinergic cell number in any group. This selective loss of cholinergic neurons may, in part, account for the cognitive deficits observed in aging and, considering previous findings in this model, may be related to oxidative stress.

  10. Severe mortality in wild Atlantic salmon Salmo salar due to proliferative kidney disease (PKD) caused by Tetracapsuloides bryosalmonae (myxozoa).

    PubMed

    Sterud, Erik; Forseth, Torbjørn; Ugedal, Ola; Poppe, Trygve T; Jørgensen, Anders; Bruheim, Torkjell; Fjeldstad, Hans-Petter; Mo, Tor Atle

    2007-10-15

    Extensive mortality in Atlantic salmon fry was reported in the River Aelva from 2002 to 2004. Dead fish were collected in late summer 2006, and live fish were sampled by electrofishing in September the same year. At autopsy and in histological sections, the fish kidneys were found to be pale and considerably enlarged. Proliferative lesions with characteristic PKX cells were seen in a majority of the fish. DNA from kidney samples of diseased fish was subjected to PCR and sequencing, and the amplified sequences matched those of Tetracapsuloides bryosalmonae. We concluded that this myxozoan transmitted from bryozoans was the main cause of the observed mortality in salmon fry in 2006. Results from quantitative electrofishing in 2005 and 2006, combined with the observed fry mortality from 2002 to 2004, show that the smolt production in the river is severely reduced and that T. bryosalmonae is the most likely explanation for this decline. The present study is the first to report a considerable negative population effect in wild Atlantic salmon due to proliferative kidney disease (PKD). It also represents the northernmost PKD outbreak in wild fish. The river is regulated for hydroelectric power purposes, causing reduced water flow and elevated summer temperatures, and the present PKD outbreak may serve as an example of increased disease vulnerability of northern fish populations in a warmer climate.

  11. Downeast anemia (dea), a new mouse model of severe nonspherocytic hemolytic anemia caused by hexokinase (HK(1)) deficiency.

    PubMed

    Peters, L L; Lane, P W; Andersen, S G; Gwynn, B; Barker, J E; Beutler, E

    2001-01-01

    A new spontaneous mutation in the A/J inbred mouse strain, downeast anemia (dea), causes severe hemolytic anemia with extensive tissue iron deposition and marked reticulocytosis. The anemia is present at birth and persists throughout life. The defect is inherited as an autosomal recessive and is transferable through bone marrow stem cells. The red cell morphology is consistent with a nonspherocytic hemolytic anemia, suggestive of a red cell enzymopathy. In linkage analysis, dea is nonrecombinant with the hexokinase-1 gene (Hk1) on mouse Chromosome 10. Expression of Hk1 is markedly decreased in dea erythroid tissues, and the transcript produced is larger than normal. Hexokinase enzyme activity is significantly decreased in dea tissues, including red cells, spleen, and kidney. Southern blot analyses revealed approximately 5.5 kb of additional sequence in the 5' portion of the dea Hk1 gene, which was identified by direct sequencing as an early transposon (ETn) insertion in intron 4. ETn insertions disrupt genes in several mouse models by a variety of mechanisms, including aberrant splicing of ETn sequences into the mRNA. We conclude that the primary gene defect in the dea mutation is in Hk1 and that dea is a model of generalized hexokinase deficiency, the first such model identified to date.

  12. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature.

    PubMed

    Abou Jamra, Rami; Philippe, Orianne; Raas-Rothschild, Annick; Eck, Sebastian H; Graf, Elisabeth; Buchert, Rebecca; Borck, Guntram; Ekici, Arif; Brockschmidt, Felix F; Nöthen, Markus M; Munnich, Arnold; Strom, Tim M; Reis, Andre; Colleaux, Laurence

    2011-06-10

    Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. Using a combination of autozygosity mapping and either Sanger sequencing of candidate genes or next-generation exome sequencing, we identified one mutation in each of three genes encoding adaptor protein complex 4 (AP4) subunits: a nonsense mutation in AP4S1 (NM_007077.3: c.124C>T, p.Arg42(∗)), a frameshift mutation in AP4B1 (NM_006594.2: c.487_488insTAT, p.Glu163_Ser739delinsVal), and a splice mutation in AP4E1 (NM_007347.3: c.542+1_542+4delGTAA, r.421_542del, p.Glu181Glyfs(∗)20). Adaptor protein complexes (AP1-4) are ubiquitously expressed, evolutionarily conserved heterotetrameric complexes that mediate different types of vesicle formation and the selection of cargo molecules for inclusion into these vesicles. Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability. Combined with previous observations, these results support the hypothesis that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning and demonstrate the existence of a clinically recognizable syndrome due to deficiency of the AP4 complex.

  13. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial

    PubMed Central

    Bishara, Jihad; Yahav, Dafna; Goldberg, Elad; Neuberger, Ami; Ghanem-Zoubi, Nesrin; Dickstein, Yaakov; Nseir, William; Dan, Michael; Leibovici, Leonard

    2015-01-01

    Objective To show non-inferiority of trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of severe infections due to meticillin resistant Staphylococcus aureus (MRSA). Design Parallel, open label, randomised controlled trial. Setting Four acute care hospitals in Israel. Participants Adults with severe infections caused by MRSA susceptible to trimethoprim-sulfamethoxazole and vancomycin. Patients with left sided endocarditis, meningitis, chronic haemodialysis, and prolonged neutropenia were excluded. Interventions Trimethoprim-sulfamethoxazole 320 mg/1600 mg twice daily versus vancomycin 1 g twice daily for a minimum of seven days and then by indication. Main outcome measures The primary efficacy outcome was treatment failure assessed at day 7, consisting of death, persistence of haemodynamic instability or fever, stable or worsening Sequential Organ Failure Assessment score, and persistence of bacteraemia. The primary safety outcome was all cause mortality at day 30. Non-inferiority was defined by a difference of less than 15% for treatment failure. Results 252 patients were included in the trial, of whom 91 (36%) had bacteraemia. No significant difference in treatment failure was seen for trimethoprim-sulfamethoxazole (51/135, 38%) versus vancomycin (32/117, 27%)—risk ratio 1.38 (95% confidence interval 0.96 to 1.99). However, trimethoprim-sulfamethoxazole did not meet the non-inferiority criterion—absolute difference 10.4% (95% confidence interval −1.2% to 21.5%). For patients with bacteraemia, the risk ratio was 1.40 (0.91 to 2.16). In a multivariable logistic regression analysis, trimethoprim-sulfamethoxazole was significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65). The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0

  14. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or ‘classical’ congenital myopathy

    PubMed Central

    Zaharieva, Irina T.; Thor, Michael G.; Oates, Emily C.; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T.; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D’Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R.; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A.; Morgan, Jennifer E.; Laing, Nigel G.; Vallance, Hilary; Ruben, Peter; Hanna, Michael G.; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope

    2016-01-01

    See Cannon (doi:10.1093/brain/awv400) for a scientific commentary on this article. Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro

  15. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy.

    PubMed

    Chong, Jessica X; Caputo, Viviana; Phelps, Ian G; Stella, Lorenzo; Worgan, Lisa; Dempsey, Jennifer C; Nguyen, Alina; Leuzzi, Vincenzo; Webster, Richard; Pizzuti, Antonio; Marvin, Colby T; Ishak, Gisele E; Ardern-Holmes, Simone; Richmond, Zara; Bamshad, Michael J; Ortiz-Gonzalez, Xilma R; Tartaglia, Marco; Chopra, Maya; Doherty, Dan

    2016-04-07

    Infantile encephalopathies are a group of clinically and biologically heterogeneous disorders for which the genetic basis remains largely unknown. Here, we report a syndromic neonatal encephalopathy characterized by profound developmental disability, severe hypotonia, seizures, diminished respiratory drive requiring mechanical ventilation, brain atrophy, dysgenesis of the corpus callosum, cerebellar vermis hypoplasia, and facial dysmorphism. Biallelic inactivating mutations in TBCK (TBC1-domain-containing kinase) were independently identified by whole-exome sequencing as the cause of this condition in four unrelated families. Matching these families was facilitated by the sharing of phenotypic profiles and WES data in a recently released web-based tool (Geno2MP) that links phenotypic information to rare variants in families with Mendelian traits. TBCK is a putative GTPase-activating protein (GAP) for small GTPases of the Rab family and has been shown to control cell growth and proliferation, actin-cytoskeleton dynamics, and mTOR signaling. Two of the three mutations (c.376C>T [p.Arg126(∗)] and c.1363A>T [p.Lys455(∗)]) are predicted to truncate the protein, and loss of the major TBCK isoform was confirmed in primary fibroblasts from one affected individual. The third mutation, c.1532G>A (p.Arg511His), alters a conserved residue within the TBC1 domain. Structural analysis implicated Arg511 as a required residue for Rab-GAP function, and in silico homology modeling predicted impaired GAP function in the corresponding mutant. These results suggest that loss of Rab-GAP activity is the underlying mechanism of disease. In contrast to other disorders caused by dysregulated mTOR signaling associated with focal or global brain overgrowth, impaired TBCK function results in progressive loss of brain volume.

  16. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy

    PubMed Central

    Chong, Jessica X.; Caputo, Viviana; Phelps, Ian G.; Stella, Lorenzo; Worgan, Lisa; Dempsey, Jennifer C.; Nguyen, Alina; Leuzzi, Vincenzo; Webster, Richard; Pizzuti, Antonio; Marvin, Colby T.; Ishak, Gisele E.; Ardern-Holmes, Simone; Richmond, Zara; Bamshad, Michael J.; Ortiz-Gonzalez, Xilma R.; Tartaglia, Marco; Chopra, Maya; Doherty, Dan

    2016-01-01

    Infantile encephalopathies are a group of clinically and biologically heterogeneous disorders for which the genetic basis remains largely unknown. Here, we report a syndromic neonatal encephalopathy characterized by profound developmental disability, severe hypotonia, seizures, diminished respiratory drive requiring mechanical ventilation, brain atrophy, dysgenesis of the corpus callosum, cerebellar vermis hypoplasia, and facial dysmorphism. Biallelic inactivating mutations in TBCK (TBC1-domain-containing kinase) were independently identified by whole-exome sequencing as the cause of this condition in four unrelated families. Matching these families was facilitated by the sharing of phenotypic profiles and WES data in a recently released web-based tool (Geno2MP) that links phenotypic information to rare variants in families with Mendelian traits. TBCK is a putative GTPase-activating protein (GAP) for small GTPases of the Rab family and has been shown to control cell growth and proliferation, actin-cytoskeleton dynamics, and mTOR signaling. Two of the three mutations (c.376C>T [p.Arg126∗] and c.1363A>T [p.Lys455∗]) are predicted to truncate the protein, and loss of the major TBCK isoform was confirmed in primary fibroblasts from one affected individual. The third mutation, c.1532G>A (p.Arg511His), alters a conserved residue within the TBC1 domain. Structural analysis implicated Arg511 as a required residue for Rab-GAP function, and in silico homology modeling predicted impaired GAP function in the corresponding mutant. These results suggest that loss of Rab-GAP activity is the underlying mechanism of disease. In contrast to other disorders caused by dysregulated mTOR signaling associated with focal or global brain overgrowth, impaired TBCK function results in progressive loss of brain volume. PMID:27040692

  17. Postretinal Structure and Function in Severe Congenital Photoreceptor Blindness Caused by Mutations in the GUCY2D Gene

    PubMed Central

    Aguirre, Geoffrey K.; Butt, Omar H.; Datta, Ritobrato; Roman, Alejandro J.; Sumaroka, Alexander; Schwartz, Sharon B.; Cideciyan, Artur V.; Jacobson, Samuel G.

    2017-01-01

    Purpose To examine how severe congenital blindness resulting from mutations of the GUCY2D gene alters brain structure and function, and to relate these findings to the notable preservation of retinal architecture in this form of Leber congenital amaurosis (LCA). Methods Six GUCY2D-LCA patients (ages 20–46) were studied with optical coherence tomography of the retina and multimodal magnetic resonance imaging (MRI) of the brain. Measurements from this group were compared to those obtained from populations of normally sighted controls and people with congenital blindness of a variety of causes. Results Patients with GUCY2D-LCA had preservation of the photoreceptors, ganglion cells, and nerve fiber layer. Despite this, visual function in these patients ranged from 20/160 acuity to no light perception, and functional MRI responses to light stimulation were attenuated and restricted. This severe visual impairment was reflected in substantial thickening of the gray matter layer of area V1, accompanied by an alteration of resting-state correlations within the occipital lobe, similar to a comparison group of congenitally blind people with structural damage to the retina. In contrast to the comparison blind population, however, the GUCY2D-LCA group had preservation of the size of the optic chiasm, and the fractional anisotropy of the optic radiations as measured with diffusion tensor imaging was also normal. Conclusions These results identify dissociable effects of blindness upon the visual pathway. Further, the relatively intact postgeniculate white matter pathway in GUCY2D-LCA is encouraging for the prospect of recovery of visual function with gene augmentation therapy.

  18. Injury pattern, hospital triage, and mortality of 1250 patients with severe traumatic brain injury caused by road traffic accidents.

    PubMed

    Leijdesdorff, Henry A; van Dijck, Jeroen T J M; Krijnen, Pieta; Vleggeert-Lankamp, Carmen L A M; Schipper, Inger B

    2014-03-01

    This epidemiological study analyzed the incidence, risk factors, hospital triage, and outcome of patients with severe traumatic brain injuries (sTBIs) caused by road traffic accidents (RTAs) admitted to hospitals in the Trauma Center West-Netherlands (TCWN) region. Trauma registry data were used to identify TBI in all RTA victims admitted to hospitals in the mid-West region of the Netherlands from 2003 to 2011. Type of head injury and severity were classified using the Abbreviated Injury Scale (AIS). Head injuries with AIS severity scores ≥ 3 were considered sTBI. Ten percent of all 12,503 hospital-admitted RTA victims sustained sTBI, ranging from 5.4% in motorcyclists, 7.4% in motorists, 9.6% in cyclists, and 12.7% in moped riders to 15.1% in pedestrians (p<0.0001). Among RTA victims admitted to hospital, sTBI was most prevalent in pedestrians (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.78-2.86) and moped riders (OR, 1.86; 95% CI, 1.51-2.30). Injury patterns differed between road user groups. Incidence of contusion ranged from 46.6% in cyclists to 74.2% in motorcyclists, whereas basilar and open-skull fractures were least common in motorcyclists (22.6%) and most common in moped riders (51.5%). Hemorrhage incidence ranged from 44.9% (motorists) to 63.6% (pedestrians). Subdural and -arachnoid bleedings were most frequent. Age, Glasgow Coma Scale, and type of hemorrhage were independent prognostic factors for in-hospital mortality after sTBI. In-hospital mortality ranged from 4.2% in moped riders to 14.1% in motorists. Pedestrians have the highest risk to sustain sTBI and, more specifically, intracranial hemorrhage. Hemorrhage and contusion both occur in over 50% of patients with sTBI. Specific brain injury patterns can be distinguished for specific road user groups, and independent prognostic risk factors for sTBI were identified. This knowledge may be used to improve vigilance for particular injuries in specific patient groups and stimulate

  19. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene

    PubMed Central

    Powell, Ellis J.; Cunnick, Joan E.; Knetter, Susan M.; Loving, Crystal L.; Waide, Emily H.; Dekkers, Jack C.M.; Tuggle, Christopher K.

    2016-01-01

    We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor cell lines, PANC-1 and A375-SM, survived after injection into these SCID pigs, but, as we demonstrate here, these cells, as well as K562 tumor cells, can be lysed in vitro by NK cells from SCID and non-SCID pigs. NK cells from both SCID and non-SCID pigs required activation in vitro with either recombinant human IL-2 or the combination of recombinant porcine IL-12 and IL-18 to kill tumor targets. We also showed that SCID NK cells could be activated to produce perforin, and perforin production was greatly enhanced in NK cells from both SCID and non-SCID pigs after IL-2 cytokine treatment. While CD16+, CD172− NK cells constituted an average of only 4% in non-SCID pigs, NK cells averaged 27% of the peripheral blood mononuclear cell population in SCID pigs. We found no significant differences in killing activity per NK cell between SCID and non-SCID pigs. We conclude that survival of human cancer cells in these SCID pigs is not due to an intrinsic defect in NK cell killing ability. PMID:27269786

  20. An outbreak of severe infections among Australian infants caused by a novel recombinant strain of human parechovirus type 3

    PubMed Central

    Nelson, Tiffanie M.; Vuillermin, Peter; Hodge, Jason; Druce, Julian; Williams, David T.; Jasrotia, Rekha; Alexandersen, Soren

    2017-01-01

    Human parechovirus types 1–16 (HPeV1–16) are positive strand RNA viruses in the family Picornaviridae. We investigated a 2015 outbreak of HPeV3 causing illness in infants in Victoria, Australia. Virus genome was extracted from clinical material and isolates and sequenced using a combination of next generation and Sanger sequencing. The HPeV3 outbreak genome was 98.7% similar to the HPeV3 Yamagata 2011 lineage for the region encoding the structural proteins up to nucleotide position 3115, but downstream of that the genome varied from known HPeV sequences with a similarity of 85% or less. Analysis indicated that recombination had occurred, may have involved multiple types of HPeV and that the recombination event/s occurred between March 2012 and November 2013. However the origin of the genome downstream of the recombination site is unknown. Overall, the capsid of this virus is highly conserved, but recombination provided a different non-structural protein coding region that may convey an evolutionary advantage. The indication that the capsid encoding region is highly conserved at the amino acid level may be helpful in directing energy towards the development of a preventive vaccine for expecting mothers or antibody treatment of young infants with severe disease. PMID:28290509

  1. A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia

    PubMed Central

    Johansson, Joel; Sahin, Christofer; Pestoff, Rebecka; Ignatova, Simone; Forsberg, Pia; Edsjö, Anders; Ekstedt, Mattias; Stenmark Askmalm, Marie

    2015-01-01

    Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency. PMID:25705527

  2. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene.

    PubMed

    Powell, Ellis J; Cunnick, Joan E; Knetter, Susan M; Loving, Crystal L; Waide, Emily H; Dekkers, Jack C M; Tuggle, Christopher K

    2016-07-01

    We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor cell lines, PANC-1 and A375-SM, survived after injection into these SCID pigs, but, as we demonstrate here, these cells, as well as K562 tumor cells, can be lysed in vitro by NK cells from SCID and non-SCID pigs. NK cells from both SCID and non-SCID pigs required activation in vitro with either recombinant human IL-2 or the combination of recombinant porcine IL-12 and IL-18 to kill tumor targets. We also showed that SCID NK cells could be activated to produce perforin, and perforin production was greatly enhanced in NK cells from both SCID and non-SCID pigs after IL-2 cytokine treatment. While CD16+, CD172- NK cells constituted an average of only 4% in non-SCID pigs, NK cells averaged 27% of the peripheral blood mononuclear cell population in SCID pigs. We found no significant differences in killing activity per NK cell between SCID and non-SCID pigs. We conclude that survival of human cancer cells in these SCID pigs is not due to an intrinsic defect in NK cell killing ability.

  3. An outbreak of severe infections among Australian infants caused by a novel recombinant strain of human parechovirus type 3.

    PubMed

    Nelson, Tiffanie M; Vuillermin, Peter; Hodge, Jason; Druce, Julian; Williams, David T; Jasrotia, Rekha; Alexandersen, Soren

    2017-03-14

    Human parechovirus types 1-16 (HPeV1-16) are positive strand RNA viruses in the family Picornaviridae. We investigated a 2015 outbreak of HPeV3 causing illness in infants in Victoria, Australia. Virus genome was extracted from clinical material and isolates and sequenced using a combination of next generation and Sanger sequencing. The HPeV3 outbreak genome was 98.7% similar to the HPeV3 Yamagata 2011 lineage for the region encoding the structural proteins up to nucleotide position 3115, but downstream of that the genome varied from known HPeV sequences with a similarity of 85% or less. Analysis indicated that recombination had occurred, may have involved multiple types of HPeV and that the recombination event/s occurred between March 2012 and November 2013. However the origin of the genome downstream of the recombination site is unknown. Overall, the capsid of this virus is highly conserved, but recombination provided a different non-structural protein coding region that may convey an evolutionary advantage. The indication that the capsid encoding region is highly conserved at the amino acid level may be helpful in directing energy towards the development of a preventive vaccine for expecting mothers or antibody treatment of young infants with severe disease.

  4. A case report of a severe musculoskeletal injury in a wheelchair user caused by an incorrect wheelchair ramp design.

    PubMed

    Edlich, Richard F; Kelley, Angela R; Morton, Karrie; Gellman, Richard E; Berkey, Richard; Greene, Jill Amanda; Hill, Larry; Mears, Roy; Long, William B

    2010-02-01

    The Americans with Disabilities Act (ADA) gives all Americans with disabilities a chance to achieve the same quality of life that individuals without disabilities enjoy. In this case report, we will be discussing the consequences of having inaccessible ramps to persons with disabilities that can result in severe musculoskeletal injuries in a wheelchair user. While going down an inaccessible ramp in the garage of a hospital, a wheelchair tipped over, causing a fracture to the user's right femur. The injured patient was taken to the Emergency Department, where the diagnosis of a fracture of the right femur was made. The fracture then had to be repaired with an intramedullary rod under general anesthesia in the hospital. It was discovered that the ramps in the hospital garage did not comply with the guidelines of the ADA. The wheelchair ramps had a ramp run with a rise > 6 inches (150 mm) and a horizontal projection > 72 inches (1830 mm). This led to the redesign and construction of safe ramps for individuals using wheelchairs as well as for pedestrians using canes, within 1 month after the patient's injury, making it safe for wheelchair users as well as pedestrians using the parking facilities. The ADA specifies guidelines for safe ramps for patients with disabilities. It is important to ensure that hospital ramps comply with these guidelines.

  5. Key Molecular Mechanisms of Chaiqinchengqi Decoction in Alleviating the Pulmonary Albumin Leakage Caused by Endotoxemia in Severe Acute Pancreatitis Rats

    PubMed Central

    Wu, Wei; Luo, Ruijie; Lin, Ziqi; Xia, Qing

    2016-01-01

    To reveal the key molecular mechanisms of Chaiqinchengqi decoction (CQCQD) in alleviating the pulmonary albumin leakage caused by endotoxemia in severe acute pancreatitis (SAP) rats. Rats models of SAP endotoxemia-induced acute lung injury were established, the studies in vivo provided the important evidences that the therapy of CQCQD significantly ameliorated the increases in plasma levels of lipopolysaccharide (LPS), sCd14, and Lbp, the elevation of serum amylase level, the enhancements of systemic and pulmonary albumin leakage, and the depravation of airways indicators, thus improving respiratory dysfunction and also pancreatic and pulmonary histopathological changes. According to the analyses of rats pulmonary tissue microarray and protein-protein interaction network, c-Fos, c-Src, and p85α were predicted as the target proteins for CQCQD in alleviating pulmonary albumin leakage. To confirm these predictions, human umbilical vein endothelial cells were employed in in vitro studies, which provide the evidences that (1) LPS-induced paracellular leakage and proinflammatory cytokines release were suppressed by pretreatment with inhibitors of c-Src (PP1) or PI3K (LY294002) or by transfection with siRNAs of c-Fos; (2) fortunately, CQCQD imitated the actions of these selective inhibitions agents to inhibit LPS-induced high expressions of p-Src, p-p85α, and c-Fos, therefore attenuating paracellular leakage and proinflammatory cytokines release. PMID:27413385

  6. Double-outlet right ventricle with intact ventricular septum in a foetus with trisomy-18.

    PubMed

    Patel, C R; Muise, K L; Redline, R W

    1999-07-01

    A rare case of double-outlet right ventricle with intact ventricular septum diagnosed by foetal echocardiography at 21 weeks of gestation is described. Amniocentesis revealed trisomy-18. The cardiac diagnosis was confirmed at autopsy.

  7. The case of a cyst hydatid localized within the interatrial septum.

    PubMed

    Karabay, Ozalp; Onen, Ahmet; Yildiz, Fidan; Yilmaz, Erkan; Erdal, Cenk A; Sanli, Aydin; Kilci, Göksel; Algin, Ibrahim; Itil, Oya; Açikel, Unal

    2004-07-01

    The ratio of cardiac involvement of Echinoccocus granulosus is 0.02-2% and although seen rarely, involvement of the interatrial septum has also been reported in the published literature. The present case was a 19-year-old male university student admitted to hospital with complaints of headache and dizziness. Computerized tomography of the cranium revealed a cystic mass located at the frontal region and enucleation of the cyst was performed during surgery. A cystic lesion 5 x 4 cm in size was detected within the interatrial septum on two-dimensional transthoracic echocardiography during the postoperative period and the patient was referred to our clinic. Open heart surgery was performed and a hydatid cyst that involved the interatrial septum was enucleated. The cyst wall was sutured to the interatrial septum. No complications developed during the postoperative period. The patient was discharged on the fifth day of hospitalization and medical therapy was started with albendazole.

  8. Deviated nasal septum hinders intranasal sprays: A computer simulation study

    PubMed Central

    Frank, Dennis O.; Kimbell, Julia S.; Cannon, Daniel; Pawar, Sachin S.; Rhee, John S.

    2013-01-01

    Background This study investigates how deviated nasal septum affects the quantity and distribution of spray particles, and examines the effects of inspiratory airflow and head position on particle transport. Methods Deposition of spray particles was analysed using a three-dimensional computational fluid dynamics model created from a computed tomography scan of a human nose with leftward septal deviation and a right inferior turbinate hypertrophy. Five simulations were conducted using Fluent™ software, with particle sizes ranging from 20-110μm, a spray speed of 3m/s, plume angle of 68°, and with steady state inspiratory airflow either present (15.7L/min) or absent at varying head positions. Results With inspiratory airflow present, posterior deposition on the obstructed side was approximately four times less than the contralateral side, regardless of head position, and was statistically significant (p<0.05). When airflow was absent, predicted deposition beyond the nasal valve on the left and right sides were between 16% and 69% lower and positively influenced by a dependent head position. Conclusions Simulations predicted that septal deviation significantly diminished drug delivery on the obstructed side. Furthermore, increased particle penetration was associated with presence of nasal airflow. Head position is an important factor in particle deposition patterns when inspiratory airflow is absent. PMID:22888490

  9. Right ventricular outflow obstruction with intact ventricular septum in adults.

    PubMed Central

    Werner, A M; Darrell, J C; Pallegrini, R V; Woelfel, G F; Grant, K; Marrangoni, A G

    1997-01-01

    Cardiothoracic surgeons whose practice is limited to adults rarely see patients with right ventricular outflow obstruction and an intact ventricular septum. Of more than 10,000 open-heart procedures performed at our institution from 1983 to 1993 (in patients 18 to 75 years old), only 5 procedures were for correction of this problem. Both the pulmonary valve and the subvalvular area were abnormal in these 5 patients, and 4 of the 5 had subvalvular stenosis. The gradient across the right ventricular outflow tract was measured by cardiac catheterization before repair in all patients and averaged 118 mmHg. Various surgical approaches were used for repair. In the 2 patients whose pressures were measured postoperatively, the gradients were 25 mmHg and 45 mmHg, respectively. There were no operative deaths. At follow-up (range, 2 months to 5 years after surgery), all patients were in New York Heart Association functional class I and all had murmurs. Those who underwent echocardiography were found to have minimal gradients across the right ventricular outflow tract. Images PMID:9205983

  10. Ecology of the Tick-Borne Phlebovirus Causing Severe Fever with Thrombocytopenia Syndrome in an Endemic Area of China

    PubMed Central

    Hu, Jianli; Liu, Wendong; Wang, Xiaochen; Zhang, Lei; Ji, Zhengmin; Feng, Zhi; Li, Luxun; Shen, Aihua; Liu, Xuejian; Zhao, Hongjun; Tan, Wenwen; Zhou, Jiangang; Qi, Xian; Zhu, Yefei; Tang, Fenyang; Cardona, Carol J.; Xing, Zheng

    2016-01-01

    Background Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a tick-borne phlebovirus in family Bunyaviridae. Studies have found that humans, domestic and wildlife animals can be infected by SFTSV. However, the viral ecology, circulation, and transmission remain largely unknown. Methodology/Principal Findings Sixty seven human SFTS cases were reported and confirmed by virus isolation or immunofluorescence assay between 2011 and 2014. In 2013–2014 we collected 9,984 ticks from either vegetation or small wild mammals in the endemic area in Jiangsu, China, and detected SFTSV-RNA by real-time RT-PCR in both questing and feeding Haemaphysalis longicornis and H. flava. Viral RNA was identified in larvae of H. longicornis prior to a first blood meal, which has never been confirmed previously in nature. SFTSV-RNA and antibodies were also detected by RT-PCR and ELISA, respectively, in wild mammals including Erinaceus europaeus and Sorex araneus. A live SFTSV was isolated from Erinaceus europaeus captured during the off tick-feeding season and with a high SFTSV antibody titer. Furthermore, SFTSV antibodies were detected in the migratory birds Anser cygnoides and Streptopelia chinensis using ELISA. Conclusions/Significance The detection of SFTSV-RNA in non-engorged larvae indicated that vertical transmission of SFTSV in H. longicornis might occur in nature, which suggests that H. longicornis is a putative reservoir host of SFTSV. Small wild mammals such as Erinaceus europaeus and Sorex araneus could be infected by SFTSV and may serve as natural amplifying hosts. Our data unveiled that wild birds could be infected with SFTSV or carry SFTSV-infected ticks and thus might contribute to the long-distance spread of SFTSV via migratory flyways. These findings provide novel insights for understanding SFTSV ecology, reservoir hosts, and transmission in nature and will help develop new measures in preventing its rapid spread both regionally and

  11. Surgical repair of rupture of the membranous septum after blunt chest trauma.

    PubMed

    Tarmiz, Amine; Lopez, Stéphane; Honton, Ben; Riu, Béatrice

    2011-01-01

    Rupture of the membranous septum is a very rare complication of blunt chest trauma. In this report, we describe a 22-year-old man who sustained multiple blunt trauma injuries during a motor vehicle accident. Rupture of the membranous septum was diagnosed 48 hours after the initial trauma and the defect was closed with Gore-Tex (W.L. Gore & Assoc, Flagstaff, AZ). However, the operation was complicated by complete atrioventricular block requiring implantation of a permanent DDD pacemaker.

  12. Medial septum lesions disrupt exploratory trip organization: evidence for septohippocampal involvement in dead reckoning.

    PubMed

    Martin, Megan M; Horn, Katharine L; Kusman, Kelly J; Wallace, Douglas G

    2007-02-28

    Rats organize their open field behavior into a series of exploratory trips focused around a central location or home base. In addition, differences in movement kinematics have been used to fractionate the exploratory trip into tour (i.e., sequences of linear movement or progressions punctuated by stops) and homeward (i.e., single progression direct to the home base) segments. The observation of these characteristics independent of environmental familiarity and visual cue availability has suggested a role for self-movement information or dead reckoning in organizing exploratory behavior. Although previous work has implicated a role for the septohippocampal system in dead reckoning based navigation, as of yet, no studies have investigated the contribution of the medial septum to dead reckoning. First, the present study examined the organization of exploratory behavior under dark and light conditions in control rats and rats receiving either electrolytic or sham medial septum lesions. Medial septum lesions produced a significant increase in homeward segment path circuity and variability of temporal pacing of linear speeds. Second, as an independent assessment of the effectiveness of the medial septum lesions, rats were trained to locate a hidden platform in the standard water maze procedure. Consistent with previous research, medial septum lesions attenuated learning the location of the hidden platform. These results demonstrate a role for the medial septum in organizing exploratory behavior and provide further support for the role of the septohippocampal system in dead reckoning based navigation.

  13. The contractile ring coordinates curvature-dependent septum assembly during fission yeast cytokinesis

    PubMed Central

    Zhou, Zhou; Munteanu, Emilia Laura; He, Jun; Ursell, Tristan; Bathe, Mark; Huang, Kerwyn Casey; Chang, Fred

    2015-01-01

    The functions of the actin-myosin–based contractile ring in cytokinesis remain to be elucidated. Recent findings show that in the fission yeast Schizosaccharomyces pombe, cleavage furrow ingression is driven by polymerization of cell wall fibers outside the plasma membrane, not by the contractile ring. Here we show that one function of the ring is to spatially coordinate septum cell wall assembly. We develop an improved method for live-cell imaging of the division apparatus by orienting the rod-shaped cells vertically using microfabricated wells. We observe that the septum hole and ring are circular and centered in wild-type cells and that in the absence of a functional ring, the septum continues to ingress but in a disorganized and asymmetric manner. By manipulating the cleavage furrow into different shapes, we show that the ring promotes local septum growth in a curvature-dependent manner, allowing even a misshapen septum to grow into a more regular shape. This curvature-dependent growth suggests a model in which contractile forces of the ring shape the septum cell wall by stimulating the cell wall machinery in a mechanosensitive manner. Mechanical regulation of the cell wall assembly may have general relevance to the morphogenesis of walled cells. PMID:25355954

  14. The role of septoplasty in the management of nasal septum fracture: a randomized quality of life study.

    PubMed

    Younes, A; Elzayat, S

    2016-11-01

    Fracture of the nasal septum is a common injury. Fracture reduction using Ash forceps is the standard treatment for non-severely comminuted cases. In this study, septoplasty was compared to Ash forceps reduction of nasal septum fractures with regard to the quality of life outcome of patient breathing. Thirty consecutive patients with non-comminuted septal fractures were divided randomly into two groups. In group I, fractures were managed by closed reduction (using Ash forceps), while in group II, fractures were managed by septoplasty surgery. Each patient completed a validated quality of life scale for breathing (Nasal Obstruction Symptom Evaluation, NOSE) preoperatively and at 3 months postoperative. In group I, the mean difference between postoperative and preoperative NOSE scores was -28.33 (range -40 to -15), while in group II the mean difference was -44.33 (range -70 to -30). There was a significant improvement in nasal breathing quality of life in group II compared with group I (t-test, P=0.001). The results of this study showed a significant improvement in quality of life outcome with the use of septoplasty compared to closed reduction for acute septal fractures. Septoplasty could be recommended for patients with acute nasoseptal fractures to ensure better nasal breathing outcomes.

  15. Piezoelectric sensing: Evaluation for clinical investigation of deviated nasal septum

    PubMed Central

    Manjunatha, Roopa G.; Mahapatra, Roy D.; Dorasala, Srinivas

    2013-01-01

    Noninvasive objective evaluation of nasal airflow is one of the important clinical aspects. The developed polyvinylidene fluoride (PVDF) sensor enables measurement of airflow through each side of the nose using its piezoelectric property. This study was designed to evaluate the diagnostic capability of the PVDF sensor in assessing the deviated nasal septum (DNS). PVDF nasal sensor uses its piezoelectric property to measure the peak-to-peak amplitude (Vp-p) of nasal airflow in both of the nostrils: right nostril (RN) and left nostril (LN), separately and simultaneously. We have compared the results of PVDF nasal sensor, visual analog scale (VAS), and clinician scale for 34 DNS patients and 28 healthy controls. Additionally, the results were further analyzed by receiver operating characteristic curve and correlation between PVDF nasal sensor and VAS in detecting DNS. We found a significant difference in the peak-to-peak amplitude values of the test group and the control group. The correlation between the PVDF nasal sensor measurements and VAS (RN and LN combined) for test group was statistically significant (−0.807; p < 0.001). Sensitivity and specificity of the PVDF nasal sensor measurements in the detection of DNS (RN and LN combined) was 85.3 and 74.4%, respectively, with optimum cutoff value ≤0.34 Vp-p. The developed PVDF nasal sensor is noninvasive and requires less patient efforts. The sensitivity and specificity of the PVDF nasal sensor are reliable. According to our findings, we propose that the said PVDF nasal sensor can be used as a new diagnostic tool to evaluate the DNS in routine clinical practice. PMID:24498519

  16. Human respiratory syncytial virus Memphis 37 grown in HEp-2 cells causes more severe disease in lambs than virus grown in vero cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and young children. A small percentage of these individuals develop severe and even fatal disease. To better understand the pathogenesis of severe disease and develop therapies unique to the less-developed infan...

  17. The effect of septoplasty on pulmonary artery pressure and right ventricular function in nasal septum deviation.

    PubMed

    Ozkececi, Gulay; Akci, Onder; Bucak, Abdulkadir; Ulu, Sahin; Yalım, Zafer; Aycicek, Abdullah; Onrat, Ersel; Avsar, Alaettin

    2016-11-01

    Nasal septum deviation (NSD) can cause obstruction of the upper airway, which may lead to increased pulmonary artery pressure (PAP) and right ventricle dysfunction. The aim of the present study was to evaluate the effect of septoplasty on right ventricular function and mean PAP of patients with marked NSD. 25 patients with marked NSD (mean age = 31.8 ± 12.3 years) and 27 healthy volunteers (mean age = 34.5 ± 10.8 years) were enrolled. Echocardiography was performed for all subjects and right ventricular function and mean PAP were evaluated before and 3 months after septoplasty. Tricuspid annular plane systolic excursion (TAPSE) and tricuspid annulus early diastolic myocardial velocity (E') were significantly lower in patients with NSD than control subjects, while right ventricle myocardial performance index (RVMPI) and mean PAP were significantly higher (respectively, p = 0.006, 0.037, 0.049, 0.046). When preoperative and postoperative findings were compared, the mean PAP decreased whereas TAPSE increased significantly (respectively, p = 0.007, 0.03). The results of the present study demonstrated that mean PAP increased and right ventricular function worsened in patients with NSD. However, mean PAP decreased and right ventricular function tended to recover after septoplasty.

  18. Effective Modulation of Male Aggression through Lateral Septum to Medial Hypothalamus Projection.

    PubMed

    Wong, Li Chin; Wang, Li; D'Amour, James A; Yumita, Tomohiro; Chen, Genghe; Yamaguchi, Takashi; Chang, Brian C; Bernstein, Hannah; You, Xuedi; Feng, James E; Froemke, Robert C; Lin, Dayu

    2016-03-07

    Aggression is a prevalent behavior in the animal kingdom that is used to settle competition for limited resources. Given the high risk associated with fighting, the central nervous system has evolved an active mechanism to modulate its expression. Lesioning the lateral septum (LS) is known to cause "septal rage," a phenotype characterized by a dramatic increase in the frequency of attacks. To understand the circuit mechanism of LS-mediated modulation of aggression, we examined the influence of LS input on the cells in and around the ventrolateral part of the ventromedial hypothalamus (VMHvl)-a region required for male mouse aggression. We found that the inputs from the LS inhibited the attack-excited cells but surprisingly increased the overall activity of attack-inhibited cells. Furthermore, optogenetic activation of the projection from LS cells to the VMHvl terminated ongoing attacks immediately but had little effect on mounting. Thus, LS projection to the ventromedial hypothalamic area represents an effective pathway for suppressing male aggression.

  19. Three or more copies of the proteolipid protein gene PLP1 cause severe Pelizaeus-Merzbacher disease.

    PubMed

    Wolf, Nicole I; Sistermans, Erik A; Cundall, Maria; Hobson, Grace M; Davis-Williams, Angelique P; Palmer, Rodger; Stubbs, Paula; Davies, Sally; Endziniene, Milda; Wu, Yvonne; Chong, Wui K; Malcolm, Sue; Surtees, Robert; Garbern, James Y; Woodward, Karen J

    2005-04-01

    We describe five boys from different families with an atypically severe form of Pelizaeus-Merzbacher disease (PMD) who have three, and in one case, five copies of the proteolipid protein (PLP1) gene. This is the first report of more than two copies of PLP1 in PMD patients and clearly demonstrates that severe clinical symptoms are associated with increased PLP1 gene dosage. Previously, duplications, deletions and mutations of the PLP1 gene were reported to give rise to this X-linked disorder. Patients with PLP1 duplication are usually classified as having either classical or transitional PMD rather than the more rare severe connatal form. The clinical symptoms of the five patients in this study included lack of stable head control and severe mental retardation, with three having severe paroxysmal disorder and two dying before the first year of life. Gene dosage was determined using interphase FISH (fluorescence in situ hybridization) and the novel approach of multiple ligation probe amplification (MLPA). We found FISH unreliable for dosage detection above the level of a duplication and MLPA to be more accurate in determination of specific copy number. Our finding that three or more copies of the gene give rise to a more severe phenotype is in agreement with observations in transgenic mice where severity of disease increased with Plp1 gene dosage and level of overexpression. The patient with five copies of PLP1 was not more affected than those with a triplication, suggesting that there is possibly a limit to the level of severity or that other genetic factors influence the phenotype. It highlights the significance of PLP1 dosage in CNS myelinogenesis as well as the importance of accurate determination of PLP1 gene copy number in the diagnosis of PMD and carrier detection.

  20. Celiac Crisis in a 64-Year-Old Woman: An Unusual Cause of Severe Diarrhea, Acidosis, and Malabsorption

    PubMed Central

    Mrad, Rachel Abou; Ghaddara, Hussein Abou; Green, Peter H.; El-Majzoub, Nadim

    2015-01-01

    Celiac disease (CD) rarely presents with life-threatening complications in older individuals. We report a 64-year-old woman who presented with profuse diarrhea, weight loss, hemodynamic instability, hypokalemia, hypoproteinemia, acidosis, and vitamin and iron deficiency. Pathologic and serologic studies confirmed CD presenting with celiac crisis with extensive and severe intestinal disease. Although celiac crisis occurs mostly in childhood and early adulthood, it should be considered in adults presenting with acute severe diarrheal illness, electrolyte abnormalities, and malabsorption. PMID:26157925

  1. [Endoscopic pleomorphic adenoma of nasal septum resection assisted by low-temperature plasm radiofrequency: a case report].

    PubMed

    Zhang, Dagong; Xiao, Liu; Tian, Huan

    2014-11-01

    We present an extremely rare case of pleomorphic adenoma of the nasal septum in a 24-year old woman who went to consultation because of right nasal neoplasm. The radiologic discoveries by computerized tomography showed a tumor in the right nasal septum. Incisional biopsy was done, with a histopathological report of pleomorphic adenoma. Later, nasal endoscopy was used to remove the neoplasm and histology revealed pleomorphic adenoma of the nasal septum.

  2. Use of Frontal Sinus and Nasal Septum Pattern as an Aid in Personal Identification and Determination of Gender: A Radiographic Study

    PubMed Central

    Nahar, Prashant; Singh, Mohit Pal; Mathur, Hemant; Bhuvaneshwari, S

    2017-01-01

    Introduction Personal identification and gender determination of unknown person has a vital importance in forensic investigation. Human skull radiography is a useful tool in human identification in natural disaster, in any accidents such as fire accident and road traffic accident where body remains become degraded or severely destroyed. Aim Present study was performed to evaluate the measurement of frontal sinus, uniqueness of various pattern of nasal septum when combined with frontal sinus observed on posterio anterior cephalogram for sex determination as well as personal identification. Materials and Methods A total of 80 individuals, 40 males and 40 females, between the age ranges of 18-30 years were selected. The selected individuals had their Posterio Anterior (PA) cephalogram performed after taking their informed consent. Right and left areas and the maximum height and width of the frontal sinus were determined and septum patterns were evaluated and both patterns were also combined and compared. The radiographs were taken on Xtropan 2000 OPG X-ray machine with cephalography attachment and KODAK CR 7400 digital radiography system. Mean and SD values of the greatest height and width of frontal sinus in male and female patients were thus evaluated. The mean values of the frontal sinus were greater in males and the left area was larger than the right area, based on student’s t-test at the 5% level of significance. Results The combination of Frontal Sinus Patterns and Nasal Septum Patterns (FP+NSP) were assessed and found that there were nine classifiable patterns in 26 (32.5%) individuals (12 males and 14 females), each of which had common representations in more than one individual. Besides these patterns, there were unique unclassifiable patterns in 54 (67.5%) individuals. Conclusion The present study supports the use of radiographic evaluation of frontal sinus dimensions, frontal sinus patterns, nasal septum deviations and the combination FP+NSP patterns for

  3. Severe parainfluenza virus type 2 supraglottitis in an immunocompetent adult host: an unusual cause of a paramyxoviridae viral infection.

    PubMed

    Vigil, K J; Mulanovich, V E; Chemaly, R F; Tarrand, J; Raad, I I; Adachi, J A

    2009-03-01

    Parainfluenza virus is a major cause of respiratory illness in humans, manifesting from mild upper respiratory tract infection to bronchiolitis and pneumonia, especially in children. We report - to our knowledge - the first case of a nonimmunocompromised adult patient with human parainfluenza type 2 supraglottitis immediately after returning from China.

  4. Antimicrobial Resistance and Virulence Characterization among Escherichia coli Clinical Isolates Causing Severe Obstetric Infections in Pregnant Women

    PubMed Central

    Guiral, Elisabet; Sáez-López, Emma; Bosch, Jordi; Goncé, Anna; López, Marta; Sanz, Sergi; Vila, Jordi

    2015-01-01

    The virulence markers and the antimicrobial resistance profiles of 78 Escherichia coli isolates causing obstetric infections accompanied by sepsis or not were studied. Adhesion-related virulence factors were the most prevalent markers. Low rates of resistance to the antimicrobial agents used as first-line therapy suggest their correct implementation in stewardship guidelines. PMID:25740771

  5. A case of severe corrosive esophagitis, gastritis, and liver necrosis caused by ingestion of methyl ethyl ketone peroxide

    PubMed Central

    Chang, Jung Oh; Choi, Jeong Woo; Hwang, Yong

    2016-01-01

    The plastic hardener methyl ethyl ketone peroxide is unstable peroxide that releases free oxygen radicals. Ingestion of this compound induces widespread liver necrosis, severe metabolic acidosis, corrosive esophagitis and gastritis, that is often fatal. A 49-year-old man unintentionally ingested approximately 100 mL (55%) of this compound in solution, which was purchased as plastic hardener. Despite resuscitation, he died about 11 hours after admission. We report a patient with poisoning due to methyl ethyl ketone peroxide who presented with corrosive esophagitis and gastritis, gastrointestinal bleeding, and developed ischemia of the bowel and necrosis of the liver and died of severe metabolic acidosis and multiorgan failure. PMID:28168233

  6. Corticosteroids for the management of severe intracranial hypertension in meningoencephalitis caused by Cryptococcus gattii: A case report and review.

    PubMed

    Maciel, R-A; Ferreira, L-S; Wirth, F; Rosa, P-D; Aves, M; Turra, E; Goldani, L-Z

    2017-03-01

    Immune reconstitution inflammatory syndrome in meningitis caused by Cryptococcus gattii in immunocompetent patients after initiation of antifungal therapy appears to be the result of paradoxical antifungal treatment-induced clinical deterioration due to improved local immune responses to cryptococcal organisms. Recent anecdotal reports have suggested a favorable clinical response to corticosteroids in select patients with C. gattii central nervous system (CNS) infections. In this report, we describe a 65-year-old patient with meningoencephalitis caused by C. gattii who developed persistent intracranial hypertension and was successfully managed with antifungal therapy, repeated lumbar puncture and corticosteroids. Our observations suggest a possible benefit of dexamethasone in the management of select cases of C. gattii CNS infection with intracranial hypertension. Further studies are necessary to evaluate the long-term use of steroids in select patients with C. gattii with intracranial hypertension.

  7. Sensory Neuronopathy Revealing Severe Vitamin B12 Deficiency in a Patient with Anorexia Nervosa: An Often-Forgotten Reversible Cause

    PubMed Central

    Franques, Jérôme; Chiche, Laurent; Mathis, Stéphane

    2017-01-01

    Vitamin B12 (B12) deficiency is known to be associated with various neurological manifestations. Although central manifestations such as dementia or subacute combined degeneration are the most classic, neurological manifestations also include sensory neuropathies. However, B12 deficiency is still rarely integrated as a potential cause of sensory neuronopathy. Moreover, as many medical conditions can falsely normalize serum B12 levels even in the context of a real B12 deficiency, some cases may easily remain underdiagnosed. We report the illustrating case of an anorexic patient with sensory neuronopathy and consistently normal serum B12 levels. After all classical causes of sensory neuronopathy were ruled out, her clinical and electrophysiological conditions first worsened after folate administration, but finally improved dramatically after B12 administration. B12 deficiency should be systematically part of the etiologic workup of sensory neuronopathy, especially in a high risk context such as anorexia nervosa. PMID:28294987

  8. Variables Associated with Severity of Bacterial Canker and Wilt Caused by Clavibacter michiganensis subsp. michiganensis in Tomato Greenhouses.

    PubMed

    Blank, L; Cohen, Y; Borenstein, M; Shulhani, R; Lofthouse, M; Sofer, M; Shtienberg, D

    2016-03-01

    Clavibacter michiganensis subsp. michiganensis, the causal agent of bacterial canker and wilt of tomato, is considered to be one of the most important bacterial pathogens worldwide. In the year 2000 there was an increase in the number of infected greenhouses and in the severity of the disease in Israel. As part of the effort to cope with the disease, a comprehensive survey was conducted. Scouts recorded disease severity monthly in 681 production units. At the end of the season the scouts met with the growers and together recorded relevant details about the crop and cultural practices employed. The results suggested an absence of anisotropy pattern in the study region. Global Moran's I analysis showed that disease severity had significant spatial autocorrelation. The strongest spatial autocorrelation occurred within a 1,500 m neighborhood, which is comparable to the distance between production units maintained by one grower (Farm). Next, we tested three groups of variables including or excluding the Farm as a variable. When the Farm was included the explained variation increased in all the studied models. Overall, results of this study demonstrate that the most influential factor on bacterial canker severity was the Farm. This variable probably encompasses variation in experience, differences in agricultural practices between growers, and the quality of implementation of management practices.

  9. Anesthetic Management of a Patient with Sustained Severe Metabolic Alkalosis and Electrolyte Abnormalities Caused by Ingestion of Baking Soda

    PubMed Central

    Lim, Jeffrey

    2014-01-01

    The use of alternative medicine is prevalent worldwide. However, its effect on intraoperative anesthetic care is underreported. We report the anesthetic management of a patient who underwent an extensive head and neck cancer surgery and presented with a severe intraoperative metabolic alkalosis from the long term ingestion of baking soda and other herbal remedies. PMID:25180100

  10. Anesthetic management of a patient with sustained severe metabolic alkalosis and electrolyte abnormalities caused by ingestion of baking soda.

    PubMed

    Soliz, Jose; Lim, Jeffrey; Zheng, Gang

    2014-01-01

    The use of alternative medicine is prevalent worldwide. However, its effect on intraoperative anesthetic care is underreported. We report the anesthetic management of a patient who underwent an extensive head and neck cancer surgery and presented with a severe intraoperative metabolic alkalosis from the long term ingestion of baking soda and other herbal remedies.

  11. Perceived causes of severe mental disturbance and preferred interventions by the Borana semi-nomadic population in southern Ethiopia: a qualitative study

    PubMed Central

    2012-01-01

    Background Culture affects the way people conceptualize causes of severe mental disturbance which may lead to a variation in the preferred intervention methods. There is a seemingly dichotomous belief regarding what causes severe mental disturbance: people living in western countries tend to focus mainly on biological and psychosocial risk factors; whereas, in non-western countries the focus is mainly on supernatural and religious factors. These belief systems about causation potentially dictate the type of intervention preferred. Studying such belief systems in any society is expected to help in planning and implementation of appropriate mental health services. Methods A qualitative study was conducted among the Borana semi-nomadic population in southern Ethiopia to explore perceived causes of severe mental disturbance and preferred interventions. We selected, using purposive sampling, key informants from three villages and conducted a total of six focus group discussions: three for males and three for females. Results The views expressed regarding the causes of mental disturbance were heterogeneous encompassing supernatural causes such as possession by evil spirits, curse, bewitchment, ‘exposure to wind’ and subsequent attack by evil spirit in postnatal women and biopsychosocial causes such as infections (malaria), loss, ‘thinking too much’, and alcohol and khat abuse. The preferred interventions for severe mental disturbance included mainly indigenous approaches, such as consulting Borana wise men or indigenous healers, prayer, holy water treatment and seeking modern mental health care as a last resort. Conclusions These findings will be of value for health care planners who wish to expand modern mental health care to this population, indicating the need to increase awareness about the causes of severe mental disturbance and their interventions and collaborate with influential people and indigenous healers to increase acceptability of modern mental

  12. A 3 Mb deletion in 14q12 causes severe mental retardation, mild facial dysmorphisms and Rett-like features.

    PubMed

    Papa, Filomena Tiziana; Mencarelli, Maria Antonietta; Caselli, Rossella; Katzaki, Eleni; Sampieri, Katia; Meloni, Ilaria; Ariani, Francesca; Longo, Ilaria; Maggio, Angela; Balestri, Paolo; Grosso, Salvatore; Farnetani, Maria Angela; Berardi, Rosario; Mari, Francesca; Renieri, Alessandra

    2008-08-01

    The present report describes a 7-year-old girl with a de novo 3 Mb interstitial deletion of chromosome 14q12, identified by oligo array-CGH. The region is gene poor and contains only five genes two of them, FOXG1B and PRKD1 being deleted also in a previously reported case with a very similar phenotype. Both patients present prominent metopic suture, epicanthic folds, bulbous nasal tip, tented upper lip, everted lower lip and large ears and a clinical course like Rett syndrome, including normal perinatal period, postnatal microcephaly, seizures, and severe mental retardation. FOXG1B (forkhead box G1B) is a very intriguing candidate gene since it is known to promote neuronal progenitor proliferation and to suppress premature neurogenesis and its disruption is reported in a patient with postnatal microcephaly, corpus callosum agenesis, seizures, and severe mental retardation.

  13. Acquired multiple acyl-CoA dehydrogenase deficiency and marked selenium deficiency causing severe rhabdomyolysis in a horse

    PubMed Central

    Gomez, Diego E.; Valberg, Stephanie J.; Magdesian, K. Gary; Hanna, Paul E.; Lofstedt, Jeanne

    2015-01-01

    This report describes a case of severe rhabdomyolysis in a pregnant mare associated with histopathologic and biochemical features of both selenium deficiency and acquired multiple acyl-CoA dehydrogenase deficiency (MADD) due to seasonal pasture myopathy (SPM). This case highlights the importance of assessing plasma selenium levels in horses with clinical signs of pasture myopathy as this deficiency may be a contributing or exacerbating factor. PMID:26538673

  14. Severe Hypertriglyceridemia Causing Pancreatitis in a Child with New-onset Type-I Diabetes Mellitus Presenting with Diabetic Ketoacidosis

    PubMed Central

    Sharma, Pradeep Kumar; Kumar, Maneesh; Yadav, Dinesh Kumar

    2017-01-01

    The triad of pancreatitis, hypertriglyceridemia, and diabetic ketoacidosis and its treatment has not been extensively discussed in the pediatric literature. We report a 4-year-old child with severe hypertriglyceridemia, pancreatitis, and diabetic ketoacidosis. Hypertriglyceridemia and pancreatitis with diabetic ketoacidosis can be successfully managed with insulin and hydration therapy in children. Early recognition of this triad is important as insulin requirements, recovery duration, and prognosis can be altered.

  15. Novel α-spectrin mutation in trans with α-spectrin causing severe neonatal jaundice from hereditary spherocytosis.

    PubMed

    Nussenzveig, Roberto H; Christensen, Robert D; Prchal, Josef T; Yaish, Hassan M; Agarwal, Archana M

    2014-01-01

    We evaluated a neonate with severe jaundice but a negative family history. Spherocytes were present and suspected hereditary spherocytosis was confirmed by osmotic fragility and eosin-5-maleimide erythrocyte staining. We found he was a compound heterozygote for two pathogenic mutations in the gene encoding α-spectrin: a previously reported α(LEPRA) inherited from his asymptomatic mother, and a novel α-spectrin mutation in intron 45 +1 disrupting the consensus splice site, from his asymptomatic father.

  16. Venlafaxine-associated serotonin syndrome causing severe rhabdomyolysis and acute renal failure in a patient with idiopathic Parkinson disease.

    PubMed

    Rajapakse, Senaka; Abeynaike, Lakshan; Wickramarathne, Thanushi

    2010-10-01

    A 43-year-old male patient with idiopathic Parkinson disease, on dopaminergic therapy, was admitted with confusion and agitation, diaphoresis, and hyperkinesia after the commencement of the serotonin-noradrenaline reuptake inhibitor venlafaxine 2 weeks prior for depression. He was found to have severe rhabdomyolysis and developed acute renal failure. The most likely diagnosis was serotonin syndrome induced by venlafaxine, although neuroleptic malignant syndrome was also considered. The differential diagnosis, atypical features in this presentation, and possible mechanisms are discussed.

  17. Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model

    PubMed Central

    Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas

    2016-01-01

    Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa. PMID:27270403

  18. Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model

    NASA Astrophysics Data System (ADS)

    Mishra, Vikas; Skotak, Maciej; Schuetz, Heather; Heller, Abi; Haorah, James; Chandra, Namas

    2016-06-01

    Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa•s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa.

  19. Acquired multiple acyl-CoA dehydrogenase deficiency and marked selenium deficiency causing severe rhabdomyolysis in a horse.

    PubMed

    Gomez, Diego E; Valberg, Stephanie J; Magdesian, K Gary; Hanna, Paul E; Lofstedt, Jeanne

    2015-11-01

    This report describes a case of severe rhabdomyolysis in a pregnant mare associated with histopathologic and biochemical features of both selenium deficiency and acquired multiple acyl-CoA dehydrogenase deficiency (MADD) due to seasonal pasture myopathy (SPM). This case highlights the importance of assessing plasma selenium levels in horses with clinical signs of pasture myopathy as this deficiency may be a contributing or exacerbating factor.

  20. Variants of the chemokine receptor CCR5 are associated with severe bronchiolitis caused by respiratory syncytial virus.

    PubMed

    Hull, Jeremy; Rowlands, Kate; Lockhart, Elizabeth; Moore, Catrin; Sharland, Mike; Kwiatkowski, Dominic

    2003-09-15

    Respiratory syncytial virus (RSV) bronchiolitis is characterized by intense inflammation of the airways, and high levels of proinflammatory cytokines and chemokines can be found in respiratory secretions of affected infants. Important among these chemokines are RANTES (regulated on activation, normal T cell-expressed and -secreted) and macrophage inflammatory-protein alpha, MIP-1alpha, both of which show correlation with severe RSV bronchiolitis. It is not clear whether high levels of these chemokines are important in disease pathogenesis, and this study addresses this question by studying genetic variants of their major receptor, CC chemokine receptor 5. Results from both a case-control and family-based genetic-association analysis show that the -2459G and -2554T variants are associated with severe RSV bronchiolitis (P=.01). It is proposed that these CCR5 variants influence the inflammatory response, and these data provide further evidence of the important role that host genetic variability plays in the determination of disease severity in RSV bronchiolitis.

  1. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice.

    PubMed

    Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi; Nishikawa, Yoshifumi

    2016-01-11

    In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality.

  2. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice

    PubMed Central

    Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi

    2016-01-01

    In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. PMID:26755155

  3. Auditory agnosia due to long-term severe hydrocephalus caused by spina bifida - specific auditory pathway versus nonspecific auditory pathway.

    PubMed

    Zhang, Qing; Kaga, Kimitaka; Hayashi, Akimasa

    2011-07-01

    A 27-year-old female showed auditory agnosia after long-term severe hydrocephalus due to congenital spina bifida. After years of hydrocephalus, she gradually suffered from hearing loss in her right ear at 19 years of age, followed by her left ear. During the time when she retained some ability to hear, she experienced severe difficulty in distinguishing verbal, environmental, and musical instrumental sounds. However, her auditory brainstem response and distortion product otoacoustic emissions were largely intact in the left ear. Her bilateral auditory cortices were preserved, as shown by neuroimaging, whereas her auditory radiations were severely damaged owing to progressive hydrocephalus. Although she had a complete bilateral hearing loss, she felt great pleasure when exposed to music. After years of self-training to read lips, she regained fluent ability to communicate. Clinical manifestations of this patient indicate that auditory agnosia can occur after long-term hydrocephalus due to spina bifida; the secondary auditory pathway may play a role in both auditory perception and hearing rehabilitation.

  4. Nature and severity of physical harm caused by child abuse and neglect: results from the Canadian Incidence Study

    PubMed Central

    Trocmé, Nico; MacMillan, Harriet; Fallon, Barbara; Marco, Richard De

    2003-01-01

    Background Despite growing public concern about child maltreatment, the scope and severity of this significant public health issue remains poorly understood. This article examines the nature and severity of the physical harm associated with reports of child maltreatment documented in the Canadian Incidence Study of Reported Child Abuse and Neglect (CIS). Methods The CIS collected information directly from child welfare investigators about cases of reported child abuse or neglect. A multistage sampling design was used to track child-maltreatment investigations conducted at selected sites from October to December 1998. The analyses were based on the sample of 3780 cases in which child maltreatment was substantiated. Results Some type of physical harm was documented in 18% of substantiated cases; most of these involved bruises, cuts and scrapes. In 4% of substantiated cases, harm was severe enough to require medical attention, and in less than 1% of substantiated cases, medical attention was sought for broken bones or head trauma. Harm was noted most often in cases of physical abuse compared to other forms of maltreatment. Interpretation Rates of physical harm were lower than expected. Current emphasis on mandatory reporting, abuse investigations and risk assessment may need to be tempered for cases in which physical harm is not the central concern. PMID:14581308

  5. Upflow bioreactor having a septum and an auger and drive assembly

    DOEpatents

    Hansen, Carl S.; Hansen, Conly L.

    2007-11-06

    An upflow bioreactor includes a vessel having an inlet and an outlet configured for upflow operation. A septum is positioned within the vessel and defines a lower chamber and an upper chamber. The septum includes an aperture that provides fluid communication between the upper chamber and lower chamber. The bioreactor also includes an auger positioned in the aperture of the septum. The vessel includes an opening in the top for receiving the auger. The auger extends from a drive housing, which is position over the opening and provides a seal around the opening. The drive housing is adjustable relative to the vessel. The position of the auger in the aperture can be adjusted by adjusting the drive housing relative to the vessel. The auger adjustment mechanism allows the auger to be accurately positioned within the aperture. The drive housing can also include a fluid to provide an additional seal around the shaft of the auger.

  6. Glutamate microinjection in the medial septum of rats decreases paradoxical sleep and increases slow wave sleep.

    PubMed

    Mukherjee, Didhiti; Kaushik, Mahesh K; Jaryal, Ashok Kumar; Kumar, Velayudhan Mohan; Mallick, Hruda Nanda

    2012-05-09

    The role of the medial septum in suppressing paradoxical sleep and promoting slow wave sleep was suggested on the basis of neurotoxic lesion studies. However, these conclusions need to be substantiated with further experiments, including chemical stimulation studies. In this report, the medial septum was stimulated in adult male rats by microinjection of L-glutamate. Sleep-wakefulness was electrophysiologically recorded, through chronically implanted electrodes, for 2 h before the injection and 4 h after the injection. There was a decrease in paradoxical sleep during the first hour and an increase in slow wave sleep during the second hour after the injection. The present findings not only supported the lesion studies but also showed that the major role of the medial septum is to suppress paradoxical sleep.

  7. Endoscopic transnasal approach for treatment of the medial orbital blowout fracture using nasal septum graft.

    PubMed

    Ballin, Carlos R; Sava, Luiz C; Maeda, Carlos A S; Nogueira, Gustavo F; Jebahi, Yasser; Sava, Henrique W; Koladicz, Karyn R J

    2009-02-01

    We present the experience of the Ear, Nose, and Throat Department of Santa Casa de Misericórdia de Curitiba and Hospital Universitário Cajuru PUC-PR in the transnasal endoscopic approach to medial orbital blowout fractures using nasal septum grafts. Seventeen patients have undergone endoscopic repair since June 2005, and septum grafts were used to maintain the orbital contents in position. All 17 patients were treated with this method. Two patients had diplopia on immediate postoperative evaluation. This symptom was corrected with orthoptic exercises in one patient, and the other had a little residual diplopia. Postoperative computed tomography scans showed anatomic reduction in 14 of 17 cases. There were no complications in these surgeries. The transnasal endoscopic approach is a reasonable method for the treatment of medial orbital blowout fractures. Use of septum graft is another surgical alternative for this technique.

  8. A case report of severely damaged hip joint caused by SAPHO syndrome treated with 2-stage total hip arthroplasty

    PubMed Central

    Yeo, Ingwon; Cha, Hoon-Suk; Yoon, Young Cheol; Park, Youn-Soo; Lim, Seung-Jae

    2016-01-01

    Abstract Introduction: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an increasingly recognized entity. The hip joint is known as a less frequently affected site in SAPHO syndrome, and there has been limited reports about hip joint diseases caused by SAPHO syndrome, and as such adequate treatment for this disease spectrum is still not fully elucidated. Case: We describe the case of a 52-year-old man admitted for SAPHO syndrome who went on to be diagnosed with advanced secondary hip arthritis associated with disabling right hip pain. The diagnosis of SAPHO syndrome was delayed; the patient was given a clinical diagnosis of osteomyelitis and treated with prolonged courses of antibiotics and open surgical debridement at previous tertiary health facility. The patient underwent 2-stage joint replacement surgery in our hospital. At 1 year after the surgery, he is well, with minimal right hip pain and the prosthesis is functioning well. Conclusion: This case shows the safety and effectiveness of the 2-stage joint replacement in treating destructive hip disease caused by SAPHO syndrome mimicking infectious arthritis. PMID:27399138

  9. Point mutation of Arg440 to his in cytochrome P450c17 causes severe 17{alpha}-hydroxylase deficiency

    SciTech Connect

    Fardella, C.E.; Hum, D.W.; Miller, W.L.; Homoki, J.

    1994-07-01

    Genetic disorders in the gene encoding P450c17 cause 17{alpha}-hydroxylase deficiency. The consequent defects in the synthesis of cortisol and sex steroids cause sexual infantilism and a female phenotype in both genetic sexes as well as mineralorcorticoid excess and hypertension. A 15-yr-old patient from Germany was seen for absent pubertal development and mild hypertension with hypokalemia, high concentrations of 17-deoxysteroids, and hypergonadotropic hypogonadism. Analysis of her P450c17 gene by polymerase chain reaction amplification and direct sequencing showed mutation of codon 440 from CGC (Arg) to CAC (His). Expression of a vector encoding this mutated form of P450c17 in transfected nonsteroidogenic COS-1 cells showed that the mutant P450c17 protein was produced, but it lacked both 17{alpha}-hydroxylase and 17,20-lyase activities. To date, 15 different P450c17 mutations have been described in 23 patients with 17{alpha}-hydroxylase deficiency, indicating that mutations in this gene are due to random events. 36 refs., 3 figs., 2 tabs.

  10. Patient With Severe Hyponatremia Caused by Adrenal Insufficiency Due to Ectopic Posterior Pituitary Lobe and Miscommunication Between Hypothalamus and Pituitary

    PubMed Central

    Grammatiki, Maria; Rapti, Eleni; Mousiolis, Athanasios C.; Yavropoulou, Maria; Karras, Spyridon; Tsona, Afroditi; Daniilidis, Michalis; Yovos, John; Kotsa, Kalliopi

    2016-01-01

    Abstract Hyponatremia may be one of the clinical manifestations of adrenal insufficiency (AI) and during the diagnostic workup of hyponatremic patients investigation of AI should be included. We report the case of an 82-year-old patient who was admitted to our hospital with clinical symptoms and laboratory findings of hyponatremia. Following the diagnostic algorithm of hyponatremia we reached the diagnosis of AI. Clinician's attention must focus on the underlying cause of AI which in this case was hidden in a miscommunication between hypothalamus and pituitary due to an ectopic posterior pituitary lobe and became apparent by a pituitary magnetic resonance imaging (MRI) scan. Treatment with oral hydrocortisone resulted in full clinical recovery and electrolyte balance, which was maintained after 7 months of follow-up. Secondary AI is related with hyponatremia through increased ADH secretion. Although a hyponatremic episode may be the first presentation of AI, clinical suspicion is of high importance in order to place the right diagnosis. Disruption of communication between hypothalamus and pituitary is a rare but considerable cause of AI. PMID:26962783

  11. Forebrain medial septum region facilitates nociception in a rat formalin model of inflammatory pain.

    PubMed

    Lee, Andy Thiam-Huat; Ariffin, Mohammed Zacky; Zhou, Mingyi; Ye, Jenn Zhou; Moochhala, Shabbir M; Khanna, Sanjay

    2011-11-01

    The medial septum is anatomically and functionally linked to the hippocampus, a region implicated in nociception. However, the role of medial septum in nociception remains unclear. To investigate the role of the region in nociception in rats, muscimol, a GABA agonist, or zolpidem, a positive allosteric modulator of GABA(A) receptors, was microinjected into medial septum to attenuate the activity of neurons in the region. Electrophysiological studies in anesthetized rats indicated that muscimol evoked a stronger and longer-lasting suppression of medial septal-mediated activation of hippocampal theta field activity than zolpidem. Similarly, microinjection of muscimol (1 or 2 μg/0.5 μl) into the medial septum of awake rats suppressed both licking and flinching behaviors in the formalin test of inflammatory pain, whereas only the latter behavior was affected by zolpidem (8 or 12 μg/0.5 μl) administered into the medial septum. Interestingly, both drugs selectively attenuated nociceptive behaviors in the second phase of the formalin test that are partly driven by central plasticity. Indeed, muscimol reduced the second phase behaviors by 30% to 60%, which was comparable to the reduction seen with systemic administration of a moderate dose of the analgesic morphine. The reduction was accompanied by a decrease in formalin-induced expression of spinal c-Fos protein that serves as an index of spinal nociceptive processing. The drug effects on nociceptive behaviors were without overt sedation and were distinct from the effects observed after septal lateral microinjections. Taken together, these findings suggest that the activation of medial septum is pro-nociceptive and facilitates aspects of central neural processing underlying nociception.

  12. Role of the medial septum cholinoceptors in anxiogenic-like effects of nicotine.

    PubMed

    Zarrindast, Mohammad-Reza; Tajik, Rohjan; Ebrahimi-Ghiri, Mohaddeseh; Nasehi, Mohammad; Rezayof, Ameneh

    2013-07-02

    The medial septum which is extensively connected to the hippocampus is involved in cholinergic theta oscillation control as well as the anxiety related disorders. In the present study, we aimed to investigate the possible involvement of the medial septum cholinoceptors in the nicotine-induced anxiogenic-like behaviors in rats, using the elevated plus-maze (EPM) test. Intraperitoneal administration of nicotine at 0.6 and 0.8 mg/kg, decreased the open-arms time percentage (%OAT) and open-arms entries percentage (%OAE); indicating an anxiogenic-like response. Intra-medial septum microinjection of mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist at the doses of 1-4 μg/rat, increased %OAT (4 μg/rat), suggesting an anxiolytic-like effect. This however, did not alter the anxiogenic-like response induced by the effective dose of nicotine (0.6 mg/kg). Moreover, co-administration of the subthreshold dose of mecamylamine (2 μg/rat) plus nicotine at the dose of 0.5 or 0.6 mg/kg, increased or decreased the anxiolytic-like behaviors, respectively. On the other hand, sole intra-medial septum infusion of atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, induced an anxiolytic (0.05 μg/rat) and anxiogenic (0.25 μg/rat)-like effects, respectively. The dose of 0.05 μg/rat however, blocked the nicotine response. Furthermore, intra-medial septum microinjection of the highest dose of mecamylamine (4 μg/rat) plus nicotine (0.6 mg/kg) decreased the locomotor activity, while other treatments had no effect on this parameter. Our results suggested that, nicotine-induced anxiogenic-like behaviors may be mediated via the activation of cholinoceptors and possibly other receptor mechanism(s) in the medial septum.

  13. Histaminergic receptors of medial septum and conditioned place preference: D1 dopamine receptor mechanism.

    PubMed

    Zarrindast, Mohammad-Reza; Moghimi, Maryam; Rostami, Parvin; Rezayof, Ameneh

    2006-09-13

    In the present study, the effects of intra-medial septum injections of histamine and/or the histamine H1 or H2 receptor antagonists on the acquisition of conditioned place preference (CPP) in male Wistar rats have been investigated. Our data showed that the conditioning treatments with intra-medial septum injection of different doses of histamine (0.5-15 microg/rat) induced a significant CPP for the drug-associated place. Using a 3-day schedule of conditioning, it was found that the histamine H1 receptor antagonist, pyrilamine (10 and 15 microg/rat, intra-medial septum) also induced a significant place preference. In addition, pyrilamine inhibited the histamine (7.5 microg/rat)-induced place preference. Intra-medial septum administration of the histamine H2 receptor antagonist, ranitidine (5-15 microg/rat) alone or in combination with histamine did not produce a significant place preference or place aversion. On the other hand, intra-medial septum administration of the dopamine D1 receptor antagonist, SCH 233390 (0.5, 0.75 and 1 microg/rat) inhibited the histamine (7.5 microg/rat) or pyrilamine (15 microg/rat)-induced place preference in a dose-dependent manner, but no effect was observed for the dopamine D2 receptor antagonist, sulpiride on the histamine or pyrilamine response. The administration of histamine (2.5-15 microg/rat) or pyrilamine (10 and 15 microg/rat) during acquisition increased locomotor activity of the animals on the testing days. The results suggest that histaminergic receptors of the medial septum may be involved in CPP and thus it is postulated that dopamine D1 receptors may play an important role in this effect.

  14. Incidence of lameness and association of cause and severity of lameness on the outcome for cattle on six commercial beef feedlots.

    PubMed

    Terrell, Shane P; Reinhardt, Christopher D; Larson, Connie K; Vahl, Christopher I; Thomson, Daniel U

    2017-02-15

    OBJECTIVE To describe the incidence of specific causes of lameness and the associations of cause and severity of lameness on the outcome for cattle on commercial feedlots. DESIGN Dynamic population longitudinal study. ANIMALS Cattle on 6 commercial feedlots in Kansas and Nebraska during a 12-month period (mean daily population, 243,602 cattle; range, 223,544 to 252,825 cattle). PROCEDURES Feedlot personnel were trained to use a standardized diagnostic algorithm and locomotion score (LMS) system to identify and classify cattle by cause and severity of lameness. Information regarding lameness cause, severity, and treatments was recorded for individual cattle. Cattle were monitored until they left the feedlot (ie, outcome; shipped with pen mates [shipped], culled prematurely because of lameness [realized], or euthanized or died [died]). Incidence rates for various causes of lameness, LMSs, and outcomes were calculated. The respective associations of cause of lameness and LMS with outcome were evaluated. RESULTS Lameness was identified in 2,532 cattle, resulting in an overall lameness incidence rate of 1.04 cases/100 animal-years. Realized and mortality rates were 0.096 cattle/100 animal-years and 0.397 deaths/100 animal-years, respectively. Injury to the proximal portion of a limb was the most frequently identified cause of lameness followed by undefined lameness, septic joint or deep digital sepsis, and interdigital phlegmon (foot rot). As the LMS (lameness severity) at lameness detection increased, the percentage of cattle that died but not the percentage of cattle that were realized increased. CONCLUSIONS AND CLINICAL RELEVANCE Results provided clinically useful prognostic guidelines for management of lame feedlot cattle.

  15. Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy.

    PubMed

    Heron, Sarah E; Smith, Katherine R; Bahlo, Melanie; Nobili, Lino; Kahana, Esther; Licchetta, Laura; Oliver, Karen L; Mazarib, Aziz; Afawi, Zaid; Korczyn, Amos; Plazzi, Giuseppe; Petrou, Steven; Berkovic, Samuel F; Scheffer, Ingrid E; Dibbens, Leanne M

    2012-11-01

    We performed genomic mapping of a family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and intellectual and psychiatric problems, identifying a disease-associated region on chromosome 9q34.3. Whole-exome sequencing identified a mutation in KCNT1, encoding a sodium-gated potassium channel subunit. KCNT1 mutations were identified in two additional families and a sporadic case with severe ADNFLE and psychiatric features. These findings implicate the sodium-gated potassium channel complex in ADNFLE and, more broadly, in the pathogenesis of focal epilepsies.

  16. The rates of de novo meiotic deletions and duplications causing several genomic disorders in the male germline

    PubMed Central

    Turner, Daniel J.; Miretti, Marcos; Rajan, Diana; Fiegler, Heike; Carter, Nigel P.; Blayney, Martyn L; Beck, Stephan; Hurles, Matthew E.

    2009-01-01

    Meiotic recombination between highly-similar duplicated sequences (non-allelic homologous recombination, NAHR) generates deletions, duplications, inversions, and translocations, and is responsible for genetic diseases known as ‘genomic disorders’, most of which are caused by altered copy number of dosage sensitive genes. NAHR Hotspots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at 4 NAHR hotspots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that: (i) these NAHR hotspots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been under-ascertained clinically, most notably the duplication of 7q11, the reciprocal of the Williams-Beuren Syndrome deletion. PMID:18059269

  17. Yo-yo reflux in an incomplete duplex system causing severe hydronephrosis in a patient with contralateral renal agenesis.

    PubMed

    Rehder, Peter; Petersen, Johannes; Hofmann, Karin J; Schenk, Claudia; Trieb, Thomas; Glodny, Bernhard

    2008-01-01

    This is a report of a case of a 26-year-old patient suffering from progressive renal insufficiency with a neurogenic bladder disorder due to a lipomyelomeningocele. She had renal agenesis on the left side and grade III hydronephrosis of both segments of a right duplex kidney with a bifid ureter joining further distal to the kidney. Both ureters were dilated. The cause was found to be a yo-yo reflux between the two halves of the kidney. Following bladder augmentation and pyelopyelostomy, renal insufficiency improved to stage III and has now been stable for four years. Due to the contralateral renal agenesis, the case is a unique illustration of the functional effect of the yo-yo reflux and pyelopyelostomy.

  18. A mutation in the amino-terminal end of the triple helix of type II collagen causing severe osteochondrodysplasia

    SciTech Connect

    Vikkula, M.; Vuorio, A.F.; Peltonen, L. ); Ritvaniemi, P.; Ala-Kokko, L. ); Kaitila, I. )

    1993-04-01

    Type II collagen is coded by a large gene (COL2A1) consisting of 54 exons on chromosome 12. During the past few years several cartilage disorders have been linked to this gene, and some specific nucleotide changes have been identified in patients. In a spondyloepiphyseal form of chondrodysplasia, the three mutations found so far are all in exon 48 in the region coding for the carboxyl-terminal end of the triple helix. Since folding of the type II collagen polypeptides to the triple helix is initiated from the carboxyl-terminal end, it has been suggested that mutations in this region typically result in severe cartilage diseases. Here the authors report a novel mutation located in the area coding for the amino-terminal part of the triple helix in a sporadic patient with spondyloepiphyseal dysplasia (SED). The mutation, a substitution of G[sup 1063] to A, which results in the conversion of Gly[sup 154] to Arg, was identified using exon-specific amplification of genomic DNA and subsequent analyses with denaturing gradient gel electrophoresis and single-strand conformation polymorphism. The substitution was not found in any other SED patient in Finland. This novel mutation demonstrates that amino acid substitutions in the amino-terminal part of the type II collagen triple helix can also result in SED. 19 refs., 2 figs., 1 tab.

  19. A Broken Drill-bit Fragment Causing Severe Radiating Pain after Cervical Total Disc Replacement: A Case Report.

    PubMed

    Lee, Chong-Suh; Chung, Sung-Soo; Park, Jae-Chul; Shin, Seong-Kee; Park, Yong-Serk; Kang, Kyung-Chung

    2011-06-01

    This is a case report of a 38-year-old man with severe radiating pain on upper extremity after cervical total disc replacement (TDR). We faced an unusual complication that has not been reported yet. He underwent cervical TDR for left central disc protrusion on C5-6. After the surgery, preoperative symptom disappeared. However, at postoperative 1 year, he complained severe right-sided radiating pain that had a sudden onset. On postoperative X-ray, a metal fragment which seemed like a broken drill bit was shown within the spinal canal. To remove that, right-sided anterior microforaminotomy on C5-6 was performed and the metal fragment was removed successfully. After that, anterior fusion was done because the motion of the artificial disc was minimal and the removed structure seemed to attenuate stability during cervical motion. The operation resulted in prompt symptomatic relief. During cervical TDR, particular attention should be paid to the procedures that require using drill-bits.

  20. Does corticosteroid treatment cause prolonged recovery and increased total bilirubin level in severe ADAMTS-13-deficient TTP patient?

    PubMed

    Sayiner, Zeynel Abidin; Acik, Didar Yanardag; Yilmaz, Mehmet; Subari, Salih; Mete, Ayse Ozlem; Dai, M Sinan

    2015-10-01

    A 41-year-old female patient complaining of fatigue, headache, mild confusion, and rush on her lower extremities was admitted to our emergency department. Laboratory tests revealed that he had anemia, thrombocytopenia, and increased levels of indirect bilirubin and lactic dehydrogenase (LDH) in blood tests. Direct and indirect Coombs tests were negative, and fragmented erythrocytes were observed in peripheral blood smears. The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). The best supportive care was provided. Therapeutic plasma exchange (TPE) and 1 mg/kg methylprednisolone treatments were administered. On the 10th day of treatment, LDH level and fragmented red blood cells in peripheral blood smear were decreased, but his direct and indirect bilirubin levels increased despite the fact that he was treated with 1 mg/kg methylprednisolone and TPE. The patient had severe ADAMTS-13 deficiency. After discontinued steroids treatment, his bilirubin level normalized within 4 days. On the 4th day after bilirubin level normalized, vincristine treatment was administered. TPE was also continued. There was no consensus about the optimal schedule for discontinuing plasmapheresis therapy, and also we observed total bilirubin level improvement with discontinued corticosteroid treatment. In this case, corticosteroid treatment was linked with the increase of total bilirubin level in severe ADAMTS-13-deficient TTP patient.

  1. Efferent projections of the septum in the Tegu lizard, Tupinambis nigropunctatus.

    PubMed

    Sligar, C M; Voneida, T J

    1981-09-01

    A H3 proline or H3 leucine mixture was injected into the septal region of the Tegu lizard in order to determine its efferent projections. The brains were processed according to standard autoradiographic technique and counterstained with cresyl violet. Septal projections were limited to either telencephalic or diencephalic areas. Intratelencephalic projections consisted of efferents to medial pallium, nucleus accumbens, bed nucleus of the anterior commissure, preoptic area and septum itself. Fibers entering the diencephalon projected to medial habenular nucleus, dorsomedial thalamic nucleus, dorsolateral thalamic area, periventricular nucleus of the hypothalamus, lateral hypothalamic area and mammillary nucleus. The results are discussed in relation to the efferent projections of the septum in other vertebrates.

  2. [One case of papillary adenocarcinoma located in the back-end of nasal septum].

    PubMed

    Zang, Jian; Liu, Qian; Jiang, Xuejun

    2015-02-01

    Patients with nasopharyngeal foreign body sensation for 3 years, and had nasal obstruction in the past six months. electric nasopharyngoscopy: a irregular ellipse shape mass occupied in the nasopharynx, the mass surface is not smooth, with erosion ulcer and filthy secretions, the mass had a root in the back-end of nasal septum, and was adjacent to the bilateral round pillow. Sinus CT showed an irregular soft tissue shadow connected to the nasal septum backend in the nasopharynx, the size is about 2.8 cm X 3.5 cm, CT value is about 43 HU. Pathological examination: papillary adenocarcinoma.

  3. Increasing severity of damage caused by floods in the Spanish Mediterranean coast (1960-2014), climate change or vulnerability?

    NASA Astrophysics Data System (ADS)

    Perez, Alfredo; Gil, Salvador; Lopez, Francisco; Barriendos, Mariano

    2016-04-01

    In recent decades, there has been an increase in physical and economic losses (WMO, CRED and UCL, 2014) that raises serious concerns in society. Climate change projections may explain the rise in flood losses; however, these shouldn't be considered yet (Bouwer, 2011). According to IPCC (2014), there is low confidence in anthropogenic climate change affecting the frequency and magnitude of fluvial floods on a global scale. In other words, this increase in flood events is not completely related to the higher frequency of heavy rainfall. To illustrate the aforementioned, a spatial example can be seen in the study area. In the Spanish Mediterranean coast, we see an increase in economic losses within the last 50 years due to flood events (Gil et al., 2014). It seems that the socio-economic growth and the rise of housing construction (Gaja, 2008) have led to an increase in vulnerability and exposure which are mainly responsible for those losses and the increase in severity of flood events (Pérez et al., 2015). Furthermore, this situation will probably become more precarious if some climate forecasts are met [IPCC, 2014; AEMET, 2015], and if the economic model fails to adopt efficient adaptive measures. Therefore, it is interesting to focus attention on social factors either within the present or future scenario in order to minimise the potential consequences and improve the adaptation. The main objective of this work focuses on the study of the evolution of the severity of the floods in the Spanish Mediterranean coast for the period (1960-2015). To do that, a statistical analysis of the data base [Gil et al., 2014; extended to the entire Spanish Mediterranean coast (MEDIFLOOD)] and a multiscale mapping (local, provincial and regional level) of the frequency of these events will take place in order to make comparisons and show spatiotemporal patterns according to the severity events evolution. Preliminary results show some interesting statistically significant

  4. A novel biallelic splice site mutation of TECTA causes moderate to severe hearing impairment in an Algerian family.

    PubMed

    Behlouli, Asma; Bonnet, Crystel; Abdi, Samia; Hasbellaoui, Mokhtar; Boudjenah, Farid; Hardelin, Jean-Pierre; Louha, Malek; Makrelouf, Mohamed; Ammar-Khodja, Fatima; Zenati, Akila; Petit, Christine

    2016-08-01

    Congenital deafness is certainly one of the most common monogenic diseases in humans, but it is also one of the most genetically heterogeneous, which makes molecular diagnosis challenging in most cases. Whole-exome sequencing in two out of three Algerian siblings affected by recessively-inherited, moderate to severe sensorineural deafness allowed us to identify a novel splice donor site mutation (c.5272+1G > A) in the gene encoding α-tectorin, a major component of the cochlear tectorial membrane. The mutation was present at the homozygous state in the three affected siblings, and at the heterozygous state in their unaffected, consanguineous parents. To our knowledge, this is the first reported TECTA mutation leading to the DFNB21 form of hearing impairment among Maghrebian individuals suffering from congenital hearing impairment, which further illustrates the diversity of the genes involved in congenital deafness in the Maghreb.

  5. Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death.

    PubMed

    Parker, J A; Connolly, J B; Wellington, C; Hayden, M; Dausset, J; Neri, C

    2001-11-06

    Huntington's disease (HD) is a dominant neurodegenerative disease caused by polyglutamine (polyQ) expansion in the protein huntingtin (htt). HD pathogenesis appears to involve the production of mutated N-terminal htt, cytoplasmic and nuclear aggregation of htt, and abnormal activity of htt interactor proteins essential to neuronal survival. Before cell death, neuronal dysfunction may be an important step of HD pathogenesis. To explore polyQ-mediated neuronal toxicity, we expressed the first 57 amino acids of human htt containing normal [19 Gln residues (Glns)] and expanded (88 or 128 Glns) polyQ fused to fluorescent marker proteins in the six touch receptor neurons of Caenorhabditis elegans. Expanded polyQ produced touch insensitivity in young adults. Noticeably, only 28 +/- 6% of animals with 128 Glns were touch sensitive in the tail, as mediated by the PLM neurons. Similar perinuclear deposits and faint nuclear accumulation of fusion proteins with 19, 88, and 128 Glns were observed. In contrast, significant deposits and morphological abnormalities in PLM cell axons were observed with expanded polyQ (128 Glns) and partially correlated with touch insensitivity. PLM cell death was not detected in young or old adults. These animals indicate that significant neuronal dysfunction without cell death may be induced by expanded polyQ and may correlate with axonal insults, and not cell body aggregates. These animals also provide a suitable model to perform in vivo suppression of polyQ-mediated neuronal dysfunction.

  6. Short communication: novel truncating mutations in the CFTR gene causing a severe form of cystic fibrosis in Italian patients.

    PubMed

    Lenarduzzi, S; Morgutti, M; Crovella, S; Coiana, A; Rosatelli, M C

    2014-11-14

    Cystic fibrosis (CF) is a common recessive genetic disease caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. More than 1800 different mutations have been described to date. Here, we report 3 novel mutations in CFTR in 3 Italian CF patients. To detect and identify 36 frequent mutations in Caucasians, we used the INNO-LiPA CFTR19 and INNO-LiPA CFTR17+Tn Update kits (Innogenetics; Ghent, Belgium). Our first analysis did not reveal both of the responsible mutations; thus, direct sequencing of the CFTR gene coding region was performed. The 3 patients were compound heterozygous. In one allele, the F508del (c.1521_1523delCTT, p.PHE508del) mutation in exon 11 was observed in each case. For the second allele, in patient No.1, direct sequencing revealed an 11-base pair deletion (GAGGCGATACT) in exon 14 (c.2236_2246del; pGlu746Alafs*29). In patient No. 2, direct sequencing revealed a nonsense mutation at nucleotide 3892 (c.3892G>T) in exon 24. In patient No. 3, direct sequencing revealed a deletion of cytosine in exon 27 (c.4296delC; p.Asn1432Lysfs*16). These 3 novel mutations indicate the production of a truncated protein, which consequently results in a non-functional polypeptide.

  7. [Disturbances of nasal aerodynamics in patients with the curved nasal septum and the rationale for its surgical correction].

    PubMed

    Tulebaev, R K; Mustafin, A A; Zholdybaeva, Z T

    2011-01-01

    Serious disturbances of nasal aerodynamics contribute to the development of diseases of the broncho-pulmonary apparatus. The early recognition of ventilation problems in patients with the curved nasal septum is paramount for the efficacious prevention and treatment of respiratory complications. The authors describe principles of rhinosurgical correction of affected nasal aerodynamics in patients with the curved nasal septum.

  8. [The infundibular septum in congenital heart defects. Morphologico-angiocardiographic study of the double-outlet heart ventricle].

    PubMed

    Tůma, S; Povýsilová, V; Skovránek, J; Tax, P

    1990-10-19

    The authors investigated the infundibular septum in 40 archival heart preparations with a double outlet right ventricle. They compared the post-mortem findings with the previous angiocardiographic examination and the skiagram of the preparation made post mortem. They present also the corresponding findings obtained by echocardiography. The infundibular septum was in all instances the dominating intracardiac structure influencing the direction of the blood flow from the ventricles into outflow tracts in the direction towards the large arteries. In 15 instances the infundibular septum was shifted in an anterosuperior direction beneath the orifice of the pulmonary artery and it derived the blood current from the left ventricle through the defect in the ventricular septum into the aorta. The restricted blood flow through the aorta led to its hypoplasia, which in 11 instances was associated with coarctation or interruption of the aorta. In seven instances of posteroinferior shift the infundibular septum was straight. These cases were associated with coarctation or interruption of the aorta. In ventricular septum and with stenosis of the pulmonary artery. Based on these findings the authors assume that the shift of the infundibular septum in a double outlet right ventricle has a decisive position as regards haemodynamic manifestations of the defect and in the development of outflow tracts and large arteries. Last not least, information on the infundibular septum is also important for surgery of the defect.

  9. A severe symptom phenotype in tomato in Mali is caused by a reassortant between a novel recombinant begomovirus (Tomato yellow leaf curl Mali virus) and a betasatellite.

    PubMed

    Chen, Li-Fang; Rojas, Maria; Kon, Tatsuya; Gamby, Kadiatou; Xoconostle-Cazares, Beatriz; Gilbertson, Robert L

    2009-05-01

    Tomato production in West Africa has been severely affected by begomovirus diseases, including yellow leaf curl and a severe symptom phenotype, characterized by extremely stunted and distorted growth and small deformed leaves. Here, a novel recombinant begomovirus from Mali, Tomato yellow leaf curl Mali virus (TYLCMLV), is described that, alone, causes tomato yellow leaf curl disease or, in combination with a betasatellite, causes the severe symptom phenotype. TYLCMLV is an Old World monopartite begomovirus with a hybrid genome composed of sequences from Tomato yellow leaf curl virus-Mild (TYLCV-Mld) and Hollyhock leaf crumple virus (HoLCrV). A TYLCMLV infectious clone induced leaf curl and yellowing in tomato, leaf curl, crumpling and yellowing in Nicotiana benthamiana and common bean, mild symptoms in N. glutinosa, and a symptomless infection in Datura stramonium. In a field-collected sample from a tomato plant showing the severe symptom phenotype in Mali, TYLCMLV was detected together with a betasatellite, identified as Cotton leaf curl Gezira betasatellite (CLCuGB). Tomato plants co-agroinoculated with TYLCMLV and CLCuGB developed severely stunted and distorted growth and small crumpled leaves. These symptoms were more severe than those induced by TYLCMLV alone, and were similar to the severe symptom phenotype observed in the field in Mali and in other West African countries. TYLCMLV and CLCuGB also induced more severe symptoms than TYLCMLV in the other solanaceous hosts, but not in common bean. The increased symptom severity was associated with hyperplasia of phloem-associated cells, but relatively little increase in TYLCMLV DNA levels. In surveys of tomato virus diseases in West Africa, TYLCMLV was commonly detected in plants with leaf curl and yellow leaf curl symptoms, whereas CLCuGB was infrequently detected and always in association with the severe symptom phenotype. Together, these results indicate that TYLCMLV causes tomato yellow leaf curl disease

  10. Oak forest exploitation and black-locust invasion caused severe shifts in epiphytic lichen communities in Northern Italy.

    PubMed

    Nascimbene, Juri; Marini, Lorenzo

    2010-10-15

    In the last two centuries, native European oak forests have undergone a dramatic decline related to increasing human pressure for agriculture and urbanization. Oak forests were either completely eradicated and transformed into agricultural landscapes or replaced by second-growth formations. Intensive forest management and the replacement of native forests with production forests or arable lands are recognized amongst the main threats to many lichens in Europe. In this study, we used historical information on the epiphytic lichen biota which was hosted in a native oak-dominated forest of Northern Italy to identify shifts of lichen communities due to the changes in land use which occurred during the last two centuries. We also compared the epiphytic lichen communities inhabiting remnant oak forests with those found in the habitats that have replaced native forests: black-locust forests and agrarian landscapes. Almost all the species sampled during the 19th century are now extinct. The loss of native habitat and the subsequent invasion by black locust were probably the most influential factors which affected the composition of lichen communities, causing the local extinction of most of the species historically recorded. Despite the fact that oak remnants host only a few species which were historically recorded, and that they currently are the lichen poorest habitat in the study region, they host lichen assemblages differing from those of black-locust forests and agrarian stands. In these habitats lichen assemblages are mainly composed of species adapted to well-lit, dry conditions and tolerating air pollution and eutrophication. This pattern is likely to be common also in other lowland and hilly regions throughout Northern Italy where oak forests are targeted among the habitats of conservation concern at the European level. For this reason, a national strategy for biodiversity conservation and monitoring of lowlands forests should provide the framework for local

  11. Bacteremic Urinary Tract Infection Caused by Multidrug-Resistant Enterobacteriaceae Are Associated With Severe Sepsis at Admission: Implication for Empirical Therapy.

    PubMed

    Lee, Yi-Chien; Hsiao, Chih-Yen; Hung, Miao-Chiu; Hung, Sheng-Che; Wang, Hung-Ping; Huang, Yun-Jhong; Wang, Jann-Tay

    2016-05-01

    The purpose of this study is to compare the clinical features and treatment outcomes among patients with bacteremic urinary tract infection (UTI) caused by multidrug-resistant (MDR) and non-MDR Enterobacteriaceae and to identify whether MDR pathogens were independently associated with severe sepsis or septic shock at presentation.The clinical data of adult patients visiting and being treated at Chia-Yi Christian Hospital due to bacteremic UTI caused by Enterobacteriaceae from January 2006 to August 2015 were retrospectively analyzed.A total of 585 patients were enrolled. Among them, 220 (37.6%) were caused by the MDR Enterobacteriaceae. A total of 206 patients (35.2%) developed severe sepsis or septic shock at presentation. Patients in the MDR group tend to be male and have a past history of gout, recurrent UTI, prior hospitalization, hydronephrosis, renal stone, ureteral stone, indwelling urinary catheter, newly development of renal dysfunction, severe sepsis or septic shock, intensive care unit (ICU) admission, receipt of ineffective empirical therapy, longer hospital stay, and higher in-hospital mortality (2.7% vs 1.9%, P = 0.569). Using multivariate logistic regression analysis, it is revealed that independent predictors associated with severe sepsis or septic shock at presentation were liver cirrhosis (OR 2.868; 95% CI 1.439-5.716; P = 0.003), indwelling urinary catheter (OR 1.936; 95% CI 1.238-3.027; P = 0.004), and MDR Enterobacteriaceae (OR 1.447; 95% CI 1.002-2.090; P = 0.049).Multidrug resistance was associated with the development of severe sepsis or septic shock upon presentation among patients with bacteremic UTI caused by Enterobacteriaceae. Therefore, empirical antibiotics therapy for patients with UTI presented with severe sepsis and/or septic shock should be more broad-spectrum to effectively cover MDR Enterobacteriaceae.

  12. Ethyl pyruvate therapy attenuates experimental severe arthritis caused by type II collagen (CII) in the mouse (CIA).

    PubMed

    Di Paola, R; Mazzon, E; Galuppo, M; Esposito, E; Bramanti, P; Fink, M P; Cuzzocrea, S

    2010-01-01

    This study tested the hypothesis that ethyl pyruvate (EP), a simple aliphatic ester with anti-inflammatory effects, can reduce type II collagen-induced mouse arthritis (CIA). DBA/1J mice were used for the study, developing erosive hind paw arthritis when immunized with CII in an emulsion in complete Freund?s adjuvant (CFA). The incidence of CIA was 100 percent by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. EP-treatment (40 mg/kg/day i.p.) starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26-35 and improved histological status in the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly (ADP-ribose) (PAR), inducible nitric oxide synthase (iNOS) revealed a positive staining in inflamed joints from mice subjected to CIA, while no staining was observed for HO-1 and Nrf-2 in the same group. The degree of staining for nitrotyrosine, PAR, iNOS, was significantly reduced in CII-challenged mice treated with the EP. Immuno-positive-staining for HO-1 and Nrf-2 was observed instead, in joints obtained from the EP-treated group. Plasma levels of TNF-α, IL-6 and the joint tissue levels of macrophage inflammatory protein (MIP)-1α and MIP-2 were also significantly reduced by EP treatment. Thirty-five days after immunization, EP-treatment significantly increased plasma levels of IL-10. These data demonstrate that EP treatment exerts an anti-inflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.

  13. Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia.

    PubMed Central

    Vulliamy, T J; D'Urso, M; Battistuzzi, G; Estrada, M; Foulkes, N S; Martini, G; Calabro, V; Poggi, V; Giordano, R; Town, M

    1988-01-01

    Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is a common genetic abnormality affecting an estimated 400 million people worldwide. Clinical and biochemical analyses have identified many variants exhibiting a range of phenotypes, which have been well characterized from the hematological point of view. However, until now, their precise molecular basis has remained unknown. We have cloned and sequenced seven mutant G6PD alleles. In the nondeficient polymorphic African variant G6PD A we have found a single point mutation. The other six mutants investigated were all associated with enzyme deficiency. In one of the commonest, G6PD Mediterranean, which is associated with favism among other clinical manifestations, a single amino acid replacement was found (serine----phenylalanine): it must be responsible for the decreased stability and the reduced catalytic efficiency of this enzyme. Single point mutations were also found in G6PD Metaponto (Southern Italy) and in G6PD Ilesha (Nigeria), which are asymptomatic, and in G6PD Chatham, which was observed in an Indian boy with neonatal jaundice. In G6PD "Matera," which is now known to be the same as G6PD A-, two separate point mutations were found, one of which is the same as in G6PD A. In G6PD Santiago, a de novo mutation (glycine----arginine) is associated with severe chronic hemolytic anemia. The mutations observed show a striking predominance of C----T transitions, with CG doublets involved in four of seven cases. Thus, diverse point mutations may account largely for the phenotypic heterogeneity of G6PD deficiency. Images PMID:3393536

  14. Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain

    PubMed Central

    2009-01-01

    Introduction Patients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain. Methods We used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay. Results Illness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 ± 3.3). Conclusions Over a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons. PMID:19747383

  15. Paradoxical relationship between RAVE (relative activity versus endocytosis) values of several opioid receptor agonists and their liability to cause dependence

    PubMed Central

    Wang, Yu-hua; Sun, Jian-feng; Tao, Yi-min; Xu, Xue-jun; Chi, Zhi-qiang; Liu, Jing-gen

    2010-01-01

    Aim: To examine the relationship between the RAVE (relative activity versus endocytosis) values of opiate agonists and their dependence liability by studying several potent analgesics with special profiles in the development of physical and psychological dependence. Methods: The effects of (−)-cis-(3R,4S,2′R) ohmefentanyl (F9202), (+)-cis-(3R,4S,2′S) ohmefentanyl (F9204), dihydroetorphine (DHE) and morphine on [35S]GTPγS binding, forskolin-stimulated cAMP accumulation, and receptor internalization were studied in CHO cells stably expressing HA-tagged μ-opioid receptors (CHO-HA-MOR). cAMP overshoot in response to the withdrawal of these compound treatments was also tested. Results: All four agonists exhibited the same rank order of activity in stimulation of [35S]GTPγS binding, inhibition of adenylyl cyclase (AC) and induction of receptor internalization: DHE>F9204>F9202>morphine. Based on these findings and the previous in vivo analgesic data obtained from our and other laboratories, the RAVE values of the four agonists were calculated. The rank order of RAVE values was morphine>F9202>F9204>DHE. For the induction of cAMP overshoot, the rank order was F9202≥morphine>F9204≥DHE. Conclusion: Taken in combination with previous findings of these compounds' liability to develop dependence, the present study suggests that the agonist with the highest RAVE value seems to have a relatively greater liability to develop psychological dependence relative to the agonist with the lowest RAVE value. However, the RAVE values of these agonists are not correlated with their probability of developing physical dependence or inducing cAMP overshoot, a cellular hallmark of dependence. PMID:20228826

  16. Morphology of tricuspid valve in pulmonary atresia with intact ventricular septum.

    PubMed

    Choi, Y H; Seo, J W; Choi, J Y; Yun, Y S; Kim, S H; Lee, H J

    1998-01-01

    Pulmonary atresia with intact ventricular septum (PAIVS) is a rare congenital cardiac anomaly that has been classified into two types: one is a more frequent type having dysplasia of tricuspid valve (TV) with a small annulus, underdeveloped right ventricle (RV) with a hypoplastic cavity and a hypertrophic wall; the other type has severe dysplasia of TV and dilatation of RV, right atrium (RA), and right atrioventricular junction with thinning of the RV wall. We performed a morphologic study on 11 autopsied hearts with PAIVS, giving particular emphasis to the variation of morphology of the TV. We could classify these hearts into 3 groups according to the degree of right ventricular development. In the first group of 7 cases (type I), the RVs were underdeveloped. Thick leaflets, restricted valve apparatus with short chordae, and small annuli were characteristics of the TV. In the second group of 3 cases (type II), the RVs showed marked enlargement of the cavity and thinning of the wall. The TV showed redundant, dysplastic, sail-like anterior leaflets, and the downward displacement of septal leaflet and/or posterior leaflet, which are the findings frequently observed in Ebstein's malformation. The RVs were dilated and with partially unguarded tricuspid orifice. The septal leaflet of the TV was dysplastic and, in two cases, the septal leaflet showed chordal structure at the upper surface facing the RA, which is a peculiar finding that has not been described in the literature. The remaining case was a heart with a moderately developed RV (type III). The TV showed mildly dysplastic appearance and we classify this as a separate type, because we could expect the best surgical results in this type. This type had optimal size of RV and the mildest degree of dysplasia of TV. In PAIVS, the morphology of TV correlates well with the type of the right ventricular development.

  17. Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number.

    PubMed

    Thompson, Kyle; Majd, Homa; Dallabona, Christina; Reinson, Karit; King, Martin S; Alston, Charlotte L; He, Langping; Lodi, Tiziana; Jones, Simon A; Fattal-Valevski, Aviva; Fraenkel, Nitay D; Saada, Ann; Haham, Alon; Isohanni, Pirjo; Vara, Roshni; Barbosa, Inês A; Simpson, Michael A; Deshpande, Charu; Puusepp, Sanna; Bonnen, Penelope E; Rodenburg, Richard J; Suomalainen, Anu; Õunap, Katrin; Elpeleg, Orly; Ferrero, Ileana; McFarland, Robert; Kunji, Edmund R S; Taylor, Robert W

    2016-10-06

    Mutations in SLC25A4 encoding the mitochondrial ADP/ATP carrier AAC1 are well-recognized causes of mitochondrial disease. Several heterozygous SLC25A4 mutations cause adult-onset autosomal-dominant progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions, whereas recessive SLC25A4 mutations cause childhood-onset mitochondrial myopathy and cardiomyopathy. Here, we describe the identification by whole-exome sequencing of seven probands harboring dominant, de novo SLC25A4 mutations. All affected individuals presented at birth, were ventilator dependent and, where tested, revealed severe combined mitochondrial respiratory chain deficiencies associated with a marked loss of mitochondrial DNA copy number in skeletal muscle. Strikingly, an identical c.239G>A (p.Arg80His) mutation was present in four of the seven subjects, and the other three case subjects harbored the same c.703C>G (p.Arg235Gly) mutation. Analysis of skeletal muscle revealed a marked decrease of AAC1 protein levels and loss of respiratory chain complexes containing mitochondrial DNA-encoded subunits. We show that both recombinant AAC1 mutant proteins are severely impaired in ADP/ATP transport, affecting most likely the substrate binding and mechanics of the carrier, respectively. This highly reduced capacity for transport probably affects mitochondrial DNA maintenance and in turn respiration, causing a severe energy crisis. The confirmation of the pathogenicity of these de novo SLC25A4 mutations highlights a third distinct clinical phenotype associated with mutation of this gene and demonstrates that early-onset mitochondrial disease can be caused by recurrent de novo mutations, which has significant implications for the application and analysis of whole-exome sequencing data in mitochondrial disease.

  18. Human respiratory syncytial virus Memphis 37 grown in HEp-2 cells causes more severe disease in lambs than virus grown in Vero cells.

    PubMed

    Derscheid, Rachel J; van Geelen, Albert; McGill, Jodi L; Gallup, Jack M; Cihlar, Tomas; Sacco, Randy E; Ackermann, Mark R

    2013-11-22

    Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and young children. A small percentage of these individuals develop severe and even fatal disease. To better understand the pathogenesis of severe disease and develop therapies unique to the less-developed infant immune system, a model of infant disease is needed. The neonatal lamb pulmonary development and physiology is similar to that of infants, and sheep are susceptible to ovine, bovine, or human strains of RSV. RSV grown in Vero (African green monkey) cells has a truncated attachment G glycoprotein as compared to that grown in HEp-2 cells. We hypothesized that the virus grown in HEp-2 cells would cause more severe clinical symptoms and cause more severe pathology. To confirm the hypothesis, lambs were inoculated simultaneously by two different delivery methods (intranasal and nebulized inoculation) with either Vero-grown or HEp-2-grown RSV Memphis 37 (M37) strain of virus to compare viral infection and disease symptoms. Lambs infected with HEp-2 cell-derived virus by either intranasal or nebulization inoculation had significantly higher levels of viral RNA in lungs as well as greater clinical disease including both gross and histopathologic lesions compared to lambs similarly inoculated with Vero-grown virus. Thus, our results provide convincing in vivo evidence for differences in viral infectivity that corroborate previous in vitro mechanistic studies demonstrating differences in the G glycoprotein expression by RSV grown in Vero cells.

  19. Ultrasonographic Evaluation of the Prevalence of an Intracompartmental Septum in Patients With de Quervain's Disease.

    PubMed

    Sato, Junko; Ishii, Yoshinori; Noguchi, Hideo

    2016-01-01

    It has been reported that more patients with de Quervain's disease who had undergone surgical treatment had a septated dorsal compartment than did normal cadavers. The purpose of this study was to sonographically evaluate the prevalence of an intracompartmental septum in patients with de Quervain's disease and to compare the prevalence between groups categorized by sex, age, and peripartum status. The authors performed an ultrasonographic examination of 112 wrists from 103 patients with de Quervain's disease. The prevalence of a septum-like structure in the first compartment was compared between men and women, between older (≥40 years) and younger (≤39 years) patients, and between pregnant or lactating women and other patients. The prevalence of intracompartmental septum in patients with de Quervain's disease was 61.6% (69 of 112). Of the 69 wrists with an intracompartmental septum-like structure, 53 showed this structure completely through the level of the radial styloid, and 16 showed it partially on the level of the distal radial styloid. There was no significant difference between any 2 groups categorized by the patients' demographics. The prevalence of intracompartmental septation in the patients with de Quervain's disease was higher than the previously reported prevalence in cadavers and lower than that of patients who underwent surgery. This result was consistent with a previous report that patients with a septated dorsal compartment may be more at risk of contracting de Quervain's disease and more prone to failure of nonoperative treatment.

  20. Transcatheter pulmonary valve perforation and balloon dilatation in neonates with pulmonary atresia and intact ventricular septum

    PubMed Central

    Gerestein, C.G.; Berger, R.M.F.; Dalinghaus, M.; Bogers, A.J.J.C.; Witsenburg, M.

    2003-01-01

    Background Pulmonary atresia and intact ventricular septum is characterised by a great morphological variety. Treatment is not uniform. Objective To evaluate our experience with transcatheter valvotomy and balloon dilatation in neonates with pulmonary atresia and intact ventricular septum. Design Retrospective. Methods Between January 1997 and September 2000 five neonates with pulmonary atresia and intact ventricular septum underwent transcatheter valvotomy and balloon dilatation. Results The catheter intervention was performed at a mean age of 27 days (range 3-95 days). The atretic pulmonary valve was successfully perforated in all neonates. Subsequent balloon dilatation was successful in four neonates. Balloon dilatation was unsuccessful in one patient, who underwent an elective surgical valvotomy of the pulmonary valve after five days. Three patients needed a modified Blalock-Taussig shunt after a mean of 23 days. Four patients required repeated balloon dilatation after a mean of 227 days. Mean follow-up was 2.7 years (range 1-5 years). Conclusions Transcatheter perforation of the pulmonary valve membrane and balloon dilatation is a good, safe initial therapy in selected neonates with pulmonary atresia and intact ventricular septum. This procedure can prevent open-heart surgery in these patients in the first months of life. ImagesFigure 1Figure 2 PMID:25696158

  1. Compact fluorescent lamp using horizontal and vertical insulating septums and convective venting geometry

    DOEpatents

    Siminovitch, M.

    1998-02-10

    A novel design is described for a compact fluorescent lamp, including a lamp geometry which will increase light output and efficacy of the lamp in a base down operating position by providing horizontal and vertical insulating septums positioned in the ballast compartment of the lamp to provide a cooler coldspot. Selective convective venting provides additional cooling of the ballast compartment. 9 figs.

  2. Compact fluorescent lamp using horizontal and vertical insulating septums and convective venting geometry

    DOEpatents

    Siminovitch, Michael

    1998-01-01

    A novel design for a compact fluorescent lamp, including a lamp geometry which will increase light output and efficacy of the lamp in a base down operating position by providing horizontal and vertical insulating septums positioned in the ballast compartment of the lamp to provide a cooler coldspot. Selective convective venting provides additional cooling of the ballast compartment.

  3. Accessory Mitral Valve Leaflet Causing Severe Left Ventricular Outflow Tract Obstruction in a Preterm Neonate with a Partial Atrioventricular Septal Defect

    PubMed Central

    Fraser, Charles D.; Seery, Thomas J.

    2016-01-01

    Atrioventricular septal defects represent a class of congenital cardiac malformations that vary in presentation and management strategy depending upon the severity of the particular lesions present. We present the case of a premature neonate who had a partial atrioventricular septal defect and an accessory mitral (or left atrioventricular) valve leaflet. The latter caused severe left ventricular outflow tract obstruction and severely depressed left ventricular function. We found only one other report of this atrioventricular valve abnormality in association with atrioventricular septal defect. To our knowledge, our patient (at a body weight of 1,800 g) is the smallest to survive corrective surgery of an accessory mitral valve leaflet with severe left ventricular outflow tract obstruction. In addition to our patient's case, we discuss the relevant medical literature. PMID:28100980

  4. Compound Mutations Cause Increased Cardiac Events in Children with Long QT Syndrome: Can the Sequence Homology-Based Tools be Applied for Prediction of Phenotypic Severity?

    PubMed

    Izumi, Gaku; Hayama, Emiko; Yamazawa, Hirokuni; Inai, Kei; Shimada, Mitsuyo; Furutani, Michiko; Nishizawa, Tsutomu; Furutani, Yoshiyuki; Matsuoka, Rumiko; Nakanishi, Toshio

    2016-06-01

    Long QT syndrome (LQTS) can cause syncope, ventricular fibrillation, and death. Recently, several disease-causing mutations in ion channel genes have been identified, and compound mutations have also been detected. It is unclear whether children who are carriers of compound mutations exhibit a more severe phenotype than those with single mutations. Although predicting phenotypic severity is clinically important, the availability of prediction tools for LQTS is unknown. To determine whether the severity of the LQTS phenotype can be predicted by the presence of compound mutations in children is needed. We detected 97 single mutations (Group S) and 13 compound mutations (Group C) between 1998 and 2012, age at diagnosis ranging 0-19 years old (median age is 9.0) and 18.0 years of follow-up period. The phenotypes and Kaplan-Meier event-free rates of the two groups were compared for cardiac events. This study investigated phenotypic severity in relation to the location of mutations in the protein sequence, which was analyzed using two sequence homology-based tools. In results, compound mutations in children were associated with a high incidence of syncope within the first decade (Group S: 32 % vs. Group C: 61 %), requiring an ICD in the second decade (Group S: 3 % vs. Group C: 56 %). Mortality in these patients was high within 5 years of birth (23 %). Phenotypic prediction tools correctly predicted the phenotypic severity in both Groups S and C, especially by using their coupling method. The coupling prediction method is useful in the initial evaluation of phenotypes both with single and compound mutations of LQTS patients. However, it should be noted that the compound mutation makes more severe phenotype.

  5. A novel mutation (4040-4045 nt. delA) in exon 14 of the factor VIII gene causing severe hemophilia A.

    PubMed

    Onsori, Habib; Feizi, Mohammad Ali Hosseinpour; Feizi, Abbas Ali Hosseinpour

    2011-09-01

    Hemophilia A is an X-linked congenital bleeding disorder caused by Factor VIII deficiency. Different mutations including point mutations, deletions, insertions and inversions have been reported in the FVIII gene, which cause hemophilia A. In the current study, with the use of conformational sensitive gel electrophoresis (CSGE) analysis, we report a novel 1-nt deletion in the A6 sequence at codons 1328-1330 (4040-4045 nt delA) occurring in exon 14 of the FVIII gene in a seven-year-old Iranian boy with severe hemophilia A. This mutation that causes frameshift and premature stop-codon at 1331 has not previously been reported in the F8 Hemophilia A Mutation, Structure, Test and Resource Site (HAMSTeRS) database.

  6. Fatal Community-acquired Pneumonia in Children Caused by Re-emergent Human Adenovirus 7d Associated with Higher Severity of Illness and Fatality Rate

    PubMed Central

    Yu, Zhiwu; Zeng, Zhiwei; Zhang, Jing; Pan, Yuxian; Chen, Manjun; Guo, Yonghui; Yu, Nan; Chodosh, James; Fu, Ning; Che, Xiaoyan; Zhang, Qiwei

    2016-01-01

    Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), such as community-acquired pneumonia. HAdV-7d, a re-emergent genomic variant, has been recently reported in Asia and the United States after a several-decade absence. However, whether HAdV-7d is associated with higher severity than other types is currently unclear. In this study, the clinical and epidemiological investigation showed that fever, cough, and sore throat were the three most common respiratory symptoms of HAdV infections. HAdV-7 caused longer duration of fever, higher morbidity of tachypnea/dyspnea, pleural effusion, diarrhea, hepatosplenomegaly, consciousness alteration, as well as higher rates of pneumonia, mechanical ventilation and higher fatality rate (28.6%) than other types, particularly HAdV-3 and HAdV-2. The genomes of seven HAdV-7d isolates from mild, severe, and fatal cases were sequenced and highly similar with each other. Surprisingly, two isolates (2011, 2012) had 100% identical genomes with an earlier strain from a fatal ARD outbreak in China (2009), which elucidates the virus origin and confirms the unexpected HAdV genomic conservation and stability. Phylogenetic analysis indicated that L1 52/55-kDa DNA packaging protein may be associated with the higher severity of illness and fatality rate of HAdV-7. Clinicians need to be aware of HAdVs in children with ARD. PMID:27848998

  7. Enterovirus 71 Infection Causes Severe Pulmonary Lesions in Gerbils, Meriones unguiculatus, Which Can Be Prevented by Passive Immunization with Specific Antisera

    PubMed Central

    Xia, Yong; Qian, Lei; Yang, Zhang-Nv; Xie, Rong-Hui; Sun, Yi-Sheng; Lu, Hang-Jing; Miao, Zi-Ping; Li, Chan; Li, Xiao; Liang, Wei-Feng; Huang, Xiao-Xiao; Xia, Shi-Chang; Chen, Zhi-Ping; Jiang, Jian-Min; Zhang, Yan-Jun; Mei, Ling-Ling; Liu, She-Lan; Gu, Hua; Xu, Zhi-Yao; Fu, Xiao-Fei; Zhu, Zhi-Yong; Zhu, Han-Ping

    2015-01-01

    Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by Enterovirus 71 (EV71). However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models. Development of a suitable animal model is important for studying EV71 pathogenesis and assessing effect of therapeutic approaches. We had found neurological disorders in EV71-induced young gerbils previously. Here, we report severe pulmonary lesions characterized with pulmonary congestion and hemorrhage in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day-old or younger gerbils presented with a sudden onset of symptoms and rapid illness progression after inoculation with 1×105.5 TCID50 of EV71 via intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination. EV71 viral titer was found to be peak at late stages of infection. EV71-induced pulmonary lesions, together with severe neurological disorders were also observed in gerbils, accurately mimicking the disease process in EV71-infected patients. Passive transfer with immune sera from EV71 infected adult gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion formation after lethal EV71 challenge. These results establish this gerbil model as a useful platform for studying the pathogenesis of EV71-induced pulmonary lesions, immunotherapy and antiviral drugs. PMID:25767882

  8. Accounting for the economic risk caused by variation in disease severity in fungicide dose decisions, exemplified for Mycosphaerella graminicola on winter wheat.

    PubMed

    Te Beest, D E; Paveley, N D; Shaw, M W; van den Bosch, F

    2013-07-01

    A method is presented to calculate economic optimum fungicide doses accounting for the risk aversion of growers responding to variability in disease severity between crops. Simple dose-response and disease-yield loss functions are used to estimate net disease-related costs (fungicide cost plus disease-induced yield loss) as a function of dose and untreated severity. With fairly general assumptions about the shapes of the probability distribution of disease severity and the other functions involved, we show that a choice of fungicide dose which minimizes net costs, on average, across seasons results in occasional large net costs caused by inadequate control in high disease seasons. This may be unacceptable to a grower with limited capital. A risk-averse grower can choose to reduce the size and frequency of such losses by applying a higher dose as insurance. For example, a grower may decide to accept "high-loss" years 1 year in 10 or 1 year in 20 (i.e., specifying a proportion of years in which disease severity and net costs will be above a specified level). Our analysis shows that taking into account disease severity variation and risk aversion will usually increase the dose applied by an economically rational grower. The analysis is illustrated with data on Septoria tritici leaf blotch of wheat caused by Mycosphaerella graminicola. Observations from untreated field plots at sites across England over 3 years were used to estimate the probability distribution of disease severities at mid-grain filling. In the absence of a fully reliable disease forecasting scheme, reducing the frequency of high-loss years requires substantially higher doses to be applied to all crops. Disease-resistant cultivars reduce both the optimal dose at all levels of risk and the disease-related costs at all doses.

  9. [The application of the nanostructured bioplastic material for the plastic reconstruction of perforations in the nasal septum].

    PubMed

    Grigor'eva, M V; Akimov, A V; Bagautdinov, A A

    2014-01-01

    The objective of the present work was to estimate the effectiveness of the application of the nanostructured bioplastic material for the plastic reconstruction of perforations in the nasal septum. A total of 80 patients were recruited for the study. Half of them underwent plastic reconstruction of perforations in the nasal septum with the application of the nanostructured bioplastic material. Forty patients were treated using no biotransplants. The functional state of nasal cavity mucosa was evaluated before and after surgery. It is concluded that the nanostructured bioplastic material used in the present study ensures efficacious reconstruction of nasal septum integrity after plastic correction of septal perforations.

  10. Morphological interaction between the nasal septum and nasofacial skeleton during human ontogeny.

    PubMed

    Goergen, Matthew J; Holton, Nathan E; Grünheid, Thorsten

    2017-05-01

    The nasal septal cartilage is thought to be a key growth center that contributes to nasofacial skeletal development. Despite the developmental influence of the nasal septum however, humans often exhibit a high frequency of septal deviation suggesting discordance in the growth between the septum and surrounding nasofacial skeleton. While there are numerous etiological factors that contribute to septal deviation, the surrounding nasofacial skeleton may also act to constrain the septum, resulting in altered patterns of growth. That is, while the nasal septum has a direct morphogenetic influence on aspects of the nasofacial skeleton, other nasofacial skeletal components may restrict septal growth resulting in deviation. Detailing the developmental relationship between these structures is important not only for understanding the causal determinants of nasal septal deviation, but also for developing a broader understanding of the complex interaction between the facial skeleton and chondrocranium. We selected 66 non-syndromic subjects from the University of Minnesota Orthodontic Clinic who ranged from 7 to 18 years in age and had an existing pretreatment cone-beam computed tomography (CBCT) scan. Using CBCT data, we examined the developmental relationship between nasal septal deviation and the surrounding nasofacial skeleton. We measured septal deviation as a percentage of septal volume relative to a modeled non-deviated septum. We then collected a series of coordinate landmark data in the region immediately surrounding the nasal septum in the midsagittal plane representing the nasofacial skeleton. First, we examined ontogenetic changes in the magnitude of nasal septal deviation relative to chronological age and nasofacial size. Next, using Procrustes-based geometric morphometric techniques, we assessed the morphological relationship between nasal septal deviation and nasofacial skeletal shape. Our results indicate that variation in the magnitude of nasal septal

  11. Dihydrofolate Reductase Deficiency Due to a Homozygous DHFR Mutation Causes Megaloblastic Anemia and Cerebral Folate Deficiency Leading to Severe Neurologic Disease

    PubMed Central

    Cario, Holger; Smith, Desirée E.C.; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

    2011-01-01

    The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate. PMID:21310277

  12. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.

    PubMed

    Cario, Holger; Smith, Desirée E C; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

    2011-02-11

    The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate.

  13. Severe hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone developed as initial manifestation of human herpesvirus-6-associated acute limbic encephalitis after unrelated bone marrow transplantation.

    PubMed

    Kawaguchi, T; Takeuchi, M; Kawajiri, C; Abe, D; Nagao, Y; Yamazaki, A; Sugita, Y; Tsukamoto, S; Sakai, S; Takeda, Y; Ohwada, C; Sakaida, E; Shimizu, N; Yokote, K; Iseki, T; Nakaseko, C

    2013-04-01

    Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo-SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus-6-associated post-transplantation acute limbic encephalitis (HHV-6 PALE) after allo-SCT. A 45-year-old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus-mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV-6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV-6 PALE, and close monitoring of serum sodium levels in high-risk patients for HHV-6 PALE is necessary for immediate diagnosis and treatment initiation.

  14. Role of Human Metapneumovirus, Influenza A Virus and Respiratory Syncytial Virus in Causing WHO-Defined Severe Pneumonia in Children in a Developing Country

    PubMed Central

    Ali, Asad; Khowaja, Asif Raza; Bashir, Maaman Zahoor; Aziz, Fatima; Mustafa, Sultan; Zaidi, Anita

    2013-01-01

    Objective The role of respiratory viruses in causing severe, life threatening pneumonia in children in developing countries is not well established. Our study aims to determine the role of human metapneumovirus (HMPV), influenza A virus and respiratory syncytial virus (RSV) in children, aged 6 weeks to 2 years, hospitalized with WHO defined severe pneumonia (tachypnea plus any general danger sign or chest in-drawing) at a public sector hospital in Karachi, Pakistan. Methods This study was conducted from November 2010 to September 2011 at Abbassi Shaheed Hospital, a large public tertiary care hospital in Karachi, Pakistan. Children admitted with WHO-defined severe pneumonia were enrolled and throat swabs were obtained to detect respiratory viruses using real time RT-PCR. Chest x-rays of all subjects were obtained and independently interpreted by two radiologists to diagnose radiologic pneumonia. Results 169 children were enrolled. HMPV was detected in 24 (14.2%), influenza A virus in 9 (5.3%) and RSV in 30 (17.8%) children admitted with severe pneumonia. Of 9 patients with influenza A, 8 tested positive for H1N1. Viral etiology was found in 18% of radiologically confirmed pneumonia. HMPV infections peaked in February and April, influenza A was prevalent in January, June and November and RSV infections were most prevalent from June to September. Conclusion HMPV, influenza A and RSV are common causes of WHO-defined severe pneumonia in hospitalized children in Karachi. Knowledge regarding the viral etiology of pediatric pneumonia and individual viral seasonality can help in the recommendation and implementation of appropriate management strategies. PMID:24058625

  15. Homozygous EXOSC3 mutation c.92G→C, p.G31A is a founder mutation causing severe pontocerebellar hypoplasia type 1 among the Czech Roma.

    PubMed

    Schwabova, Jaroslava; Brozkova, Dana Safka; Petrak, Borivoj; Mojzisova, Mahulena; Pavlickova, Klara; Haberlova, Jana; Mrazkova, Lenka; Hedvicakova, Petra; Hornofova, Ludmila; Kaluzova, Marie; Fencl, Filip; Krutova, Marcela; Zamecnik, Josef; Seeman, Pavel

    2013-12-01

    Pontocerebellar hypoplasia type 1 (PCH1) is characterized by cerebellar and anterior horn motor neuron degeneration and loss, signs of spinal muscular atrophy plus. Patients manifest severe perinatal weakness, hypotonia, and respiratory insufficiency, causing death frequently before the age of 1 year. Recently, causative mutations in EXOSC3 were reported in a majority of PCH1 patients, but the detailed clinical phenotype caused by EXOSC3 mutations, genotype-phenotype correlations, and prevalent mutations in specific ethnic groups is not yet known. Three unrelated Czech Roma patients with PCH1 were investigated clinically, electrophysiologically, neuroradiologically, and neuropathologically (patients 1 and 2). The entire coding region of the EXOSC3 gene, including the adjacent intron sequences, was sequenced in all three patients. The same mutation c.92G→C, p.G31A in EXOSC3 was found in all three affected patients in homozygous state and in heterozygous state in the parents from two of the families. Haplotype analysis with four flanking microsatellite markers showed identical haplotype in 9 out of 11 haplotypes carrying the c.92G→C, p.G31A mutation. Furthermore, four heterozygotes for this mutation were found in anonymous DNA samples from 90 unrelated Roma individuals. All four of these samples shared the same haplotype. No heterozygous sample was found among 120 anonymous DNA samples from Czech non-Roma individuals with no familial relation. It may therefore be concluded that EXOSC3 c.92G→C, p.G31A mutation is a founder mutation with high prevalence among the Czech Roma causing a similar and particularly severe phenotype of PCH1. These observations from the Czech Roma may have consequences also for other Roma from other countries. PCH1 caused by EXOSC3 founder mutation c.92G→C, p.G31A extends the list of autosomal recessive disorders rare among the general population but more frequent among Roma at least in the Czech Republic.

  16. Severe 2010 Cold-Water Event Caused Unprecedented Mortality to Corals of the Florida Reef Tract and Reversed Previous Survivorship Patterns

    PubMed Central

    Lirman, Diego; Schopmeyer, Stephanie; Manzello, Derek; Gramer, Lewis J.; Precht, William F.; Muller-Karger, Frank; Banks, Kenneth; Barnes, Brian; Bartels, Erich; Bourque, Amanda; Byrne, James; Donahue, Scott; Duquesnel, Janice; Fisher, Louis; Gilliam, David; Hendee, James; Johnson, Meaghan; Maxwell, Kerry; McDevitt, Erin; Monty, Jamie; Rueda, Digna; Ruzicka, Rob; Thanner, Sara

    2011-01-01

    Background Coral reefs are facing increasing pressure from natural and anthropogenic stressors that have already caused significant worldwide declines. In January 2010, coral reefs of Florida, United States, were impacted by an extreme cold-water anomaly that exposed corals to temperatures well below their reported thresholds (16°C), causing rapid coral mortality unprecedented in spatial extent and severity. Methodology/Principal Findings Reef surveys were conducted from Martin County to the Lower Florida Keys within weeks of the anomaly. The impacts recorded were catastrophic and exceeded those of any previous disturbances in the region. Coral mortality patterns were directly correlated to in-situ and satellite-derived cold-temperature metrics. These impacts rival, in spatial extent and intensity, the impacts of the well-publicized warm-water bleaching events around the globe. The mean percent coral mortality recorded for all species and subregions was 11.5% in the 2010 winter, compared to 0.5% recorded in the previous five summers, including years like 2005 where warm-water bleaching was prevalent. Highest mean mortality (15%–39%) was documented for inshore habitats where temperatures were <11°C for prolonged periods. Increases in mortality from previous years were significant for 21 of 25 coral species, and were 1–2 orders of magnitude higher for most species. Conclusions/Significance The cold-water anomaly of January 2010 caused the worst coral mortality on record for the Florida Reef Tract, highlighting the potential catastrophic impacts that unusual but extreme climatic events can have on the persistence of coral reefs. Moreover, habitats and species most severely affected were those found in high-coral cover, inshore, shallow reef habitats previously considered the “oases” of the region, having escaped declining patterns observed for more offshore habitats. Thus, the 2010 cold-water anomaly not only caused widespread coral mortality but also

  17. Atypical severe combined immunodeficiency caused by a novel homozygous mutation in Rag1 gene in a girl who presented with pyoderma gangrenosum: a case report and literature review.

    PubMed

    Patiroglu, Turkan; Akar, H Haluk; Gilmour, Kimberly; Ozdemir, M Akif; Bibi, Shahnaz; Henriquez, Frances; Burns, Siobhan O; Unal, Ekrem

    2014-10-01

    Severe combined immunodeficiency (SCID) is a heterogeneous group of inherited defects involving the development of T- and/or B-lymphocytes. We report a female with atypical severe combined immunodeficiency caused by a novel homozygous mutation at cDNA position 2290 (c.2290C > T) in exon 2 of the RAG1 gene. The patient presented with bronchopneumonia, pyoderma gangrenosum (PG), pancytopenia and splenomegaly. She presented to us with pancytopenia and splenomegaly at the age of 11. Her condition was complicated by PG on left lower ankle at the age of 12. She experienced bronchopneumonia at the age of 15. She was diagnosed with RAG1 deficiency at the age of 16. Her immunological presentation included leucopenia and diminished number of B cells.

  18. [A case of severe motor and intellectual disability with tracheal stenosis due to granulation caused by metal stents treated successfully by silicone stents].

    PubMed

    Kotani, Haruko; Hino, Hiroyuki; Shiraishi, Taisuke; Ogura, Hideo

    2002-11-01

    A silicone stent (Dumon stent) was used in a severe motor and intellectual disability with severe tracheal stenosis due to granulation caused by an implanted the expanded metal stent (Ultraflex Nitinol Stent). To treat tracheobronchial malacia, diagnosed in infancy, expanded metalic stent was implanted at the ages of 30 and 32 years. However, a few months after the second implantation, progressive dyspnea appeared, and he had to use a respirator under intravenous anesthesia. Bronchoscopy showed re-stenosis of the trachea due to a granulation tissue within the stent. A Dumon stent was applied to control the re-stenosis. He was successfully weaned from a respirator. Since granulation tissue had recurred at the end of the Dumon stent after 3 months, a long term care of the airway and regular observation is necessary after implantation of stents.

  19. Treatment of Virgin OHVIRA Syndrome with Haematometrocolpos by Complete Incision of Vaginal Septum without Hymenotomy

    PubMed Central

    Tug, Niyazi; Çelik, Ayhan; Alp, Turgut; Yenidede, Ilter

    2015-01-01

    Mullerian malformations result from defective fusion of the Mullerian ducts during development of the female reproductive system and have an incidence of 2-3%. The American Fertility Society classification of Mullerian anomalies is the most commonly utilized standardized classification. The least common form of these malformations is Herlyn-Werner-Wunderlich syndrome characterized by obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). This syndrome has been described with case reports since 1922. Early diagnosis and surgery that include drainage of fluid and resection of the vaginal septum is necessary for OHVIRA to prevent late complications (i.e. pyocolpos, chronic cryptomenorrhea). Here in we report a case of Herlyn-Werner-Wunderlich syndrome that hymen has been preserved during the operation of non-fenestrated transverse vaginal septum resection with hysteroscopy. PMID:26676254

  20. Persistent Truncus Arteriosus With Intact Ventricular Septum: Clinical, Hemodynamic and Short-term Surgical Outcome

    PubMed Central

    Ajami, Gholamhossein; Amirghofran, Ahmad Ali; Amoozgar, Hamid; Borzouee, Mohammad

    2015-01-01

    Introduction: Truncus arteriosus with intact ventricular septum is a rare and unique variant of persistent truncus arteriosus (PTA) which usually presents with central cyanosis and congestive heart failure in neonate and early infancy. Associated cardiac and non-cardiac anomalies may affect morbidity and mortality of these patients. Case Presentation: We describe clinical presentation, echocardiography and angiographic features of a 7-month old boy with PTA and intact ventricular septum who underwent surgical repair of the anomaly at our institution. Operative findings, surgical procedure and short-term outcome are reported. Conclusions: While our patient had systemic pulmonary arterial pressure at the time of complete surgical repair, it was improved after surgery. PMID:26495090

  1. It takes two DNA translocases to untangle chromosomes from the division septum.

    PubMed

    Wu, Ling Juan

    2009-11-01

    The DNA translocase function of Bacillus subtilis SpoIIIE is essential for spore development and is important during vegetative growth for moving trapped chromosomal DNA away from division septa. Two papers in this issue of Molecular Microbiology, from the teams of Peter Graumann and William Burkholder, have characterized a second SpoIIIE/FtsK-like protein in B. subtilis, SftA. This protein lacks any recognizable transmembrane domain possessed by the other characterized members of the family, yet the protein is shown to be associated with the division septum and, like SpoIIIE, is required for clearing DNA from the septum. However, SftA and SpoIIIE act at different stages of septation and together they ensure maximum fidelity in chromosome segregation.

  2. Electrophysiological identification of mesencephalic ventromedial tegmental (VMT) neurons projecting to the frontal cortex, septum and nucleus accumbens.

    PubMed

    Deniau, J M; Thierry, A M; Feger, J

    1980-05-12

    The electrophysiological properties of neurons located in the mesencephalic ventromedial tegmentum (VMT) and the organization of the efferents of these neurons to the frontal cortex, the septum, the nucleus accumbens and the head of the striatum were studied in ketamine-anesthetized rats. The projections of the VMT cells were determined through use of the antidromic activation method. Our results show that VMT projections to different target areas originate mainly from different VMT neurons. However, in some cases single VMT neurons were found to send axon collaterals to two different areas. Three branching patterns were observed: septum-cortex, septum--nucleus accumbens and septum--striatum. The occasional observation of temporally distinct antodromic responses from a single area was considered to result from activation of different branches of the arborizing axon. The distribution of antidromic response latencies for VMT projections to each structure is discussed in relation to the question of dopaminergic versus non-dopaminergic mesolimbic and mesocortical systems.

  3. ALOBAR HOLOPROSENCEPHALY, CLEFT LIP/PALATE, URORECTAL SEPTUM MALFORMATION SEQUENCE AND CONGENITAL PERINEAL HERNIA IN A FETUS.

    PubMed

    Girisha, K M; Nayak, S S; Shukla, A; Bhat, S K

    2015-01-01

    We report on a fetus with alobar holoprosencephaly, complete cleft lip and palate, urorectal septum malformation sequence and perineal hernia. To our knowledge this appears to be a novel fetal malformation syndrome.

  4. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion: A case report in a patient with metastatic pancreatic adenocarcinoma.

    PubMed

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-06-01

    Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date.We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy.Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited.

  5. Lupus vulgaris leading to perforation of nasal septum in a child.

    PubMed

    Singal, Archana; Arora, Rahul; Pandhi, Deepika

    2015-01-01

    Lupus vulgaris (LV) is a common form of cutaneous tuberculosis in India, mostly involving the lower half of the body. Facial involvement is uncommon. Untreated disease may lead to significant morbidity due to atrophic scarring, mutilation, and deformity. We report a case of multi-focal LV in a 10-year-old boy affecting the nose and cheek that resulted in perforation of the nasal septum, a rarely reported complication.

  6. Types and synaptic connections of hippocampal inhibitory neurons reciprocally connected with the medial septum.

    PubMed

    Takács, Virág T; Freund, Tamás F; Gulyás, Attila I

    2008-07-01

    The morphological properties and connectivity of gamma-aminobutyric acid (GABA)ergic hippocampal cells projecting to the medial septum (HS cells) were examined in the rat. Two types of HS cells are located in different layers of the hippocampus: sparsely-spiny cells are in CA1-3 str. oriens and CA3 str. radiatum, where recurrent axons of pyramidal cells arborize. Densely-spiny HS cells with spiny somata are located in the termination zone of granule cell axons. In the hilus, intermediate morphologies can also be found. HS cells receive GABAergic medial septal afferents in all layers where they occur, thus the connectivity of the septum and the hippocampus is reciprocal at cell level. HS cells receive extremely dense innervation, sparsely-spiny cells are innervated by approximately 19,000 excitatory inputs, while densely-spiny cells get an even larger number (approximately 37,000). While 14% of the inputs are inhibitory for the sparsely-spiny cells, it is only 2.3% in the case of densely-spiny cells. Because a high proportion (up to 54.5% on somata and 27.5% on dendrites) of their GABAergic inputs derived from labelled septal terminals, their predominant inhibitory input probably arises from the medial septum. CA1 area HS cells possessed myelinated projecting axons, as well as local collaterals, which targeted mostly pyramidal cell dendrites and spines in str. oriens and radiatum. The synaptic organization suggests that by sampling the activity of large populations of principal cells HS cells can reliably broadcast hippocampal activity level to the medial septum.

  7. Diastolic Function in Paced Children with Cardiac Defects: Septum vs Apex

    PubMed Central

    Ortega, Michel Cabrera; Morejon, Adel Eladio Gonzalez; Serrano, Giselle Ricardo; Ramos, Dunia Barbara Benitez

    2015-01-01

    In children with structural congenital heart disease (CHD), the effects of chronic ventricular pacing on diastolic function are not well known. On the other hand, the beneficial effect of septal pacing over apical pacing is still controversial. The aim of this study was to evaluate the influence of different right ventricular (RV) pacing site on left ventricular (LV) diastolic function in children with cardiac defects. Twenty-nine pediatric patients with complete atrioventricular block (CAVB) and CHD undergoing permanent pacing were prospectively studied. Pacing sites were RV apex (n = 16) and RV septum (n = 13). Echocardiographic assessment was performed before pacemaker implantation and after it, during a mean follow‑up of 4.9 years. Compared to RV septum, transmitral E-wave was significantly affected in RV apical pacing (95.38 ± 9.19 vs 83 ± 18.75, p = 0.038). Likewise, parameters at the lateral annular tissue Doppler imaging (TDI) were significantly affected in children paced at the RV apex. The E´ wave correlated inversely with TDI lateral myocardial performance index (Tei index) (R2= 0.9849, p ≤ 0.001). RV apex pacing (Odds ratio, 0.648; confidence interval, 0.067-0.652; p = 0.003) and TDI lateral Tei index (Odds ratio, 31.21; confidence interval, 54.6-177.4; p = 0.025) predicted significantly decreased LV diastolic function. Of the two sites studied, RV septum prevents pacing-induced reduction of LV diastolic function. PMID:26352178

  8. [Aneurysms of the interauricular septum. Review of the literature apropos of 8 cases].

    PubMed

    Herpin, D; Ciber, M A; Boutaud, P; Amiel, A; Gaudeau, B; Guillem, J P; Demange, J

    1986-01-01

    The authors present 8 cases of aneurysms of the interauricular septum (AIAS). The diagnosis was established in all cases by two-dimensional echocardiography (E2D) which was requested, three times following a cerebral vascular accident (CVA). The AIAS manifest themselves as localised "hernias" of the inter-auricular septum, mobile during the cardiac cycle. Their topography was strictly right inter-auricular in 6 cases, whereas in the other 2 patients the AIAS passed into the left atrium at protosystole and returned to the right atrium at telesystole. Catheterization with angiography was carried out 5 times: the inter-auricular septum was crossed 4 times without gasometric reasons for an associated shunt; the AIAS was opacified in all cases. An anti-coagulant treatment was prescribed for 3 patients who had suffered a CVA, and for a fourth presenting numerous supraventricular extrasystoles which were sometimes grouped. A review of the literature of the last fifty years enabled a compilation of 93 cases of AIAS to be made, 49 of which had been examined by E2D, 35 had had a hemodynamic and angiographic exploration and 47 an anatomical and/or surgical confirmation. The main results obtained are described and commented on. The diagnostic, etiopathological and prognostic problems raised by the "updating" of this pathology are discussed.

  9. Phospholipase C beta 4 in the medial septum controls cholinergic theta oscillations and anxiety behaviors.

    PubMed

    Shin, Jonghan; Gireesh, Gangadharan; Kim, Seong-Wook; Kim, Duk-Soo; Lee, Sukyung; Kim, Yeon-Soo; Watanabe, Masahiko; Shin, Hee-Sup

    2009-12-09

    Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C beta 4 (PLC-beta 4(-/-)) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-beta 4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-beta 4 knockdown in the medial septum produced a phenotype similar to that of PLC-beta 4(-/-) mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-beta 4(-/-) mice. These findings suggest that (1) PLC-beta 4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.

  10. Activation of the medial septum reverses age-related hippocampal encoding deficits: a place field analysis.

    PubMed

    Sava, Simona; Markus, Etan J

    2008-02-20

    When a rat runs through a familiar environment, the hippocampus retrieves a previously stored spatial representation of the environment. When the environment is modified a new representation is seen, presumably corresponding to the hippocampus encoding the new information. The medial septum is hypothesized to modulate whether the hippocampus engages in retrieval or encoding. The cholinergic agonist carbachol was infused into the medial septum, and hippocampal CA1 place cells were recorded in freely moving rats. In a familiar environment, septal activation impaired the retrieval of a previously stored hippocampal place cell representation regardless of age. When the environment was changed, medial septal activation impaired the encoding process in young, but facilitated the encoding of the new information in aged rats. Moreover, the improved encoding was evident during a subsequent exposure to the modified environment 24 h later. The findings support the role the septum plays in modulating hippocampal retrieval/encoding states. Furthermore, our data indicate a mechanism of age-related cognitive impairment.

  11. Novel mutations in DNAJB6 gene cause a very severe early-onset limb-girdle muscular dystrophy 1D disease.

    PubMed

    Palmio, Johanna; Jonson, Per Harald; Evilä, Anni; Auranen, Mari; Straub, Volker; Bushby, Kate; Sarkozy, Anna; Kiuru-Enari, Sari; Sandell, Satu; Pihko, Helena; Hackman, Peter; Udd, Bjarne

    2015-11-01

    DNAJB6 is the causative gene for limb-girdle muscular dystrophy 1D (LGMD1D). Four different coding missense mutations, p.F89I, p.F93I, p.F93L, and p.P96R, have been reported in families from Europe, North America and Asia. The previously known mutations cause mainly adult-onset proximal muscle weakness with moderate progression and without respiratory involvement. A Finnish family and a British patient have been studied extensively due to a severe muscular dystrophy. The patients had childhood-onset LGMD, loss of ambulation in early adulthood and respiratory involvement; one patient died of respiratory failure aged 32. Two novel mutations, c.271T > A (p.F91I) and c.271T > C (p.F91L), in DNAJB6 were identified by whole exome sequencing as a cause of this severe form of LGMD1D. The results were confirmed by Sanger sequencing. The anti-aggregation effect of the mutant DNAJB6 was investigated in a filter-trap based system using transient transfection of mammalian cell lines and polyQ-huntingtin as a model for an aggregation-prone protein. Both novel mutant proteins show a significant loss of ability to prevent aggregation.

  12. Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness.

    PubMed

    Delmaghani, Sedigheh; Aghaie, Asadollah; Bouyacoub, Yosra; El Hachmi, Hala; Bonnet, Crystel; Riahi, Zied; Chardenoux, Sebastien; Perfettini, Isabelle; Hardelin, Jean-Pierre; Houmeida, Ahmed; Herbomel, Philippe; Petit, Christine

    2016-06-02

    By genetic linkage analysis in a large consanguineous Iranian family with eleven individuals affected by severe to profound congenital deafness, we were able to define a 2.8 Mb critical interval (at chromosome 1p21.2-1p21.1) for an autosomal-recessive nonsyndromic deafness locus (DFNB). Whole-exome sequencing allowed us to identify a CDC14A biallelic nonsense mutation, c.1126C>T (p.Arg376(∗)), which was present in the eight clinically affected individuals still alive. Subsequent screening of 115 unrelated individuals affected by severe or profound congenital deafness of unknown genetic cause led us to identify another CDC14A biallelic nonsense mutation, c.1015C>T (p.Arg339(∗)), in an individual originating from Mauritania. CDC14A encodes a protein tyrosine phosphatase. Immunofluorescence analysis of the protein distribution in the mouse inner ear showed a strong labeling of the hair cells' kinocilia. By using a morpholino strategy to knockdown cdc14a in zebrafish larvae, we found that the length of the kinocilia was reduced in inner-ear hair cells. Therefore, deafness caused by loss-of-function mutations in CDC14A probably arises from a morphogenetic defect of the auditory sensory cells' hair bundles, whose differentiation critically depends on the proper growth of their kinocilium.

  13. Special function of nestin(+) neurons in the medial septum-diagonal band of Broca in adult rats.

    PubMed

    Zhao, Yuhong; Guo, Kaihua; Li, Dongpei; Yuan, Qunfang; Yao, Zhibin

    2014-02-01

    Nestin(+) neurons have been shown to express choline acetyltransferase (ChAT) in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin(+) neurons to the olfactory bulb and the time course of nestin(+) neurons in the medial septum-diagonal band of Broca in adult rats during injury recovery after olfactory nerve transection. This study observed that all nestin(+) neurons were double-labeled with ChAT in the medial septum-diagonal band of Broca. Approximately 53.6% of nestin(+) neurons were projected to the olfactory bulb and co-labeled with fast blue. A large number of nestin(+) neurons were not present in each region of the medial septum-diagonal band of Broca. Nestin(+) neurons in the medial septum and vertical limb of the diagonal band of Broca showed obvious compensatory function. The number of nestin(+) neurons decreased to a minimum later than nestin(-)/ChAT(+) neurons in the medial septum-diagonal band of Broca. The results suggest that nestin(+) cholinergic neurons may have a closer connection to olfactory bulb neurons. Nestin(+) cholinergic neurons may have a stronger tolerance to injury than Nestin(-)/ChAT(+) neurons. The difference between nestin(+) and nestin(-)/ChAT(+) neurons during the recovery process requires further investigations.

  14. A reduced progenitor pool population accounts for the rudimentary appearance of the septum, medial pallium and dorsal pallium in birds.

    PubMed

    Charvet, Christine J

    2010-01-01

    To date, most studies comparing birds and mammals have focused on the similarities in brain development, architecture and connectivity. However, major differences in size, anatomy and organization exist in the telencephalon of adult birds and mammals. For instance, the septum, medial pallium and dorsal pallium of birds appear rudimentary compared with those of mammals. To identify the developmental processes that give rise to this difference in size and anatomy of the septum, medial pallium and dorsal pallium, the thickness of the ventricular zone that encompasses these regions was measured in embryonic birds (i.e. chickens, sparrows) and mammals (i.e. rabbits, hedgehogs, shrews, platypus). Cumulative bromodeoxyuridine (BrdU) labeling in chickens at embryonic day 7 and 8 was also used to examine levels of cell proliferation in the ventricular zone of the septum, medial pallium and dorsal pallium. The study's main finding is that the ventricular zone of the septum, medial pallium and dorsal pallium is thinner in birds than in mammals. In chickens, the septum, medial pallium and dorsal pallium ventricular zone harbor few proliferating (i.e. BrdU+) cells. Collectively, these findings suggest that a reduced progenitor pool population account for the 'rudimentary' appearance of the avian septum, medial pallium and dorsal pallium.

  15. Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes

    PubMed Central

    Yu, Huimin; Smallwood, Philip M.; Wang, Yanshu; Vidaltamayo, Roman; Reed, Randall; Nathans, Jeremy

    2010-01-01

    The closure of an open anatomical structure by the directed growth and fusion of two tissue masses is a recurrent theme in mammalian embryology, and this process plays an integral role in the development of the palate, ventricular septum, neural tube, urethra, diaphragm and eye. In mice, targeted mutations of the genes encoding frizzled 1 (Fz1) and frizzled 2 (Fz2) show that these highly homologous integral membrane receptors play an essential and partially redundant role in closure of the palate and ventricular septum, and in the correct positioning of the cardiac outflow tract. When combined with a mutant allele of the planar cell polarity gene Vangl2 (Vangl2Lp), Fz1 and/or Fz2 mutations also cause defects in neural tube closure and misorientation of inner ear sensory hair cells. These observations indicate that frizzled signaling is involved in diverse tissue closure processes, defects in which account for some of the most common congenital anomalies in humans. PMID:20940229

  16. Severity and pattern of injuries caused by the traditional Swiss team sport ‘Hornussen’: first retrospective study at a level I trauma centre in Switzerland

    PubMed Central

    Waterkamp, Volkmar; Ricklin, Meret; Schaller, Benoît; Katsoulis, Konstantinos; Exadaktylos, Aristomenis

    2016-01-01

    Background This article addresses typical injury patterns related to the traditional Swiss team sport of Hornussen. A small plastic disk is struck with a special elastic racket and then intercepted in the field. Severe injuries have occasionally been reported. We present a systematic review of all cases of Hornussen injuries treated in the University Hospital of Bern from 2000 to 2014. Methods To assess the frequency, type and outcome of Hornussen injuries, we performed a database search of all inpatient and outpatient cases related to Hornussen and that were admitted to and/or treated in Bern University Hospital from 2000 to 2014. Results A total of 28 such patients could be identified. Apart from 1 woman injured as a bystander and treated as an outpatient, all patients were male and active players. Typical injury patterns comprised midfacial fractures and severe ocular traumata, very often in combination. Almost all of these patients had to be hospitalised due to the severity of the trauma suffered and underwent surgery. 1 patient had to be admitted to the intensive care unit prior to the operation. Conclusions Eye and face injuries caused by Hornussen can be devastating. This resembles the potential risk of other bat-and-ball sports, such as cricket and baseball. Apart from the economic loss due to treatment costs and sick leave, these injuries can be disabling for life. It should therefore be mandatory for all players to wear protective gear, as is already the case for Hornussen players born in 1984 or later. PMID:27900183

  17. Infection with a Mouse-Adapted Strain of the 2009 Pandemic Virus Causes a Highly Severe Disease Associated with an Impaired T Cell Response

    PubMed Central

    Meunier, Isabelle; Morisseau, Olivier; Garneau, Émilie; Marois, Isabelle; Cloutier, Alexandre; Richter, Martin V.

    2015-01-01

    Despite a relatively low fatality rate, the 2009 H1N1 pandemic virus differed from other seasonal viruses in that it caused mortality and severe pneumonia in the young and middle-aged population (18–59 years old). The mechanisms underlying this increased disease severity are still poorly understood. In this study, a human isolate of the 2009 H1N1 pandemic virus was adapted to the mouse (MAp2009). The pathogenicity of the MAp2009 virus and the host immune responses were evaluated in the mouse model and compared to the laboratory H1N1 strain A/Puerto Rico/8/1934 (PR8). The MAp2009 virus reached consistently higher titers in the lungs over 14 days compared to the PR8 virus, and caused severe disease associated with high morbidity and 85% mortality rate, contrasting with the 0% death rate in the PR8 group. During the early phase of infection, both viruses induced similar pathology in the lungs. However, MAp2009-induced lung inflammation was sustained until the end of the study (day 14), while there was no sign of inflammation in the PR8-infected group by day 10. Furthermore, at day 3 post-infection, MAp2009 induced up to 10- to 40-fold more cytokine and chemokine gene expression, respectively. More importantly, the numbers of CD4+ T cells and virus-specific CD8+ T cells were significantly lower in the lungs of MAp2009-infected mice compared to PR8-infected mice. Interestingly, there was no difference in the number of dendritic cells in the lung and in the draining lymph node. Moreover, mice infected with PR8 or MAp2009 had similar numbers of CCR5 and CXCR3-expressing T cells, suggesting that the impaired T cell response was not due to a lack of chemokine responsiveness or priming of T cells. This study demonstrates that a mouse-adapted virus from an isolate of the 2009 pandemic virus interferes with the adaptive immune response leading to a more severe disease. PMID:26381265

  18. Garvicin A, a Novel Class IId Bacteriocin from Lactococcus garvieae That Inhibits Septum Formation in L. garvieae Strains

    PubMed Central

    Cárdenas, Nivia; Martínez, Beatriz; Ruiz-Barba, José Luis; Fernández-Garayzábal, José F.; Rodríguez, Juan M.; Gibello, Alicia

    2013-01-01

    Lactococcus garvieae 21881, isolated in a human clinical case, produces a novel class IId bacteriocin, garvicin A (GarA), which is specifically active against other L. garvieae strains, including fish- and bovine-pathogenic isolates. Purification from active supernatants, sequence analyses, and plasmid-curing experiments identified pGL5, one of the five plasmids found in L. garvieae [M. Aguado-Urda et al., PLoS One 7(6):e40119, 2012], as the coding plasmid for the structural gene of GarA (lgnA), its putative immunity protein (lgnI), and the ABC transporter and its accessory protein (lgnC and lgnD). Interestingly, pGL5-cured strains were still resistant to GarA. Other putative bacteriocins encoded by the remaining plasmids were not detected during purification, pointing to GarA as the main inhibitor secreted by L. garvieae 21881. Mode-of-action studies revealed a potent bactericidal activity of GarA. Moreover, transmission microscopy showed that GarA seems to act by inhibiting septum formation in L. garvieae cells. This potent and species-specific inhibition by GarA holds promise for applications in the prevention or treatment of infections caused by pathogenic strains of L. garvieae in both veterinary and clinical settings. PMID:23666326

  19. Severe glomerular disease in juvenile grey snapper Lutjanus griseus L. in the Gulf of Mexico caused by the myxozoan Sphaerospora motemarini n. sp.

    PubMed

    Holzer, Astrid S; Pecková, Hanka; Patra, Sneha; Brennan, Nathan P; Yanes-Roca, Carlos; Main, Kevan L

    2013-12-01

    In the eastern Gulf of Mexico, off the coast of Florida, grey snapper, Lutjanus griseus was found to be infected with the myxozoan parasite Sphaerospora motemarini n. sp., with high prevalence (83%) and intensity of infection occuring in age-0 fish, and with parasite levels decreasing with age (age-1 snapper 40%; age-2 snapper 0%). The morphological, molecular and phylogenetic characterisation of the myxozoan showed that it is a member of the typically marine, polysporoplasmid Sphaerospora spp. which form a subclade within the Sphaerospora sensu stricto clade of myxozoans, which is characterised by large expansion segments in their SSU rDNA sequences. Presporogonic stages of S. motemarini n. sp. were detected in the blood, using PCR. Pseudoplasmodia and spores were found to develop in the renal corpuscles of the host, causing their massive expansion. Macroscopic and histopathological changes were observed in age-0 fish and show that S. motemarini n. sp. causes severe glomerulonephritis in L. griseus leading to a compromised host condition, which makes it more susceptible to stress (catch-and-release, predators, water quality) and can result in mortalities. These results are discussed in relation to the exploitation of grey snapper populations by commercial and recreational fisheries and with the observed increased mortalities with temperature along the coast of Florida. In the future, we would like to determine prevalence and intensity of infection with S. motemarini n. sp. in juvenile L. griseus in different areas of the Gulf of Mexico in order to be able to estimate the temperature dependence of S. motemarini n. sp. proliferation and to be able to predict its distribution and severity during climatic changes in the Gulf.

  20. Severe glomerular disease in juvenile grey snapper Lutjanus griseus L. in the Gulf of Mexico caused by the myxozoan Sphaerospora motemarini n. sp.

    PubMed Central

    Holzer, Astrid S.; Pecková, Hanka; Patra, Sneha; Brennan, Nathan P.; Yanes-Roca, Carlos; Main, Kevan L.

    2013-01-01

    In the eastern Gulf of Mexico, off the coast of Florida, grey snapper, Lutjanus griseus was found to be infected with the myxozoan parasite Sphaerospora motemarini n. sp., with high prevalence (83%) and intensity of infection occuring in age-0 fish, and with parasite levels decreasing with age (age-1 snapper 40%; age-2 snapper 0%). The morphological, molecular and phylogenetic characterisation of the myxozoan showed that it is a member of the typically marine, polysporoplasmid Sphaerospora spp. which form a subclade within the Sphaerospora sensu stricto clade of myxozoans, which is characterised by large expansion segments in their SSU rDNA sequences. Presporogonic stages of S. motemarini n. sp. were detected in the blood, using PCR. Pseudoplasmodia and spores were found to develop in the renal corpuscles of the host, causing their massive expansion. Macroscopic and histopathological changes were observed in age-0 fish and show that S. motemarini n. sp. causes severe glomerulonephritis in L. griseus leading to a compromised host condition, which makes it more susceptible to stress (catch-and-release, predators, water quality) and can result in mortalities. These results are discussed in relation to the exploitation of grey snapper populations by commercial and recreational fisheries and with the observed increased mortalities with temperature along the coast of Florida. In the future, we would like to determine prevalence and intensity of infection with S. motemarini n. sp. in juvenile L. griseus in different areas of the Gulf of Mexico in order to be able to estimate the temperature dependence of S. motemarini n. sp. proliferation and to be able to predict its distribution and severity during climatic changes in the Gulf. PMID:24533325

  1. Sex Differences in Somatotrope Dependency on Leptin Receptors in Young Mice: Ablation of LEPR Causes Severe Growth Hormone Deficiency and Abdominal Obesity in Males

    PubMed Central

    Odle, Angela; Haney, Anessa; Childs, Gwen

    2015-01-01

    Leptin receptor (LEPR) signaling controls appetite and energy expenditure. Somatotrope-specific deletion of the LEPRb signaling isoform causes GH deficiency and obesity. The present study selectively ablated Lepr exon 1 in somatotropes, which removes the signal peptide, causing the loss of all isoforms of LEPR. Excision of Lepr exon 1 was restricted to the pituitary, and mutant somatotropes failed to respond to leptin. Young (2–3 mo) males showed a severe 84% reduction in serum GH levels and more than 60% reduction in immunolabeled GH cells compared with 41%–42% reductions in GH and GH cells in mutant females. Mutant males (35 d) and females (45 d) weighed less than controls and males had lower lean body mass. Image analysis of adipose tissue by magnetic resonance imaging showed that young males had a 2-fold increase in abdominal fat mass and increased adipose tissue density. Young females had only an overall increase in adipose tissue. Both males and females showed lower energy expenditure and higher respiratory quotient, indicating preferential carbohydrate burning. Young mutant males slept less and were more restless during the dark phase, whereas the opposite was true of females. The effects of a Cre-bearing sire on his non-Cre-recombinase bearing progeny are seen by increased respiratory quotient and reduced litter sizes. These studies elucidate clear sex differences in the extent to which somatotropes are dependent on all isoforms of LEPR. These results, which were not seen with the ablation of Lepr exon 17, highlight the severe consequences of ablation of LEPR in male somatotropes. PMID:26168341

  2. De novo loss-of-function mutations in X-linked SMC1A cause severe ID and therapy-resistant epilepsy in females: expanding the phenotypic spectrum.

    PubMed

    Jansen, S; Kleefstra, T; Willemsen, M H; de Vries, P; Pfundt, R; Hehir-Kwa, J Y; Gilissen, C; Veltman, J A; de Vries, B B A; Vissers, L E L M

    2016-11-01

    De novo missense mutations and in-frame coding deletions in the X-linked gene SMC1A (structural maintenance of chromosomes 1A), encoding part of the cohesin complex, are known to cause Cornelia de Lange syndrome in both males and females. For a long time, loss-of-function (LoF) mutations in SMC1A were considered incompatible with life, as such mutations had not been reported in neither male nor female patients. However, recently, the authors and others reported LoF mutations in females with intellectual disability (ID) and epilepsy. Here we present the detailed phenotype of two females with de novo LoF mutations in SMC1A, including a de novo mutation of single base deletion [c.2364del, p.(Asn788Lysfs*10)], predicted to result in a frameshift, and a de novo deletion of exon 16, resulting in an out-of-frame mRNA splice product [p.(Leu808Argfs*6)]. By combining our patients with the other recently reported females carrying SMC1A LoF mutations, we ascertained a phenotypic spectrum of (severe) ID, therapy-resistant epilepsy, absence/delay of speech, hypotonia and small hands and feet. Our data show the existence of a novel phenotypic entity - distinct from CdLS - and caused by de novo SMC1A LoF mutations.

  3. Mutation of the zebrafish glass onion locus causes early cell-nonautonomous loss of neuroepithelial integrity followed by severe neuronal patterning defects in the retina.

    PubMed

    Pujic, Z; Malicki, J

    2001-06-15

    Mutation of the glass onion locus causes drastic neuronal patterning defects in the zebrafish retina and brain. The precise stratified appearance of the wild-type retina is absent in the mutants. The glass onion phenotype is first visible shortly after the formation of optic primordia and is characterized by the rounding of cells and disruption of the ventricular surface in the eye and brain neuroepithelia. With exception of the dorsal- and ventral-most regions of the brain, neuroepithelial cells lose their integrity and begin to distribute ectopically. At later stages, the laminar patterning of retinal neurons is severely disrupted. Despite the lack of lamination, individual retinal cell classes differentiate in the glass onion retina. Mosaic analysis reveals that the glass onion mutation acts cell nonautonomously within the retina and brain, as neuroepithelial cell morphology and polarity in these tissues are normal when mutant cells develop in wild-type hosts. We conclude that the glass onion mutation affects cell-cell signaling event(s) involved in the maintenance of the neuroepithelial cell layer shortly after its formation. The disruption of neuroepithelial integrity may be the cause of the neuronal patterning defects following neurogenesis. In addition, the expression of the glass onion phenotype in a subset of neuroepithelial cells as well as its onset following the initial formation of the neuroepithelial sheets indicate the presence of genetically distinct temporal and spatial subdivisions in the development of this histologically uniform tissue.

  4. L712V mutation in the androgen receptor gene causes complete androgen insensitivity syndrome due to severe loss of androgen function.

    PubMed

    Rajender, Singh; Gupta, Nalini J; Chakrabarty, Baidyanath; Singh, Lalji; Thangaraj, Kumarasamy

    2013-12-11

    Inability to respond to the circulating androgens is named as androgen insensitivity syndrome (AIS). Mutations in the androgen receptor (AR) gene are the most common cause of AIS. A cause and effect relationship between some of these mutations and the AIS phenotype has been proven by in vitro studies. Several other mutations have been identified, but need to be functionally validated for pathogenicity. Screening of the AR mutations upon presumptive diagnosis of AIS is recommended. We analyzed a case of complete androgen insensitivity syndrome (CAIS) for mutations in the AR gene. Sequencing of the entire coding region revealed C>G mutation (CTT-GTT) at codon 712 (position according to the NCBI database) in exon 4 of the gene, resulting in replacement of leucine with valine in the ligand-binding domain of the AR protein. No incidence of this mutation was observed in 230 normal male individuals analyzed for comparison. In vitro androgen binding and transactivation assays using mutant clone showed approximately 71% loss of ligand binding and about 76% loss of transactivation function. We conclude that CAIS in this individual was due to L712V substitution in the androgen receptor protein.

  5. Somatic-cell selection is a major determinant of the blood-cell phenotype in heterozygotes for glucose-6-phosphate dehydrogenase mutations causing severe enzyme deficiency

    SciTech Connect

    Filosa, S.; Giacometti, N.; Wangwei, C.; Martini, G.

    1996-10-01

    X-chromosome inactivation in mammals is regarded as an essentially random process, but the resulting somatic-cell mosaicism creates the opportunity for cell selection. In most people with red-blood-cell glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme-deficient phenotype is only moderately expressed in nucleated cells. However, in a small subset of hemizygous males who suffer from chronic nonspherocytic hemolytic anemia, the underlying mutations (designated class I) cause more-severe G6PD deficiency, and this might provide an opportunity for selection in heterozygous females during development. In order to test this possibility we have analyzed four heterozygotes for class I G6PD mutations: two with G6PD Portici (1178G{r_arrow}A) and two with G6PD Bari (1187C{r_arrow}T). We found that in fractionated blood cell types (including erythroid, myeloid, and lymphoid cell lineages) there was a significant excess of G6PD-normal cells. The significant concordance that we have observed in the degree of imbalance in the different blood-cell lineages indicates that a selective mechanism is likely to operate at the level of pluripotent blood stem cells. Thus, it appears that severe G6PD deficiency affects adversely the proliferation or the survival of nucleated blood cells and that this phenotypic characteristic is critical during hematopoiesis. 65 refs., 6 figs., 3 tabs.

  6. Mutations in BCAP31 Cause a Severe X-Linked Phenotype with Deafness, Dystonia, and Central Hypomyelination and Disorganize the Golgi Apparatus

    PubMed Central

    Cacciagli, Pierre; Sutera-Sardo, Julie; Borges-Correia, Ana; Roux, Jean-Christophe; Dorboz, Imen; Desvignes, Jean-Pierre; Badens, Catherine; Delepine, Marc; Lathrop, Mark; Cau, Pierre; Lévy, Nicolas; Girard, Nadine; Sarda, Pierre; Boespflug-Tanguy, Odile; Villard, Laurent

    2013-01-01

    BAP31 is one of the most abundant endoplasmic reticulum (ER) membrane proteins. It is a chaperone protein involved in several pathways, including ER-associated degradation, export of ER proteins to the Golgi apparatus, and programmed cell death. BAP31 is encoded by BCAP31, located in human Xq28 and highly expressed in neurons. We identified loss-of-function mutations in BCAP31 in seven individuals from three families. These persons suffered from motor and intellectual disabilities, dystonia, sensorineural deafness, and white-matter changes, which together define an X-linked syndrome. In the primary fibroblasts of affected individuals, we found that BCAP31 deficiency altered ER morphology and caused a disorganization of the Golgi apparatus in a significant proportion of cells. Contrary to what has been described with transient-RNA-interference experiments, we demonstrate that constitutive BCAP31 deficiency does not activate the unfolded protein response or cell-death effectors. Rather, our data demonstrate that the lack of BAP31 disturbs ER metabolism and impacts the Golgi apparatus, highlighting an important role for BAP31 in ER-to-Golgi crosstalk. These findings provide a molecular basis for a Mendelian syndrome and link intracellular protein trafficking to severe congenital brain dysfunction and deafness. PMID:24011989

  7. Mutations in BCAP31 cause a severe X-linked phenotype with deafness, dystonia, and central hypomyelination and disorganize the Golgi apparatus.

    PubMed

    Cacciagli, Pierre; Sutera-Sardo, Julie; Borges-Correia, Ana; Roux, Jean-Christophe; Dorboz, Imen; Desvignes, Jean-Pierre; Badens, Catherine; Delepine, Marc; Lathrop, Mark; Cau, Pierre; Lévy, Nicolas; Girard, Nadine; Sarda, Pierre; Boespflug-Tanguy, Odile; Villard, Laurent

    2013-09-05

    BAP31 is one of the most abundant endoplasmic reticulum (ER) membrane proteins. It is a chaperone protein involved in several pathways, including ER-associated degradation, export of ER proteins to the Golgi apparatus, and programmed cell death. BAP31 is encoded by BCAP31, located in human Xq28 and highly expressed in neurons. We identified loss-of-function mutations in BCAP31 in seven individuals from three families. These persons suffered from motor and intellectual disabilities, dystonia, sensorineural deafness, and white-matter changes, which together define an X-linked syndrome. In the primary fibroblasts of affected individuals, we found that BCAP31 deficiency altered ER morphology and caused a disorganization of the Golgi apparatus in a significant proportion of cells. Contrary to what has been described with transient-RNA-interference experiments, we demonstrate that constitutive BCAP31 deficiency does not activate the unfolded protein response or cell-death effectors. Rather, our data demonstrate that the lack of BAP31 disturbs ER metabolism and impacts the Golgi apparatus, highlighting an important role for BAP31 in ER-to-Golgi crosstalk. These findings provide a molecular basis for a Mendelian syndrome and link intracellular protein trafficking to severe congenital brain dysfunction and deafness.

  8. Cellular mechanisms underlying the increased disease severity seen for patients with long QT syndrome caused by compound mutations in KCNQ1.

    PubMed

    Harmer, Stephen C; Mohal, Jagdeep S; Royal, Alice A; McKenna, William J; Lambiase, Pier D; Tinker, Andrew

    2014-08-15

    The KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) gene encodes the Kv7.1 potassium channel which forms a complex with KCNE1 (potassium voltage-gated channel Isk-related family member 1) in the human heart to produce the repolarizing IKs (slow delayed rectifier potassium current). Mutations in KCNQ1 can perturb IKs function and cause LQT1 (long QT syndrome type 1). In LQT1, compound mutations are relatively common and are associated with increased disease severity. LQT1 compound mutations have been shown to increase channel dysfunction, but whether other disease mechanisms, such as defective channel trafficking, contribute to the increase in arrhythmic risk has not been determined. Using an imaging-based assay we investigated the effects of four compound heterozygous mutations (V310I/R594Q, A341V/P127T, T391I/Q530X and A525T/R518X), one homozygous mutation (W248F) and one novel compound heterozygous mutation (A178T/K422fs39X) (where fs denotes frameshift) on channel trafficking. By analysing the effects in the equivalent of a homozygous, heterozygous and compound heterozygous condition, we identify three different types of behaviour. A341V/P127T and W248F/W248F had no effect, whereas V310I/R594Q had a moderate, but not compound, effect on channel trafficking. In contrast, T391I/Q530X, A525T/R518X and A178T/K422fs39X severely disrupted channel trafficking when expressed in compound form. In conclusion, we have characterized the disease mechanisms for six LQT1 compound mutations and report that, for four of these, defective channel trafficking underlies the severe clinical phenotype.

  9. Increased frequency of mitral valve prolapse in patients with deviated nasal septum.

    PubMed

    Arslan, Hasan Huseyin; Aparci, Mustafa; Arslan, Zekeriya; Ozturk, Cengiz; Isilak, Zafer; Balta, Sevket; Celik, Turgay; Iyisoy, Atila

    2015-07-01

    Any abnormality of collagen may affect the tissues with higher collagen content, e.g., joints, heart valves, and great arteries. Mitral valve prolapse (MVP) is a characteristic of generalized collagen abnormality. Nasal septum (NS) is constituted by osseous and cartilaginous septums that are highly rich in collagen. We evaluated the co-existence of deviation of NS (DNS) in patients with MVP. We retrospectively evaluated the recordings of echocardiographic and nasal examinations of subjects with MVP and DNS. We analyzed the features of MVP and anatomical classification of DNS among subjects. Totally, 74 patients with DNS and 38 subjects with normal nasal passage were enrolled to the study. Presence of MVP was significantly higher in patients with DNS compared to normal subjects (63 vs 26%, p < 0.001). Prolapse of anterior, posterior and both leaflets was higher in patients with DNS. Thickness of anterior mitral leaflet was significantly increased in patients with DNS (3.57 ± 0.68 vs 4.59 ± 1.1 mm, p < 0.001) compared to normal subjects. Type I, II, and III, IV DNS were higher in frequency in patients with MVP while type V and VI were higher in normal subjects. DNS is highly co-existent with MVP and increased thickness of mitral anterior leaflet. Generalized abnormality of collagen which is the main component of mitral valves and nasal septum may be accounted for co-existence of MVP and DNS. Also co-existence of them may exaggerate the symptoms of patients with MVP due to limited airflow through the nasal passage.

  10. Stimulation of the medial septum should benefit patients with temporal lobe epilepsy.

    PubMed

    Fisher, Robert S

    2015-06-01

    Electrical stimulation of the septal nuclei via deep brain stimulating electrodes is proposed as a potentially beneficial therapy for medication-resistant temporal lobe epilepsy. In a multicenter study, stimulation of anterior thalamus was shown to reduce numbers of seizures, but decrease was only in the range of 40%. This might be improved with septal stimulation, which has strong and direct reciprocal connections with the hippocampal formation, the structure most involved in temporal lobe epilepsy. Medial septal neurons drive a 3-12 Hz theta rhythm in hippocampus of rodents. Theta rhythm is less obvious in human hippocampus, but it is present and it varies with cognitive tasks. The hippocampal theta rhythm is disrupted by seizures. In animal models, restoration of theta by sensory stimulation, septal electrical stimulation or cholinergic drugs infused into septum ameliorates seizures. Seizure activity in hippocampus is faithfully reflected in septal nuclei, and septum sometimes leads the seizure activity. A subset of patients with temporal lobe epilepsy have structural enlargement of their septal nuclei. At high levels of intensity, septal stimulation is subjectively pleasurable and strongly reinforcing. Rats will repeatedly press a bar to stimulate their septum. Initial experience with human septal stimulation in the 1950s was not favorable, with ineffective therapy for schizophrenia and a high rate of surgical complications. Subsequent experience in 50-100 pain patients employing modern neurosurgical techniques was more favorable and demonstrated septal stimulation to be safe and tolerable. The current state of knowledge is sufficient to consider design of a clinical trial of medial septal stimulation in selected patients with medication-resistant temporal lobe epilepsy.

  11. Ulnar entrapment neuropathy along the medial intermuscular septum in the midarm.

    PubMed

    Nakajima, Masashi; Ono, Nobuko; Kojima, Tomoko; Kusunose, Koichi

    2009-05-01

    We report a patient with primary ulnar entrapment neuropathy in the midarm. Stimulation of multiple sites along the ulnar nerve showed a motor conduction block at a distance of 7.5-10 cm proximal to the medial epicondyle, where the nerve was compressed by the medial intermuscular septum. Anatomically, the possibility of ulnar nerve entrapment in this segment has long been suggested, and stimulation at least 10 cm above the medial epicondyle may reveal the entrapment. Muscle Nerve 39: 707-710, 2009.

  12. Deviated Septum

    MedlinePlus

    ... Copyright © 2016 American Academy of Otolaryngology–Head and Neck Surgery. Reproduction or republication strictly prohibited without prior written ... Copyright 2017. American Academy of Otolaryngology — Head and Neck Surgery 1650 Diagonal Rd Alexandria, VA 22314 tel (703) ...

  13. Human SOD1 ALS Mutations in a Drosophila Knock-In Model Cause Severe Phenotypes and Reveal Dosage-Sensitive Gain- and Loss-of-Function Components.

    PubMed

    Şahin, Aslı; Held, Aaron; Bredvik, Kirsten; Major, Paxton; Achilli, Toni-Marie; Kerson, Abigail G; Wharton, Kristi; Stilwell, Geoff; Reenan, Robert

    2017-02-01

    Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage. Thus, issues of whether the ALS-like phenotypes of these models stem from overexpression of mutant alleles or from aspects of the SOD1 mutation itself are not easily deconvolved. To address concerns about levels of mutant SOD1 in disease pathogenesis, we have genetically engineered four human ALS-causing SOD1 point mutations (G37R, H48R, H71Y, and G85R) into the endogenous locus of Drosophila SOD1 (dsod) via ends-out homologous recombination and analyzed the resulting molecular, biochemical, and behavioral phenotypes. Contrary to previous transgenic models, we have recapitulated ALS-like phenotypes without overexpression of the mutant protein. Drosophila carrying homozygous mutations rendering SOD1 protein enzymatically inactive (G85R, H48R, and H71Y) exhibited neurodegeneration, locomotor deficits, and shortened life span. The mutation retaining enzymatic activity (G37R) was phenotypically indistinguishable from controls. While the observed mutant dsod phenotypes were recessive, a gain-of-function component was uncovered through dosage studies and comparisons with age-matched dsod null animals, which failed to show severe locomotor defects or nerve degeneration. We conclude that the Drosophila knock-in model captures important aspects of human SOD1-based ALS and provides a powerful and useful tool for further genetic studies.

  14. Repercussions of Surgically Assisted Maxillary Expansion on Nose Width and Position of Septum and Inferior Nasal Conchae

    PubMed Central

    Landim, Fabrício Souza; Freitas, George Borba; Malouf, Andreana Braga; Studart, Liana P. Carvalho; Rocha, Nelson Studart; de Souza Andrade, Emanuel Sávio; Caubi, Antônio Figueiredo; Filho, José Rodrigues Laureano; Oliveira e Silva, Emanuel Dias

    2011-01-01

    The aim of the present study was to assess the clinical and radiographic repercussions of surgically assisted maxillary expansion on the septum, nasal cavity and nasal conchae. The sample was made up of 15 patients with skeletal maturity (9 females and 6 males between 16 and 45 years of age) and maxillary transverse deficiency. Assessments were performed through anterior rhinoscopy and frontal cephalometric radiographs on three occasions: (T0) preoperative period, (T1) locking of the expander and (T2) six months following the locking procedure. An increase was observed in the basal portion of the pyriform aperture and distances between the lateral wall of the basal portion of the pyriform aperture and the septum. The radiographic exam revealed that the nasal septum did not undergo any statistically significant change in its position. Moreover, no significant changes in the position of the nasal septum or nasal conchae were detected throughout the three evaluation times. The results suggest that surgically assisted maxillary expansion is capable of widening the basal portion of the pyriform aperture, with little repercussion on the anterior position of the nasal septum and inferior nasal conchae. PMID:22135612

  15. The medial septum mediates impairment of prepulse inhibition of acoustic startle induced by a hippocampal seizure or phencyclidine.

    PubMed

    Ma, Jingyi; Shen, Bixia; Rajakumar, N; Leung, L Stan

    2004-11-05

    The involvement of the septohippocampal system on the impaired sensorimotor gating induced by phencyclidine (PCP) or by an electrically induced hippocampal seizure was examined in behaving rats. An impaired sensorimotor gating, measured by prepulse inhibition (PPI) of the acoustic startle response, was observed following a hippocampal afterdischarge (AD) or systemic injection of PCP and was accompanied with an increase in hippocampal gamma waves (30-70 Hz). The medial septum infusion with muscimol (0.25 microg), a GABA(A) receptor agonist, 15 min prior to PCP or a hippocampal AD, prevented the impairment of sensorimotor gating and the increase in gamma waves. By itself, muscimol (0.25 microg) injection into the medial septum did not affect PPI, although it significantly suppressed spontaneous gamma waves. In order to identify subpopulations of neurons mediating the sensorimotor gating deficit and the hippocampal gamma wave increase, 0.14-0.21 microg of p75 antibody conjugated to saporin (192 IgG-saporin) was injected into the medial septum to selectively lesion the septohippocampal cholinergic neurons. Neither the PPI deficit nor the gamma wave increase induced by PCP or a hippocampal AD was affected by 192 IgG-saporin lesion of the medial septum. It is concluded that increase in neural activity in the medial septum participates in the impairment of sensorimotor gating and the increase in hippocampal gamma waves induced by PCP or a hippocampal AD. It is suggested that the GABAergic but not the cholinergic septohippocampal neurons mediate the sensorimotor gating deficit.

  16. Herbicides implicated as the cause of severe mangrove dieback in the Mackay region, NE Australia: consequences for marine plant habitats of the GBR World Heritage Area.

    PubMed

    Duke, Norman C; Bell, Alicia M; Pederson, Dan K; Roelfsema, Chris M; Bengtson Nash, Susan

    2005-01-01

    Herbicides, particularly diuron, were correlated with severe and widespread dieback of the dominant mangrove, Avicennia marina (Forsk.) Vierh. var. eucalyptifolia (Val.) N.C. Duke (Avicenniaceae), its reduced canopy condition, and declines in seedling health within three neighbouring estuaries in the Mackay region of NE Australia. This unusual species-specific dieback, first observed in the early 1990s, had gotten notably worse by 2002 to affect >30 km(2) of mangroves in at least five adjacent estuaries in the region. Over the past century, agricultural production has responded well to the demands of increasing population with improvements in farm efficiency assisted by significant increases in the use of agricultural chemicals. However, with regular and episodic river flow events, these chemicals have sometimes found their way into estuarine and nearshore water and sediments where their effects on marine habitats have been largely unquantified. Investigations over the last three years in the Mackay region provide compelling evidence of diuron, and possibly other agricultural herbicides, as the most likely cause of the severe and widespread mangrove dieback. The likely consequences of such dieback included declines in coastal water quality with increased turbidity, nutrients and sediment deposition, as well as further dispersal of the toxic chemicals. The implications of such findings are immense since they describe not only the serious deterioration of protected and beneficial mangrove habitat but also the potential for significant direct and indirect effects on other highly-valued estuarine and marine habitats in the region, including seagrass beds and coral reefs of the Great Barrier Reef lagoon. This article reviews all key findings and observations to date and describes the essential correlative and causative evidence.

  17. Cortactin deficiency causes increased RhoA/ROCK1-dependent actomyosin contractility, intestinal epithelial barrier dysfunction, and disproportionately severe DSS-induced colitis.

    PubMed

    Citalán-Madrid, A F; Vargas-Robles, H; García-Ponce, A; Shibayama, M; Betanzos, A; Nava, P; Salinas-Lara, C; Rottner, K; Mennigen, R; Schnoor, M

    2017-01-25

    The intestinal epithelium constitutes a first line of defense of the innate immune system. Epithelial dysfunction is a hallmark of intestinal disorders such as inflammatory bowel diseases (IBDs). The actin cytoskeleton controls epithelial barrier integrity but the function of actin regulators such as cortactin is poorly understood. Given that cortactin controls endothelial permeability, we hypothesized that cortactin is also important for epithelial barrier regulation. We found increased permeability in the colon of cortactin-KO mice that was accompanied by reduced levels of ZO-1, claudin-1, and E-cadherin. By contrast, claudin-2 was upregulated. Cortactin deficiency increased RhoA/ROCK1-dependent actomyosin contractility, and inhibition of ROCK1 rescued the barrier defect. Interestingly, cortactin deficiency caused increased epithelial proliferation without affecting apoptosis. KO mice did not develop spontaneous colitis, but were more susceptible to dextran sulfate sodium colitis and showed severe colon tissue damage and edema formation. KO mice with colitis displayed strong mucus deposition and goblet cell depletion. In healthy human colon tissues, cortactin co-localized with ZO-1 at epithelial cell contacts. In IBDs patients, we observed decreased cortactin levels and loss of co-localization with ZO-1. Thus, cortactin is a master regulator of intestinal epithelial barrier integrity in vivo and could serve as a suitable target for pharmacological intervention in IBDs.Mucosal Immunology advance online publication, 25 January 2017; doi:10.1038/mi.2016.136.

  18. Toxic epidermal necrolysis caused by acetaminophen featuring almost 100% skin detachment: Acetaminophen is associated with a risk of severe cutaneous adverse reactions.

    PubMed

    Watanabe, Hideaki; Kamiyama, Taisuke; Sasaki, Shun; Kobayashi, Kae; Fukuda, Kenichiro; Miyake, Yasufumi; Aruga, Tohru; Sueki, Hirohiko

    2016-03-01

    Toxic epidermal necrolysis (TEN) is an adverse reaction that can be induced by various drugs; the associated mortality rate is 20-25%. A previous report showed a weak association between TEN and acetaminophen. Recently, the US Food and Drug Administration declared that acetaminophen is associated with a risk of serious skin reactions, including TEN. Here, we describe the case of a 43-year-old Japanese woman with TEN caused by acetaminophen. She had poorly controlled ulcerative colitis and was treated with high doses of prednisolone, infliximab, acetaminophen and lansoprazole. Nine days after administrating acetaminophen, targetoid erythematous and bullous lesions appeared on the patient's trunk, palms and the soles of her feet. The skin lesions expanded rapidly; within 3 weeks, skin detachment was detected across nearly 100% of the patient's body. However, no mucosal involvement of the eyes, oral cavity or genitalia was found. We performed lymphocyte transformation tests using various drugs; however, a high stimulation index was obtained only with acetaminophen. The patient recovered following treatment with plasmapheresis, i.v. immunoglobulin therapy, topical medication and supportive therapy. Acetaminophen is included in many prescription and over-the-counter products; thus, clinicians should monitor their patients for severe drug reactions, including TEN.

  19. Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections

    PubMed Central

    Meester, Josephina A.N.; Vandeweyer, Geert; Pintelon, Isabel; Lammens, Martin; Van Hoorick, Lana; De Belder, Simon; Waitzman, Kathryn; Young, Luciana; Markham, Larry W.; Vogt, Julie; Richer, Julie; Beauchesne, Luc M.; Unger, Sheila; Superti-Furga, Andrea; Prsa, Milan; Dhillon, Rami; Reyniers, Edwin; Dietz, Harry C.; Wuyts, Wim; Mortier, Geert; Verstraeten, Aline; Van Laer, Lut; Loeys, Bart L.

    2016-01-01

    Purpose Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene only explain a small number of X-linked TAAD families. Methods We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was carried out. Results We found five individuals with loss-of-function mutations in BGN, encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures and mild skeletal dysplasia. Fluorescent stainings revealed an increase in TGF-β signalling, evidenced by an increase in nuclear pSMAD2 in aortic wall. Our results are in line with prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture. Conclusion In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD, associated with preservation of elastic fibres and increased TGF-β signalling. PMID:27632686

  20. A series of abnormal climatic conditions caused the most severe outbreak of first-generation adults of the meadow moth ( Loxostege sticticalis L.) in China

    NASA Astrophysics Data System (ADS)

    Chen, Xiao; Zeng, Juan; Zhai, Baoping

    2016-06-01

    The meadow moth, Loxostege sticticalis L., is a destructive migratory pest in the northern temperate zone. The outbreak mechanism of first-generation adults in China remains unclear. In 2008, the density of first-generation larvae was very low or even negligible in most sites in China. However, a great number of first-generation adults appeared unexpectedly in late July, and their offspring caused the most severe infestation on record. The present study aims to determine where the large influx of immigrant adults originated from and how this unprecedented population was established. Source areas were explored by trajectory analysis, and climatic patterns related to the population increase were investigated. Results showed that the outbreak population mainly immigrated from Northeast Mongolia and the Chita State of Russia, and the buildup of such a large population could be attributed to an exceptional northward migration of overwintered adults from North China to East Mongolia in the spring of 2007 and unusually favourable climatic conditions in the next two growth seasons. These results indicated that the population dynamics of meadow moth in Northeast Asia would be difficult to predict when only considering local climatic factors and population size within one country. International joint monitoring and information sharing related to this pest between China, Mongolia and Russia should be implemented.

  1. Interaction of a vasopressin antagonist with vasopressin receptors in the septum of the rat brain

    SciTech Connect

    Dorsa, D.M.; Brot, M.D.; Shewey, L.M.; Meyers, K.M.; Szot, P.; Miller, M.A.

    1988-01-01

    The ability of d(CH2)5-Tyr(Me)-arginine-8-vasopressin, an antagonist of peripheral pressoric (V1-type) vasopressin receptors, to label vasopressin binding sites in the septum of the rat brain was evaluated. Using crude membrane preparations from the septum, /sup 3/H-arginine-8-vasopressin (AVP) specifically labels a single class of binding sites with a Kd of 2.9 nM and maximum binding site concentration of 19.8 fmole/mg protein. /sup 3/H-Antag also labels a single class of membrane sites but with higher affinity (Kd = 0.47 nM) and lower capacity (10.1 fmole/mg protein) than /sup 3/H-AVP. The rank order of potency of various competitor peptides for /sup 3/H-AVP and /sup 3/H-Antag binding was similar. Oxytocin was 100-1,000 fold less potent than AVP in competing for binding with both ligands. /sup 3/H-AVP and /sup 3/H-Antag showed similar labeling patterns when incubated with septal tissue slices. Unlabeled Antag also effectively antagonized vasopressin-stimulated phosphatidylinositol hydrolysis in septal tissue slices.

  2. Fine structure and synaptology of the nitrergic neurons in medial septum of the rat brain.

    PubMed

    Halasy, Katalin; Szőke, Balázs; Janzsó, Gergely

    2017-03-01

    The nitrergic neuron population and certain aspects of their connectivity (peptidergic inputs, co-localization with GABA, synaptic target distribution) were studied in the medial septum of the rat brain. The histochemical localization of NADPH diaphorase and immunohistochemical identification of nNOS at light and electron microscopic level was applied. Double-labeling experiments with galanin and leucine enkephalin, moreover the postembedding GABA immunogold staining was also carried out. NADPH diaphorase- and nNOS-immunopositive neurons could be identified inside the borders of medial septum. Out of their peptidergic inputs galanin- and leucine enkephaline-immunopositive varicose fibers were found in close apposition with nNOS-immunopositive neurons. Based on fine structural characteristics (large indented nucleus, thin cytoplasmic rim, lack of axosomatic synapses) the nitrergic neurons are suggested to be identical with the septal cholinergic nerve cells. Their boutons established asymmetrical synapses mainly on dendritic shafts and spines, some of which were also nNOS-immunopositive. A lower amount of nNOS-immunopositive boutons of presumably extrinsic origin were found to be GABAergic.

  3. Maturation and maintenance of cholinergic medial septum neurons require glucocorticoid receptor signaling.

    PubMed

    Guijarro, Christian; Rutz, Susanne; Rothmaier, Katharina; Turiault, Marc; Zhi, Qixia; Naumann, Thomas; Frotscher, Michael; Tronche, Francois; Jackisch, Rolf; Kretz, Oliver

    2006-05-01

    Glucocorticoids have been shown to influence trophic processes in the nervous system. In particular, they seem to be important for the development of cholinergic neurons in various brain regions. Here, we applied a genetic approach to investigate the role of the glucocorticoid receptor (GR) on the maturation and maintenance of cholinergic medial septal neurons between P15 and one year of age by using a mouse model carrying a CNS-specific conditional inactivation of the GR gene (GRNesCre). The number of choline acetyltransferase and p75NTR immuno-positive neurons in the medial septum (MS) was analyzed by stereology in controls versus mutants. In addition, cholinergic fiber density, acetylcholine release and cholinergic key enzyme activity of these neurons were determined in the hippocampus. We found that in GRNesCre animals the number of medial septal cholinergic neurons was significantly reduced during development. In addition, cholinergic cell number further decreased with aging in these mutants. The functional GR gene is therefore required for the proper maturation and maintenance of medial septal cholinergic neurons. However, the loss of cholinergic neurons in the medial septum is not accompanied by a loss of functional cholinergic parameters of these neurons in their target region, the hippocampus. This pinpoints to plasticity of the septo-hippocampal system, that seems to compensate for the septal cell loss by sprouting of the remaining neurons.

  4. Myoepithelioma of the Nasal Septum: A Rare Case of Extrasalivary Gland Involvement

    PubMed Central

    Camurugy, Tatiane Costa; Ribeiro, Thiago Cavalcante; Costa, Nara Nunes Barbosa; Azevedo, Amanda Canário Andrade; Vinhaes, Eriko Soares de Azevedo; de Andrade, Nilvano Alves

    2017-01-01

    Introduction. The myoepithelioma is a rare benign tumor, most frequently found in the salivary glands. The extrasalivary gland involvement is even rarer and few cases involving the nasal cavity have been reported in the literature. Case Report. MES, a 54-year-old woman, complaining of progressive nasal obstruction and mild epistaxis through the right nostril which had developed 1 year previously. Computed tomography scan showed tumor with heterogeneous contrast enhancement occupying the right nasal cavity, moving contralaterally in the nasal septum. Excisional biopsy was performed through endoscopic surgery of the mass that was inserted at the nasal septum. Pathological and immunohistochemical exams concluded myoepithelioma. Discussion. The main symptoms of nasal myoepitheliomas are nasal obstruction and epistaxis. Immunohistochemistry is necessary to confirm the diagnosis, typically positive for cytokeratin and S-100, calponin, smooth muscle actin, myosin, vimentin, glial fibrillary acidic protein (GFAP), and carcinoembryonic antigen. The main marker for myoepithelioma is the S-100 protein. In our case, it was positive for cytokeratin, S-100, calponin, actin smooth muscle, and GFAP. In all cases reported in the literature surgical treatment was performed and the recurrence was associated with incomplete tumor resection. Final Comments. The myoepithelioma is a rare differential diagnosis of nasal tumors and its treatment is the total lesion excision. PMID:28168074

  5. A New Membrane Protein Sbg1 Links the Contractile Ring Apparatus and Septum Synthesis Machinery in Fission Yeast

    PubMed Central

    Sethi, Kriti; Palani, Saravanan; Cortés, Juan C. G.; Sato, Mamiko; Sevugan, Mayalagu; Ramos, Mariona; Vijaykumar, Shruthi; Osumi, Masako; Naqvi, Naweed I.; Ribas, Juan Carlos; Balasubramanian, Mohan

    2016-01-01

    Cytokinesis in many organisms requires a plasma membrane anchored actomyosin ring, whose contraction facilitates cell division. In yeast and fungi, actomyosin ring constriction is also coordinated with division septum assembly. How the actomyosin ring interacts with the plasma membrane and the plasma membrane-localized septum synthesizing machinery remains poorly understood. In Schizosaccharomyces pombe, an attractive model organism to study cytokinesis, the β-1,3-glucan synthase Cps1p / Bgs1p, an integral membrane protein, localizes to the plasma membrane overlying the actomyosin ring and is required for primary septum synthesis. Through a high-dosage suppressor screen we identified an essential gene, sbg1+ (suppressor of beta glucan synthase 1), which suppressed the colony formation defect of Bgs1-defective cps1-191 mutant at higher temperatures. Sbg1p, an integral membrane protein, localizes to the cell ends and to the division site. Sbg1p and Bgs1p physically interact and are dependent on each other to localize to the division site. Loss of Sbg1p results in an unstable actomyosin ring that unravels and slides, leading to an inability to deposit a single contiguous division septum and an important reduction of the β-1,3-glucan proportion in the cell wall, coincident with that observed in the cps1-191 mutant. Sbg1p shows genetic and / or physical interaction with Rga7p, Imp2p, Cdc15p, and Pxl1p, proteins known to be required for actomyosin ring integrity and efficient septum synthesis. This study establishes Sbg1p as a key member of a group of proteins that link the plasma membrane, the actomyosin ring, and the division septum assembly machinery in fission yeast. PMID:27749909

  6. Pyroglutamyl peptidase II inhibition enhances the analeptic effect of thyrotropin-releasing hormone in the rat medial septum.

    PubMed

    Lazcano, Ivan; Uribe, Rosa Maria; Martínez-Chávez, Erick; Vargas, Miguel Angel; Matziari, Magdalini; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2012-07-01

    Thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH(2)) has multiple, but transient, homeostatic functions in the brain. It is hydrolyzed in vitro by pyroglutamyl peptidase II (PPII), a narrow specificity ectoenzyme with a preferential localization in the brain, but evidence that PPII controls TRH communication in the brain in vivo is scarce. We therefore studied in male Wistar rats the distribution of PPII mRNA in the septum and the consequence of PPII inhibition on the analeptic effect of TRH injected into the medial septum. Twelve to 14% of cell profiles expressed PPII mRNA in the medial septum-diagonal band of Broca; in this region the specific activity of PPII was relatively high. Twenty to 35% of PPII mRNA-labeled profiles were positive for TRH-receptor 1 (TRH-R1) mRNA. The intramedial septum injection of TRH reduced, in a dose-dependent manner, the duration of ethanol-induced loss of righting reflex (LORR). Injection of the PPII inhibitor pGlu-Asn-Pro-7-amido-4-methylcoumarin into the medial septum enhanced the effect of TRH. The injection of a phosphinic TRH analog, a higher-affinity inhibitor of PPII, diminished the duration of LORR by itself. In contrast, the intraseptal injection of pGlu-Asp-Pro-NH(2), a peptide that did not inhibit PPII activity, or an inhibitor of prolyl oligopeptidase did not change the duration of LORR. We conclude that in the medial septum PPII activity may limit TRH action, presumably by reducing the concentration of TRH in the extracellular fluid around cells coexpressing PPII and TRH-R1.

  7. Environmental conditions that contribute to development and severity of Sugar Beet Fusarium Yellows caused by Fusarium oxysporum f. sp. betae: temperature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium yellows in sugar beet, caused by Fusarium oxysporum f. sp. betae, continues to cause significant problems to sugar beet production by causing considerable reductions in root yield, sucrose percentage, and juice purity in affected sugar beets. Environment plays a critical role in pathogen i...

  8. A case of ring chromosome 22 with deletion of the 22q13.3 region associated with agenesis of the corpus callosum, fornix and septum pellucidum.

    PubMed

    Delcán, José; Orera, María; Linares, Rafael; Saavedra, Dolores; Palomar, Angustias

    2004-08-01

    We report a 16-week-gestation foetus obtained by voluntary abortion after prenatal diagnosis, in which a ring chromosome 22 was observed with deletion of the 22q13.3 region. A prenatal study of the amniotic fluid by standard chromosome technique with G bands and FISH (fluorescence in situ hybridisation) was performed. After the abortion, the anatomopathological study of the obtained foetus was carried out. Morphological and histological analysis of the foetus did not reveal severe physical abnormalities, although alterations of the nervous system were observed consisting of corpus callosum, fornix and septum pellucidum agenesia. It could be that the genes in this region that were involved in the development of the central nervous system were responsible for the alterations found in the morphological study. The wide range of manifestations observed in patients with this cytogenetic alteration is probably due to size differences in the deleted region.

  9. Retrograde cell changes in medial septum and diagonal band following fimbria-fornix transection: quantitative temporal analysis.

    PubMed

    Gage, F H; Wictorin, K; Fischer, W; Williams, L R; Varon, S; Bjorklund, A

    1986-09-01

    Complete unilateral fimbria-fornix transections, including the overlying cingulate cortex, were administered to female rats. At time points from 1 day to 6 weeks, the septal-diagonal band region was examined using acetylcholinesterase histochemistry, Cresyl Violet cell staining, and choline acetyltransferase biochemistry. As early as 1 day following the transection a decrease in acetylcholinesterase positive cell body staining was observed in the medial septum; however, no loss of Nissl-stained neurons was measured in Cresyl Violet stained sections until 1 week after the lesion. Maximal loss of acetylcholinesterase-positive cells, as visualized after irreversible acetylcholinesterase inhibition, was measured at 1 week, and no further change was observed at time points up to 6 weeks after operation. The loss of acetyltransferase-positive cells was greatest in the medial septal area (-65%) and the vertical limb of the diagonal band (-55%). Little cell loss was measured in the horizontal limb of the diagonal band. This is consistent with the known projections of these cell bodies. Remaining acetylcholinesterase-positive cell bodies in the medial septum had shrunk by about 20% (measured as the diameter along the major axis). A marked neuronal cell loss (about 50%) was demonstrable in the medial septum and vertical limb of the diagonal band in the Cresyl Violet-stained sections, too. A pile-up of acetylcholinesterase-stained material was observed in the dorsal-lateral quadrant of the septal area just proximal to the lesion at 1 day following transection. This pile-up occurred in the medial septum and diagonal band area up to 1 week following the transection, and had nearly disappeared by 2 weeks post-transection. Choline acetyltransferase biochemical activity, measured in samples of whole septum, decreased significantly at 1 day but subsequently returned to control levels. By 2 weeks following transection, an increase in acetylcholinesterase-positive stained fibers was

  10. Double-outlet right ventricle with an intact interventricular septum and concurrent hypoplastic left ventricle in a calf.

    PubMed

    Newhard, D K; Jung, S W; Winter, R L; Kuca, T; Bayne, J; Passler, T

    2017-01-19

    A 3-day-old Hereford heifer calf presented for evaluation of lethargy and dyspnea, with persistent hypoxia despite supplemental oxygen therapy. A grade III/VI right apical systolic murmur was noted during cardiac auscultation. Echocardiography revealed a double-outlet right ventricle with an intact interventricular septum and concurrent hypoplastic left ventricle and tricuspid valve dysplasia. Post-mortem examination revealed additional congenital anomalies of ductus arteriosus, patent foramen ovale, and persistent left cranial vena cava. This report illustrates the use of echocardiographic images to diagnose a double-outlet right ventricle with an intact interventricular septum and a hypoplastic left ventricle in a calf.

  11. Moderate-to-Severe Iodine Deficiency in the "First 1000 Days" Causes More Thyroid Hypofunction in Infants Than in Pregnant or Lactating Women.

    PubMed

    Stinca, Sara; Andersson, Maria; Herter-Aeberli, Isabelle; Chabaa, Laila; Cherkaoui, Mohamed; El Ansari, Nawal; Aboussad, Abdelmounaim; Weibel, Sandra; Zimmermann, Michael B

    2017-04-01

    Background: Iodine deficiency early in the life cycle-the "first 1000 days"-can cause hypothyroidism and irreversibly impair neuromotor development. However, the relative vulnerability among women and infants during this critical period is unclear, making it difficult for country-based programs with limited resources to prioritize their iodine interventions.Objective: Our aim was to determine the prevalence of thyroid hypofunction in women and infants living in an area of moderate-to-severe iodine deficiency.Methods: In a cross-sectional survey in Morocco, we measured urinary iodine concentrations (UICs) and concentrations of thyroid-stimulating hormone (TSH) and total or free thyroxine (TT4 or fT4, respectively) in women of reproductive age (n = 156), pregnant women (n = 245), and lactating women (n = 239) and their young infants (n = 239). We calculated daily iodine intakes and measured iodine concentrations in breast milk and household salt. We compared the incidence of hypothyroidism between the 3 groups of women and with the infants.Results: Women of reproductive age, pregnant women, and lactating women had median (IQR) UICs of 41 (29-63), 32 (17-58), and 35 (19-62) μg/L; and estimated iodine intakes were ∼60%, 22%, and 26% of Recommended Nutrient Intakes (RNIs). The infants' median UIC was 73 (28-157) μg/L, which was greater than for all 3 groups of women (P < 0.001), and their dietary intakes were 27% of the RNI. The prevalence of hypothyroidism was not significantly different between the 4 groups, whereas the prevalence of hypothyroxinemia was higher in infants (40%) than in the 3 groups of women (11-14%) (P < 0.001). The median breast-milk iodine concentration was 42 (26-81) μg/L. Only 6% of salt samples were adequately iodized to a concentration of ≥15 ppm; 54% were inadequately iodized and 40% contained no measurable iodine.Conclusions: In an area of moderate-to-severe iodine deficiency, the prevalence of thyroid hypofunction is ∼4-fold higher

  12. Severe Psychological Distress of Evacuees in Evacuation Zone Caused by the Fukushima Daiichi Nuclear Power Plant Accident: The Fukushima Health Management Survey

    PubMed Central

    Kunii, Yasuto; Suzuki, Yuriko; Shiga, Tetsuya; Yabe, Hirooki; Yasumura, Seiji; Maeda, Masaharu; Niwa, Shin-ichi; Otsuru, Akira; Mashiko, Hirobumi; Abe, Masafumi

    2016-01-01

    Background Following the Great East Japan Earthquake on March 11, 2011, the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant has continued to affect the mental health status of residents in the evacuation zone. To examine the mental health status of evacuee after the nuclear accident, we conducted the Mental Health and Lifestyle Survey as part of the ongoing Fukushima Health Management Survey. Methods We measured mental health status using the Kessler 6-item psychological distress scale (K6) in a total of 73,569 (response rate: 40.7%) evacuees aged 15 and over who lived in the evacuation zone in Fukushima Prefecture. We then dichotomized responders using a 12/13 cutoff on the K6, and compared the proportion of K6 scores ≥13 and ≤12 in each risk factor including demographic information, socioeconomic variables, and disaster-related variables. We also performed bivariate analyses between mental health status and possible risk factors using the chi-square test. Furthermore, we performed multivariate regression analysis using modified Poisson regression models. Results The median K6 score was 5 (interquartile range: 1–10). The number of psychological distress was 8,717 (14.6%). We found that significant differences in the prevalence of psychological distress by almost all survey items, including disaster-related risk factors, most of which were also associated with increased Prevalence ratios (PRs). Additionally, we found that psychological distress in each evacuation zone was significantly positively associated with the radiation levels in their environment (r = 0.768, p = 0.002). Conclusion The earthquake, tsunami and subsequent nuclear accident likely caused severe psychological distress among residents in the evacuation zone in Fukushima Prefecture. The close association between psychological distress and the radiation levels shows that the nuclear accident seriously influenced the mental health of the residents, which might be exacerbated by

  13. Mutation analyses and prenatal diagnosis in families of X-linked severe combined immunodeficiency caused by IL2Rγ gene novel mutation.

    PubMed

    Bai, Q L; Liu, N; Kong, X D; Xu, X J; Zhao, Z H

    2015-06-11

    We investigated the feasibility of interleukin-2 receptor gamma (IL2Rγ) gene based on gene mutation analysis and pre-natal diagnosis of X-linked severe combined immunodeficiency (X-SCID). Blood samples of patients and their parents of X-SCID (family 1) and X-SCID (family 2) were collected. IL2Rγ gene sequences of the 2 families were analyzed using bi-directional direct sequencing by polymerase chain reaction. DNA sequence changes in the IL2Rγ gene exon region and shear zone were also analyzed. We also sequenced the IL2Rγ gene in 100 healthy individuals. Prenatal genetic diagnoses for a high-risk fetus in family 1 were performed by chorionic villus sampling after determining each family's genotypes. The suspect fe-male in family 1 underwent carrier detection. Two novel mutations of IL2Rγ gene were identified, including c.361-363delGAG (p.E121del) in the patient and his mother in family 1, and c.510-511insGAACT (p.W173X) heterozygous mutation in the proband's mother in family 2. These mutations were absent in the 100 controls. Prenatal diagnosis of early pregnancy in the female fetus of family 1 was performed; the fetus was heterozygous, which was confirmed at postnatal follow-up. The suspect female in family 1 showed no mutation in carrier detection. The novel p.E121del and p.W173X mutations in IL2Rγ may have been the primary causes of disease in 2 families with X-SCID. In couples with an X-SCID reproductive history, prenatal gene mutation analysis of IL2Rγ can effectively prevent the birth of children with X-SCID and carrier detection for suspected females.

  14. High-dose cefepime as an alternative treatment for infections caused by TEM-24 ESBL-producing Enterobacter aerogenes in severely-ill patients.

    PubMed

    Goethaert, K; Van Looveren, M; Lammens, C; Jansens, H; Baraniak, A; Gniadkowski, M; Van Herck, K; Jorens, P G; Demey, H E; Ieven, M; Bossaert, L; Goossens, H

    2006-01-01

    This study evaluated retrospectively the efficacy of treatment with cefepime vs. a carbapenem, in combination with amikacin or ciprofloxacin, for seriously-ill patients infected with ESBL-producing Enterobacter aerogenes who were admitted to an intensive care unit. Forty-four episodes of infection were investigated in 43 patients: 21 treated with cefepime; 23 with a carbapenem. The two treatment groups did not differ statistically in terms of age, APACHE II scores, and infection sites, but the average duration of antibiotic exposure was significantly shorter in the cefepime group (8.5 days vs. 11.4 days; p 0.04). Clinical improvement was seen in 62% of patients receiving cefepime vs. 70% of patients receiving a carbapenem (p 0.59). Bacteriological eradication was achieved in 14% of patients receiving cefepime vs. 22% of patients receiving a carbapenem (p 0.76). The 30-day mortality rates related to infection were 33% in the cefepime group and 26% in the carbapenem group (p 0.44). Thus, outcome parameters did not differ significantly between the two groups. Nevertheless, a statistically significant increase in failure to eradicate ESBL-producing E. aerogenes was observed as the MICs of cefepime rose (p 0.017). Pulsed-field gel electrophoresis revealed three distinct clones, but one predominant clone harbouring the bla(TEM-24) gene was associated with most (42/44) of the episodes of infection. It was concluded that cefepime may be an alternative agent for therapy of severe infections caused by TEM-24 ESBL-producing E. aerogenes, although further studies are required to confirm these observations.

  15. Molecular composition and size distribution of sugars, sugar-alcohols and carboxylic acids in airborne particles during a severe urban haze event caused by wheat straw burning

    NASA Astrophysics Data System (ADS)

    Wang, Gehui; Chen, Chunlei; Li, Jianjun; Zhou, Bianhong; Xie, Mingjie; Hu, Shuyuan; Kawamura, Kimitaka; Chen, Yan

    2011-05-01

    Molecular compositions and size distributions of water-soluble organic compounds (WSOC, i.e., sugars, sugar-alcohols and carboxylic acids) in particles from urban air of Nanjing, China during a severe haze event caused by field burning of wheat straw were characterized and compared with those in the summer and autumn non-haze periods. During the haze event levoglucosan (4030 ng m -3) was the most abundant compound among the measured WSOC, followed by succinic acid, malic acid, glycerol, arabitol and glucose, being different from those in the non-haze samples, in which sucrose or azelaic acid showed a second highest concentration, although levoglucosan was the highest. The measured WSOC in the haze event were 2-20 times more than those in the non-hazy days. Size distribution results showed that there was no significant change in the compound peaks in coarse mode (>2.1 μm) with respect to the haze and non-haze samples, but a large difference in the fine fraction (<2.1 μm) was found with a sharp increase during the hazy days mostly due to the increased emissions of wheat straw burning. Molecular compositions of organic compounds in the fresh smoke particles from wheat straw burning demonstrate that sharply increased concentrations of glycerol and succinic and malic acids in the fine particles during the haze event were mainly derived from the field burning of wheat straw, although the sources of glucose and related sugar-alcohols whose concentrations significantly increased in the fine haze samples are unclear. Compared to that in the fresh smoke particles of wheat straw burning an increase in relative abundance of succinic acid to levoglucosan during the haze event suggests a significant production of secondary organic aerosols during transport of the smoke plumes.

  16. Effect of Elevated Atmospheric CO2 and Temperature on the Disease Severity of Rocket Plants Caused by Fusarium Wilt under Phytotron Conditions.

    PubMed

    Chitarra, Walter; Siciliano, Ilenia; Ferrocino, Ilario; Gullino, Maria Lodovica; Garibaldi, Angelo

    2015-01-01

    The severity of F. oxysporum f.sp. conglutinans on rocket plants grown under simulated climate change conditions has been studied. The rocket plants were cultivated on an infested substrate (4 log CFU g-1) and a non-infested substrate over three cycles. Pots were placed in six phytotrons in order to simulate different environmental conditions: 1) 400-450 ppm CO2, 18-22°C; 2) 800-850 ppm CO2, 18-22°C; 3) 400-450 ppm CO2, 22-26°C, 4) 800-850 ppm CO2, 22-26°C, 5) 400-450 ppm CO2, 26-30°C; 6) 800-850 ppm CO2, 26-30°C. Substrates from the infested and control samples were collected from each phytotron at 0, 60 and 120 days after transplanting. The disease index, microbial abundance, leaf physiological performances, root exudates and variability in the fungal profiles were monitored. The disease index was found to be significantly influenced by higher levels of temperature and CO2. Plate counts showed that fungal and bacterial development was not affected by the different CO2 and temperature levels, but a significant decreasing trend was observed from 0 up to 120 days. Conversely, the F. oxysporum f.sp. conglutinans plate counts did not show any significantly decrease from 0 up to 120 days. The fungal profiles, evaluated by means of polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE), showed a relationship to temperature and CO2 on fungal diversity profiles. Different exudation patterns were observed when the controls and infested plants were compared, and it was found that both CO2 and temperature can influence the release of compounds from the roots of rocket plants. In short, the results show that global climate changes could influence disease incidence, probably through plant-mediated effects, caused by soilborne pathogens.

  17. Effect of Elevated Atmospheric CO2 and Temperature on the Disease Severity of Rocket Plants Caused by Fusarium Wilt under Phytotron Conditions

    PubMed Central

    Chitarra, Walter; Siciliano, Ilenia; Ferrocino, Ilario; Gullino, Maria Lodovica; Garibaldi, Angelo

    2015-01-01

    The severity of F. oxysporum f.sp. conglutinans on rocket plants grown under simulated climate change conditions has been studied. The rocket plants were cultivated on an infested substrate (4 log CFU g-1) and a non-infested substrate over three cycles. Pots were placed in six phytotrons in order to simulate different environmental conditions: 1) 400–450 ppm CO2, 18–22°C; 2) 800–850 ppm CO2, 18–22°C; 3) 400–450 ppm CO2, 22–26°C, 4) 800–850 ppm CO2, 22–26°C, 5) 400–450 ppm CO2, 26–30°C; 6) 800–850 ppm CO2, 26–30°C. Substrates from the infested and control samples were collected from each phytotron at 0, 60 and 120 days after transplanting. The disease index, microbial abundance, leaf physiological performances, root exudates and variability in the fungal profiles were monitored. The disease index was found to be significantly influenced by higher levels of temperature and CO2. Plate counts showed that fungal and bacterial development was not affected by the different CO2 and temperature levels, but a significant decreasing trend was observed from 0 up to 120 days. Conversely, the F. oxysporum f.sp. conglutinans plate counts did not show any significantly decrease from 0 up to 120 days. The fungal profiles, evaluated by means of polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE), showed a relationship to temperature and CO2 on fungal diversity profiles. Different exudation patterns were observed when the controls and infested plants were compared, and it was found that both CO2 and temperature can influence the release of compounds from the roots of rocket plants. In short, the results show that global climate changes could influence disease incidence, probably through plant-mediated effects, caused by soilborne pathogens. PMID:26469870

  18. Rapid facilitation of ultrasound production and lordosis in female hamsters by horizontal cuts between the septum and preoptic area.

    PubMed

    Floody, Owen R; Czipri, Sheena L

    2014-01-17

    Horizontal cuts between the septum and preoptic area (anterior roof deafferentation, or ARD) dramatically affect sexual behavior, and in ways that could explain a variety of differences across behavioral categories (precopulatory, copulatory), species, and the sexes. Yet little is known about how these effects develop. Such information would be useful generally and could be pivotal in clarifying the mechanism for ultrasonic vocalization in female hamsters. Ultrasounds serve these animals as precopulatory signals that can attract males and help initiate mating. Their rates can be increased by either ARD or lesions of the ventromedial hypothalamus (VMN). If these effects are independent, they would require a mechanism that includes multiple structures and pathways within the forebrain and hypothalamus. However, it currently is not clear if they are independent: VMN lesions could affect vocalization by causing incidental damage to the same fibers targeted by ARD. Fortunately, past studies of VMN lesions have described a response with a very distinctive time course. This raises the possibility of assessing the independence of the two lesion effects by describing just the development of the response to ARD. To accomplish this, female hamsters were observed for levels of ultrasound production and lordosis before and after control surgery or ARD. As expected, both behaviors were facilitated by these cuts. Further, these effects began to appear by two days after surgery and were fully developed by six days. These results extend previous descriptions of the ARD effect by describing its development and time course. In turn, the rapid responses to ARD suggest that these cuts trigger disinhibitory changes in pathways that differ from those affected by VMN lesions.

  19. Modeling synchronous theta activity in the medial septum: key role of local communications between different cell populations.

    PubMed

    Mysin, Ivan E; Kitchigina, Valentina F; Kazanovich, Yakov

    2015-08-01

    It is widely believed that the theta rhythm in the hippocampus is caused by the rhythmic input from the medial septum-diagonal band of Broca (MSDB). The main MSDB output is formed by GABAergic projection neurons which are divided into two subpopulations and fire at different phases of the hippocampal theta rhythm. The MSDB also contains projection cholinergic, glutamatergic, and non-projection GABAergic neurons. These cell populations innervate each other and also GABAergic projection neurons and participate in the formation of the synchronous rhythmic output to the hippocampus. The purpose of this study is to work out a model of interactions between all neural populations of the MSDB that underlie the formation of the synchronous septal theta signal. The model is built from biologically plausible neurons of the Hodgkin-Huxley type and its architecture reflects modern data on the morphology of neural connections in the MSDB. The model satisfies the following requirements: (1) a large portion of neurons is fast-spiking; (2) the subpopulations of GABAergic projection neurons contain endogenous pacemaker neurons; (3) the phase shift of activity between subpopulations of GABAergic projection neurons is equal to about 150°; and (4) the strengths of bidirectional connections between the subpopulations of GABAergic projection cells are different. It is shown that the theta rhythm generation can be performed by a system of glutamatergic and GABAergic non-projection neurons. We also show that bursting pacemaker neurons in the subpopulation of projection GABAergic neurons play a significant role in the formation of stable antiphase outputs from the MSDB to the hippocampus.

  20. Stimulation of the medial septum improves performance in spatial learning following pilocarpine-induced status epilepticus.

    PubMed

    Lee, Darrin J; Izadi, Ali; Melnik, Mikhail; Seidl, Stacey; Echeverri, Angela; Shahlaie, Kiarash; Gurkoff, Gene G

    2017-02-01

    Temporal lobe epilepsy often leads to hippocampal sclerosis and persistent cognitive deficits, including difficulty with learning and memory. Hippocampal theta oscillations are critical in optimizing hippocampal function and facilitating plasticity. We hypothesized that pilocarpine-induced status epilepticus would disrupt oscillations and behavioral performance and that electrical neuromodulation to entrain theta would improve cognition specifically in injured rats. Rats received a pilocarpine (n=30) or saline injection (n=27) and unilateral bi-polar electrodes were implanted into the medial septum and hippocampus the following day. Hippocampal and septal theta were recorded in a Plexiglas box over the first week following implantation. Control and pilocarpine-treated rats were split into stimulation (continuous 7.7Hz, 80μA, 1ms pulse width) and non-stimulation groups for behavioral analysis. Continuous stimulation was initiated one-minute prior to and throughout an object exploration task (post-injury day seven) and again for each of six trials on the Barnes maze (post-injury days 12-14). There was a significant reduction in hippocampal theta power (p<0.05) and percentage of time oscillating in theta (p<0.05). In addition there was a significant decrease in object exploration in rats post-pilocarpine (p<0.05) and an impairment in spatial learning. Specifically, pilocarpine-treated rats were more likely to use random search strategies (p<0.001) and had an increase in latency to find the hidden platform (p<0.05) on the Barnes maze. Stimulation of the medial septum at 7.7Hz in pilocarpine-treated rats resulted in performance similar to shams in both the object recognition and Barnes maze tasks. Stimulation of sham rats resulted in impaired object exploration (p<0.05) with no difference in Barnes maze latency or strategy. In conclusion, pilocarpine-induced seizures diminished hippocampal oscillations and impaired performance in both an object exploration and a

  1. Our experience with transcanalicular laser-assisted endoscopic dacryocystorhinostomy (TCLADCR) in patients of chronic dacryocystitis with deviated nasal septum.

    PubMed

    Goel, Ruchi; Nagpal, Smriti; Kumar, Sushil; Kamal, Saurabh; Dangda, Sonal; Bodh, Sonam Angmo

    2015-12-01

    The purpose of this study is to study the operative difficulties and success rate of transcanalicular laser-assisted endoscopic dacryocystorhinostomy in patients of chronic dacryocystitis with deviated nasal septum (DNS). A prospective interventional clinical study of 36 consecutive patients suffering from chronic dacryocystitis with nasolacrimal duct obstruction with DNS undergoing primary TCLADCR from March to June 2011 was carried out. Diode laser was used to create a 16-mm(2) ostium which was enlarged to 64 mm(2) using Blakesley's forceps. Success was defined as anatomical patency and absence of symptoms at 12 months of follow-up. Out of the 36 patients, 25 were females with ages 20-72 years, and 19 were left sided. There were 12 high, 12 mid and 12 basal DNS towards the side of surgery, mild to moderate in severity. Intraoperatively there was difficulty in visualising the aiming beam in the nose, tedious manipulation of endoscope and excessive bleeding in 3 patients. Increased bleeding and failures were significantly higher in high DNS (Fisher exact test-2 tailed: 0.0045). The procedure was successful in 94.4 % cases with average ostium size of 21.94 mm(2) at 12 months and no statistically significant difference in success rates between mild and moderate DNS (Fisher exact test-2 tailed: 1.000). Also there was no difference in the complication rate between mild and moderate DNS (Fisher exact test-2 tailed: 0.0841). TCLADCR is an effective procedure in patients with mild to moderate mid and basal DNS and obviates the need for multiple procedures and a cutaneous scar.

  2. An excitatory ventral hippocampus to lateral septum circuit that suppresses feeding

    PubMed Central

    Sweeney, Patrick; Yang, Yunlei

    2015-01-01

    Previous research has focused on feeding circuits residing in the hindbrain and midbrain that govern homeostatic or hedonic control of food intake. However, the feeding circuits controlling emotional or cognitive aspects of food intake are largely unknown. Here we use chemical genetics and optogenetic techniques to dissect appetite control circuits originating from ventral hippocampus (vHPC), a brain region implicated in emotion and cognition. We find that the vHPC projects functional glutamatergic synaptic inputs to the lateral septum (LS) and optogenetic activation of vHPC projections in LS reduces food intake. Consistently, food intake is suppressed by chemogenetic activation of glutamatergic neurons in the vHPC that project to the LS and inactivation of LS neurons blunts vHPC-induced suppression of feeding. Collectively, our results identify an anorexigenic neural circuit originating from vHPC to LS in the brain, revealing a potential therapeutic target for the treatment of anorexia or other appetite disorders. PMID:26666960

  3. Static lung compliance and body pressures in Tupinambis merianae with and without post-hepatic septum.

    PubMed

    Klein, Wilfried; Abe, Augusto S; Perry, Steven F

    2003-04-15

    The surgical removal of the post-hepatic septum (PHS) in the tegu lizard, Tupinambis merianae, significantly reduces resting lung volume (V(Lr)) and maximal lung volume (V(Lm)) when compared with tegus with intact PHS. Standardised for body mass (M(B)), static lung compliance was significantly less in tegus without PHS. Pleural and abdominal pressures followed, like ventilation, a biphasic pattern. In general, pressures increased during expiration and decreased during inspiration. However, during expiration pressure changes showed a marked intra- and interindividual variation. The removal of the PHS resulted in a lower cranio-caudal intracoelomic pressure differential, but had no effect on the general pattern of pressure changes accompanying ventilation. These results show that a perforated PHS that lacks striated muscle has significant influence on static breathing mechanics in Tupinambis and by analogy provides valuable insight into similar processes that led to the evolution of the mammalian diaphragm.

  4. Basal cell adenoma of nasal septum: report of a case and review of literature.

    PubMed

    Wang, Qinying; Chen, Haihong; Wang, Shenqing

    2015-01-01

    Basal cell adenoma is an uncommon benign salivary gland neoplasm, presenting isomorphic basaloid cells with a prominent basal cell layer. Basal cell adenoma arising from the nasal septum is exceptionally rare. Reports on positron emission tomography with 2-deoxy-2-fluorine-18-fluoro-D-glucose (18FDG-PET) imaging for basal cell adenoma are limited. Here, we present the case of a 49-year-old man who had the symptoms of intermittent repeated bleeding from the left nose for half a year. 18FDG-PET scanning showed increased accumulation of 18FDG with its characteristic benign pathology has a potential to malignancy. After removal of the mass, the patient became symptom free. Pathology showed basal cell adenoma. The evidence of active and growing cells was present in the specimen.

  5. Partial urorectal septum malformation sequence in a kitten with disorder of sexual development.

    PubMed

    Reynolds, Brice S; Pain, Amélie; Meynaud-Collard, Patricia; Nowacka-Woszuk, Joanna; Szczerbal, Izabela; Switonski, Marek; Chastant-Maillard, Sylvie

    2014-12-01

    A 2-month-old kitten exhibited simultaneously an imperforate anus, hypospadias, rectourethral fistula and genital dysgenesis (penis restricted to the glans, absence of prepuce and bifid scrotum). Surgical correction consisted of separation of the urinary and digestive tracts, perineal urethrostomy and connection of the rectum to the newly made anal opening. Pathological examination of the testes, conventionally removed at 9 months of age, showed no mature spermatozoa and underdevelopment of germ and Leydig cells. In humans, the absence of an anal opening in association with abnormal sexual development defines the urorectal septum malformation sequence. Here, we describe the first case of this syndrome in a kitten with a normal male karyotype (38,XY) and a normal coding sequence for the SRY gene. Both the rectourethral fistula and observed genital abnormalities might have been induced by a disturbance in the hedgehog signalling pathway. However, although four polymorphic sites were identified by DHH gene sequencing, none cosegregated with the malformation.

  6. Modified Quilting Sutures: ANew Technique for Hematoma and Abscess of Nasal Septum.

    PubMed

    Ahmed, Shoaib; Ashfaq, Muhammed; Shabbir, Asad

    2016-06-01

    This study aimed to analyze the results of a modified continuous quilting sutures technique in a series of patients presenting with hematoma and/or abscess of nasal septum (HANS). Only patients with a confirmed diagnosis of HANS without co-morbid conditions (which could predispose to a bleeding tendency), were selected. Following incision and drainage, nasal septal flaps were coapted by applying continuous quilting sutures only. The success rate of this technique in terms of recurrence requiring re-exploration and drainage was 100%. Quilting sutures were generally well tolerated with few complaints. Saddle deformity was the most obvious complication of HANS, seen with septal abscess. Quilting sutures can be considered as an alternative treatment option for HANS. The modified technique employed in this study demonstrated impressive results and avoided the morbidity of nasal packing with fewer complications.

  7. Conservative treatment of cysts of the cavum septum pellucidum presenting in childhood: report of 3 cases.

    PubMed

    Bot, Gyang Markus; Constantini, Shlomi; Roth, Jonathan

    2015-09-01

    Cavum septum pellucidum (CSP) cysts are relatively rare. The most common presenting symptom is headache, which is thought to be secondary to elevated intracranial pressure. Many CSP cysts are treated surgically; conservative treatment is seldom recommended. The authors describe 3 cases of pediatric CSP cysts that were managed without surgery. The patients ranged in age from 5 months to 8 years old. Two presented with headaches, which were associated with mild ventricular enlargement in 1 case. Over the course of 5-15 months, 2 cysts became markedly reduced in size, and in one of these 2 cases a substantial reduction in ventricle size was also observed. At last follow-up, all 3 children were asymptomatic. The authors note that CSP cysts are often associated with headaches. In the absence of hydrocephalus, they recommend conservative management with clinical and radiological follow-up.

  8. Species and individual differences in juvenile female alloparental care are associated with oxytocin receptor density in the striatum and the lateral septum.

    PubMed

    Olazábal, D E; Young, L J

    2006-05-01

    The neuropeptide oxytocin has been implicated in the regulation of affiliative behavior and maternal responsiveness in several mammalian species. Rodent species vary considerably in the expression of juvenile alloparental behavior. For example, alloparental behavior is spontaneous in juvenile female prairie voles (approximately 20 days of age), takes 1-3 days of pup exposure to develop in juvenile rats, and is nearly absent in juvenile mice and meadow voles. Here, we tested the hypothesis that species differences in pup responsiveness in juvenile rodents are associated with oxytocin receptor (OTR) density in specific brain regions. We found that OTR density in the nucleus accumbens (NA) is highest in juvenile prairie voles, intermediate in juvenile rats, and lowest in juvenile mice and meadow voles. In the caudate putamen (CP), OTR binding was highest in prairie voles, intermediate in rats and meadow voles, and lowest in mice. In contrast, the lateral septum (LS) shows an opposite pattern, with OTR binding being high in mice and meadow voles and low in prairie voles and rats. Thus, alloparental responsiveness in juvenile rodents is positively correlated with OTR density in the NA and CP and negatively correlated with OTR density in the LS. We then investigated whether a similar receptor-behavior relationship exists among juvenile female prairie voles by correlating individual variation in alloparental behavior with variation in OTR density. The time spent adopting crouching postures, the most distinctive component of alloparental behavior in juveniles, was positively correlated with OTR density in the NA (r = 0.47) and CP (r = 0.45) and negatively correlated with OTR density in the lateral septum (r = -0.53). Thus, variation in OTR density in the NA, CP, and LS may underlie both species and individual differences in alloparental care in rodents.

  9. A New Approach to Suppress the Effect of Machining Error for Waveguide Septum Circular Polarizer at 230 GHz Band in Radio Astronomy

    NASA Astrophysics Data System (ADS)

    Hasegawa, Yutaka; Harada, Ryohei; Tokuda, Kazuki; Kimura, Kimihiro; Ogawa, Hideo; Onishi, Toshikazu; Nishimura, Atsushi; Han, Johnson; Inoue, Makoto

    2017-02-01

    A new stepped septum-type waveguide circular polarizer (SST-CP) was developed to operate in the 230 GHz band for radio astronomy, especially submillimeter-band VLBI observations. For previously reported SST-CP models, the 230 GHz band is too high to achieve the design characteristics in manufactured devices because of unexpected machining errors. To realize a functional SST-CP that can operate in the submillimeter band, a new method was developed, in which the division surface is shifted from the top step of the septum to the second step from the top, and we simulated the expected machining error. The SST-CP using this method can compensate for specified machining errors and suppress serious deterioration. To verify the proposed method, several test pieces were manufactured, and their characteristics were measured using a VNA. These results indicated that the insertion losses were approximately 0.75 dB, and the input return losses and the crosstalk of the left- and right-hand circular polarization were greater than 20 dB at 220-245 GHz on 300 K. Moreover, a 230 GHz SST-CP was developed by the proposed method and installed in a 1.85-m radio telescope receiver systems, and then had used for scientific observations during one observation season without any problems. These achievements demonstrate the successful development of a 230 GHz SST-CP for radio astronomical observations. Furthermore, the proposed method can be applicable for observations in higher frequency bands, such as 345 GHz.

  10. The answer is blowing in the wind: an uncommon cause for severe ARDS accompanied by circulatory insufficiency requiring extracorporeal membrane oxygenation.

    PubMed

    Einecke, Gunilla; Beutel, Gernot; Hoeper, Marius M; Kielstein, Jan T

    2017-03-24

    We report a rare complication in an immunosuppressed patient with IgA nephropathy who suffered from severe acute respiratory distress syndrome, severe capillary leakage and shock after placement of a double lumen central venous catheter. He could be successfully treated by extracorporeal membrane oxygenation (ECMO) and therapeutic plasma exchange. This report highlights the severity of late-onset complications of catheter placements and shows the potential of ECMO treatment for the management of acute illnesses with bridge to recovery.

  11. Enhanced frustrative nonreward effect following 6-hydroxydopamine lesions of the lateral septum in the rat.

    PubMed

    Taghzouti, K; Le Moal, M; Simon, H

    1985-12-01

    The effect of local injections of 6-hydroxydopamine (6-OHDA) into the lateral septum was tested in a paradigm known to lead to an energizing behavior, through a possible frustrative effect, induced by partial or total omission of reward in hungry rats. Biochemical assays in the septum showed that 6-OHDA reduced endogenous dopamine and, to a lesser extent, noradrenaline concentrations and left intact noncatecholaminergic neurons such as serotoninergic terminals. The first behavioral experiment was conducted in a double straight alley. The animals were submitted to three phases of testing with differing degrees of reinforcement: (a) an acquisition phase, in which the reinforcement was continuously delivered in the goal box of the two alleys, (b) a partial reinforced phase, in which animals received 50% partial reinforcement in the first alley and continuous reinforcement in the second alley, and (c) an extinction phase performed in one alley without any reinforcement. Animals with lesions ran faster for food than controls in the partial reinforcement or extinction situation, although there was no difference between the two groups in the acquisition phase of the continuous schedule of reinforcement or in the 50% reinforced trials of the partial reinforcement phase. The two groups also behaved similarly after the first six trials of the extinction phase. In a second experiment, the animals were tested in a lever-press conditioning task. Animals with lesions and control animals learned this task equally well, both with respect to the number of lever presses and the time to obtain a fixed number of food pellets.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Acute and Subchronic Toxicity Study of the Median Septum of Juglans regia in Wistar Rats

    PubMed Central

    Ravanbakhsh, Asma; Mahdavi, Majid; Jalilzade-Amin, Ghader; Javadi, Shahram; Maham, Masoud; Mohammadnejad, Daryosh; Rashidi, Mohammad Reza

    2016-01-01

    Purpose: Median septum of Juglans regia L. (Juglandaceae) with anti-diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities. Methods: In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600, 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME), and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days. Antioxidant status and biochemical examinations were fulfilled, and the vital organs were subjected to pathological analyses. Results: The extract did not produce any toxic signs or deaths; the medium lethal dose must be higher than 5000 mg/kg. In subchronic study, No significant morphological and histopathological changes were observed in the studied tissues. There was a significant increase in serum malondialdehyde (MDA) level in treated group compared to control after 4 weeks of JRSME intake. The treatment of rats resulted in a significant reduction of serum urea level (p<0.05), kidney’s xanthine dehydrogenase (XDH) activity (p<0.001) and elevation of aldehyde oxidase (AO) activity (p<0.05) in kidney. In the treated group, the mean diameter of glomerulus and proximal urine tube epithelium stature was slightly greater than control group. A significant increase in serum MDA level is subject for further studies. Conclusion: This study showed that the extract has no acute or subacute adverse effects with dose of 1000 mg/kg. The administration of JRSME may improve kidney structure and function and help in treatment of some chronic diseases. PMID:28101461

  13. The presence of pacemaker HCN channels identifies theta rhythmic GABAergic neurons in the medial septum.

    PubMed

    Varga, Viktor; Hangya, Balázs; Kránitz, Kinga; Ludányi, Anikó; Zemankovics, Rita; Katona, István; Shigemoto, Ryuichi; Freund, Tamás F; Borhegyi, Zsolt

    2008-08-15

    The medial septum (MS) is an indispensable component of the subcortical network which synchronizes the hippocampus at theta frequency during specific stages of information processing. GABAergic neurons exhibiting highly regular firing coupled to the hippocampal theta rhythm are thought to form the core of the MS rhythm-generating network. In recent studies the hyperpolarization-activated, cyclic nucleotide-gated non-selective cation (HCN) channel was shown to participate in theta synchronization of the medial septum. Here, we tested the hypothesis that HCN channel expression correlates with theta modulated firing behaviour of MS neurons by a combined anatomical and electrophysiological approach. HCN-expressing neurons represented a subpopulation of GABAergic cells in the MS partly overlapping with parvalbumin (PV)-containing neurons. Rhythmic firing in the theta frequency range was characteristic of all HCN-expressing neurons. In contrast, only a minority of HCN-negative cells displayed theta related activity. All HCN cells had tight phase coupling to hippocampal theta waves. As a group, PV-expressing HCN neurons had a marked bimodal phase distribution, whereas PV-immunonegative HCN neurons did not show group-level phase preference despite significant individual phase coupling. Microiontophoretic blockade of HCN channels resulted in the reduction of discharge frequency, but theta rhythmic firing was perturbed only in a few cases. Our data imply that HCN-expressing GABAergic neurons provide rhythmic drive in all phases of the hippocampal theta activity. In most MS theta cells rhythm genesis is apparently determined by interactions at the level of the network rather than by the pacemaking property of HCN channels alone.

  14. Transcatheter pulmonary valve perforation using chronic total occlusion wire in pulmonary atresia with intact ventricular septum

    PubMed Central

    Bakhru, Shweta; Marathe, Shilpa; Saxena, Manish; Verma, Sudeep; Saileela, Rajan; Dash, Tapan K; Koneti, Nageswara Rao

    2017-01-01

    Background: Perforation of pulmonary valve using radiofrequency ablation in pulmonary atresia with intact ventricular septum (PA IVS) is a treatment of choice. However, significant cost of the equipment limits its utility, especially in the developing economies. Objective: To assess the feasibility, safety, and efficacy of perforation of pulmonary valve using chronic total occlusion (CTO) wires in patients with PA IVS as an alternative to radiofrequency ablation. Methods: This is a single-center, nonrandomized, retrospective study conducted during June 2008 to September 2015. Twenty-four patients with PA IVS were selected for the procedure during the study period. The median age and weight of the study population were 8. days and 2.65 kg, respectively. Four patients were excluded after right ventricular angiogram as they showed right ventricular-dependent coronary circulation. The pulmonary valve perforation was attempted using various types of CTO wires based on the tip load with variable penetrating characteristics. Results: The procedure was successful in 16 of twenty patients using CTO wires: Shinobi in nine, Miracle in four, CROSS-IT in two, and Conquest Pro in one. Two patients had perforation of right ventricular outflow tract (RVOT). Pericardiocentesis was required in one patient to relieve cardiac tamponade. Later, the same patient underwent successful hybrid pulmonary valvotomy. The other patient underwent ductus arteriosus (DA) stenting. Balloon atrial septostomy was needed in three cases with systemic venous congestion. Desaturation was persistent in five cases necessitating DA or RVOT stenting to augment pulmonary blood flow. There were two early and two late deaths. The mean follow-up was 22.66 ± 16 months. Three patients underwent one and half ventricle repair and one Blalock–Taussig shunt during follow-up. Conclusion: Perforation of the pulmonary valve can be done successfully using CTO wires in selected cases of pulmonary atresia with intact

  15. The resistance of the septum of the medium giant axon of the earthworm

    PubMed Central

    Brink, P; Barr, L

    1977-01-01

    It is generally thought that nexuses constitute low-resistance pathways between cell interiors in epithelial, neural, muscular, and even connective tissues. However, there are no reliable estimates of the specific resistance of a nexus. The reason for this is that in most cases the surfaces of nexuses between cells are geometrically complex and therefore it has been very hard to accurately estimate nexal areas. However, the septa of the median giant axon have a relatively simple shape. Moreover, in this preparation, it is possible to make a measuring current flow parallel to the axon axis so that from the voltage difference appearing between intracellular electrodes during current flow, the specific septal membrane resistance could be calculated. The average specific nexal resistance obtained was 5.9 ω cm(2) if one assumes that 100 percent of the septum is nexus. The steady state I-V curve for the septum is linear (+/- 10 mV). Placement of electrodes was validated by septa even though the septa were found to be permeable to fluorescein and TEA. Exposure of the axon to hypertonic saline impedes the movement of fluorescein across the septa. By analogy with other tissues it is concluded that hypertonic solutions disrupt nexuses. A mathematical model was derived which predicts the steady- state transmembrane potential vs. distance from a point source of intracellular current. When the specific nexal membrane resistance is 5.9 ω cm(2), the prediction closely approximates the fall of transmembrane potential vs. distance in an ordinary infinite cable. This is commensurate with the electrophysiological behavior of this multicellular “axon.” PMID:864430

  16. Interneurons are the local targets of hippocampal inhibitory cells which project to the medial septum.

    PubMed

    Gulyás, A I; Hájos, N; Katona, I; Freund, T F

    2003-05-01

    A subset of GABAergic neurons projecting to the medial septum has long been described in the hippocampus. However, the lack of information about their local connectivity pattern or their correspondence with any of the well-established hippocampal interneuron types has hampered the understanding of their functional role. Retrograde tracing combined with immunostaining for neurochemical markers in the adult rat hippocampus showed that nearly all hippocampo-septal (HS) neurons express somatostatin (>95%) and, in the hilus and CA3 stratum lucidum, many contain calretinin (>45%). In contrast, in stratum oriens of the CA1 and CA3 subfields, the majority of HS neurons contain somatostatin (>86%) and calbindin (>73%), but not calretinin. Because somatostatin-positive hippocampal interneurons have been most extensively characterized in the stratum oriens of CA1, we focused our further analysis on HS cells found in this region. In 18-20-day-old rats, intracellularly filled CA1-HS cells had extensive local axon collaterals crossing subfield boundaries and innervating the CA3 region and the dentate gyrus. Electron microscopic analysis provided evidence that the axon terminals of CA1-HS cells form symmetrical synapses selectively on GABAergic interneurons, both locally and in the CA3 region. In addition, double retrograde labelling experiments revealed that many CA1-HS neurons of the dorsal hippocampus also have collateral projections to the ventral hippocampus. Thus, CA1-HS cells innervate inhibitory interneurons locally and in remote hippocampal regions, in addition to targeting mostly GABAergic neurons in the medial septum. This dual projection with striking target selectivity for GABAergic neurons may be ideally suited to synchronize neuronal activity along the septo-hippocampal axis.

  17. Alcohol May Not Cause Partner Violence but It Seems to Make It Worse: A Cross National Comparison of the Relationship between Alcohol and Severity of Partner Violence

    ERIC Educational Resources Information Center

    Graham, Kathryn; Bernards, Sharon; Wilsnack, Sharon C.; Gmel, Gerhard

    2011-01-01

    This study assesses whether severity of physical partner aggression is associated with alcohol consumption at the time of the incident, and whether the relationship between drinking and aggression severity is the same for men and women and across different countries. National or large regional general population surveys were conducted in 13…

  18. Chronic rhino-orbital mucormycosis caused by Mucor irregularis (Rhizomucor variabilis) in India

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We describe a chronic case of rhino-orbital zygomycosis caused by Mucor irregularis, formerly known as Rhizomucor variabilis var. variabilis, a rare mycotic agent in humans. The infection caused progressive destruction of the nasal septum, soft and hard palate, leading to collapse of the nose bridge...

  19. Direct interaction of a small-molecule modulator with G551D-CFTR, a cystic fibrosis-causing mutation associated with severe disease.

    PubMed

    Pasyk, Stan; Li, Canhui; Ramjeesingh, Mohabir; Bear, Christine E

    2009-02-15

    CF (cystic fibrosis) is caused by mutations in CFTR (CF transmembrane conductance regulator), which cause its mistrafficking and/or dysfunction as a regulated chloride channel on the apical surface of epithelia. CFTR is a member of the ABC (ATP-binding-cassette) superfamily of membrane proteins and a disease-causing missense mutation within the ABC signature sequence; G551D-CFTR exhibits defective phosphorylation and ATP-dependent channel gating. Studies of the purified and reconstituted G551D-CFTR protein revealed that faulty gating is associated with defective ATP binding and ATPase activity, reflecting the key role of G551 in these functions. Recently, high-throughput screens of chemical libraries led to identification of modulators that enhance channel activity of G551D-CFTR. However, the molecular target(s) for these modulators and their mechanism of action remain unclear. In the present study, we evaluated the mechanism of action of one small-molecule modulator, VRT-532, identified as a specific modulator of CF-causing mutants. First, we confirmed that VRT-532 causes a significant increase in channel activity of G551D-CFTR using a novel assay of CFTR function in inside-out membrane vesicles. Biochemical studies of purified and reconstituted G551D-CFTR revealed that potentiation of the ATPase activity of VRT-532 is mediated by enhancing the affinity of the mutant for ATP. Interestingly, VRT-532 did not affect the ATPase activity of the Wt (wild-type) CFTR, supporting the idea that this compound corrects the specific molecular defect in this mutant. To summarize, these studies provide direct evidence that this compound binds to G551D-CFTR to rescue its specific defect in ATP binding and hydrolysis.

  20. Alcohol may not cause partner violence but it seems to make it worse: a cross national comparison of the relationship between alcohol and severity of partner violence.

    PubMed

    Graham, Kathryn; Bernards, Sharon; Wilsnack, Sharon C; Gmel, Gerhard

    2011-05-01

    This study assesses whether severity of physical partner aggression is associated with alcohol consumption at the time of the incident, and whether the relationship between drinking and aggression severity is the same for men and women and across different countries. National or large regional general population surveys were conducted in 13 countries as part of the GENACIS collaboration. Respondents described the most physically aggressive act done to them by a partner in the past 2 years, rated the severity of aggression on a scale of 1 to 10, and reported whether either partner had been drinking when the incident occurred. Severity ratings were significantly higher for incidents in which one or both partners had been drinking compared to incidents in which neither partner had been drinking. The relationship did not differ significantly for men and women or by country. We conclude that alcohol consumption may serve to potentiate violence when it occurs, and this pattern holds across a diverse set of cultures. Further research is needed that focuses explicitly on the nature of alcohol's contribution to intimate partner aggression. Prevention needs to address the possibility of enhanced dangers of intimate partner violence when the partners have been drinking and eliminate any systemic factors that permit alcohol to be used as an excuse. Clinical services for perpetrators and victims of partner violence need to address the role of drinking practices, including the dynamics and process of aggressive incidents that occur when one or both partners have been drinking.

  1. Long-term administration of Wilms tumor-1 peptide vaccine in combination with gemcitabine causes severe local skin inflammation at injection sites.

    PubMed

    Soeda, Atsuko; Morita-Hoshi, Yuriko; Kaida, Miho; Wakeda, Takako; Yamaki, Yuni; Kojima, Yasushi; Ueno, Hideki; Kondo, Shunsuke; Morizane, Chigusa; Ikeda, Masafumi; Okusaka, Takuji; Heike, Yuji

    2010-12-01

    The skin toxicity of vaccine therapy at injection sites is generally limited to Grades 1-2 due to the nature of their function. We experienced two cases of severe and prolonged local adverse effects in 25 patients following a Phase I study of gemcitabine and Wilms tumor-1 peptide vaccine mixed with incomplete Freund's adjuvant for inoperable pancreatic or biliary tract cancer. These patients requested to continue the treatment after the study period; however, in the course of compassionate use, they developed unacceptable local skin reactions and terminated their vaccine treatment. One patient (human leukocyte antigen, A0201, 3 mg) developed Grade 3 ulceration at the 10th vaccination and another (human leukocyte antigen, A2402, 1 mg) developed Grade 2 indulation and fibrosis at the 16th vaccination. Skin toxicity occurred at 6.4-8.4 months and continued for several months after the final vaccination during gemcitabine treatment. In these cases, activation or induction of Wilms tumor-1-specific T lymphocytes was not apparent in the peripheral blood despite their severe local reactions. Therefore, we need to monitor patients for late-onset, severe and long-lasting skin reactions at injection sites in Wilms tumor-1 cancer vaccine therapy, particularly for combination treatment with gemcitabine.

  2. First Report of Severe Outbreaks of Bacterial Leaf Spot of Leafy Brassica Greens Caused by Xanthomonas Campestris pv. Campestris in South Carolina

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Severe outbreaks of leaf spot disease of leafy vegetable Brassica have occurred from early spring to late fall for at least the past five years in Lexington County, the major growing region for leafy greens in South Carolina. Significant economic losses to this disease have been reported by both la...

  3. Combined microdeletions and CHD7 mutation causing severe CHARGE/DiGeorge syndrome: clinical presentation and molecular investigation by array-CGH.

    PubMed

    Kaliakatsos, Marios; Giannakopoulos, Aristeidis; Fryssira, Helena; Kanariou, Maria; Skiathitou, Anna-Venetia; Siahanidou, Tania; Giannikou, Krinio; Makrythanasis, Periklis; Kanavakis, Emmanuel; Tzetis, Maria

    2010-11-01

    Phenotypic variation in CHARGE syndrome remains unexplained. A subcategory of CHARGE patients show overlapping phenotypic characteristics with DiGeorge syndrome (thymic hypo/aplasia, hypocalcemia, T-cell immunodeficiency). Very few have been tested or reported to carry a mutation of the CHD7 (chromodomain helicase DNA-binding domain) gene detected in two-thirds of CHARGE patients. In an attempt to explore the genetic background of a severe CHARGE/DiGeorge phenotype, we performed comparative genomic array hybridization in an infant carrier of a CHD7 mutation. The high-resolution comparative genomic array hybridization revealed interesting findings, including a deletion distal to the DiGeorge region and disruptions in other chromosomal regions of genes implicated in immunological and other functions possibly contributing to the patient's severe phenotype and early death.

  4. Differing Causes of Lactic Acidosis and Deep Breathing in Cerebral Malaria and Severe Malarial Anemia May Explain Differences in Acidosis-Related Mortality

    PubMed Central

    Brand, Nathan R.; Opoka, Robert O.; Hamre, Karen E. S.

    2016-01-01

    Lactic acidosis (LA) is a marker for mortality in severe malaria, but the mechanisms that lead to LA in the different types of severe malaria and the extent to which LA-associated mortality differs by type of severe malaria are not well described. We assessed the frequency of LA in children admitted to Mulago Hospital, Kampala, Uganda with cerebral malaria (CM, n = 193) or severe malarial anemia (SMA, n = 216). LA was compared to mortality and measures of parasite biomass and sequestration (P. falciparum histidine-rich protein-2 (PfHRP2) concentration, platelet count), and to a measure of systemic tissue oxygen delivery (hemoglobin level). LA was more frequent in children with SMA than CM (SMA, 47.7%, CM, 34.2%, P = 0.006), but mortality was higher in children with CM (13.0%) than SMA (0.5%, P<0.0001). In CM, LA was associated with increased PfHRP2 concentration and decreased platelet count but was not associated with hemoglobin level. In contrast, in SMA, LA was associated with a decreased hemoglobin level, but was not associated with PfHRP2 concentration or platelet count. LA was related to mortality only in CM. In multivariable regression analysis of the effect PfHRP2 and hemoglobin levels on LA and DB, only PfHRP2 level increased risk of LA and DB in CM, while in SMA, elevated hemoglobin strongly decreased risk of LA and DB, and PfHRP2 level modestly increased risk of LA. The study findings suggest that LA in CM is due primarily to parasite sequestration, which currently has no effective adjunctive therapy, while LA in SMA is due primarily to anemia, which is rapidly corrected with blood transfusion. Differing etiologies of LA in CM and SMA may explain why LA is associated with mortality in CM but not SMA. PMID:27684745

  5. CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature.

    PubMed

    Lilles, Stella; Talvik, Inga; Noormets, Klari; Vaher, Ulvi; Õunap, Katrin; Reimand, Tiia; Sander, Valentin; Ilves, Pilvi; Talvik, Tiina

    2016-12-01

    Cyclin-dependent kinase-like 5 (CDKL5) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 of CDKL5. All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact, CDKL5 gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future.

  6. Complex reconstruction of facial deformity and function after severe gunshot injury: one case report

    PubMed Central

    Wang, Weijian; Duan, Jianmin; Wang, Qiao; Kuang, Wei

    2015-01-01

    In this report, we described clinical outcomes of a multi-stage surgery integrating multiple techniques in restoration of facial morphology and function of a 17-year-old boy with severe gunshot injuries. This multi-stage surgery was applied in treatment of one rare case of gunshot-caused complicated facial deformities involving most parts of the face (labrum, left nose wing, nasal columella, nasal septum, maxillary alveolar process, hard palate, soft palate, bilateral maxillary bones, left zygoma, suborbital bone defects) and clinical efficacy upon restoring facial form and function were retrospectively evaluated. The patient was diagnosed with massive facial defects and deformities caused by gunshot, which led to feeding difficulty, severe articulation disorders and serious facial disfigurement. To reconstruct facial form and restore functions of mastication and articulation, multiple examinations and surgical procedures including mirror imaging, rapid prototyping technique, porous titanium implants, microscopic surgical technique, dental implants, osteomyocutaneous flap, muscular flap, shifting and repairing of adjacent tissue flaps and free bone graft reconstruction were undertaken. Postoperatively, reconstruction of severe facial disfigurement and restoring basic functions including articulation and feeding for the first time and relatively sound clinical outcomes have been obtained, which may add clinical evidence to the treatment of similar cases of severe facial deformities. PMID:25785151

  7. Development of septum-free injector for gas chromatography and its application to the samples with a high boiling point.

    PubMed

    Ito, Hiroshi; Hayakawa, Kazuichi; Yamamoto, Atsushi; Murase, Atsushi; Hayakawa, Kazumi; Kuno, Minoru; Inoue, Yoshinori

    2006-11-03

    A novel apparatus with a simple structure has been developed for introducing samples into the vaporizing chamber of a gas chromatograph. It requires no septum due to the gas sealing structure over the carrier gas supply line. The septum-free injector made it possible to use injection port temperatures as high as 450 degrees C. Repetitive injection of samples with boiling points below 300 degrees C resulted in peak areas with relative standard deviations between 1.25 and 3.28% (n=5) and good linearity (r(2)>0.9942) for the calibration curve. In the analysis of polycyclic aromatic hydrocarbons and a base oil, the peak areas of components with high boiling points increased as the injection port temperature was increased to 450 degrees C.

  8. The nasal septum and the development of the midface. A longitudinal study of a pair of monozygotic twins.

    PubMed

    Grymer, L F; Bosch, C

    1997-03-01

    The development of the nose and the growth of the midface has been followed in a pair of identical twins. One of them (twin A) had nasal septum destruction after septal haematoma and abscess at the age of 7 years, and was treated by immediate implantation of homologous septal cartilage from a tissue bank. From 7-17 years of age the growth and development of the nose and face were followed. Lateral cephalograms, photographs, acoustic rhinometry and rhinoscopy were performed. Twin B presented a normal nasal and facial growth and served as control. Twin A developed a saddle nose, an upward displacement of the anterior part of the maxilla, diminished vertical development of the nasal cavity, and a retrognathically positioned maxilla due to decreased anteroposterior maxillary growth. This case report seems to indicate that the cartilaginous nasal septum is an important factor influencing vertical and sagittal growth of the maxilla.

  9. Opening-wedge osteotomy, allografting with dual buttress plate fixation for severe genu recurvatum caused by partial growth arrest of the proximal tibial physis: a case report.

    PubMed

    Chen, Liang-Chin; Chan, Yi-Sheng; Wang, Ching-Jen

    2004-07-01

    Injuries to the proximal tibial physis are among the least common epiphyseal injuries. We present a case of severe genu recurvatum deformity (45 degrees) with leg length discrepancy (4 cm) following a neglected proximal tibial physeal injury incurred 6 years previously. The 16-year-old patient was successfully treated by open-wedge osteotomy, allograft reconstruction, and dual buttress plate fixation. At 3 years' follow-up, the patient was asymptomatic, fully active with a full range of motion (0 - 140 degrees) of the leg, and equal leg lengths. There were no signs of genu recurvatum clinically.

  10. Age differences in the impact of forced swimming test on serotonin transporter levels in lateral septum and dorsal raphe

    PubMed Central

    2014-01-01

    Background Forced swimming test (FST) is an animal model which evaluates behavioral despair and the effect of antidepressants such as the selective serotonin reuptake inhibitors; the FST modifies the expression of some receptors related to antidepressant response, but it is not known whether serotonin transporter (SERT), their main target, is affected by this test in animals of different ages. Antidepressant response has shown age-dependent variations which could be associated with SERT expression. The aim of the present study was to analyze changes in the SERT immunoreactivity (SERT-IR) in dorsal raphe and lateral septum of male rats from different age groups with or without behavioral despair induced by their exposure to the FST, since these two structures are related to the expression of this behavior. Methods Prepubertal (24 PN), pubertal (40 PN), young adult (3–5 months) and middle-aged (12 months) male rats were assigned to a control group (non-FST) or depressed group (FST, two sessions separated by 24 h). Changes in SERT-IR in dorsal raphe and lateral septum were determined with immunofluorescence. Results Pubertal and middle-aged rats showed higher levels of immobility behavior compared to prepubertal rats on the FST. SERT-IR showed an age-dependent increase followed by a moderate decrease in middle-aged rats in both structures; a decreased in SERT-IR in lateral septum and dorsal raphe of pubertal rats was observed after the FST. Conclusions Age differences were observed in the SERT-IR of structures related to behavioral despair; SERT expression was modified by the FST in lateral septum and dorsal raphe of pubertal rats. PMID:24490994

  11. Hypoplastic left heart syndrome with restrictive atrial septum and advanced heart block documented with a novel fetal electrocardiographic monitor

    PubMed Central

    NARAYAN, H. K.; FIFER, W.; CARROLL, S.; KERN, J.; SILVER, E.; WILLIAMS, I. A.

    2012-01-01

    Hypoplastic left ventricle with congenital heart block has been reported previously in a fetus with concurrent left atrial isomerism and levo-transposition of the great arteries. We present the unusual case of an infant diagnosed in utero with hypoplastic left heart syndrome, a restrictive atrial septum and advanced heart block but with D-looping of the ventricles and no atrial isomerism. In addition, fetal heart rhythm was documented with the assistance of a new fetal electrocardiographic monitor. PMID:21374749

  12. Deep brain stimulation of the medial septum or nucleus accumbens alleviates psychosis-relevant behavior in ketamine-treated rats.

    PubMed

    Ma, Jingyi; Leung, L Stan

    2014-06-01

    Deep brain stimulation (DBS) has been shown to be effective for relief of Parkinson's disease, depression and obsessive-compulsive disorder in humans, but the effect of DBS on psychosis is largely unknown. In previous studies, we showed that inactivation of the medial septum or nucleus accumbens normalized the hyperactive and psychosis-related behaviors induced by psychoactive drugs. We hypothesized that DBS of the medial septum or nucleus accumbens normalizes the ketamine-induced abnormal behaviors and brain activity in freely moving rats. Male Long-Evans rats were subcutaneously injected with ketamine (3 mg/kg) alone, or given ketamine and DBS, or injected with saline alone. Subcutaneous injection of ketamine resulted in loss of gating of hippocampal auditory evoked potentials (AEPs), deficit in prepulse inhibition (PPI) and hyperlocomotion, accompanied by increased hippocampal gamma oscillations of 70-100 Hz. Continuous 130-Hz stimulation of the nucleus accumbens, or 100-Hz burst stimulation of the medial septum (1s on and 5s off) significantly attenuated ketamine-induced PPI deficit and hyperlocomotion. Medial septal stimulation also prevented the loss of gating of hippocampal AEPs and the increase in hippocampal gamma waves induced by ketamine. Neither septal or accumbens DBS alone without ketamine injection affected spontaneous locomotion or PPI. The results suggest that DBS of the medial septum or nucleus accumbens may be an effective method to alleviate psychiatric symptoms of schizophrenia. The effect of medial septal DBS in suppressing both hippocampal gamma oscillations and abnormal behaviors induced by ketamine suggests that hippocampal gamma oscillations are a correlate of disrupted behaviors.

  13. H9N2 influenza viruses isolated from poultry in Korean live bird markets continuously evolve and cause the severe clinical signs in layers.

    PubMed

    Kim, Jin A; Cho, Sung Hwan; Kim, Hyun Soo; Seo, Sang Heui

    2006-12-20

    H9N2 influenza viruses are endemic in many Asian countries. We demonstrated that H9N2 influenza viruses isolated from poultry in Korean live bird markets are genetically changing and could cause the clinical signs in layers. Genetic analysis showed that Korean avian H9N2 influenza viruses are distinct from H9N2 influenza viruses circulating in poultry in China and Hong Kong. When we infected layers with H9N2 isolates, layers showed about 30% mortality and the reduction of egg productions. Considering that H9N2 influenza virus is one of potential pandemic candidates, the continuous surveillance is needed to monitor avian H9N2 influenza viruses for the poultry industry and humans.

  14. Interactions between hippocampus and medial septum during sharp waves and theta oscillation in the behaving rat.

    PubMed

    Dragoi, G; Carpi, D; Recce, M; Csicsvari, J; Buzsáki, G

    1999-07-15

    The medial septal region and the hippocampus are connected reciprocally via GABAergic neurons, but the physiological role of this loop is still not well understood. In an attempt to reveal the physiological effects of the hippocamposeptal GABAergic projection, we cross-correlated hippocampal sharp wave (SPW) ripples or theta activity and extracellular units recorded in the medial septum and diagonal band of Broca (MSDB) in freely moving rats. The majority of single MSDB cells (60%) were significantly suppressed during SPWs. Most cells inhibited during SPW (80%) fired rhythmically and phase-locked to the negative peak of the CA1 pyramidal layer theta waves. Because both SPW and the negative peak of local theta waves correspond to the maximum discharge probability of CA1 pyramidal cells and interneuron classes, the findings indicate that the activity of medial septal neurons can be negatively (during SPW) or positively (during theta waves) correlated with the activity of hippocampal interneurons. We hypothesize that the functional coupling between medial septal neurons and hippocampal interneurons varies in a state-dependent manner.

  15. GABAergic Projections from the Medial Septum Selectively Inhibit Interneurons in the Medial Entorhinal Cortex

    PubMed Central

    Gonzalez-Sulser, Alfredo; Parthier, Daniel; Candela, Antonio; McClure, Christina; Pastoll, Hugh; Garden, Derek; Sürmeli, Gülşen

    2014-01-01

    The medial septum (MS) is required for theta rhythmic oscillations and grid cell firing in the medial entorhinal cortex (MEC). While GABAergic, glutamatergic, and cholinergic neurons project from the MS to the MEC, their synaptic targets are unknown. To investigate whether MS neurons innervate specific layers and cell types in the MEC, we expressed channelrhodopsin-2 in mouse MS neurons and used patch-clamp recording in brain slices to determine the response to light activation of identified cells in the MEC. Following activation of MS axons, we observed fast monosynaptic GABAergic IPSPs in the majority (>60%) of fast-spiking (FS) and low-threshold-spiking (LTS) interneurons in all layers of the MEC, but in only 1.5% of nonstellate principal cells (NSPCs) and in no stellate cells. We also observed fast glutamatergic responses to MS activation in a minority (<5%) of NSPCs, FS, and LTS interneurons. During stimulation of MS inputs at theta frequency (10 Hz), the amplitude of GABAergic IPSPs was maintained, and spike output from LTS and FS interneurons was entrained at low (25–60 Hz) and high (60–180 Hz) gamma frequencies, respectively. By demonstrating cell type-specific targeting of the GABAergic projection from the MS to the MEC, our results support the idea that the MS controls theta frequency activity in the MEC through coordination of inhibitory circuits. PMID:25505326

  16. Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio-venous connections.

    PubMed

    Cano, Elena; Carmona, Rita; Ruiz-Villalba, Adrián; Rojas, Anabel; Chau, You-Ying; Wagner, Kay D; Wagner, Nicole; Hastie, Nicholas D; Muñoz-Chápuli, Ramón; Pérez-Pomares, José M

    2016-01-19

    Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1(Cre)) and previously undescribed (G2-Gata4(Cre)) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio-venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms' tumor suppressor gene (Wt1) in the ST/PE of G2-Gata4(Cre) mice and in the endothelium of Tie2(Cre) mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesis.

  17. Developmental stage-dependent protective effect of NGF against lead cholinotoxicity in the rat septum.

    PubMed

    Zhou, M; Tian, X; Suszkiw, J B

    2000-06-02

    The ability of nerve growth factor (NGF) to ameliorate developmental cholinotoxicity of inorganic lead (Pb) for the septal neurons was investigated by making intracerebroventricular injections of single doses of 30 microg 2.5S NGF into maternally lead-exposed suckling rats on postnatal days P2, P4, P11, or P18. Administration of NGF on P4 or later induced septal choline acetyltransferase (ChAT) activity to the same relative extent in both Pb-exposed as in control rats but failed to reverse the net reductions of ChAT activity induced by Pb. In contrast, injection of NGF at P2 completely restored ChAT activity in Pb-exposed pups to control levels by preventing the loss of ChAT-immunoreactive cells in the septum. It is concluded that although NGF retains the capacity to upregulate ChAT throughout the period of Pb exposure, it protects against the Pb-induced loss of septal cholinergic neurons only when applied within the critical period of Pb-vulnerability between postnatal days 2 and 4.

  18. Pulmonary vascular disease in transposition of the great vessels and intact ventricular septum.

    PubMed

    Newfeld, E A; Paul, M H; Muster, A J; Idriss, F S

    1979-03-01

    Eight of 135 (6%) children with d-transposition of the great vessels and with intact ventricular septum and no patent ductus arteriosus had evidence of progressive pulmonary vascular disease. Seven of 101 (7%) patients for whom histologic data was available, had Heath-Edwards grades IV or V pulmonary vascular disease, six had grade II, and 88 had either normal or grade I findings. One of 34 patients for whom histologic data was not available had hemodynamic evidence of pulmonary vascular disease at cardiac catheterization after the Mustard operation. When infants younger than 3 months old were excluded, eight of 85 (9%) had advanced pulmonary vascular disease. Twenty-three patients had microthrombi in their pulmonary arteries and arterioles, and in one patient thrombi were observed before the development of pulmonary vascular disease. Clinically unrecognized pulmonary microthrombi are suggested as a possible etiologic agent in the development of pulmonary vascular disease in patients with transposition of the great vessels. Progressive pulmonary vascular disease can first be discovered after the Mustard operation, even in patients without preoperative evidence of pulmonary hypertension or elevated pulmonary vascular resistance.

  19. Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio–venous connections

    PubMed Central

    Cano, Elena; Ruiz-Villalba, Adrián; Rojas, Anabel; Chau, You-Ying; Wagner, Kay D.; Wagner, Nicole; Hastie, Nicholas D.; Muñoz-Chápuli, Ramón; Pérez-Pomares, José M.

    2016-01-01

    Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1Cre) and previously undescribed (G2-Gata4Cre) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio–venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms’ tumor suppressor gene (Wt1) in the ST/PE ofG2-Gata4Cre mice and in the endothelium of Tie2Cre mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesis. PMID:26739565

  20. GABAergic projections from the medial septum selectively inhibit interneurons in the medial entorhinal cortex.

    PubMed

    Gonzalez-Sulser, Alfredo; Parthier, Daniel; Candela, Antonio; McClure, Christina; Pastoll, Hugh; Garden, Derek; Sürmeli, Gülşen; Nolan, Matthew F

    2014-12-10

    The medial septum (MS) is required for theta rhythmic oscillations and grid cell firing in the medial entorhinal cortex (MEC). While GABAergic, glutamatergic, and cholinergic neurons project from the MS to the MEC, their synaptic targets are unknown. To investigate whether MS neurons innervate specific layers and cell types in the MEC, we expressed channelrhodopsin-2 in mouse MS neurons and used patch-clamp recording in brain slices to determine the response to light activation of identified cells in the MEC. Following activation of MS axons, we observed fast monosynaptic GABAergic IPSPs in the majority (>60%) of fast-spiking (FS) and low-threshold-spiking (LTS) interneurons in all layers of the MEC, but in only 1.5% of nonstellate principal cells (NSPCs) and in no stellate cells. We also observed fast glutamatergic responses to MS activation in a minority (<5%) of NSPCs, FS, and LTS interneurons. During stimulation of MS inputs at theta frequency (10 Hz), the amplitude of GABAergic IPSPs was maintained, and spike output from LTS and FS interneurons was entrained at low (25-60 Hz) and high (60-180 Hz) gamma frequencies, respectively. By demonstrating cell type-specific targeting of the GABAergic projection from the MS to the MEC, our results support the idea that the MS controls theta frequency activity in the MEC through coordination of inhibitory circuits.

  1. Medial entorhinal cortex and medial septum contribute to self-motion-based linear distance estimation.

    PubMed

    Jacob, Pierre-Yves; Gordillo-Salas, Marta; Facchini, Justine; Poucet, Bruno; Save, Etienne; Sargolini, Francesca

    2017-02-04

    Path integration is a navigation strategy that requires animals to integrate self-movements during exploration to determine their position in space. The medial entorhinal cortex (MEC) has been suggested to play a pivotal role in this process. Grid cells, head-direction cells, border cells as well as speed cells within the MEC collectively provide a dynamic representation of the animal position in space based on the integration of self-movements. All these cells are strongly modulated by theta oscillations, thus suggesting that theta rhythmicity in the MEC may be essential for integrating and coordinating self-movement information during navigation. In this study, we first show that excitotoxic MEC lesions, but not dorsal hippocampal lesions, impair the ability of rats to estimate linear distances based on self-movement information. Next, we report similar deficits following medial septum inactivation, which strongly impairs theta oscillations in the entorhinal-hippocampal circuits. Taken together, these findings demonstrate a major role of the MEC and MS in estimating distances to be traveled, and point to theta oscillations within the MEC as a neural mechanism responsible for the integration of information generated by linear self-displacements.

  2. Melanin concentrating hormone induces hippocampal acetylcholine release via the medial septum in rats.

    PubMed

    Lu, Zhi-Hong; Fukuda, Satoru; Minakawa, Yoichi; Yasuda, Atsushi; Sakamoto, Hidetoshi; Sawamura, Shigehito; Takahashi, Hidenori; Ishii, Noriko

    2013-06-01

    Among various actions of melanin concentrating hormone (MCH), its memory function has been focused in animal studies. Although MCH neurons project to various areas in the brain, one main target site of MCH is hippocampal formation for memory consolidation. Recent immunohistochemical study shows that MCH neurons directly project to the hippocampal formation and may indirectly affect the hippocampus through the medial septum nucleus (MS). It has been reported that sleep is necessary for memory and that hippocampal acetylcholine (ACh) release is indispensable for memory consolidation. However, there is no report how MCH actually influences the hippocampal ACh effluxes in accordance with the sleep-wake cycle changes. Thus, we investigated the modulatory function of intracerebroventricular (icv) injection of MCH on the sleep-wake cycle and ACh release using microdialysis techniques. Icv injection of MCH significantly increased the rapid eye movement (REM) and non-REM episode time and the hippocampal, not cortical, ACh effluxes. There was a significant correlation between REM episode time and hippocampal ACh effluxes, but not between REM episode time and cortical ACh effluxes. Microinjection of MCH into the MS increased the hippocampal ACh effluxes with no influence on the REM episode time. It appears that the effect sites of icv MCH for prolongation of REM episode time may be other neuronal areas than the cholinergic neurons in the MS. We conclude that MCH actually increases the hippocampal ACh release at least in part through the MS in rats.

  3. Autoimmune-related nasal septum perforation: A case report and systematic review

    PubMed Central

    Guntupalli, Lohitha; Patel, Kunjan; Faraji, Farhoud

    2017-01-01

    Background: Inflammatory injury of nasal respiratory mucosa is a common feature of multisystem autoimmune disease. Certain autoimmune disorders are associated with nasal septum perforation (NSP). We performed a systematic review of the literature to better understand the association of NSP with specific autoimmune disorders. This is a case report of a 29-year-old woman with a history of arthralgia, autoreactive antibody titers, platelet dysfunction, and NSP. The constellation of symptoms and potential familial involvement indicated that the NSP in this patient was an early sign of an autoimmune disorder, an unknown autoimmune disorder, or a known disease with incomplete penetrance. Methods: A systematic review of the literature was performed by two independent reviewers. Relevant articles were reviewed, and data that pertained to autoimmune-related NSP were extracted and analyzed. Results: Overall, 140 cases of autoimmune-associated NSPs were reported. Granulomatosis with polyangiitis (48%), relapsing polychondritis (26%), and cocaine-induced midline lesions (15%) constituted 89.3% of the reported cases. Conclusion: NSP is a potential sign of systemic disease. The identification of an NSP, especially in the context of other unexplained symptoms or workup suggestive of an autoimmune disorder, should prompt clinical evaluation for multisystem autoimmune disease with consideration of granulomatosis with polyangiitis, relapsing polychondritis, or cocaine-induced midline lesions. PMID:28381327

  4. Visualization and functional dissection of coaxial paired SpoIIIE channels across the sporulation septum

    DOE PAGES

    Shin, Jae Yen; Lopez-Garrido, Javier; Lee, Sang-Hyuk; ...

    2015-05-07

    SpoIIIE is a membrane-anchored DNA translocase that localizes to the septal midpoint to mediate chromosome translocation and membrane fission during Bacillus subtilis sporulation. Here we use cell-specific protein degradation and quantitative photoactivated localization microscopy in strains with a thick sporulation septum to investigate the architecture and function of the SpoIIIE DNA translocation complex in vivo. We were able to visualize SpoIIIE complexes with approximately equal numbers of molecules in the mother cell and the forespore. Cell-specific protein degradation showed that only the mother cell complex is required to translocate DNA into the forespore, whereas degradation in either cell reversesmore » membrane fission. Our data suggest that SpoIIIE assembles a coaxially paired channel for each chromosome arm comprised of one hexamer in each cell to maintain membrane fission during DNA translocation. We show that SpoIIIE can operate, in principle, as a bi-directional motor that exports DNA.« less

  5. Identical Mutation in SH3BP2 Gene Causes Clinical Phenotypes with Different Severity in Mother and Daughter – Case Report

    PubMed Central

    Preda, L.; Dinca, O.; Bucur, A.; Dragomir, C.; Severin, E.

    2010-01-01

    Cherubism is a particular form of fibrous dysplasia of the jaws. Familial occurrence was reported in most cases. The condition is a rare hereditary disorder with autosomal dominant inheritance, with complete penetrance in males and incomplete penetrance in females and variable expressivity. It is known to be caused by mutations in the gene encoding SH3-domain binding protein 2, SH3BP2 gene. Major diagnostic criteria are cherubic facial appearance, painless hard enlargement of the jaws, and frequently associated dental abnormalities. The aim of the study was to analyze clinical and genetic features of cherubism in a family with 3 daughters in which the youngest one was affected. Clinical and radiographic examinations, hematological and biochemical evaluations and biopsy were performed. Molecular genetic analysis consisted of PCR amplification and direct sequencing of selected exons of the SH3BP2 gene. Cherubism was suspected based on clinical and radiographic examinations of the 9-year-old daughter. She presented asymmetrical enlargement of the mandible, speech and swallowing problems and dental abnormalities on the lower jaw. There was no history of similar clinical findings in any of the daughters or the parents of the affected girl. Abnormal results were obtained by genetic analysis. A c.1244G>A mutation was identified in exon 9 of the SH3BP2 gene in the asymptomatic mother and her affected daughter. The identified mutation in the SH3BP2 gene is probably disease-causing. The asymptomatic mother transmitted the gene mutation to her affected daughter. Our results confirm the reduced penetrance and variable expression of the gene mutation. PMID:21045962

  6. Transplantable rat glucagonomas cause acute onset of severe anorexia and adipsia despite highly elevated NPY mRNA levels in the hypothalamic arcuate nucleus.

    PubMed Central

    Jensen, P B; Blume, N; Mikkelsen, J D; Larsen, P J; Jensen, H I; Holst, J J; Madsen, O D

    1998-01-01

    We have isolated a stable, transplantable, and small glucagonoma (MSL-G-AN) associated with abrupt onset of severe anorexia occurring 2-3 wk after subcutaneous transplantation. Before onset of anorexia, food consumption is comparable to untreated controls. Anorexia is followed by adipsia and weight loss, and progresses rapidly in severity, eventually resulting in reduction of food and water intake of 100 and 80%, respectively. During the anorectic phase, the rats eventually become hypoglycemic and hypothermic. The tumor-associated anorexia shows no sex difference, and is not affected by bilateral abdominal vagotomy, indicating a direct central effect. The adipose satiety factor leptin, known to suppress food intake by reducing hypothalamic neuropeptide Y (NPY) levels, was not found to be expressed by the tumor, and circulating leptin levels were reduced twofold in the anorectic phase. A highly significant increase in hypothalamic (arcuate nucleus) NPY mRNA levels was found in anorectic rats compared with control animals. Since elevated hypothalamic NPY is among the most potent stimulators of feeding and a characteristic of most animal models of hyperphagia, we conclude that the MSL-G-AN glucagonoma releases circulating factor(s) that overrides the hypothalamic NPY-ergic system, thereby eliminating the orexigenic effect of NPY. We hypothesize a possible central role of proglucagon-derived peptides in the observed anorexia. PMID:9435324

  7. The influence of the lower beak on the interorbital septum-prenasal process complex in the chick embryo.

    PubMed

    Wouterlood, F G; van Pelt, W

    1979-01-01

    The effect of removal of the lower beak on the development of the interorbital septumprenasal process (ISPP) complex was studied in chick embryos. In normal development the angle between the ventral contour of the interorbital septum and the long axis of the prenasal process increases. At the same time the angle between the ventral contour of the interorbital septum and the basal plate increases. After surgical removal of the prospective lower beak at stage 29, the position of the entire ISPP complex was altered in stage-38 embryos and the prenasal process showed elongation. In stage-38 embryos in which the prospective upper beak had been removed at stage 29, Meckel's cartilage was elongated. It is concluded that straightening of the angle between the ventral contour of the interorbital septum and the long axis of the prenasal process is not influenced by the lower beak, whereas the position of the entire ISPP complex and the size of the prenasal process are under the epigenetic influence of the lower beak. The position and size of Meckel's cartilage are under the epigenetic influence of the upper beak.

  8. Interaction of the tracheal tubules of Scutigera coleoptrata (Chilopoda, Notostigmophora) with glandular structures of the pericardial septum

    PubMed Central

    Hilken, Gero; Edgecombe, Gregory D.; Müller, Carsten H.G.; Sombke, Andy; Wirkner, Christian S.; Rosenberg, Jörg

    2015-01-01

    Abstract Notostigmophora (Scutigeromorpha) exhibit a special tracheal system compared to other Chilopoda. The unpaired spiracles are localized medially on the long tergites and open into a wide atrium from which hundreds of tracheal tubules originate and extend into the pericardial sinus. Previous investigators reported that the tracheal tubules float freely in the hemolymph. However, here we show for the first time that the tracheal tubules are anchored to a part of the pericardial septum. Another novel finding is this part of the pericardial septum is structured as an aggregated gland on the basis of its specialized epithelium being formed by hundreds of oligocellular glands. It remains unclear whether the pericardial septum has a differently structure in areas that lack a connection with tracheal tubules. The tracheal tubules come into direct contact with the canal cells of the glands that presumably secrete mucous substances covering the entire luminal cuticle of the tracheal tubules. Connections between tracheae and glands have not been observed in any other arthropods. PMID:26257546

  9. Short-term oral administration of several manganese compounds in mice: Physiological and behavioral alterations caused by different forms of manganese

    SciTech Connect

    Komura, Junko; Sakamoto, Michiko )

    1991-06-01

    In Kanazawa, Japan, air pollution from a Mn treatment factory was found to affect local junior high school students, who showed reduced respiratory function relative to their exposure to Mn. The use of Mn as an antiknock ingredient in automobile fuels has recently been introduced, placing the general population at risk of chronic low-level exposure. There are few animal studies on the effects of compounds other than manganese chloride (MnCl{sub 2}). In the case of environmental pollution by Mn, the differing physiological effects of the various chemical forms of Mn must be considered. The present study therefore examined the differences in the effects of several Mn compounds on the physiology and behavior of mice by short-term oral administration.

  10. Percutaneous transluminal angioplasty and stenting for severe stenosis of the intracranial extradural internal carotid artery causing transient ischemic attack or minor stroke

    PubMed Central

    Ko, Jun Kyeung; Choi, Chang Hwa; Cha, Seung Heon; Choi, Byung Kwan; Cho, Won Ho; Kang, Tae Ho; Sung, Sang Min; Cho, Han Jin

    2015-01-01

    The purpose of this study is to assess the technical feasibility and clinical efficacy of percutaneous transluminal angioplasty and stenting (PTAS) for symptomatic stenosis of the intracranial extradural (petrous and cavernous) internal carotid artery (ICA). Review of medical records identified 26 consecutive patients who underwent PTAS using a balloon-expandable coronary stent (n = 15, 57.7%) or a Wingspan self-expandable stent (n = 11, 42.3%) for treatment of severe stenosis (>70%) involving the intracranial extradural ICA. The inclusion criteria were transient ischemic attack with an ABCD2 score of ≥3 (n = 12, 46.2%) or minor stroke with an NIHSS score of ≤4 (n = 14, 53.8%). Technical success rates, complications, and angiographic and clinical outcomes were analyzed retrospectively. PTAS was technically successful in all patients. The mean stenosis ratio decreased from 77.1% to 10.0% immediately after PTAS. The overall incidence of procedural complications was 23.1%, and the postoperative permanent morbidity/mortality rate was 7.7%. A total of 22 patients were tracked over an average period of 29.9 months. During the observation period, 20 patients (90.9%) had no further cerebrovascular events and stroke recurrence occurred in two patients (9.1%), resulting in an annual stroke risk of 3.7%. Two cases (11.1%) of significant in-stent restenosis (>50%) were found on follow-up angiography (n = 18). PTAS for severe stenosis (>70%) involving the intracranial extradural ICA showed a good technical feasibility and favorable clinical outcome in patients with transient ischemic attack or minor stroke. PMID:26063697

  11. Association of Single-Nucleotide Polymorphisms in IL28B, but Not TNF-α, With Severity of Disease Caused by Andes Virus

    PubMed Central

    Angulo, Jenniffer; Pino, Karla; Echeverría-Chagas, Natalia; Marco, Claudia; Martínez-Valdebenito, Constanza; Galeno, Héctor; Villagra, Eliecer; Vera, Lilian; Lagos, Natalia; Becerra, Natalia; Mora, Judith; Bermúdez, Andrea; Cárcamo, Marcela; Díaz, Janepsy; Miquel, Juan Francisco; Ferrés, Marcela; López-Lastra, Marcelo

    2015-01-01

    Background. Andes virus (ANDV) is the sole etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile, with a fatality rate of about 35%. Individual host factors affecting ANDV infection outcome are poorly understood. In this case-control genetic association analysis, we explored the link between single-nucleotide polymorphisms (SNPs) rs12979860, rs8099917 and rs1800629 and the clinical outcome of ANDV-induced disease. The SNPs rs12979860 and rs8099917 are known to play a role in the differential expression of the interleukin 28B gene (IL28B), whereas SNP rs1800629 is implicated in the expression of tumor necrosis factor α gene (TNF-α). Methods. A total of 238 samples from confirmed ANDV-infected patients collected between 2006 and 2014, and categorized according to the severity of the disease, were genotyped for SNPs rs12979860, rs8099917, and rs1800629. Results. Analysis of IL28B SNPs rs12979860 and rs8099917 revealed a link between homozygosity of the minor alleles (TT and GG, respectively), displaying a mild disease progression, whereas heterozygosity or homozygosity for the major alleles (CT/CC and TG/TT, respectively) in both IL28B SNPs is associated with severe disease. No association with the clinical outcome of HCPS was observed for TNF-α SNP rs1800629 (TNF −308G>A). Conclusions. The IL28B SNPs rs12979860 and rs8099917, but not TNF-α SNP rs1800629, are associated with the clinical outcome of ANDV-induced disease, suggesting a possible link between IL28B expression and ANDV pathogenesis. PMID:26394672

  12. A Severe Accident Caused by an Ocellate River Stingray (Potamotrygon motoro) in Central Brazil: How Well Do We Really Understand Stingray Venom Chemistry, Envenomation, and Therapeutics?

    PubMed Central

    da Silva, Nelson Jorge; Clementino Ferreira, Kalley Ricardo; Leite Pinto, Raimundo Nonato; Aird, Steven Douglas

    2015-01-01

    Freshwater stingrays cause many serious human injuries, but identification of the offending species is uncommon. The present case involved a large freshwater stingray, Potamotrygon motoro (Chondrichthyes: Potamotrygonidae), in the Araguaia River in Tocantins, Brazil. Appropriate first aid was administered within ~15 min, except that an ice pack was applied. Analgesics provided no pain relief, although hot compresses did. Ciprofloxacin therapy commenced after ~18 h and continued seven days. Then antibiotic was suspended; however, after two more days and additional tests, cephalosporin therapy was initiated, and proved successful. Pain worsened despite increasingly powerful analgesics, until debridement of the wound was performed after one month. The wound finally closed ~70 days after the accident, but the patient continued to have problems wearing shoes even eight months later. Chemistry and pharmacology of Potamotrygon venom and mucus, and clinical management of freshwater stingray envenomations are reviewed in light of the present case. Bacterial infections of stingray puncture wounds may account for more long-term morbidity than stingray venom. Simultaneous prophylactic use of multiple antibiotics is recommended for all but the most superficial stingray wounds. Distinguishing relative contributions of venom, mucus, and bacteria will require careful genomic and transcriptomic investigations of stingray tissues and contaminating bacteria. PMID:26094699

  13. Dwarfism in mice lacking collagen-binding integrins α2β1 and α11β1 is caused by severely diminished IGF-1 levels.

    PubMed

    Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F; Ehlen, Harald W A; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

    2012-02-24

    Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis.

  14. Random Splicing of Several Exons Caused by a Single Base Change in the Target Exon of CRISPR/Cas9 Mediated Gene Knockout

    PubMed Central

    Kapahnke, Marcel; Banning, Antje; Tikkanen, Ritva

    2016-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)-associated sequence 9 (CRISPR/Cas9) system is widely used for genome editing purposes as it facilitates an efficient knockout of a specific gene in, e.g. cultured cells. Targeted double-strand breaks are introduced to the target sequence of the guide RNAs, which activates the cellular DNA repair mechanism for non-homologous-end-joining, resulting in unprecise repair and introduction of small deletions or insertions. Due to this, sequence alterations in the coding region of the target gene frequently cause frame-shift mutations, facilitating degradation of the mRNA. We here show that such CRISPR/Cas9-mediated alterations in the target exon may also result in altered splicing of the respective pre-mRNA, most likely due to mutations of splice-regulatory sequences. Using the human FLOT-1 gene as an example, we demonstrate that such altered splicing products also give rise to aberrant protein products. These may potentially function as dominant-negative proteins and thus interfere with the interpretation of the data generated with these cell lines. Since most researchers only control the consequences of CRISPR knockout at genomic and protein level, our data should encourage to also check the alterations at the mRNA level. PMID:27983621

  15. A Severe Accident Caused by an Ocellate River Stingray (Potamotrygon motoro) in Central Brazil: How Well Do We Really Understand Stingray Venom Chemistry, Envenomation, and Therapeutics?

    PubMed

    da Silva, Nelson Jorge; Ferreira, Kalley Ricardo Clementino; Pinto, Raimundo Nonato Leite; Aird, Steven Douglas

    2015-06-18

    Freshwater stingrays cause many serious human injuries, but identification of the offending species is uncommon. The present case involved a large freshwater stingray, Potamotrygon motoro (Chondrichthyes: Potamotrygonidae), in the Araguaia River in Tocantins, Brazil. Appropriate first aid was administered within ~15 min, except that an ice pack was applied. Analgesics provided no pain relief, although hot compresses did. Ciprofloxacin therapy commenced after ~18 h and continued seven days. Then antibiotic was suspended; however, after two more days and additional tests, cephalosporin therapy was initiated, and proved successful. Pain worsened despite increasingly powerful analgesics, until debridement of the wound was performed after one month. The wound finally closed ~70 days after the accident, but the patient continued to have problems wearing shoes even eight months later. Chemistry and pharmacology of Potamotrygon venom and mucus, and clinical management of freshwater stingray envenomations are reviewed in light of the present case. Bacterial infections of stingray puncture wounds may account for more long-term morbidity than stingray venom. Simultaneous prophylactic use of multiple antibiotics is recommended for all but the most superficial stingray wounds. Distinguishing relative contributions of venom, mucus, and bacteria will require careful genomic and transcriptomic investigations of stingray tissues and contaminating bacteria.

  16. Propagation of vibration caused by electrical excitation in the normal human heart.

    PubMed

    Kanai, Hiroshi

    2009-06-01

    The ability to noninvasively detect regional dynamic myocardial damage related to action potentials and mechanical properties affected by heart disease is of great clinical importance. Though there are invaluable clinical tools for diagnosis of a broad range of cardiac conditions, such myocardial properties cannot be evaluated. We have previously shown that pulsive vibration occurs on the myocardium after electrical stimulation of an isolated heart. In this study, using a novel technique for ultrasonic measurement of the myocardial motion, we detected pulsive vibrations spontaneously caused by electrical excitation and by valve closure. Using a sparse sector scan, the vibrations were measured almost simultaneously at about 10,000 points set in the heart wall at a high temporal resolution. The consecutive spatial distributions of the phase of the vibrations revealed wave propagation along the wall in healthy subjects for the first time in vivo. At around the time of the Q-wave of the electrocardiogram, the propagation started from the interventricular septum and extended to both the base and apical sides of the heart with a speed of 1 m/s, which corresponds to the propagation of electrical excitation from the Purkinje fiber-myocyte junction in the interventricular septum. Other vibrations then propagated from the base at several m/s, although some of them had dispersion properties. These are shear waves caused by the mitral-valve closure, corresponding to the first heart sound. These phenomena have potential for detection of regional myocardial tissue damage related to propagation of the action potentials and regional myocardial viscoelasticity.

  17. Dominant-Negative Mutations in α-II Spectrin Cause West Syndrome with Severe Cerebral Hypomyelination, Spastic Quadriplegia, and Developmental Delay

    PubMed Central

    Saitsu, Hirotomo; Tohyama, Jun; Kumada, Tatsuro; Egawa, Kiyoshi; Hamada, Keisuke; Okada, Ippei; Mizuguchi, Takeshi; Osaka, Hitoshi; Miyata, Rie; Furukawa, Tomonori; Haginoya, Kazuhiro; Hoshino, Hideki; Goto, Tomohide; Hachiya, Yasuo; Yamagata, Takanori; Saitoh, Shinji; Nagai, Toshiro; Nishiyama, Kiyomi; Nishimura, Akira; Miyake, Noriko; Komada, Masayuki; Hayashi, Kenji; Hirai, Syu-ichi; Ogata, Kazuhiro; Kato, Mitsuhiro; Fukuda, Atsuo; Matsumoto, Naomichi

    2010-01-01

    A de novo 9q33.3-q34.11 microdeletion involving STXBP1 has been found in one of four individuals (group A) with early-onset West syndrome, severe hypomyelination, poor visual attention, and developmental delay. Although haploinsufficiency of STXBP1 was involved in early infantile epileptic encephalopathy in a previous different cohort study (group B), no mutations of STXBP1 were found in two of the remaining three subjects of group A (one was unavailable). We assumed that another gene within the deletion might contribute to the phenotype of group A. SPTAN1 encoding α-II spectrin, which is essential for proper myelination in zebrafish, turned out to be deleted. In two subjects, an in-frame 3 bp deletion and a 6 bp duplication in SPTAN1 were found at the initial nucleation site of the α/β spectrin heterodimer. SPTAN1 was further screened in six unrelated individuals with WS and hypomyelination, but no mutations were found. Recombinant mutant (mut) and wild-type (WT) α-II spectrin could assemble heterodimers with β-II spectrin, but α-II (mut)/β-II spectrin heterodimers were thermolabile compared with the α-II (WT)/β-II heterodimers. Transient expression in mouse cortical neurons revealed aggregation of α-II (mut)/β-II and α-II (mut)/β-III spectrin heterodimers, which was also observed in lymphoblastoid cells from two subjects with in-frame mutations. Clustering of ankyrinG and voltage-gated sodium channels at axon initial segment (AIS) was disturbed in relation to the aggregates, together with an elevated action potential threshold. These findings suggest that pathological aggregation of α/β spectrin heterodimers and abnormal AIS integrity resulting from SPTAN1 mutations were involved in pathogenesis of infantile epilepsy. PMID:20493457

  18. Two unique mutations in the interleukin-2 receptor gamma chain gene (IL2RG) cause X-linked severe combined immunodeficiency arising in opposite parental germ lines

    SciTech Connect

    Puck, J.M.; Pepper, A.E.

    1994-09-01

    The gene encoding the gamma chain of the lymphocyte receptor for IL-2 lies in human X13.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID). 27 X-linked SCID mutations have been found in our laboratory. Single strand conformation polymorphism (SSCP) analysis of genomic DNA using primers flanking each of the 8 exons was followed by direct sequencing of abnormally migrating fragments from SCID patients and family members. A 9 bp in-frame duplication insertion was found in IL2RG exon 5 of a patient from a large X-linked SCID pedigree; the resulting duplication of 3 extracellular amino acids, including the first tryptophan of the {open_quotes}WSXWS{close_quotes} cytokine binding motif, is predicted to disrupt interaction of the cytokine receptor chain with its ligand. Genetic linkage studies demonstrated that the grandmaternal X chromosome associated with SCID was contributed to 3 daughters, 2 obligate carriers and 1 woman of unknown status. However, this grandmother`s genomic DNA did not contain the insertion mutation, nor did she have skewed X-chromosome inactivation in her lymphocytes. That both obligate carrier daughters, but not the third daughter, had the insertion proved the grandmother to be a germline mosaic. A second proband had X-linked SCID with a branch point mutation due to substitution of T for A 15 bp 5{prime} of the start of IL2RG exon 3. This mutation resulted in undetectable IL2RG mRNA by Northern blot. Linkage analysis and sequencing of IL2RG DNA in this family proved the mutation to have originated in the germline of the proband`s grandfather, an immunocompetent individual who contributed an X chromosome with normal IL2RG to one daughter and a mutated X to the another.

  19. Applying phylogenomics to understand the emergence of Shiga-toxin-producing Escherichia coli O157:H7 strains causing severe human disease in the UK

    PubMed Central

    Ashton, Philip M.; Byrne, Lisa; Perry, Neil T.; Petrovska, Liljana; Ellis, Richard; Allison, Lesley; Hanson, Mary; Holmes, Anne; Gunn, George J.; Chase-Topping, Margo E.; Woolhouse, Mark E. J.; Grant, Kathie A.; Gally, David L.; Wain, John; Jenkins, Claire

    2015-01-01

    Shiga-toxin-producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the emergence of this serotype in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains observed today. In this study, the genomes of over 1000 isolates from both human clinical cases and cattle, spanning the history of STEC O157:H7 in the UK, were sequenced. Phylogenetic analysis revealed the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimated the time to evolution of the most recent common ancestor of the current circulating global clone to be 175 years ago. This event was followed by rapid diversification. We show the acquisition of specific virulence determinates has occurred relatively recently and coincides with its recent detection in the human population. We used clinical outcome data from 493 cases of STEC O157:H7 to assess the relative risk of severe disease including haemolytic uraemic syndrome from each of the defined clades in the population and show the dramatic effect Shiga toxin repertoire has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years, one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. There is a need to understand the selection pressures maintaining Shiga-toxin-encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations.

  20. Antiplatelet effects of clopidogrel and aspirin after interventional patent foramen ovale/ atrium septum defect closure.

    PubMed

    Polzin, Amin; Dannenberg, Lisa; Sophia Popp, Valérie-; Kelm, Malte; Zeus, Tobias

    2016-06-01

    The optimal antiplatelet therapy after patent foramen ovale (PFO)/ atrium septum defect (ASD) closure is a matter of discussion. It is challenging as inter-individual responses to antiplatelet medication vary significantly and common complications are bleeding and ischemic events. In this study, we aimed to analyze the incidence of high on-treatment platelet reactivity (HTPR) to antiplatelet medication in patients undergoing PFO/ASD closure as well as clinical complications and thrombus formation on the occluder during six-month follow-up. This hypothesis generating pilot study was observed, which included 140 patients undergoing PFO/ASD closure. The primary endpoint was pharmacodynamic response to antiplatelet medication. A composite of death, myocardial infarction, bleeding, stroke and thrombus formation on the occluder during six-month follow-up was the secondary endpoint. HTPR to clopidogrel was analyzed using the vasodilator-stimulated protein phosphorylation (VASP), HTPR to aspirin by light-transmission aggregometry (LTA). In 71% of patients HTPR to clopidogrel was detected, HTPR to aspirin in only 4%. We observed 12 complications, 9 bleeding events (including 3 major bleeding events) and 3 transient ischemic attacks. No stroke and no thrombus formation on the occluder occurred. The primary endpoint was not associated with the secondary endpoint. The incidence of HTPR to clopidogrel in PFO/ASD closure patients is very high. Despite this high incidence, no stroke or thrombus formation on the occluder occurred at all. This leads to the hypothesis, that the benefit of additional clopidogrel medication is questionable and has to be investigated in large-scale clinical trials.

  1. [Left ventricular synchrony with septum stimulation vs. septal ventricular outflow tract in complete atrioventricular block].

    PubMed

    Rodríguez-Serrano, Gustavo; Lara-Vaca, Susano; Pereyra-Nobara, Texar; Bernal-Ruiz, Enrique

    2016-01-01

    Introducción: el objetivo del presente estudio fue determinar si existe diferencia en la función sistólica y la sincronía del ventrículo izquierdo con estimulación del septum medio o tracto de salida del ventrículo derecho en pacientes con bloqueo auriculoventricular portadores de marcapaso. Métodos: estudio observacional, analítico, transversal. Se seleccionaron todos los pacientes mayores de 18 años portadores de marcapaso con diagnóstico de bloqueo auriculoventricular. Se analizaron dos grupos acorde al sitio de colocación del electrodo de estimulación en región septal media o tracto de salida del ventrículo derecho. Se determinó la fracción de expulsión y sincronía del ventrículo izquierdo. Resultados: se incluyeron 54 pacientes por cada grupo, siendo las características de ambos similares, excepto el tiempo de colocación del electrodo de estimulación ventricular (p = < 0.001). No hubo diferencia significativa en la fracción de expulsión o sincronía del ventrículo izquierdo. Conclusiones: no se encontró diferencia en la fracción de expulsión o sincronía del ventrículo izquierdo independientemente del sitio de colocación del electrodo de estimulación.

  2. Neuroanatomy and sex differences of the lordosis-inhibiting system in the lateral septum

    PubMed Central

    Tsukahara, Shinji; Kanaya, Moeko; Yamanouchi, Korehito

    2014-01-01

    Female sexual behavior in rodents, termed lordosis, is controlled by facilitatory and inhibitory systems in the brain. It has been well demonstrated that a neural pathway from the ventromedial hypothalamic nucleus (VMN) to the midbrain central gray (MCG) is essential for facilitatory regulation of lordosis. The neural pathway from the arcuate nucleus to the VMN, via the medial preoptic nucleus, in female rats mediates transient suppression of lordosis, until female sexual receptivity is induced. In addition to this pathway, other regions are involved in inhibitory regulation of lordosis in female rats. The lordosis-inhibiting systems exist not only in the female brain but also in the male brain. The systems contribute to suppression of heterotypical sexual behavior in male rats, although they have the potential ability to display lordosis. The lateral septum (LS) exerts an inhibitory influence on lordosis in both female and male rats. This review focuses on the neuroanatomy and sex differences of the lordosis-inhibiting system in the LS. The LS functionally and anatomically links to the MCG to exert suppression of lordosis. Neurons of the intermediate part of the LS (LSi) serve as lordosis-inhibiting neurons and project axons to the MCG. The LSi-MCG neural connection is sexually dimorphic, and formation of the male-like LSi-MCG neural connection is affected by aromatized testosterone originating from the testes in the postnatal period. The sexually dimorphic LSi-MCG neural connection may reflect the morphological basis of sex differences in the inhibitory regulation of lordosis in rats. PMID:25278832

  3. Glutamic acid decarboxylase isoform distribution in transgenic mouse septum: an anti-GFP immunofluorescence study.

    PubMed

    Verimli, Ural; Sehirli, Umit S

    2016-09-01

    The septum is a basal forebrain region located between the lateral ventricles in rodents. It consists of lateral and medial divisions. Medial septal projections regulate hippocampal theta rhythm whereas lateral septal projections are involved in processes such as affective functions, memory formation, and behavioral responses. Gamma-aminobutyric acidergic neurons of the septal region possess the 65 and 67 isoforms of the enzyme glutamic acid decarboxylase. Although data on the glutamic acid decarboxylase isoform distribution in the septal region generally appears to indicate glutamic acid decarboxylase 67 dominance, different studies have given inconsistent results in this regard. The aim of this study was therefore to obtain information on the distributions of both of these glutamic acid decarboxylase isoforms in the septal region in transgenic mice. Two animal groups of glutamic acid decarboxylase-green fluorescent protein knock-in transgenic mice were utilized in the experiment. Brain sections from the region were taken for anti-green fluorescent protein immunohistochemistry in order to obtain estimated quantitative data on the number of gamma-aminobutyric acidergic neurons. Following the immunohistochemical procedures, the mean numbers of labeled cells in the lateral and medial septal nuclei were obtained for the two isoform groups. Statistical analysis yielded significant results which indicated that the 65 isoform of glutamic acid decarboxylase predominates in both lateral and medial septal nuclei (unpaired two-tailed t-test p < 0.0001 for LS, p < 0.01 for MS). This study is the first to reveal the dominance of glutamic acid decarboxylase isoform 65 in the septal region in glutamic acid decarboxylase-green fluorescent protein transgenic mice.

  4. The role of NMDA receptors of the medial septum and dorsal hippocampus on memory acquisition.

    PubMed

    Khakpai, Fatemeh; Nasehi, Mohammad; Zarrindast, Mohammad-Reza

    2016-04-01

    The glutamatergic neurons in the medial septal/diagonal band of broca (MS/DB) affect the hippocampal functions by modulating the septo-hippocampal neurons. Our study investigated the possible role of NMDA receptors of the medial septum nucleus (MS) and dorsal hippocampus (CA1) on memory acquisition in male Wistar rats. Animals were bilaterally implanted with chronic cannulae in the MS and CA1. Rats were trained in a step-through type inhibitory avoidance task, and tested 24h after training to measure step-through latency as memory retrieval. Our results indicated that pre-training intra-MS or intra-CA1 infusions of NMDA (0.125 μg/rat) and D-AP7 (0.012 μg/rat) increased and decreased memory acquisition, respectively when compared to saline control group. Also, pre-training intra-CA1 and intra-MS injection of an effect dose of D-AP7 (0.012 μg/rat) along with an effect dose of NMDA (0.125 μg/rat) impaired memory acquisition. Interestingly, pre-training intra-CA1/MS infusion of D-AP7 (0.012 μg/rat) diminished memory response produced by pre-training injection of NMDA (0.125 μg/rat) in the MS/CA1, respectively (cross injection or bilateral injection). Also, all above doses of drugs did not alter locomotor activity. These results suggest that the glutamatergic pathway between the MS and CA1 regions is involved in memory acquisition process.

  5. Gain Modulation of Cholinergic Neurons in the Medial Septum-Diagonal Band of Broca Through Hyperpolarization.

    PubMed

    Melonakos, Eric D; White, John A; Fernandez, Fernando R

    2016-12-01

    Hippocampal network oscillations are important for learning and memory. Theta rhythms are involved in attention, navigation, and memory encoding, whereas sharp wave-ripple complexes are involved in memory consolidation. Cholinergic neurons in the medial septum-diagonal band of Broca (MS-DB) influence both types of hippocampal oscillations, promoting theta rhythms and suppressing sharp wave-ripples. They also receive frequency-dependent hyperpolarizing feedback from hippocamposeptal connections, potentially affecting their role as neuromodulators in the septohippocampal circuit. However, little is known about how the integration properties of cholinergic MS-DB neurons change with hyperpolarization. By potentially altering firing behavior in cholinergic neurons, hyperpolarizing feedback from the hippocampal neurons may, in turn, change hippocampal network activity. To study changes in membrane integration properties in cholinergic neurons in response to hyperpolarizing inputs, we used whole-cell patch-clamp recordings targeting genetically labeled, choline acetyltransferase-positive neurons in mouse brain slices. Hyperpolarization of cholinergic MS-DB neurons resulted in a long-lasting decrease in spike firing rate and input-output gain. Additionally, voltage-clamp measures implicated a slowly inactivating, 4-AP-insensitive, outward K(+) conductance. Using a conductance-based model of cholinergic MS-DB neurons, we show that the ability of this conductance to modulate firing rate and gain depends on the expression of an experimentally verified shallow intrinsic spike frequency-voltage relationship. Together, these findings point to a means through which negative feedback from hippocampal neurons can influe