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Dongfen Yuan, Frederik Rode, Yanguang Cao
We proposed here a minimal physiologically based pharmacokinetic (mPBPK) model for a group of novel engineered antibodies in mice and humans. These antibodies are designed with altered binding properties of their Fc domain with neonatal Fc receptor (FcRn) or the Fab domain with their cognate targets (recycling antibodies) in acidic endosomes. To enable simulations of such binding features in the change of antibody pharmacokinetics and its target suppression, we nested an endothelial endosome compartment in parallel with plasma compartment based on our previously established mPBPK model...
March 14, 2018: AAPS Journal
Afroditi-Despina Lalou, Virginia Levrini, Matthew Garnett, Eva Nabbanja, Dong-Joo Kim, Laurent Gergele, Anna Bjornson, Zofia Czosnyka, Marek Czosnyka
INTRODUCTION: The so-called Davson's equation relates baseline intracranial pressure (ICP) to resistance to cerebrospinal fluid outflow (Rout), formation of cerebrospinal fluid (If ) and sagittal sinus pressure (PSS ) There is a controversy over whether this fundamental equation is applicable in patients with normal pressure hydrocephalus (NPH). We investigated the relationship between Rout and ICP and also other compensatory, clinical and demographic parameters in NPH patients. METHOD: We carried out a retrospective study of 229 patients with primary NPH who had undergone constant-rate infusion studies in our hospital...
March 8, 2018: Acta Neurochirurgica
Andreas Spiegelberg, Matthias Krause, Juergen Meixensberger, Burkhardt Seifert, Vartan Kurtcuoglu
OBJECTIVE: We aimed to test whether there is an association of slow vasogenic wave (SVW) occurrence with positive response to external lumbar drainage (ELD) and ventriculoperitoneal shunting and to design a method for the recognition and quantification of SVWs in the intracranial pressure (ICP) signal. MATERIALS AND METHODS: We constructed SVW templates using normalized sine waves. We calculated the cross-correlation between the respective SVW template and the ICP signal...
2018: Acta Neurochirurgica. Supplement
Eva Nabbanja, Marek Czosnyka, Nicole C Keong, Matthew Garnett, John D Pickard, Despina Afroditi Lalou, Zofia Czosnyka
OBJECTIVE: The term "hydrocephalus" encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. MATERIALS AND METHODS: We compared retrospective pre-shunting infusion test results performed in 310 adult patients diagnosed with normal pressure hydrocephalus (NPH) and their improvement after shunting...
2018: Acta Neurochirurgica. Supplement
Katarzyna Kaczmarska, Magdalena Kasprowicz, Antoni Grzanka, Wojciech Zabołotny, Peter Smielewski, Despina Afroditi Lalou, Georgios Varsos, Marek Czosnyka, Zofia Czosnyka
OBJECTIVES: The objectives were to compare three methods of estimating critical closing pressure (CrCP) in a scenario of a controlled increase in intracranial pressure (ICP) induced during an infusion test in patients with suspected normal pressure hydrocephalus (NPH). METHODS: We retrospectively analyzed data from 37 NPH patients who underwent infusion tests. Computer recordings of directly measured intracranial pressure (ICP), arterial blood pressure (ABP) and transcranial Doppler cerebral blood flow velocity (CBFV) were used...
2018: Acta Neurochirurgica. Supplement
Despina Afroditi Lalou, Marek Czosnyka, Joseph Donnelly, Andrea Lavinio, John D Pickard, Matthew Garnett, Zofia Czosnyka
OBJECTIVES: Slow waves of intracranial pressure (ICP) are spontaneous oscillations with a frequency of 0.3-4 cycles/min. They are often associated with pathological conditions, following vasomotor activity in the cranial enclosure. This study quantifies the effects of general anaesthesia (GA) on the magnitude of B-waves compared with natural sleep and the conscious state. MATERIALS AND METHODS: Four groups of 30 patients each were formed to assess the magnitude of slow waves...
2018: Acta Neurochirurgica. Supplement
V Moreno-Pérez, Jll Elvira, J Fernandez-Fernandez, F J Vera-Garcia
Background: Glenohumeral internal rotation deficit and external rotation strength have been associated with the development of shoulder pain in overhead athletes. Objective: To examine the bilateral passive shoulder rotational range of motion (ROM), the isometric rotational strength and unilateral serve speed in elite tennis players with and without shoulder pain history (PH and NPH, respectively) and compare between dominant and non-dominant limbs and between groups...
February 2018: International Journal of Sports Physical Therapy
Andreas Liebl, Viswanathan Mohan, Wenying Yang, Krzysztof Strojek, Sultan Linjawi
Since clinical experience with biphasic insulin aspart 30 (BIAsp 30) in type 2 diabetes mellitus (T2DM) was reviewed in 2012 after 10 years of use worldwide, additional studies have been published that highlight new aspects, including use in real-world populations. Evidence from 35 new studies confirms and builds upon previous work indicating that BIAsp 30 continues to have pharmacodynamic and clinical advantages over biphasic human insulin (BHI 30), including in real-world practice with unselected populations of patients...
February 21, 2018: Drugs in R&D
Charlotte Selge, Florian Schoeberl, Andreas Zwergal, Georg Nuebling, Thomas Brandt, Marianne Dieterich, Roman Schniepp, Klaus Jahn
OBJECTIVE: To test whether quantitative gait analysis of gait under single- and dual-task conditions can be used for a differential diagnosis of progressive supranuclear palsy (PSP) and idiopathic normal-pressure hydrocephalus (iNPH). METHODS: In this cross-sectional study, temporal and spatial gait parameters were analyzed in 38 patients with PSP (Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy diagnostic criteria), 27 patients with iNPH (international iNPH guidelines), and 38 healthy controls...
February 21, 2018: Neurology
James Pavela, Rahul Suresh, Rebecca S Blue, Charles H Mathers, L Maria Belalcazar
OBJECTIVE: Individuals with diabetes are increasingly seeking pretravel advice, but updated professional recommendations remain scant. We performed a systematic review on diabetes management during air travel to summarize current recommendations, assess supporting evidence, and identify areas of future research. METHODS: A systematic review of the English literature on diabetes management during air travel was undertaken utilizing PubMed and MEDLINE. Publications regarding general travel advice; adjustment of insulin and noninsulin therapies; and the use of insulin pumps, glucometers and subcutaneous glucose sensors at altitude were included...
February 2018: Endocrine Practice
Aaron Carass, Muhan Shao, Xiang Li, Blake E Dewey, Ari M Blitz, Snehashis Roy, Dzung L Pham, Jerry L Prince, Lotta M Ellingsen
Numerous brain disorders are associated with ventriculomegaly; normal pressure hydrocephalus (NPH) is one example. NPH presents with dementia-like symptoms and is often misdiagnosed as Alzheimer's due to its chronic nature and nonspecific presenting symptoms. However, unlike other forms of dementia NPH can be treated surgically with an over 80% success rate on appropriately selected patients. Accurate assessment of the ventricles, in particular its sub-compartments, is required to diagnose the condition. Existing segmentation algorithms fail to accurately identify the ventricles in patients with such extreme pathology...
September 2017: Patch-based techniques in medical imaging: third International Workshop, Patch-MI 2017, held in conjunction with MICCAI 2017, Quebec City, QC, Canada, September 14, 2017, Proceedings
I Jonathan Pomeraniec, Davis G Taylor, Aaron E Bond, M Beatriz Lopes
BACKGROUND: Patients with normal pressure hydrocephalus (NPH) and Alzheimer's dementia (AD) can often present with similar symptoms. NPH remains a clinical diagnosis and there are reported shared underlying dynamics of cerebrospinal fluid (CSF) flow and histopathology with patients with biopsy-proven AD. METHODS: This is a review on the histopathology and cerebrospinal fluid dynamics of both NPH and AD. In a prior study at the University of Virginia, the authors reviewed patients over a 15 year period who were shunted for a preoperative diagnosis of NPH...
February 13, 2018: Journal of Neurosurgical Sciences
Carl P C Chen, Yin-Cheng Huang, Chen-Nen Chang, Jean-Lon Chen, Chih-Chin Hsu, Wan-Ying Lin
Normal pressure hydrocephalus (NPH) was the first type of dementia ever described that can be treated using ventriculoperitoneal shunting surgery. Three typical clinical symptoms of NPH include gait disturbance, progressive cognitive dysfunction, and urinary incontinence. Although there are articles that have discovered several cerebrospinal fluid (CSF) protein biomarkers associated with NPH; however, studies examining individual and total protein concentrations from the ventricular CSF before and after shunting surgery are lacking...
February 1, 2018: Experimental Gerontology
Marc Núnez-Ollé, Travis H Stracker, Gabriel Gil-Gómez
No abstract text is available yet for this article.
February 3, 2018: Aging
Chun-Xiao Cui, Shikuo Ren, Zaozao Qiu, Zuowei Xie
A variety of carborane-fused carbo- and heterocycles were prepared in good to high isolated yields via the reaction of carborane-fused zirconacyclopentane with a series of substrates such as S8, Se, Te, CO, XylNC, MeOOC-CH[double bond, length as m-dash]N2, PhPCl2, nBu2SnCl2 and Me2GeCl2. However, it was found that the Zr-C bond in the zirconacyclopentane did not show any reactivity towards PhBCl2, PhCN and PhCH[double bond, length as m-dash]NPh. This approach represents a promising route to functionalized carboranes that are difficult to access by conventional methods...
January 31, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
S Mishra, L Connors, B Tugwell
BACKGROUND: Insulin allergy is a rare yet severe side effect of exogenous insulin use. Management typically involves use of alternative antihyperglycaemic agents, symptom control with antihistamines, use of different insulin formulations, and induction of tolerance with incremental doses of insulin. This treatment regimen is not always successful, and the use of omalizumab, an anti-IgE monoclonal antibody, has been used to induce tolerance to insulin. CASE REPORT: G...
January 30, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Okko T Pyykkö, Ossi Nerg, Hanna-Mari Niskasaari, Timo Niskasaari, Anne M Koivisto, Mikko Hiltunen, Jussi Pihlajamäki, Tuomas Rauramaa, Maria Kojoukhova, Irina Alafuzoff, Hilkka Soininen, Juha E Jääskeläinen, Ville Leinonen
OBJECT: To investigate incidence, comorbidities, mortality, and causes of death in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A cohort of 536 patients with possible NPH from a defined population with a median follow-up time of 5.1 years (range 0.04-19.9) was included in the study. Patients were evaluated by brain imaging and intraventricular pressure monitoring with a brain biopsy immunostained against amyloid-β and hyperphosphorylated tau. Hospital records were reviewed for vascular diseases and type 2 diabetes mellitus (T2DM)...
January 25, 2018: World Neurosurgery
Alan J Garber, Martin J Abrahamson, Joshua I Barzilay, Lawrence Blonde, Zachary T Bloomgarden, Michael A Bush, Samuel Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Vivian A Fonseca, Jeffrey R Garber, W Timothy Garvey, George Grunberger, Yehuda Handelsman, Irl B Hirsch, Paul S Jellinger, Janet B McGill, Jeffrey I Mechanick, Paul D Rosenblit, Guillermo E Umpierrez
A1C = hemoglobin A1C; AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick release; BMI = body mass index; BP = blood pressure; CCB = calcium channel blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 = dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER = extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea; SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes Trial...
January 2018: Endocrine Practice
Paulo H R F Almeida, Thales B C Silva, Francisco de Assis Acurcio, Augusto A Guerra Júnior, Vania E Araújo, Leonardo M Diniz, Brian Godman, Alessandra M Almeida, Juliana Alvares
INTRODUCTION: Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemic episodes improves the quality of life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, there is a need to assess their impact on QoL to provide future guidance to health authorities...
January 10, 2018: Patient
Hua Shu, Juming Lu, Puhong Zhang, Dongshan Zhu, Xian Li, Jiachao Ji, Fang Zhao, Linong Ji
BACKGROUND: We aimed to determine the clinical characteristics of type 2 diabetes patients on basal insulin therapy with inadequate glucose control due to discordance between glycated haemoglobin (HbA1c ) and fasting plasma glucose (FPG) in the real world. METHODS: This was a retrospective analysis of data from the ORBIT study in China. Clinical characteristics of patients with discordance between HbA1c and FPG at baseline and at the end of 6 months of follow-up were analysed using multinomial logistic regression in 4 study groups divided by HbA1c and FPG...
January 3, 2018: Diabetes/metabolism Research and Reviews
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