scholarly journals A Mathematical Model Relating Pitocin Use During Labor with Offspring Autism Development in Terms of Oxytocin Receptor Desensitization in the Fetal Brain

2018 ◽  
Author(s):  
Mark M. Gottlieb
Keyword(s):  
Mathematical Model ◽  
Half Life ◽  
Medical Information ◽  
Epidemiological Studies ◽  
Oxytocin Receptor ◽  
List Type ◽  
Receptor Desensitization ◽  
Infusion Time ◽  
Maternal Weight ◽  
Maternal Circulation

ABSTRACTThis paper develops a mathematical model describing the potential buildup of high oxytocin concentrations in the maternal circulation during labor in terms of continuous Pitocin infusion rate, half-life and maternal weight. Oxytocin override of the degradation of oxytocin by placental oxytocinase is introduced to model the potential transfer of oxytocin from the maternal circulation across the placenta into the fetal circulation, and from there into the brain of the fetus. The desensitization unit D equal to 1.8E6 (pg-min)/ml is employed to establish a desensitization threshold, and by extension; a down-regulation threshold as a function of oxytocin override concentration and continuous Pitocin infusion time, that could be a factor in the subsequent development of autism among offspring. Epidemiological studies by Duke University (S.G. Gregory, 2013), Yale University (O. Weisman, 2015) and Harvard University (A.S. Oberg, 2016) are discussed regarding Pitocin use and offspring autism development for an explanation of the weak correlations they identified. The findings of the Harvard epidemiological study are re-interpreted regarding Pitocin use, and its conclusion questioned. Further evaluations of the findings of these three epidemiological studies are called for to incorporate medical information on quantity of Pitocin used, continuous Pitocin infusion rate, length of labor and maternal weight to determine if a correlation can be established with offspring autism development above an empirically determined desensitization threshold for Pitocin use. Suggestions for research are discussed, including an alternative to continuous Pitocin infusion, pulsatile infusion of Pitocin during labor induction, that may mitigate possible offspring autism development.HIGHLIGHTSBuildup of oxytocin (OT) in the maternal circulation mathematically modeled.Relationship of OT half-life and OT concentration in maternal circulation identified.OTR Desensitization related to Pitocin infusion time and OT override concentration.Weak correlations for autism development in epidemiological studies explained.Examination called for of medical records of Pitocin use in epidemiological studies.OUTLINE OF PAPERIntroductionDevelopment and application of mathematical model – Sections 1 through 6, notably: Figures 1 through 4Discussion of oxytocin receptor desensitization as it pertains to mathematical model – Sections 7 and 8Influence of mathematical model on interpretation of epidemiological studies – Sections 9 and 10Research considerations – Section 11, notably:Subsection 11.1 – Call for detailed epidemiological analysis of selected medical information indicated by mathematical model Subsection 11.2 – Review of pulsatile Pitocin infusion to mitigate possible offspring autism development indicated by mathematical model

scholarly journals A Mathematical Model Relating Pitocin Use during Labor with Offspring Autism Development in terms of Oxytocin Receptor Desensitization in the Fetal Brain

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mark M. Gottlieb
Keyword(s):  
Mathematical Model ◽  
Infusion Rate ◽  
Medical Information ◽  
Fetal Brain ◽  
Subsequent Development ◽  
Epidemiological Studies ◽  
Maternal Weight ◽  
Yale University ◽  
Maternal Circulation ◽  
Duke University

This paper develops a mathematical model describing the potential buildup of high oxytocin concentrations in the maternal circulation during labor in terms of continuous Pitocin infusion rate, half-life, and maternal weight. Oxytocin override of the degradation of oxytocin by placental oxytocinase is introduced to model the potential transfer of oxytocin from the maternal circulation across the placenta into the fetal circulation and from there into the brain of the fetus. The desensitization unit D equal to 1.8E6 (pg·min)/ml is employed to establish a desensitization threshold and by extension, a downregulation threshold as a function of oxytocin override concentration and continuous Pitocin infusion time, that could be a factor in the subsequent development of autism among offspring. Epidemiological studies by Duke University [1], Yale University [2], and Harvard University [3] are discussed regarding Pitocin use and offspring autism development for an explanation of the weak correlations they identified. The findings of the Harvard epidemiological study are reinterpreted regarding Pitocin use and its conclusion questioned. Further evaluations of the findings of these three epidemiological studies are called for to incorporate medical information on quantity of Pitocin used, continuous Pitocin infusion rate, length of labor, and maternal weight to determine if a correlation can be established with offspring autism development above an empirically determined desensitization threshold for Pitocin use. Suggestions for research are discussed, including an alternative to continuous Pitocin infusion, pulsatile infusion of Pitocin during labor induction, which may mitigate possible offspring autism development.

OGO 6355 Mathematical model of foeto-maternal circulation: Application to the hypoxic situations

1997 ◽  
Vol 23 ◽  
pp. S108
Author(s):  
E. Ménigault ◽  
B. Lepoivre ◽  
P. Vieyres ◽  
J.L. Lacaze ◽  
M. Berson ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Maternal Circulation

Mathematical machine usage in medical information systems

2021 ◽  
Vol 65 (04) ◽  
pp. 75-85
Author(s):  
İradə Hətəm qızı Mirzəzadə ◽  
◽  
Gülçin Gülhüseyn qızı Abdullayeva ◽  
Həsənağa Rauf oğlu Nağızadə ◽  
◽  
...  
Keyword(s):  
Mathematical Model ◽  
Integral Equations ◽  
Medical Information ◽  
Simple Approach ◽  
Bayes Method ◽  
Medical Information Systems ◽  
Nonlinear Algebra ◽  
Artifical Neural Networks ◽  
Mathematical Machine ◽  
Differential And Integral Equations

Biosystem of the human body is viewed as a whole. First of all adequate mathematical machine selection and class of biosystems needs to be assigned for creation of mathematical model of biological system. Biosystem has two types of appoach. One of them is supposed to be a simple approach, the other is likely to be very complex – indexed approach. Different biosystems with determination properties are usually described by differential and integral equations, linear and nonlinear algebra. In some cases, algebraic polynoms with timed argument are used for presenting determined biosystem dynamics. Adequate mathematical modeling machine, probability theory, Markov and random processes theory and the laws are applied for the description of likely characterized biosystems. Key words: biosystem, biocybernetic issues, differential and integral equations, mathematical model, Markov chains, Bayes method, artifical neural networks

Abstract 1728: The Defect in HDL Function and Reverse Cholesterol Transport Found in Diabetic Mice with the Haptoglobin 2–2 Genotype Can Be Corrected with High Dose Antioxidant Therapy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rabea O Asleh ◽  
Rachel Miller-Lotan ◽  
Zaid Abassi ◽  
Andrew P Levy
Keyword(s):  
Half Life ◽  
Reverse Cholesterol Transport ◽  
Fold Increase ◽  
Oxidative Modification ◽  
Antioxidant Therapy ◽  
Cholesterol Transport ◽  
High Dose ◽  
List Type ◽  
Free Hemoglobin ◽  
Hdl Function

Background. The primary function of the haptoglobin (Hp) protein is to clear free hemoglobin (Hb). Two common alleles exist at the Hp locus (1 and 2). We recently demonstrated that reverse cholesterol transport is impaired in individuals with Diabetes Mellitus (DM) and the Hp 2–2 genotype which may explain the increased incidence of cardiovascular disease in this population. We sought to test the hypothesis that clearance of the Hp 2-Hb complex is slower in DM allowing more complex to bind to HDL thereby resulting in increased oxidative modification of HDL and inhibition of reverse cholesterol transport and determine if antioxidant therapy could restore normal HDL function in Hp 2–2 DM mice. Methods and Results. Injection of 125 I-labeled Hp 1 or Hp 2-Hb complexes into non-DM mice demonstrated that the half-life of the Hp 2-Hb complex was 2–3 fold longer than the Hp 1-Hb complex (57.8 ± 2.8 vs. 20.4 ± 1.7 min). Moreover, in DM the half-life of the Hp 2-Hb complex was doubled while the half-life of the Hp 1-Hb complex was unchanged (103 ± 3.9 vs. 18.6 ± 1.8 min). Coimmunoprecipitation studies demonstrated that over 25% of the injected Hp 2-Hb complex was associated with HDL in DM mice representing a greater than 10 fold increase compared to Hp 1-Hb complex in non-DM mice. Coimmunoprecipitation studies in Hp 0 (knockout) mice demonstrated that the Hp protein was absolutely necessary for the interaction of Hb with HDL. Reverse cholesterol transport was impaired by DM in Hp 2 mice but this impairment was prevented by high dose antioxidant supplementation to these mice. Conclusions. These data may explain why the Hp 2 genotype promotes less efficient reverse cholesterol transport in DM and suggests that strategies targeted to decrease oxidation of HDL by the Hp 2-Hb complex may improve HDL function.

Pharmacokinetic parameters of nandrolone (19-nortestosterone) after intramuscular administration of nandrolone decanoate (Deca-Durabolin®) to healthy volunteers

1985 ◽  
Vol 110 (3_Suppla) ◽  
pp. S19-S30 ◽  
Author(s):  
Herman P. Wijnand ◽  
Anneke M. G. Bosch ◽  
Catharina W. Donker
Keyword(s):  
Healthy Volunteers ◽  
Half Life ◽  
General Circulation ◽  
Serum Levels ◽  
Pharmacokinetic Parameters ◽  
Combined Processes ◽  
List Type ◽  
Nandrolone Decanoate ◽  
Serum Clearance ◽  
Hydrolysis Of

Abstract. Nandrolone decanoate (Deca-Durabolin®) was injected intramuscularly into healthy volunteers. One group of females received one injection of 100 mg and three groups of males received one injection of 200 mg, two repeat injections of 100 mg or four repeat injections of 50 mg respectively. The serum levels of nandrolone (19-nortestosterone) were determined by radioimmunoassay and used to estimate pharmacokinetic parameters. The following pharmacokinetic parameters were found: — a mean half-life of 6 days for the release of the ester from the muscular injection depot into the general circulation;— a mean half-life of 4.3 h for the combined processes of hydrolysis of nandrolone decanoate and of distribution and elimination of nandrolone;— a mean nandrolone serum clearance of 1.55 1 · h−1 · kg−1. The half-life of hydrolysis of nandrolone decanoate in serum was of the order of one hour or less. The data are consistent with linear kinetics.

Oxytocin Pretreatment Attenuates Oxytocin-induced Contractions in Human Myometrium In Vitro

2013 ◽  
Vol 119 (3) ◽  
pp. 552-561 ◽  
Author(s):  
Mrinalini Balki ◽  
Magda Erik-Soussi ◽  
John Kingdom ◽  
Jose C. A. Carvalho
Keyword(s):  
Dose Response ◽  
Area Under The Curve ◽  
Oxytocin Receptor ◽  
Control Group ◽  
Physiological Salt Solution ◽  
Dependent Manner ◽  
Receptor Desensitization ◽  
Chi Square ◽  
Motility Index

Abstract Background: Oxytocin receptor desensitization has been shown to occur in humans at biomolecular level and in isolated rat myometrium; however, its effect on human myometrial contractility has not been demonstrated. The objective of this in vitro study was to investigate the contractile response of human pregnant myometrium to oxytocin after pretreatment with different concentrations of oxytocin for variable durations. Methods: Myometrial samples were obtained from 62 women undergoing elective cesarean deliveries under regional anesthesia. The strips were pretreated with oxytocin 10−10, 10−8, 10−5M, or physiological salt solution (control) for 2, 4, 6, or 12 h, followed by a dose–response testing with oxytocin 10−10 to 10−5M. Amplitude and frequency of contractions, motility index, and area under the curve during the dose–response period were recorded, analyzed with linear regression models, and compared among groups. Results: Pretreatment with oxytocin 10−5 and 10−8M significantly reduced motility index (estimate [standard error]: −0.771 [0.270] square root units, P = 0.005 and −0.697 [0.293], P = 0.02, respectively) and area under the curve (−3.947 [1.909], P = 0.04 and −4.241 [2.189], P = 0.05, respectively) compared with control group, whereas pretreatment with oxytocin 10−10M did not significantly attenuate contractions. Increase in duration of oxytocin pretreatment from 2 to 12 h significantly decreased amplitude (type 3 generalized estimating equation analysis: chi-square = 14.0; df = 3; P = 0.003), motility index (chi-square = 9.3; df = 3; P = 0.03), and area under the curve (chi-square = 10.5; df = 3; P = 0.02), but not the frequency of oxytocin-induced contractions. Conclusion: Pretreatment with oxytocin decreases oxytocin-induced myometrial contractions in a concentration and time-dependent manner, likely as a function of the oxytocin receptor desensitization phenomenon.

Culture, vultures and the politics of post-neoliberalism a foot sodier’s perspective

2011 ◽  
Vol 26 (S2) ◽  
pp. 458-458
Author(s):  
D. Goel
Keyword(s):  
Mental Health ◽  
Research Evidence ◽  
Epidemiological Studies ◽  
Institutional Racism ◽  
Biomedical Science ◽  
Current Status ◽  
Political Agenda ◽  
Pathways To Care ◽  
List Type ◽  
Cultural Research

AimsTo review the current status, directions and distortions in the field of culture and mental health, and their interface with politics.Background reviewArising from the ruins of Adam Smith's shattered capitalist dream, shattered by the Great Depression, Keynesenian economics underpinned post-neoliberal thought and shaped politics, culture and science in ways few could have imagined.Biomedical science did not remain immune, and mental health provided a soft target to political activists and reformers. Research evidence relating to ethnic variations in the prevalence, pathways to care and outcomes in schizophrenia, generated from epidemiological studies on migrant populations and a series of WHO-sponsored cross-cultural studies, has become enmeshed in the dialectic around alleged institutional racism in psychiatry, with deeply entrenched and highly adversarial posturing on both sides.MethodExamine research evidence linking schizophrenia and culture, and how the politics of post-neoliberalism impacts scientific inquiry, with illustrations from different countries, and attempt to identify islands of credible research and outline possible future directions.ResultsFragmented and often contradictory evidence in this area does not lend itself to coherent inferences, with the problem being compounded by allegations of institutional racism.ConclusionsThere are many unanswered questions:•Does cultural research improve clinical practice?•Or does it merely distract attention from core/ important secular issues?•Does it tend to demonise mainstream services and alienate ethnic minority patients?•Does what some term cultural gimmickry serve a hidden political agenda?•Has cultural research evidence lead to meaningful macro or micro-level interventions?

P38 An audit to assess influenza vaccination uptake amongst asthmatic children in a city in the northwest of england

2018 ◽  
Vol 103 (2) ◽  
pp. e1.42-e1
Author(s):  
Aragon Cuevas Octavio ◽  
King Elisha ◽  
Morecroft Charles ◽  
Lilley Andrew
Keyword(s):  
Influenza Vaccine ◽  
Medical Information ◽  
Inappropriate Prescribing ◽  
Asthma Medication ◽  
British Thoracic Society ◽  
List Type ◽  
Asthmatic Children ◽  
National Review ◽  
Flu Vaccination ◽  
Tract Infections

AimsOne of the most common triggers of asthma exacerbations are respiratory tract infections such as influenza.1 Furthermore, the National Review of Asthma Deaths (NRAD) in 2014 linked inappropriate prescribing in primary care to patient deaths.1 The primary aim of this study was to assess the uptake of the influenza vaccine in asthmatic children in Liverpool during the 2016–2017 flu season. The secondary aim of this audit was to assess if children are being prescribed asthma medication in accordance with BTS guidelines.2MethodThe inclusion criteria for this retrospective study included children aged 16 and under, diagnosed with asthma and registered at a GP surgery within the Liverpool Care Commissioning Group (CCG). The practice managers at all 95 surgeries were invited to participate in this study via email. Participation included conducting a search using EMIS (Egton Medical Information Systems) to produce a paediatric asthma list that included the child’s age, gender, their current regular asthma medication, if and when the child had received the flu vaccination. Depending on their preference, the surgeries either completed an audit form or generated an anonymous EMIS search report. These documents were collected from the surgery by the researcher or returned via email. The data was analysed in SPSS using the chi-square test to determine if there were any significant associations between demographics, flu vaccination status and compliance to guidelines.ResultsInformation regarding flu vaccination was collected for 475 patients from seven surgeries. In total 148 (31.2%) children had received the flu vaccination during the 2016–2017 influenza season. Being registered at a GP surgery in an area of low deprivation and being aged 5 and under was associated with higher vaccination rates (p<0.05).Data containing current asthma treatment was obtained for 297 patients. In total 194 of those (65.3%) prescriptions followed current BTS guidelines. The most common reasons for not following BTS guidelines were patients being prescribed salbutamol monotherapy or no asthma medication at all. Being male and registered at a GP surgery in an area of low deprivation was associated with being prescribed asthma medication in accordance to guidelines (p<0.05).ConclusionThe uptake of the influenza vaccine in asthmatic children in Liverpool during the 2016–2017 flu season was very low (31.2%). The majority of children were prescribed regular asthma medications in line with BTS guidelines, although there are still multiple instances of poor prescribing practice. The results suggest that age, gender and deprivation level according to postcode affect whether a child’s medication will follow BTS guidelines or whether the child will be vaccinated. More research is required to fully establish these links.ReferencesRoyal College of Physicians. National Review of Asthma Deaths 2014. Available at https://www.rcplondon.ac.uk/projects/national-review-asthma-deaths (Accessed 12.12.17).British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma 2016. Available at https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2016/ (Accessed 12.12.17).

scholarly journals Bioinformation analysis of rotavirus vaccine efficiency

2019 ◽  
pp. 97-104
Author(s):  
S. O. Soloviov ◽  
I. V. Dziublyk ◽  
V. V. Trokhymchuk
Keyword(s):  
Mathematical Model ◽  
Vaccine Strain ◽  
General Circulation ◽  
Molecular Genetic ◽  
Epidemiological Data ◽  
Epidemiological Studies ◽  
Rotavirus Vaccine ◽  
Leading Role ◽  
Clinical Observations ◽  
Severe Gastroenteritis

A couple of studies have shown that viruses cause from 25 to 60% of acute intestinal infections (AII) cases, among which rotaviruses play a leading role in the structure of children's AII of viral etiology. According to the WHO recommendations, vaccination against rotavirus infection should be included into national immunization programs. Due to a wide diversity of circulating rotavirus genotypes, the issue of RVI vaccine efficiency, taking into account the dynamics of the molecular-genetic spectrum of RVI pathogens over time, remains relevant. The aim of the work – мodeling the dynamics of the molecular genetic spectrum of RVI pathogens and bioinformation analysis of f rotavirus vaccine efficiency. The object of the analysis was the results of molecular and epidemiological studies of RVI in Kyiv, conducted from 2007 to 2015. The dynamics of the genotypic spectrum was modeled using a Markov model, which involved replacing shares of the molecular genetic spectrum of rotaviruses with others ones according to homology with the vaccine strain: homology in both G and P genotypes, homology in G genotype or P genotype, no homology in both G and P genotypes. The method of rotavirus vaccine efficiency evaluation is based on data from clinical observations of vaccine efficiency, where different degrees of its efficiency against severe gastroenteritis caused by rotaviruses with different genotypes were shown. The shares of each genotype group in the general circulation of genotypes were taken as weights of the degree of homology relative to the vaccine strain, and the effectiveness of the vaccine against the strains of a specific homology group was obtained from clinical observations. The results of the analysis based on the constructed distribution curves of the molecular genetic spectrum of rotaviruses due to rotavirus vaccine strain  homology in Kiev showed that, despite the observed dynamics of the molecular genetic spectrum of RVI pathogens, the expected genotype-specific efficiency of rotavirus vaccine would be constant with a value of 0.835 or 83.5% against rotavirus gastroenteritis with a Vesikari severity of > 11 points. It was proposed mathematical model for prediction of molecular genetic spectrum of rotaviruses dynamics, taking into account the homology of the genotypes of RVI pathogens with respect to the vaccine strain. According to the literature data of molecular and epidemiological studies of rotaviruses in Kyiv, the parameters of the proposed mathematical model and the dynamics of the molecular genetic spectrum of RVI pathogens were determined. Using mathematical modeling, the expected genotype-specific efficiency of the rotavirus vaccine was determined based on Kyiv regional retrospective molecular and epidemiological data.

scholarly journals Acute development of Cushing syndrome in an HIV-infected child on atazanavir/ritonavir based antiretroviral therapy

2017 ◽  
Vol 2017 ◽  
Author(s):  
Gueorgui Dubrocq ◽  
Andrea Estrada ◽  
Shannon Kelly ◽  
Natella Rakhmanina
Keyword(s):  
Drug Interaction ◽  
Weight Gain ◽  
Hpa Axis ◽  
Cortisol Level ◽  
Half Life ◽  
Cushing Syndrome ◽  
Stimulation Test ◽  
List Type ◽  
Free Cortisol ◽  
Triamcinolone Injection

Summary An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom), didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 µg/L). This prompted further evaluation of the hypothalamic–pituitary axis (HPA) by standard dose adrenocorticotropic hormone (ACTH) stimulation test. A 250 µg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 µg/dL and stimulated cortisol level at 30 min was 3.8 µg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV) and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout surgery and postoperative period. Learning points: Drug–drug interaction between ritonavir and triamcinolone can cause Cushing syndrome. Although triamcinolone has a half-life of 3 h, an intra-articular injection may be systematically absorbed for 3 weeks after injection, and adrenal suppression may last as long as 30 days. Co-administration of ritonavir and corticosteroids may result in an increase of plasma levels of corticosteroids levels, as they are both eliminated by CYP3A metabolism, and this interaction has the potential to prolong the half-life of triamcinolone several fold. No specific guidelines are available for the management of iatrogenic Cushing syndrome secondary to ritonavir and corticosteroids. One treatment option includes replacing ritonavir with a non-protease inhibitor-based regimen. Initiating hydrocortisone replacement therapy to prevent an adrenal crisis is also an alternate option.

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