THESIS Presented to THE FACULTY OF MEDICINE, University of the Witwatergrand. In Partial Fulfillment of the requirements for the Degree DOCTOR OF MEDICINE. / Every morbid condition, occurring in Medicine is based fundamentally on the genetic constitution of the individual, but only diseases whloh are significantly related to hereditary factors are regarded as hereditary diseases. In the thesis presented by the writer, an attempt is made to show how the environment affects the development and expression of factors genetical in origin. The first part of this work is really only a sketchy introduction to the genetic processes involved, and is presented as a background on which to paint the picture of certain conditions regarded as slgnifioantally environmental in origin,. Hence the early chapters cannot be regarded as being vety complete or detailed, but an attempt has been made to present the basic genetic laws, and to Interpret various morbid processes in the foetus and newborn In the light of these laws. Some of these pathological conditions have only recently been understood, and a few are enumerated In the hope of producing an over-all picture. Some are touched upon as being of some practical importance either . at the present date, or possibly in the near future, This brings us to the conception of "prenatal paediatrics." There is a tendency at the present time for a closer relationship to develop between obstetrician and paediatrician Just because of the newer knowledge regarding the reciprocal relationship between maternal and foetal status. Maternal nutri- Importance* Obstetricians, today, in introducing newer and safer procedures, operations, and analgaesic methods for delivering their patients, consider more and more, the management of labour in terms of the effect upon the foetus. Psychological, as well as physiological care of the pregnant woman must be instituted beoause psychological disturbances may significantly affect the actual physiology of pregnancy and parturition. Paediatric attention, initiated early in pregnancy, is therefore not necessarily an impractical procedure. As the genetlo constitution cannot be Varied the aim of “prenatal paediatrics” must be directed towards modification of adverse environmental factors. One of the great aims of Eugenics is to prevent the action of adverse genetio factors, but the scope of eugenics at.the present time Is limited in its application. There appears to be a tendency, as the centuries roll on, for balanced genetical systems to evolve, whioh seem to be resistant to change. Whether the future use of atomic radiation, either in Peace or in War, may change this, remains to be seen. The effects of maternal rubella, as described in the second part of this work, appear to be so diverse in different instances, that the operation of co-existent genetical background factors oannot entirely be excluded. It is essential to obtain better statistical Information regarding gene frequencies. Biochemistry, physiology, and Serology should be allied to Clinical and Social Medicine In an attempt to discover v i i i . and diabetes, and also various types of defedtfe fend malformations, such as congenital morbus cordis * deaf-mutism, mental defioienoy, eto. Art Investigation of the relationship between neonatal stattie fend the development of subsequent disease patterns during later childhood, or even adulthood, will undoubtedly » prove to be of the greatest import. In this work reference has been made to the value of epidemiological Btudies as a means of uncovering mechanisms which produce congenital defects. It should be remembered that, due to differences in diet, medical care, and a thousand other factors of changed environment, maternal status today is different to what it was fifty or one hundred years ago, and any effects for good or ill on the foetal population can. be unearthed by careful, prolonged statistical study. It is obvious that the correlated efforts of many branches of Ollnlcal, Experimental and Social Medicine over long.periods, are essential to produoe useful results. For lnstanoe, mongolism occurring in two slbs may not necessarily represent an hereditary condition, as one of the cases may be incidental, or dependant on environmental factors obtaining for both affected sibs. Similarly, many of the less typloal congenital defects, which in late years have been described as appearing in children born after maternal rubella may be incidental, and either represent the risk to the foetal population at large, or may yet be the means of uncovering the operation of other environmental factors as well. Hence we see the need for a oloser follow up of all morbid or abnormal conditions during pregnancy, particularly/*«,. particularly virus infections, with complete reports on the infants subsequently born, whether normal or otherwise. This need becomes clear, when the latter part of this work is consulted. The investigations carried out on maternal rubella as an aetiological factor in the production of congenital defects is presented as a most important step in the understanding and prevention of unfortunate accidents of foetal development. The present thesis is essentially a review of the literature, but several oases are presented on account.of the paucity of reports in the xrorld literature. In this connection, the writer would like to acknowledge case histories given by Doctors D. G. Melle, 0.N..Javett, M. Chitters, W, Tope, M, Epstein and C-. Faerber all of Johannesburg, and Doctors B. Epstein, P. Oosterhagen and J. Rudolph of Pretoria. Valuable assistance and great courtesy has been offered by the Matron, St. Vinoentfs School for the Deaf, Johannesburg, Mr. Wentworth of.the National Council for the Blind, Pretoria, Dr. le Riche of the Union Health Department, Pretoria, Ma.^or Dreisenstock at Defence Headquarters, Pretoria and those most efficient librarians, Miss A.C. Dick.and Miss Krige of the Witwatersrand Medical Library. My thanks are also due to the doctors at Union Health Department, Pretoria who so graciously plaoed their excellent library material at my disposal* Last but not least, I am indebted to Mrs, T. Mellet, Miss E. Marcus and my wife for clerical assistance. X. E„ F. Pretoria, January, 1951. / IT2017

Diss. (sammanfattning) Uppsala : Univ., 2005. / Härtill 4 uppsatser.

Caffeine and retinoic acid were examined for effects upon limb morphogenesis and upon creatine kinase (CK) as a measure of limb myogenesis. Caffeine at 200 mg/kg, i.p., on E11 produced a low level of forelimb (1.2%) and hindlimb (2.0%) defects. Retinoic acid, at 50 mg/kg given orally as an oily suspension, induced a high level of reduction deformities. Hindlimbs (100%) were affected more than forelimbs (88%). Limbs (E16) were examined for CK isoenzymes using DEAE-Sephacel column chromatography. Untreated limbs had 88.04% skeletal muscle (MM), 6.98% hybrid (MB) and 5.08% brain (BB) CK isoenzyme. Caffeine had no effect. However, retinoic acid increased MM-CK to 92.67%, and decreased BB-CK to 2.24%. This is the first evidence that suggests that retinoic acid may modify the phenotypic expression of developing muscle.

No description available.

Thesis (Ph. D.)--University of Chicago, Department of History, June 2000. / Includes bibliographical references. Also available on the Internet.

Abstract   This essay is analysing the presence of cleaning and grooming in the novels Shakespeare’s Landlord and Dead Until Dark, both by Charlaine Harris. Against the backdrop of teratology, the essay demonstrates how cleaning and grooming are means for the female protagonists Lily and Sookie to get rid of their inner and outer monstrosities. Their respective monstrosity is defined against the definition of monstrosity by David J. Skal in Monster Theory Seven Theses and the need to get rid of monstrosity is discussed against the theories of Julia Kristeva and Mary Douglas.

A Cynara scolymus, popularmente conhecida como alcachofra, é uma planta hepatoprotetora com função colerética e colagoga. O extrato de C.scolymus foi recentemente liberado para a confecção de medicamentos fitoterápicos sem a necessidade de testes toxicológicos específicos, por ser uma planta utilizada há muito tempo e ter eficácia comprovada. Devido à falta de estudos sobre os efeitos dessa planta e por ela ser muito utilizada, o presente estudo visou avaliar os possíveis efeitos imunotóxicos, teratogênicos e de toxicidade geral do extrato seco da Cynara scolymus. O extrato seco da planta foi administrado a ratos Wistar adultos, machos e fêmeas, nas doses de 1, 2 e 4g/Kg, por gavagem, durante 28 dias, de acordo com o protocolo de testes de toxicidade da OECD Organization for Economic Co-operation and Development, para avaliação de toxicidade geral e imunotoxicidade. Foi avaliado o ganho de peso, consumo de alimento e água, os órgãos linfóides e a fenotipagem de suas células; a atividade de fagócitos, as respostas imunes humoral e celular e a atividade proliferativa de linfócitos também foram avaliados. No estudo da teratogenicidade, ratas prenhes receberam as mesmas doses do extrato seco de C.scolymus do 6° ao 19° dia de gestação. Avaliou-se o tamanho, peso, viabilidade e malformações externas dos fetos, bem como procedeu-se à análise óssea e visceral. O presente estudo revelou que o extrato de alcachofra não promoveu toxicidade geral nos ratos adultos tratados subagudamente; por outro lado, o extrato seco de C.scolymus promoveu aumento no peso relativo e celularidade do baço, aumento no peso relativo dos rins, diminuição na celularidade do timo e diminuição no DTH Delayed-type hypersensivity . Apesar disso a análise destes dados em conjunto não permite sugerir efeito imunotóxico dessa planta. O estudo da teratogenicidade mostrou que fêmeas gestantes tratadas com a C.scolymus apresentaram diminuição no ganho de peso; além disso, foi observada diminuição do peso uterino e fetal, menor comprimento fetal e queda do número de fetos vivos por ninhada. Assim, pode-se sugerir que embora a alcachofra não apresente toxicidade geral, nem efeito imunotóxico, não deve ser utilizado durante a gestação, tendo em vista que foi observada toxicidade fetal. / Cynara scolymus, commonly known as artichoke, is popular used as hepatoprotectant, choleretic and colagogue agent. The C.scolymus extrat was recently approved by Brazilian regulatory agency, for production of phytotherapeutic drugs, without toxicological tests, because it has been considered both harmless and effective. Due to lack of toxicological studies and its widely usage, the aim of this study is evaluate the immune system and the teratogenic effects as well as the general toxicity of C. scolymus extracts. Therefore, the extract was administered to adult male and female Wistar rats by gavage at 1, 2 and 4g/Kg doses for 28 days, according to the OECD (Organization for Economic Co-operation and Development) protocols. Body weight gain, food and water consumption, lymphoid organs and their cell phenotype were evaluated as well as the phagocyte analysis, humoural and cellular immune responses, and lymphocyte proliferation. In teratogenic study, pregnant rats received the same doses of C.scolymus extract from the 6th to the 19th gestational day. Fetuses size, weight, viability and external malformations were evaluated and subjected to bone and visceral analysis. The present study showed that C. scolymus extracts did not promote sub-acute toxicity in adult rats; however, the relative spleen weight and it cellularity were increased just as the kidney weight, but the thymus cellularity and DTH (Delayed-type hypersensivity) decreased. None of those results represent immunotoxic effect. The teratogenic study showed a decrease of body weight gain, uterus weight, fetal weight and number of fetuses, in practically all doses of the extract. Thus, these results showed that the C. scolymus extract is not toxic or immunotoxic but should not be used in pregnancy, due to fetal toxicity.

No description available.

A Cynara scolymus, popularmente conhecida como alcachofra, é uma planta hepatoprotetora com função colerética e colagoga. O extrato de C.scolymus foi recentemente liberado para a confecção de medicamentos fitoterápicos sem a necessidade de testes toxicológicos específicos, por ser uma planta utilizada há muito tempo e ter eficácia comprovada. Devido à falta de estudos sobre os efeitos dessa planta e por ela ser muito utilizada, o presente estudo visou avaliar os possíveis efeitos imunotóxicos, teratogênicos e de toxicidade geral do extrato seco da Cynara scolymus. O extrato seco da planta foi administrado a ratos Wistar adultos, machos e fêmeas, nas doses de 1, 2 e 4g/Kg, por gavagem, durante 28 dias, de acordo com o protocolo de testes de toxicidade da OECD Organization for Economic Co-operation and Development, para avaliação de toxicidade geral e imunotoxicidade. Foi avaliado o ganho de peso, consumo de alimento e água, os órgãos linfóides e a fenotipagem de suas células; a atividade de fagócitos, as respostas imunes humoral e celular e a atividade proliferativa de linfócitos também foram avaliados. No estudo da teratogenicidade, ratas prenhes receberam as mesmas doses do extrato seco de C.scolymus do 6° ao 19° dia de gestação. Avaliou-se o tamanho, peso, viabilidade e malformações externas dos fetos, bem como procedeu-se à análise óssea e visceral. O presente estudo revelou que o extrato de alcachofra não promoveu toxicidade geral nos ratos adultos tratados subagudamente; por outro lado, o extrato seco de C.scolymus promoveu aumento no peso relativo e celularidade do baço, aumento no peso relativo dos rins, diminuição na celularidade do timo e diminuição no DTH Delayed-type hypersensivity . Apesar disso a análise destes dados em conjunto não permite sugerir efeito imunotóxico dessa planta. O estudo da teratogenicidade mostrou que fêmeas gestantes tratadas com a C.scolymus apresentaram diminuição no ganho de peso; além disso, foi observada diminuição do peso uterino e fetal, menor comprimento fetal e queda do número de fetos vivos por ninhada. Assim, pode-se sugerir que embora a alcachofra não apresente toxicidade geral, nem efeito imunotóxico, não deve ser utilizado durante a gestação, tendo em vista que foi observada toxicidade fetal. / Cynara scolymus, commonly known as artichoke, is popular used as hepatoprotectant, choleretic and colagogue agent. The C.scolymus extrat was recently approved by Brazilian regulatory agency, for production of phytotherapeutic drugs, without toxicological tests, because it has been considered both harmless and effective. Due to lack of toxicological studies and its widely usage, the aim of this study is evaluate the immune system and the teratogenic effects as well as the general toxicity of C. scolymus extracts. Therefore, the extract was administered to adult male and female Wistar rats by gavage at 1, 2 and 4g/Kg doses for 28 days, according to the OECD (Organization for Economic Co-operation and Development) protocols. Body weight gain, food and water consumption, lymphoid organs and their cell phenotype were evaluated as well as the phagocyte analysis, humoural and cellular immune responses, and lymphocyte proliferation. In teratogenic study, pregnant rats received the same doses of C.scolymus extract from the 6th to the 19th gestational day. Fetuses size, weight, viability and external malformations were evaluated and subjected to bone and visceral analysis. The present study showed that C. scolymus extracts did not promote sub-acute toxicity in adult rats; however, the relative spleen weight and it cellularity were increased just as the kidney weight, but the thymus cellularity and DTH (Delayed-type hypersensivity) decreased. None of those results represent immunotoxic effect. The teratogenic study showed a decrease of body weight gain, uterus weight, fetal weight and number of fetuses, in practically all doses of the extract. Thus, these results showed that the C. scolymus extract is not toxic or immunotoxic but should not be used in pregnancy, due to fetal toxicity.

BACKGROUND: Teratology Information Services (TIS) educate the public and health professionals via telephone regarding the safety of drugs and other exposures during pregnancy and lactation. Currently TIS consultations are free, but funding is eroding. A cost-benefit analysis may inform resource allocation. It was hypothesized that an individual TIS consultation regarding anti-depressant use during pregnancy provides a positive net benefit compared to a family doctor (FD) consultation. METHODS: A survey of international TIS was conducted to gauge TIS costs. A discrete choice experiment (DCE) was designed to assess preferences and willingness-to-pay (WTP, an estimate of benefit) for teratology counseling. DCE respondents (local community volunteers) chose between potential counseling services following an anti-depressant exposure during pregnancy. Services were described by five service attributes and one cost attribute, which were generated in focus groups. Preferences and WTP were estimated using logit regression. Incremental benefits and costs of counseling by TIS and FD were compared in a probabilistic sensitivity analysis to obtain the incremental net benefit from both a societal (productivity costs included) and health system perspective. The FD consultation was costed through OHIP billing codes. The TIS consultation was micro-costed. RESULTS: Eighteen TIS in North America and 16 international TIS completed the survey. Most TIS are small (median two employees, median budget US$69,000). The DCE had 175 respondents. The most important attribute of counseling was receiving very helpful information; information delivery methods were less important. WTP for the TIS scenario was CDN$124 (SD $12); WTP for the FD scenario was CDN$79 (SD $8). Service costs were similar for TIS and FD (approximately $32/consultation); FD had higher productivity costs. Incremental TIS benefits were likely to outweigh costs under both the societal and health system perspectives (probability 99% and 97% respectively). CONCLUSIONS: An economic evaluation of a program that delivers pregnancy health information via telephone required a novel approach. While there are some methodological challenges to valuing benefits through willingness-to-pay, it may be appropriate for valuing counseling. TIS should emphasize their ability to provide high quality information. The benefits of an individual TIS consultation on anti-depressant use during pregnancy are likely greater than the costs.