Thesis (M.S.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2031-01-01

Cheung Kwok Lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 123-136). / ABSTRACT (English) --- p.i / ACKNOWLEDGMENTS --- p.1 / LIST OF FIGURES --- p.3 / LIST OF TABLES --- p.5 / LIST OF ABBREVIATIONS --- p.7 / Chapter I. --- INTRODUCTION AND OBJECTIVES --- p.8 / Chapter II. --- LITERATURE REVIEWS --- p.11 / Chapter II.A. --- Maternal Serum Alpha-fetoprotein Screeningin Singleton Pregnancies --- p.11 / Chapter II.A.1. --- Physiology of Alpha-fetoprotein --- p.12 / Chapter II.A.2. --- Historical Background of Screening by Alpha- fetoprotein --- p.12 / Chapter II.A.3. --- Factors that Influence Maternal Serum Alpha- fetoprotein Concentration --- p.13 / Chapter ILA.4. --- Elevated Maternal Serum Alpha-fetoprotein Concentration and Adverse Pregnancy Outcomes and Complications --- p.14 / Chapter II.A.4.a. --- Low Birth Weight --- p.16 / Chapter II.A.4.b. --- Fetal Loss --- p.17 / Chapter II.A.4.c. --- Pregnancy Induced Hypertension --- p.18 / Chapter II.B. --- Maternal Serum Human Chorionic Gonadotrophin Screening in Singleton Pregnancies --- p.18 / Chapter II.B.1. --- Physiology of Human Chorionic Gonadotrophin --- p.18 / Chapter II.B.2. --- Historical Background of Screening by Human Chorionic Gonadotrophin --- p.20 / Chapter II.B.3. --- Factors that Influence Maternal Serum Human Chorionic Gonadotrophin --- p.21 / Chapter II.B.4. --- Elevated Maternal Serum Human Chorionic Gonadotrophin Concentration and Pregnancy Complications --- p.21 / Chapter II.B.5. --- Maternal Serum AFP and hCG Concentrations and Adverse Outcomes or Complications in Twin Pregnancies --- p.23 / Chapter II.C. --- Mechanism for the Association between Adverse Outcomes and Elevated Maternal Serum Alpha- fetoprotein and Human Chorionic Gonadotrophin --- p.25 / Chapter III. --- METHODS --- p.28 / Chapter III.A. --- Study Population --- p.28 / Chapter III.B. --- Sample Collection and Analysis --- p.29 / Chapter III.C. --- Clinical Information --- p.30 / Chapter III.D. --- Microparticle Enzyme Immunoassay --- p.30 / Chapter III.D.1. --- Principles --- p.30 / Chapter III.D.1.a. --- Reaction Process --- p.31 / Chapter III.D.1.b. --- MEIA Assembly --- p.33 / Chapter III.D.1.c. --- Operation --- p.34 / Chapter III.D.2. --- AFP Assay --- p.34 / Chapter III.D.2.a. --- AFP Reagents --- p.34 / Chapter III.D.2.b. --- Sample Dilution --- p.36 / Chapter III.D.3. --- Total p-hCG Assay --- p.37 / Chapter III.D.3.a. --- Total p-hCG Reagents --- p.37 / Chapter III.D.3.b. --- Sample Dilution --- p.39 / Chapter III.D.4. --- Intra- and Inter-assay Variation --- p.39 / Chapter III.E. --- Data Handling --- p.42 / Chapter III.F. --- Statistical Analysis --- p.42 / Chapter III.F.1. --- Calculations of Median Values of Maternal Serum Alpha-fetoprotein and Human Chorionic Gonadotrophin Concentrations --- p.42 / Chapter III.F.2. --- Analysis for Adverse Outcomes or Complications --- p.43 / Chapter III.F.3. --- Adjustment of Alpha-fetoprotein and Human Chorionic Gonadotrophin for Gestational Age and Maternal Weight --- p.46 / Chapter IV. --- RESULTS --- p.48 / Chapter IV.A. --- Median Values of Maternal Serum Alpha-fetoprotein Human Chorionic Gonadotrophin --- p.48 / Chapter IV.B. --- Prediction of Adverse Outcomes by Maternal Serum Alpha-fetoprotein and Human Chorionic Gonadotrophin --- p.60 / Chapter IV.B. l. --- Preterm Delivery --- p.60 / Chapter IV.B.2. --- Spontaneous Preterm Delivery --- p.64 / Chapter IV.B.3. --- Premature Delivery --- p.68 / Chapter IV.B.4. --- Spontaneous Premature Delivery --- p.68 / Chapter IV.B.5. --- Other Outcomes or Complications --- p.72 / Chapter IV.B.6. --- Single Predictor for Most Adverse Outcomes --- p.74 / Chapter IV.C. --- Adjustment of Maternal Serum Alpha-fetoprotein and Human Chorionic Gonadotrophin for Maternal Weight and Gestational Age --- p.75 / Chapter IV.C.1. --- Distribution of Alpha-fetoprotein and Human Chorionic Gonadotrophin during Mid-trimester --- p.76 / Chapter IV.C.2. --- Adjustment of Alpha-fetoprotein for Maternal Weight and Gestational Age --- p.79 / Chapter IV.C.3. --- Adjustment of Human Chorionic Gonadotrophin for Maternal Weight and Gestational Age --- p.80 / Chapter IV.D. --- Predictiveness of Alpha-fetoprotein and Human Chorionic Gonadotrophin for Adverse Outcomes after Adjusted for Maternal Weight and Gestational Age --- p.83 / Chapter IV.D.l. --- Preterm Delivery --- p.86 / Chapter IV.D.2. --- Spontaneous Preterm Delivery --- p.86 / Chapter IV.D.3. --- Premature Delivery --- p.92 / Chapter IV.D.4. --- Spontaneous Premature Delivery --- p.92 / Chapter IV.D.5. --- Other Adverse Outcomes or Complications --- p.98 / Chapter IV.D.6. --- Single Predictor for Most Adverse Outcomes --- p.98 / Chapter V. --- DISCUSSIONS --- p.100 / Chapter V.A. --- Median Values of Maternal Serum Alpha-fetoprotein and Human Chorionic Gonadtrophin --- p.100 / Chapter V.B. --- Maternal Serum Alpha-fetoprotein and Human Chorionic Gonadotrophin Screening for Adverse Outcomes --- p.103 / Chapter V.C. --- Adjustment of Alpha-fetoprotein and Human Chorionic Gonadotrophin for Maternal Weight and Gestational Age --- p.109 / Chapter V.D. --- Predictiveness of Alpha-fetoprotein and Human Chorionic Gonadotrophin for Adverse Outcomes after Maternal Weight and Gestational Age Adjustment --- p.112 / Chapter V.E. --- Conclusions --- p.113 / Chapter V.F. --- Future Directions --- p.116 / APPENDIX 1 DATA BASE OF CLINICAL INFORMATION --- p.117 / APPENDIX 2 SEVERITY AND CLASSIFICATION OF PREGNANCY INDUCED HYPERTENSION --- p.122 / REFERENCES --- p.123

Dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science in Medicine. Johannesburg, 2014 / Background: The causes of renal dysfunction in children treated for childhood cancers are multifactorial and clinical manifestations of dysfunction include hypertension, proteinuria and varying degrees of renal insufficiency. This study aimed to determine the different residual effects of cancer therapy on the renal system and factors associated with the residual effects in children treated for childhood cancers. Patients and Methods: The study was a descriptive cross sectional study that assessed 130 children, between the age of 1 and 18 years, who had completed treatment at Charlotte Maxeke Johannesburg Academic Hospital and were being followed up at the paediatric oncology clinic of the hospital. Results: After a median follow-up post treatment of 2 years, the various manifestations of renal dysfunction identified in the survivors included; decreased GFR, hypomagnesaemia, hypophosphataemia, proteinuria, haematuria and hypertension. In total, 34 survivors (26.15%) had at least one manifestation of renal dysfunction after completing treatment. The most prevalent manifestation of renal dysfunction detected was decreased GFR (17.69%). Hypomagnesaemia and hypophosphataemia were present in 8 (6.15%) and 6 (4.62%) of the survivors respectively. Patients who had renal dysfunction pre-treatment were three times more likely to have renal dysfunction post-treatment. Ifosfamide, Carboplatinum, and nephrectomy were significantly associated with a reduction in GFR Conclusion: A significant number of the survivors had a decreased GFR while some of them had hypomagnesaemia and hypophosphataemia. There was a strong association between pre-treatment and post-treatment renal dysfunction. These findings are very important in terms of decision making for individual patients with respect to selecting treatment modalities and dosages and also with respect to instituting nephro-protective measures to avoid further damage to the kidneys during and after treatment.

Diss. (sammanfattning) Linköping : Univ. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Esophageal and biliary stents are indwelling devices used in the treatment of selected gastrointestinal and biliary disorders. Stenting is accepted as a standard procedure for palliation of malignant obstruction of the esophagus and biliary system. Review of the early and late complications associated with these devices is made with emphasis on the clinical and radiographic features. A suggested approach to diagnosis and treatment recommendations are made for each complication that the emergency department physician may encounter.

Indiana University-Purdue University Indianapolis (IUPUI) / External apical root resorption (EARR) is a common complication of orthodontic treatment. Genetic factors account for approximately 50% of the variation in EARR. Data have indicated variation in histological root resorption associated with orthodontic force (RRAOF) among different inbred strains of mice. Differences in expression of RANKL and OPG were investigated in two strains of mice with different susceptibility to RRAOF using irnmunohistochemistry. Increased localization of RANKL was detected in the tissues surrounding the root of the susceptible strain compared to the resistant strain and the controls. In contrast, increased localization of OPG was found in the tissues surrounding the roots in the resistant A/J strain compared to the susceptible DBA/2J strain. We conclude that differences in the expression of these key bone resorption mediators play a role in determining RRAOF susceptibility. Changes in serum TRAP 5b level in response to orthodontic force were investigated among female A/J, DBA/2J and BALB/cJ mice. The three strains differed in their TRAP positive cell numbers as well as their serum TRAP 5b level at baseline and when treated. A significant increase in the serum TRAP 5b level with treatment was only detected in the RRAOF susceptible DBA/2J strain, and not in RRAOF resistant strains. Our analysis indicates that differences in osteoclast/odontoclast activity play a role in susceptibility to RRAOF that is genetically determined. Serum TRAP 5b levels have a potential role in screening for individuals with greater susceptibility to root resorption. RRAOF was determined for male and female mice of the A/J, DBA/2J and BALB/cJ strains, as well as A/J x DBA/2J and A/J x BALB/cJ crosses. Sex differences were observed among the BALB/cJ strain only, with females more resistant to RRAOF when compared to males. Fis from the A/J x BALB/cJ cross were resistant suggesting that the A/J have dominant resistance alleles, while Fis from the A/J x DBA/2J cross had RRAOF intermediate between their parental A/J and DBA/2J mice, suggesting a polygenic trait. We concluded that the mode of inheritance of RRAOF in mice was polygenic in nature.

Indiana University-Purdue University Indianapolis (IUPUI) / According to one theory of root resorption, occlusal trauma during orthodontic tooth movement damages the cementum covering the root dentin. The body detects the exposed dentin and seeks to remove it, and the result is root resorption. This experiment will explore an aspect of this theory by quantifying the amount and location of damage in mechanically fatigued teeth. Nine dog mandibles were sectioned at the mandibular symphysis. Each half was mounted in orthodontic resin with the incisors upright and exposed. The block was inserted into a jig and placed into a servohydraulic mechanical testing machine. The left central incisor was fatigue loaded with a 2Hz, 10-90 N sinusoidal force for 100,000 cycles (approximately 14 hours). The right central incisor served as the control. Both specimens were scanned with a micro-CT unit, stained with basic fuchsin, and then sectioned along the sagittal plane. Because the experimental and control specimens were stained before sectioning, only microdamage due to the loading process would be evident in the sections. Microdamage which occurred during the sectioning process would not be stained. Central sections through the long axes of the samples were examined for the presence of microdamage with a light microscope and a micro-CT unit. Based on preliminary findings, two types of staining patterns were measured and recorded. The first was called "diffuse stain" and consisted of large stained areas in the dentinal tubules. Diffuse stain was not associated with any visible features at the dentinocemental junction. The second type of staining pattern was called "stained defects." Stained defects were stained irregularities at the dentinocemental junction. For statistical analysis, the roots were divided into buccal-cervical, buccal-middle, buccal-apical, lingual-cervical, lingual-middle, and lingual-apical regions. Comparisons between the fatigued and non-fatigued teeth for differences in area, length, and depth were made under the generalized estimating equation (GEE) framework applied to normally-distributed data. Because the measurements were not normally distributed, a rank transformation of the measurements was performed before conducting the analyses. Comparisons between the fatigued and non-fatigued teeth for differences in presence or absence of stain or defects were made using Cochran-Mantel-Haenszel tests. Repeatability of the measurements was assessed using intraclass correlation coefficients (ICCs), paired t-tests, and Bland-Altman plots. The ICC's ranged from 0 .85 to 1.00, thus making the repeatability of the measurements generally very good. The statistical analysis showed there were no significant differences between the experimental and control teeth for stained defects or diffuse staining for length, depth, or area measurements. However, analyses comparing the distribution of stained defects and diffuse stain within the control and experimental specimens showed significant differences in the distribution of stained defects within the experimental specimens. In the experimental specimens, the stained defects were distributed in a gradient, with the most in the apical region and progressing to the least amount in the cervical region. In the control specimens, there was only a difference in the stained defects between the cervical and apical regions. This distribution is consistent with the biomechanical model which shows increasing stress moving from the cervical region towards the apex. These results show that the test and control specimens differed in how the stained defects were distributed throughout the root, even though there were no differences in the amount of staining between the control and experimental specimens. Whole tooth and histologic slides were scanned with the micro-CT unit, but the dentinocemental junction could not be delineated enough to make any measurements. No data could be collected regarding microdamage in this area using the micro-CT unit. It was recommended that future studies use a tomography unit with better resolution, use a larger samples size, employ a contrast agent when trying to visualize microdamage with the micro-CT unit, and incorporate a way to measure the intensity of the staining in addition to the location and size.

Os efeitos tóxicos decorrentes da exposição ambiental e ocupacional ao benzeno são amplamente descritos na literatura. Seus produtos de biotransformação fenólicos, entre os quais os compostos hidroxilados como FE e hidroquinona HQ, são indutores importantes de efeitos citotóxicos e genotóxicos responsáveis pela toxicidade ao sistema imune. No entanto, a contribuição de cada metabólito e os mecanismos envolvidos não estão completamente esclarecidos. Desta forma, o presente trabalho teve por objetivo estudar a capacidade da resposta inflamatória em ratos expostos à HQ, ao FE, ou a ambos simultaneamente (HQ+FE). Para tanto, ratos Wistar machos foram expostos aos agentes químicos por período de tempo prolongado (doses diárias de 5 ou 10mg/kg; i.p.; com 5 doses/semana no período de 17 ou 23 dias). Animais controles receberam o veículo pela mesma via. As respostas inflamatórias foram induzidas 24 horas após a última dose administrada. Foram avaliadas a resposta inflamatória inespecífica, decorrente da instilação intranasal de LPS de Salmonella abortus e a resposta inflamatória específica em animais previamente sensibilizados e desafiados pela OVA. Na resposta inflamatória inespecífica, as exposições à HQ e à HQ+FE provocaram redução acentuada no influxo de leucócitos para o pulmão inflamado, pelo menor número de leucócitos no LBA e pela atividade enzimática da MPO reduzida no tecido pulmonar. O efeito não é dependente de modificações no número de leucócitos circulantes nem de alterações nas expressões de moléculas de adesão nos leucócitos circulantes (L-selectina e β2 integrina) e no endotélio pulmonar (ICAM-1 , VCAM-1 e PECAM-1) envolvidas na interação leucócito-endotélio. Na vigência de resposta inflamatória específica, as exposições à HQ, FE ou HQ+FE reduziram significativamente a migração de leucócitos para o LBA e para o tecido pulmonar. Da mesma forma que a RI induzida pelo LPS, não foram detectados alterações nos número de leucócitos circulantes e na expressão de moléculas de adesão. No entanto, os resultados obtidos em ensaios de anafilaxia passiva cutânea e reação anafilática in vitro mostraram que o efeito é dependente, pelo menos em parte, da menor concentração de imunoglobulinas anafiláticas circulantes e, consequentemente, da menor habilidade de desgranulação mastocitária. Em conjunto, os dados obtidos demonstram que as exposições à HQ, ao FE ou à HQ+FE prejudicam a migração de leucócitos para o foco de lesão na vigência de respostas inflamatórias de origem inata ou adquirida. / The toxic effects of the ambiental and occupational exposures to benzene is widely described in the literature. Phenolic hydroxylated compounds obtainded from its biotransformation, such as phenol (PHE) and hydroquinone (HQ), induce important of cytotoxic and genotoxic effects responsible for the immunotoxicity. However, the role of each metabolite and mechanisms of toxicity are unknown. Then, the present work aimed to study the inflammatory response in rats exposed to HQ, PHE, ar both simultaneously (HQ+PHE). Male Wistar rats were exposed to they chemical agents for extended period of time (5 or 10mg/kg/day; ip.; during 17 or 23 days; 2 days intervals each 5 doses). Control animais received the vehicle. Inflammatory reactions were induced 24 hours after the last dose by they intranasal instillation of lipopolysaccharide of Salmonella aborlus (non-specific response) or by inhalation of ovalbumin in animals previously sensitized to the same antigen (specific response, produced by anaphylactic immunoglobulins). Animais exposed to HQ or HQ/PHE presented reduced n,3umbers of PMN and MN cells in the bronchoalveolar lavage fluid (BALF) and lesser myeloperoxidase (MPO) activity in the pulmonary tissue. The reduced influx of leukocytes is not dependent oh alterations on the numbers of circulating leukocytes either adhesion molecules expressions on leukocytes (L-selectin or β2 integrin) and on lung microvascular endothelium (ICAM-1, V CAM-1 or PECAM-1) responsible for leukocyte-endothelial interactions. On the other hand, rats exposed to ali schedules of exposures presented reduced numbers of leukocytes in the BALF and lesser MPO activity in the pulmonary tissue after an antigenic stimulus. As shown to inflammation induced by LPS, no alterations on circulating leukocyte numbers and adhesion molecules expressions were detected. However, the impaired leukocyte migration to the inflamed lung may be dependent, at last in part, on reduced levels of circulating anaphylactic antibodies, as detected by passive cutaneous anaphylaxis test, and by consequent reduced ability of mast cell desgranulation, evidenced by in vitro trachea contraction. Together, our data show that HQ and PHE exposure differently affect the specific and non-specific ínflammatory reactions.