Thesis (M.S.)--University of Michigan, 1962.

Ectopic thyroid gland is a developmental anomaly that results from the arrest of thyroid tissue along its path of descent from the floor of mouth to the pre tracheal position in the lower neck. It is typically found along the thyroglossal duct with the base of the tongue being the most common site. Apart from mediastinal extension of goiter, the incidence of true intrathoracic ectopic thyroid tissue is rare. Presence of ectopic thyroid has been reported not only in the chest but also in the abdomen and pelvis. Pericardial and intracardiac locations are extremely uncommon and right ventricle location is predominant among the described cases. We describe a case of incidentally detected ectopic thyroid tissue in a rarer location—adjacent to the left atrium. The patient, who had undergone a nephrectomy for renal oncocytoma 5 years ago, presented with unintentional weight loss and left sided flank pain, prompting a workup to rule out abdominal malignancy. Findings on the computed tomography (CT) scan of the abdomen and pelvis prompted further investigation including a chest CT which showed a heterogeneously enhancing mass near the left atrium. Given its location, further radiological investigations played an important role in eliminating the differential diagnosis of paraganglioma. The mass was surgically resected and discovered to be a hyperplastic thyroid nodule on histologic examination.

The temporal nature of ectopic activity is important to elucidating the mechanisms that can lead to arrhythmogenesis. However, challenges remain in distinguishing between ectopic and non-ectopic beats. A new methodology was developed and validated to distinguish between beat types. Rapid pacing was used to induce both ectopic and non-ectopic beats. Using an electrocardiogram, the post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced beats with RCL ratios that increased with rapid pacing, suggestive of non-ectopic activity. Hypercalcemia and digoxin both produced significantly earlier beats with wider QRS durations, suggestive of ectopic activity. Increasing pacing further shortened RCL during digoxin + hypothermia, a mechanistic identifier of ectopic activity. When tested against a previously validated analysis, our algorithm performed well. Therefore, this electrocardiogram based algorithm distinguishes between ectopic and non-ectopic beats. In a prospective study, tetrodotoxin increased RCL ratio without changing the QRS duration of excited beats, suggesting neuronal sodium channels play an important role in ectopic beat timing. The next goal was to create a consistent model of ectopic activity. Both sympathetic and parasympathetic stimulation independently potentiate arrhythmogenesis, and we investigated the effects of independent and simultaneous stimulation on the temporal nature of arrhythmogenesis. Isoproterenol (ISO), a sympathetic agonist, transiently produced ectopic activity and increased heart rate. Acetylcholine (ACh), a parasympathetic agonist, did not significantly produce ectopic activity but did slow heart rate. ACh added after ISO also transiently produced ectopic activity, while heart rate remained slowed. Importantly, ISO following ACh persistently increased ectopic activity and heart rate. Therefore, ISO following ACh is an ideal model for creating sustained ectopic activity. Mature animals exhibited sustained arrhythmogenesis while young animals did not. When ACh was removed and then followed by ISO, ectopic activity and heart rate transiently increased, similar to ISO alone. This suggests that maintained ACh perfusion can sustain ISO sensitivity, in contrast to ISO perfusion alone. The data in this dissertation provide an insight into the mechanisms that affect the ectopic beat timing and arrhythmia propensity. / Ph. D.

Despite the development of new biomarkers predicting prognosis in rheumatoid arthritis (RA) remains challenging and targeting of powerful biologics difficult. The presence of ectopic germinal centres (GC) within synovium has long been recognised (ectopic lymphoneogenesis [ELN]) and data have suggested that they manufacture antibody (Ab). High affinity class switched Ab production occurs through class switch recombination (CSR) and somatic hypermutation (SHM) both critically dependent on activation induced cytidine deaminase (AID). However, whether ectopic GCs express AID has not been known. Nonetheless data associating ELN with disease severity suggest a role for ELN in RA pathogenesis and as a potential biomarker. A classification system for RA synovium, based on the concept of ELN has been proposed as: (i) aggregate, (ii) aggregate GC+ and, (iii) an unorganised infiltrate. However whether these distinct pathotypes and/or degree of aggregation equate to disease severity is unclear. Thus my first aim was to develop and validate a pathological scoring system for rheumatoid synovium capable of quantifying the degree of ELN. My second aim was to investigate whether the presence and/or degree of ELN within the synovial membrane correlated with both clinical phenotype and predicted erosive damage. I demonstrate that the aggregational score developed is highly reliable and that ELN within synovial tissue associates with a higher level of synovial inflammation but is not predictive of damage. My third aim was to investigate whether GCs within RA synovium were functional. I provide evidence of functionality by demonstrating that ectopic GCs invariably express AID, are surrounded by anti-CCP+ plasma cells, support ongoing CSR and the manufacture of anti-CCP Abs. My final aim was to characterise a cohort of synovial B cells consistently found surrounding ectopic GCs. I identify a novel B cell subset within RA synovium, interfollicular large B cells, (5)(5)(5) and demonstrate that interfollicular large B cells in lymph node express a somatically mutated IgH.

published_or_final_version / Obstetrics and Gynaecology / Doctoral / Doctor of Philosophy

Purpose: To retrospectively assess the incidence and predictive factors for self-correction of ectopic eruption of maxillary permanent first molars (EE) and the prevailing attitudes amongst surveyed specialists regarding intervention in cases of EE. Methods: Charts of patients diagnosed with EE were assessed for predictive clinical and radiographic factors. An online survey was sent to pediatric dentists and orthodontists. Results: The rate of self-correction was 71%. One third of self-corrections occurred after age 9. Increased amount of impaction (r(43)=0.59, p<.001) and degree of resorption (r(57)=0.41, p=.001) were positively correlated with irreversibility. Orthodontists estimated the spontaneous self-correction rate to be lower (t(1178)=19.2, p<.001) than pediatric dentists. Conclusions: One third of self-corrections occurred after 9 years of age and delaying treatment of EE may be a viable option when uncertain of the outcome. Reliable predictive factors of irreversibility of EE were identified. Differences exist between pediatric dentists and orthodontists regarding management of EE.

OBJECTIVE: To describe the patient profile, clinical features, risk factors, management options and complications in women with ectopic pregnancy. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: King Edward VIII Hospital, Congella, Durban from July 2005 – June 2006. MATERIALS AND METHODS: 130 case notes of women with the final diagnosis with ectopic pregnancy were examined retrospectively. Data was retrieved through a structured proforma. The variables studied included age, parity, signs and symptoms, treatment, management, complications and associated maternal morbidity and mortality. RESULTS: One hundred and twenty women diagnosed with ectopic pregnancy were included in this study. Ten patients were excluded due to failure to obtain clinical records. Women’s ages ranged from 17-40 years with 32 patients (26.7%) being nulliparous and 88 patients (73.3%) between parity 1-4. Twelve patients (10%) had a history of previous ectopic pregnancy. The commonest presenting symptom was abdominal pain in 106 (88.3%) patients whereas amenorrhoea and vaginal bleeding were found in 88 (73.3%) and 84 (70%) patients respectively. The most common physical sign was tenderness: Adnexal tenderness in 99 (82.5%) and pelvic tenderness in 91 (75.8%) of women. Fourteen women (11.7%) presented to the gynaecological outpatient’s department in acute shock with a blood pressure < 90/60 mmHg. The commonest ultrasound findings were the presence of an adnexal mass and an empty uterus in 82 (68.3%) and 80 (66.7%) women respectively. The most frequent risk factors were previous genital infection in 34 patients (28.3%) and multiple sexual partners in 32 patients (26.7%). One hundred and eleven 92.4%) women were managed by laparotomy: One hundred and four (87.4%) women via emergency laparotomy and 6 women (5%) had an elective laparotomy. One patient (0.8%) had a diagnostic laparoscopy which was converted to laparotomy. Only 8 patients (6.7%) were managed laparoscopically. Surgical treatment consisted of salpingectomy 101/120 (84.9%) and salpingotomy in 4 (3.4%) patients. Post- operation complications were minimal however the one maternal death was probably due to a pulmonary embolus. CONCLUSION: Risk factors may not always be present, hence ectopic pregnancy should be suspected in every women of reproductive age who present with unexplained abdominal pain, amenorrhoea and vaginal bleeding. Most women presented with ruptured ectopic pregnancies at King Edward VIII Hospital warranting emergency laparotomy. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.

Purpose: To retrospectively assess the incidence and predictive factors for self-correction of ectopic eruption of maxillary permanent first molars (EE) and the prevailing attitudes amongst surveyed specialists regarding intervention in cases of EE. Methods: Charts of patients diagnosed with EE were assessed for predictive clinical and radiographic factors. An online survey was sent to pediatric dentists and orthodontists. Results: The rate of self-correction was 71%. One third of self-corrections occurred after age 9. Increased amount of impaction (r(43)=0.59, p<.001) and degree of resorption (r(57)=0.41, p=.001) were positively correlated with irreversibility. Orthodontists estimated the spontaneous self-correction rate to be lower (t(1178)=19.2, p<.001) than pediatric dentists. Conclusions: One third of self-corrections occurred after 9 years of age and delaying treatment of EE may be a viable option when uncertain of the outcome. Reliable predictive factors of irreversibility of EE were identified. Differences exist between pediatric dentists and orthodontists regarding management of EE.

Ectopic pregnancy (EP) is a rare condition that occurs in 1% of all pregnancies. However, women of lower socioeconomic status (SES) and ethnic minority groups are at greater risk of adverse outcomes associated with EP than White women. The purpose of this study was to examine data from the 2014 National Inpatient Sample to identify predictors of complications from EP in 2,626 females ages 15-44 in the United States. The theoretical framework used to guide this study was the theory of fundamental causes to explain why the association between SES and mortality has persisted despite progressive advances in the diseases and risk factors that are believed to explain it. Independent t-tests were conducted to determine whether significant differences in patient outcomes existed between EP participants who required one medical intervention during hospitalization and those with two or more medical interventions. Multiple linear regression analyses were used to examine the association between race, primary expected payer, income, number of procedure codes on record, number of diagnoses on record, and length of stay. The key findings were that for every increase in number of procedures (β = 0.13, p <.001) the length of stay also increased by 0.13 units; for every increase in number of diagnoses (β = 0.37, p <.001) length of stay increased by .37 units, and within the Black racial/ethnicity (β = 0.05, p < .05) length of stay increased by 0.05 units. Finally, for females within a higher income quartile of $45,000 or more (β = .08, p < .001), length of stay decreased by -0.08 units. Positive social change implications may include assistance to public health professionals in identifying individual factors that place women at increased risk for EP and the ability to increase EP prevention activity in populations that may be more susceptible to the condition and complications.

Eight children, age between 4.5 and 19 years were treated with moricizine for supraventricular tachycardia during the last 3 years. The tachycardia was documented by surface electrocardiogram (EGG), and/or by ambulatory ECG in all the children and the mechanism of tachycardia was determined by previously published surface ECG and electrophysiologic criteria in all but one child. Of the eight children, three had atrial ectopic tachycardia, three had automatic junctional ectopic tachycardia, one had atrioventricular (AV) nodal reentry tachycardia and one had atrial reentry. All the children except one had failed trial of two or more antiarrhythmic drugs prior to moricizine therapy. The duration of moricizine therapy ranged from 4 days to 25 months. In three of the eight children (patients 3, 5 and 7), who presented with AV nodal reentrant tachycardia, automatic junctional ectopic tachycardia and atrial ectopic tachycardia, respectively, moricizine therapy was effective in restoring sinus rhythm and controlling the clinical tachycardia. Only one child (patient 1) developed proarrhythmia, an episode of fast, narrow-QRS supraventricular tachycardia lasting for 30 s, on the third day of therapy. This was subsequently confirmed by electrophysiologic study to be AV nodal reentrant tachycardia. The other side effects noted were non-cardiac, not dose-dependant and did not require discontinuation of therapy. Based on our small series and those of others, moricizine, a newer class I anti-arrhythmic agent, has a limited but useful role in the management of recalcitrant type of supraventricular tachycardia, such as ectopic atrial and junctional tachycardia in children.