The accurate differentiation of a ventricular from a supraventricular origin of a wide QRS tachycardia (QRS > 120 milliseconds) is an important clinical problem. Misdiagnosis of this arrhythmia can lead to institution of inappropriate drug therapy acutely with potentially catastrophic consequences. Various diagnostic aids have been used to obtain electrocardiographic potentials to aid in the differentiation. This report assesses the clinical usefulness of oesophageal electrocardiography in the differentiation of wide complex tachycardias and describes a simple, safe technique to obtain oesophageal electrocardiograms. Eighteen consecutive patients between the ages of 27 and 71 years who were haemodynamically stable were selected for this study. The technique was performed in the following manner: A temporary pacing catheter was lubricated and passed nasally and advanced with the patient being instructed to swallow. Adjustments in catheter depth were made as necessary to obtain an optimal recording on a standard electrocardiograph recorder. Satisfactory placement with minimal patient discomfort was achieved within 6.5 minutes (average 4.5 minutes) in all cases. High quality tracings were obtained in every instance. In the 18 patients with tachyarrhythmia, AV dissociation consistent with ventricular tachycardia was demonstrated in 11 instances; in the remainder the diagnosis was supraventricular tachycardia. Of the 11 patients diagnosed as ventricular tachycardia, 9 were initially misdiagnosed as supraventricular tachycardia, whilst only 1 of 7 patients with supraventricular tachycardia was misdiagnosed. This study has demonstrated that oesophageal electrocardiography is useful in the differentiation of wide complex tachycardias. The technique outlined in this report is simple and offers the following advantages: the temporary pacing catheter is associated with minimal discomfort; the catheter allows easy manoeuverability within the oesophagus which allows proper depth to be easily obtained; the equipment used is routinely available. Therefore the technique offers a rapid, safe and simple method of obtaining an oesophageal electrocardiogram which is invaluable in the electrocardiographic differentiation of a wide complex tachycardia. / Thesis (M.Med.)-University of Natal, Durban, 1990.

Faculty of Science; School of molecular and Cell Biology; MSC Dissertation / Background: Cancer of the oesophagus ranks as the ninth most common malignancy in the world, and recent evidence shows that its incidence is increasing. Apoptosis is a process of programmed cell death, which is as essential as cell growth, for the maintenance of homeostasis. When these processes lose integration, such as cancer, then uncontrolled cell growth occurs. There are at least five ACBP subgroups and the two being focused on in this study is B-ACBP (brain specific) and 1-ACBP (found in nearly all tissues). ACBPs act as intracellular carrier-proteins for medium to long chain acyl-coA, mediating fatty acid transport to the mitochondrion for ß-oxidation. ACBPs are also believed to be putative ligands of PBR (Peripheral Benzodiazepine Receptor), and bound to this receptor facilitates mitochondrial membrane permeabilization giving the notion that it favours apoptosis. Aim: To establish the expression patterns of 1-ACBP, B-ACBP, and PBR in oesophageal cancer, and to characterize their roles in this disease. Methodology: Paraffin-embedded sections of normal and malignant oesophageal tissues were utilized for localization studies. RNA probes was synthesized and labelled using Digoxigenin for colorimetric and fluorescent detection during the in situ hybridization (ISH) technique for localization. Real time quantitative RT-PCR was performed to determine the expression levels of the three genes in oesophageal cancer RNA using the Roche Lightcylcer .Results: All three genes showed substantial upregulation within the malignant tissue sections compared to normal oesophageal sections, all three transcripts localized specifically to plasma cells and lymphocytes in diseased and normal tissue section. In the diseased tissue B-ACBP and 1-ACBP mRNA localized to endothelial cells of blood vessels in the submucosa. B-ACBP also localized to the nucleus of squamous epithelium cells. PBR localization occurred in tumour islands in invasive tissue sections. Quantitative RT-PCR also illustrated PBR expression level was the highest compared to the ACBP genes expression in tumours. Conclusion: These results show that 1-ACBP, B-ACBP and PBR play a role in the pathogenesis of oesophageal cancer as well as immunology. Further experiments are still required to determine the function of these genes and the role they play in apoptosis and oesophageal cancer.

The UK has experienced an increase in the incidence of oesophageal adenocarcinoma (OAC) in recent years. The prognosis for patients with OAC remains poor with currently available treatments prompting a search for alternative ‘chemopreventive’ treatments that inhibit oesophageal carcinogenesis. Both non-steroidal anti-inflammatory drugs (NSAIDS) and flavonoids are associated with a significant risk reduction for developing OAC in epidemiological studies. The aim of this study was to validate Levrat’s surgical model of OAC in the rat, and assess the chemopreventive effects of the NSAID aspirin, and the flavonoid quercetin on the development of OAC in the validated rat model. METHODS: Levrat’s model was validated in a time course experiment. Morphological and molecular events occurring in the distal oesophagus during disease progression were determined and compared to human disease. The effect of aspirin and quercetin on disease initiation and progression was determined by commencing treatment either before the onset of reflux, or 4-weeks afterwards. The incidence of Barrett’s oesophagus (BO) and OAC within each group was determined, along with methylation levels of the ESR-1, p16 and HPP1 gene promoter regions. RESULTS: The morphological and molecular changes in the distal oesophagus of the rat model are broadly consistent with those reported in human disease. The incidence of OAC was significantly lower in aspirin treated rats. A non-significant reduction in incidence of OAC was observed with quercetin treatment. Timing of treatment with regard to onset of reflux had no significant effect on OAC development in either treatment group. Neither treatment significantly effected methylation levels within the gene promoters examined. CONCLUSION: Use of Levrat’s model as a model of human OAC seems justified. Aspirin inhibits development of oesophageal adenocarcinoma induced by reflux in this rat model. No additional reduction in cancer incidence is observed if treatment is commenced prior to inception of reflux disease.

Barrett's oesophagus (BO) arises from chronic gastro-oesophageal reflux disease(GORD). Patients have an increased risk of adenocarcinoma (ADC), which is the sixth most common cause of cancer mortality in the UK. All ADC develop from BO, and over the last twenty years there has been a marked increase in both conditions. The reasons for this are not known, however, as with some forms of gastric cancer, it is possible that there may be a bacterial aetiology. This study employed both culturebased and molecular techniques to characterise microbial communities colonising the distal oesophageal mucosae in individuals with GORD, BO and ADC, together with healthy controls. Furthermore, in vitro models were designed to create an oral microbiota, from which an oesophageal community could develop. Microbial analysis identified a shift in oesophageal population composition with disease progression, with an incremental increase in total eubacterial scores related to the metaplasia-dysplasia sequence. Additionally, an increased proportion of Gram negative species and potentially pathogenic organisms, such as Peptostreptococcus were identified. Campylobacter spp. were isolated from 75%, 50% and 60% of GORD, BO and ADC patients, respectively, compared with 20% of controls. Helicobacter pylori, which has been proposed to be protective in oesophageal disease, was significantly reduced in disease, especially in ADC patients. In vitro models were successful, with a simple oral microbiota leading to the development of unique, varied oesophageal populations representative of those found in vivo. Additionally, after exposure of this community to bile acid, population dynamics were altered, with an increase in Gram negative species, associated with a rise in haemolytic and mucinolytic activities. Exposure of oesophageal cell lines to these stressed biofilms resulted in increased cell death, and in some cases, amplified expression of p53 and COX-2. In conclusion, this research proved an association between bacterial composition and oesophageal disease. With progression to adenocarcinoma, the community becomes increasingly diversified and Gram negative in character, and therefore, is proposed to be more pathogenic. Further research is required to investigate causal relationships, through which mechanisms for disease initiation and/or maintenance can be understood.

The development and progression of carcinogenesis is a major area of interest to many scientists. Numerous factors, including both environmental and genetic have been implicated in the causation of cancer. It is clear that both these factors and others contribute to neoplastic development and progression. Microsatellites are short tandem repeat sequences which are located in the intron segments of the genome. These noncoding sequences range from 2 to 6 base pairs. An increase or decrease in the number of repeat sequences is referred to as microsatellite instability, also referred to as genetic instability. It is thought that microsatellite instability arises as a result of defects in DNA repair process. During DNA synthesis, the DNA repair genes ensure that the correct nucleotide is incorporated into the newly synthesised DNA strand, so when a mismatch base is incorporated, this is promptly removed and replaced with the correct base. However, if the repair system is defective this would give rise to numerous genetic aberrations along that region of the genome. Recently, microsatellite instability and allelic imbalance/loss of heterozygosity have been shown to play an important role in the development of many cancers, especially colorectal cancer (CRC) associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. This study was undertaken to investigate microsatellite instability and allelic imbalance in colorectal and oesophageal carcinomas in the KwaZulu Natal region of South Africa. The molecular analysis was correlated with clinicopathological data to establish a baseline level on which further studies could be performed. In addition, this study represents the first fluorescent based microsatellite analysis of these two common cancers in South Africa. Normal and tumour DNA was isolated from formalin fIxed paraffin embedded tissue. Fluorescent-based DNA technology using an automated DNA sequencer (Alf Express Automated DNA Sequencer) was employed. CY5 labelled primers for microsatellite markers (DCC, D18S34, D18S58, D3S659, D2S123 and D3S1255) were used. The data was captured and analysed using the Fragment Manager Software. The informativity of the microsatellite markers used in this study ranged from 50% to 71.8%. LOH/AI in the region of the DCC gene in the under 35 years of age CRC was 39.1%, while MSI in this region occurred in 31.25% of cases. The DNA repair gene status in these young patients was as follows: LOH/AI: 31.3% and MSI: 40.4%. In the over 50 years of age CRC, LOH/AI in the 18q region was 28% and MSI was 38%. The DNA repair genes (hMSH2 and hMLH1) in this cohort showed LOH/AI in 24% and MSI also in 24%. As regards oesophageal cancer, LOH/AI in the 18q region was 20.5% and MSI 7.7%. The repair genes showed LOH/AI in 17.9% and MSI in 10.25% of cases. When the molecular events were correlated with clinicopathological features, no statistically significant pattern emerged. However, it must be remembered that relatively small numbers of cases (39) were analysed.In conclusion: • No statistical correlation was found between clinicopathological characteristics and the molecular analysis in either CRC and oesophageal cancer. • LOH/AI and MSI was higher in the under 35 age group. • LOH/AI and MSI in 18q, 2p and 3p in sporadic CRC were similar to other fluorescent-based studies in patients over 50 years of age. • LOH/AI and MSI in 18q, 2p and 3p in oesophageal cancer was similar to studies from other geographical areas. • Finally, fluorescent-based microsatellite PCR and analysis was found to be an objective and efficient technique. / Thesis (Ph.D.)-University of Natal, 1998.

M.Sc. / The ideal cancer treatment modality should not only cause tumour regression and eradication but also induce a systemic antitumour response, which is essential for the control of metastatic tumours and long-term tumour resistance. Photodynamic Therapy (PDT) is a current approach in the treatment of various cancers. It involves the administration of a tumour-localizing photoreactive compound, which is activated at a specific wavelength of light. This therapy results in a sequence of photochemical and photobiological processes that cause irreversible photodamage to tumour tissues. Eradication is achieved by anti-tumour effects induced in the parenchyma and tumour vascular network. PDT can lead to a rapid cell death response in malignant cells, which has provided insight into the mechanisms behind photokilling. Oesophageal cancer is the seventh leading cause of cancer death worldwide, and in South Africa remains a problem of epidemic proportions affecting predominantly black males. The appearance of a number of new photosensitizers being developed will not only extend the number of choices for treating specific cancers, but also aid in the effective destruction of various tumour tissues. PDT has been an experimental clinical modality for the past two xii decades and has been shown to be successful for the treatment of advanced oesophageal cancer where other options have failed. The full potential of PDT as a treatment modality has not been clearly evaluated, which is one of the objectives of this study. Overall, PDT has the potential of being a promising therapeutic option in the effective treatment of oesophageal cancer, and through this study and the elucidation of the mechanisms of PDT action, it will provide a better future for those suffering from oesophageal cancer. A new photosensitizer known as Zinc Sulphophthalo-cyanine (ZnPcSmix) was studied on an oesophageal SNO cancer cell line in order to determine treatment-induced cell viability, cytotoxicity and the pathway followed to cell death. The major observations of this study revealed that PDT using ZnPcSmix resulted in a decrease in cell viability and proliferation, resulting in a cytotoxic response experienced by the cell. The outcome of this study revealed that the SNO cells experience a necrotic mode of cell death after using ZnPcSmix to induce photodamage. This was examined by light microscopy and confirmed by the lack of DNA fragmentation and decreased caspase-3 and caspase-7 expression levels. Hsp70 levels decreased resulting in lowered cytokine TNF-α release from necrotic cells. Hoechst nuclear staining revealed a disorganized nuclear pattern characteristic of necrotic release of cellular contents. The major findings of this study revealed the efficacy of ZnPcSmix as a new photosensitizing drug used during PDT to treat oesophageal cancer resulting in a decrease in cell viability and proliferation. Necrosis was the primary mechanism by which cells pursued death, which was dependent on the photosensitizer dose, cell type and irradiation fluence. ZnPcSmix–induced photodamage seen during PDT offers a new treatment option for patients suffering from oesophageal cancer and shows great promise in effectively treating early-stage oesophageal cancer.

In view of the paucity of detailed information in the literature relevant to the upper digestive tract of the Nile crocodile, this study describes the morphological and histological features of the oral cavity (gingivae, palate and tongue), pharyngeal cavity and oesophagus of the Nile crocodile, Crocodylus niloticus (Laurenti, 1768) using light microscopy. The findings, which were supplemented by scanning electron microscopy, were compared with published information. The ciliated component of the oesophagus was also examined using transmission electron microscopy. The oral cavity had the form of a triangle and was dorso-ventrally flattened. The dorsal limit was formed by the palate and the ventral limit by the broad-based tongue. The close proximity of the tongue and palate severely limited the space within the cavity. The caudal border of the cavity was formed by the dorsal and ventral components of the gular valve. The epithelium of the palate, gingivae and tongue was stratified squamous in nature and appeared lightly keratinised. Specialised epithelial structures in the palate, gingivae and tongue, revealed by both light microscopy (LM) and scanning electron microscopy (SEM), bore characteristics resembling structures responsible for pressure and taste reception. Glandular tissue in the tongue was arranged in a triangular formation in the posterior region and displayed morphological features ascribed to salt secreting glands described in other Crocodilia. There were no palatine glands in the oral region of the palate, except that the oral surface of the dorsal gular fold contained branched tubular mucus secreting glands. The pharyngeal cavity was also dorso-ventrally flattened and was bordered rostrally by the flaccid dorsal gular fold, which displayed a median apical notch, and the ventral gular fold, which was supported internally by the broad rostral tip of the basihyal plate (hyaline cartilage). In the occluded mouth, the dorsal gular fold and the more rostrally positioned ventral component of the gular valve isolated the pharyngeal cavity. This arrangement is essential in preventing the crocodile from drowning (flooding of the pharyngeal cavity) while capturing prey. The roof of the pharyngeal cavity was characterised by the opening to the internal nares (an extension of the nasal passage from the external nares), the fibrous Eustachian plug sealing the common opening to the paired Eustachian ducts and a nodular tonsillar region, which was situated caudo-laterally to the Eustachian plug. Throughout this region, the epithelium was typically ciliated with goblet cells. However, the tonsillar nodules displayed regions of partial or no ciliation on their surface. SEM and stereomicroscopic observations showed fine longitudinal mucosal folding throughout the pharynx the distension of which, together with the large capacity for mucus production (produced by intraepithelial glands and mucus secreting glands), would facilitate the swallowing of large chunks of food in the living state. The ventrally situated laryngeal mound containing the slit-like glottis also displayed longitudinal folds and a ciliated epithelium. Anatomically, the oesophagus could be divided into two clear regions. The cranial, approximate two-thirds appeared broad and flabby. At the tracheal bifurcation, the oesophagus narrowed significantly and indicated a greater muscular content, confirmed by light microscopy. LM and SEM examination of the oesophagus, however, revealed three regional components, viz., the cranial, mid- and caudal regions. In the cranial region, the epithelium was densely ciliated with intervening goblet cells being present. In the mid-region the ciliated component decreased with a concomitant increase in the goblet cell component. In the caudal region there was a further decrease in the number of ciliated cells and a higher concentration of goblet cells. Transmission electron microscopy (TEM) of the ciliated component of the oesophagus showed typical ultrastructural features of both the ciliated and goblet cells. / Dissertation (MSc (Veterinary Science))--University of Pretoria, 2002. / Anatomy and Physiology / unrestricted

A Distrofia Muscular de Duchenne (DMD) é um tipo de miopatia grave, degenerativa e progressiva, geneticamente determinada e ligada ao cromossomo X. Além dos graves distúrbios cardiorrespiratórios e da motricidade, o paciente apresenta disfunções do sistema digestório, caracterizadas pelas desordens da motilidade. Entretanto, sabe-se que tais disfunções não ocorrem no camundongo MDX. O objetivo deste estudo foi estimar a densidade numérica por área da população total de neurônios (QA[T]) e dos neurônios nitrérgicos (QA[N]); assim como a área de secção transversal média do corpo celular destes neurônios (A[T] e A[N]) do plexo mioentérico esofágico e a largura média das fibras estriadas (L) das camadas musculares. Foram utilizados 40 camundongos machos da linhagem C57BL/10 nas idades de 4 e 10 semanas, distribuídos entre grupos experimentais (MDX4 e MDX10), e controles (C4 e C10). As estimativas foram analisadas em preparados de membrana dos esôfagos, e técnicas histoquímicas de NADH-diaforase (NADH-d) e NADPH-diaforase (NADPH-d) foram utilizadas para evidenciar toda a população de neurônios e os neurônios nitrérgicos, respectivamente. Os resultados mostraram que a QA[T] foi significativamente maior no grupo MDX10 em relação ao C10 (p<0.05); enquanto a QA[N] foi menor no grupo MDX4 em relação ao C4 (p<0.05). A A[T] foi menor no grupo MDX10 em relação ao MDX4 e ao C10 (p<0.05); enquanto que para a A[N] não houve diferença significativa entre os grupos controle e experimental, e tampouco entre os grupos de 4 e de 10 semanas. A variável L foi maior nos grupos MDX4 e MDX10 em relação aos seus respectivos controles de mesma idade (p<0.05). Concluímos que no plexo mioentérico esofágico de camundongos MDX existe uma redução dos neurônios mediadores do relaxamento, especialmente em animais jovens (MDX4), provavelmente porque o organismo tenta manter íntegra a função peristáltica do órgão. Esse fato pode explicar a adaptação e ausência de disfunções esofágicas durante quase toda a vida desses animais. / Duchenne Muscular Dystrophy (DMD) is the most common and the most severe muscular dystrophy of childhood. DMD is degenerative, progressive and a genetic X-linked disease. Besides the cardiomyopathy and the movement disorders, the patients have serious disfunctions in the alimentary system, characterized by motility disorders. However, it is known that such changes do not exist in MDX mice. The aim of this study was to estimate the neuronal numerical density/area of total (QA[T]) and nitregic neurons (QA[N]), the average cross-sectional area of total (A[T]) and nitregic (A[N]) neurons in myenteric plexus of the oesophagus and the average width of striped muscle of muscular layer (L). Forty C57BL/10 male mice were studied from four to ten weeks of age, divided into four groups: MDX mice formed the experimental groups (MDX4 and MDX10) and C57BL/10 male mice without the mutation formed the control groups (C4 and MDX10). Whole mounts preparations were obtained from the samples and histochemistry for NADH-diaphorase (NADH-d) and NADPH-diaphorase (NADPH-d) were used for morphometric evaluation. The results showed a significant increase of the QA[T] in the MDX10 than C10 (p<0.05), and a decrease of the QA[N] in MDX4 comparing to C4 (p<0.05). The A[T] decreased significantly in MDX10 comparing to both MDX4 and C10 (p<0.05), while no significant differences were observed among all the groups regarding the A[N]. The groups MDX4 and MDX10 showed a significant increase in L when compared to its controls at the same age (p<0.05). We conclude that in the myenteric plexus of the oesophagus in MDX mice there is a reduction of the inhibitory neurons, manly in the young animals (MDX4), probably to keep normal the peristaltic functions. Thus, it may explain the adaptation and the absence of oesophageal disfunction during almost the whole life in this animal model.

1. Nustatyti erozinio ezofagito ir jo komplikacijos – ikivėžinio susirgimo, Bareto stemplės, dažnį tarp endoskopiniam tyrimui atsiųstų pacientų, turinčių viršutiniojo virškinamojo trakto skundų ir/ar „pavojaus“ simptomų. 2. Nustatyti klinikinius, endoskopinius ir morfologinius požymius, susijusius su gastroezofaginio reflukso ligos sunkumu. 3. Nustatyti klinikinius, endoskopinius ir morfologinius požymius, susijusius su ikivėžiniu susirgimu – Bareto stemple. 4. Nustatyti skrandžio, skrandžio – stemplės jungties ir stemplės gleivinės morfologinius pakitimus, sergant įvairaus sunkumo GERL ir Bareto stemple. 5. Išanalizuoti trumpo ir ilgo segmento Bareto stemple sergančių asmenų klinikinius, endoskopinius ir morfologinius ypatumus. 6. Nustatyti rizikos veiksnius, įtakojančius ikivėžinio susirgimo - Bareto stemplės - progresavimą dvejų metų stebėjimo laikotarpiu. / 1. To investigate the prevalence of erosive esophagitis and its complication -precancerous disease, Barrett‘s oesophagus, in patients referred to upper diagnostic endoscopy with upper gastrointestinal and/or „alarm“ symptoms. 2. To establish clinical, endoscopic and morphological signs associated with severity of gastro-oesophageal reflux disease. 3. To establish clinical, endoscopic and morphological signs associated with precancerous disease - Barrett‘s oesophagus. 4. To determine morphological alterations of stomach, gastro-oesophageal junction and oesophagus mucosa of different severity of GORD and Barrett‘s oesophagus. 5. To analyse clinical, endoscopic and morphological peculiarities of long and short segments of Barrett’s oesophagus. 6. To investigate risk factors associated with progression of precancerous disease, Barrett‘s oesophagus, during two years follow-up period.

Squamous cell carcinoma of the oesophagus (OSCC) is a common malignancy that occurs with high frequency in certain parts of the world, including South Africa. The aetiology of OSCC has remained unclear although many studies suggest that it is caused by a combination of variable risk factors. Recent reports implicate a variety of genetic factors in the carcinogenesis of OSCC but their involvement is yet to be defined. / Thesis (M.Med)-University of KwaZulu-Natal, Durban, 2010.