Increased pre-surgical numbers of endothelial progenitor cells and circulating endothelial cells in colorectal cancer fail to predict outcome.

INTRODUCTION: The endothelium and angiogenesis are therapeutic targets in cancer. Response to treatment may be assessed by laboratory plasma markers such as circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), von Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor (VEGF) and angiogenin. We hypothesised that these markers, obtained before surgery, would predict 2-year outcome after surgery with or without anti-angiogenic therapy for colorectal cancer (CRC). METHODS: We recruited 154 patients with CRC, of whom 51 were treated with surgery alone, 74 were treated with standard chemotherapy (5-fluorouracil) and 29 were treated with standard chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before surgery. CD34(+)/CD45(-)/CD146(+) CECs and CD34(+)/CD45(-)/CD309 [KDR](+) EPCs were measured by flow cytometry and plasma markers by ELISA. RESULTS: After a mean of 2.1 years follow-up (range 1.9-2.3 years), 52 of the patients (33.7 %) experienced a poor outcome (radiological and/or histological evidence of tumour spread or recurrence, or death [n = 26]). In univariate analysis, poor outcome was linked to Dukes' stage (p < 0.001), American Joint Committee on Cancer (AJCC) stage (p < 0.001), type of treatment (surgery alone, standard chemotherapy with or without anti-antigenic therapy) (p = 0.047), CECs (p < 0.02) and EPCs (p < 0.01). In subsequent binary logistic regression analysis, only Dukes' stage (hazard ratio 2.3, 95 % confidence interval 1.0-5.3, p = 0.047) and modified AJCC stage (4.62, 1.88-11.33, p < 0.001) predicted a poor outcome. CONCLUSION: Endothelial cell markers (CECs, EPCs, vWf, soluble E selectin) and growth factors (VEGF and angiogenin), measured before surgery, have nothing extra to offer in predicting 2-year outcome in colorectal cancer when compared to Dukes' or AJCC stage.

Oxidative stress and air pollution exposure during pregnancy: A molecular assessment.

Chronic air pollution exposure during pregnancy can cause oxidative stress leading to adverse birth outcomes. The aim of this study was to assess and compare oxidative stress response in peripheral lymphocytes isolated from pregnant women from a highly industrialized locale (south Durban (SD); n = 50) and a control with lower air pollutant levels (north Durban (ND); n = 50). Oxidative stress response was measured by quantifying malondialdehyde (MDA) levels and a SuperArray gene panel. Mitochondrial function (adenosine triphosphate (ATP) levels and mitochondrial depolarization), DNA integrity (comet assay and mitochondrial DNA (mtDNA) viability) and DNA repair (OGG1) were assessed. Antioxidant response was assessed by quantification of glutathione (GSH) and SOD2, nuclear factor erythroid 2-related factor 2 (Nrf2) and uncoupling protein 2 (UCP2) protein and messenger RNA (mRNA) expression. Levels of MDA (p = 0.9), mitochondrial depolarization (p = 0.88), ATP (1.89-fold), SOD2 (1.23-fold) and UCP2 (1.58-fold) gene expression were elevated in the SD group with significantly higher UCP2 protein levels (p = 0.05) and longer comet tail length (p = 0.0004). The expression of Nrf2 protein (p = 0.03) and mRNA levels (-1.37-fold), GSH concentration (p < 0.0001), mtDNA amplification (-2.04-fold) and OGG1 mRNA (-2.78-fold) activity were decreased in the SD group. Of the 84 oxidative stress-related genes evaluated, 26 were differentially regulated. Pregnant women exposed to higher air pollutant levels showed increased markers for oxidative stress and compromised DNA integrity and repair.

Effect of standard chemotherapy and antiangiogenic therapy on plasma markers and endothelial cells in colorectal cancer.

INTRODUCTION: The importance of the endothelium in angiogenesis and cancer is undisputed, and its integrity may be assessed by laboratory markers such as circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), plasma von Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor (VEGF) and angiogenin. Antiantigenic therapy may be added to standard cytotoxic chemotherapy as a new treatment modality. We hypothesised that additional antiangiogenic therapy acts in a contrasting manner to that of standard chemotherapy on the laboratory markers. METHODS: We recruited 68 patients with CRC, of whom 16 were treated with surgery alone, 32 were treated with surgery followed by standard chemotherapy (5-flurouracil), and 20 were treated with surgery followed by standard chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before surgery, and again 3 months and 6 months later. CD34(+)/CD45(-)/CD146(+) CECs and CD34(+)/CD45(-)/CD309[KDR](+) EPCs were measured by flow cytometry, plasma markers by ELISA. RESULTS: In each of the three groups, CECs and EPCs fell at 3 months but were back at pre-surgery levels at 6 months (P<0.05). VEGF was lower in both 3-and 6-month samples in the surgery-only and surgery plus standard chemotherapy groups (P<0.05), but in those on surgery followed by standard chemotherapy plus anti-VEGF therapy, low levels at 3 months (P<0.01) increased to pre-surgery levels at 6 months. In those having surgery and standard chemotherapy, soluble E selectin was lower, whereas angiogenin was higher at 6 months than at baseline (both P<0.05). CONCLUSIONS: We found disturbances in endotheliod cells regardless of treatment, whereas VEGF returned to levels before surgery in those on antiangiogenic therapy. These observations may have clinical and pathophysiological implications.

Myasthenia Gravis in South Trinidad / Miastenia Gravis en el sur de Trinidad

OBJECTIVE: There is no previous research on Myasthenia Gravis (MG) in Trinidad and Tobago. This study sought to determine the prevalence and to characterize MG in South Trinidad. METHODS: A cross-sectional study was performed over 30 months in South Trinidad to identify, interview and statistically analyse data on MG cases. RESULTS: Among 36 prevalent patients, female:male ratio was 1.6:1. Estimated MG point prevalence in South Trinidad on March 31, 2010 was 78 per million. Mean age ofprevalent patients was 50.5 years. Mean age of onset was 35 years. A higher prevalence was detected in Africans than East Indians (178 vs 68 per million; p = 0.003). Ocular and extremity muscle weakness were the most common initial symptoms. Autoimmune conditions (mainly thyroid disease) co-existed in 25.7%. Treatment involved pyridostigmine and/or immunosuppressants for all except two that went into remission with just steroids. Generalized MG occurred in 60%; 42.9% expressed social and/or professional handicap. One case with suggestive clinical features tested positive for muscle specific tyrosine kinase antibody. CONCLUSIONS: While many features of MG in South Trinidad were similar to international data, the unique, statistically significant higher prevalence in Africans than East Indians warrants further research, given the paucity of reports from Africa and India. Patients with MG suffered a diminished quality of life, necessitating improved health planning.

OBJETIVO: No existen investigaciones previas sobre la miastenia gravis (MG) en Trinidad y Tobago. Este estudio tuvo por objeto determinar la prevalencia y caracterización de la MG en el sur de Trinidad. MÉTODOS: Se realizó un estudio transversal por espacio de más de 30 meses en el sur de Trinidad, con el fin de identificar, entrevistar, y analizar estadísticamente los datos sobre los casos de MG. RESULTADOS: Entre los 36 pacientes prevalentes, la proporción hembra:varón fue 1.6:1. La prevalencia puntual estimada MG en el sur de Trinidad el 31 de marzo de 2010, fue 78 por millón. La edad promedio de los pacientes prevalentes fue 50,5 años. La edad promedio al inicio de la enfermedad fue de 35 años. Se detectó una mayor prevalencia en los africanos que en los indios orientales (178 vs 68 por millón; p = 0. 003). La debilidad del músculo ocular y las extremidades fueron los síntomas iniciales más comunes. Las condiciones autoinmunes (principalmente la enfermedad de tiroides) coexistían en 25,7%. El tratamiento implicó la administración depiridostigmina y/o inmunosupresores para todos, excepto dos que entraron en remisión con esteroides solamente. La MG generalizada se produjo en un 60%; el 42,9% expresaron sus handicaps sociales y profesionales. Un caso con características clínicas sugestivas resultó positivo en la prueba de anticuerpos de tirosina quinasa específica del músculo. CONCLUSIONES: Si bien muchas características de la MG en el sur de Trinidad fueron similares a las que aparecen en los datos internacionales, la prevalencia única, y según las estadísticas significativamente mayor en los africanos que en los indios orientales, indica la necesidad de que se realicen investigaciones ulteriores, dada la escasez de informes procedentes de Africa y la India. Los pacientes con MG sufrieron una disminución en la calidad de vida, lo cual requiere una planificación para mejorar la salud.

Myasthenia gravis in South Trinidad.

OBJECTIVE: There is no previous research on Myasthenia Gravis (MG) in Trinidad and Tobago. This study sought to determine the prevalence and to characterize MG in South Trinidad. METHODS: A cross-sectional study was performed over 30 months in South Trinidad to identify, interview and statistically analyse data on MG cases. RESULTS: Among 36 prevalent patients, female:male ratio was 1.6:1. Estimated MG point prevalence in South Trinidad on March 31, 2010 was 78 per million. Mean age of prevalent patients was 50.5 years. Mean age of onset was 35 years. A higher prevalence was detected in Africans than East Indians (178 vs 68 per million; p = 0.003). Ocular and extremity muscle weakness were the most common initial symptoms. Autoimmune conditions (mainly thyroid disease) co-existed in 25.7%. Treatment involved pyridostigmine and/or immunosuppressants for all except two that went into remission with just steroids. Generalized MG occurred in 60%; 42.9% expressed social and/or professional handicap. One case with suggestive clinical features tested positive for muscle specific tyrosine kinase antibody. CONCLUSIONS: While many features of MG in South Trinidad were similar to international data, the unique, statistically significant higher prevalence in Africans than East Indians warrants further research, given the paucity of reports from Africa and India. Patients with MG suffered a diminished quality of life, necessitating improved health planning.

The angiome: a new concept in cancer biology.

Angiogenesis is a key process in cancer biology, and justifies focus on the endothelium. Separate studies have looked at different aspects of angiogenesis and vascular biology, primarily focusing on certain laboratory and imaging techniques that generally reflect one particular aspect of the assessment of the endothelium. These techniques include the secretion/release of molecules (such as growth factors) into the plasma, by the presence of mature and progenitor endothelial cells themselves in the circulation, but also by examination of peripheral blood flow and the local circulation of the tumour, and cells of the tumour itself. However, a limitation of this approach is that these methods, although themselves being useful, have often been viewed in isolation and thus can provide only a part of the vascular picture. The authors submit that this approach is weak, and introduce 'the angiome' as a term which fuses several different aspects of endothelial and tumour biology into a single concept. The authors suggest that the adoption of the concept of the angiome will bring improved insights into angiogenesis and thus cancer cell biology. In justifying this concept, the authors review the current understanding of endothelial biology and the methods of its assessment, and hypothesise that a more multifactorial approach to the angiome will be a crucial determinant of outcomes of and treatment strategies for diseases, in particular antiangiogenics for cancer therapy.

An in vitro evaluation of shear bond strengths of glass ionomer/amalgam combinations

Purpose: The purpose of this study was to assess the shear bond strength of amalgam when bonded to dentine with various cements. Materials and Methods: Eighty human molars were divided into five groups and ground dentine surfaces treated, with one of five cements (Fuji I, Vitrebond, Rely X, Fuji II and Panavia F). Spherical amalgam (Tytin) was condensed onto the unset cement and shear bond strengths were measured after one week. Results: The mean shear bond strength of Panavia F (25.3 MPa) was significantly higher compared with Fuji I (16.8 MPa), Fuji II (10.3 MPa) and Vitrebond (5.1 MPa) however there was no significant difference with Rely X (19.0 MPa). Conclusion: The combination of a resin modified glass ionomer luting cement with a spherical alloy may enhance bonding of amalgam to dentine.

Iodine stability in salt double-fortified with iron and iodine.

Deficiencies in small quantities of micronutrients, especially iodine and iron, severely affect more than a third of the world's population, resulting in serious public health consequences, especially for women and young children. Salt is an ideal carrier of micronutrients. The double fortification of salt with both iodine and iron is an attractive approach to the reduction of both anemia and iodine-deficiency disorders. Because iodine is unstable under the storage conditions found during the manufacturing, distribution, and sale of salt in most developing countries, the effects of packaging materials and environmental conditions on the stability of salt double-fortified with iron and iodine were investigated. Salt was double-fortified with potassium iodide or potassium iodate and with ferrous sulfate or ferrous fumarate. The effects of stabilizers on the stability of iodine and iron were followed by storing the salt under three conditions that represent the extremes of normal distribution and sale for salt in developing countries: room temperature (25 degrees C) with 50%-70% relative humidity, 40 degrees C with 60% relative humidity, and 40 degrees C with 100% relative humidity. The effects of stabilizers, such as sodium hexametaphosphate (SHMP), calcium carbonate, calcium silicate, and dextrose were investigated. None of the combinations of iron and iodine compounds was stable at elevated temperatures. Essentially all of the iodine was lost over a period of six months. SHMP effectively slowed down the iodine loss, whereas magnesium chloride, a typical hygroscopic impurity, greatly accelerated this process. Calcium carbonate did not have a sparing effect on iodine, despite contrary indications in the literature. Ferrous sulfate-fortified salts generally turned yellow and developed an unpleasant rusty flavor. Salt fortified with ferrous fumarate and potassium, iodide was reasonably stable and maintained its organoleptic properties, making it more likely to be acceptable to consumers. We confirmed that application of the iodine compounds as solutions resulted in a more even distribution of the iodine throughout the sample. The effect of the packaging materials was overshadowed by the other variables. None of the packaging materials was clearly better than any other. This may have been due to the fact that the polymer bags were not heat sealed, and thus some moisture penetration was possible. The results indicate that with careful control of processing, packaging, and storage conditions, a double-fortified salt could be stabilized for the six-month period required for distribution and consumption. Unfortunately, the processing and storage required are difficult to attain under typical conditions in developing countries.

Papillary thyroid adenocarcinoma arising in a thyroglossal tract remnant following excision of a thyroglossal cyst: the importance of the Sistrunk procedure.

Carcinoma of the thyroglossal tract is a rarity--over the past 85 years only 160 cases have been reported. We report the first case of carcinoma arising in a thyroglossal tract remnant 10 years after simple excision of a thyroglossal cyst. This case highlights the importance of the Sistrunk procedure, (the removal of the entire thyroglossal tract) for preventing not only cyst recurrence, sinus and fistula formation, but also the occurrence of carcinoma.

Prospective study of primary anastomosis without colonic lavage for patients with an obstructed left colon.

BACKGROUND: Traditionally, left-sided colon obstruction is managed by a multistaged defunctioning colostomy and resection. However, there is growing acceptance of one-stage primary resection and anastomosis with on-table antegrade irrigation. This paper presents a series of patients managed prospectively by primary anastomosis without intraoperative colonic lavage. METHODS: Emergency resection of acutely obstructed left-sided colonic carcinomas was performed. This was followed by primary anastomosis without on-table lavage after bowel decompression using a new technique. RESULTS: Fifty-eight consecutive, unselected patients underwent bowel decompression, resection and primary colocolic anastomosis. Only one patient developed a leak at the anastomotic site, requiring pelvic abscess drainage and transverse loop colostomy. One death occurred 12 h following surgery. Autopsy confirmed that this was due to myocardial infarction. Mean hospital stay was 9.8 days. CONCLUSION: Emergency surgery on the obstructed left colon can be carried out safely after decompression alone, without intraoperative colonic lavage.

Prospective study of primary anastomosis without colonic lavage for patients with an obstructed left colon

BACKGROUND: Traditionally, left-sided colon obstruction is managed by a multistaged defunctioning colostomy and resection. However, there is growing acceptance of one-stage primary resection and anastomosis with on-table antegrade irrigation. This paper presents a series of patients managed prospectively by primary anastomosis without intraoperative colonic lavage. METHODS: Emergency resection of acutely obstructed left-sided colonic carcinomas was performed. This was followed by primary anastomosis without on-table lavage after bowel decompression using a new technique. RESULTS: Fifty-eight consecutive, unselected patients underwent bowel decompression, resection and primary colocolic anastomosis. Only one patient developed a leak at the anastomotic site, requiring pelvic abscess drainage and transverse loop colostomy. One death occurred 12h following surgery. Autopsy confirmed that this was due to myocardial infarction. Mean hospital stay was 9.8 days. CONCLUSION: Emergency surgery on the obstructed left colon can be carried out safely after decompression alone, without intraoperative colonic lavage (AU)

Sick sinus syndrome and primary systemic amyloidosis.

A sixty-eight-year-old woman with documented sick sinus syndrome was found to have, five year later, florid clinical features of systemic amyloidosis which only then led to recognition of an underlying IgA, Kappa paraproteinaemia. The literature on this association is outlined. Underlying plasma cell dyscrasias should be excluded in cases of unexplained sick sinus syndrome.

Sick sinus syndrome and primary systemic amyloidosis

A sixty-eight-year-old woman with documented sick sinus syndrome was found to have, five years later, florid clinical features of systemic amyloidosis which only then led to recognition of an underlying IgA, Kappa paraproteinaemia. The literature on this association is outlined. Underlying plasma cell dyscrasias should be excluded in cases of unexplained sick sinus syndrome.

Malignant carcinoid syndrome. Failure of anti-oestrogenic therapy.

A pre-menopausal patient with a six-year history of symptoms of the metastatic carcinoid syndrome leading to progressively worsening carcinoid heart disease is described. The failure of anti-oestrogenic therapy (sequential bilateral oophorectomy and Tamoxifen therapy) to halt progression of disease was documented. Death resulted from right ventricular failure associated with pulmonary and tricuspid valvular disease.