Disordered vascular compliance in haemochromatosis.

BACKGROUND: A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk. AIMS: To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls. METHODS: Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured. RESULTS: Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 µmol/L, p = 0.011), retinol (1.17 vs. 1.81 µmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 µmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32). CONCLUSIONS: Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.

Cyclooxygenase-2 expression correlates with phaeochromocytoma malignancy: evidence for a Bcl-2-dependent mechanism.

AIMS: Phaeochromocytomas are rare but potentially life-threatening neuroendocrine tumours of the adrenal medulla or sympathetic nervous system ganglia. There are no histological features which reliably differentiate benign from malignant phaeochromocytomas. The aim of the study was to evaluate cyclooxygenase (COX)-2 and Bcl-2 as tissue-based biomarkers of phaeochromocytoma prognosis. METHODS AND RESULTS: COX-2 and Bcl-2 expression were examined immunohistochemically in tissue from 41 sporadic phaeochromocytoma patients followed up for a minimum of 5 years after diagnosis. There was a statistically significant association between COX-2 histoscore (intensity x proportion) and the development of tumour recurrence or metastases (P = 0.006). A significant relationship was observed between coexpression of COX-2 and Bcl-2 in the primary tumour and the presence of recurrent disease (P = 0.034). A highly significant association was observed between (i) tumour-associated expression of these two oncoproteins (P = 0.001) and (ii) COX-2 histoscore and the presence of Bcl-2 expression (P = 0.002). COX regression analysis demonstrated no significant relationship between (i) the presence or absence of either COX-2 or Bcl-2 and patient survival or (ii) COX-2 histoscore and patient survival. CONCLUSIONS: COX-2 and Bcl-2 may promote phaeochromocytoma malignancy, and these oncoproteins may be valuable surrogate markers of an aggressive tumour phenotype.

Review article: possible beneficial effects of coffee on liver disease and function.

BACKGROUND: Coffee is consumed by 50 percent of Americans every day. After oil, coffee is the second most valuable commodity in the world. In recent years a number of studies have suggested potential health risks associated with coffee consumption; however, the results are controversial. Whilst coffee has been reported to increase cardiovascular risk factors, other investigators have demonstrated its protective effects on diseases ranging from type 2 diabetes to Parkinson's disease. A number of investigators have focused their attention on the relationship between the consumption of coffee and liver disease. AIM: To examine the published literature to date in an attempt to establish the presence of an hepatoprotective effect of coffee. METHODS: Using PubMed, we identified published studies and review articles relating to the effect of coffee consumption on diseases of the liver. CONCLUSION: A number of studies have reported the beneficial effects of coffee on abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. At the present time the mechanism of this effect remains unclear as does the ''dose'' required to achieve these benefits.

An investigation into the role of Bcl-2 in neuroendocrine differentiation.

INTRODUCTION: In addition to its role in apoptosis suppression, Bcl-2 has been reported to be co-expressed with neuroendocrine markers in several tissues, leading to speculation that this oncoprotein may promote neuroendocrine differentiation. AIM: This study investigated whether Bcl-2 modulated neuroendocrine biopeptide expression. METHODS: Levels of chromogranin A, neurone specific enolase, protein gene peptide 9.5, pancreatic polypeptide, and the chromogranin-derived peptides, intervening peptide and vasostatin-1 were examined by immunocytochemistry in rat phaeochromocytoma (PC12) cell lines genetically engineered to over-express Bcl-2 and their mock-transfected controls. Intensity of fluorescence was graded using a semi-quantitative scale from (-) indicating negative expression to (+++) indicating intense positivity. RESULTS: Mann-Whitney U analysis indicated that no significant differences in expression existed between control and Bcl2 over-expressing cell lines for any of the six peptides examined. CONCLUSIONS: The results of this study do not support the hypothesis that Bcl-2 promotes the acquisition of a neuroendocrine phenotype.

Dapsone-induced methhaemoglobinaemia: a source of diagnostic confusion.

Arterial desaturation as measured using pulse oximetry may not reflect cardiorespiratory disease; other possible causes, including certain drugs, should be sought. Within the literature, examples exist of dapsone-induced methaemoglobinaemia causing diagnostic confusion, particularly where respiratory disease is a feature. Few cases have been reported that demonstrate the potential of relatively low levels of methaemoglobinaemia to upset pulse oximetry readings. We describe three examples of dapsone-induced methaemoglobinaemia emphasising the potential for low-grade methaemoglobinaemia to cause diagnostic confusion. Widespread use of the pulse oximeter indicates this problem may occur more regularly, hence there is a need for increased awareness.

Investigating paediatric airways by non-bronchoscopic lavage: normal cellular data.

BACKGROUND: Bronchoscopic bronchoalveolar lavage in children to investigate bronchial disorders such as asthma has both ethical and procedural difficulties. OBJECTIVE: The aim of this study was to establish a standardized non-bronchoscopic method to perform bronchoalveolar lavage in children attending for elective surgery to obtain normal cellular data. METHODS: Bronchoalveolar lavage was performed on normal children (n = 55) by infusing saline (20 mL) through an 8 FG suction catheter passed after endotracheal intubation. Oxygen saturation, heart and respiratory rate were monitored during the bronchoalveolar lavage procedure. Cellular analysis and total protein estimation of the lavage fluid were performed. Epithelial lining fluid volume was calculated (n = 15) using the urea dilution method. RESULTS: The procedure was well tolerated by all children. Total cell count and differential cell count for children (macrophages 70.8 +/- 2.3%, lymphocytes 3.8 +/- 0.6%, neutrophils 5.7 +/- 1.0%, eosinophils 0.14 +/- 0.03%, epithelial cells 19.6 +/- 2.1%, mast cells 0.21 +/- 0.02%) were similar to those reported for adults. Age and sex comparisons revealed no differences between groups. The mean total protein recovered in the cell free supernatant was 49.72 +/- 4.29 mg/L and epithelial lining fluid volume was 0.82 +/- 0.11% of return lavageate. CONCLUSION: This method allows bronchoalveolar lavage to be performed safely and quickly on children attending for routine elective surgery. Using this method and taking the 'window of opportunity' of elective surgery, the presence or absence of airway inflammation could be studied in children with various patterns of asthma during relatively asymptomatic periods.