Ethnic differences in outcome of serum screening for Down's syndrome. Differences in median values may account for differences in false positive rates.
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Biomedical subjects
Publications and source records attributed to A F Jones.
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We have previously demonstrated that modest sodium restriction has a hypotensive effect in hypertensive diabetic subjects. A randomised blind controlled study has therefore been performed to study the effect of replacement of added salt intake using a salt substitute (50% NaCl, 40% KCL, 10% Mg2+, supplied by Cederroth, Sweden), compared to added whole salt intake over a 9 month period of 40 hypertensive Type II diabetic subjects (mean age 62.5 +/- 7.8 years; 24 males and 16 females). After 3 months, there was a significant reduction in systolic blood pressure (SBP) in the salt substitution group (163.2 +/- 24.2 to 153.6 +/- 20.8 mm Hg; P < 0.03) which was maintained at 9 months, when compared to the whole salt group (151.5 +/- 20.6 vs 173 +/- 18.9 mm Hg; P < 0.05). No significant changes were observed in mean weight, fasting lipid or insulin levels or diabetic control (measured by glycosylated haemoglobin). A greater number of patients were withdrawn during the study period owing to consistent BP > 160/95 in the whole salt group (n = 10) compared to salt substitute (n = 4). No significant changes were observed in diastolic pressure, 24-h urine sodium or magnesium excretion, but urine potassium was significantly increased in the salt substitute group (58.8 to 77.3: P < 0.05). The results of this study suggest that substitution of sodium, by potassium and magnesium, produces a clinically significant reduction in SBP in hypertensive Type II diabetic patients, and should be a useful antihypertensive therapy in this patient group.
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Fecal alpha 1-antitrypsin measurement may be of value for the detection of colorectal neoplasia and is compared with the HemoQuant test in 119 subjects with either a screen-positive Hemoccult result (N = 78) or iron-deficiency anaemia (N = 41). Nineteen patients were found to have colorectal cancer, 35 had colorectal adenomatous polyps, 5 had inflammatory bowel disease, and 60 had no detected cause of occult blood loss. Of the cancer patients, 63% (12/19) were detected by fecal alpha 1-antitrypsin and 63% (12/19) by HemoQuant. Of the adenomas > 1 cm in diameter 33% (7/23) were detected by fecal alpha 1-antitrypsin and 26% (6/23) by HemoQuant. There was a poor correlation between fecal alpha 1-antitrypsin and HemoQuant results for colorectal cancers (r = 0.37, P > 0.05), and combining the tests, the sensitivity for colorectal cancer was increased to 84% (16/19). Fecal protein loss, as measured using alpha 1-antitrypsin, appears to involve largely different mechanisms from that of blood loss from colorectal cancers.
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This study evaluates the diagnostic accuracy of a faecal occult blood test and faecal alpha 1-antitrypsin in the investigation of patients with gastrointestinal symptoms or iron deficiency anaemia. One hundred and seventy nine patients with either iron deficiency anaemia (n = 67), changed bowel habit and aged > 39 years (n = 107), or a history suggestive of melaena (n = 5) provided faecal samples. After investigation, 32 patients had a diagnosis of possible gastrointestinal bleeding and 139 patients had no evidence of gastrointestinal bleeding. Eight patients had a cause of enteric protein loss in the absence of gastrointestinal bleeding and were excluded from subsequent analysis. The faecal alpha 1-antitrypsin test was diagnostically more accurate than the guaiac test in identifying probable gastrointestinal bleeding (82% and 72% respectively, p < 0.05). This faecal alpha 1-antitrypsin test was also more specific (83% and 72% respectively, p < 0.05), but was not significantly more sensitive (78% and 72% respectively). The sensitivity of these tests was insufficient to recommend their use for most patients in this study.
Lipoprotein (a) [Lp(a)] has been recognized for nearly 30 years, and increasingly, associated with the processes of atherogenesis and thrombogenesis. Despite this, the physiological and pathological function (and factors that influence levels) of Lp(a) remain largely unknown. Most experimental evidence supporting the mechanisms of vascular disease, thrombogenesis and atherogenesis have been generated in vitro, and to date, no in vivo confirmation exists. There is also a lack of sound evidence for Lp(a) as a risk factor in prospective as opposed to case-controlled studies. A fuller understanding of Lp(a) is still required in the molecular biology of atherogenesis and thrombogenesis.
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Faecal samples from patients with symptomatic colorectal cancer (n = 19) and from control subjects (n = 54) were analysed for alpha-1-antitrypsin (A1AT) and compared with Haemoccult and Okokit II. A1AT was also measured in paired samples of normal colonic mucosa and cancer tissue (n = 16) and in media from four human colorectal cell lines (COLO 320 DM, SW620, HT29, LS 174T). Faecal A1AT concentrations were greater than controls (P < 0.0001) and detected 12 (63%) patients with cancer compared to 10 (53%) by Okokit II and 7 (37%) by Haemoccult (P > 0.05). A1AT concentrations from colonic mucosa (median, range: 0.46, 0.17-0.79 mg/g wet wt) were greater (P = 0.01) than cancer tissue (0.29, 0.13-0.74 mg/g wt wt). Adjusting for albumin, A1AT concentrations from mucosa (12.0, 3.8-32.2 mg/g albumin) remained greater (P = 0.003) than for cancer tissue (5.9, 2.4-21.4 mg/g albumin). A1AT was not detected in any of the cell-line media. The most likely mechanisms for increased faecal A1AT concentrations, apart from increased blood loss, are increased cell turnover or leakage from epithelial tight junctions. The use of faecal A1AT measurement for the detection of colorectal cancer deserves further assessment.
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Statins and fibrates are both effective in the treatment of hyperlipidaemias but are not recommended in combination because episodes of rhabdomyolysis have followed combined lovastatin-gemfibrozil therapy. We assessed treatment with dual bezafibrate-simvastatin therapy in routine clinical practice. In 22 patients, total cholesterol, LDL-cholesterol and triglycerides fell by 20.1% (P < 0.0001), 35.1% (P < 0.001) and 31% (P < 0.05) respectively, and HDL-cholesterol rose by 18.4% (P < 0.05) on combination therapy. The reduction in cholesterol followed the introduction of simvastatin, while the decrease in triglycerides followed treatment with bezafibrate. No patient developed myopathy. We conclude that dual simvastatin-bezafibrate therapy is well tolerated and may reduce triglyceride concentrations, but offers no advantage in cholesterol reduction over treatment with simvastatin alone.
The occurrence of hypophosphataemia in paracetamol overdose suggests that nephrotoxicity is common, impaired renal tubular reabsorption of phosphate indicating renal damage. To investigate the potential nephrotoxicity of paracetamol, we studied 148 consecutive patients with paracetamol overdose. Serial clinical and biochemical measurements were made, and a fasting overnight urine collection was obtained for creatinine (Cr), phosphate and retinol-binding protein (RBP) determination. Renal threshold phosphate concentration (TmPO4/GFR) was determined from urinary parameters by an established nomogram. The degree of hypophosphataemia correlated with the severity of overdose, and with TmPO4/GFR. The median RBP/Cr ratio was higher in those patients exhibiting biochemical hepatotoxicity compared with those without hepatotoxicity, in whom median RBP/Cr was not significantly higher than controls. Within the group of patients showing biochemical hepatotoxicity, there was a correlation between log RBP/Cr and TmPO4/GFR. RBP/Cr ratio is a less sensitive marker of renal tubular toxicity than phosphaturia in these patients, and may indicate a different mechanism of toxicity.
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