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Biomedical subjects

D Vallance

Publications and source records attributed to D Vallance.

8 recordsLinked to original sources
PubMed2003

Severe hypokalaemia and weakness due to Nurofen misuse.

Nephrotoxicity from non-steroidal anti-inflammatory drugs (NSAID) is well recognized. We report a case of severe hypokalaemia and weakness due to renal tubular acidosis in a young woman who was taking 40-60 tablets per day of Nurofen Plus (ibuprofen 200 mg and codeine phosphate 12.8 mg). Proprietary brands of ibuprofen are freely available to the public and those containing codeine may be potentially subject to abuse. This case highlights the need to be aware of this potential and of the life-threatening electrolyte and acid-base disturbances that might be encountered with the widespread availability of these types of NSAID.

Acidosis, Renal Tubular↗
PubMed1996

The pathology of cornea in Tangier disease (familial high density lipoprotein deficiency).

AIMS: To clarify the underlying causes of corneal opacification in Tangier disease. METHODS: Both corneas were removed at death from a 62 year old man with Tangier disease, and were examined by direct and transmission electron microscopy, histochemistry, biochemical analysis by thin-layer and gas-liquid chromatography after extraction, and by differential scanning calorimetry. RESULTS: Membranous inclusions in the stroma were seen on transmission electron microscopy. Direct analysis confirmed enrichment with phospholipids and cholesterol, with acyl patterns and proportions as ester broadly similar to those of normal cornea. Tangier cornea showed major thermotropic phase transitions in the range 28-37 degrees C, peak 30-33 degrees C, extending above profiles of normal clear cornea and without the complexity of those seen with cornea with heavy arcus involvement. CONCLUSIONS: Lipid accumulation underlies corneal opacification in Tangier disease. The excess material is mainly phospholipid and cholesterol esters. As at other sites which are below body core temperature, notably tonsil, accumulation may be enhanced by local impaired mobilisation of material as the phase transitions of the excess lipid present extend above ambient corneal temperatures.

Calorimetry, Differential Scanning↗
PubMed1995

A common variant in the gene for lipoprotein lipase (Asp9-->Asn). Functional implications and prevalence in normal and hyperlipidemic subjects.

Subjects with combined hyperlipidemia (CHL) were screened for mutations in the lipoprotein lipase (LPL) gene by single-strand conformational polymorphism, and a previously reported G-->A DNA sequence change in exon 2, causing substitution of Asp by Asn at position 9, was identified in 2 individuals. Because this substitution destroys a recognition site for Taq I, pooling of DNA samples, amplification, and digest with Taq I allowed the rapid screening of 1563 healthy individuals and patients of Dutch, Swedish, English, and Scottish origin. In the general populations of all four countries, healthy carriers of the mutation were detected at a frequency of 1.6% to 4.4% (mean, 3.0%; 95% confidence interval, 2.0% to 4.0%). The frequency of carriers was roughly twice as high (range, 4.0% to 9.8%) in selected patients with CHL or type IV hyperlipoproteinemia or in subjects with angiographically assessed atherosclerosis; the frequency was consistently higher in each patient group compared with its matched control group. In 773 healthy men from two general practices in the United Kingdom, 25 carriers and 2 homozygotes for the mutation were identified. In these 27, plasma triglyceride but not plasma cholesterol levels were significantly higher than in noncarriers (2.25 versus 1.82 mmol/L, P < .02), and this difference was maintained in three subsequent annual measurements. Postheparin LPL activity data were available for some carriers and for 7 of 9 individuals from the patient groups, and 6 of 6 individuals from the control groups had LPL activity that was lower than the respective group mean. In vitro mutagenesis and transient expression in COS cells showed that compared with the LPL-Asp9 construct, LPL-Asn9 activity and mass were reduced by 20% to 30% in the culture media. Overall however, LPL-Asn9 had only slightly reduced specific activity (by 18%). Thus, although the precise mechanism of the effect is unclear, the data strongly suggest that the LPL-Asn9 variant is associated with and may play a direct role in predisposing carriers to develop hypertriglyceridemia.

Adult↗
PubMed1994

Lipoprotein lipase activity in patients with combined hyperlipidaemia.

The aetiology of familial combined hyperlipidaemia remains obscure, with both genetic and environmental factors contributing to the phenotype, which is frequently associated with premature coronary heart disease. We have studied lipoprotein lipase (LPL) activity and hepatic lipase (HL) activity in patients with coronary heart disease to determine whether variation in lipase activities contributes to this phenotype. Forty-one patients (mean age 50 years; 30 male) were selected on the basis of cholesterol levels above 6.5 mmol/l and triglyceride levels above 2.2 mmol/l, with apoprotein B values over the 90th percentile. There was a family history of premature coronary heart disease in 78% and a personal history in 64%, at mean age 44, the patient group therefore predominantly corresponded to the common definition of familial combined hyperlipidaemia, appropriate in the absence of molecular markers. None of the patients was diabetic; hypertension and smoking were not over represented. Blood samples were taken following intravenous administration of heparin (100 IU/kg body wt), and LPL and HL activities were measured. Mean post-heparin LPL was significantly lower in patients than controls 10 min after heparin administration (2.98 +/- 1.04 and 3.86 +/- 0.93 mumol ml-1 h-1, respectively, P = 0.001), and 37% patients had values below the 10th percentile of controls. Both male and female patients had significantly higher HL activities than their respective controls at 5, 10, 20 and 30 minutes post-heparin. As expected, both female patients and controls had lower HL activities than males, although this sex difference did not reach statistical significance in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Brisk walking and serum lipoprotein variables in formerly sedentary men aged 42-59 years.

1. The purpose of this study was to examine the influence of brisk walking on serum lipoprotein variables. 2. Seventy-two apparently healthy but physically inactive men (aged 42-59 years) were recruited. These men were normotensive non-smokers without a history of dyslipidaemia. Subjects were randomly allocated on a 2 to 1 basis into either a walking group (n = 48) or a control group (n = 24). Walkers followed a self-monitored programme of brisk walking for 1 year, whereas control subjects maintained their habitual lifestyle. 3. Treadmill walking tests were conducted to examine changes in fitness. Concentrations of serum lipids and lipoproteins were determined in fasting subjects. The amount of body fat was measured by body density. Circumferences at the waist and hip and skinfold thicknesses were used to determine the distribution of body fat. Dietary intakes were assessed by weighed food inventories. 4. Seven subjects (six walkers and one control subject) dropped out during the study. Walkers did an average of 28 (SEM 1.4; n = 42) min of brisk walking/day. This improved endurance fitness but did not influence serum concentrations of total cholesterol, high-density lipoprotein cholesterol, triacylglycerol, apolipoprotein A-1, apolipoprotein B or lipoprotein (a). Neither body mass nor the amount of body fat changed, relative to control subjects. 5. These data suggest that brisk walking does not modify lipoprotein metabolism in normolipidaemic middle-aged men.

Adult↗
PubMed1989

Clinical application of a new enzyme-linked assay for the estimation of brain-specific creatine kinase in head injured patients.

The clinical value of serum brain specific creatine kinase (CK-BB) was assessed in head injured patients (group A) using a new enzyme-linked immunosorbent assay (ELISA). The results were compared to healthy controls (group B) and patients post-myocardial infarction (group C). None of the head injured patients had undergone a surgical procedure or ventricular puncture. CK-BB was significantly higher in group A than in controls. The level of CK-BB in group A was inversely proportional to the Glasgow Coma Scale on admission. All patients with a CK-BB greater than 100 micrograms/l died. The ELISA technique is a simple and reliable assay with prognostic significance in patients with head injury and has wider clinical application than the previously described radioimmunoassay methods.

Brain Injuries↗
PubMed1988

Role of duodenal bile crystal analysis in the investigation of 'idiopathic' pancreatitis.

Duodenal bile crystal analysis for the detection of gallstones was assessed in 26 patients with acute pancreatitis of known aetiology (11 attributable to gallstones and 15 to alcohol) and in 37 patients without a history of acute pancreatitis (21 with gallstones and 16 without). The sensitivity was 64-67 per cent and the specificity was 94-100 per cent in these groups. Analysis of duodenal bile from 14 patients with 'idiopathic' pancreatitis revealed calcium bilirubinate crystals (but not cholesterol crystals) in 5 patients (36 per cent). Gallstones were confirmed at cholecystectomy in three of these patients and also in one other patient who had a gallstone on a 'late' ultrasound examination but was negative for crystals. Thus 29 per cent of the original 'idiopathic' group had gallstones confirmed. Gallstone analysis showed that pigment stones were present in 7 of 31 (23 per cent) non-pancreatitis controls compared with 9 of 13 (69 per cent) pancreatitis patients (P = 0.0048). These results suggest that duodenal bile crystal analysis (involving both calcium bilirubinate and cholesterol crystals) may be a useful technique for the investigation of patients with 'idiopathic' pancreatitis.

Acute Disease↗