Carol A. Seymour

Relative contributions of history-taking, physical examination, and laboratory investigation to diagnosis and management of medical outpatients.

To evaluate the relative importance of the medical history, the physical examination, and laboratory investigations in the diagnosis and management of medical outpatients some physicians recorded their diagnosis and a prediction of the method of managementafter reading the patients referral letter, again after taking the history, and againafter performing the physical examination. These diagnoses and predictions were compared with the diagnosis and method of management which had been adopted two months after the patients initial attendance. A diagnosis that agreed with the one finally accepted was made after reading the referral letter and taking the history in 66 out of 80 new patients; the physical examination was useful in only seven patients, and the laboratory investigations in a further seven. In only one of six patients in whom the physician was unable to make any diagnosis after taking the history and examining the patient did laboratory investigations lead to a positive diagnosis.

Early evidence of ethnic differences in cardiovascular risk: cross sectional comparison of British South Asian and white children

Abstract Objectives: To examine whether British South Asian children differ in insulin resistance, adiposity, and cardiovascular risk profile from white children. Design: Cross sectional study. Setting: Primary schools in 10 British towns. Participants: British children aged 8 to 11 years (227 South Asian and 3415 white); 73 South Asian and 1287 white children aged 10 and 11 years provided blood samples (half fasting, half after glucose load). Main outcome measures: Insulin concentrations, anthropometric measures, established cardiovascular risk factors. Results: Mean ponderal index was lower in South Asian children than in white children (mean difference −0.43 kg/m3, 95% confidence interval −0.13 kg/m3 to −0.73 kg/m3). Mean waist circumferences and waist:hip ratios were similar. Mean insulin concentrations were higher in South Asian children (percentage difference was 53%, 14% to 106%, after fasting and 54%, 19% to 99%, after glucose load), though glucose concentrations were similar. Mean heart rate and triglyceride and fibrinogen concentrations were higher among South Asian children; serum total, low density lipoprotein, and high density lipoprotein cholesterol concentrations were similar in the two groups. Differences in insulin concentrations remained after adjustment for adiposity and other potential confounders. However, the relations between adiposity and insulin concentrations (particularly fasting insulin) were much stronger among South Asian children than among white children. Conclusions: The tendency to insulin resistance observed in British South Asian adults is apparent in children, in whom it may reflect an increased sensitivity to adiposity. Action to prevent non-insulin dependent diabetes in South Asian adults may need to begin during childhood. What is already known on this topic Compared with white people British South Asians are at increased risk of coronary heart disease, stroke, and non-insulin dependent diabetes There is evidence that these conditions originate in early life What this study adds British South Asian children show higher average levels of insulin and insulin resistance than white children These ethnic differences in insulin resistance in childhood are not associated with corresponding differences in adiposity, particularly central adiposity Insulin metabolism seems to be more sensitive to a given degree of adiposity among the South Asian children compared with white children The prevention of insulin resistance and its consequences may need to begin during childhood, particularly in South Asians

Organelle Pathology in Primary and Secondary Haemochromatosis with Special Reference to Lysosomal Changes

Summary. The organelle pathology of liver biopsy specimens from patients with either primary or secondary haemochromatosis was investigated by analytical subcellular fractionation in combination with enzymic microanalysis. The most striking changes were found in the lysosomes. Increased total activities but decreased latent activities of enzymes selectively localized to the high density population of lysosomes was demonstrated in the iron overloaded biopsies. Depletion of the iron, where possible, by venesection was accompained by a return to normal of these changes.

Elevated Plasma Lipoprotein(a) Is Associated With Coronary Artery Disease in Patients With Chronic Stable Angina Pectoris

OBJECTIVES We sought to assess the relation between plasma lipoprotein(a) [Lp(a)] levels, clinical variables and angiographic coronary artery disease (CAD) in patients with chronic stable angina. BACKGROUND The relation between plasma Lp(a) levels and the severity and extent of angiographic CAD has not been studied in well characterized patients with stable angina pectoris. METHODS We investigated clinical variables, lipid variables and angiographic scores in 129 consecutive white patients (43 women) undergoing coronary angiography for chronic stable angina. RESULTS Plasma Lp(a) levels were significantly higher in patients with than in those without significant angiographic stenoses (> or =70%) (372 mg/liter [interquartile range 87 to 884] vs. 105 mg/liter [interquartile range 56 to 366], respectively, p=0.002). This difference remained significant when patients with mild or severe angiographic disease were compared with those with completely normal coronary arteries (312 mg/liter [interquartile range 64 to 864] vs. 116 mg/liter [interquartile range 63 to 366], respectively, p=0.02). However, subset analysis indicated that this difference achieved statistical significance only in women. Multiple logistic regression analysis indicated that Lp(a) concentration was independently predictive of significant angiographic stenoses (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 2.0 to 42.1, p=0.006) and remained true even after exclusion of patients receiving lipid-lowering treatment (n=27) (OR 10.4, 95% CI 1.1 to 102.9, p=0.05). Lp(a) also had independent predictive value in a similar analysis using mild or severe angiographic disease as the outcome variable (OR 11.8, 95% CI 1.5 to 90.8, p=0.02). CONCLUSIONS Our results indicate that elevated plasma Lp(a) is an independent risk factor for angiographic CAD in chronic stable angina and may have particular significance in women.

Secondary analysis of economic data: a review of cost-benefit studies of neonatal screening for phenylketonuria.

STUDY OBJECTIVE: To estimate the net financial benefit of neonatal screening for phenylketonuria (PKU): by a simple pooling of cost data from the literature; and by a more complex modelling approach. DESIGN: A systematic literature review was conducted to identify papers containing data on the monetary costs and benefits of neonatal screening for PKU. The methodological quality of the studies was appraised, and data were extracted on resource use and expenditure. Monetary data were converted to common currency units, and standardised to UK incidence rates. Net benefits were calculated for median, best case and worst case scenarios, and the effect of excluding poor quality studies and data was tested. The net benefit was also estimated from a model based on data from the literature and assumptions appropriate for the current UK situation. Extensive sensitivity analysis was conducted. MAIN RESULTS: The direct net benefit of screening based on the median costs and benefits from the 13 studies identified was 143,400 Pounds per case detected and treated (39,000 Pounds and 241,800 Pounds for worst case and best case scenarios respectively). The direct net benefit obtained by the modelling approach was lower at 93,400 Pounds per case detected and treated. Screening remained cost saving under sensitivity analysis, except with low residential care costs (less than 12,300 Pounds per annum), or very low incidence rates (less than 1 in 27,000). CONCLUSIONS: The economic literature on PKU screening is of variable quality. The two methods of secondary analysis lead to the same conclusion: that neonatal PKU screening is worthwhile in financial terms alone in the UK, and that it justifies the infrastructure for collecting and testing neonatal blood samples. This result cannot necessarily be extrapolated to other countries.

South-east Asian ovalocytic (SAO) erythrocytes have a cold sensitive cation leak: Implications for in vitro studies on stored SAO red cells

South-east Asian ovalocytosis (SAO) results from the heterozygous presence of an abnormal band 3, which causes several alterations in the properties of the erythrocytes. Although earlier studies suggested that SAO erythrocytes are refractory to invasion in vitro by the malarial parasite Plasmodium falciparum, a more recent study showed that fresh SAO cells were invaded by the parasites, but became resistant to invasion on storage because intracellular ATP was depleted more rapidly than normal. Here we show that SAO red cells are much more leaky to sodium and potassium than normal red cells when stored in the cold. This leak was much less marked when the cells were stored at 25 or 37 degreesC. Incubation for 3.5 h at 37 degreesC of cold-stored SAO red cells did not restore sodium and potassium to normal levels, probably because the depleted ATP level in cold-stored SAO red cells is further reduced with incubation at 37 degreesC. The increased leakiness of SAO red cells is non-specific and extends to calcium ions, taurine, mannitol and sucrose. These results suggest that SAO red cells undergo a structural change on cooling. Since many of the reports describing altered properties of SAO red cells have used cells which have been stored in the cold, these results need re-evaluation using never-chilled SAO red cells to assess whether the cells have the same abnormal properties under in vivo conditions.

Defective biliary copper excretion in Wilson's disease: the role of caeruloplasmin

Abstract. Previous studies have failed to explain the link between copper accumulation and abnormal caeruloplasmin expression in Wilsons disease. Furthermore, despite the isolation of a candidate gene for Wilsons disease, which predicts a defective copper transport protein, the localization of this putative protein and its relationship to the pathway involved in copper excretion and to caeruloplasmin remain unknown. We now present evidence that caeruloplasmin, the major plasma copper‐carrying protein, is present in the liver in Wilsons disease, and thus that reduced circulating levels of the protein result from a post‐translational defect in the secretory pathway. We have also identified a novel form of caeruloplasmin, molecular weight 125 kD, which we propose may act as the carrier for excretory copper into bile, since it is normally present in both liver and bile, although largely absent from serum, and undetectable in bile from Wilsons disease patients. The presence of this form of caeruloplasmin in Wilsons disease liver suggests that a related post‐translational defect may also be responsible for its absence from bile in Wilsons disease. This study thus provides the first plausible explanation of a link between the defective copper excretion and the reduced plasma caeruloplasmin, which characterize Wilsons disease.

Acute renal failure after cardiopulmonary bypass: a possible association with drugs of the fibrate group.

Background: Renal failure is a recognized, but infrequent, complication following cardiac surgery. The causes for this condition are multifactorial, and a major concern is that the occurrence of postoperative acute renal failure is still associated with a high mortality rate. Methods and Materials: We report unexpected acute renal failure occurring in 4 patients after uncomplicated cardiac surgery. Each patient was taking a fibric acid derivative at the time of surgery. Renal failure occurred rapidly within 3 days of surgery and was associated with increased concentrations of skeletal muscle-derived creatine kinase (CK). One patient devel oped myoglobinuria, and another developed a malignant hyperthermia-like syndrome. Conclusions: These cases show that patients receiving lipid lowering medications could be at higher risk of developing acute renal failure after cardiac surgery. This association merits careful evaluation in large prospective studies and, if proved, would suggest that patients taking either statins or fibrates should discontinue doing so before cardiac surgery.

Effect of stanozolol on itching in primary biliary cirrhosis

related complex present diagnostic difficulties. The lymphadenopathy in this group may result from a treatable infection or neoplasm. To our knowledge these are the first reported cases in which ultrasound guided percutaneous biopsy has been done in such patients. We performed Tru-Cut biopsy rather than fine needle aspiration because this technique is capable of yielding a tissue specific diagnosis so that lymphomas may be characterised by their nodal architecture and immunohistological features. Percutaneous ultrasound guided biopsy is a simple method of obtaining tissue in patients with symptoms resulting from infection with HIV. It may remove the need for laparotomy, which has many disadvantages, including the use of considerable resources to provide appropriate precautions for the larger number of staff at risk of contact with infected blood. With this technique a skilled operator can achieve millimetric precision in placing the biopsy needle. In our experience of over 200 abdominal biopsies it is a safe technique even when the needle crosses bowel or includes bowel wall in the biopsy specimen (unpublished data). Furthermore, it is cheap and puts only the operator at risk of needlestick injury.