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E S Kilpatrick

Publications and source records attributed to E S Kilpatrick.

At least 19 recordsLinked to original sources
PubMed2006

Dehydroepiandrosterone sulphate interferes with the Abbott Architect direct immunoassay for testosterone.

BACKGROUND: There are known difficulties in measuring testosterone in women using 'direct' (non-extraction) immunoassays. The positive bias encountered in many of these assays has been attributed to an unidentified interfering substance. We have evaluated the potential for dehydroepiandrosterone sulphate (DHEA-S) to cross-react in the Abbott Architect testosterone assay. METHODS: Samples (n = 81) from female patients who had DHEA-S, direct and extracted testosterone measured were examined retrospectively. Possible cross-reactivity was evaluated by spiking both testosterone free assay diluent and serum from a woman with exogenous DHEA-S. RESULTS: The retrospective patient analysis of the data demonstrated a relationship between interference and DHEA-S (r = 0.78, P < or = 0.0001). Spiking studies revealed a linear relationship between added DHEA-S and the measured testosterone concentration. Consistent with the retrospective study, for every 1 micromol/L increase in DHEA-S, 0.23 nmol/L of testosterone was measured in the diluent. Spiking DHEA-S into serum gave only a 0.12 nmol/L increase in measured testosterone for every 1 micromol/L rise in DHEA-S. CONCLUSION: DHEA-S cross-reacts in the Abbott Architect direct immunoassay for testosterone to a clinically significant effect. This cross-reactivity is likely to be responsible for much of the interference observed when measuring testosterone in women by this method.

Cross Reactions↗
PubMed2006

Investigation into possible causes of interference in serum testosterone measurement in women.

BACKGROUND: Direct (non-extracted) testosterone immunoassays may give spuriously high results in women. The presumed interferents may be removed if testosterone is extracted into an organic phase before being measured. We aimed to clarify possible causes and effects of interference in testosterone measurement in women. METHODS: Women who had a blood sample referred to Hope Hospital Clinical Biochemistry laboratory for measurement of serum testosterone concentration over a six-month period were studied. Clinical and treatment data were recorded. A difference (direct-minus-extracted testosterone) of less than 1.0 nmol/L was used to define a group with low interference. A difference of 2.5 nmol/L or more was used to define a group with significant interference. RESULTS: The distribution of interference in 1271 serum samples from female patients was unimodal. There were no group differences in clinical presentation or treatment. The median degree of interference was 1.4 nmol/L. In 42 female patients with varying degrees of interference, identified on routine assay, regression analysis showed strong association between dehydroepiandrosterone sulphate (DHEA-S) and interference (direct-minus-extracted testosterone) (r = 0.77, P < 0.001). CONCLUSIONS: Given that DHEA-S is present in very variable amounts in blood, it is possible that even with a low cross reactivity, DHEA-S or one of its metabolites significantly interferes in the testosterone assay when at higher concentrations.

Adult↗
PubMed2005

Improvement of glycaemic control with rebound following orlistat initiation and cessation associated with minimal weight change.

A 57-year-old Caucasian woman with Type 2 diabetes treated for seven years with diet and oral combination hypoglycaemic therapy was referred because of the progressive deterioration of glycaemic control. She was obese (77 kg, BMI = 39.9), hypertensive, hypercholesterolaemic with marked osmotic symptoms (HbA(1c) 12.2%), therefore she was started on insulin (Human Mixtard 30 b.d.) with metformin therapy. Dietary counselling, recommendations to increase physical activity, and supervised self-injection technique with titration of her insulin were also provided. She was routinely followed-up to assess her progress. Two years later, her glycaemic control remained suboptimal. Average HbA(1c) was 10.4% despite an increasingly high dose of insulin (94 units/day) although it improved when metformin was increased to 1 g t.d.s. (HbA(1c) = 9.3%). Her BMI progressively rose from 39.9 to 42.1 (77 to 82.5 kg) despite dietary advice. A trial of orlistat (three months) was commenced, after intensive dietary counselling, that reduced her body weight by 1.5 kg (2% reduction, BMI 41.3). However, her HbA(1c) improved by 0.5% (from 9.3 to 8.8%). Six months after orlistat was stopped her HbA(1c) rose to 10.5% and weight increased to 81.8 kg (BMI 41.8). Despite the orlistat treatment broaching NICE guidelines should it have been continued?

Diabetes Mellitus, Type 2↗
PubMed2004

Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome.

The objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS). Twenty-one Caucasian women with PCOS [mean (+/-SEM) age 27 +/- 0.9 yr and body mass index 36.7 +/- 3.3 kg/m(2)] participated in this prospective, randomized, open-labeled study. All subjects had an 8-wk run-in period of dietary modification and then randomized to receive either metformin (500 mg three times daily) or orlistat (120 mg three times daily) for 3 months. Weight, blood pressure, and fasting blood samples were taken at screening, randomization, and on completion. Insulin resistance (IR) was calculated using the homeostasis model of assessment (HOMA)-IR method [HOMA-IR = (insulin x glucose)/22.5]. The results are expressed as mean +/- SEM. When compared with baseline, treatment with both orlistat [93.5 +/- 11.5 ng/dl (3.24 +/- 0.4 nmol/liter) vs. 114.5 +/- 11.5 ng/dl (3.97 +/- 0.4 nmol/liter), P = 0.039] and metformin [97.2 +/- 11.5 ng/dl (3.37 +/- 0.4 nmol/liter) vs. 120.0 +/- 8.7 ng/dl (4.16 +/- 0.3 nmol/liter), P = 0.048] produced a significant reduction in total testosterone. Treatment with orlistat produced a 4.69% reduction in weight (99.0 +/- 6.0 vs. 94.6 +/- 6.1 kg, P = 0.002), and this reduction was more significant than the reduction produced by metformin (4.69 vs. 1.02%, P = 0.006). There was no significant reduction seen after either treatment group for fasting insulin, HOMA-IR, SHBG, or any of the lipid parameters studied. In this study, orlistat produced a significant reduction in weight and total testosterone. The reduction in total testosterone was similar to that seen after treatment with metformin. Therefore, orlistat may prove to be a useful adjunct in the treatment of PCOS.

Adult↗
PubMed2004

HbA1c measurement.

Explore the source record for details and available documents.

Glycated Hemoglobin↗
PubMed2004

Can the addition of interpretative comments to laboratory reports influence outcome? An example involving patients taking thyroxine.

INTRODUCTION: There is little evidence that the addition of interpretative comments to biochemistry reports can influence outcome for patients. Interpretative comments on thyroid function test (TFT) requests were introduced in Hull in August 1999, providing the opportunity to determine whether feedback on hypothyroid patients taking thyroxine could lead to a reduction in the proportion whose thyroxine was inadequately replaced. PATIENTS AND METHODS: The study comprised 15 584 TFT requests, made from 1 August 1999 to 30 August 2002 by general practitioners (GPs), for 8281 patients taking thyroxine. Under-replacement of thyroxine, defined as a TSH concentration above the upper reference limit (i.e. 4.7 mU/L), was usually commented on in the biochemical report. RESULTS: In the first, second and third years following introduction of interpretative comments, the proportions of samples with a TSH concentration of >4.7 mU/L were 21.3%, 17.6% and 16.6%, respectively (chi(2)(trend) = 43.1, P <0.0001). The proportion with a TSH concentration of <0.1 mU/L showed a more modest change, from 12.5% in year 1 to 14.0% and 14.8% in years 2 and 3, respectively (chi(2)(trend) = 22.3, P <0.0001). CONCLUSION: This study shows that in the three years following the introduction of interpretative comments there was a 22% reduction in the number of GPs' samples indicating thyroxine under-replacement. It seems likely that these data provide evidence that comments can indeed influence the biochemical outcome of patients.

Antithyroid Agents↗
PubMed2003

The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance.

This study was designed to assess the biological variability of total testosterone and SHBG in polycystic ovarian syndrome (PCOS) and to determine the use of SHBG as a surrogate marker of insulin resistance in PCOS. Fasting blood samples were collected at 4-d intervals on 10 consecutive occasions from 12 PCOS patients and 11 age- and weight-matched controls. Duplicate samples were analyzed for SHBG, testosterone, and insulin in a single batch, and insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR). The PCOS group had higher testosterone (mean +/- SD, 3.9 +/- 0.8 vs. 3.2 +/- 1.3 nmol/liter; P = 0.001), lower SHBG (28.6 +/- 17.1 vs. 57.6 +/- 30.2 nmol/liter; P = 0.001), and greater HOMA-IR (5.85 +/- 5.3 vs. 1.67 +/- 0.63 U; P = 0.001) than the controls. In contrast to HOMA-IR (1.09 vs. 0.48 U; P = 0.001), the intraindividual variation in SHBG was lower in the PCOS group (mean, 3.4 vs. 6.3 nmol/liter; P = 0.041). The index of individuality for SHBG and testosterone in PCOS was 0.49 and 0.69, respectively. This study shows that for patients with PCOS, SHBG is an integrated marker of insulin resistance that may be of use to identify insulin-resistant individuals for targeted treatment with insulin-sensitizing agents. However, SHBG and testosterone concentrations measured in isolation are inherently unsuitable for use as tests to detect hyperandrogenemia.

Adult↗
PubMed2002

The biological variation of insulin resistance in polycystic ovarian syndrome.

Increased insulin resistance (IR) is a cardinal feature of overweight patients with polycystic ovarian syndrome (PCOS). However, there are no data on the variability of IR for subjects with PCOS. The biological variation of IR (homeostasis model assessment model) was assessed by measuring IR at 4-d intervals on 10 consecutive occasions in 12 overweight PCOS patients (median age, 28 yr; range, 18-31 yr) and 11 weight-matched control women having regular menses and without PCOS (median age, 30 yr; range, 19-33 yr). The distribution of IR was log Gaussian in PCOS and Gaussian distribution in the control group. The IR in PCOS subjects was significantly greater than in the controls [mean (range), 5.85 U (1-42.1) vs. 1.67 U (0.48-3.49); P = 0.001]. After accounting for analytical variation, the mean intraindividual variance was also substantially greater in PCOS patients than in controls (mean, 1.19 vs. 0.23). As a consequence, at any level of IR, a subsequent sample must rise by more than 322% or fall by more than 31% to be considered significantly different from the first. IR, measured using the homeostasis model assessment model, is significantly greater and more variable for overweight patients with PCOS. Therefore, this inherent variability needs to be accounted for in studies of IR in PCOS.

Adult↗
PubMed2001

Use of computer terminals on wards to access emergency test results: a retrospective audit.

OBJECTIVE: To assess delay in clinicians obtaining emergency biochemistry test results when the telephoning of results by laboratory staff is supplanted by installation of computer ward terminals. DESIGN: Retrospective observational study. SETTING: Accident and emergency department and acute medical admissions ward of a teaching hospital. SAMPLE: 3228 emergency requests for biochemistry tests sent from the accident and emergency department and 1836 from the medical admissions ward during August 1999 to January 2000 when there was no recorded telephone contact for results. MAIN OUTCOME MEASURES: Proportion of emergency biochemistry results accessed via a ward terminal within 1 or 3 hours of becoming available and the proportion never seen by this means. RESULTS: The results from 1443/3228 (45%) of urgent requests from accident and emergency and 529/1836 (29%) from the admissions ward were never accessed via the ward terminal. Results from 794/3228 (25%) of accident and emergency requests and 413/1836 (22%) of admissions ward requests were seen within 1 hour of becoming available while a further 491/3228 (15%) and 341/1836 (19%) respectively were accessed between 1 and 3 hours. In up to 43/1443 (3%) of the accident and emergency test results that were never looked at the findings might have led to an immediate change in patient management. CONCLUSIONS: When used as the sole substitute for telephoning results, the provision of terminal access to laboratory results on wards can hinder rather than promote the communication of emergency blood results to healthcare staff.

Blood Chemical Analysis↗
PubMed2000

Determinants of raised C-reactive protein concentration in type 1 diabetes.

As a marker of systemic inflammation, raised C-reactive protein (CRP) concentrations which are still within the normal range have been associated with an increased incidence of coronary heart disease (CHD) in non-diabetic subjects. This study aimed to establish potential determinants of raised CRP concentrations in type 1 diabetic patients. We used a sensitive assay to measure 'low-level' CRP concentrations in 167 type 1 patients (93M, 74F, median age 30 years, range 13-67). Stepwise multivariate analysis was used to relate these CRP levels to known cardiovascular risk factors and demographic data. Only six patients had established CHD (median CRP 3.34 mg/l vs. 0.83 mg/l, p=0.032). In subjects without overt CHD, multivariate analysis showed increases in subject age (p=0.0025), BMI (p=0.001) and HbA(1) (p=0.012) to be associated with a higher CRP concentration, as was female sex (p=0.026) and a history of CHD in a first-degree relative (p=0.018, n=57). The duration of diabetes, current smoking status, presence of microvascular complications, lipid status and presence of hypertension were unrelated. This study suggests that some of the risk factors associated with CHD in type 1 patients are also independently predictive of high CRP concentrations. The reasons for this, and whether intervention would prove useful, require further investigation.

Adolescent↗
PubMed2000

Does adjustment of GFR to extracellular fluid volume improve the clinical utility of cystatin C?

BACKGROUND: Cystatin C measurement has been proposed as a replacement for creatinine as a serum measure of glomerular filtration rate (GFR). It has also been suggested that GFR itself should be adjusted to the extracellular fluid volume (ECV) of a child rather than the body surface area (BSA). AIMS: To assess the potential of cystatin C compared to serum creatinine in assessing GFR and to establish whether adjustment of GFR to ECV rather than BSA affects the potential usefulness of cystatin C. METHODS: Cystatin C and plasma creatinine were measured in 64 paediatric patients undergoing 77 (51)Cr-EDTA GFR measurements over a six month period. RESULTS: 1/cystatin C concentrations were more closely related to GFR (median 98 ml/min/1.73 m(2), range 8-172) after adjustment for patient BSA (r = 0.81 versus r = 0.44). 1/Creatinine concentrations appeared to be an inferior estimate of BSA adjusted GFR (r = 0.41), even following the use of the Schwartz formula (r = 0.37). Bland Altman statistics showed cystatin C could still only predict 95% of GFR values to within +/-41 ml/min/1.73 m(2) of the (51)Cr-EDTA method. The relation between GFR and 1/cystatin C was not improved by adjusting (51)Cr-EDTA GFR to ECV rather than BSA (r = 0.76 versus r = 0.81). CONCLUSIONS: Cystatin C appears superior to serum creatinine in paediatric subjects although its performance is unlikely to supplant (51)Cr-EDTA GFR measurement. This performance is not being underestimated because of adjusting GFR to BSA rather than ECV.

Adolescent↗
PubMed1999

Plasma 1,5-anhydroglucitol concentrations are influenced by variations in the renal threshold for glucose.

AIMS: Measurement of serum 1,5-anhydroglucitol (1,5AG) concentrations has been proposed as an alternative to HbA1c as both a marker of diabetic glycaemic control and as a screening test for diabetes. The sugar competes with glucose for renal tubular reabsorption, so hyperglycaemia leads to reduced serum 1,5AG concentrations through increased urinary loss. This study has sought to establish whether plasma 1,5AG can be influenced by not only hyperglycaemia, but by variations in renal threshold for glucose. METHODS: Thirty-eight pregnant women (median age 30 years, range 20-43) found to be normoglycaemic after a 75-g carbohydrate load had plasma 1,5AG and urine glucose measured. RESULTS: Using multivariate analysis, the presence and degree of detectable glycosuria at 2 h post glucose load was strongly predictive of a low plasma 1,5AG concentration (P=0.0012) independently of fasting plasma glucose (P=0.96), 2 h glucose (P=0.029), subject age (P=0.97) and gestation (P=0.36). Thus, when matched for plasma glucose areas under the glucose load curve, 16 glycosuric subjects had significantly lower 1,5AG concentrations compared to 16 nonglycosuric ones (median 1,5AG 46 micromol/l (IQR 30-56) vs. 72 micromol/l (IQR 55-79, P=0.017). CONCLUSIONS: People with the same glucose tolerance may demonstrate variable plasma 1,5AG concentrations depending on their renal threshold for glucose. This inherent characteristic is likely to limit the usefulness of the test when monitoring or screening for diabetes.

Adult↗
PubMed1998

Are European standard deviation targets for haemoglobin A1c too strict?

The Diabetes Control and Complications Trial (DCCT) has provided objective evidence for desirable glycaemic control in Type 1 patients and defines the benefits of good glycaemic control in terms of haemoglobin A1c (HbA1c) values. However, HbA1c assays vary, leading to suggestions that glycaemic control be classified according to numbers of standard deviations (SD) from a local non-diabetic population mean. We have classified the glycaemic control of 339 UK Type 1 diabetic patients (182 male, 157 female, median age 36 (range 15-74) years) using the DCCT to set HbA1c targets and compared this with the SD method. Using age matched controls (mean HbA1c 4.02%, SD 0.28%, n=106), SD guidelines classified 1% of patients into good (HbA1c <3SD from reference mean), 4% into borderline (3-5SD) and 95% into poor (>5SD) glycaemic control. When calibrating the same instrument to the DCCT analyser (r=0.996), 37% of patients had HbA1c results lower than the 7% median value found in the intensively treated DCCT group, while only 12% of patients had values greater than the 9% conventionally treated median HbA1c. DCCT subjects with HbA1c values of less than 8% belonged predominantly to the intensively treated group. In this study, 71% of patients fell into this category. Thus, guidelines based on numbers of SD away from a non-diabetic mean may overestimate the glycaemic control required to reduce microvascular complications in Type 1 patients. Standardizing to DCCT targets is more appropriate.

Adolescent↗