Stephen Holding

Combining inhibin a with existing second-trimester markers in maternal serum screening for Down's syndrome

To assess the value of inhibin A as an additional second‐trimester maternal serum marker of Downs syndrome we studied 56 affected and 280 unaffected pregnancies matched for gestational age. The median level in the cases was 1·62 multiples of the gestation‐specific median (MOM) in the controls, with 95 per cent confidence limits of 1·34–1·96. The distribution of inhibin levels in affected and unaffected pregnancies was approximately log Gaussian, with means about 1 standard deviation apart. This degree of separation was similar to that for human chorionic gonadotropin (hCG), free β‐hCG, and unconjugated oestriol (uE3), but about double that of alpha‐fetoprotein (AFP) measured in the same samples. Inhibin was largely uncorrelated with AFP and uE3, whereas the log correlation coefficient with hCG was 0·29 (P=0·19) for Downs syndrome and 0·41 (P<0·0001) for unaffected pregnancies; with free β‐hCG, it was 0·18 (P=0·38) and 0·38 (P<0·0001), respectively. On the basis of these results and other pubished studies, we estimate that measuring inhibin A in addition to AFP and hCG or free β‐hCG (with or without uE3) will increase the detection rate for a fixed 5 per cent false‐positive rate by about 7 per cent.

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

abstract 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. What is already known on this topic Providing computer terminals on wards to access laboratory results is usually regarded as a service improvement for healthcare staff Many laboratories that transmit results to ward terminals dispense with telephoning emergency blood results What this study adds Many urgently requested results are not looked at if hospital staff need to access a computer terminal to obtain them If ward terminals are used as a complete substitute for the telephone, results that would have led to an immediate change in patient management may pass unnoticed

Immediate hypersensitivity to chlorhexidine is increasingly recognised in the United Kingdom

BACKGROUNDnChlorhexidine is widely used as an antiseptic agent. It is a potentially allergenic substance that can cause severe hypersensitivity reactions.nnnOBJECTIVEnWe describe six patients who had anaphylactic reactions attributed to chlorhexidine during surgery. These patients were exposed to chlorhexidine in gels, swabs and catheters.nnnMATERIALS AND METHODSnSix patients from three UK centres with clinical history suggestive of anaphylaxis during surgery are reported. Detailed history, review of case notes, determination of chlorhexidine specific IgE, mast cell tryptase and skin tests were performed.nnnRESULTSnOn detailed assessment five of six patients demonstrated a previous history of reactions on re-exposure to chlorhexidine. All six patients had elevated specific IgE to chlorhexidine. Skin prick test with chlorhexidine was performed in four of the six patients and was found to be positive.nnnCONCLUSIONnImmediate hypersensitivity to chlorhexidine appears to be common but underreported in the UK. We recommend that centres investigating patients with reactions during anaesthesia and surgery should routinely include testing for chlorhexidine allergy.

The effect of newly diagnosed hypothyroidism on serum sodium concentrations: a retrospective study

1 Petridou, E., Mantzoros, C.S., Belechri, M., Skalkidou, A., Dessypris, N., Papathoma, E., Salvanos, H., Lee, J.H., Kedikoglou, S., Chrousos, G. & Trichopoulos, D. (2005) Neonatal leptin levels are strongly associated with female gender, birth length, IGF-I levels and formula feeding. Clinical Endocrinology , 62 , 366–371. 2 Garnett, S.P., Hayen, A. & Peat, J. (2005) The art and science of regression modelling: methods for building valid models to explore hormone and body composition interactions. Pediatric Endocrinology Reviews , 3 , 24–28. 3 Weigle, D.S., Breen, P.A., Matthys, C.C., Callahan, H.S., Meeuws, K.E., Burden, V.R. & Purnell, J.Q. (2005) High-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. American Journal of Clinical Nutrition , 82 , 41–48. 4 Barb, D., Wadhwa, S.G., Kratzsch, J., Gavrila, A., Chan, J.L., Williams, C.J., Karchmer, A.W. & Mantzoros, C.S. (2005) Circulating resistin levels are not associated with fat redistribution, insulin resistance, or metabolic profile in patients with the highly active antiretroviral therapy-induced metabolic syndrome. Journal of Clinical Endocrinology and Metabolism , 90 , 5324–5328. 5 Kratzsch, J., Schubring, C., Stitzel, B., Böttner, A., Berthold, A., Thiery, J. & Kiess, W. (2005) Inverse changes in the serum levels of the serum levels of the soluble leptin receptor and leptin in neonates: relations to anthropometric data. Journal of Clinical Endocrinology and Metabolism , 90 , 2212–2217. 6 Cripps, R.L., Martin-Gronert, M.S. & Ozanne, S.E. (2005) Fetal and perinatal programming of appetite. Clinical Science , 109 , 1–11. 7 Wynne, K., Stanley, S., McGowan, B. & Bloom, S. (2005) Appetite control. Journal of Endocrinology , 184 , 291–318. 8 Savino, F., Costamagna, M., Prino, A., Oggero, R. & Silvestro, L. (2002) Leptin levels in breast-fed and formula-fed infants. Acta Paediatrica , 91 , 897–902. 9 Savino, F., Nanni, G.E., Maccario, S., Costamagna, M., Oggero, R. & Silvestro, L. (2004) Breast-fed infants have higher leptin values than formula-fed infants in the first four months of life. Journal of Pediatric Endocrinology and Metabolism , 17 , 1527–1532. 10 Savino, F., Fissore, M.F., Grassino, E.C., Nanni, G.E., Oggero, R. & Silvestro, L. (2005) Ghrelin, leptin and IGF-I levels in breast-fed and formula-fed infants in the first years of life. Acta Pediatrica , 94 , 531– 537. 11 Lage, M., Baldelli, R., Camina, J.P., Rodriguez-Garcia, J., Penalva, A., Dieguez, C. & Casanueva, F.F. (2002) Presence of bovine leptin in edible commercial milk and infant formula. Journal of Endocrinological Investigation , 25 , 670–674. 12 O’Connor, D., Funanage, V., Locke, R., Spear, M. & Leef, K. (2003) Leptin is not present in infant formulas. Journal of Endocrinological Investigation , 26 , 490.

The LH/FSH ratio has little use in diagnosing polycystic ovarian syndrome

Background: The luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is often requested to help diagnose polycystic ovarian syndrome (PCOS) despite a recent consensus recommending against its use. This study aimed to compare the variability of the LH/FSH ratio in PCOS with that of normal menstruating women over a full cycle in order to establish the diagnostic utility, or otherwise, of the test. Methods: Twelve women with PCOS and 11 matched controls had blood collected at four-day intervals on 10 consecutive occasions over a complete menstrual cycle. Results: The median LH/FSH ratio for individual subjects did not differ significantly between the PCOS and the non-affected group (1.6 versus 1.2, P=0.14). Only 7.6% of samples from PCOS patients had an LH/FSH ratio above three, compared with 15.6% of samples from normal subjects. Conclusion: This study confirms that measurement of the LH/FSH ratio is of limited use in the diagnosis of PCOS.

Do ribosomopathies explain some cases of common variable immunodeficiency

The considerable clinical heterogeneity of patients with common variable immunodeficiency disorders (CVID) shares some similarity with bone‐marrow failure disorders such as Diamond–Blackfan anaemia (DBA) and Shwachman–Diamond syndrome (SDS), now recognized as defects in ribosome biogenesis or ribosomopathies. The recognition of a patient with DBA who subsequently developed CVID lends support to our previous finding of a heterozygous mutation in the SBDS gene of SBDS in another CVID patient, suggesting that ribosome biogenesis defects are responsible for a subset of CVID. Genetic defects in the ribosomal translational machinery responsible for various bone marrow failure syndromes are recognized readily when they manifest in children, but diagnosing these in adults presenting with complex phenotypes and hypogammaglobulinaemia can be a challenge. In this perspective paper, we discuss our clinical experience in CVID patients with ribosomopathies, and review the immunological abnormalities in other conditions associated with ribosomal dysfunction. With genetic testing available for various bone marrow failure syndromes, our hypothesis that ribosomal abnormalities may be present in patients with CVID could be proved in future studies by testing for mutations in specific ribosomal genes. New knowledge might then be translated into novel therapeutic strategies for patients in this group of immunodeficiency disorders.

Limited value of testing for intrinsic factor antibodies with negative gastric parietal cell antibodies in pernicious anaemia

Background: The appropriate testing strategy for diagnosing pernicious anaemia using gastric parietal cell (GPC) and/or intrinsic factor antibodies (IFA) is controversial. Intrinsic factor antibodies are found in only about 70% of cases. Indirect immunofluorescence screening for gastric parietal cell antibodies is more sensitive, labour intensive, and less specific. Methods: The frequency of antibody positivity (IFA and/or GPC) was retrospectively examined in patients tested for both autoantibodies over a three-year period. It was investigated whether B12 levels were related to antibody status. These findings were validated in a prospective study of IFA in 91 GPC negative patients with low B12 levels. Results: Of 847 samples identified in the retrospective study, 4 (0.47%) were positive for only intrinsic factor antibodies, 731 (86.3%) positive for GPC alone, and 112 (13.2%) for both. Student t test on log-transformed data showed B12 levels had no bearing on autoantibody status. 91 consecutive patients with low B12 levels were tested for both autoantibodies; all were negative for gastric parietal cell antibodies. Only one sample was positive for intrinsic factor antibody using the porcine intrinsic factor assay, but was negative by a human recombinant intrinsic factor-based ELISA. Conclusions: This study provides evidence that testing for gastric parietal cell antibodies is an appropriate screening test for pernicious anaemia, with intrinsic factor antibodies reserved for confirmatory testing or in patients with other autoantibodies that mask the GPC pattern; B12 levels are not related to autoantibody status.

Maternal serum screening for Down syndrome: are women’s perceptions changing?

Objectivesu2002 To document trends in serum screening for Downs syndrome.

Use of serum free light chain analysis and urine protein electrophoresis for detection of monoclonal gammopathies.

Abstract Background: Serum free light chain (FLC) analysis is used in the prognostic assessment and monitoring of patients with monoclonal gammopathies (MG). Its use in detection of MG is less widespread despite good sensitivity for diseases poorly detected by serum protein electrophoresis (SPE), e.g., FLC disease and AL amyloidosis. FLC analysis may facilitate earlier diagnosis in these diseases. However, if replacing urine protein electrophoresis (UPE) in an initial screening algorithm, this must be balanced against any loss of detection of Bence Jones proteinuria (BJP). Methods: We assessed the effect of replacing UPE with FLC. Sensitivity of FLC for BJP was assessed in 126 clinical cases where UPE and FLC analyses were performed. Impact on disease detection was assessed from 753 patient sera tested by SPE and FLC and 128 patients matched associated urine samples. Results: Sensitivity of FLC for BJP was 98%. Use of FLC in routine testing increased the number of MG detected by 7%. Conclusions: Using FLC alongside or in place of UPE can give clinical benefit through earlier diagnosis and hence treatment earlier in the patients disease.

Calculated globulin (CG) as a screening test for antibody deficiency

Calculated globulin (total protein – albumin) is usually tested as part of a liver function test profile in both primary and secondary care and determines the serum globulin concentration, of which immunoglobulins are a major component. The main use hitherto of calculated globulin is to detect paraproteins when the level is high. This study investigated the potential to use low levels of calculated globulin to detect antibody deficiency. Serum samples with calculated globulin cut‐offu2009<u200918u2009g/l based on results of a pilot study were collected from nine hospitals in Wales over a 12‐month period. Anonymized request information was obtained and the samples tested for immunoglobulin levels, serum electrophoresis and, if appropriate, immunofixation. A method comparison for albumin measurement using bromocresol green and bromocresol purple was undertaken. Eighty‐nine per cent (737 of 826) samples had an immunoglobulin (Ig)G level of <u20096u2009g/l using the bromocresol green methodology with a cut‐off of <u200918u2009g/l, and 56% (459) had an IgG of <u20094u2009g/l. Patients with both secondary and primary antibody deficiency were discovered and serum electrophoresis and immunofixation showed that 1·2% (10) had previously undetected small paraproteins associated with immune‐paresis. Using bromocresol purple, 74% of samples had an IgG of <u20096u2009g/l using a cut‐off of <u200923u2009g/l. Screening using calculated globulin with defined cut‐off values detects both primary and secondary antibody deficiency and new paraproteins associated with immune‐paresis. It is cheap, widely available and under‐utilized. Antibody‐deficient patients have been discovered using information from calculated globulin values, shortening diagnostic delay and time to treatment with immunoglobulin replacement therapy.