Factors associated with the quality of laboratory performance in the United Kingdom external quality assessment scheme for serum growth hormone

A search was made for associations between poor performance in the UK External Quality Assessment Scheme (EQAS) for serum growth hormone (GH), and a range of factors including assay method, laboratory workload and staffing, and Internal Quality Control (IQC) procedures. On the basis of the factors identified as being associated with poor performance we recommend the following. 1. Laboratories using RIA for GH should routinely analyse samples at two dilutions and report a mean result. 2. The use of 125I-GH which is 5 or more weeks old should be avoided. Tracer should also be chromatographed to remove aggregate before use. 3. Laboratories using RIA should avoid using a standard curve which covers too wide a range concentration; a curve midpoint (ie GH concentration to reduce the zero standard binding by 50%) of about 8 mU/l or less is probably acceptable. 4. It should be noted that high workloads present a risk of some loss in quality of responsible for checking IQC data. 6. Laboratories which do not have the resources to maintain fully their own RIA as outlined above should carefully consider use of an unbiased, precise IRMA. The UK EQAS has identified two assays (Boots-Celltech Sucrosep, NETRIA) that appear to meet these criteria [2]. The above observations may also be relevant to immunoassays for other peptide hormones.     

Effect of testosterone on the testicular atrophy caused by di(2-ethylhexyl)phthalate (DEHP)

The involvement of testosterone in di(2-ethylhexyl)phthalate (DEHP) induced testicular injury has been examined by coadministration of testosterone (1 mg/kg) along with DEHP (2000 mg/kg) daily for 15 days. The coadministration of testosterone and DEHP appears to have prevented the testicular injury as judged by the biochemical and histopathological changes. The sperm count and the activity of the testicular enzymes, gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), sorbitol dehydrogenase (SDH), beta-glucuronidase and acid phosphatase, related with the maturation of sperm, which were significantly altered by DEHP treatment were found to be within normal levels after the combination treatment of DEHP and testosterone. The histopathological studies also showed more or less normal spermatogenic events. The results of this study have suggested the involvement of testosterone in DEHP induced testicular atrophy.     

Genetic variation in serotonin transporter alters resting brain function in healthy individuals.

BACKGROUND: Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals. METHODS: Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores. RESULTS: Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood. CONCLUSIONS: The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

Doppler velocimetry, placental morphology and outcome in insulin-dependent diabetes.

The purpose of this study was to determine the underlying cause of abnormal umbilical artery Doppler velocimetry in pregnancies complicated by insulin-dependent diabetes, by evaluating placental morphology and correlating Doppler results with pregnancy outcome. Our study population consisted of 14 pregnancies with normal Doppler results and 11 pregnancies with abnormal Doppler results. Quantitative placental examinations were performed. Maternal and perinatal characteristics were analyzed. Infants from the abnormal Doppler group had a statistically significantly higher incidence than those from the normal Doppler group of hyperbilirubinemia, Cesarean delivery for fetal distress, and neonatal intensive care stay of 2 or more days. Women with abnormal Doppler results delivered earlier (36 vs. 38 weeks) and had infants of lower birth weight (3079 vs. 3629 g). They were also three times more likely to have poor glycemic control (relative risk = 3.2; p = 0.0067). The placentae of both groups showed no statistically significant differences in placental weight, number of tertiary stem villi, number of small muscular arteries, or mean arterial width. Our findings suggest a functional rather than structural placental process as the cause of the abnormal Doppler results in pregnancies complicated by diabetes. An association between glycemic control and Doppler velocimetry is suggested.     

Shockwave treatment of ureteric stones in situ with second-generation lithotriptor

During a 17-month period we treated in situ 334 patients with ureteric stones with a second-generation electromagnetic lithotriptor. Anxiety and discomfort were relieved with diazepam and pethidine chloride only. Ureteral stenting was used in 8.1% of upper, 36.4% of mid- and 5.7% of lower ureteric stones. The retreatment rate was 15%, but no patient had more than 3 sessions. The success rate of the treatment at 3 months was 88% for upper, 65% for mid- and 83% for lower ureteric stones. Open surgery had to be performed in 5 cases and ureteroscopies in 6 cases.     

Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis.

BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA.