Hypersecretion of the alpha-subunit in clinically non-functioning pituitary adenomas: Diagnostic accuracy is improved by adding alpha-subunit/gonadotropin ratio to levels of alpha-subunit.

Background: In vitro, the majority of clinically non-functioning pituitary adenomas (NFPAs) produce gonadotropins or their alpha-subunit; however, in vivo, measurements of alpha-subunit levels may not accurately detect the hypersecretion of the alpha-subunit.

Aim: We wanted to estimate the reference intervals and decision limits for gonadotropin alpha-subunit, LH and FSH levels, and aratio (alpha-subunit/LH+FSH), especially taking into consideration patient gender and menstrual status. Furthermore, we wanted to examine if the diagnostic utility of alpha-subunit hypersecretion was improved when the alpha-ratios, rather than simply the alpha-subunit levels, were measured in patients with NFPAs.

Biological variation of thyroid autoantibodies and thyroglobulin.

Background: It has been shown that the level of serum thyroid antibodies affects serum thyrotropin (TSH) concentrations in men and women, and that these autoantibodies in combination with serum TSH are predictive of future thyroid disease. As the biological variation of these autoantibodies is unknown, we investigated this in fertile women during one complete regular menstrual cycle.

Methods: A total of 24 healthy women (23-46 years) were investigated twice a week between 07:30 and 11:00 h.

Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb).

Background: The National Academy of Clinical Biochemistry (NACB) stresses that the reference intervals for thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyroid stimulating hormone (TSH)-receptor antibodies (TRAb) should be based on young men who lack certain risk factors and have serum TSH between 0.5 and 2.0 mIU/L.

Establishment of a serum thyroid stimulating hormone (TSH) reference interval in healthy adults. The importance of environmental factors, including thyroid antibodies.

It has previously been shown that thyroid antibodies affect thyroid stimulating hormone (TSH) concentrations in men and women and that TSH levels are predictive of future thyroid disease. We investigated the validity of the National Academy of Clinical Biochemistry (NACB) guidelines regarding the TSH reference interval by studying 1512 individuals. Two hundred and fifty had at least one thyroid antibody, 121 were taking medications other than estrogens and occasional analgesics, and 105 reported a family history of thyroid disease.

Graphical interpretation of confidence curves in rankit plots.

A well-known transformation from the bell-shaped Gaussian (normal) curve to a straight line in the rankit plot is investigated, and a tool for evaluation of the distribution of reference groups is presented. It is based on the confidence intervals for percentiles of the calculated Gaussian distribution and the percentage of cumulative points exceeding these limits. The process is to rank the reference values and plot the cumulative frequency points in a rankit plot with a logarithmic (In=log(e)) transformed abscissa.

Expression of leptin receptor isoforms and effects of leptin on the proliferation and hormonal secretion in human pituitary adenomas.

Objective: To pursue whether leptin regulates anterior pituitary cells, we studied the ex vivo expression of several isoforms of the leptin receptor (OB-R) as well as the in vitro effects of leptin administration in human pituitary adenomas.

Methods: OB-R mRNA expression and in vitro response to leptin were studied in 39 pituitary macroadenomas.

Results: All 4 OB-R subtypes were expressed in most adenomas.

Minimally processed fresh frozen human reference sera: preparation, testing, and application to international external quality assurance.

The preparation of unmodified or minimally processed fresh frozen human sera is described, as well as the previous use of such sera, e.g. in Nordic and international external quality assurance (EQA) activities.

Growth hormone receptor expression and function in pituitary adenomas.

Objective And Design: Hypopituitarism, in particular GH deficiency, is prevalent in patients with clinically nonfunctioning pituitary adenomas (NFPAs) both before and after surgery. The factors regulating the growth of pituitary adenomas in general and residual tumour tissue in particular are not fully characterized, and the effect of GH and IGF-I on human pituitary cell proliferation has not previously been reported. In NFPA tissue from 14 patients we evaluated GH receptor (GHR) expression and signal transduction, and the effect of GH and IGF-I exposure on cell proliferation and hormone secretion in vitro.

Serum lactate dehydrogenase isoenzyme 1 in patients with seminoma stage I followed with surveillance.

Serum lactate dehydrogenase isoenzyme I catalytic concentration (S-LD-1) was measured in patients with testicular seminoma clinical stage I followed with surveillance after orchiectomy. The serum samples were obtained before orchiectomy in 110 patients (group A) and soon after orchiectomy in 55 patients (group B). In group A, 60 patients (55%) had elevated S-LD-1 and 10 patients (9%) had elevated serum human chorionic gonadotropin concentrations (S-hCG).

Magnesium reduces insulin-stimulated glucose uptake and serum lipid concentrations in type 1 diabetes.

A magnesium (Mg) deficit has been described in patients with type 1 diabetes, and it has been related to the development of cardiovascular disease. We tested the hypothesis that type 1 diabetic patients have deficits in dietary Mg intake and that proper long-term (24 weeks) oral Mg supplementation would reduce cardiovascular risk factors. Therefore, the Mg status, dietary Mg intake, and the effect of Mg supplementation were evaluated in 10 type 1 diabetic patients and 5 control subjects.

Serum lactate dehydrogenase isoenzyme 1 and relapse in patients with nonseminomatous testicular germ cell tumors clinical stage I.

Serum lactate dehydrogenase isoenzyme 1 catalytic concentration (S-LD-1) was measured at the time of orchiectomy in 104 patients with nonseminomatous testicular germ cell tumors (NSTGCT) clinical stage I who participated in a randomized study comparing surveillance after orchiectomy (group I) and radiotherapy (group II). For 68 patients, S-LD-1 was measured in a serum sample before or on the day of the orchiectomy. Twenty-seven patients (40%) had elevated S-LD-1; median 102 U/L (range 41-335).

Serum lactate dehydrogenase isoenzyme 1 and prediction of death in patients with metastatic testicular germ cell tumors.

The International Germ Cell Cancer Collaborative Group study of patients with metastatic testicular germ cell tumors showed that catalytic concentration of serum lactate dehydrogenase (S-LD), serum alpha-fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) predicted death from tumor. The recent international TNM classification (T primary tumor, N lymph node metastasis, M distant metastasis) is based on these results. The aim of our study was to evaluate whether catalytic concentration of S-LD isoenzyme 1 (S-LD-1) was a better predictor than the criteria used for the international classification.

Analytical quality specifications for serum lactate dehydrogenase isoenzyme 1 based on clinical goals.

The aim of the study was to deduce analytical quality specifications for the determination of catalytic concentration of serum lactate dehydrogenase isoenzyme 1 (S-LD-1) according to clinical goals (the clinical utility model). We defined clinical goals for false positive and false negative S-LD-1 measurements in the monitoring of patients with testicular germ cell tumors (TGCT), clinical stage I, on a surveillance only program. The absolute S-LD-1 catalytic concentrations were routinely corrected for contamination from preanalytical hemolysis.

Effect of moderate improvement in metabolic control on magnesium and lipid concentrations in patients with type 1 diabetes.

Objective: To evaluate the effect of clinically obtainable improvements in metabolic control in patients with type 1 diabetes on biochemical cardiovascular risk factors.

Research Design And Methods: Blood and 24-h urinary samples were obtained from 49 patients with type 1 diabetes before and after a run-in period and after 3 months of intervention, with frequent adjustment of insulin dosage according to measured blood glucose concentrations.

Results: The intervention caused a mean insulin dosage increment of 10%, a 20% decrease in fasting plasma glucose concentration, a 10% decrease in albumin corrected serum fructosamine, and a somewhat lesser decrease in HbAlc.

Evaluation of growth hormone assays using ratio plots.

To permit comparison between growth hormone (GH) results obtained using the Pharmacia polyclonal assay and the Delfia monoclonal assay, we used both methods to measure GH concentrations in peak GH responses to the pyridostigmine-growth-hormone-releasing-hormone (PD-GHRH) test and in unstimulated samples from 40 healthy adults and 31 patients with suspected GH deficiency. Ratio plots were used for the comparison, and acceptability criteria were based on inherent analytical imprecision and on analytical quality specifications. The mean ratio (r; Pharmacia/Delfia) for the peak GH responses in 40 healthy adults was calculated to be 1.

Graphical interpretation of analytical data from comparison of a field method with reference method by use of difference plots.

Various viewpoints have been offered regarding the appropriate use of scatter plots or difference plots (bias plots or residual plots) in comparing analytical methods. In many of these discussions it seems the basic concepts of identity (within inherent imprecision) and acceptability based on analytical goals (analytical quality specifications) have been forgotten. With the increasing number of Reference Methods in laboratory medicine, these basic concepts are becoming more important in validation of field methods.

The influence of analytical bias on diagnostic misclassifications.

Quality specifications for analytical imprecision and bias based on the state of the art; 'biology' and 'analysis of clinical situations' have been proposed by several scientists. Most interesting is the assessment of 'diagnostic misclassifications' based on direct evaluation of the consequences of analytical bias on the percentage of false positives and false negatives from a clinical decision situation, or based on the percentage of healthy individuals outside each reference limit when common reference intervals are used. With use of graphical or computer simulations assuming increasing (positive or negative) analytical bias, the expected percentage of misclassifications can be estimated- and, for the error for which the outcome (the fraction of misclassifications) is considered unacceptable, the maximum allowable analytical bias can be defined.

Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP Reference Material (CRM 470). International Federation of Clinical Chemistry. Community Bureau of Reference of the Commission of the European Communities. College of American Pathologists.

The release in 1993 of a new reference material for serum proteins, CRM 470/RPPHS 5 has given rise to a great improvement in the between-laboratory variability of serum protein measurements worldwide. Conversion to the new reference material results in significant changes in reference values for some proteins. The establishment of new reference ranges will take a considerable time, and in the interim several professional societies and diagnostic companies have agreed to use consensus reference ranges based on studies already undertaken.

Robust nonradioactive oligonucleotide ligation assay to detect a common point mutation in the CYP2D6 gene causing abnormal drug metabolism.

A new nonradioactive oligonucleotide ligation assay for the detection of a common point mutation in the CYP2D6 gene is presented. The assay takes advantage of simultaneous time-resolved fluorescence measurements of lanthanide-labeled probes and the specificity of T4-DNA ligase in combination with the polymerase chain reaction. This strategy makes it possible to perform the assay using both the wild-type-specific and mutant-specific probes simultaneously, securing an internal control in each reaction.

Serum lactate dehydrogenase isoenzyme 1. An early indicator of relapse in patients with testicular germ cell tumors.

The present study aimed to evaluate serum lactate dehydrogenase isoenzyme 1 (S-LD-1) as an indicator of relapse for patients with testicular germ cell tumors. Twenty-seven patients were investigated with repeated determinations of S-LD-1 from diagnosis to relapse; 9 had seminoma and 18 nonseminomatous tumors. Eleven of 21 had raised S-LD-1 at relapse (4 with seminoma).

An enzyme-linked immunosorbent assay for plasma-lactoferrin. Concentrations in 362 healthy, adult blood donors.

Very different concentrations of plasma-lactoferrin in healthy adults have been reported in the literature. We compared three commercially available lactoferrins and lactoferrin purified in our laboratory as calibrators in an ELISA. No statistical differences among these preparations of lactoferrin were detected.