Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-ß2 glycoprotein I domain 1 antibodies.

OBJECTIVE: The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti-ß2 glycoprotein I (anti-ß2GPI) in healthy pregnant and non-pregnant women of different ethnicities. METHODS: Healthy Sudanese pregnant women (n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-ß2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-ß2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti-cyclic citrullinated peptide 2 (anti-CCP2) and anti-thyroid peroxidase (anti-TPO) were investigated in Sudanese females. RESULTS: Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-ß2GPI (p < 0.0001 for both antibodies using two assays) and IgM anti-ß2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-ß2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-ß2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased. CONCLUSIONS: IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.

The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring.

It has been estimated that 20% of pregnant women suffer from depression and it is well-documented that maternal depression can have long-lasting effects on the child. Currently, common treatment for maternal depression has been the selective serotonin reuptake inhibitor medications (SSRIs) which are used by 2-3% of pregnant women in the Nordic countries and by up to 10% of pregnant women in the United States. Antidepressants cross the placenta and are transferred to the fetus, thus, the question arises as to whether children of women taking antidepressants are at risk for altered neurodevelopmental outcomes and, if so, whether the risks are due to SSRI medication exposure or to the underlying maternal depression. This review considers the effects of maternal depression and SSRI exposure on offspring development in both clinical and preclinical populations. As it is impossible in humans to study the effects of SSRIs without taking into account the possible underlying effects of maternal depression (healthy pregnant women do not take SSRIs), animal models are of great value. For example, rodents can be used to determine the effects of maternal depression and/or perinatal SSRI exposure on offspring outcomes. Unraveling the joint (or separate) effects of maternal depression and SSRI exposure will provide more insights into the risks or benefits of SSRI exposure during gestation and will help women make informed decisions about using SSRIs during pregnancy.

A method for measurement of free testosterone in premenopausal women involving equilibrium dialysis, chromatography, and radioimmunoassay.

A three-step procedure to evaluate the quantity of true free testosterone in female serum was established. Unbound and bound testosterone were first separated by equilibrium dialysis using undiluted serum. Testosterone in dialysate was extracted and separated from cross-reactive steroids by column chromatography and finally quantified with a sensitive radioimmunoassay. The detection limit of the radioimmunoassay was 2.7 pmol/L and the detection limit of the whole method was 6 pmol/L. The intra-assay coefficients of variation of the method were 20.6%, 16.8%, and 9.5% for free testosterone concentrations 12.0 pmol/L, 21.4 pmol/L, and 31.4 pmol/L, respectively. The interassay coefficients of variation were 26.3% and 14.8% for free testosterone concentrations 10.4 pmol/L and 21.3 pmol/L, respectively. Serum free testosterone concentrations were determined in 27 regularly menstruating control women. The mean concentration of actual free testosterone was 10.0 +/- 4.9 pmol/L (mean +/- SD, range from below 6 to 19 pmol/L, n = 27).

Steroid hormone receptors and flow cytometric DNA ploidy in ovarian carcinoma.

The biochemical and immunohistochemical estrogen (ER) and progesterone receptor (PR) content and flow cytometric DNA ploidy was analyzed in five semimalignant and 35 malignant epithelial ovarian tumours. By biochemical assay, 67% of the tumours were ER-positive (> or = 5 fmol/mg protein) and 56% were PR-positive (> or = 10 fmol/mg protein). The corresponding values by immunohistochemical assay (with a HSCORE of 10 as the cutoff level) were 22% and 27%, respectively. DNA histogram measured from paraffin embedded specimens were diploid in 20% (7/35) and aneuploid in 80% (28/35) of the malignant tumours. All semimalignant tumours were diploid. The mean receptor values in the diploid and aneuploid tumours did not differ significantly and receptor-positive and receptor-negative tumours were evenly distributed in all stages and grades. In contrast, flow cytometric DNA ploidy was clearly associated with tumour stage (G2 = 10.52, Df = 3, P = 0.015) and histological differentiation (G2 = 20.57, Df = 3, P = 0.0001).

A quality manual for the clinical laboratory including the elements of a quality system. Proposed guidelines.

Development of quality manuals is a means for the promotion of quality in clinical laboratories by describing the total quality system. It also provides opportunity of checking whether the quality system is implemented in reality and demonstrates to the hospital administration and the clinicians that the laboratory is committed to quality. The intention of these guidelines is to describe the elements of the quality system for a large clinical laboratory, and to present such a system in the form of a quality manual. The proposed guidelines comply, where relevant, with ISO/IEC guide 25 'General requirements for the technical competence of testing laboratories' and EN 45001 'General criteria for the operation of testing laboratories'. The document may be used as an aid for laboratories wishing to be accredited according to EN 45001, or intending to apply for formal certification of their quality systems, according to ISO 9001 'Quality systems--Model for quality assurance in design/development, production, installation, and servicing' utilizing ISO 9004 'Quality management and quality system elements--guidelines; Part 2 Guidelines for service'. However, information about the minimum requirements for official recognition should be obtained from the particular accreditation or certification body concerned.

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

OBJECTIVE: To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. DESIGN: Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). SETTING: Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS: Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. MAIN OUTCOME MEASURES: Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. RESULTS: The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. CONCLUSIONS: The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Reference intervals for serum sex steroids and gonadotropins in regularly menstruating women.

Reference intervals for novel fluoro-immunoassays for serum luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P) were established in 40 healthy regularly menstruating women. Serum samples for sex steroids, including testosterone (T), androstenedione (A) and dehydroepiandrosterone sulphate (DHEAS), as well as sex hormone binding globulin (SHBG) and gonadotropins, were collected in the early follicular and mid-luteal phases of the menstrual cycle. The need for the timing of androgen and gonadotropin samples was also determinated. Serum E2 and P were measured by radio-immuno- and time-resolved fluoro-immunoassays. Various assay methods correlated closely, but the reference intervals varied considerably from one method to another. In the early follicular phase the LH/FSH ratio only ranged between 0.2 and 1.7 (mean +/- S.D.; 0.8 +/- 0.3); the variation was greater (from 0.3 to 3.5) in the luteal phase, when the mean was also significantly higher (1.5 +/- 0.9, p = 0.0001). Similarly the mean values of T and SHBG were higher in the luteal phase, while the other androgen concentrations and calculated androgen indexes were equal, compared with the follicular phase values. Thus the timing of hormone determinations is warranted in the investigation of the gonadotropin and androgen status in normally menstruating women. Moreover, the upper limit of the LH/FSH ratio examined with new, sensitive methods is lower than that previously stated. The use of an intra-uterine contraceptive device (IUD) had no effect on hormone levels.

Two new two-step immunoassays for free thyroxin evaluated: solid-phase radioimmunoassay and time-resolved fluoroimmunoassay.

We measured concentrations of free thyroxin (FT4) in serum by using two new two-step FT4 assays--a solid-phase two-step radioimmunoassay. Spectria, and a time-resolved fluoroimmunoassay. Delfia--and compared the results with those by a two-step FT4 assay (RIA-gnost), a one-step FT4 analog assay (Amerlex-M), and FT4 measured after equilibrium dialysis. The new FT4 assays classified 30 hypothyroid and 43 hyperthyroid patients (untreated) well. In 138 patients with nonthyroidal illness (NTI) and in late pregnancy (n = 36), fewer subnormal FT4 values were reported by Spectria (P less than 0.001), Delfia (P less than 0.001), and RIA-gnost (P less than 0.01) than by Amerlex-M. The results of the Spectria and Delfia methods correlated with the results of the dialysis method (r = 0.76) in NTI patients and pregnancy, and were in better agreement with the clinical state than was FT4 by Amerlex-M. The FT4 values by Amerlex-M, but not by other methods, correlated with albumin concentration. We conclude that these new two-step methods present good alternatives for FT4 analysis.

[Quality control of laboratory services in primary health care in Finland]. / Kvalitetskontroll av laboratorietjänster inom primärvården i Finland.

Finland is the only Nordic country with a nationwide system of quality control of the activities of the clinical laboratories, which covers both specialized and primary medical care. Practical experience of this quality control is reported. In empirical terms the organization functions well and the level attained by the health centre laboratories matches that of those at the central hospitals. Thus tests performed on patients at the health centres need not be repeated in hospital by reason of inferior quality.

Androgen parameters in hirsute women: correlations with body mass index and age.

The recent work was designed for studying the effects of body mass index (BMI) and age on serum hormone values in hirsute women of reproductive years with nontumorous hyperandrogenism. Two hundred patients were studied in the follicular phase of the cycle. The serum levels of testosterone (T), androstenedione (A), or dehydroepiandrosterone sulfate (DHEAS) were not associated with BMI, whereas the T/sex hormone-binding globulin (T/SHBG) ratio was significantly correlated with BMI independently of the effect of age. All serum androgens were significantly negatively correlated with age, and the serum levels were significantly lower in women older than 41 years when compared with women aged 25 years or less. After correcting for the effect of BMI, there was also a negative correlation between the T/SHBG ratio and age. The correlations between serum androgen parameters were calculated. We conclude that already in reproductive years, the age of the patient has modulating effects on serum androgens, and it should be taken into account when studying the hormone profile of hirsute women.

Endocrine status and growth after malignancy treated in childhood or adolescence.

Six girls and three boys, asymptomatic after treatment for acute lymphoblastic leukemia (ALL) or endodermal sinus tumor (EST), were investigated for endocrine status and growth. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), testosterone binding capacity (TeBC), 17 alpha-hydroxyprogesterone (17-OHP), progesterone (P), thyroxine (T4), thyroid stimulating hormone (TSH), and cortisol were measured, and pubertal stage and bone age were determined. Growth was evaluated according to accepted curves for height and weight. Four of the girls had normal pubertal development, with serum FSH, LH, and E2 levels correlating to the phase of the menstrual cycle. Only one of the girls had ovulatory cycles (increase in P level). The girl treated for EST by abdominal irradiation had gonadal failure, with postmenopausal serum levels of FSH, LH, and E2. Her karyotype was normal. One of the girls was still prepubertal. None of them was hyperandrogenemic. One boy who was treated with bone marrow transplantation and total body irradiation had gonadal failure. One boy was still prepubertal, and the third boy showed normal pubertal maturation and normal serum FSH, LH, and T levels. All the patients except the boy treated with bone marrow transplantation and irradiation were normoprolactinemic; in addition, all had normal thyroid and adrenal function. Height and weight curves were normal in seven of the patients after the cancer therapy. The girl with EST had finished her growth before the irradiation therapy began. The boy treated with bone marrow transplantation and irradiation failed to exhibit further growth after beginning leukemia therapy at the age of 9.3 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative evaluation of serum thyroxine, free thyroxine and thyrotropin determinations in screening of thyroid function.

We assessed a highly sensitive immunoradiometric thyrotropin (TSH) assay in screening thyroid dysfunction in 130 consecutive outpatients from a department of medicine and 224 patients from a municipal health centre. In addition to clinical examination, three routine tests were done: a thyroxine radioimmunoassay, an analogue-based free thyroxine assay and an immunoradiometric TSH assay. Triiodothyronine and the TRH test were done, if the findings were discrepant. Discrepancy existed in 24% of cases. The TSH assay had no false negative results (sensitivity 100%). Therefore TSH could screen all patients with thyroid dysfunction. Free thyroxine was the most specific assay (specificity 96%), but many subclinically or overtly hypothyroid patients would have been missed, if that assay had been used alone. We conclude that TSH(IRMA) is the best first-line measurement for thyroid dysfunction testing among outpatients. An abnormal TSH result alone is not diagnostic, but should be followed by the measurement of thyroxine or free thyroxine.

Serum hCG levels measured by time-resolved fluoroimmunoassay in first-trimester pregnancy and after pregnancy termination.

Time-resolved fluoroimmunoassay (TR-FIA) reliably shows the concentrations of serum hCG during the first trimester of normal pregnancy. After first-trimester induced abortion the mean disappearance of hCG in serum (under 10 IU/l) takes place in three weeks. TR-FIA is a convenient and ultrarapid method for diagnosing pregnancy-related disorders.

Serum antibody-bound insulin as a measure of insulin antibodies in diabetic children.

The usefulness of the measurement of serum antibody-bound and total immunoreactive insulin (IRI) concentrations in the assessment of insulin antibodies was evaluated in a material comprising 49 insulin-dependent diabetic children with a mean age at onset of 8.6 years (range 0.8-16 years) treated with highly purified porcine insulins. Serum antibody-bound and total IRI concentrations of individual patients were compared with insulin antibody levels measured with 3 different insulin antibody assays. The correlation coefficients of insulin antibody levels with concentrations of serum antibody-bound IRI ranged from 0.75-0.79. In serum samples with moderate or high insulin antibody levels most of the insulin was in the form of insulin-insulin antibody immunocomplexes. Thereby a very close correlation was found between antibody-bound and total serum IRI concentrations (r = 0.98) in this material. Residual endogenous insulin secretion decreased with increasing duration of diabetes. No significant correlation was found between the duration of diabetes and serum antibody-bound IRI concentrations. High serum antibody-bound IRI concentrations were associated with low glucagon-stimulated plasma C-peptide levels. Although the determination of serum antibody-bound IRI concentrations does not characterize insulin antibodies with regard to binding capacity and affinity constants, it yields information of the actual degree of insulin binding in the circulation. This information may be useful in assessing the benefits of transferring diabetics with high insulin antibody titers from conventional to highly purified porcine or human insulin therapy.

Sex steroid, gonadotropin, cortisol, and prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size and effect of weight reduction.

To examine hormonal status in obese, gynecologically normal women we studied 25 regularly menstruating, massively obese (mean weight, 120 kg) women participating in a weight reduction program and 25 age-matched normal weight (mean weight, 60 kg) women. Serum 17 beta-estradiol (E2), estrone (E1), androstenedione (A), dehydroepiandrosterone sulfate, testosterone, LH, FSH, PRL, and cortisol concentrations were measured during the follicular phase of the menstrual cycle. Waist to hip ratio and abdominal fat cell size were measured at the beginning of the study. The serum levels of E2 (P less than 0.04) as well as those of A, SHBG, and LH (P less than 0.002) were lower in the obese group. Consequently, the testosterone to SHBG ratio and the E1 to A ratio were higher and the LH to FSH ratio was lower in this group. Waist to hip ratio did not correlate with the levels of circulating hormones or SHBG, but an inverse correlation was found between abdominal fat cell size and A as well as the LH to FSH ratio in the nonhirsute women of the obese group. Subsequent to moderate weight reduction (13.2 kg), serum A and E1 levels (P less than 0.01) increased, and serum cortisol levels decreased (P less than 0.001). Thus, massive obesity is associated with abnormalities in hormonal balance in gynecologically symptomless women, there being an association between E1, E2, A, LH, cortisol, and relative weight and/or abdominal fat cell size.

Plasma and urinary C-peptide in the classification of adult diabetics.

Plasma and urinary C-peptide determinations in the discrimination between insulin-requiring and non-insulin-requiring diabetes were elevated in 61 adult diabetics. Specimens for C-peptide determinations were taken on two consecutive days: on the first day plasma C-peptide concentrations were determined before and 6 min after intravenous glucagon administration. On the second day 2- and 4-h urinary C-peptide excretion was measured after an individual breakfast. Results of urinary C-peptide analyses were expressed as molar concentration and also as molar quantity excreted (without any corrections and related to creatinine excretion). Glucagon-stimulated plasma C-peptide turned out to be a reliable criterion for the detection of insulin requirement. Sixty-nine per cent of diabetics included in this study were classifiable by basal plasma C-peptide concentrations. Two-hour postprandial urinary C-peptide/creatinine quotient turned out to be slightly less sensitive (89%) than the glucagon test (94%) and of equal specificity (96%). Glucagon-stimulated plasma C-peptide and postprandial urinary C-peptide excretion correlated significantly among insulin-requiring diabetics (r = 0.73), but not among non-insulin-requiring diabetics (r = 0.23). We regard determination of stimulated plasma C-peptide as a primary investigation for the direct assessment of endogenous insulin secretory reserves for clinical management decisions. Determination of postprandial urinary C-peptide is applicable in selected situations for non-invasive assessment of insulin secretion.

Haematological laboratory findings in the elderly: influence of age and sex.

The effects of age and sex on haematological laboratory parameters were studied in connection with a population study in people over the age of 65 years (n = 347). Serum vitamin B12 was the only parameter which decreased significantly with advancing age. Blood leucocyte count, haemoglobin concentration, haematocrit, erythrocyte count, mean erythrocyte volume, mean erythrocyte haemoglobin and serum ferritin values were significantly higher in males than in females. Serum iron, serum transferrin, and plasma and erythrocyte folate levels did not differ between males and females. Thirteen subjects were anaemic and three of them had iron deficiency anaemia. Five subjects had iron deficiency based on serum iron and transferrin but no anaemia. Serum ferritin measurement did not reveal any further subjects with iron deficiency. No case of folate deficiency anaemia was revealed. Although many of the participants were on medication, most of them were living at home and taking care of themselves and represent relatively fit elderly people. Therefore we suggest that these laboratory data can also serve as reference values for the elderly people.

C-peptide determination in the choice of treatment in diabetes mellitus.

The predictive value of the intravenous glucagon test in assessing the requirement of insulin therapy in diabetes mellitus was evaluated in 105 adult diabetics. Basal and stimulated C-peptide concentrations and increments of C-peptide concentration were examined separately among newly and previously diagnosed diabetics. The poststimulatory C-peptide concentration of 0.6 nmol/l (Novo, antibody M 1230) proved to be the most reliable basis for the choice of therapy. Adequate therapy could have been assessed in 70 cases (67%) without glucagon stimulation. To derive maximal information of plasma C-peptide concentrations, a biphasic scheme of the use for C-peptide determinations and glucagon stimulation is presented. Basal and stimulated C-peptide levels of insulin-requiring diabetics correlated negatively with the duration of diabetes but they did not correlate with the relative body weights. Basal and stimulated C-peptide levels of non-insulin-requiring diabetics did not correlate with the duration of diabetes, but they correlated positively with the relative body weights.