Maternal thyrotropin is independently related to small for gestational age neonates at term.

OBJECTIVE: Small for gestational age (SGA) newborns constitute still a major cause of perinatal morbidity and mortality. Overt thyroid disease is a known cause of preterm birth and low birthweight but in its untreated condition it is rare today. In this study, we investigated the possible relation between maternal thyroid function assessed in euthyroid women at each trimester and the incidence of term born SGA neonates. DESIGN: A prospective cohort study was performed. PATIENTS: Thyroid function was assessed at 12, 24 and 36 weeks gestation in 1051 healthy Caucasian women who delivered at ≥ 37 weeks gestation. MEASUREMENTS: One-way anova was used to compare mean TSH and FT4 levels between women with SGA neonates and controls. Multiple logistic regression analysis was performed to adjust for known risk factors of SGA. RESULTS: Seventy (6·7%) SGA neonates were identified and they were significantly more often born to women with a TSH ≥ 97·5th at first and third trimester. Multiple logistic regression analysis showed that smoking (OR: 4·4, 95% CI: 2·49-7·64), pre-eclampsia (OR: 2·8, 95% CI: 1·19-6·78) and TSH ≥ 97·5th percentile (OR 3·3, 95% CI 1·39-7·53) were significantly related to SGA. Maternal FT4 levels and TPO-Ab status were not associated with SGA offspring. CONCLUSIONS: Our data show that TSH levels in the upper range of the reference interval at different trimesters (3·0-3·29 mIU/l) are independently related to an increased risk of delivering SGA neonates at term.

Neonatal thyroid screening results are related to gestational maternal thyroid function.

OBJECTIVE: To study the relationship between maternal thyroid function at each pregnancy trimester and neonatal screening results. BACKGROUND: Overt maternal thyroid dysfunction during gestation is associated with poor neonatal thyroid function. However, research on the relationship between suboptimal maternal thyroid function (assessed at three trimesters) and neonatal thyroid screening outcome is scarce. DESIGN/PATIENTS: Prospective follow-up study during three trimesters of gestation in 886 Dutch Caucasian healthy pregnant women followed from 12-week gestation until term delivery (>37 weeks) and their neonates. MEASUREMENTS: The relation between neonatal data from the Congenital Hypothyroidism (CH) screening and maternal thyroid determinants [TSH, FT4 and thyroid peroxidase (TPO)-Ab] assessed at 12-, 24- and 36-week gestation. RESULTS: Boys have lower screening TT4 levels and their mothers have higher TSH levels at 24- and 36-week gestation. Higher maternal TSH levels (>97·5th percentile, as defined in 810 women without TPO-Ab at 12 weeks) at one or more times during pregnancy (O.R: 2·26, 95% CI: 1·20-4·29) and lower gestational age (O.R: 1·22, 95% CI: 1·05-1·41) are independently related to lower screening TT4 levels. CONCLUSIONS: Maternal thyroid function during gestation is related to neonatal TT4 at screening. The finding of both lower neonatal TT4 levels in boys and higher TSH levels in mothers carrying boys is worthy of further investigation, as both observations may be meaningfully related.

High thyrotrophin levels at end term increase the risk of breech presentation.

OBJECTIVE: To study the relationship between maternal thyrotrophin (TSH) and breech presentation at term. DESIGN: Combined data sets of two prospective studies to obtain adequate epidemiological power. PATIENTS: One thousand and fifty-eight healthy pregnant women (58 breech, 1000 cephalic) and 131 women who presented in breech at an obstetrical outpatient clinic. MEASUREMENTS: Maternal thyroid parameters [TSH, free thyroid hormone (FT4), thyroid peroxidase antibody (TPO-Ab)] and foetal presentation were assessed in both groups between 35 and 38 weeks gestation. Power calculations suggested that at least 148 breech cases were required. RESULTS: The characteristics of the women in breech in both samples were similar. Women in breech (n = 58 + 131) had significantly higher TSH (but not FT4) than those (n = 1000) with cephalic presentation (Mann-Whitney U-test, P = 0·003). Different cut-offs were used to define high TSH in the 916 TPO-Ab-negative women with cephalic presentation: the 90th, 95th and 97·5th percentiles were 2·4 mIU/l (n = 149), 2·7 mIU/l (n = 77) and 3·2 mIU/l (n = 37). The prevalence rates of breech presentation in these women were all higher compared to the prevalence of breech in women below these cut-offs (df = 1, P < 0·01). The relative risk of the 149 women with a TSH >90th percentile (>2·4 mIU/l) to present in breech was 1·82 (95% CI: 1·30-2·56). CONCLUSIONS: Women with high TSH at end term are at risk for breech presentation. Substantial evidence for a relation between breech presentation and neurodevelopmental delay exists. As high TSH during gestation has also been linked to poor neurodevelopment, the relation between breech presentation and poor neurodevelopment might be thyroid-related.

Maternal thyroid function during gestation is related to breech presentation at term.

OBJECTIVE: To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term. DESIGN: Prospective follow-up study during three trimesters of gestation. PATIENTS: A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (>or=37 weeks) delivery. MEASUREMENTS: Maternal thyroid parameters [TSH, free T4 (FT4) and auto-antibodies to thyroid peroxidase] were assessed at 12, 24 and 36 weeks gestation as well as foetal presentation at term. RESULTS: At term, 58 women (5.5%) presented in breech. Compared with women with foetuses in the cephalic position, those women who presented in breech at term had significantly higher TSH concentrations, but only at 36 weeks gestation (P = 0.007). No between group differences were obtained for FT4 level at any assessment. The prevalence of breech presentation in the subgroup of women with TSH >or= 2.5 mIU/l (90th percentile) at 36 weeks gestation was 11%, compared with 4.8% in the women with TSH < 2.50 mIU/l (P = 0.006). Women with TSH below the 5th percentile had no breech presentations. Breech position was significantly and independently related to high maternal TSH concentration (>or=2.5 mIU/l) at 36 weeks gestation (O.R.: 2.23, 95% CI: 1.14-4.39), but not at 12 and 24 weeks gestation. CONCLUSIONS: Women with TSH levels above 2.5 mIU/l during end gestation are at risk for breech presentation, and as such for obstetric complications.

[Estimating renal function based on creatinine clearance: application of different formulas and correction for obese patients]. / Schatting van de nierfunctie op grond van de creatinineklaring: bruikbaarheid van enkele formules en correctie bij obese patiënten.

OBJECTIVE: To determine whether glomerular filtration rate (GFR) is best estimated by the Cockcroft-Gault formula or the formula used in the 'Modification ofdiet in renal disease' (MDRD) study. DESIGN: Descriptive inventory. METHOD: Passing-Bablok regression analysis was performed using the statistics program 'Analyse it' for the estimated GFR derived by both formulas based on 467 patients who had data on height, weight and creatinine clearance entered into the laboratory information system of the Máxima Medical Centre, Veldhoven, the Netherlands, during a 2-year period. The performance of each formula was analysed in different patient groups based on weight. RESULTS: The MDRD formula and the Cockcroft-Gault formula performed similarly in all weight groups with adequate precision, particularly when the corrected Cockcroft-Gault formula was used for patients with a body-mass index (BMI) >25 kg/m2. The fact that outcomes using the BMI-corrected Cockcroft-Gault formula strongly correlated with outcomes calculated using the so-called Salazar-Corcoran formula, which was developed specifically for use in obese patients, confirms the validity of the BMI-corrected approach. CONCLUSION: The Cockcroft-Gault formula and the MDRD formula both provided appropriate estimates of GFR and were also considerably more suitable for screening for renal function than assessment of plasma creatinine concentration. However, the best non-invasive way to determine GFR remains a carefully performed assessment ofcreatinine clearance using plasma and 24-hour urine samples.

Cell-mediated immunity and postpartum thyroid dysfunction: a possibility for the prediction of disease?

Postpartum (pp) thyroid dysfunction (PPTD) is thought to be caused by an autoimmune (AI) destruction of thyroid follicles during the pp period. The chronic thyroid AI process [already present in pregnancy, as shown by the positivity for thyroid peroxidase antibodies (TPO-Ab)] becomes overt disease in the pp period, and one assumes that this exacerbation represents a rebound phenomenon after a general immunosuppression during pregnancy. The presence of TPO-Ab in pregnancy has been suggested as a predictor for later PPTD development. Apart from B cells, e.g. production of autoantibodies, various functions of the cell-mediated immune (CMI) system, including those of peripheral T cells, monocytes, and dendritic cells (DC), are also disturbed in AI states. The objectives of the present study were: determining alterations in various CMI parameters in pregnancies followed by PPTD vs. those not followed by PPTD; and determining the usefulness of these parameters in the prediction of PPTD. In a prospective study (region: Kempenland, southeast Netherlands), a random sample of 291 women were tested at 12 and 32 weeks gestation and 4 weeks pp for TPO-Ab. Women were followed until 9 months pp, for developing PPTD. PPTD was defined as both: an abnormal TSH, and fT4 pp women developing PPTD and/or being positive for TPO-Ab (n = 26); and thyroidological uneventful control women of the same cohort, matched for age and parity (n = 21), were tested for thyroid-stimulating antibodies, percentages of peripheral blood lymphocyte subsets using fluorescence-activated cell sorter analysis (CD3, CD4, CD8, CD16, CD56, major histocompatibility complex-class II), for monocyte polarization, and for cluster capability of monocyte-derived DC. Results were: 1) 31 women (10.7%) were positive for TPO-Ab (TPO-Ab+) in gestation (12 and/or 32 weeks); 2) 15 women (5.2%) developed PPTD, of whom 10 were TPO-Ab+ in gestation; 3) pregnancy-related CMI alterations consisted of low percentages of CD16+CD56+ natural killer (NK), cells and a low DC cluster capability at 12 weeks gestation (these functions were normalized at 32 weeks gestation); 4) the TPO-Ab+ PPTD+ women (4 hyper, 5 hypo, and 1 hyper/hypo) were characterized by a persistently low percentage of NK cells, a lowered monocyte polarization, and a raised percentage of major histocompatibility complex-class II+CD3+ T cells; 5) the TPO-Ab- PPTD+ women (all 5 hyper) had neither thyroid-stimulating antibodies nor CMI alterations, apart from those normally seen in pregnancy; 6) 21 women were positive for TPO-Ab in pregnancy but did not develop PPTD (they had the same lowered NK cell percentages and monocyte polarization as the TPO-Ab+ PPTD+ cases, but they had normal percentages of activated peripheral T cells and a lower titer of TPO-Ab); 7) determination of the number of NK cells and monocyte polarization hardly contributed to the prediction of PPTD (as compared with TPO-Ab status), because of strong interindividual variation and close association with the presence of TPO-Ab; and 8) combining TPO-Ab assays with testing for activated T cells was the most optimal parameter for the prediction of TPO-Ab+ cases of PPTD in our small test set. We conclude that TPO-Ab+ pregnant women who develop PPTD show several CMI abnormalities other than those seen in normal pregnant women, such as persistently lower percentage of NK cells, a lowered monocyte polarization, and a raised percentage of activated T cells. The latter seems rather specific for the actual PPTD development and is not found in TPO-Ab+ (but PPTD) uncomplicated pregnancies. TPO-Ab- (but PPTD+) women had no signs of CMI abnormalities (apart from those specific for the pregnancy state). Although studied cases are low in number, our data are suggestive for the existence of two forms of PPTD: a TPO-Ab+ (AI) form (two-thirds of patients, classical PPTD pattern); and a TPO-Ab- (non-AI) form (one-third of patients, only hyper). Such assumption implies that, at best, two

Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development?

Women with antibodies against the enzyme thyroid peroxidase [TPO-Ab; formerly microsomal antibodies (MsAb)] are at particular risk for developing postpartum thyroid dysfunction; the latter is significantly associated with postpartum depression. Although the negative effect of postpartum maternal depression on child development is well documented, the consequences of elevated titers of TPO-Ab during pregnancy and subsequent postpartum thyroid dysfunction on child development are not known. In a prospective study of a cohort of 293 pregnant women, the occurrence of TPO-Ab during gestation, thyroid dysfunction, and depression was investigated. Five years after delivery, child development was assessed in 230 children of the original cohort using the Dutch translation of the McCarthy Scales of Children's Abilities. Children of women with TPO-Ab during late gestation (n = 19, with normal thyroid function) had significantly lower scores (by t test) on the McCarthy Scales of Children's Abilities than antibody-negative women. The difference on the General Cognitive Scale, which reflects IQ scores, was substantial (10.5 points; t = 2.8; P = 0.005). After correction for possibly confounding variables, maternal TPO-Ab during gestation was found to be the most important factor related to the scores on the General Cognitive Scale (odds ratio = 10.5; 95% confidence interval = 3-34; P = 0.003). We conclude that children of pregnant women who had elevated titers of TPO-Ab but normal thyroid function are at risk for impaired development.

Prediction of post partum thyroid dysfunction: can it be improved?

BACKGROUND: Screening pregnant women for thyroid peroxidase antibodies (TPOAb) to identify those at risk for post partum thyroid dysfunction (PPTD) is controversial, mainly because of the low positive predictive value (ppv) of TPOAb. OBJECTIVES: To evaluate if the ppv of TPOAb can be enhanced, either by taking into account the time of TPOAb testing, or by combining this parameter with other putative determinants of PPTD such as smoking, family history or other autoimmune diseases. METHODS: A prospective study was performed in the Kempenland region (southeastern Netherlands). Three hundred and ten unselected women were visited at 12 and 32 weeks gestation and 4, 12, 20, 28 and 36 weeks post partum. Serial thyroid stimulating hormone (TSH), free thyroxine (fT4) and TPOAb testing was performed. Thyroid dysfunction (TD) was defined as abnormal TSH either in combination with abnormal fT4 (overt TD) or without abnormal fT4 (subclinical TD). PPTD was defined as overt TD post partum. Multivariate regression analysis was performed for determining independent risk factors for PPTD. The sensitivity and specificity of TPOAb at different time points and at different concentrations were calculated and presented in receiver operating characteristic (ROC) curves. Women who had experienced PPTD were followed for 2.5-3 years. RESULTS: Data from 291 women were available for analysis. Serum fT4 declined during pregnancy and returned to baseline values post partum. TD in gestation was present in 23 women (7.9%): serum TSH was transiently decreased in 13 (6 had overt gestational thyrotoxicosis (2.1%)) and increased in 10 (2 had TPOAb). Both point prevalence and concentration of TPOAb decreased during gestation and returned to baseline levels within 12 weeks post partum. TD in post partum was present in 36 women (12.4%): 21 had subclinical and 15 overt TD. Out of the 15 women with overt TD (incidence of PPTD: 5.2%) 10 were positive for TPOAb (TPOAb+): 9 had thyrotoxicosis (4 TPOAb+), 5 hypothyroidism (5 TPOAb+) and 1 thyrotoxicosis followed by hypothyroidism (TPOAb+). Independent risk factors for PPTD were TPOAb (relative risk (RR) = 2 7.2), bottle feeding (RR = 11.1) and smoking habits (ever smoked: RR = 3.1; women with PPTD had smoked more cigarettes for a longer period of time). The sensitivity of TPOAb testing was highest at 12 weeks gestation (0.67). The ppv of TPOAb was 0.31-0.75 (depending on time of testing and concentration), increasing slightly to 0.38-0.80 when combined with bottle feeding or smoking habits. There appeared to be an autoimmune form of PPTD in 2/3 of cases and a non-autoimmune form; women with the autoimmune form were at risk for developing permanent hypothyroidism. CONCLUSIONS: A maximum of 2/3 of PPTD cases can be predicted from the presence of TPOAb because 1/3 remained negative for TPOAb. The most appropriate time for TPOAb testing is in the first trimester of pregnancy. The combination of TPOAb testing with anamnestic determinants of PPTD does not increase ppv substantially.

Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum.

OBJECTIVE: Depression is not adequately diagnosed in many cases. Therefore, the question arises as to whether markers exist for depression. We investigated whether the presence of thyroperoxidase antibodies (TPOAbs) during pregnancy can be regarded as a marker for depression in the first year postpartum, particularly in relation to (overt or subclinical) thyroid dysfunction and other determinants of depression. DESIGN: This work was a prospective observational study. PATIENTS: A cohort of 310 unselected women (residing in the Kempen Region, southeastern Netherlands) were visited at 12 and 32 weeks gestation and at 4, 12, 20, 28 and 36 weeks postpartum. METHODS: At each visit, TSH, free thyroxine and TPOAb testing was performed, determinants associated with depression were asked for, and depression was assessed (according to the Research Diagnostic Criteria). Multiple logistic regression was performed to determine independent risk factors (odds ratios, ORs) for depression in gestation and/or postpartum depression. RESULTS: Data for 291 women were available for analysis; 41 women (14.1%) had TPOAbs at one or more time points, and 117 women (40.1%) had depression at one or more time points postpartum. The multiple logistic regression analysis showed that TPOAbs were independently associated with depression at 12 weeks gestation and at 4 and 12 weeks postpartum (OR, 95% confidence interval: 2.4 (1.1-6.0), 3.8 (1.3-7.3) and 3.6 (1.2-7.1) respectively). After the exclusion of women who were depressed at 12 weeks gestation (n=70), the presence of TPOAbs during early pregnancy was still found to be associated with the development of postpartum depression (OR, 95% confidence interval: 2.8 (1.7-4.5); after exclusion of women who had had depression in earlier life (n=51), TPOAb during early gestation was still associated with postpartum depression (OR, 95% confidence interval: 2.9 (1.8-4.3). CONCLUSIONS: The presence of TPOAbs during gestation is associated with the occurrence of subsequent depression during the postpartum period and as such can be regarded as a marker for depression.

The influence of viscosity on dilution methods. Its problems in the determination of serum sodium.

Dilution with a roller-pump is a well known procedure in clinical chemistry. This method may be influenced by viscosity. A higher viscosity of the sample yields a lower sample output and consequently a larger dilution. If the substance to be determined in the diluted sample can be measured accurately, the influence of viscosity may be analysed easily. This was performed for serum sodium. It was shown that with extreme pathological viscosities (as are found e.g. in multiple myeloma and Waldenström's macroglobinemia) underestimations of more than 15% may occur. Especially for serum sodium, the physiological range of which is fairly small, this may provoke serious diagnostic and therapeutic problems. We propose to use viscosity independent dilution systems.

Gelatin derivatives in blood: interference with the determination of inorganic phosphate in serum.

The method of Goldenberg and Fernandez (1966) Clin. Chem. 12, 871--882) for the determination of inorganic phosphate in serum is significantly influenced by turbidity after intravenous application of gelatin derivatives, even at low quantities. This turbidity can be eliminated by the addition of sodium dodecyl sulphate to the reaction solution.

Influence of ions on the antigen-antibody complex formation as measured by radioimmunoassay.

In this study, using radioimmunoassay techniques, we found that ions at concentrations in the order of 0.1 molar influence the antigen-antibody complex formation. The angiotensin I/anti-angiotensin I reaction was studied in detail. Particularly bivalent cations and anions with a strong chaotropic effect (SCN-, I- and ClO4-) were found to influence strongly the specific immunological reaction. However, NO3- had also a remarkably strong influence. We found that the equilibrium constant, rather than the number of binding sites of the antibody, is influenced by the ions. It should be borne in mind that relatively high concentrations of electrolyte (as compared with the concentrations of antigen and antibody) show this effect. Consequently, this effect is of less practical importance for routine radioimmunoassay than is, for example, the effect of pH. However, this phenomenon shows that the radioimmunoassay technique might be valuable not only for quantization of very low hormone concentrations in biological fluids, but has also important potential applications in physical and protein chemistry. Particularly, the high sensitivity of this technique and the possibility of studying a homogeneous reaction system might give it advantages over other techniques.

Influence of the pH on the antigen-antibody coupling in angiotensin I radioimmunoassay. Its consequences for the determination of the plasma renin activity.

The antigen-antibody complex formation in the angiotensin I radioimmunoassay appears to be influenced by the pH of the radioimmunoassay incubation mixture. This may lead to erroneous results in the determination of the plasma renin activity, when an aliquot of a plasma sample, buffered at pH 6 for optimum renin activity is brought into a radioimmunoassay mixture of another pH, while the radioimmunoassay standards are not corrected for this pH shift. In our experiments we studied this general pH effect, and evaluated the effect on the New England Nuclear Angiotensin I radioimmunoassay procedure. We propose a slight modification of this radioimmunoassay kit.

On standardizing the determination of the plasma renin activity.

Basically, the determination of the plasma renin activity (PRA) consists of the in vitro generation of angiotensin I and the radioimmunological determination of angiotensin I. Since both steps can be performed in several ways, the results from different laboratories can hardly be compared. In this paper we have described the results of our attempts to standardize both steps of the PRA determination currently in use in our laboratory, against Research Standard A for Angiotensin I and the International Reference Preparation of Human Renin, both obtained from the Medical Research Council.

Androgen turnover during marathon running.

The purpose of the study was to investigate the effect of prolonged physical stress on peripheral androgen turnover. Venous blood samples were taken from 18 athletes 24 h before finishing a competitive marathon run and directly after running the race. Serum cortisol, testosterone (T), dehydroepiandrosteronesulfate (DHEAS), sex hormone binding globulin (SHBG), and 5 alpha-androstane- 3 alpha, 17 beta-diolglucuronide (3 alpha-AdiolG) were determined and corrected for hemoconcentration. Marathon running caused a rise in serum cortisol concentration in all athletes. Furthermore, a significant (P < 0.01) rise in serum T and T-index (index of free T) was observed. The significant (P < 0.01) rise in serum DHEAS concentration, a mainly adrenal cortical androgen, pointed toward a stimulation of the adrenal cortex or a reduced hepatic metabolic clearance rate. Finally, 3 alpha-AdiolG, an androgen metabolite exclusively formed in peripheral tissues, was increased in the sera of all athletes. These results suggest that marathon running leads to increased concentrations of serum adrenal and gonadal androgens. The simultaneously increased 3 alpha-AdiolG levels may be caused by increased androgen turnover in peripheral tissues containing 5 alpha-reductase.

Serum cholesterol decline and depression in the postpartum period.

We examined the relation between total serum cholesterol decline and depression in the postpartum period in a prospective study of 266 Dutch women, who were followed until 34 weeks after delivery. The decline in serum cholesterol between week 32 of pregnancy and week 10 postpartum was similar for women who became depressed (n = 63) in the subsequent period and women who did not (difference, 0.10 mmol/l; 95% confidence interval [CI] -0.16 to 0.37). Adjusting for age, multiparity, education level, smoking status, concurrent illness, and social support, the odds ratio of depression was 1.4 (95% CI, 0.64 to 2.9) for women in the highest tertile of serum cholesterol decline and 0.61 (95% CI, 0.28 to 1.3) for women in the intermediate tertile, as compared with women in the lowest tertile. Our results do not support the hypothesis that rapid serum cholesterol decline increases risk of depression in the postpartum period.

The effect of hysterectomy and endometrial ablation on follicle stimulating hormone (FSH) levels up to 1 year after surgery.

OBJECTIVES: In this study the hypothesis was tested, that in premenopausal patients FSH-levels would rise after 'simple hysterectomy'. As endometrial ablation is not supposed to compromise ovarian bloodflow, there would be no such change in ablated patients. METHODS: Between January 1995 and April 1996, consecutive premenopausal patients with dysfunctional uterine bleeding who were scheduled for hysterectomy or endometrial ablation were asked to participate in the study. Bloodsamples were drawn before surgery, six weeks, six months and one year after surgery. FSH and oestradiol (E2) were assayed. In all patients data about length and weight were collected to calculate Body Mass Index (BMI). Every visit patients filled in a questionnaire, containing questions about typical climacteric complaints, combined in a five-point scale. RESULTS: Except for a significant difference in preoperative FSH-level between both groups, there were no significant differences regarding age, Body Mass Index (BMI), oestradiol (E2) or the percentage of women with vasomotor complaints. Compared to the preoperative starting level, six weeks, six months and one year after surgery a significant rise in serum FSH in the hysterectomy group, as well as in the ablation group was found. However there was no significant difference in FSH increase between both groups. One third of the patients in both groups had typical climacteric complaints as flushing and nocturnal sweating. CONCLUSIONS: Assaying serum FSH-levels before and after uterine surgery and comparing hysterectomized patients and patients after endometrial ablation, we found a significant rise in FSH-level up to one year after surgery in both groups postoperatively, indicating impaired ovarian function. There was no difference in FSH-levels between both groups. Therefore major uterine surgery (hysterectomy, ablation) may prelude an earlier onset of menopause.

Influence of erythrocytes on direct potentiometric determination of sodium and potassium.

We have shown that the sodium concentration in whole blood measured by direct potentiometry is higher than in plasma. The 'erythrocyte-effect', already described by Siggaard Andersen, is most pronounced for instruments equipped with a reference electrode with an open static liquid junction and is thus a general phenomenon. Instruments with a modified liquid junction show less interference. The same phenomenon appears for the determination of the potassium concentration, although the difference between whole blood and plasma, when measured with instruments equipped with a modified liquid junction, can be neglected in practice.

On the standardisation of the direct spectrophotometric bilirubin determination. Influence of the albumin source and the molar bilirubin: albumin ratio.

The influence of different albumin solutions and of the molar bilirubin/albumin ratio on the bilirubin concentration determined by the method for Hertz et al. was studied. There is good agreement between the true-bilirubin concentrations and those obtained by the Hertz method for bilirubin-HSA and bilirubin-serum solutions. Moreover the observed concentration is scarcely influenced by the molar ratio. Bilirubin standards in HSA-solutions can thus be used to standardise this method. Errors are introduced by preparing standards in BSA-solutions as the absorption spectrum of bilirubin-BSA is different from that of bilirubin-HSA.

Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?

BACKGROUND: Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion. METHODS: In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance. RESULTS: Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2. CONCLUSIONS: The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy.