Plasma oestrogen fractions in postmenopausal women receiving hormone replacement therapy: influence of route of administration and cigarette smoking.

The aim of this study was to determine the impact of the administration route and cigarette smoking on plasma oestrogen levels during oral and parenteral oestrogen replacement therapy (ERT). Fourteen healthy postmenopausal women (six smokers and eight non-smokers) were recruited for a prospective, randomised, crossover study at a private outpatient medical centre in Oslo, Norway. All patients were randomised to receive cyclic therapy with oestradiol and norethisterone orally or by the transdermal route each for a 6-month period. Plasma levels of oestrone (Oe(1)), oestradiol (Oe(2)) and oestrone sulphate (Oe(1)S) were determined using highly sensitive RIA methods before and during hormone replacement therapy given by the oral and transdermal route. Comparing smokers and non-smokers, plasma levels of Oe(1), Oe(2) and Oe(1)S were all found to be 40-70% lower in smokers compared with non-smokers when ERT was given orally (Oe(1)S, P<0.05; Oe(1) and Oe(2), P<0.01 for both). Oe(2) given orally caused a higher Oe(1)S/Oe(2) ratio but also a higher Oe(1)/Oe(2) ratio compared with parenteral therapy in smokers (40.2 versus 7(.)0, P<0.01; and 3.2 versus 0.8, P<0.05 respectively). No significant differences in these parameters in the different test-situations were seen in non-smokers. Except for a lower level of Oe(1)S in smokers (non-significant), no difference in plasma oestrogen levels between smokers and non-smokers was observed during parenteral therapy. In conclusion, cigarette smoking has been shown to have major impact on plasma oestrogen levels during oral but not during parenteral Oe(2) replacement.

Discrimination of smoking status by thiocyanate and cotinine in serum, and carbon monoxide in expired air.

To develop a procedure for maximizing the discrimination of smoking status, the authors analysed parallel samples of thiocyanate and cotinine in serum, and carbon monoxide (CO) in expired air in a cohort of 145 male subjects aged 45-65 years. The sensitivity and specificity were 93% and 82%, 97% and 83%, and 98% and 100% for thiocyanate, cotinine, and CO respectively. The results were not significantly improved when combining two or three methods as compared with CO separately. Also, cotinine in urine was analysed in a subgroup of 21 subjects. The correlation coefficient between cotinine in serum and urine was 0.92. In a subgroup of 44 subjects with extensive information on smoking habits, CO was the only indicator significantly related to the quantity of tobacco smoked. We conclude that CO seems sufficient for validating smoking status, but as atypical smokers who are vulnerable to misclassification may be overrepresented in smoking cessation programmes, combining two methods could still be useful. Validating the amount of tobacco smoked is of limited use with the current methods.

Comparison of three methods for estimating environmental tobacco smoke exposure among children aged between 12 and 36 months.

BACKGROUND: The methods currently used for measuring environmental tobacco smoke (ETS) exposure among small children all have their limitations. The aim of this study was to compare the results of questionnaire assessments of children's ETS exposure with cotinine measurements in urine and nicotine measurements in hair, a new method for estimating average ETS exposure. METHODS: Questionnaire information on ETS exposure and a sample of hair were collected from 94 children aged 12-36 months. A urine sample for cotinine analysis was obtained from 72 of the children. RESULTS: Nicotine was found in all hair samples and cotinine in all urine samples. Compared to children registered as unexposed by the questionnaire, hair nicotine levels were 12.4 times higher among children exposed to more than 10 DNC (daily number of cigarettes) (P < 0.001) and 3.6 times higher among children exposed to 1-10 DNC (P < 0.001). The median cotinine creatinine ratio (CCR) was 2.4 times higher among children exposed to more than 10 DNC compared to unexposed children (P < 0.001). No significant difference in median CCR was found between unexposed children and children exposed to 1-10 DNC. The correlation coefficient was 0.64 between children's hair nicotine levels and DNC, 0.50 between CCR and DNC and 0.56 between children's hair nicotine levels and CCR. CONCLUSION: Nicotine measurement in hair is a practical and valid method for estimating average ETS exposure in children. An underreporting of ETS exposure was indicated.

Radioimmunological assays for triiodothyronine(T3) or thyroxine(T4) in sera containing antibodies against the hormones.

For serum samples containing antibodies in vivo against triiodothyronine or thyroxine, the radioimmunoassays in use may give highly erroneous results. We wanted to compare the effects of two different radioimmunoassay systems on such sera, and to develop a suitable extraction procedure for use before such assays. Very different results were obtained with the use of single antibody or double antibody techniques on unextracted sera. The highest recoveries of total T3 and T4 from sera were found with two successive ethanol extractions.

Long-term treatment with slow-release frusemide compared with thiazide treatment in arterial hypertension.

The effect of 30 mg/day slow-release frusemide given orally for 12 months was studied in 64 patients previously treated with thiazides for mild to moderate essential hypertension. Frusemide had a significant antihypertensive effect (P less than 0.001), and compared to thiazides significantly reduced fasting serum glucose (P less than 0.015), haemoglobin A1c (P less than 0.025), albumin (P less than 0.025) and serum calcium (P less than 0.025), and significantly increased serum sodium and chloride concentrations (P less than 0.0001). There was also a non-significant trend for frusemide to reduce serum total cholesterol, triglycerides and urate, and to increase serum potassium. Frusemide was well tolerated in all but three patients. It is concluded that slow-release frusemide has a comparable antihypertensive effect to that of thiazide diuretics, but has fewer metabolic side-effects, and should be used in-preference to thiazides for the treatment of arterial hypertension when a diuretic is indicated.

Urinary concentration of a specific peptide of type I collagen of bone (CrossLaps): correlation to hydroxyproline.

Urinary bone resorption markers, CrossLaps and hydroxyproline are compared in a non-selected group of 93 women. The correlation between CrossLaps and hydroxyproline is satisfactory. The r value is 0.79. Furthermore, it is investigated whether CrossLaps can substitute for hydroxyproline in the estimation of bone loss, using a model based on the combination of several biochemical markers. The results indicate that the two systems reflect related or parallel events, and show that CrossLaps is suitable for use in a normal clinical chemistry laboratory.

Triiodothyronine (T3) binding to immunoglobulin G subclasses in a slightly hypothyroid woman.

A 44-year-old woman, with an earlier history of myxoedema, had stopped taking thyroxine and was found to have both a slightly elevated basal TSH level and an increased TSH response after thyroliberin stimulation. The T4 value was low borderline, and using a radioimmunoassay that separated free and antibody-bound hormone by polyethylene glycol precipitation, the T3 value was found to be less than zero. This last finding was explained by the existence of T3 antibodies in the patient's serum. The antibodies, being of the IgG class, did not bind T4, thyroglobulin or cytoplasmic thyroid antigen. The subclass IgG2, and to a lesser extent IgG1, IgG3 and IgG4, did bind T3. A Scatchard plot gave an antibody avidity constant of 4.28 x 10(8) l/mol and a binding site concentration of 3.8 x 10(-9) mol/l. Radioimmunoassay of total T3, after extraction with ethanol gave a high value. The concentration of free T3 was, however, just above the lower reference limit.

Fetal exposure to tobacco smoke products: a comparison between self-reported maternal smoking and concentrations of cotinine and thiocyanate in cord serum.

BACKGROUND: The objective of the study was to assess the relationship between maternal smoking habits and biomarkers of tobacco smoke measured in cord serum. METHODS: The study population comprised 202 mothers, 42 daily smokers, 24 occasional smokers and 136 nonsmokers. Information on maternal smoking habits was collected in a self-administered questionnaire at birth and compared with cotinine and thiocyanate concentrations in cord serum. RESULTS: In linear regression analysis, a unit increase in daily cigarette smoking corresponded to a 4.4 ng/ml (95% CI: 1.1-7.6) increase in cotinine concentration and 2.3 mumol/l(0.8-3.8) in thiocyanate. A cut-off point of 14 ng/ml cotinine separated well between daily smokers (88% above) and nonsmokers (96% below), but revealed a classification problem in occasional smokers (46% above). CONCLUSION: Cord serum cotinine and thiocyanate concentrations are related to daily smoking rate during pregnancy, but these concentrations vary considerably among occasional smokers. Detailed information on smoking habits is the key issue in understanding the adverse fetal effects of occasional smoking during pregnancy.