Iron-fortified and unfortified cow's milk: effects on iron intakes and iron status in young children.

UNLABELLED: Iron intakes and iron status were evaluated in 36 young Swedish children given either iron-fortified or unfortified cow's milk. All children had good iron status and had received breast milk or iron-fortified formulae during infancy. Twenty 1-y-old children were randomized to a diet with iron-fortified milk (7.0 or 14.9 mg Fe l(-1) and 16 to a diet with unfortified milk. The iron intakes in the unfortified group at 15 and 18 mo (mean +/- SD 5.19 +/- 2.29 and 5.84 +/- 1.62 mg d(-1)) were low in relation to Nordic Nutrition Recommendations, while the intakes in the iron-fortified group (10.20 +/- 2.60 and 10.87 +/- 2.79mg d(-1)) were normal in relation to recommendations. The gain (increase) from receiving fortified diet during the study period was at most [upper limit for 95% confidence interval (CI)] 2.6 g l(-1) in blood haemoglobin, 1.9 fl in mean corpuscular volume, 2.7 micromol in serum iron and 4.5% in transferrin iron saturation, and the gain (decrease) was at most (lower limit for 95% CI) 0.29g l(-1) in serum transferrin and 0.9mg l(-1) in serum transferrin receptor (TfR). None of these differences was statistically significant. There was an almost significantly higher increase in serum ferritin (1.4 times higher relation of values at the end compared with the beginning, p = 0.06) and a significantly higher (1.2; p = 0.047) decrease in TfR/ log10 ferritin ratio in the fortified group. CONCLUSION: One-year-old children starting out with good iron status given either iron-fortified or unfortified cow's milk from 12 to 18 mo maintain sufficient iron status during this period. However, children fed unfortified cow's milk have an iron intake which is low in relation to recommendations and the quantitative development of their reserve iron in iron stores seems to be weaker than that of the fortified group. The consequences of this require further study.

Platelet dysfunction after intravenous ketorolac or propacetamol.

BACKGROUND: Paracetamol is a weak cyclo-oxygenase inhibitor in vitro. A recent study in children has shown that high doses of paracetamol are effective and safe. We studied the effect of propacetamol on haemostasis in adult volunteers. METHODS: Ten volunteers were investigated in a double-blind, randomized, crossover study. They received propacetamol 60 mg kg(-1) or ketorolac 0.4 mg kg(-1) in saline i.v. (30 min) in two different sessions. Platelet function was evaluated before the test infusion (S-0), two (S-2) and 24 h (S-24) after the start of the infusion. Coagulation parameters (PT, APTT, factor V and VII activities) were measured at S-0, S-24 and 48 h (S-48). RESULTS: One of the volunteers had no secondary platelet aggregation in S-0 and was excluded from the final analysis. Two hours (S-2) after propacetamol and ketorolac administration the adrenaline (0.9 microg ml(-1) and 9.0 microg ml(-1)) induced maximal platelet aggregation was decreased compared with S-0. At S-2 platelet aggregation was inhibited more after ketorolac than after propacetamol. At 24 h after ketorolac, but not after propacetamol, there was still a decrease in the adrenaline-induced maximal platelet aggregation. Propacetamol did not affect adenosine diphosphate (ADP)-induced maximal platelet aggregation, whereas ketorolac decreased 3 and 6 microM ADP-induced maximal platelet aggregation at S-2 and S-24. However, 2 h after both ketorolac and propacetamol, thromboxane B2 (TxB2) concentration decreased in platelet rich plasma after 5 min aggregation induced by 8 microM ADP. Coagulation was unaffected. CONCLUSION: Propacetamol 60 mg kg(-1) i.v. causes reversible platelet dysfunction demonstrated by a decrease in maximal platelet aggregation and TxB2 concentration. After 0.4 mg kg(-1) ketorolac i.v. platelet aggregation and TxB2 formation are inhibited more in comparison with propacetamol, and platelet dysfunction is still seen after 24 h.

Higher concentrations of serum transferrin receptor in children than in adults.

BACKGROUND: The serum transferrin receptor (TfR) concentration in adults is suggested to provide a sensitive measure of iron depletion and together with the serum ferritin concentration to indicate the entire range of iron status, from iron deficiency to iron overload. However, little is known about TfR concentrations in children. OBJECTIVE: Our objective was to compare serum TfR and ferritin concentrations and their ratios in children and adults and look for correlations between TfR concentrations and other measures of iron status. DESIGN: Our study groups were healthy 1-y-old infants (n = 36), 11-12-y-old prepubertal boys (n = 35), and 20-39-y-old men (n = 40). RESULTS: TfR concentrations were higher in infants (x; 95% reference interval: 7.8 mg/L; 4.5, 11.1) than in prepubertal boys (7.0 mg/L; 4.7, 9.2) and higher in prepubertal boys than in men (5.8 mg/L; 3.1, 8.5). Geometric mean TfR-ferritin ratios were higher in infants (316; 95% reference interval: 94, 1059) than in prepubertal boys (219; 78, 614) and higher in prepubertal boys than in men (72; 23, 223). By multiple linear regression analysis, the best predictors of TfR concentration were serum iron (P = 0.004) and log serum ferritin (P < 0.0001), both being inverse correlations (R2 = 0.32). Mean corpuscular volume, blood hemoglobin, transferrin iron saturation, transferrin, and even age seemed to not have an influence on the TfR concentration and erythropoiesis was not a determinant of TfR concentration. CONCLUSIONS: Low serum ferritin and iron concentrations, even within the normal physiologic range, result in high TfR concentrations. The lower the iron stores, the stronger the influence of ferritin on TfR. A high TfR concentration in children, especially in infants, is a response to physiologically low iron stores. Age-specific reference concentrations for TfR are needed.

Effect of antiestrogen regimen on prostacyclin and thromboxane A2 in postmenopausal patients with breast cancer: evidence of significance of hypertension, smoking or previous use of estrogen therapy.

To explore the mechanism(s) by which antiestrogens may protect against the development of cardiovascular disorders, we measured the production of vasodilatory, antiaggregatory prostacyclin (PGI2) and that of vasoconstrictive, proaggregatory thromboxane A2 (TxA2) before and after 6 months' use of antiestrogens in postmenopausal patients after operation for stage II breast cancer (n = 38). Urine samples were assayed by high performance liquid chromatography and radio-immunoassays for 2,3-dinor-6-ketoprostaglandin F1 alpha (= metabolite of PGI2, dinor-6-keto) and for 2,3-dinor-thromboxane B2 (= metabolite of TxA2, dinor-TxB2). In addition, in 35 of these 38 patients we assayed the capacity of platelets to produce thromboxane A2 during standardized blood clotting. The 4 patients using low-dose aspirin had low thromboxane production, and were excluded from further analysis of the data. An antiestrogen regimen consisting either of tamoxifen (n = 15) or of toremifene (n = 19) caused no changes in production of PGI2 or TxA2, or in their ratio, and in this regard, these antiestrogens behaved similarly. Hypertensive patients (n = 7) using different anti-hypertensive agents were characterized by reduced urinary out-put of dinor-6-keto (18.5 +/- 6.1 vs 35.5 +/- 18.5 ng/mmol, mean +/- SD, p < 0.05) and reduced platelet capacity to produce TxA2 (62.6 +/- 67.8 vs 134.6 +/- 75.6 ng/mL, p < 0.05). The patients (n = 15) who had used estrogen replacement therapy (ERT) up until diagnosis of breast cancer showed reduced dinor-TxB2 excretion (15.5 +/- 12.7 vs 29.9 +/- 20.9 ng/mmol, p < 0.05) before initiation of antiestrogens, and elevated dinor-6-keto output during the antiestrogen regimen (32.4 +/- 21.2 vs 22.7 +/- 8.7 ng/mmol, p = 0.07). Smokers (n = 6) had elevated dinor-TxB2 output before and during antiestrogen use. Thus we conclude that the cardiovascular protection provided by an antiestrogen regimen is unlikely to be mediated through vaso- and platelet active PGI2 and TxA2.

Marathon running accompanied by transient decreases in urinary calcium and serum osteocalcin levels.

We evaluated the effects of marathon running on bone metabolism in 23 noncompetitive athletes (15 women, 8 men, age range 23-55 years). The volunteers were studied 10 days before, immediately after, and 1, 3, and 5 days after the run. Serum osteocalcin levels were decreased on average by 20% (from 4.9 to 3.9 micrograms/liter, P = 0.005) in men and by 10% (from 4.9 to 4.4 micrograms/liter, P < 0.05) in women at the end of the marathon, with lowest osteocalcin levels (67-55% of the prerun levels) encountered 1 day after the marathon. The activity of bone alkaline phosphatase was decreased in women (from 66.3 to 62.3 U/liter, P < 0.05) after the run, and this drop was detectable at each checkup after the run. Urinary excretion of calcium was lowered on average by 82% in men (from 2.8 to 0.5 mumol/minute, P < 0.05) and by 76% in women (from 2.5 to 0.6 mumol/minute, P < 0.005) after the run, but had already returned to prerun levels 1 day after the marathon. Urinary excretion of hydroxyproline tended to rise in both men and women, but the change did not reach statistical significance in either sex. These changes suggest a transient suppression in osteoblast function during the marathon.

Urinary excretion of degradation products of prostacyclin and thromboxane is increased in patients with gestational choriocarcinoma.

Gestational choriocarcinoma metastasizes rapidly, in which process the vasoactive prostanoids may be significant. We therefore compared the urinary excretion of prostacyclin and thromboxane A2 (TxA2) metabolites in 19 women with gestational choriocarcinoma and 20 healthy age-matched women by assessing spot urine samples for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha) (degradation products of prostacyclin) as well as for thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (degradation products of TxA2) by high-pressure liquid chromatography, followed by radioimmunoassay; the data were related to urinary creatinine concentration. The urinary output of 6-keto-PGF1 alpha [29.56 +/- 7.0 versus 25.08 +/- 3.91 ng/mmol creatinine (SE)] in patients with choriocarcinoma was normal, but that of 2,3-dinor-6-keto-PGF1 alpha in cancer patients was higher than in controls (24.44 +/- 5.20 versus 14.84 +/- 1.94, P less than 0.02), as was that of TxB2 (22.72 +/- 4.69 versus 9.69 +/- 1.52, P less than 0.001) and 2,3-dinor-TxB2 (114.21 +/- 30.81 versus 51.81 +/- 10.40, P less than 0.01). The ratio of net prostacyclin output (6-keto-PGF1 alpha plus 2,3-dinor-6-keto-PGF1 alpha) to the net TxA2 output (TxB2 plus 2,3-dinor-TxB2) in cancer patients [0.52 +/- 0.1 (SE)] was lower (P less than 0.03) than in the controls (0.83 +/- 0.1), and in an inverse relation (r = -0.54, P less than 0.05) to the scoring index of poor prognosis for the disease. We conclude that the prostanoid excess in gestational trophoblastic disease, as evidenced for the first time in this study, may originate from choriocarcinoma cells, or may be a paraneoplastic phenomenon, and we conclude also that TxA2 excess may contribute to the tumor growth and/or formation of metastases.

Increased synthesis of prostacyclin and thromboxane in human ovarian malignancy.

To study the production of antiaggregatory prostacyclin (PGI2) and proaggregatory thromboxane (TxA2) by ovarian tumors, we incubated pieces of benign and malignant ovarian tissue in vitro, and measured by radioimmunoassay the release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (a hydration product of PGI2) and thromboxane B2 (TxB2) (a hydration product of TxA2). Healthy ovary (n = 10) produced both 6-keto-PGF1 alpha [mean, 8.9; 95% confidence interval (CI) from 5.4 to 15.2 ng/mg protein/min] and TxB2 (mean, 1.9 ng/mg protein/min; 95% CI from 1.0 to 3.7 ng/mg protein/min). The production of 6-keto-PGF1 alpha (mean, 12.2; 95% CI from 7.7 to 19.3 ng/mg protein/min) and that of TxB2 (mean, 4.8; 95% CI from 2.1 to 11.9 ng/mg protein/min) by benign cystic tumors (n = 12) was normal. Ovarian anaplastic cancer and adenocarcinoma (n = 12) produced 6-keto-PGF1 alpha on average 11.6-fold (95% CI from 5.2 to 26.0) 6-keto-PGF1 alpha and TxB2 on average 30.0-fold (95% CI from 13.5 to 66.7) over production by healthy ovaries, and the ratio of 6-keto-PGF1 alpha to TxB2 shifted to the dominance of TxB2. Similarly ovarian metastases of breast cancer, tubal cancer, and colon cancer produced increasingly 6-keto-PGF1 alpha (mean, 20.7 ng/mg protein/min) and TxB2 (5.1 ng/mg protein/min). The dominance of TxA2 in human ovarian cancer may contribute to the aggressing growth and spreading of this tumor.