The effect of perinatal factors on cord thyroxine concentration

Cord blood thyroxine (T4) concentrations were measured in 4,068 infants from 28 wk gestation to term. Each chart was reviewed for the following factors: delivery by cesarean section, prolonged rupture of membranes, neonatal asphyxia, meconium-stained amniotic fluid, maternal diabetes mellitus and twinning. Each neonate was evaluated for the Idiopathic Respiratory Distress Syndrome, and low (SGA) or high (LGA) birthweight for gestational age. Within each gestational age group, the mean cord T4 value was similar except for a significantly lower mean cord T4 concentration for the term SGA subgroup. Thus, inclusion of the infant with a complicated neonatal course or the infant born to a high-risk mother in mass screening programs for congenital hypothyroidism using cord serum will not increase the number of false-positive T4 values.     

Correction of the biochemical effects of neonatal hypothyroidism by daily low doses of thyroxine. Comparative effects of hyperthyroidism and these corrections

The purpose of the present communication was to study the corrective effects of low daily thyroxine doses, on the cerebellum biochemical maturation in propylthiouracile (PTU)-treated rats during the early postnatal life. The corrected hypothyroid animals were compared to the normal, hypo- and hyperthyroid ones. The protein, RNA and DNA cerebellar contents were evaluated at 6, 10, 14, 18 and 35 days old animals.
At all ages hypothyroidism and hyperthyroidism decreased cerebellar protein, RNA and DNA contents, except in 35-day-old hyperthyroid animals, where DNA content returned to normal level. In these two experimental groups, protein/DNA and RNA/DNA ratios were higher than those of controls at 10 days and lower at 35 days.
In hypothyroid animals treated by corrective doses of T4, cerebellar protein, RNA and DNA contents and DNA concentration were not different from hyperthyroid animal values at all stages, while protein/DNA and RNA/DNA ratios were higher than those of hyperthyroid animals.
Administration of physiological doses of T4 to hypothyroid animals led to the same effects as higher doses in normal animals. Thus, neonatal hypothyroidism seems to lower the sensitivity threshold of the cerebellum to thyroid hormone effects.     

Life before birth: effects of cortisol on future cardiovascular and metabolic function

The concept of fetal programming is an area that is now under rigorous investigation in many laboratories throughout the world. We need to engender a fascination in all segments of society, not just pregnant women, about life in the womb.

Conclusion: Everyone needs to understand that improving the condition of the fetus will have personal, social and economic benefits. The time has come to realize that, in a sense, it is not just women who are pregnant but it is the family and the whole of society.     

Effect of 16, 16-dimethyl prostaglandin E2 on small intestinal mucosa in suckling rats

Suckling rats were treated every 8 h by intragastric instillation of 16,16-dimethyl prostaglandin E2 (PG) in a dose of 25 micrograms kg-1 (PG25), or 100 micrograms kg-1 (PG100), or saline from postnatal day 7-11. PG increased small intestinal villus length and crypt depth, most markedly in the duodenum, leading to a mucosal height of 543 +/- 24 microns after saline, 670 +/- 26 microns after PG25 and 823 +/- 40 microns after PG100. In the proximal small bowel, PG100 raised the mean activities of sucrase by 439%, maltase by 98%, trehalase by 584%, lactase by 58% and alkaline phosphatase by 76%. In the distal small intestine, only sucrase and trehalase activities were stimulated whereas other enzymes were depressed. PG25 caused similar but less pronounced changes of enzyme activities. Eight hours after both the last PG25 and the last PG100 dose, plasma gastrin and corticosterone levels were decreased while thyroxine remained unchanged. The effect of a single dose of 100 micrograms kg-1 PG or saline was also tested on 5- and 11-day-old rats; they were killed 16 h after PG administration. An increase in villus length occurred along the entire small intestine of rats treated on day 5, and also in the ileum of rats treated on day 11. In the proximal intestine, maltase and trehalase were stimulated after early and late treatment and, in addition, sucrase and lactase after late treatment. Serum corticosterone levels were found to be significantly higher 2-6 h after PG100 than in the controls and then decreased gradually.(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiotensin-converting enzyme inhibition and physical training in heart failure.

A total of 12 patients (mean age +/- SEM 63 +/- 2.6 years) with moderate to severe heart failure (ejection fraction = 23 +/- 3.2%) were included in a placebo-controlled crossover trial. Patients were randomly allocated to 4 periods of 6 weeks each: placebo, placebo and physical training, lisinopril 10 mg daily, and lisinopril and physical training. The exercise time increased from 13.6 +/- 0.9 min with placebo to 15 +/- 1 min with training alone, and to 16.1 +/- 0.7 min with lisinopril and training. With lisinopril alone there was a non-significant increase in exercise time, to 14.5 +/- 0.6 min. Improvements in exercise time were accompanied by a similar increase in peak oxygen consumption. Overall, the most significant improvements in symptoms and indices of cardiorespiratory fitness were achieved with a combination of lisinopril and training. Thus physical training is not only a useful adjunct to the existing medical therapy for heart failure, but it may also provide symptomatic benefits in its own right.     

Reference intervals for free thyroxine, total triiodothyronine, thyrotropin and thyroglobulin for Quebec newborns, children and teenagers

OBJECTIVE: Paediatric reference values, although essential for interpreting patients' results, are scarce. Moreover, they are often population- and instrument-dependent. We have measured free thyroxine (Free T(4)), total triiodothyronine (Total T(3)), thyroglobulin (Tg) and thyrotropin (TSH) in samples obtained from groups of newborns, children and adolescents. SUBJECTS AND METHODS: Blood samples collected from healthy children and teenagers (100 girls and 100 boys) of age groups ranging between 9-10, 11-14 and 15-17 years and selected randomly from a cohort representative of the Quebec population, were used. Samples from infants of age ranging between 1 day and 2 years (n = 99) were obtained from a hospital-based population with benign conditions unlikely to affect thyroid function. Variables were measured on the Access 2 immunosystem. RESULTS: Free T(4), Tg and TSH levels declined significantly with age. However, Total T(3) level presented a nonlinear variation with age, being lower in the first month of life.     

Suppressive effects of minocycline on the pituitary-thyroid axis in humans

Minocycline has been thought to induce “black thyroid”, a condition marked by discoloration due to brown deposits. However, its effect on thyroid function in humans is still obscure. We conducted a prospective study of thyroid hormone levels in 17 patients who were administered 200 mg minocycline daily for 10 days. We found that minocycline significantly reduced the serum total thyroxine level (8.43±0.61 to 7.09±0.45 μg/dl, mean ± SEM;P<0.01), and free thyroxine level (1.12±0.10 to 1.01±0.08 ng/dl, mean ± SEM;P<0.01). There was also a slight, but insignificant, elevation of thyroid stimulating hormone (TSH) in patients treated with minocycline. Similar suppression of thyroxine and free thyroxine was not observed in control patients treated with β-lactam and/or aminoglycoside antibiotics. Risk factors for the reduction in these thyroxine levels included age and a high serum baseline level of free thyroxine. We found a significant correlation between the free baseline thyroxine level and a reduction in free thyroxine after minocycline administration (Y=0.420X−0.377, r=0.597;P<0.01). Despite the observed alterations, the serum levels of all thyroid hormones after minocycline therapy were still within the normal range. This antibiotic does not appear to induce clinical hypothyroidism, yet given the results of this study, we would like to recommend pituitary-thyroid axis monitoring during the use of this antibiotic.     

Evaluation of UMELISA® T4 NEONATAL and UMELISA® T4 using polystyrene plates coated with anti-thyroxine (T4) monoclonal antibodies

Congenital hypothyroidism is one of the most common preventable causes of mental retardation. The Center of Immunoassay has developed the UMELISA® T4 NEONATAL and UMELISA® T4 to determine neonatal T4 levels in dried blood and serum samples. Both reagent kits use the same polystyrene plates coated with anti-thyroxine (T4) polyclonal antibodies as solid phase. This work shows the re-standardization of the UMELISA® T4 NEONATAL and UMELISA® T4 using plates coated with anti-T4 monoclonal antibodies (T4Mabs).

Polystyrene plates of the modified assays were firstly coated with polyclonal IgG sheep-anti-mouse IgG for 18 hours. T4Mabs were added to the plates and incubated for 2 hours at room temperature. Different performance parameters were evaluated and correlation studies with the commercial kits done.

Using polystyrene plates coated with T4Mabs increases the slope of the calibration curve in the clinical interest zone. The assay conjugates work twice diluted in respect to the ones of the commercial kits. Recovery percentages (90.8–110.7 for UMELISA® T4 NEONATAL and 92.1–109.3 for UMELISA® T4) and intra (7.2–7.6 for UMELISA® T4 NEONATAL and 6.9–7.2 for UMELISA® T4) and inter (7.4–8.5 for UMELISA® T4 NEONATAL and 7.1–8.5 for UMELISA® T4) coefficients of variation were similar to the ones described for the commercial kits. Limits of detection and quantification were 9.0 and 21.1 nmol/L for UMELISA® T4 NEONATAL, and 8.9 and 20.5 nmol/L for UMELISA® T4, respectively. The results also showed high overall concordance between assays (n = 244, r = 0.92, ρc = 0.91 for UMELISA® T4 NEONATAL and n = 492, r = 0.92, ρc = 0.9 for UMELISA® T4).

The analytical sensibility of UMELISA® T4 NEONATAL and UMELISA® T4 is improved by using polystyrene plates coated with T4Mabs, without affecting the precision and accuracy of the results.

Abbreviations: T4: L-Thyroxine; ELISA: Enzyme-linked immunosorbent assay; SUMA: Ultra Micro Analytic System; UMELISA: Ultramicro enzyme-linked immunosorbent assay; TSH: Thyroid-stimulating hormone.     

固相亲合素在游离甲状腺素免疫检测中的应用

目的：以亲合素－生物素分离技术为基础,尝试通过固化抗原（标记抗体）或固化抗体（标记抗原衍生物）两种免疫分析构型实现具有代表性的游离激素－游离甲状腺素（FT4）的固相免疫分析测定。方法：应用牛血清白蛋白－亲合素联接物制备固相亲合素,以此为基础制备固相生物素化甲状腺素衍生物或固相生物素化抗甲状腺素抗体,并分别用于标记抗体法或标记抗原衍生物法的FT4免疫分析。结果：标准曲线的四参数非线性拟合度良好;标记抗标法测定的灵敏度为0.42pmol/L,批内批间的CV％均小于7％,标记衍生物法的灵敏度为0.36pmol/L,批内批间的CV％均小于7％,两种方法相关性良好（r=0．9734,P＜0．01）。结论：通过应用固相亲合素固化抗原或固化抗体两种方式,进一步肯定了固相亲合素作为通用固相分离技术在免疫分析中的应用价值,为游离甲状腺素测定提供了实验 依据。