[Iodine deficiency in infancy - a risk for cognitive development]. / Jodmangel im Säuglingsalter - ein Risiko für die kognitive Entwicklung.

Severe iodine deficiency during pregnancy seriously influences fetal brain development and in the worst case induces cretinism. Recent studies have shown that even a mild iodine deficiency during pregnancy and during the first years of life adversely affects brain development. The World Health Organisation (WHO) considers iodine deficiency as the most common preventable cause of early childhood mental deficiency. In this context, the insufficient production of the four iodine atoms containing thyroxine seems to play a causal role, i. e., due to the iodine substrate deficiency the neuronally particularly relevant free-thyroxine level falls. Due to the very limited iodine storage capacity, the infantile thyroid is eminently dependent on an adequate and steady iodine supply. In the first month of life, when milk is the only energy- and nutrient provider, infants fed a commercial formula regularly have a sufficient iodine supply. However, breastfed infants, who depend on maternal iodine status, frequently show an inadequate iodine intake. Furthermore, iodine intake is critical when complementary food (CF) is introduced. Especially homemade CF is poor in iodine, but also commercial CFs are only partly fortified. A simultaneous inadequate iodine supply of the breastfeeding mother and the preferential use of mostly iodine-poor organic milk cannot ensure an adequate iodine supply of the infant. In terms of an improvement of nutrient supply, especially concerning an unhindered brain development, the corresponding German reference value for iodine intake of infants until age 4 month should be raised from currently 40 microg/d to at least 60 microg/d (WHO-reference: 90 microg/d).

Selenium supplementation does not decrease thyroid peroxidase antibody concentration in children and adolescents with autoimmune thyroiditis.

In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab) concentrations in patients with autoimmune thyroiditis (AIT). Our aim in this study was to investigate if selenium supplementation decreased TPO Ab and thyroglobulin antibody (Tg Ab) concentrations in children with AIT. Forty-nine patients (33 females) with newly diagnosed AIT and hypothyroidism were randomized to daily oral therapy with levothyroxine alone (group A, n=18), levothyroxine plus 100 microg sodium-selenite (group B, n=13), or levothyroxine plus 200 microg sodium-selenite (group C, n=18). Mean age at diagnosis was 12.2+/-2.2 years. All 49 patients needed a mean levothyroxine dose of 1.6+/-0.5 microg/kg body weight to lower TSH to the treatment goal of 1-2 microU/ml, with no significant difference between groups. At study entry and after 12 months, TPO Ab concentrations were comparable in all three groups. Tg Ab concentrations decreased significantly after 12 months in group A and group C (p=0.03 and p=0.01), but not in group B (p=0.06). It is our conclusion that selenium supplementation with sodium-selenite does not decrease TPO Ab concentrations in children and adolescents, neither given in the reduced dose of 100 microg daily nor given in the "adult" supplementation dose of 200 microg daily.

[Thyroid disorders during pregnancy]. / Schilddrüsenerkrankungen in der Schwangerschaft.

Thyroid disorders may not only be the cause infertility but also increases the incidence of miscarriages and the morbidity of the pregnancies. During pregnancy the demand of thyroid hormones increases to about 30 - 50 % and the thyroid has to cope with this increase. In Germany the iodine intake has improved significantly during the last 20 years, but still is borderline low with an mean intake of about 120 microg iodide per day. Therefore it is still recommended that pregnant women are supplemented with about 100 - 150 microg of iodide during pregnancy and the time of breast-feeding, to avoid hypothyroidism of the foetus with concomitant delay of the brain development. Not only women with subclinical hypothyroidism, but only elevated TPO antibodies have a significant increase in early miscarriage and preterm delivery. An early supplementation with Levothyroxin despite euthyroidism might reduce these risks. Those women also more frequently develop postpartum thyroiditis. This risk can be reduced by a supplementation with selenium during and after pregnancy. Graves' disease is a rare disorder and only about 0,1 - 0,4 pregnancies are affected. The course of the disease is biphasic, with an exacerbation within the first trimester and an improvement thereafter, but a recurrence after delivery. Overt thyrotoxicosis has to be treated with propylthiouracil, to maintain euthyroidism during pregnancy. The TSH receptor antibodies are transferred to the foetus with the risk of thyrotoxicosis. Special care of the foetus is therefore necessary. Transient mild hyperthyroidism may occur in women with very high HCG levels during the first three months of pregnancy. This often is associated with hyperemesis gravidarum. Subclinical hypothyroidism of the mother will disturb the normal development of the foetus and therefore has to be treated even when TSH is within the upper normal level. Special care is necessary in women with elevated TPO antibodies, because these more often develop postpartum thyroiditis.

[Is iodine deficiency still relevant?]. / Das Ziel der WHO wurde verfehlt. Immer noch Jodmangel in Deutschland.

In Germany, iodine deficiency and its consequences is still a problem, although it is of less importance than it was twenty years ago. In accordance with the WHO definition, Germany still belongs among those countries with mild iodine deficiency and too low an intake of iodine. As a result groups at particular risk, such as pregnant and nursing women, must still receive iodine supplementation, since, in the absence of supplemental iodine,the amount of iodine in the mother's milk continues to be below average throughout Germany. Both in private households and in the food industry, the aim is to increase the use of iodized salt to more than go%. This entails no risk of an iodine overdose. The current average daily uptake of iodine of approximately 120 micrograms is responsible neither for the development or progression of an autoimmune disease nor a functional disorder of the thyroid gland.

Influence of iodide and iodolactones on thyroid apoptosis. Evidence that apoptosis induced by iodide is mediated by iodolactones in intact porcine thyroid follicles.

Iodine induced thyroid involution is caused by apoptosis rather than necrosis. This effect of iodide on apoptosis of thyroid epithelial cells may be not a direct one but mediated by iodinated derivatives i.e. of polyunsaturated fatty acids, especially of iodolactones, which have previously shown to inhibit thyroid cell proliferation. We studied the influence on apoptosis of iodide (2 microM and 20 microM) and iodolactone (0.05 microM and 0.5 microM), with and without TSH (1 mU/ml), using a well characterized ex vivo- culture system of intact porcine thyroid follicles in three-dimensional culture. Apoptosis and necrosis was evaluated by electron-microscopy. Stimulation with 2 and 20 microM iodide rapidly induced a rate of apoptosis (4 - 6 %) comparable to about 40-fold lower doses of delta-iodolactone (0.05 microM and 0.5 microM). Addition of TSH (1 mU/ml) caused a slight but not significant further increase of the incidence of apoptotic cells. The rate of necrotic thyroid epithelial cells (1 - 2 %) was similar in all experiments. As delta-iodolactone in very low concentrations--comparable to iodide in higher concentrations--not only inhibits growth but also induces apoptosis, it has to be supposed that the effect of iodide is mediated by this iodinated compound. However, further experiments are necessary to confirm this hypothesis. In addition it could be demonstrated, that apoptosis is a very rapid and limited process in intact follicles. This also may explain, why iodine supplementation even in high doses does not lead to thyroid atrophy but only normalisation of thyroid size. These results confirm that apoptosis is an important regulated and limited mechanism in goiter involution.

The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn and trauma.

Patients with systemic inflammatory response syndrome (SIRS) and sepsis exhibit decreased plasma selenium and glutathione peroxidase activity. This has been shown in several clinical studies. Moreover, the degree of selenium deficiency correlates with the severity of the disease and the incidence of mortality. Patients with SIRS and sepsis are exposed to severe oxidative stress. Selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and are involved in the regulation of inflammatory processes. Therefore, selenium substitution in those patients might be effective in the prevention of multiorgan failure. The results of randomised clinical trials investigating selenium substitution in critical ill patients with inflammation are reviewed. In two independently performed randomised, prospective clinical trials, including patients with systemic inflammatory response syndrome or sepsis, the supplementation of selenium revealed a significant reduction in multiorgan failure and, especially, a lower incidence of acute renal failure and respiratory distress syndrome. One of those trials also could demonstrate a significant reduction of mortality in the most severely ill patients. Two other studies, where selenium together with other trace elements or a mixture of antioxidants were used in the treatment of patients with severe burn injuries or trauma showed a significant reduction in the secondary infection rate, including sepsis. Thus, selenium supplementation seems to improve the outcome of patients with SIRS, sepsis and severe injury, however, pivotal prospective clinical trials with sufficient statistical power are now necessary to finally prove the efficacy of a selenium supplementation in these diseases.

Selenium in biology: facts and medical perspectives.

Several decades after the discovery of selenium as an essential trace element in vertebrates approximately 20 eukaryotic and more than 15 prokaryotic selenoproteins containing the 21st proteinogenic amino acid, selenocysteine, have been identified, partially characterized or cloned from several species. Many of these proteins are involved in redox reactions with selenocysteine acting as an essential component of the catalytic cycle. Enzyme activities have been assigned to the glutathione peroxidase family, to the thioredoxin reductases, which were recently identified as selenoproteins, to the iodothyronine deiodinases, which metabolize thyroid hormones, and to the selenophosphate synthetase 2, which is involved in selenoprotein biosynthesis. Prokaryotic selenoproteins catalyze redox reactions and formation of selenoethers in (stress-induced) metabolism and energy production of E. coli, of the clostridial cluster XI and of other prokaryotes. Apart from the specific and complex biosynthesis of selenocysteine, selenium also reversibly binds to proteins, is incorporated into selenomethionine in bacteria, yeast and higher plants, or posttranslationally modifies a catalytically essential cysteine residue of CO dehydrogenase. Expression of individual eukaryotic selenoproteins exhibits high tissue specificity, depends on selenium availability, in some cases is regulated by hormones, and if impaired contributes to several pathological conditions. Disturbance of selenoprotein expression or function is associated with deficiency syndromes (Keshan and Kashin-Beck disease), might contribute to tumorigenesis and atherosclerosis, is altered in several bacterial and viral infections, and leads to infertility in male rodents.

[Significance of selenium in intensive care medicine. Clinical studies of patients with SIRS/sepsis syndrome]. / Die Bedeutung von Selen in der Intensivmedizin. Klinische Studien bei Patienten mit SIRS/Sepsis.

Selenium is an essential component of the intracellular antioxidant system as a structural component of the active center of the glutathione peroxidase enzymes. These selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and selenium seems to play a direct role in the regulation of inflammatory processes. In conditions of systemic inflammatory response or sepsis, patients are exposed to severe oxidative stress. These patients already have both, a decreased plasma selenium and glutathione peroxidase activity at admission to the ICU as has been shown in several studies. The degree of selenium deficiency is correlated with the severity of disease and the incidence of mortality. The reason for the low plasma selenium levels is unknown. Especially it would be of interest a) if the low plasma selenium is the consequence of the systemic inflammatory response with distribution of selenium in other compartments of the body, b) most important, whether the substitution of selenium might improve the outcome and decrease the mortality rate of these patients. In 2 independently performed intention-to-treat studies including patients with systemic inflammatory response syndrome or sepsis a beneficial effect of selenium supplementation on multiple organ function and outcome could already be demonstrated as well as a tendency of an improved mortality rate. A prospective analytical study clearly could demonstrate the inverse relationship between low plasma selenium and morbidity and mortality of patients with SIRS/sepsis. The results of these studies are so convincing, that we propose a randomized, prospective, double blind multicenter phase-III study including patients with systemic inflammatory response syndrome or sepsis to investigate, whether a high-dose selenium substitution in addition to the recommended treatment strategies for patients with sepsis improves outcome and mortality rate of these patients.

Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

BACKGROUND: Accelerated bone loss is a well-recognized complication after cardiac transplantation (HTx) due to immunosuppressive therapy. The purpose of this prospective, longitudinal, randomized, placebo-controlled, double-blind study was to investigate the effect of calcitriol (1,25-dihydroxyvitamin D3) in the prevention of bone loss and fracture rate after HTx. METHODS: Basic therapy included 1000 mg of calcium daily and sex hormone replacement in hypogonadal patients. A total of 132 patients (111 male, 21 female; mean age: 51+/-10 years; 35+/-25 months after HTx) were randomized to 0.25 microg of calcitriol or placebo. Bone mineral density (BMD, g/cm2; T score, %) of the lumbar spine and x-rays for the assessment of vertebral fractures were performed at baseline and after 12, 24, and 36 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall BMD was significantly decreased after HTx (T score 87+/-13%). BMD increased continuously within the study period in the calcitriol group (1 year: 2.2+/-4.8%; 2 years: 3.9+/-5.4%; 3 years: 5.7+/-4.4%) as well as in the placebo group (1 year: 1.8+/-4.9%; 2 years: 3.7+/-6.5%; 3 years: 6.1+/-7.8%) without statistical difference between the groups. Fracture incidence was low during the study interval (1 year: 2.0%; 2 years: 3.4%; 3 years: 0%). Hypogonadism (20%) was associated with a lower BMD (78+/-12% vs. 88+/-12%; P<0.01) and a higher increase (35%) after hormone replacement in comparison to normogonadal patients. Increased intact parathyroid hormone and bone resorption markers decreased significantly during therapy. CONCLUSIONS: Calcium supplementation and sex hormone replacement in hypogonadism proved a sufficient long-term prevention therapy to improve decreased BMD and to prevent fractures after HTx. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role in the long-term bone loss and should therefore be monitored and treated adequately. Low-dose calcitriol demonstrated no significant extra benefit regarding BMD and fracture rate in the long-term period after HTx.

Influence of knowledge on iodine content in foodstuffs and prophylactic usage of iodized salt on urinary iodine excretion and thyroid volume of adults in southern Germany.

Thyroid volume, urinary iodine excretion as well as personal nutritional knowledge and individual iodine prophylaxis were determined during a health education program on iodine deficiency and prophylaxis in 1992. Participants were 472 male and 568 female (mean age 27.7 years) students and employees of five universities in the southern part of Germany. The study aimed to clarify the relationship between personal knowledge on iodine, individual iodine prophylaxis and parameters of iodine deficiency (thyroid volume, iodine excretion) in a well known iodine deficient area. Mean thyroid volume (mean +/- SD) was 19.7 +/- 8.3 ml in males and 15.8 +/- 7.1 ml in females. 25.5% of females and 19.9% of males showed thyroid volume above the upper normal values. Total mean urinary iodine excretion was 70.7 +/- 42 micrograms I/g creatinine reflecting WHO-grade-I iodine deficiency. 80.8% of total subjects used iodized salt and 43.2% stated to consume salt-water fish to meet their iodine requirement. The female non-users had significantly lower iodine excretion (no iodized salt, no salt-water fish: 61.4 +/- 31.3 vs. +iodized salt, +salt-water fish: 83.9 +/- 47.6 micrograms I/g creatinine; p < 0.05), however, thyroid volume was identical in these groups. The area of residence over the last 10 years did not significantly influence the thyroid volume. The goiter incidence increased with age. Although our study population was highly educated (81.8% students) and the subjects were provided with educational brochures immediately prior to the study, knowledge about iodine content of food was poor. We conclude that despite a high degree of voluntary iodine prophylaxis and educational programs the iodine intake is insufficient. The use of iodized salt in households, cafeterias, and also in food manufacturing must be increased for sufficient iodine prophylaxis.

[Chemical burns of the hand and upper limb: therapeutic approach]. / Brûlures chimiques de la main et du membre supérieur: conduite à tenir.

Clinical burns of the hand and the upper limb induce various lesions, depending on the degree of tissue penetration and their aggressive properties; strong acids, particularly sulfuric acid and strong bases such as lime are the most dangerous. The clinical attitude should be surgical. Early skin excision, as economic as possible, will be indicated, taking into account the difficulties of precisely determining the limit between normal and necrotic tissues; fluorhydric acid, rapidly dissociates into H+ and Fl- which, because of its small size, will rapidly penetrate deeply into the blood circulation. Moreover this molecule has the peculiar power to provoke marked hypocalcemia able to cause death, due to its avidity for Ca++, with a subsequent cellular lysis. There is currently an increase in domestic accidents, as fluorhydric acid is present in several scouring solutions; in every case of chemical burns, the main treatment remains emergency washing with water possibly, followed by a specific neutralization; skin excision must be the rule when the power of neutralization is limited, because of the risk of progressively deepening lesions due to the presence of residual scouring solutions.

Control of nutritional secondary hyperparathyroidism in grazing horses with calcium plus phosphorus supplementation.

A supplement system for the control of equine nutritional secondary hyperparathyroidism (NSH) was evaluated on 4 farms in the Arcadia Valley of the Queensland brigalow region. Thirty-three local stock horses (of which 13 had clinical NSH and 7 were recent introductions) were grazed on buffel grass (Cenchrus ciliaris) for the 6 months from September 1979 to February 1980. Each horse was fed 1.0 kg of a mixture of ground limestone plus dicalcium phosphate (1:2) in 1.5 kg molasses each week. The pasture was hazardous during this time (total oxalate content above 0.5% and calcium: oxalate ratio below 0.5), but no new NSH cases occurred and those horses with clinical NSH improved, most becoming normal. After the first 6 months of supplementation, 3 new cases occurred on one farm. Doubling of the supplement dose and substituting rock phosphate in molasses for the previous mixture corrected the problem. The breakdown was thought to be partly because the supplement dose was slightly inadequate and partly because of behavioural factors.

The family life cycle: developmental crises and their structural impact on families in a community mental health center.

A typology for troubled families was developed based on the configuration of family members and the position of the identified patient within the family structure. This typology was investigated by surveying the demographic and clinical characteristics of 110 families of patients treated in a day hospital. Four types or "constellations" were found in the sample population. The families in the four Constellations differed significantly from one another in the gender, age, and diagnoses of the identified patient and the income level of the families. The Constellations thus appeared to constitute distinct clinical entities in the population studied. The reasons for the differences among Constellations are discussed in terms of the stress families experience during developmental crises involving structural change.

The effect of potassium on the sodium requirements of growing steers with and without alpha-tocopherol supplementation.

1. Hereford steers, housed in concreted yards and given demineralized water, were offered ad lib. a low-sodium (0.07 g Na and 4.5 g potassium/kg) basal diet of sorghum grain, urea and minerals, to which 0, 15 or 30 g K as KHCO3/KG diet had been added. Mean daily intakes of K were 26, 107 and 168 g/steer respectively. 2. The steers were given daily supplements of 0, 3.25 or 6.50 g Na as NAHCO3/steer, added to the food; mean daily intakes of Na (food plus supplemental NaHCO3 minus residues) were 0.41, 3.06 and 6.26 g/steer respectively. 3. Rate of gain of body-weight was positively related to the rate of Na supplementation and negatively related to the K content of the diet, but there was no interaction between Na and K contents of the diet. 4. the Na:K ratios for the parotid saliva from steers not given Na supplements was 0.3, whereas steers ingesting either 3.1 or 6.3 g Na/d had Na:K ratios of about 12. Increasing the amount of K in the diet had no consistent effect on the saliva Na:K ratio. The Na:K ratios for rumen fluid reflected changes in the saliva Na:K ratio in response to Na supplements and were inversely related to the amount of K in the diet. 5. The width of the adrenal zona glomerulosa from steers receiving the basal diet, without Na supplements, was significantly greater than that from steers given the Na supplements, but it was not affected by the amount of K in the diet. 6. Both Na supplements and the diet containing 30 g added K/kg significantly increased the Na:K ratio of the plasma. 7. The addition of 200 mg DL-alpha-tocopheryl acetate/steer per d to the diet had no significant effects on the growth rate of the steers. 8. It was concluded that the Na requirement of steers for growth was not signficantly affected by the amount of K in the diet up to 168 g/d.