Hepatic failure with neonatal tissue siderosis of hemochromatotic type in an infant presenting with meconium ileus. Case report and differential diagnosis of the perinatal iron storage disorders.

We report on a female preterm infant with hepatic failure and neonatal tissue siderosis of hemochromatotic type diagnosed by using both histochemistry and atomic absorption spectroscopy. The infant presented with meconium ileus, signs of rapidly progressive hepatic failure, and hyperferritinemia (7132 ng/ml). Despite surgery and intensive care the infant died 32 days after birth. Postmortem examination showed a wrinkled liver with extensive collapse of the hepatic architecture and regenerating nodules as well as hepatic and extrahepatic iron accumulation of hemochromatotic type, sparing the reticuloendothelial system. Atomic absorption spectroscopy confirmed an increase in the iron content of various organs: liver, heart, pancreas, oral salivary gland, kidney, and adrenal gland. The increase in the iron content of various organs was determined by comparing the analysis of the propositus with those of 5 gestationally age-related preterm infants who had died in the intensive care unit: 2 died of meconium aspiration syndrome, the other 3 of hyaline membrane disease, bronchopulmonary dysplasia, and immaturity, respectively. We also compared the analysis of 15 fetuses having a a condition predisposing to iron accumulation (trisomy 21, trisomy 18, cytomegalovirus, amnion infection syndrome, Rhesus- and ABO-incompatibility, congenital hemolysis, anti-phospholipid syndrome, congenital heart disease). Delta F508, the most frequent mutation seen in cystic fibrosis patients, was excluded by gene sequencing. Different noxae causing iron accumulation in the neonatal period have led to the statement that neonatal hemochromatosis may collect different etiologies, such as metabolic disorders, infections, chromosomal aberrations, and immunological disorders. In this study, we report the singular evidence of neonatal iron accumulation of hemochromatotic type in an infant presenting with meconium ileus and propose a classification of the neonatal disorders associated with iron accumulation.

[Reference values of Na(+) and Cl(-) concentrations in adult sweat]. / Untersuchungen zum Referenzbereich der Na(+)- und Cl(-)-Konzentrationen im Schweiss Erwachsener.

The results of the investigations to reference values for Na(+)- and Cl(-)-concentrations in sweat of adults are as follows: The normal range of electrolyte values in sweat in adults is up to 70 mmol/l (Na+) and 55 mmol/l (Cl-) respectively in infants (40 mmol/l for Na+ and Cl-). There are no sex and age differences. Adults with chronical bronchitis and bronchiectasis don't show different results in comparison with healthy persons. Adults with cystic fibrosis have significantly increased sweat electrolyte concentrations (90-120 mmol/l). Variations in the electrolyte values of a day or of a month are important and much higher than the analytical one.

[Alloxan induced long term diabetes in the domestic pig. I]. / Alloxaninduzierter Langzeitdiabetes beim Hausschwein. I. Mitteilung.

An insulin-deficient diabetes of long duration was induced by intravenous injection of alloxanmonohydrate (200 mg/kg and 100 mg/kg body mass, respectively) in 23 pigs (Landrace, Duroc) of 20-44 kg body mass. The dose of 200 mg/kg body mass was too high and there were fatal outcomes only. With the dose of 100 mg/kg and an initial body mass of 30-35 kg it is possible to induce a chronic diabetes mellitus in the pig. As complications we observed intoxications caused by alloxan, hypoglycemic situations from the 6th hour after application of alloxan with possible hypoglycemic damages, and septic complications by the intravenous catheter. Five out of 23 animals are still alive, 2 animals for 31 months and the others for 19 months. All the living animals have plasma glucose levels between 11 and 17 mmol/1 with very low values of plasma insulin. The serum triglycerides increased slightly in some cases, but not the serum cholesterol. The weight gain is retarded.

[Peripheral thyroid function and TRH-TSH test in patients with acromegaly]. / Periphere Schilddrüsenfunktion und TRH-TSH-Test bei Patienten mit Akromegalie.

In 11 patients with acromegaly the peripheral thyroid hormones were determined and a TRH-TSH-test was carried out. Depending on the result of the determination of the growth hormone the patients were classified into two groups (active and inactive acromegaly). The serum thyroxin level and the T3-binding capacity were normal. Only in a few patients decreased triiodotyronine levels were found. Independent of the degree of activity of the acromegaly positive as well as negative TRH-TSH-tests were found. The struma in patients with acromegaly which is frequently to be observed seems to be in a causal connection with this disease. The examination show altogether that the control of the function of the thyroid gland and the TRH-TSH-test do not deliver an essential contribution for the diagnostics of acromegaly itself.

[Understanding disorders in the regulatory cycle of the thyroid. Significance for diagnosis and therapy]. / Erfassung von Störungen im Regelkreis der Schilddrüse. Bedeutung für Diagnostik und Therapie

In the regulating circle for the regulation of the functions of the thyroid gland interactions exist between hypothalamus, anterior lobe of the pituitary gland, thyroid gland and the concentrations of the thyroid hormone at the periphery. By means of the TRH-test the secretory work of the thyrotropic function of the hypophysis depending on the activity of the thyroid hormone can be judged. On the other hand, the T3-suppression test (radioiodine test before and after application of T3) allows a statement on the hypophyseal-thyroidal regulation. In contrast to the exclusive determination of the peripheral thyroid hormones by means of the TRH-test an etiologic differentiation of hypothyreoses and an essential improvement in the diagnosis and conduction of the therapy of thyroidal diseases and functional disturbances is made possible, as it is demonstrated at instances. By means of the T3-suppression test it is possible to establish, still under the treatment of a diffuse hyperthyreosis, whether the function of the thyroid gland is again regulated by the hypophysis or is still autonomous. Together with the result of the TRH-test decisions may be rendered on the end of the treatment or on the further course of the therapy.

[Adaptation of lipogenic enzymes of liver and adipose tissue to starvation and refeeding (author's transl)]. / Adaptation lipogener Enzyme der Leber und des Fettgewebes an Hunger und Wiederfütterung in Abhängigkeit vom Alter.

The lipogenic enzymes-6-phosphate dehydrogenase, citrate cleavage enzyme and malic enzyme of both liver and adipose tissue of rate of the wistar strain show a diminished activity in dependence on age. In the liver exists no age difference of the characteristic adaptation under the conditions of starvation and refeeding, but in adipose tissue of 18 months old rats the lipogenic enzymes show a poorer elevation of activity during refeeding after a 48 h period of starvation than in 3 months old animals. The serum inulin level and his variation in starvation and refeeding are independent of age.

Insulin secretion in maturity-onset-diabetes. Function of isolated islets.

An impaired insulin response to glucose is a characteristic finding in maturity onset diabetes (MOD). To clarify whether the decreased insulin response in vivo is related to a primary defect of the beta-cells, isolated islets of MOD - obtained by intraoperative biopsy - were examined for their insulin content, biosynthesis and release. The in vitro experiments showed that despite a missing or significantly reduced insulin response in vivo the isolated beta-cells of the same patients had a normal insulin content, a normal or even high biosynthesis, and insulin release could be induced by glucose. These results suggest that the primary defect in MoD cannot be related to an intrinsic failure of the beta-cells to response to glucose; extrapancreatic factors seem to influence their reaction to glucose. These factors may be of a higher level in those patients or the reaction of the beta-cells is more inhibited by the same concentrations in diabetic patients.

[Endocrine and exocrine functional disorders in pancreatic diabetes]. / Endokrine und exokrine Funktionsstörungen beim Pankreasdiabetes.

In diabetic diseases of pancreatic origin we find three typical patterns of insulin secretion. The different insulin secretion allows a clear distinction of a diabetes of the maturity onset type and of the juvenile onset type type on the one hand and of a diabetes caused by a pancreatitis on the other hand. In a pancreatitis we see the expected reduction of the exocrine function. In the so called maturity onset diabetes a slight reduction of excretory functions could be seen. These results suggest that in maturity onset diabetes only a selective defect of the beta-cells exists, while in juvenile onset diabetes a destruction or reduction of beta-cells but an intact excretory function may be assumed.

Diminished insulin response in highly trained athletes.

Insulin secretion and glucose tolerance were examined in 6 highly conditioned athletes in comparison with a control group of 115 normal healthy persons. During glucose infusion the athletes showed low insulin secretion although there was no difference in the levels of blood glucose compared to the control group. It is concluded that under physiologic conditions the extent of insulin secretion is not dependent only upon the blood glucose levels. The results show that a lack of insulin response can occur as a consequence of adaption to physical training. A reduced insulin response, therefore, does not necessarily indicate a diabetic or prediabetic state.

[Behavior of the lipid and carbohydrate metabolism in patients with hypertriglyceridemia during exertion]. / Verhalten des Fett- und Kohlenhydratstoffwechsels bei Patienten mit Hypertriglyzeridämie unter körperlicher Belastung.

In pateints with hypertriglyceridaemia in rest and during ergometer load an increased rate of lipolysis with increased metabolism of free fatty acids could be proved. This led to a disturbance of the glucose tolerance with hyperinsulinism and during muscle work to a limitation of the capacity of the oxidative glucose metabolism in musculature.

[The effect of physical training on lipid parameters in the blood]. / Einfluss des körperlichen Trainings auf Fettparameter im Blut.

Physical training leads to an improved metabolic capacity of musculature. At the same time through a decreased liberation of catecholamines a reduction of the increased lipolysis develops. The two factors together condition an improved glucose tolerance and a decrease of the reactive insulin secretion. Thus, among others, the synthesis of triglycerides is reduced and an essential factor of risk is favourably influenced for the development of arteriosclerosis.

[Control of therapy for hyperthyroidism. Comparison of in-vitro and in-vivo methods]. / Therapiekontrolle der Hyperthyreose Vergleich von In-vitro- und In-vivo-Methoden.

55 patients with treated hyperthyroidism (thyreostatics) underwent a T3 suppression test and a TRH stimulation test. 60% of the patients had a positive and 40% a negative T3 suppression test. While patients with a positive T3 suppression test always showed a positive TRH test, the behaviour of the TRH test in negative suppression test was different (68.2% positive, 31.8% negative). These discrepant findings are to be explained from the establishment of different phases of regulation. In negative TRH test the concentrations of hormones were significantly higher. Increased basal TSH values are an expression of an overtreatment with thyreostatics. In positive suppression test and TRH test after a therapy lasting at least one year the medication can be stopped. In negative suppression test, however, the therapy should be changed. The TRH test allows only evidence about the quality of the regulation of therapy. Finally it can be established that the two tests on account of their different working points in the regulatory system are necessary and not changeable between each other.

[Diagnostic staged program in thyroid diseases]. / Diagnostisches Stufenprogramm bei Schilddrüsenerkrankungen

After some physiological principal remarks the modern possibilities of the in-vitro-diagnostics specific for the thyroid gland are briefly explained. The essential factors of disturbance which are necessary for the avoidance of false interpretations are mentioned. From the sequence of the description (BEJ, T4-test, T3-test, FT4-index, RIA-T3 and RIA-TSH) results the diagnostic step programme proposed by us, by means of which the majority of the functional disturbances of the thyroid gland existing may certainly be classified. Only after exhaustion of the in-vitro-diagnostics the radio-iodine-test should be performed.