[Hyperprolactinemia and antipsychotics: it's not always what it seems to be]. / Jongeren met hyperprolactinemie bij antipsychoticagebruik: denk aan macroprolactine.

Hyperprolactinemia is a relatively frequent laboratory abnormality (30-80%) as a result of antipsychotics and a reason to reduce or stop them. We describe two youngsters with autism spectrum disorder whose hyperprolactinemia was based on a false-positive laboratory finding due to macroprolactin. The consequences were: unnecessary endocrinological evaluation including a brain MRI, and undesirable antipsychotic dose reduction. Thus, hyperprolactinemia can be due to a falsely elevated prolactin concentration. There should be an addition to the current guidelines in which a work-up for macroprolactin screening is included.

[Diagnostic image (361). A boy with headache and vomiting 2 days after a head injury]. / Diagnose in beeld (361). Een jongen met hoofdpijn en braken 2 dagen na een trauma capitis.

An 11-year-old boy presented 2 days after a head injury with headache and vomiting. There were no neurological abnormalities. CT of the head demonstrated a large epidural haematoma and a cranial fracture.

[Leukocyte-adhesion deficiency: a rare disorder of inflammation]. / Leukocytenadhesiedeficiëntie: een zeldzame erfelijke stoornis in de ontstekingsreactie.

In a 6-week-old male infant who was referred because of an umbilical hernia and a non-purulent omphalitis, type-I leukocyte-adhesion deficiency was diagnosed. Additional clues were persisting leukocytosis upon clinical improvement under antibiotic treatment and a late falling off of the umbilical remnant in the patient's history. After cure by antibiotic therapy, life-long antibiotic prophylaxis was prescribed. Leukocyte-adhesion deficiency syndromes are rare, autosomal recessive, hereditary immunological disorders. The basis of these disorders is found in the absence or defective function of adhesion molecules that are needed for an interaction between the leukocytes, especially neutrophilic granulocytes, and endothelial surfaces. On the basis of clinical signs and symptoms and laboratory findings, two types of leukocyte-adhesion deficiency can be distinguished. Type I is marked by a disorder in the migration of granulocytes through the endothelium, in which integrins are involved. In type II, there is a disorder in the first step in the adhesion of granulocytes to the endothelium, in which selectins are involved. These conditions already become manifest in childhood. Therapy is generally symptomatic and consists mainly of the prevention and treatment of infection. Cure is sometimes possible by means of allogenic bone-marrow transplantation.

Inhibition of T3-receptor binding by Nitrofen.

Lung development is controlled by various hormones, including thyroid hormone. The herbicide 2,4-dichlorophenyl-p-nitrophenyl ether (Nitrofen) induces lung hypoplasia in fetal rats, when administered to the mother during gestation. Nitrofen might be teratogenic by an anti-thyroid activity. The present study shows that Nitrofen decreases the binding of T3 to the alpha 1 and beta 1 form of the thyroid hormone receptor in a non-competitive way. Consequently, rat lung hypoplasia might result from the decreased binding of T3 to its receptor, via exposure to Nitrofen during fetal development.

Alveolar epithelial composition and architecture of the late fetal pulmonary acinus: an immunocytochemical and morphometric study in a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia.

The aim of the present study was to compare the architecture and alveolar epithelial cell composition of the pulmonary acinus in hypoplastic and normal fetal rat lungs. For this purpose, a rat model of pulmonary hypoplasia in association with congenital diaphragmatic hernia (CDH) induced by Nitrofen (100 mg on day 10 of pregnancy) was studied. Sections (5 microns) from lungs of control and Nitrofen-exposed fetal Sprague Dawley rats with or without CDH aged 18-22 days (vaginal plug on day 1, birth on day 23) were stained with hematoxylin and eosin. To identify developing alveolar epithelial cells, sections were incubated with anti-surfactant protein A (SP-A; rabbit anti-mouse) or preimmunization serum (indirect immunofluorescence). On days 18 and 19, control lungs and exposed lungs from fetuses with and without CDH looked similar (pseudoglandular stage of lung development). The prospective pulmonary acinus consisted of acinar tubules with small round lumens, lined by cuboid, fluorescent type II cells. Morphometric analysis on day 19 showed significantly smaller lung volumes and lung tissue volumes after Nitrofen exposure. On day 20 (canalicular stage), some tubules were slightly dilated and lined by cuboid and thinner fluorescent cells; these dilated tubules were less numerous in lungs from exposed fetuses with CDH. On days 21 and 22 (saccular stage), the saccular lining consisted of cuboid to thin fluorescent cells in exposed lungs from fetuses with and without CDH, and fluorescent (low) cuboid cells interspersed with dark zones (type I cell areas) in control lungs. In the exposed lungs from fetuses with CDH, the lumens of all airspaces were frequently slit-like, and the septa were thicker. These phenomena gave the lungs a primitive, compact aspect. Morphometric analysis on day 22 showed smaller lung volumes and lung tissue volumes, smaller airspace/tissue ratios, smaller epithelial surface areas, and more type II cells per surface area in Nitrofen-exposed lungs than in normal control lungs. The results suggest that Nitrofen-exposed, and thus hypoplastic, fetal rat lungs are retarded with respect to the differentiation of cuboid type II cells into squamous type I cells whether or not CDH is present, and with respect to the development of the future airspaces between days 20 and 22 if CDH is present.

Ultrastructural features of alveolar epithelial cells in the late fetal pulmonary acinus: a comparison between normal and hypoplastic lungs using a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia.

The aim of this study was to describe and compare the ultrastructural features and functional maturity of alveolar epithelial cells in hypoplastic and normal fetal rat lungs. Pulmonary hypoplasia in association with congenital diaphragmatic hernia was induced in fetuses by administration of 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) to pregnant Sprague Dawley rats (100 mg on day 10 of gestation). Lung tissue of Nitrofen-exposed and control fetal rats aged 19-22 days (vaginal plug day 1, birth day 23) was embedded in Epon. Semithin (1 micron) toluidine blue-stained sections were examined by light microscopy; ultrathin sections (approximately 80 nm) were studied via transmission electron microscopy. In bronchoalveolar lavage fluid from control and Nitrofen-exposed fetuses (day 22), phospholipid fractions and surfactant protein A content were measured semiquantitatively. On day 19 both control and Nitrofen-exposed lungs contained only cuboid alveolar epithelial cells; from day 20 there were cuboid, low cuboid, and thinner epithelial cells. The (low) cuboid cells contained large glycogen fields, some precursory stages of multilamellar bodies (MLBs), and just a few mature MLBs on day 19 and 20; smaller glycogen fields, more precursory stages, and more mature MLBs on day 21; and little or no glycogen but many precursory stages and mature MLBs on day 22. The thinner cells contained little or no glycogen and a few precursory stages of MLBs on days 20-22; very thin cells on day 22 contained neither glycogen nor any precursory stages of MLBs. MLBs and tubular myelin were seen in the lumens of future air spaces from day 20 onward. Nitrofen-exposed lungs differed from control lungs in that inclusion bodies (IBs) were less numerous in (low) cuboid alveolar cells on days 19 and 20, and more glycogen was seen on day 22. In addition intra- and extracellular "MLBs" in exposed lungs more often had an unusual appearance, i.e., a confluent structure and higher electron density. However, despite morphologic differences, there was no clear difference in phospholipid composition and SP-A content per mol phospholipid in bronchoalveolar lavage fluid. We conclude that morphologically hypoplastic lungs are less mature near term, without an apparent effect on surfactant composition.

Accumulation of aluminium in rat liver: association with constituents of the cytosol.

Aluminium (Al) accumulation occurs in the liver of renal patients and in patients on parenteral nutrition. Human hepatotoxicity is not proven. The role of the liver in storage and biotransformation of Al and in development of osteo- and neurotoxicity is not clarified as yet. The aim of the present investigation was to study the storage of Al in total liver and in subcellular liver fractions, and its association with soluble cytosolic molecular species. Therefore, rats were loaded with Al prior to liver fractionation by ultracentrifugation, and equilibrium gel filtration chromatography of the cytosol, using a previously described method for Al speciation in serum. Al accumulated dose-dependently in liver and subcellular liver fractions, the lowest levels occurring in the cytosol. A dose-dependent elevation of Al in the blood was also observed. Gelfiltration of the cytosol indicated that Al was associated with a low molecular weight form which was not a citrate complex, and a high molecular weight form, which was larger than transferrin. No induction of and association with metallothionein occurred.