Effect of human and recombinant IFN-alpha and IFN-beta on the sister-chromatid exchange (SCE) frequency in amniotic fluid cells in vitro.

Sister-chromatid exchange (SCE) and rates of proliferation in human amniotic fluid cells from healthy donors exposed to human IFN-alpha and IFN-beta and recombinant IFN-alpha and -beta were investigated. Amniotic fluid cells were obtained from pregnant women undergoing genetic amniocentesis. For 46 h, cells were treated with IFNs at concentrations of 10(3)-10(5) U/l. A dose-depending decrease of SCE rate with IFN-alpha and IFN-beta was observed. Our studies in amniotic fluid cells show that the mean SCE frequencies are reduced after incubation with IFN-alpha as well as with IFN-alpha. In contrast to IFN-gamma, the type I IFNs IFN-alpha and IFN-beta cause a genetic effect on DNA repair or a protection from DNA damage. Previously we had shown that a significant dose-depending increase of SCE rates was found in amniotic fluid cultures after addition of IFN-gamma. Therefore, IFN-alpha and IFN-beta (both human IFNs) and also recombinant IFN-alpha and IFN-beta, also in high doses, are neither genotoxic/clastogenic nor embryotoxic. Amniotic cells are vulnerable human cells, which may be well suited for examining the effects of agents like interferon.

Hirschsprung disease: paternal transmission to a son.

Hirschsprung disease (HD) is genetically heterogeneous with approximately 4% familial occurrence. The recurrence risk is higher in patients with severe involvement. We describe the transmission of histotopochemically proven HD from a father with long aganglionic segment disease to a son with ultrashort segment disease. This observation suggests that the length of involvement in HD is related to the variable expression of the gene defect. It also suggests autosomal dominant inheritance of HD.

[Increased rate of sister chromatid exchange following therapy of acute lymphoblastic leukemias and non-Hodgkin lymphomas in childhood]. / Erhöhte Schwesterchromatidenaustauschrate nach Therapie kindlicher akuter lymphoblastischer Leukämien und Non-Hodgkin-Lymphome.

Sister chromatid exchanges rates (SCE) were studied in peripheral blood lymphocytes of 10 patients with acute lymphoblastic leukaemia (ALL) or leukaemic transformed non-Hodgkin-lymphomas (NHL) and in lymphocytes of 10 healthy juvenile donors (control). Following treatment the patient group has been in continuous complete remission for 11 months on the average. In the number of SCE's significant differences were found: 10,90/metaphases in the patients versus 7,56/metaphases in the controls. These results significantly show a long time influence of the treatment on the SCE rates, possibly inducing chromosome aberrations.

Monosomy 18p and pure trisomy 18p in a family with translocation (7;18).

A three generation pedigree is described in which there are two carriers of translocation t(7;18). Two members of the family have trisomy 18p and a stillborn child had monosomy 18p and holoprosencephaly. Another stillborn child probably had holoprosencephaly; the karyotype was not analysed. Based on this observation, the occasional occurrence of holoprosencephaly in monosomy 18p (10% of previously reported cases) may not be the result of the expression of a recessive mutant gene in the hemizygous state, as assumed up to now.

[Diagnostic possibilities of the function of the fetal thyroid gland by amniocentesis (author's transl)]. / Diagnostik der fötalen Schilddrüsenfunktion durch Amniocentese.

The assessment of fetal thyroid function by measurement of reverse triiodothyronine (RT3) in amniotic fluid (AF) seems to be a valuable diagnostic tool in detecting fetal hypothyroidism. The concentrations of RT3 were measured by radioimmunoassay in 346 samples of AF which were obtained by transabdominal amniocentesis. Among these, 323 were obtained from normal pregnancies between weeks 8 and 41 of gestation and the remaining 23 from various complications of pregnancy: Rh-isoimmune disease, Down's syndrome, Klinefelter's syndrome (XXY), M. Krabbe, and anencephaly. The highest concentrations of RT3 in AF were observed between weeks 15 to 20 of gestation, followed by a gradual decrease with advancing gestational age. In complicated pregnancies a similar distribution of RT3 values was found. It is suggested that RT3 in AF should be measured in order to assess fetal thyroid function whenever amniocentesis is performed between weeks 16 and 20 of gestation, in particular when hypothyroidism of the fetus is suspected.

[True XX/XY hermaphrotide, HY antigen positive, without detectable testicular tissue. Observation from birth to the age of ten years (author's transl)]. / Echter XX/XY hermaphrodit mit positivem H-Y-Antigen ohne aufgefundenes Testisgewebe. Beobachtung von Geburt bis zum 10. Lebensjahr.

A rare modification of true Hermaphroditism is demonstrated in a ten-year-old child we have observed since birth. The cytogenetic analysis revealed a XX/XY-mosaicism. Two kinds of origin are discussed: 1. an ovum with two nuclei was fertilized by two different sperm cells, 2. two heterosexual zygotes fused. -- We could not find tissue of the testes but confirmed the diagnosis of a hermaphroditism by the detection of the HY-antigen and by typical endocrinological findings. Two different cell populations found in erythrocytes and by GPT-isoenzymes indicated a chimerism. By knowledge of these findings, we could help the child to undergo a positive psychological and social development.

Chromosomal investigations in epileptic children during long-term therapy with phenytoin or primidone.

In epileptic children the long-term therapy with anticonvulsant drugs is absolutely necessary. However, anticonvulsant drugs have been suspected to be mutagenic and teratogenic. To investigate this problem metaphase chromosome observations were performed using short-time culture of peripheral blood lymphocytes from twenty children. Ten of the children had been treated with phenytoin and the other ten with primidone on monotherapy. The long-term administration of anticonvulsant drugs was monitored by measurement of the serum concentrations of phenytoin and primidone, by seizure anamnesis, and by repeated EEG investigations. Analyzing 100 mitoses from each proband, we found no increase of structural or numerical aberrations in our patients compared with six controls. In adults, however, anticonvulsant drugs have been found to cause structural aberrations and chromosomal damage. The absence of these lesions in children may reflect the higher efficiency of DNA-repair in local DNA-damage.

The dup(3q) syndrome: report of eight cases and review of the literature.

Clinical and cytogenetic examinations were performed on eight unrelated infants with duplication of part of the long arm of chromosome 3. A review of published cases shows a clinical syndrome characterized by statomotoric retardation, shortened life span, and a multiple congenital anomalies (MCA) syndrome of abnormal head configuration, hypertrichosis, hypertelorism, ocular anomalies, anteverted nostrils, long philtrum, maxillary prognathia, down-turned corners of the mouth, highly arched or cleft plate, micrognathia, malformed auricles, short, webbed neck, clinodactyly, simian crease, talipes, and congenital heart disease. The dup(3q) syndrome is a clinically easily recognizable entity.

[Prenatal diagnosis of trisomy 18 via hydramnion detected by echosonography (author's transl)]. / Pränatale Diagnose eine Trisomie 18 aufgrund eine echosonographisch nachgewiesenen Hydramnions.

Amniocentesis was prompted by an hydramnion which existed before the 30th week of pregnancy. Examination of amniotic fluid revealed trisomy 18 with increased alpha-fetoprotein values. Interruption of pregnancy was considered but refused by the patient. This enabled control fetal development during the subsequent weeks. After the patient has given birth to a dead female fetus in the 18th of pregnancy, pathological examination of the foetus confirmed the existence of trisomy 18.

[Diabetic ketoacidosis in children. Effectivity of therapy with small doses of insulin applicated intravenously versus conventional therapy (author's transl)]. / Diabetische Ketoazidosis im Kindesalter. Effektivität der Behandlung mit kleinen intravenösen Insulindosen im Vergleich zur herkömmlichen Therapie.

Since 1972, the treatment of diabetic coma, ketoacidotic or hyperosmolar, with regular infusions of low doses of insulin, is a well-established form of therapy. Pediatricians all over the world apply this regimen regularly since 1975. In contrast to this there is the regime of intravenous or intramuscular application of high doses of insulin. To control the effectivity of these two methods, we compared two approximately identical groups of patients and analysed 17 different parameters. The patients of the low dose insulin infusion regimen needed less insulin, potassium and bicarbonate and reached earlier a bloodglucose level of 300 mg/dl. They also had a rapid and uneventful restoration of their electrolyte metabolism. Hypoglycaemia did not occur. There was no significant hypokalaemia or hypernatraemia. In contrast to this, the conventionally treated group showed much more complications. The hospital stay and the daily requirement of insulin was significantly higher. We believe that the low dose infusion regimen of insulin is a safe and easy therapeutic method. It surely is an alternative way for treating diabetic coma.

Partial trisomy 13q21toqter de novo due to a recombinant chromosome rec(13)dup q.

A female is described who has a karyotype with an additional distal half of 13q in a recombinant rec(13)dup q chromosome. Since her parents have normal karyotypes, the origin of her karyotype is assumed to be a premeiotic pericentric inversion de novo with crossing-over within the inversion loop at meiosis. By means of various banding techniques, the breaks preceding the rearrangement could be located exactly. The joint between the duplicated segment and the satellites of the receptor chromosome is of special note. The phenotype of the patient stated at the age of 9 months and at the age of 7 1/2 years was found to be related to the segments involved in the partial trisomy. The clinical features were largely in accordance with previous case reports having an identical extent of the triplicated 13q segment.

Cranial morphology in the 18p-syndrome.

Three of four recently described children with the 18p- syndrome were reinvestigated using cranial computerized tomography (CCT). More severe deformities were found in the cases with severe cerebral malformation, but there was no correlation with the degree of mental retardation.

Trisomy 9p and unusual translocation mongolism in siblings due to different 3:1 segregations of maternal translocation rcp(9;21)(p11;q11).

Two sisters are described, each with a specific retardation syndrome due to a balanced reciprocal translocation 9p;21q in the mother. As a result of different 3:1 segregations, one of them has a trisomy 9p with all typical features; the other one reveals a typical Down's syndrome having an unusual translocation karyotype.