Prenatal diagnosis of mosaic tetrasomy 5p.

We report the prenatal diagnosis of a fetus with tetrasomy 5p mosaicism resulting from a supernumerary isochromosome for the short arm of chromosome 5. The pregnancy was terminated and fetal autopsy revealed minor facial abnormalities (long philtrum, up-slanting palpebral fissures and a broad nasal bridge). Cultures were established from fetal skin, kidney, and pancreas for cytogenetic analysis; the i(5p) was observed only in the skin fibroblasts. To our knowledge, this is the fourth report of mosaic tetrasomy 5p and the first report of prenatal diagnosis of this abnormality.

Immunological quantitation and localization of ACAT-1 and ACAT-2 in human liver and small intestine.

By using specific anti-ACAT-1 antibodies in immunodepletion studies, we previously found that ACAT-1, a 50-kDa protein, plays a major catalytic role in the adult human liver, adrenal glands, macrophages, and kidneys but not in the intestine. Acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in the intestine may be largely derived from a different ACAT protein. To test this hypothesis, we produced specific polyclonal anti-ACAT-2 antibodies that quantitatively immunodepleted human ACAT-2, a 46-kDa protein expressed in Chinese hamster ovary cells. In hepatocyte-like HepG2 cells, ACAT-1 comprises 85-90% of the total ACAT activity, with the remainder attributed to ACAT-2. In adult intestines, most of the ACAT activity can be immunodepleted by anti-ACAT-2. ACAT-1 and ACAT-2 do not form hetero-oligomeric complexes. In differentiating intestinal enterocyte-like Caco-2 cells, ACAT-2 protein content increases by 5-10-fold in 6 days, whereas ACAT-1 protein content remains relatively constant. In the small intestine, ACAT-2 is concentrated at the apices of the villi, whereas ACAT-1 is uniformly distributed along the villus-crypt axis. In the human liver, ACAT-1 is present in both fetal and adult hepatocytes. In contrast, ACAT-2 is evident in fetal but not adult hepatocytes. Our results collectively suggest that in humans, ACAT-2 performs significant catalytic roles in the fetal liver and in intestinal enterocytes.

Early diagnosis of fetal bladder outlet obstruction.

Prenatal ultrasonography has facilitated early diagnosis of in utero bladder outlet obstruction. This represents one of the earliest diagnoses of prune-belly syndrome and sheds light on the natural history of the bladder outlet obstruction in the fetus.

Virilization during pregnancy with spontaneous resolution postpartum: a case report and review of the English literature.

The incidence of gestational hyperandrogenism secondary to ovarian pathology is low. However, when the condition does exist, diagnosis should be made with minimally invasive modalities. It is important to provide appropriate medical/surgical intervention without disturbing the pregnancy iatrogenically or causing unnecessary maternal morbidity. This case report adds to the existing radiographic data concerning this rare obstetrical condition. Presented is a review of the English literature on virilizing ovarian tumors during pregnancy, and a discussion of an approach to managing these tumors when they occur during pregnancy.

Flow cytometric reticulocyte maturity index: a useful laboratory parameter of erythropoietic activity in anemia.

Flow cytometric reticulocyte analysis is superior to manual reticulocyte counting with respect to precision and sensitivity. Furthermore, because the fluorescence intensity of reticulocytes is directly proportional to the erythrocyte RNA content, flow cytometric analysis using thiazole orange gives a quantitative reticulocyte maturity index (RMI). Previous studies have demonstrated that the RMI parameter is the earliest indicator of bone marrow engraftment following transplantation. In the present study, we analyzed the correlation of the RMI to standard red cell parameters, reticulocyte percentage, and absolute reticulocyte count in 413 anemic patients. The correlation of RMI to serum erythropoietin (Epo) and serum transferrin receptor (TfR) was analyzed in a subset of anemic blood samples. We found weak correlations between the RMI and hemoglobin (r2 = 0.041), hematocrit (r2 = 0.038), reticulocyte percentage (r2 = 0.078), and absolute reticulocyte count (r2 = 0.087). Stronger correlations were observed between the RMI and Epo (r2 = 0.181) and the TfR (r2 = 0.191). The results indicate that the RMI represents a cost-effective measurement of erythropoietic activity and provides an additional parameter to classify anemic patients into categories of high and low erythropoietic activity, especially in hypoproductive anemias.

[Langerhans-cell histiocytosis (histiocytosis X) in children]. / Langerhans-cellehistiocytosis (histiocytosis X) hos børn.

Langerhans cell histiocytosis (LCH), formerly histiocytosis X, is a rare disorder of unknown aetiology and pathogenesis which is characterized by clinical heterogeneity and an unpredictable course. LCH is considered to be a reactive, proliferative disease. The pathognomonic cell in the lesion has been shown to be identical or very similar to the Langerhans cell. Immunophenotyping studies have shown the cell to be CD1a (OKT-6), S-100 protein, HLA-DR, and CD4 positive; ultrastructurally, the presence of intracytoplasmic Birbeck granules is the hallmark of the entity. The lesions may be localized or generalized. Due to the lack of an accepted classification system for the stage of the disease and its rarity, very few comparative therapy studies have been carried out. Recently, the Histiocyte Society has suggested diagnostic criteria for LCH, and established a program of initial evaluation of the patient in order to start controlled treatment trials. Traditionally, chemotherapy has been preferred with a trend over time towards a more conservative approach. The rate of sequelae is high and connected to a chronic course of recurrent multiosseous disease. Case fatality is strongly associated to development of organ dysfunction seen in disseminated disease, which is especially seen at low age (< 2 years) of onset.

Tumours classified as "malignant histiocytosis" in children are T-cell neoplasms.

During the last five years increasing evidence has accumulated that many tumours classified as 'histiocytic' in the past do not originate from macrophages, but from transformed (or anaplastic) large lymphoid cells. Most of these studies have focused upon adult neoplasms. Knowledge concerning the lineage of 'histiocytic' tumours in the paediatric age group is more limited. In this study we have examined the clinical, morphological and immunophenotypical features of six childhood malignancies originally diagnosed as being of histiocytic origin. Three patients showed an aggressive course with involvement of internal organs and very short survival times. Two patients were brought into remission: one is alive without active disease after seven years; the other died after seven years due to treatment-related cardiomyopathy. The remaining patient had a protracted course for two and a half years, but subsequently deteriorated and died three years after diagnosis. The histomorphological features in five cases were those of anaplastic large cell lymphomas. The remaining case consisted of pleomorphic (rather than anaplastic) large lymphoid cells. In all cases the immunophenotypical examination showed features characteristic of activated T lymphocytes. All cases were positive for Ki-1 (CD30), and three were positive for epithelial membrane antigen (EMA). Histiocyte-associated markers were positive in residual reactive macrophages, but nowhere could unequivocal positivity for macrophage-associated markers be seen in the neoplastic cells. It is concluded that most childhood malignancies in the past classified as 'histiocytic' are examples of anaplastic large cell (Ki-1) lymphomas of T-cell type and that true histiocytic malignancies are exceedingly rare in the paediatric age group.

Aspergillus terreus as a cause of septic olecranon bursitis.

A 72-year-old, non-insulin-dependent diabetic man with a 2-month history of painful right olecranon bursitis was examined after a fall on the sidewalk that resulted in some abrasion of the skin overlying the elbow. Fluid aspirated from the bursa showed growth of Aspergillus terreus, as did tissue from a bursectomy performed 1 week later. Septic bursitis is an uncommon disease that is nearly always caused by Staphylococcus aureus or hemolytic streptococci. Mycotic bursitis is very rare and this is the first reported instance of any Aspergillus species causing septic bursitis.

Prognostic importance of DNA flow cytometrical, histopathological and immunohistochemical parameters in neuroblastomas.

In 42 tumour samples of human neuroblastoma, histological classification by differentiation (Shimada) was significantly correlated with strong positivity for neuron-specific enolase (NSE) and inversely correlated with rosette formation. Most ganglioneuroblastomas were positive for S-100 protein and reacted strongly with NSE antibody. Histological signs of high proliferative activity included intermediate or high mitosis-karyorrhexis index, necrosis and lack of calcification, which were significantly correlated with each other. Flow cytometric DNA analysis demonstrated that 88% of the tumour samples had DNA aneuploid stem lines. High S phase fraction (greater than or equal to 0.20) was significantly correlated with necrosis and lack of calcification. Univariate analysis of prognosis for 26 patients whose tumour samples were obtained before adjuvant treatment showed that five factors were significantly related to a better outcome: early stage of the disease (stages I, II, IV-S), S phase fraction less than 0.20, favourable Shimada histology, positivity for S-100 protein, and strong positivity for NSE. In multivariate analysis, only S phase fraction or stage of disease remained significantly associated with prognosis. DNA index did not correlate with prognosis in this study.

[Early amnion rupture or amniotic band syndrome]. / Tidlig amnionruptursekvens eller amnionbåndsyndromet.

Early rupture of the amnion with resultant oligohydramnios and subsequent development of mesodermal bands between the chorion and the fetus can cause various deformities. The degree of deformity depending on the extent of the band formation and the gestational age at which this occurs. The condition may involve all parts of the fetus and comprizes a spectrum ranging from clinically insignificant small constricting bands on the extremities to large craniofacial and visceral defects which may be fatal and cause abortion. Prenatal diagnosis relies mainly on ultrasonic investigation, and the treatment--quo ad vitam--consists mainly of reconstructive surgery. A case is reported.

Magnesium supplement in pregnancy-induced hypertension. A clinicopathological study.

The placenta and the umbilical cord obtained from 18 women with pregnancy-induced hypertension were investigated by light microscopy. The umbilical artery was studied by electron microscopy. 10 placentae and umbilical cords from normal pregnancies served as controls. The study was performed as a double-blind randomized controlled study in which 11 women were allocated to magnesium and 7 to placebo treatment. The treatment comprised a 48-hour intravenous magnesium/placebo infusion followed by daily oral magnesium/placebo intake until one day after delivery. Magnesium supplement increased birth weight and placental weight significantly. Light microscopic study of the placentae and the umbilical cord arteries showed no difference between the three groups concerning the occurrence of infarctions, cytotrophoblastic hyperplasia, vasculo-syncytial membranes, basement membrane thickening, stromal fibrosis or intervillous fibrin. Ultrastructurally, the endothelial cells of the umbilical arteries from women with pregnancy-induced hypertension showed a significant increase in the amount of dilated endoplasmic reticulum and basal laminae thickness when all 18 cases were compared with the controls. There was no significant difference when the magnesium group, the placebo group and the control group were compared separately. The present study suggests that magnesium supplement has a beneficial effect on fetal growth in pregnancy-induced hypertension. With regard to the light and electron microscopic changes we were unable to demonstrate any significant difference between the magnesium, placebo and control groups.

Flow cytometric DNA analysis of lesions from 18 children with langerhans cell histiocytosis (histiocytosis x).

The DNA content in 26 formalin-fixed, paraffin-embedded histologic specimens from 18 children with Langerhans cell histiocytosis (LCH) was analyzed by flow cytometry. In two cases, the propidium iodide fluorescence histograms showed small (5 and 3% of the analyzed nuclei) but significant aneuploid subpopulations with DNA indices of approximately 1.5. This was confirmed by analysis of unfixed, frozen material in one patient. Both patients had disseminated disease without organ dysfunction and were treated with prednisone. Currently, they are without signs of disease activity after 1 and 10 years. DNA histograms were normal from a patient who died from disseminated disease and from two patients with disseminated disease who experienced several relapses and various chemotherapeutical regimens. The histograms were also normal in lesions from four patients with unifocal bone involvement. Our results show that DNA aneuploidy occurs in LCH lesions in the pediatric age group. Further investigation is necessary to reveal whether DNA aneuploidy is restricted to disseminated LCH or its presence has any value in predicting the course and outcome of the disease.

Immunohistochemical study of the abnormal cells in Langerhans cell histiocytosis (histiocytosis x).

The immunophenotypic properties of the abnormal cells in routine specimens from 16 cases of Langerhans cell histiocytosis (LCH) were examined. In five cases, cryostat sections were also available. The abnormal cells expressed a similar phenotype and were positive for HLA-DR, S-100 protein, peanut agglutinin (PNA), CD1a, CD4 and several macrophage-associated markers, including CD11c, CDw32 and CD68 (the latter detectable in routine sections with antibody KP1). Staining with CD14, CD35 (C3b receptor), and CD11b (C3bi receptor) was negative with the exception of one of the cases in which a proportion of the cells showed faint positivity with CD11b. Staining for pan-T-cell (CD2, CD3, CD5) and pan-B-cell (CD19, CD22) antigens was negative in all lesions. It is concluded that LCH expresses a characteristic phenotype with some heterogeneity with regard to macrophage markers and that immunohistochemical methods in cryostat sections and routine specimens form a useful supplement to other techniques for the diagnosis of this condition.

[Familial hemophagocytic histiocytosis in 2 siblings]. / Familiaer haemofagocyterende lymfohistiocytose hos søskendepar.

Two siblings presented with fever, hepatosplenomegaly and pancytopenia at the age of six weeks. Subsequent investigations showed hypofibrinogenaemia, hypertriglyceridaemia, cellular-mediated immunodeficiency and hepatic and splenic lymphohistiocytic infiltrates showing haemophagocytosis. These findings are consistent with the diagnosis of familial haemophagocytic histiocytosis. Splenectomy in one infant was followed by brief improvement in the haematological parameters. Both infants died by the age of five months.

Kala-azar in a four-year-old child 18 months after brief exposure in Malta.

A four-year-old Danish boy developed kala-azar 18 months after a holiday in Malta. Splenectomy, with liver biopsy, was performed six months after onset of symptoms because of hypersplenism, and the diagnosis of kala-azar was only made four months later, when the histopathological specimens were reviewed. Previous bone marrow biopsies did not show Leishmania. Treatment with sodium stibogluconate was successful. The development of kala-azar after one week's stay in an endemic area stresses the importance of including this potentially fatal disease in the differential diagnosis of cases presenting with fever, splenomegaly, and pancytopenia.

Fatal familial cholestatic syndrome in Greenland Eskimo children. A histomorphological analysis of 16 cases.

We report the first detailed study of hepatic morphology in 28 biopsies from 16 Greenland Eskimo children with fatal familial cholestatic syndrome. The changes were categorized as early, intermediate and late. In the early stage, until 5 months of age, changes were restricted to zone 3, consisting of cholestasis and rosette formation without fibrosis. In the intermediate stage, from 5 to 14 months, cholestasis persisted and rosette formation increased, both with further extension into zone 2. Perisinusoidal fibrosis developed, first in zone 3 and later in zone 1. The late stage, from 17 to 60 months, showed a further increase in cholestasis and rosette formation, and fibrosis of zones 3 and 1 in nearly all biopsies. Portal to portal and portal to central fibrosis was evident with resulting cirrhosis in 2 of 7 patients. The morphological features can be summarized as pure cholestasis with prominent rosette formation followed by zone 3 fibrosis, zone 1 fibrosis, and, cirrhosis. Other characteristics are the virtual absence of inflammation and the lack of anatomical abnormalities such as paucity of bile ducts. The changes and their progression resemble those of Byler disease. Clinical and biochemical features are also largely similar, except for the presence of thrombocytosis in many of the Eskimo patients.

Immature ovarian teratoma in a postmenopausal woman.

We report the first case of immature ovarian teratoma occurring after menopause in a 57-year-old, 3 years postmenopausal woman. Within one year after resection of the teratoma she developed peritoneal botryoid rhabdomyosarcoma, which probably originated from initially unrecognized rhabdomyoblasts in the teratoma. The patient died 6 months later from progressive disease after a transient adriamycin-induced tumor response. The literature on ovarian immature teratoma and ovarian rhabdomyosarcoma is briefly reviewed, and the available treatment is discussed.