Predictive value of fetal ultrasonography in the diagnosis of a lethal skeletal dysplasia.

BACKGROUND: Certain ultrasonographic findings identified in a fetus suspected of having a skeletal dysplasia may be predictive of a lethal outcome. METHODS: We evaluated 27 fetuses suspected of having a skeletal dysplasia using targeted ultrasonography between 16 and 31 weeks' gestation. Clinical examination and skeletal radiography were done after delivery. RESULTS: A skeletal dysplasia was confirmed and a diagnosis established in all but one case. The skeletal dysplasia was lethal in 23 cases and, in each case, the outcome was accurately predicted prenatally; however, three of the infants survived several months. In 11 of the 23 cases (48%), the specific diagnosis was correctly determined before birth. Ultrasonographic findings not considered to reflect a lethal outcome, were accurately predicted in two other cases. In an additional two, sonographic examination suggested a lethal osteochondrodysplasia, though both survived. Findings consistent with a lethal skeletal dysplasia included a femur length < 1st centile, combined with either a bell-shaped thorax, decreased bone echogenicity, or both. Using these criteria provided a positive-predictive value for neonatal deaths of 80% (20/25), and 92% (23/25) if the three that died in infancy were included. CONCLUSIONS: In the fetus suspected of having a skeletal dysplasia, certain findings on targeted ultrasonography frequently are predictive of a lethal outcome; the ability to predict this appears greatest when more than one of these abnormalities is present.

Expression of chemokine receptors by subsets of neurons in the central nervous system.

IL-8 is expressed by activated and neoplastic astrocytes and enhances the survival of hippocampal neurons in vitro. Since mRNA encoding chemokine receptors have been demonstrated in brain, the expression of chemokine receptors by specific cell types in anatomic regions of the central nervous system (CNS) was investigated. Archival tissues from various regions of the CNS were stained with specific mAbs to the Duffy Ag/receptor for chemokines, a promiscuous receptor that binds selected chemokines; the specific receptor for IL-8 (CXCR1); and the receptor (CXCR2) shared by IL-8 and melanoma growth stimulatory activity. The Duffy Ag/receptor for chemokines was expressed exclusively by Purkinje cells in the cerebellum. Chemokine binding and radioligand cross-linking confirmed the presence of a high affinity, promiscuous chemokine receptor in the cerebellum. Although CXCR1 was not expressed in the CNS, CXCR2 was expressed at high levels by subsets of projection neurons in diverse regions of the brain and spinal cord, including the hippocampus, dentate nucleus, pontine nuclei, locus coeruleus, and paraventricular nucleus, and in the anterior horn, interomediolateral cell column, and Clarke's column of the spinal cord. Fibers that express CXCR2 included those in the superior cerebellar peduncle and the substantia gelatinosa. Immunohistochemical analysis of the involved brain tissues from patients with Alzheimer's disease revealed expression of CXCR2 in the neuritic portion of plaques surrounding deposits of amyloid. These data suggest that chemokines may play a role in reactive processes in normal neuronal function and neurodegenerative disorders.

Distinct biological activities of recombinant forms of human interleukin-2 in vivo.

The biological activity of all recombinant forms of interleukin-2 (IL-2) is based upon an in vitro lymphocyte proliferation assay and measured in international units (IU). Numerous in vitro investigations have suggested that there may be different cellular effects of recombinant human IL-2 retaining the natural sequence (nIL-2) as compared to another recombinant form containing a serine substitution at amino acid position 125 ([Ser]IL-2). In the present study we investigated whether nIL-2 and [Ser]IL-2 cause similar patterns of systemic toxicities. C57BL/6 mice were treated with identical doses of either nIL-2 or [Ser]IL-2, as measured in IU, for 3 days and had blood and tissues removed for analysis of lymphocyte activation and organ dysfunction. The administration of nIL-2 had considerably greater effects on lymphocyte activation than did [Ser]IL-2, causing much greater up-regulation of the alpha subunit of the IL-2 receptor and the adhesion molecule lymphocyte function-associated antigen-1. Furthermore, nIL-2 induced more organ edema than did [Ser]IL-2 and caused hepatocellular injury, which was absent in mice treated with [Ser]IL-2. These data demonstrate that equivalent doses, measured in IU, of nIL-2 and [Ser]IL-2 have profoundly different effects on the induction of organ toxicity, suggesting that the IU standard may not be appropriate for the measurement of many in vivo biological activities.

A non-trophoblastic tumor co-existing with a triploid fetus.

Non-trophoblastic neoplasms are the most frequent, benign tumors of the placenta, occurring in approximately 1% of all placentas examined. A case is described of a 24-year-old woman who presented with severe, early-onset pre-eclampsia, high human chorionic gonadotropin (hCG) levels, and a triploid fetus and who was found to have a small choriohemangioma. The woman, gravida 2 para 1, was referred to our hospital for perinatal evaluation. The fetus, gestational age 18 weeks 3 days, had fetal growth restriction with multiple congenital anomalies. The fetal karyotype was 69,XXY. Compared with the normal range for this gestational age, the beta-hCG level was significantly elevated (1,054,000 mIU/ml) as was the maternal serum alpha-feto-protein measurement (539.1 ng/ml). Sonographically, the placenta appeared hydropic, irregularly shaped, and gelatinous. A suction dilatation and evacuation under sonographic guidance was performed. Histological examination of placental tissue revealed hydropic degeneration of the chorionic villi. The specific histological features of a partial molar pregnancy were not present. However, there were changes consistent with a choriohemangioma. Flow cytometric DNA analysis performed on formalin-fixed, paraffin-embedded tissue blocks of placenta showed triploidy. Immunohistochemical staining with human placental alkaline phosphatase was consistent with a hydropic degeneration pattern. We conclude, first, that triploidy does not always imply the presence of a partial mole. Second, the dictum, that pre-eclampsia, if it occurs under 20 weeks' gestation, must be associated with a molar pregnancy, may not hold when placental aneuploidy is present. Although the findings in this pregnancy could have been incidental, there may be an association between a choriohemangioma and polyploidy.