Malignant ectomesenchymoma in childhood.

Five childhood malignant ectomesenchymomas are reported from three centers in three countries. The children were all younger than 3 years (four less than 12 months), four were boys, and four tumors were sited in the pelvis or external genitalia. All tumors had distinctive light microscopic features of rhabdomyosarcoma and three also demonstrated small numbers of included neuronal cells. Immunohistochemical studies and transmission electron microscopy revealed the additional presence of neurogenic components in the remaining two patients. An additional epithelial component was found by immunohistochemistry in one tumor, which suggests a pluripotential origin that still requires karyotypic investigation. Aggressive chemotherapy and adequate surgical excision have thus far been effective in providing disease-free follow-up for periods of 7 to 50 months. It is implied that because the biological behavior and morphology closely resemble those of rhabdomyosarcoma and because the neurogenic component is often inconspicuous, many malignant ectomesenchymomas may be misdiagnosed as rhabdomyosarcomas.

The effects of prior gravidity on the outcomes of ovum donor and own oocyte cycles.

OBJECTIVE: To determine the effects of prior gravidity on hormonal parameters, medication regimen, oocyte parameters, fertilization, and clinical pregnancy rates (PRs) in donor and own oocyte cycles. DESIGN: A retrospective study of 64 first-attempt ovum donor cycles and 102 first-attempt IVF and ZIFT cycles using own oocytes conducted during a 2.5-year time period. Analyses of covariance and t-tests using gravidity of oocyte source (gravida versus nulligravida) and controlling for sperm parameters were used to assess differences in hormonal, endometrial, medication, and demographic parameters and were performed separately for donor cycles and for own oocyte cycles. SETTING: Private fertility center. PATIENTS: In ovum donation cycles, oocyte parameters, medication administered, and hormonal parameters of 64 oocyte donors between the ages of 21 and 35, 34 of whom were never pregnant, i.e., nulligravida and 30 who had ever been pregnant, regardless of the outcome of that pregnancy, i.e., gravida, were studied. In own oocyte cycles, oocyte parameters, medication administered, and hormonal parameters of 102 women, 54 nulligravida and 48 gravida, between the ages of 23 and 44 were studied. MAIN OUTCOME MEASURE: Medication requirements, hormonal response, seminal parameters, oocyte quality, fertilization, and clinical PRs. RESULTS: For patients using their own oocytes, there were no significant differences in any of the parameters studied. In contrast, compared with their nulligravida counterparts, gravida oocyte donors had fewer poor quality oocytes, had more high quality oocytes that fertilized, had a higher proportion of their oocytes fertilize, and had a higher PR per transfer. CONCLUSION: A prior history of gravidity is an important predictor of clinical pregnancy in donor oocyte cycles but not in cycles in which patients use their own oocytes. Oocyte recipients may wish to consider donor gravidity in selecting their donor.

Ocular findings in conjoined (Siamese) twins.

Conjoined twinning is a rare form of congenital anomaly. The ocular findings in six sets of conjoined twins as well as those reported elsewhere include abnormal optic nerve decussation, pseudosynophthalmos, microphthalmia, abnormal eyelids, orbital encephalocele, occipital encephalocele, and eyelid coloboma. These findings are interpreted as due to deformations from appositional fusion-related factors or malformations from developmental factors.

Multiple congenital anomalies associated with a 47,XXX chromosome constitution.

An infant with a 47,XXX chromosome constitution, who died shortly after birth, had laryngeal atresia, pulmonary hypoplasia, craniofacial anomalies, urogenital malformations including unilateral renal agenesis, hydrometrocolpos and ovarian dysgenesis, and mildly abnormal endochondral ossification. Implications for genetic counseling are presented.

Coarctation as a deformation.

Several aspects of coarctation of the aorta conform with the concept of a deformation, a disorder of morphogenesis resulting from altered fetal hemodynamics. Based on its location at the junction of the aortic isthmus and the ductus arteriosus, the continuity of the ductal wall with the fibromuscular curtain, and the association with cardiovascular malformations causing decreased blood flow through the ascending aorta, coarctation of the aorta is interpreted as the result of diminished blood flow through the fetal aorta, which leads to persistence and aggravation of the normally narrow isthmus and subsequent development of the curtain.

Electron microscopy in the diagnosis of lysosomal storage diseases.

Lysosomal storage diseases (LSD) affect cells of the conjunctiva in the absence of clinical eye findings. Consequently conjunctiva was added to skin, rectal mucosa, and peripheral blood lymphocytes as a biopsy site for electron microscopic examination in suspected LSD. The abnormally stored substrates in LSD are the result of diminished lysosomal enzyme activity. Although all cells lack the deficient lysosomal enzyme, the quantity of stored material varies with the extent of breakdown of substrate in the cell under normal circumstances. The stored material does not accumulate in all cells and may have a different cellular morphology at different sites. Although no one tissue provides universally diagnostic material for electron microscopy, skin and conjunctiva are optimal for most LSD. Rectal mucosa and peripheral blood lymphocytes are also useful in many cases. Biochemical assays have replaced brain biopsy for diagnosis but these techniques may give equivocal or non-diagnostic results, and in some diseases the enzyme defect remains undefined. Of the 359 biopsies of conjunctiva, skin, rectal mucosa, and lymphocytes we evaluated for LSD and other neurodegenerative diseases, 65 showed abnormal lysosomal storage; in 41 a specific diagnosis was made by biochemical assay or morphology. Ultrastructural examination of tissue from patients with clinically suspected storage disease may disclose pathognomonic alterations or suggest a differential diagnosis even in the absence of clinically evident involvement of the biopsied tissue. Biopsy has particular value in those diseases with incompletely characterized biochemical abnormalities.

Cardiovascular effects of congenital infections.

In the course of gestation, many bacteria, parasites, and viruses may infect the pregnant woman, but few cross the placenta to affect the fetus and fewer still affect the fetal heart. Although the incidence of fetal cardiac infection is low, the effect on the fetus is major. In terms of frequency, rubella virus, Toxoplasma gondii, and Coxsackie virus B are the principal infectious agents affecting the fetal heart, but any number of organisms may cross the placenta to affect the fetus. The pathogenesis of infection of the fetal heart relates to the agent and to the time of gestation when the infection occurs. The agent affects the heart along one or more of three separate pathways: inhibition of cell growth, cytolysis, and interference with the blood supply. Most agents cause cytolysis, stimulating inflammation and scarring. Although several agents carry the suspicion of teratogenicity, only rubella virus has been incriminated with certainty as capable of functioning along each of the three pathways with the potential to serve as teratogen.

Cytomegalovirus infection and fetal death in a twin. A case report.

In a diamnionic-dichorionic male twin pregnancy, one twin was stillborn, with disseminated cytomegalovirus (CMV) identified morphologically, and the other was liveborn, without clinical or laboratory evidence of CMV infection. The placenta of the affected twin had chronic villitis; that of the liveborn was normal. Although the discordance went unexplained, it illustrates the clinical variability of congenital CMV infection. Dissimilar immune responses between the affected and unaffected twin or direct extension of uterine CMV infection to only one twin may have been responsible for the discordance.

Glutamyl ribose-5-phosphate storage disease: nephrotic syndrome and cerebral atrophy.

Storage of glutamyl ribose-5-phosphate was identified at autopsy in the brain and kidney of an 8-year-old male who had presented clinically with progressive renal failure and neurological deterioration. In a renal biopsy during life, glomeruli were focally sclerotic and contained foam cells. By electron microscopy, lysosomal accumulation was present in renal tubular and glomerular epithelial cells, hepatic Kupffer cells, and conjunctival connective tissue cells. Ganglion cells in the brain stem had swollen, PAS-positive cytoplasm with central chromatolysis. The cerebral cortex was atrophic and there was loss of Purkinje cells in the cerebellum. The identification of storage was based on biochemical isolation of the compound from the tissues at autopsy. The enzyme deficiency responsible for the storage has not yet been identified.

The endocrine glands in Pompe's disease. Report of two cases.

Pompe's disease (type II glycogenosis), an infantile form of generalized glycogenosis, is characterized biochemically by deficiency of lysosomal acid alpha-1,4-glucosidase and morphologically by intralysosomal glycogen storage in multiple organs, notably the central nervous system, heart, liver, and skeletal muscles. The endocrine system has not been described in detail in the literature. In two infants with Pompe's disease, intralysosomal glycogen was identified in the adrenal cortex and medulla, thyroid gland, parathyroid glands, pancreatic islets, and pituitary gland. Of special interest is the severe glycogen accumulation in the zona fasciculata of the adrenal glands.

Pulmonary endodermal tumor resembling fetal lung. Report of a case with immunohistochemical studies.

A tumor of a 12-year-old boy was studied immunohistochemically by utilizing an extensive battery of antisera against active amines and peptides. The tumor contained argyrophilic cells and resembled fetal lung. The positive immunoreaction in tumor cells for active amines and peptides further supports the probable derivation of the tumor from bronchopulmonary endocrine cells.

Progressive neurologic deterioration and renal failure due to storage of glutamyl ribose-5-phosphate.

A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 mumol per gram, wet weight) and kidney (0.60 mumol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate.

Laryngeal fibromatosis in the neonate.

Infants with a fibromatosis that originates in the laryngeal mucosa have uniform clinical appearances and morphologic features that identify a clinicopathologic syndrome. Based on data obtained from the two cases in the present study and from previously reported cases, the lesion may appear at birth or appear later in childhood, with symptoms referable to the degree of laryngeal obstruction. Fibroblasts and myofibroblasts make up the cytologic composition of these lesions. These lesions can be identified among the fibromatoses that occur in infants and children. Fibromatosis of the larynx in infants and children may have the same behavior as other fibromatoses, eg, local invasion and potential recurrence; this behavior should be considered in the clinical management.

Focal glomerulosclerosis. Extent of involvement related to steroid resistance.

Biopsies were done for 27 nephrotic children whose presentations were compatible with minimal lesion nephrotic syndrome. Percentages of glomeruli involved by focal glomerular sclerosis and its subtypes were calculated. The presence or absence of interstitial disease was noted. These histologic findings were correlated with steroid responsiveness. All patients who had greater than 5% of glomeruli involved by focal glomerular sclerosis resistant to steroids. Interstitial disease was present in ten of the 27 patients studied; eight of the ten were resistant to steroids. Steroid resistance was found to be associated not with the mere presence of focal glomerular sclerosis but rather with its extent and the presence of interstitial disease.