Fetal drug exposure and its possible implications for learning in the preschool and school-age population.

For the past 5 years there has been an exponential increase in the use of cocaine, phenylcyclidine hydrochloride (PCP), and other central nervous system (CNS) active drugs. A significant amount of this accelerated usage is in sexually active females, resulting in some urban hospitals reporting positive drug screens in over 16% of the infants born on their busy obstetrical service. There is a growing body of data showing that fetal exposure to cocaine, phenylcyclidine hydrochloride (PCP), and other CNS-active drugs results in infants and children with abnormal brain wave patterns, short-term neurologic signs, depression of interactive behavior, and poor organizational responses to environmental stimuli.

Cell therapy in children with Down syndrome: a retrospective study.

Cell therapy, the administration of freeze-dried or lyophilized cells derived from fetal tissue of animals, has been suggested and accepted by some parents as a treatment for Down syndrome. Such therapy regimens have been purported to ameliorate dysmorphic features and to result in improvement in IQ, motor skills, social behavior, height, language, and memory. Interest in this therapy continues despite a lack of empirical support for its use and its illegality in the United States.

Physician perceptions of and management practices for significant fetal drug exposure.

A random sample by questionnaire in 1989 of U.S. physicians' perceptions of and management practices for significant fetal drug exposure in the specialty/sub-specialty areas of genetics, neonatology, pediatrics, family practice, neurology, and obstetrics and gynecology was analyzed.

Characterization of human laryngeal primary and metastatic squamous cell carcinoma cell lines UM-SCC-17A and UM-SCC-17B.

The squamous cell carcinoma (SCC) cell lines UM-SCC-17A and -17B were derived, respectively, from the primary laryngeal cancer and a metastatic neck tumor of a patient who failed to respond to radiation therapy but achieved long-term remission after surgery. The karyotypes of both cell lines and a subline of 17A were pseudodiploid and stable in multiple in vitro passages. Several karyotypic abnormalities were common to all three cell lines and therefore represent mutations present in the tumor before the divergence of the metastatic and subline populations whereas those rearrangements observed only in one cell are more likely to be secondary.

Fusiform bacterial sepsis. Metastases with osteomyelitis and hepatic abscess occurring in a chaotic family.

Cases of fusiform bacteria sepsis have been reported infrequently in the pediatric literature. This case demonstrates the severe metastatic complications of fusiform bacterial sepsis including osteomyelitis, with multiple pathological fractures, sepsis, and abscesses of the liver. In the diagnostic evaluation of the etiology for this uncommon infection, child abuse was discovered in all children of this family.

Secondary trisomy or mosaic "tetrasomy" 8p.

We report on two patients with mosaic tetrasomy of 8p[46,XY/47,XY,+i(8p)], a previously unreported cytogenetic anomaly. The first patient had a low percentage of tetrasomic (secondary trisomic) cells in lymphocytes and fibroblasts, an only mildly abnormal phenotype, and a rather benign clinical course. The second patient had a considerably larger percentage of tetrasomic cells in lymphocytes and fibroblasts, and had more severe congenital anomalies that led to his death at 8 months.

A dicentric recombinant 9 derived from a paracentric inversion: phenotype, cytogenetics, and molecular analysis of centromeres.

A 4-year-old girl with multiple malformations and severe developmental delay has been shown to have a karyotype of 46,XX-9,+rec(9),dup p,inv(9) (q22.1q34.3)mat, with duplication 9pter-q22.

MEN-2 tumor associations suggest a linear order of specific endocrine tumor genes.

The variation in tumor involvement between families and consistent pattern within 12 MEN-2A and 4 MEN-2B families studied suggest that the tumors in MEN-2 result from separate, specific mutations in a specific linear order of adjacent genes.

Increased sharing of maternal HLA haplotypes among children exposed to diphenylhydantoin during pregnancy.

During investigation of HLA types among children exposed to diphenylhydantoin (DPH) in utero, we found no evidence of a distortion in haplotype sharing among affected sib pairs. Unexpectedly, however, we found a marked increase in the proportion of all sib pairs (not just affected ones) sharing maternal haplotypes. Among 14 two child families, 12 shared the maternal haplotype (expected would be seven); among families with more than two children the distortion was also pronounced.

Down syndrome. Cervical spine abnormalities and problems.

A review of the radiographs of 34 individuals with Down syndrome (DS), between 5 and 21 years of age, demonstrated subluxation of atlantoaxial instability (C1-C2) greater than 5 mm in three of the 34 individuals (9 percent). This is in general agreement with previously reported ranges of 10 to 20 percent. A review of the cervical spine radiographs of adults with DS, between 26 and 42 years of age, showed no subluxation but significant degenerative changes of the cervical spine with spur formation, narrowing of foramina, narrowing of the disc inner space, and osteophyte formation.

Family studies in fetal phenytoin exposure.

Sixty-two families with fetal diphenylhydantoin exposure were studied during two or more pregnancies. In 15 of these families at least one of the exposed children had some of the physical effects of DPH exposure ("affected" families); in the remaining 47 families no exposed child was affected ("unaffected" families). Review of 62 family histories and pedigrees was not helpful in differentiating these two groups for counseling purposes.

UM-EC-1, a new hypodiploid human cell line derived from a poorly differentiated endometrial cancer.

The University of Michigan endometrial carcinoma cell line UM-EC-1 was derived from a poorly differentiated endometrial adenocarcinoma of a 66-yr-old white female. Cell cultures were started using both tumor explants and a cell suspension obtained from collagenase-treated tumor tissue. The collagenase-derived cell suspension gave rise to monolayer cultures which grew rapidly from the outset.

Tumor behavior in transitional cell carcinoma of the bladder in relation to chromosomal markers and histopathology.

Tumor cells from direct harvests and short term cultures were karyotyped from 15 patients with transitional cell carcinoma of the bladder. There were two tumors with an apparently normal diploid karyotype, eight with counts up to 50 and with marker chromosomes, and five with counts of 60 or more and with markers. The median duration between recurrences was 3 months for the near-diploid, and 3 months for the near-polyploid tumors.

Elevated glucocorticoid receptor levels in lymphocytes of children with the fetal hydantoin syndrome (FHS).

Our recent studies of the teratogenic mechanisms of phenytoin (DPH) and glucocorticoids in mice have indicated that DPH utilizes the anti-inflammatory pathway of glucocorticoids in producing congenital defects, such as cleft palate. This pathway is influenced by H-2 and H-3 histocompatibility-linked genes in the mouse, such that congenic strains have H-2 or H-3 alleles that confer susceptibility to DPH-induced congenital defects, and susceptible H-2 congenic strains have high glucocorticoid receptor levels. However, other H-2 or H-3 alleles confer resistance to these defects in their otherwise genetically identical congenic partner strains, and "resistant" H-2 alleles are associated with low levels of these receptors.

The human inactivated X chromosome folds in early metaphase, prometaphase, and prophase.

The inactivated X chromosome has a site of unusually frequent folding in region Xq1, whereas a fold in Xq1 is uncommon on the active X. We investigated the pattern of X chromosome folding in high-resolution GTG- and RBG-stained preparations from four women. In early metaphase cells, slightly more than 50% of late-replicating Xs folded at Xq1----Xq21, compared with about 6% of early replicating Xs.

Chromosome 20 deletion in multiple endocrine neoplasia type 2: expanded double-blind studies.

Multiple endocrine neoplasia (MEN) type 2A and 2B are autosomal dominant syndromes in which medullary thyroid cancers are associated with adrenal pheochromocytomas. We have expanded our double-blind studies of high-resolution G-banded chromosomes from lymphocytes to a total of 12 MEN-2A families, 7 MEN-2B (mucosal neuroma phenotype) families and 23 non-MEN control subjects. Eighteen of 23 different control subjects were scored as having normal chromosomes 20, and 15 of 21 MEN-2A and 4 of 8 MEN-2B patients were scored as having an interstitial deletion: del(20) (p12.

Duplication 3p21----3pter and cyclopia.

We report on a patient with an interchromosomal duplication of 3p, from 3p21 to 3pter, which apparently arose de novo. The infant had multiple malformations including holoprosencephaly and cyclopia. It is possible that duplication 3p has a generalized effect on the holoprosencephalon or the cleavage of the embryonic forebrain.

Dysgenetic male pseudohermaphroditism in a 45,X/46,X,del(Y)(q11.1) mosaic infant.

We describe an infant with dysgenetic male pseudohermaphroditism and the karyotype 45,X/46,X,del(Y)(q11.1). Histologic examination of the resected gonads showed cortical dysplasia indicative of incipient gonadoblastoma.

Hypospadias and urethral abnormalities in Down syndrome.

In the course of general medical evaluations of 149 children and adolescents (younger than 21 years of age) and 11 adults with Down syndrome, five of the 77 males were noted to have dorsal urethral duplications. In all instances, there proved to be a single urethral meatus. The second opening led into a pit or blind channel, reflecting the presence of a distal hypospadias.