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Biomedical subjects

D B Singer

Publications and source records attributed to D B Singer.

At least 19 recordsLinked to original sources
PubMed2001

Atypical squamous metaplastic cells: reproducibility, outcome, and diagnostic features on ThinPrep Pap test.

BACKGROUND: Atypical squamous metaplastic (ASM) cells are associated with high-grade squamous intraepithelial lesions (HGSIL) in many cases. The reproducibility of the diagnosis and biopsy follow-up results of cases designated as ASM were studied at Women and Infants' Hospital of Rhode Island. METHODS: Of 180 patients with ASM who the authors examined from January 1, 1998 to September 30, 1998, 147 (81.7%) had subsequent biopsies. Results of the biopsies were tallied. Twenty cases were rescreened in a blinded fashion to determine intra- and interobserver agreement and to identify diagnostic features. RESULTS: Sixty-five (44.2%) cases of ASM had HGSIL on biopsy, 26 (17.7%) had low-grade squamous intraepithelial lesion, and 56 cases (38.1%) were benign. Overall individual consistency is 8 of 16 (50%), and overall agreement is 13 of 64 (20%). CONCLUSIONS: Sixty-two percent of cases designated as ASM cytologically were associated with SIL, primarily HGSIL, at biopsies. The findings underscore the importance of this subcategory of atypical squamous cells. However, poor reproducibility suggests the need for refined criteria and/or continuing education, and obtaining second opinion. Cancer (Cancer Cytopathol)

Adult↗
PubMed2001

Hsal 1 is related to kidney and gonad development and is expressed in Wilms tumor.

Townes-Brocks syndrome (TBS) is a human genetic disorder with features including urogenital, limb, anal and cardiac malformations associated with mutations of the TBS gene, Hsal 1. To begin to understand the role of the Hsal 1 protein (p140) in both normal development and disease pathogenesis, both message and protein expression were evaluated in specific tissues associated with TBS. DNA sequence information for Hsal 1 predicts that this homeotic, Drosophila homologue (Sal) encodes a zinc-finger protein consistent with a transcription factor. mRNA for Hsal 1 was highly expressed in fetal kidney and brain, with detectable production in thymus and heart. p140 was found in fetal ureteric bud, fetal and postnatal renal tubular epithelium, and renal blastema. In the 14-week fetal testis, the Hsal 1 protein was specifically expressed in the testosterone producing Leydig cells while in adult gonads Hsal 1 was also found in both Leydig and Sertoli cells, spermatogonia of the testis, and granulosa cells of the ovary. Evaluation of Wilms tumor revealed consistently high expression of the gene product in the epithelial and blastemal components. These spatial and temporal patterns of expression for Hsal 1, and the phenotypic effects associated with TBS, suggest that Hsal 1 plays an important role in the development and functional maintenance of the kidney and gonads. Furthermore, the Hsal 1 gene product may play a part in the pathogenesis of specific neoplasms occurring in these organs in addition to its specific role in Townes-Brocks syndrome.

Abnormalities, Multiple↗
PubMed2001

The placenta in pseudoxanthoma elasticum: clinical, structural and immunochemical study.

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder clinically characterized by skin, cardiovascular and eye manifestations, mainly due to calcification and fragmentation of elastic fibres. Although infrequent, complications during pregnancy in women affected by PXE have been reported. The aim of the present study was to compare structural features of placentae at term from 14 control and 15 PXE-affected women, in order to better understand if and how abnormal mineral and/or matrix accumulation might affect placental function in PXE. In all cases, pregnancy, fetus growth and delivery were normal. Both gross and light microscopy examination did not reveal dramatic differences between placentae of PXE patients and controls, with regard to weight, dimensions, infarcts, thrombi, inflammatory lesions or vessels. However, necrotic changes and mineralization appeared statistically more pronounced in PXE. By electron microscopy the most remarkable differences between PXE and control placentae were observed in the localization and morphology of mineral precipitates; a significant higher deposition of mineral precipitates was observed associated with the "matrix"-type fibrinoid and among collagen fibrils, especially on the maternal side. Immunocytochemistry revealed the presence of vitronectin and fibronectin associated with the PXE-specific mineralizations and the absence of mineralization on the small and scarce elastic fibres in either controls or in PXE.

Adult↗
PubMed1998

First trimester pregnancy loss associated with varicella zoster virus infection: histological definition of a case.

Pathological demonstration of varicella infection in first trimester aborted tissue is reported. A 24-year-old primigravida manifested chickenpox infection about 38 days after her last menstrual period or at 24 days age of the embryo. The conceptus survived another 4 to 5 weeks. The macerated embryo and placental tissue revealed nuclear changes consistent with varicella infection. Immunohistochemical stains and electron microscopy were confirmatory.

Adult↗
PubMed1993

Detection of human parvovirus B19 in early spontaneous abortuses using serology, histology, electron microscopy, in situ hybridization, and the polymerase chain reaction.

OBJECTIVE: To determine whether there is an association between parvovirus B19 infection and early spontaneous abortion at less than 20 weeks' gestation. METHODS: Eighty samples of early spontaneous abortions were analyzed. Each sample was examined histologically for the presence of viral inclusions, and selected cases were analyzed for parvovirus using electron microscopy and in situ hybridization. Polymerase chain reaction DNA amplification for the virus was done in each case. Maternal sera were analyzed for immunoglobulin (Ig) M and IgG parvovirus antibodies and compared with temporally matched controls. RESULTS: Five cases in the study group had evidence of seroconversion for parvovirus, compared with two controls. Products of conception from two of these five cases were positive for virus by polymerase chain reaction amplification, and only one of these two had a characteristic inclusion of parvovirus histologically. Conversely, five chorionic vesicles from mothers who had not seroconverted had histologic changes suggesting parvovirus infection, but all of these cases were negative for parvovirus using in situ hybridization, polymerase chain reaction, and electron microscopy. CONCLUSIONS: Parvovirus B19 DNA was found in two of 80 early spontaneous abortuses. Although viral DNA was detected in two cases, there was no clear evidence that the infections caused fetal death. Neither case showed erythroblastosis with large numbers of inclusions, as is seen in hydropic fetuses with parvovirus infection. In addition, in five cases in which parvovirus infection was not documented serologically or by the polymerase chain reaction, there was erythroid nuclear clearing suggestive of parvovirus B19 inclusions. This indicates that histologic evaluation for parvoviral inclusions is not always reliable in early spontaneous abortuses.

Abortion, Spontaneous↗
PubMed1992

Estimating the time of death in stillborn fetuses: III. External fetal examination; a study of 86 stillborns.

OBJECTIVE: To determine how accurately the time of fetal death can be predicted from the extent of external maceration in a stillborn fetus. METHODS: Autopsy photographs of 86 stillborns with well-timed deaths were studied retrospectively. Sixty randomly chosen fetuses (learning set) were assessed unblinded to develop proposed gross criteria for timing fetal death; 26 fetuses (test set) were then randomly and blindly assessed to test the accuracy of the proposed criteria. RESULTS: The two earliest changes in the learning cases were areas of desquamation measuring at least 1 cm in diameter and brown-red discoloration of the umbilical cord stump. Both changes occurred primarily in fetuses with death-to-delivery intervals of 6 or more hours. Other early changes included desquamation involving the face, abdomen, or back (12 or more hours); desquamation involving 5% or more of the body surface (18 or more hours); brown skin discoloration (24 or more hours); and a moderate or severe extent of desquamation (24 or more hours). The only late change that correlated with a specific duration of intrauterine retention was mummification (2 or more weeks). When the 26 test fetuses were randomly and blindly assessed using these gross criteria, 18 (69%) were classified correctly with respect to the approximate time of fetal death. CONCLUSION: External fetal examination is useful for estimating the time of death in many stillborns; this information may be helpful when a complete autopsy cannot be performed.

Autopsy↗
PubMed1991

Type-specific identification of herpes simplex and varicella-zoster virus antigen in autopsy tissues.

To identify antigens of herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV) in human tissue, polyclonal antisera and an immunoperoxidase method were used to examine formalin-fixed, paraffin-embedded tissues from autopsy cases and experimentally infected animals. These antisera readily distinguished between HSV and VZV antigen, with no evident cross-reactivity. Antiser ato HSV-1 and HSV-2 were more strongly reactive with antigen of the homologous virus than with that of heterologous virus. This difference in immunoreactivity was used to discriminate between HSV-1 and HSV-2 antigens in experimentally infected animal tissues containing HSV antigens of known type and, by extrapolation, to distinguish between these antigens in human autopsy tissues. Thus, with appropriate antisera and tissue controls, HSV-1, HSV-2, and VZV can be identified in paraffin sections.

Adult↗
PubMed1991

Infections, preterm delivery, and perinatal death in midgestation.

Amniotic fluid infection results in considerable pregnancy wastage in the second and early third trimesters. In our study of 1119 perinatal autopsies amniotic sac infection was associated with death in 133 fetuses and neonates in midgestation. These cases accounted for almost 12% of all perinatal autopsies and for 20% of all perinatal autopsies in midgestation at Women and Infants Hospital during the past decade. Gram-positive organisms, especially coagulase negative staphylococcus, group B streptococcus and Streptococcus viridans, were the most common pathogens isolated.

Adolescent↗
PubMed1988

Abnormalities of diaphragmatic muscle in neonates with ventilated lungs.

Several infants and neonates who had received long-term ventilatory assistance had subnormal diaphragmatic muscle mass on gross necropsy examination. We conducted a retrospective study of our hospital infant necropsy files to determine whether prolonged ventilatory support was associated with diminution in myofiber cross-sectional area selectively affecting the diaphragm. We found that long-term ventilatory assistance may predispose diaphragmatic myofibers to disuse atrophy or to failure or normal growth. This phenomenon may contribute to difficulties in weaning infants from ventilatory support.

Diaphragm↗
PubMed1988

Parathyroid gland hemorrhage in perinatally lethal osteogenesis imperfecta.

In four neonates with perinatally lethal osteogenesis imperfecta (OI) who survived for more than 9 days after birth, vascular congestion and acute hemorrhage were found in 10 of 11 parathyroid glands; in one neonate, all four parathyroid glands, including the only gland without acute hemorrhage, contained abundant deposits of stainable iron. One neonate had hypocalcemia, and one had both hyperphosphatemia and hypocalcemia. In four neonates with OI who died within 72 minutes of birth, all 10 parathyroid glands demonstrated were free of hemorrhage and hemosiderin deposition. Only minor foci of acute hemorrhage were seen in three of 170 glands in 113 comparison neonates and infants. We conclude that parathyroid gland hemorrhage is common in perinatally lethal OI with survival beyond the immediate period of birth, and is otherwise rare. We speculate that parathyroid hemorrhage may be related to difficulty in maintaining postnatal calcium homeostasis in the absence of adequate calcium reserves in bone. Acute parathyroid gland hemorrhage causes fluctuations in serum calcium levels that have on occasion proved fatal, and parathyroid hemorrhage may be a proximate cause of death in some neonates with OI.

Female↗
PubMed1988

Lethal osteogenesis imperfecta associated with 46,XY,inv(7)(p13q22) karyotype.

An infant who died of complications of osteogenesis imperfecta (OI) at 22 days of age had a 46,XY,inv(7)(p13q22) karyotype. His mother carried the same inversion. One breakpoint of the inversion was within the region of the gene for alpha 2(I) procollagen. The product of this gene is a component of type I collagen, the principal collagen synthesised by osteoblasts. Karyotypic abnormalities involving type I collagen gene sites have not previously been reported in association with OI.

Chromosome Aberrations↗
PubMed1988

Electron microscopic identification of parvovirus virions in erythroid-line cells in fatal hydrops fetalis.

Intrauterine infection with parvovirus B19 may lead to fatal hydrops fetalis. Intranuclear particles, consistent with parvovirus virions, within erythroid cells were readily identified on transmission electron microscopy of formalin-preserved material obtained at necropsy from a neonate and two fetuses in whom clinical and light microscopic criteria for parvovirus B19 infection were met. No such particles were seen in similar material from a neonate and two fetuses with erythroblastosis fetalis due to alpha-thalassemia, maternofetal Rh incompatibility, and an erythrocyte membrane protein defect. When other means of investigation are impracticable transmission electron microscopy is widely available and easily performed and may be of value in establishing a diagnosis of parvovirus B19 infection.

Adult↗
PubMed1988

Hydrocephalus of intrauterine onset in perinatally lethal osteogenesis imperfecta: clinical, sonographic, and pathologic correlations.

Five neonates with perinatally lethal osteogenesis imperfecta (OI) have come to necropsy at Women & Infants' Hospital of Rhode Island in the past eight years. Four had true hydrocephalus, defined as enlargement of the lateral ventricles with thinning of the cortical mantle. In all 4 hydrocephalus was diagnosed by sonography before birth. All 4 died almost immediately after birth, whereas the neonate without hydrocephalus lived for 22 days. Significant necropsy findings in the 4 with hydrocephalus included healing occipital-bone fractures with stenosis of the foramen magnum, remote and recent cerebral parenchymal and intraventricular hemorrhage, and remote and recent subarachnoid hemorrhage. True hydrocephalus of intrauterine onset has rarely been described in perinatally lethal OI, but its high incidence (80%) in this population suggests that it may be a common phenomenon. Hydrocephalus of intrauterine onset in perinatally lethal OI may indicate relatively more severe disease.

Female↗