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Biomedical subjects

S G Driscoll

Publications and source records attributed to S G Driscoll.

At least 19 recordsLinked to original sources

Vaginal adenosis in stillborns and neonates exposed to diethylstilbestrol and steroidal estrogens and progestins.

A histologic study was conducted of sagittal sections of the genital tracts of 281 autopsied female stillborns and neonates. The prevalence of vaginal adenosis among 43 offspring exposed in utero to diethylstilbestrol (DES) was 70%, a frequency 18 times greater than the 4% prevalence among 159 unexposed offspring. The relationship of the prevalence of vaginal adenosis to the gestational age at initial exposure was highly significant: 81% of those first exposed during the period of vaginogenesis had adenosis, whereas none exposed after 21 weeks' gestation had adenosis (P1 = 1 X 10(-4)). The relationship of the prevalence of vaginal adenosis to the total dose of DES prior to 22 weeks' gestation also was significant (P1 = 0.02), and this relationship was independent of gestational age at first exposure (P1 =0.01). In contrast, the prevalence of adenosis among 23 offspring exposed to steroidal estrogens and progestins was about the same as that among the unexposed offspring. Vaginal adenosis was unrelated to the complications of pregnancy for which the hormones were given, the calendar year of birth, and the gestational age at delivery.

Diethylstilbestrol

Gestational trophoblastic neoplasms: morphologic correlates of therapeutic response.

GTN were evaluated histologically in reference to biologic behavior and response to chemotherapy. GTN requiring more intensive, multiple drug chemotherapy usually exhibited increased mitotic activity, nuclear atypias, compact growth of cytotrophoblast, and little maturation, as compared to lesions that responded more favorably. Fibrinoid at the interface of tumor and host tissues was associated with a favorable response to drug therapy. Patients requiring more intensive chemotherapy were more likely to present with distant metastases and high levels of hCG prior to treatment and to reach remission only after many courses of treatment. The clinical and morphologic features of fatal cases suggest that these represented the extreme of a biologic continuum, with collapse of defense mechanisms despite chemotherapy. The early recognition by the pathologist of those lesions that may be resistant to chemotherapy is important to the clinician in selection of an optimal treatment protocol.

Adolescent

Maternal betamethasone and fetal growth and development in the monkey.

Bethamethasone was administered to pregnant rhesus monkeys of 134 to 150 days' gestation. At operative delivery, umbilical venous plasma cortisol concentrations were significantly lower in the treated group than in the control group, indicating that the agent crossed the placenta. In the treated group, accelerated differentiation was present in several fetal organs including lung, liver, kidney, and adrenal gland. Brain histologic changes suggestive of neuronal injury were found in some instances. There were no differences in the weights of these fetal organs except for liver. It was markedly increased in steroid-treated fetuses and this was accompanied by a fourfold rise in total hepatic glycogen content. These observations suggest that in the subhuman fetal primate, the differentiation of fetal organs in addition to lung is enhanced by short-term corticosteroid treatment while growth is not affected.

Animals

Gestational trophoblastic neoplasms: morphologic considerations.

Abnormal trophoblastic proliferation is the hallmark of a spectrum of lesions constituting the gestational trophoblastic neoplasms. Rapid proliferation, infiltration, vascular invasion, hematogenous dissemination, and spontaneous regression are features of both normal and neoplastic trophoblast. Trophoblastic hyperplasia without hydrops, hydatidiform mole, invasive mole, and gestational choriocarcinoma are related lesions, characterized by increasingly aberrant trophoblastic growth and worsening prognosis, if untreated. Difficulties in diagnosis may arise with respect to the normal early implantation site, the hydropic abortus, and postgestational, involuting, residual trophoblast. Histologic grading or hydatidiform moles is relevant to their prognosis and biologic behavior. Trophoblastic neoplasia may begin at any stage of pregnancy or puerperally with immediate or late and local or distant manifestations in the mother or the child. Cognizance of the capricius potential behavior of trophoblast permits successful management of its proliferative lesions, monitored by serial measurement of gonadotropin secretion.

Choriocarcinoma

Experimental toxemia of pregnancy in the monkey, with a preliminary report on renin and aldosterone.

Experimental toxemia of pregnancy was induced in 8 pregnant monkeys (Macacamulatta) by reducing the abdomiinal aorta to one-third of its original diameter during the last month of gestation. It was characterized by hypertension and proteinuria. In the kidney, light and electron microscopy and immunofluorescence revealed findings similar to those in human toxemia. Focal necrosis in the liver and diffuse hemorrhagic infarctions in the placenta were also observed. Plasma renin activity and aldosterone levels, as determined in blood from the uterine vein, were elevated. None of these changes were found in 4 control animals.

Aldosterone

Placental lesions in experimental toxemia in the rabbit.

Unlike the normal human placenta, the normal rabbit placenta, near term, is essentially free of such stigmas of aging as infarcts and syncytial knots. When experimental toxemia is produced in the pregnant rabbit by ligating the terminal aorta to a specific degree of stricture, placental lesions resembling those found in human toxemia are observed; namely, diffuse congestion, old and recent infarcts, and syncytial knots. All the treated animals who exhibited anatomical and clinical signs of toxemia presented, in association, obvious placental lesions; there were, however, some animals which showed infarct but no other signs of toxemia.

Animals

Etiologic heterogeneity of neural-tube defects.

We classified 106 stillborn and live-born infants with anencephaly, meningomyelocele, meningocele and encephalocele according to the recognized causes of these malformations. Six different causes were identified, including both genetic and nongenetic disorders; 12 per cent had nongenetic disorders, a chromosome abnormality, or an encephalocele as part of the autosomal recessive Meckel syndrome. Therefore, for this 12 per cent genetic counseling normally provided for isolated anencephaly, meningomyelocele or encephalocele would have been incorrect. If all infants were considered together regardless of cause, the precurrence and recurrence rates of similar malformations in the sibs were 5.2 and 1.7 per cent respectively. However, if infants with other disorders, especially the Meckel syndrome, were excluded, the precurrence and recurrence rates for isolated anencephaly, meningomyelocele and encephalocele among white infants were only 1.7 per cent and 0 per cent. These rates are much lower than the risk of 5 per cent currently being used in genetic counseling in the United States.

Abnormalities, Multiple

A comparison of early-onset group B streptococcal neonatal infection and the respiratory-distress syndrome of the newborn.

In attempting to differentiate early-onset Group B streptococcal infection from hyaline-membrane disease we found features of severe Group B infection to be rupture of the membranes for more than 12 hours before delivery (four or eight versus one of nine), gram-positive cocci in the gastric aspirate (four or four versus none of one), apnea and shock in the first 24 hours of life (seven of eight versus none of nine), and the generation of lower peak inspiratory pressures on avolume-cycled respirator (mean of 36.5 +/- 2.8 versus 63.9 +/- 6.2 cm of water; P = 0.005). In eight fatal cases of Group B infection, four patients had radiographic features indistinguishable from hyaline-membrane disease whereas the other cases were consistent with neonatal pneumonia. Seven of the eight infected infants had no histologic evidence of coexisting hyaline-membrane disease. Microscopical features of Group B infection included cocci in unevenly distributed hyaline membranes and minimal atelectasis. Group B streptococcal infection differs clinically and pathologically from hyaline-membrane disease. Differentiating clinical features include early apnea and shock and lower inspiratory pressures on mechanical ventilation.

Diagnosis, Differential

Developmental phase-specific alkaline phosphatase isoenzymes of human placenta and their occurrence in human cancer.

Alkaline phosphatase electrophoretic patterns characteristic of three phases in early human trophoblast development are described in this preliminary communication. Phase 1 (6 to 10 weeks) consists entirely of two heat-sensitive, L-homoarginine-inhibited bands, the slower one of which possesses antigenic determinants of live-bone-type alkaline phosphatase, whereas the fast band lacks any of the known alkaline phosphatase antigenic determinants. Phase 2 pattern (11 to 13 weeks) is that of a mixture of Phase 1 and Phase 3 isozyme components, the latter exhibiting two isozyme bands with the characteristics of term placental alkaline phosphatases correspond in order to non-Regan isoenzyme, a mixture of Regan and non-Regan isoenzymes and Regan isoenzyme in a variety of human cancer tissues. The biochemical profile characteristic of trophoblast developmental Phase 1 alkaline phosphatase is expressed as 78.5% heat-sensitive inhibition (5 min at 65 degrees), 66.3% L-homoarginine inhibition, and 17.3% L-phenylalanine inhibition where n = 12. It is hypothesized that the alkaline phosphatase of human tumor tissues reflects the expression of placental genes corresponding to one or more phases of trophoblastic development.

Alkaline Phosphatase

Production of experimental toxemia in the pregnant dog.

The aortas of 14 pregnant bitches were treated 1 to 3 weeks before term, producing a stricture that reduced the lumen from an average normal of 7-11 mm to 2.1 mm in diameter. Nine animals developed hypertension, 3 had significant proteinuria, and 1 had fluid retention. Light microscopy revealed moderate or severe glomerular lesions in 9 animals characterized by endotlial cell swelling, mesangial cell proliferation, and focal basement membrane thickening; electron microscopy revealed mesangial enlargement and electron-dense deposits. Immunofluorescence with rabbit anti-dog fibrinogen showed glomerular deposition of fibrinogen or its breakdown products in 11 of 12 cases so studied. Focal necrosis was seen in the liver in 5 cases, and diffuse hemorrhagic infarction of the placenta was present in all animals. None of these changes was found in nonpregnant or in sham-operated controls.

Animals

Chorioamnionitis and colonization of the newborn infant with genital mycoplasmas.

To study the role of Mycoplasma hominis and T-mycoplasmas (Ureaplasma urealyticum) in chorioamnionitis, we obtained culture from 249 puerperal women and their babies. The placentas were examined histologically. Infants whose placentas showed inflammation (chorioamnionitis) had cultures positive for T-mycoplasmas more frequently (37.5 per cent) than those with normal placentas (19.0 per cent) (P = 0.021). Colonization with M. hominis was found in 16.0 per cent of the babies and was not significantly associated with chorioamnionitis. Material colonization with mycoplasmas was more frequent (73.4 per cent) and was not correlated with placental inflammation. We conclude that a substantial proportion of cases of chorioamnionitis may be caused by prenatal infection with T-mycoplasmas. The fact that these organisms are not highly virulent could explain the frequent finding of inflammed placentas from otherwise normal pregnacies. No adverse clinical effects of the placental lesions or of mycoplasmal colonization could be detected in this small study.

Amnion