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Biomedical subjects

W A Blanc

Publications and source records attributed to W A Blanc.

At least 19 recordsLinked to original sources

Time-trends in necropsy prevalence and birth prevalence of lung hypoplasia.

Congenital lung hypoplasia (LH) has been identified with increasing frequency in perinatal and neonatal necropsy reviews. The available prevalence figures have been derived using various diagnostic criteria in different populations and at various times. We therefore reviewed our experience in 15 years of consecutive early neonatal necropsies using one constant set of diagnostic criteria for LH and looked for a time-trend. We determined the necropsy prevalence (no. of cases of LH/no. of necropsies) and the birth prevalence (no. of cases of LH documented at necropsy per 1000 livebirths for inborn patients, and per 1000 referrals for outborn patients) between 1971 and 1985. We then divided this 15-year period into five consecutive 3-year periods to determine if a time-trend was discernible. Whereas early neonatal mortality for neonatal intensive care unit (NICU) admissions progressively decreased from 11.4% to 4.0% between the first and the last 3-year periods, the number of cases of LH per 3-year period did not vary appreciably. As a result, the prevalence of LH at necropsy showed a slight upward trend with time. The overall prevalence was 18%; it was 13% during the first and 23% during the last 3-year period. We found no time-trend in birth or referral prevalence for this lesion, which averaged 1.1 per 1000 livebirths and 9.8 per 1000 referrals. We conclude that lung hypoplasia appears to be emerging as an increasingly prevalent necropsy finding as a result of a shift in proportionate mortality, with the number of patients dying of other causes (denominator) decreasing, and the number of patients dying with lung hypoplasia remaining constant.

Cause of Death

Hemangioma with Kaposi's sarcoma-like features: report of two cases.

We describe two children with vascular neoplasms that resembled Kaposi's sarcoma in places. Both presented with intraabdominal masses and severe thrombocytopenia. At autopsy the tumors extensively infiltrated the peritoneum and retroperitoneum and surrounded or invaded numerous organs including the kidneys, pancreas, adrenal glands, gastrointestinal tract, mesentery, and lymph nodes in both cases, and spleen or bone marrow in one case each. The neoplasms were histologically identical and displayed two patterns: dilated vascular spaces (angiomatous areas) lined by flat endothelial-like cells and areas of spindle cells forming slitlike vascular spaces similar to those described in Kaposi's sarcoma. Tumor cells in both cases expressed markers for endothelial cells. The clinical and histologic character of these neoplasms differentiates them from Kaposi's sarcoma, hemangioendothelioma, and from conventional juvenile hemangioma.

Child, Preschool

Abnormalities of the coronary circulation in pulmonary atresia and intact ventricular septum.

To identify developmental aspects and establish morphologic criteria useful for clinical recognition of sinusoids and coronary artery abnormalities in pulmonary atresia and intact ventricular septum, we studied 17 autopsy hearts with this lesion. Hearts from age- and weight-matched infants served as controls. There were two stillborn fetuses, 12 full-term neonates, and 3 infants. None of the eight hearts with normal or large-sized right ventricular chambers had sinusoids or coronary artery abnormalities. Five of nine hearts with small right ventricular chambers had sinusoids; all five lacked trabecular and outlet portions of the ventricle. Four of these five contained major coronary artery abnormalities: atrophy of one or both coronaries proximal to a communication between a sinusoid and the coronary artery. We conclude (1) there is a strong association between the presence of sinusoids and coronary anomalies, supporting the developmental concept of abnormal persistence of embryonic right ventricular sinusoid--coronary artery communications in pulmonary atresia and intact ventricular septum; (2) the absence of trabecular and outlet portions of the small right ventricle indicates a strong possibility of coronary artery abnormalities; and (3) this initial report of a fully-developed lesion in a mid-gestation fetus documents that the coronary artery problem may arise early in fetal life.

Coronary Vessel Anomalies

Umbilical cord length in Down's syndrome.

Fetal motor activity is believed to influence umbilical cord growth. As Down's syndrome is associated with hypotonicity and reduced fetal activity, we hypothesized that newborn infants with this syndrome have short umbilical cords. We identified 21 infants with Down's syndrome and compared each individual cord length to mean standard values derived from the same population and matched for sex, race, and gestational age. Infants with Down's syndrome were found to have significantly shorter umbilical cords (mean of 45.1 cm compared with 57.3 cm for matched standards). It is not clear whether their cords are shorter on the basis of decreased fetal activity, genetics, or both. If it is on the basis of decreased fetal activity, it would be interesting to see if those with the shortest cords (presumed to have been the most hypoactive in utero) could be predicted to have worse neurodevelopmental outcomes.

Down Syndrome

Morphometric analysis of the growth of the normal fetal guinea pig lung.

The structural development of the fetal guinea pig lung is described and quantified morphometrically in this report. At 35 days gestation the lung is in the pseudoglandular phase of growth, by 40 days it is in the canalicular phase, and at 50 days the saccular growth phase has begun. At term (67 days), the fetal guinea pig lung appears mature. From the beginning of the canalicular to the end of the saccular phases, the correlation coefficient between lung volume and gestational age is +.98, between internal surface area and gestational age is +.94 and between total number of saccules and gestational age is +.97. Internal surface area (ISA) correlates closely with lung volume (r = +.99) and the correlation coefficient between total number of saccules and lung volume is +.98. At term, lung volume is 4.22 ml. ISA is 0.5 M2, and total number of saccules is 253 million. Parenchymal growth is achieved by increases in both number and size of airspaces in the canalicular phase, primarily by increases in number during the early saccular phase and largely by increases in airspace size near term. The total length of parenchymal elastic tissue increases from 223 M at 45 days gestation to 5,253 M at term. Elastic tissue fibers first appear in the parenchyma of the fetal guinea pig lung during the canalicular phase, when the rate of saccule formation is high. The quantitative increase in elastic tissue correlates closely with the increase in the total number of saccules from day 45 to day 60 of gestation (r = +.99). The rate of elastic tissue growth increases sharply in the late saccular phase, coinciding with the period of greatest saccular expansion. These data suggest an interdependent relationship between saccular growth, i.e., proliferation and expansion, and the development of lung parenchymal elastic tissue.

Animals

Oligohydramnios-induced lung hypoplasia: the influence of timing and duration in gestation.

We drained amniotic fluid for periods of 5 and 10 days at various times in gestation between days 40 and 55 in the guinea pig (term is 67 days). We analyzed the impact of this procedure on fetal lung growth and used untouched littermate fetuses as controls. During the canalicular stage of lung development, total lung DNA per gram of fetal weight was significantly reduced after only 5 days of oligohydramnios and the percent change did not vary between the two consecutive 5-day periods studied (period A, days 40 to 45, delta of -0.047 mg, p = 0.004; period B, days 45 to 50, delta of -0.042 mg, p = 0.002). The impact of the same duration of oligohydramnios on lung growth later in gestation, during the terminal sac stage of lung development, was less (period C, days 50 to 55, delta of -0.027 mg, p = 0.097). This reduction in effect between period A or B and C was significant at the 0.05 level using a one-way analysis of variance. Two overlapping 10-day periods were also studied. In both experiments, the percent changes in lung DNA per gram of fetal weight between experimental and littermate controls were significant (period D, days 40 to 50, delta of -0.072 mg, p = 0.001; period E, days 45 to 55, delta of -0.047 mg, p = 0.001). The inhibitory effect of oligohydramnios on lung growth was more marked in period D than E (significant at the 0.05 level).(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid

Morphometry of hypoplastic fetal guinea pig lungs following amniotic fluid leak.

Deficient quantity of amniotic fluid causes fetal guinea pig lung hypoplasia. Oligohydramnios that lasts only 5 days in early gestation is sufficient to reduce fetal lung growth significantly. We quantitated lung structural alterations at 50 days gestation (term is 67 days) of fetal guinea pigs whose amniotic fluid was drained on day 45 gestation. The study period spans the late canalicular-early saccular phases of guinea pig lung growth. Compared to littermate controls (n = 4), experimental fetuses (n = 5) have reduced lung:body weight ratio (2.81 +/- 0.16 versus 3.21 +/- 0.20 X 10(-2), p less than 0.01), indicating lung hypoplasia. Lung volume is significantly decreased in the experimental fetuses (1.17 +/- 0.15 versus 1.34 +/- 0.07 ml, p less than 0.05). The proportion of lung containing parenchyma (i.e. developing alveoli and alveolar ducts) is reduced following oligohydramnios (0.83 +/- 0.04 versus 0.90 +/- 0.02, p less than 0.025). The hypoplastic lungs contain fewer saccules (fetal "alveoli") (46 +/- 20 versus 69 +/- 23 X 10(6), p less than 0.1) and the surface area that would be available for gas exchange is decreased (698 +/- 234 versus 974 +/- 80 cm2, p less than 0.05). Lung volume and volume proportion of parenchyma are reduced in the experimental lung and therefore diminished parenchymal elastic tissue is anticipated. However, the total length of parenchymal elastic tissue in the experimental lungs is decreased to a surprising degree and is little more than half the length in control lungs (504 +/- 222 versus 974 +/- 70 m, p less than 0.0025). Such marked reduction in total length suggests that factors other than smaller lung size have contributed to the decrease of elastic tissue in the experimental group. In fact, elastic tissue length per unit volume is significantly reduced (509 +/- 189 versus 809 +/- 115 m/cm3, p less than 0.025) indicating an absolute decrease in parenchymal elastic tissue in the hypoplastic lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid

Malformations and chromosome anomalies in spontaneously aborted fetuses with single umbilical artery.

Presence of a single umbilical artery was noted 13 times among a series of 879 consecutively collected, spontaneously aborted embryos and fetuses. This rate of 1.5% is approximately twice that reported from the largest series of term births. Eight of the 13 fetuses had additional serious malformations. Of nine successfully karyotyped fetuses, six had chromosome anomalies. All six occurred in fetuses with severe malformations in addition to the single umbilical artery. The presence of single umbilical artery with other major anatomic defects may be a significant predictor of the presence of chromosome anomalies in live births. Early recognition of offspring with chromosome anomalies will be useful in counseling the family and in managing the care of the infant.

Abnormalities, Multiple

Fetal lung hypoplasia associated with maternal smoking: a morphometric analysis.

Our recently reported animal (rat) model of maternal cigarette smoke exposure during pregnancy is characterized by fetal growth retardation and lung hypoplasia. We have further defined the fetal lungs using quantitative histologic techniques. Compared to controls, lung volume at term is reduced in the experimental animals (0.28 versus 0.33 ml, p less than 0.005). Saccules (fetal "alveoli") are reduced in number (3 X 10(6) versus 5.5 X 10(6), p less than 0.005) and increased in size (average saccular volume: 35 X 10(-9) versus 21 X 10(-9) ml, p less than 0.025). These changes in size and number are consequences of reduced formation of saccule partitions (septal crests) in the experimental lungs (volume density: 0.013 versus 0.018, p less than 0.025). Internal surface area is decreased in the hypoplastic lungs (161 versus 198 cm2, p less than 0.001). The total length of parenchymal elastic tissue is diminished (224 versus 354 M, p less than 0.05). In short the hypoplastic lungs contain fewer, larger saccules and the surface potentially available for gas exchange is reduced. These results show that maternal smoking in rats adversely modifies fetal lung growth. If these observations are applicable to humans, then reduced lung growth in children of smoking mothers may begin antenatally.

Animals

Healing of ischemic colonic anastomoses in the rat: role of antibiotic preparation.

In this study we evaluated the relative effects of ischemia with and without antibiotic bowel preparation on colonic wound healing. Thirty-two Sprague-Dawley rats (185 to 300 gm) were divided into five study groups: Groups I and II (n = 14) had no colonic ischemia, half receiving antibiotic bowel preparation before colocolostomy. Groups III, IV, and V (n = 18) had colonic ischemia induced by division of the marginal artery and ligation of the arteries to the splenic flexure and pelvic colon, assuring that all blood supply to the left side of the colon was intramural. Enteral (neomycin and erythromycin) antibiotic preparation was given in group III, no antibiotics were given in group IV, and parenteral (clindamycin and gentamicin) preparation was given in group V. The mid-left side of the colon was transected and an everting anastomosis was constructed with continuous 6.0 silk sutures. All animals were killed on the seventh postoperative day. Anastomotic healing in unprepared, ischemic rat colon was severely impaired, with an 83% dehiscence rate. In the colon prepared with enteral antibiotics, no adverse effect of ischemia was found. No animal had dehiscence, proximal dilation of the colon, or intra-abdominal abscess. This study may have clinical relevance in patients with ischemic intestinal disorders.

Administration, Oral

Chemotherapy and its effect on testicular morphology in children.

Bilateral testicular biopsies were performed on 25 boys between 4 and 16 years old with the diagnosis of acute lymphocytic leukemia after the induction of regression with vincristine and prednisone, followed by cyclic maintenance therapy with a combination of 6-mercaptopurine, methotrexate, L-asparaginase, cyclophosphamide and doxorubicin for 2 years. These drugs were given in accordance with children's cancer study group protocols. Only 3 boys had positive biopsies (12 per cent), although post-treatment testicular morphology was abnormal in the overwhelming majority. Interstitial fibrosis was present in 16 children (70 per cent), basement membrane thickening in 12 (50 per cent) and, most importantly, a reduction in the tubular fertility index of greater than 50 per cent in 20 (80 per cent). There was no relationship between the abnormal morphology encountered and the age of the patient when treated. Most of these changes may be reversible with time but only a biopsy at a later date can establish the long-term effects of treatment on testicular morphology and, perhaps, help to predict future fertility potential.

Adolescent

The significance of cystic hygroma in fetuses.

Cystic hygroma of the neck was observed in seven spontaneously aborted, severely autolyzed female fetuses. Four of five karyotyped cases had the 45,XO karyotype; one was a normal female, 46,XX. Diagnostic features associated with monosomy X in fetuses, which were observed in six of these cases, include large cystic hygromas, generalized edema, edematous chorionic villi with scalloped borders and trophoblastic inclusions, and, possibly, a small heart. In contrast, the single euploid fetus in this series had a small cystic hygroma, no hydrops, and chorionic villi of normal size. These features may differentiate cystic hygromas associated with the XO karyotype, which are not associated with recurrence risk, from those associated with a familial syndrome.

Abortion, Spontaneous

Immunocytochemical localization of lysozyme and alpha-1-antichymotrypsin in the term human placenta: an attempt to characterize the Hofbauer cell.

The intracellular localization of lysozyme (LSZ) and alpha-1-antichymotrypsin (A1Ac), glycoproteins associated with macrophages, was used to confirm the monocytic lineage of the Hofbauer cell and to assess the maturity of its macrophage function. The peroxidase-labeled antigen method was used to localize these proteins, as well as immunoglobulins, light chains, and albumin, in Bouin-fixed, paraffin-embedded sections of 24 normal term placentas. The demonstration of the latter substances was used as an indication of passive diffusion or phagocytosis of serum proteins resulting in intracellular localization unrelated to synthesis. In all the placentas examined a strong cytoplasmic reaction for A1Ac was seen in the Hofbauer cells. The same cells on adjacent sections did not stain for LSZ, while the occasional maternal macrophage and numerous polymorphonuclear leukocytes in the intervillous spaces gave a positive reaction. The detection of A1Ac supports the contention that these cells are macrophages, previously suggested by their phagocytic capability and the demonstration of Fc receptors and nonspecific esterases. Since they do not appear to contain LSZ, a bactericidal enzyme, we propose that these cells are not fully differentiated macrophages, and the lack of this enzyme may have some relevance to the pathogenesis of certain placental infections.

Chymotrypsin

Fetal growth retardation due to maternal tobacco smoke exposure in the rat.

Smoking during pregnancy results in offspring with an average birth weight 200 g less than those of non-smoking mothers. The pathogenesis of this effect is still unknown and there is no general agreement about the causal relationship between maternal smoking and subsequent fetal growth retardation. In the present study, a model of maternal smoking during pregnancy in the rat was established using the P & I Walton Exposure Machine. The study consisted of three groups: control, pair-fed, and smoke-exposed. Smoke-exposed animals were exposed continuously to tobacco smoke for cycles of 7 min, 16 times a day from d 5 to d 20 of gestation. On d 21 of gestation, fetuses from all groups were removed by cesarean section, weighed, and dissected. The fetal brain, liver, and lungs as well as the placentas were weighed and analyzed for nucleic acid content. Fetal weight was found to be significantly reduced in both pair-fed and smoke-exposed groups compared with the control group. There was also a significant reduction in fetal body weight of the animals in the smoke-exposed group in comparison to those in the pair-fed group. Exposing the mother to smoke affected neither fetal brain weight nor nucleic acid content whereas fetal liver and lungs showed a significant decrease in both weight and nucleic acid content. These results indicate that the fetal growth retardation associated with maternal exposure to tobacco smoke in the rat corresponds to a disproportionate type.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Experimental production of pulmonary hypoplasia following amniocentesis and oligohydramnios.

We have analyzed the impact of a single needle puncture of the fetal rat membranes on day 15 of gestation on growth and development at term (day 21). Untouched littermate fetuses served as controls. The procedure led to persistent oligohydramnios. The experimental fetuses weighed less, 94% of the weight of controls, P less than 0.01. Both lungs and liver weighed significantly less, 72% (P less than 0.01) and 89% (P less than 0.03) of controls respectively and there was no effect on brain weight. When the values were expressed as organ/body weight ratio only the lung/body weight ratio was significantly lower, 77% of controls, P less than 0.01. DNA per lung was less, 83%, as was lung DNA per gram of fetal weight, 89%, and the lung protein/DNA ratio was lower, 79%, indicating lung hypoplasia and hypotrophy (all three P values less than 0.01). There were no significant differences in either liver or brain biochemical analysis. We conclude that pulmonary hypoplasia associated with oligohydroamnios in the rat is a suitable animal model of the human condition.

Amniocentesis

Identification of erythrocytes in intervillous thrombi: a study using immunoperoxidase identification of hemoglobins.

The origin of the erythrocytes in intervillous thrombi has never been definitively established. Fetal hemoglobin-containing erythrocytes were identified in histologic sections of intervillous thrombi using the peroxidase-antiperoxidase unlabeled antibody method. In 85 per cent of intervillous thrombi containing well-preserved erythrocytes, fetal hemoglobin-containing cells were found in quantities well in excess of the number seen in maternal blood. This definitely demonstrates the presence of erythrocytes of fetal origin in intervillous thrombi. Possible pathogenic mechanisms of intervillous thrombosis and fetal-maternal hemorrhage are discussed.

Chorionic Villi