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Biomedical subjects

J E Gillan

Publications and source records attributed to J E Gillan.

At least 19 recordsLinked to original sources

Analyses of the potential oxygen transfer capability in placentae from infants succumbing to sudden infant death syndrome.

BACKGROUND: Morphometric oxygen diffusive conductance (Dp) was estimated to assess the potential efficiency of oxygen transfer across the materno-fetal interface in placentae obtained from victims of sudden infant death syndrome (SIDS). STUDY DESIGN: SIDS placentae were retrieved from archived storage and classified into normal birth weight (NBW, n=16), or small for gestational age (SGA, n=9) and compared against control placentae (n=40) or SGA (n=24) placentae. A combination of stereological techniques and physiological constants were used to estimate total Dp. RESULTS: SIDS NBW cases showed a crucial reduction in fetal capillary surface area when compared with control placentae. SIDS SGA showed a number of deficiencies in basic volumetric and surface area parameters. Values for total and specific Dp in placentae in both SIDS groups were maintained at levels comparable with control and SGA cases, respectively. CONCLUSION: Since more reductions were observed in SIDS SGA group, this suggests that factors responsible for these reductions maybe associated with SGA rather than being SIDS-specific factors.

Adult↗

Choriocarcinoma-presenting as a primary lesion of the cervix.

A 25 year old nulliparous Russian lady presented to the hospital complaining of abdominal pain and mild vaginal bleeding. In 1999 she was diagnosed with a molar gestation and required a dilatation and curettage. On this occasion, Beta human Chorionic Gonadotrophin (BhCG) levels were elevated and a trans-vaginal ultrasound scan suggested the presence of a left-sided pelvic mass. Investigations confirmed the presence of a choriocarcinoma of the cervix. Complete assessment by a multidisciplinary team was performed and chemotherapy (methotrexate) was commenced. This case of a twenty-five year old nulliparous woman highlights the importance of appropriate follow-up in cases of irregular genital tract bleeding with a past history of trophoblastic disease.

Adult↗

Morphometric assessment of the oxygen diffusion conductance in placentae from pregnancies complicated by intra-uterine growth restriction.

The morphometric oxygen diffusive conductance (D(p)) of the placenta provides a measure of the efficiency of oxygen transfer between the mother and the developing fetus. Any change in the D(p)may point towards possible adaptation in the light of altered oxygen transfer. Placentae from normal (n=40) and small for gestational age SGA (n=24) pregnancies were analysed using stereological techniques. Each placenta was uniform randomly sampled and tissue samples processed to wax infiltration and embedding using conventional histological preparatory methods. A combination of stereological techniques and physiological constants were used to estimate the partial conductances across the five major tissue compartments involved in oxygen transfer. There was a significant reduction in both fetal birthweight and placental weight in the SGA group when compared with controls. A decrease in both chorionic (S(cv)) and fetal capillary (S(fc)) surface area was also observed in SGA placentae when compared with controls (P>0.001). Villous membrane harmonic thickness (T(vm)) was reduced in the SGA placentae (2.33 microm) when compared with controls (2.67 microm P=0.019). This resulted in a reduction in the minimum D(p)in SGA placentae when compared with controls (P=0.023). Adjusting for fetal weight resulted in no difference in the specific diffusive conductance. Changes in T(vm)in SGA placentae combined with changes in basic surface areas were insufficient to maintain overall D(p)values comparable with control placentae.

Adaptation, Physiological↗

Massive perivillous fibrinoid causing recurrent placental failure.

OBJECTIVE: To establish the incidence, recurrence rate and consequences of massive perivillous fibrinoid. DESIGN: Retrospective analysis of the histology of all placentas with a diagnosis of massive perivillous fibrinoid between 1991 and 1998, together with the maternal case records. SETTING: The histopathology department of the Rotunda Hospital, Dublin, Ireland. POPULATION: A relatively homogeneous group of pregnant women in the northern part of Dublin City, which is the catchment area for the Rotunda Hospital, delivered between 1991 and 1998. METHODS: Retrospective review of archival placental pathology and maternal charts. MAIN OUTCOME MEASURES: The incidence of massive perivillous fibrinoid, perinatal outcome and recurrence rate. RESULTS: The incidence of massive perivillous fibrinoid was 0.028%, with a recurrence rate of approximately 18%. All the infants suffered intrauterine growth restriction; there was a 31% fetal loss rate and a 33% preterm delivery rate. CONCLUSIONS: Massive perivillous fibrinoid is associated with intrauterine death, intrauterine growth restriction and preterm delivery. It has a significant recurrence rate and both the clinical findings of intrauterine growth restriction and the postmortem findings imply a syndrome of chronic placental insufficiency.

Abortion, Habitual↗

Chronic reduction in fetal blood flow is associated with placental infarction.

The placenta receives two arterial blood supplies, i.e. one maternal and one fetal. It has been suggested that placental infarction should occur only if both blood supplies are compromised (Wigglesworth, 1984). This hypothesis has not been tested. Haemosiderosis of the trophoblast basement membrane (TBMH) has recently been identified as a feature of fetal artery thrombosis and suggested as a marker of impaired fetal blood flow which is identifiable in both viable and necrotic tissue. We examined 50 placental infarcts for evidence of TBMH, both grossly and microscopically. These were compared with four types of control tissue. Eleven placentae from cases of prolonged intrauterine death, in which this feature was first described, and 35 fetal artery thromboses were used as positive controls and 20 placentae from uncomplicated pregnancies were available as negative controls. Non-infarcted tissue adjacent to infarcts served as an internal negative control. Non-infarcted tissue adjacent to infarcts served as an internal negative control. Microscopically, 36 per cent of infarcts showed TBMH in at least 5 per cent of villi within the lesion and 60 per cent of infarcts showed at least one cluster of villi with the feature. These findings point to a disturbance in fetal blood flow intimately associated with but pre-dating the placental infarction. These findings represent the first experimental evidence to support Wigglesworth's theory and suggest that reduction in fetal blood flow prior to thrombosis of maternal vessels contributes to the pathophysiology of placental infarction.

Chorion↗

Trophoblast basement membrane haemosiderosis in the placental lesion of fetal artery thrombosis: a marker for disturbance of maternofetal transfer?

The placental lesion of fetal artery thromboses is characterized by collapse and obliteration of chorionic vasculature, an increase in stromal connective tissue and syncytial knots, with a thickening of trophoblast basement membrane. An additional feature, not previously described in association with the lesion, is linear trophoblast basement membrane haemosiderosis. Thirty-five such lesions were examined for this feature which was identified in 32. Random tissue sections of placentae from cases of intrauterine death showed a similar basement membrane haemosiderosis and were used as positive controls. None of 20 normal control cases examined demonstrated the feature. Electron microscopy demonstrated electron-dense bodies within the basement membrane. Spectrographic analyses confirmed the presence of iron within these deposits. The significance of this finding lies not so much in the fact that it is an additional finding in fetal artery thrombosis but rather in the underlying pathophysiology.

Basement Membrane↗

Comparison of ploidy analysis by flow cytometry and image analysis in hydatidiform mole and non-molar abortion.

Determination of DNA ploidy is useful in the diagnosis and classification of hydatidiform mole. Most reports of ploidy analysis in molar tissue have used DNA flow cytometry. Although image analysis cytometry offers theoretical advantages over flow cytometry, there have been few reports of ploidy analysis by image analysis in hydatidiform mole. We selected 47 cases and measured DNA ploidy by flow cytometry and image analysis cytometry in complete hydatidiform mole, partial hydatidiform mole and non-molar abortion. The two cytometry modalities were compared using kappa statistics. There was reasonable overall agreement between the two modalities (kappa = 0.69) and when ploidy was stratified into diploid/polyploid and triploid categories there was near perfect agreement (kappa = 0.93). Aneuploid cell populations, which were not evident on flow cytometry, were identified by image analysis in a significant proportion of complete and partial hydatidiform moles and in a small number of non-molar abortions. Flow cytometry and image analysis cytometry yield comparable ploidy information, useful in the diagnosis and classification of hydatidiform mole. Image analysis cytometry offers greater sensitivity in the detection of small non-diploid cell populations but the significance of this latter finding is uncertain.

Abortion, Spontaneous↗

Comparison of villous trophoblast proliferation rate in hydatidiform mole and non-molar abortion by assessment of proliferating cell nuclear antigen expression.

This study examines the proliferative activity of trophoblast in hydatidiform mole, non-molar hydropic abortion and non-molar spontaneous abortion. Nine cases of complete mole, 10 cases of partial mole, eight cases of non-molar hydropic abortion and six cases of non-hydropic second trimester abortion were examined by routine histopathology and the rate of cell proliferation was assessed by immunoreactivity for proliferating cell nuclear antigen (PCNA). Hydropic abortion showed a significantly lower PCNA index than complete mole and partial mole. There was no significant difference in PCNA index between partial mole and non-hydropic abortion. The trophoblast of partial hydatidiform mole demonstrates significant cell proliferation but this, although higher than that of hydropic abortion, is no higher than that of non-hydropic abortion of a similar gestational age. The role of partial mole as a precursor of persistent gestational trophoblastis disease remains unclear.

Abortion, Spontaneous↗

Chorionic villous haemorrhage is associated with retroplacental haemorrhage.

OBJECTIVE: To examine the frequency of occurrence of chorionic villous haemorrhage in placentas with retroplacental haemorrhage, and to discuss the pathogenesis of these conditions. DESIGN: A retrospective study using histological sections of formalin-fixed, paraffin-embedded placental tissue stained with haematoxylin and eosin. SETTING: Department of Histopathology, Rotunda Hospital, Dublin. SUBJECTS: Sixty cases of retroplacental haemorrhage, 34 cases of chorioamnionitis, and 24 histologically normal placentas. MAIN OUTCOME MEASUREMENT: Presence or absence of chorionic villous haemorrhage. RESULTS: Chorionic villous haemorrhage was present in 31 of 60 cases of retroplacental haemorrhage (51%), one of 34 cases of chorioamnionitis (2.9%) and in no normal placentas. CONCLUSIONS: It is postulated that chorionic villous haemorrhage reflects a disturbance of fetal vascular dynamics and precedes retroplacental haemorrhage. Such a disturbance could trigger the events leading to abruption.

Chorioamnionitis↗

Partial hydatidiform mole: a common but underdiagnosed condition. A 3-year retrospective clinicopathological and DNA flow cytometric analysis.

This retrospective study reports the incidence of hydatidiform mole in a population of 19,457 pregnancies over a 3-year period. During the study period all "products of conception" from first and second trimester abortions were referred for pathological examination. Coded histologic sections were reviewed using the published histologic criteria for hydatidiform mole. Ploidy was estimated by DNA flow cytometry. Clinical data were retrieved from maternal case notes. Thirty-eight cases were confirmed as hydatidiform mole, 10 (26%) as complete mole, and 28 (74%) as partial mole. Twenty-three cases of partial mole (88%) were triploid, and nine of 10 complete moles were diploid. The incidence of hydatidiform mole was 1:512 pregnancies, (complete mole, 1:1,945; partial mole, 1:695). Only one case (3.5%) of partial mole was suspected clinically. One case of persistent gestational trophoblastic disease occurred following a complete mole. No sequelae were encountered following partial mole. We conclude that hydatidiform mole is a common condition and the majority of cases are partial moles. Quantitatively imprecise morphologic criteria contribute to the inaccuracy in reporting of partial mole; analysis of ploidy is useful in the evaluation of problem cases. Follow-up of partial mole is warranted because its true biological potential is as yet unclear.

Abortion, Spontaneous↗

Perinatal placental pathology.

Examination of the placenta may be viewed as a diary of the pregnancy. Apart from its immediate diagnostic value, it can also broadly serve two purposes: 1) it provides a method of auditing antenatal clinical judgment by clinicopathologic correlation, and 2) it makes an important contribution in the context of unsolved clinical problems. The placenta's strategic location at the fetomaternal interphase mirrors disorders of both mother and fetus; however, "merged images" still cause some confusion, eg, villitis. This review summarizes recent areas of clinicopathologic correlation that have enhanced our understanding of placental function and the fetoplacental unit.

Abruptio Placentae↗

Abnormal patterns of pulmonary neuroendocrine cells in victims of sudden infant death syndrome.

Ventilatory dysfunction has become the main focus of current research in sudden infant death syndrome (SIDS). This has been correlated with structural abnormalities in the carotid body and respiratory nuclei of the brainstem. In recent studies, the denervating effect of asphyxial brainstem dysfunction on the pulmonary neuroendocrine cells, which probably function as chemoreceptors, was demonstrated and prompted the following study. The pulmonary neuroendocrine system was evaluated in 25 victims of SIDS and 20 control infants, ranging in age from 3 weeks to 7 months and 1 to 12 months, respectively. The pulmonary neuroendocrine cells were stained by the Churukian-Schenk method and the neuroendocrine cell-positive airway values expressed as a percentage of the total number of airways. The range of positive airway values for victims of SIDS was 2% to 97% with a median of 73%. In contrast, the range for the control infants was 1% to 44% with a median of 25.5%. The SIDS victims' percentage was significantly greater than the control infants' percentage (P less than .0001). The number of pulmonary neuroendocrine cells in positive airway was also increased among SIDS victims compared with control infants. The altered pulmonary neuroendocrine cell pattern could be attributable to either brainstem dysfunction or chronic hypoxia. These explanations are not, however, mutually exclusive of one another; in fact, it is possible that both mechanisms may be operative.

APUD Cells↗

Association of changes in bombesin immunoreactive neuroendocrine cells in lungs of newborn infants with persistent fetal circulation and brainstem damage due to birth asphyxia.

The pulmonary neuroendocrine (NE) cells, from 16 term infants dying at 1-4 days of age from birth asphyxia, were immuno stained for bombesin-like immunoreactivity by the immunoperoxidase method. The distribution and frequency of bombesin-immunoreactive NE cells were quantified morphometrically and correlated with the presence or absence of brainstem function and persistent fetal circulation (PFC). In infants with loss of brainstem function, the frequency of bombesin immunoreactive NE cells was significantly increased compared to infants with intact brainstem function, i.e. meconium aspiration with PFC. Infants with brainstem injury, with one exception, failed to develop PFC. Pathological changes in the tegmentum of the brainstem, i.e. containing the respiratory center, correlated in nine of 10 cases with loss of brainstem function. These data suggest an inverse relationship between brainstem function, release of bombesin-like peptide from the pulmonary NE cells and the functional state of the pulmonary vasculature. Intact brainstem function appears to be essential for both the release of bombesin-like peptide from the NE cells and for pulmonary vasoconstriction leading to PFC; absence of brainstem function is, on the other hand, associated with failure to release bombesin-like peptide and loss of PFC type reactivity in the pulmonary vasculature. However, it appears unlikely that bombesin itself is a direct mediator of pulmonary vasoconstriction.

Asphyxia Neonatorum↗

Myocardial ischaemia in asphyxia neonatorum. Electrocardiographic, enzymatic and histological correlations.

Serial electrocardiograms and creatine kinase (CK) isoenzyme activities were studied prospectively in 20 asphyxiated term newborn infants and 43 normal neonates. By adapting a previously described grading system for ischaemic changes, a degree of electrocardiographic ischaemia was defined which occurred almost solely in asphyxiated infants. Infants with this degree of abnormality had significantly higher mean CK-MB and MM activities than other asphyxiated infants at 0, 8 and 28 hours. Histological changes of peripartum myocardial necrosis were seen in 4 of the 5 infants on whom an autopsy was performed, and either electrocardiogram or CK-MB was abnormal in all four. It is concluded that myocardial injury in the newborn period is often associated with CK-MB release, but in view of the lack of cardiac-specificity of CK-MB in newborn infants, caution is urged in the interpretation of elevated isoenzyme activity in the neonate.

Asphyxia Neonatorum↗

Congenital ascites as a presenting sign of lysosomal storage disease.

Neonatal ascites is usually attributed to hematologic, genitourinary, gastrointestinal tract, or congenital heart disease. When these lesions have been excluded, metabolic storage disorders should be considered in the differential diagnosis. We report eight cases of neonatal ascites associated with different types of lysosomal storage disease: infantile sialidosis, Salla disease, GM1 gangliosidosis, and Gaucher disease. In each case there was a history of sibling of perinatal death resulting from the disease. In three cases the diagnosis of ascites was made in utero by ultrasound examination. These diseases are characterized by excretion in the fetal urine of abnormal catabolic products or by measurement of decreased activity of specific lysosomal hydrolases in cultured amniocytes. Thin-layer chromatography of the oligosaccharides in amniotic fluid may be indicated when a diagnosis of persistent fetal ascites has been established.

Adult↗