Circulating pro- and anticoagulant levels in normal and complicated primigravid pregnancies and their relationship to placental pathology.

We aimed to compare the changes in factor VIII:C, antithrombin, protein C, protein S and fibrinogen in a cohort of low-risk primigravida who developed maternal or fetal complications to those who had uncomplicated pregnancies and to correlate these findings with placental pathology. This is a case-control study of 170 cases and 122 controls selected from a prospective cohort of 1,011 low-risk primigravida. Significantly elevated levels of factor VIII:C and significantly decreased levels of antithrombin were seen in women who developed pre-eclampsia (p <0.001), placental infarction (p < 0.001) or had infants with a birth weight < 3rd centile (p < 0.001). Placental villous dysmaturity was significantly associated with raised factor VIII:C (p < 0.001). Women who developed pre-eclampsia showed elevated fibrinogen at 14 weeks (p = 0.03). Significantly higher than normal pregnancy levels of factor VIII:C, in tandem with significantly lower antithrombin levels associated with certain adverse pregnancy outcomes, may be related to underlying placental insufficiency. This is supported by associated placental findings.

Ponderal index (PI) vs birth weight centiles in the low-risk primigravid population: which is the better predictor of fetal wellbeing?

Our objective was to compare Ponderal index (PI) with birth weight centiles as predictors of perinatal morbidity and to determine which best reflects the presence of placental disease. We prospectively recruited 1,011 low-risk primigravidas and calculated PI and birth weight centiles following delivery. Perinatal morbidity was defined as: pre-term birth (PTB); fetal acidosis; an Apgar score <7 at 5 min or neonatal resuscitation. Placental disease was defined as chronic uteroplacental insufficiency (CUPI); villous dysmaturity; infection or vascular pathology. Ponderal index was statistically reduced (25.33 vs 27.79 p =0.001) and the incidence of infant birth weight <9th centile was statistically higher (11.1% vs 5.1%; p =0.004) in cases with PTB and in CUPI (26.23 vs 27.84; p =0.001 and 28.2.1% vs 10.4%; p =0.002). Both PI and infant birth weight centile <9th centile for gestational age correlate with PTB, however overall, both are poor predictors of neonatal and placental disease.

An evaluation of Brix refractometry instruments for measurement of colostrum quality in dairy cattle.

Acquisition of high quality colostrum is an important factor influencing neonatal calf health. Many methods have been used to assess the Ig concentration of colostrum; however, improved, validated evaluation tools are needed. The aims of this study were to evaluate both optical and digital Brix refractometer instruments for the measurement of Ig concentration of colostrum as compared with the gold standard radial immunodiffusion assay laboratory assessment and to determine the correlation between Ig measurements taken from fresh and frozen colostrum samples for both Brix refractometer instruments. This research was completed using 288 colostrum samples from 3 different farms. It was concluded that the optical and digital Brix refractometers were highly correlated for both fresh and frozen samples (r=0.98 and r=0.97, respectively). Correlation between both refractometer instruments for fresh and frozen samples and the gold standard radial immunodiffusion assay were determined to be very similar, with a correlation coefficient between 0.71 and 0.74. Both instruments exhibited excellent test characteristics, indicating an appropriate cut-off point of 22% Brix score for the identification of good quality colostrum.

The lens of the eye: exposures in the UK medical sector and mechanistic studies of radiation effects.

The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most appropriate risk and protection framework to adopt. This brief paper provides an overview of some of the drivers behind the move to a lower recommended dose limit. The issue of implementation in the medical sector in the UK has been addressed through a small-scale survey of doses to the lens of the eye amongst interventional cardiologists and radiologists. In addition, a mechanistic study of early and late post-irradiation changes in the lens of the eye in in-vivo-exposed mice is outlined. Surveys and studies such as those described can contribute to a deeper understanding of fundamental and practical issues, and therefore contribute to a robust evidence base for ensuring adequate protection of the eye while avoiding undesirable restrictions to working practices.

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.

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.

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.

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.

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.

Lacrimal sac mucoepidermoid carcinoma.

A single case of mucoepidermoid carcinoma of the lacrimal sac was considered worth reporting as there are only four other cases described in the literature. The importance of the correct histological diagnosis and the management are discussed. This appears to be the first study of the ultrastructure of lacrimal sac mucoepidermoid tumour.

Neuroendocrine cells in the developing human lung: morphologic and functional considerations.

The structure, distribution, and frequency of neuroendocrine (NE) cells in human fetal lung from early stages of development to term are described. Neuroendocrine cells were studied by electron microscopy and immunostaining for serotonin and bombesin, recently identified markers of these cells in human lung. The differentiation of NE cells within the airway epithelium proceeded centrifugally and followed the development of the bronchial tree. The first NE cells, identified at 8 weeks' gestation, appeared well-differentiated compared with adjacent epithelial cells, and were immunoreactive for serotonin. The first bombesin-immunoreactive cells were detected at 10 weeks' gestation. Fetal lungs from midgestation contained several ultrastructurally distinct NE cell types, distributed singly and in groups. Serotonin-immunoreactive cells were more frequent during early stages of development and were predominantly located in larger airways. Bombesin-immunoreactive cells became more numerous towards term and were concentrated in small peripheral airways. The well-differentiated appearance and large number of NE cells in fetal lung, and their increase in number towards term, suggest an important role for these cells during intrauterine life and neonatal adaptation. Whether this role involves neurohormonal regulation of fetal-neonatal pulmonary circulation or local (paracrine) or endocrine function requires further investigation.

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.

Non-ionic surfactants and membrane transport of thioridazine in goldfish.

Polysorbate 80, which has been widely used in studies of the effects of surfactants on drug absorption, increases the rate of absorption of some drugs at concentrations near its critical micelle concentration (cmc). To determine whether all non-ionic surfactants were capable of inducing this effect, the effects of six commercial non-ionic surfactants on thioridazine absorption in goldfish have been compared with the effect of polysorbate 80. The reciprocal death time (T-1) determined when the fish were immersed in the solution under study was the index of absoprtion rate used. Not all surfactants tested increased T-1. Cremophor EL (polyoxyethylated castor oil), Atlas G1295 (a polyoxyethylene fatty glyceride), Atlas G1300 (a polyoxyethylene glyceride ester) had no effect below their cmc's. Those surfactants that did increase T-1 [polysorbate 80 (a polyoxyethylene lanolin derivative), G2162 (a polyoxyethylene oxypropylene monosterate) and Renex 650 (a polyoxyethylene alkyl aryl ether)] display the concentration-dependent behaviour reported previously - a decrease in absorption rate when the surfactant concentration is increased above its cmc. The factor determining whether or not the surfactant will increas absorption rate appears to be the configuration of the surfactant molecule rather than its hydrophile-lipophile balance or its surface activity.

Bardet-Biedl syndrome and retinitis punctata albescens in an isolated northern Canadian community.

Autosomal recessive inheritance of various conditions is well documented among inbreeding groups. In northern Canada inbreeding occurs in communities as a result of language and cultural uniqueness as well as geographic isolation. In one such community--Rae, in the Northwest Territories--two autosomal recessive disorders, the Bardet-Biedl syndrome and retinitis punctata albescens, are segregating. This report outlines the major clinical features of the disorders, establishes for both conditions the high frequency of the heterozygous carrier genotype in the community and suggests a possible way to reduce the likelihood of increased numbers of affected individuals in forthcoming generations.

Strategies for reduction of neonatal mortality.

Infant mortality rates in developed countries have shown significant decreases in recent years. Two-thirds of infant mortality still occurs in the neonatal period and our aim in this study was to review the causes of these neonatal deaths and see where further improvements may be possible. A 6-yr review of all neonatal deaths of live-born infants over 500 g birthweight from 1991 to 1996 was made. The 1989 amended Wigglesworth classification was used to categorize cause of death and other perinatal variables were also recorded. Results show there were 34,375 births and 153 neonatal deaths. Classification of these deaths by Wigglesworth found 78 (51 per cent) due to congenital malformations, 58 (38 per cent) due to prematurity, 6 (4 per cent) due to asphyxia and 11 (7 per cent) due to specific other causes. The corrected neonatal mortality was 2.18. Neural tube defects alone accounted for 10 per cent of the total neonatal mortality. Fifty-five out of 58 infants who died due to prematurity had birthweight < 1000 g and survival rates in this group compared well to international standards. We conclude that a reduction in neonatal mortality is possible but is most likely to result from community focused measures such as increased use of pre- and peri-conceptional folate.

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.

The right to know: the nurse's role in informing patients.

This paper analyses a situation often found in practice and demonstrates an ethical issue in truth-telling and its effect on nursing practice for patients. The situation identified occurred in a surgical unit, where the author was a night sister.