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J Crossley

Publications and source records attributed to J Crossley.

At least 19 recordsLinked to original sources

Frequency and clinical consequences of extremely high maternal serum PAPP-A levels.

A multicentre study was carried out to determine the frequency and clinical consequences of extremely high maternal serum pregnancy-associated plasma protein (PAPP)-A. There was a total of 79 pregnancies with PAPP-A exceeding 5.0 multiples of the gestation-specific median in a series of 46 776 pregnancies tested (0.2%) at the 7 collaborating centres. Five pregnancies were lost to follow-up, one miscarried and one with Noonan's syndrome was terminated. Of the remaining 72 that ended in a live birth, one infant had gastroschisis and five pregnancies had obstetric complications: pre-eclampsia, pregnancy-induced hypertension, gestational diabetes and two with growth retardation. Among women with high PAPP-A and no complications or adverse outcomes, there was no evidence of a substantial change in the levels of other Down syndrome markers or the extent of nuchal translucency. Three analytical methods were used to assay PAPP-A and yielded different frequencies of extremely high levels (0.05%, 0.4% and 0.6%) possibly owing to cross-reaction with another substance. We conclude that women with high PAPP-A can be reassured that there is no reason to suppose that the outcome of pregnancy will differ from those with normal levels, provided other markers are normal. If, as more centres move their Down syndrome screening practice to the first trimester, additional cases emerge with Noonan's syndrome or gastroschisis and raised PAPP-A, this advice will need to be modified.

Adult↗

Urinary free beta hCG, beta core fragment and total oestriol as markers of Down syndrome in the second trimester of pregnancy.

In a study of 69 random urine samples from cases of Down syndrome and 405 samples from unaffected pregnancies, we have assessed the value of various candidate markers that have been proposed as tools for screening for Down syndrome. We found that the marker urine free beta hCG in Down syndrome had a median MoM of 3.53 (95 per cent confidence interval 2.48-4.68) and at a 5 per cent cut-off would have identified 49 per cent (34/69) of cases. Urine beta core had a median MoM of 4.95 (3.87-8.62) and at a 5 per cent cut-off would have identified 39 per cent (27/69) of cases. Total oestriol had a median MoM of 0.65 (0.55-0.80) and at a 5 per cent cut-off would have identified 35 per cent (24/69) of cases. In conjunction with maternal age, the modelled detection rate increased to 55.8 per cent for free beta hCG, 49.8 per cent for beta core and 48.8 per cent for total oestriol. In combination free beta hCG, total oestriol and maternal age would have detected 68 per cent of cases for a 5 per cent false-positive rate. Using analyte ratios to obviate the need to correct for urine dilution in our study (rather than correcting to a fixed creatinine concentration) was not shown to be as effective as correcting using urine creatinine. Urine markers on the whole are unlikely to be of practical screening value considering the 85 per cent to 90 per cent detection rates achievable in the first trimester using a combination of ultrasound and maternal serum biochemistry.

Adult↗

Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo.

For resolution of inflammation to occur, it is necessary both to limit leukocyte influx and to clear now redundant cells from the tissues. Recent evidence from in vitro studies suggests that clearance may be an active process, accomplished in part by macrophage engulfment of intact cells that have undergone programmed cell death or apoptosis. However, the kinetics of these events and their association with the resolution of acute inflammatory responses in vivo remain to be elucidated. To investigate these events, we examined an animal model of acute, limited, neutrophilic pulmonary inflammation. Cells were obtained by bronchoalveolar lavage (BAL) of rats at various time points after intratracheal administration of lipopolysaccharide (LPS). Apoptotic neutrophils were rarely seen in BAL from control animals but were detected after neutrophil influx had occurred in response to LPS challenge. Macrophage engulfment of these cells was identified at light microscopy and confirmed at electron microscopy. The proportion of macrophages that had engulfed apoptotic neutrophils was maximal 24 h after LPS challenge and declined thereafter as total neutrophil numbers fell. During the resolution phase, the alveolar macrophages became positive for peroxidase, indicating the presence of neutrophil granule contents in their cytoplasm. These observations demonstrate that apoptosis of leukocytes indeed occurs during the course of an acute inflammatory response in vivo and that the emergence of apoptotic neutrophils and macrophage engulfment of these cells are temporally correlated with the resolution of acute inflammation.

Animals↗

[Unexplained increase in maternal plasma in alpha-fetoproteins in the second trimester of pregnancy: perinatal results].

To determine the relation between adverse perinatal events and an unexplained mid-trimester elevation in maternal serum alpha-fetoprotein (MSAFP) in an unselected population, 16,093 women with a singleton pregnancy delivered between January 1985 and November 1991, at the Queen Mother's Hospital, Glasgow, Scotland, were studied. The elevated MSAFP group (n = 606) was associated with an increased risk of preterm delivery (odds ratios/95% confidence intervals) (3.7/2.6-5.2), small or gestational age (4.5/3.3-6.1), intrauterine death (3.9/1.7-9.4), and placental abruption (3.2/1.5-6.7). The risks increased with MSAP concentration. An unexplained mid-trimester elevation of MSAFP is associated with increased risk of adverse perinatal events, thus acting as a non-specific marker o a "high risk pregnancy". Alterations to current antenatal management in this group may improve prognosis.

Female↗

Midtrimester chorionic villus sampling: an alternative approach?

OBJECTIVE: Our purpose was to audit midtrimester chorionic villus sampling after a positive maternal serum screening test for autosomal trisomy. STUDY DESIGN: From January 1990 until July 1993 chorionic villus sampling was offered to all screened positive women. RESULTS: Five hundred fifty-one mothers had chorionic villus sampling. The mean age was 31.7 years. The mean gestational age was 18.2 weeks. The mean time for direct karyotyping was 4.4 days and for culture results 20.2 days. Results were obtained in 99.6% of samples: direct plus culture results in 94%, direct results alone in 2.3%, and culture results alone in 3.3%. Fourteen pregnancies had abnormal karyotypes. There were five cases of placental mosaicism and one false-positive result. The loss rate was 0.4%. CONCLUSION: Midtrimester chorionic villus sampling, which is easier to perform than cordocentesis, provides a rapid and reliable karyotype. The complication rate is comparable to that of other invasive procedures.

Adult↗

Effect of terminal (dry) heat treatment on non-enveloped viruses in coagulation factor concentrates.

Terminal dry heat treatment effectively inactivated hepatitis A virus (HAV) and canine parvovirus added to high-purity factor VIII. After 24 h at 80 degrees C, HAV infectivity was reduced by > or = 4.3 log10 TCID50, as measured in a newly developed infectivity assay. The same reduction in virus titer was achieved after 2 h and before 6 h at 90 degrees C. Inactivation of hepatitis A virus was also seen in the freeze-drying step prior to heat treatment with an approximately 2.0 log10 reduction in titer. Similar results were obtained with a high-purity factor IX concentrate. Canine parvovirus was also inactivated at both temperatures, with residual infectivity being undetected after 48 h at 80 degrees C or 10 h at 90 degrees C. Canine parvovirus was not affected by lyophilisation. Canine parvovirus measurements by PCR did not reflect the levels of infectivity measured by the tissue-culture-based method. The addition of the terminal dry heat treatment to solvent/detergent could effectively eliminate the potential contamination of solvent/detergent-treated coagulation factor concentrates by non-lipid-enveloped viruses. However, careful evaluation for any increased induction of non-antigens for factor VIII, as a consequence of such treatment, is needed before use in patients can be recommended.

Animals↗

Pyrrolizidine alkaloidosis of cattle associated with Senecio lautus.

Serious incidents of pyrrolizidine alkaloidosis of cattle in 10 herds exposed to the Australian native plant, Senecio lautus (Asteraceae), were seen in central Queensland during 1988-1992. The deaths of 226 cattle were recorded. A mean of 8% of cattle died in affected groups (range 2 to 58%). Sickness and deaths usually occurred some months after access to S lautus. Typically, affected cattle lost body condition to the point of emaciation before dying and had persistent diarrhoea. Some animals developed abnormal behaviour and died after a shorter illness. Liver specimens from affected cattle in all herds contained lesions consistent with pyrrolizidine alkaloidosis. Thin layer chromatography of extracts of blood and liver samples from cattle from 5 herds detected pyrrolic metabolites. The identity of these was confirmed by mass spectroscopy on samples from one herd. Unseasonal autumn and winter rain after a dry summer appeared to favour growth of S lautus at the expense of other pasture species. A subsequent dry period promoted consumption of S lautus and was followed by a cluster of poisoning incidents.

Animals↗

Prenatal testosterone levels in XXY and XYY males.

It has been postulated that behavioural differences between normal males and those with an additional X or Y chromosome may be related to pre- or postnatal hormonal variations. The prenatal hormone status was investigated using amniotic fluid obtained at antenatal diagnosis between 16 and 20 weeks gestation from fetuses with sex chromosome abnormalities and from controls of the same gestational age. After log transformation, the (geometric) mean testosterone levels were XY 439.4 pmol/l, range 165-1,027 (n = 29), XYY 490.7 pmol/l, range 224-1,092 (n = 20); and XXY 419 pmol/l, range 87-1,021 (n = 20). There were no significant differences between the three male groups and all three were significantly higher than the XX fetuses at 147.0 pmol/l, range 41-474 (p < 0.001). These findings give no support to the hypothesis that prenatal testosterone levels contribute to later behavioural characteristics.

Amniotic Fluid↗

Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes.

The regulation of the activity of potentially harmful proteinases secreted by neutrophils during inflammation is important for the prevention of excessive tissue injury. Secretory leukocyte proteinase inhibitor (SLPI), also called antileukoprotease (ALP) or mucus proteinase inhibitor (MPI), is a serine proteinase inhibitor that has been found in a variety of mucous secretions and that is secreted by bronchial epithelial cells. We recently reported the presence of SLPI and of an elastase-specific inhibitor (ESI), also called elafin, in the supernatants of two cell lines, NCI-H322 and A549, which have features of Clara cells and type II alveolar cells, respectively. We showed in addition that epithelial cell lines produce the elastase-specific inhibitor as a 12 to 16 kD precursor of the elafin molecule (6 kD) called pre-elafin. In the present study, we show that NCI-H322 cells produced higher amounts of both inhibitors than A549 cells and that basal production of SLPI in both cell lines is higher than the production of elafin/pre-elafin. In addition, we show that interleukin-1 beta and tumor necrosis factor induce significant SLPI expression and are major inducers of elafin/pre-elafin expression. Moreover, induction is greater in A549 cells than in NCI-H322 cells. The implications of these findings for the peripheral airways are twofold: (1) alveolar epithelial cells may respond to cytokines secreted during the onset of inflammation by increasing their antiprotease shield; (2) elafin/pre-elafin seems to be a true local "acute phase reactant" whereas SLPI, in comparison, may be less responsive to local inflammatory mediators.

Cathepsin G↗

Prenatal diagnosis and management of anterior abdominal wall defects in the west of Scotland.

An attempt was made to identify all the cases of abdominal wall defects occurring in the West of Scotland over a 7-year period to determine the current incidence, prenatal diagnosis, management, and prognosis for fetuses and neonates with abdominal wall defects. Cases were identified because they presented either for prenatal diagnosis, or to the Department of Pathology following termination or spontaneous pregnancy loss, or as neonates to the Neonatal Surgical Department. The incidence of abdominal wall defects was found to be 1 in 2500 births. Exomphalos was diagnosed before birth in 66 per cent of cases, and in 30 per cent of cases it was associated with another major abnormality. There was a 20 per cent intact survival in the cases diagnosed prenatally who had no fetal anomaly and who opted to continue with the pregnancy. Gastroschisis was diagnosed before delivery in 70 per cent of cases, and in the group who continued with the pregnancy there was an intact survival of 77 per cent. Body stalk anomalies were all diagnosed prenatally and terminated. Maternal serum alpha-fetoprotein was elevated in 89 per cent of the cases with exomphalos and in 100 per cent of the cases with gastroschisis and body stalk anomalies in which it was tested.

Abdominal Muscles↗

Immunomodulatory properties of diazepam-binding inhibitor: effect on human interleukin-6 secretion, lymphocyte proliferation and natural killer cell activity in vitro.

We have examined the influence of diazepam binding inhibitor (octadecaneuro-peptide, DBI33-50) on cell mediated immune responses including LPS-stimulated monocyte IL-6 secretion, PHA induced lymphocyte proliferation and NK cell function in humans. All studies were performed in vitro on isolated human peripheral blood mononuclear cells in the absence or presence of synthetic DBI33-50. It has been shown that DBI33-50, in concentration between 10(-6)-10(-8) M, enhances the LPS-induced secretion of IL-6, as determined by specific bioassay for this monokine. On the other hand DBI33-50 (10(-6)-10(-12) M), had no significant effect on either PHA-induced lymphocyte proliferation or NK cell function. This data suggests a possible immunomodulatory role for DBI33-50 as an endogenous neuropeptide, which stimulates IL-6 secretion by human monocytes.

Adult↗

Factors limiting the effectiveness of prenatal screening for anencephaly and spina bifida in a high-risk area.

The effectiveness of a prenatal screening programme in reducing the birth prevalence of anencephaly and spina bifida (ASB) is influenced by three principal factors: the proportion of affected pregnancies screened (uptake), the proportion of affected pregnancies detected on screening (sensitivity) and the proportion of affected pregnancies terminated when detected (compliance). The purpose of the study was two-fold: to develop an epidemiologically-based method for the retrospective monitoring of these three factors and to attempt to quantify their relative importance in relation to the outcome of screening. Data on births and terminations associated with ASB for the period 1976-1986 were obtained from the Glasgow Register of Congenital Anomalies and from the Department of Medical Genetics, Yorkhill Hospitals. Increasing proportions of affected pregnancies screened, detected and terminated were observed, to a greater degree for anencephaly than for spina bifida. The relationships between uptake, sensitivity, compliance and terminations are described in the form of a simple arithmetic expression. In policy terms, further efforts are required to increase all three in order to improve the effectiveness of screening for spina bifida.

Abortion, Therapeutic↗