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Biomedical subjects

D James

Publications and source records attributed to D James.

At least 19 recordsLinked to original sources

Bizarre fetal behaviour associated with lethal congenital anomalies: a case report.

Prolonged recording of behaviour was performed in a fetus at 36 weeks gestation, who was severely small for dates with no apparent aetiology. Detailed analysis of fetal behaviour was grossly abnormal. Behavioural states were absent and there were no intervals during which linkage of the state variables was demonstrated in a total of 120 min of observation. On repeated conventional biophysical testing the non-stress test was normal and the biophysical score was equivocal, varying from 4/10 to 8/10. Following delivery a lethal multiple congenital abnormality syndrome was identified. Close linkage of the fetal behavioural state variables is almost universal by this gestation, and has been associated with a good outcome in high-risk fetuses. Behavioural recordings may have a useful role in the evaluation of such fetuses, particularly where the aetiology is not apparent.

Abnormalities, Multiple

Human fetal mouthing movements: a potential biophysical variable for distinguishing state 1F from abnormal fetal behavior; report of 4 cases.

In late pregnancy, when fetal behavioural states are well developed, human fetuses spend about one third of their time in a quiescent state, 1F. In healthy fetuses biophysical tests often appear suboptimal if recording happens to occur in this state, and as a result prolonged recording may be necessary. We have examined fetal mouthing movements during state 1F in 65 fetuses beyond 36 weeks, with and without risk factors, but in whom there was no immediate evidence of compromise. We found that periodic rhythmical mouthing movements were a characteristic feature of state 1F, occurring in 93.0% of episodes, when the fetal mouth was visible. This compares favourably with variables of the biophysical profile, which were less likely to be satisfactory in state 1F - fetal breathing 53.8%, fetal movements 46.2%, fetal heart rate 69.2%, and overall biophysical score of 8 or 10, 60.0%. We identified objective evidence of fetal compromise (of various aetiologies) in four other fetuses of the same gestational age, and mouthing movements were absent in all four.

Adult

Automated quantitative microcolumn chromatography of haemoglobin A2.

Automated cation exchange microcolumn chromatography of haemoglobins has been modified for the analysis of haemoglobin A2. It provides the quantitative data of sufficient precision and specificity for the investigation of potential heterozygotes for beta-thalassaemia. Results have been compared with an established method of electrophoresis followed by densitometry of the eluted bands.

Chromatography, Ion Exchange

Tumour suppression associated with expression of human insulin-like growth factor II.

Recent circumstantial evidence has implicated Insulin-like growth factor II in the genesis of several tumour types, notably developmental tumours (Scott et al., 1985; Schofield & Tate, 1987; Wilkins et al., 1989). This type of tumour, thought to originate during the defective differentiation of organ precursors (Miereau et al., 1987), often expresses greatly elevated levels of mRNA for IGF-II, a known mitogen for these cells and abundantly expressed in their presumed normal counterparts (Scott et al., 1985; Schofield & Tate, 1987; Gray et al., 1987). It has been proposed that continued, inappropriate expression of this gene drives tumour growth by an autocrine mechanism. In order to examine the potential role of IGF-II in the growth of tumour cells an IGF-II cDNA was introduced into a retroviral expression vector, and used to infect a cloned fibroblast cell line. Expression of IGF-II conferred a degree of serum independence of growth in cell culture, however, when cells were injected into nude mice as subcutaneous grafts, clones expressing IGF-II from the retrovirus were found to have a greatly increased (five fold) latency of sarcoma formation. After a prolonged lag all cell lines eventually gave rise to tumours in which the introduced IGF-II genes had either been lost or inactivated, suggesting that in this system IGF-II acts as a tumour suppressor gene.

Animals

Surgical access to the base of skull and upper cervical spine by extended maxillotomy.

An extended maxillotomy has been developed to permit wider surgical access to the base of the skull. It has proven particularly useful in the management of the previously untreatable neuraxial compression caused by basilar invagination in cases of osteogenesis imperfecta. In addition, patients with extensive extradural space-occupying lesions have been treated. The surgical technique is described and the results of its use in nine patients are presented.

Adult

Continuation of normal neurobehavioural development in fetuses with absent umbilical arterial end diastolic velocities.

Detailed serial observations of behaviour were made in four singleton fetuses who were very small for dates and who had persistently absent umbilical artery end diastolic velocities for 2 to 9 weeks duration. All were born preterm for deteriorating maternal disease, and in two there were additional fetal indications for delivery. Behavioural comparison with 45 low risk singleton fetuses, at comparable gestations, revealed no significant differences in the development of behavioural cycles, the proportion of time spent in quiet cycles, or the amount of fetal breathing. None of the fetuses developed an abnormal heart rate pattern. We conclude that prenatal neurobehavioural development may continue apparently unimpaired in the presence of absent umbilical artery end-diastolic velocity of several weeks duration. Long term data of infant outcome are necessary before the clinical significance of this can be assessed.

Apgar Score

Are the behavioural states of the newborn comparable to those of the fetus?

Comparisons were made between ultrasound behavioural recordings of 18 healthy term fetuses and recordings of the same variables of the same individuals at 3 to 5 days postnatally. Statistical comparison of the frequency of eye movements, limb and body movements revealed that the fetal states 1F and 2F were comparable to quiet sleep (S1), and rapid eye movement (REM) sleep (S2), respectively in the newborn. Comparisons between the fetal states and wakefulness were less clear-cut. The heart rate in each of the three states in the fetus was about 20 beats per min higher than in the corresponding postnatal state, although the patterns were similar. States 1F and 2F accounted for a higher percentage of the fetal observations (86%) than states S1 and S2 in the neonatal observations (64%), but the ratio of the different types of sleep was similar in both recordings (30% quiet sleep to 70% REM sleep). State S3 (quiet awake) always and only occurred in the postnatal observations in association with feeding. No comparable behaviour occurred during the prenatal observations (2050 min in 18 fetuses). Numerically the movements observed in S5 (crying) were not significantly different from 2F, however qualitatively there were marked differences, and also S5 was characterized by a heart rate pattern quite unlike anything observed prenatally (often with a rate in excess of 200 beats per min). We postulate that S3 and S5 are postnatal behavioural adaptations to extrauterine existence.

Behavior

The development of fetal heart rate patterns during normal pregnancy.

Characteristics of the fetal heart rate (FHR) were studied longitudinally throughout the second and third trimesters in 43 low-risk singleton fetuses. The second trimester was characterized by an FHR pattern showing minimal differences between quiet and active intervals of fetal behavior. Few movements were accompanied by accelerations of small magnitude. Brief decelerations of variable magnitude exceeded the number of accelerations, and their frequency declined with advancing maturity. The percentage of body movements accompanied by FHR acceleration, the amplitude of these accelerations, and the rate of rise in heart rate increased with gestational age. Up to 30 weeks, the characteristics of the baseline FHR were similar in both periods of fetal rest and activity, with the baseline variability becoming significantly greater with advancing gestation. However, during quiet cycles of fetal behavior after 30 weeks, the baseline variability became progressively narrower, so that in late pregnancy different behavioral states could be determined reliably from characteristics of the baseline FHR alone.

Embryonic and Fetal Development

The importance of the behavioural state in biophysical assessment of the term human fetus.

We have examined how the different behavioural states exhibited by 78 healthy fetuses at term influence the result of the non-stress test (NST) and biophysical profile score (BPS). In association with state 1F the average recording time to obtain a satisfactory NST and BPS was 27.0 and 26.3 min respectively, and 52.6% and 44.0% respectively failed to achieve a 'normal' result. In contrast, satisfactory results were always obtained in the two active states (2F and 4F), and the average time was 3-5 min. Mature fetuses spend on average one third of the time in state 1F, and knowledge of its characteristics is therefore important, for the interpretation of biophysical tests. Our results suggest that continuation of biophysical recording for at least 40 min is necessary before an unreactive NST or low BPS should be regarded as suspicious. We suggest that interpretation of the NST and BPS should be made in the light of knowledge of normal patterns of behavioural development rather than using an arbitrarily defined scoring system.

Amniotic Fluid

Hiccups and breathing in human fetuses.

Serial recording in 45 low risk fetuses throughout the second and third trimesters showed that hiccups were the predominant diaphragmatic movement before 26 weeks' gestational age and that there was a significant negative correlation with gestational age. There was a pronounced reduction between 24 and 26 weeks, which was the result of a decrease in the number of episodes of hiccups rather than a change in the duration of episodes. In contrast, fetal breathing was positively correlated with gestational age, the greatest increase in breathing occurring between 26 and 32 weeks' gestation. This was the result of both an increase in the number and duration of episodes. From the time that rest-activity cycles of behaviour could be determined in recordings, both breathing and hiccups were dependent on behavioural state or cycle, occurring predominantly during active episodes. This association between quiet and active behaviour and breathing did not alter with increasing gestational age, and the variables in fetal behavioural state became increasingly closely linked. The importance of prolonged and repeated recording, and also the need to take account of other variables in fetal behaviour, before any sinister conclusions can be drawn about the absence of fetal breathing is emphasised.

Diaphragm

Behavioural states in normal mature human fetuses.

Behaviour was studied by real time ultrasound in a group of 80 low risk fetuses between 36 and 42 weeks' gestation. There was close linkage of fetal eye movements, somatic movements and heart rate pattern reflecting three different states. Quiescence (state 1F) was characterised by no eye movements, no somatic movements except for the occasional startle, and a fetal heart rate pattern with little baseline variability. There were two active states: state 2F characterised by continuous eye movements, frequent bursts of somatic movements, and wide baseline variability with accelerations with movement, and state 4F characterised by continuous eye movements with almost continuous somatic movements and a sustained tachycardia. These fulfilled criteria for three of four behavioural states previously described in human fetuses. Cycling of quiescent and active states occurred in 77 (96%) of the fetuses within 100 minutes of starting the recording. 2F was the commonest behavioural state, being seen 58% of the time. 1F was seen 30% of the time, and 4F 9% of the time. During the remaining 3% of observation time the behavioural state was indeterminate.

Eye Movements

Surfactant abnormality and the sudden infant death syndrome--a primary or secondary phenomenon?

A prospective study of 46 infant deaths occurring between 3 and 100 weeks of age was performed and comprised a structured necropsy followed by collection of lung washings for surfactant phospholipid analysis and samples for microbiological examination. Of the 46 infants studied, 23 died from sudden infant death syndrome (SIDS) alone; SIDS was the cause of death in a further 12 but there were additional clinical or pathological findings insufficient in themselves to account for the death ('SIDS-plus'). In 11 there were other causes of death ('non-SIDS'). The lung washings from infants dying from SIDS had significantly lower concentrations of phosphatidylcholine and a significantly lower palmitate content in the phosphatidylcholine. There was no association between surfactant phospholipid abnormality and the presence of recognised pathogens, histological evidence of pulmonary inflammation, aspiration of stomach contents, age at death, sex, and death-postmortem interval. There were, however, lower concentrations of phosphatidylcholine and phosphatidylcholine palmitate content in infants colonised by organisms with reported phospholipase A2 activity.

Age Factors