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Biomedical subjects

J S Wigglesworth

Publications and source records attributed to J S Wigglesworth.

At least 19 recordsLinked to original sources
PubMed1979

Intracranial haemorrhage in the preterm sheep fetus.

The germinal layer in the brain of the sheep fetus at 58--85 days of gestation was found to resemble that of the human infant at 28--30 wk of gestation. Experiments were done on 65 exteriorized fetuses to explore the effect of various combinations of asphyxia and raised intravascular pressures in causing bleeding into the germinal layer, ventricles and other parts of the brain. Asphyxia by itself did not produce an increase in the incidence of intracranial hemorrhages when compared with control fetuses. The combination of asphyxia with intermittent increases in arterial or venous pressure, or both, did cause haemorrhages. Large increases in arterial pressure without asphyxia also caused intracranial haemorrhages, whereas increases in venous pressure without asphyxia did not. The types of haemorrhage observed closely resembled those seen in the preterm human infant, although massive intraventricular haemorrhages (IVHs) were rare. We conclude that: (1) the sheep fetus can be used for investigating factors associated with intracranial haemorrhage in the preterm brain; (2) the most effective method of producing haemorrhages into the germinal layer was by a combination of asphyxia with intermittent increases in cerebral intravascular pressure. Similar mechanisms may be at work in the newborn human infant, and could lead to IVH.

Animals↗
PubMed1979

Effect on lung growth of cervical cord section in the rabbit fetus.

Experiments were performed to clarify the mechanism by which cervical cord transection retards lung growth in the fetal rabbit. In 10 sets of fetuses operated on at 24 1/2 days gestation and studied 3--4 days later, cord section at C1--C3 (high section) caused a significantly greater reduction in lung weight and lung DNA than cord section at C5--C8 (low section) as compared with control littermates. Comparison with the lungs of additional control fetuses removed at the time of operation showed that high section had reduced lung growth by 70% and low section had reduced growth by 40% relative to sham-operated controls. The hypoplastic lungs of the high-section group had poorly expanded, thick-walled terminal sacs, while those of the low section group more nearly resembled the controls. Fetal weights and weights of liver, kidneys, thymus and diaphragm did not differ significantly between the groups, but the hearts of the low-section group were unduly large. In a separate 6 sets of fetuses tracheal ligation at the time of high-cord section was found to result in large fluid-filled lungs with a normal DNA content. The results indicate that preservation of an upper motor neurone supply to the phrenic nucleus is of critical importance for fetal lung growth, and confirm the growth-promoting effects of liquid distension of the fetal lungs. We conclude that normal fetal lung growth depends on development and maintenance of a sophisticated form of function involving integration of respiratory movements and lung lipid secretion. This functional control of fetal lung growth has important implications for perinatal medicine.

Animals↗
PubMed1978

An integrated model for haemorrhagic and ischaemic lesions in the newborn brain.

The vascular anatomy of the developing brain changes from a predominantly basal ganglia orientated pattern at 24 wk to a cortically orientated pattern by 34 wk. This information, combined with other known data on cerebral vascular anatomy and physiology, allows us to develop a model for haemorrhagic and ischaemic lesions in the newborn brain based on two main series of reactions. One series involves the effects of hypoxia and hypercapnia in leading to breakdown of the blood--brain barrier with resultant oedema or haemorrhage. The other links a fall in perfusion pressure and factors causing vasoconstriction with the development of ischaemic lesions. Application of the model involves additional consideration of the state of development of the cerebral vessels at the gestational age concerned. The model helps to explain the observed findings in germinal layer haemorrhage/intraventricular haemorrhage, periventricular leukomalacia and venous infarction, in the preterm brain. Its use also suggests that there are three patterns of vulnerability in the term infant brain. The model carries several implications for the neonatal management of preterm infants. Routine continuous monitoring of blood pressure is of critical importance as cerebral blood flow may vary with blood pressure in the ill newborn. It is important to avoid head compression which may lead to impaired cerebral perfusion. Finally, control of the acid--base status is essential for maintenance of the blood--brain barrier. Correction of abnormal values must be carried out without provoking rapid swings in either the serum osmolarity or the blood pressure.

Blood Pressure↗
PubMed1977

Intracranial birth trauma in vaginal breech delivery: the continued importance of injury to the occipital bone.

Between 1966 and 1976, postmortem examinations revealed significant intracranial birth trauma in 17 infants delivered breech first and in ten infants delivered head first; separation of the squamous and lateral parts of the occipital bone (occipital osteodiastasis) was found in five of the infants who died after breech delivery. The finding of the lesions in these infants is attributed to the adoption, since 1971, of a postmortem technique involving dissection of the suboccipital region before opening the skull. Review of earlier necropsy reports suggests that the lesion was sometimes missed. Analysis of the fresh stillbirths and neonatal deaths occurring in the 477 vaginal breech deliveries at the Hammersmith Hospital (1966 to 1976) showed that all neonatal deaths in infants weighing more than 3000 g at birth associated with intracranial birth trauma: 2 out of 3 had occipital osteodiastasis which seems to be more common than is generally recognized and is only found with careful autopsy technique.

Adult↗
PubMed1977

Influence of the central nervous system on fetal lung development. Experimental study.

Upper cervical cord injury was produced in fetal rabbits at 22-26 days' gestation. In 11 setuses with severe cord injury delivered at 28-29 days' gestation there was a median reduction in lung weight (expressed as a proportion of body weight) of 43% and a median reduction in estimated total lung DNA of 16% in comparison with paired operated littermates with intact cords. The hypoplastic lungs showed collapse on histology; if cord damage had been inflicted before 24 days' gestation there was retarded maturation. We conclude that the central nervous system plays a vital role in fetal lung growth and maturation, probably by maintenance of fetal respiratory movements.

Animals↗
PubMed1977

Intraventricular haemorrhage in the preterm infant without hyaline membrane disease.

The clinicopathological associations of 33 singleton infants who died with intraventricular haemorrhage (IVH) without hyaline membrane disease (HMD) ('IVH only') were compared with those of 39 infants who died with IVH+HMD over the same gestation range in order to determine what factors other than those related to HMD may contribute to the pathogenesis of IVH. The incidence of 'IVH only' was inversely related to gestational age in the Hammersmith birth population, whereas the incidence of IVH+HMD rose to a peak at 28-29 weeks' gestation. Infants with 'IVH only' lived longer on average than those with IVH+HMD despite a lower birthweight and shorter gestation. Infants who died in the first 12 hours from 'IVH only' had suffered severe birth asphyxia but in those who died later the main symptom was recurrent apnoea. Fewer infants with asphyxia but in those who died later the main symptom was.recurrent apnoea. Fewer infants with 'IVH only' were given alkali therapy or were connected to the ventilator as compared to those with IVH+HMD, but there were no differences in alkali therapy in those who lived for 12 hours or more. In the 'IVH only' group there was a high incidence of haemorrhage from other sites and of bacterial infections. It is suggested that, in the absence of HMD, extreme immaturity is the main factor determining the occurrence of IVH. Birth asphyxia, apnoeic attacks, haemorrhage, and infections may play subsidiary roles, possibly through development of metabolic acidosis.

Cerebral Hemorrhage↗
PubMed1977

Early neonatal bacteraemia. Comparison of group B streptococcal, other Gram-positive and Gram-negative infections.

All cases of neonatal bacteraemia associated with clinical illness occurring at Hammersmith Hospital, over a 9-year period, 1967-1975 inclusive, have been reviewed. The infants studied were those born in the hospital's maternity unit and those admitted from other hospitals from a wide area round London who were ill or of low birthweight. Positive blood cultures occurred in 91 infants, 47 of them in the first 48 hours of life. These 47 infants were analysed separately and divided into three groups, 13 with group B streptococcal infections, 11 with other Gram-positive infections, and 23 with Gram-negative infections. There were no significant differences in birthweight or gestation, in mortality, in incidence of clinically diagnosed respiratory distress syndrome or recurrent apnoea, or in the need for mechanical ventilation between the three groups. The age at which a diagnosis of infection was suspected, and the age at death were both significantly earlier in the group infected with group B streptococcus than in those obtained with other organisms (P less than 0-01 for both comparisons). There were no significant differences in the incidence of hyaline membrane formation or pneumonia seen at necropsy among the three groups. In some of the earliest deaths in the Gram-negative bacteraemic group, Gram-negative rods comprised the bulk of the hyaline membrane as did cocci in the group B streptoccal group.

Age Factors↗
PubMed1976

Hyaline membrane disease, alkali, and intraventricular haemorrhage.

The relation between intraventricular haemorrhage (IVH) and hyaline membrane disease (HMD) was studied in singletons that came to necropsy at Hammersmith Hospital over the years 1966-73. The incidence of IVH in singleton live births was 3-22/1000 and of HMD 4-44/1000. Although the high figures were partily due to the large number of low birthweight infants born at this hospital, the incidence of IVH in babies weighing 1001-1500 g was three times as great as that reported in the 1658 British Perinatal Mortality Survey. Most IVH deaths were in babies with HMD, but the higher frequency of IVH was not associated with any prolongation of survival time of babies who died with HMD as compared with the 1958 survey. IVH was seen frequently at gestations of up to 36 weeks in babies with HMD but was rare above 30 weeks' gestation in babies without HMD. This indicated that factors associated with HMD must cause most cases of IVH seen at gestations above 30 weeks. Comparison of clinical details in infants with HMD who died with or without IVH (at gestations of 30-37 weeks) showed no significant differences between the groups other than a high incidence of fits and greater use of alkali therapy in the babies with IVH. During the 12 hours when most alkali therapy was given, babies dying with IVD received a mean total alkali dosage of 10-21 mmol/kg and those dying without IVH 6-34 mmol/kg (P less than 0-001). There was no difference in severity of hypoxia or of metabolic acidosis between the 2 groups. Babies who died with HMD and germinal layer haemorrhage (GLH) without IVH had received significantly more alkali than those who died with HMD alone, whereas survivors of severe respiratory distress syndrome had received lower alkali doses than other groups. It is suggested that the greatly increased death rate from IVH in babies with HMD indicates some alteration of management of HMD (since 1958) as a causative factor. Liberal use of hypertonic alkali solutions is the common factor which distinguishes babies dying with GLH and IVH from other groups of babies with HMD. Although the causal nature of this association remains unproved, it seems justifiable to lrge caution in alkali usage.

Acid-Base Equilibrium↗
PubMed1976

Origin of intraventricular haemorrhage in the preterm infant.

A technique has been developed for the injection and stereomicroscopic examination of blood vessels in the preterm newborn brain. Using this technique it can be seen that in the immature brain there is a rich capillary bed in the germinal layer region supplied mainly by Heubner's artery. Capillary channels drain directly into the terminal vein and its main branches. Study of 19 cases with spontaneous germinal layer haemorrhage (GLH) with or without intraventricular haemorrhage (IVH) failed to show rupture of the terminal vein or germinal layer infarction. In babies of up to 28 weeks' gestation GLH developed most frequently over the body of the caudate nucleus, whereas in babies of 29 weeks' gestation or more the haemorrhages were usually over the head of the caudate nucleus. Histological study of 10 cases of GLH failed to show rupture either of arteries or veins, though evidence of rupture at a capillary-vein junction was seen in one case and masses of fibrin adjacent to the vein wall in 2 others. Injection through the carotid artery caused prominent leaks of injection mass within the germinal layer capillary bed, often adjacent to the veins. Injection through the jugular veins in 2 cases failed to rupture the terminal vein but caused multiple vein ruptures at the junction of deep and cortical venous systems. Additional small ruptures in the germinal layer occurred in one of the cases only. It is suggested that the capillaries within the germinal layer may be ruptured by a rise in arterial pressure, particularly in conditions of hypercapnia and hypoxia.

Autopsy↗