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Biomedical subjects

A R Wilkinson

Publications and source records attributed to A R Wilkinson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neurologic and developmental disability after extremely preterm birth. EPICure Study Group.

BACKGROUND AND METHODS: Small studies show that many children born as extremely preterm infants have neurologic and developmental disabilities. We evaluated all children who were born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland from March through December 1995 at the time when they reached a median age of 30 months. Each child underwent a formal assessment by an independent examiner. Development was evaluated with use of the Bayley Scales of Infant Development, and neurologic function was assessed by a standardized examination. Disability and severe disability were defined by predetermined criteria. RESULTS: At a median age of 30 months, corrected for gestational age, 283 (92 percent) of the 308 surviving children were formally assessed. The mean (+/-SD) scores on the Bayley Mental and Psychomotor Developmental Indexes, referenced to a population mean of 100, were 84+/-12 and 87+/-13, respectively. Fifty-three children (19 percent) had severely delayed development (with scores more than 3 SD below the mean), and a further 32 children (11 percent) had scores from 2 SD to 3 SD below the mean. Twenty-eight children (10 percent) had severe neuromotor disability, 7 (2 percent) were blind or perceived light only, and 8 (3 percent) had hearing loss that was uncorrectable or required aids. Overall, 138 children had disability (49 percent; 95 percent confidence interval, 43 to 55 percent), including 64 who met the criteria for severe disability (23 percent; 95 percent confidence interval, 18 to 28 percent). When data from 17 assessments by local pediatricians were included, 155 of the 314 infants discharged (49 percent) had no disability. CONCLUSIONS: Severe disability is common among children born as extremely preterm infants.

Cohort Studies↗
PubMed2000

Maximum length sequence brainstem auditory evoked responses in term neonates who have perinatal hypoxia-ischemia.

Maximum length sequence brainstem auditory evoked response (BAER) was studied within the first week after birth in 28 term neonates who had perinatal hypoxia-ischemia, or asphyxia. In the BAER recorded using conventional averaging techniques (click rate 21/s), the only abnormality was a slight increase in III-V interval, in addition to an increase in wave latencies when including those who had an elevated threshold (t test, all p<0.05). In the maximum length sequence BAER, however, both the III-V and I-V intervals in the asphyxiated infants were significantly increased at all the 91/s, 227/s, 455/s, and particularly 910/s click rates (p<0.05-0.001). The I-III interval was also increased significantly at 455/s and 910/s click rates (both p< 0.05). Wave V amplitude was significantly reduced at all the click rates used (ANOVA, p<0.05-0.001), particularly at 910/s, which sometimes was the only abnormality indicative of brain damage. Both the amplitude ratios V/I and V/III were significantly decreased at 455/s and 910/s click rates (p<0.01 or 0.001). A general trend was that BAER abnormalities after hypoxia-ischemia became more prominent as click rate was increased. Significant abnormalities occurred mainly at very high click rates (455/s and 910/s), which can be achieved using the maximum length sequence technique but not by using conventional averaging techniques. Thus, this technique, which can be used at the cribside, appears to be a better method for the early detection of brain damage after hypoxia-ischemia than using conventional averaging techniques, enhancing the diagnostic value of the BAER.

Acoustic Stimulation↗
PubMed2000

The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability.

OBJECTIVE: To evaluate the outcome for all infants born before 26 weeks of gestation in the United Kingdom and the Republic of Ireland. This report is of survival and complications up until discharge from hospital. METHODOLOGY: A prospective observational study of all births between March 1, 1995 and December 31, 1995 from 20 to 25 weeks of gestation. RESULTS: A total of 4004 births were recorded, and 811 infants were admitted for intensive care. Overall survival was 39% (n = 314). Male sex, no reported chorioamnionitis, no antenatal steroids, persistent bradycardia at 5 minutes, hypothermia, and high Clinical Risk Index for Babies (CRIB) score were all independently associated with death. Of the survivors, 17% had parenchymal cysts and/or hydrocephalus, 14% received treatment for retinopathy of prematurity (ROP), and 51% needed supplementary oxygen at the expected date of delivery. Failure to administer antenatal steroids and postnatal transfer for intensive care within 24 hours of birth were predictive of major scan abnormality; lower gestation was predictive of severe ROP, while being born to a black mother was protective. Being of lower gestation, male sex, tocolysis, low maternal age, neonatal hypothermia, a high CRIB score, and surfactant therapy were all predictive of oxygen dependency. Intensive care was provided in 137 units, only 8 of which had >5 survivors. There was no difference in survival between institutions when divided into quintiles based on their numbers of extremely preterm births or admissions. CONCLUSIONS: This study provides outcome data for this geographically defined cohort; survival and neonatal morbidity are consistent with previous data from the United Kingdom and facilitate comparison with other geographically based data.

Analysis of Variance↗
PubMed1999

Congenital diaphragmatic hernia: prenatal diagnosis, outcome and continuing morbidity in survivors.

OBJECTIVE: To improve counselling by investigating the prenatal diagnosis, outcome and morbidity in survivors of congenital diaphragmatic hernia. SETTING: Prenatal Diagnosis Unit, Oxford Radcliffe Women's Centre, Oxford. DESIGN: Cohort study. SAMPLE: Babies with congenital diaphragmatic hernia diagnosed postnatally and born to women scanned prenatally identified between January 1991 and December 1996. METHODS: Associated anomalies, outcome of pregnancy and final diagnoses were determined from hospital records. A report from the general practitioner and paediatrician recorded health and development information. MAIN OUTCOME MEASURES: Accuracy of prenatal diagnosis, survival of cases of congenital diaphragmatic hernia and presence of ongoing morbidity in survivors. RESULTS: There were 35 pregnancies with congenital diaphragmatic hernia, nine of which were not diagnosed prenatally. In 22 pregnancies with isolated congenital diaphragmatic hernia, four were terminated, there were six perinatal deaths and two later deaths. Thirteen of 35 cases (37%) with congenital diaphragmatic hernia were associated with other abnormalities: four with abnormal karyotype and nine with other structural anomalies. Five of these women continued with their pregnancy; there were two neonatal deaths and three survivors. Thirteen of 35 infants (37%) survived, eight with chronic disorders requiring specialist intervention including respiratory problems (n = 6); developmental delay (n = 4); poor growth (n = 5); artificial feeding (n = 3); gastro-oesophageal reflux (n = 3); recurrent hospital admissions (n = 6); and further surgery (n = 4). CONCLUSIONS: The survival for infants born alive with congenital diaphragmatic hernia was 56% (13/23), 61% of whom have persistent disorders. Despite advances in neonatology there is a high mortality and morbidity with congenital diaphragmatic hernia. Prenatal counselling should reflect this.

Cohort Studies↗
PubMed1999

Brainstem auditory evoked response recorded using maximum length sequences in term neonates.

Brainstem auditory evoked response (BAER) was studied in term neonates using maximum length sequences (MLS), which allows presentation of acoustic stimuli at much higher rate than possible with conventional averaging technique. The response waveforms, especially for waves III and V, were well defined at the click rates of 91-455/s. Wave latencies and interpeak intervals at various click rates were all significantly longer and wave V amplitude was smaller in the neonates than in the adults. As click rate was increased, wave latencies increased and amplitudes progressively reduced. The slopes of wave latency-rate functions were progressively steeper for the later waves. The slopes of both III-V and I-V interval-rate functions were significantly steeper in the neonates than in the adults, indicating greater rate-dependent changes in the central components of the neonatal MLS BAER. These rate-dependent changes in the neonatal MLS BAER are generally similar to those in neonatal conventional BAER, although there are some differences. The results indicate that the neonatal brainstem can process rapid acoustic stimulation up to 455/s, although this ability remains immature.

Adult↗
PubMed1998

Immaturity of electrophysiological response of the neonatal auditory brainstem to high repetition rates of click stimulation.

Changes in brainstem auditory evoked response (BAER) with varying stimulus repetition primarily represent neural processes concerning the efficacy of synaptic transmission in the brainstem auditory pathway. In this study the BAER to different rates of clicks was recorded from 16 term neonates. The results were compared with those from 16 adults to examine whether the degree of maturation of synaptic transmission of the neonatal brainstem auditory pathway parallels that of general function of the pathway. All BAER wave latencies and interpeak intervals increased linearly and wave amplitudes reduced with increasing click rate. The absolute rate-dependent changes in BAER measures were much greater in the neonates than in the adults, reflecting a significant immaturity in the efficacy of synaptic transmission in the neonatal auditory brainstem and in the ability of the neonatal brainstem to process rapid acoustic stimulation. When the data obtained at higher click rates at various age groups were analyzed as percentages, using the BAER measurements at conventionally used slow rate (21/s) of clicks as the denominators, the changing rates (%), or relative changes, of most BAER measures at higher rates in the neonates were still greater than those in the adults. Therefore, the rate-dependent BAER changes in the neonates are relatively less mature than general aspects of the BAER, reflected by the BAER elicited with conventionally used slow rates of clicks. These findings suggest that synaptic efficacy in the neonatal brainstem auditory pathway is relatively less mature than general function of the pathway and thus may be more susceptible to unfavourable perinatal conditions.

Acoustic Stimulation↗
PubMed1998

Accuracy of carotid duplex is laboratory specific and must be determined by internal audit.

OBJECTIVE: To assess the accuracy of carotid duplex in a single vascular laboratory at the prediction of an angiographic 70% internal carotid artery stenosis. DESIGN: A retrospective review of all patients who underwent both carotid duplex and angiography in a 1-year period at a vascular unit which participates in the ACST trial. METHODS: Peak systolic velocity was used as a primary end-point in carotid duplex examinations with a PSV > 130 cm/s used as an indication for angiographic assessment. Biplanar arch aortography and selective carotid catheterisation were performed as indicated and diameter reduction calculated by the ECST method. RESULTS: The sensitivity of 130 cm/s for the detection of a 70% stenosis was 96% and the specificity 67%. If a PSV of 250 cm/s were used the sensitivity would be only 37% and specificity 96%. CONCLUSIONS: Applying duplex criteria from one centre to another is inappropriate. Laboratory specific audit of duplex and angiography is essential before deciding to abandon preoperative angiography for carotid disease.

Aortography↗
PubMed1998

Natural history of innocent heart murmurs in newborn babies: controlled echocardiographic study.

AIM: To define the origin and the natural history of innocent heart murmurs in newborn infants. METHODS: Fifty healthy babies born at term with the clinical diagnosis of an innocent heart murmur and 50 controls without a murmur were studied. Each baby had a complete two dimensional and pulsed Doppler echocardiogram and those with any abnormality were followed up at 6 weeks, 3 months, and 6 months until the murmur had disappeared or the heart was totally normal. Babies with congenital heart disease were excluded from the study. RESULTS: Pulmonary branch stenosis (PBS) was found in 25 (50%) of the study group and in six (12%) controls; patent ductus arteriosus (PDA) in 30 (60%) subjects and in six (12%) controls; and a patent foramen ovale (PFO) in 50 (100%) subjects and in 41 (82%) controls. At 6 weeks the murmur had disappeared in 64% of babies. PBS was still present in eight of 22 (36%) babies at 6 weeks, in 12% at 3 months, but in none at 6 months. At 6 weeks, seven of the eight with PBS still had a murmur compared with two of 14 (14%) babies in which the PBS had resolved (P < 0.005). At 6 weeks the PDA had closed in all patients but the foramen ovale was still patent in 29 of 44 (66%) subjects and nine of 33 (27%) controls. The closure of the PFO was not influenced by its size at birth. CONCLUSIONS: An innocent heart murmur in a baby born at term is often related to PBS, particularly if the murmur is still present after 24 hours of age, when most PDA have closed. At 6 weeks the murmur had disappeared and the PBS had resolved in 64% of the babies. PBS had resolved in all babies at 6 months.

Ductus Arteriosus, Patent↗
PubMed1998

Early onset group B streptococcal neonatal infection in Oxford 1985-96.

Of 74,920 babies live born in Oxford between 1985 and 1996, 41 (0.5 per 1000 95% CI 0.4-0.7) developed definite, culture confirmed, early onset (< 48 hours) group B streptococcal infection and 32 (0.4 per 1000 95% CI 0.3-0.6) developed probable infection (sepsis plus colonisation). There was no significant variation in incidence with time. The mortality from definite infection was 19.5%, and from probable infection 6%. These data suggest that the incidence of group B streptococcal infection in Oxford is considerably lower than that reported in the USA.

Confidence Intervals↗
PubMed1998

Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn.

The relationship between GH, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin may be critical to the understanding of variation in early growth, especially in the small for gestational age (SGA) baby. To investigate these relationships, we have undertaken 12-h hormone profiles in 26 babies (13 SGA) at a median of 4.5 days of age. GH levels were measured every 10 min; insulin and IGFBP-1 were measured every 20 min. Mean levels of these hormones and IGF-I levels (from a single sample) were related to size at birth. The GH data were analyzed by Pulsar and time series analysis to characterize hormone pulsatility and relationship with feeds. IGF-I levels correlated with birth weight and length (r2 = 0.47; P = 0.004, and r2 = 0.5; P = 0.0005, respectively, after allowing for gestation), whereas mean GH levels were negatively related to birth size (r2 = -0.18; P = 0.04 and r2 = -0.2; P = 0.03 for weight and length, respectively). No direct relationship between mean GH levels and IGF-I was identified. IGF-I levels were higher in appropriate for gestational age (AGA; mean +/- SD, 82+/-61 ng/mL) than in SGA (34+/-22 ng/mL; P = 0.03) babies. Baseline (mean +/- SD, 25.9+/-11.9), mean (33.9+/-14.0), and peak (45.0+/-18.1 microg/L) GH levels were higher in SGA than in AGA babies [17.1+/-8.2 (P = 0.04), 22.5+/-10.4 (P = 0.03), and 30.7+/-15.4 microg/L (P = 0.04), respectively]. Mean IGFBP-1 levels were also higher in SGA than AGA babies (157.4+/-90.7 vs. 62.7+/-43.8 ng/mL; P = 0.01). A positive correlation was identified between changes in insulin and coincident pulses of GH (r = 0.147; P < 0.01), whereas there was an inverse relationship between insulin and IGFBP-1, with a lag time 120 min (r = -0.33; P < 0.0001). In conclusion, these studies indicate that the GH-IGF-I axis is closely related to feeding in the newborn. In SGA babies, low IGF-I and elevated IGFBP-1 reflect the slow growth, but elevated GH and rapid GH pulsatility may be a signal for lipolysis.

Eating↗
PubMed1997

The use of an automated microsampling system for the characterization of growth hormone pulsatility in newborn babies.

To overcome the difficulties of studying hormone pulsatility in the newborn, we have developed an automated microsampling system that permits the measurement of hormones in small prediluted samples of blood (40 microL) taken at 10-min intervals over 12 h. The system has been validated in adult volunteers, and the error attributable to the dilution was <4%. Using this method in 10 preterm babies, we have been able to describe pulsatile changes in GH and have demonstrated a clear postprandial elevation in GH levels peaking 60 min after a feed. Fourier transform analysis indicated a pulse periodicity of 180 min in babies who were appropriate for gestational age (n = 6), but faster, co-dominant pulse periodicities of 90-100 and 140 min in babies who were small for gestational age (weight and length below the 10th centile) (n = 4). There was no significant difference between mean, peak, and baseline GH levels between the two groups.

Adult↗
PubMed1996

Effect of carotid endarterectomy on the ocular circulation and on ocular symptoms unrelated to emboli.

OBJECTIVE: To evaluate haemodynamic changes in the ophthalmic artery and the retina following carotid endarterectomy and their effect on the pathophysiology of the eye. DESIGN: Prospective study. METHOD: Twenty-two consecutive patients with severe carotid stenosis underwent 23 carotid endarterectomies and one subclavian-carotid bypass. The following measurements were made preoperatively and 3 months after operation; Ophthalmic artery (OA) and retinal arteriole (RA) peak systolic velocity (PSV) and peak diastolic velocity (PDV), macular photostress recovery time, visual acuity, intraocular pressures, colour vision and visual fields testing. RESULT: The RA PSV increased by 50% (p = 0.005) and PDV increased by 22% (p = 0.03). The OA PSV increased by 51% (p = 0.001). Macular photostress testing decreased from 58 s to 42 s (p = 0.001). Visual acuity improved in four and was unchanged in 13 eyes ipsilateral to the endarterectomy which had abnormal preoperative measurements. One patient experienced a dramatic increase in the ipsilateral intraocular pressure associated with visual deterioration. In two patients there was resolution of periorbital pain. CONCLUSION: Our results demonstrate an increase in the PSV of the RA and OA following carotid surgery. There are pathophysiological changes in the eye, which accompany tight stenotic extracranial carotid artery disease and these may be influenced by carotid endarterectomy.

Aged↗
PubMed1995

Geleophysic dysplasia: a report of three affected boys--prenatal ultrasound does not detect recurrence.

Geleophysic dysplasia is characterized by short stature with short limbs and brachydactyly, a "happy" facial appearance, and joint contractures. Infiltration of heart valves and liver with a mucopolysaccharide-like substance has been demonstrated in some patients. A metabolic pathogenesis is suspected, but has not yet been identified. We report on 3 boys with the condition, 2 of whom are brothers. Serial ultrasound scans were performed on 2 of the cases during pregnancy, but short limbs did not become obvious until after 28 weeks of gestation, making it an uninformative procedure for prenatal diagnosis.

Abnormalities, Multiple↗
PubMed1994

Comparison of mortality and rates of cerebral palsy in two populations of very low birthweight infants.

Comparisons of mortality and rates of cerebral palsy in different populations can be confusing. This is illustrated by comparing two populations of very low birthweight infants born in the 1980s, one from the Netherlands, the other from the UK (Oxford region). Although a number of biases were controlled for while comparing two large geographically defined populations, by assessing the survivors at similar ages and describing their health status in a standard way, some problems in interpretation of outcome remained. Differences in registration practice of live births at early gestational ages, as well as differences in withholding or withdrawing treatment, which occurred in about half of the cases of neonatal death in the Netherlands and in about one third of those in the Oxford region, may have influenced the incidence of registered live births, neonatal mortality, and the rate of cerebral palsy.

Blindness↗
PubMed1993

Functional abilities at age 4 years of children born before 29 weeks of gestation.

OBJECTIVES: To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN: Cohort study of a geographically defined population of babies. SETTING: Oxford Regional Health Authority. SUBJECTS: All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES: Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS: Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS: With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.

Child, Preschool↗
PubMed1993

Electrical impedance plethysmography: its use in studying the cerebral circulation of the rabbit.

Electrical impedance plethysmography (EIP) is a noninvasive method that may be useful for both the continuous and serial measurement of changes in pulsatile cerebral blood volume and perhaps cerebral blood flow (CBF). It has not been well validated by comparison with other methods. To attempt to validate the EIP technique, the relationship between the peak amplitude of the transcranial, cardiac-synchronous impedance waveform (dZp) and cerebral blood flow measured by the radiolabelled microsphere technique (CBFrlm) and laser Doppler spectroscopy (CBFlds) was studied in rabbits. CBF was altered by inducing hypertension using metaraminol, hypotension by controlled haemorrhage or hypocarbia by hyperventilation. Twenty-three comparisons between dZp and CBFlds and 19 comparisons with CBFrlm were made in eight rabbits. The percentage change between each measurement using the three techniques in each animal was calculated. Using pooled data from all the animals, the linear regression equations were dZp = 0.5 CBFrlm + 33 (r = 0.38, p = 0.22, SE = 79) and dZp = 0.84 CBFlds + 19.6 (r = 0.46, p = 0.09, SE = 72). It is concluded that, in the anaesthetised rabbit, when large changes in CBF are induced by the manoeuvres described above, changes in dZp correlate very weakly with changes in either cortical or global CBF, and are influenced by other factors such as pulsatile intracranial blood volume.

Animals↗
PubMed1993

Prospective surveillance of neonatal meningitis.

Neonatal meningitis is a serious problem with a high mortality and frequent neurological sequelae. The incidence of neonatal meningitis was calculated and the aetiology, clinical and laboratory features, and the treatment of cases recorded prospectively over a 7 year 8 month period was documented. It was further investigated whether secondary meningitis had occurred after lumbar puncture. The estimated incidence of bacterial, viral, and fungal meningitis was 0.25, 0.11, and 0.02 per 1000 live births respectively. There were eight cases of early onset meningitis (seven definite, one probable) and group B streptococci accounted for six (75%) of these. Blood cultures were negative in only one of seven cases of definite early bacterial meningitis. Of the 15 late onset cases, Gram negative organisms accounted for six of the seven bacterial cases. The overall mortality was 26%. Of the 11 survivors of bacterial meningitis, three (27%) had significant neurological sequelae at follow up (between three months to three years later). As in the first 48 hours after birth an initial blood culture is unlikely to be negative if bacterial meningitis is present, lumbar puncture can be deferred if the procedure might exacerbate respiratory distress. Although approximately 1880 infants had a lumbar puncture during the review period, only one case of meningitis was found where it was possible that lumbar puncture in a bacteraemic infant may have caused meningeal infection. The incidence of this potential complication must therefore be low.

Birth Weight↗