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Biomedical subjects

A R Wilkinson

Publications and source records attributed to A R Wilkinson.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

Value of cerebrospinal fluid examination in the diagnosis of meningitis in the newborn.

Between 1 October 1988 and 30 September 1991 the results of all 896 cerebrospinal fluid examinations from 736 neonates were correlated with clinical diagnosis, treatment, and outcome. The prevalence of fungal or bacterial meningitis in babies requiring lumbar puncture was only 0.95%. Gram staining had a sensitivity of 68% and a positive predictive value of only 46% for the diagnosis of meningitis. Primary cultures directly onto agar plates had a sensitivity of 81% and positive predictive value of 46%. Broth enrichment cultures did not improve sensitivity and were frequently found to be false positive. Empirical treatment should not be altered unless more than a few organisms are seen on Gram staining. Primary cultures are adequate for the diagnosis of fungal and bacterial meningitis. Enrichment cultures should be performed only when the Gram stain and/or cell count suggests meningitis is likely. Clinicians should be aware that diagnostic tests performed in populations with a low prevalence of disease are likely to generate many false positive results and have a low positive predictive value.

Bacteriological Techniques

Flavin adenine dinucleotide levels in erythrocytes of very low birthweight infants under vitamin supplementation.

Despite the potential dangers of over- and undersupplementation with riboflavin (vitamin B2), little is known about status, requirements and metabolism of this vitamin in very low birthweight (VLBW) infants. As reported here, it is possible to calculate the intraerythrocytic concentration of free flavin adenine dinucleotide (FAD), the predominant coenzyme form of riboflavin, on the basis of the erythrocyte glutathione reductase activation coefficient (EGRAC). This parameter was determined in 9 VLBW infants (median of birthweight 634 g, median of gestational age 24 weeks + 3 days) at intervals over a period of 6 weeks. All infants received riboflavin supplementation, either in milk (average intake: 175 micrograms/kg/day) and a multivitamin preparation (200 micrograms/day) or via total parenteral nutrition (TPN; 720 micrograms/kg/day). The average EGRAC was 1.07 (1.00-1.24) during enteral nutrition and 1.05 (1.00-1.18) during TPN. These values correspond to free FAD levels of 757 and 1,060 nM, which is 4 to 5 times higher than in cord blood or in breast-fed infants. EGRAC values between 1.15 and 1.35, representing free intracellular FAD levels of 350-150 nM, should be adequate in VLBW infants in order to minimize the hazards of flavin-induced radical reactions.

Enteral Nutrition

Reduced use of surface cultures for suspected neonatal sepsis and surveillance.

Data on infection in a neonatal unit were collected prospectively for seven years. After the first four years, the number of surface cultures obtained from neonates with suspected sepsis and for surveillance was reduced. Rates of systemic infection (sepsis and meningitis) were not significantly different in the four years before and the three years after this change. Reduction in surface culture information made no observable difference to detection of colonisation in neonates with early onset sepsis (within first 48 hours of life) nor to antibiotic choice in late onset sepsis. Decisions concerning the length of antibiotic course in suspected infection were not adversely affected. Reduction in the number of surface cultures led to considerable saving of time, effort, and cost while appearing safe in terms of clinical practice and outcome.

Anti-Bacterial Agents

[Evoked auditive potentials in hydrocephalic neonates].

Auditory evoked potentials were measured in 10 newborn babies who had hydrocephalus of different etiologies. Eight showed abnormal results in the initial study with the most frequent anomaly being an absence of all waves that was unrelated to the postconceptional age. The results changed with time in one case who, after 10 weeks, showed the appearance of waves. Furthermore, in two cases the insertion of a ventriculo-peritoneal shunt provoked striking changes consisting of the appearance and normalization of the waves I, III and V latencies.

Evoked Potentials, Auditory

Predicting death from initial disease severity in very low birthweight infants: a method for comparing the performance of neonatal units.

OBJECTIVES: To investigate (a) which clinical variables and physiological measures of disease severity best predict death in very low birthweight infants and (b) their use in comparing mortality between two neonatal units. DESIGN: Retrospective study of two cohorts of very low birthweight infants from overlapping time periods who received mechanical ventilation. SETTING: Two neonatal intensive care units (hospitals A and B). SUBJECTS: 262 Very low birthweight infants, 130 in hospital A, 132 in hospital B. MAIN OUTCOME MEASURE: Death in hospital. RESULTS: In hospital A the mean level of oxygenation in the first 12 hours of life, whether measured as inspired oxygen requirement (FIO2), arterial/alveolar oxygen (a/AO2) ratio, or alveolar-arterial oxygen difference (A-aDO2), was more closely associated with death than any of four "traditional" risk factors: low birth weight, short gestation, the diagnosis of respiratory distress syndrome, and male sex. Mean pH in the first 12 hours was as strongly associated with death as birth weight. Multiple logistic regression models were derived in infants from hospital A using the four traditional risk factors with measures of oxygenation and pH. The validity of each model was then tested in infants from hospital B. The model based on the four traditional risk factors alone predicted death in hospital B with only 31% sensitivity. Adding mean a/AO2 ratio and mean pH increased its sensitivity to 75%, and when mean a/AO2 ratio was replaced by mean FIO2 its sensitivity increased further to 81%. Based on crude mortality rates alone, the odds of death in hospital A versus hospital B were 0.67 (95% confidence interval 0.37 to 1.23). After correcting for traditional risk factors and mean FIO2 and mean pH, however, the odds of death in hospital A increased to 3.27 (1.35 to 7.92; p less than 0.01). This increased risk persisted after adjusting for the time difference between each cohort. CONCLUSIONS: Crude comparisons of hospital mortality can be highly misleading. Reliable assessment of neonatal outcome is impossible without correcting for major risk factors, particularly initial disease severity. International agreement on a minimum core dataset of clinical and physiological information could improve neonatal audit and help to identify effective treatments and policies.

Gestational Age

Prenatal deficiency of phosphate, phosphate supplementation, and rickets in very-low-birthweight infants.

A preliminary study showed that placental histology was abnormal for babies who subsequently had rickets. The findings--low plasma phosphate concentration; maximum percentage tubular reabsorption of phosphate; and high urinary calcium loss--are those of renal conservation of phosphate in the presence of phosphate deficiency. In a controlled trial no baby receiving phosphate supplements (50 mg per day) had radiological evidence of rickets whereas bone changes were apparent in 42% of the control group. Prenatal deficiency of phosphate, due to placental insufficiency, can be corrected by phosphate supplementation thereby preventing rickets of prematurity.

Calcium

Continuous cerebral electrical impedance monitoring in sick preterm infants.

Cerebral electrical impedance (dZ) and intra-arterial blood pressure were measured continuously during the first 48 h after birth in 26 sick ventilated preterm infants with a birth weight less than 1500 g. The aim was to establish whether any patterns of dZp or the variability of either blood pressure or dZp would allow identification of those infants who developed intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) or a poor neurological outcome. IVH and PVL were diagnosed by ultrasound image obtained every 6 h. Cerebral electrical impedance recordings were unsuitable for analysis in three patients and a further three died within 14 h of birth. In the remaining 20 patients, no step changes that may have been related to the onset of IVH or PVL were evident and whilst three patterns of dZp were identified, they were not useful in distinguishing between normal infants or those who developed IVH, PVL or had a poor neurological outcome. Using multiple linear regression, the coefficient of variation of dZp was significantly associated with both IVH and outcome, as was the coefficient of variation of blood pressure. Continuous measurement of cerebral electrical impedance, whilst technically feasible in sick preterm infants, was not found useful as a method of identifying those who developed IVH, PVL or had a poor neurological outcome.

Blood Pressure Determination

Outpatient arteriography--a safe and practical proposition?

Ninety-five patients, who underwent fine catheter peripheral angiography as outpatients, were followed up and assessed to determine the safety of this procedure. No patients reported any major side effects and in particular no patients experienced a rebleed from the arterial puncture site. This procedure could be safely adopted in any radiology department.

Ambulatory Care

Neonatal pneumonia.

All babies admitted to the neonatal unit during a period of 41 months were prospectively studied to find out the incidence, aetiology, and outcome of neonatal pneumonia, and the value of routine cultures of endotracheal tubes. Pneumonia of early onset (before age 48 hours) occurred in 35 babies (incidence 1.79/1000 live births). In 20 (57%) it was caused by group B streptococci. Blood cultures showed the presence of organisms in 16 of the 35 (46%). There were 41 episodes of pneumonia of late onset in 39 babies. Thirty six of the 39 were preterm, and 34 were artificially ventilated (10% of all ventilated babies). Endotracheal tube colonisation had occurred in 94% of these, most commonly by Gram negative organisms and Staphylococcus epidermidis. In only one of seven cases with simultaneous bacteraemia was the same organism grown from cultures of the blood. After controlling for gestational age and duration of artificial ventilation there was no difference in the incidence or timing of endotracheal tube colonisation between babies who did and did not have pneumonia of late onset. Ten babies with pneumonia of early onset (29%) died; all were preterm infants. Only one death (2%) was associated with an episode of pneumonia of late onset. Routine surveillance cultures were not helpful in predicting and managing pneumonia of late onset.

Anti-Bacterial Agents

Conservative management of an echovirus 11 outbreak in a neonatal unit.

Two babies in a neonatal unit presented on the same day with meningitis due to echovirus 11, which was thought to have been introduced by staff. At this time echovirus 11 was also isolated from the stools of eight other babies; five of them did not have signs of infection. No intervention was made except to emphasise the importance of handwashing. There was evidence of secondary spread to two babies who were both clinically well. The attack rate was twelve (29%) of forty-one babies exposed. Seven of the twelve infected babies were born before 30 weeks' gestation and would have had little or no maternal antibody, yet only two of the seven babies had signs of infection. Despite lack of special measures, all babies recovered. Most cases of horizontally acquired neonatal echovirus infection are mild: extreme measures in the management of outbreaks are unnecessary.

Anti-Bacterial Agents