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Biomedical subjects

P J Fleming

Publications and source records attributed to P J Fleming.

At least 19 recordsLinked to original sources
PubMed1992

Can the fall in Avon's sudden infant death rate be explained by changes in sleeping position?

OBJECTIVE: To examine the impact of changing practice with regard to infant sleeping position on mortality from the sudden infant death syndrome. DESIGN: A population based study of all infants dying suddenly and unexpectedly during February 1990 to July 1991, and two groups of controls; one comprising every 125th baby born to Avon residents and the other comprising pairs of infants matched to each index case for age, neighbourhood, and date of study. Information about sleeping position was collected at home visits soon after the index baby's death or, for the population based controls, on several occasions in the first six months of life. The design was comparable to that of an earlier study of the same population. SETTING: County of Avon. SUBJECTS: 35 infants who died suddenly and unexpectedly (32 of the sudden infant death syndrome), 70 matched controls, and 152 population based controls. RESULTS: The prevalence of prone sleeping in the matched controls was much lower than that found in an earlier study in Avon (28% (18/64) 1990-1 v 58% (76/131) 1987-9; p less than 0.001) and was comparable with the prevalence in population based controls (29%). This would be expected to lead to a reduction in the incidence of the sudden infant death syndrome to 2.0/1000 live births (95% confidence interval 1.8/1000 to 2.5/1000). The actual mortality fell from 3.5/1000 in 1987-9 to 1.7/1000. CONCLUSION: The fall in mortality can be almost entirely accounted for by the reduction in prone sleeping, suggesting a causal relation exists between them. Side and supine positions confer protection but the side position is unstable and the infant may roll prone. We therefore recommend supine as the safest sleeping position for babies.

Case-Control Studies↗
PubMed1992

Evaluation of the Oxford and Sheffield SIDS risk prediction scores.

STUDY OBJECTIVE: To evaluate the clinical usefulness (sensitivity and specificity) of the Oxford and Sheffield birth scores for prospective identification of infants at high risk of SIDS. DESIGN: Retrospective medical record reviews of prospectively identified, autopsy-validated SIDS and living control infants. STUDY SUBJECTS: Consecutive sample of 140 infants, born between 1/1/83 and 12/31/87, who died suddenly and unexpectedly in the Avon Area Health Authority in southwest England between 1/1/84 and 12/31/88. Seventeen of the cases were excluded: 6 because they lacked adequate clinical records, 11 because they were not SIDS. The 637 control infants were comprised of every 80th delivery between 1/1/83 and 12/31/87 in the three major hospitals in the area. RESULTS: SIDS incidence was 2.85/1,000 live births. Using standard cut scores to define high SIDS risk (2.0 for Oxford and 500 for Sheffield), sensitivities were 0.55 and 0.35 and specificities were 0.78 and 0.89 for the Oxford and Sheffield scores, respectively. SIDS risk for infants in the high risk group was 7.3/1,000 (Oxford) and 9.3/1,000 (Sheffield). CONCLUSIONS: Since there is no intervention with proven efficacy for SIDS prevention, and since approximately one half of SIDS cases occur in low risk groups, clinical use of these scoring systems for allocation of health care resources or personnel for the sole purpose of SIDS prevention is not justified.

Cohort Studies↗
PubMed1992

Validation of a portable indirect calorimetry system for measurement of energy expenditure in sick preterm infants.

A portable indirect calorimeter adapted from adult use was validated for use in preterm infants. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were subsequently measured in 16 preterm infants breathing spontaneously in room air (canopy mode) and in nine preterm infants receiving intermittent positive pressure ventilation (ventilator mode). Validation of the system was performed using a gas injection technique with nitrogen to simulate VO2 and carbon dioxide for VCO2. Mean errors in validation of the canopy mode were 1.4% and 0.2% for VO2 and VCO2 with limits of agreement of 0.6 (+2SD) ml/min and -1.3 (-2SD) ml/min, and 0.9 (+2SD) ml/min and -2.3 (-2SD) ml/min respectively. In validation of the ventilator mode mean errors were -1.8% and -5.05% for VO2 and VCO2 with limits of agreement of 1.02 (+2SD) ml/min and -0.74 (-2SD) ml/min, and 0.93 (+2SD) ml/min and -1.45 (-2SD) ml/min respectively. Values of VO2 and VCO2 in 16 preterm infants in the canopy mode were 6.2 ml/kg/min (0.5 1SD) and 6.7 ml/kg/min (0.6 1SD) and in nine preterm infants in the ventilator mode 4.98 ml/kg/min (1.09 1SD) and 4.74 ml/min/kg (1.08 1SD) respectively. Mean energy expenditure was 45.5 kcal (191 kJ)kg/day for infants measured in the canopy mode and 35.5 kcal (149 kJ)/kg/day for ventilated infants. This metabolic system can be adapted for use in the newborn but accuracy is reduced when it is used in those weighing less than 1000 g.

Calorimetry, Indirect↗
PubMed1992

Combined effect of infection and heavy wrapping on the risk of sudden unexpected infant death.

Three methods were used to investigate the role of infection in sudden unexpected infant death (SUD): (i) microbiological comparison of SUD victims and matched, live, community controls; (ii) postmortem classification of the contribution of infection to death; and (iii) case-control analysis of the relative risk associated with both infection and heavy wrapping. Limited sampling from the upper respiratory tract and gut in SUD victims and controls showed no significant excess of viral infection in the SUD victims (odds ratio = 1.98, 95% confidence interval (CI) 0.9 to 4.5). At postmortem examination, infection explained death in 3/95 babies and may have contributed to death in 37/95. Over 70 days of age, the combined presence of viral infection and wrapping in excess of 10 togs produced an odds ratio of SUD of 51.5 (95% CI 5.64 to 471.48) compared with wrapping of less than 6 togs. Viral infection was not a major risk factor as long as babies were lightly wrapped. In heavily wrapped babies the presence of a viral infection greatly increased the risk of SUD.

Bacterial Infections↗
PubMed1992

The relationship between environmental temperature, metabolic rate, sleep state, and evaporative water loss in infants from birth to three months.

We have investigated the effect of changing environmental temperature on metabolic rate, sleep state, and water loss in a longitudinal study of 22 lightly clothed babies from 2 d to 3 mo of age. Studies were performed in a modified barometric plethysmograph while recording sleep state, oxygen consumption, and skin and axillary temperatures. Oxygen consumption was higher in rapid eye movement sleep than in quiet sleep at all ages and varied widely between infants at each temperature. Within the first week, there was a 19% rise in oxygen consumption on cooling to 19-22 degrees C during rapid eye movement sleep and a 6% rise during quiet sleep. The median duration of quiet sleep periods was reduced from 17 to 12 min on cooling within the first week. No such change was seen at 1, 2, and 3 mo. Axillary temperature was reduced at 3 mo during cooling. This may be a part of normal patterns of change in temperature during sleep, unrelated to cooling. At each age, total evaporative water loss fell linearly with falling environmental temperature both within and below the temperature range at which metabolic rate was minimal. The evaporative water losses were greater than expected and suggested that sweating was occurring, both at temperatures at which metabolic rate was minimal and at those at which it was increased. The metabolic response to cooling and the process of sweating appear to be in dynamic equilibrium across this temperature range. Thus, it was not possible to define a temperature range over which both metabolic rate and evaporative water loss were at minimum values.

Body Temperature Regulation↗
PubMed1992

Development of thermoregulation in infancy: possible implications for SIDS.

Over the first three months of life the infant's metabolic rate rises, which, together with the rise in ratio of mass to surface area, means that the net heat loss per unit surface area is 50% higher in a 3 month old infant than in a neonate. This, together with the thicker layer of subcutaneous fat and more effective peripheral vasomotor response to cold in a 3 month old infant, means that thermal balance is shifted in favour of heat conservation. The head is the site of 40% of heat production and of up to 85% of heat loss in an infant in bed: covers rising up over the head could therefore result in acute thermal imbalance with a rise in brain temperature not necessarily accompanied by a rise in body temperature. In animal studies relatively small changes in hypothalamic temperature have profound effects on the control of respiration. Alternatively, a rise in metabolic rate (from an acute infection, for example) could result in a significant change in thermal balance. There is anecdotal evidence that heat stress may be associated with sudden infant death or with severe hypoventilation. In the Avon studies infants with SIDS, particularly those over 70 days of age, were more heavily wrapped and were more likely to have had the heating on all night than control infants matched for age, date, and neighbourhood. There was no significant excess of viral infections in the infants with SIDS, but those who had virus infections were much more heavily wrapped than control infants with similar infections, suggesting that the combination of heavy wrapping and virus infection may be more important than either factor alone. There is, therefore, some physiological evidence that infants of 2 to 3 months of age may be more vulnerable to heat stress than younger infants, and limited evidence, from clinical studies, that this may occur and be associated with some sudden deaths. The precise contribution of thermal stress and the mechanism by which it could cause death remain unclear.

Body Temperature Regulation↗
PubMed1991

Multiple forms of human dopamine beta-hydroxylase in SH-SY5Y neuroblastoma cells.

Dopamine beta-hydroxylase exists as three forms in human neuroblastoma (SH-SY5Y) cells. The membrane-bound form of the hydroxylase contains three different species with apparent relative molecular weights of 73,000, 77,000, and 82,000. The intracellular soluble form of dopamine beta-hydroxylase was present as a single species with an apparent molecular weight of 73,000. Pulse-chase experiments showed that membranous dopamine beta-hydroxylase contains two subunit forms of 73,000 and 77,000 after short chase times. The soluble hydroxylase was synthesized as a single species of 73,000 at approximately the same rate as the lower molecular weight species of the membranous enzyme. A constitutively secreted third form of the enzyme with an intermediate apparent molecular weight also incorporated [35S]sulfate, whereas no significant amount of [35S]sulfate was observed in the cellular forms of the enzyme. The [35S]sulfate was incorporated on N-linked oligosaccharides. Approximately 12% of the enzyme is released constitutively within 1 h. These results demonstrate that neuronal cells have the ability to constitutively secrete a specific form of dopamine beta-hydroxylase which may contribute to the levels of this enzyme found in plasma.

Cell Line↗
PubMed1991

Stimulation of rat adrenal medulla can induce differential changes in the peptide and mRNA levels of chromogranins, neuropeptides and other constituents of chromaffin granules.

The levels of various components of chromaffin granules were determined in rat adrenals after treatment with several stimulants. After reserpine the levels of calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and chromogranin B but not those of chromogranin A and secretogranin II were elevated. On the other hand, the mRNA of chromogranins A, B and secretogranin II were significantly increased. Treatment with oxotremorine or nicotine (multiple injections for 2 or 3 days) induced analogous changes for peptide and mRNA levels, however, the increases were smaller and for the mRNA less consistent. A single injection of oxotremorine or nicotine raised only the levels of CGRP and NPY and of the NPY mRNA whereas those of the chromogranins and their respective mRNAs remained unaltered. Amongst the membrane proteins only the levels of dopamine beta-hydroxylase are increased after prolonged stimulation, whereas those of cytochrome b-561, carboxypeptidase H and synaptin/synaptophysin (SYN) remain unaltered. Thus, the biosynthesis of chromaffin granules can be regulated in quite sophisticated patterns.

Adrenal Medulla↗
PubMed1991

Development of visual evoked potentials following intrauterine growth retardation.

Visual evoked potentials to flash (FVEP) were recorded in 23 symmetrically growth retarded newborns of between 32 and 39 weeks gestational age and 41 normally grown controls. At 9 months post term FVEP recordings were repeated in 14 of the growth retarded and 26 of the control infants. The development of two long latency negative components of the wave form of the neonatal FVEP was delayed in the growth retarded infants. The amplitude of a long latency negative peak in the 9 month post term FVEP was reduced in the growth retarded infants. We suggest that intrauterine growth retardation may affect the development of secondary activity in the visual cortex.

Cerebral Cortex↗
PubMed1991

Cytochrome b561, ascorbic acid, and transmembrane electron transfer.

Cytochrome b561 is a transmembrane protein unique to neuroendocrine secretory vesicles. It acts as an electron channel and mediates equilibration of ascorbate-semidehydroascorbate inside the secretory vesicle with the ascorbate redox pair in the cytoplasm. The role for this function is to regenerate ascorbate inside the secretory vesicle for use by monooxygenases. Elucidation of the structure and mechanism of redox activity of cytochrome b561 may demonstrate paradigms for other ascorbate-utilizing enzymes as well as provide insights into long-range biological electron transfer.

Amino Acid Sequence↗
PubMed1991

Baby Check and the Avon infant mortality study.

Thirty seven sudden, unexpected infant deaths from the Avon study were scored retrospectively for serious illness using a modified version of Baby Check. Three cases (8%) scored very highly. In a small proportion of sudden deaths, Baby Check could have identified serious illness before death and led to hospital admission.

Humans↗
PubMed1990

Cytochrome b561 is fatty acylated and oriented in the chromaffin granule membrane with its carboxyl terminus cytoplasmically exposed.

Two polyclonal antibodies were raised to synthetic peptides corresponding to amino acids Ser21-Tyr35 and Lys247-Phe261 of cytochrome b561. These antibodies were used to test the native orientation of the amino and carboxyl termini of this transmembrane electron transport protein. Carboxyl-terminal epitopes were lost when intact chromaffin granules were treated with Pronase. This result indicates that the carboxyl terminus is cytoplasmically exposed and confirms a theoretical prediction obtained from hydropathy plots. Epitopes that were recognized by an amino-terminal antipeptide antibody were not removed under the same conditions. This finding implied that the amino terminus was not proteolytically accessible on the exterior of the granule. The abundance of threonine and serine residues in the amino-terminal region suggested that the amino terminus could be held in the membrane by covalent fatty acylation. Treatment of purified delipidated cytochrome b561 with hydroxylamine resulted in the release of a fatty acid hydroxamate. Sulfhydryl analysis of purified cytochrome b561 showed that all 3 cysteine residues were in the free sulfhydryl form. These observations indicate that cytochrome b561 is covalently fatty acylated and that the lipid is bound through ester linkages of serine or threonine residues.

Acylation↗
PubMed1990

Genomic organization and chromosomal localization of the human nucleolin gene.

Nucleolin, a eukaryotic nucleolar phosphoprotein, is involved in the synthesis and maturation of ribosomes. To characterize the genomic organization and regulatory sequences of this gene, two overlapping lambda clones containing the human nucleolin gene plus flanking regions were isolated from a genomic library using human nucleolin cDNA. Southern blots of genomic DNA from human, several mammals, chicken, and yeast revealed that the nucleolin gene is well conserved across these species. The gene consists of 14 exons with 13 intervening sequences and spans approximately 11 kilobases of DNA. Analysis of the splice junctions indicated that the amino-terminal domain and the four RNA binding domains plus the nuclear localization signal are split into adjacent exons. Sequences from the 5'-flanking and the first intron contain a high content of GC residues which is consistent with nucleolin being a "housekeeping" gene. Promoter elements include an atypical TATA box (GTTA), one CCAAT box much further from the initiation site, three reverse compliments of CCAAT (ATTGG), and two pyrimidine-rich nucleotide stretches. In addition, this region and the first intron contain numerous potential Sp1, GCF, CRE-fos, GCN, AP-1, AP-2, UCE, and sequences similar to the glucocorticoid receptor binding site. The transcription start site was determined by primer extension and S1 nuclease mapping of RNA from human liver. One Kpn and three Alu repeats were found within two of the middle introns. The 3'-untranslated portion of the gene contains five homology blocks in a 100-base pair region that are highly conserved among human, mouse, and hamster genomes. Finally, we have determined that the human nucleolin gene is located on chromosome 2q12-qter and is present at one copy per haploid genome. A restriction fragment length polymorphism with EcoRI has been detected in the gene.

Amino Acid Sequence↗
PubMed1990

Interaction between bedding and sleeping position in the sudden infant death syndrome: a population based case-control study.

OBJECTIVE: To determine the relation between sleeping position and quantity of bedding and the risk of sudden unexpected infant death. DESIGN: A study of all infants dying suddenly and unexpectedly and of two controls matched for age and date with each index case. The parents of control infants were interviewed within 72 hours of the index infant's death. Information was collected on bedding, sleeping position, heating, and recent signs of illness for index and control infants. SETTING: A defined geographical area comprising most of the county of Avon and part of Somerset. SUBJECTS: 72 Infants who had died suddenly and unexpectedly (of whom 67 had died from the sudden infant death syndrome) and 144 control infants. RESULTS: Compared with the control infants the infants who had died from the sudden infant death syndrome were more likely to have been sleeping prone (relative risk 8.8; 95% confidence interval 7.0 to 11.0; p less than 0.001), to have been more heavily wrapped (relative risk 1.14 per tog above 8 tog; 1.03 to 1.28; p less than 0.05), and to have had the heating on all night (relative risk 2.7; 1.4 to 5.2; p less than 0.01). These differences were less pronounced in the younger infants (less than 70 days) than the older ones. The risk of sudden unexpected death among infants older than 70 days, nursed prone, and with clothing and bedding of total thermal resistance greater than 10 tog was increased by factors of 15.1 (2.6 to 89.6) and 25.2 (3.7 to 169.0) respectively compared with the risk in infants of the same age nursed supine or on their side and under less than 6 tog of bedding. CONCLUSIONS: Overheating and the prone position are independently associated with an increased risk of sudden unexpected infant death, particularly in infants aged more than 70 days. Educating parents about appropriate thermal care and sleeping position of infants may help to reduce the incidence of the sudden infant death syndrome.

Age Factors↗
PubMed1990

Signs of illness preceding sudden unexpected death in infants.

OBJECTIVE: To determine whether signs of illness reported by parents can be used to identify babies at risk from the sudden infant death syndrome. DESIGN: A two year prospective case-controlled study based in a geographically defined area. SETTING: Four health districts in Avon and north Somerset. SUBJECTS: Babies who had died suddenly and unexpectedly aged between 1 week and 2 years (index babies) and two control babies for each index baby selected from the same health visitor's list and matched for age, time of year of the interview, and area of residence. MAIN OUTCOME MEASURES: Major and minor signs of illness during two weeks before the index babies' death, or before the interview for control babies, and consultations with the general practitioner during the same period. RESULTS: Parents reported major and minor signs of illness in the previous week in 66 of the 95 index babies compared with 77 of the 190 controls. No significant difference was found in the incidence of major signs reported (34 out of 95 index babies and 44 out of 190 controls), but a higher proportion of the index babies had been seen by their general practitioner during the previous week (17/95 v 11/190). CONCLUSION: Major and minor signs of illness are neither a sensitive nor a specific indicator of sudden unexpected death of infants and have no predictive value. Better understanding of the reasons why a higher proportion of parents of babies who died took them to their general practitioners may help to identify babies at risk before death.

Age Factors↗