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Biomedical subjects

A C Fenton

Publications and source records attributed to A C Fenton.

16 recordsLinked to original sources

Cerebrovascular carbon dioxide reactivity and failure of autoregulation in preterm infants.

Changes in cerebral blood flow velocity (CBFV) in response to a rise in arterial carbon dioxide tension (PaCO2) in 94 ventilated preterm infants were determined using Doppler ultrasound to assess whether the nature of this change might predict subsequent neurological injury. Concomitant changes in mean arterial pressure (MAP) were recorded. Both CBFV and MAP rose significantly in response to the rise in PaCO2, the response being significantly less in the first 24 hours. Analysis indicated that the change in CBFV in the first day of life in infants less than or equal to 30 weeks' gestation was dependent to a great extent on the concomitant change in MAP. Similar dependence also occurred after administration of pancuronium to infants whose CBFV response was previously independent of changes in MAP. This dependency lasted for the duration of paralysis. Changes in CBFV after a rise in PaCO2 did not predict subsequent neurological injury. The influence of pancuronium on cerebrovascular regulation warrants further study.

Blood Flow Velocity

Neonatal cerebral venous flow velocity measurement using a color flow Doppler system.

Color flow Doppler provides a simple means for studying blood flow velocity from the central cerebral veins in newborn infants. Twenty-two term infants were examined during the first four days of life to establish a normal range for velocity from the vein of Galen. A wide range of velocities was found between individuals (2.3 cm.s-1 to 9.5 cm.s-1), but short-term intraindividual variation was small (root mean square variation 1.1 cm.s-1). Light bilateral jugular venous compression was performed in 17 of the infants and produced a fall of up to 63% in venous flow velocity in 12 infants (p = 0.0005).

Blood Flow Velocity

Bacteriophage P22 accessory recombination function.

The accessory recombination function (arf) gene of bacteriophage P22 is located immediately upstream of the essential recombination function (erf) gene. Three mutant alleles of arf were constructed and installed in P22 in place of the wild-type allele: an out-of-frame internal deletion, an in-frame internal deletion, and an amber mutation. The deletion mutant phages are partially defective in homologous recombination and plaque formation in wild-type and recA hosts; their defects are more severe in recB and recA recB hosts. The amber mutant phage exhibits the same growth phenotypes in nonsuppressing hosts, but not in an amber-suppressor host. Plasmids that express arf complement the growth defect of arf- phages. These plasmids stimulate erf-mediated recombination; they were also found to cause a small stimulation of recA-recBCD-mediated homologous recombination of phage lambda.

Amino Acid Sequence

Shortfall of equipment for neonatal intensive care and the introduction of budget holding contracts.

As adequate allowance must be made for the costs of purchasing, maintaining, and updating equipment during the development of contracts the current standing of neonatal units with regard to available equipment was assessed. Data were collected as part of a one year prospective survey of the 17 perinatal units in the Trent region. Adequacy of provision of equipment for recognised intensive care cost was assessed using the recommendations of the British Paediatric Association and British Association of Perinatal Paediatrics. It was assumed that units without recognised intensive care cost had to be able to equip one cot to a standard of intensive care level 1 in the short term. Equipment more than 5 years old was considered likely to warrant replacement or major maintenance within the next two years. With these guidelines over 600,000 pounds would be required to provide sufficient equipment for all recognised level 1 intensive care cost and to allow units without funded cost to provide this level of care in the short term and to replace existing equipment more than 5 years old for these cost alone. This amount could be reduced by 25% by subdividing intensive care cost into levels 1 and 2, thereby reducing equipment requirements, but this would impair the units' ability to perform level 1 care at funded provision, which has already been shown to need expansion. Neither figure takes account of equipment requirements for infants requiring special care. In addition, no allowance has been made for purchase or update of ultrasound scanners or blood gas analysers. If the government's proposed reforms are to be implemented clinicians need to revise guidelines regarding essential equipment, and plans must be made to correct any existing shortfalls so that they do not become inherited financial liabilities for future budget holders.

Budgets

Attitudes to viability of preterm infants and their effect on figures for perinatal mortality.

OBJECTIVE: To examine how local attitudes to management of extreme preterm labour can influence data on perinatal mortality. DESIGN: One year prospective study in a geographically defined population. SETTING: The 17 perinatal units of Trent region. PATIENTS: All preterm infants of less than or equal to 32 weeks' gestation in the Trent region. INTERVENTIONS: Infants who had been considered viable at birth were referred for intensive care; those who had been considered non-viable received terminal care. MAIN OUTCOME MEASURES: Whether each infant was born alive, dead, or alive but considered non-viable. RESULTS: Large differences were observed among units in the rates of delivery of infants of less than or equal to 27 weeks' gestation (rates varied from 7.2 to 0 per 1000 births). These differences were not present in the data relating to infants of between 28 and 32 weeks' gestation. The variation seemed to result from different approaches to the management of extreme preterm labour--that is, whether management took place in a labour ward or a gynaecology ward. CONCLUSIONS: Place of delivery of premature babies (less than or equal to 27 weeks' gestation) may influence classification and hence figures for perinatal mortality. In addition, the fact that the onus of judgment regarding viability and classification is often placed on relatively junior staff might also affect the figures for perinatal mortality. The introduction of a standard recording system for all infants greater than 500 g would be advantageous.

Attitude to Health

Normal range for blood flow velocity in cerebral arteries of newly born term infants.

A cross-sectional study of 128 healthy full term infants was made using duplex Doppler ultrasonography in order to establish a normal range for cerebral blood flow velocity (CBFV) in the first week of life. Recordings were made from both the anterior (ACA) and middle cerebral arteries (MCA). There was a statistically significant increase in CBFV in both the ACA and MCA over the first four days of life, which was particularly obvious in the first 24 h. There is a close relationship between measurement of CBFV from the ACA and the MCA, although the velocity tends to be higher in the MCA.

Age Factors

The use of a calcium-channel blocker, nicardipine, for severely asphyxiated newborn infants.

A continuous infusion of nicardipine was given to four severely asphyxiated fullterm infants who were at high risk for adverse outcome and had abnormal cerebral Doppler haemodynamic studies. The heart rate increased in all four infants and mean arterial blood pressure (MAP) fell in three. Two infants had a sudden and marked fall in MAP, together with severe impairment of skin blood-flow and a concurrent fall in cerebral blood-flow velocity. The serum level of nicardipine was less than 40ng/mL in all cases. The use of nicardipine, and possibly other calcium-channel blockers, may be associated with marked hypotension, and if there is no cerebral autoregulation, may cause further cerebral hypoperfusion, so use of these drugs in asphyxiated newborn infants should only be attempted if blood pressure is carefully monitored.

Asphyxia Neonatorum

On line cerebral blood flow velocity and blood pressure measurement in neonates: a new method.

To test the hypothesis that impairment of cerebral perfusion and cerebrovascular autoregulation play a part in the pathogenesis of neurological injury in the critically sick neonate, we tested in 33 infants a small, light-weight probe and cable that are attached to the infant's skin to record cerebral blood flow velocity from the middle cerebral artery over a period of hours. This considerably reduced the amount of handling of the infant compared with conventional assessment. Captured data were analysed and displayed graphically at the cotside. The system is applicable for use on infants over a wide range of gestational ages and may give information on the complex haemodynamic changes occurring in the cerebral circulation.

Blood Flow Velocity

Circulatory effects of fast ventilator rates in preterm infants.

High frequency positive pressure ventilation has been suggested to result in a lower incidence of respiratory complications in preterm infants with idiopathic respiratory distress syndrome compared with ventilation at conventional rates. A possible disadvantage is compromise of the infant's cardiovascular condition secondary to inadvertent positive end expiratory pressure (PEEP). In a group of 20 such infants treated with high frequency positive pressure ventilation (rates of up to 100/minute) and analysed, changes in arterial blood pressure and cerebral blood flow velocity were largely influenced by changes in arterial blood gases, and no effect could be attributed to inadvertent PEEP. In addition, the observed fall in both arterial carbon dioxide and oxygen tensions could be readily predicted for theoretical reasons. Under certain conditions at the fastest rates used, cerebral blood flow velocity was significantly influenced by changes in blood pressure, which may indicate impaired cerebrovascular regulation. Though other factors (such as the severity of the infants' illness or the use of paralysis) may have been responsible for this apparent blood pressure passivity, the role of high frequency positive pressure ventilation in such infants warrants further study.

Blood Flow Velocity

Severe birth asphyxia and abnormal cerebral blood-flow velocity.

Thirty-four fullterm infants with postasphyxial encephalopathy (PAE) were studied with ultrasound to assess cerebral blood-flow velocity (CBFV). A control group of 126 healthy infants also had CBFV recordings during the first week of life. Measurements for the majority of the asphyxiated group fell into two abnormal patterns in relation to the control group: four had low CBFV (less than 2 SD below the mean) and 17 had high CBFV (greater than or equal to 2 SD above the mean); all had severe PAE. Median age at the first high measurement was 26 hours. There were no statistically significant differences between infants with normal and abnormal CBFV in measurements of PaCO2 or mean arterial blood-pressure. A Pourcelot Resistance Index (PRI) less than 0.55 was common in the presence of high CBFV, but never seen with low measurements. 21 of the 34 infants died of their asphyxial insult and four of the survivors have severe cerebral palsy at a median age of two years. Three of the four with low CBFV died, and no infant with CBFV greater than 3 SD survived without severe impairment. The positive predictive value of CBFV measurements less than 2 SD or greater than 3 SD for death or severe impairment is 94 per cent, compared with 83 per cent for low PRI alone. The authors believe that high CBFV is the result of vasoparalysis of cerebral arterioles and that it represents a form of irreversible cerebral injury.

Asphyxia Neonatorum

Modulation of Escherichia coli RecBCD activity by the bacteriophage lambda Gam and P22 Abc functions.

Plasmids that express the bacteriophage lambda gam gene or the P22 abc2 gene (with and without abc1) at controllable levels were placed in Escherichia coli and tested for effects on the activity of RecBCD. Like Gam, Abc2 inhibited the ATP-dependent exonuclease activity of RecBCD, apparently not by binding to DNA. However, Abc2-mediated inhibition was partial, while Gam-mediated inhibition was complete. Both Abc2 and Gam inhibited host system-mediated homologous recombination in a Chi-containing interval in the chromosome of a hybrid lambda phage; Abc2 inhibited it more strongly than Gam. Gam but not Abc2 spared a phage T4 gene 2 mutant from restriction by RecBCD; Abc2 exhibited weak sparing activity in combination with Abc1 and substantial activity in combination with both Abc1 and P22 homologous recombination function Erf. Either Gam or the combination of the lambda recombination functions Exo and Bet was sufficient to induce a mode of plasmid replication that produced linear multimers. The combination of Abc2, Abc1, and Erf also exhibited this activity. However, Erf was inactive, both by itself and in combination with Abc1; Abc2 had weak activity. These results indicate that Gam and Abc2 modulate the activity of RecBCD in significantly different ways. In comparison with lambda Gam, P22 Abc2 has a weak effect on RecBCD nuclease activity but a strong effect on its recombination-promoting activity.

Bacteriophage lambda

Sequence of the bacteriophage P22 anti-recBCD (abc) genes and properties of P22 abc region deletion mutants.

The nucleotide sequence of a segment of the bacteriophage P22 chromosome to the left (downstream in the PL operon) of the erf gene was determined. Previous studies (A. C. Fenton and A. R. Poteete, 1984, Virology 134, 148-160) have shown that this region encodes a function that is required for efficient growth of P22 in wild-type, but not in recB- Salmonella. The gene or genes encoding this function were designated abc (anti-recBCD). The DNA sequence reveals three open reading frames that potentially encode polypeptides with molecular weights of 10,900, 11,600, and 6600 (in order of transcription). P22 deletion mutants lacking each of the open reading frames were constructed. In addition, plasmids were constructed placing each of the open reading frames under control of the lac UV5 promoter. The phenotypes of the deletion mutants, and the results of plasmid-phage complementation tests, indicate that Abc activity depends primarily on sequences that encode the 11.6-kDa polypeptide; the 10.9-kDa polypeptide-encoding sequence makes a minor contribution to Abc activity as well. These sequences have been designated abc2 and abc1, respectively. The 6.6-kDa polypeptide is apparently uninvolved.

Amino Acid Sequence

Cotransformation of temperature sensitivity and nutritional markers in Neisseria gonorrhoeae.

Cotransformation remains the only tool for establishing linkage in Neisseria gonorrhoeae. Because of the difficulty of inducing auxotrophic markers via mutagenesis in this species, most previous studies have utilized antibiotic resistance and naturally occurring (auxotypic) auxotrophic markers. We have succeeded in isolating auxotrophic and temperature-sensitive mutants. The temperature-sensitive mutants have been characterized by their growth on complex and defined media at 31, 37, and 40 degrees C. Two of the mutants exhibited an unusual pattern of temperature sensitivity--growth on the defined medium but absence of growth on the complex medium at 37 degrees C. Both mutants, however, were temperature-sensitive on the two media at 40 degrees C. We have demonstrated linkages between markers isolated in our laboratory and the auxotypic markers of the clinical isolate RUG208. Ts-2 exhibited 85 to 95% linkage to Arg- and his-2 exhibited 40% linkage to Val-. In addition weak linkages were shown between his-2 and Arg- (2 to 6%) and between Arg- and Val- (3 to 5%). Linkages among his-2, Arg-, and Val- which could be demonstrated when deoxyribonucleic acid from strain F62 was used to transform RUG208 were absent when F62 was used as recipient for RUG208 DNA. Our data are consistent with a tentative map order of his-2, Val-, Arg-, Ts-2.

Amino Acids

Cardiovascular effects of carbon dioxide in ventilated preterm infants.

Sick preterm infants may, under certain conditions, demonstrate blood pressure passive cerebral blood flow in response to changes in arterial carbon dioxide tension. Blood pressure in turn depends on cardiac output and peripheral resistance. A Doppler technique for assessing cardiac output compared favourably in terms of reproducibility to a thermodilution technique in a group of infants undergoing cardiac catheterization for congenital heart disease. Doppler was subsequently used to monitor changes in cardiac output following an increase in arterial carbon dioxide tension of 1 kPa in 25 ventilated preterm infants. Blood pressure increased significantly (p = 0.006). However, heart rate did not change significantly (p = 0.16) and, in addition, both stroke and minute volume decreased (p = 0.023, p = 0.02, respectively). This suggests that accompanying changes in components of peripheral resistance exert important effects on blood pressure in the preterm neonate in response to changes in arterial carbon dioxide tension.

Blood Pressure