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T A Clarke

Publications and source records attributed to T A Clarke.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of the structural and kinetic properties of the cytochrome c nitrite reductases from Escherichia coli, Wolinella succinogenes, Sulfurospirillum deleyianum and Desulfovibrio desulfuricans.

The recent crystallographic characterization of NrfAs from Sulfurospirillum deleyianum, Wolinella succinogenes, Escherichia coli and Desulfovibrio desulfuricans allows structurally conserved regions to be identified. Comparison of nitrite and sulphite reductase activities from different bacteria shows that the relative activities vary according to organism. By comparison of both amino acid sequences and structures, differences can be identified in the monomer-monomer interface and the active-site channel; these differences could be responsible for the observed variance in substrate activity and indicate that subtle changes in the NrfA structure may optimize the enzyme for different roles.

Amino Acid Sequence↗
PubMed2005

Workload and short-term outcome of babies weighing 2,500 grams or more at birth admitted to the paediatric unit of the Rotunda Hospital.

BACKGROUND: Audit is important in ensuring adequate use of resources and maintaining optimum standards of care. Most of the emphasis in neonatal audit is focused on very low birth weight infants. However, term and near-term infants account for a significant proportion of the workload in neonatal units and warrant regular audit. In addition, audit of these infants may be useful as a marker of the organisation of the perinatal service. METHODS: A retrospective audit was performed of all infants with birth weights greater than or equal to 2,500 grams admitted to the neonatal department in the first week of life over a two-year period, examining mode of delivery, level of care, duration of stay, diagnosis and short-term outcome. RESULTS: Eight hundred and seventy infants were admitted greater than or equal to 2,500 grams birth weight, 54% of all neonatal admissions, during the study period. Six hundred and eighty seven of these infants were admitted in the first week of life and were included in the study; this was 5.8% of infants born with a birth weight 2500 grams or more. Infants born by caesarean section were twice as likely to require admission (9.8%) compared with infants born by vaginal delivery (4.5%). The median length of stay was 3 days (3 hours to 45 days). One hundred and six (15.4%) infants required level 1 or level 2 care. One hundred and eleven infants received normal care, only. Most of these infants were admitted for maternal or social reasons. Other common reasons for admission were jaundice, respiratory disease, neonatal abstinence syndrome and congenital abnormality. Forty-one infants required transfer to another hospital, most commonly for surgical or cardiac conditions. Six infants died after admission. However, only one normally formed infant delivered in our hospital died prior to discharge or transfer. One infant was born at home and four infants who had a lethal congenital abnormality are known to have died following transfer. CONCLUSION: Term and near-term infants account for a significant proportion of neonatal admissions and deserve regular audit. Many admissions are potentially avoidable. Survival for infants weighing 2,500 grams or greater is excellent. Only one normally formed infant died following admission during the study period. The number of "social" admissions of "well" infants highlighted by this study reflects poorly on the services available for well infant whose mothers are unable to care for them for whatever reason. We recommend regular audit of these infants in order to ensure efficient use of neonatal resources and to ensure optimum levels of neonatal intensive care.

Birth Weight↗
PubMed2004

The value of the perinatal and neonatal autopsy.

The postmortem historically has been considered a valuable diagnostic exercise which contributes to medical knowledge. Despite this, there has been a significant reduction in autopsy rates throughout the developed world. This audit was a retrospective study of autopsy reports of stillbirths and neonates [corrected] greater than 500 grams over a five year period from 1995 to 1999. The audit was performed to assess the impact of autopsy on the current practice of perinatal medicine. The audit compared the final pathological diagnosis to the clinical diagnosis. The pathological diagnosis was categorised as (I) diagnostic, (II) confirmative, (III) unexplained. The recurrence risk estimates as a result of necropsy were also identified, as were any additional findings that were felt to be relevant but did not belong to any of the above categories. A total of 262 perinatal deaths (including stillbirths) and neonatal deaths greater than 500 grams birth weight were recorded during this period. The autopsy rate was 81%. The 213 autopsies performed were assessed, of which 76 (36%) were found to be diagnostic, 108 (51%) confirmatory, and 29 (13%) were unexplained or revealed no new findings. Change in recurrence risk estimates was identified in 24 (11%) and additional relevant information was obtained in 38 (18%). There were a number of cases where an unexpected diagnosis was made as a result of autopsy; these diagnoses included a respiratory chain disorder in a twenty nine week infant, and an occult necrotising enterocolitis presenting with severe haemolysis post transfusion in a preterm infant. The perinatal post mortem examination remains an indispensable part of clinical management. It contributes to medical education and quality assurance. It can aid in the identification of inheritable diseases and provide information for accurate parental counseling.

Adult↗
PubMed2000

Formation of a tight 1:1 complex of Clostridium pasteurianum Fe protein-Azotobacter vinelandii MoFe protein: evidence for long-range interactions between the Fe protein binding sites during catalytic hydrogen evolution.

It has been well documented that the combination of the MoFe protein of Azotobacter vinelandii nitrogenase (Av1) with the Fe protein (Cp2) from Clostridium pasteurianum nitrogenase produces an inactive, stable complex. However, we report that this heterologous nitrogenase has a low level of activity for H(2) evolution, with a specific activity of 12 nmol min(-)(1) mg(-)(1) of Av1. This activity does not arise from contaminating hydrogenase since it required the presence of both Cp2 and Av1 and showed saturation kinetics when increasing amounts of Cp2 were added to the assay. Incubation of the two proteins at a 4:1 Cp2:Av1 ratio in the absence of MgATP followed by analytical gel filtration showed, surprisingly, that the stoichiometry of the isolated complex was Av1.Cp2 instead of Av1.(Cp2)(2) as determined previously. The presence of MgATP in the elution buffer did not change the elution profile of the complex. The hydrodynamic radius of the isolated complex determined by dynamic light scattering was 5.93 +/- 0.14 nm, intermediate between Av1 and a stable 2:1 nitrogenase complex, consistent with a 1:1 assignment for the Av1.Cp2 complex. When assayed with Av2, the isolated Av1.Cp2 complex showed full half-site reactivity with a specific activity of 750 nmol of C(2)H(2) reduced min(-)(1) mg(-)(1) of Av1. The EPR spectrum of the isolated complex showed the Cp2 to be oxidized and the Av1 to retain the S = (3)/(2) signal characteristic of FeMoco. In the presence of MgATP, under turnover conditions at a 2:1 ratio of Cp2:Av1, the [4Fe-4S] center of Cp2 was protected from the chelator 2,2'-bipyridyl. This is consistent with the formation of a tight 2:1 complex of Av1.(Cp2)(2) which is more stable than the homologous Cp nitrogenase. Assuming that the Lowe-Thorneley model for nitrogenase applies and that a rate-limiting dissociation of the complex is required for H(2) evolution, then with a rate of 0.032 s(-)(1) the 1:1 complex is too stable to be involved in catalysis. The differences in the stability of the 2:1 and 1:1 complexes indicate cooperativity between the Fe protein binding sites of Av1, which structural data show to be separated by 105 A. On the basis of these observations, we propose a model for nitrogenase catalysis in which the stable 1:1 complex formed between oxidized Fe protein and the one-electron-reduced MoFe protein plays an essential role. In this scheme, the two Fe protein binding sites of the MoFe protein alternately bind and release Fe protein in a shuttle mechanism associated with long-range conformational changes in the MoFe protein.

Adenosine Triphosphate↗
PubMed1999

Klebsiella pneumoniae nitrogenase: formation and stability of putative beryllium fluoride-ADP transition state complexes.

Incubation of the MoFe protein (Kp1) and Fe protein (Kp2), the component proteins of Klebsiella pneumoniae nitrogenase, with BeF(3)(-) and MgADP resulted in a progressive inhibition of nitrogenase activity. We have shown that at high Kp2 to Kp1 molar ratios this inhibition is due to the formation of an inactive complex with a stoichiometry corresponding to Kp1.{Kp2.(MgADP.BeFx)2}2. At lower Kp2:Kp1 ratios, an equilibrium between this 2:1 complex, the partially active 1:1 Kp1.Kp2.(MgADP. BeFx)2 complex, and active nitrogenase components was demonstrated. The inhibition was reversible since incubation of the 1:1 complex in the absence of MgADP and beryllium resulted in complete restoration of activity over 30 h. Under pseudo-first-order conditions with regard to nitrogenase components and MgADP, the kinetics of the rate of inhibition with increasing concentrations of BeF(3)(-) showed a square dependence on [BeF(3)(-)], consistent with the binding of two Be atoms by Kp2 in the complex. Analytical fplc gel filtration profiles of Kp1.Kp2 incubation mixtures at equilibrium resolved the 2:1 complex and the 1:1 complex from free Kp1. Deconvolution of the equilibrium profiles gave concentrations of the components allowing constants for their formation of 2.1 x 10(6) and 5.6 x 10(5) M(-1) to be calculated for the 1:1 and 2:1 complexes, respectively. When the active site concentration of the different species was taken into account, values for the two constants were the same, indicating the two binding sites for Kp2 are the same for Kp1 with one or both sites unoccupied. The value for K(1) we obtain from this study is comparable with the value derived from pre-steady-state studies of nitrogenase. Analysis of the elution profile obtained on gel filtration of a 1:1 ratio incubation mixture containing 20 microM nitrogenase components showed 97% of the Kp2 present initially to be complexed. These data provide the first unequivocal demonstration that Fe protein preparations which may contain up to 50% of a species of Fe protein defective in electron transfer is nevertheless fully competent in complex formation with MoFe protein.

Adenosine Diphosphate↗
PubMed1997

The Marshall-Smith syndrome: a review of the laryngeal complications.

UNLABELLED: The Marshall-Smith syndrome is characterised by a triad of facial dysmorphism, failure to thrive and accelerated osseous maturation. We report a further case of this rare syndrome with the unusual but previously reported complication of laryngeal hypoplasia and review the associated laryngeal anomalies that have been reported to date. CONCLUSION: Severe airway obstruction due to congenital anomalies must be excluded in any dysmorphic child presenting with respiratory distress at birth. Rapid airway assessment will enable early and appropriate intervention and may be important when deciding on the long-term plan for the infant.

Abnormalities, Multiple↗
PubMed1993

Surfactant therapy in respiratory distress syndrome: the effect of a learning curve in improving outcome.

A retrospective study of all premature neonates who received artificial surfactant (Curosurf) at the Rotunda Hospital was performed. The period from October 1990 to June 1992 (n = 48) was compared with the initial experience from June 1987 to January 1988 (n = 15). In the initial period mortality rate was 67% in surfactant treated infants, and use of surfactant was not associated with an improvement in outcome compared with the previous six years. In the more recent period overall mortality was 21%. Overall survival in normally formed very low birthweight infants improved from 59% in 1986 to 86% in 1991-1992. Improvement in survival rates was most noticeable in infants with birthweight 750-999 grams, with survival increasing from 44% (before introduction of surfactant treatment) to 91% (in 1991-1992). It is probable that a certain level of experience with use of surfactant is required before optimal effects can be obtained.

Female↗
PubMed1993

Isolated single umbilical artery--the case for routine renal screening.

To determine the incidence of silent renal anomalies in infants with isolated single umbilical artery (SUA), all infants with SUA and without other obvious congenital anomalies, identified over a six year period, were screened using renal ultrasonography. Over 35,000 placentas were examined. An isolated single umbilical artery was identified in 112 (0.32%). Nineteen infants had abnormal renal imaging. Eight of 112 (7.1%) had significant persisting abnormalities. Vesicoureteric reflux was found in five infants (4.5%). It is recommended that renal ultrasonography be performed for all infants with isolated SUA.

Female↗
PubMed1992

Blood cultures and antibiotic use in a neonatal intensive care unit.

A review of the duration of antibiotic courses in our Neonatal Intensive Care Unit (N.I.C.U.) has shown that in a significant number of cases there was non compliance with the antibiotic policy. An audit of neonatal sepsis and antibiotic usage over a six month period was performed in the N.I.C.U. at the Rotunda Hospital. Three hundred and forty-nine of the 3,163 infants born during this time were admitted to the N.I.C.U. One hundred and fifty-two infants had one or more episodes of suspected sepsis. In 168 instances this preceded a course of antibiotic therapy lasting longer than 48 hours. In 56 (33%) the infant was clinically septic and in 16 (9.5%) of those there was bacteriological proven sepsis. There were 112 episodes (60%) where there was no strong clinical evidence of sepsis and a negative investigation for sepsis where antibiotics were continued for more than 48 hours. The possible reasons why antibiotics were not stopped include the non specific nature of signs of sepsis in neonates, physicians' reluctance to discontinue antibiotics once started, and the logistic difficulty of obtaining routine culture results at weekends. The study emphasizes the need for regular surveillance of antibiotic usage in a N.I.C.U.

Anti-Bacterial Agents↗
PubMed1992

Alcohol and cigarette use in a pregnant Irish population.

One hundred women were selected at random and interviewed. All were postnatal. The object was to establish the level of alcohol and cigarette consumption and the level of knowledge to potential adverse effects. Of the 100 women interviewed 89% drank prior to pregnancy, six drank between 100-120 grams/week and 19 drank > 120 grams/week. 11 women stopped drinking when they became pregnant. In the group which drank 100-120 grams/week, 66% decreased their alcohol consumption considerably ie > 100 grams/week while pregnant, while in the group which drank > 120 grams/week only 15% decreased their alcohol consumption. 38 women binged on at least one occasion while 21 said they had binged on at least one occasion during the first trimester. 58% of women were aware of the harmful effects of alcohol during pregnancy. They compared with 93% who were aware of the harmful effects of smoking during pregnancy. Only 11% of women said a doctor had mentioned alcohol as harmful, while 57% said that a doctor had mentioned the hazard of smoking in pregnancy. The overall results show a general ignorance to the effects of alcohol consumption in pregnancy compared to the level of knowledge about smoking. The results also highlight the fact that doctors do not make patients aware of the effects of alcohol in pregnancy while they make an effort to educate people about the problems of smoking during pregnancy.

Alcohol Drinking↗
PubMed1991

Bronchopulmonary dysplasia: a longitudinal study of 23 cases.

Bronchopulmonary dysplasia (B.P.D.) is a condition reflecting the reaction of the immature lung to the intensive support (barotrauma from mechanical ventilation and oxygen toxicity) required for survival in critically ill newborn infants. This study examines all infants who developed B.P.D. over a 2 year period in the Rotunda Hospital. Between 1st January 1986-31st December 1987 there were 1,360 N.I.C.U. admissions, 198 with respiratory problems and 76 requiring assisted ventilation (I.P.P.V.); 23 infants developed B.P.D. with a mean gestational age of 28.7 weeks (SD 2.5), mean birth weight 1,243 g. (SD 523 g.). One infant died at 4 months from S.I.D.S. and one was lost to follow-up (both had been clinically normal). At one year post term the weight was 7,843 g. (SD 1,134) (normal population mean 9.75 Kg. third percentile 8 Kg.) and head circumference 46 cm. (SD 2.5) (normal population mean 47 cm., third percentile 45 cm). During the 1st year of life 11 infants required re-hospitalisation (5 bronchiolitis, 2 urinary tract infections, 2 failure to thrive, 2 myringotomies/grommets) and a further 8 attended hospital with respiratory infections. Only 6/21 received 3 in 1 vaccine (all in hospital O.P.D.) and 14/21 received 2 in 1 vaccine. At one year 15 infants were normal, 2 had cerebral palsy, 2 mild motor delay (one with arrested hydrocephalus), 1 sensorineural deafness and 1 arrested hydrocephalus with mild motor delay. Five infants developed retinopathy of prematurity but none required treatment.

Bronchopulmonary Dysplasia↗
PubMed1990

Transportation of newborn infants.

The benefit of an organized neonatal transport system is well established. Over a 30 month period, January 1987 to June 1989, 172 babies were transported to the Dublin maternity hospitals. Birth weights ranged from 640 to 5,180g 106 (62%) were less than 37 weeks gestation. Indications for transport included respiratory distress syndrome (54), prematurity only (43), convulsions and/or neurologic dysfunction (23), jaundice (11) and apnoea (11). One hundred and sixty-eight were transferred by ambulance and four by helicopter. Twenty travelled more than 100 miles. Forty (23%) received assisted ventilation during transport. On arrival 37 (21%) had temperature less than 36 degrees C; 22 (13%) had blood sugar less than 2.2 m mol/l and 34 (20%) had arterial ph less than 7.25. Fifty per cent of referral letters had incomplete information. Treatment and care given en route was recorded in only 28 babies. Twenty-four babies (14%) died. Infants who died were more likely to have been of low birth weight, travelled a long distance, been hypothermic, had poor arterial gases, had blood sugars less than 2.2 m mol/l, and had poor referral letters. This review indicates that death and morbidity continue to be associated with the present system of postnatal transfer of newborn infants. The urgent need for an organized neonatal transport service remains unmet.

Emergency Medical Services↗
PubMed1989

Infant care: the value of the six week check.

A review of the routine six week post-natal examination of the well-baby was performed. Eighty-one percent of infants born in the Rotunda attended for a hospital based review during the study period and 42% of these had experienced some problem during the six weeks from birth (rashes 20%, snuffles 10.7%, irritability 7.6% and eye infections, constipation, diarrhoea, vomiting, cyanotic/breath holding episodes). These problems were dealt with by the hospital outpatient department (55%), the mothers themselves (30%), general practitioners (12.5%) and public health nurses (2.5%). Significant problems not detected at birth were present in 12 infants (3%) and eight infants (2%) required hospital admission. This review illustrates a relatively low rate of problems not previously detected and that the majority of problems arising in the first six weeks of life require advice alone. There is also clearly scope for improving the community based services and increasing their involvement in this aspect of infant health.

Community Health Services↗
PubMed1989

Cost of neonatal intensive and special care.

A detailed costing of neonatal intensive and special care was made for the year 1986 at the Rotunda Hospital. Cost was expressed at 1986 prices in punts. There was 1,364 admissions including external transfers giving a total of 10,086 bed days, divided into 1,044 intensive care and 9,042 special care bed days. The total cost of intensive and special care was 1,342,500 pounds. Costs per inpatient day were 288 pounds for intensive and 115 pounds for special care. Sixty percent of the intensive care bed days were used by infants weighting less than 1,500 g birth weight and 93% by infants less than 2,500 g birth weight; this emphasizes the effect of population mix on resource use. The average cost of intensive care survivors by birth weight were: less than 1,000 g - 16,226 pounds (8,052 pounds-23,535 pounds); 1,000 g-1,499 g - 13,412 pounds (1,898 pounds-22,456 pounds); 1,500 g-2,499 g - 8,864 pounds (633 pounds-17,666 pounds); 2,500 g + - 5,123 pounds (384 pounds-12,636 pounds). The average cost of all admissions to special or intensive care was 984.24 pounds. Using this figure (984.24 pounds) and assuming that 13% of all births in 1986 required special or intensive care the total health care expenditure on neonatal special or intensive care in 1986 amounts to 8.03 million pounds of a total Department of Health budget of 1,269 million pounds. By allocating infants to the currently used neonatal diagnostic related groupings (DRGs) and assigning costs at 1987 US reimbursement levels, the total cost to the Rotunda would be 1,878,750 pounds punts. The current level of DRGs derived from the reimbursement rates in the United States which is insufficient to meet the actual cost incurred there, is 40% greater than current total funding of neonatal intensive and special care in the Rotunda. Current funding levels in the United Kingdom are 13% to 80% greater than in the Rotunda.

Costs and Cost Analysis↗