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Biomedical subjects

C M Cook

Publications and source records attributed to C M Cook.

67 records · Page 4Linked to original sources

Linear growth measurement: a comparison of single arm-lengths and arm-span.

An investigation was done to determine whether the arm-lengths of 44 children with myelomeningocele differed from those of 96 control children; whether the level of the meningocele lesion has any effect on arm-length; and to compare the relationship between arm-length and both stature and age. Mean total arm-lengths did not differ significantly between the two groups of children. However, the mean arm-spans of children with high myelomeningocele lesions differed significantly from those of control children. Within the myelomeningocele group, the height of the lesion had no significant effect on any of the arm-length variables. Very high positive correlations were found between upper-arm and total arm-lengths and stature, and between arm-span and stature in the control children. These results suggest that arm-length may be used as an alternative measure of linear growth in children, and that a single arm-length will be the most accurate indicator of growth of children with myelomeningocele.

Arm↗

A comparison of fetal heart rate monitoring and umbilical artery waveforms in the recognition of fetal compromise.

Antenatal fetal heart rate monitoring was compared with the study of umbilical artery flow velocity waveforms for the recognition of fetal compromise in 170 patients considered at high fetal risk. In 53 patients the infant had a 5-min Apgar score of less than 7 and/or a birthweight less than 10th centile of weight for gestation. Fetal heart rate traces were classified as reactive or non-reactive and also assessed with a modified Fischer score. The systolic/diastolic A/B ratio was measured in the umbilical artery waveform. Fetal compromise was more efficiently recognized by study of the umbilical artery waveforms. The sensitivity of assessment by umbilical artery waveforms was 60% compared with 17% and 36% respectively, for the two methods of scoring fetal heart rate traces. This was not associated with an increase in false-positive results as the predictive value of both positive (64% compared with 69 and 58%) and negative (83% compared with 72 and 75%) results was similar when umbilical artery waveform analysis was compared with the two methods of scoring fetal heart rate traces. Specificity was also similar (85% compared with 97 and 88%).

Blood Flow Velocity↗

Flow velocity waveforms in the maternal uteroplacental and fetal umbilical placental circulations.

A simple continuous-wave Doppler ultrasound system was used to record arterial flow velocity time waveforms from branches of the maternal uterine artery in the placental bed and the fetal umbilical arteries. The systolic-diastolic ratio of flow velocities was measured as an index of peripheral resistance. In normal pregnancy both circulations exhibit high diastolic flow velocities caused by low resistance. The study group consisted of 172 pregnancies with high fetal risk of which 53 resulted in delivery of a small-for-gestational age infant. The last study-to-delivery interval was less than 10 days. In the small-for-gestational age fetuses in whom both umbilical and uterine studies were normal there was good fetal outcome (19 cases). Neonatal morbidity occurred among those with abnormal umbilical studies with low diastolic flow velocities, indicating high resistance. Of these studies there were two subgroups. An abnormal uterine study (13 cases) indicated a primary maternal uteroplacental lesion and a normal study (21 cases) a primary fetal lesion. In cases of severe maternal hypertension, abnormal uterine artery waveforms were associated with abnormal umbilical artery waveforms.

Adult↗

Inhibition and stimulation of ribulose-1,5-bisphosphate carboxylase/oxygenase by glyoxylate.

Glyoxylate is a slowly reversible inhibitor of the CO2/Mg2+-activated form of ribulose-1,5-bisphosphate carboxylase/oxygenase from spinach leaves. Inactivation occurred with an apparent dissociation constant of 3.3 mM and a maximum pseudo-first-order rate constant of 7 X 10(-3) s-1. The rate constant for reactivation was 1.2 X 10(-2) s-1. Glyoxylate did not cause differential inhibition of ribulosebisphosphate carboxylase or oxygenase activities. 6-Phosphogluconate protected the enzyme from inactivation by glyoxylate. Glyoxylate was incorporated irreversibly into the large subunit of ribulosebisphosphate carboxylase after reduction with sodium borohydride. Activated enzyme incorporated 1.3 mol of glyoxylate per mole protomer, while enzyme treated with carboxyarabinitol 1,5-bisphosphate (CABP) to protect the active sites incorporated only 0.3 mol glyoxylate per mole protomer. The data suggest that glyoxylate forms a Schiff base with a lysyl residue in the region of the catalytic site. Glyoxylate stimulated the activity of the unactivated enzyme by about twofold. Pseudo-first-order inactivation also occurred with the unactivated enzyme after the initial stimulation by glyoxylate, although at a much slower rate than with the activated enzyme. Glyoxylate treatment of partially activated enzyme did not stimulate formation of the quaternary complex of enzyme X CO2 X Mg2+ X CABP.

Enzyme Activation↗

Characterization of an active-site peptide modified by glyoxylate and pyridoxal phosphate from spinach ribulosebisphosphate carboxylase/oxygenase.

Activated ribulosebisphosphate carboxylase/oxygenase from spinach was treated with glyoxylate plus or minus the transition-state analog, carboxyarabinitol bisphosphate, or the inactive enzyme with pyridoxal phosphate plus or minus the substrate, ribulose bisphosphate. Covalently modified adducts with glyoxylate or pyridoxal phosphate were formed following reduction with sodium borohydride. The derivatized enzymes were carboxymethylated and digested with trypsin; the labeled peptides which were unique to the unprotected samples were purified by ion-exchange chromatography and gel filtration. Both glyoxylate and pyridoxal phosphate were associated with only one major peptide, which in each case was subjected to amino acid analysis and sequencing. The sequence was -Tyr-Gly-Arg-Pro-Leu-Leu-Gly-Cys(Cm)-Thr-Ile-Lys-Lys*-Pro-Lys-, with both reagents exhibiting specificity for the same lysine residue as indicated by the asterisk. This peptide is identical to that previously isolated from spinach carboxylase labeled with either of two different phosphorylated affinity reagents and homologous to one from Rhodospirillum rubrum carboxylase modified by pyridoxal phosphate. The species invariance of this lysine residue, number 175, and the substantial conservation of adjacent sequence support the probability for a functional role in catalysis of the lysyl epsilon-amino group.

Amino Acid Sequence↗

Umbilical waveforms in twin pregnancy.

Continuous wave Doppler ultrasound was used to study the twin fetus in 76 multiple pregnancies. The technique is not difficult and allowed the identification of the small for gestational age twin in both intrauterine growth failure and twin to twin transfusion syndrome.

Birth Weight↗

Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance.

Since the umbilical arteries carry fetal blood to the placenta we studied flow velocity waveforms in these vessels with a simple continuous wave Doppler system to assess placental blood flow. The ratio of peak systolic to least diastolic (A/B) flow velocity was measured as an index of placental flow resistance. In 15 normal pregnancies there was a small but significant decrease in this ratio through the last trimester. The A/B ratio was measured on 436 occasions in 168 high-risk pregnancies. In 32 of 43 fetuses subsequently shown to be small for gestational age there was an increase in placental flow resistance with reduced, absent or even reversed flow in diastole. This finding was also present in the one fetus which died in utero. Serial studies in patients with fetal compromise indicated increasing flow resistance, a reverse of the normal trend. These results were not available to the clinician yet of 24 fetuses born before 32 weeks 13 had a high A/B ratio, and all of them were born electively. Maternal hypertension was associated with an increase in fetal placental flow resistance. The umbilical artery A/B ratio provides a new and non-invasive measure of feto-placental blood flow resistance.

Adult↗

Uteroplacental blood flow velocity-time waveforms in normal and complicated pregnancy.

A simple continuous wave Doppler ultrasound system for recording arterial flow velocity waveforms in branches of the uterine artery in the placental bed is described. Twelve normal pregnancies were studied serially from 20 weeks to delivery. The diastolic flow velocity expressed as a percentage of the systolic provides an index of downstream vascular bed resistance and perfusion. This always exceeded 50% in normal pregnancy and there was a small increase with gestational age indicative of a decreasing flow resistance. Of the 91 complicated pregnancies, studied because of potential uteroplacental insufficiency and fetal risk, 25 resulted in the birth of an infant small-for-gestational-age. In 15 the uterine artery flow velocity waveform revealed a pattern of low diastolic flow velocity. It is postulated that these represent a subgroup of growth-retarded fetuses in whom there is reduced uterine artery perfusion. Reduced uterine artery diastolic flow velocity in these patients was associated with reduced umbilical artery diastolic flow velocity on the fetal side of the placenta. In contrast the 10 small-for-gestation infants associated with normal uterine artery waveforms suggest a primary fetal cause. Twelve patients with severe hypertensive disease of pregnancy were studied. Nine were associated with reduced uterine artery diastolic flow velocity (reduced uterine artery perfusion) consistent with vasospasm in the branches of the uterine artery in the placental bed.

Arteries↗

Fetal umbilical artery flow velocity-time waveforms in twin pregnancies.

The umbilical artery flow velocity-time waveforms were studied in 76 twin pregnancies. The ratio of peak systolic (A) to least diastolic (B) velocity was calculated for each fetus as an index of umbilical placental flow resistance. Seventy-one sets of twins were studied within 14 days before delivery. In 65 cases both twins were alive at the time of study. In 32 pregnancies both fetuses were of birthweight appropriate for gestational age (AGA) and had A/B ratios within the normal singleton range. In 33 pregnancies one or both of the liveborn infants were small for gestational age (SGA) and in 78% of these at least one fetus had an elevated A/B ratio. Discordancy in birthweight and A/B ratio was associated with growth retardation. Clinically manifest twin-to-twin transfusions occurred in five of the ten pregnancies resulting in an SGA infant (eight with discordant weight) associated with a normal and concordant A/B ratio. Two twin-to-twin transfusions were associated with perinatal death. The placentas were examined in 61 patients. In 43 dichorionic pairs the A/B ratio was elevated in 12 of the 18 where there was at least one SGA infant. There was a greater incidence of growth retardation in the monochorionic pairs (12 of 18). Only seven of these were identified by an elevated A/B ratio. In 10 of these 18 pairs vascular anastomoses were demonstrated on placental inspection and in a further two there was evidence of twin-to-twin transfusion by haemoglobin discrepancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

Umbilical and uterine artery flow velocity waveforms in pregnancy associated with major fetal abnormality.

Flow velocity waveforms from the umbilical artery and branches of the uterine artery in the placental bed were recorded using continuous wave Doppler ultrasound. The records of 26 patients with pregnancy complicated by major fetal abnormality were reviewed to determine the changes of a primary fetal disturbance. The systolic/diastolic (A/B) ratio was used as an index of blood flow resistance. In 13 of the 26 patients the umbilical artery waveform systolic/diastolic ratio was high. It is postulated that in these patients there is a process of obliteration of small arteries in the placenta that is triggered by the abnormal fetus. In all patients the uterine artery waveform was normal. In seven of these 13 patients the infant had a birthweight greater than 10th centile. Placental weights were examined. A small placenta expressed as either low weight for gestational age or low placental/fetal weight ratio was associated with a normal umbilical artery waveform. It is suggested that fetuses in these groups have a low growth potential. In contrast a high placental/fetal weight ratio was associated with an abnormal umbilical artery waveform pattern.

Arteries↗

In vitro and in vivo comparison of sulfur donors as antidotes to acute cyanide intoxication.

Antidotes for cyanide (CN) intoxication include the use of sulfane sulfur donors (SSDs), such as thiosulfate, which increase the conversion of CN to thiocyanate by the enzyme rhodanese. To develop pretreatments that might be useful against CN, SSDs with greater lipophilicity than thiosulfate were synthesized and assessed. The ability of SSDs to protect mice against 2LD50 of sodium cyanide (NaCN) administered either 15 or 60 min following administration of an SSD was assessed. To study the mechanism of action of the SSD, the candidate compounds were examined in vitro for their effect on rhodanese and 3-mercaptopyruvate sulfurtransferase (MST) activity under increasing SSD concentrations. Tests were conducted on nine candidate SSDs: ICD1021 (3-hydroxypyridin-2-yl N-[(N-methyl-3-aminopropyl)]-2-aminoethyl disulfide dihydrochloride), ICD1022, (3-hydroxypyridin-2-yl N-[(N-methyl-3-aminopropyl)]-2-aminoethyl disulfide trihydrochloride), ICD1584 (diethyl tetrasulfide), ICD1585 (diallyl tetrasulfide), ICD1587 (diisopropyl tetrasulfide); ICD1738 (N-(3-aminopropyl)-2-aminoethyl 2-oxopropyl disulfide dihydrochloride), ICD1816 (3,3'-tetrathiobis-N-acctyl-L-alanine), ICD2214 (2-aminoethyl 4-methoxyphenyl disulfide hydrochloride) and ICD2467 (bis(4-methoxyphenyl) disulfide). These tests demonstrated that altering the chemical substituent of the longer chain sulfide modified the ability of the candidate SSD to protect against CN toxicity. At least two of the SSDs at selected doses provided 100% protection against 2LD50 of NaCN, normally an LD99. All compounds were evaluated using locomotor activity as a measure of potential adverse behavioral effects. Positive hypoactivity relationships were found with several disulfides but none was found with ICD1584, a tetrasulfide. Separate studies suggest that the chemical reaction of potassium cyanide (KCN) and cystine forms the toxic metabolite 2-iminothiazolidine-4-carboxylic acid. An alternative detoxification pathway, one not primarily involving the sulfur transferases. may be important in pretreatment for CN intoxication. Although studies to elucidate the precise mechanisms are needed. it is clear that these newly synthesized compounds provide a new rationale for anti-CN drugs, with fewer side-effects than the methemoglobin formers.

Animals↗

Doppler ultrasound waveforms in the fetal umbilical artery: quantitative analysis technique.

Doppler ultrasound waveforms from the fetal umbilical artery were analyzed by a new quantitative technique. Normal pregnancy and cases of fetal growth failure were considered. Data from the spectrum analyzer were dumped to a microcomputer, the velocity waveforms calculated and a representative waveform obtained by ensemble averaging. This curve was then fitted by a 4-parameter analytic function. We introduce R, the relative flow rate index, which measures the ratio of the average flow rate before the systolic peak to the average rate during the remainder of the cardiac cycle. In cases of fetal growth failure this ratio was significantly greater than in normal pregnancy. Other new quantities defined are the normalized systolic decay time index and the constant flow ratio. The AB ratio was also calculated. Fetal growth failure has been associated with raised placental resistance. We suggest that the fetus can initially compensate for this by increasing cardiac contractility. This can be seen by interpreting the R and AB values together. Our analysis technique enables the waveform to be efficiently described, and provides useful diagnostic information about placental function and fetal wellbeing.

Blood Flow Velocity↗