Biomedical subjects

R J Cooke

Publications and source records attributed to R J Cooke.

At least 37 records · Page 2Linked to original sources

PubMed1997

Pharmacokinetics and tissue distribution of cisplatin and conjugates of cisplatin with carboxymethyldextran and A5B7 monoclonal antibody in CD1 mice.

The plasma disposition kinetics and tissue distribution of platinum was evaluated following intravenous bolus administration to CD1 immune-competent mice of cisplatin, cisplatin conjugated to anti-CEA monoclonal antibody A5B7 via a carboxymethyl dextran (CMdextran) carrier molecule, and cisplatin coupled to the CMdextran in the absence of antibody. In addition, the in vivo characteristics of 125I-labeled A5B7 were compared with and without conjugation to CMdextran. Conjugation of cisplatin [clearance (CL = 0.62 mL/min/g, volume of distribution at steady-state (Vdss) = 16 mL/g] to CMdextran restricted its tissue distribution (Vdss = 0.43 mL/g) and reduced its systemic clearance (CL = 0.055 mL/min/g). Subsequent conjugation of the complex to A5B7 further reduced both its distribution (Vdss = 0.20 mL/g) and clearance (CL = 0.016 mL/min/g). Clearance of A5B7 (CL = 0.002 mL/min/g) was increased by conjugation to CMdextran (CL = 0.014 mL/min/g); tissue distribution was unchanged. A5B7-CMdextran-cisplatin was relatively stable in plasma and other tissues, except the liver. The extent of distribution of platinum into tissues (lung, liver, muscle, kidney) was markedly influenced by conjugation, with the influence being greatest for unmodified cisplatin and least for the A5B7-CMdextran conjugate. However, the time courses of tissue distribution, expressed in mean residence time scales, were similar, implying a common mechanism controlling tissue uptake.

Animals↗

PubMed1996

DNA profiling and plant variety registration: 1. The use of random amplified DNA polymorphisms to discriminate between varieties of oilseed rape.

Before they can be marketed in the UK, newly bred varieties of crop species have to undergo a process of statutory testing, part of which involves the examination of the distinctness, uniformity and stability (DUS) of the variety. DUS testing is also used as the basis for the award of Plant Breeders' Rights. This paper examines the potential of DNA polymorphisms, amplified using arbitrary primers (RAPDs) for use in DUS testing of varieties of oilseed rape. RAPDs using suitable primers can produce high levels of discrimination (> 95%) between varieties, although there are certain problems in gel 'scoring' that are only partially resolved by computerised gel scanning/evaluation techniques. Varieties of oilseed rape are also heterogeneous in their RAPD profiles using certain primers, which could cause problems in the DUS testing context. DNA profiling with RAPDs could be used for discrimination between and identification of oilseed rape varieties, but its use for DUS testing needs to be considered carefully.

Base Sequence↗

PubMed1994

Photoaffinity labelling of the active site of the rat glutathione transferases 3-3 and 1-1 and human glutathione transferase A1-1.

The glutathione transferases (GSTs) form a group of enzymes responsible for a wide range of molecular detoxications. The photoaffinity label S-(2-nitro-4-azidophenyl)glutathione was used to study the hydrophobic region of the active site of the rat liver GST 1-1 and 2-2 isoenzymes (class Alpha) as well as the rat class-Mu GST 3-3. Photoaffinity labelling was carried out using a version of S-(2-nitro-4-azidophenyl)glutathione tritiated in the arylazido ring. The labelling occurred with higher levels of radioisotope incorporation for the Mu than the Alpha families. Taking rat GST 3-3, 1.18 (+/- 0.05) mol of radiolabel from S-(2-nitro-4-azidophenyl)glutathione was incorporated per mol of dimeric enzyme, which could be blocked by the presence of the strong competitive inhibitor, S-tritylglutathione (Ki = 1.4 x 10(-7) M). Radiolabelling of the protein paralleled the loss of enzyme activity. Photoaffinity labelling by tritiated S-(2-nitro-4-azidophenyl)glutathione on a preparative scale (in the presence and absence of S-tritylglutathione) followed by tryptic digestion and purification of the labelled peptides indicated that GST 3-3 was specifically photolabelled; the labelled peptides were sequenced. Similarly, preparative photoaffinity labelling by S-(2-nitro-4-azidophenyl)glutathione of the rat liver 1-1 isoenzyme, the human GST A1-1 and the human-rat chimaeric GST, H1R1/1, was carried out with subsequent sequencing of radiolabelled h.p.l.c.-purified tryptic peptides. The results were interpreted by means of molecular-graphics analysis to locate photoaffinity-labelled peptides using the X-ray-crystallographic co-ordinates of rat GST 3-3 and human GST A1-1. The molecular-graphical analysis indicated that the labelled peptides are located within the immediate vicinity of the region occupied by S-substituted glutathione derivatives bound in the active-site cavity of the GSTs investigated.

Affinity Labels↗

PubMed1994

Effect of vitamin A supplementation of intravenous lipids on early vitamin A intake and status of premature infants.

Preterm infants were randomly assigned to receive routine vitamin A supplementation (Regular A) or additional vitamin A in intravenous lipids (High A). Because infants with bronchopulmonary dysplasia (BPD) have poorer vitamin A status than infants who do not develop BPD, High A and Regular A infants were divided by BPD (no or yes) before determining the effects of treatment on intake and plasma concentration of retinol in the first month. Compared with infants without BPD, those with BPD received less retinol (RE.kg-1.d-1) if assigned to Regular A and more if assigned to High A (BPD by vitamin A interaction, P < 0.002). High A-BPD infants compared with Regular A-BPD infants had significantly higher plasma retinol concentrations in the first month. Retinyl palmitate appears to be an effective adjunct to routine vitamin A administration. Infants most likely to benefit from receiving vitamin A in intravenous lipids are those advanced more slowly to full enteral feeding.

Analysis of Variance↗

PubMed1993

Arachidonic acid status correlates with first year growth in preterm infants.

Diets deficient in the omega-6 fatty acid linoleic acid reduce arachidonic acid (Ach) concentrations and retard growth of developing animals and humans. Nevertheless, plasma phosphatidylcholine Ach concentrations declined from 84 +/- 23 mg/liter at birth to a nadir of 38 +/- 11 mg/liter at 4 mo of age in preterm infants fed commercial formulas with linoleic acid, and weight normalized to that of term infants fell progressively beginning at 2 mo of age. The nadir of plasma phosphatidylcholine Ach (31 +/- 7 mg/liter) and growth were further reduced by formula containing marine oil compared with the commercial formulas. Ach status (defined as the mean plasma phosphatidylcholine Ach concentration at 2, 4, and 6.5 mo) correlated with one or more measures of normalized growth through 12 mo. Ach status and maternal height accounted for as much as 59% of the weight variance and 68% of the length variance in infants fed standard formulas. Better Ach status was not from higher energy intakes. A conditional Ach deficiency in preterm infants may contribute to growth over the first year of life. On the strength of the relationship between Ach status and growth, we hypothesize that dietary Ach could improve first year growth of preterm infants.

Arachidonic Acid↗

PubMed1993

Postnatal growth in infants born between 700 and 1,500 g.

Our purpose was to examine postnatal growth in very low birth weight (VLBW) infants (n = 54). A high frequency of intrauterine growth retardation was noted that was corrected by plotting birth weight against crown-heel length and not gestational age. No differences in postnatal growth were noted between infants whose size was appropriate for gestational age (n = 37) and those small for gestational age (n = 17). Overall, growth tended to exceed that previously published. Weight but not length or head gain was less in the smaller (< or = 1,000 g) when compared to the larger (> 1,000 g) VLBW infant. Poorer weight gain could not be related to more "illness" or less nutrient intake in the smaller infants.

Aging↗

PubMed1993

Effects of intrauterine growth on intestinal length in the human fetus.

Standards for human fetal intestinal length are not well established but have important implications for the care of the preterm and intra-uterine growth-retarded (IUGR) infant. Our purpose was to examine the relationship between intra-uterine growth and intestinal length in the human fetus. One hundred infants were studied. Birth weight and gestational age ranged from 76 to 4,385 g and from 12 to 42 weeks, respectively. Twenty-one infants were noted to be IUGR. Intestinal length (total, small, large) increased (p < 0.0001) with birth weight, gestational age, and crown-heel length but was reduced in IUGR infants. The ratio of body weight to intestinal length increased with gestation but was also reduced in IUGR infants. In conclusion, a reduced functional mass, as suggested by decreased intestinal length or body weight:intestinal length ratio, may contribute to the poor weight sometimes seen in the very-low-birth weight or IUGR infant.

Birth Weight↗

PubMed1992

First year growth of preterm infants fed standard compared to marine oil n-3 supplemented formula.

Very low birth weight (VLBW) infants (748-1390 g, n = 65) were randomly assigned to receive control or marine oil-supplemented formula when they achieved intakes > 454 kJ (110 kcal)/kg/d of a formula designed for VLBW infants. Study formulas with or without marine oil were provided until 79 wk of postconceptional age (PCA), first in a formula designed for preterm infants followed by a formula designed for term infants. Infants were studied at regular intervals through 92 wk PCA. Weight, length, and head circumference were determined by standardized procedures and normalized to the National Center for Health Statistics figures for growth of infants born at term of the same age and gender. Mean normalized weight, weight-to-length, and head circumference were greatest at 48 wk and decreased thereafter. The decline in normalized weight was greater in infants fed the marine oil-supplemented formula. Beginning at 40 wk, marine oil-supplemented infants compared to controls had significantly poorer Z-scores for weight, length and head circumference. In addition, birth order (negatively) and maternal height (positively) influenced weight and length achievement in infancy as shown previously in infants born at term.

Aging↗

PubMed1992

Effect of vegetable and marine oils in preterm infant formulas on blood arachidonic and docosahexaenoic acids.

Adding docosahexaenoic acid (DHA) (22:6n-3) to formulas is more effective than increasing formula alpha-linolenic acid (18:3n-3) in maintaining blood phospholipid DHA levels similar to those in breast-fed infants. However, in long-term trials supplementary DHA given as marine oil reduces blood phospholipid arachidonic acid (AA) in preterm infants. This effect is not seen in short-term trials unless the total n-3 intake from marine oil exceeds 0.5% of the total fatty acids. In addition, there is considerable variability among individual preterm infants in blood phospholipid AA and DHA levels that is not dependent on diet. Within dietary treatments, a significant positive correlation between AA and DHA concentrations suggests that factor(s) other than marine oil supplementation affect both AA and DHA status. Docosahexaenoic acid and AA concentrations in plasma phospholipids are significantly correlated with DHA and AA concentrations in red blood cell phospholipids, suggesting that the observed individual differences in DHA and AA within groups represent true differences in fatty acid status. Preterm infants appear to be vulnerable to a poor status of both DHA and AA; further feeding trials are needed to identify the optimal balance of fatty acids for feeding these infants.

Arachidonic Acid↗

PubMed1992

Effects of type of dietary protein on acid-base status, protein nutritional status, plasma levels of amino acids, and nutrient balance in the very low birth weight infant.

STUDY OBJECTIVE: To determine the effect of the type of dietary protein (3.3 gm/kg per day) on acid-base status, protein nutritional status, plasma amino acid concentrations, and nutrient (nitrogen, fat, mineral, trace element) balance. SUBJECTS: Preterm infants (birth weight less than or equal to 1250 gm, gestational age less than or equal to 32 weeks) with no evidence of systemic disease, who had achieved a minimal enteral intake of 110 kcal/kg per day by 21 days of age. INTERVENTIONS: Each infant was fed three study formulas that differed only with respect to the ratio of whey to casein (60:40, 35:65, 18:82). Each formula was given for 1 week. At the end each week, blood was drawn and a 48-hour balance was determined. MAIN RESULTS: Late metabolic acidosis, uremia, and hyperammonemia were not observed. No differences in pH or serum bicarbonate were noted. Base excess was greater with the casein-predominant formula (18:82 greater than 35:65, 60:40) but remained within normal limits for the preterm infant. Plasma concentrations of threonine (60:40 greater than 35:65 greater than 18:82), phenylalanine, and tyrosine (18:82 greater than 35:65 greater than 60:40) differed. Nitrogen absorption (60:40 less than 35:65, 18:82), nitrogen retention (60:40 less than 35:65, 18:82), fat absorption (60:40, 35:65 greater than 18:82), and phosphorus absorption (60:40 less than 35:65, 18:82) also differed. CONCLUSIONS: At an intake of 3.3 gm/kg per day, the type of dietary protein had little effect on metabolic status. Differences in plasma amino acid concentrations and nutrient balance suggest that a formula containing protein with a whey/casein ratio of 35:65 may be preferable to that with a whey/casein ratio of 60:40 or 18:82 for the very low birth weight infant.

Acid-Base Equilibrium↗

PubMed1991

Evaluation of lymphocyte phenotype and phytohemagglutinin response in healthy very low birth weight infants.

Sixteen healthy very low birth weight infants (VLBWI) were studied in a serial fashion over a 3-week period. Subjects were evaluated for lymphocyte phenotype, phytohemagglutinin (PHA) response, and metabolic status including weight, blood urea nitrogen, creatinine, albumin, pH, calcium, phosphorus, and ammonia. Lymphocyte phenotype determination showed a decreased proportion of CD3+ cells (66.8 +/- 10.4 vs 75.9 +/- 6.1, P less than 0.02) in VLBWI. When subsets of the CD4+ population were examined, VLBWI had a lower proportion of CD4+/CD29+ cells (8.2 +/- 5.8% vs 23.5 +/- 8.0%, P less than 0.0001) than adults and a higher proportion of CD4+/CD45R+ cells (35.6 +/- 12.4% vs 22.2 +/- 7.4%, P less than 0.03). The CD4+ subsets in VLBWI were similar to those seen in term infants. The peak PHA response in VLBWI was greater than that of adults (P less than 0.01). There was little change in the immune measurements over the 3-week study period. There were no strong correlations between any of the immunological measurements and the metabolic measurements except that the proportion of CD8+ cells increased with birth weight. Our findings demonstrate that immune measurements in healthy VLBWI differ from values found in adults but are similar to those of full-term infants. Lower proportions of the CD4+/CD29+ cells (the helper/inducer subset for antibody production) may contribute to some of the differences in immune function reported in neonates.

Ammonia↗

PubMed1991

Vitamin A status of preterm infants during infancy.

Plasma retinol and retinol-binding protein (RBP) were measured in 67 enterally fed preterm infants (750-1398 g) at 33 +/- 2 wk postconceptional age (PCA), and at regular intervals during infancy. Retinol and RBP declined by 35 +/- 2 wk PCA and remained low at 38 wk after discharge, with the infants fed a term-infant formula. At 38 +/- 2 wk PCA, 48% (32 of 67) of these infants had plasma retinol concentrations less than 0.35 mumol/L. Mean retinol and RBP rose over the next 7 mo, but large numbers of infants (26 of 59 at 48 wk, 10 of 61 at 57 wk) had hyporetinolemia (0.35-0.67 mumol/L). Plasma RBP leveled off at 57 +/- 2 wk PCA and remained low (less than 0.95 mumol/L) in many infants throughout the first year of life. Lower plasma retinol and RBP concentrations at 33 and 38 wk correlated with longer periods of intravenous nutrition. At 57 and 69 wk, lower retinol and RBP correlated with higher birth order. Suboptimal vitamin A status may occur for many months after preterm infants are discharged from the hospital.

Age Factors↗

PubMed1991

Long-term feeding of formulas high in linolenic acid and marine oil to very low birth weight infants: phospholipid fatty acids.

Red blood cell (RBC) phospholipids of infants fed human milk compared with formula have more arachidonic acid (AA) and docosahexanoic acid (DHA). The addition of low levels of marine oil to infant formula with 0.6 to 2.0% alpha-linolenic acid (LLA, 18:3n-3) prevented declines in DHA in formula-fed infants; however, the feeding trials were short (4 to 6 wk), LLA concentrations were low compared with current formulas (3.0 to 5.0% LLA), and the formulas were unstable. Trials with stable formulas were necessary to determine if dietary DHA could maintain phospholipid DHA after discharge from the hospital and, in fact, if it was necessary with higher intakes of LLA. The results of acute (4 wk) and extended (to 79 wk postconception) feeding of such formulas on RBC and plasma phospholipid AA and DHA are reported here. Control formulas were identical to commercially available formulas. Experimental formulas differed only in the addition of small amounts of marine oil. DHA in RBC and plasma phosphatidylethanolamine (PE) declined during four weeks of feeding but not if marine oil provided DHA (0.2% or 0.4%) and plasma phospholipid AA (g/100 g) decreased with time and marine oil feeding. Extended feeding with marine oil accounted for half the DHA in RBC and plasma phosphatidylethanolamine at equilibrium; however, RBC (g/100 g) and plasma AA (g/100 g; mg/L plasma) decreased progressively until late infancy and were depressed further by marine oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid↗

PubMed1989

Nutrient balance in the preterm infant. 3. Effect of balance duration on outcome measurements.

To determine the effect of balance duration on outcome measurements 18 84-h balances were performed in a group of formula-fed preterm infants (birth weight = 1,362 +/- 125 g; gestational age = 32.3 +/- 1.7 weeks). Each 84-h balance was broken into contiguous 48- and 36-h periods. Comparisons (paired t tests, paired variance tests, and linear regression analysis) were made between the 48-h and 36-h (paired t and F tests) and between the 48-h and 84-h collections (simple linear regression). Nitrogen absorption (mean +/- SD) during 48-h collection (365 +/- 58 mg/kg/day and 87 +/- 3%) was not significantly different from that of the 36-h collection (381 +/- 66 mg/kg/day and 84 +/- 4%). Nitrogen retention during the 48-h collection (301 +/- 59 mg/kg/day, 72 +/- 6%) also was not significantly different from that of the 36-h collection (318 +/- 64 mg/kg/day, 72 +/- 6%). Moreover, nitrogen absorption and retention during the 48-h collection were significantly related (p less than 0.0001 for linear regression comparisons) to that of the 84-h collection. Similar observations were noted for calcium, phosphorus, magnesium, zinc, and copper absorption and retention. We conclude that a 48-h collection may be used in place of an 84-h collection without compromising the accuracy of the balance data in the enterally fed preterm infant.

Birth Weight↗

PubMed1989

Rickets in a very low birth weight infant.

A report on a case of rickets in a very low birth weight infant (VLBWI) is presented. The infant had no high-risk factors for rickets and was fed a specialized preterm formula with vitamin D supplementation (200 IU daily) by 10 days of age. Feeds were advanced so that an enteral intake of 120 cal/kg/day was achieved by the 20th day of life. Mean calcium, phosphorus, and vitamin D intakes between the 20th and 61st days of life were 185 mg/kg/day, 93 mg/kg/day, and 367 IU/day, respectively. On the 62nd day of life, a diagnosis of rickets was made, and a nutrient balance study was performed. Urinary calcium excretion was low (1.3 mg/kg/day), suggesting calcium deficiency. However, retention of calcium (127 mg/kg/day) and phosphorus (76 mg/kg/day) was occurring at intrauterine rates. Thus, while calcium absorption was adequate at 10 weeks of age, the same was not true earlier in life. We suggest that there is a limiting role of calcium absorption on bone mineralization during early life in the VLBWI.

Calcification, Physiologic↗

PubMed1989

Urine output measurement in premature infants.

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Hot Temperature↗

PubMed1987

Soybean oil emulsion administration during parenteral nutrition in the preterm infant: effect on essential fatty acid, lipid, and glucose metabolism.

To examine the effect of a soybean oil emulsion on essential fatty acid, lipid, and glucose metabolism, preterm infants were randomized to receive 0.5 g/kg/d lipid for 5 days (n = 10, group 1) or 0.5 increased to 2.0 g/kg/d over 5 days (n = 11, group 2). Triene/tetraene ratios did not change in group 1, but decreased in group 2. In both groups, plasma phospholipid linoleate (percent and micrograms per milliliter) increased, the increase being greater in group 2. In both groups, percent content of arachidonate and 5,8,11-eicosatrienoate decreased, and that of oleate remained unchanged. In contrast, absolute content of arachidonate and oleate tended to increase, and that of 5,8,11-eicosatrienoate remained unchanged. At a lipid intake of 0.5 g/kg/d, no infants had hyperlipemia. When lipid intake exceeded 1.0 g/kg/d, the frequency of hypertriglyceridemia (triglycerides greater than 200 mg/dL) and free fatty acidemia, with the free fatty acid/molar albumin ratio exceeding 6:1, increased. Plasma glycerol increased slightly, but was substantially less than the rise in enzymatically determined triglycerides. Hyperglycemia was self-limiting and did not require alteration in dextrose intake. Thus, (1) infusion of a soybean oil emulsion at 0.5 to 2.0 g/kg/d maintains essential fatty acid status and phospholipid arachidonate concentrations; (2) significant hyperlipemia occurs when lipid intake exceeds 1.0 g/kg/d; (3) hyperglycemia associated with lipid infusion tends to be self-limiting and may not require alteration in lipid or dextrose intake; and (4) enzymatically determined triglycerides may be used to monitor lipid tolerance, provided that allowance is made for a small but systematic overestimation resulting from the rise in plasma glycerol.

8,11,14-Eicosatrienoic Acid↗

PubMed1986

Nutrient retention in preterm infants fed standard infant formulas.

Our purpose was to compare nitrogen, mineral, and zinc balance in preterm infants fed standard infant formulas, Similac With Iron and Similac With Whey + Iron. Nitrogen and magnesium balances were similar during both feeds, and met estimated fetal requirements. Infants absorbed and retained (milligrams per kilogram per day) more calcium, phosphorus, and zinc when fed Similac With Iron. However, retention of calcium, phosphorus (both formulas), and zinc (Similac With Whey + Iron) was inadequate to meet estimated fetal requirements. These findings are important in the rapidly growing preterm infant, who is already at risk for the development of rickets and zinc deficiency and may be fed either formula on discharge from the newborn nursery.

Anthropometry↗