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G G Graham

Publications and source records attributed to G G Graham.

At least 55 records · Page 3Linked to original sources
PubMed1990

Stereoselective disposition of ibuprofen and flurbiprofen in rats.

(R)-2-Arylpropionates are often inverted to the pharmacologically active S-enantiomers in vivo, although there is significant interspecies variability in inversion. In order to provide a basis for determining the biochemical consequences of this unique process using rats as a model, it was important to establish the pharmacokinetic disposition of the enantiomers of ibuprofen, a drug well inverted in man and flurbiprofen, a drug apparently poorly inverted in man. Rats were dosed i.v. with a single dose of (R)- or (S)-ibuprofen (20 mg/kg), (R,S)-ibuprofen (40 mg/kg), (R)- or (S)-flurbiprofen (10 mg/kg), or (R,S)-flurbiprofen (20 mg/kg). Each treatment group consisted of six animals. Serial blood samples were withdrawn over a period of 6 h for ibuprofen and 10 h for flurbiprofen. These drugs were assayed in plasma by a stereospecific HPLC assay. The pharmacokinetics of the ibuprofen and flurbiprofen enantiomers were evaluated using a two-compartment open model with conversion of the R- to S-enantiomers in the central compartment. There was 50 +/- 4% inversion of (R)-ibuprofen, a figure similar to that observed in man and (R)-ibuprofen had a higher clearance (12.6 +/- 1.3 ml/min/kg) than (S)-ibuprofen (7.7 +/- 0.7 ml/min/kg; P less than 0.01). The clearance of (R)-flurbiprofen after racemate (2.3 +/- 0.1 ml/min/kg) was higher than its clearance when administered alone (1.7 +/- 0.2 ml/min/kg; P less than 0.01), indicating a pharmacokinetic interaction between the enantiomers (most probably at plasma protein binding sites). A corresponding difference was not observed for ibuprofen. There was a small amount of inversion of (R)-flurbiprofen as determined by area analysis (4.5 +/- 1.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The gold complexes.

Explore the source record for details and available documents.

Arthritis, Rheumatoid↗
PubMed1990

A simplified approach to the effect kinetics of atracurium.

The combination of the Hill equation, which describes the concentration-effect relation, with the monoexponential function for the terminal decline of plasma concentration, yields a compound time constant, T beta s1/2. This constant is a combination of the terminal elimination half-life (T beta 1/2) and the exponent (s) of the Hill equation and may be used to describe the time course of recovery from neuromuscular block. The constant may be estimated by non-linear curve fitting to f, the effect expressed as fraction of maximal effect, or by linear regression of the logit function of f. The methods were validated using plasma concentration and effect data from seven patients administered atracurium. The two methods utilizing effect data alone yielded values of 4.2 (0.7) min and 4.3 (0.5) min (mean (SEM)), respectively, for T beta s1/2 compared with 4.1 (0.6) min when the constant was calculated using plasma concentration data for T beta 1/2 and curve fitting to the concentration-effect data to determine s. These methods offer an objective measure of the rate of recovery and a means of testing if redistribution or elimination is the primary process in the termination of drug effect.

Atracurium↗
PubMed1990

The nutritional value of oat flour for very young children.

Whole groat flour was consumed by nine infants and young children as 22.5, 45, or 67% of total diet energy (one half of 6.4%, all of 6.4%, or all of 9.6% protein energy). Isonitrogenous and isoenergetic casein control diets were given. Apparent absorption of oat nitrogen (N) was consistently around 75% of intake (casein, 87%), but absorptions of oat energy, carbohydrate, and fat, as percentages of intake, decreased disproportionately as oat flour intake was doubled and then tripled. Apparent retentions were 39 +/- 5% of mixed oat-casein protein intake in the 22.5% diet, the preceding and following casein controls being 38 +/- 8% (NS) and 44.4% (p less than 0.05) of the intakes; 32 +/- 6% from oats in the 45% diet, controls 38 +/- 5 and 46 +/- 5% (both p less than 0.05), and 33 +/- 11% from oats in the 67% diet, controls, 36 +/- 9% (NS). Fasting plasma free total essential amino acid (TEAA) levels of children consuming 45% oats were low (562 +/- 119 mumol of TEAA/L) and did not change significantly after meals. Fasting molar proportions of individual essentials (millimoles of EAA per mole of TEAA) were similar to those from milk protein diets and did not vary significantly 3 and 4 h after feeding, suggesting that no individual amino acid, but rather protein digestibility, was first limiting to N retention. Oats are a satisfactory source of energy, protein, and fat for very young children and many infants.

Amino Acids, Essential↗
PubMed1990

Acceptability, tolerance, and nutritional value of a rice-based infant formula.

An infant formula based on high protein rice flour, with added lysine and threonine, was evaluated in recovering malnourished infants. Acceptability, tolerance, and the digestibility of most major nutrients (energy 93.9 +/- 0.7%, fat 96.9 +/- 0.3%, carbohydrate 96.8 +/- 0.6% of intake) were excellent. Digestibility of protein, as with all rice products, was moderately low (80.1 +/- 3.3%), but its high biological value made N retention equal to that from casein. Plasma-free amino acids were consistent with the low essential/total amino acids ratio found in cereals, with slower absorption, and with the possibility that leucine was the first-limiting amino acid. Absorptions of Ca, Mg, PO4, and Zn were considered satisfactory. Energy costs of weight gain and the estimated percentage N in the weight gained during 14 days were comparable to those attained with the highest quality cow's milk-derived formulas in children of similar ages and nutritional status.

Diarrhea, Infantile↗
PubMed1990

Neuromuscular sensitivity to atracurium in humans.

The relation between plasma concentration and the effects of atracurium was studied in seven patients anaesthetised with thiopentone, fentanyl and nitrous oxide-oxygen. The response to train-of-four stimulation at ten-second intervals with tetanic stimuli applied every five minutes were recorded. The first sign of transmission returning after complete blockade was usually the post-tetanic facilitated twitch, which was noted when the mean atracurium concentration was 1.15 mg 1(-1) (SD 0.77). The most sensitive parameter was the train-of-four ratio, which recovered to 0.5 when the concentration was 0.217 mg 1(-1) (SD 0.56), compared with a concentration of 0.271 (SD 0.85) at 50% recovery for twitch height, 0.221 (SD 0.029) for tetanic peak and 0.231 (SD 0.079) for tetanic fade. The value for the train-of-four ratio differed significantly (P less than 0.05) from that for the twitch height, but other differences were not significant. Once recovery commenced, these four parameters recovered at similar rates, with recovery indices (25 to 75% responses) of 14.8 (SD 1.7), 14.0 (SD 1.0), 14.3 (SD 1.8) and 13.7 (SD 2.1) minutes respectively. Post-tetanic facilitation was most marked during severe but incomplete blockade and tetanic stimulation temporarily reversed the atracurium-induced decrease in train-of-four ratio. Clinically, the use of tetanic stimulation did not improve the sensitivity of neuromuscular monitoring, but post-tetanic count may be useful where monitoring of profound relaxation is required.

Atracurium↗
PubMed1990

Quality-protein maize as the sole source of dietary protein and fat for rapidly growing young children.

Earlier studies demonstrated that quality protein maize (QPM), with increased lysine and tryptophan and decreased leucine contents, was more digestible and supported 45% greater nitrogen retention than common maize. Ten recovering malnourished children (ages 13 to 29 months, height-ages 5 to 15 months, weight-ages 3 to 11 months) have now received 90% of their diet energy and 100% of protein and fat from QPM. Energy intake was adjusted to allow them to reach the 50th centile of weight-for-length (according to the National Center for Health Statistics) in 90 days (two completed 60 days only). Growth was compared with that of 10 children receiving modified cow's milk formula (CMF). Energy intakes (QPM 110 +/- 15, CMF 106 +/- 12, corrected for absorption to 94 and 97 kcal/kg.d), crude energy costs of gain (43 +/- 9 and 40 +/- 10, corrected to 37 and 37 kcal/g), linear growth (1.23 +/- 0.24 and 1.33 +/- 0.26 cm/mo), gains in height-age (3.1 +/- 0.7 and 3.3 +/- 1.2 mo), weight gain (2.6 +/- 0.6 and 2.6 +/- 0.8 g/kg.d), and final sums of fat folds (24.3 +/- 3.5 and 27.2 +/- 2.9 mm) were not different. Gains in weight-age were greater (7.5 +/- 2.3 vs 5.4 +/- 1.6 months, P less than .05) and serum albumin decreased (4.10 +/- 0.24 to 3.77 +/- 0.31 g/dL, P less than .01) during QPM feeding. Plasma-free total essential amino acids and ratio of these to total essential amino acids were less after QPM than after CMF diets. Equal growth rates with QPM and CMF diets offer great potential for developing- and developed-country children.

Animals↗
PubMed1990

Post-prandial plasma aminograms in the assessment of protein quality for young children: maize and grain amaranth, alone and combined.

Post-prandial (p.p.) changes in plasma free amino acid (AA) concentrations of children consuming a single source of protein at critical levels are determined by its digestibility and total essential AA/total AA ratios; the molar proportion of the limiting EAA (EAA/TEAA), if any, will fall significantly in plasma as it is utilized more completely than others. Grain amaranths (Am), reputedly rich in lysine (Lys) and tryptophan (Trp), but moderately deficient in leucine (Leu), should be ideal complements to Lys and Trp-poor, Leu-rich maize (M). Most animal studies confirm this. In children, 20, 30 and even 50 per cent replacement of M proteins with toasted Am proteins had failed to show any gains over M or Am alone: heat losses of Lys were suspected. Plasma obtained during the above studies, before and 3 h and 4 h after the first meal of the last day of consuming Am alone, three M-toasted Am mixtures, or M alone, were analysed for free AAs. Toasted, popped or flaked Am consumption caused significant p.p. falls in molar proportions of Leu from 99 to 85, 88 to 82, and 92 to 75, and of threonine (Thr) from 118 to 108 (popped) and 109 to 97 (flaked) mmol/mol TEAA, suggesting that these were first- and second-limiting EAAs. Post-prandial fall in Lys proportion was questionably significant. The M diet produced highly significant 3-h Leu elevation from 132 to 187, Lys fall from 167 to 135, and Trp fall from 62 to 46 mmol/mol TEAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1989

Concentration-response relationships for salicylate-induced ototoxicity in normal volunteers.

1. Ototoxicity is a common and troublesome side-effect of high-dose aspirin treatment but there has been little previous study of the relationships between the degree of ototoxicity and the plasma concentrations of salicylate. 2. In order to investigate the relationships between aspirin dose, total and unbound plasma salicylate concentrations and ototoxicity, eight normal volunteers were dosed with aspirin 1.95, 3.25, 4.55 and 5.85 g day-1 for 1 week at each dose level, the doses being administered in random order and double-blind, 2 weeks apart. 3. Ototoxic effects measured were hearing loss in decibels (dB) over six frequencies and tinnitus intensity, estimated both by electronic matching and a fixed interval scale (FIS). Measurements were taken after steady-state concentrations of salicylate had been achieved. 4. Total and unbound plasma salicylate concentrations increased disproportionately with increasing daily doses of aspirin. The increase in the unbound salicylate was relatively greater since the percentage of salicylate unbound in plasma increased over the dose range investigated from a mean of 3.9% to 10.4%. 5. Hearing loss and tinnitus intensity increased progressively with the aspirin dosage and increasing concentrations of total and unbound plasma salicylate concentrations. These ototoxic symptoms were observed at lower concentrations of total salicylate than previously reported. 6. There was a linear relationship between hearing loss and unbound salicylate concentrations. 7. Further work is required to test the hypothesis that unbound plasma salicylate concentration is a better predictor of salicylate-induced ototoxicity than total plasma salicylate concentration.

Adult↗
PubMed1989

Quality protein maize: digestibility and utilization by recovering malnourished infants.

The opaque-2 gene was shown years ago to increase the nitrogen, lysine, and tryptophan contents of maize and to markedly increase its nutritional value for small children. Concerns about decreased yield, resistance, and acceptability discouraged further development of the gene. Quality protein maize, while retaining the opaque-2 characteristics, has overcome those constraints. Six recovering malnourished infants received diets in which all of the 6.4% protein energy was supplied by casein, quality protein maize, or common maize. The quality protein maize supplied 60% and common maize 75% of total energy. Vegetable oil was added to increase fat contents to 10% of total energy in all diets. Energy digestibility was less (87% and 84%) from quality protein maize and common maize than from casein diets (94%); most of the difference was due to carbohydrate digestibility. Apparent N absorptions from quality protein maize (70 +/- 5%) and common maize (69% +/- 7%) were much lower (P less than .01) than from casein (82% +/- 4%). Apparent retention of N from quality protein maize (34 +/- 4%) was less (P less than .01) than from casein (41% +/- 9%) but greater (P less than .01) than from common maize (22% +/- 10%). Breath hydrogen excretions were usually greater during quality protein maize consumption than during casein diets but not nearly as much as those during common maize diets. The nutritional advantages of quality protein maize v common maize are of a magnitude that must be exploited for the advantage of children in maize-consuming poor countries.

Developing Countries↗
PubMed1988

Stereoselective disposition of ibuprofen enantiomers in synovial fluid.

The simultaneous disposition of the enantiomers of ibuprofen in synovial fluid and plasma was studied in eight patients with arthritis. Concentrations of the active S-enantiomer in synovial fluid exceeded those of the R-enantiomer at all times in all patients with the ratio of S to R concentrations being 2.1 +/- 0.3 (mean +/- SE). Synovial fluid concentrations fluctuated much less than in plasma and exceeded plasma concentrations from 5.4 +/- 0.3 hours for R-ibuprofen and 5.5 +/- 0.6 hours for S-ibuprofen. Pharmacokinetic analysis suggested that, although the enantiomers diffuse into synovial fluid primarily in the unbound form, there may be significant diffusion of the enantiomers out of synovial fluid in the protein-bound form in some patients. Interpatient differences in the disposition of the enantiomers of ibuprofen in synovial fluid were evident and may contribute to the interindividual variability in response to treatment with ibuprofen.

Female↗
PubMed1988

Nutritional value for young children of grain amaranth and maize-amaranth mixtures: effect of processing.

Amaranthus caudatus L. toasted flour, popped grain and flakes were each fed to nine young children as the source of all diet protein and fat and 50% of diet energy, preceded and followed by casein control diets. All provided 6.4-6.7% of energy as protein and 9.3-10.1% as fat. Balances were carried out during the last 6 d of the three 9-d amaranth periods and during the four control periods. Fecal wet and dry weights during amaranth diets were 129-157% of those during casein control diets; fecal energy, fat and carbohydrate from the toasted flour periods were 193, 268 and 256%; from the popped grain 253, 586 and 195%; and from the flakes 225, 356 and 255% of those during casein diets. Apparent N absorptions were 84.1-84.6% of the casein values (P less than 0.001); apparent retentions from toasted, popped and flaked amaranth were 70.9, 65.9 and 59.0% of casein (P less than 0.001). The last of these was significantly lower than the first (P less than 0.05). Fecal fat was much higher (P less than 0.001) from the popped than from the flaked grain and the toasted flour. Toasted flour was then added to maize meal so that amaranth provided 20 or 30% of the protein. Seven young children received diets in which 6.4% of total energy came from one of the above mixes, or from casein, as protein. Soya-cottonseed oils completed 25% lipid energy in all three diets; balance of energy was from sucrose in the experimental diets and from sucrose, corn syrup solids and cornstarch in the casein diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Amaranthus↗
PubMed1988

Effects of cassava variety and processing on energy and protein digestibility and utilization by young children.

Two varieties of cassava, processed as Nigerian fermented flour (gari) or as Brazilian flour (farinha), were fed to two groups of eight infants and young children, each group receiving both forms of one variety, with preceding, intervening and following casein control diets. The flours provided 50% of diet energy, with casein added to make 8% energy as protein, vegetable oils to make 20% as fat and corn syrup solids and sugar to make 72% carbohydrate (CHO) energy. Fecal wet weight increased (P less than 0.05) from approximately 100 g/d (casein diets) to means (+/- SD) of 202 +/- 72, 171 +/- 58, 154 +/- 46 and 190 +/- 67 g/d; dry weights from means of 14.7-18.3 g/d to means of 22.9-24.4 g/d (P less than 0.05); fecal energy from means of 50-60 kcal/d to means of 89-94 kcal/d (P less than 0.01); fetal fat was generally not affected; and fecal CHO nearly tripled (P less than 0.01) from approximately 4 to 12 g/d. Apparent nitrogen absorptions and retentions from the cassava + casein diets were modestly lower than from casein diets. Rates of weight gain were very variable and not significantly different by diet; serum albumin levels were essentially unchanged. The results with these flours were indistinguishable from each other and from those previously found with freeze-dried cassava flour in otherwise identical diets. Variety and processing method had no effect on the digestibility of cassava starch and oligosaccharides and on the great resistance to digestion and the water-holding capacity of cassava fiber.

Body Weight↗
PubMed1988

Relationship between plasma oxipurinol concentrations and xanthine oxidase activity in volunteers dosed with allopurinol.

1. 1-methyl xanthine (1-MX) is metabolized exclusively to 1-methyl uric acid (1-MU) by the enzyme xanthine oxidase. 2. The ratio of 1-MU to 1-MX in the urine, following a dose of 50 mg of 1-MX infused intravenously over 20 min, was used to measure the inhibition of xanthine oxidase induced by different doses of allopurinol. 3. Normal volunteers (n = 8) were given allopurinol 50, 100, 300 and 600 mg daily for 1 week each, in random order and 1 week separated each treatment. Inhibition of xanthine oxidase was assessed twice, on the last 2 days of each treatment week. 4. Steady-state oxipurinol concentrations increased linearly with increasing dose of allopurinol. 5. There was a hyperbolic relationship between the 1-MU/1-MX ratio and plasma oxipurinol concentrations, with an initial steep decline in the ratio which plateaued when plasma oxipurinol was around 4-6 mg l-1. This reduction in the ratio was quickly reversible upon cessation of allopurinol. 6. The 50% and 90% effective inhibitory oxipurinol concentrations, in relation to the 1-MU-/1-MX ratio were 1.4 +/- 0.46 and 4.08 +/- 2.03 mg l-1 respectively. 7. The concentration of oxipurinol required for almost complete inhibition of the enzyme was substantially less than those often observed in clinical practice.

Adult↗
PubMed1988

Interaction of salicylate and corticosteroids in man.

Corticosteroids have been reported to decrease the plasma concentrations of salicylate when salicylates have been administered chronically at high doses. In the present study, two single, oral doses of sodium salicylate, 10 mg kg-1 were administered to six adult subjects with a variety of inflammatory conditions both before and during treatment with daily oral doses of prednisone (12-60 mg). Concomitant prednisone therapy did not increase the whole body clearance of single doses of salicylate in these subjects (0.0275 +/- 0.08 l kg-1 h-1 before prednisone; 0.0247 +/- 0.03 l kg-1 h-1 during prednisone therapy; P greater than 0.05). These results indicate that corticosteroids do not alter the clearance of single doses of salicylate in man.

Adrenal Cortex Hormones↗