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Biomedical subjects

G G Graham

Publications and source records attributed to G G Graham.

At least 73 records · Page 4Linked to original sources
PubMed1988

Dose response studies and longterm evaluation of auranofin in rheumatoid arthritis.

Fifty-eight patients with rheumatoid arthritis (RA) entered a double blind trial of auranofin (AF) designed to assess dose response relationships and longterm outcome. Multivariate analysis of repeated measures with trend analysis and discriminant function analysis of standard measures of RA activity were applied to a randomized double blind trial of AF at daily doses of 4, 6 and 8 mg over 6 months. Improvement occurred in each group. There was a highly significant (p less than 0.001) linear trend in the 6 mg group, 73% of whom showed linear improvement. A significant correlation (p less than 0.05) was found between response of individual patients and AF dose (mg/kg/day), but there was no significant correlation between dosage and mean steady state serum gold concentration. No significant correlation was seen between outcome and pretreatment demographic and disease variables. In a subsequent 6 month phase of dosage adjustment, aiming for optimal dosage, no advantage resulted from increasing the dose above 6 mg/day. Patients apparently benefiting from treatment continued an open long-term trial of AF. By 45 months, 33.5% had stopped treatment due to lack of efficacy and 14.5% due to toxicity, mainly rash and diarrhea.

Actuarial Analysis↗
PubMed1987

Salicyl phenolic glucuronide pharmacokinetics in patients with rheumatoid arthritis.

The pharmacokinetics of salicyl phenolic glucuronide (SPG) and other salicylic acid (SA) metabolites were studied at three aspirin dosage regimens in eight patients with rheumatoid arthritis. Each patient received 1, 2 and 4 g enteric coated aspirin (ASA) daily in ascending order. At the end of each 2-week dosage period, plasma and urine were collected over a dosage interval for the estimation of various pharmacokinetic parameters. With increasing ASA dosage, mean clearance of SA to SPG was approximately constant (1.8 +/- 0.3, 1.7 +/- 0.2, and 1.5 +/- 0.2 ml/min at 1, 2 and 4 g/day, respectively) when related to plasma concentrations of total SA. The percentage of the ASA dosage recovered in urine as SPG increased from 5.2 +/- 1.1 to 7.1 +/- 1.1 to 10.5 +/- 1.7 at 1, 2 and 4 g/day, respectively. It was concluded, however, that the conversion of SA to SPG is saturable, since the mean clearance of SA to SPG decreased when calculated with respect to the plasma concentration of unbound SA (13.4 +/- 1.6, 11.0 +/- 1.4, and 6.6 +/- 1.9 ml/min at 1, 2 and 4 g/day, respectively). The kinetics of the formation and excretion of salicylurate and the excretion of gentisate were similar to those found in previous studies.

Adult↗
PubMed1987

Digestibility of boiled and oven-dried cassava in infants and small children.

Boiled fresh cassava or oven-dried cassava flour provided 50% of the energy and less than 10% of the protein in diets of convalescent malnourished infants; casein was added to complete 8% of energy as protein, and vegetable oil (soybean-cottonseed) was added to make 20% of energy as fat. Despite high wet weights of feces (172 +/- 42 and 214 +/- 41 g/d), their dry weights (20 +/- 3 and 22 +/- 2 g/d) and their energy (6.9 +/- 0.7 and 7.6 +/- 0.5% of intake) and nitrogen (17 +/- 3 and 20 +/- 3% of intake) contents were low, and their fat content (4.4 +/- 1.3 and 5.2 +/- 1.2% of intake) was very low. Cassava is a surprisingly effective source of energy which interferes little or not at all with digestion of added protein and fat in weaning diets. For its safe use, it is important that home or industrial processing almost completely eliminate its potential hydrocyanic acid content, and that a good quality protein supplement be consumed regularly in nutritionally adequate amounts.

Body Weight↗
PubMed1987

Effect of amounts consumed on the digestion of cassava by young children.

To determine whether increasing proportions of cassava could be consumed and satisfactorily digested, eight recovering malnourished children (20-38 mo old) received 25, 50 and 75% of their diet energy as freeze-dried cassava flour during 9-d periods, with intervening casein control diets. Enough casein was added to all cassava diets to bring protein energy to 8% of the total. When compared to the control diet, the 25% diet had no significant effect on consumption time or measures of protein and energy digestion. With the 50% diet, fecal wet and dry weights were moderately higher than with the 25% diet (196 +/- 44 and 24 +/- 4 vs. 121 +/- 36 and 16 +/- 3 g/d, respectively), as were fecal energy (89 +/- 16 vs. 63 +/- 16 kcal/d) and calculated carbohydrate (11 +/- 2 vs. 5 +/- 1 g/d); apparent nitrogen absorption (mostly from casein) was slightly lower (79 +/- 5 vs. 83 +/- 6%) and consumption time slightly higher (5-25, median 10, vs. 4-18, median 6 min/feeding). When energy from cassava was increased to 75%, fecal weights (240 +/- 49 and 31 +/- 5 g/d), energy (124 +/- 27 kcal/d) and carbohydrate (16 +/- 4 g/d) were all higher than when cassava provided 50 or 25% of energy. Consumption required 8-34, median 17 min/feeding and apparent nitrogen absorption was 76 +/- 6% of intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1987

The pharmacokinetics of atracurium isomers in vitro and in humans.

Atracurium is a mixture of ten isomers. By high-performance liquid chromatography, using acidified methanol as the mobile phase and silica support, it was separated into its three geometrical isomer groups, cis-cis, cis-trans, and trans-trans, which contain three, four, and three isomers, respectively. The clinically available form of atracurium was made up of 58% cis-cis, 36% cis-trans, and 6% trans-trans isomers. In buffered saline, pH 7.4, at 37 degrees C, the half-lives of the three isomer groups were 57.1 +/- 0.9, 59.7 +/- 0.9, and 66.4 +/- 2.7 min, respectively, for the cis-cis, cis-trans, and trans-trans groups. In whole blood, under similar conditions, the three groups showed different behavior. The cis-cis group broke down in a monoexponential manner with a half-life of 23.3 +/- 2.8 min. The cis-trans group showed bi-exponential breakdown with a rapid phase of 2.3 +/- 0.4 min and a slow phase of 22.1 +/- 2.9 min. The trans-trans group decayed rapidly, but, because of the low concentration of this group in the mixture, kinetic parameters could not be obtained. In eight patients, the mean elimination half-life and apparent clearance of the cis-cis group were 20.6 +/- 1.5 min and 5.3 +/- 0.4 ml.kg-1.min-1, respectively. For the cis-trans group, the apparent elimination half-life and clearance were 17.7 +/- 1.8 min and 9.0 +/- 1.0 ml.kg-1.min-1, but these figures require care in interpretation, as this isomer group contains isomers of widely varying rates of decomposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Digestibility and utilization of protein and energy from Nasha, a traditional Sudanese fermented sorghum weaning food.

Whole grain sorghum flour was fermented into Nasha, a traditional Sudanese food, and freeze-dried or drum-dried. It was cooked and fed to convalescent malnourished infants and small children as 61% of total diet calories and all of 6.4% protein calories, with (Lys+) and without lysine supplementation to 3% of protein. Apparent absorptions of nitrogen were 73 +/- 5 and 74 +/- 6% of intake, significantly (P less than 0.01) less than those from preceding (Cas-1, 86 +/- 3%) and following (Cas-2, 85 +/- 3%) isonitrogenous casein diets. Apparent retentions of nitrogen from Nasha (26 +/- 10%) were significantly lower than those from Lys + (34 +/- 9%, P less than 0.05), Cas-1 (35 +/- 11%, P less than 0.01) or Cas-2 (49 +/- 9%, P less than 0.01). Retentions from Cas-2 were higher than those from Cas-1 or Lys + (P less than 0.01). Fecal wet and dry weights were higher (P less than 0.02) during both Nasha diets and Cas-2 than during Cas-1. Fecal energy and carbohydrate were significantly (P less than 0.01) higher from either Nasha diet than from either casein diet; fecal fat was not different. Two children received drum-dried Nasha without further cooking; digestibilities were not different from those of the cooked product but biological value was much lower. When properly cooked and consumed along with small amounts of a good source of lysine, Nasha is a satisfactory weaning food.

Absorption↗
PubMed1986

Relationship of train-of-four ratio to twitch depression during pancuronium-induced neuromuscular blockade.

The relationship of train-of-four (TOF) ratio to the depression of the first twitch (TD) was investigated in 16 patients given pancuronium in doses insufficient to eliminate the fourth response in the train. In ten patients the block was allowed to spontaneously recover (Group 1) and in six it was reversed with neostigmine (Group 2) once maximum depression of TOF ratio had occurred. Maximum depression of the first response occurred in 6.5 +/- 4.3 min (mean +/- SD). Maximum depression of the TOF ratio was not present until 28.0 +/- 11.0 min. TOF ratio was usually still decreasing when recovery of TD had begun. However, once the TOF ratio began to recover, the recovery rates for TD and TOF ratio were similar in both the spontaneously recovering and the reversed groups. TOF ratio at complete TD recovery was 74.9 +/- 15.7 and 86.2 +/- 15.4% for the two groups. A kinetic analysis yielded significantly different elimination rate constants for the two effects from the "effect compartment." These findings suggest that these two effects of pancuronium are exerted at different sites.

Dose-Response Relationship, Drug↗
PubMed1985

1H, 13C NMR, and electronic absorption spectroscopic studies of the interaction of cyanide with aurothiomalate.

The reaction between cyanide and aurothiomalate (Autm) has been studied by 1H and 13C NMR spectroscopy and by uv spectroscopy. At cyanide:Autm ratios greater than or equal to 2, aurocyanide, [Au(CN)2]-, is the sole product but was also produced at lower ratios. Two intermediates were also identified. These were a mixed ligand complex, [tmAuCN]-, which accounted for over 80% of the gold at a ratio of cyanide to Autm of 1, and a bisthiomalato complex, [Autm2]-, which accounted for 6.8% of the total gold at this ratio of cyanide to Autm. The formation of these complexes may be significant in the antiarthritic activity of Autm since cyanide is produced by potential target cells such as polymorphonuclear leukocytes.

Chemical Phenomena↗
PubMed1984

The effect of cyanide on the uptake of gold by red blood cells.

Cyanide markedly increased the rate of uptake of gold by red blood cells when incubated with sodium aurothiomalate, a polymeric gold complex. Thiocyanate had no significant effect on gold uptake. The effect of cyanide was demonstrated to be due to the conversion of aurothiomalate to the complexion, aurocyanide, which is rapidly taken up by red blood cells. At a low ratio (1:20) of cyanide to aurothiomalate, cyanide appeared to act as a shuttle to carry gold into red blood cells. Tobacco smoking is known to increase the concentrations of gold in red blood cells in patients treated with aurothiomalate. The present data indicate that this effect of smoking is most likely due to cyanide inhaled in tobacco smoke and not to thiocyanate, a circulating metabolite of cyanide. An effect of cyanide on the uptake of polymeric gold complexes to target cells such as polymorphonuclear leukocytes and monocytes is suggested.

Aurothioglucose↗
PubMed1984

Liquid chromatographic determination and plasma concentration profile of optical isomers of ibuprofen in humans.

A sensitive and specific high-performance liquid chromatographic assay for the optical isomers of ibuprofen in plasma is reported. The isomers were converted to their diastereoisomeric S(+)-2-octyl esters and were resolved with two silica columns in series and a mobile phase containing 0.05% isopropyl alcohol in heptane. The lower limit of sensitivity was 0.5 micrograms/mL. The plasma concentrations of the optical isomers in a normal volunteer following administration of racemic, S(+)-, and R(-)-ibuprofen are reported. Following administration of R(-)-ibuprofen, there was stereoselective inversion of R(-)- to S(+)-ibuprofen.

Chromatography, High Pressure Liquid↗
PubMed1984

Kinetics of thiopentone in relation to the site of sampling.

Plasma concentrations of thiopentone were determined at frequent intervals over the first 12 min following injection i.v. in eight patients. Samples of arterial and peripheral venous blood were obtained in all subjects. In six, central venous and in two, internal jugular samples were obtained also. Thiopentone concentrations in arterial and central venous plasma did not differ significantly after 2 min. Differences between arterial and peripheral samples were significant for 2 min although, in some patients, considerable variability persisted for up to 9 min. In both patients from whom jugular venous samples were obtained, the difference between these and the peripheral plasma concentrations was marked. This difference may account for the appearance of acute tolerance. A computer model for this hypothesis is presented.

Arm↗
PubMed1984

The influence of sampling site upon the distribution phase kinetics of thiopentone.

In six sheep anaesthetised with ketamine blood was sampled from the jugular and femoral veins and the femoral artery at frequent intervals for 12 minutes following the intravenous administration of 5 or 10 mg/kg sodium thiopentone. Samples were also taken from cubital veins and radial arteries of five patients who received 5 mg/kg thiopentone. The plasma concentration of thiopentone was determined by an HPLC assay. The time course of plasma concentration of thiopentone showed considerable variation according to sampling site as well as variation between individuals. Such sampling site-dependent variation may result in the appearance of acute tolerance.

Animals↗
PubMed1984

Body water measurements in premature and older infants using H218O isotopic determinations.

Total body water was measured by H218O stable isotope dilution in two groups: in premature infants without complications, who were studied from 8 d of age until discharge; and in Peruvian subjects aged 6-36 mo, who were in the long-term convalescent stage of recovery from malnutrition. Results indicated that reliable total body water estimates can be obtained from sample volumes as small as 50 microliters of urine or plasma using a gas-isotope-ratio mass spectrometer equipped with an automated purification inlet system. Results from 21 studies in 10 Peruvian infants indicated substantially completed isotope equilibration in plasma by 2 h after the dose; total body water estimates from the 2-h samples averaged 98.7% (+/- 4.1) of 6-h values. Samples obtained at 4-h postdose gave total body water estimates that averaged 99.0% (+/- 2.9) of the 6-h value, showing essentially complete equilibration and reduced variability. Total body water estimates from urine samples collected 3-5 h postdose were closely correlated with 6-h, plasma-based total body water values in both premature and older infants; however, some reduction in variability was observed when urine collection was extended to 5-7 h, at which time urine-based estimates averaged 98.8% (+/- 2.0) and 100.7% (+/- 3.1) of plasma-based values for prematures and older Peruvian infants, respectively. The correlation between 5-7 h urine-based estimates of total body water with plasma-based values was r = 0.96 for 30 studies in prematures and r = 0.99 for 57 studies in older Peruvian infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗