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Biomedical subjects

E Holmes

Publications and source records attributed to E Holmes.

At least 55 records · Page 3Linked to original sources

Intravascular and total body platelet equilibrium in healthy volunteers and in thrombocytopenic patients transfused with single donor platelets.

Instrument platelet counts used in corrected count increment (CCI) and percent platelet recovery (PPR) formulas presume the transfused platelets are in equilibrium during the first hour after platelet transfusion. The timing of the pre-transfusion count affects CCI results, and we postulate that timing of CCI post transfusion affects CCI results. Platelet equilibrium using indium-111 platelet transfusions has not been reported. Platelet redistribution was studied in 16 healthy volunteers and 12 thrombocytopenic patients by generally infusing less than 72-hr stored single-donor platelets along with an aliquot of indium-111-labeled platelets by intravenous push. Counts were measured at 10, 15, 20, 60, and 120 min, and 24, 48, 72 hr along with continuous body scanning for 2 hr in healthy volunteers, and static organ scanning in patients and volunteers. Results indicated transfused platelets do not reach intravascular equilibrium for 60 min post-infusion and that the 10-min count cannot detect platelet refractoriness. However, total body equilibrium varies considerably between normal volunteers and thrombocytopenic patients. It is recommended to continue with the 1-hr post transfusion count.

Antigens, Human Platelet↗

Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins.

1H NMR spectroscopy of urine combined with pattern recognition (PR) methods of data analysis has been used to investigate the time-related biochemical changes induced in Sprague-Dawley rats by three model hepatotoxins: alpha-naphthyl isothiocyanate (ANIT), d-(+)-galactosamine (GalN), and butylated hydroxytoluene (BHT). The development of hepatic lesions was monitored by conventional plasma analysis and liver histopathology. Urine was collected continuously postdosing up to 144 h and analyzed by 600-MHz 1H NMR spectroscopy. NMR spectra of the urine samples showed a number of time-dependent perturbations of endogenous metabolite levels that were characteristic for each hepatotoxin. Biochemical changes common to all three hepatotoxins included a reduction in the urinary excretion of citrate and 2-oxoglutarate and an increased excretion of taurine and creatine. Increased urinary excretion of betaine, urocanic acid, tyrosine, threonine, and glutamate was characteristic of GalN toxicity. Both GalN and ANIT caused increased urinary excretion of bile acids, while glycosuria was evident in BHT- and ANIT-treated rats. Data reduction of the NMR spectra into 256 integrated regions was used to further analyze the data. Mean values of each integrated region were analyzed by principal components analysis (PCA). Each toxin gave a unique time-related metabolic trajectory that could be visualized in two-dimensional PCA maps and in which the maximum distance from the control point corresponded to the time of greatest cellular injury (confirmed by conventional toxicological tests). Thereafter, the metabolic trajectories changed direction and moved back toward the control region of the PR map during the postdose recovery phase. The combination of urinary metabolites which were significantly altered at various time points allowed for differentiation between biliary and parenchymal injury. This NMR-PR approach to the noninvasive detection of liver lesions will be of value in furthering the understanding of hepatotoxic mechanisms and assisting in the discovery of novel biomarkers of hepatotoxicity.

1-Naphthylisothiocyanate↗

Haptic perception of texture gradients.

To pick up 3-D aspects of pictures is arguably the most difficult problem concerning tactile pictorial perception by the blind. The aim of the experiments reported was to examine the potential utility of texture gradients in this context. Since there is no theoretical basis for predicting absolute values of 3-D properties from 2-D patterns read by the finger pads, the abilities of participants to perceive gradients lying between known maxima and minima were assessed. Experiment 1 involved blindfolded sighted participants making verbal magnitude estimations of texture-gradient magnitudes corresponding to plane surfaces at different slants. In experiment 2 the participants' task was to orient a surface at a slant corresponding to the texture gradients depicted tactually, and experiment 3 required early-blind participants to attempt the same task. The results revealed that participants can scale the magnitudes of texture gradients with high precision and that they can also accurately produce surface slants from depictions, providing the extreme conditions are clearly defined and there are opportunities for learning. Texture gradients appear as informative to the blind as they do to the sighted. To what extent these data can be generalised to other gradients and textures or to other projections of 3-D scenes remains to be investigated.

Adult↗

SWAN: sliding window analysis of nucleotide sequence variability.

RESULTS: This paper describes a new program which reveals, analyses and graphically represents patterns of variability along nucleotide sequences. AVAILABILITY: The program, 'SWAN', is available from the WWW at http://evolve.zoo.ox.ac.uk/ or from the authors upon request. CONTACT: Vitali.Proutski@zoology.oxford.ac.uk

Algorithms↗

Assessment of left ventricular wall motion and delineation of the endocardial border after intravenous injection of Infoson during dobutamine stress echocardiography.

OBJECTIVES: To investigate whether intravenous injection of Infoson facilitates the assessment of left ventricular wall motion and definition of endocardial border and thereby reduces inter- and intra-observer variability during dobutamine stress echocardiography. BACKGROUND: Clear detection of the endocardial border is essential during dobutamine stress echocardiography. Although several contrast agents have been tested for their efficacy in enhancing definition of left ventricular endocardium, their usefulness during dobutamine stress echocardiography has not been evaluated. METHODS: Thirty coronary artery disease patients underwent dobutamine stress echocardiography. Infoson was injected at 0.2 ml/kg in both apical four- and two-chamber views. Detection of the left ventricular endocardial borders was scored from 0 (undetectable) to 10 (best) and expressed as a percentage of image quality at rest and peak stress by two independent observers. Regional wall motion was also evaluated and the total wall motion score index calculated each time. RESULTS: Delineation of the left ventricular endocardium improved from 76 +/- 4% to 84 +/- 2% at rest (P < 0.01) and from 75 +/- 4% to 89 +/- 1% at peak stress (P < 0.01) after administration of Infoson. The greatest improvement was seen in the basal and middle regions of the lateral and anterior walls. Inter- and intra-observer variability was reduced after administration of Infoson. At rest, the probability of concordance between two observers increased from 0.86 (0.82-0.89) to 0.91 (0.88-0.94) (P < 0.05) and at peak stress from 0.86 (0.82-0.9) to 0.90 (0.86-0.92) after administration of Infoson (P < 0.05). The probability of concordance between on- and off-line assessment by one observer also increased from 0.84 (0.8-0.88) to 0.90 (0.86-0.93) (P < 0.01) at rest and from 0.90 to 0.92 (NS) at peak stress. Overall, a change in wall motion score index occurred in 16 of 30 (53%) patients after administration of Infoson, thus improving the accuracy of the stress test compared with coronary angiography. The wall motion score index was overestimated in 11 of 16 (37%) patients without Infoson while the detection of new wall motion abnormalities increased in 5 of 16 (17%) (P < 0.01). CONCLUSIONS: Intravenous administration of Infoson facilitates the assessment of wall motion, particularly of the basal lateral and anterior walls where endocardial border drop-out frequently occurs during dobutamine stress echocardiography; it thus reduces the inter- and intra-observer variability.

Adult↗

750 MHz 1H NMR spectroscopy characterisation of the complex metabolic pattern of urine from patients with inborn errors of metabolism: 2-hydroxyglutaric aciduria and maple syrup urine disease.

750 MHz 1H NMR spectroscopy has been used to characterise in detail the abnormal low molecular weight metabolites of urine from two patients with inborn errors of metabolism. One case of the rare condition 2-hydroxyglutaric aciduria has been examined. There is at present no rapid routine method to detect this genetic defect, although NMR spectroscopy of urine is shown to provide a distinctive pattern of resonances. Assignment of a number of prominent urinary metabolites not normally seen in control urine could be made on the basis of their known NMR spectral parameters including the diagnostic marker 2-hydroxyglutaric acid, which served to confirm the condition. In addition, 750 MHz 1H NMR spectroscopy has been used to characterise further the abnormal metabolic profile of urine from a patient with maple syrup urine disease. This abnormality arises from a defect in branched chain keto-acid decarboxylase activity and results in a build up in the urine of high levels of branched chain oxo- and hydroxy-acids resulting from altered metabolism of the branched chain amino acids, valine, leucine and isoleucine. A number of previously undetected abnormal metabolites have been identified through the use of one-dimensional and two-dimensional J-resolved and COSY 750 MHz 1H NMR spectroscopy, including ethanol, 2-hydroxy-isovalerate, 2,3-dihydroxy-valerate, 2-oxo-3-methyl-n-valerate and 2-oxo-isocaproate. NMR spectroscopy of urine, particularly when combined with automatic data reduction and computer pattern recognition using a combination of biochemical markers, promises to provide an efficient alternative to other techniques for the diagnosis of inborn errors of metabolism.

Amino Acid Metabolism, Inborn Errors↗

1H NMR spectroscopic and histopathological studies on propyleneimine-induced renal papillary necrosis in the rat and the multimammate desert mouse (Mastomys natalensis).

The renal papillary toxin, propyleneimine (PI), was administered at 20 or 30 microliters/kg i.p. to male Sprague Dawley (SD) rats (n = 5), Fischer 344 (F344) rats (n = 4), and to multimammate desert mice (Mastomys natalensis, n = 4). Urine was collected at time points up to 4 days p.d. and the toxicological response of the different animal models to PI compared using 1H NMR spectroscopy of urine, renal histopathology, and urinary assays for alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (gamma GT). The renal papillae of both F344 and SD rats showed extensive necrotic lesions 4 days post-dosing and in some cases sloughing of the papilla. However, only slight renal papillary necrosis (RPN) was observed in Mastomys treated with 20 microliters/kg PI and, although slight to moderate damage was observed at 30 microliters/kg, PI-treated Mastomys showed substantially less RPN than either group of PI-treated rats. 1H NMR urinalysis showed that PI treatment caused a decrease in the urinary concentrations of succinate (0-24 hr p.d.) and citrate (24-48 hr p.d.) and an increase in creatine (0-48 hr p.d.) in all animal models. Trimethylamine-N-oxide (24-48 hr) and 2-oxoglutarate concentrations decreased initially following the administration of PI and then rose above control levels. The 1H NMR-detected urinary biochemical effects of PI in all three models were similar. However, taurine concentrations were elevated in the urine of Mastomys following PI treatment, perhaps indicating a degree of liver damage, whereas taurinuria was not seen in either SD or F344 rats. These observations are discussed in relation to the potential mechanism of PI-toxicity.

Animals↗

Use of the critical incident technique in primary care in the audit of deaths by suicide.

OBJECTIVE: To explore the usefulness of the critical incident technique in primary care to improve policy and practice to prevent cases of suicide. DESIGN: Inviting all primary care teams in County Durham with a patient who committed suicide between 1 June 1993 and 31 May 1994 to take part in a critical incident audit with an external facilitator. RESULTS: 49 cases of suicide were available for study, registered with 31 practices. 19 (61%) practices accounting for 27 (55%) cases agreed to take part. Case discussions showed areas where practice could be improved, but no substantive preventive measures were identified within primary care, which would reduce the number of people committing suicide. The wider social and economic context was thought to be more important. CONCLUSIONS: The use of the critical incident technique in primary care may have only a limited role in improving the management of people at risk from suicide. However, one of the potential strengths of this approach is to encourage reflection on practice in a difficult emotional area.

England↗

Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels.

Fucosylated glycoproteins carrying alpha1-4 fucose residues are of importance for cell adhesion and as tumor markers. The Lewis gene, FUT3, encodes the only known alpha1-4-fucosyltransferase (FucT), and individuals who are deficient in this enzyme type as Lewis-negative on erythrocytes. We examined the mutational spectrum of the Lewis gene in Denmark and found 6 different mutations. Five, T59G, T202C, C314T, G508A, and T1067A, were frequent, and one, C445A, was only detected in one out of 40 individuals. Allele-specific polymerase chain reaction as well as cloning of FUT3 alleles showed that the 202 and 314 mutations were co-located on the same allele. COS7 cells transfected with an allele having the 202/314 mutations lacked enzyme activity. Polymerase chain reaction-cleavage assays were established for the genotyping of healthy individuals as well as 20 genuine Lewis-negative cancer patients and 10 non-genuine. The latter have Lewis-negative erythrocytes but saliva alpha1-4FucT activity. The genuine Lewis-negative individuals had mutations on both FUT3 alleles. In 66 healthy individuals, a gene dosage effect was detected as FUT3 heterozygous individuals had a lower alpha1-4FucT activity in saliva than did homozygous wild-type individuals. The lower enzyme level in heterozygous individuals resulted in a significantly (p < 0.04) lower level of circulating sialyl-Lewis a structure in serum. This has the clinical impact that cut-off levels in tumor marker assays should be defined on the basis of genotyping. In the group of non-genuine Lewis-negative cancer patients, whose erythrocytes convert from Lewis-positive to Lewis-negative during the disease, FUT3 heterozygosity was significantly (p < 0.05) more common.

ABO Blood-Group System↗

Comparative biochemical effects of low doses of mercury II chloride in the F344 rat and the multimammate mouse (Mastomys natalensis).

The biochemical effects and comparative nephroxicity of mercury II chloride (HgCl2) dosed at 0.75 mg/kg i.p. was investigated in the Fisher 344 rat (F344) and Mastomys natalensis using high resolution 1H nuclear magnetic resonance (NMR) spectroscopy of urine, histopathology and clinical chemical techniques. The effects of HgCl2 treatment were followed for up to 4 days post-dosing (p.d.). In F344 rats there was extensive proximal tubular damage and renal cortical necrosis together with elevated levels of urinary gamma-glutamyl transpeptidase (gamma GT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The 1H NMR spectra of urine obtained from Hg-treated F344 rats also showed increased levels of glucose, alanine, lactate, valine and hippurate (0-48h p.d.) with decreased levels of citrate, succinate and 2-oxoglutarate (24-48h p.d.). Mastomys were found to be highly resistant to HgCl2 toxicity at 0.75 mg/kg and the histological appearance of the renal cortex of treated animals was virtually identical to controls. There were no elevations in urinary ALP, gamma GT and LDH activities in HgCl2-treated Mastomys and there were no biochemical abnormalities in low MW components of Mastomys urine following HgCl2-treatment, as shown by 1H NMR spectroscopy. Urinary gamma GT activity was found to be much higher in F344 rats than Mastomys. Since gamma GT activity is involved in the tubular reabsorption of Hg2+, the lower levels of gamma GT in Mastomys might partially account for the lower toxicity of Hg2+ in this species.

Animals↗

1H and 19F-nmr spectroscopic studies on the metabolism and urinary excretion of mono- and disubstituted phenols in the rat.

1. 1H and 19F-nmr spectroscopy was used to investigate quantitatively the urinary excretion of the metabolites of 15 substituted phenols in the rat. The compounds studied were: 2-, 3-, and 4-fluorophenols; 2-, 3-, and 4-trifluoromethylphenol; 2,4-, 2,6- and 3,4-difluorophenol; 2-fluoro-5-trifluoromethylphenol, 3-fluoro-5-trifluoromethylphenol, 2-trifluoromethyl-4-fluorophenol; 3-chloro-4-fluorophenol, 3-fluoro-4-chlorophenol, and 3-methyl-4-fluorophenol. All compounds were dosed to the Sprague-Dawley rat (10 mg/kg i.p.) and urine was collected over the periods 0-8, 8-24 and 24-48 h post-dosing and analyzed using nmr spectroscopy. 2. The compounds were excreted in the urine mainly as glucuronide or sulphate conjugates or as the unchanged parent compound. There was considerable variation in the urinary excretion of the compounds over 48 h ranging from 22.1 to 93.6% of the dose. There was no apparent relationship between the molecular weight of compounds or their metabolites and the percentage molar recovery of each in the urine. 3. Ortho-substituted phenols in general showed a greater propensity for glucuronidation than did either meta- or para-substituted compounds, irrespective of the substituent group. The molar glucuronide-to-sulphate ratio for ortho-substituted compounds was found to be 2.2 +/- 0.9 whereas the ratio for both meta- and para-substituted compounds was 0.8 +/- 0.2 (p < 0.0001). 4. There were characteristic substituent effects of phenolic glucuronidation or sulphation on the 19F-nmr chemical shifts for both F- and CF3-substituted phemols and these substituent effects were a useful aid to metabolite signal assignment. 5. These studies show that nmr spectroscopy provides a rapid and convenient approach to the construction of metabolic databases of simple xenobiotics for the investigation of structure-metabolism relationships.

Animals↗

1H and 2H NMR spectroscopic studies on the metabolism and biochemical effects of 2-bromoethanamine in the rat.

Male Fischer 344 rats were dosed with 2-bromoethanamine hydrobromide (BEA, N = 6) or [1,2,2,-2H4]-bromoethanamine hydrobromide (BEA-d4, N = 6) at 150 mg/kg i.p. and urine was collected -24 to 0 hr pre-dose and at 0-2 hr, 2-4 hr, 4-8 hr and 8-12 hr post-dose (p.d.). Urine samples were analysed directly using 500 and 600 MHz 1H NMR and 92.1 MHz 2H NMR spectroscopy. The major observed effect of BEA treatment was the induction of transient elevations in urinary glutaric acid (GTA) and adipic acid (ADA) excretion lasting up to 24 hr p.d. Most of the GTA was excreted in the 0-8 hr p.d. with maximal rates of 100-120 microM/hr for each rat occurring between 4 and 8 hr p.d. in animals treated with BEA or BEA-d4. GTA and ADA were shown to be of endogenous origin as there was no detectable incorporation of the 2H label into either compound following treatment of rats with BEA-d4. Following BEA-treatment there was an initial decrease in the levels of urinary citrate, succinate, 2-oxoglutarate and trimethylamine-N-oxide. A subsequent recovery of citrate and succinate was noted following the onset of medullary nephropathy. The abnormal urinary metabolite profiles were similar to that observed in the urine of humans with glutaric aciduria type II (an inborn error of metabolism) caused by a lack of mitochondrial fatty acyl coenzyme A dehydrogenases indicating that BEA or its metabolites have similar metabolic consequences. The BEA metabolite aziridine was detected by 1H and 2H NMR spectroscopy of the urine 8 hr p.d. together with BEA itself and two novel metabolites 2-oxazolidone (OX) and 5-hydroxy-2-oxazolidone (HOX). The formation of OX requires the reaction of BEA with endogenous bicarbonate followed by a cyclisation reaction eliminating HBr. Dosing rats with authentic OX resulted in the excretion of HOX but did not cause glutaric or adipic aciduria indicating that either aziridine or BEA itself was responsible for the presumed defect in mitochondrial metabolism.

Adipates↗

Comparative studies on the nephrotoxicity of 2-bromoethanamine hydrobromide in the Fischer 344 rat and the multimammate desert mouse (Mastomys natalensis).

Renal papillary necrosis (RPN) was induced in Fischer 344 (F344) rats (n = 4) using 2-bromoethanamine hydrobromide (BEA) dosed at 150 mg/kg, and in multimammate desert mice (Mastomys natalensis) at 150 and 250 mg/kg (n = 4 per group). Control rats and Mastomys were dosed with 0.9% saline (n = 4 per group). Urine was collected at regular intervals for up to 4 days post-dosing and analysed for low MW metabolites using high resolution 1H NMR spectroscopy. The urinary activity of lactate dehydrogenase, gamma-glutamyl transpeptidase and alkaline phosphatase was determined using conventional biochemical assays. On termination, histopathological examination of papillae was performed showing the development of extensive lesions in F344 rats at 150 mg/kg BEA. Mastomys appeared much more resistant to BEA and showed normal renal histology at 150 mg/kg and patchy lesions at 250 mg/kg BEA. Enzyme analysis of control urine showed F344 rats to have > 1000% higher gamma-glutamyl transpeptidase activity than Mastomys. 1H NMR spectroscopic analysis showed that BEA caused a substantial decrease in urinary concentrations of succinate and citrate (0-24 h p.d.) and an increase in creatine (0-96 h p.d.) in both animal models. A decrease in the urinary concentration of 2-oxoglutarate with a subsequent increase by 72-96 h p.d. was also noted in both animal models. Glutaric and adipic aciduria were also induced in both F344 rats and Mastomys 0-24 h post-BEA treatment, indicative of an enzyme deficiency in the acyl CoA dehydrogenases. Urinary taurine levels were elevated in Mastomys following the administration of BEA, indicating some degree of liver toxicity. Urinary taurine was not elevated in F344 rats following BEA administration, demonstrating further species difference in BEA toxicity.

Animals↗

An outbreak of cryptosporidiosis in south London: what value the p value?

An outbreak of cryptosporidiosis which affected 44 people in January and February 1991 was identified through local surveillance at a South London Public Health Laboratory. Preliminary enquiries revealed that more than half the patients were adult and that there were no common factors other than geographical association. A case-control study showed a significant association between illness and consumption of tap water supplied by a particular water company, as well as a dose response effect. There were no apparent breaches or irregularities in the water distribution system and no indication of a problem through routine monitoring indices. This incident demonstrates the problems of establishing the source of cryptosporidiosis outbreaks in the absence of evidence of environmental abnormality, as well as possibly indicating that water conforming to current treatment standards may occasionally contain sufficient numbers of Cryptosporidium oocysts to cause sporadic cases or clusters.

Adolescent↗

1H NMR spectroscopic studies on the reactions of haloalkylamines with bicarbonate ions: formation of N-carbamates and 2-oxazolidones in cell culture media and blood plasma.

1H NMR spectroscopic methods have been applied to compare the in vitro reactivity of the renal papillary nephrotoxin 2-bromoethanamine (BEA) with those of selected halide-substituted nephrotoxic analogues, 2-chloroethanamine (CEA), 2-fluoroethanamine (FEA), and 1-phenyl-2-iodoethanamine (PIEA). The primary 1H NMR-detectable transformation during a 24 h incubation of confluent Madin Darby canine kidney (MDCK) cells with BEA, CEA, and FEA (at concentrations up to the IC50 determined by neutral red uptake) was the appearance in cell culture media of 2-oxazolidone (OX). Additional novel signals assigned as FEA carbamate (N-carbamoyl-2-fluoroethanamine) were observed in media collected following incubation of cells with FEA. We propose that N-carbamate intermediates are formed from the spontaneous reaction of these haloalkylamines with HCO(3-)-buffered growth media and that OX is formed from the carbamate via elimination of the hydrogen halide. Further 1H NMR experiments, conducted for up to 8 h at 25 degrees C on 5 mM solutions of BEA, CEA, and FEA in 2H2O containing a 20-fold excess of HCO3- at pH 7.6, demonstrated a time-dependent decrease in the concentration of the free haloalkylamines accompanied by the production of N-carbamate intermediates and OX. Under these pseudo-first-order reaction conditions, the formation of OX from BEA was complete within approximately 6 h. In similar reaction conditions OX formation from CEA (24 h after initiation) had reached 54% of its final equilibrium concentration. Equivalent experiments demonstrated that PIEA was almost completely converted to 4-phenyl-2-oxazolidinone (PHOX) within 2 h. These observations reveal the strong disposition of this series of haloalkylamines toward reaction with HCO3- and indicate that the compounds in this family may exist only transiently as free amines in vivo, where there will virtually always be excess HCO3-. The physiological relevance of the in vitro findings is further indicated by the NMR-detectable conversion of BEA to OX and also an alkylating aziridine (AZ) moiety in rat plasma containing BEA. The ability to form carbamoylated species and OX (or PHOX) may mediate the toxicity of this series of haloalkylamines and hence is potentially of considerable significance.

Animals↗

Prediction of urinary sulphate and glucuronide conjugate excretion for substituted phenols in the rat using quantitative structure-metabolism relationships.

1. The quantitative urinary excretion of the sulphate and glucuronide metabolites of 15 substituted phenols dosed to rat has been determined using high resolution 19F-nmr spectroscopy. 2. The urinary metabolic fate of each of the compounds was related to a series of calculated physicochemical properties for each compound to produce quantitative structure-metabolism relationships (QSMRs). Using these calculated molecular properties it was possible to predict the urinary recovery of xenobiotic material as a percentage of the administered dose, to classify the compounds according to their 'dominant' metabolite pattern and to predict quantitatively the proportions of glucuronide and sulphate conjugates in the urine by the use of multiple linear regression. 3. The quantitative predictions were tested by cross-validation and good prediction of total xenobiotic urinary recovery as a percentage of the administered dose was achieved based on an equation involving the electrophilic superdelocalizability at C4 (para to the hydroxyl function), the smallest principal ellipsoid axis dimension and the heat of formation. The largest moment of inertia and the electrophilic superdelocalizability at C3 were found to be the most significant factors for the prediction of the percentage glucuronide in the urine, and the urinary excretion of sulphate conjugates as a percentage of total urinary recovery was negatively correlated with the glucuronide excretion as little parent compound was excreted.

Animals↗