992 results found
Gartland KP, Sanins SM, Nicholson JK, et al., 1990, Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data., NMR Biomed, Vol: 3, Pages: 166-172, ISSN: 0952-3480
A computer-based pattern recognition (PR) approach has been applied to the interpretation of 1H NMR generated urinalysis data in a variety of experimental toxicity states in the rat. 1H NMR signal intensities for each endogenous metabolite in urine were regarded as coordinates in multi-dimensional space and analysed using computer pattern recognition methods through which the dimensionality was reduced for display and categorization purposes. Initially 17 metabolic dimensions were used which were defined by the scored relative concentrations of a variety of urinary metabolites detected in 1H NMR spectra. By employing the unsupervised learning methods of 2- and 3-dimensional nonlinear mapping (NLM) different types of toxin (hepatotoxins, cortical and papillary nephrotoxins) could be classified according to NMR-detectable biochemical effects in the urine. The robustness of the classification methods, and the influence of the addition of new scored biochemical data reflecting dose response situations, nutritional effects on toxicity, sex differences in biochemical response to toxins and addition of a new toxin class (testicular toxin) to the pattern recognition analysis were also evaluated. We find that the initial training set maps are fundamentally stable to the addition of all data types and that the PR methods correctly 'predicted' the toxicological effects of the test compounds. These results confirm the power and wide applicability of linked PR and 1H NMR urinalysis as an approach to the generation and classification of acute toxicological data.
, 1990, Regression dilution bias., Lancet, Vol: 335, Pages: 1230-1231, ISSN: 0140-6736
POWELL JJ, GARTLAND KPR, LOMBARD M, et al., 1990, PROTON NMR-SPECTROSCOPY OF BILE AS A MARKER OF LIVER-FUNCTION IN LIVER-TRANSPLANT PATIENTS, CLINICAL SCIENCE, Vol: 78, Pages: P13-P13, ISSN: 0143-5221
SEQUEIRA S, SO PW, EVERETT JR, et al., 1990, H-1-NMR SPECTROSCOPY OF BIOFLUIDS AND THE INVESTIGATION OF XENOBIOTIC-INDUCED CHANGES IN LIVER BIOCHEMISTRY, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 945-949, ISSN: 0731-7085
WADE KE, WILSON ID, TROKE JA, et al., 1990, F-19 AND H-1 MAGNETIC-RESONANCE STRATEGIES FOR METABOLIC STUDIES ON FLUORINATED XENOBIOTICS - APPLICATION TO FLURBIPROFEN [2-(2-FLUORO-4-BIPHENYLYL)PROPIONIC ACID], JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 401-410, ISSN: 0731-7085
GARTLAND KPR, BEDDELL CR, LINDON JC, et al., 1990, A PATTERN-RECOGNITION APPROACH TO THE COMPARISON OF PMR AND CLINICAL CHEMICAL-DATA FOR CLASSIFICATION OF NEPHROTOXICITY, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 963-968, ISSN: 0731-7085
HOLMES E, FOXALL PJD, NICHOLSON JK, 1990, PROTON NMR ANALYSIS OF PLASMA FROM RENAL-FAILURE PATIENTS - EVALUATION OF SAMPLE PREPARATION AND SPECTRAL-EDITING METHODS, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 955-958, ISSN: 0731-7085
HOLMES E, BONNER FW, GARTLAND KPR, et al., 1990, PROTON NMR MONITORING OF THE ONSET AND RECOVERY OF EXPERIMENTAL RENAL DAMAGE, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 959-962, ISSN: 0731-7085
GARTLAND KPR, ANTHONY ML, BEDDELL CR, et al., 1990, PROTON NMR-STUDIES ON THE EFFECTS OF URANYL-NITRATE ON THE BIOCHEMICAL-COMPOSITION OF RAT URINE AND PLASMA, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 951-954, ISSN: 0731-7085
SANINS SM, NICHOLSON JK, ELCOMBE C, et al., 1990, HEPATOTOXIN-INDUCED HYPERTAURINURIA - A PROTON NMR-STUDY, ARCHIVES OF TOXICOLOGY, Vol: 64, Pages: 407-411, ISSN: 0340-5761
GRAY J, NICHOLSON JK, CREASY DM, et al., 1990, STUDIES ON THE RELATIONSHIP BETWEEN ACUTE TESTICULAR DAMAGE AND URINARY AND PLASMA CREATINE CONCENTRATION, ARCHIVES OF TOXICOLOGY, Vol: 64, Pages: 443-450, ISSN: 0340-5761
GARTLAND KPR, EASON CT, BONNER FW, et al., 1990, EFFECTS OF BILIARY CANNULATION AND BUTHIONINE SULFOXIMINE PRETREATMENT ON THE NEPHROTOXICITY OF PARA-AMINOPHENOL IN THE FISCHER-344 RAT, ARCHIVES OF TOXICOLOGY, Vol: 64, Pages: 14-25, ISSN: 0340-5761
SPURWAY TD, GARTLAND KPR, WARRANDER A, et al., 1990, PROTON NUCLEAR-MAGNETIC-RESONANCE OF URINE AND BILE FROM PARACETAMOL DOSED RATS, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 969-973, ISSN: 0731-7085
Wade KE, Wilson ID, Troke JA, et al., 1990, <sup>19</sup>F and <sup>1</sup>H magnetic resonance strategies for metabolic studies on fluorinated xenobiotics: Application to flurbiprofen [2-(2-fluoro-4-biphenylyl)propionic acid], Journal of Pharmaceutical and Biomedical Analysis, Vol: 8, Pages: 401-410, ISSN: 0731-7085
Strategies for the use of 1H and 19F nuclear magnetic resonance (NMR) spectroscopy as an aid to the study of the metabolic fate of fluorinated drugs are discussed with reference to the application of these methods to flurbiprofen metabolism in man. 1H and 19F NMR analysis of untreated urine enabled the detection of two major and eight minor metabolites of the drug. The two major metabolites were identified using a combination of NMR spectroscopy, solid-phase extraction chromatography with 19F and 1H NMR detection and chemical hydrolysis to a flurbiprofen glucuronide and the glucuronide of the 4-hydroxy metabolite. 1H-19F 2D shift correlated spectroscopy and spin-echo difference experiments are discussed in relation to their use in the structural identification of drug metabolites. © 1990.
Sequeira S, So PW, Everett JR, et al., 1990, <sup>1</sup>H-NMR spectroscopy of biofluids and the investigation of xenobiotic-induced changes in liver biochemistry, Journal of Pharmaceutical and Biomedical Analysis, Vol: 8, Pages: 945-949, ISSN: 0731-7085
Glen RC, 1990, Recent progress in computational chemistry and molecular graphics applied to drug design, Drug News and Perspectives, Vol: 3, Pages: 332-336, ISSN: 0214-0934
GHAURI FYK, BLACKLEDGE CA, WILSON ID, et al., 1990, STUDIES ON THE METABOLISM OF FLUORINATED XENOBIOTICS IN THE RAT USING F-19-NMR AND H-1-NMR SPECTROSCOPY, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 939-944, ISSN: 0731-7085
WILSON ID, WADE KE, NICHOLSON JK, 1989, ANALYSIS OF BIOLOGICAL-FLUIDS BY HIGH-FIELD NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY, TRAC-TRENDS IN ANALYTICAL CHEMISTRY, Vol: 8, Pages: 368-374, ISSN: 0165-9936
FOXALL PJD, BENDING MR, GARTLAND KPR, et al., 1989, ACUTE RENAL-FAILURE FOLLOWING ACCIDENTAL CUTANEOUS ABSORPTION OF PHENOL - APPLICATION OF NMR URINALYSIS TO MONITOR THE DISEASE PROCESS, HUMAN TOXICOLOGY, Vol: 8, Pages: 491-496, ISSN: 0144-5952
Dyer AR, Elliott P, 1989, The INTERSALT study: relations of body mass index to blood pressure. INTERSALT Co-operative Research Group., J Hum Hypertens, Vol: 3, Pages: 299-308, ISSN: 0950-9240
In INTERSALT, the relationship between body mass index (kg/m2) and blood pressure was studied in 10,079 men and women aged 20-59, sampled from 52 centres around the world, based on a standardised protocol with central training of observers, a central laboratory and extensive quality control. Body mass index-blood pressure relationships were first studied in men and women within each centre, and results of these regression analyses were then pooled for all 52 centres. With adjustment for age, alcohol intake, smoking, and sodium and potassium excretion, body mass index was positively associated with systolic blood pressure among men in 51 of 52 centres and among women in 47, significantly so in 24 and 27, respectively. Body mass index was positively associated with diastolic blood pressure in 51 and 49 centres in men and women, respectively, significantly so in 33 and 31. When the within centre regression coefficients were pooled, the pooled coefficients were highly significant in all analyses (P less than 0.001), and were similar for those aged 20-39 and 40-59. Overall, a 10 kg difference in body weight was associated on average with a 3.0 mmHg difference in systolic and a 2.2 mmHg difference in diastolic pressure. In further analyses across centres, median body mass index was related significantly to median systolic blood pressure, median diastolic pressure and the prevalence of hypertension in both men and women. Body mass index was related to the slopes of systolic and diastolic blood pressure with age in women, but not in men. These INTERSALT findings confirm the importance of the association between body weight and blood pressure. Differences of 2-3 mmHg in systolic blood pressure on a population basis have been shown to be associated with differences in stroke mortality rates of 6-9 per cent and in coronary death rates of 4-6 per cent.
CARVALHO JJM, BARUZZI RG, HOWARD PF, et al., 1989, BLOOD-PRESSURE IN 4 REMOTE POPULATIONS IN THE INTERSALT STUDY, HYPERTENSION, Vol: 14, Pages: 238-246, ISSN: 0194-911X
NICHOLSON JK, HIGHAM DP, TIMBRELL JA, et al., 1989, QUANTITATIVE HIGH-RESOLUTION H-1-NMR URINALYSIS STUDIES ON THE BIOCHEMICAL EFFECTS OF CADMIUM IN THE RAT, MOLECULAR PHARMACOLOGY, Vol: 36, Pages: 398-404, ISSN: 0026-895X
Nicholson JK, Gartland KP, 1989, 1H NMR studies on protein binding of histidine, tyrosine and phenylalanine in blood plasma., NMR Biomed, Vol: 2, Pages: 77-82, ISSN: 0952-3480
The binding of histidine (His), phenylalanine (Phe) and tyrosine (Tyr) to macromolecules in blood plasma and serum has been investigated by high resolution 1H NMR spectroscopy. In single pulse and spin-echo spectra of quality control bovine serum and normal human plasma, there are no resonances in the chemical shift range to high frequency of delta = 5.3 ppm when measured in the pH* (meter reading, uncorrected for the presence of 2H2O) range 3 to 8.5. On acidification of the plasma to pH* less than 2.5, resonances from His and Phe are observable. In plasma from patients with Wilson's disease, weak signals from His and Tyr are seen in spin-echo spectra at pH* 7.6, but increase in strength on acidification and signals from Phe appear at pH* 1.8. Addition of standard solutions containing Tyr, His and especially Phe and Trp to plasma at neutral pH* results in poor recovery of their expected signal intensity in spin-echo spectra. Addition of 2 M urea to bovine plasma at pH* 4.5 results in the appearance of Phe signals. These data are consistent with Phe and Tyr (and to a lesser extent His) being bound in or to a macromolecular structure at neutral pH from which there is relatively slow exchange with the free solution environment. Experiments with model solutions suggest that serum albumin has a high capacity for binding aromatic amino acids (stabilized by hydrophobic interactions) at neutral pH and this is responsible for the NMR-invisibility of Tyr and Phe in blood plasma.
JOHNSON AM, WADSWORTH J, ELLIOTT P, et al., 1989, A PILOT-STUDY OF SEXUAL LIFESTYLE IN A RANDOM SAMPLE OF THE POPULATION OF GREAT-BRITAIN, AIDS, Vol: 3, Pages: 135-141, ISSN: 0269-9370
GARTLAND KPR, BONNER FW, NICHOLSON JK, 1989, INVESTIGATIONS INTO THE BIOCHEMICAL EFFECTS OF REGION-SPECIFIC NEPHROTOXINS, MOLECULAR PHARMACOLOGY, Vol: 35, Pages: 242-250, ISSN: 0026-895X
NICHOLSON JK, WILSON ID, 1989, HIGH-RESOLUTION PROTON MAGNETIC-RESONANCE SPECTROSCOPY OF BIOLOGICAL-FLUIDS, PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY, Vol: 21, Pages: 449-501, ISSN: 0079-6565
GARTLAND KPR, EASON CT, WADE KE, et al., 1989, PROTON NMR-SPECTROSCOPY OF BILE FOR MONITORING THE EXCRETION OF ENDOGENOUS AND XENOBIOTIC METABOLITES - APPLICATION TO PARA-AMINOPHENOL, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 7, Pages: 699-707, ISSN: 0731-7085
TULIP K, NICHOLSON JK, TIMBRELL JA, 1989, A STUDY OF THE METABOLISM OF DIMETHYLFORMAMIDE IN THE RAT BY HIGH-RESOLUTION PROTON NMR-SPECTROSCOPY, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 7, Pages: 499-505, ISSN: 0731-7085
GARTLAND KPR, BONNER FW, TIMBRELL JA, et al., 1989, BIOCHEMICAL-CHARACTERIZATION OF PARA-AMINOPHENOL-INDUCED NEPHROTOXIC LESIONS IN THE F344 RAT, ARCHIVES OF TOXICOLOGY, Vol: 63, Pages: 97-106, ISSN: 0340-5761
Marmot MG, Elliott P, 1989, Public health measures for blood pressure control in the whole community., Clin Exp Hypertens A, Vol: 11, Pages: 1171-1186, ISSN: 0730-0077
One approach to the prevention of blood pressure-associated cardiovascular disease is to find increased numbers of "hypertensives" and bring them under treatment. A complementary approach is to attempt to change the blood pressure distribution of the whole population. It can be calculated that, if the association between blood pressure level and mortality were reversible, a reduction of diastolic blood pressure of 5 mmHg in the population mean would be associated with a substantial reduction in cardiovascular mortality. The assumption of reversibility of risk of coronary heart disease may be more reasonable in the long than in the short term. The evidence from INTERSALT and other studies suggests that readily achievable changes in sodium and potassium intake, in body mass index and in alcohol intake, could lead to average blood pressure change across a whole population of 5 mmHg. A major task for public health is the implementation of such life-style changes among different social class and ethnic groups.
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