Glyoxal: an artefact from metronidazole and glyoxylic acid in urinary organic acid analysis.
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Biomedical subjects
Publications and source records attributed to V Walker.
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Using analytical procedures that are widely used by laboratories investigating metabolic disorders, we investigated urinary organic acid excretion by premature neonates who were receiving the usual clinical care. Our purpose was to provide a basis for the diagnosis of inherited organic acid defects. We analyzed 127 random (untimed) urine samples collected weekly from 22 infants of 25-32 weeks of gestation (median, 28 weeks). A wide variety of organic acids was excreted. After oximation, they were extracted with ethyl acetate and diethyl ether, derivatized to trimethylsilyl forms, and analyzed by gas-liquid chromatography on a nonpolar fused silica capillary column, with mass spectrometry for identification. Profiles for individual babies varied markedly on different occasions, reflecting their metabolic status and bacterial activity in the gut. There was no significant ketonuria. Three metabolites identified for the first time in urine from normal neonates were 2,3-butanediol, 3-hydroxy-2-butanone (acetoin), and 4-hydroxy-3-methoxyphenyllactic acid. Significantly increased excretion of 4-hydroxyphenyllactic acid and other phenolic acids occurred during parenteral feeding.
High-performance liquid chromatography is being used increasingly as a screening method to detect organic acid-urias, an important group of inherited metabolic disorders. Analysis is hampered by lack of a suitable specific detection system. We have carried out preliminary investigations to assess the potential value of liquid chromatography/mass spectrometry with a plasmaspray interface. Spectra of standard acids yielded intense [M-H]- ions with little fragmentation. Organic acids could not be identified in urine samples from healthy neonates because of poor sensitivity. However, urine from a baby with the inherited disorder methylmalonic aciduria showed a distinct peak of methylmalonic acid, easily identified owing to its high sample concentration.
1. The renal handling of calcium and magnesium was studied in six patients with persistent hypomagnesaemia after cis-platinum treatment for testicular tumours. 2. In comparison with normal subjects, the patients showed hypomagnesaemia (mean 0.54 mmol/l), which was associated with a normal urinary magnesium excretion (mean 4.83 mmol/24 h). Urinary calcium excretion was significantly lower in the patients than in the normal subjects (mean 2.05 vs 5.15 mmol/24 h, respectively; P less than 0.01), despite slightly higher total serum calcium levels (2.53 vs 2.38 mmol/l, respectively; P less than 0.05). During magnesium chloride infusion, when serum magnesium levels were comparable in patients and controls, urinary calcium excretion remained lower in the patients, indicating that hypomagnesaemia was not the cause of the hypocalciuria. 3. Dietary magnesium supplementation resulted in a significant increase in the serum magnesium levels in the patients, while dietary magnesium deprivation resulted in a comparable decrease in urinary magnesium excretion in patients and controls (to 1.46 and 2.00 mmol/day, respectively), although the serum magnesium level fell further (to 0.46 mmol/l) in the patients. 4. The dissociation of renal calcium and magnesium excretion appears to be part of the intrinsic tubular defect caused by cis-platinum. This dissociation of urinary calcium and magnesium excretion, which resembles that seen in Bartter's syndrome, may result from a lesion in the distal convoluted tubule.
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An ACTH-producing thymic carcinoid tumour was diagnosed in a 10-year-old girl, 8 years after bilateral adrenalectomy for Cushing's syndrome. The peptides produced by the tumour were characterised thoroughly. High circulating levels of beta-endorphin and other peptides may have contributed to mood and behaviour disturbances.
The calcium antagonist nimodipine blocks the effects of many vasoconstrictors of cerebrovascular smooth muscle and may reduce the incidence of delayed cerebral ischaemia following subarachnoid haemorrhage though not necessarily by inhibiting the development of angiographic cerebral vasospasm. Post-haemorrhagic CSF contains abnormally large quantities of various eicosanoids that partly reflect enhanced production by cerebral arteries. Does nimodipine affect this process? The extra-arterial and intra-arterial production of PG6 keto-F1 alpha, PGE2, PGF2 alpha and TXB2 were measured in perfused common carotid arteries taken from rabbits in which the arteries had been ensheathed by blood clot in vivo for 7 days. All rabbits were given the antifibrinolytic agent tranexamic acid to retard resolution of the clot, and half were given oral nimodipine (2 mg/kg/day) for 10 days. Nimodipine significantly reduced the extra-arterial production of TXB2 during the third and fourth hours of perfusion and, less consistently, the production of PGF2 alpha, PGE2 and PG6 keto-F1 alpha. Lutrol, the solvent for nimodipine, had no such effect.
The zinc status of 19 patients with chronic or recurrent genital infections and 18 patients with non-recurrent genital infections was assessed by measuring plasma and leucocyte zinc concentrations. Neither group of patients had plasma or leucocyte zinc concentrations that differed significantly from those of matched healthy controls. Each of six patients with chronic candidiasis had anergy to candidal antigen, as shown by delayed cutaneous hypersensitivity to intradermal injection of the antigen, but their zinc status was normal. This study provided no evidence of zinc deficiency in this small number of patients with acute non-recurrent or chronic recurrent genital infections.
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From its conception in the mid-1970s to the present, attention to fitness and education regarding preventive measures has increased at a phenomenal rate. Companies are involved in the attempt to keep employees healthy and health care cost-efficient. Reduced absenteeism, less turnover, more positive work attitudes, less strain and tension, improved work performance and health-related savings are but a few of the benefits cited by those involved in maintaining healthy lifestyles. At a time when the health care industry is undergoing major cost containment efforts, it seems most reasonable to adopt a preventive mindset and be concerned with employee fitness and lifestyle programs that lead to a decrease in immediate health care utilization.
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A premature infant with duplication of material from chromosome 11 and some features of the Beckwith-Wiedemann syndrome developed the bronze baby syndrome when exposed to phototherapy. He subsequently developed hepatocellular dysfunction and died aged 5 weeks. Post mortem examination revealed striking hypoplasia of intralobular bile ducts but little inflammatory change or necrosis in the liver.
The antitumor antibiotic mitomycin C is shown to form a covalent complex with calf thymus DNA under anaerobic conditions in the presence of either NADPH cytochrome c reductase/NADPH, xanthine oxidase/NADH, or the chemical reducing system H2/PtO2. Digestion of the complex with DNase I/snake venom diesterase/alkaline phosphatase yields a single mitomycin deoxyguanosine adduct as the major DNA alkylation product, identified as N2-(2'' beta,7''-diaminomitosen-1'' alpha-yl) 2'-deoxyguanosine (Structure 2). Two minor adducts, 2-5% each of the total adduct pool, are isolated and identified as the 1'' beta stereoisomer of 2 (Structure 3), and 10''-decarbamoyl-2 (Structure 7). The same results were obtained with M13 DNA and poly(dG-dC).poly(dG-dC); however, in the latter case, a minor adduct apparently possessing two deoxyguanosine and one mitomycin unit is isolated. Digestion of the covalent mitomycin-calf thymus DNA complex with nuclease P1 yields four dinucleotide adducts, all of which consist of 2 linked at its 3' end to each of the four possible 5' nucleotides (A, T, G, and C). Upon treatment of each dinucleotide adduct with snake venom diesterase/alkaline phosphatase, 2 is released along with the corresponding free nucleoside. In apparent conflict with the present results, previous reports from another laboratory have indicated that modification of calf thymus DNA by mitomycin C under conditions identical to those described here result in the isolation of three mitomycin C mononucleotide adducts possessing linkages of the drug to N2 and O6 of guanine and N6 of adenine. Evidence is shown suggesting that the latter adducts are actually three of the above four dinucleotide derivatives of 2 obtained independently by us and, thus, all of them in fact possess an identical N2-mitosenylguanine adduct moiety. Model-building studies indicate an excellent fit of the guanine N2-linked drug molecule inside the minor groove of B-DNA with no appreciable distortion of the DNA structure.
The sodium intake of preschool children in their home environment was investigated and the major sources of sodium other than added table salt identified. Thirty five children from a Southampton general practice were studied. Twenty four hour urinary sodium excretion was measured as a reliable indicator of daily total sodium intake. The daily intake of sodium other than that from added table salt, and of potassium and other nutrients, was also calculated from three day dietary diaries collected using the household measures method. Median excretion of sodium was 62 mmol/24h (range 28-105, 28 urine collections) and of potassium was 25 mmol/24 h (range 14-46). The sodium:potassium ratio was 2.7 (1.4-5.2). From the diaries, the average daily intake of sodium was 68 mmol (32-98) and of potassium was 47 mmol (24-95), and the sodium:potassium ratio was 1.4 (0.5-2.7) (median and ranges, 35 children). Foods contributing more than 30 mmol sodium to one day's intake were mainly processed convenience foods.