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The present study was performed to investigate the effect of amino acids during the intestinal and postabsorptive phase of digestion on proximal gastric motor function measured with an electronic barostat. Eight healthy volunteers participated in three experiments performed during continuous infusion of: (1) intravenous and intraduodenal saline, (2) intraduodenal amino acids, and (3) intravenous amino acids. Both intraduodenal and intravenous amino acids induced gastric relaxation and increased gastric compliance. Only during intraduodenal amino acids did plasma CCK levels increase significantly. Correlation between intragastric volume measurements (with pressure set at MDP + 2 mm Hg) and plasma CCK levels was 0.90 (P < 0.001) during the early intestinal phase. Relaxation of the proximal stomach is related to plasma CCK in the early intestinal phase, whereas in the postabsorptive phase of amino acids other mechanisms play a role in proximal gastric relaxation.

To assess the prevalence of impaired homocysteine metabolism in young adults with arterial occlusive disease, 80 consecutive patients under 45 years old were screened. Various laboratory blood investigations and a standardized methionine loading test were performed. In the first 52 patients plasma levels of free homocysteine were determined; thereafter the levels of total homocysteine (a more sensitive measure of impaired homocysteine metabolism) were measured. The methionine loading test was abnormal in 15 patients (19 per cent) who did not differ from the other 65 with respect to prevalence of other risk factors, clinical characteristics, and electrocardio-graphic and angiographic findings. Blood levels of glucose, vitamins B6and B12, folate, protein C and protein S, fibrinogen and low-density lipoprotein cholesterol did not differ significantly between the two groups. The prevalence of impaired homocysteine metabolism in young patients with arterial occlusive disease is greater than the 1–2 per cent found in the normal population.

The electron impact mass spectral behaviour of 14 synthetically prepared mercapturic acid methyl esters was examined. The most important and characteristic fragmentation reactions are discussed and special emphasis is made on the occurrence and the mechanism of two fragmentation pathways, which were recognized as ‘retro-Michael’ reactions. In principle, each reaction may result in the formation of two typical ions. In addition, three characteristic ‘key-ions’ originating from the N-acetyl(-l-)cysteine methyl ester part of the mercapturic acids were recognized in all mercapturic acid methyl esters investigated; these ‘key-ions’ can most probably be used as a tool for the qualitative as well as the quantitative analysis of mercapturic acids by gas chromatogra–phy mass spectrometry in biological fluids.

A large family with adrenoleukodystrophy is described and the case histories of two clinically symptomatic and related male patients are presented. Clinical, biochemical and genetic screening of their family demonstrated two clinically affected males, one biochemically affected male and five carrier females. Two women were symptomatic; one suffered an acute exacerbation. One female was diagnosed as a carrier, based on genetic analysis and the family history only. Endocrinological screening was performed in the five affected males, demonstrating an elevated adrenocorticotrophic hormone level and a normal cortisol level in two, as evidence of compensated adrenocortical failure.

Z- and E-1,3-dichloropropene, mutagenic geometric isomers and major constituents of commercial soil fumigants, were found to be metabolized to mercapturic acid derivatives by the rat. Extremely small quantities of mixtures of the parent compounds were administered intraperitoneally to the rat and the isomeric urinary mercapturic acids were quantified in three ways. Gas chromatographic procedures with nitrogen selective, sulphur selective and mass spectrometric detection, using negative chemical ionization with single ion detection, were evaluated with respect to selectivity and sensitivity. Applying the former two techniques, urinary mercapturic acids could still be quantified following 5 µg doses of each of the dichloropropene isomers. With gas chromatography-negative chemical ionization mass spectrometry, only mercapturic acid metabolites arising from 25 µg doses and higher could be quantified because of interference from endogenous compounds. These results suggest that all three analytical methods can be used to determine exposure of men to soil fumigants containing low levels of 1,3-dichloropropene.

An infant with feeding difficulties, hypotonia, lactic acidemia, and severe hypoketotic hypoglycemia died at the age of 7 months of liver disease. Electron microscopy revealed abnormal mitochondria. Biochemical studies of mitochondria) enzymes in liver showed a decreased activity of complexes I, III, and IV. Mitochondrial DNA (mtDNA) content was reduced in liver (7% of the mean value in control subjects) and in muscle (50%). In kidney, brain, and heart, the mtDNA content was normal. The liver-specific mtDNA depletion syndrome in this patient manifested itself with features of both a respiratory chain defect and a mitochondria) fatty acid oxidation defect. Syndromes involving depletion of mtDNA can be diagnosed only when both the activity of the respiratory chain enzymes and the content of mtDNA are investigated in the most affected tissues.

Very long chain acyl‐coenzyme A (acyl‐CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial β‐oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified stongly elevated levels of tetradecenoic acid, 14:1(n‐9), tetradecadienoic acid, 14:2(n‐6), and hexadecadienoic acid, 16:2(n‐6). Palmitoyl‐CoA and behenoyl‐CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L‐carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis.

Background: Intraluminal nutrients increase superior mesenteric artery (SMA) blood flow. Little is known about the effect of circulating nutrients. Methods: The effect of a commercially available mixed amino acids solution, given either intravenously (IVAA) or intraduodenally (IDAA), on SMA hemodynamics was investigated in five healthy volunteers (three men, two women; 20-30 years old). Amino acids were given at a rate of 250 mg protein/kg/h for 2 h. Saline was used as control solution. Doppler ultrasound measurements of SMA hemodynamics were performed after 0, 30, 60, and 120 min. Results: IVAA had no significant effect on SMA hemodynamics. In contrast, IDAA significantly (P < 0.05) increased SMA flow volume by 60-80% over basal and the IVAA experiment. This increase in SMA flow volume during IDAA resulted primarily from a significant (P < 0.05) increase in time-averaged velocity. During IDAA both the peak systolic velocity and the end-diastolic velocity increased significantly (P < 0.05). Conclusions: In healthy subjects intraduodenal, hut not intravenous, amino acids significantly increase SMA blood flow.

A 2.5-year-old girl presented with severely delayed speech development and mild motor retardation. Urinary organic acid analysis showed the presence of 4-hydroxybutyric acid and other metabolites consistent with the diagnosis 4-hydroxybutyric aciduria. Succinic semialdehyde dehydrogenase activity was absent in lymphocyte lysates. The clinical symptoms in this case were unusually mild compared to previously reported patients. No correlation was found between the mild symptoms and the levels of metabolite excretion or the residual succinic semialdehyde dehydrogenase activity in this patient compared to more severely affected cases.

Background. Intestinal mucosal ischaemia can occur in infants and children during and after cardiac surgery. Severe decreases in mucosal perfusion may cause complications such as necrotizing enterocolitis and postoperative mortality. We investigated gut permeability in paediatric patients undergoing cardiac surgery using the dual sugar permeability test and absorption of two other saccharides. Methods. Thirty-four patients undergoing palliative or corrective surgical procedures with and without cardiopulmonary bypass were investigated. Intestinal permeability was measured using 3-O-methyl-d-glucose, d-xylose, l-rhamnose and lactulose, given orally after induction of anaesthesia and 12 and 24 h later. Results. Lactulose/rhamnose ratios were raised from the outset [median 0.39 (confidence interval 0.07–1.8 for patients undergoing operations without cardiopulmonary bypass and 0.30 (0.02–2.6) with cardiopulmonary bypass]. The highest lactulose/rhamnose ratios were recorded 12 h after surgery 0.32 (0.07–6.9), when cardiopulmonary bypass was used. This is approximately seven times the value expected in healthy children. There was an improvement in patients not undergoing cardiopulmonary bypass: 0.22 (0.03–0.85) 12 h and 0.11 (0–0.48) 24 h after induction of anaesthesia. Patients undergoing repair of aortic coarctation showed the fastest recovery: 0.09 (0.03–0.31) 12 h and 0.07 (0.04–0.35) 24 h after induction of anaesthesia. Conclusions. Patients with congenital heart defects have abnormal gut permeability when compared with healthy children of similar age. Cardiopulmonary bypass seems to affect the intestinal barrier morphologically (lactulose and rhamnose absorption) and functionally (3-O-methyl-d-glucose and d-xylose absorption).

Solutions of the generally rather unstable title reagents (III) are obtained by treating (I) or (II) with NCS or Br2, respectively.