Propionic acid and dipropylacetic acid in the urine of patients treated with dipropylacetic acid.

We report the gas Chromatographie estimation of propionic acid and dipropylacetic acid (an antiepileptic drug) in urine. The excretion of propionic acid in patients treated with dipropylacetic acid is comparable to the propionic acid excretion in vitamin B-12 anemia. The formation of propionic acid by degradation of dipropylacetic acid is discussed.     

Identification and quantitation of hydrazine in the urine of patients treated with hydralazine.

Hydrazine has been identified by gas chromatography-mass spectrometry in the 0- to 24-hr urine of patients administered hydralazine. With a specific gas chromatographic assay procedure, the amount of hydrazine in the 0- to 24-hr urine was determined in patients treated with various doses of hydralazine. The amount of hydrazine detected in the urine was greater in the slow acetylator phenotype than in the rapid acetylator phenotype. Studies indicated that hydrazine was not produced by chemical breakdown of hydralazine or its known metabolites in urine and therefore was unlikely to be a urinary artefact formed by chemical decomposition in the urine.     

Phenylpropionic acid in the urine of patients with phenylketonuria and normals

Normal urine and normal phenylketonuric urine contain very little phenylpropionic acid. A normal adult rapidly metabolized ingested deuterium-labelled phenylpropionic acid to deuterated benzoic acid. A single urine specimen from an atypical phenylketonuric patient contained a large amount of phenylpropionic acid. It is suggested that this was arising by the action of gut bacteria on poorly absorbed phenylalanine and escaped oxidation because of a temporary overloading of the oxidation pathways. In this patient a significant proportion of phenylalanine was being degraded in this way. Differences in gut flora may be a contributing factor to the apparent heterogeneity of phenylketonuria.     

Identification of childhood disability in Jamaica: the ten question screen.

This is the first in a series of papers that report the testing of two instruments for the identification and assessment of childhood disability by community workers (CWs) in Third World countries. It is part of the International Epidemiologic Study on Childhood Disability. The Ten Question Screen (TQ) was used as the main instrument to identify disability in a two stage population-based survey of 5478 children aged 2-9 years in Clarendon, Jamaica. In the second stage, TQ positive and 8% of the screen negative controls were professionally assessed by a doctor and a psychologist using standard criteria based on the main classification system of the ICIDH. Sensitivity of the TQ as a whole varied in different strata of the group and amongst different disabilities, from perfect in girls under 6 years, fits and motor disabilities and for serious disability in all group except boys over 5 years with cognitive disability. Specificity was good but the false positive rate was unacceptably high at 74%. It was concluded, firstly, that the validation of a simple questionnaire of perceptions of behaviour against objective measurements of impairments was perhaps not fair to the TQ. In spite of this, the TQ would be a very useful instrument in collecting disability data or for identifying people in need of rehabilitation help, if a way of reducing false positives could be found.     

Bile acid profiles in urine of patients with liver diseases

Abstract. Quantitative gas chromatography-mass spectrometry was used to study the metabolic profiles of unconjugated, conjugated and sulphated bile acids in urine of patients with intermittent intrahepatic cholestasis of unknown aetiology, cirrhosis of the liver, primary biliary cirrhosis, viral and toxic hepatitis and extrahepatic cholestasis. A large number of bile acids was present which can broadly be classified into four groups: cholic and chenodeoxycholic acids constituted between 49·4% and 77·9% of the total bile acids (mean values of the groups); deoxycholic and other 3,12-disubstituted bile acids between 1·3% and 12·3%, monohydroxy bile acids between 6·7% and 14·4% and bile acids hydroxylated at C-1 or C-6 between 4·6% and 14·6%. The high proportion of bile acids from the latter group, and the presence of tetrahydroxylated bile acids, clearly distinguished hepatic disease from the normal state. The metabolic profiles were very variable and there were few consistent differences between the groups of diseases studied. Norcholic acid constituted a significantly higher percentage of the total bile acids in cirrhotic patients (6·2 ± 6·8%) than in non-cirrhotic patients (1·3±1·8%, P<0·001). With this exception, no profile was specific for any type of intra- or extra-hepatic cholestasis. The excretion rates of the major l-hydroxylated bile acids were positively correlated to each other. The same was true for the major 6-hydroxylated bile acids. This may indicate that cholic, chenodeoxycholic and deoxycholic acids act as substrates for common 1- and 6-hydroxylating enzymes. Possibly the taurine conjugates are preferred substrates since 1-hydroxylated bile acids and hyocholic acid were found mainly in this fraction. A positive correlation between the excretion of sulphated 3β-hydroxy-5-cholenoic acid and 3β,12α-dihydroxy-5-cholenoic acid indicates a direct metabolic relationship between these compounds. Confirming previous data, a high proportion of bile acids was sulphated. The degree of sulphation increased with decreasing number of hydroxyl groups, reaching 100% for the monohydroxy and most of the dihydroxy acids. Tetrahydroxycholanoates were not sulphated, and sulphation of trihydroxycholanoates was positively correlated to the renal bile acid excretion rate. Bile from patients with intermittent intrahepatic cholestasis did not contain the tetrahydroxylated bile acids present in urine. Hyocholic acid was a very minor, mainly taurine conjugated, bile acid. Monohydroxy bile acids were usually below the detection limit. These data do not support the hypothesis that lithocholic acid participates in the initiation or perpetuation of intermittent intrahepatic cholestasis of unknown aetiology.     

Identification of fatty acid methyl esters in kidneys and livers of two patients with Reye's syndrome

An unusual lipid, having an Rf value between that of cholesterol ester and of triglyceride on thin-layer chromatography, was clearly demonstrated in lipids from kidneys and livers of two Japenese children with Reye's syndrome. Gas chromatography-mass spectrometry revealed that the unusual lipid from viscera of the patients was a mixture of fatty acid methyl esters. Whether the occurrence of fatty acid methyl ester is the result of an inborn error of metabolism common to both patients, who were the progeny of consanguineous marriages, or whether it is a common biochemical feature in Reye's syndrome remains the subject of future studies.     

Identification of N-ethylglycine in urine of cancer patients with metastatic bone disease

BACKGROUND: Previously, a HPLC method for the determination of N-terminal prolyl dipeptides, proline and hydroxyproline in urine with fluorescence detection after pre-column derivatization with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride (DMS-Cl) [Inoue H, Iguchi H, Kono A, Tsuruta Y. Highly sensitive determination of N-terminal prolyl dipeptides, proline and hydroxyproline in urine by high-performance liquid chromatography using a new fluorescent labelling reagent, 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride. J Chromatogr 1999;724:221-230] was developed to study the relation between those analytes and bone diseases. When the urinary analytes were measured, a large peak due to an unknown substance was recognized in the chromatograms of cancer patients with metastatic bone disease, although it was scarcely present in normal subjects. In this study, we identified the unknown substance. METHODS: The fluorescent fraction based on the unknown substance was collected using HPLC and the structure of the fluorescence product was analyzed with MS, (1)H NMR and (13)C NMR. RESULTS: The fluorescence product based on the unknown substance was established to be a DMS-derivative of N-ethylglycine. CONCLUSIONS: Excretion of N-ethylglycine in the urine of cancer patients with metastatic bone disease is recognized, although N-ethylglycine is scarcely excreted in the urine of normal subjects.     

Increased excretion of two sialic acid-containing trisaccharides in the urine of patients with rheumatoid arthritis

The urinary excretion of sialic acid-containing trisaccharides in patients with active rheumatoid arthritis was studied. Sialyl-lactose and sialyl-N-acetyllactosamine were identified and their excretion patterns studied by thin layer and gas chromatography. The urinary output of sialyl-lactose was greater in patients with active rheumatoid arthritis (48.2 +/- 6.1 mg/24 h, SEM, n = 6) than in healthy subjects (19.8 +/- 3.7 mg/24 h, SEM, n = 5; P less than 0.01). The excretion of sialyl-N-acetyllactosamine was also higher in the rheumatoid group (18.5 +/- 2.1 mg/24 h, SEM, n = 6) than in the controls (11.1 +/- 1.2 mg/24 h, SEM, n = 5; P less than 0.05). The qualitative excretion patterns of the sialyl-oligosaccharide fraction were similar for the two groups as judged from the thin layer chromatograms. Correlating the results with the clinical state of the patients with rheumatoid arthritis suggests that the urinary level of the sialyl-oligosaccharides reflects the activity of the disease. A proposed mechanism for the increased excretion of sialic acid-containing trisaccharides in rheumatoid arthritis is presented.     

Identification of a specific interleukin 1 inhibitor in the urine of febrile patients

The urine of febrile patients has been found to contain high concentrations of an inhibitor of interleukin 1 (IL-1)-induced thymocyte proliferation. The inhibitor is specific for IL-1 and does not block the effects of interleukin 2 (IL-2) or phytohemagglutin (PHA) on thymocytes, and it is not nonspecifically toxic for these cells. IL- 1 inhibitor can be found in the urine of normal individuals and afebrile patients, but is present in increased concentrations in the urine of patients with fever of diverse etiologies. Preliminary physicochemical characterization indicates that the inhibitor is a 20- 40-kdalton protein.     

七氟醚麻醉对降低肝癌患者术后恶心呕吐发生率的临床观察

目的探讨七氟醚麻醉降低肝癌患者术后恶心呕吐发生率的效果。方法选取80例肝癌患者,将其随机分为七氟醚麻醉组（A组）和异氟醚组（B组）,每组各40例。常规麻醉诱导后,A组麻醉维持用2%～3%七氟醚吸入麻醉,B组给予1.0%～1.5%异氟醚吸入。观察两组患者麻醉诱导后血压、心率变化、苏醒时间、术后疼痛、恶心呕吐情况。结果血流动力学变化平稳检测中A组血流动力学变化较平稳,优于B组（P〈0.05）,术后苏醒时间检测上A组短于B组（P〈0.05）;术后恶心呕吐情况检查上A组呕吐情况较少,优于B组（P〈0.05）,术后疼痛两组比较差异无统计学意义（P〉0.05）。结论七氟醚维持全静脉麻醉用于肝癌手术中麻醉平稳,血流动力学变化平稳,术后苏醒较快,术后恶心呕吐较少。     

Service needs of children with disabilities in Jamaica.

We investigated the service needs of children attending a medical assessment as part of a two stage survey of 2 to 9-year-old children in mid and south Clarendon, Jamaica. Parents were asked about symptoms relating to six different disabilities: visual, hearing, speech, motor, cognitive and fits. Following medical and psychological assessment, a diagnosis of mild, moderate, severe or no disability was made. For children with disabilities, the frequencies of five possible types of intervention recommended by the physician were analysed and related to the prevalence of the six disabilities in the parish. To estimate the needs of the Jamaican child population the figures were extrapolated based on an estimate of 1 million children under the age of 15 years. These needs were then compared with places in existing services. Of the disabled children, 62% needed special education, 29.5% needed community-based services, 21% needed spectacles, 21% needed specialist referral, and 6% required medical treatment. Although the vast majority of these needs are not met, many more could be met in the community if existing health and education personnel are trained in basic techniques of screening and assessment.     

Identification of undescribed medium-chain acylcarnitines present in urine of patients with propionic and methylmalonic acidemias

In urine of patients with propionyl-CoA carboxylase deficiency or with methylmalonic acidemia, carnitine esters of 2-methyl-branched fatty acids of all chain lengths between 4 and 9 atoms of carbon were identified during the acute phase of the diseases. The chemical structure of these compounds was obtained by gas chromatography-mass spectrometry analysis of their fatty acid moieties in their free and picolinyl ester forms. We suggest mechanisms for the biosynthesis of these branched fatty acids, and their accumulation in urine during episodes of caloric imbalance.     

Characterization of the acid beta-D-galactosidases from human urine.

Acid beta-D-galactosidases (EC 3.2.1.23) from human urine samples have been characterized using GM1-ganglioside, asialofetuin, and 4-MU-beta-D galactopyranoside. Sepharose 6-B column chromatography of crude urine supernatant fluids resolved three forms of acid beta-D-galactosidase activity with apparent molecular weights of 500 X 10(3)--700 X 10(3) (I), 90 X 10(3)--120 X 10(3) (II), and 20 X 10(3)--27 X 10(3) (III), which hydrolyzed 4-MU-beta-D-galactopyranoside, GM1-ganglioside and asialofetuin. The crude urine supernatant fluids and the separated forms of acid beta-D-galactosidase exhibited similar apparent KM values for the respective substrates. Starch gel electrophoresis of urine samples at pH 7.0 revealed a slow anodally migrating form of acid beta-D-galactosidase which electrophoretically corresponded to form I and a faster anodally migrating form corresponding to form II. Form III migrated as a composite of forms I and II suggesting that aggregation to the larger molecular weight activity forms occurred during starch gel electrophoresis. This report represents the first characterization of urinary acid beta-D-galactosidase with respect to naturally occurring glycolipid and glycoprotein substrates. In addition, data is presented to indicate that the enzyme may be composed of an enzymatically active form with an apparent molecular weight of 20 X 10(3)--27 X10(3), which is also capable of hydrolyzing the glycolipid and glycoprotein substrates.