Search PubMed⌕ Search

Biomedical subjects

V Walker

Publications and source records attributed to V Walker.

At least 19 recordsLinked to original sources
PubMed1999

Quantitative determination of trimethylamine in urine by solid-phase microextraction and gas chromatography-mass spectrometry.

Trimethylaminuria (fish odour syndrome) is diagnosed from an increase in urinary excretion of trimethylamine with decreased trimethylamine oxide. We report a new quantitative stable isotope dilution gas chromatography-mass spectrometry procedure for the analysis of these metabolites using solid-phase microextraction (SPME). Both polydimethylsiloxane and mixed Carboxen-polydimethylsiloxane SPME fibres were found to be suitable for the headspace extraction of TMA. This new sampling technique could have wide application for the analysis of volatile and semi-volatile compounds by metabolic screening laboratories.

Gas Chromatography-Mass Spectrometry↗
PubMed1998

Antisense to MDR1 mRNA reduces P-glycoprotein expression, swelling-activated C1- current and volume regulation in bovine ciliary epithelial cells.

Native ciliary epithelial cells from the ciliary epithelium of the eye exhibit anti-P-glycoprotein (P-gp) immunofluorescence. We have used an antisense 'knock-down' approach to investigate the relationship between P-gp and the volume-activated chloride current (IC1,swell) and its role in volume regulation. An antisense oligonucleotide to the human multidrug resistance (MDR1) gene, taken up by the cells in a dose-dependent manner, reduced P-gp immunofluorescence, inhibited IC1,swell and significantly increased the latency of activation of IC1,swell. Increasing the hypotonic stress did not result in an increased activation of ICl,swell. MDR1 antisense 'knock-down' also reduced the ability of the cells to volume regulate following a hypotonic challenge. These cells are known to express at least two volume-activated chloride channels, and the data suggest that P-gp is involved in the activation pathway of a subset of channels that contribute to whole-cell IC1,swell and participate in volume regulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Molecular analysis and prenatal diagnosis of human fumarase deficiency.

Fumarase deficiency is a rare autosomal recessive disorder of the citric acid cycle causing severe neurological impairment. The cDNA for both the rat and human enzymes has been cloned previously and shown to encode a coding region of 1.46 kb. To scan for mutations in fumarase-deficient patients we amplified the coding region of fumarase from fibroblast/lymphoblast cDNA employing the oligonucleotide primers designed from the published human and rat cDNA sequence. We then directly sequenced the polymerase chain reaction product. In seven unrelated patients, we detected four missense mutations (A265T, D383V, F269C, K187R), a nonsense mutation (W458X), a 3-bp AAA insertion that introduces an additional lysine residue at codon 435, and a spontaneous new mutation resulting in a 74-bp deletion (66del74). Seven at-risk pregnancies were monitored with one prenatal diagnosis of fumarase deficiency by molecular analysis and favorable outcome of the other pregnancies as predicted by enzyme assay of cultured fetal cells or molecular analysis.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Cultural sensitivity and readability of breast and prostate printed cancer education materials targeting African Americans.

Cancer prevention materials such as pamphlets, booklets, and fact sheets play a significant role in reducing cancer disparities. Little is documented in the literature about the cultural sensitivity of materials targeting African Americans. The Cancer Prevention Materials and African Americans project was conducted to assess the cultural sensitivity and readability of printed cancer education materials targeting African Americans. Results showed current breast and cancer materials are not written at appropriate reading levels, and only 54% of the breast and 40% of the prostate cancer materials were found to be culturally sensitive. Even though the materials are being developed and disseminated in health fairs, physician offices, barber shops, and other locations, the materials are still not reflective of the African-American populations and do not consider literacy, visual, written messages, and format as factors in their utilization. Future studies should assess the appropriateness of materials for African Americans to promote and prevent cancer in African Americans.

Black or African American↗
PubMed1997

Neonatal encephalopathy with a pungent body odour.

A neonate had transient unexplained bleeding into the gut, severe encephalopathy, and an abnormal pungent body odour. An inherited metabolic defect was excluded. The malodour was due to methanethiol and hydrogen sulphide, identified in urine. These sulphur compounds may have contributed to encephalopathy. Colonic bacteria were the probable source.

Brain Diseases↗
PubMed1996

Effects of hypoxia on urinary organic acid and hypoxanthine excretion in fetal sheep.

Severe birth asphyxia leads to a transient organic aciduria and increased hypoxanthine excretion. To investigate its origin and timing, we analyzed urine from 12 late gestation fetal sheep in utero subjected to moderately severe isocapnic hypoxia for 1 h. In six fetuses the carotid sinus nerves were cut to determine whether reflex peripheral vasoconstriction contributed to the changes in excretion. After a control period of 1 h, maternal inspired oxygen was reduced for 1 h so that fetal arterial oxygen tension fell significantly from 2.86 +/- 0.12 kPa (mean +/- SEM) to 1.55 +/- 0.04 kPa. The ewes were returned to normoxia, and monitoring was continued for 1 h. Fetal heart rate, arterial blood pressure, and femoral arterial blood flow (intact fetuses only) were recorded, and arterial pH, blood gases, and lactate were measured. Urine collected via a bladder catheter was analyzed for organic acids and hypoxanthine with gas chromatography-mass spectrometry. In intact fetuses, hypoxia increased excretion of hypoxanthine and several organic acids, notably lactic acid and intermediates of valine catabolism. Changes were apparent by 15 min, significant by 45 min, and maximal after reoxygenation. In denervated fetuses, there were small, significant, increases in organic acids and hypoxanthine by 45 min of hypoxia, but there was no surge in excretion posthypoxia. Hypoxia caused a large, significant, fall in femoral arterial blood flow in intact fetuses. We conclude that the extent of the reflex peripheral vasoconstriction, particularly in skeletal muscle, determines the amount of organic acid and hypoxanthine excretion and may explain similar biochemical disturbances after birth asphyxia. Urinary lactic acid measurement has a potential value for grading birth asphyxia.

Animals↗
PubMed1995

Health-related quality of life in patients with major depression who are treated with moclobemide.

A total of 651 depressed patients completed self-administered health-related quality-of-life (HRQOL) questionnaires during treatment with moclobemide in order to evaluate whether general and psychopathology-specific HRQOL questionnaires could detect changes in depressed patients receiving treatment. Patients were treated with moclobemide on an outpatient basis over an 8-week period; questionnaires were completed at weeks 0, 2, 4, and 8. At each assessment, patients completed one of two HRQOL questionnaires: namely, the General Health Questionnaire (GHQ), a psychopathology-specific HRQOL questionnaire, or the Short-Form 36 (SF-36), a general HRQOL instrument. Physicians were randomized to one of the two HRQOL questionnaires for all of their patients. Because the French version of the SF-36 was not available in the public domain, the patients of all Francophone physicians completed the GHQ, whereas the patients enrolled by Anglophone physicians completed either the SF-36 or the GHQ. The GHQ provides an overall score that measures the emotional dimensions of HRQOL, whereas the SF-36 provides scores in the following eight domains: physical functioning (PF), physical role functioning (PRF), emotional role functioning (ERF), social functioning (SF), bodily pain (BP), mental health (MH), vitality (VT), and general health perceptions (GHP). The GHQ and seven domains of the SF-36 detected a statistically significant linear trend (improvement) over time (p < 0.05). The change in the BP domain of the SF-36 was not statistically significant (p = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effect of intraventricular haemorrhage and rebleeding following subarachnoid haemorrhage on CSF eicosanoids.

CSF eicosanoid levels are raised following subarachnoid haemorrhage but not sufficiently to be vasoactive per se within the cerebral circulation. Rebleeding and intraventricular haemorrhage are two factors associated with a worse outcome after aneurysmal SAH. We have examined the effects of these two factors on the CSF levels of TXB2 (TXA2 metabolite), PG6-keto F1 alpha (prostacyclin metabolite), PGF2 alpha and PGE2 in 44 patients following subarachnoid haemorrhage. In 15 patients who had received no non-steroidal anti-inflammatory agent or dexamethasone, intraventricular haemorrhage increased the median levels of all four eicosanoids in ventricular CSF by 2.1-5.1-fold. In 4 patients who rebled, the CSF median levels of all four eicosanoids were raised up to 250-fold over the normal range. These concentrations are just sufficient to have cerebrovascular and neuromodulatory effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

The Canadian Multicenter Double-blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis.

Ursodeoxycholic acid, a dihydroxyl bile acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile acids are retained in the liver and are hepatotoxic. Ursodeoxycholic acid is the least-known hepatotoxic bile acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p < 0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether ursodeoxycholic acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis.

Adult↗
PubMed1993

Automated headspace gas chromatographic analysis of faecal short-chain fatty acids.

A method was developed and validated for analysis of faecal short-chain fatty acids using automated headspace gas chromatography. Quantification was by standard addition. Ghosting was minimized by lining the transfer tube from the headspace sampler to the gas chromatograph with deactivated fused silica and addition of formic acid to sample vials. Saturation of samples with lithium sulphate increased recoveries. The method was used to analyse small amounts of faecal matter collected from premature babies. Advantages of the technique are rapid, accurate, analysis of faecal specimens in batches, with minimum sample preparation.

Artifacts↗
PubMed1993

Hyperphosphataemia after enemas in childhood: prevention and treatment.

The case of a child with severe hyperphosphataemia and symptomatic hypocalcaemia secondary to retention of phosphate administered through an antegrade continence enema is reported. Caution should be exercised with the use of phosphate enemas and prompt action taken to remedy retention. The use of glucose with insulin in the emergency management of acute hyperphosphataemia is discussed.

Acute Disease↗
PubMed1993

Enteral feeding of premature infants with Lactobacillus GG.

The objectives of this study were to determine whether or not the probiotic Lactobacillus GG can colonise the immature bowel of premature infants and if so, does colonisation result in a reduction of the size of the bowel reservoir of nosocomial pathogens such as enterobacteriaceae, enterococci, yeasts or staphylococci, and does colonisation with Lactobacillus GG have any effect on the clinical progress and outcome. Twenty preterm infants with a gestational age of 33 weeks or less who were resident on a neonatal unit were studied from the initiation of milk feeds until discharge. The infants were randomised to receive either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8) colony forming units twice a day for two weeks. The clinical features of the two groups of infants were similar. Orally administered Lactobacillus GG was well tolerated and did colonise the bowel of premature infants. However, colonisation with Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and there was no evidence that colonisation had any positive clinical benefit for this particular group of infants.

Bacteria, Anaerobic↗
PubMed1993

Effects of feeding premature infants with Lactobacillus GG on gut fermentation.

The study aimed to find out whether gut colonisation of premature babies with a probiotic, Lactobacillus GG, modified enteric carbohydrate fermentation. Twenty preterm infants were randomised to receive Lactobacillus GG 10(8) colony forming units twice a day for two weeks or to a control group. Faecal short chain fatty acids (SCFAs), ethanol, and urinary 2,3-butanediol, were measured in parallel with microbiological studies. Lactobacillus GG colonised nine babies. From 1-28 days of age faecal SCFAs did not differ significantly from controls. Median and ranges were (treated and controls, respectively): acetic acid: 173 (trace-799), 166 (trace-700); propionic acid: 44 (trace-169), 37 (11-229); butyric acid: 31 (5-107), 37 (2-118) mumol/g dry weight. Ethanol was detected in more faecal samples from treated babies (65% v 37%), and at higher concentration (6.3 (trace-40) v 3.3 (0.6-8.8; one 229) mumol/g). 2,3-Butanediol was found in 66% of urine samples from treated babies and 58% from controls. On 83% of these occasions Klebsiella sp, Enterobacter sp, or Serratia sp were cultured from faeces. Lactobacillus GG had no obvious adverse effects on nutritionally important SCFAs. The small increase in ethanol excretion is unlikely to have clinical significance.

Anti-Bacterial Agents↗
PubMed1992

Effects of birth asphyxia on urinary organic acid excretion.

Using capillary gas chromatography-mass spectrometry, the effects of birth asphyxia on the urinary organic acid profile of term babies was investigated. Random urine samples were collected on days 1 and 8 from 19 babies with fetal distress, 19 with moderate birth asphyxia and 12 with severe asphyxia causing encephalopathy. Controls were 27 well neonates. Statistically significant abnormalities were found only for the severely asphyxiated group: increased concentrations of lactic, pyruvic, 3-hydroxybutyric, 4-hydroxyphenyllactic and 4-hydroxy-3-methoxymandelic acids, and excretion of four abnormal metabolites, 2-hydroxybutyric, 2-oxoisocaproic, 2-hydroxyisovaleric and 2-oxo-3-methylvaleric acids. Six other babies had increased lactic acid excretion, associated in four with transient 'jitterness' or hypotonia. Organic acid studies may help to grade the severity of perinatal asphyxia in the outcome or intervention studies.

3-Hydroxybutyric Acid↗
PubMed1991

Eicosanoid production by brain tumours in vivo--evidence for intracranial compartmentation.

Brain tumours produce prostaglandins in vitro; their in vivo production has been studied by determining the levels of prostaglandin F2 alpha, prostaglandin E2, 6-ketoprostaglandin F1 alpha and thromboxane B2 in tumour cyst fluid and ventricular CSF taken from 21 patients with a variety of intracranial tumours. The levels were high in tumour cyst fluid but there was no overall increase in ventricular CSF. Hence, brain tumours do not produce a consistent pattern of abnormality of eicosanoid concentrations in the ventricular CSF that would be useful for diagnosis. If brain tumours produce excess quantities of these prostaglandins in vivo as they do in vitro, these prostaglandins may be rapidly cleared by the cerebral microvasculature unless compartmentalized within a tumour cyst.

6-Ketoprostaglandin F1 alpha↗