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Biomedical subjects

N B Roberts

Publications and source records attributed to N B Roberts.

At least 37 records · Page 2Linked to original sources
PubMed1999

Urinary catecholamine excretion in relation to renal function.

The urinary excretions of the free catecholamines noradrenaline, adrenaline and dopamine were measured in 50 patients (33 men and 17 women) with chronic renal failure. Stability studies showed that the catecholamines were stable in unacidified urine as long as the pH was not greater than 7.5 and the urine was acidified within 2-3 h of collection. The outputs of noradrenaline and dopamine correlated positively with creatinine clearance and in patients with clearances above 40 mL/min were similar to those in healthy volunteers (n = 20). However, adrenaline output was not correlated with creatinine clearance although it was lower in patients with renal failure compared with healthy volunteers. The urinary free catecholamine output during the first 10 days after a renal transplant was significantly less than normal, presumably because renal function was still impaired. However, in patients treated with cyclosporin A (CyA) combined with prednisolone the catecholamine excretion was lower compared with those treated with CyA and azathioprine. Impairment in renal function can have a marked effect on the output of free catecholamines and must be borne in mind when interpreting values that may have pathological significance.

Case-Control Studies↗
PubMed1999

Measurement of platinum in saliva of patients treated with cisplatin.

A procedure for the measurement of platinum (Pt) in the saliva of patients treated with cisplatin has been developed. The saliva is collected and solubilized in hyamine hydroxide before analysis by graphite furnace atomic absorption spectrometry using assay by standard additions. The method has an analytical detection limit of 0.025 microgram/mL and is precise, with coefficients of variation of 3-10.0% over a range of 0.05-2.0 micrograms/mL. Platinum was measured in saliva collected during an 8-h infusion of cisplatin from five patients, at the end of a 30-min infusion in nine, and 24 and 48 h later from a further 15 patients, all of whom were treated with cisplatin for squamous cell carcinoma of the neck. The platinum concentration in saliva taken at the end of a 30-min infusion was 0.27 +/- 0.23 microgram/mL (mean +/- 1 SD) but was below the detection limit of 0.025 microgram/mL at 24 and 48 h. After an 8-h infusion the salivary Pt was significantly less (0.12 +/- 0.04 microgram/mL; P < 0.05). The plasma Pt concentrations after 30-min and 8-h infusions were 2.98 +/- 1.03 and 2.54 +/- 0.59 micrograms/mL, respectively, and were not significantly different. The results indicate higher concentrations of free platinum in plasma after 30 min compared with an 8-h infusion. The monitoring of salivary concentrations of platinum may therefore provide a non-invasive way to study the unbound fraction of cisplatin in blood and facilitate optimization of cisplatin treatment.

Adult↗
PubMed1999

Evaluation of a new method for the analysis of free catecholamines in plasma using automated sample trace enrichment with dialysis and HPLC.

BACKGROUND: Analysis of urinary free catecholamines was automated recently, but analysis of plasma samples posed special difficulties. The present study was undertaken to evaluate a new method for the automated analysis of plasma catecholamines. METHODS: The procedure is based on an improved sample handling system that includes dialysis and sample clean-up on a strong cation trace-enrichment cartridge. The catecholamines norepinephrine, epinephrine, and dopamine are then separated by reversed-phase ion-pair chromatography and quantified by electrochemical detection. RESULTS: Use of a 740- microL sample is required to give the catecholamine detection limit of 0.05 nmol/L and analytical imprecision (CV) between 1.1% and 9.3%. The assay can be run unattended, although >12 h of analysis time is not recommended without cooling of the autosampler rack. Comparison (n = 68) of the automated cation-exchange clean-up with the well-established manual alumina procedure gave excellent agreement (mean, 3.78 +/- 2.76 and 3.8 +/- 2.89 nmol/L for norepinephrine and 0.99 +/- 1.72 and 1.08 +/- 1.78 nmol/L for epinephrine). Hemodialysis had no clear effect on plasma norepinephrine. Epinephrine concentrations were similar (0.05 < P < 0.1) in chronic renal failure patients (0.24 +/- 0.3 nmol/L; n = 15) and healthy controls (0.5 +/- 0.24 nmol/L; n = 31). Dopamine was not quantified, being usually <0.2 nmol/L. CONCLUSION: The availability of such a fully automated procedure should encourage the more widespread use of plasma catecholamine estimation, e.g., after dialysis, exercise, or trauma/surgery and in the investigation of catecholamine-secreting tumors, particularly in the anuric patient.

Autoanalysis↗
PubMed1998

Increased absorption of aluminium from a normal dietary intake in dementia.

Serum aluminium was significantly raised (p < 0.01) up to 2-3-fold, in patients with dementia including Alzheimers Disease (AD) 0.66 +/- 0.2 (mumol/l mean +/- 1 s.d.) and patients on regular aluminium hydroxide therapy 0.54 +/- 0.17, compared with healthy volunteers 0.21 +/- 0.13, although not as high as in patients with end stage renal failure on regular dialysis 0.88 +/- 0.42. The urine outputs (mumol/l mean +/- 1 s.d.) of aluminium and silicon, respectively, were also significantly increased up to 5-fold in dementia 2.89 +/- 1.78 (n = 23) and 1587 +/- 645 (n = 22) and patients on regular aluminium hydroxide therapy 5.03 +/- 2.08 (n = 8) and 998 +/- 364 (n = 21) compared with healthy volunteers 0.95 +/- 0.82 (n = 84) and 471 +/- 332 (n = 114). The increase in urine aluminium was thus associated with a similarly marked increase in the output of silicon. The increased absorption of aluminium in dementia patients is equivalent to the intestinal loading in Aludrox therapy. Also silicon appears to be important in the renal excretion of the absorbed aluminium. Whether this is a phenomenon related to the elderly or the process of dementia warrants further study.

Adult↗
PubMed1998

The relative merits of haemoglobin A1c and fasting plasma glucose as first-line diagnostic tests for diabetes mellitus in non-pregnant subjects.

HbA1c was measured by high-performance ion-exchange chromatography in 401 non-pregnant patients undergoing oral glucose tolerance tests (OGTT). All those with HbA1c>6.2% (reference range 3.8-5.5%) had diabetic OGTT (sensitivity 41%, specificity 100%). Although a fasting plasma glucose (FPG) cut-off > or =7.0 mmol l(-1), as recommended by the American Diabetes Association (ADA), had greater sensitivity (78%), false positives (12%) limited its usefulness, so more diagnostic confidence could be placed in a positive HbA1c. In agreement with the ADA, we found FPG gave only slightly lower diabetes prevalence than the OGTT, but this masked a significant number of individual discrepancies (false positives and negatives) cancelling out each other. The new ADA category of impaired fasting glucose did not correlate well with impaired glucose tolerance. HbA1c is insufficiently sensitive as a direct substitute for the OGTT. A third of subjects diabetic on OGTT had normal HbA1c values, so it cannot exclude diabetes as currently defined, but HbA1c screening could make sufficient positive diagnoses to reduce our non-pregnant OGTTs by one-fifth. If a 'risk threshold' for diabetic complications could be applied to HbA1c, it could replace the OGTT as a more pragmatic diagnostic/prognostic test.

Adolescent↗
PubMed1998

Measuring quality of life in children with rhinoconjunctivitis.

OBJECTIVE: The objective of this study was to develop, pretest, and validate a questionnaire to measure quality of life in children with seasonal allergic rhinoconjunctivitis (SAR). METHODS (DEVELOPMENT STUDY): Thirty-four children with SAR were enrolled from summer camps, notices in the media, and an allergy clinic (Southern Ontario). After generating a pool of 48 potentially important quality of life items, the children identified the ones that they experienced with their SAR and scored each for bother (1 = a little bothered to 4 = extremely bothered). Items identified most frequently and with the highest bother score were included in the Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ). The PRQLQ was pretested for ease completion and accuracy of understanding. RESULTS (DEVELOPMENT STUDY): The PRQLQ has 23 items in five domains (nose symptoms, eye symptoms, practical problems, other symptoms, and activities). Responses are given on a seven-point scale, and children are asked to score their experiences during the previous 7 days. METHODS (VALIDATION STUDY): Seventy-five children with symptomatic SAR were enrolled from notices in the media and a pediatric allergy clinic (Austin, Tex.). A single cohort design was used, with children assessed at 0, 1, and 3 weeks. The PRQLQ was administered to the children by a trained interviewer at 1 and 3 weeks. A conventional nasal symptom daily diary was completed for 1 week before each of these clinic visits. Global ratings were completed at the final visit. RESULTS (VALIDATION STUDY): In patients who were stable between clinic visits, the PRQLQ demonstrated good reliability (intraclass correlation coefficient = 0.93). The questionnaire was very responsive to change (p < 0.001) and was able to differentiate between patients who were in a stable clinical state and those whose clinical state changed between visits (p = 0.005). Correlations between the PRQLQ and diary scores were close to predicted and supported both the cross-sectional and longitudinal validity of the PRQLQ. CONCLUSIONS: The PRQLQ measures the quality of life impairments important to children with SAR. Children provide reliable and accurate responses, the measurement properties are strong, and the questionnaire can be used with confidence in clinical trials, clinical practice, and surveys.

Child↗
PubMed1998

Increased L-arginine transport in human erythrocytes in chronic heart failure.

1. Transport of L-arginine was investigated under zero-trans conditions in human erythrocytes from healthy donors and patients with heart failure. 2. Saturable influx of L-arginine was mediated by the classical cationic amino acid transport systems y+ and y+L. 3. The Vmax for L-arginine transport via system y+ increased from 292 to 490 mumol h-1 l-1 of cells in heart failure. 4. With system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), the Vmax for the transport of L-arginine via system y+L was unaffected in erythrocytes from patients with heart failure. 5. The inhibition of L-arginine and L-leucine influx by NG-monomethyl-L-arginine was similar in erythrocytes from control and heart failure patients. 6. Plasma L-arginine levels were reduced in patients with heart failure (59 mumol/l) compared with controls (125 mumol/l). Plasma from patients with heart failure also contained the endogenous L-arginine analogue NG-monomethyl-L-arginine, which was undetectable in plasma from controls. 7. Intracellular concentrations of L-arginine and NG-monomethyl-L-arginine were significantly elevated in erythrocytes from patients with heart failure compared with controls, consistent with an increased transport capacity for L-arginine and NG-monomethyl-L-arginine. 8. The present study provides the first evidence that system y+ mediates the increased transport of L-arginine in human erythrocytes from patients with chronic heart failure. These findings are similar to our previous results obtained in patients with chronic renal failure. Since both pathologies seem to present with an increased synthesis of nitric oxide, studies of L-arginine transport in erythrocytes may provide a valuable paradigm to study abnormalities of the L-arginine-nitric oxide signalling pathway.

Amino Acids↗
PubMed1998

Silicon and aluminium interactions in haemodialysis patients.

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.

Aluminum↗
PubMed1998

The incorporation of lamotrigine into the routine automated sequential trace enrichment of dialysates assay of anticonvulsants.

We have extended automated sequential trace enrichment of dialysates and high performance liquid chromatography to include the simultaneous assay of lamotrigine with other anticonvulsant drugs: phenobarbitone, carbamazepine and phenytoin. The procedure is reliable and precise (between-batch coefficients of variation < 2.8%) with no interference from other commonly prescribed drugs. Patients on lamotrigine presented with serum concentrations up to 67 mumol/L with no adverse effects, suggesting that the therapeutic range may need re-appraisal.

Anticonvulsants↗
PubMed1998

Hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, codon 143 CAC-->TAC--a variant with altered oxygen affinity that compromises measurement of glycated hemoglobin in diabetes mellitus: structure, function, and DNA sequence.

OBJECTIVE: To determine the nature and characteristics of a unique hemoglobin variant that causes a spurious increase in glycated hemoglobin (HbA1c). MATERIAL AND METHODS: Blood specimens from four unrelated persons with this hemoglobin variant were examined by conventional laboratory methods, including electrophoresis, high-performance ion-exchange chromatography, and isoelectric focusing; by amino acid sequence analysis, polymerase chain reaction-based DNA sequence analysis, and electrospray ionization mass spectrometry, to establish the molecular structure; and by studies of oxygen affinity under varied conditions, to define the functional characteristics of the hemoglobin variant. RESULTS: The unique hemoglobin variant observed in these four cases is due to the mutation CAC-->TAC, at beta-globin gene codon 143, corresponding to beta 143 (H21) His-->Tyr. This amino acid substitution affects an important 2,3-diphosphoglycerate binding site and slightly increases the oxygen affinity of the hemoglobin variant. CONCLUSION: A hitherto unrecognized hemoglobin variant, encountered in four unrelated persons of Irish or Scots-Irish ancestry, hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, has now been characterized at the molecular, structural, and functional levels. Although it is associated with a slight increase in oxygen affinity, it is without hematologic effect, and its only clinical significance is that it coelutes with HbA1c on ion-exchange chromatography and thereby causes a spurious increase in HbA1c and compromises the use of this analyte to monitor the treatment of diabetes mellitus.

Adult↗
PubMed1997

Transport of L-arginine and the nitric oxide inhibitor NG-monomethyl-L-arginine in human erythrocytes in chronic renal failure.

1. Transport of L-arginine and the nitric oxide synthase inhibitors NG-monomethyl-L-arginine and NG-nitro-L-arginine was investigated in human erythrocytes from healthy donors and uraemic patients on haemodialysis. 2. Although K(m) values for total L-arginine influx were not significantly different in erythrocytes freshly isolated from controls or uraemic patients, uraemia was associated with an increase in the Vmax for transport (826 compared with 1176 mumol h-1 l-1 of cells) which was reduced to control values after dialysis. 3. Saturable influx of L-arginine was mediated by the classical cationic amino acid transport system y+ and system y+L, known to transport cationic and neutral amino acids with higher affinity. 4. Under zero-trans conditions, the Vmax for L-arginine transport via system y+increased from 271 to 700 mumol h-1 l-1 of cells in uraemia, while K(m) values increased from 44 to 94 mumol/l. Dialysis had no significant effect on the kinetic parameters altered by uraemia. 5. Under zero-trans conditions, and with system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), transport of L-arginine via system y+L was unaffected by uraemia. 6. Saturable influx of NG-monomethyl-L-arginine was also mediated by systems y+ (K(m) = 56 mumol/l, Vmax = 353 mumol h-1 l-1 of cells) and y+L (K(m) = 17 mumol/l, Vmax = 51.3 mumol h-1 l-1 of cells) and, as with L-arginine, uraemia increased the transport capacity for NG-monomethyl-L-arginine. 7. Influx of the neutral nitric oxide synthase inhibitor NG-nitro-L-arginine was not readily saturable. 8. Intracellular concentrations of L-arginine and NG-monomethyl-L-arginine were significantly increased in erythrocytes from uraemic patients when compared with controls, consistent with an increased transport capacity for L-arginine and NG-monomethyl-L-arginine. 9. The present study provides evidence that system y+ mediates the increased transport of L-arginine and NG-monomethyl-L-arginine in human erythrocytes from patients with chronic renal failure. Our findings may have implications for the activity of the L-arginine-nitric oxide signalling pathway in vascular endothelial and smooth-muscle cells in uraemia.

Adult↗