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Biomedical subjects

V Grey

Publications and source records attributed to V Grey.

10 recordsLinked to original sources

Inaccuracy of high-performance liquid chromatography estimation of haemoglobin F in the presence of increased haemoglobin A1c.

Increasingly high-performance liquid chromatography is being used for identification and quantification of normal and variant haemoglobins. In many laboratories, the Beta Thal Short programme of the Bio-Rad Variant II instrument is used for this purpose. We noted that a factitious elevation of haemoglobin F was sometimes observed in diabetic patients and therefore carried out a systematic study of this phenomenon. We found discrepant results in 41% of samples from diabetic patients but in no normal volunteers. This factitious elevation could be predicted from a retention time for haemoglobin F of more than 1.15 min, the normal retention time being 1.08-1.15 min. Haemoglobinopathy laboratories need to be alert to the possibility of this erroneous result.

Chromatography, High Pressure Liquid↗

Sweat collection for testing in Canadian Cystic Fibrosis Centers, is it optimal?

OBJECTIVES: The goal of this study was to examine the ability of the current Canadian CF center network to conduct sweat testing, with a particular focus on testing in infants less than 3 months old. METHODS: Surveys were sent to the 37 CF centers in Canada supported by the Canadian CF Foundation, and results were interpreted with respect to their ability to obtain adequate sweat volumes in children less than 3 months and potential factors influencing these results. RESULTS: Ten centers that care for adult patients referred patients to their local pediatric CF center for sweat testing; the remaining 27 centers conducted sweat tests and 26 responded. Insufficient sweat volume results in children <3 months occurred in a median of 18.3% of tests. The corresponding proportion for the remaining population was 4.5% (P < 0.001). 15 of 19 centers had an incidence of >5% of insufficient tests in children <3 months of age, and 9 of 19 had an incidence of <20% in this age group. Six of 19 had an incidence of >5% of insufficient sweat volumes in older children and adults. CONCLUSIONS: Standardization of testing procedures is required to reduce the rates of insufficient sweat volumes in both infants less than 3 months old and children >3 months old. This will decrease the need for repeat testing and delay in diagnosis.

Adult↗

Monitoring of 25-OH vitamin D levels in children with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are at risk for malabsorption of fat-soluble vitamins, and those with low 25-OH vitamin D levels have a higher risk of low bone mineral density and long-term skeletal complications. It is currently recommended that vitamins A and E be monitored yearly; however, no recommendations exist for 25-OH vitamin D. Because all three vitamins are fat-soluble, the hypothesis in the current study was that low levels of vitamins A and E could identify patients at risk for low 25-OH vitamin D, so that 25-OH vitamin D measurements could be obtained in only selected circumstances. METHODS: Forty (21 girls) patients with CF, age 10.5 +/- 3.9 (SD) years, were assessed in a cross-sectional survey for ideal weight for height (percentage of predicted), spirometry (percentage of predicted FEV1, 33/40 patients), and serum levels of vitamins A, E, 25-OH vitamin D, and cholesterol (37/40 patients). RESULTS: Nine (22.5%) of 40 patients were malnourished (percentage of predicted ideal weight for height <85%), 7 (21.2%) of 33 had moderate to severe lung disease (FEV1 <60%), 4 (10%) of 40 had low levels of vitamin A, 3 (7.5%) of 40 had low vitamin E levels, 4 (10.8%) of 37 low vitamin E/cholesterol levels, and 4 (10%) of 40 had marginal or low levels of 25-OH vitamin D (<40 mmol/l). The patients with low 25-OH vitamin D were older, with no child < 12 years of age having a 25-OH vitamin D level less than 40 mmol/l. They also had lower vitamin E and vitamin E/cholesterol levels than those with normal 25-OH vitamin D levels. The groups did not differ in percentage of predicted ideal weight for height, lung function, or vitamin A levels. The best positive predictor for 25-OH vitamin D less than 40 mmol/l was low vitamin E (66.7%), with a negative predictive value of 94.6%. 25-OH vitamin D levels correlated with vitamin E/cholesterol levels (r = 0.41, P < 0.01) and weakly with vitamin E levels (r = 0.28, P < 0.08), but not with vitamin A levels. CONCLUSIONS: These results suggest that children aged less than 12 years and older children with normal vitamin E levels are especially unlikely to have low 25-OH vitamin D levels, and this measure can therefore be omitted. In contrast, those children with low vitamin E levels may warrant monitoring.

Adolescent↗

Treatment of obstructive airway disease with a cysteine donor protein supplement: a case report.

Oxidant/antioxidant imbalance can occur in obstructive airways disease as a result of ongoing inflammation. Glutathione (GSH) plays a major role in pulmonary antioxidant protection. As an alternative or complement to anti-inflammatory therapy, augmenting antioxidant protection could diminish the effects of inflammation. We describe a case of a patient who had obstructive lung disease responsive to corticosteroids, and low whole blood GSH levels. After 1 month of supplementation with a whey-based oral supplement designed to provide GSH precursors, whole blood GSH levels and pulmonary function increased significantly and dramatically. The potential for such supplementation in pulmonary inflammatory conditions deserves further study.

Administration, Oral↗

Lymphocyte glutathione levels in children with cystic fibrosis.

OBJECTIVE: Lung disease in cystic fibrosis (CF) is characterized by a neutrophilic inflammatory response. This can lead to the production of oxidants, and to oxidative stress in the lungs. Glutathione (GSH) represents the primary intracellular antioxidant, and provides an important defense in the epithelial lining fluid. Evidence suggests that lymphocyte GSH reflects lung GSH concentrations, and so could potentially serve as a peripheral marker of lung inflammation. METHODS: We assessed peripheral blood lymphocyte GSH concentrations in 20 children (13 boys) with CF who were in stable condition at the time of evaluation. Values were compared with nutritional status and lung function parameters. RESULTS: Patients were 11.7+/-3.03 years old (mean +/- SD). Their percentage of ideal body weight was 101.8+/-17.92%; FEV1, 79.5+/-19.22% predicted; FEV1/FVC, 75.0+/-10.08%; and residual volume (RV)/total lung capacity (TLC), 31.3+/-10.47%. For the group, the GSH concentration was 1.31+/-0.52 micromol/10(6) lymphocytes, which was not different from laboratory control values. GSH values were correlated with nutritional status (percentage of ideal body weight: r = 0.49, p < 0.03) and the degree of gas trapping (RV/TLC: r = 0.50, p < 0.03), and were correlated inversely with airflow limitation (FEV1, percent predicted: r = -0.45, p < 0.05; FEV1/FVC: r = -0.48, p < 0.04), but not with age, height, or weight (p > 0.1). CONCLUSIONS: We interpret the inverse correlation between lymphocyte GSH concentration and lung function as a reflection of upregulation of GSH production by lung epithelial tissue in response to oxidative stress. We interpret the correlation between lymphocyte GSH concentration and nutritional status as a reflection of the role of cysteine in hepatic glutamine metabolism. Peripheral blood lymphocyte GSH concentration may potentially serve as a convenient marker of lung inflammation. Furthermore, the increased demand for GSH production in the face of ongoing inflammation suggests a potential role for supplementation with cysteine donors.

Child↗

Specific antibody responses to diphtheria/tetanus revaccination in children evaluated for immunodeficiency.

BACKGROUND: Assaying specific antibody levels against well-defined antigens such as diphtheria (D), tetanus (T), and more recently Haemophilus is used as one indicator of humoral immune reactivity when evaluating patients for immunodeficiency. The nature of the response to booster vaccine in this group of patients is not well defined. OBJECTIVE: To define the response to D/T booster vaccination in patients with nonprotective antibody levels in order to distinguish immunocompetent from immunodeficient children. METHODS: Patients between the ages of 16 months and 17 years referred for possible immunodeficiency were assessed for specific antibody levels as part of a standard immunologic evaluation. Twenty-six previously immunized patients had antibody titers less than or equal to 0.2 IU against D and/or T or another abnormal vaccine response. All of these patients received boosters of diphtheria and tetanus vaccine (D2T5). Diphtheria and tetanus antibody levels were assayed 4 weeks following booster vaccination. RESULTS: Of the twenty-six subjects, a subset of patients (6) failed to show significant elevations in specific-serum antibody titers to diphtheria and/or tetanus and were thus labeled nonresponders. These patients were retrospectively compared with their responder counterparts examining specific antibody titers pre-immunization and post-immunization, serum immunoglobulins, and clinical presentation. The groups showed no significant difference in baseline specific antibody measures but following re-immunization responders showed a 31.34-fold and 22.33-fold increase in D and T antibody levels, respectively. In contrast, nonresponders produced only a 2.62-fold to D and 6.15-fold increase to T (all group comparisons P < .05). Clinical presentation also tended to be more severe in the nonresponder group. CONCLUSIONS: These data stress the importance of specific antibody titers pre-immunization and post-immunization in the assessment of immunodeficiency states, and emphasize the different characteristics of responses between diphtheria and tetanus toxoids. The ability to achieve the minimum protective antibody level does not necessarily denote immune competence. Serum immunoglobulin levels and baseline antibody titers are insufficient for the functional assessment of the immune response. The ability to generate antibody responses following booster vaccination is a more complete measure of overall immune competence and should be considered when evaluating patients for replacement immunoglobulin therapy.

Adolescent↗

Insulin-like growth factor II/mannose-6-phosphate receptors are transiently increased in the rat distal intestinal epithelium after resection.

The levels of insulin-like growth factor II/mannose-6-phosphate (IGF-II/Man-6-P) receptor and the insulin-like growth factor I (IGF-I) receptor were measured in the intestinal epithelium after 50% resection of the small intestine. Controls were either pair-fed to match the reduced food intake of the resected group or fed ad libitum. [125I]IGF-II binding was transiently increased 2-fold in the distal segment of the small intestine 3 days after resection compared with the pair-fed control. Receptor levels increased from 2.60 nmol/mg protein (pair-fed) to 4.63 nmol/mg protein (resected; p less than 0.001) with no significant change in affinity of IGF-II binding (Kd = 11.2 vs. 9.8 nmol/l). The increase in IGF-II/Man-6-P receptors coincided with increased activity of thymidine kinase in the distal intestinal segment after the resection. [125I]IGF-I binding remained unchanged after the resection. However, the decreased food intake of the pair-fed and resected groups caused a 2-fold increase in the amount of IGF-I receptors (0.18 nmol/mg protein; p less than 0.001) compared with the control fed ad libitum (0.08 nmol/mg protein). IGF-II/Man-6-P receptors were only moderately increased during restricted food intake (2.60 vs. 1.78 nmol/mg protein; p less than 0.005). These results suggest that the IGF-II/Man-6-P receptor may play a role in the adaptive regenerative response of the intestinal epithelium.

Animals↗